bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluorescent GLP1R/GIPR dual agonist probes reveal cell targets in the pancreas and brain
Authors: Hodson David , de Bray Anne , Tong Jason , Huhn Christiane , Roßmann Kilian , Shilleh Ali , Jiang Wanqing , Roberts Anna , Viloria Katrina , Nasteska Daniela , Pearce Abigail , Miyazaki Satsuki , Tomlinson Jeremy , Owen Dylan , Nieves Daniel , Ast Julia , Cyranka Malgorzata , Epanchintsev Alexey , Ämmälä Carina Ämmälä , Reimann Frank , Ladds Graham , Adriaenssens Alice , Trapp Stefan , Jones Ben , Broichhagen Johannes 
Published: August 2024

Abstract

Dual agonists targeting the glucagon-like peptide-1 receptor (GLP1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) are breakthrough treatments for type 2 diabetes and overweight. Compared to GLP1R agonists, dual agonists show superior efficacy for glucose lowering and weight reduction. However, delineation of dual agonist cell targets remains challenging. Here, we develop and test Tirzepa3 and Tirzepa5, fluorescent GLP1R/GIPR dual agonist probes. Tirzepa3 and Tirzepa5 have similar pharmacological profiles to tirzepatide, but advantageously show less functional selectivity for mouse GLP1R over mouse GIPR. Both probes specifically label GLP1R and GIPR in cells and tissue. Tirzepa3 and Tirzepa5 label all major rodent and human pancreatic islet cells, with signal intensity beta cells > alpha cells = delta cells. Systemic administration of Tirzepa5 strongly labels the median eminence, area postrema and other circumventricular organs characterized by an incomplete blood-brain barrier, but does not readily penetrate into the brain beyond this. Upon intracerebroventricular administration in the brain, Tirzepa5 co-localizes widely with GLP1R + and GIPR + neurons, with evidence of uptake by ventricle-lining cells in the 3rd ventricle. At the single molecule level, Tirzepa5 targets endogenous GLP1R-GIPR nanodomains, which differ in organization and composition to those targeted by single agonist. Tirzepa3 and Tirzepa5 thus reveal dual agonist targets in the pancreas and brain, and further inform the different modes of action of dual agonists versus single agonists.
Activin B improves glucose metabolism via induction of Fgf21 and hepatic glucagon resistance
Authors: Ueki Kohjiro , Kobayashi Naoki , Okazaki Yukiko , Iwane Aya , Hara Kazuo , Horikoshi Momoko , Awazawa Motoharu , Soeda Kotaro , Matsushita Maya , Sasako Takayoshi , Yoshimura Kotaro , Itoh Nobuyuki , Kobayashi Kenta , Seto Yasuyuki , Yamauchi Toshimasa , Aburatani Hiroyuki , Blüher Matthias , Kadowaki Takashi 
Published: August 2024

Abstract

Orchestrated hormonal interacts in response to feeding and fasting play a pivotal role in regulating glucose homeostasis. Here, we show that in obesity, the production of follistatin-like 3 (FSTL3), an endogenous inhibitor of Activin B, in adipose tissue is increased in both mice and humans. However, the knockdown of FSTL3 improves insulin sensitivity and glucose tolerance in diabetic obese db/db mice. Notably, the overexpression of Activin B, a member of TGFβ superfamily, induced in liver sinusoidal endothelial cells (LSECs) by fasting, has multiple metabolically beneficial effects, including improvement insulin sensitivity, suppression of hepatic glucose production, and enhancement of glucose-stimulated insulin secretion, which are attenuated by the overexpression of FSTL3. Activin B increases insulin sensitivity and reduces fat by inducing fibroblast growth factor 21 (FGF21) while suppressing glucagon action in the liver by increasing phosphodiesterase 4 B (PDE4B), leading to hepatic glucagon resistance and resultant hyperglucagonemia. Activin B-induced hyperglucagonemia enhances glucose-stimulated insulin secretion by stimulating glucagon-like peptide-1 (GLP-1) receptor in pancreatic β-cells. Thus, enhancing the action of Activin B by improving multiple components of the pathogenesis of diabetes may be a promising strategy for diabetes treatment.
Muscle-specific gene editing therapy via mammalian fusogen-directed virus-like particles
Authors: Wang Jun , Zhou Shi-Kun , Luo Jing-Tong , Chen Yi-Fang , Lu ZiDong , Jian Qiu-Hong , Jiang Shui-Qing , Li Jing , Zhang Xue-Qin , Tan Xin-Yu , Yang Xianzhu , Xu Cong-Fei 
Published: August 2024

