bluuebunny/crossref_metadata_2025 huggingface dataset:
Left atrial size predicts outcome in severe but asymptomatic mitral regurgitation
Authors: Zilberszac Robert , Gleiss Andreas , Massetti Massimo , Wisser Wilfried , Binder Thomas , Gabriel Harald , Rosenhek Raphael
Published: March 2023

Patients with severe asymptomatic primary mitral regurgitation (MR) can be safely managed with an active surveillance strategy. Left atrial (LA) size is affected by MR severity, left ventricular function and is also associated with the risk of atrial fibrillation and may be an integrative parameter for risk stratification. The present study sought to determine the predictive value of LA size in a large series of asymptomatic patients with severe MR. 280 consecutive patients (88 female, median age 58 years) with severe primary MR and no guideline-based indications for surgery were included in a follow-up program until criteria for mitral surgery were reached. Event-free survival was determined and potential predictors of outcome were assessed. Survival free of any indication for surgery was 78% at 2 years, 52% at 6 years, 35% at 10 years and 19% at 15 years, respectively. Left atrial (LA) diameter was the strongest independent echocardiographic predictor of event-free survival with incremental predictive value for the thresholds of 50, 60 and 70 mm, respectively. In a multivariable analysis that encompassed age at baseline, previous history of atrial fibrillation, left ventricular end systolic diameter), LA diameter, sPAP > 50 mmHg and year of inclusion, LA diameter was the strongest independent echocardiographic predictor of event-free survival (adjusted HR = 1.039, p < 0.001). LA size is a simple and reproducible predictor of outcome in asymptomatic severe primary MR. In particular, it may help to identify patients who may benefit from early elective valve surgery in heart valve centers of excellence.
Development of an inhibiting antibody against equine interleukin 5 to treat insect bite hypersensitivity of horses
Authors: Langreder Nora , Schäckermann Dorina , Meier Doris , Becker Marlies , Schubert Maren , Dübel Stefan , Reinard Thomas , Figge-Wegener Stefanie , Roßbach Kristine , Bäumer Wolfgang , Ladel Simone , Hust Michael
Published: March 2023

Insect bite hypersensitivity (IBH) is the most common allergic skin disease of horses. It is caused by insect bites of the Culicoides spp. which mediate a type I/IVb allergy with strong involvement of eosinophil cells. No specific treatment option is available so far. One concept could be the use of a therapeutic antibody targeting equine interleukin 5, the main activator and regulator of eosinophils. Therefore, antibodies were selected by phage display using the naïve human antibody gene libraries HAL9/10, tested in a cellular in vitro inhibition assay and subjected to an in vitro affinity maturation. In total, 28 antibodies were selected by phage display out of which eleven have been found to be inhibiting in the final format as chimeric immunoglobulin G with equine constant domains. The two most promising candidates were further improved by in vitro affinity maturation up to factor 2.5 regarding their binding activity and up to factor 2.0 regarding their inhibition effect. The final antibody named NOL226-2-D10 showed a strong inhibition of the interleukin 5 binding to its receptor (IC50 = 4 nM). Furthermore, a nanomolar binding activity (EC50 = 8.8 nM), stable behavior and satisfactory producibility were demonstrated. This antibody is an excellent candidate for in vivo studies for the treatment of equine IBH.
Multiparameter prediction model of immune checkpoint inhibitors combined with chemotherapy for non-small cell lung cancer based on support vector machine learning
Authors: Zhou Zihan , Guo Wenjie , Liu Dingqi , Micha Jose Ramon Nsue , Song Yue , Han Shuhua
Published: March 2023

The reliable predictive markers to identify which patients with advanced non-small cell lung cancer tumors (NSCLC) will achieve durable clinical benefit (DCB) for chemo-immunotherapy are needed. In this retrospective study, we collected radiomics and clinical signatures from 94 patients with advanced NSCLC treated with anti-PD-1/PD-L1 combined with chemotherapy from January 1, 2018 to May 31, 2022. Radiomics variables were extracted from pretreatment CT and selected by Spearman correlation coefficients and clinical features by Logistics regression analysis. We performed effective diagnostic algorithms principal components analysis (PCA) and support vector machine (SVM) to develop an early classification model among DCB and non-durable benefit (NDB) groups. A total of 26 radiomics features and 6 clinical features were selected, and then principal component analysis was used to obtain 6 principal components for SVM building. RC-SVM achieved prediction accuracy with AUC of 0.91 (95% CI 0.87–0.94) in the training set, 0.73 (95% CI 0.61–0.85) in the cross-validation set, 0.84 (95% CI 0.80–0.89) in the external validation set. The new method of RC-SVM model based on radiomics-clinical signatures provides a significant additive value on response prediction in patients with NSCLC preceding chemo-immunotherapy.
Gene expression response of the non-target gastropod Physella acuta to Fenoxycarb, a juvenile hormone analog pesticide
Authors: Caballero Patricia , Prieto-Amador Marina , Martínez-Guitarte José-Luis
Published: March 2023

