bluuebunny/crossref_metadata_2025 huggingface dataset:
ML-driven segmentation of microvascular features during histological examination of tissue-engineered vascular grafts
Authors: Danilov Viacheslav V. , Laptev Vladislav V. , Klyshnikov Kirill Yu. , Stepanov Alexander D. , Bogdanov Leo A. , Antonova Larisa V. , Krivkina Evgenia O. , Kutikhin Anton G. , Ovcharenko Evgeny A.
Published: June 2024

Introduction

The development of next-generation tissue-engineered medical devices such as tissue-engineered vascular grafts (TEVGs) is a leading trend in translational medicine. Microscopic examination is an indispensable part of animal experimentation, and histopathological analysis of regenerated tissue is crucial for assessing the outcomes of implanted medical devices. However, the objective quantification of regenerated tissues can be challenging due to their unusual and complex architecture. To address these challenges, research and development of advanced ML-driven tools for performing adequate histological analysis appears to be an extremely promising direction.

Methods

We compiled a dataset of 104 representative whole slide images (WSIs) of TEVGs which were collected after a 6-month implantation into the sheep carotid artery. The histological examination aimed to analyze the patterns of vascular tissue regeneration in TEVGs in situ. Having performed an automated slicing of these WSIs by the Entropy Masker algorithm, we filtered and then manually annotated 1,401 patches to identify 9 histological features: arteriole lumen, arteriole media, arteriole adventitia, venule lumen, venule wall, capillary lumen, capillary wall, immune cells, and nerve trunks. To segment and quantify these features, we rigorously tuned and evaluated the performance of six deep learning models (U-Net, LinkNet, FPN, PSPNet, DeepLabV3, and MA-Net).

Results

After rigorous hyperparameter optimization, all six deep learning models achieved mean Dice Similarity Coefficients (DSC) exceeding 0.823. Notably, FPN and PSPNet exhibited the fastest convergence rates. MA-Net stood out with the highest mean DSC of 0.875, demonstrating superior performance in arteriole segmentation. DeepLabV3 performed well in segmenting venous and capillary structures, while FPN exhibited proficiency in identifying immune cells and nerve trunks. An ensemble of these three models attained an average DSC of 0.889, surpassing their individual performances.

Conclusion

This study showcases the potential of ML-driven segmentation in the analysis of histological images of tissue-engineered vascular grafts. Through the creation of a unique dataset and the optimization of deep neural network hyperparameters, we developed and validated an ensemble model, establishing an effective tool for detecting key histological features essential for understanding vascular tissue regeneration. These advances herald a significant improvement in ML-assisted workflows for tissue engineering research and development.
Patient-derived and gene-edited pluripotent stem cells lacking NPHP1 recapitulate juvenile nephronophthisis in abnormalities of primary cilia and renal cyst formation
Authors: Arai Yutaka , Ito Hidenori , Shimizu Tomoya , Shimoda Yuzuno , Song Dan , Matsuo-Takasaki Mami , Hayata Tadayoshi , Hayashi Yohei
Published: June 2024

Juvenile nephronophthisis is an inherited renal ciliopathy with cystic kidney disease, renal fibrosis, and end-stage renal failure in children and young adults. Mutations in the NPHP1 gene encoding nephrocystin-1 protein have been identified as the most frequently responsible gene and cause the formation of cysts in the renal medulla. The molecular pathogenesis of juvenile nephronophthisis remains elusive, and no effective medicines to prevent end-stage renal failure exist even today. No human cellular models have been available yet. Here, we report a first disease model of juvenile nephronophthisis using patient-derived and gene-edited human induced pluripotent stem cells (hiPSCs) and kidney organoids derived from these hiPSCs. We established NPHP1-overexpressing hiPSCs from patient-derived hiPSCs and NPHP1-deficient hiPSCs from healthy donor hiPSCs. Comparing these series of hiPSCs, we found abnormalities in primary cilia associated with NPHP1 deficiency in hiPSCs. Kidney organoids generated from the hiPSCs lacking NPHP1 formed renal cysts frequently in suspension culture with constant rotation. This cyst formation in patient-derived kidney organoids was rescued by overexpression of NPHP1. Transcriptome analysis on these kidney organoids revealed that loss of NPHP1 caused lower expression of genes related to primary cilia in epithelial cells and higher expression of genes related to the cell cycle. These findings suggested the relationship between abnormality in primary cilia induced by NPHP1 loss and abnormal proliferative characteristics in the formation of renal cysts. These findings demonstrated that hiPSC-based systematic disease modeling of juvenile nephronophthisis contributed to elucidating the molecular pathogenesis and developing new therapies.
Advances in virus-like particle-based SARS-CoV-2 vaccines
Authors: Hao Xiaoting , Yuan Feifei , Yao Xuan
Published: June 2024

