bluuebunny/crossref_metadata_2025 huggingface dataset:
Key Factors of the Strong Cold Wave Event in the Winter of 2020/21 and Its Effects on the Predictability in CMA-GEPS
Authors: Ren Pengfei , Gao Li , Zheng Jiawen , Cai Hongke
Published: March 2023

During the 2020/2021 winter season, three nationwide cold waves took place from 28 to 31 December 2020, as well as from 5 to 8 January and 14 to 17 January 2021. These cold waves resulted in extreme cold weather in northern and eastern China. In this study, the common features of these cold waves were analyzed, and the key factors contributing to cold waves were illustrated, and the performance of the CMA-GEPS numerical model was evaluated in predicting the cooling effect of the cold waves, and its predictability source was discussed. The results indicated that the cold waves were caused by synergistic effects in the mid- to high-latitude atmospheric circulation of both the upper and lower atmosphere, including polar vortex splitting, enhancement of blocking high, and increased meridional circulation anomaly in the Siberian high area. During the time of cold waves, the mid- to high-latitude atmospheric circulation was undergoing low-frequency adjustment, with the Arctic oscillation continuously weakening, while the blocking high and Siberian high gradually increased to historically high-intensity states. The outbreaks of the three cold waves occurred at the peak and declining points of the blocking high and Siberian high, respectively, acting as short- to medium-term forecast factors. The CMA-GEPS model demonstrated high forecasting ability for the cooling of the cold waves due to its ability to accurately predict the evolution of the Siberian high and blocking high prior to and after the cold wave with a long lead time. Predictability analysis suggested the strong variability of key factors (such as the Siberian high and blocking) in cold wave events may benefit the model’s prediction of cold wave events. These findings contribute to the understanding of the physical mechanisms behind cold waves and the potential for improved forecasting of extreme cold weather events.
Design and Analysis of a Deep Learning Ensemble Framework Model for the Detection of COVID-19 and Pneumonia Using Large-Scale CT Scan and X-ray Image Datasets
Authors: Xue Xingsi , Chinnaperumal Seelammal , Abdulsahib Ghaida Muttashar , Manyam Rajasekhar Reddy , Marappan Raja , Raju Sekar Kidambi , Khalaf Osamah Ibrahim
Published: March 2023

Recently, various methods have been developed to identify COVID-19 cases, such as PCR testing and non-contact procedures such as chest X-rays and computed tomography (CT) scans. Deep learning (DL) and artificial intelligence (AI) are critical tools for early and accurate detection of COVID-19. This research explores the different DL techniques for identifying COVID-19 and pneumonia on medical CT and radiography images using ResNet152, VGG16, ResNet50, and DenseNet121. The ResNet framework uses CT scan images with accuracy and precision. This research automates optimum model architecture and training parameters. Transfer learning approaches are also employed to solve content gaps and shorten training duration. An upgraded VGG16 deep transfer learning architecture is applied to perform multi-class classification for X-ray imaging tasks. Enhanced VGG16 has been proven to recognize three types of radiographic images with 99% accuracy, typical for COVID-19 and pneumonia. The validity and performance metrics of the proposed model were validated using publicly available X-ray and CT scan data sets. The suggested model outperforms competing approaches in diagnosing COVID-19 and pneumonia. The primary outcomes of this research result in an average F-score (95%, 97%). In the event of healthy viral infections, this research is more efficient than existing methodologies for coronavirus detection. The created model is appropriate for recognition and classification pre-training. The suggested model outperforms traditional strategies for multi-class categorization of various illnesses.
Nectin Family Ligands Trigger Immune Effector Functions in Health and Autoimmunity
Authors: Hermans Doryssa , van Beers Lisa , Broux Bieke
Published: March 2023

The superfamily of immunoglobulin cell-adhesion molecules (IgCAMs) is a well-known family of cell-adhesion molecules used for immune-cell extravasation and cell–cell interaction. Amongst others, this family includes DNAX accessory molecule 1 (DNAM-1/CD226), class-I-restricted T-cell-associated molecule (CRTAM/CD355), T-cell-activated increased late expression (Tactile/CD96), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), Nectins and Nectin-like molecules (Necls). Besides using these molecules to migrate towards inflammatory sites, their interactions within the immune system can support the immunological synapse with antigen-presenting cells or target cells for cytotoxicity, and trigger diverse effector functions. Although their role is generally described in oncoimmunity, this review emphasizes recent advances in the (dys)function of Nectin-family ligands in health, chronic inflammatory conditions and autoimmune diseases. In addition, this review provides a detailed overview on the expression pattern of Nectins and Necls and their ligands on different immune-cell types by focusing on human cell systems.
Structure of Photosystem I Supercomplex Isolated from a Chlamydomonas reinhardtii Cytochrome b6f Temperature-Sensitive Mutant
Authors: Schwartz Tom , Fadeeva Mariia , Klaiman Daniel , Nelson Nathan
Published: March 2023