Pesticides are an environmental problem. The search for new pest control methods has focused on compounds with low or no toxic effects in non-target organisms. Analogs of the juvenile hormone (JH) interfere endocrine system of arthropods. However, the lack of effect on non-target species requires confirmation. This article analyzes the impact of Fenoxycarb, an analog of JH, on Physella acuta, an aquatic gastropod. For 1 week, animals were exposed to 0.01, 1, and 100 μg/L and the RNA was isolated to analyze the gene expression by retrotranscription and Real-Time PCR. Forty genes related to the endocrine system, the DNA repair mechanisms, the detoxification mechanisms, oxidative stress, the stress response, the nervous system, hypoxia, energy metabolism, the immune system, and apoptosis were analyzed. Three of the genes, AchE, HSP17.9, and ApA, showed responses to the presence of Fenoxycarb at 1 μg/L, with no statistically significant responses in the rest of the genes and at the remaining concentrations. From the results, it can be concluded that Fenoxycarb shows a weak response at the molecular level in P. acuta in the tested time and concentrations. However, Aplysianin-A, a gene related to immunity, was altered so the long-term effect could be relevant. Therefore, additional research is required to confirm the safety of Fenoxycarb in non-arthropod species in the long term.
Multi-arm U-Net with dense input and skip connectivity for T2 lesion segmentation in clinical trials of multiple sclerosis
Authors: Krishnan Anitha Priya , Song Zhuang , Clayton David , Jia Xiaoming , de Crespigny Alex , Carano Richard A. D.
Published: March 2023

T2 lesion quantification plays a crucial role in monitoring disease progression and evaluating treatment response in multiple sclerosis (MS). We developed a 3D, multi-arm U-Net for T2 lesion segmentation, which was trained on a large, multicenter clinical trial dataset of relapsing MS. We investigated its generalization to other relapsing and primary progressive MS clinical trial datasets, and to an external dataset from the MICCAI 2016 MS lesion segmentation challenge. Additionally, we assessed the model’s ability to reproduce the separation of T2 lesion volumes between treatment and control arms; and the association of baseline T2 lesion volumes with clinical disability scores compared with manual lesion annotations. The trained model achieved a mean dice coefficient of ≥ 0.66 and a lesion detection sensitivity of ≥ 0.72 across the internal test datasets. On the external test dataset, the model achieved a mean dice coefficient of 0.62, which is comparable to 0.59 from the best model in the challenge, and a lesion detection sensitivity of 0.68. Lesion detection performance was reduced for smaller lesions (≤ 30 μL, 3–10 voxels). The model successfully maintained the separation of the longitudinal changes in T2 lesion volumes between the treatment and control arms. Such tools could facilitate semi-automated MS lesion quantification; and reduce rater burden in clinical trials.
Contrast-enhanced CT-based Radiomics for the Differentiation of Anaplastic or Poorly Differentiated Thyroid Carcinoma from Differentiated Thyroid Carcinoma: A Pilot Study
Authors: Moon Jayoung , Lee Jeong Hoon , Roh Jin , Lee Da Hyun , Ha Eun Ju
Published: March 2023

Differential diagnosis of anaplastic thyroid carcinoma/poorly differentiated thyroid carcinoma (ATC/PDTC) from differentiated thyroid carcinoma (DTC) is crucial in patients with large thyroid malignancies. This study creates a predictive model using radiomics feature analysis to differentiate ATC/PDTC from DTC. We compared the clinicoradiological characteristics and radiomics features extracted from a volume of interest on contrast-enhanced computed tomography (CT) between the groups. Estimations of variable importance were performed via modeling using the random forest quantile classifier. The diagnostic performance of the model with radiomics features alone had the area under the receiver operating characteristic (AUROC) curve value of 0.883. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 81.7%, 93.3%, 97.7%, 64.5%, and 84.6%, respectively, for the differential diagnosis of ATC/PDTC and DTC. The model with both radiomics and clinicoradiological information showed the AUROC of 0.908, with sensitivity, specificity, PPV, NPV, and accuracy of 82.9%, 97.6%, 99.2%, 67.1%, and 86.5% respectively. Distant metastasis, moment, shape, age, and gray-level size zone matrix features were the most useful factors for differential diagnosis. Therefore, we concluded that a radiomics approach based on contrast-enhanced CT features can potentially differentiate ATC/PDTC from DTC in patients with large thyroid malignancies.
Experimental verification of seafloor crustal deformation observations by UAV-based GNSS-A
Authors: Yokota Yusuke , Kaneda Masata , Hashimoto Takenori , Yamaura Shusaku , Kouno Kenji , Hirakawa Yoshiaki
Published: March 2023

The Global Navigation Satellite System-Acoustic ranging combination technique (GNSS-A) is the only geodetic observation method that can precisely detect absolute horizontal and vertical seafloor crustal deformations at the centimetre scale. GNSS-A has detected many geophysical phenomena and is expected to make great contributions to earthquake disaster prevention science and geodesy. However, current observation methods that use vessels and buoys suffer from high cost or poor real-time performance, which leads to low observation frequency and delays in obtaining and transmitting disaster prevention information. To overcome these problems, a new sea surface platform is needed. Here, we present an unmanned aerial vehicle (UAV) system developed for GNSS-A surveys capable of landing on the sea surface. Submetre-level seafloor positioning is achieved based on real-time single-frequency GNSS data acquired over an actual site. UAV-based GNSS-A allows high-frequency, near real-time deployment, and low-cost seafloor geodetic observations. This system could be deployed to acquire high-frequency observations with centimetre-scale accuracies when using dual-frequency GNSS.
Longitudinal analysis of long-term outcomes of abdominal flap-based microsurgical reconstruction and two-stage prosthetic reconstruction
Authors: Lee Kyeong-Tae , Kim Jina , Jeon Byung Joon , Pyon Jai Kyong , Bang Sa Ik , Mun Goo-Hyun
Published: March 2023

