bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of microRNA carried by small extracellular vesicles in urological tumors
Authors: Mao Yiping , Zhang Mengting , Wang Lanfeng , Lu Yukang , Hu Xinyi , Chen Zhiping
Published: June 2023

Small extracellular vesicles (sEVs) are minute vesicles secreted by various cells that are capable of transporting cargo, including microRNAs, between donor and recipient cells. MicroRNAs (miRNAs), small non-coding RNAs approximately 22 nucleotides in length, have been implicated in a wide array of biological processes, including those involved in tumorigenesis. Emerging evidence highlights the pivotal role of miRNAs encapsulated in sEVs in both the diagnosis and treatment of urological tumors, with potential implications in epithelial-mesenchymal transition, proliferation, metastasis, angiogenesis, tumor microenvironment and drug resistance. This review provides a brief overview of the biogenesis and functional mechanisms of sEVs and miRNAs, followed by a summarization of recent empirical findings on miRNAs encapsulated in sEVs from three archetypal urologic malignancies: prostate cancer, clear cell renal cell carcinoma, and bladder cancer. We conclude by underscoring the potential of sEV-enclosed miRNAs as both biomarkers and therapeutic targets, with a particular focus on their detection and analysis in biological fluids such as urine, plasma, and serum.
Detection of sulfur mustard simulants using the microwave atmospheric pressure plasma optical emission spectroscopy method
Authors: Xu Dexin , Li Cong , Yang Liu , Zhu Wenchao , Huang Bangdou , Zhang Cheng , Shao Tao
Published: June 2023

Sulfur mustard (SM) is one kind of highly toxic chemical warfare agent and easy to spread, while existing detection methods cannot fulfill the requirement of rapid response, good portability, and cost competitiveness at the same time. In this work, the microwave atmospheric pressure plasma optical emission spectroscopy (MW-APP-OES) method, taking the advantage of non-thermal equilibrium, high reactivity, and high purity of MW plasma, is developed to detect three kinds of SM simulants, i.e., 2-chloroethyl ethyl sulfide, dipropyl disulfide, and ethanethiol. Characteristic OES from both atom lines (C I and Cl I) and radical bands (CS, CH, and C2) is identified, confirming MW-APP-OES can preserve more information about target agents without full atomization. Gas flow rate and MW power are optimized to achieve the best analytical results. Good linearity is obtained from the calibration curve for the CS band (linear coefficients R2 > 0.995) over a wide range of concentrations, and a limit of detection down to sub-ppm is achieved with response time on the order of second. With SM simulants as examples, the analytical results in this work indicate that MW-APP-OES is a promising method for real-time and in-site detection of chemical warfare agents.
Prevalence of ideal cardiovascular health and its relationship with relative handgrip strength in rural northeast China
Authors: Shao Jingan , Yao Bin , Yu Zhecong , Xu Jiahui , Wu Jing , Ma Yanan , Zheng Liqiang , Sun Zhaoqing
Published: June 2023

Objectives

We aimed to investigate ideal cardiovascular health (CVH), its relationship with handgrip strength, and its components in rural China.

Methods

We conducted a cross-sectional study of 3,203 rural Chinese individuals aged ≥35 years in Liaoning Province, China. Of these, 2,088 participants completed the follow-up survey. Handgrip strength was estimated using a handheld dynamometer and was normalized to body mass. Ideal CVH was assessed using seven health indicators (smoking, body mass index, physical activity, diet, cholesterol, blood pressure, and glucose). Binary logistic regression analyses were performed to assess the correlation between handgrip strength and ideal CVH.

Results

Women had a higher rate of ideal cardiovascular health (CVH) than men (15.7% vs. 6.8%, P < 0.001). Higher handgrip strength correlated with a higher proportion of ideal CVH (P for trend <0.001). After adjusting for confounding factors, the odds ratios (95% confidence interval) of ideal CVH across increasing handgrip strength tripartite were 1.00 (reference), 2.368 (1.773, 3.164), and 3.642 (2.605, 5.093) in the cross-sectional study and 1.00 (reference), 2.088 (1.074, 4.060), and 3.804 (1.829, 7.913) in the follow-up study (all P < 0.05).

Conclusion

In rural China, the ideal CVH rate was low, and positively correlated with handgrip strength. Grip strength can be a rough predictor of ideal CVH and can be used to provide guidelines for improving CVH in rural China.
Coronary microvascular dysfunction in heart failure patients
Authors: Toya Takumi , Nagatomo Yuji , Ikegami Yukinori , Masaki Nobuyuki , Adachi Takeshi
Published: June 2023

Coronary microcirculation has multiple layers of autoregulatory function to maintain resting flow and augment hyperemic flow in response to myocardial demands. Functional or structural alterations in the coronary microvascular function are frequently observed in patients with heart failure with preserved or reduced ejection fraction, which may lead to myocardial ischemic injury and resultant worsening of clinical outcomes. In this review, we describe our current understanding of coronary microvascular dysfunction in the pathogenesis of heart failure with preserved and reduced ejection fraction.
Public attitudes towards automated external defibrillators: results of a survey in the Australian general population
Authors: Kovoor Joshua G. , Marschner Simone , Amarasekera Anjalee , Nageswaran Meera , Page Gregory J. , Chow Clara K. , Thiagalingam Aravinda , Kovoor Pramesh
Published: June 2023

Background

Swift defibrillation by lay responders using automated external defibrillators (AEDs) increases survival in out-of-hospital cardiac arrest (OHCA). This study evaluated newly designed yellow–red vs. commonly used green–white signage for AEDs and cabinets and assessed public attitudes to using AEDs during OHCA.

