Miracle-dz/UniFAR-FTUs huggingface dataset:
Carbamazepine Increases the Risk of Sudden Cardiac Arrest by a Reduction of the Cardiac Sodium Current

Aim: To assess the risk of sudden cardiac arrest (SCA) associated with the use of carbamazepine (CBZ) and establish the possible underlying cellular electrophysiological mechanisms. Methods: The SCA risk association with CBZ was studied in general population cohorts using a case–control design (n = 5,473 SCA cases, 21,866 non-SCA controls). Effects of 1–100 µM CBZ on action potentials (APs) and individual membrane currents were determined in isolated rabbit and human cardiomyocytes using the patch clamp technique. Results: CBZ use was associated with increased risk of SCA compared with no use (adjusted odds ratio 1.90 [95% confidence interval: 1.12–3.24]). CBZ reduced the AP upstroke velocity of rabbit and human cardiomyocytes, without prominent changes in other AP parameters. The reduction occurred at ≥30 µM and was frequency-dependent with a more pronounced reduction at high stimulus frequencies. The cardiac sodium current (INa) was reduced at ≥30 μM; this was accompanied by a hyperpolarizing shift in the voltage-dependency of inactivation. The recovery from inactivation was slower, which is consistent with the more pronounced AP upstroke velocity reduction at high stimulus frequencies. The main cardiac K+ and Ca2+ currents were unaffected, except reduction of L-type Ca2+ current by 100 µM CBZ. Conclusion: CBZ use is associated with an increased risk of SCA in the general population. At concentrations of 30 µM and above, CBZ reduces AP upstroke velocity and INa in cardiomyocytes. Since the concentration of 30 µM is well within the therapeutic range (20–40 µM), we conclude that CBZ increases the risk of SCA by a reduction of the cardiac INa.
PCOS and Role of Cumulus Gene Expression in Assessing Oocytes Quality

The global infertility rate has been declining from year to year. PCOS is one of the treatable accountable causes contributing to anovulatory infertility. Nevertheless, the success rate of treatments and live-birth outcomes especially involving assisted reproductive techniques is still not very promising. There is a reduction in the development potential of oocytes and high-quality embryos in PCOS patients compared to non-PCOS patients. A critical step in IVF treatment is the assessment of oocyte and embryo competence before embryo transfer. Oocytes in metaphase II are very fragile. Repeated morphological assessment on these oocytes may directly impair the quality and affect the whole process. Identification of potential biomarkers especially in the cumulus cells oocytes complex will help to predict the outcome and may create space for improvement. This review has explored gene expression in cumulus cells with regards to oocytes quality in both normal and PCOS women. The gene expression was classified according to their physiological function such as the contribution on cumulus expansion, cumulus cells apoptosis, and glucose metabolism. Collectively, the review suggested that positive expression of HAS2, PTX3, GREM1, and VCAN may correlate with good quality oocytes and can be used as an indicator among PCOS women.
Research Review of the Knowledge Graph and its Application in Power System Dispatching and Operation

With the construction of a new power system and the proposal of a double carbon goal, power system operation data are growing explosively, and the optimization of power system dispatching operation is becoming more and more complex. Relying on traditional pure manual dispatching is difficult to meet the dispatching needs. The emerging knowledge graph technology in the field of the artificial intelligence technology is one of the effective methods to solve this problem. Because the topological structure of the power system itself is consistent with the relational structure of graph theory, through the establishment of a relevant knowledge graph, the real operating state of the power system can be restored to the maximum extent by effectively preserving the correlation implicit in the data. Meanwhile, expressing the hidden knowledge in the power system dispatching operation in the form of a knowledge graph has become the focus of research at home and abroad. This study summarizes the development of the knowledge graph technology from the aspects of knowledge extraction, knowledge representation learning, knowledge mining, knowledge reasoning, knowledge fusion, and the application of knowledge graph and introduces the application and prospect of knowledge graph in the power system dispatching operation from the aspects of the auxiliary optimization decision, vertical risk control, operation mode analysis, optimization model improvement experience, and super regulation parameters.
Coupling Imaging and Omics in Plankton Surveys: State-of-the-Art, Challenges, and Future Directions