Two-stage tissue expander/implant (TE/I) and deep inferior epigastric perforator (DIEP) flaps are the two main pillars of breast reconstruction. This study aimed to conduct a longitudinal analysis of long-term outcomes after immediate DIEP- and TE/I-based reconstruction. This retrospective cohort study included patients with breast cancer who underwent immediate DIEP- or TE/I-based reconstruction between 2012 and 2017. The cumulative incidence of major complications, defined as unplanned reoperation/readmission due to complications, was analyzed by the reconstruction modality and its independent association. In total, 1,474 cases (1,162 TE/I and 312 DIEP cases) were analyzed, with a median follow-up of 58 months. The 5-year cumulative incidence of major complications was significantly higher in the TE/I group (10.3% vs. 4.7%). On the multivariable analyses, the use of DIEP flap was associated with a significantly reduced risk of major complications compared to that of TE/I. A more prominent association was observed in the analysis of patients who received adjuvant radiotherapy. Restricting analysis to those who received adjuvant chemotherapy revealed no differences between the two groups. The rate of reoperation/readmission for improving aesthetic outcomes was similar in the two groups. Long-term risks for unexpected reoperation/readmission may differ between DIEP- and TE/I-based immediate reconstruction.
A neural network-based PDE solving algorithm with high precision
Authors: Jiang Zichao , Jiang Junyang , Yao Qinghe , Yang Gengchao
Published: March 2023

The consumption of solving large-scale linear equations is one of the most critical issues in numerical computation. An innovative method is introduced in this study to solve linear equations based on deep neural networks. To achieve a high accuracy, we employ the residual network architecture and the correction iteration inspired by the classic iteration methods. By solving the one-dimensional Burgers equation and the two-dimensional heat-conduction equation, the precision and effectiveness of the proposed method have been proven. Numerical results indicate that this DNN-based technique is capable of obtaining an error of less than 10–7. Moreover, its computation time is less sensitive to the problem size than that of classic iterative methods. Consequently, the proposed method possesses a significant efficiency advantage for large-scale problems.
The relationship between minor coronal asymmetry of the spine and measures of spinal sagittal shape in adolescents without visible scoliosis
Authors: Gardner Adrian , Berryman Fiona , Pynsent Paul
Published: March 2023

The purpose of this work is to identify what features of overall spinal sagittal shape are associated with coronal asymmetry in those without scoliosis. Using a longitudinal analysis of Integrated Shape Imaging System 2 (ISIS2) surface topography images of those without scoliosis, measures of coronal asymmetry, along with measures of spinal sagittal shape (kyphosis, lordosis and sagittal imbalance, which is a measure of the position of the top of the thoracic spine relative to the sacrum) were analysed using linear mixed effect models (LMEM), which is a method of analysing the components of a complex model (such as that describing overall spinal shape), to ascertain the relative relationships between the parameters. Data was also analysed when subdivided for the anatomical level of coronal asymmetry (thoracic or thoracolumbar/lumbar pattern). There were 784 measures from 196 children. Kyphosis had little effect on coronal asymmetry for males and females, lordosis increased with coronal asymmetry in females only and sagittal imbalance increased with coronal asymmetry in males only. The results of the LMEM modelling were that the parameters related to coronal asymmetry were lordosis and sagittal imbalance. In thoracic coronal asymmetry, whilst lordosis was predominant, kyphosis played more of a role. In thoracolumbar/lumbar coronal asymmetry, lordosis and sagittal imbalance were the larger coefficients. Coronal asymmetry of the spine in those without scoliosis is related to features of spinal sagittal shape, particularly lordosis and sagittal imbalance. This knowledge adds to the understanding of the aetiology of adolescent idiopathic scoliosis.
Polyamine-mediated mechanisms contribute to oxidative stress tolerance in Pseudomonas syringae
Authors: Solmi Leandro , Rossi Franco R. , Romero Fernando. M. , Bach-Pages Marcel , Preston Gail M. , Ruiz Oscar A. , Gárriz Andrés
Published: March 2023

Bacterial phytopathogens living on the surface or within plant tissues may experience oxidative stress because of the triggered plant defense responses. Although it has been suggested that polyamines can defend bacteria from this stress, the mechanism behind this action is not entirely understood. In this study, we investigated the effects of oxidative stress on the polyamine homeostasis of the plant pathogen Pseudomonas syringae and the functions of these compounds in bacterial stress tolerance. We demonstrated that bacteria respond to H2O2 by increasing the external levels of the polyamine putrescine while maintaining the inner concentrations of this compound as well as the analogue amine spermidine. In line with this, adding exogenous putrescine to media increased bacterial tolerance to H2O2. Deletion of arginine decarboxylase (speA) and ornithine decarboxylate (speC), prevented the synthesis of putrescine and augmented susceptibility to H2O2, whereas targeting spermidine synthesis alone through deletion of spermidine synthase (speE) increased the level of extracellular putrescine and enhanced H2O2 tolerance. Further research demonstrated that the increased tolerance of the ΔspeE mutant correlated with higher expression of H2O2-degrading catalases and enhanced outer cell membrane stability. Thus, this work demonstrates previously unrecognized connections between bacterial defense mechanisms against oxidative stress and the polyamine metabolism.
Effect of propolis on mood, quality of life, and metabolic profiles in subjects with metabolic syndrome: a randomized clinical trial
Authors: Sajjadi Sana Sadat , Bagherniya Mohammad , Soleimani Davood , Siavash Mansour , Askari Gholamreza
Published: March 2023

