bluuebunny/crossref_metadata_2025 huggingface dataset:
PRDM16 regulates γδT17 cell differentiation via controlling type 17 program and lipid-dependent cell fitness
Authors: Nah Jinwoo , Lee Youngjin , Seong Rho H.
Published: January 2024

γδT17 cells are a subset of γδT cells producing IL-17, which is crucial for protection against bacterial and fungal infections. It has recently been shown that γδT17 cells have enriched lipid storage and lipid metabolism. However, the regulation of γδT17 cell function and differentiation with respect to lipids remains unknown. Here, we report that PRDM16 is a critical regulator of γδT17 cell differentiation, controlling type 17 immunity gene expression program and lipid-dependent cell fitness. We demonstrated that γδT17 cells have higher lipid-dependent cell fitness, which is negatively correlated with the expression of Prdm16. Loss of Prdm16 enhances the function and differentiation of γδT17 cells, and increases their fitness in lipid-rich environments. Specifically, loss of Prdm16 exacerbates development of psoriasis in the skin, a lipid-rich organ, and Prdm16 controls lipid-mediated differentiation of Vγ4+ γδT17 cells, which are the major source of IL-17 during the onset of psoriasis. Our study highlights the potential impact of PRDM16 on lipid-dependent fitness and protective immune function of γδT cells and also on the immunotherapy of psoriasis and inflammatory diseases.
Prediction of six macrophage phenotypes and their IL-10 content based on single-cell morphology using artificial intelligence
Authors: Selig Mischa , Poehlman Logan , Lang Nils C. , Völker Marita , Rolauffs Bernd , Hart Melanie L.
Published: January 2024

Introduction

The last decade has led to rapid developments and increased usage of computational tools at the single-cell level. However, our knowledge remains limited in how extracellular cues alter quantitative macrophage morphology and how such morphological changes can be used to predict macrophage phenotype as well as cytokine content at the single-cell level.

Methods

Using an artificial intelligence (AI) based approach, this study determined whether (i) accurate macrophage classification and (ii) prediction of intracellular IL-10 at the single-cell level was possible, using only morphological features as predictors for AI. Using a quantitative panel of shape descriptors, our study assessed image-based original and synthetic single-cell data in two different datasets in which CD14+ monocyte-derived macrophages generated from human peripheral blood monocytes were initially primed with GM-CSF or M-CSF followed by polarization with specific stimuli in the presence/absence of continuous GM-CSF or M-CSF. Specifically, M0, M1 (GM-CSF-M1, TNFα/IFNγ-M1, GM-CSF/TNFα/IFNγ-M1) and M2 (M-CSF-M2, IL-4-M2a, M-CSF/IL-4-M2a, IL-10-M2c, M-CSF/IL-10-M2c) macrophages were examined.

Results

Phenotypes were confirmed by ELISA and immunostaining of CD markers. Variations of polarization techniques significantly changed multiple macrophage morphological features, demonstrating that macrophage morphology is a highly sensitive, dynamic marker of phenotype. Using original and synthetic single-cell data, cell morphology alone yielded an accuracy of 93% for the classification of 6 different human macrophage phenotypes (with continuous GM-CSF or M-CSF). A similarly high phenotype classification accuracy of 95% was reached with data generated with different stimuli (discontinuous GM-CSF or M-CSF) and measured at a different time point. These comparably high accuracies clearly validated the here chosen AI-based approach. Quantitative morphology also allowed prediction of intracellular IL-10 with 95% accuracy using only original data.

Discussion

Thus, image-based machine learning using morphology-based features not only (i) classified M0, M1 and M2 macrophages but also (ii) classified M2a and M2c subtypes and (iii) predicted intracellular IL-10 at the single-cell level among six phenotypes. This simple approach can be used as a general strategy not only for macrophage phenotyping but also for prediction of IL-10 content of any IL-10 producing cell, which can help improve our understanding of cytokine biology at the single-cell level.
The outbreak of Drupella snails and its catastrophic effects on coral reefs: a comprehensive review
Authors: Zhang Fang , Jia Xiwang , Lin Zhenni , Jiang Yiyi , Qu Mengjie
Published: January 2024

The recurring outbreaks of Drupella snails are a significant threat to coral reef ecosystems on a global scale. However, research on Drupella snails is currently very fragmentary. This article explores the ecological impacts and mitigation methods of Drupella snails and its outbreaks, and draws the following main conclusions. 1) Drupella snails inhabit the tropical oceans of the Indo-Pacific, utilizing their specialized radula to feed on coral polyps, and they predominantly spawn during summer, attaching egg capsules onto coral skeletons. 2) An outbreak of Drupella snails is defined by a density of > 2 ind/m2, but large aggregations alone do not necessarily indicate an outbreak. 3) The damage of coral reef ecosystem is the primary cause of Drupella snail outbreaks, with the hypotheses of “terrestrial nutrient input” and “overfishing of predator” being widely accepted but not fully explaining all outbreak events. 4) Countering Drupella snail outbreaks involves improving the health of coral reef ecosystems, protected areas, biological control and manual removal, though manual removal is the most direct and effective in short-term. 5) The understanding of the physiological and ecological characteristics of Drupella snails is inadequate at present, with larval development and population ecology being areas of particular under-investigation. 6) Studies of Drupella snail outbreaks have focused mainly on mid-outbreak stages, with little attention to early warnings beforehand or adverse outcomes afterwards. Despite significant challenges, addressing knowledge gaps in the biology of Drupella snails is crucial to determine the true causes of their outbreaks and identify corresponding solutions.
Godzilla mineral dust and La Soufrière volcanic ash fallout immediately stimulate marine microbial phosphate uptake
Authors: Elliott Hope Elizabeth , Popendorf Kimberly J. , Blades Edmund , Royer Haley M. , Pollier Clément G. L. , Oehlert Amanda M. , Kukkadapu Ravi , Ault Andrew , Gaston Cassandra J.
Published: January 2024

