bluuebunny/crossref_metadata_2025 huggingface dataset:
Trehalose promotes atherosclerosis regression in female mice
Authors: Robichaud Sabrina , Rochon Valérie , Emerton Christina , Laval Thomas , Ouimet Mireille
Published: February 2024

Introduction

Atherosclerosis is a chronic inflammatory disease caused by the deposition of lipids within the artery wall. During atherogenesis, efficient autophagy is needed to facilitate efferocytosis and cholesterol efflux, limit inflammation and lipid droplet buildup, and eliminate defective mitochondria and protein aggregates. Central to the regulation of autophagy is the transcription factor EB (TFEB), which coordinates the expression of lysosomal biogenesis and autophagy genes. In recent years, trehalose has been shown to promote TFEB activation and protect against atherogenesis. Here, we sought to investigate the role of autophagy activation during atherosclerosis regression.

Methods and results

Atherosclerosis was established in C57BL/6N mice by injecting AAV-PCSK9 and 16 weeks of Western diet feeding, followed by switching to a chow diet to induce atherosclerosis regression. During the regression period, mice were either injected with trehalose concomitant with trehalose supplementation in their drinking water or injected with saline for 6 weeks. Female mice receiving trehalose had reduced atherosclerosis burden, as evidenced by reduced plaque lipid content, macrophage numbers and IL-1β content in parallel with increased plaque collagen deposition, which was not observed in their male counterparts. In addition, trehalose-treated female mice had lower levels of circulating leukocytes, including inflammatory monocytes and CD4+ T cells. Lastly, we found that autophagy flux in male mice was basally higher than in female mice during atherosclerosis progression.

Conclusions

Our data demonstrate a sex-specific effect of trehalose in atherosclerosis regression, whereby trehalose reduced lipid content, inflammation, and increased collagen content in female mice but not in male mice. Furthermore, we discovered inherent differences in the autophagy flux capacities between the sexes: female mice exhibited lower plaque autophagy than males, which rendered the female mice more responsive to atherosclerosis regression. Our work highlights the importance of understanding sex differences in atherosclerosis to personalize the development of future therapies to treat cardiovascular diseases.
When all computers shut down: the clinical impact of a major cyber-attack on a general hospital
Authors: Abbou Benyamine , Kessel Boris , Ben Natan Merav , Gabbay-Benziv Rinat , Dahan Shriki Dikla , Ophir Anna , Goldschmid Nimrod , Klein Adi , Roguin Ariel , Dudkiewicz Mickey
Published: February 2024

Importance

Healthcare organizations operate in a data-rich environment and depend on digital computerized systems; thus, they may be exposed to cyber threats. Indeed, one of the most vulnerable sectors to hacks and malware is healthcare. However, the impact of cyberattacks on healthcare organizations remains under-investigated.

Objective

This study aims to describe a major attack on an entire medical center that resulted in a complete shutdown of all computer systems and to identify the critical actions required to resume regular operations.

Setting

This study was conducted on a public, general, and acute care referral university teaching hospital.

Methods

We report the different recovery measures on various hospital clinical activities and their impact on clinical work.

Results

The system malfunction of hospital computers did not reduce the number of heart catheterizations, births, or outpatient clinic visits. However, a sharp drop in surgical activities, emergency room visits, and total hospital occupancy was observed immediately and during the first postattack week. A gradual increase in all clinical activities was detected starting in the second week after the attack, with a significant increase of 30% associated with the restoration of the electronic medical records (EMR) and laboratory module and a 50% increase associated with the return of the imaging module archiving. One limitation of the present study is that, due to its retrospective design, there were no data regarding the number of elective internal care hospitalizations that were considered crucial.

Conclusions and relevance

The risk of ransomware cyberattacks is growing. Healthcare systems at all levels of the hospital should be aware of this threat and implement protocols should this catastrophic event occur. Careful evaluation of steady computer system recovery weekly enables vital hospital function, even under a major cyberattack. The restoration of EMR, laboratory systems, and imaging archiving modules was found to be the most significant factor that allowed the return to normal clinical hospital work.
Origin analysis of paleo-overpressure in source rocks based on logging response characteristics: a case study of the Chang 7 member in the Triassic Yanchang formation, Longdong area, Ordos Basin, China
Authors: Xu Kaitong , Huang Yujia , Tang Minggang , Wu Jiahao , Ma Tengfei
Published: February 2024

The identification of the origins of source rock palaeo-overpressure based on logging response parameters is frequently influenced by the presence of organic matter. To accurately identify the paleo-overpressure origin of source rocks and employ an appropriate method for paleo-pressure calculation, this study proposes a quantitative approach to assess the influence of organic matter content on overpressure analysis. The findings demonstrate that the presence of organic matter in Chang 7 shale leads to an increase in acoustic time difference and a decrease in density. After incorporating the multi-component rock equivalent volume model correction, it is evident that the paleo-overpressure observed in the Chang 7 member is not attributed to undercompaction but rather to fluid expansion mechanisms. In conjunction with the acoustic velocity-density palte method, the paleo-overpressure of the Chang 7 member is attributed to undercompaction and expansion resulting from hydrocarbon generation. The pressure evolution of the Chang 7 member has been reconstructed based on the identification of its paleo-overpressure origin. The distribution characteristics of paleo-pressure recovered based on hydrocarbon generation expansion exhibit a strong correlation with the reservoir. The reliability of the correction method for organic matter influence is demonstrated. The proposed method is not only applicable for the investigation of paleo-pressure, but also holds significant implications for the assessment of pressure within organic-rich intervals.
Prediction of permeability in a tight sandstone reservoir using a gated network stacking model driven by data and physical models
Authors: Shi Pengyu , Shi Pengda , Bie Kang , Han Chuang , Ni Xiaowei , Mao Zhiqiang , Zhao Peiqiang
Published: February 2024