Metabolic syndrome (MeS) is a common multifaceted disorder. Plants contain antioxidant bioactive compounds, which are beneficial to improve the health condition of patients with MeS. Propolis is a hive natural product that is composed of various constituent. We aimed to assess the effects of Iranian propolis as a natural and safe agent on indicators of MeS, quality of life and mood status in individuals with MeS. In total, 66 interested eligible patients recruited to the present study. Participants were randomly assigned to consume a tablet at dose of 250 mg of propolis extract, twice daily for 12 weeks or placebo. Propolis supplementation could lead to a significant reduction in waist circumference (WC), increase in physical functioning, general health and the overall score of SF-36 compared with placebo group (P-value < 0.05). However, no significant differences were observed regarding other anthropometric indices and biochemical parameters between two groups (P-value > 0.05). The current study indicated that propolis can be effective in decreasing WC and improving physical health and quality of life, while had no significant effects on other components of MeS among subjects with this syndrome.

Clinical trials registration Iran Registry of Clinical Trials.ir IRCT20121216011763N49, registration date 23/12/2020.
Genetic analysis of allogenic donor cells after successful allo-limbal epithelial transplantation in simple and cultivated limbal epithelial transplantation procedures
Authors: Chotikavanich Suksri , Poriswanish Nitikorn , Luangaram Angkoon , Numnoi Parwana , Thamphithak Ranida , Pinitpuwadol Warinyupa , Uiprasertkul Mongkol , Chirapapaisan Chareenun , Sikarinkul Rosanun , Prabhasawat Pinnita
Published: March 2023

This non-comparative cohort study investigated long-term donor cell survival after allogenic simple/cultivated limbal epithelial transplantations (allo-SLET/allo-CLET, respectively) by genetic analysis. Transplanted corneal epithelial cells, which underwent impression cytology and/or corneal-button biopsy, were examined for personal identities of autosomal short-tandem repeats; the percentages of donor cells were calculated based on matching recipient or donor buccal-DNA references. Twelve patients were included; 4 underwent allo-CLET, 8 underwent allo-SLET. Eight patients (67%) had total limbal stem cell deficiency (LSCD). Genetic analysis was performed postoperatively (mean, 55.3 months). Donor cells were detected in 4 of 12 patients (25%), all of whom underwent allo-SLET; 1 patient had a donor genotype and 3 patients had a mixed donor/recipient genotype. The longest time of donor cell detection was 30 months. Seven patients (58%) used systemic immunosuppressives at the time of genetic analysis (mean use, 22.5 months). Allogenic donor cells survived in both procedures for the long term postoperatively, which encourages the long-term use of systemic immunosuppressives. Donor cells may not be the only factor in graft survival, in that most successful cases had a recipient profile. Their presence for a specific time may promote niches for the patients’ own cells to repopulate, especially for partial LSCD.
Predicting metastasis in gastric cancer patients: machine learning-based approaches
Authors: Talebi Atefeh , Celis-Morales Carlos A. , Borumandnia Nasrin , Abbasi Somayeh , Pourhoseingholi Mohamad Amin , Akbari Abolfazl , Yousefi Javad
Published: March 2023

Gastric cancer (GC), with a 5-year survival rate of less than 40%, is known as the fourth principal reason of cancer-related mortality over the world. This study aims to develop predictive models using different machine learning (ML) classifiers based on both demographic and clinical variables to predict metastasis status of patients with GC. The data applied in this study including 733 of GC patients, divided into a train and test groups at a ratio of 8:2, diagnosed at Taleghani tertiary hospital. In order to predict metastasis in GC, ML-based algorithms, including Naive Bayes (NB), Random Forest (RF), Support Vector Machine (SVM), Neural Network (NN), Decision Tree (RT) and Logistic Regression (LR), with 5-fold cross validation were performed. To assess the model performance, F1 score, precision, sensitivity, specificity, area under the curve (AUC) of receiver operating characteristic (ROC) curve and precision-recall AUC (PR-AUC) were obtained. 262 (36%) experienced metastasis among 733 patients with GC. Although all models have optimal performance, the indices of SVM model seems to be more appropiate (training set: AUC: 0.94, Sensitivity: 0.94; testing set: AUC: 0.85, Sensitivity: 0.92). Then, NN has the higher AUC among ML approaches (training set: AUC: 0.98; testing set: AUC: 0.86). The RF of ML-based models, which determine size of tumor and age as two essential variables, is considered as the third efficient model, because of higher specificity and AUC (84% and 87%). Based on the demographic and clinical characteristics, ML approaches can predict the metastasis status in GC patients. According to AUC, sensitivity and specificity in both SVM and NN can be regarded as better algorithms among 6 applied ML-based methods.
Ecological drivers of breeding periodicity in four forest neotropical eagles
Authors: Blank Marcel Henrique , Guimarães Jr Paulo Roberto , do Nascimento Lucas Ferreira , Pereira Ricardo Jose Garcia
Published: March 2023