The unicellular green alga, Chlamydomonas reinhardtii, has been widely used as a model system to study photosynthesis. Its possibility to generate and analyze specific mutants has made it an excellent tool for mechanistic and biogenesis studies. Using negative selection of ultraviolet (UV) irradiation–mutated cells, we isolated a mutant (TSP9) with a single amino acid mutation in the Rieske protein of the cytochrome b6f complex. The W143R mutation in the petC gene resulted in total loss of cytochrome b6f complex function at the non-permissive temperature of 37 °C and recovery at the permissive temperature of 25 °C. We then isolated photosystem I (PSI) and photosystem II (PSII) supercomplexes from cells grown at the non-permissive temperature and determined the PSI structure with high-resolution cryogenic electron microscopy. There were several structural alterations compared with the structures obtained from wild-type cells. Our structural data suggest that the mutant responded by excluding the Lhca2, Lhca9, PsaL, and PsaH subunits. This structural alteration prevents state two transition, where LHCII migrates from PSII to bind to the PSI complex. We propose this as a possible response mechanism triggered by the TSP9 phenotype at the non-permissive temperature.
Pretreatment Frequency of Circulating Th17 Cells and FeNO Levels Predicted the Real-World Response after 1 Year of Benralizumab Treatment in Patients with Severe Asthma
Authors: Sandhu Yuuki , Harada Norihiro , Sasano Hitoshi , Harada Sonoko , Ueda Shoko , Takeshige Tomohito , Tanabe Yuki , Ishimori Ayako , Matsuno Kei , Abe Sumiko , Nagaoka Tetsutaro , Ito Jun , Chiba Asako , Akiba Hisaya , Atsuta Ryo , Izuhara Kenji , Miyake Sachiko , Takahashi Kazuhisa
Published: March 2023

Benralizumab treatment reduces exacerbations and improves symptom control and quality of life in patients with severe eosinophilic asthma. However, the determination of biomarkers that predict therapeutic effectiveness is required for precision medicine. Herein, we elucidated the dynamics of various parameters before and after treatment as well as patient characteristics predictive of clinical effectiveness after 1 year of benralizumab treatment in severe asthma in a real-world setting. Thirty-six patients with severe asthma were treated with benralizumab for 1 year. Lymphocyte subsets in peripheral blood samples were analyzed using flow cytometry. Treatment effectiveness was determined based on the ACT score, forced expiratory volume in 1 s (FEV1), and the number of exacerbations. Benralizumab provided symptomatic improvement in severe asthma. Benralizumab significantly decreased peripheral blood eosinophil and basophil counts and the frequencies of regulatory T cells (Tregs), and increased the frequencies of Th2 cells. To our knowledge, this is the first study to show benralizumab treatment increasing circulating Th2 cells and decreasing circulating Tregs. Finally, the ROC curve to discriminate patients who achieved clinical effectiveness of benralizumab treatment revealed that the frequency of circulating Th17 cells and FeNO levels might be used as parameters for predicting the real-world response of benralizumab treatment in patients with severe asthma.
Influence of a Physiologically Formed Blood Clot on Pre-Osteoblastic Cells Grown on a BMP-7-Coated Nanoporous Titanium Surface
Authors: Zuardi Leonardo Raphael , Silva Cleide Lúcia Araújo , Rego Eduardo Magalhães , Carneiro Giovana Vacilotto , Spriano Silvia , Nanci Antonio , de Oliveira Paulo Tambasco
Published: March 2023

Titanium (Ti) nanotopography modulates the osteogenic response to exogenous bone morphogenetic protein 7 (BMP-7) in vitro, supporting enhanced alkaline phosphatase mRNA expression and activity, as well as higher osteopontin (OPN) mRNA and protein levels. As the biological effects of OPN protein are modulated by its proteolytic cleavage by serum proteases, this in vitro study evaluated the effects on osteogenic cells in the presence of a physiological blood clot previously formed on a BMP-7-coated nanostructured Ti surface obtained by chemical etching (Nano-Ti). Pre-osteoblastic MC3T3-E1 cells were cultured during 5 days on recombinant mouse (rm) BMP-7-coated Nano-Ti after it was implanted in adult female C57BI/6 mouse dorsal dermal tissue for 18 h. Nano-Ti without blood clot or with blood clot at time 0 were used as the controls. The presence of blood clots tended to inhibit the expression of key osteoblast markers, except for Opn, and rmBMP-7 functionalization resulted in a tendency towards relatively greater osteoblastic differentiation, which was corroborated by runt-related transcription factor 2 (RUNX2) amounts. Undetectable levels of OPN and phosphorylated suppressor of mothers against decapentaplegic (SMAD) 1/5/9 were noted in these groups, and the cleaved form of OPN was only detected in the blood clot immediately prior to cell plating. In conclusion, the strategy to mimic in vitro the initial interfacial in vivo events by forming a blood clot on a Ti nanoporous surface resulted in the inhibition of pre-osteoblastic differentiation, which was minimally reverted with an rmBMP-7 coating.
Effect of an Integrated Active Lessons Programme through Playful Maths Games on Self-Concept, Self-Esteem and Social Skills in Preschool Children
Authors: Cámara-Martínez Alba , Ruiz-Ariza Alberto , Suárez-Manzano Sara , Cruz-Cantero Rosa M. , Martínez-López Emilio J.
Published: March 2023

The aim of this study was to analyse the effects of an integrated active lessons programme based on playful math games, of 10 weeks’ duration (30 min/day × 2 days/week), on self-concept, self-esteem and social skills in preschool children. One hundred and ninety-four preschool children (53.6% girls) aged 53.36 ± 11.82 months were split into a control group (CG) and an experimental group (EG). The EG improved significantly in self-concept compared to the CG in boys and girls (6.8% and 7.1%, respectively). Personal and academic self-esteem levels increased significantly (8.1% and 5.5%, respectively, only in girls). Although the EG obtained significant improvements in social self-esteem and social skills compared to the beginning of the study, these results were not found in comparison with the CG. The introduction of active lessons based on playful maths games within the classroom is recommended as support for the improvement in self-concept, self-esteem and social skills in early childhood education.
Long-Term Impacts of Temperature Gradients on a Concrete-Encased Steel I-Girder Experiment—Field-Monitored Data
Authors: Lakshmi Narayanan Sabarigirivasan , Nambiappan Umamaheswari
Published: March 2023