Introduction: Permeability is one of the most important parameters for reservoir evaluation. It is commonly measured in laboratories using underground core samples. However, it cannot describe the entire reservoir because of the limited number of cores. Therefore, petrophysicists use well logs to establish empirical equations to estimate permeability. This method has been widely used in conventional sandstone reservoirs, but it is not applicable to tight sandstone reservoirs with low porosity, extremely low permeability, and complex pore structures.

Methods: Machine learning models can identify potential relationships between input features and sample labels, making them a good choice for establishing permeability prediction models. A stacking model is an ensemble learning method that aims to train a meta-learner to learn an optimal combination of expert models. However, the meta-learner does not evaluate or control the experts, making it difficult to interpret the contribution of each model. In this study, we design a gate network stacking (GNS) model, which is an algorithm that combines data and model-driven methods. First, an input log combination is selected for each expert model to ensure the best performance of the expert model and selfoptimization of the hyperparameters. Petrophysical constraints are then added to the inputs of the expert model and meta-learner, and weights are dynamically assigned to the output of the expert model. Finally, the overall performance of the model is evaluated iteratively to enhance its interpretability and robustness.

Results and discussion: The GNS model is then used to predict the permeability of a tight sandstone reservoir in the Jurassic Ahe Formation in the Tarim Basin. The case study shows that the permeability predicted by the GNS model is more accurate than that of other ensemble models. This study provides a new approach for predicting the parameters of tight sandstone reservoirs.
Engaging kindergarten pre-service teachers in the design and implementation of STEM lessons
Authors: Evagorou Maria
Published: February 2024

Introduction

Engaging young students in integrated STEM early on can support them to develop their competences linked to problem solving and critical thinking. Despite the importance of STEM education in younger ages, teachers still lack the skills and competences to implement STEM in their classes. The purpose of this study is to explore how pre-service kindergarten teachers (PSTs) understand STEM education, how they design lesson plans to teach STEM and how they implement STEM in their teaching.

Methods

Participants of the study were 21, 3rd, and 4th year students studying to become kindergarten teachers. The participants of the current study attended a Science Methods Course for Kindergarten which is a 36 h long course. Data collected included questionnaires, reflections, lesson plans, interviews, and classroom observations.

Results

Findings for the first research question reveal that kindergarten PSTs were not familiar with STEM education and did not have any previous experience with STEM education either as school students or during their studies at the university. Another important finding is that teachers’ views on STEM education improved after the theoretical introduction to STEM, but considerable improvement and understanding of STEM education was evident after they engaged as learners in a STEM lesson specially designed for kindergarten students.

Discussion

Findings from the lesson plans designed by the PSTs showed that when working in groups PSTs designed lessons which offered integration between two subjects, mainly math and science. Finally, when implementing STEM lessons PSTs had similar difficulties as when designing lessons. Additionally, PSTs reported that they did not have support from their mentors, or their mentors did not act as role models during the implementation of their designs. What this study supports is the need for teacher preparation programs to prepare kindergarten teachers in understanding what STEM is, but also supporting them in the process of designing and implementing STEM lessons. Implications from this study include the design of a teacher training course to support PSTs during their studies and in their early career, but also include mentors as part of the training course to support them to act as positive role models.
Assessing the release, transport, and retention of radioactive aerosols from hypothetical breaches in spent fuel storage canisters
Authors: Sasikumar Yadukrishnan , Chatzidakis Stylianos , Dahm Zachery , Durbin Samuel G. , Montgomery Rose
Published: February 2024

Interim dry storage of spent nuclear fuel involves storing the fuel in welded stainless-steel canisters. Under certain conditions, the canisters could be subjected to environments that may promote stress corrosion cracking leading to a risk of breach and release of aerosol-sized particulate from the interior of the canister to the external environment through the crack. Research is currently under way by several laboratories to better understand the formation and propagation of stress corrosion cracks, however little work has been done to quantitatively assess the potential aerosol release. The purpose of the present work is to introduce a reliable generic numerical model for prediction of aerosol transport, deposition, and plugging in leak paths similar to stress corrosion cracks, while accounting for potential plugging from particle deposition. The model is dynamic (changing leak path geometry due to plugging) and it relies on the numerical solution of the aerosol transport equation in one dimension using finite differences. The model’s capabilities were also incorporated into a Graphical User Interface (GUI) that was developed to enhance user accessibility. Model validation efforts presented in this paper compare the model’s predictions with recent experimental data from Sandia National Laboratories (SNL) and results available in literature. We expect this model to improve the accuracy of consequence assessments and reduce the uncertainty of radiological consequence estimations in the remote event of a through-wall breach in dry cask storage systems.
Advanced manufacturing and digital twin technology for nuclear energy*
Authors: Mondal Kunal , Martinez Oscar , Jain Prashant
Published: February 2024

