bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel substitution-box generation using group theory for secure medical image encryption in E-healthcare
Authors: Razaq Abdul , Maghrabi Louai A. , Ahmad Musheer , Naith Qamar H.
Published: February 2024

With the increasing need for secure transmission and storage of medical images, the development of robust encryption algorithms is of paramount importance. Securing sensitive digital medical imagery information during transmission has emerged as a critical priority in the e-Healthcare systems. Recent research has highlighted the significance of developing advanced medical image encryption algorithms to ensure secure transmission during telediagnosis and teleconsultations. In this study, we propose a novel medical image encryption algorithm which is based on a novel substitution-box generation algebraic method using a combination of a multiplicative cyclic group with an order of 256 and a permutation group with a large order. To evaluate the security performance of the proposed generated S-box, various standard security indicators are assessed and analyzed. The newly proposed medical image encryption algorithm utilizes the generated S-box, along with bit-plane slicing, circular shifting, and XOR operations, to achieve enhanced security and robustness for encrypting sensitive imagery data. In order to assess the effectiveness of the proposed encryption algorithm, a comprehensive benchmarking analyses, specifically designed for evaluating image encryption schemes, have been conducted. The results obtained from the comparison and other analyses serve to validate the optimal features and high cryptographic strength exhibited by the proposed method. Hence, the proposed algorithm demonstrates significant effectiveness and holds considerable promise in the realm of medical image encryption for secure e-Healthcare systems.
Grey parameter estimation method for extreme value distribution of short-term wind speed data
Authors: Lv Yichen , Xiao Xinping
Published: February 2024

Accurate parameter estimation of extreme wind speed distribution is of great importance for the safe utilization and assessment of wind resources. This paper emphatically establishes a novel grey generalized extreme value method for parameter estimation of annual wind speed extremum distribution (AWSED). Considering the uncertainty and frequency characteristics of the parent wind speed, the generalized extreme value distribution (GEVD) is selected as the probability distribution, and the Weibull distribution is utilized as the first-order accumulation generating operator. Then, the GEVD differential equation is derived, and it is transformed into the grey GEVD model using the differential information principle. The least squares method is used to estimate the grey GEVD model parameters, and then a novel estimation method is proposed through grey parameters. A hybrid particle swarm optimization algorithm is used to optimize distribution parameters. The novel method is stable under different sample sizes according to Monte Carlo comparison simulation results, and the suitability for the novel method is confirmed by instance analysis in Wujiaba, Yunnan Province. The new method performs with high accuracy in various indicators, the hypothesis test results are above 95%, and the statistical errors such as MAPE and Wasserstein distance yield the lowest, which are 3.33% and 0.2556, respectively.
Boyd-Wong type functional contractions under locally transitive binary relation with applications to boundary value problems
Authors: Alamer Ahmed , Khan Faizan Ahmad
Published: February 2024

The area of metric fixed point theory applied to relational metric spaces has received significant attention since the appearance of the relation-theoretic contraction principle. In recent times, a number of fixed point theorems addressing the various contractivity conditions in the relational metric space has been investigated. Such results are extremely advantageous in solving a variety of boundary value problems, matrix equations, and integral equations. This article offerred some fixed point results for a functional contractive mapping depending on a control function due to Boyd and Wong in a metric space endued with a local class of transitive relations. Our findings improved, developed, enhanced, combined and strengthened several fixed point theorems found in the literature. Several illustrative examples were delivered to argue for the reliability of our findings. To verify the relevance of our findings, we conveyed an existence and uniqueness theorem regarding the solution of a first-order boundary value problem.
Novel categories of spaces in the frame of fuzzy soft topologies
Authors: Al-shami Tareq M. , Saleh Salem , Abd El-latif Alaa M. , Mhemdi Abdelwaheb
Published: February 2024

In the present paper, we introduce and discuss a new set of separation properties in fuzzy soft topological spaces called $ FS\delta $-separation and $ FS\delta $-regularity axioms by using fuzzy soft $ \delta $-open sets and the quasi-coincident relation. We provide a comprehensive study of their properties with some supporting examples. Our analysis includes more characterizations, results, and theorems related to these notions, which contributes to a deeper understanding of fuzzy soft separability properties. We show that the $ FS\delta $-separation and $ FS\delta $-regularity axioms are harmonic and heredity property. Additionally, we examine the connections between $ FS{\delta }^* $-compactness and $ FS\delta $-separation axioms and explore the relationships between them. Overall, this work offers a new perspective on the theory of separation properties in fuzzy soft topological spaces, as well as provides a robust foundation for further research in the transmission of properties from fuzzy soft topologies to fuzzy and soft topologies and vice-versa by swapping between the membership function and characteristic function in the case of fuzzy topology and the set of parameters and a singleton set in the case of soft topology.
Understanding the maternal-infant nexus from dental histology and high-resolution compositional biogeochemistry: implications for bioarchaeological research
Authors: Nava Alessia
Published: February 2024