Methods

New yellow–red signage was designed to enable easy identification of AEDs and cabinets. A prospective, cross-sectional study of the Australian public was conducted using an electronic, anonymised questionnaire between November 2021 and June 2022. The validated net promoter score investigated public engagement with the signage. Likert scales and binary comparisons evaluated preference, comfort and likelihood of using AEDs for OHCA.

Results

The yellow–red signage for AED and cabinet was preferred by 73.0% and 88%, respectively, over the green–white counterparts. Only 32% were uncomfortable with using AEDs, and only 19% indicated a low likelihood of using AEDs in OHCA.

Conclusion

The majority of the Australian public surveyed preferred yellow–red over green–white signage for AED and cabinet and indicated comfort and likelihood of using AEDs in OHCA. Steps are necessary to standardise yellow–red signage of AED and cabinet and enable widespread availability of AEDs for public access defibrillation.
Supporting the journey of architecture students towards graduation through a design ePortfolio
Authors: Colabella Sofia , Pugnale Alberto , Mack Michael , Woo Catherine Mei Min
Published: June 2023

This paper presents the different steps of the journey that led to the development and implementation of a design ePortfolio as part of the “Architecture Major” of the “Bachelor of Design” (BDes) at The University of Melbourne, Australia. This design ePortfolio was developed over 2 years through interviews, focus groups with students, and the development of exercises and assignment guidelines. The implementation took place in different phases, starting with the introduction of four thematic exercises in the Capstone Architecture Design Studio of the BDes, and then, more broadly, at the curriculum level, with similar activities that prepared the students to already start developing a reflective journal from the first year of their studies. The objective of this research has been to explore the potential of integrating a design ePortfolio with traditional design portfolios on the curricular activities of an undergraduate architecture degree to prioritise the students’ reflections on their personal qualities, growth, career trajectory and goals, as well as on the relationship between curricular and extracurricular activities rather than those of a conventional design portfolio, which tend to be focused more on showcasing skills and competencies. The results of this two-year project illustrate the potential of such a teaching/learning tool to link the personal and professional interests and achievements of students holistically, therefore highlighting the relationship between curricular and extracurricular activities, as well as indirect connections between design studios and seminar-based subjects, that is, history and architectural technology subjects. So far, our design ePortfolio has been successfully used to encourage architecture students to reframe problems through a different lens and, as a key to creativity, to distinguish themselves from the homogeneity of students the university produces through its degree structure and modes of operation. The significance of this teaching and learning project lies in the identification of patterns in the curricular and extracurricular experiences of students that helps them define their identity, goals, and purpose. For this reason, this research has the potential to be linked to the University’s “Student Life” project, which is related to academic advice, personal growth, mentorship, and the well-being of students.
Faculty experiences and motivations in design thinking teaching and learning
Authors: McLaughlin Jacqueline E. , Lake Danielle , Chen Elizabeth , Guo Wen , Knock McKenna , Knotek Steve
Published: June 2023

Introduction

Design thinking (DT) is a creative, iterative approach to generating solutions that are desirable, feasible, and viable. Given its role in fostering creativity and innovation, a growing number of higher education instructors are teaching DT. Exploring how and what instructors know about DT and why they might teach it could provide critical insight into the ways in which DT is operationalized in higher education teaching and learning.

Materials and methods

A convergent parallel mixed methods design was used for data collected from online surveys administered to faculty teaching DT. The survey included items about DT practices, outcomes from DT, demographic characteristics, and course characteristics. Five open-text survey items queried participants about their definition of DT, why they teach DT, and what additional outcomes they observed. Descriptive statistics were used to analyze quantitative items and thematic analysis was used to analyze qualitative items.

Results

Participants (n = 49) represented various academic ranks, disciplines, types of institutions, and geographic locations. Analyses indicated clear congruence between quantitative and qualitative data. Definitions of DT aligned with well-known models of DT. Motivations for teaching DT included the promotion of personal development, DT proficiency, impact, and interpersonal skill development. Other positive student outcomes observed included increases in enthusiasm, self-awareness, empowerment, optimism, and a sense of belonging. Negative student outcomes included time constraints, teamwork conflicts, and student frustration.

Conclusion

Faculty believe that DT leads to highly valuable social innovation skill sets for students. This cross-institutional, multi-disciplinary study provides critical insight into faculty experiences and motivations for teaching DT, offering various strategies for instructors and institutions interested in fostering the uptake of DT within higher education.
Studying trabecular bone samples demonstrates a power law relation between deteriorated structure and mechanical properties - a study combining 3D printing with the finite element method
Authors: Huang Xiuhong , Zheng Liqin , Zheng Desheng , Li Shaobin , Fan Yueguang , Lin Ziling , Huang Shaohong
Published: June 2023

Introduction

The bone volume fraction (BV/TV) significantly contributes to the mechanical properties of trabecular bone. However, when studies compare normal trabeculae against osteoporotic trabeculae (in terms of BV/TV decrease), only an “average” mechanical result has been determined because of the limitation that no two trabecular structures are the same and that each unique trabecular structure can be mechanically tested only once. The mathematic relation between individual structural deterioration and mechanical properties during aging or the osteoporosis process has yet to be further clarified. Three-dimensional (3D) printing and micro-CT-based finite element method (μFEM) can assist in overcoming this issue.