Advanced manufacturing techniques and digital twin technology are rapidly transforming the nuclear industry, offering the potential to enhance productivity, safety, and cost-effectiveness. Customized parts are being produced using additive manufacturing, automation, and robotics, while digital twin technology enables the virtual modeling and optimization of complex systems. These advanced technologies can significantly improve operational efficiency, predict system behavior, and optimize maintenance schedules in the nuclear energy sector, leading to heightened safety and reduced downtime. However, the nuclear industry demands the highest levels of safety and security, as well as intricate manufacturing processes and operations. Thus, challenges such as data management and cybersecurity must be addressed to fully realize the potential of advanced manufacturing techniques and digital twin technology in the nuclear industry. This comprehensive review highlights the critical role of digital twin technology with advanced manufacturing toward nuclear energy to improve performance, minimize downtime, and heighten safety, ultimately contributing to the global energy mix by providing dependable and low-carbon electricity.
Lightweight land cover classification via semantic segmentation of remote sensing imagery and analysis of influencing factors
Authors: Wang Guoying , Chen Jiahao , Mo Lufeng , Wu Peng , Yi Xiaomei
Published: February 2024

Land cover classification is of great value and can be widely used in many fields. Earlier land cover classification methods used traditional image segmentation techniques, which cannot fully and comprehensively extract the ground information in remote sensing images. Therefore, it is necessary to integrate the advanced techniques of deep learning into the study of semantic segmentation of remote sensing images. However, most of current high-resolution image segmentation networks have disadvantages such as large parameters and high network training cost. In view of the problems above, a lightweight land cover classification model via semantic segmentation, DeepGDLE, is proposed in this paper. The model DeepGDLE is designed on the basis of DeeplabV3+ network and utilizes the GhostNet network instead of the backbone feature extraction network in the encoder. Using Depthwise Separable Convolution (DSC) instead of dilation convolution. This reduces the number of parameters and increases the computational speed of the model. By optimizing the dilation rate of parallel convolution in the ASPP module, the “grid effect” is avoided. ECANet lightweight channel attention mechanism is added after the feature extraction module and the pyramid pooling module to focus on the important weights of the model. Finally, the loss function Focal Loss is utilized to solve the problem of category imbalance in the dataset. As a result, the model DeepGDLE effectively reduces the parameters of the network model and the network training cost. And extensive experiments compared with several existing semantic segmentation algorithms such as DeeplabV3+, UNet, SegNet, etc. show that DeepGDLE improves the quality and efficiency of image segmentation. Therefore, compared to other networks, the DeepGDLE network model can be more effectively applied to land cover classification. In addition, in order to investigate the effects of different factors on the semantic segmentation performance of remote sensing images and to verify the robustness of the DeepGDLE model, a new remote sensing image dataset, FRSID, is constructed in this paper. This dataset takes into account more influences than the public dataset. The experimental results show that on the WHDLD dataset, the experimental metrics mIoU, mPA, and mRecall of the proposed model, DeepGDLE, are 62.29%, 72.85%, and 72.46%, respectively. On the FRSID dataset, the metrics mIoU, mPA, and mRecall are 65.89%, 74.43%, and 74.08%, respectively. For the future scope of research in this field, it may focus on the fusion of multi-source remote sensing data and the intelligent interpretation of remote sensing images.
Identification of new variants in patients with mucopolysaccharidosis in consanguineous Iranian families
Authors: Zabihi Rezvan , Zamani Mina , Aminzadeh Majid , Chamanrou Niloofar , Kiani Fatemeh Zahra , Seifi Tahere , Zeighami Jawaher , Yadegari Tahere , Sedaghat Alireza , Saberi Alihossein , Hamid Mohammad , Shariati Gholamreza , Galehdari Hamid
Published: February 2024

Introduction: Mucopolysaccharidoses are a group of lysosomal storage disorders that include seven types that are classified based on the enzymes that are disrupted. Malfunction of these enzymes leads to the accumulation of glycosaminoglycans (GAGs) in various tissues. Due to genetic and clinical heterogeneity, diagnosing and distinguishing the different types is challenging. Genetic methods such as whole exome sequencing (WES) and Sanger sequencing are accurate methods for detecting pathogenic variants in patients.

Methods: Thirty-two cases of mucopolysaccharidosis, predominantly from families with consanguineous marriages, were genetically examined. Out of these, fourteen cases underwent targeted sequencing, while the rest underwent WES. The results of WES were analyzed and the pathogenicity of the variants was examined using bioinformatics tools. In addition, a segregation analysis within families was carried out.

Results: In most cases, a pathogenic or likely pathogenic variant was detected. Sixteen previously reported variants and six new variants were detected in the known IDS (c.458G>C, c.701del, c.920T>G), GNS (c.1430A>T), GALNS (c.1218_1221dup), and SGSH (c.149T>C) genes. Furthermore, we discovered a c.259G>C substitution in the NAGLU gene for the first time in three homozygous patients. This substitution was previously reported as heterozygous. Except for the variants related to the IDS gene, which were hemizygous, all the other variants were homozygous.