La relation intime entre la mère et l’enfant pendant la grossesse et la petite enfance est un aspect encore peu exploré chez les humains du passé. L’étude des tissus dentaires minéralisés permet d’obtenir des informations sur ce lien à la fois biologique et culturel. En effet, les dents conservent un enregistrement permanent de l’histoire biologique de l’individu, de la vie intra-utérine aux premières années après la naissance et jusqu’au début de l’âge adulte. En outre, les tissus formés pendant la période prénatale enregistrent l’état de santé, le régime alimentaire et la mobilité de la dyade mère-enfant pendant la grossesse. L’histomorphométrie classique et l’histomorphométrie virtuelle non destructive constituent les approches les plus modernes pour étudier les trajectoires de croissance des nourrissons, les stress physiologiques et l’état de santé de la mère et du nourrisson. En outre, l’alimentation maternelle, les pratiques d’allaitement, le début du sevrage et les schémas de mobilité peuvent être reconstitués avec une haute résolution temporelle grâce à des analyses biogéochimiques élémentaires et isotopiques de l’émail dentaire basées sur le laser. En effet, la croissance et le développement humains, dès les premières phases de l’ontogenèse, sont fortement corrélés aux comportements alimentaires, y compris ceux de la mère pendant la grossesse. Des modèles sur l’incorporation des oligo-éléments dans l’émail dentaire et leur corrélation avec les principaux changements alimentaires ont été dérivés de l’analyse des dents déciduales exfoliées de nourrissons contemporains dont l’histoire biologique est bien connue. Ces modèles constituent la boîte à outils interprétative permettant de démêler les variations, même subtiles, des régimes alimentaires individuels à une résolution infra-hebdomadaire. Cette contribution présente une vue d’ensemble de la biogéochimie compositionnelle à haute résolution couplée à l’histomorphométrie dentaire en tant qu’outils permettant d’approfondir notre connaissance du lien mère-enfant à partir des tissus dentaires minéralisés et d’étudier, avec la plus haute résolution temporelle possible, les stratégies de survie et d’adaptation des femmes et des enfants.
Dynamique linguistique de l’arabe dialectal marocain sur les espaces numériques du web 2.0 : émergence d’une langue commune ou renforcement des variétés dialectales locales
Authors: El Baroudi Mourad
Published: February 2024

L’arabe dialectal marocain était principalement utilisé à l’oral. Cependant, avec l’avènement du web 2.0, son utilisation écrite s’est répandue sur les espaces numériques, entraînant une dynamique linguistique importante. Cet article vise à examiner si les espaces numériques interactifs favorisent l’émergence d’un arabe marocain commun et uniforme, ou renforcent plutôt les différentes variétés locales.
Safety and Effectiveness of Dulaglutide in the Treatment of Type 2 Diabetes Mellitus: A Korean Real-World Post-Marketing Study
Authors: Han Jeonghee , Lee Woo Je , Hur Kyu Yeon , Cho Jae Hyoung , Lee Byung Wan , Park Cheol-Young
Published: February 2024

Background: To investigate the real-world safety and effectiveness of dulaglutide in Korean adults with type 2 diabetes mellitus (T2DM).Methods: This was a real-world, prospective, non-interventional post-marketing safety study conducted from May 26, 2015 to May 25, 2021 at 85 Korean healthcare centers using electronic case data. Data on patients using dulaglutide 0.75 mg/0.5 mL or the dulaglutide 1.5 mg/0.5 mL single-use pens were collected and pooled. The primary objective was to report the frequency and proportion of adverse and serious adverse events that occurred. The secondary objective was to monitor the effectiveness of dulaglutide at 12 and 24 weeks by evaluating changes in glycosylated hemoglobin (HbA1c ), fasting plasma glucose, and body weight.Results: Data were collected from 3,067 subjects, and 3,022 subjects who received ≥1 dose (of any strength) of dulaglutide were included in the safety analysis set (53% female, mean age 56 years; diabetes duration 11.2 years, mean HbA1c 8.8%). The number of adverse events reported was 819; of these, 68 (8.3%) were serious adverse events. One death was reported. Adverse events were mostly mild in severity; 60.81% of adverse events were considered related to dulaglutide. This study was completed by 72.73% (2,198/3,022) of subjects. At 12/24 weeks there were significant (P<0.0001) reductions from baseline in least-squares mean HbA1c (0.96%/0.95%), fasting blood glucose (26.24/24.43 mg/dL), and body weight (0.75/1.21 kg).Conclusion: Dulaglutide was generally well tolerated and effective in real-world Korean individuals with T2DM. The results from this study contribute to the body of evidence for dulaglutide use in this population.
Supplementation of Clostridium butyricum Alleviates Vascular Inflammation in Diabetic Mice
Authors: Zhou Tian , Qiu Shuo , Zhang Liang , Li Yangni , Zhang Jing , Shen Donghua , Zhao Ping , Yuan Lijun , Zhao Lianbi , Duan Yunyou , Xing Changyang
Published: February 2024