This article delves into an investigation of an experimental steel I-girder section encased in concrete and its instrumentation for the purpose of analyzing temperature distributions in concrete bridges. The study aims to examine the effect of differing air temperatures and thermal loads resulting from solar radiation. Structural health monitoring sensors, including a range of temperature sensors, were connected with the girder to monitor the structural performance using the data acquisition system constantly. The collection of experimental data took place during an exceptionally cold season, and the results of the study revealed both the lateral and vertical distribution of thermal gradients, as well as the fluctuations in these gradients over time. On the premise of the accumulated thermal data, empirical equations were suggested in order to forecast peak lateral as well as vertical temperature gradients, in accordance with the girder’s highest daily and lowest mean temperatures. This temperature variation may lead to longitudinal expansion and contraction in the structure during seasonal variations.
Data-Driven Assisted Decision Making for Surgical Procedure of Hepatocellular Carcinoma Resection and Prognostic Prediction: Development and Validation of Machine Learning Models
Authors: Wang Liyang , Song Danjun , Wang Wentao , Li Chengquan , Zhou Yiming , Zheng Jiaping , Rao Shengxiang , Wang Xiaoying , Shao Guoliang , Cai Jiabin , Yang Shizhong , Dong Jiahong
Published: March 2023

Background: Currently, surgical decisions for hepatocellular carcinoma (HCC) resection are difficult and not sufficiently personalized. We aimed to develop and validate data driven prediction models to assist surgeons in selecting the optimal surgical procedure for patients. Methods: Retrospective data from 361 HCC patients who underwent radical resection in two institutions were included. End-to-end deep learning models were built to automatically segment lesions from the arterial phase (AP) of preoperative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Clinical baseline characteristics and radiomic features were rigorously screened. The effectiveness of radiomic features and radiomic-clinical features was also compared. Three ensemble learning models were proposed to perform the surgical procedure decision and the overall survival (OS) and recurrence-free survival (RFS) predictions after taking different solutions, respectively. Results: SegFormer performed best in terms of automatic segmentation, achieving a Mean Intersection over Union (mIoU) of 0.8860. The five-fold cross-validation results showed that inputting radiomic-clinical features outperformed using only radiomic features. The proposed models all outperformed the other mainstream ensemble models. On the external test set, the area under the receiver operating characteristic curve (AUC) of the proposed decision model was 0.7731, and the performance of the prognostic prediction models was also relatively excellent. The application web server based on automatic lesion segmentation was deployed and is available online. Conclusions: In this study, we developed and externally validated the surgical decision-making procedures and prognostic prediction models for HCC for the first time, and the results demonstrated relatively accurate predictions and strong generalizations, which are expected to help clinicians optimize surgical procedures.
Optimisation Models for Pathway Activity Inference in Cancer
Authors: Chen Yongnan , Liu Songsong , Papageorgiou Lazaros G. , Theofilatos Konstantinos , Tsoka Sophia
Published: March 2023

Background: With advances in high-throughput technologies, there has been an enormous increase in data related to profiling the activity of molecules in disease. While such data provide more comprehensive information on cellular actions, their large volume and complexity pose difficulty in accurate classification of disease phenotypes. Therefore, novel modelling methods that can improve accuracy while offering interpretable means of analysis are required. Biological pathways can be used to incorporate a priori knowledge of biological interactions to decrease data dimensionality and increase the biological interpretability of machine learning models. Methodology: A mathematical optimisation model is proposed for pathway activity inference towards precise disease phenotype prediction and is applied to RNA-Seq datasets. The model is based on mixed-integer linear programming (MILP) mathematical optimisation principles and infers pathway activity as the linear combination of pathway member gene expression, multiplying expression values with model-determined gene weights that are optimised to maximise discrimination of phenotype classes and minimise incorrect sample allocation. Results: The model is evaluated on the transcriptome of breast and colorectal cancer, and exhibits solution results of good optimality as well as good prediction performance on related cancer subtypes. Two baseline pathway activity inference methods and three advanced methods are used for comparison. Sample prediction accuracy, robustness against noise expression data, and survival analysis suggest competitive prediction performance of our model while providing interpretability and insight on key pathways and genes. Overall, our work demonstrates that the flexible nature of mathematical programming lends itself well to developing efficient computational strategies for pathway activity inference and disease subtype prediction.
Exact Probability Distribution for the ROC Area under Curve
Authors: Ekström Joakim , Åkerrén Ögren Jim , Sjöblom Tobias
Published: March 2023

The Receiver Operating Characteristic (ROC) is a de facto standard for determining the accuracy of in vitro diagnostic (IVD) medical devices, and thus the exactness in its probability distribution is crucial toward accurate statistical inference. We show the exact probability distribution of the ROC AUC-value, hence exact critical values and p-values are readily obtained. Because the exact calculations are computationally intense, we demonstrate a method of geometric interpolation, which is exact in a special case but generally an approximation, vastly increasing computational speeds. The method is illustrated through open access data, demonstrating superiority of 26 composite biomarkers relative to a predicate device. Especially under correction for testing of multiple hypotheses, traditional asymptotic approximations are encumbered by considerable imprecision, adversely affecting IVD device development. The ability to obtain exact p-values will allow more efficient IVD device development.
Do Biliary Stents Affect EUS-Guided Tissue Acquisition (EUS-TA) in Solid Pancreatic Lesions Determining Biliary Obstruction? A Literature Review with Meta-Analysis
Authors: Facciorusso Antonio , Chandan Saurabh , Gkolfakis Paraskevas , Ramai Daryl , Mohan Babu P. , Lisotti Andrea , Conti Bellocchi Maria Cristina , Papanikolaou Ioannis S. , Mangiavillano Benedetto , Triantafyllou Konstantinos , Manthopoulou Eleni , Mare Ruxandra , Fusaroli Pietro , Crinò Stefano Francesco
Published: March 2023