During the “Godzilla” dust storm of June 2020, unusually high fluxes of mineral dust traveled across the Atlantic from the Sahara Desert, reaching the Caribbean Basin, Gulf Coast, and southeastern United States. Additionally, an eruption of the La Soufrière volcano on St. Vincent in April 2021 generated substantial ashfall in the southeastern Caribbean. While many studies have analyzed mineral dust’s ability to relieve nutrient limitation of phosphorus (P) in the P-stressed North Atlantic, less is known about the impact of extreme events and other natural aerosols on fluxes of P into seawater and from seawater into marine microbial cells. We quantified P and iron (Fe) content in mineral dust from the Godzilla dust storm and volcanic ash from the La Soufrière eruption collected at Ragged Point, Barbados. We also performed seawater incubations to assess the marine microbial response to aerosol deposition. Using environmentally-relevant concentrations of atmospheric particles for within the ocean’s mixed layer allowed us to draw realistic conclusions about how these deposition events impacted P cycling in situ. Volcanic ash has lower P content than mineral dust, and P in volcanic ash is far less soluble (~1%) than assumed in current atmospheric deposition models. Adding mineral dust and the volcanic ash leachate in concentrations representing different deposition scenarios increased soluble reactive phosphorus (SRP) concentrations in coastal seawater by ~7-32 nM. Phosphate uptake rate was stimulated in coastal seawater after either mineral dust or volcanic ash deposition at aerosol concentrations relevant to the Godzilla dust event, with ash eliciting the fastest uptake rate. Furthermore, high concentrations of both the mineral dust and volcanic ash led to slightly elevated alkaline phosphatase activity (APA) compared to the relevant controls, indicating higher potential for use of dissolved organic phosphorus (DOP) as a P source. Quantifying these aerosols’ impacts on P cycling is a significant step towards achieving a better understanding of their potential roles in relieving nutrient limitation and fueling the biological carbon pump.
Analysis of the relationship between axial length, optic disc morphology, and regional variations in retinal vessel density in young adults with healthy eyes
Authors: Chen Yanhui , Rong Hua , Liu Yuling , Gao Huijuan , Sun Ziwen , Dang Weiyu , Lu Kunpeng , Mi Baoyue , Li Jing , Wei Ruihua
Published: January 2024

Purpose

To investigate the relationship between optic disc morphology, axial length, and regional distribution of retinal vessels in healthy eyes of young adults.

Methods

Nine hundred and two healthy eyes were enrolled in this university-based, cross-sectional study. Spectral-domain optical coherence tomography angiography was used to measure the parapapillary retinal vessel density. We automated the process of calculating optic disc tilt and rotation by using a program written in Python. Relationships between optic disc rotation, optic disc tilt, parapapillary vessel density, and other ocular parameters were analyzed using regression models.

Results

As axial length increased, optic disc morphology became more tilted and rotated inferiorly. The superficial vessel density (SVD) and radial peripapillary capillary density (RPCD) gradually decreased in all regions except for the temporal quadrant. Increased temporal SVD (OR [95% CI] = 1.081 [1.039, 1.124], p < 0.001), reduced nasal SVD (OR [95% CI] = 0.898 [0.861, 0.937], p < 0.01), and short relative lens position (OR [95% CI] = 0.126 [0.032, 0.495], p = 0.003) were significantly associated with the presence of a tilted optic disc. Inferior disc rotation was associated with decreased superior deep vessel density (DVD) and increased inferior DVD and temporal DVD after adjusting for sex and axial length.

Conclusion

The tilted and rotated optic discs were associated with the distribution of SVD and DVD, respectively. We should fully consider the influence of optic disc morphology on parapapillary vessel density in eyes with myopia.
DBPF-net: dual-branch structural feature extraction reinforcement network for ocular surface disease image classification
Authors: Wan Cheng , Mao Yulong , Xi Wenqun , Zhang Zhe , Wang Jiantao , Yang Weihua
Published: January 2024

Pterygium and subconjunctival hemorrhage are two common types of ocular surface diseases that can cause distress and anxiety in patients. In this study, 2855 ocular surface images were collected in four categories: normal ocular surface, subconjunctival hemorrhage, pterygium to be observed, and pterygium requiring surgery. We propose a diagnostic classification model for ocular surface diseases, dual-branch network reinforced by PFM block (DBPF-Net), which adopts the conformer model with two-branch architectural properties as the backbone of a four-way classification model for ocular surface diseases. In addition, we propose a block composed of a patch merging layer and a FReLU layer (PFM block) for extracting spatial structure features to further strengthen the feature extraction capability of the model. In practice, only the ocular surface images need to be input into the model to discriminate automatically between the disease categories. We also trained the VGG16, ResNet50, EfficientNetB7, and Conformer models, and evaluated and analyzed the results of all models on the test set. The main evaluation indicators were sensitivity, specificity, F1-score, area under the receiver operating characteristics curve (AUC), kappa coefficient, and accuracy. The accuracy and kappa coefficient of the proposed diagnostic model in several experiments were averaged at 0.9789 and 0.9681, respectively. The sensitivity, specificity, F1-score, and AUC were, respectively, 0.9723, 0.9836, 0.9688, and 0.9869 for diagnosing pterygium to be observed, and, respectively, 0.9210, 0.9905, 0.9292, and 0.9776 for diagnosing pterygium requiring surgery. The proposed method has high clinical reference value for recognizing these four types of ocular surface images.
Efficacy of the DRL orthokeratology lens in slowing axial elongation in French children
Authors: Queirós António , Rolland le Moal Pauline , Angioi-Duprez Karine , Berrod Jean-Paul , Conart Jean-Baptiste , Chaume Aurélia , Pauné Jaume
Published: January 2024