A major challenge in characterizing plankton communities is the collection, identification and quantification of samples in a time-efficient way. The classical manual microscopy counts are gradually being replaced by high throughput imaging and nucleic acid sequencing. DNA sequencing allows deep taxonomic resolution (including cryptic species) as well as high detection power (detecting rare species), while RNA provides insights on function and potential activity. However, these methods are affected by database limitations, PCR bias, and copy number variability across taxa. Recent developments in high-throughput imaging applied in situ or on collected samples (high-throughput microscopy, Underwater Vision Profiler, FlowCam, ZooScan, etc) has enabled a rapid enumeration of morphologically-distinguished plankton populations, estimates of biovolume/biomass, and provides additional valuable phenotypic information. Although machine learning classifiers generate encouraging results to classify marine plankton images in a time efficient way, there is still a need for large training datasets of manually annotated images. Here we provide workflow examples that couple nucleic acid sequencing with high-throughput imaging for a more complete and robust analysis of microbial communities. We also describe the publicly available and collaborative web application EcoTaxa, which offers tools for the rapid validation of plankton by specialists with the help of automatic recognition algorithms. Finally, we describe how the field is moving with citizen science programs, unmanned autonomous platforms with in situ sensors, and sequencing and digitalization of historical plankton samples.
Hematopoietic Stem Cell-Derived Adipocytes Modulate Adipose Tissue Cellularity, Leptin Production and Insulin Responsiveness in Female Mice

A subpopulation of adipocytes in the major adipose depots of mice is produced from hematopoietic stem cells rather than mesenchymal progenitors that are the source of conventional white and brown/beige adipocytes. To analyze the impact of hematopoietic stem cell-derived adipocytes (HSCDAs) in the adipose niche we transplanted HSCs in which expression of a diphtheria toxin gene was under the control of the adipocyte-specific adiponectin gene promoter into irradiated wild type recipients. Thus, only adipocytes produced from HSC would be ablated while conventional white and brown adipocytes produced from mesenchymal progenitor cells would be spared. Wild type mice transplanted with HSCs from mice containing a reporter gene, but not the diphtheria toxin gene, regulated by the adiponectin gene promoter served as controls. In mice in which HSCDA production was suppressed, adipocyte size declined while adipose depot weights were unchanged and the number of conventional adipocyte progenitors significantly increased. We also measured a paradoxical increase in circulating leptin levels while physical activity was significantly decreased in the HSCDA depleted mice. Finally, insulin sensitivity was significantly reduced in HSCDA depleted mice. In contrast, loss of HSCDA production had no effect on body weight, components of energy balance, or levels of several circulating adipokines and tissue-resident inflammatory cells. These data indicate that ablation of this low-abundance subpopulation of adipocytes is associated with changes in circulating leptin levels and leptin-regulated endpoints associated with adipose tissue function. How they do so remains a mystery, but our results highlight the need for additional studies to explore the role of HSCDAs in other physiologic contexts such as obesity, metabolic dysfunction or loss of sex hormone production.
Hepatitis C Co-infection in People Living With HIV—Epidemiologic Differences Between Men Who Have Sex With Men MSM and Non-MSM