Methods

In this study, we 3D printed structural-identical but BV/TV value-attenuated trabecular bones (scaled up ×20) from the distal femur of healthy and ovariectomized rats and performed compression mechanical tests. Corresponding μFEM models were also established for simulations. The tissue modulus and strength of 3D printed trabecular bones as well as the effective tissue modulus (denoted as Ez) derived from μFEM models were finally corrected by the side-artifact correction factor.

Results

The results showed that the tissue modulus corrected, strength corrected and Ez corrected exhibited a significant power law function of BV/TV in structural-identical but BV/TV value-attenuated trabecular samples.

Discussion

Using 3D printed bones, this study confirms the long-known relationship measured in trabecular tissue with varying volume fractions. In the future, 3D printing may help us attain better bone strength evaluations and even personal fracture risk assessments for patients who suffer from osteoporosis.
Causal relationship between nonalcoholic fatty liver disease and different sleep traits: a bidirectional Mendelian randomized study
Authors: Sun Zijin , Ji Jing , Zuo Ling , Hu Yifan , Wang Kai , Xu Tian , Wang Qingguo , Cheng Fafeng
Published: June 2023

Background and aims

Non-alcoholic fatty liver disease(NAFLD) is common worldwide and has previously been reported to be associated with sleep traits. However, it is not clear whether NAFLD changes sleep traits or whether the changes in sleep traits lead to the onset of NAFLD. The purpose of this study was to investigate the causal relationship between NAFLD and changes in sleep traits using Mendelian randomization.

Methods

We proposed a bidirectional Mendelian randomization (MR) analysis and performed validation analyses to dissect the association between NAFLD and sleep traits. Genetic instruments were used as proxies for NAFLD and sleep. Data of genome-wide association study(GWAS) were obtained from the center for neurogenomics and cognitive research database, Open GWAS database and GWAS catalog. Three MR methods were performed, including inverse variance weighted method(IVW), MR-Egger, weighted median.

Results

In total,7 traits associated with sleep and 4 traits associated with NAFLD are used in this study. A total of six results showed significant differences. Insomnia was associated with NAFLD (OR(95% CI)= 2.25(1.18,4.27), P = 0.01), Alanine transaminase levels (OR(95% CI)= 2.79(1.70, 4.56), P =4.71×10-5) and percent liver fat(OR(95% CI)= 1.31(1.03,1.69), P = 0.03). Snoring was associated with percent liver fat (1.15(1.05,1.26), P =2×10-3), alanine transaminase levels (OR(95% CI)= 1.27(1.08,1.50), P =0.04).And dozing was associated with percent liver fat(1.14(1.02,1.26), P =0.02).For the remaining 50 outcomes, no significant or definitive association was yielded in MR analysis.

Conclusion

Genetic evidence suggests putative causal relationships between NAFLD and a set of sleep traits, indicating that sleep traits deserves high priority in clinical practice. Not only the confirmed sleep apnea syndrome, but also the sleep duration and sleep state (such as insomnia) deserve clinical attention. Our study proves that the causal relationship between sleep characteristics and NAFLD is the cause of the change of sleep characteristics, while the onset of non-NAFLD is the cause of the change of sleep characteristics, and the causal relationship is one-way.
Urinary levels of organophosphate flame retardants metabolites in a young population from Southern Taiwan and potential health effects
Authors: Chen Feng-Shun , Chen Chih-Cheng , Tsai Ching-Chang , Lu Jian-He , You Huey-Ling , Chen Ching-Mei , Huang Wan-Ting , Tsai Kai-Fan , Cheng Fu-Jen , Kung Chia-Te , Li Shau-Hsuan , Wang Chin-Chou , Ou Yu-Che , Lee Wen-Chin , Chang Yu-Ting , Hashim Fahimah , Chao How-Ran , Wang Liang-Jen
Published: June 2023

Background

Organophosphate flame retardants (OPFRs) are widely distributed in the environment and their metabolites are observed in urine, but little is known regarding OPFRs in a broad-spectrum young population from newborns to those aged 18 years.

Objectives

Investigate urinary levels of OPFRs and OPFR metabolites in Taiwanese infants, young children, schoolchildren, and adolescents within the general population.

Methods

Different age groups of subjects (n=136) were recruited from southern Taiwan to detect 10 OPFR metabolites in urine samples. Associations between urinary OPFRs and their corresponding metabolites and potential health status were also examined.

Results

The mean level of urinary Σ10 OPFR in this broad-spectrum young population is 2.25 μg/L (standard deviation (SD) of 1.91 μg/L). Σ10 OPFR metabolites in urine are 3.25 ± 2.84, 3.06 ± 2.21, 1.75 ± 1.10, and 2.32 ± 2.29 μg/L in the age groups comprising of newborns, 1-5 year-olds, 6-10 year-olds, and 11-18 year-olds, respectively, and borderline significant differences were found in the different age groups (p=0.125). The OPFR metabolites of TCEP, BCEP, DPHP, TBEP, DBEP, and BDCPP predominate in urine and comprise more than 90% of the total. TBEP was highly correlated with DBEP in this population (r=0.845, p<0.001). The estimated daily intake (EDI) of Σ5OPFRs (TDCPP, TCEP, TBEP, TNBP, and TPHP) was 2,230, 461, 130, and 184 ng/kg bw/day for newborns, 1-5 yr children, 6-10 yr children, and 11-17 yr adolescents, respectively. The EDI of Σ5OPFRs for newborns was 4.83-17.2 times higher than the other age groups. Urinary OPFR metabolites are significantly correlated with birth length and chest circumference in newborns.