Abstract

Muscle genetic defects can lead to impaired movement, respiratory failure, and other severe symptoms. The development of curative therapies is challenging due to the need for the delivery of gene-editing tools into skeletal muscle cells throughout the body. Here, we used muscular fusogens (Myomaker and Myomerger) to engineer muscle-specific virus-like particles (MuVLPs) for the systemic delivery of gene-editing tools. We demonstrated that MuVLPs can be loaded with diverse payloads, including EGFP, Cre and Cas9/sgRNA ribonucleoproteins (Cas9 RNPs), and can be delivered into muscle cells via targeted membrane fusion. Systemic administration of MuVLPs carrying Cas9 RNPs enabled muscle-specific gene editing, which excised the exon containing a premature terminator codon mutation in mice with Duchenne muscular dystrophy. This treatment restored dystrophin expression in various muscle tissues, including the diaphragm, quadriceps, tibialis anterior, gastrocnemius, and triceps. As a result, the treated mice exhibited a significantly increased capacity for exercise and endurance. This study established a platform for precise gene editing in muscle tissues.
Villification of the intestinal epithelium is driven by Foxl1
Authors: Kaestner Klaus , Zhu Guoli , Lahori Deeksha , Schug Jonathan 
Published: August 2024

Abstract

The primitive gut tube of mammals initially forms as a simple cylinder consisting of the endoderm-derived, pseudostratified epithelium and the mesoderm-derived surrounding mesenchyme. During mid-gestation a dramatic transformation occurs in which the epithelium is both restructured into its final cuboidal form and simultaneously folded and refolded to create intestinal villi and intervillus regions, the incipient crypts. Here we show that the mesenchymal winged helix transcription factor Foxl1, itself induced by epithelial hedgehog signaling, controls villification by activating BMP and PDGFRa as well as planar cell polarity genes in epithelial-adjacent telocyte progenitors, both directly and in a feed- forward loop with Foxo3. In the absence of Foxl1-dependent mesenchymal signaling, villus formation is delayed, the separation of epithelial cells into mitotic intervillus and postmitotic villus cells impaired, and the differentiation of secretory progenitors blocked. Thus, Foxl1 orchestrates key events during the epithelial transition of the fetal mammalian gut.
A watershed-scale impact assessment on a second-generation transgenic soybean yield due to climate change
Authors: Romagnoli Martín , Bulacio Enrique Montero , Portapila Margarita 
Published: August 2024

Abstract

Global estimates suggest that climate change will lead to significant crop yield losses, mainly caused by drought and heat stress. Second-generation transgenic crops are expected to alleviate these constraints. HaHB4-soybean is a second-generation transgenic crop tolerant to high temperatures and dry growing conditions created in Argentina carrying the sunflower HaHB4 gene. In this study, the Soil andWater Assessment Tool (SWAT) was used to estimate the potential impacts of climate change on the HaHB4-soybean yield in the Carcarañá River Lower Basin (CRLB) by considering two greenhouse emission scenarios (Representative Concentration Pathway 4.5 and 8.5) projected by four Global Circulation Models for two future 18-year periods (near future, 2022-2039, and far future, 2082-2099). Synthetic HaHB4-soybean yield data were generated for the baseline period (1998-2015) using the calibrated CROPGRO-soybean model. This dataset was considered for calibration and validation of HaHB4-soybean yield in SWAT.
The results indicate that average annual runoff, soil water content, and percolation increased by 90%-214%, 0.7%-24%, and 69%-270%, respectively, under the climate change scenarios compared to the baseline period. Thus, a higher frequency of severe flooding and an increase in the amount of water that recharges the aquifer should be expected in the CRLB for the rest of the 21st century. Our findings suggest that climate change will positively impact HaHB4-soybean yields under both RCP scenarios. The percentage change of the average annual HaHB4-soybean yield at the basin scale ranged from 2.8%-28% relative to the baseline period. These increments could be associated with a combined effect of increased rainfall and CO2 concentration plus the tolerance of HaHB4-soybean to higher temperatures. In terms of spatial distribution, the positive impact of climate change on HaHB4-soybean yield was found to be more significant in the upper (southwest) than in the middle-lower (northeast) region of the CRLB.
Epidemiology of Overweight in Under-Five Children in India: Insights from National Family Health Survey
Authors: Manapurath Rukman , Chowdhury Ranadip , taneja Sunita , Bhandari Nita , Strand Tor 
Published: August 2024