The Coronavirus Disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has incurred devastating human and economic losses. Vaccination remains the most effective approach for controlling the COVID-19 pandemic. Nonetheless, the sustained evolution of SARS-CoV-2 variants has provoked concerns among the scientific community regarding the development of next-generation COVID-19 vaccines. Among these, given their safety, immunogenicity, and flexibility to display varied and native epitopes, virus-like particle (VLP)-based vaccines represent one of the most promising next-generation vaccines. In this review, we summarize the advantages and characteristics of VLP platforms, strategies for antigen display, and current clinical trial progress of SARS-CoV-2 vaccines based on VLP platforms. Importantly, the experience and lessons learned from the development of SARS-CoV-2 VLP vaccines provide insights into the development of strategies based on VLP vaccines to prevent future coronavirus pandemics and other epidemics.
Understanding the relationship between AI and gender on social TV content selection
Authors: Habes Mohammed , Alhazmi Amal Hassan , Elareshi Mokhtar , Attar Razaz Waheeb
Published: June 2024

As technological advancements continue to shape our daily lives, and social TV has emerged as an interactive platform that fosters connections between families and friends. This study investigates the selection of social TV content by examining the influence of AI and other contributing factors, with gender proposed as a mediating factor. Involving 300 students from two randomly selected public universities in Irbid, Jordan, data were collected through an online survey with self-reported responses. The study revealed that AI enhances characteristics such as information gathering, social awareness, and knowledge sharing, subsequently affecting user attitudes and content selection on social TV platforms. Both AI and user attitudes significantly contribute to content selection, while gender acts as a mediator, influencing AI integration and attitudinal shifts. Ultimately, AI provides seamless access to preferred content and improves ease of use, enriching content recommendation systems and fostering increased user interest and satisfaction. This positive experience with AI services shapes user attitudes towards technology. This study offers a comprehensive examination of the intersection between AI, gender, attitudes, and social TV content selection within the context of Jordanian young users, marking a pioneering contribution to the field of media studies in the MENA region.
The controlling effect of sedimentary characteristics on the heterogeneity of the Chang 6 reservoir in the Wuliwan area
Authors: Zou Xinzhe , Song Xinmin , Wang Youjing , Yan Dezhi , Qin Guosheng , Fang Bo
Published: June 2024

The sedimentary system of the delta front is complex. The hydrodynamic conditions, changes in sediment supply, and mineral composition are crucial factors that influence the quality of reservoirs. Reservoir quality varies among different sedimentary units. In this field of research, there is a general tendency to mainly use core data and logging curves for reservoir characterization and prediction, while neglecting the combination with the microscopic scale of the reservoir. This article proposes a new method to characterize reservoir heterogeneity by studying the sedimentary characteristics of reservoirs. This method uses casting thin-section data to aid in core and logging research. This study consists of five parts: core analysis, casting thin-section study, logging facies study, geological analysis, and single-well prediction. Combining macroscopic and microscopic methods helps clarify the controlling effect of sedimentary characteristics on reservoir heterogeneity. The research results indicate that this research method effectively solves the challenge of characterizing reservoir heterogeneity in the middle and later stages of development of low-permeability reservoirs. The research outputs serve as valuable references for the advancement of analytical matching fields.
Late Quaternary right-lateral slip rate along the Tangyuan segment of the Yilan–Yitong Fault Zone on the NE China Plain
Authors: Yu Zhongyuan , Yin Na , Yang Yanlin , Li Luwei , Ma Yanli
Published: June 2024

The slip rate of strike-slip active faults is crucial for fault rupture behavior analysis and seismic hazard assessment. Although many segments of the Yilan–Yitong Fault Zone (YYFZ) in NE China have been strongly deformed since the late Quaternary, little progress has been made on its slip rate. With the help of high-resolution satellite images, detailed field investigations, seismic reflections, and Quaternary chronological dating, we mainly studied the late Quaternary right-slip rate of the YYFZ. Field investigations revealed an ∼15 km long by ∼1–2 m high-surface scarp belt extending along the Tangyuan graben interior, with a series of sag ponds and small parallel bulges. Research has revealed that the most recent paleoearthquake (∼M 7.0) occurred between 2,800± 600 a BP and 1,700 ± 200 a BP, with evidence of coseismic surface rupture. The T2 terrace abandonment age of the Heijin River is approximately 55.13 ± 1.78 ka (OSL), and the maximum cumulative right-lateral offset may reach 110 ± 5 m. Thus, the maximum right-slip rate of the Tangyuan segment of the YYFZ since the late Quaternary is constrained to 1–2 mm/a according to the upper terrace model. This study suggests that the presence of a new fault in the basin interior merits more attention when assessing the influential surface range and earthquake potential along the YYFZ, and the features of “low tectonic loading rate, activity migration in space, and clustering in time separated by ten thousand years of seismic quiescence” observed along the YYFZ are highly important for earthquake model construction and tectonic deformation studies in stable continental regions (SCRs).
Does energy-consuming rights trading policy achieve urban pollution and carbon reduction? A quasi-natural experiment from China
Authors: Wang Mengyu , Wang Yichun , Yang Ziyi , Guo Bingnan
Published: June 2024