We explore the potential factors that affect clutch initiation in four Neotropical large raptors (Harpy eagle—HE, Crested eagle—CE, Ornate hawk-eagle—OHE, and Black hawk-eagle—BHE) by analyzing 414 clutch events mostly obtained from captive individuals. Differences in how clutch initiation is associated with changes in photoperiod were found between HE and both hawk-eagles, and between CE and BHE. Changes in temperature at the time of clutch initiation only differed between HE and OHE, whereas changes in precipitation varied between BHE and all other species. Principal Component Analysis of these environmental cues showed that ellipses in the dataset of each species overlap, but only ellipses from CE and OHE had the same variation trends. This means that although these species live under similar ecological conditions, they exhibit three different patterns of response to environmental cues. Apparently, these patterns are not associated with phylogenetic relatedness because species belonging to the same clade do not show the same response pattern. Diet diversity analysis revealed that HE has the least varied diet, and CE and OHE the most varied diet. The fact that species who fit the same reproductive timing response to environmental cues show similar diets leads us to hypothesize that breeding in these eagles was most likely shaped by food availability.
DNA methyltransferase inhibition induces dynamic gene expression changes in lung CD4+ T cells of neonatal mice with E. coli pneumonia
Authors: Michki Nigel S. , Ndeh Roland , Helmin Kathryn A. , Singer Benjamin D. , McGrath-Morrow Sharon A.
Published: March 2023

Bacterial pulmonary infections are a major cause of morbidity and mortality in neonates, with less severity in older children. Previous studies demonstrated that the DNA of CD4+T cells in the mouse lung, whose primary responsibility is to coordinate the immune response to foreign pathogens, is differentially methylated in neonates compared with juveniles. Nevertheless, the effect of this differential DNA methylation on CD4+T cell gene expression and response to infection remains unclear. Here we treatedE. coli-infected neonatal (4-day-old) and juvenile (13-day-old) mice with decitabine (DAC), a DNA methyltransferase inhibitor with broad-spectrum DNA demethylating activity, and performed simultaneous genome-wide DNA methylation and transcriptional profiling on lung CD4+T cells. We show that juvenile and neonatal mice experienced differential demethylation in response to DAC treatment, with larger methylation differences observed in neonates. By cross-filtering differentially expressed genes between juveniles and neonates with those sites that were demethylated in neonates, we find that interferon-responsive genes such asIfit1are the most down-regulated methylation-sensitive genes in neonatal mice. DAC treatment shifted neonatal lung CD4+T cells toward a gene expression program similar to that of juveniles. Following lung infection withE. coli, lung CD4+T cells in neonatal mice exhibit epigenetic repression of important host defense pathways, which are activated by inhibition of DNA methyltransferase activity to resemble a more mature profile.
CRISPR-Cas9 editing of TLR4 to improve the outcome of cardiac cell therapy
Authors: Schary Yeshai , Rotem Itai , Caller Tal , Lewis Nir , Shaihov-Teper Olga , Brzezinski Rafael Y. , Lendengolts Daria , Raanani Ehud , Sternik Leonid , Naftali-Shani Nili , Leor Jonathan
Published: March 2023

Inflammation and fibrosis limit the reparative properties of human mesenchymal stromal cells (hMSCs). We hypothesized that disrupting the toll-like receptor 4 (TLR4) gene would switch hMSCs toward a reparative phenotype and improve the outcome of cell therapy for infarct repair. We developed and optimized an improved electroporation protocol for CRISPR-Cas9 gene editing. This protocol achieved a 68% success rate when applied to isolated hMSCs from the heart and epicardial fat of patients with ischemic heart disease. While cell editing lowered TLR4 expression in hMSCs, it did not affect classical markers of hMSCs, proliferation, and migration rate. Protein mass spectrometry analysis revealed that edited cells secreted fewer proteins involved in inflammation. Analysis of biological processes revealed that TLR4 editing reduced processes linked to inflammation and extracellular organization. Furthermore, edited cells expressed less NF-ƙB and secreted lower amounts of extracellular vesicles and pro-inflammatory and pro-fibrotic cytokines than unedited hMSCs. Cell therapy with both edited and unedited hMSCs improved survival, left ventricular remodeling, and cardiac function after myocardial infarction (MI) in mice. Postmortem histologic analysis revealed clusters of edited cells that survived in the scar tissue 28 days after MI. Morphometric analysis showed that implantation of edited cells increased the area of myocardial islands in the scar tissue, reduced the occurrence of transmural scar, increased scar thickness, and decreased expansion index. We show, for the first time, that CRISPR-Cas9-based disruption of the TLR4-gene reduces pro-inflammatory polarization of hMSCs and improves infarct healing and remodeling in mice. Our results provide a new approach to improving the outcomes of cell therapy for cardiovascular diseases.
Optimization of Parylene C and Parylene N thin films for use in cellular co-culture and tissue barrier models
Authors: Gholizadeh Shayan , Lincoln Daniela M. , Allahyari Zahra , Widom Louis P. , Carter Robert N. , Gaborski Thomas R.
Published: March 2023

Parylene has been used widely used as a coating on medical devices. It has also been used to fabricate thin films and porous membranes upon which to grow cells. Porous membranes are integral components of in vitro tissue barrier and co-culture models, and their interaction with cells and tissues affects the performance and physiological relevance of these model systems. Parylene C and Parylene N are two biocompatible Parylene variants with potential for use in these models, but their effect on cellular behavior is not as well understood as more commonly used cell culture substrates, such as tissue culture treated polystyrene and glass. Here, we use a simple approach for benchtop oxygen plasma treatment and investigate the changes in cell spreading and extracellular matrix deposition as well as the physical and chemical changes in material surface properties. Our results support and build on previous findings of positive effects of plasma treatment on Parylene biocompatibility while showing a more pronounced improvement for Parylene C compared to Parylene N. We measured relatively minor changes in surface roughness following plasma treatments, but significant changes in oxygen concentration at the surface persisted for 7 days and was likely the dominant factor in improving cellular behavior. Overall, this study offers facile and relatively low-cost plasma treatment protocols that provide persistent improvements in cell-substrate interactions on Parylene that match and exceed tissue culture polystyrene.
Effects of endovascular recanalization on symptomatic non-acute occlusion of intracranial arteries
Authors: Xia Jinchao , Gao Huili , Zhang Kun , Gao Bulang , Li Tianxiao , Wang Ziliang
Published: March 2023