Discussion: It appears that the high rate of consanguineous marriages in the families being studied has had a significant impact on the occurrence of this disease. Overall, these findings could expand the spectrum of pathogenic variants in mucopolysaccharidoses. Genetic methods, especially WES, are very accurate and can be used alone or in conjunction with other diagnostic methods for a more precise and rapid diagnosis of mucopolysaccharidoses. Additionally, they could be beneficial for family screening and disease prevention.
Genome-wide identification of U-box gene family and expression analysis in response to saline-alkali stress in foxtail millet (Setaria italica L. Beauv)
Authors: Zhou Xiaoke , Li Yun , Wang Jian , Zhao Yuxue , Wang Huimin , Han Yucui , Lin Xiaohu
Published: February 2024

E3 ubiquitin ligases are central modifiers of plant signaling pathways that regulate protein function, localization, degradation, and other biological processes by linking ubiquitin to target proteins. E3 ubiquitin ligases include proteins with the U-box domain. However, there has been no report about the foxtail millet (Setaria italica L. Beauv) U-box gene family (SiPUB) to date. To explore the function of SiPUBs, this study performed genome-wide identification of SiPUBs and expression analysis of them in response to saline-alkali stress. A total of 70 SiPUBs were identified, which were unevenly distributed on eight chromosomes. Phylogenetic and conserved motif analysis demonstrated that SiPUBs could be clustered into six subfamilies (I–VI), and most SiPUBs were closely related to the homologues in rice. Twenty-eight types of cis-acting elements were identified in SiPUBs, most of which contained many light-responsive elements and plant hormone-responsive elements. Foxtail millet had 19, 78, 85, 18, and 89 collinear U-box gene pairs with Arabidopsis, rice, sorghum, tomato, and maize, respectively. Tissue specific expression analysis revealed great variations in SiPUB expression among different tissues, and most SiPUBs were relatively highly expressed in roots, indicating that SiPUBs may play important roles in root development or other growth and development processes of foxtail millet. Furthermore, the responses of 15 SiPUBs to saline-alkali stress were detected by qRT-PCR. The results showed that saline-alkali stress led to significantly differential expression of these 15 SiPUBs, and SiPUB20/48/70 may play important roles in the response mechanism against saline-alkali stress. Overall, this study provides important information for further exploration of the biological function of U-box genes.
Crosstalk between keratinocytes and neutrophils shapes skin immunity against S. aureus infection
Authors: Focken Jule , Schittek Birgit
Published: February 2024

Introduction

Staphylococcus aureus (S. aureus) infection of the skin leads to a rapid initial innate immune response with keratinocytes in the epidermis as the initial sensors. Polymorphonuclear neutrophils (PMNs) are the first innate immune cells to infiltrate infection sites where they provide an effective first-line of defense. Previous work of our group showed that in inflamed skin a crosstalk between PMNs and keratinocytes results in enhanced S. aureus skin colonization.

Methods

In this work, we used an in vitro co-culture model to studied the crosstalk between primary human keratinocytes (PHKs) and PMNs in a sterile environment and upon S. aureus infection. We investigated the influence of PHKs on PMN activation by analyzing PMN lifespan, expression of degranulation markers and induction of proinflammatory cytokines. Furthermore, we analyzed the influence of PMNs on the inflammatory response of PHKs. Finally, we investigated the influence of the skin microbiome on PMN-mediated skin inflammation.

Results

We show that co-culture of PMNs with PHKs induces activation and degranulation of PMNs and significantly enhances their lifespan compared to PMN cultivation alone by an IL-8 mediated mechanism and, furthermore, primes PMNs for enhanced activity after S. aureus infection. The prolonged incubation with PMNs also induces inflammatory responses in PHKs which are further exacerbated in the presence of S. aureus and induces further PMN recruitment thus fueling skin inflammation. Interestingly, infection of PHKs with the skin commensal S. epidermidis reduces the inflammatory effects of PMNs in the skin and exhibits an anti-inflammatory effect.

Discussion

Our data indicate that skin infiltrating PMNs and PHKs influence each other in such a way to enhance skin inflammation and that commensal bacteria are able to reduce the inflammatory effect.
Regulation mechanisms of disulfidptosis-related genes in ankylosing spondylitis and inflammatory bowel disease
Authors: Li Lin , Fang Haixin , Li Fuzhen , Xie Kunpeng , Zhou Pengyi , Zhu Haiyan , Jin Xuemin , Song Ruifeng , Yang Peizeng , Liping Du
Published: February 2024

Introduction

Disulfidptosis is a recently identified form of cell death that contributes to maintaining the internal environment balance of an organism. However, the molecular basis of disulfidptosis in ulcerative colitis (UC), ankylosing spondylitis (AS), and Crohn’s disease (CD) has not been thoroughly explored.

Methods

Firstly, the differentially expressed genes (DEGs) and disulfidptosis-associated genes (DAGs) were obtained through differential analysis between diseases (AS, CD, and UC) and control groups. After the disulfidptosis score was acquired using the single-sample gene set enrichment analysis (ssGSEA) algorithm, the DE-DAGs were screened by overlapping DAGs and DEGs of the three diseases. Next, the feature genes were selected through a combination of machine learning algorithms, receiver operating characteristic (ROC) curves, and expression analysis. Based on these feature genes, nomograms were created for AS, CD and UC. The co-feature genes were then identified by taking the intersections of the genes featured in all three diseases. Meanwhile, single-gene set enrichment analysis (GSEA) and the TF-mRNA-miRNA network were utilized to investigate the molecular mechanisms of the co-feature genes. To validate the expression differences of the co-feature genes between healthy controls and patients (AS and IBD), RT-PCR was performed. Lastly, mendelian randomization (MR) analysis was utilized to explore the causality between genetic variants of S100A12 with AS, UC and CD.