Background: Gut microbiota is closely related to the occurrence and development of diabetes and affects the prognosis of diabetic complications, and the underlying mechanisms are only partially understood. We aimed to explore the possible link between the gut microbiota and vascular inflammation of diabetic mice.Methods: The db/db diabetic and wild-type (WT) mice were used in this study. We profiled gut microbiota and examined the and vascular function in both db/db group and WT group. Gut microbiota was analyzed by 16s rRNA sequencing. Vascular function was examined by ultrasonographic hemodynamics and histological staining. Clostridium butyricum (CB) was orally administered to diabetic mice by intragastric gavage every 2 days for 2 consecutive months. Reactive oxygen species (ROS) and expression of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were detected by fluorescence microscopy. The mRNA expression of inflammatory cytokines was tested by quantitative polymerase chain reaction.Results: Compared with WT mice, CB abundance was significantly decreased in the gut of db/db mice, together with compromised vascular function and activated inflammation in the arterial tissue. Meanwhile, ROS in the vascular tissue of db/db mice was also significantly increased. Oral administration of CB restored the protective microbiota, and protected the vascular function in the db/db mice via activating the Nrf2/HO-1 pathway.Conclusion: This study identified the potential link between decreased CB abundance in gut microbiota and vascular inflammation in diabetes. Therapeutic delivery of CB by gut transplantation alleviates the vascular lesions of diabetes mellitus by activating the Nrf2/HO-1 pathway.
Deficiency of ASGR1 Alleviates Diet-Induced Systemic Insulin Resistance via Improved Hepatic Insulin Sensitivity
Authors: Yu Xiaorui , Tao Jiawang , Wu Yuhang , Chen Yan , Li Penghui , Yang Fan , Tang Miaoxiu , Sammad Abdul , Tao Yu , Xu Yingying , Li Yin-Xiong
Published: February 2024

Background: Insulin resistance (IR) is the key pathological basis of many metabolic disorders. Lack of asialoglycoprotein receptor 1 (ASGR1) decreased the serum lipid levels and reduced the risk of coronary artery disease. However, whether ASGR1 also participates in the regulatory network of insulin sensitivity and glucose metabolism remains unknown.Methods: The constructed ASGR1 knockout mice and ASGR1-/- HepG2 cell lines were used to establish the animal model of metabolic syndrome and the IR cell model by high-fat diet (HFD) or drug induction, respectively. Then we evaluated the glucose metabolism and insulin signaling in vivo and in vitro.Results: ASGR1 deficiency ameliorated systemic IR in mice fed with HFD, evidenced by improved insulin intolerance, serum insulin, and homeostasis model assessment of IR index, mainly contributed from increased insulin signaling in the liver, but not in muscle or adipose tissues. Meanwhile, the insulin signal transduction was significantly enhanced in ASGR1-/- HepG2 cells. By transcriptome analyses and comparison, those differentially expressed genes between ASGR1 null and wild type were enriched in the insulin signal pathway, particularly in phosphoinositide 3-kinase-AKT signaling. Notably, ASGR1 deficiency significantly reduced hepatic gluconeogenesis and glycogenolysis.Conclusion: The ASGR1 deficiency was consequentially linked with improved hepatic insulin sensitivity under metabolic stress, hepatic IR was the core factor of systemic IR, and overcoming hepatic IR significantly relieved the systemic IR. It suggests that ASGR1 is a potential intervention target for improving systemic IR in metabolic disorders.
Harnessing Metabolic Indices as a Predictive Tool for Cardiovascular Disease in a Korean Population without Known Major Cardiovascular Event
Authors: Kim Hyun-Jin , Kim Byung Sik , Lee Yonggu , Ahn Sang Bong , Kim Dong Wook , Shin Jeong-Hun
Published: February 2024

Background: This study evaluated the usefulness of indices for metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), and insulin resistance (IR), as predictive tools for cardiovascular disease in middle-aged Korean adults.Methods: The prospective data obtained from the Ansan-Ansung cohort database, excluding patients with major adverse cardiac and cerebrovascular events (MACCE). The primary outcome was the incidence of MACCE during the follow-up period.Results: A total of 9,337 patients were included in the analysis, of whom 1,130 (12.1%) experienced MACCE during a median follow-up period of 15.5 years. The metabolic syndrome severity Z-score, metabolic syndrome severity score, hepatic steatosis index, and NAFLD liver fat score were found to significantly predict MACCE at values above the cut-off point and in the second and third tertiles. Among these indices, the hazard ratios of the metabolic syndrome severity score and metabolic syndrome severity Z-score were the highest after adjusting for confounding factors. The area under the receiver operating characteristic curve (AUC) of the 10-year atherosclerotic cardiovascular disease (ASCVD) score for predicting MACCE was 0.716, and the metabolic syndrome severity Z-score had an AUC of 0.619.Conclusion: The metabolic syndrome severity score is a highly reliable indicator and was closely associated with the 10-year ASCVD risk score in predicting MACCE in the general population. Given the specific characteristics and limitations of metabolic syndrome severity scores as well as the indices of NAFLD and IR, a more practical scoring system that considers these factors is essential to achieve greater accuracy in forecasting cardiovascular outcomes.
Enhancing Diabetes Care through a Mobile Application: A Randomized Clinical Trial on Integrating Physical and Mental Health among Disadvantaged Individuals
Authors: Bae Jae Hyun , Park Eun Hee , Lee Hae Kyung , Yoon Kun Ho , Won Kyu Chang , Kim Hyun Mi , Kim Sin Gon
Published: February 2024