Background

This study aims to assess and compare the impact of Orthokeratology Double Reservoir Lens (DRL) versus Single Vision Lenses (SVL) on axial elongation and anterior chamber biometric parameters in myopic children over a 6- and 12-month treatment period in France.

Methods

A retrospective study involving 48 patients aged 7 to 17 years, who underwent either orthokeratology treatment or single-vision spectacle correction, was conducted. Changes in refractive error, axial length, and anterior chamber depth were examined.

Results

Twenty-five patients comprised the Orthokeratology (OK) group, while twenty-three were in the control group (single-vision spectacle group). Significant increases in mean axial length were observed over time in both the control (0.12 ± 0.13 mm and 0.20 ± 0.17 mm after 6 and 12 months, respectively; F (2,28.9) = 27.68, p < 0.001) and OK groups (0.02 ± 0.07 mm and 0.06 ± 0.13 mm after 6 and 12 months, respectively; F (2,29.1) = 5.30, p = 0.023). No statistically significant differences in axial length were found between male and female children (p > 0.620). Age-specific analysis revealed no significant axial elongation after 12 months in the 14–17 years group in the OK group. Anterior biometric data analysis at 6 and 12 months showed statistical significance only for the DRL group.

Conclusion

Orthokeratology resulted in an 86 and 70% reduction in axial elongation after 6 and 12 months of lens wear, respectively, compared to the single-vision spectacles group. Myopia progression was more pronounced in younger children, underscoring the importance of initiating myopia control strategies at early ages.
Arbuscular mycorrhizal fungal communities in soils where astragalus had grown for 2 years were similar to those in the abandoned farmland
Authors: An Zhi-Gang , Shang Hu-Shan , Cui Zhi-Jia , Huang Yu-Fang , Wu Rui , Li Run-Hong
Published: January 2024

Purpose

Astragalus-cultivated soils are enriched in arbuscular mycorrhizal fungi (AMF); however, the community changes of AMF between years in stragalus-cultivated soils are still unclear.

Methods

To illustrate this, using high-throughput amplicon sequencing and quantitative real-time PCR, we analyzed the AMF communities of the abandoned farmlands and interannual astragalus-cultivated soils for 1-, 2-, 3-, and 4-years, including community composition, dominant, core, specific and significantly fluctuating AMF, co-occurrence network, alpha diversity, and beta diversity.

Results

A total of 74 OTUs were classified into one phylum, Glomeromycota; one class, Glomeromycetes; four orders; four families; and six genera. The 2-year soil had the highest number of reads among the interannual soils. Only one OTU was shared among all interannual soils. The treatments significantly affected the Ace, Shannoneven, and Shannon estimators of the communities. The 2-year soil had the highest richness, evenness, and diversity among all interannual soils and was the closest to the abandoned farmland in terms of alpha diversity. Glomus of the family Glomeraceae was the dominant genus present in all treatments, and the composition of the dominant genus in interannual soils was different. Both Glomus and Diversispora were the core AMF in interannual soils, and specific AMF existed in different interannual soils. Glomus is a genus that exhibits significant interannual variation. The interannual time significantly affected the network connectivity. The results of the principal coordinate analysis showed that the community composition of the interannual soils was close to each other and separated from the abandoned farmland, and that the interannual time significantly affected the community composition.

Conclusion

Among the interannual soils, the 2-year soil may be more suitable for A. sinensis seedling rotation.
Transcriptome reveals the role of the htpG gene in mediating antibiotic resistance through cell envelope modulation in Vibrio mimicus SCCF01
Authors: Qin Zhenyang , Peng Kun , Feng Yang , Wang Yilin , Huang Bowen , Tian Ziqi , Ouyang Ping , Huang Xiaoli , Chen Defang , Lai Weimin , Geng Yi
Published: January 2024

HtpG, a bacterial homolog of the eukaryotic 90 kDa heat-shock protein (Hsp90), represents the simplest member of the heat shock protein family. While the significance of Hsp90 in fungal and cancer drug resistance has been confirmed, the role of HtpG in bacterial antibiotic resistance remains largely unexplored. This research aims to investigate the impact of the htpG gene on antibiotic resistance in Vibrio mimicus. Through the creation of htpG gene deletion and complementation strains, we have uncovered the essential role of htpG in regulating the structural integrity of the bacterial cell envelope. Our transcriptomics analysis demonstrates that the deletion of htpG increases the sensitivity of V. mimicus to antimicrobial peptides, primarily due to upregulated lipopolysaccharide synthesis, reduced glycerophospholipid content, and weakened efflux pumps activity. Conversely, reduced sensitivity to β-lactam antibiotics in the ΔhtpG strain results from decreased peptidoglycan synthesis and dysregulated peptidoglycan recycling and regulation. Further exploration of specific pathway components is essential for a comprehensive understanding of htpG-mediated resistance mechanisms, aiding in the development of antimicrobial agents. To our knowledge, this is the first effort to explore the relationship between htpG and drug resistance in bacteria.
Overgrazing on unmanaged grassland interfered with the restoration of adjacent grazing-banned grassland by affecting soil properties and microbial community
Authors: Fang Mengchao , Lu Guang , Zhang Shuping , Liang Wei
Published: January 2024