Conclusion

To our knowledge, this is the first investigation of urinary OPFR metabolite levels in a broad-spectrum young population. There tended to be higher exposure rates in both newborns and pre-schoolers, though little is known about their exposure levels or factors leading to exposure in the young population. Further studies should clarify the exposure levels and factor relationships.
NOD mouse dorsal root ganglia display morphological and gene expression defects before and during autoimmune diabetes development
Authors: Corral-Pujol Marta , Arpa Berta , Rosell-Mases Estela , Egia-Mendikute Leire , Mora Conchi , Stratmann Thomas , Sanchez Alex , Casanovas Anna , Esquerda Josep Enric , Mauricio Didac , Vives-Pi Marta , Verdaguer Joan
Published: June 2023

Introduction

During the development of Autoimmune Diabetes (AD) an autoimmune attack against the Peripheral Nervous System occurs. To gain insight into this topic, analyses of Dorsal Root Ganglia (DRG) from Non-Obese Diabetic (NOD) mice were carried out.

Methods

Histopathological analysis by electron and optical microscopy in DRG samples, and mRNA expression analyzes by the microarray technique in DRG and blood leukocyte samples from NOD and C57BL/6 mice were performed.

Results

The results showed the formation of cytoplasmic vacuoles in DRG cells early in life that could be related to a neurodegenerative process. In view of these results, mRNA expression analyses were conducted to determine the cause and/or the molecules involved in this suspected disorder. The results showed that DRG cells from NOD mice have alterations in the transcription of a wide range of genes, which explain the previously observed alterations. In addition, differences in the transcription genes in white blood cells were also detected.

Discussion

Taken together, these results indicate that functional defects are not only seen in beta cells but also in DRG in NOD mice. These results also indicate that these defects are not a consequence of the autoimmune process that takes place in NOD mice and suggest that they may be involved as triggers for its development.
Ghrelin does not impact the blunted counterregulatory response to recurrent hypoglycemia in mice
Authors: Shankar Kripa , Varshney Salil , Gupta Deepali , Mani Bharath K. , Osborne-Lawrence Sherri , Metzger Nathan P. , Richard Corine P. , Zigman Jeffrey M.
Published: June 2023

Introduction

Recurrent episodes of insulin-induced hypoglycemia in patients with diabetes mellitus can result in hypoglycemia-associated autonomic failure (HAAF), which is characterized by a compromised response to hypoglycemia by counterregulatory hormones (counterregulatory response; CRR) and hypoglycemia unawareness. HAAF is a leading cause of morbidity in diabetes and often hinders optimal regulation of blood glucose levels. Yet, the molecular pathways underlying HAAF remain incompletely described. We previously reported that in mice, ghrelin is permissive for the usual CRR to insulin-induced hypoglycemia. Here, we tested the hypothesis that attenuated release of ghrelin both results from HAAF and contributes to HAAF.

Methods

C57BL/6N mice, ghrelin-knockout (KO) + control mice, and GhIRKO (ghrelin cell-selective insulin receptor knockout) + control mice were randomized to one of three treatment groups: a “Euglycemia” group was injected with saline and remained euglycemic; a 1X hypoglycemia (“1X Hypo”) group underwent a single episode of insulin-induced hypoglycemia; a recurrent hypoglycemia (“Recurrent Hypo”) group underwent repeated episodes of insulin-induced hypoglycemia over five successive days.

Results

Recurrent hypoglycemia exaggerated the reduction in blood glucose (by ~30%) and attenuated the elevations in plasma levels of the CRR hormones glucagon (by 64.5%) and epinephrine (by 52.9%) in C57BL/6N mice compared to a single hypoglycemic episode. Yet, plasma ghrelin was equivalently reduced in “1X Hypo” and “Recurrent Hypo” C57BL/6N mice. Ghrelin-KO mice exhibited neither exaggerated hypoglycemia in response to recurrent hypoglycemia, nor any additional attenuation in CRR hormone levels compared to wild-type littermates. Also, in response to recurrent hypoglycemia, GhIRKO mice exhibited nearly identical blood glucose and plasma CRR hormone levels as littermates with intact insulin receptor expression (floxed-IR mice), despite higher plasma ghrelin in GhIRKO mice.

Conclusions

These data suggest that the usual reduction of plasma ghrelin due to insulin-induced hypoglycemia is unaltered by recurrent hypoglycemia and that ghrelin does not impact blood glucose or the blunted CRR hormone responses during recurrent hypoglycemia.
Positive correlation between fatty liver index and hyperuricemia in hypertensive Chinese adults: a H-type hypertension registry study
Authors: Yu Chao , Zhou Xinlei , Wang Tao , Zhu Lingjuan , Zhou Wei , Bao Huihui , Cheng Xiaoshu
Published: June 2023

Background

Few studies have examined the relationship between fatty liver index (FLI) and hyperuricemia (HUA). This study explores the relationship between FLI and HUA in hypertensive patients.