Background: This study examines integrating physical and mental healthcare for disadvantaged persons with type 2 diabetes mellitus and mild-to-moderate depression in the community, using a mobile application within a public-private-academic partnership.Methods: The Korean Diabetes Association has developed a mobile application combining behavioral activation for psychological well-being and diabetes self-management, with conventional medical therapy. Participants were randomly assigned to receive the application with usual care or only usual care. Primary outcomes measured changes in psychological status and diabetes selfmanagement through questionnaires at week 12 from the baseline. Secondary outcomes assessed glycemic and lipid control, with psychological assessments at week 16.Results: Thirty-nine of 73 participants completed the study (20 and 19 in the intervention and control groups, respectively) and were included in the analysis. At week 12, the intervention group showed significant reductions in depression severity and perceived stress compared to the control group. Additionally, they reported increased perceived social support and demonstrated improved diabetes self-care behavior. These positive effects persisted through week 16, with the added benefit of reduced anxiety. While fasting glucose levels in the intervention group tended to improve, no other significant differences were observed in laboratory assessments between the groups.Conclusion: This study provides compelling evidence for the potential efficacy of a mobile application that integrates physical and mental health components to address depressive symptoms and enhance diabetes self-management in disadvantaged individuals with type 2 diabetes mellitus and depression. Further research involving larger and more diverse populations is warranted to validate these findings and solidify their implications.
Temporal Changes in Resting Heart Rate and Risk of Diabetes Mellitus
Authors: Son Mi Kyoung , Lee Kyoungho , Park Hyun-Young
Published: February 2024

Background: To investigate the association between the time-varying resting heart rate (RHR) and change in RHR (∆RHR) over time and the risk of diabetes mellitus (DM) by sex.Methods: We assessed 8,392 participants without DM or atrial fibrillation/flutter from the Korean Genome and Epidemiology Study, a community-based prospective cohort study that was initiated in 2001 to 2002. The participants were followed up until December 31, 2018. Updating RHR with biennial in-study re-examinations, the time-varying ∆RHR was calculated by assessing the ∆RHR at the next follow-up visit.Results: Over a median follow-up of 12.3 years, 1,345 participants (16.2%) had DM. As compared with RHR of 60 to 69 bpm, for RHR of ≥80 bpm, the incidence of DM was significantly increased for both male and female. A drop of ≥5 bpm in ∆RHR when compared with the stable ∆RHR group (–5< ∆RHR <5 bpm) was associated significantly with lower risk of DM in both male and female. However, an increase of ≥5 bpm in ∆RHR was significantly associated with higher risk of DM only in female, not in male (hazard ratio for male, 1.057 [95% confidence interval, 0.869 to 1.285]; and for female, 1.218 [95% confidence interval, 1.008 to 1.471]).Conclusion: In this community-based longitudinal cohort study, a reduction in ∆RHR was associated with a decreased risk of DM, while an increase in ∆RHR was associated with an increased risk of DM only in female.
Pioglitazone as Add-on Therapy in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Dapagliflozin and Metformin: Double-Blind, Randomized, Placebo-Controlled Trial
Authors: Heo Ji Hye , Han Kyung Ah , Hong Jun Hwa , Seo Hyun-Ae , Hong Eun-Gyoung , Yu Jae Myung , Jung Hye Seung , Cha Bong-Soo
Published: February 2024

Background: This study assessed the efficacy and safety of triple therapy with pioglitazone 15 mg add-on versus placebo in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and dapagliflozin.Methods: In this multicenter, double-blind, randomized, phase 3 study, patients with T2DM with an inadequate response to treatment with metformin (≥1,000 mg/day) plus dapagliflozin (10 mg/day) were randomized to receive additional pioglitazone 15 mg/day (n=125) or placebo (n=125) for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin (HbA1c) levels from baseline to week 24 (ClinicalTrials.gov identifier: NCT05101135).Results: At week 24, the adjusted mean change from baseline in HbA1c level compared with placebo was significantly greater with pioglitazone treatment (–0.47%; 95% confidence interval, –0.61 to –0.33; P<0.0001). A greater proportion of patients achieved HbA1c <7% or <6.5% at week 24 with pioglitazone compared to placebo as add-on to 10 mg dapagliflozin and metformin (56.8% vs. 28% for HbA1c <7%, and 23.2% vs. 9.6% for HbA1c <6.5%; P<0.0001 for all). The addition of pioglitazone also significantly improved triglyceride, highdensity lipoprotein cholesterol levels, and homeostatic model assessment of insulin resistance levels, while placebo did not. The incidence of treatment-emergent adverse events was similar between the groups, and the incidence of fluid retention-related side effects by pioglitazone was low (1.5%).Conclusion: Triple therapy with the addition of 15 mg/day of pioglitazone to dapagliflozin plus metformin was well tolerated and produced significant improvements in HbA1c in patients with T2DM inadequately controlled with dapagliflozin plus metformin.
Associations of Ultra-Processed Food Intake with Body Fat and Skeletal Muscle Mass by Sociodemographic Factors
Authors: Jung Sukyoung , Seo Jaehee , Kim Jee Young , Park Sohyun
Published: February 2024