People living with human immunodeficiency virus (PLHIV) constitute a unique group at higher risk of hepatitis C virus (HCV) co-infection. In light of the diverse profiles of PLHIV, we differentiated between men who have sex with men (MSM) and non-MSM in the characterization of the epidemiologic features of HIV/HCV co-infection. Clinical data of HCV co-infection patients from the HIV specialist clinic in Hong Kong were retrospectively collected in conjunction with their HIV subtypes and HCV genotypes. Logistic regression models were used to identify factors associated with HIV/HCV co-infection in MSM. Survival analysis was performed to compare the time lag between HIV and HCV diagnoses between two groups. Latent class analysis was conducted to describe the features of different classes of co-infections. Four classes of HIV/HCV co-infections were identified: local MSM acquiring HCV after HIV diagnosis, local MSM with HIV/HCV co-diagnoses, local non-MSM, and non-local non-MSM. Accounting for over half of the co-infections, MSM were more likely to be younger, local residents, and associated with HCV genotype 3, compared to genotypes 1 and 6 in non-MSM. Overall, MSM had higher odds of achieving HIV viral suppression and co-diagnosing with a sexually transmitted infection at HCV diagnosis, and having a longer time lag between HIV and HCV diagnoses. Drug injection accounted for a majority of non-MSM HCV infection. There were distinctive epidemiologic differences between MSM and non-MSM co-infected with HIV and HCV, the characteristics of which could inform intervention strategies for achieving HCV micro-elimination.
Long Noncoding RNA and Circular RNA: Two Rising Stars in Regulating Epithelial-Mesenchymal Transition of Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with especially poor prognosis. However, the molecular mechanisms of pancreatic oncogenesis and malignant progression are not fully elucidated. Epithelial-mesenchymal transition (EMT) process is important to drive pancreatic carcinogenesis. Recently, long noncoding RNAs (lncRNAs) and circular RNAs(circRNAs) have been characterized to participate in EMT in PDAC, which can affect the migration and invasion of tumor cells by playing important roles in epigenetic processes, transcription, and post-transcriptional regulation. LncRNAs can act as competing endogenous RNAs (ceRNA) to sequester target microRNAs(miRNAs), bind to the genes which localize physically nearby, and directly interact with EMT-related proteins. Currently known circRNAs mostly regulate the EMT process in PDAC also by acting as a miRNA sponge, directly affecting the protein degradation process. Therefore, exploring the functions of lncRNAs and circRNAs in EMT during pancreatic cancer might help pancreatic cancer treatments.
Microbial Community Structure Is Most Strongly Associated With Geographical Distance and pH in Salt Lake Sediments

Salt lakes are globally significant microbial habitats, hosting substantial novel microbial diversity and functional capacity. Extremes of salinity and pH both pose major challenges for survival of microbial life in terrestrial and aquatic environments, and are frequently cited as primary influences on microbial diversity across a wide variety of environments. However, few studies have attempted to identify spatial and geochemical contributions to microbial community composition, functional capacity, and environmental tolerances in salt lakes, limiting exploration of novel halophilic and halotolerant microbial species and their potential biotechnological applications. Here, we collected sediment samples from 16 salt lakes at pH values that ranged from pH 4 to 9, distributed across 48,000 km2 of the Archaean Yilgarn Craton in southwestern Australia to identify associations between environmental factors and microbial community composition, and used a high throughput culturing approach to identify the limits of salt and pH tolerance during iron and sulfur oxidation in these microbial communities. Geographical distance between lakes was the primary contributor to variation in microbial community composition, with pH identified as the most important geochemical contributor to variation in microbial community composition. Microbial community composition split into two clear groups by pH: Bacillota dominated microbial communities in acidic saline lakes, whereas Euryarchaeota dominated microbial communities in alkaline saline lakes. Iron oxidation was observed at salinities up to 160 g L–1 NaCl at pH values as low as pH 1.5, and sulfur oxidation was observed at salinities up to 160 g L–1 NaCl between pH values 2–10, more than doubling previously observed tolerances to NaCl salinity amongst cultivable iron and sulfur oxidizers at these extreme pH values. OTU level diversity in the salt lake microbial communities emerged as the major indicator of iron- and sulfur-oxidizing capacity and environmental tolerances to extremes of pH and salinity. Overall, when bioprospecting for novel microbial functional capacity and environmental tolerances, our study supports sampling from remote, previously unexplored, and maximally distant locations, and prioritizing for OTU level diversity rather than present geochemical conditions.
Evaluating 12 Years of Implementing a Multidisciplinary Specialist Child and Adolescent Obesity Treatment Service: Patient-Level Outcomes