There is a paucity of evidence regarding whether biliary stents influence endoscopic ultrasound-guided tissue acquisition using either fine-needle biopsy (EUS-FNB) or fine-needle aspiration (EUS-FNA), among patients with head of pancreas (HOP) lesions. We aimed at assessing the diagnostic accuracy of endoscopic ultrasound-guided tissue sampling in patients with or without bile duct stents. A total of seven studies with 2458 patients were included. The main aim was to assess overall pooled diagnostic accuracy. A pairwise meta-analysis was performed using a random effects model. Outcomes were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). We found that pooled accuracy was 85.4% (CI 78.8–91.9) and 88.1% (CI 83.3–92.9) in patients with and without stents, respectively. There was no statistically significant difference between the two (OR 0.74; p = 0.07). Furthermore, patients with metal stents demonstrated a significant difference (OR 0.54, 0.17–0.97; p = 0.05), which was not seen with plastic stents. EUS-FNB showed poorer diagnostic accuracy with concurrent biliary stenting (OR 0.64, 0.43–0.95; p = 0.03); however, the same was not observed with EUS-FNA. Compared to plastic stents, metal biliary stenting further impacted the diagnostic accuracy of EUS-guided tissue acquisition for pancreatic head lesions. There was no difference in the rate of procedure-related adverse events between the stent and no-stent groups.
NKG2D Fine-Tunes the Local Inflammatory Response in Colorectal Cancer
Authors: Curio Sophie , Lin Wanzun , Bromley Christian , McGovern Jenny , Triulzi Chiara , Jonsson Gustav , Ghislat Ghita , Zelenay Santiago , Guerra Nadia
Published: March 2023

Treating colorectal cancer (CRC) is a major challenge due to the heterogeneous immunological, clinical and pathological landscapes. Immunotherapy has so far only proven effective in a very limited subgroup of CRC patients. To better define the immune landscape, we examined the immune gene expression profile in various subsets of CRC patients and used a mouse model of intestinal tumors to dissect immune functions. We found that the NK cell receptor, natural-killer group 2 member D (NKG2D, encoded by KLRK1) and NKG2D ligand gene expression is elevated in the most immunogenic subset of CRC patients. High level of KLRK1 positively correlated with the mRNA expression of IFNG and associated with a poor survival of CRC patients. We further show that NKG2D deficiency in the Apcmin/+ mouse model of intestinal tumorigenesis led to reduced intratumoral IFNγ production, reduced tumorigenesis and enhanced survival, suggesting that the high levels of IFNγ observed in the tumors of CRC patients may be a consequence of NKG2D engagement. The mechanisms governing the contribution of NKG2D to CRC progression highlighted in this study will fuel discussions about (i) the benefit of targeting NKG2D in CRC patients and (ii) the need to define the predictive value of NKG2D and NKG2D ligand expression across tumor types.
Revisiting the Syndecans: Master Signaling Regulators with Prognostic and Targetable Therapeutic Values in Breast Carcinoma
Authors: Motta Juliana Maria , Hassan Hebatallah , Ibrahim Sherif Abdelaziz
Published: March 2023

Syndecans (SDC1 to 4), a family of cell surface heparan sulfate proteoglycans, are frequently expressed in mammalian tissues. SDCs are aberrantly expressed either on tumor or stromal cells, influencing cancer initiation and progression through their pleiotropic role in different signaling pathways relevant to proliferation, cell-matrix adhesion, migration, invasion, metastasis, cancer stemness, and angiogenesis. In this review, we discuss the key roles of SDCs in the pathogenesis of breast cancer, the most common malignancy in females worldwide, focusing on the prognostic significance and molecular regulators of SDC expression and localization in either breast tumor tissue or its microenvironmental cells and the SDC-dependent epithelial–mesenchymal transition program. This review also highlights the molecular mechanisms underlying the roles of SDCs in regulating breast cancer cell behavior via modulation of nuclear hormone receptor signaling, microRNA expression, and exosome biogenesis and functions, as well as summarizing the potential of SDCs as promising candidate targets for therapeutic strategies against breast cancer.
Effects of Different Reductive Agents on Zn-Promoted Iron Oxide Phases in the CO2–Fischer–Tropsch to Linear α-Olefins
Authors: Pan Yueshen , Ding Xiaoxu , Zhang Chao , Zhu Minghui , Yang Zixu , Han Yi-Fan
Published: March 2023