Abstract

Childhood overweight is not only an immediate health concern due to its implications but also significantly increases the risk of persistent obesity and consequently cardiovascular diseases in the future, posing a serious threat to public health. The objective of this study was to examine the trends and associated factors of childhood overweight in India, using nationally representative data from three rounds of the National Family Health Survey. For the primary analysis, we used data from 199,375 children aged 0 - 59 months from NFHS-5. Overweight was defined as Body mass index-for-age Z (BMI Z) score >+2 SD above the World Health Organization growth standards median. We compared the prevalence estimates of childhood overweight with NFHS-3 and NFHS-4. Potential risk factors were identified through multiple logistic regression analyses. The prevalence of overweight increased from 1·9% in NFHS-3 to 4·0% in NFHS-5, a trend seen across most states and union territories, with the Northeast region showing the highest prevalence. The BMI Z-score distributions from the latest two surveys indicated that the increase in overweight was substantially larger than the decrease in underweight. The consistent upward trend in the prevalence across different demographic groups raises important public health concerns. While undernutrition rates have remained relatively stable, there has been a noticeable rise in the incidence of overweight during the same time frame. The increasing trend of overweight among children in India calls for immediate action.
Friction dynamics: Fluctuations in sliding distance and force
Authors: Xu Ruibin , Zhou Feng , Persson B. N. J. 
Published: August 2024

Abstract

We investigated the fluctuations (noise) in the positions and friction forces of rectangular blocks, made from rubber or polymethyl methacrylate (PMMA), sliding on various substrates under constant driving forces. The experimental results are compared to simulations and analytical results using simple models for the interaction between the solids at the sliding interface. In particular, we use spring-block and asperity-force models, and an analytical wear-particle model. In the spring-block model, small (mini) blocks, representing the asperity contact regions, are connected by viscoelastic springs to a larger block. The miniblocks interact with the substrate with forces that fluctuate randomly in time and magnitude. The wear particle model considers the irregular motion of different-sized wear particles at the interface. The spring-block and wear-particle models predict displacement and force power spectra which, in wide frequency regions, are power-laws, with exponents in agreement with the experiments. The asperity-force model assumes a sliding block with a smooth surface and a randomly rough substrate. In this case the force on the big block results from fluctuations in the number and the size of asperity contact regions. This model gives power spectra that disagree with experimental observations.
Predicting the distribution of Ixodes ricinus in Europe: Integrating microclimatic factors into ecological niche models
Authors: Kuyucu Arda Cem , Hekimoglu Olcay 
Published: August 2024

Abstract

Ixodes ricinus, commonly known as the castor bean tick and sheep tick, is a significant vector of various diseases such as tick-borne encephalitis and Lyme borreliosis. Due to climate change, the distribution and activity of I. ricinus are expected to increase, leading to a rise in diseases transmitted by this species. Most of the distribution models and ecological niche models utilize macroclimate datasets such as Worldclim or CHELSA in order to map the distribution of disease transmitting ticks. However, microclimatic factors are crucial for the activity and survival of small arthropods. In this study, an ecological niche modeling approach was followed in order to assess the climatic suitability of I. ricinus using both microclimatic and macroclimatic parameters. A Microclimate model was built combining parameters from Soiltemp and Wordclim databases while a Macroclimate model was built with the CHELSA dataset. Also future suitabilities were projected using the Macroclimate model under SSP370 and SSP585 scenarios. Both Macroclimate and Microclimate models showed similar distributions, confirming the current distribution of I. ricinus. The most important climatic factors were seasonality, annual temperature range, humidity and precipitation. Future projections suggest a significant expansion in northern and eastern Europe with notable declines in southern regions.
Radiologic Evaluation of Developmental Anomalies of The Odontoid Process: a Cone-beam-compated Tomography Study
Authors: ÇAM Kübra , ZENGİN Ayşe Zeynep 
Published: August 2024