To investigate the effect and safety of recanalization surgery for non-acute occlusion of large intracranial arteries and factors affecting clincial outcomes. Patients with non-acute occlusion of internal carotid artery (ICA), middle cerebral artery (MCA), and vertebrobasilar artery (VBA) treated with recanalization were retrospectively enrolled. The clinical and angiographic data were analyzed. 177 patients were enrolled, including 67 patients with intracranial ICA occlusion, 52 with MCA occlusion, and 58 with VBA occlusion. Successful recanalization was achieved in 152 (85.9%) patients. Complications occurred in 15 patients (8.5%). Followed up for 3–7 months, the 90 day mRS was significantly improved compared with that before the procedure. Among 152 patients with successful recanalization, eight patients experienced reocclusion (5.3%), and 11 patients experienced restenosis (7.2%). Successful recanalization was significantly (P < 0.05) associated with occlusion duration, calcification or angulation of the occluded segment. Complications were significantly (P < 0.05) associated with location of occlusion, hyperlipidemia, and patients’ height. Restentosis or reocclusion at follow-up was significantly (P < 0.05) associated with complications and mRS at 90 days. The significant (P < 0.05) independent risk factors were angulation and calcification for successful recanalization, hyperlipidemia for complications, and mRS at 90 days for restenosis or reocclusion at follow-up. Recanalization surgery may be a safe and effective approach for patients with non-acute symptomatic occlusion of large intracranial arteries, and factors significantly independently associated with successful recanalization, periprocedural complications and restenosis or reocclusion after surgery have been identified for future reference to improve clinical outcomes.
Downregulation of PSAT1 inhibits cell proliferation and migration in uterine corpus endometrial carcinoma
Authors: Wang Min , Yue Song , Yang Zhu
Published: March 2023

Phosphoserine aminotransferase 1 (PSAT1) has been associated with the occurrence and development of various carcinomas; however, its function in uterine corpus endometrial carcinoma (UCEC) is unknown. We aimed to explore the relationship between PSAT1 and UCEC using The Cancer Genome Atlas database and functional experiments. PSAT1 expression levels in UCEC were employed using the paired sample t-test, Wilcoxon rank-sum test, the Clinical Proteomic Tumor Analysis Consortium database, and the Human Protein Atlas database, while survival curves were constructed using the Kaplan–Meier plotter. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to explore the possible functions and related pathways of PSAT1. Furthermore, single-sample gene set enrichment analysis was performed to detect the relationship between PSAT1 and tumor immune infiltration. StarBase and quantitative PCR were used to predict and verify the interactions between miRNAs and PSAT1. The Cell Counting Kit-8, EdU assay, clone formation assay, western blotting and flow cytometry were used to evaluate cell proliferation. Finally, Transwell and Wound healing assays were used to assess cell invasion and migration. Our study found that PSAT1 was significantly overexpressed in UCEC, and this high expression was associated with a worse prognosis. A high level of PSAT1 expression was associated with a late clinical stage and, histological type. In addition, the results of GO and KEGG enrichment analysis showed that PSAT1 was mainly involved in the regulation of cell growth, immune system and cell cycle in UCEC. In addition, PSAT1 expression was positively correlated with Th2 cells and negatively correlated with Th17 cells. Furthermore, we also found that miR-195-5P negatively regulated the expression of PSAT1 in UCEC. Finally, the knockdown of PSAT1 resulted in the inhibition of cell proliferation, migration, and invasion in vitro. Overall, PSAT1 was identified as a potential target for the diagnosis and immunotherapy of UCEC.
Metal-tolerant and siderophore producing Pseudomonas fluorescence and Trichoderma spp. improved the growth, biochemical features and yield attributes of chickpea by lowering Cd uptake
Authors: Syed Asad , Elgorban Abdallah M. , Bahkali Ali H. , Eswaramoorthy Rajalakshmanan , Iqbal Rana Khalid , Danish Subhan
Published: March 2023