The pretreatment atmosphere has a significant impact on the performance of iron-based catalysts in carbon dioxide (CO2) hydrogenation. In this study, we investigated the effects of carbon monoxide (CO), syngas (H2/CO), and hydrogen (H2) on the performance of iron-based catalysts during the pretreatment process. To evaluate the structural changes in catalysts after activation and reaction, we analyzed their morphology and particle size, the surface and bulk phase composition, carbon deposition, the desorption of linear α-olefins and reaction intermediates using transmission electron microscope (TEM), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), Mössbauer spectroscopy (MES), temperature-programmed desorption (TPD), and in situ diffuse reflectance infrared Fourier transform spectroscopy (in situ DRIFTS). Raman and XPS showed that the H2 pretreatment catalyst caused the absence of iron carbides due to the lack of carbon source, and the CO and syngas pretreatment catalysts promoted the formation of carbon deposits and iron carbides. While the bulk phase of the CO and syngas pretreatment catalyst mainly consists of iron carbide (FeCx), XRD and MES revealed that the bulk phase of the H2 pretreatment catalyst primarily consisted of metallic iron (Fe) and iron oxide (FeOx). The composition of the phase is closely associated with its performance at the initial stage of the reaction. The formation of olefins and C5+ products is more encouraged by CO pretreatment catalysts than by H2 and syngas pretreatment catalysts, according to in situ DRIFTS evidence. Ethylene (C2H4)/propylene (C3H6)-TPD indicates that the CO pretreatment catalyst is more favorable for the desorption of olefins which improves the olefins selectivity. Based on the analysis of the TEM images, H2 pretreatment stimulated particle agglomeration and sintering. In conclusion, the results show that the CO-pretreatment catalyst has higher activity due to the inclusion of more FeOX and Fe3C. In particular, the presence of Fe3C was found to be more favorable for the formation of olefins and C5+ hydrocarbons. Furthermore, carbon deposition was relatively mild and more conducive to maintaining the balance of FeOx/FeCx on the catalyst surface.
Characterization of BV6-Induced Sensitization to the NK Cell Killing of Pediatric Rhabdomyosarcoma Spheroids
Authors: Särchen Vinzenz , Reindl Lisa Marie , Wiedemann Sara , Shanmugalingam Senthan , Bukur Thomas , Becker Julia , Suchan Martin , Ullrich Evelyn , Vogler Meike
Published: March 2023

Although the overall survival in pediatric rhabdomyosarcoma (RMS) has increased over the last decades, the most aggressive subtype of alveolar RMS is in dire need of novel treatment strategies. RMS cells evade cell death induction and immune control by increasing the expression of inhibitors of apoptosis proteins (IAPs), which can be exploited and targeted with stimulation with Smac mimetics. Here, we used the Smac mimetic BV6 to re-sensitize RMS spheroids to cell death, which increased killing induced by natural killer (NK) cells. Single BV6 treatment of RMS spheroids did not reduce spheroidal growth. However, we observed significant spheroidal decomposition upon BV6 pre-treatment combined with NK cell co-cultivation. Molecularly, IAPs s are rapidly degraded by BV6, which activates NF-κB signal transduction pathways in RMS spheroids. RNA sequencing analysis validated NF-κB activation and identified a plethora of BV6-regulated genes. Additionally, BV6 released caspases from IAP-mediated inhibition. Here, caspase-8 might play a major role, as knockdown experiments resulted in decreased NK cell-mediated attack. Taken together, we improved the understanding of the BV6 mechanism of RMS spheroid sensitization to cytotoxic immune cells, which could be suitable for the development of novel combinatory cellular immunotherapy with Smac mimetics.
Investigating the Impact of Delivery Routes for Exon Skipping Therapies in the CNS of DMD Mouse Models
Authors: Saoudi Amel , Fergus Claire , Gileadi Talia , Montanaro Federica , Morgan Jennifer E. , Kelly Vincent P. , Tensorer Thomas , Garcia Luis , Vaillend Cyrille , Muntoni Francesco , Goyenvalle Aurélie
Published: March 2023

Nucleic acid-based therapies have demonstrated great potential for the treatment of monogenetic diseases, including neurologic disorders. To date, regulatory approval has been received for a dozen antisense oligonucleotides (ASOs); however, these chemistries cannot readily cross the blood–brain barrier when administered systemically. Therefore, an investigation of their potential effects within the central nervous system (CNS) requires local delivery. Here, we studied the brain distribution and exon-skipping efficacy of two ASO chemistries, PMO and tcDNA, when delivered to the cerebrospinal fluid (CSF) of mice carrying a deletion in exon 52 of the dystrophin gene, a model of Duchenne muscular dystrophy (DMD). Following intracerebroventricular (ICV) delivery (unilateral, bilateral, bolus vs. slow rate, repeated via cannula or very slow via osmotic pumps), ASO levels were quantified across brain regions and exon 51 skipping was evaluated, revealing that tcDNA treatment invariably generates comparable or more skipping relative to that with PMO, even when the PMO was administered at higher doses. We also performed intra-cisterna magna (ICM) delivery as an alternative route for CSF delivery and found a biased distribution of the ASOs towards posterior brain regions, including the cerebellum, hindbrain, and the cervical part of the spinal cord. Finally, we combined both ICV and ICM injection methods to assess the potential of an additive effect of this methodology in inducing efficient exon skipping across different brain regions. Our results provide useful insights into the local delivery and associated efficacy of ASOs in the CNS in mouse models of DMD. These findings pave the way for further ASO-based therapy application to the CNS for neurological disease.
Effect of Remote Ischaemic Preconditioning on Perioperative Endothelial Dysfunction in Non-Cardiac Surgery: A Randomised Clinical Trial
Authors: Wahlstrøm Kirsten L. , Hansen Hannah F. , Kvist Madeline , Burcharth Jakob , Lykkesfeldt Jens , Gögenur Ismail , Ekeloef Sarah
Published: March 2023