Abstract

Background: The odontoid process is an anchoring pivot for the craniovertebral junction and has many congenital anomalies. Ossiculum terminale persistans (OTP) and os odontoideum (OO) are believed to be raredevelopmental anomalies of the odontoid process. The OTP is defined as an ossification center that gives rise to the tip of the dens failing to fuse properly with the body of the axis. OO is described as an oval-shaped, well-corticated bony ossicle that is positioned cephalad to the body of the axis. Both of these conditions may cause neurological signs and atlantoaxial instability.
Aim: To evaluate the prevalence of developmental anomalies of the odontoid process on tomographic images and to assess the presence of atlantoaxial instability.
Material and Methods: Cone-beam computed tomography (CBCT) images of 1950 patients were evaluated. Radiologically, developmental anomalies were identified. Only OTP and OO were distinguished, and the dimensions of extra ossicles, extraossicle-dental interval (EDI), anterior atlanto-dental interval (AADI), posterior atlanto-dental interval (PADI), difference between lateral atlanto-dens intervals (LADI), basion-dens interval (BDI), and atlanto-occipital joint angle (AOJA) were assessed. Measurements were performed in 1 mm thick slices by using the “distance toolbar” feature of the CBCT tool in sagittal, coronal and axial images.
Results: Fourteen patients (0.7%) exhibited developmental anomalies of the odontoid process. OTP was found in ten (0.5%) patients, and OO was observed in four (0.2%) patients. Radiologic measurements of OTP and OO for craniocervical relationships were not different from normal previously accepted data,and atlantoaxial instability was not detected.
Conclusion: Developmental anomalies of the odontoid process were rare on large-FOV CBCT images. Dentomaxillofacial radiologists should be able to identify these anomalies, especially for atlantoaxial instability,and point them out in their reports.
Application of miniaturized most probable number method for bacterial detection in water samples: detection of multi-drug-resistant Ralstonia insidiosa in drinking water
Authors: Ilsan Noor Andryan , Nurfajriah Siti , Inggraini Maulin , Krishanti Ni Putu Ratna Ayu , Yunita Melda , Sipriyadi  , Anindita Reza , Huang Tzu-Wen 
Published: August 2024

ABSTRACT

The detection of bacterial contamination in drinking water is essential for monitoring the spread of foodborne diseases. We developed a simple, portable, and low-cost method of mini most probable number (mini MPN) to semi-enumerate bacterial suspension in water as a drinking water analogue. In this study, there is no significant difference between mini MPN and the standard method, technique plate count (TPC), at 10 and 100 CFU/ml Klebsiella pneumoniae suspension with a P-value of 0.28. For the ease-of-use aspect of this method, we tested several variables to prove it can be mass-applied in society. The usage of a sterile-plastic pipette, sample inoculation conducted in a biosafety cabinet (BSC), the usage of a 3-month storage medium, and incubation temperature conducted at room temperature compared to aseptic standard laboratory technique showed P-value &gt; 0.05. In a trial for this method, we used commercialized drinking water for bacterial enumeration and characterization. We found multi-drug resistant (MDR) Ralstonia insidiosa which was resistant to at least four antimicrobial classes, including aminoglycosides, penicillins, cephalosporin, and carbapenem. Vitek 2 Compact was used for bacterial identification and antimicrobial susceptibility testing. A virulence test in Omphisa fuscidentalis larvae showed R. insidiosa strain D had a low virulence.
Use of tyrosinase nanobiosensor for detection of atrazine and simazine and its application in real water samples
Authors: Ballen Sandra Cristina , Machado Eliel Pereita , Da Silva Diego Maroso , Steffens Clarice , Steffens Juliana 
Published: August 2024

ABSTRACT
This study presents the development and characterization of cantilever nanobiosensors functionalized with the tyrosinase enzyme (0.05–0.001%) for the detection of atrazine and simazine in water. The optimization of tyrosinase activity through precise immobilization and sensitive layer adjustments was evaluated. Topographical analysis revealed the successful immobilization of the tyrosinase enzyme using the self-assembled monolayer technique, enhancing sensor sensitivity. Upon comparing the enzyme concentrations, it was found that the 0.006% exhibited remarkable results, including a limit of detection (LOD = 0.0080 ppb) and a limit of quantification (LOQ = 0.0267 ppb), along with enhanced storage stability for 15 days for atrazine detection. For simazine, the nanobiosensor exhibited high sensitivity (8.1532 nm/ppb) and LOD (0.0117 ppb). They demonstrated excellent reversibility (99%) over six cycles and selectivity against interfering pesticides commonly found in agricultural environments, indicating their suitability for complex sample matrices. Real water samples met regulatory standards for atrazine levels, further validating the efficacy of the nanobiosensors in detecting pesticide contamination. The enzymatic nanobiosensor achieved recoveries ranging from 97 to 101%, indicating high reproducibility. These findings demonstrate the potential of the developed nanobiosensors for sensitive and reliable pesticide detection in environmental monitoring, with implications for future applications.
Associated Factors of Sexual Initiation among Male Vocational High School Students in Zhejiang Province, China: A Cross-sectional Study
Authors: Zhao Xiang , Yang Zhongrong , Wang Hui , Huang Yu , Chen Weiyong 
Published: August 2024