Results

In this study, 11 DE-DAGs were obtained. Functional enrichment analysis revealed their involvement in cytokine production and fatty acid biosynthesis. Latterly, AS/CD/UC -feature genes were derived, and they all had decent diagnostic performance. Through evaluation, the performance of the nomogram was decent for three diseases. Then, 2 co-feature genes (S100A12 and LILRA5) were obtained. The GSEA enrichment results indicated that the co-feature genes were mainly enriched in the cytokine-cytokine receptor interaction and drug metabolism cytochrome P450. As shown by functional experiments, there was a correlation between the mRNA expression of S100A12 with AS, UC and CD. Additionally, a causal connection between S100A12 and IBD was detected through MR analysis.

Discussion

In this study, 2 co-feature genes (S100A12 and LILRA5) were screened, and their functions were investigated in AS, CD and UC, providing a basis for further research into diagnosis and treatment.
Brucella abortus triggers the differential expression of immunomodulatory lncRNAs in infected murine macrophages
Authors: Flores-Concha Manuel , Gómez Leonardo A. , Soto-Shara Rodrigo , Molina Raúl E. , Coloma-Rivero Roberto F. , Montero David A. , Ferrari Ítalo , Oñate Ángel
Published: February 2024

Introduction

The lncRNAs (long non-coding RNAs) are the most diverse group of non-coding RNAs and are involved in most biological processes including the immune response. While some of them have been recognized for their influence on the regulation of inflammatory activity, little is known in the context of infection by Brucella abortus, a pathogen that presents significant challenges due to its ability to manipulate and evade the host immune system. This study focuses on characterize the expression profile of LincRNA-cox2, Lethe, lincRNA-EPS, Malat1 and Gas5 during infection of macrophages by B. abortus.

Methods

Using public raw RNA-seq datasets we constructed for a lncRNA expression profile in macrophages Brucella-infected. In addition, from public RNA-seq raw datasets of RAW264.7 cells infected with B. abortus we constructed a transcriptomic profile of lncRNAs in order to know the expression of the five immunomodulating lncRNAs studied here at 8 and 24 h post-infection. Finally, we performed in vitro infection assays in RAW264.7 cells and peritoneal macrophages to detect by qPCR changes in the expression of these lncRNAs at first 12 hours post infection, a key stage in the infection cycle where Brucella modulates the immune response to survive.

Results

Our results demonstrate that infection of macrophages with Brucella abortus, induces significant changes in the expression of LincRNA-Cox2, Lethe, LincRNA-EPS, Gas5, and Malat1.

Discussion

The change in the expression profile of these immunomodulatory lncRNAs in response to infection, suggest a potential involvement in the immune evasion strategy employed by Brucella to facilitate its intracellular survival.
A carbonate system time series in the Eastern Mediterranean Sea. Two years of high-frequency in-situ observations and remote sensing
Authors: Frangoulis C. , Stamataki N. , Pettas M. , Michelinakis S. , King A. L. , Giannoudi L. , Tsiaras K. , Christodoulaki S. , Seppälä J. , Thyssen M. , Borges A.V. , Krasakopoulou E.
Published: February 2024

The rate of ocean uptake of anthropogenic CO2 has declined over the past decade, so a critical question for science and policy is whether the ocean will continue to act as a sink. Large areas of the ocean remain without observations for carbonate system variables, and oceanic CO2 observations have declined since 2017. The Mediterranean Sea is one such an area, especially its eastern part, where there is a paucity of carbonate system data, with large areas not sampled or only sampled by ship-based discrete measurements as opposed to high frequency, sensor-equipped time-series fixed stations. The aim of this study was to analyze a multi-year time-series of high-frequency (hourly) partial pressure CO2 (pCO2) and pH measurements in the Eastern Mediterranean, along with low-frequency (monthly) measurements of total dissolved inorganic carbon and total alkalinity. The pCO2 time-series was the first obtained in the Eastern Mediterranean. The study was conducted at a fixed platform of the POSEIDON system (Heraklion Coastal Buoy) located near Crete Island. Temperature was the dominant factor controlling the temporal variability of pCO2 and pH, while the remaining non-thermal variability appeared to be related to evaporation, water mixing, and biological remineralization-production. The air-sea CO2 fluxes indicated a transition from a winter-spring sink period to a summer-autumn source period. The annual air-sea CO2 flux was too low (-0.16 ± 0.02 mol m-2 yr-1) and variable to conclusively characterize the area as a net source or sink of CO2, highlighting the need for additional high frequency observation sites. Algorithms were developed using temperature, chlorophyll and salinity data to estimate pCO2 and total alkalinity, in an effort to provide tools for estimates in poorly observed areas/periods from remotely sensed products. The applicability of the algorithms was tested using Surface Ocean CO2 Atlas (SOCAT) data from the Eastern Mediterranean Sea (1999 to 2020) which showed that the algorithm pCO2 estimates were generally within ±20 μatm of the pCO2 values reported by SOCAT. Finally, the integration and analysis of the data provided directions on how to optimize the observing strategy, by readapting sensor location and using estimation algorithms with remote sensing data.
Trap-assisted monolayer ReSe2/Si heterojunction with high photoconductive gain and self-driven broadband photodetector.
Authors: Jo Beomsu , Seo Kanghoon , Park Kyumin , Jeong Chaewon , Poornaprakash Bathalavaram , Lee Moonsang , Ramu Singiri , Hahm Myung Gwan , Kim Young Lae
Published: February 2024