Energy-consuming rights trading (ECRT) policy represents a critical policy instrument for China striving to achieve its “dual carbon” objectives, captivating significant attention for its potential to reduce pollution and carbon emissions. This study utilizes panel data from 290 Chinese cities spanning 2010 to 2021, leveraging the ECRT policy as a quasi-natural experiment. Employing Difference-in-Differences (DID) and Propensity Score Matching-Difference-in-Differences (PSM-DID) methodologies, we assess the effect of the ECRT policy on urban pollution and carbon reduction levels. The findings indicate: 1) Relative to non-demonstration cities, the ECRT policy significantly enhances pollution and carbon reduction levels in demonstration cities; this conclusion remains robust after rigorous testing. 2) Heterogeneity analysis indicates that the policy’s effect on pollution and carbon reduction is more significant in the central and western regions, and particularly evident in key and resource-based cities. 3) Mechanism tests demonstrate that the policy facilitates urban pollution and carbon reduction by cultivating green technological innovation and industrial structure upgrading. Therefore, to further advance the ECRT policy, it is necessary to expand the breadth, depth, and flexibility of policy implementation, while also optimizing environmental regulations to fully leverage the system’s potential in enhancing urban pollution and carbon emissions.
Population and spatial dynamics of desert bighorn sheep in Grand Canyon during an outbreak of respiratory pneumonia
Authors: Epps Clinton W. , Holton P. Brandon , Monello Ryan J. , Crowhurst Rachel S. , Gaulke Sarah M. , Janousek William M. , Creech Tyler G. , Graves Tabitha A.
Published: June 2024

Introduction

Terrestrial species in riverine ecosystems face unique constraints leading to diverging patterns of population structure, connectivity, and disease dynamics. Desert bighorn sheep (Ovis canadensis nelsoni) in Grand Canyon National Park, a large native population in the southwestern USA, offer a unique opportunity to evaluate population patterns and processes in a remote riverine system with ongoing anthropogenic impacts. We integrated non-invasive, invasive, and citizen-science methods to address questions on abundance, distribution, disease status, genetic structure, and habitat fragmentation.

Methods

We compiled bighorn sightings collected during river trips by park staff, commercial guides, and private citizens from 2000–2018 and captured bighorn in 2010–2016 to deploy GPS collars and test for disease. From 2011–2015, we non-invasively collected fecal samples and genotyped them at 9–16 microsatellite loci for individual identification and genetic structure. We used assignment tests to evaluate genetic structure and identify subpopulations, then estimated gene flow and recent migration to evaluate fragmentation. We used spatial capture-recapture to estimate annual population size, distribution, and trends after accounting for spatial variation in detection with a resource selection function model.

Results and discussion

From 2010–2018, 3,176 sightings of bighorn were reported, with sightings of 56–145 bighorn annually on formal surveys. From 2012–2016, bighorn exhibiting signs of respiratory disease were observed along the river throughout the park. Of 25 captured individuals, 56% were infected by Mycoplasma ovipneumoniae, a key respiratory pathogen, and 81% were recently exposed. Pellet sampling for population estimation from 2011–2015 yielded 1,250 genotypes and 453 individuals. We detected 6 genetic clusters that exhibited mild to moderate genetic structure (FST 0.022–0.126). The river, distance, and likely topography restricted recent gene flow, but we detected cross-river movements in one section via genetic recaptures, no subpopulation appeared completely isolated, and genetic diversity was among the highest reported. Recolonization of one large stretch of currently empty habitat appears limited by the constrained topology of this system. Annual population estimates ranged 536–552 (95% CrI range 451–647), lamb:ewe ratios varied, and no significant population decline was detected. We provide a multi-method sampling framework useful for sampling other wildlife in remote riverine systems.
Proteomic and metabolomic profiling of methicillin resistant versus methicillin sensitive Staphylococcus aureus using a simultaneous extraction protocol
Authors: Boucherabine Syrine , Giddey Alexander , Nassar Rania , Al-Hroub Hamza M. , Mohamed Lobna , Harb Mohammad , Soares Nelson Cruz , Senok Abiola
Published: June 2024

Background

Understanding the biology of methicillin resistant Staphylococcus aureus (MRSA) is crucial to unlocking insights for new targets in our fight against this antimicrobial resistant priority pathogen. Although proteomics and metabolomic profiling offer the potential to elucidating such biological markers, reports of methodological approaches for carrying this out in S. aureus isolates remain limited. We describe the use of a dual-functionality methanol extraction method for the concurrent extraction of protein and metabolites from S. aureus and report on the comparative analysis of the proteomic and metabolomic profiles of MRSA versus methicillin sensitive S. aureus (MSSA).

Methods

Bacterial reference strains MRSA ATCC43300 and MSSA ATCC25923 were used. The conventional urea methodology was used for protein extraction and a methanol based method was used for concurrent proteins and metabolites extraction. Proteomic and metabolomic profiling was carried out using TimsTOF mass spectrometry. Data processing was carried out using the MaxQuant version 2.1.4.0.

Results

This study represents the first report on the utilization of the methanol extraction method for concurrent protein and metabolite extraction in Gram positive bacteria. Our findings demonstrate good performance of the method for the dual extraction of proteins and metabolites from S. aureus with demonstration of reproducibility. Comparison of MRSA and MSSA strains revealed 407 proteins with significantly different expression levels. Enrichment analysis of those proteins revealed distinct pathways involved in fatty acid degradation, metabolism and beta-lactam resistance. Penicillin-binding protein PBP2a, the key determinant of MRSA resistance, exhibited distinct expression patterns in MRSA isolates. Metabolomic analysis identified 146 metabolites with only one exclusive to the MRSA. The enriched pathways identified were related to arginine metabolism and biosynthesis.