Background: The effects of excessive ultra-processed food (UPF) consumption on body composition measures or sociodemographic disparities are understudied in Korea. We aimed to investigate the association of UPF intake with percent body fat (PBF) and percent appendicular skeletal muscle mass (PASM) by sociodemographic status in adults.Methods: This study used data from the Korea National Health and Nutrition Examination Survey 2008–2011 (n=11,123 aged ≥40 years). We used a NOVA system to classify all foods reported in a 24-hour dietary recall, and the percentage of energy intake (%kcal) from UPFs was estimated. PBF and PASM were measured by dual-energy X-ray absorptiometry. Tertile (T) 3 of PBF indicated adiposity and T1 of PASM indicated low skeletal muscle mass, respectively. Multinomial logistic regression models were used to estimate odds ratios (OR) with 95% confidence interval (CI) after adjusting covariates.Results: UPF intake was positively associated with PBF-defined adiposity (ORper 10% increase, 1.04; 95% CI, 1.002 to 1.08) and low PASM (ORper 10% increase, 1.05; 95% CI, 1.01 to 1.09). These associations were stronger in rural residents (PBF: ORper 10% increase, 1.14; 95% CI, 1.06 to 1.23; PASM: ORper 10% increase, 1.15; 95% CI, 1.07 to 1.23) and not college graduates (PBF: ORper 10% increase, 1.06; 95% CI, 1.02 to 1.11; PASM: ORper 10% increase, 1.07; 95% CI, 1.03 to 1.12) than their counterparts.Conclusion: A higher UPF intake was associated with higher adiposity and lower skeletal muscle mass among Korean adults aged 40 years and older, particularly in those from rural areas and with lower education levels.
Insulin Resistance, Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Clinical and Experimental Perspective
Authors: Jung Inha , Koo Dae-Jeong , Lee Won-Young
Published: February 2024

It has been generally accepted that insulin resistance (IR) and reduced insulin secretory capacity are the basic pathogenesis of type 2 diabetes mellitus (T2DM). In addition to genetic factors, the persistence of systemic inflammation caused by obesity and the associated threat of lipotoxicity increase the risk of T2DM. In particular, the main cause of IR is obesity and subjects with T2DM have a higher body mass index (BMI) than normal subjects according to recent studies. The prevalence of T2DM with IR has increased with increasing BMI during the past three decades. According to recent studies, homeostatic model assessment of IR was increased compared to that of the 1990s. Rising prevalence of obesity in Korea have contributed to the development of IR, non-alcoholic fatty liver disease and T2DM and cutting this vicious cycle is important. My colleagues and I have investigated this pathogenic mechanism on this theme through clinical and experimental studies over 20 years and herein, I would like to summarize some of our studies with deep gratitude for receiving the prestigious 2023 Sulwon Award.
Balancing act: The dilemma of rapid hyperglycemia correction in diabetes management
Authors: Zhang Ke-Xin , Kan Cheng-Xia , Sun Xiao-Dong
Published: February 2024

The global diabetes surge poses a critical public health challenge, emphasizing the need for effective glycemic control. However, rapid correction of chronic hyperglycemia can unexpectedly trigger microvascular complications, necessitating a reevaluation of the speed and intensity of glycemic correction. Theories suggest swift blood sugar reductions may cause inflammation, oxidative stress, and neurovascular changes, resulting in complications. Healthcare providers should cautiously approach aggressive glycemic control, especially in long-standing, poorly controlled diabetes. Preventing and managing these complications requires a personalized, comprehensive approach with education, monitoring, and interdisciplinary care. Diabetes management must balance short and long-term goals, prioritizing overall well-being. This editorial underscores the need for a personalized, nuanced approach, focusing on equilibrium between glycemic control and avoiding overcorrection.
Genotype-based precision nutrition strategies for the prediction and clinical management of type 2 diabetes mellitus
Authors: Ramos-Lopez Omar
Published: February 2024

Globally, type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders. T2DM physiopathology is influenced by complex interrelationships between genetic, metabolic and lifestyle factors (including diet), which differ between populations and geographic regions. In fact, excessive consumptions of high fat/high sugar foods generally increase the risk of developing T2DM, whereas habitual intakes of plant-based healthy diets usually exert a protective effect. Moreover, genomic studies have allowed the characterization of sequence DNA variants across the human genome, some of which may affect gene expression and protein functions relevant for glucose homeostasis. This comprehensive literature review covers the impact of gene-diet interactions on T2DM susceptibility and disease progression, some of which have demonstrated a value as biomarkers of personal responses to certain nutritional interventions. Also, novel genotype-based dietary strategies have been developed for improving T2DM control in comparison to general lifestyle recommendations. Furthermore, progresses in other omics areas (epigenomics, metagenomics, proteomics, and metabolomics) are improving current understanding of genetic insights in T2DM clinical outcomes. Although more investigation is still needed, the analysis of the genetic make-up may help to decipher new paradigms in the pathophysiology of T2DM as well as offer further opportunities to personalize the screening, prevention, diagnosis, management, and prognosis of T2DM through precision nutrition.
Identification of hub genes associated with Helicobacter pylori infection and type 2 diabetes mellitus: A pilot bioinformatics study
Authors: Chen Han , Zhang Guo-Xin , Zhou Xiao-Ying
Published: February 2024

BACKGROUND

Helicobacter pylori (H. pylori ) infection is related to various extragastric diseases including type 2 diabetes mellitus (T2DM). However, the possible mechanisms connecting H. pylori infection and T2DM remain unknown.

AIM

To explore potential molecular connections between H. pylori infection and T2DM.