A “grazing ban” policy has been implemented in some pastoral areas in China to fence degraded grasslands for restoration. However, fencing increased grazing pressures in unmanaged grasslands. Based on the mechanism of negative edge effect, we investigated whether overgrazing on unmanaged grassland interfered with the restoration of adjacent grazing-banned grassland by affecting soil properties and microbial community using a sample in Hulun Buir of Inner Mongolia, in order to optimize the “grazing ban” policy. Plant and soil were sampled in areas 30 m away from the fence in unmanaged grassland (UM) and in areas 30 m (adjacent to UM) and 30–60 m (not adjacent to UM) away from the fence in the grazing-banned grassland (F-30 m and F-60 m). The species richness and diversity of plant communities and the ASV number of fungal communities significantly decreased in F-30 m and UM, and the Simpson index of the bacterial community significantly decreased in F-30 m compared with F-60 m. The abundance of fungi involved in soil organic matter decomposition significantly decreased and the abundance of stress-resistant bacteria significantly increased, while the abundance of bacteria involved in litter decomposition significantly decreased in UM and F-30 m compared with F-60 m. The simplification of plant communities decreased in soil water and total organic carbon contents can explain the variations of soil microbial communities in both UM and F-30 m compared with F-60 m. The results of PLS-PM show that changes in plant community and soil microbial function guilds in UM may affect those in F-30 m by changing soil water and total organic carbon contents. These results indicate that overgrazing on unmanaged grassland interfered with the restoration of adjacent grazing-banned grassland by affecting soil properties and microbial community. The grazing-banned grasslands should be adjusted periodically in order to avoid negative edge effects.
Adaptive laboratory evolution to obtain furfural tolerant Saccharomyces cerevisiae for bioethanol production and the underlying mechanism
Authors: Yao Lan , Jia Youpiao , Zhang Qingyan , Zheng Xueyun , Yang Haitao , Dai Jun , Chen Xiong
Published: January 2024

Introduction

Furfural, a main inhibitor produced during pretreatment of lignocellulose, has shown inhibitory effects on S. cerevisiae.

Method

In the present study, new strains named 12–1 with enhanced resistance to furfural were obtained through adaptive laboratory evolution, which exhibited a shortened lag phase by 36 h, and an increased ethanol conversion rate by 6.67% under 4 g/L furfural.

Results and Discussion

To further explore the mechanism of enhanced furfural tolerance, ADR1_1802 mutant was constructed by CRISPR/Cas9 technology, based on whole genome re-sequencing data. The results indicated that the time when ADR1_1802 begin to grow was shortened by 20 h compared with reference strain (S. cerevisiae CEN.PK113-5D) when furfural was 4 g/L. Additionally, the transcription levels of GRE2 and ADH6 in ADR1_ 1802 mutant were increased by 53.69 and 44.95%, respectively, according to real-time fluorescence quantitative PCR analysis. These findings suggest that the enhanced furfural tolerance of mutant is due to accelerated furfural degradation. Importance: Renewable carbon worldwide is vital to achieve “zero carbon” target. Bioethanol obtained from biomass is one of them. To make bioethanol price competitive to fossil fuel, higher ethanol yield is necessary, therefore, monosaccharide produced during biomass pretreatment should be effectively converted to ethanol by Saccharomyces cerevisiae. However, inhibitors formed by glucose or xylose oxidation could make ethanol yield lower. Thus, inhibitor tolerant Saccharomyces cerevisiae is important to this process. As one of the main component of pretreatment hydrolysate, furfural shows obvious impact on growth and ethanol production of Saccharomyces cerevisiae. To get furfural tolerant Saccharomyces cerevisiae and find the underlying mechanism, adaptive laboratory evolution and CRISPR/Cas9 technology were applied in the present study
Mild cognitive impairment prediction and cognitive score regression in the elderly using EEG topological data analysis and machine learning with awareness assessed in affective reminiscent paradigm
Authors: Rutkowski Tomasz M. , Komendziński Tomasz , Otake-Matsuura Mihoko
Published: January 2024

Introduction

The main objective of this study is to evaluate working memory and determine EEG biomarkers that can assist in the field of health neuroscience. Our ultimate goal is to utilize this approach to predict the early signs of mild cognitive impairment (MCI) in healthy elderly individuals, which could potentially lead to dementia. The advancements in health neuroscience research have revealed that affective reminiscence stimulation is an effective method for developing EEG-based neuro-biomarkers that can detect the signs of MCI.

Methods

We use topological data analysis (TDA) on multivariate EEG data to extract features that can be used for unsupervised clustering, subsequent machine learning-based classification, and cognitive score regression. We perform EEG experiments to evaluate conscious awareness in affective reminiscent photography settings.

Results

We use EEG and interior photography to distinguish between healthy cognitive aging and MCI. Our clustering UMAP and random forest application accurately predict MCI stage and MoCA scores.