Introduction Childhood obesity is a chronic disease that requires multidisciplinary and specialist intervention to address its complex pathophysiology, though access to treatment is limited globally. Evaluating the impact of evidence-based interventions implemented in real-world clinical settings is essential, in order to increase the translation of research into practice and enhance child health outcomes. In Ireland, the National Model of Care for Obesity highlighted the need to develop and improve healthcare services for children and adolescents with obesity. Aims This study aims to evaluate the impact of a family-based, Tier 3 multi-disciplinary child and adolescent obesity outpatient service (www.w82go.ie) on standardized body mass index (BMI-SDS). Methods Following referral by pediatricians, patients were assessed by a pediatric multidisciplinary team (physiotherapist, dietician, and psychologist) and personalized obesity treatment plans were developed. Anthropometric and demographic information were recorded at baseline and final visit. Descriptive statistics were used to explore distribution, central tendency and variation in the demographic data, change in BMI-SDS over time was assessed using a t-test, and multiple linear regression analysis was used to investigate the association of demographic factors on the change in BMI-SDS. Results The overall mean BMI-SDS reduction across the whole cohort (n = 692) was −0.17 (95% CI = −0.20, −0.13; P < 0.001). Younger age at admission and longer duration of treatment were associated with greater BMI-SDS reduction but there was no significant association between change in BMI-SDS and any of the other parameters (deprivation score, treatment type, sex, obesity category at admission or presence of comorbid condition). Conclusion Engagement in a specialist Tier 3 pediatric obesity service was associated with reductions in BMI-SDS in children and adolescents with obesity.
Assessing Neurokinematic and Neuromuscular Connectivity During Walking Using Mobile Brain-Body Imaging

Gait is a common but rather complex activity that supports mobility in daily life. It requires indeed sophisticated coordination of lower and upper limbs, controlled by the nervous system. The relationship between limb kinematics and muscular activity with neural activity, referred to as neurokinematic and neuromuscular connectivity (NKC/NMC) respectively, still needs to be elucidated. Recently developed analysis techniques for mobile high-density electroencephalography (hdEEG) recordings have enabled investigations of gait-related neural modulations at the brain level. To shed light on gait-related neurokinematic and neuromuscular connectivity patterns in the brain, we performed a mobile brain/body imaging (MoBI) study in young healthy participants. In each participant, we collected hdEEG signals and limb velocity/electromyography signals during treadmill walking. We reconstructed neural signals in the alpha (8–13 Hz), beta (13–30 Hz), and gamma (30–50 Hz) frequency bands, and assessed the co-modulations of their power envelopes with myogenic/velocity envelopes. Our results showed that the myogenic signals have larger discriminative power in evaluating gait-related brain-body connectivity with respect to kinematic signals. A detailed analysis of neuromuscular connectivity patterns in the brain revealed robust responses in the alpha and beta bands over the lower limb representation in the primary sensorimotor cortex. There responses were largely contralateral with respect to the body sensor used for the analysis. By using a voxel-wise analysis of variance on the NMC images, we revealed clear modulations across body sensors; the variability across frequency bands was relatively lower, and below significance. Overall, our study demonstrates that a MoBI platform based on hdEEG can be used for the investigation of gait-related brain-body connectivity. Future studies might involve more complex walking conditions to gain a better understanding of fundamental neural processes associated with gait control, or might be conducted in individuals with neuromotor disorders to identify neural markers of abnormal gait.
Chimeric Antigen Receptor (CAR) Regulatory T-Cells in Solid Organ Transplantation

Solid organ transplantation is the treatment of choice for various end-stage diseases, but requires the continuous need for immunosuppression to prevent allograft rejection. This comes with serious side effects including increased infection rates and development of malignancies. Thus, there is a clinical need to promote transplantation tolerance to prevent organ rejection with minimal or no immunosuppressive treatment. Polyclonal regulatory T-cells (Tregs) are a potential tool to induce transplantation tolerance, but lack specificity and therefore require administration of high doses. Redirecting Tregs towards mismatched donor HLA molecules by modifying these cells with chimeric antigen receptors (CAR) would render Tregs far more effective at preventing allograft rejection. Several studies on HLA-A2 specific CAR Tregs have demonstrated that these cells are highly antigen-specific and show a superior homing capacity to HLA-A2+ allografts compared to polyclonal Tregs. HLA-A2 CAR Tregs have been shown to prolong survival of HLA-A2+ allografts in several pre-clinical humanized mouse models. Although promising, concerns about safety and stability need to be addressed. In this review the current research, obstacles of CAR Treg therapy, and its potential future in solid organ transplantation will be discussed.
15-Hydroxyprostaglandin Dehydrogenase Is a Predictor of Stroke-Associated Pneumonia