Endothelial dysfunction result from inflammation and excessive production of reactive oxygen species as part of the surgical stress response. Remote ischemic preconditioning (RIPC) potentially exerts anti-oxidative and anti-inflammatory properties, which might stabilise the endothelial function after non-cardiac surgery. This was a single centre randomised clinical trial including 60 patients undergoing sub-acute laparoscopic cholecystectomy due to acute cholecystitis. Patients were randomised to RIPC or control. The RIPC procedure consisted of four cycles of five minutes of ischaemia and reperfusion of one upper extremity. Endothelial function was assessed as the reactive hyperaemia index (RHI) and circulating biomarkers of nitric oxide (NO) bioavailability (L-arginine, asymmetric dimethylarginine (ADMA), L-arginine/ADMA ratio, tetra- and dihydrobiopterin (BH4 and BH2), and total plasma biopterin) preoperative, 2–4 h after surgery and 24 h after surgery. RHI did not differ between the groups (p = 0.07). Neither did levels of circulating biomarkers of NO bioavailability change in response to RIPC. L-arginine and L-arginine/ADMA ratio was suppressed preoperatively and increased 24 h after surgery (p < 0.001). The BH4/BH2-ratio had a high preoperative level, decreased 2–4 h after surgery and remained low 24 h after surgery (p = 0.01). RIPC did not influence endothelial function or markers of NO bioavailability until 24 h after sub-acute laparoscopic cholecystectomy. In response to surgery, markers of NO bioavailability increased, and oxidative stress decreased. These findings support that a minimally invasive removal of the inflamed gallbladder countereffects reduced markers of NO bioavailability and increased oxidative stress caused by acute cholecystitis.
Mitochondrial Haemoglobin Is Upregulated with Hypoxia in Skeletal Muscle and Has a Conserved Interaction with ATP Synthase and Inhibitory Factor 1
Authors: Ebanks Brad , Katyal Gunjan , Taylor Chris , Dowle Adam , Papetti Chiara , Lucassen Magnus , Moisoi Nicoleta , Chakrabarti Lisa
Published: March 2023

The globin protein superfamily has diverse functions. Haemoglobin has been found in non-erythroid locations, including within the mitochondria. Using co-immunoprecipitation and in silico methods, we investigated the interaction of mitochondrial haemoglobin with ATP synthase and its associated proteins, including inhibitory factor 1 (IF1). We measured the expression of mitochondrial haemoglobin in response to hypoxia. In vitro and in silico evidence of interactions between mitochondrial haemoglobin and ATP synthase were found, and we report upregulated mitochondrial haemoglobin expression in response to hypoxia within skeletal muscle tissue. Our observations indicate that mitochondrial pH and ATP synthase activity are implicated in the mitochondrial haemoglobin response to hypoxia.
Elemental Analysis of Heated Soil Samples Using Laser-Induced Breakdown Spectroscopy Assisted with High-Voltage Discharges
Authors: Amador-Mejía Mitzi , Sobral Hugo , Robledo-Martinez Arturo
Published: March 2023

In this study, a high-voltage (HV) oscillatory square pulse was used to re-excite the laser-induced breakdown spectroscopy (LIBS) signal produced by a nanosecond laser on different loamy soil samples at two different temperatures: ambient and 400 °C. The optimal delay was found for each experimental scheme to maximize the emission signal-to-noise ratio. The detection limits of various contaminants in the soil were studied for different experimental configurations. It was found that the lowest detection limits were achieved by combining HV discharges with LIBS on heated samples, resulting in improvements of up to a factor of 7 compared to LIBS on room temperature samples. Plasma characterization shows that the increased detection sensitivity is due to the rise in plasma temperature and electron density with HV re-excitation, while an increase in removed matter contributes to the emission intensification observed when samples are heated.
Translation, Cross-Cultural Adaptation, and Psychometric Properties of Writing Readiness Inventory Tool in Context (WRITIC)
Authors: Delgado Paulo , Melo Filipe , de Vries Liesbeth , Hartingsveldt Margo , Matias Ana Rita
Published: March 2023

This article describes the translation and cultural adaptation process of the WRITIC (Writing Readiness Inventory Tool in Context) into European Portuguese. We examined the content and convergent validity, test-retest, and interrater reliability on the norm-referenced subdomain of the Portuguese (PT) WRITIC Task Performance (TP). To establish content validity, we consulted six experts in handwriting. Internal consistency was found with 70 children, test-retest reliability with 65, inter-rater reliability with 69, and convergent validity with 87. All participants were typically developing kindergarten children. Convergent validity was examined with the Beery–Buktenica Developmental Test of Visual-Motor Integration (Beery™VMI-6) and the Nine Hole Peg-Test (9-HPT). On content validity, we found an agreement of 93%, a good internal consistency with Cronbach’s alpha of 0.72, and an excellent test-retest and inter-rater reliability with ICCs of 0.88 and 0.93. Correlations with Beery™VMI-6 and 9-HPT were moderate (r from 0.39 to 0.65). Translation and cross-cultural adaptation of WRITIC into European Portuguese was successful. WRITIC-PT-TP is stable over time and between raters; it has excellent internal consistency and moderate correlations with Beery™VMI-6 and 9-HPT. This analysis of the European Portuguese version of WRITIC gives us the confidence to start the implementation process of WRITIC-PT in Portugal.
Comparison of MAFLD and NAFLD Characteristics in Children
Authors: Xing Yunfei , Fan Jiangao , Wang Hai-Jun , Wang Hui
Published: March 2023