Methods

A total of 13,716 hypertensive subjects were included in the current study. FLI, a simple index calculated from triglycerides (TG), waist circumference (WC), body mass index (BMI), and γ -glutamyltransferase (GGT), was used as a useful predictor of nonalcoholic fatty liver disease (NAFLD) distribution. HUA was defined as serum uric acid ≥ 360 μmol/L for females and ≥ 420 μmol/L for males.

Results

The mean value of total FLI was 31.8 ± 25.1. Multiple logistic analyses revealed a significant positive correlation between FLI and HUA (OR, 1.78; 95% CI: 1.69–1.87). A subgroup analysis demonstrated that the correlation between FLI (< 30 vs. ≥ 30) and HUA was significant in both sexes (P for interaction = 0.006). Further analyses stratified by sex indicated a positive correlation between FLI and HUA prevalence among male and female subjects. However, the correlation between FLI and HUA was stronger in female subjects than in males (male: OR, 1.70; 95% CI: 1.58–1.83; female: 1.85; 95% CI: 1.73–1.98).

Conclusion

This study demonstrates a positive correlation between FLI and HUA in hypertensive adults, but stronger in females than males.
Screening of lipids and kidney function in children and adolescents with Type 1 Diabetes: does age matter?
Authors: Catamo Eulalia , Robino Antonietta , Dovc Klemen , Tinti Davide , Tamaro Gianluca , Bonfanti Riccardo , Franceschi Roberto , Rabbone Ivana , Battelino Tadej , Tornese Gianluca
Published: June 2023

Introduction

The purpose of this study was to evaluate lipid profile and kidney function in children and adolescents with Type 1 Diabetes.

Methods

This was a retrospective study including 324 children and adolescents with Type 1 Diabetes (48% females, mean age 13.1 ± 3.2 years). For all participants, demographic and clinical information were collected. The prevalence of dyslipidemia and kidney function markers were analyzed according to age. Multivariate linear regression analyses were performed to test the association of lipids or markers of renal function with demographic and clinical information (sex, age, disease duration, BMI SDS, HbA1c).

Results

In our study the rate of dyslipidemia reached 32% in children <11 years and 18.5% in those ≥11 years. Children <11 years presented significantly higher triglyceride values. While the albumin-to-creatinine ratio was normal in all individuals, 17% had mildly reduced estimated glomerular filtration rate. Median of HbA1c was the most important determinant of lipids and kidney function, being associated with Total Cholesterol (p-value<0.001); LDL Cholesterol (p-value=0.009), HDL Cholesterol (p-value=0.045) and eGFR (p-value=0.001).

Conclusion

Dyslipidemia could be present both in children and adolescents, suggesting that screening for markers of diabetic complications should be performed regardless of age, pubertal stage, or disease duration, to optimize glycemia and medical nutrition therapy and/or to start a specific medical treatment.
Heritability and circulating concentrations of pregnancy-associated plasma protein-A and stanniocalcin-2 in elderly monozygotic and dizygotic twins
Authors: Hjortebjerg Rikke , Pedersen Dorthe Almind , Mengel-From Jonas , Jørgensen Louise Helskov , Christensen Kaare , Frystyk Jan
Published: June 2023

Introduction

Pregnancy-associated plasma protein-A (PAPP-A) is an IGF-activating enzyme suggested to influence aging-related diseases. However, knowledge on serum PAPP-A concentration and regulation in elderly subjects is limited. Therefore, we measured serum PAPP-A in elderly same-sex monozygotic (MZ) and dizygotic (DZ) twins, as this allowed us to describe the age-relationship of PAPP-A, and to test the hypothesis that serum PAPP-A concentrations are genetically determined. As PAPP-A is functionally related to stanniocalcin-2 (STC2), an endogenous PAPP-A inhibitor, we included measurements on STC2 as well as IGF-I and IGF-II.

Methods

The twin cohort contained 596 subjects (250 MZ twins, 346 DZ twins), whereof 33% were males. The age ranged from 73.2 to 94.3 (mean 78.8) years. Serum was analyzed for PAPP-A, STC2, IGF-I, and IGF-II by commercial immunoassays.

Results

In the twin cohort, PAPP-A increased with age (r=0.19; P<0.05), whereas IGF-I decreased (r=-0.12; P<0.05). Neither STC2 nor IGF-II showed any age relationship. When analyzed according to sex, PAPP-A correlated positively with age in males (r=0.18; P<0.05) and females (r=0.25; P<0.01), whereas IGF-I correlated inversely in females only (r=-0.15; P<0.01). Males had higher levels of PAPP-A (29%), STC2 (18%) and IGF-I (19%), whereas serum IGF-II was 28% higher in females (all P<0.001). For all four proteins, within-pair correlations were significantly higher for MZ twins than for DZ twins, and they demonstrated substantial and significant heritability, which after adjustment for age and sex averaged 59% for PAPP-A, 66% for STC2, 58% for IGF-I, and 52% for IGF-II.