The development of photodetectors is crucial in fields such as optical communication, image sensing, medical devices and military equipment, where high sensitivity is paramount. We fabricated an ambipolar photodiode using monolayer triclinic ReSe2, synthesized by chemical vapor deposition on p-type Si substrate. The photodetector has a broadband response range from 405 to 1100 nm. The device exhibits high sensitivity to NIR radiation with a high Iph/Idark (ON/OFF) ratio of 5.8 × 104, responsivity (R) of 465 A/W, and specific detectivity (D) of 4.8 × 1013 Jones at open circuit voltage (Voc), indicating photovoltaic behavior. Our ReSe2/Si heterojunction photodetector also exhibits low dark current of 1.4 × 10-9 A and high external quantum efficiency (EQE) of 54368.2% for 1060 nm at -3 V, demonstrating a photoconductive gain. The maximum responsivity (R = 465 A/W) can be achieved at -3 V reverse bias under 1060 nm. The device has a high ideality factor (4.8) and power coefficient (α = 0.5), indicating the presence of interface and sub-gap states that enhance device responsivity at lower illumination intensities by re-exciting trapped carriers into the conduction band. Our results offer important insights into the underlying photo-physics of the ReSe2/Si heterojunction and propose promising avenues for developing advanced broadband photodetectors of high performance.
Decreased IL-4 is the risk factor of depression in patients with Takayasu arteritis
Authors: Zhang Yaxin , Yang Shiyu , Fan Anyuyang , Du Juan , Gao Na , Pan Lili , Li Taotao
Published: February 2024

Objective

Depression is a common complication in Takayasu arteritis (TA). Disorders of the immune system play an important role in both diseases. This study aimed to clarify the feature of cytokines in TA patients with depression.

Methods

In this cross-sectional study, serum cytokines were tested in 40 TA patients and 11 healthy controls using the Bio-Plex Magpix System (Bio-Rad®). The state of depression was measured by the Zung Self-Rating Depression Scale (SDS) in TA patients. Logistic regression analysis was performed to find the risk factors of depression in patients with TA.

Results

TA patients with depression had higher ESR, hsCRP, NIH, and ITAS.A than patients without depression (16.00 [10.00, 58.50]mm/H vs. 7.50 [4.50, 17.75]mm/H, p = 0.013; 7.60 [2.32, 46.52]mg/L vs. 0.71 [0.32, 4.37]mg/L, p = 0.001; 2.00 [2.00, 3.00] vs. 1.00 [0.00, 2.00], p = 0.007; 7.00 [4.00, 9.50] vs. 1.50 [0.00, 5.75], p = 0.012, respectively). Additionally, the lower age of onset and levels of IL-4, IL-13, eotaxin, and IP-10 were observed in the depressed group compared with the non-depressed (23.50 [19.25, 32.50]pg./ml vs. 37.00 [23.25, 42.50]pg./ml, p = 0.017; 2.80 [2.17, 3.18]pg./ml vs. 3.51 [3.22, 4.66]pg./ml, p < 0.001; 0.66 [0.60, 1.12]pg./ml vs. 1.04 [0.82, 1.25]pg./ml, p = 0.008; 46.48 [37.06, 61.75]pg./ml vs. 69.14 [59.30, 92.80]pg./ml, p = 0.001; 184.50 [138.23, 257.25]pg./ml vs. 322.32 [241.98, 412.60]pg./ml, p = 0.005, respectively). The lower level of IL-4 and age of onset were the independent risk factors for depression in TA patients (OR [95% CI] 0.124 [0.018, 0.827], p = 0.031; 0.870 [0.765, 0.990], p = 0.035, respectively).

Conclusion

Our data suggested that lower cytokine levels, especially IL-4, might be involved in the development of TA patients with depression. Clinicians can probably use serum IL-4 level testing as a potential indicator of depression in TA.
The Italian breakthrough in CRISPR trials for rare diseases: a focus on beta-thalassemia and sickle cell disease treatment
Authors: Greco Francesca , Cosentino Marco , Marino Franca
Published: February 2024