METHODS

We extracted gene expression arrays from three online datasets (GSE60427, GSE27411 and GSE115601). Differentially expressed genes (DEGs) commonly present in patients with H. pylori infection and T2DM were identified. Hub genes were validated using human gastric biopsy samples. Correlations between hub genes and immune cell infiltration, miRNAs, and transcription factors (TFs) were further analyzed.

RESULTS

A total of 67 DEGs were commonly presented in patients with H. pylori infection and T2DM. Five significantly upregulated hub genes, including TLR4 , ITGAM , C5AR1 , FCER1G , and FCGR2A , were finally identified, all of which are closely related to immune cell infiltration. The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links. TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs, the largest number of TFs among the 5 hub genes.

CONCLUSION

We identified five hub genes that may have molecular connections between H. pylori infection and T2DM. This study provides new insights into the pathogenesis of H. pylori -induced onset of T2DM.
Experience of humanistic nursing in hemodialysis nursing for patients with diabetic kidney disease
Authors: Chai Xiao-Ying , Bao Xiao-Yan , Dai Ying , Dai Xing-Xing , Zhang Yu , Yang Yu-Ling
Published: February 2024

BACKGROUND

Diabetic kidney disease (DKD) is a prevalent complication of diabetes that often requires hemodialysis for treatment. In the field of nursing, there is a growing recognition of the importance of humanistic care, which focuses on the holistic needs of patients, including their emotional, psychological, and social well-being. However, the application of humanistic nursing in the context of hemodialysis for DKD patients remains relatively unexplored.

AIM

To explore the experience of humanistic nursing in hemodialysis nursing for DKD patients.

METHODS

Ninety-six DKD patients treated with hemodialysis from March 2020 to June 2022 were included in the study and divided into the control cluster (48 cases) and the study cluster (48 cases) according to different nursing methods; the control cluster was given routine nursing and the study cluster was given humanized nursing. The variances of negative emotion mark, blood glucose, renal function, the incidence of complications, life mark and nursing satisfaction before and after nur-sing were contrasted between the two clusters.

RESULTS

No significant difference in negative emotion markers between the two clusters were observed before nursing (P > 0.05), and the negative emotion markers of the two clusters decreased after nursing. The Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale markers were lower in the study cluster than the control cluster. The healing rate of patients in the study cluster was significantly higher than the control cluster (97.92% vs 85.42%, P < 0.05). Blood glucose parameters were not significantly different between the groups prior to nursing (P > 0.05). However, after nursing, blood urea nitrogen and serum creatinine (SCr) levels in the study cluster were lower than those in the control cluster (P < 0.05). The incidence rate of complications was significantly lower in the study group compared to the control cluster (6.25% vs 20.83%, P < 0.05). There was no significant difference in the life markers between the two clusters before nursing. While the life markers increased after nursing for both groups, the 36-item health scale markers in the study cluster were higher than those within the control cluster (P < 0.05). Finally, the nursing satisfaction rate was 93.75% in the study cluster, compared to 75% in the control cluster (P < 0.05).

CONCLUSION

In hemodialysis for DKD patients, the implementation of humanistic nursing achieved ideal results, effectively reducing patients’ psychological negative emotion markers so that they can actively cooperate with the diagnosis and nursing, facilitate the control of blood glucose and the maintenance of residual renal function, reduce the occurrence of complications, and finally enhance the life quality and nursing satisfaction of patients. It is worthy of being widely popularized and applied.
Vitamin D, selenium, and antidiabetic drugs in the treatment of type 2 diabetes mellitus with Hashimoto's thyroiditis
Authors: Feng Fen , Zhou Bin , Zhou Ci-La , Huang Ping , Wang Gang , Yao Kuang
Published: February 2024

BACKGROUND

Diabetes and thyroiditis are closely related. They occur in combination and cause significant damage to the body. There is no clear treatment for type-2 diabetes mellitus (T2DM) with Hashimoto's thyroiditis (HT). While single symptomatic drug treatment of the two diseases is less effective, combined drug treatment may improve efficacy.

AIM

To investigate the effect of a combination of vitamin D, selenium, and hypo-glycemic agents in T2DM with HT.

METHODS

This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023. Fifty patients were assigned to the control group, test group A, and test group B according to different treatment methods. The control group received low-iodine diet guidance and hypoglycemic drug treatment. Test group A received the control treatment plus vitamin D treatment. Test group B received the group A treatment plus selenium. Blood levels of markers of thyroid function [free T3 (FT3), thyroid stimulating hormone (TSH), free T4 (FT4)], autoantibodies [thyroid peroxidase antibody (TPOAB) and thyroid globulin antibody (TGAB)], blood lipid index [low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triacylglycerol (TG)], blood glucose index [fasting blood glucose (FBG), and hemoglobin A1c (HbA1c)] were measured pre-treatment and 3 and 6 months after treatment. The relationships between serum 25-hydroxyvitamin D3 [25 (OH) D3] level and each of these indices were analyzed.