Discussion

This twin study confirms our hypothesis that the heritability of PAPP-A serum concentrations is substantial, and the same is true for STC2. As regards the age relationship, PAPP-A increases with age, whereas STC2 remains unchanged, thereby supporting the idea that the ability of STC2 to inhibit PAPP-A enzymatic activity decreases with increasing age.
Climate change effects on the potential distribution of the endemic Commiphora species (Burseraceae) on the island of Socotra
Authors: La Montagna Dario , Attorre Fabio , Hamdiah Salem , Maděra Petr , Malatesta Luca , Vahalík Petr , Van Damme Kay , De Sanctis Michele
Published: June 2023

The Socotra Archipelago (Yemen) is an interesting biodiversity hotspot, with a significant proportion of endemic species that have evolved to survive in an arid subtropical environment, inscribed as a World Heritage Site by UNESCO. The terrestrial ecosystems of Socotra face several threats, including climate change, overgrazing and soil degradation. Socotra Island has four endemic species of the genus Commiphora (Burseraceae). Little is known about their local distribution and ecology, yet these trees could be useful indicator species. Our study focuses on the distribution and niche characterisation of the four endemic Commiphora species of Socotra and how climate change may affect them. The aim is to improve insights into their habitats and to provide an essential basis for future local management plans and ecological restoration. We compared the current distribution with the forecasted potential distribution under a CMIP6 (Coupled Model Intercomparison Project) climate scenario, allowing us to define target conservation areas and assess potential local extinction risks. To achieve this, we collected distribution data in the field throughout Socotra Island, covering the current distribution ranges of the four species. To assess the potential distribution of these species, we applied three models (GAM, MaxEnt, RandomForest) using bioclimatic, topographic and soil variables. Forecasts under a climate change scenario were made using bioclimatic variables from the CMCC-CESM2 climate model for two different socioeconomic pathways. The distribution of three endemic Socotran Commiphora is mainly correlated to clay content in the soil and winter precipitation, while C. socotrana is affected by seasonal precipitation and temperature. Under different potential future climate scenarios, the distribution of C. ornifolia is predicted to remain stable or increase, while C. parvifolia distribution could increase, yet C. planifrons and C. socotrana are predicted to undergo a strong reduction of suitable areas and an upward shift in the mountains. Our results highlight that it is essential to conserve the unique terrestrial ecosystems in Socotra and to preserve these endemic trees which have a wide range of ecosystem services. Updates on the predicted extinction risk assessment are fundamental to understand conservation priorities and strategize future actions to ensure the persistence of Socotran myrrh trees and other endangered endemic tree taxa on the island.
Understanding the impact of an AI-enabled conversational agent mobile app on users’ mental health and wellbeing with a self-reported maternal event: a mixed method real-world data mHealth study
Authors: Inkster Becky , Kadaba Madhura , Subramanian Vinod
Published: June 2023

Background

Maternal mental health care is variable and with limited accessibility. Artificial intelligence (AI) conversational agents (CAs) could potentially play an important role in supporting maternal mental health and wellbeing. Our study examined data from real-world users who self-reported a maternal event while engaging with a digital mental health and wellbeing AI-enabled CA app (Wysa) for emotional support. The study evaluated app effectiveness by comparing changes in self-reported depressive symptoms between a higher engaged group of users and a lower engaged group of users and derived qualitative insights into the behaviors exhibited among higher engaged maternal event users based on their conversations with the AI CA.

Methods

Real-world anonymised data from users who reported going through a maternal event during their conversation with the app was analyzed. For the first objective, users who completed two PHQ-9 self-reported assessments (n = 51) were grouped as either higher engaged users (n = 28) or lower engaged users (n = 23) based on their number of active session-days with the CA between two screenings. A non-parametric Mann–Whitney test (M–W) and non-parametric Common Language effect size was used to evaluate group differences in self-reported depressive symptoms. For the second objective, a Braun and Clarke thematic analysis was used to identify engagement behavior with the CA for the top quartile of higher engaged users (n = 10 of 51). Feedback on the app and demographic information was also explored.

Results

Results revealed a significant reduction in self-reported depressive symptoms among the higher engaged user group compared to lower engaged user group (M–W p = .004) with a high effect size (CL = 0.736). Furthermore, the top themes that emerged from the qualitative analysis revealed users expressed concerns, hopes, need for support, reframing their thoughts and expressing their victories and gratitude.

Conclusion

These findings provide preliminary evidence of the effectiveness and engagement and comfort of using this AI-based emotionally intelligent mobile app to support mental health and wellbeing across a range of maternal events and experiences.
Exploration of T cell immune responses by expression of a dominant-negative SHP1 and SHP2
Authors: Taylor Julia , Bulek Anna , Gannon Isaac , Robson Mathew , Kokalaki Evangelia , Grothier Thomas , McKenzie Callum , El-Kholy Mohamed , Stavrou Maria , Traynor-White Charlotte , Lim Wen Chean , Panagiotou Panagiota , Srivastava Saket , Baldan Vania , Sillibourne James , Ferrari Mathieu , Pule Martin , Thomas Simon
Published: June 2023