Aims:
This study aims to investigate the factors associated with sexual initiation
among male vocational high school students (MVHSS) in Zhejiang Province, and provide a scientific
basis for preventing unsafe sexual behavior and sexual health issues among adolescents.

Background:
The prevalence of sexual behavior among young students has risen significantly in
recent years. Contracting HIV poses a serious physical and psychological burden on young individuals
and their families. Thus, it is imperative to promptly and effectively address the spread of
HIV among young people.

Objective:
The objectives of this study are to investigate the demographic characteristics of male
vocational high school students (MVHSS) who have engaged in sexual activity and to identify associated
factors, such as sexual attitudes and lifestyle, that may influence sexual initiation among
this population, and to offer recommendations for interventions and policy development aimed at
promoting healthy sexual behaviors among MVHSS.

Methods:
A survey was conducted among vocational high school students in grades one and two
in Zhejiang Province. Variables that were statistically significantly associated with sexual initiation
in bivariate analyses were included in a multivariate logistic regression model, which adopted
a backward elimination procedure with a p-value > 0.10 as the exclusion criterion. Odds ratios
(ORs) and 95% confidence intervals (CIs) were used to describe the relationship between dependent
and outcome variables.

Results:
Of the 1032 male participants, 17.4% had initiated sexual behavior. The multivariate analysis
results indicated thatThose who were frequent smokers (adjusted OR[AOR] =4.89, 95% CI:
2.36–10.13), those who reported having been in love (AOR=2.86, 95% CI: 1.84–4.44), those currently
in love (AOR=4.47, 95% CI: 2.68–7.45), those willing to have sex with a high school student
(AOR =2.63, 95% CI: 3.31–6.50), those willing to pay for sex (AOR =1.90, 95% CI:
1.10–3.27), and those who had received sex education and STDs/AIDS prevention education in
school (AOR =2.21, 95% CI: 1.53–3.18) were more likely to initiate sexual behavior.

Conclusion:
Sexual attitudes among MVHSS are liberal, and the prevalence of sexual initiation is
high. Interventions targeted at improving sexual safety education, reducing the rate of early initiation
of sexual behavior, and promoting condom use among students must be implemented to reduce
the risk of HIV infections and STDs among sexually active MVHSS.
A Bibliometric Study from 1992 to 2023 on the Relationship between Biological Clock and Diabetes
Authors: Zhong Dayuan , Cheng Hui , Li Huanjie , Kong Xiangbo 
Published: August 2024

Aims:
A bibliometric study was conducted to gain deeper insights into the current state
of research on diabetes and the biological clock (BC).

Methods:
The study involved a comprehensive search for literature related to diabetes and BC
published between 1992 and 2023 in the Web of Science database.

Results:
Ninety-five articles were published in 65 journals, with six of these journals not included
in the Journal Citation Reports as of 2022. Among the remaining 59 journals, 10 had an impact
factor (IF) greater than 10, and 21 had an IF greater than 5. Twenty-nine journals belonged to
Quartile 1, while 16 journals were part of Quartile 2. The articles were contributed by researchers
from 22 countries, with the Netherlands and the USA being the most prolific contributors. However,
the total number of citations for articles from the USA was significantly higher than that of the
Netherlands. The co-occurrence analysis of title and abstract keywords primarily focused on investigating
the mechanisms of BC. Regarding author keywords and keyword-plus, the co-occurrence
analysis centered around diabetes and BC. International collaboration was prominent among
developed countries, with the Netherlands, the USA, and France being major participants. Institution-
wise cooperation primarily occurred between two research institutions in the Netherlands. In
total, the 95 articles received 5,157 citations, averaging 54.28 citations per article.

Conclusion:
To foster advancements in this area, more attention and international cooperation are
necessary. Emphasizing collaborative efforts can drive the development of novel approaches to
manage diabetes and regulate blood glucose levels effectively.