Conclusion

Our findings demonstrate the effectiveness of the methanol-based dual-extraction method, providing simultaneous insights into the proteomic and metabolomic landscapes of S. aureus strains. These findings demonstrate the utility of proteomic and metabolomic profiling for elucidating the biological basis of antimicrobial resistance.
Roles of transcriptional factor PsrA in the regulation of quorum sensing in Pseudomonas aeruginosa PAO1
Authors: Kok Li-Ching , Tsai Chia-Chun , Liao Yu-Hsuan , Lo Yi-Ling , Cheng Nai-Wei , Lin Ching-Ting , Chang Hwan-You
Published: June 2024

The transcription factor PsrA regulates fatty acid metabolism, the type III secretion system, and quinolone signaling quorum sensing system in Pseudomonas aeruginosa. To explore additional roles of PsrA in P. aeruginosa, this study engineered a P. aeruginosa PAO1 strain to carry a recombinant plasmid with the psrA gene (pMMBpsrA) and examined the impact of elevated psrA expression to the bacterium. Transcriptomic analysis revealed that PsrA significantly downregulated genes encoding the master quorum-sensing regulators, RhlR and LasR, and influenced many quorum-sensing-associated genes. The role of PsrA in quorum sensing was further corroborated by testing autoinducer synthesis in PAO1 [pMMBpsrA] using two reporter bacteria strains Chromobacterium violaceum CV026 and Escherichia coli [pSB1075], which respond to short- and long-chain acyl homoserine lactones, respectively. Phenotypic comparisons of isogenic ΔpsrA, ΔlasR, and ΔpsrAΔlasR mutants revealed that the reduced elastase, caseinase, and swarming activity in PAO1 [pMMBpsrA] were likely mediated through LasR. Additionally, electrophoretic mobility shift assays demonstrated that recombinant PsrA could bind to the lasR promoter at a 5’-AAACGTTTGCTT-3′ sequence, which displays moderate similarity to the previously reported consensus PsrA binding motif. Furthermore, the PsrA effector molecule oleic acid inhibited PsrA binding to the lasR promoter and restored several quorum sensing-related phenotypes to wild-type levels. These findings suggest that PsrA regulates certain quorum-sensing phenotypes by negatively regulating lasR expression, with oleic acid acting as a crucial signaling molecule.
An enhanced pattern detection and segmentation of brain tumors in MRI images using deep learning technique
Authors: Kiran Lubna , Zeb Asim , Rehman Qazi Nida Ur , Rahman Taj , Shehzad Khan Muhammad , Ahmad Shafiq , Irfan Muhammad , Naeem Muhammad , Huda Shamsul , Mahmoud Haitham
Published: June 2024

Neuroscience is a swiftly progressing discipline that aims to unravel the intricate workings of the human brain and mind. Brain tumors, ranging from non-cancerous to malignant forms, pose a significant diagnostic challenge due to the presence of more than 100 distinct types. Effective treatment hinges on the precise detection and segmentation of these tumors early. We introduce a cutting-edge deep-learning approach employing a binary convolutional neural network (BCNN) to address this. This method is employed to segment the 10 most prevalent brain tumor types and is a significant improvement over current models restricted to only segmenting four types. Our methodology begins with acquiring MRI images, followed by a detailed preprocessing stage where images undergo binary conversion using an adaptive thresholding method and morphological operations. This prepares the data for the next step, which is segmentation. The segmentation identifies the tumor type and classifies it according to its grade (Grade I to Grade IV) and differentiates it from healthy brain tissue. We also curated a unique dataset comprising 6,600 brain MRI images specifically for this study. The overall performance achieved by our proposed model is 99.36%. The effectiveness of our model is underscored by its remarkable performance metrics, achieving 99.40% accuracy, 99.32% precision, 99.45% recall, and a 99.28% F-Measure in segmentation tasks.
Association between oxidative balance score and skeletal muscle mass and strength: NHANES from 2011 to 2018
Authors: Zhao Xiaoxuan , Hua Lijiangshan , Jin Kaili , Sun Qiuhua , Wang Rongyun
Published: June 2024

Objective

Oxidative stress is a risk factor for sarcopenia. The Oxidative Balance Score (OBS) is a widely employed tool for evaluating the oxidative stress-related exposures from dietary and lifestyle factors. In this study, we aimed to conducted to explore the relationship between OBS and skeletal muscle mass and strength.

Methods

6,438 subjects from 2011 to 2018 and 5,414 from 2011 to 2014 from the National Health and Nutrition Examination Survey (NHANES) were selected for analysis. The correlations between OBS and skeletal muscle mass and handgrip strength were investigated using multivariate logistic regression and linear regression analysis.

Results

Compared with lowest OBS, participants with OBS in the highest quartile had lower risk of low skeletal muscle mass (OR = 0.173 (0.120 ~ 0.248), p < 0.0001) and low handgrip strength (β = 0.173 (0.120 ~ 0.248), p = 0.011). The negative association also were found between dietary/lifestyle OBS and skeletal muscle mass (OR = 0.268 (0.178 ~ 0.404), p < 0.0001; OR = 0.231 (0.130 ~ 0.410), p < 0.0001) and handgrip strength (β = 1.812 (0.555 ~ 3.071), p = 0.008; β = −2.255 (−3.430 ~ −1.079), p < 0.001) independently. The positive association remains significant, especially among men and those with higher education levels by subgroup analysis.