Discussion

Our team has successfully implemented TDA feature extraction, MCI classification, and an initial regression of MoCA scores. However, our study has certain limitations due to a small sample size of only 23 participants and an unbalanced class distribution. To enhance the accuracy and validity of our results, future research should focus on expanding the sample size, ensuring gender balance, and extending the study to a cross-cultural context.
Cerebral venous biomarkers and veno-arterial gradients: untapped resources in Alzheimer’s disease
Authors: Suhocki Paul V. , Doraiswamy P. Murali
Published: January 2024

Blood based biomarkers (BBB) derived from forearm veins for estimating brain changes is becoming ubiquitous in Alzheimer’s Disease (AD) research and could soon become standard in routine clinical diagnosis. However, there are many peripheral sources of contamination through which concentrations of these metabolites can be raised or lowered after leaving the brain and entering the central venous pool. This raises the issue of potential false conclusions that could lead to erroneous diagnosis or research findings. We propose the use of simultaneous sampling of internal jugular venous and arterial blood to calculate veno-arterial gradient, which can reveal either a surplus or a deficit of metabolites exiting the brain. Methods for sampling internal jugular venous and arterial blood are described along with examples of the use of the veno-arterial gradient in non-AD brain research. Such methods in turn could help better establish the accuracy of forearm venous biomarkers.
Evaluation of tractography-based myelin-weighted connectivity across the lifespan
Authors: Bosticardo Sara , Schiavi Simona , Schaedelin Sabine , Battocchio Matteo , Barakovic Muhamed , Lu Po-Jui , Weigel Matthias , Melie-Garcia Lester , Granziera Cristina , Daducci Alessandro
Published: January 2024

Introduction

Recent studies showed that the myelin of the brain changes in the life span, and demyelination contributes to the loss of brain plasticity during normal aging. Diffusion-weighted magnetic resonance imaging (dMRI) allows studying brain connectivity in vivo by mapping axons in white matter with tractography algorithms. However, dMRI does not provide insight into myelin; thus, combining tractography with myelin-sensitive maps is necessary to investigate myelin-weighted brain connectivity. Tractometry is designated for this purpose, but it suffers from some serious limitations. Our study assessed the effectiveness of the recently proposed Myelin Streamlines Decomposition (MySD) method in estimating myelin-weighted connectomes and its capacity to detect changes in myelin network architecture during the process of normal aging. This approach opens up new possibilities compared to traditional Tractometry.

Methods

In a group of 85 healthy controls aged between 18 and 68 years, we estimated myelin-weighted connectomes using Tractometry and MySD, and compared their modulation with age by means of three well-known global network metrics.

Results

Following the literature, our results show that myelin development continues until brain maturation (40 years old), after which degeneration begins. In particular, mean connectivity strength and efficiency show an increasing trend up to 40 years, after which the process reverses. Both Tractometry and MySD are sensitive to these changes, but MySD turned out to be more accurate.

Conclusion

After regressing the known predictors, MySD results in lower residual error, indicating that MySD provides more accurate estimates of myelin-weighted connectivity than Tractometry.
An end-to-end LSTM-Attention based framework for quasi-steady-state CEST prediction
Authors: Yang Wei , Zou Jisheng , Zhang Xuan , Chen Yaowen , Tang Hanjing , Xiao Gang , Zhang Xiaolei
Published: January 2024

Chemical exchange saturation transfer (CEST)-magnetic resonance imaging (MRI) often takes prolonged saturation duration (Ts) and relaxation delay (Td) to reach the steady state, and yet the insufficiently long Ts and Td in actual experiments may underestimate the CEST measurement. In this study, we aimed to develop a deep learning-based model for quasi-steady-state (QUASS) prediction from non-steady-state CEST acquired in experiments, therefore overcoming the limitation of the CEST effect which needs prolonged saturation time to reach a steady state. To support network training, a multi-pool Bloch-McConnell equation was designed to derive wide-ranging simulated Z-spectra, so as to solve the problem of time and labor consumption in manual annotation work. Following this, we formulated a hybrid architecture of long short-term memory (LSTM)-Attention to improve the predictive ability. The multilayer perceptron, recurrent neural network, LSTM, gated recurrent unit, BiLSTM, and LSTM-Attention were included in comparative experiments of QUASS CEST prediction, and the best performance was obtained by the proposed LSTM-Attention model. In terms of the linear regression analysis, structural similarity index (SSIM), peak signal-to-noise ratio (PSNR), and mean-square error (MSE), the results of LSTM-Attention demonstrate that the coefficient of determination in the linear regression analysis was at least R2 = 0.9748 for six different representative frequency offsets, the mean values of prediction accuracies in terms of SSIM, PSNR and MSE were 0.9991, 49.6714, and 1.68 × 10−4 for all frequency offsets. It was concluded that the LSTM-Attention model enabled high-quality QUASS CEST prediction.
Adverse events of immune checkpoint therapy alone versus when combined with vascular endothelial growth factor inhibitors: a pooled meta-analysis of 1735 patients
Authors: Kovalenko Iuliia , Lynn Ng Wern , Geng Yimin , Wang Yinghong , Msaouel Pavlos , Bhatia Shailender , Grivas Petros , Benkhadra Raed , Alhalabi Omar
Published: January 2024

Background

Combining immune checkpoint therapy (ICT) and vascular endothelial growth factor inhibitors (VEGFi) may result in increased treatment-related and immune-related adverse events (TRAEs and irAEs) compared to ICT alone. This metanalysis was conducted to identify prospective phase II or III clinical studies that evaluated the toxicity profile of ICT + VEGFi compared to ICT alone.