Background and Purpose Stroke is a serious fatal and disabling disease. Stroke-associated pneumonia (SAP) is the most common complication of stroke, which may further aggravate the stroke. The prevention and early prediction of SAP is a key clinical strategy. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is involved in pneumonia, while its relationship with SAP has yet to be determined. Therefore, we investigated the predictive value of 15-PGDH for SAP and visualized their relationship. Methods Stroke patients were recruited and divided into SAP group and Non-SAP group. Baseline demographic and clinical data were obtained from the medical record system, blood samples were collected to detect relevant variables and 15-PGDH levels. Patient characteristics were compared with a t-test. Binary logistic regression analysis was performed to determine the predictive value of 15-PGDH for SAP. Restricted cubic splines (RCS) were performed to visualize the relationship between 15-PGDH and SAP risk. Finally, the SAP patient characteristics between the severe group and mild group were compared. Results 50 patients were enrolled and divided into SAP group (n = 26) and Non-SAP group (n = 24). 15-PGDH in the SAP group was lower than that in the Non-SAP group (0.258 ± 0.275 vs. 0.784 ± 0.615, p = 0.025). Binary logistic regression analysis revealed that the lower 15-PGDH, the higher the risk of SAP (OR = 0.04, 95%CI, 0.010–0.157, p < 0.001). The RCS model showed the L-shaped relationship between 15-PGDH and SAP. Conclusions In stroke patients, serum 15-PGDH is a valuable biomarker for predicting SAP. There is an L-shaped relationship between the level of 15-PGDH and the risk of SAP.
Editorial: Metabolic Adaptation of Muscle Tissue in Diseases Associated With Cachexia

Laboratory of Stem Cells for Tissue Engineering, IRCCS Policlinico San Donato, San Donato Milanese, Italy, Institute for Molecular and Translational Cardiology (IMTC), San Donato Milanese, Italy, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, United States, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, United States, Indiana Center of Musculoskeletal Health, Indianapolis, IN, United States, Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, IN, United States, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy, Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
Mechanical Distribution and New Bone Regeneration After Implanting 3D Printed Prostheses for Repairing Metaphyseal Bone Defects: A Finite Element Analysis and Prospective Clinical Study

Critical metaphyseal bone defects caused by nonunion and osteomyelitis are intractable to repair in clinical practice owing to the rigorous demanding of structure and performance. Compared with traditional treatment methods, 3D printing of customized porous titanium alloy prostheses offer feasible and safe opportunities in repairing such bone defects. Yet, so far, no standard guidelines for optimal 3D printed prostheses design and fixation mode have been proposed to further promote prosthesis stability as well as ensure the continuous growth of new bone. In this study, we used a finite element analysis (FEA) to explore the biomechanical distribution and observed new bone regeneration in clinical practice after implanting 3D printed prostheses for repairing metaphyseal bone defects. The results reflected that different fixation modes could result in diverse prosthesis mechanical conductions. If an intramedullary (IM) nail was applied, the stress mainly conducted equally along the nail instead of bone and prosthesis structure. While the stress would transfer more to the lateral bone and prosthesis’s body when the printed wing and screws are selected to accomplish fixation. All these fixation modes could guarantee the initial and long-term stability of the implanted prosthesis, but new bone regenerated with varying degrees under special biomechanical environments. The fixation mode of IM nail was more conducive to new bone regeneration and remodeling, which conformed to the Wolff’s law. Nevertheless, when the prosthesis was fixed by screws alone, no dense new callus could be observed. This fixation mode was optional for defects extremely close to the articular surface. In conclusion, our innovative study could provide valuable references for the fixation mode selection of 3D printed prosthesis to repair metaphyseal bone defect.