Industrialization and human urbanization have led to an increase in heavy metal (HM) pollution which often cause negative/toxic effect on agricultural crops. The soil-HMs cannot be degraded biologically however, microbe-mediated detoxification of toxic HMs into lesser toxic forms are reported. Considering the potentiality of HMs-tolerant soil microbes in metal detoxification, Pseudomonas fluorescence PGPR-7 and Trichoderma sp. T-4 were recovered from HM-affected areas. Under both normal and cadmium stress, the ability of both microorganisms to produce different plant hormones and biologically active enzymes was examined. Strains PGPR-7 and T-4 tolerated cadmium (Cd) an up-to 1800 and 2000 µg mL−1, respectively, and produced various plant growth regulating substances (IAA, siderophore, ACC deaminase ammonia and HCN) in Cd-stressed condition. The growth promoting and metal detoxifying ability of both strains were evaluated (either singly/combined) by applying them in chickpea (Cicer arietinum L.) plants endogenously contaminated with different Cd levels (0–400 µg kg−1 soils). The higher Cd concentration (400 µg kg−1 soils) negatively influenced the plant parameters which, however, improved following single/combined inoculation of P. fluorescence PGPR-7 and Trichoderma sp. T-4. Both microbial strains increased the growth of Cd-treated chickpeas however, their combined inoculation (PGPR-7 + T-4) caused the most positive effect. For instance, 25 µg Cd Kg−1 + PGPR-7 + T4 treatment caused maximum increase in germination percentage (10%), root dry biomass (71.4%) and vigour index (33%), chl-a (38%), chl-b (41%) and carotenoid content (52%). Furthermore, combined inoculation of P. fluorescence PGPR-7 and Trichoderma sp. T-4 maximally decreased the proline, MDA content, POD and CAT activities by 50%, 43% and 62%, respectively following their application in 25 µg Cd kg−1 soils-treated chickpea. Additionally, microbial strains lowered the plant uptake of Cd. For example, Cd-uptake in root tissues was decreased by 42 and 34% when 25 µg Cd Kg−1- treated chickpea plants were inoculated with P. fluorescence PGPR-7, Trichoderma sp. T-4 and co-inoculation (PGPR-7 + T4) of both strains, respectively. Therefore, from the current observation, it is suggested that dual inoculation of metal tolerant P. fluorescence and Trichoderma sp. may potentially be used in detoxification and reclamation of metal-contaminated soils.
Exploring the potential of artificial intelligence in improving skin lesion diagnosis in primary care
Authors: Escalé-Besa Anna , Yélamos Oriol , Vidal-Alaball Josep , Fuster-Casanovas Aïna , Miró Catalina Queralt , Börve Alexander , Ander-Egg Aguilar Ricardo , Fustà-Novell Xavier , Cubiró Xavier , Rafat Mireia Esquius , López-Sanchez Cristina , Marin-Gomez Francesc X.
Published: March 2023

Dermatological conditions are a relevant health problem. Machine learning (ML) models are increasingly being applied to dermatology as a diagnostic decision support tool using image analysis, especially for skin cancer detection and disease classification. The objective of this study was to perform a prospective validation of an image analysis ML model, which is capable of screening 44 skin diseases, comparing its diagnostic accuracy with that of General Practitioners (GPs) and teledermatology (TD) dermatologists in a real-life setting. Prospective, diagnostic accuracy study including 100 consecutive patients with a skin problem who visited a participating GP in central Catalonia, Spain, between June 2021 and October 2021. The skin issue was first assessed by the GPs. Then an anonymised skin disease picture was taken and uploaded to the ML application, which returned a list with the Top-5 possible diagnosis in order of probability. The same image was then sent to a dermatologist via TD for diagnosis, as per clinical practice. The GPs Top-3, ML model’s Top-5 and dermatologist’s Top-3 assessments were compared to calculate the accuracy, sensitivity, specificity and diagnostic accuracy of the ML models. The overall Top-1 accuracy of the ML model (39%) was lower than that of GPs (64%) and dermatologists (72%). When the analysis was limited to the diagnoses on which the algorithm had been explicitly trained (n = 82), the balanced Top-1 accuracy of the ML model increased (48%) and in the Top-3 (75%) was comparable to the GPs Top-3 accuracy (76%). The Top-5 accuracy of the ML model (89%) was comparable to the dermatologist Top-3 accuracy (90%). For the different diseases, the sensitivity of the model (Top-3 87% and Top-5 96%) is higher than that of the clinicians (Top-3 GPs 76% and Top-3 dermatologists 84%) only in the benign tumour pathology group, being on the other hand the most prevalent category (n = 53). About the satisfaction of professionals, 92% of the GPs considered it as a useful diagnostic support tool (DST) for the differential diagnosis and in 60% of the cases as an aid in the final diagnosis of the skin lesion. The overall diagnostic accuracy of the model in this study, under real-life conditions, is lower than that of both GPs and dermatologists. This result aligns with the findings of few existing prospective studies conducted under real-life conditions. The outcomes emphasize the significance of involving clinicians in the training of the model and the capability of ML models to assist GPs, particularly in differential diagnosis. Nevertheless, external testing in real-life conditions is crucial for data validation and regulation of these AI diagnostic models before they can be used in primary care.
Paleo-biodegradation and hydrocarbon mixing in a major hybrid petroleum reservoir
Authors: Cesar Jaime , Ardakani Omid H. , Watt Elizabeth , Song Yishu , Kingston Andrew , Ahad Jason M. E.
Published: March 2023

Some of the parental material for hydrocarbons produced from low-permeability reservoirs in Western Canada corresponds to thermal products from biodegraded oil. This has been proved by the occurrence of framboidal pyrite, which is often formed during microbial sulfate reduction (MSR). In addition, the identified pyrite framboids are associated with the presence of phosphorus (P). Phosphorus (as phosphate) is a key nutrient and energy carrier for sulfate-reducing bacteria. The pyrite-P assemblage occurs embedded in solid bitumen (thermal residue), which confirms that migrated hydrocarbons provided the environment for microbial growth. Molecular products of severe biodegradation such as 17-nortricyclic terpanes were also detected. Biodegradation effects have been masked not only by thermal degradation of biodegraded oil during maximum burial, but also due to hydrocarbon mixing with late gas-condensate charges. Suitable conditions for biodegradation (< 80 °C, basin uplift) occurred during the Early Cretaceous. The confirmation of paleo-biodegradation means that there was a significant hydrocarbon loss that we have not accounted for. Likewise, MSR and Early Cretaceous seawater sulfate might have played an important role in the generation of the hydrogen sulfide (H2S) detected today.
A novel natural scaffold layer improving efficiency, stability and reproducibility of Perovskite solar cells
Authors: Yenel Esma , Kus Mahmut
Published: March 2023