Background & aims: An international panel proposed a diagnostic framework for metabolic-associated fatty liver disease (MAFLD) in children. The aim was to compare the clinical features of MAFLD and nonalcoholic fatty liver disease (NAFLD) in children. Methods: The characteristic differences between NAFLD and MAFLD in children were compared with the National Health and Nutrition Examination Survey (NHANES) 2017–2018 in the U.S. and the Comprehensive Prevention Project for Overweight and Obese Adolescents (CPOOA) study in China. Results: In NHANES 2017–2018, regardless of which criteria were implemented, participants with hepatic steatosis were more likely to have higher BMI z-scores, a higher prevalence of hypertension or higher metabolic indices and higher non-invasive liver fibrosis scores (all p < 0.05). The cases diagnosed by those two definitions had a similarity of over 75%. More obese children were diagnosed with MAFLD than NAFLD (p < 0.001). However, approximately 19% of children with NAFLD present with normal weight and fasting glucose levels and cannot be diagnosed with MAFLD. The CPOOA study excluded viral infected liver disease and certain kinds of congenital causes of liver steatosis patients, resulting in children with NAFLD being identical with MAFLD children. Conclusions: Most clinical features were similar between children with MAFLD and children with NAFLD, and more than 75% of children with NAFLD can also be diagnosed with MAFLD. However, approximately 19% of children with NAFLD cannot be categorized as MAFLD. Therefore, to gain greater benefits from renaming NAFLD to MAFLD in pediatrics, the prevalence of different causes of hepatic steatosis in children needs to be understood.
Amniotic Fluid Disorders: From Prenatal Management to Neonatal Outcomes
Authors: Huri Mor , Di Tommaso Mariarosaria , Seravalli Viola
Published: March 2023

Amniotic fluid volume assessment has become standard in the surveillance of fetal well-being, especially in high-risk pregnancies. Amniotic fluid disorders are a frequent and important topic in fetal and perinatal medicine. However, although important advances have been achieved, many important and challenging questions remain unanswered to date. An abnormally low amniotic fluid volume, referred to as oligohydramnios, has been traditionally considered a possible indicator of placental insufficiency or fetal compromise and is associated with an increased rate of obstetric interventions. An excess of amniotic fluid, referred to as polyhydramnios, may be secondary to fetal or maternal conditions and has been associated with a variety of adverse pregnancy outcomes, especially when it is severe. The ultrasonographic detection of an amniotic fluid disorder should prompt a proper workup to identify the underlying etiology. Data on the association of isolated oligohydramnios or idiopathic polyhydramnios with adverse obstetric and perinatal outcomes are conflicting. While the management of secondary oligohydramnios is usually guided by the underlying condition, the management of isolated oligohydramnios is poorly defined. Similarly, the management of idiopathic and secondary polyhydramnios is not yet standardized. There is an urgent need for randomized clinical trials to provide stronger recommendations on the management of these two common conditions.
Association between Soccer Participation and Liking or Being Proficient in It: A Survey Study of 38,258 Children and Adolescents in China
Authors: Gao Yibo , Pan Xiang , Wang Huan , Wu Dongming , Deng Pengyu , Jiang Lupei , Zhang Aoyu , He Jin , Zhang Yanfeng
Published: March 2023

Soccer participation among children and adolescents is low in China. To achieve a coordinated development of soccer in all regions and to promote the physical health of children and adolescents, this study aims to identify the influencing factors regarding the participation of children and adolescents in soccer programs through a cross-sectional analysis of the “soccer population” of children and adolescents. A total of 38,258 children and adolescents aged 7–18 years were included in this study. In addition, the analysis was conducted by dividing the regions where the children and adolescents live into three parts according to socioeconomic status, and by incorporating five dimensions, including environment, family, school, community, and individual levels to find the influencing factors of children and adolescents’ participation in soccer. Chi-square test, Pearson’s correlation, and one-way logistic regression analyses were used. The results showed that the area (r = 0.487) and the average annual precipitation (r = −0.367) were associated with the participation of children and adolescents in soccer programs. Moreover, the percentage of children and adolescents who participated in soccer programs (24.5%) was higher than those who liked soccer or were proficient in it (14.4%). Meanwhile, parental encouragement and support (OR = 0.627; 95% CI, 1.102–3.179), as well as the accessibility (OR = 0.558; 95% CI, 1.418–2.155), availability (OR = 1.419; 95% CI, 1.179–1.707), and safety of sports facilities (OR = 0.316; 95% CI, 0.614–0.865), influence children and adolescents’ participation in soccer programs.
Comparison of Corrosion Behavior of WE43 and AZ80 Alloys in NaCl and Na2SO4 Solutions
Authors: Li Chenxu , Zhao Yuming , Liu Jinhui , Xu Jilei , Guo Dong , Zhang Huanghua , Zhou Xianghong , Yang Peixu , Zhang Shaojun
Published: March 2023

The corrosion behavior and corrosion resistance of WE43 and AZ80 immersed in NaCl and Na2SO4 solutions were investigated, respectively. Two alloys were immersed in 0.6 M NaCl and Na2SO4 solution to observe the corrosion morphologies. Hydrogen evolution and weight loss experiments were conducted to obtain the corrosion rates. Electrochemical tests were used to characterized detailed corrosion situation. The results show that, when immersed in Na2SO4 solution, WE43 alloy shows a unique micro-galvanic corrosion behavior. On the other hand, the corrosion rate of WE43 in Na2SO4 solution is much faster than that in NaCl solution, which is the direct opposite of AZ80 and most magnesium alloys. The protection of the surface film maybe the key factor to the unexpected phenomena.
Plasma Electrolytic Oxidation Treatment of AZ31 Magnesium Alloy for Biomedical Applications: The Influence of Applied Current on Corrosion Resistance and Surface Characteristics
Authors: Acquesta Annalisa , Russo Pietro , Monetta Tullio
Published: March 2023