The development of gene therapy and the current advantageous method of clustered regularly interspaced short palindromic repeats (CRISPRs) has allowed the implementation of several clinical trials aimed at studying the possible efficacy of gene therapy for rare diseases. Rare diseases pose a global challenge, in that their collective impact on health systems is considerable, whereas their individually rare occurrence hinders research and development of efficient therapies. Despite the low prevalence of individual rare diseases, there are more than 7,000 defined rare diseases affecting 3.5–5.9% of the global population. Rare diseases are mostly chronic and approximately 80% are caused by genetic mutation with an early-life onset. In Italy, in 2021 were recorded more than 400,000 people with rare disease. Because of its location and history, Italy has an unfortunate statistic regarding the presence and prevalence of two rare genetic diseases, namely beta-thalassemia, of which there are about 90 million carriers worldwide, 400,000 of whom are actually affected, and sickle cell disease, with about 300 million carriers and 6.5 million people affected worldwide. Advancements in genomic studies allowed Italy to join clinical trials to study effective and resolving gene therapies for BT and SCD. This study reports on the impact of rare diseases in Italy, ongoing studies, and recent achievements in BT and SCD trials using the CRISPR method and remaining hurdles in the application of CRISPR technology to rare diseases, also taking a glimpse at the newest challenges and future opportunities in the genetic treatment for rare diseases.
Genomic and ecological approaches to identify the Bifidobacterium breve prototype of the healthy human gut microbiota
Authors: Argentini Chiara , Lugli Gabriele Andrea , Tarracchini Chiara , Fontana Federico , Mancabelli Leonardo , Viappiani Alice , Anzalone Rosaria , Angelini Leonora , Alessandri Giulia , Longhi Giulia , Bianchi Massimiliano G. , Taurino Giuseppe , Bussolati Ovidio , Milani Christian , van Sinderen Douwe , Turroni Francesca , Ventura Marco
Published: February 2024

Members of the genus Bifidobacterium are among the first microorganisms colonizing the human gut. Among these species, strains of Bifidobacterium breve are known to be commonly transmitted from mother to her newborn, while this species has also been linked with activities supporting human wellbeing. In the current study, an in silico approach, guided by ecology- and phylogenome-based analyses, was employed to identify a representative strain of B. breve to be exploited as a novel health-promoting candidate. The selected strain, i.e., B. breve PRL2012, was found to well represent the genetic content and functional genomic features of the B. breve taxon. We evaluated the ability of PRL2012 to survive in the gastrointestinal tract and to interact with other human gut commensal microbes. When co-cultivated with various human gut commensals, B. breve PRL2012 revealed an enhancement of its metabolic activity coupled with the activation of cellular defense mechanisms to apparently improve its survivability in a simulated ecosystem resembling the human microbiome.
Analyzing and computing humans by means of the brain using Brain-Computer Interfaces - understanding the user – previous evidence, self-relevance and the user’s self-concept as potential superordinate human factors of relevance
Authors: Herbert Cornelia
Published: February 2024

Brain–computer interfaces (BCIs) are well-known instances of how technology can convert a user’s brain activity taken from non-invasive electroencephalography (EEG) into computer commands for the purpose of computer-assisted communication and interaction. However, not all users are attaining the accuracy required to use a BCI consistently, despite advancements in technology. Accordingly, previous research suggests that human factors could be responsible for the variance in BCI performance among users. Therefore, the user’s internal mental states and traits including motivation, affect or cognition, personality traits, or the user’s satisfaction, beliefs or trust in the technology have been investigated. Going a step further, this manuscript aims to discuss which human factors could be potential superordinate factors that influence BCI performance, implicitly, explicitly as well as inter- and intraindividually. Based on the results of previous studies that used comparable protocols to examine the motivational, affective, cognitive state or personality traits of healthy and vulnerable EEG-BCI users within and across well-investigated BCIs (P300-BCIs or SMR-BCIs, respectively), it is proposed that the self-relevance of tasks and stimuli and the user’s self-concept provide a huge potential for BCI applications. As potential key human factors self-relevance and the user’s self-concept (self-referential knowledge and beliefs about one’s self) guide information processing and modulate the user’s motivation, attention, or feelings of ownership, agency, and autonomy. Changes in the self-relevance of tasks and stimuli as well as self-referential processing related to one’s self (self-concept) trigger changes in neurophysiological activity in specific brain networks relevant to BCI. Accordingly, concrete examples will be provided to discuss how past and future research could incorporate self-relevance and the user’s self-concept in the BCI setting – including paradigms, user instructions, and training sessions.
Clinically approved immunomodulators ameliorate behavioral changes in a mouse model of hereditary spastic paraplegia type 11
Authors: Hörner Michaela , Popp Sandy , Branchu Julien , Stevanin Giovanni , Darios Frédéric , Klebe Stephan , Groh Janos , Martini Rudolf
Published: February 2024

We have previously demonstrated that neuroinflammation by the adaptive immune system acts as a robust and targetable disease amplifier in a mouse model of Spastic Paraplegia, type 11 (SPG11), a complicated form of Hereditary Spastic Paraplegia (HSP). While we identified an impact of neuroinflammation on distinct neuropathological changes and gait performance, neuropsychological features, typical and clinically highly relevant symptoms of complicated HSPs, were not addressed. Here we show that the corresponding SPG11 mouse model shows distinct behavioral abnormalities, particularly related to social behavior thus partially reflecting the neuropsychological changes in patients. We provide evidence that some behavioral abnormalities can be mitigated by genetic inactivation of the adaptive immune system. Translating this into a clinically applicable approach, we show that treatment with the established immunomodulators fingolimod or teriflunomide significantly attenuates distinct behavioral abnormalities, with the most striking effect on social behavior. This study links neuroinflammation to behavioral abnormalities in a mouse model of SPG11 and may thus pave the way for using immunomodulators as a treatment approach for SPG11 and possibly other complicated forms of HSP with neuropsychological involvement.
Olfactory deficit: a potential functional marker across the Alzheimer’s disease continuum
Authors: Liu Dongming , Lu Jiaming , Wei Liangpeng , Yao Mei , Yang Huiquan , Lv Pin , Wang Haoyao , Zhu Yajing , Zhu Zhengyang , Zhang Xin , Chen Jiu , Yang Qing X. , Zhang Bing
Published: February 2024