Methods

A systematic search was performed across all cancer types and major databases until August 10, 2022, and screening was done by two independent investigators. Inclusion criteria included phase 2 or 3 studies with at least one arm of patients treated with combination therapy and one arm treated with monotherapy. Adverse event data were pooled using a restricted maximum likelihood fixed effects model, and heterogeneity using Cochran’s Q (chi-square) test.

Results

7 out of 9366 studies met the inclusion criteria, and 808 and 927 patients were treated with ICT monotherapy and a combination of ICT with VEGFi, respectively. Only one study reported irAEs, so the analysis was restricted to TRAEs. The total number of TRAEs was significantly higher in the ICT + VEGFi group (RR:1.49; 95% CI 1.37 -1.62; p=1.5×10-21), and more frequent treatment withdrawals were attributed to TRAEs (RR:3.10; 95% CI 1.12-8.59; p=0.029). The highest TRAE effect size increases noted for rash (RR 6.50; 95% CI 3.76 – 11.25; p=2.1×10-11), hypertension (RR:6.07; 95% CI 3.69–10.00; p=1.3×10-12), hypothyroidism (RR:5.02; 95% CI 3.08 – 8.19; p=8.9×10-11), and diarrhea (RR:4.94; 95% CI 3.21–7.62; p=3.8×10-13). Other significantly more frequent TRAEs included nausea, anemia, anorexia, and proteinuria.

Conclusion

Combination therapy with ICT and VEGFi carries a higher risk of certain TRAEs, such as rash, hypertension, hypothyroidism, diarrhea, nausea, anorexia, and proteinuria, compared to ICT monotherapy. More granular details on the cause of AEs, particularly irAEs, should be provided in future trials of such regimens.
Multimodality treatment in recurrent/metastatic squamous cell carcinoma of head and neck: current therapy, challenges, and future perspectives
Authors: Pannunzio Sergio , Di Bello Armando , Occhipinti Denis , Scala Alessandro , Messina Gloria , Valente Giustina , Quirino Michela , Di Salvatore Mariantonietta , Tortora Giampaolo , Cassano Alessandra
Published: January 2024

Squamous cell carcinoma of the head and neck is a complex group of diseases that presents a challenge to the clinician. The prognosis in the recurrent/metastatic disease is particularly dismal, with a median survival of approximately 12 months. Recently, the personalized and multimodal approach has increased prognosis by integrating locoregional strategies (salvage surgery and stereotactic radiotherapy) and systemic treatments (chemotherapy, immunotherapy, and target therapy). Malnutrition is a significant clinical problem that interferes with dose intensity, and thus, feeding supplementation is critical not only to increase the quality of life but also to improve overall survival. With this review, we want to emphasize the importance of the multidisciplinary approach, quality of life, and nutritional supportive care and to integrate the latest updates of predictive biomarkers for immunotherapy and future therapeutic strategies.
Prospective deployment of an automated implementation solution for artificial intelligence translation to clinical radiation oncology
Authors: Kehayias Christopher E. , Yan Yujie , Bontempi Dennis , Quirk Sarah , Bitterman Danielle S. , Bredfeldt Jeremy S. , Aerts Hugo J. W. L. , Mak Raymond H. , Guthier Christian V.
Published: January 2024

Introduction

Artificial intelligence (AI)-based technologies embody countless solutions in radiation oncology, yet translation of AI-assisted software tools to actual clinical environments remains unrealized. We present the Deep Learning On-Demand Assistant (DL-ODA), a fully automated, end-to-end clinical platform that enables AI interventions for any disease site featuring an automated model-training pipeline, auto-segmentations, and QA reporting.

Materials and methods

We developed, tested, and prospectively deployed the DL-ODA system at a large university affiliated hospital center. Medical professionals activate the DL-ODA via two pathways (1): On-Demand, used for immediate AI decision support for a patient-specific treatment plan, and (2) Ambient, in which QA is provided for all daily radiotherapy (RT) plans by comparing DL segmentations with manual delineations and calculating the dosimetric impact. To demonstrate the implementation of a new anatomy segmentation, we used the model-training pipeline to generate a breast segmentation model based on a large clinical dataset. Additionally, the contour QA functionality of existing models was assessed using a retrospective cohort of 3,399 lung and 885 spine RT cases. Ambient QA was performed for various disease sites including spine RT and heart for dosimetric sparing.

Results

Successful training of the breast model was completed in less than a day and resulted in clinically viable whole breast contours. For the retrospective analysis, we evaluated manual-versus-AI similarity for the ten most common structures. The DL-ODA detected high similarities in heart, lung, liver, and kidney delineations but lower for esophagus, trachea, stomach, and small bowel due largely to incomplete manual contouring. The deployed Ambient QAs for heart and spine sites have prospectively processed over 2,500 cases and 230 cases over 9 months and 5 months, respectively, automatically alerting the RT personnel.

Discussion

The DL-ODA capabilities in providing universal AI interventions were demonstrated for On-Demand contour QA, DL segmentations, and automated model training, and confirmed successful integration of the system into a large academic radiotherapy department. The novelty of deploying the DL-ODA as a multi-modal, fully automated end-to-end AI clinical implementation solution marks a significant step towards a generalizable framework that leverages AI to improve the efficiency and reliability of RT systems.
Simulating neuronal development: exploring potential mechanisms for central nervous system metastasis in acute lymphoblastic leukemia
Authors: Li Ziping , Guo Zhi , Xiao Haitao , Chen Xuexing , Liu Wei , Zhou Hao
Published: January 2024

Background

Acute lymphoblastic leukemia (ALL) is prone to metastasize to the central nervous system (CNS), which is an important cause of poor treatment outcomes and unfavorable prognosis. However, the pathogenesis of CNS metastasis of ALL cells has not been fully illuminated. Recent reports have shed some light on the correlation between neural mechanisms and ALL CNS metastasis. These progressions prompt us to study the relationship between ALL central nervous system metastasis and neuronal development, exploring potential biomarkers and therapeutic targets of CNS metastasis.