Conclusion

All of these results indicated a negative association between OBS and low skeletal muscle mass and handgrip strength. An antioxidant-rich diet and healthy lifestyle are crucial for enhancing skeletal muscle mass and strength.
Low progesterone receptor levels in high-grade DCIS correlate with HER2 upregulation and the presence of invasive components
Authors: Schandiz Hossein , Farkas Lorant , Park Daehoon , Liu Yan , Andersen Solveig N. , Geisler Jürgen , Sauer Torill
Published: June 2024

Objective

In this study, we investigated pivotal molecular markers in human high-grade breast ductal carcinoma in situ (DCIS). Expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor 2 (HER2) was measured among various subtypes (Luminal (Lum) A, LumB HER2-, LumB HER2+, HER2-enriched and triple-negative).

Methods

In total, 357 DCIS cases were classified into respective subtypes, according to the 2013 St. Gallen guidelines. Each subtype was categorized into three subcategories: “Pure” (those without an invasive component), “W/invasive” (those with an invasive component), and “All” (the entire group of the given subtype). ER and PR expression were registered as intervals. Equivocal HER2 immunohistochemistry (IHC) cases (2+) were further investigated using dual-color in situ hybridization.

Results

The majority of patients (71%) were over the age of 50. We discovered no significant differences in the proportion of age between the “Pure” and “W/invasive” groups. There was no significant difference in ER/PR expression between “Pure” luminal subtypes of DCIS and “W/invasive” cases. We compared the HER2 IHC scores of “0”, “1+”, and “2+” among LumA and LumB HER2 subtypes and identified no statistically significant differences between “Pure” and “W/invasive” (p = 0.603). ER and PR expression ≥ 50% cutoff value was present in > 90% of all LumA cases. The incidences of cases with ER expression at cutoff values of < 10% and ≥ 50% in LumA were significantly different compared to other luminal subtypes (p < 0.0001). The proportion of cases with PR expression < 20% showed significant differences in the various luminal subtypes. In luminal B subtypes, low PR expression (< 20%) was significantly associated with both strong HER2 expression (3+) and the presence of an invasive component (p = 0.0001 and p = 0.0365, respectively).

Conclusions

ER and PR expression at ≥ 50% cutoff values were found in more than 90% of LumA cases. Samples with ER < 10% and ≥ 50% in LumA were significantly different compared to other luminal subtypes (p < 0.0001). Low PR expression in high-grade DCIS was strongly associated with HER2 overexpression (3+) and an invasive component (p = 0.0001 and p = 0.0365, respectively).
Multiple immune-related adverse events secondary to checkpoint inhibitor therapy in patients with advanced cancer: association with treatment effectiveness
Authors: Olsson Ladjevardi Cecilia , Koliadi Anthoula , Rydén Viktoria , El-Naggar Ali Inan , Digkas Evangelos , Valachis Antonios , Ullenhag Gustav J.
Published: June 2024

Introduction

Checkpoint inhibitors (CPI) are widely used in cancer treatment with a potential of causing immune-related adverse events (IRAEs). Several studies have reported a positive correlation between development of IRAEs and improved survival outcome. However, few studies have focused on the potential role of multiple IRAEs on treatment effectiveness. This study aimed at investigating the association between multiple IRAEs and treatment effectiveness in terms of progression-free survival (PFS) and overall survival (OS) in advanced cancer patients.

Methods

We performed a retrospective cohort study at three Swedish centers. All patients (n=600) treated with PD-L1 or PD-1 inhibitor, in monotherapy or in combination for advanced cancer between January 2017 and December 2021 were included. Multiple IRAEs were defined as IRAEs involving more than one organ system either simultaneously or sequentially. Time-depending Cox-regression model to mitigate the risk for immortal time bias (ITB) was applied.

Results

The major tumor types were non-small cell lung cancer (205 patients; 34.2%) and malignant melanoma (196 patients; 32.7%). Of all patients,32.8% developed single IRAE and 16.2% multiple IRAEs. Patients with multiple IRAEs showed significantly improved PFS (Hazard Ratio, HR=0.78 95% Confidence Interval, CI: 0.57–0.98) and OS (HR=0.65 95% CI: 0.44–0.95) compared to patients with single IRAE or no IRAE (HR=0.46 95% CI:0.34–0.62 for PFS vs HR=0.41 95% CI: 0.28-0.60 for OS).

Conclusion

In conclusion, our data supports a stronger association between development of multiple as opposed to single IRAEs and clinical effectiveness in advanced cancer patients treated with CPIs.
A comprehensive in-vitro/in-vivo screening toolbox for the elucidation of glucose homeostasis modulating properties of plant extracts (from roots) and its bioactives
Authors: Bauer Ilka , Rimbach Gerald , Cordeiro Sönke , Bosy-Westphal Anja , Weghuber Julian , Ipharraguerre Ignacio R. , Lüersen Kai
Published: June 2024