Magnesium alloys are an exciting challenge for the biomaterials field given their well-established biodegradability and biocompatibility. However, when exposed to biological fluids, their rapid degradation and hydrogen release are the main drawbacks for clinical applications. This work aimed to investigate the influence of the current density applied during the plasma electrolytic oxidation (PEO) treatment on the durability of an AZ31 magnesium alloy. In particular, specific interest was directed to the degradation rate undergone by the PEO coating, obtained under two different current density conditions, when exposed to Hank’s solution at 37 °C to simulate the physiological environment, employing the techniques of potentiodynamic polarization and electrochemical impedance spectroscopy. Experimental results highlighted that the plasma electrolytic oxidation technique resulted in an improvement in the corrosion resistance of the magnesium alloy in the test solution. The current density affected the morphology of the coating. In particular, the anodic oxide coating obtained by applying the highest current density showed a higher thickness and fewer but larger pores, while the lowest current density generated a thinner PEO coating characterized by several but smaller pores. Surprisingly, the best corrosion resistance has been exhibited by the anodic oxide coating grown at the highest current density.
Choroidal and Retinal Vascular Findings in Patients with COVID-19 Complicated with Pneumonia: Widefield Imaging
Authors: D’Aloisio Rossella , Ruggeri Maria Ludovica , D’Onofrio Giada , Formenti Federico , Gironi Matteo , Di Nicola Marta , Porreca Annamaria , Toto Lisa , Mastropasqua Rodolfo
Published: March 2023

Purpose: The purpose of this study was to analyze choroidal and retinal vascular alterations of both the macula and midperiphery areas in patients hospitalized for COVID-19 infection complicated with pneumonia within 30 days from discharge. Methods: A total of 46 eyes of 23 subjects with a history of symptomatic COVID-19 infection and recent hospitalization for pneumonia were enrolled in this observational study. Patients had not been previously vaccinated against COVID-19. A group of patients homogenous for age and sex was enrolled as controls. Microvascular retinal and choroidal features of the enrolled patients were studied with widefield optical coherence tomography angiography (OCT-A). Perfusion parameters in terms of the vessel density (VD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) and the choroidal vascularity index (CVI) on enhanced depth imaging (EDI) mode OCT scans were analyzed. Results: Our cohort of patients showed a trend of reduction in VD, significantly in the SCP VD of the superior and inferior midperiphery sectors, whereas the CVI did not show significant differences between the cases and controls. Moreover, a positive correlation between CVI and vessel density in the deep capillary plexus in the macular area (VD-DCP-MAC) was found. Conclusion: The systemic disease due to COVID-19 can also involve the retina and choroid with multiple mechanisms: ischemic and inflammatory. Our study showed changes in perfusion occurring in the eyes of patients with a recent hospitalization for COVID-19 complicated with pneumonia and without any possible ocular effect due to the vaccines. There is still the need to better comprise how long COVID-19 actually affects vascular changes in the eye.
A Deep Learning Framework for Cardiac MR Under-Sampled Image Reconstruction with a Hybrid Spatial and k-Space Loss Function
Authors: Al-Haidri Walid , Matveev Igor , Al-antari Mugahed A. , Zubkov Mikhail
Published: March 2023

Magnetic resonance imaging (MRI) is an efficient, non-invasive diagnostic imaging tool for a variety of disorders. In modern MRI systems, the scanning procedure is time-consuming, which leads to problems with patient comfort and causes motion artifacts. Accelerated or parallel MRI has the potential to minimize patient stress as well as reduce scanning time and medical costs. In this paper, a new deep learning MR image reconstruction framework is proposed to provide more accurate reconstructed MR images when under-sampled or aliased images are generated. The proposed reconstruction model is designed based on the conditional generative adversarial networks (CGANs) where the generator network is designed in a form of an encoder–decoder U-Net network. A hybrid spatial and k-space loss function is also proposed to improve the reconstructed image quality by minimizing the L1-distance considering both spatial and frequency domains simultaneously. The proposed reconstruction framework is directly compared when CGAN and U-Net are adopted and used individually based on the proposed hybrid loss function against the conventional L1-norm. Finally, the proposed reconstruction framework with the extended loss function is evaluated and compared against the traditional SENSE reconstruction technique using the evaluation metrics of structural similarity (SSIM) and peak signal to noise ratio (PSNR). To fine-tune and evaluate the proposed methodology, the public Multi-Coil k-Space OCMR dataset for cardiovascular MR imaging is used. The proposed framework achieves a better image reconstruction quality compared to SENSE in terms of PSNR by 6.84 and 9.57 when U-Net and CGAN are used, respectively. Similarly, it demonstrates SSIM of the reconstructed MR images comparable to the one provided by the SENSE algorithm when U-Net and CGAN are used. Comparing cases where the proposed hybrid loss function is used against the cases with the simple L1-norm, the reconstruction performance can be noticed to improve by 6.84 and 9.57 for U-Net and CGAN, respectively. To conclude this, the proposed framework using CGAN provides the best reconstruction performance compared with U-Net or the conventional SENSE reconstruction techniques. The proposed framework seems to be useful for the practical reconstruction of cardiac images since it can provide better image quality in terms of SSIM and PSNR.