RESULTS

The levels of 25 (OH) D3, FT3, FT4, and LDL-C increased in the order of the control group, test group A, and test group B (all P < 0.05). The TPOAB, TGAB, TC, TG, FBG, HbA1c, and TSH levels increased in the order of test groups B, A, and the control group (all P < 0.05). All the above indices were compared after 3 and 6 months of treatment. Pre-treatment, there was no divergence in serum 25 (OH) D3 level, thyroid function-related indexes, autoantibodies level, blood glucose, and blood lipid index between the control group, test groups A and B (all P > 0.05). The 25 (OH) D3 levels in test groups A and B were negatively correlated with FT4 and TGAB (all P < 0.05).

CONCLUSION

The combination drug treatment for T2DM with HT significantly improved thyroid function, autoantibody, and blood glucose and lipid levels.
Effect of viral hepatitis on type 2 diabetes: A Mendelian randomization study
Authors: Yu Yun-Feng , Hu Gang , Tong Ke-Ke , Yang Xin-Yu , Wu Jing-Yi , Yu Rong
Published: February 2024

BACKGROUND

The effects of viral hepatitis (VH) on type 2 diabetes (T2D) remain controversial.

AIM

To analyze the causal correlation between different types of VH and T2D using Mendelian randomization (MR).

METHODS

Single nucleotide polymorphisms of VH, chronic hepatitis B (CHB), chronic hepatitis C (CHC) and T2D were obtained from the BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Inverse variance weighted, MR-Egger, and weighted median were used to test exposure-outcome associations. The MR-Egger intercept analysis and Cochran’s Q test were used to assess horizontal pleiotropy and heterogeneity, respectively. Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results.

RESULTS

The MR analysis showed no significant causal relationship between VH and T2D in Europeans [odds ratio (OR) = 1.028; 95% confidence interval (CI): 0.995-1.062, P = 0.101]. There was a negative causal association between CHB and T2D among East Asians (OR = 0.949; 95%CI: 0.931-0.968, P < 0.001), while there was no significant causal association between CHC and T2D among East Asians (OR = 1.018; 95%CI: 0.959-1.081, P = 0.551). Intercept analysis and Cochran’s Q test showed no horizontal pleiotropy or heterogeneity (P > 0.05). Sensitivity analysis showed that the results were robust.

CONCLUSION

Among East Asians, CHB is associated with a reduced T2D risk, but this association is limited by HBV load and cirrhosis. Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D, focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHC-mediated pathways of hepatic steatosis, liver fibrosis, and cirrhosis.
Serum tumor markers expression (CA199, CA242, and CEA) and its clinical implications in type 2 diabetes mellitus
Authors: Meng Mei , Shi Li-Li
Published: February 2024

BACKGROUND

Glucose and lipid metabolic disorder in patients with type 2 diabetes mellitus (T2DM) is associated with the levels of serum tumor markers of the digestive tract, such as cancer antigen (CA)199. Therefore, tumor markers in T2DM are important.

AIM

To evaluate the expression of serum tumor markers [CA199, CA242, and car-cinoembryonic antigen (CEA)] and the clinical implications of the expression in T2DM.

METHODS

For this observational study conducted at Hefei BOE Hospital, China, we enrolled 82 patients with first-onset T2DM and 51 controls between April 2019 and December 2020. Levels of fasting blood glucose (FBG), tumor markers (CA199, CEA, and CA242), glycosylated hemoglobin (HbA1c), etc . were measured and group index levels were compared. Moreover, FBG and HbA1c levels were correlated with tumor marker levels. Tumor markers were tested for diagnostic accuracy in patients with > 9% HbA1c using the receiver operating curve (ROC) curve.

RESULTS

The T2DM group had high serum FBG, HbA1c, CA199, and CEA levels (P < 0.05). A comparative analysis of the two groups based on HbA1c levels (Group A: HbA1c ≤ 9%; Group B: HbA1c > 9%) revealed significant differences in CEA and CA199 levels (P < 0.05). The areas under the ROC curve for CEA and CA199 were 0.853 and 0.809, respectively. CA199, CEA, and CA242 levels positively correlated with HbA1c (r = 0.308, 0.426, and 0.551, respectively) and FBG levels (r = 0.236, 0.231, and 0.298, respectively).

CONCLUSION

As compared to controls, serum CEA and CA199 levels were higher in patients with T2DM. HbA1c and FBG levels correlated with CA199, CEA, and CA242 levels. Patients with poorly controlled blood sugar must be screened for tumor markers.
Age-specific differences in the association between prediabetes and cardiovascular diseases in China: A national cross-sectional study
Authors: Xie Shuo , Yu Li-Ping , Chen Fei , Wang Yao , Deng Rui-Fen , Zhang Xue-Lian , Zhang Bo
Published: February 2024

BACKGROUND

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide, the global burden of which is rising. It is still unclear the extent to which prediabetes contributes to the risk of CVD in various age brackets among adults. To develop a focused screening plan and treatment for Chinese adults with prediabetes, it is crucial to identify variations in the connection between prediabetes and the risk of CVD based on age.

AIM

To examine the clinical features of prediabetes and identify risk factors for CVD in different age groups in China.

METHODS

The cross-sectional study involved a total of 46239 participants from June 2007 through May 2008. A thorough evaluation was conducted. Individuals with prediabetes were categorized into two groups based on age. Chinese atherosclerotic CVD risk prediction model was employed to evaluate the risk of developing CVD over 10 years. Random forest was established in both age groups. SHapley Additive exPlanation method prioritized the importance of features from the perspective of assessment contribution.