Plant extracts are increasingly recognized for their potential in modulating (postprandial) blood glucose levels. In this context, root extracts are of particular interest due to their high concentrations and often unique spectrum of plant bioactives. To identify new plant species with potential glucose-lowering activity, simple and robust methodologies are often required. For this narrative review, literature was sourced from scientific databases (primarily PubMed) in the period from June 2022 to January 2024. The regulatory targets of glucose homeostasis that could be modulated by bioactive plant compounds were used as search terms, either alone or in combination with the keyword “root extract”. As a result, we present a comprehensive methodological toolbox for studying the glucose homeostasis modulating properties of plant extracts and its constituents. The described assays encompass in-vitro investigations involving enzyme inhibition (α-amylase, α-glucosidase, dipeptidyl peptidase 4), assessment of sodium-dependent glucose transporter 1 activity, and evaluation of glucose transporter 4 translocation. Furthermore, we describe a patch-clamp technique to assess the impact of extracts on KATP channels. While validating in-vitro findings in living organisms is imperative, we introduce two screenable in-vivo models (the hen’s egg test and Drosophila melanogaster). Given that evaluation of the bioactivity of plant extracts in rodents and humans represents the current gold standard, we include approaches addressing this aspect. In summary, this review offers a systematic guide for screening plant extracts regarding their influence on key regulatory elements of glucose homeostasis, culminating in the assessment of their potential efficacy in-vivo. Moreover, application of the presented toolbox might contribute to further close the knowledge gap on the precise mechanisms of action of plant-derived compounds.
A key ABA biosynthetic gene OsNCED3 is a positive regulator in resistance to Nilaparvata lugens in Oryza sativa
Authors: Li Jitong , Liu Hao , Lv Xinyi , Wang Wenjuan , Liang Xinyan , Chen Lin , Wang Yiping , Liu Jinglan
Published: June 2024

The gene encoding 9-cis-epoxycarotenoid dioxygenase 3 (NCED3) functions in abscisic acid (ABA) biosynthesis, plant growth and development, and tolerance to adverse temperatures, drought and saline conditions. In this study, three rice lines were used to explore the function of OsNCED3, these included an OsNCED3-overexpressing line (OsNCED3-OE), a knockdown line (osnced3-RNAi) and wild-type rice (WT). These rice lines were infested with the brown plant hopper (BPH; Nilaparvata lugens) and examined for physiological and biochemical changes, hormone content, and defense gene expression. The results showed that OsNCED3 activated rice defense mechanisms, which led to an increased defense enzyme activity of superoxide dismutase, peroxidase, and polyphenol oxidase. The overexpression of OsNCED3 decreased the number of planthoppers and reduced oviposition and BPH hatching rates. Furthermore, the overexpression of OsNCED3 increased the concentrations of jasmonic acid, jasmonyl-isoleucine and ABA relative to WT rice and the osnced3-RNAi line. These results indicate that OsNCED3 improved the stress tolerance in rice and support a role for both jasmonates and ABA as defense compounds in the rice-BPH interaction.
Research advances on the hard seededness trait of soybean and the underlying regulatory mechanisms
Authors: Sun Yongwang , Gong Yujie
Published: June 2024

Soybean is one of the world’s most economically significant crops and is widely utilized as an essential source of vegetable protein and edible oil. Cultivated soybean is domesticated from its annual counterpart, wild soybean, which is considered valuable germplasm for soybean breeding. However, wild soybean accessions generally produce seeds with impermeable coats, a trait known as hard seededness (HS), which is beneficial for long-term seed survival but is undesirable for the uniform water absorption and germination of seeds, thus limiting the utilization of wild soybeans in breeding. In addition, moderate HS can isolate the embryo from the surrounding environment and is thus beneficial for long-term seed storage and germplasm preservation. The HS trait is primarily associated with the structure and chemical composition of the seed coat. Moreover, its development is also influenced by various environmental conditions, such as water and temperature. Genetic analysis has revealed that HS of soybean is a complex quantitative trait controlled by multiple genes or minor quantitative trait loci (QTL), with many QTLs and several causal genes currently identified. Investigating the physiological and molecular mechanisms underlying this trait is crucial for soybean breeding, production, and food processing. For this article, the literature was reviewed and condensed to create a well-rounded picture of the current understanding of internal and external factors, QTLs, causal genes, and the regulatory mechanisms related to the HS of soybean, with the aim of providing reference for future research and utilization of this trait.
Initial validation of the Turkish version of the defense mechanisms rating scales-self-report-30
Authors: Yılmaz Meltem , Taş Berke , Çelik Deniz , Perry J. Christopher , Tanzilli Annalisa , Di Giuseppe Mariagrazia , Lingiardi Vittorio
Published: June 2024

The Defense Mechanisms Rating Scales-Self Report-30 (DMRS-SR-30) was recently developed to add a self-report alternative to the assessment of defenses, reflecting their generally accepted hierarchical organization. In this study, we aimed to examine psychometric properties and factor structure of the Turkish language version of the DMRS-SR-30. The sample consisted of 1.002 participants who filled out a survey comprising the DMRS-SR-30, the Brief Symptom Inventory, and the Inventory of Personality Organization through Qualtrics. Confirmatory Factor Analysis indicated a three-factor structure (CFI = 0.89, RMSEA = 0.05) that confirms the DMRS theoretical frame with a relatively acceptable fit. Defensive categories and total scale scores showed good to excellent reliability (α values ranging from 0.64 to 0.89). Correlations between defenses, symptoms, and personality functioning demonstrated good convergent and discriminant validity. The individuals with clinically significant BSI scores (T-score ≥ 63) differed on the DMRS-SR-30 scores from the individuals in the non-clinical range. The Turkish version of the DMRS-SR-30 is a reliable and valid instrument to self-assess the hierarchy of defense mechanisms and overall defensive functioning. Moreover, the current study supports the validity of the tripartite model of defenses in a language and culture different from the origins of the DMRS and DMRS-SR-30.
Stannous fluoride forms aggregates between outer and inner membranes leading to membrane rupture of Porphyromonas gingivalis and Prevotella pallens
Authors: Xie Sancai , Iberi Vighter , Boissy Ying , Tansky Cheryl S. , Huggins Tom , Ramji Niranjan , Biesbrock Aaron R.
Published: June 2024