Materials and methods

ALL central nervous system metastasis- and neuronal development-related differentially expressed genes (DEGs) were identified by analyzing gene expression datasets GSE60926 and GSE13715. Target prediction and network analysis methods were applied to assess protein–protein interaction networks. Gene Ontology (GO) terms and pathway enrichment for DEGs were assessed. Co-expressed differentially expressed genes (co-DEGs) coupled with corresponding predicted microRNAs (miRNAs) were studied as well. Reverse transcription–polymerase chain reaction (RT–PCR) and flow cytometry were employed for the validation of key co-DEGs in primary ALL cells. Furthermore, ALL cells were treated with a vascular endothelial growth factor (VEGF) inhibitor to block neuronal development and assess changes in the co-DEGs.

Results

We identified 216, 208, and 204 DEGs in ALL CNS metastasis specimens and neuronal development samples (GSE60926 and GSE13715). CD2, CD3G, CD3D, and LCK may be implicated in ALL CNS metastasis. LAMB1, MATN3, IGFBP3, LGALS1, and NEUROD1 may be associated with neuronal development. Specifically, four co-DEGs (LGALS1, TMEM71, SHISA2, and S100A11) may link ALL central nervous system metastasis and neuronal development process. The miRNAs for each co-DEG could be potential biomarkers or therapeutic targets for ALL central nervous system metastasis, especially hsa-miR-22-3p, hsa-miR-548t-5p, and hsa-miR-6134. Additionally, four co-DEGs (LGALS1, TMEM71, SHISA2, and S100A11) were validated in CNS-infiltrated ALL cells. The VEGF inhibitor demonstrated a suppressive effect on mRNA and protein expression of key co-DEGs.

Conclusion

The bioinformatic survey and key gene validation suggest a possible correlation between ALL CNS metastasis and the neuronal development process. Simulating the neuronal development process might be a possible strategy for CNS metastasis in ALL. LGALS1, TMEM71, SHISA2, and S100A11 genes are promising and novel biomarkers and targets in ALL CNS metastasis.
Orbital corticosteroid injections for the treatment of active thyroid eye disease
Authors: Eid Kevin T. , Kally Peter M. , Kahana Alon
Published: January 2024

Purpose

To study the efficacy of orbital injections of triamcinolone acetonide mixed 1:1 with dexamethasone in the treatment of active thyroid eye disease.

Methods

Patients that received orbital injection(s) of triamcinolone acetonide mixed 1:1 with dexamethasone for thyroid eye disease were included in this retrospective study. Demographic and clinical data were collected from the pre-treatment and 1 month follow up evaluations. Clinical data included subjective pain and diplopia scores, best-corrected visual acuity, Intraocular pressure, extraocular motility, clinical activity score, Hertel exophthalmometry, and upper eyelid margin to reflex distance.

Results

Fifteen patients, 33 orbital injections, were included in the study. The average patient age was 59.2 years (SD ± 13.0) and 89% female. Subjectively, 67% of patients reported improvement of orbital pain and pressure versus 28% stable and 5% worse (p <0.001). Post-procedure clinical activity score decreased from 3.84 to 3.00 (p = 0.0004). There were no significant differences in upper eyelid margin to reflex distance (4.1 ± 1.4 mm vs. 4.3 ± 2.6 mm, p = 0.45), Hertel exophthalmometry (21.7 ± 9.4 mm vs. 21.8 ± 7.6 mm, p = 0.56), or extraocular motility (21% improved vs. 72% stable and 7% worsening, p = 0.50). No steroid-responsive increases in intraocular pressure or injection-related complications were reported.

Conclusion

Orbital steroid injections can successfully reduce symptoms of TED and may be a reliable tool in the treatment of TED as a relatively safe, fast-acting, efficacious treatment option, particularly as a bridge to other therapies.
Case Report: Stüve–Wiedemann syndrome—a rare cause of persistent pulmonary hypertension of the newborn
Authors: Jin Jessica , Rothämel Paula , Büchel Johanna , Kammer Birgit , Brunet Theresa , Pattathu Joseph , Flemmer Andreas W. , Nussbaum Claudia , Schroepf Sebastian
Published: January 2024

Introduction

Persistent pulmonary hypertension of the newborn (PPHN) is a life-threatening condition characterized by hypoxemia due to elevated pulmonary vascular resistance. PPHN commonly arises secondary to various underlying conditions, including infection, meconium aspiration, and respiratory distress syndrome. Management includes pulmonary vasodilators, mechanical ventilation, oxygen supplementation, vasopressors, and volume replacement. Stüve–Wiedemann syndrome (SWS), a rare genetic disorder characterized by bone dysplasia, respiratory distress, hyperthermia, and swallowing difficulties, may present with pulmonary hypertension, indicating a poor prognosis.

Case description

A term female neonate presented with secondary respiratory failure and severe PPHN of unknown etiology on the second day of life, necessitating intubation. Clinical findings included facial dysmorphia, camptodactyly, skeletal anomalies, and generalized muscular hypotonia. High-frequency oscillation ventilation and surfactant administration yielded marginal improvement. On the third day of life, a severe pulmonary hypertensive crisis necessitated inhaled and systemic pulmonary vasodilators along with volume and catecholamine therapy. Whole exome sequencing revealed a homozygous mutation in the leukemia inhibitory factor receptor (LIFR) gene, consistent with Stüve–Wiedemann syndrome.