In this study, our hypothesis was to demonstrate the usability of a natural clay structure as scaffold layer in perovskite solar cells (PSCs). Sepiolite, which is a natural and environmentally friendly clay structure, has a very high active surface area and can easily be dispersed in solvents. In addition we predicted that crystallization could easily occur on their surfaces due to their surface chemistry. In the study, we firstly used a natural clay as scaffold layer in PSCs. It is observed that, efficiency, reproducibility and stability of PSCs have been significantly improved. Improvements in efficiency have been observed to be between 30 and 50% depending on the type of perovskite solvent used. In addition, the surface chemistry of the sepiolite resulted in better crystallization as well as stability. Due to its high-water adsorption capability, sepiolite makes the perovskite crystal more stable by trapping the residual water molecules as well as penetrated water molecules from environment. Consequently, we demonstrated that, a natural, low-cost and environmentally friendly clay may be an alternative material which may contribute to the commercialization of PSCs.
Effects of Thymbra capitata essential oil on in vitro fermentation end-products and ruminal bacterial communities
Authors: Ranilla María José , Andrés Sonia , Gini Chiara , Biscarini Filippo , Saro Cristina , Martín Alba , Mateos Iván , López Secundino , Giráldez F. Javier , Abdennebi-Najar Latifa , Pereira David , Falleh Hanen , Ksouri Riadh , Cremonesi Paola , Castiglioni Bianca , Ceciliani Fabrizio
Published: March 2023

An in vitro trial was carried out to investigate the effects of natural Thymbra capitata essential oil (NEO) and its main compounds [including carvacrol, p-cymene, γ-terpinene given alone or in a synthetic combination (SEO)] on ruminal fermentation and the bacterial community using batch cultures inoculated with ruminal digesta and incubating two different basal diets [high-forage (F) and high-concentrate (C) diet]. After 24 h of incubation, primary fermentation end-products [gas, methane, volatile fatty acids (VFAs) and ammonia] and rumen microbial diversity were determined. NEO reduced the total VFA concentration (P < 0.05) only in the C diet. In contrast, SEO and carvacrol decreased the total VFA concentration (P < 0.05) only in the F diet. Methane production was not affected (P > 0.05) by any of the experimental treatments or diets evaluated. Microbial diversity analysis showed only a moderate effect of carvacrol and SEO on 13 genera, including, mainly, Atopobium and Blautia (involved in subacute ruminal acidosis) or Candidatus Saccharimonas (related to laminitis). In conclusion, T. capitata EO has a limited potential to attain nutritional or environmental benefits, but further research should be carried out to clarify its effects on animal health and microbial food safety.
Effects of social deprivation on risk factors for suicidal ideation and suicide attempts in commercially insured US youth and adults
Authors: Xi Wenna , Banerjee Samprit , Olfson Mark , Alexopoulos George S. , Xiao Yunyu , Pathak Jyotishman
Published: March 2023

We used US nationwide commercial insurance claims data (2011–2015) to study the effect of social deprivation on clinical and demographic risk factors for suicidal ideation (SI) and suicide attempts (SA) among US youth and adults < 65 years, after having a mental health or substance use disorder-related outpatient encounter. Neighborhood social deprivation level was summarized by the quintile of social deprivation index (SDI) at individuals’ zip code level. Cox proportional hazard models were used to evaluate the effect of social deprivation on demographic and clinical risk factors for SI and SA. The study cohort consisted of 317,383 individuals < 65 years, with 124,424 aged < 25 (youth) and 192,959 aged between 25 and 64 (adults). Neighborhood social deprivation impacted risk factors for SI and SA differently for youth and adults. Among youth, SDI interacted with multiple risk factors for both SI and SA. The effects of the risk factors were larger on youth from middle socioeconomic neighborhoods. Among adults, risk of SI was the strongest in the most deprived neighborhoods, but risk of SA did not vary by neighborhood deprivation level. Our findings suggest community-based suicide prevention initiatives should be tailored according to neighborhood deprivation level and the targeted individual’s age to maximize the impact.
Inoculation with black soldier fly larvae alters the microbiome and volatile organic compound profile of decomposing food waste
Authors: Michishita Rena , Shimoda Masami , Furukawa Seiichi , Uehara Takuya
Published: March 2023

The black soldier fly (BSF; Hermetia illucens) is used in sustainable processing of many types of organic waste. However, organic waste being decomposed by BSF produces strong odors, hindering more widespread application. The odor components and how they are produced have yet to be characterized. We found that digestion of food waste by BSF significantly alters the microbial flora, based on metagenomic analyses, and the odor components generated, as shown by thermal desorption gas chromatography mass spectrometry analysis. Inoculation with BSF significantly decreased production of volatile organic sulfur compounds (dimethyl disulfide and dimethyl trisulfide), which are known to be released during methionine and cysteine metabolism by Lactobacillus and Enterococcus bacteria. BSF inoculation significantly changed the abundance of Lactobacillus and Enterococcus and decreased microbial diversity overall. These findings may help in optimizing use of BSF for deodorization of composting food waste.