Alzheimer’s disease (AD) is a prevalent form of dementia that affects an estimated 32 million individuals globally. Identifying early indicators is vital for screening at-risk populations and implementing timely interventions. At present, there is an urgent need for early and sensitive biomarkers to screen individuals at risk of AD. Among all sensory biomarkers, olfaction is currently one of the most promising indicators for AD. Olfactory dysfunction signifies a decline in the ability to detect, identify, or remember odors. Within the spectrum of AD, impairment in olfactory identification precedes detectable cognitive impairments, including mild cognitive impairment (MCI) and even the stage of subjective cognitive decline (SCD), by several years. Olfactory impairment is closely linked to the clinical symptoms and neuropathological biomarkers of AD, accompanied by significant structural and functional abnormalities in the brain. Olfactory behavior examination can subjectively evaluate the abilities of olfactory identification, threshold, and discrimination. Olfactory functional magnetic resonance imaging (fMRI) can provide a relatively objective assessment of olfactory capabilities, with the potential to become a promising tool for exploring the neural mechanisms of olfactory damage in AD. Here, we provide a timely review of recent literature on the characteristics, neuropathology, and examination of olfactory dysfunction in the AD continuum. We focus on the early changes in olfactory indicators detected by behavioral and fMRI assessments and discuss the potential of these techniques in MCI and preclinical AD. Despite the challenges and limitations of existing research, olfactory dysfunction has demonstrated its value in assessing neurodegenerative diseases and may serve as an early indicator of AD in the future.
Dosimetric benefit of online treatment plan adaptation in stereotactic ultrahypofractionated MR-guided radiotherapy for localized prostate cancer
Authors: Fink Christoph A. , Buchele Carolin , Baumann Lukas , Liermann Jakob , Hoegen Philipp , Ristau Jonas , Regnery Sebastian , Sandrini Elisabetta , König Laila , Rippke Carolin , Bonekamp David , Schlemmer Heinz-Peter , Debus Juergen , Koerber Stefan A. , Klüter Sebastian , Hörner-Rieber Juliane
Published: February 2024

Background

Apart from superior soft tissue contrast, MR-guided stereotactic body radiation therapy (SBRT) offers the chance for daily online plan adaptation. This study reports on the comparison of dose parameters before and after online plan adaptation in MR-guided SBRT of localized prostate cancer.

Materials and methods

32 consecutive patients treated with ultrahypofractionated SBRT for localized prostate cancer within the prospective SMILE trial underwent a planning process for MR-guided radiotherapy with 37.5 Gy applied in 5 fractions. A base plan, derived from MRI simulation at an MRIdian Linac, was registered to daily MRI scans (predicted plan). Following target and OAR recontouring, the plan was reoptimized based on the daily anatomy (adapted plan). CTV and PTV coverage and doses at OAR were compared between predicted and adapted plans using linear mixed regression models.

Results

In 152 out of 160 fractions (95%), an adapted radiation plan was delivered. Mean CTV and PTV coverage increased by 1.4% and 4.5% after adaptation. 18% vs. 95% of the plans had a PTV coverage ≥95% before and after online adaptation, respectively. 78% vs. 100% of the plans had a CTV coverage ≥98% before and after online adaptation, respectively. The D0.2cc for both bladder and rectum were <38.5 Gy in 93% vs. 100% before and after online adaptation. The constraint at the urethra with a dose of <37.5 Gy was achieved in 59% vs. 93% before and after online adaptation.

Conclusion

Online adaptive plan adaptation improves target volume coverage and reduces doses to OAR in MR-guided SBRT of localized prostate cancer. Online plan adaptation could potentially further reduce acute and long-term side effects and improve local failure rates in MR-guided SBRT of localized prostate cancer.
Management of pediatric obesity as a pathway towards kidney transplantation
Authors: Altemose K. E. , Nailescu C.
Published: February 2024

Obesity is an increasing problem in pediatrics, leading to cardiovascular, metabolic and psychosocial complications. Additionally, for patients with chronic kidney disease (CKD), obesity can lead to CKD progression towards end-stage renal disease (ESRD) needing renal-replacement therapy (RRT). It is well-established that the optimal type of RRT for children with ESRD is kidney transplantation, as it provides significantly better life expectancy and quality of life. Unfortunately, pediatric patients with CKD/ESRD and obesity face barriers getting to kidney transplantation and often remain on dialysis for a long time, which negatively impacts their life expectancy and quality of life. One barrier to kidney transplant is that Body Mass Index (BMI) is still considered by most transplant centers as the main criterion for obesity assessment, although more recent evidence suggests that BMI is not the best measure of adiposity. Clearcut evidence is lacking that obesity has a long-term negative impact upon the graft. Another barrier to transplant can be bias on the part of referring providers that can deter or delay referral to an obesity treatment program. Our article describes the barriers that pediatric obese patients with CKD and ESRD face in their way towards kidney transplantation. In addition, our article encourages pediatric nephrologists to early refer their patients with CKD and ESRD who suffer from obesity to a specialized obesity treatment program and/or bariatric surgery. Our article also describes the treatment options for pediatric patients with CKD and ESRD who suffer from obesity in order to make them eligible for a kidney transplant.