Objective

Stannous has been shown to bind to free lipopolysaccharides, thus preventing them from binding to TLR receptors. This study was undertaken to determine the histomorphological mechanism of stannous binding to anaerobic bacteria.

Methods

Two bacteria associated with gingivitis and advanced periodontal disease, Porphyromonas gingivalis (P. gingivalis) and Prevotella pallens (P. pallens), were cultured in 25–1,000 μM of stannous fluoride and stannous chloride for 48 h. The growth rate was estimated using absorbance OD600. Bacterial cells were then fixed and processed for transmission electron microscopy (TEM) analysis.

Results

Stannous fluoride inhibited proliferation of both P. gingivalis and P. pallens in a dose-dependent manner. There was a statistically significant suppression of the growth curve starting at 100 μM for P. pallens (P = 0.050) and 200 μM for P. gingivalis (P = 0.039). TEM analysis revealed a thick layer of polysaccharides (19.8 nm) in P. gingivalis. The outer and inner membranes were clearly visible with low electron densities in both bacteria. Stannous diffused into bacterial membranes and formed precipitates in the areas spanning outer and inner membranes and below inner membranes. Precipitates varied in size ranging from 46.4 to 84.5 nm in length, and 18.4 to 35.9 nm in width. The membranes were disintegrated in the region where stannous formed precipitates. Cytosolic contents were leaked out, and in several cases, small vesicles were formed. Stannous precipitates were more abundant in numbers and larger in size in bacteria treated with high concentrations (100–300 μM) than in low concentrations (25–50 μM) of stannous fluoride. Furthermore, most of the bacteria were disintegrated in the groups treated with 100–300 μM stannous fluoride. At low concentrations (25 μM), stannous fluoride formed complexes primarily around outer membranes, to which lipopolysaccharides are anchored. Stannous chloride results showed similar trends, but it was less potent than stannous fluoride.

Conclusion

Stannous fluoride can penetrate bacteria, bind to the constituents of the membrane and form precipitates between outer and inner membranes and beneath inner membranes. These large precipitates damaged the integrity of membranes and allowed cytosolic contents to be leaked out. Stannous complexes formed at the outer membranes, even at low concentrations (25 μM).
The influence of Survivor stories and a virtual reality representation of a residential school on reconciliation in Canada
Authors: Starzyk Katherine B. , Efimoff Iloradanon H. , Neufeld Katelin Helene Siemens , Woolford Andrew , Fontaine Aleah S. M. , Young James E. , Bunt Andrea , Trickey Jessica , Sinclair Struan , Muller Adam
Published: June 2024

Indigenous Peoples in Canada have endured many genocidal efforts, such as residential schools. Across the country, initiatives to promote critical historical education about residential schools are underway, ranging in duration, content, and immersion. In this study, we tested whether a promising high-immersion approach, a virtual reality residential school, could improve non-Indigenous participants' attitudes and feelings toward Indigenous people. We compared the effects of the virtual residential school to a transcript condition, in which participants read the transcripts of the narration that accompanied the virtual residential school, and an empty control condition. The study had three time points: Baseline (N = 241), intervention (N = 241), and follow-up (N = 132). Immediately following the intervention, what participants learned about the residential school, both through virtual reality and reading the transcripts, increased non-Indigenous participants' empathy, political solidarity, and outgroup warmth for Indigenous people, relative to the control. The virtual reality school, but not transcripts, also increased privity relative to the control. These effects decreased over time. In summary, though both written and virtual reality forms of critical historical education were effective in the short term, to maintain the long-term effects of critical historical education, ongoing or recurring education is likely necessary. These results extend the virtual reality literature to unstudied concepts (political solidarity, privity) and critical historical education literature to a new form of media (virtual reality). We discuss the findings in relation to literature on critical historical education and virtual reality as well as outline future directions.
Investigating college students' green food consumption intentions in China: integrating the Theory of Planned Behavior and Norm Activation Theory
Authors: He Jiaxin , Sui Dangchen
Published: June 2024

Introduction

The global trend toward consuming green food is on the rise. College students, as the future consumer base, have sparked significant interest in their inclination toward consuming environmentally-friendly foods. This paper integrates the Theory of Planned Behavior with the Norm Activation Theory to investigate the factors influencing college students' propensity to choose green foods, establishing a comprehensive model.

Methods

This study utilized online and paper questionnaires for data collection, distributing them among college students and receiving 350 valid responses. In the data analysis phase, SPSS was employed for statistical data analysis, including descriptive statistics and regression analysis, while AMOS was used for structural equation modeling.