SHP1 and SHP2 are SH2 domain-containing proteins which have inhibitory phosphatase activity when recruited to phosphorylated ITIMs and ITSMs on inhibitory immune receptors. Consequently, SHP1 and SHP2 are key proteins in the transmission of inhibitory signals within T cells, constituting an important point of convergence for diverse inhibitory receptors. Therefore, SHP1 and SHP2 inhibition may represent a strategy for preventing immunosuppression of T cells mediated by cancers hence improving immunotherapies directed against these malignancies. Both SHP1 and SHP2 contain dual SH2 domains responsible for localization to the endodomain of inhibitory receptors and a protein tyrosine phosphatase domain which dephosphorylates and thus inhibits key mediators of T cell activation. We explored the interaction of the isolated SH2 domains of SHP1 and SHP2 to inhibitory motifs from PD1 and identified strong binding of both SH2 domains from SHP2 and more moderate binding in the case of SHP1. We next explored whether a truncated form of SHP1/2 comprising only of SH2 domains (dSHP1/2) could act in a dominant negative fashion by preventing docking of the wild type proteins. When co-expressed with CARs we found that dSHP2 but not dSHP1 could alleviate immunosuppression mediated by PD1. We next explored the capacity of dSHP2 to bind with other inhibitory receptors and observed several potential interactions. In vivo we observed that the expression of PDL1 on tumor cells impaired the ability of CAR T cells to mediate tumor rejection and this effect was partially reversed by the co-expression of dSHP2 albeit at the cost of reduced CAR T cell proliferation. Modulation of SHP1 and SHP2 activity in engineered T cells through the expression of these truncated variants may enhance T cell activity and hence efficacy in the context of cancer immunotherapy.
Influences of resolvin D1 and D2 on the risk of type 2 diabetes mellitus: a Chinese community-based cohort study
Authors: Sun Qian , Wang Junrong , Jing Yang , Liu Jingchao , Jin Jianrong , Wang Sudan , Zhang Jin , Liu Kaili , Chen Xiaofang , Zhou Hui , Dong Chen
Published: June 2023

Background

Although cellular and animal studies have reported that resolvin D1 (RvD1) and resolvin D2 (RvD2) are mechanisms involved in the development of type 2 diabetes mellitus (T2DM), the impact of RvD1 and RvD2 on the risk of T2DM at a population level remains unclear.

Methods

We included 2755 non-diabetic adults from a community-based cohort in China and followed them for seven years. Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of RvD1 and RvD2 with T2DM probability. Time-dependent receiver operator characteristics (ROC) curve was used to evaluate the predictive performance of RvD1 and RvD2 for the risk of T2DM based on the Chinese CDC T2DM prediction model (CDRS).

Results

A total of 172 incident T2DM cases were identified. Multivariate-adjusted HRs (95% CI) for T2DM across quartiles of RvD1 levels (Q1, Q2, Q3 and Q4) were 1.00, 1.64 (1.03-2.63), 1.80 (1.13-2.86) and 1.61 (1.01-2.57), respectively. Additionally, body mass index (BMI) showed a significant effect modification in the association of RvD1 with incident T2DM (Pinteraction = 0.026). After multivariate adjustment, the HR (95% CI) for T2DM in the fourth compared with the first quartile of RvD2 was 1.94 (95% CI: 1.24-3.03). Time-dependent ROC analysis showed that the area under time-dependent ROC curves of the “CDRS+RvD1+RvD2” model for the 3-, 5- and 7-year risk of T2DM were 0.842, 0.835 and 0.828, respectively.

Conclusions

Higher RvD1 and RvD2 levels are associated with a higher risk of T2DM at the population level.
Host-mediated beneficial effects of phytochemicals for prevention of avian coccidiosis
Authors: Park Inkyung , Nam Hyoyoun , Wickramasuriya Samiru S. , Lee Youngsub , Wall Emma H. , Ravichandran Sripathy , Lillehoj Hyun S.
Published: June 2023

Both in vitro and in vivo studies were conducted to evaluate the beneficial effects of green tea extract (GT), cinnamon oil (CO), and pomegranate extract (PO) on avian coccidiosis. In experiment (EXP) 1, an in vitro culture system was used to investigate the individual effects of GT, CO, and PO on the proinflammatory cytokine response and integrity of tight junction (TJ) in chicken intestinal epithelial cells (IEC), on the differentiation of quail muscle cells and primary chicken embryonic muscle cells, and anticoccidial and antibacterial activities against Eimeria tenella sporozoites and Clostridium perfringens bacteria, respectively. In EXP 2 and 3, in vivo trials were carried out to study the dose-dependent effect of blended phytochemicals (GT, CO, PO) on coccidiosis in broiler chickens infected with E. maxima. For EXP 2, one hundred male broiler chickens (0-day-old) were allocated into the following five treatment groups: Control group for non-infected chickens (NC), Basal diet group for E. maxima-infected chickens (PC), PC group supplemented with phytochemicals at 50 (Phy 50), 100 (Phy 100), and 200 (Phy 200) mg/kg feed diets for E. maxima-infected chickens. For EXP 3, one hundred twenty male broiler chickens (0-day-old) were allocated into the following six treatment groups: NC, PC, PC supplemented with phytochemicals at 10 (Phy 10), 20 (Phy 20), 30 (Phy 30), and 100 (Phy 100) mg/kg feed for E. maxima-infected chickens. Body weights (BW) were measured on days 0, 7, 14, 20, and 22, and jejunum samples were used to measure cytokine, TJ protein, and antioxidant enzyme responses at 8 days post-infection (dpi). Fecal samples for oocyst enumeration were collected from 6 to 8 dpi. In vitro, CO and PO reduced LPS-induced IL-1β and IL-8 in IEC, respectively, and GT enhanced the gene expression of occludin in IEC. PO at 1.0 and 5.0 mg/mL exerted antimicrobial effect against E. tenella sporozoites and C. perfringens bacteria, respectively. In vivo, chickens fed a diet supplemented with phytochemicals showed enhanced BW, reduced oocyst shedding, and decreased proinflammatory cytokines following E. maxima challenge. In conclusion, the combination of GT, CO, and PO in the diet of broiler chickens infected with E. maxima induced enhanced host disease resistance including innate immunity and gut health, which contributed to improved growth and reduced disease responses. These findings provide scientific support for the development of a novel phytogenic feed additive formula that enhances the growth and intestinal health of broiler chickens infected with coccidiosis.
Mechanosensitive Piezo1 protein as a novel regulator in macrophages and macrophage-mediated inflammatory diseases
Authors: Tang Yu , Zhao Chuanxiang , Zhuang Ying , Zhong Anjing , Wang Ming , Zhang Wei , Zhu Liqun
Published: June 2023