Discussion/conclusion

The case underscores the importance of considering and prompting evaluation of rare genetic causes in the differential diagnosis of PPHN, especially when other abnormalities are present and conventional therapies prove inadequate. Therapeutic strategies must account for the different pathophysiology of primary PPHN including vascular remodeling, as seen in SWS, which may not respond to pulmonary vasodilators typically employed in secondary PPHN due to vasoconstriction. In this case, the patient responded well to treatment for primary PPHN, but the use of high-frequency oscillation ventilation and surfactant was not helpful.
Investigations of potential non-amino acid SNAT2 inhibitors
Authors: Jakobsen Sebastian , Petersen Emilie Fynbo , Nielsen Carsten Uhd
Published: January 2024

The sodium-coupled neutral amino acid transporter 2 (SNAT2, SLC38A2) has been implicated in cancer for its ability to supply cancer cells with glutamine and sarcosine. A recent high-throughput screen published by Gauthier-Coles et al. identified the non-amino acid 3-(N-methyl (4-methylphenyl)sulfonamido)-N-(2-trifluoromethylbenzyl)thiophene-2-carboxamide (MMTC or 57E) as a potent and selective SNAT2 inhibitor. Here we have investigated the ability of MMTC and four other compounds selected from the screen by Gauthier-Coles et al. to decrease 3H-Gly uptake in hyperosmotically treated human prostate cancer PC-3 cells. In these cells, SNAT2 is highly upregulated when the cells are hyperosmotically stressed for 24 h and is the primary contributor to glycine uptake. The five compounds were investigated at concentrations of 1–50 µM based on their equilibrium solubility. At 37°C the equilibrium solubility in HEPES buffered HBSS at pH 7.4 was measured to be 24.9 (53B), 56.1 (54F), 13.3 (55B), and 27.5 (57B) µM, respectively. The equilibrium solubility of MMTC was below the detection limit of the HPLC-UV method, thus less than 1.8 µM. However, a kinetic solubility of approximately 2.5–10 µM could be achieved during the course of the uptake study. In contrast to the previous publication, MMTC showed no inhibition of SNAT2-mediated 3H-Gly uptake in PC-3 cells at a concentration of 1 or 5 μM, despite a published IC50 of 0.8 µM. Similarly, 53B, 55B, and 57B showed no inhibition at soluble conditions, whereas 54F showed approximately 20% inhibition at 50 µM. In our experimental setup, the investigated compounds showed limited potential as SNAT2 inhibitors.
Digital twin for multi-scenario emergency of railway passenger stations
Authors: Wang Xiaoshu , Bai Wei , Su Yuanqi , Yang Guoyuan , Li Chao , Lv Xiaojun , Peng Kaibei , Li Jun
Published: January 2024

Emergency disposal is a critical aspect for railway stations to ensure safety. This requires the implementation of emergency plan simulations and cost-effective immersive drills. In the paper, we incorporate a set of disposals for events into emergency processes and model the personnel, supplies, and equipment to create multiple emergency scenarios. Additionally, we introduce a digital twin-based solution for multiple scenarios of emergencies. This solution completely restores the key components of a station in the information space and provides an immersive way for emergency disposals. The four-dimensional model used in the solution simulates and interacts with the station, and it is composed of the details of passenger station physical entity, multi-scenario emergency virtual entity, digital twin connection, and emergency twin service. The digital twin for versatile emergency events such as fire disaster, natural disaster (e.g., flood, earthquake), social security incident, and public health event have been constructed using the model. The solution was tested at Qinghe, a station during Beijing-Zhangjiakou high-speed railway in China. By utilizing the actual operation data of Qinghe, we validated the multi-scenario emergency drills, simulated the corresponding emergency disposal plans, and assessed the proposed solution from three aspects: the fidelity of the real-world simulation, coverage of the multiple emergency scenarios, and the user-friendliness. The evaluations indicate that the proposed solution attains good score and the acceptable level of system usability scale.
X-ray beam test of fabricated photo-diodes for Pohang-Accelerator-Laboratory X-ray free-electron laser
Authors: Lee S. C. , Hyun H. J. , Baek J. M. , Hwang S. M. , Jang H. , Kim J. Y. , Kim S. H. , Park H.
Published: January 2024

The Pohang-Accelerator-Laboratory X-ray free-electron laser (PAL-XFEL) emits intense, ultra-short X-ray pulses, enabling studies on ultra-small and -fast dynamics in various fields. We designed and fabricated silicon p-intrinsic-n photo-diodes (PDs) to detect strong X-ray pulses. Four types of PDs were fabricated with different metal shapes on the P- and N-sides. The fabrication process was split into two parts, based on the thickness of the Al metal and anti-reflective coating (ARC) layers, to evaluate the fabrication process feasibility and the detection performance. A beam test was performed with X-ray pulses at the soft X-ray beamline of the PAL-XFEL using the proposed PDs and a commercial PD. The test was designed to evaluate the effects of the metal and ARC layers and compare the detection efficiency depending on the X-ray entrance side and signal readout side. The waveforms were saved during the test and integrated to obtain the charges. Thereafter, they were analyzed and normalized, and compared. This paper presents the preparation, setup, and procedure of the beam test, and the test results are described.