Results and discussion

The data analysis results indicate that subjective norms, behavioral attitudes, and individual norms have a significant positive influence on college students' inclination to purchase green food. Purchase intention is indirectly influenced by personal norms and behavioral attitudes through perceptions of consequences. Responsibility attribution indirectly impacts purchase intention of green food through personal norms. Personal norms are indirectly influenced by responsibility attribution through perceptions of consequences.
Owner experience and veterinary involvement with unlicensed GS-441524 treatment of feline infectious peritonitis: a prospective cohort study
Authors: Negash Rosa , Li Emma , Jacque Nicole , Novicoff Wendy , Evans Samantha J. M.
Published: June 2024

Introduction

Feline Infectious Peritonitis (FIP) has historically been a fatal coronavirus disease in cats. In recent years, the therapeutic agent GS-441524, developed by Gilead Sciences, was found to be a successful treatment for FIP in most patients in clinical trials. However, this particular drug has remained stalled in the therapeutic pipeline, leaving patients and cat owners without a licensed medication. In the meantime, online social media platforms began to emerge, connecting cat owners with a community of citizen non-veterinary professionals sourcing unlicensed GS-441524.

Methods

This study prospectively followed participants (N = 141) that successfully completed 12 weeks of treatment, capturing their treatment experiences with self-administered GS-441524-like medication. A one-time survey was administered to enrolled participants with mixed format of questions (open-ended and multiple-choice) asking about treatment administration techniques, observed side effects of GS-441524, accrued cost, veterinarian involvement, impact on the cat-human bond, and social media usage.

Results

Our results show cat owners experienced a shift in treatment modality from injectable GS-441524 to pill formulation across the treatment period. The average total cost of medication has decreased since 2021 to approximately USD 3100, and participants reported the human–animal bond being affected negatively. Additionally, there was an increased trend in veterinarian awareness of GS-441524-like therapeutics and monitoring of clients undergoing treatment. Social media usage was reported as being important at the beginning of treatment to establish treatment administration but lessened by the end of treatment.

Discussion

This study is the first detailed, prospective account of owner experiences with unlicensed GS-441524, raising an important discussion surrounding citizen veterinary medicine.
Bromide: the good, the bad, and the ugly of the oldest antiseizure medication
Authors: Gouveia Diogo , Mandigers Paul , Cherubini Giunio Bruto
Published: June 2024

Bromide is the first effective antiseizure medication used in human medicine since the XIX century. Initially met with skepticism, bromide quickly gained enthusiasm within the medical field until being largely replaced by newer antiseizure medications with significantly fewer adverse effects in people. In veterinary medicine, bromide continues to be used in the management of epileptic patients for over 30 years, yet adverse effects can impact owners and patients alike. We sought to provide the general practitioner and veterinary neurologist with insightful information on both the positive and negative attributes of bromide, explore factors that may influence its desirability as an antiseizure medication in specific veterinary cases and elucidate its current role in modern epilepsy treatment for veterinary patients. It’s also our endeavor to discuss the current use as an alternative or add-on with other known antiseizure medications and potential future studies that might enhance our understanding and use of this medication.
RANS-Based Aerodynamic Shape Optimization of a Wing with a Propeller in Front of the Wingtip
Authors: Chauhan Shamsheer S. , Martins Joaquim R. R. A.
Published: June 2024

Accounting for propeller–wing interaction allows for the design of more efficient propeller aircraft through strategic propulsion integration. In this paper, the cruise drag of a wing with a propeller located in front of the wingtip is minimized using twist and airfoil-shape design variables. Reynolds-averaged Navier–Stokes computational fluid dynamics with an actuator-disk approach is used for the flow simulations, and a gradient-based algorithm is used for the optimization. Changing the rotation direction of the propeller and optimizing the twist and airfoil shapes of the wing are found to impact the aerodynamic performance significantly, as expected. However, optimizing the wing while accounting for the propeller slipstream during optimization provides little benefit over optimizing it without accounting for the propeller slipstream—a difference of less than one drag count.
Application of Lee–Tarver Model for Energetic Materials Safety Assessment Utilized in Aerospace Applications
Authors: Awan Muhammad Saqib , Huang Zhengxiang , Zu Xudong , Xiao Qiangqiang , Ma Bin
Published: June 2024

Energetic materials, essential for rocket propulsion, play a crucial role in aerospace systems. These materials lack sufficient safety assessments and pose significant risks to life and infrastructure. The slow progress in this field is hindered by prohibitively high experimental costs and the inherently destructive nature of these experiments. This study aimed to evaluate modeling-based safety assessments, primarily utilizing the Lee–Tarver model. It specifically addressed the threat posed by shaped charges during transportation. Experimental analyses employed 50 mm JH-2 shaped charges, targeting RDX-based JH-2 formulation, since RDX is widely used in various rocket motor propellant formulations. TNT was also used to enhance the validation of the Lee–Tarver model findings. Various logistical configurations were explored, testing steel container walls ranging from 10 mm thickness to reinforced walls of 50 mm, 60 mm, and 65 mm steel. Comparative analysis with experiments reinforced the accuracy of the Lee–Tarver model’s numerical predictions. Both simulations and experiments affirmed that a 65 mm steel protection suffices for the safe transportation of RDX-based JH-2 formulations and TNT within a 10 mm storage box in logistical setups. Furthermore, this study emphasizes the Lee–Tarver model’s reliability for most energetic materials safety assessments, while acknowledging certain limitations.