Macrophages are the most important innate immune cells in humans. They are almost ubiquitous in peripheral tissues with a large variety of different mechanical milieus. Therefore, it is not inconceivable that mechanical stimuli have effects on macrophages. Emerging as key molecular detectors of mechanical stress, the function of Piezo channels in macrophages is becoming attractive. In this review, we addressed the architecture, activation mechanisms, biological functions, and pharmacological regulation of the Piezo1 channel and review the research advancements in functions of Piezo1 channels in macrophages and macrophage-mediated inflammatory diseases as well as the potential mechanisms involved.
A hepatitis B virus-derived peptide combined with HBsAg exerts an anti-HBV effect in an HBV transgenic mouse model as a therapeutic vaccine
Authors: Choi Yu-Min , Kim Dong Hyun , Jang Junghwa , Kim Bum-Joon
Published: June 2023

Introduction

For complete or functional cure of hepatitis B virus (HBV) infection, application of immunotherapy is now being attempted. Recently, we reported that a 6-mer hepatitis B virus (HBV)-derived peptide, Poly6, exerts a strong anticancer effect in tumor-implanted mice through inducible nitric oxide synthase (iNOS)-producing DCs (Tip-DCs) in a type 1 interferon (IFN-I)-dependent manner, suggesting its potential as a vaccine adjuvant.

Methods

In this study, we explored the potential of Poly6 in combination with HBsAg as a therapeutic vaccine against hepatitis B virus infection. We investigated the immunotherapeutic potential of Poly6 combined with HBsAg vaccination against hepatitis B virus infection in C57BL/6 mice or an HBV transgenic mouse model.

Results

In C57BL/6 mice, Poly6 enhanced DC maturation and DC migration capacity in an IFN-I-dependent manner. Moreover, the addition of Poly6 to alum in combination with HBsAg also led to enhanced HBsAg-specific cell-mediated immune (CMI) responses, suggesting its potential as an adjuvant of HBsAg-based vaccines. In HBV transgenic mice, vaccination with Poly6 combined with HBsAg exerted a strong anti-HBV effect via induction of HBV-specific humoral and cell-mediated immune responses. In addition, it also induced HBV-specific effector memory T cells (TEM).

Discussion

Our data indicated that vaccination with Poly6 in combination with HBsAg exerts an anti-HBV effect in HBV transgenic mice, which is mainly mediated by HBV-specific CMI and humoral immune responses via IFN-I-dependent DC activation, suggesting the feasibility of Poly6 as an adjuvant for an HBV therapeutic vaccine.
The presence of senescent peripheral T-cells is negatively correlated to COVID-19 vaccine-induced immunity in cancer patients under 70 years of age
Authors: Orillard E. , Spehner L. , Mansi L. , Bouard A. , Falcoz A. , Lepiller Q. , Renaude E. , Pallandre JR. , Vienot A. , Kroemer M. , Borg C.
Published: June 2023

Purpose

Cancer patients are at risk of severe COVID-19 infection, and vaccination is recommended. Nevertheless, we observe a failure of COVID-19 vaccines in this vulnerable population. We hypothesize that senescent peripheral T-cells alter COVID-19 vaccine-induced immunity.

Methods

We performed a monocentric prospective study and enrolled cancer patients and healthy donors before the COVID-19 vaccination. The primary objective was to assess the association of peripheral senescent T-cells (CD28-CD57+KLRG1+) with COVID-19 vaccine-induced immunity.

Results

Eighty cancer patients have been included, with serological and specific T-cell responses evaluated before and at 3 months post-vaccination. Age ≥ 70 years was the principal clinical factor negatively influencing the serological (p=0.035) and specific SARS-CoV-2 T-cell responses (p=0.047). The presence of senescent T-cells was correlated to lower serological (p=0.049) and specific T-cell responses (p=0.009). Our results sustained the definition of a specific cut-off for senescence immune phenotype (SIP) (≥ 5% of CD4 and ≥ 39.5% of CD8 T-cells), which was correlated to a lower serological response induced by COVID-19 vaccination for CD4 and CD8 SIPhigh (p=0.039 and p=0.049 respectively). While CD4 SIP level had no impact on COVID-19 vaccine efficacy in elderly patients, our results unraveled a possible predictive role for CD4 SIPhigh T-cell levels in younger cancer patients.

Conclusions

Elderly cancer patients have a poor serological response to vaccination; specific strategies are needed in this population. Also, the presence of a CD4 SIPhigh affects the serological response in younger patients and seems to be a potential biomarker of no vaccinal response.