RESULTS

In total, 6948 people were diagnosed with prediabetes in this study. In pre-diabetes, prevalences of CVD were 5 (0.29%) in the younger group and 148 (2.85%) in the older group. Overall, 11.11% of the younger group and 29.59% of the older group were intermediate/high-risk of CVD for prediabetes without CVD based on the Prediction for ASCVD Risk in China equation in ten years. In the younger age group, the 10-year risk of CVD was found to be more closely linked to family history of CVD rather than lifestyle, whereas in the older age group, resident status was more closely linked.

CONCLUSION

The susceptibility to CVD is age-specific in newly diagnosed prediabetes. It is necessary to develop targeted approaches for the prevention and management of CVD in adults across various age brackets.
Long noncoding RNA protein-disulfide isomerase-associated 3 regulated high glucose-induced podocyte apoptosis in diabetic nephropathy through targeting miR-139-3p
Authors: He Yin-Xi , Wang Ting , Li Wen-Xian , Chen Yan-Xia
Published: February 2024

BACKGROUND

Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy (DN). The regulatory relationship between long noncoding RNAs (lncRNAs) and podocyte apoptosis has recently become another research hot spot in the DN field.

AIM

To investigate whether lncRNA protein-disulfide isomerase-associated 3 (Pdia3) could regulate podocyte apoptosis through miR-139-3p and revealed the underlying mechanism.

METHODS

Using normal glucose or high glucose (HG)-cultured podocytes, the cellular functions and exact mechanisms underlying the regulatory effects of lncRNA Pdia3 on podocyte apoptosis and endoplasmic reticulum stress (ERS) were explored. LncRNA Pdia3 and miR-139-3p expression were measured through quantitative real-time polymerase chain reaction. Relative cell viability was detected through the cell counting kit-8 colorimetric assay. The podocyte apoptosis rate in each group was measured through flow cytometry. The interaction between lncRNA Pdia3 and miR-139-3p was examined through the dual luciferase reporter assay. Finally, western blotting was performed to detect the effect of lncRNA Pdia3 on podocyte apoptosis and ERS via miR-139-3p.

RESULTS

The expression of lncRNA Pdia3 was significantly downregulated in HG-cultured podocytes. Next, lncRNA Pdia3 was involved in HG-induced podocyte apoptosis. Furthermore, the dual luciferase reporter assay confirmed the direct interaction between lncRNA Pdia3 and miR-139-3p. LncRNA Pdia3 overexpression attenuated podocyte apoptosis and ERS through miR-139-3p in HG-cultured podocytes.

CONCLUSION

Taken together, this study demonstrated that lncRNA Pdia3 overexpression could attenuate HG-induced podocyte apoptosis and ERS by acting as a competing endogenous RNA of miR-139-3p, which might provide a potential therapeutic target for DN.
Assessment of pathogenicity and functional characterization of APPL1 gene mutations in diabetic patients
Authors: Shi Ping , Tian Yang , Xu Feng , Liu Lu-Na , Wu Wan-Hong , Shi Ying-Zhou , Dai An-Qi , Fang Hang-Yu , Li Kun-Xia , Xu Chao
Published: February 2024

BACKGROUND

Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) plays a crucial role in regulating insulin signaling and glucose metabolism. Mutations in the APPL1 gene have been associated with the development of maturity-onset diabetes of the young type 14 (MODY14). Currently, only two mutations [c.1655T>A (p.Leu552*) and c.281G>A p.(Asp94Asn)] have been identified in association with this disease. Given the limited understanding of MODY14, it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 mutations.

AIM

To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 domain.

METHODS

Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the study. Whole exome sequencing was performed on the patients as well as their family members. The pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics analysis. In addition, the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional experiments. Finally, the impact of these variants on APPL1 protein expression and the insulin pathway were assessed, and the potential mechanism underlying the interaction between the APPL1 protein and the insulin receptor was further explored.

RESULTS

A total of five novel mutations were identified, including four missense mutations (Asp632Tyr, Arg633His, Arg532Gln, and Ile642Met) and one intronic mutation (1153-16A>T). Pathogenicity prediction analysis revealed that the Arg532Gln was pathogenic across all predictions. The Asp632Tyr and Arg633His variants also had pathogenicity based on MutationTaster. In addition, multiple alignment of amino acid sequences showed that the Arg532Gln, Asp632Tyr, and Arg633His variants were conserved across different species. Moreover, in in vitro functional experiments, both the c.1894G>T (at Asp632Tyr) and c.1595G>A (at Arg532Gln) mutations were found to downregulate the expression of APPL1 on both protein and mRNA levels, indicating their pathogenic nature. Therefore, based on the patient’s clinical and family history, combined with the results from bioinformatics analysis and functional experiment, the c.1894G>T (at Asp632Tyr) and c.1595G>A (at Arg532Gln) mutations were classified as pathogenic mutations. Importantly, all these mutations were located within the phosphotyrosine-binding domain of APPL1, which plays a critical role in the insulin sensitization effect.

CONCLUSION

This study provided new insights into the pathogenicity of APPL1 gene mutations in diabetes and revealed a potential target for the diagnosis and treatment of the disease.