A comprehensive review for artificial intelligence on neuroimaging in rehabilitation of ischemic stroke.

Stroke is the second leading cause of death worldwide, with ischemic stroke accounting for a significant proportion of morbidity and mortality among stroke patients. Ischemic stroke often causes disability and cognitive impairment in patients, which seriously affects the quality of life of patients. Therefore, how to predict the recovery of patients can provide support for clinical intervention in advance and improve the enthusiasm of patients for rehabilitation treatment. With the popularization of imaging technology, the diagnosis and treatment of ischemic stroke patients are often accompanied by a large number of imaging data. Through machine learning and Deep Learning, information from imaging data can be used more effectively. In this review, we discuss recent advances in neuroimaging, machine learning, and Deep Learning in the rehabilitation of ischemic stroke.

Nitrogen-Doped Biochar for Enhanced Peroxymonosulfate Activation to Degrade Phenol through Both Free Radical and Direct Oxidation Based on Electron Transfer Pathways.

Nowadays, super nitrogen-doped biochar (SNBC) material has become one of the most promising metal-free catalysts for activating peroxymonosulfate (PMS) to degrade organic pollutants. To understand the evolution of SNBC properties with fabrication conditions, a variety of SNBC materials were prepared and characterized by elemental analysis, N2 adsorption-desorption, scanning electron microscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction. We systematically investigated the activation potential of these SNBC materials for PMS to degrade phenol. SN1BC-800 with the best catalytic performance was obtained by changing the activation temperatures and the ratio of biochar to melamine. The effects of catalyst dosage, the PMS concentration, pH, and reaction temperature on phenol degradation were studied in detail. In the presence of 0.3 g/L SN1BC-800 and 1 g/L PMS, the removal rate of 20 mg/L phenol could reach 100% within 5 min. According to electron paramagnetic resonance spectra and free radical quenching experiments, a nonfree radical pathway of phenol degradation dominated by 1O2 and electron transfer was proposed. More interestingly, the excellent catalytic performance of the SN1BC-800/PMS system is universally applicable in the degradation of other typical organic pollutants. In addition, the degradation rate of phenol is still over 80% after five reuses, which shows that the SN1BC-800 catalyst has high stability and good application prospects in environmental remediation.

Two maize homologs of mammalian proton-coupled folate transporter, ZmMFS_1-62 and ZmMFS_1-73, are essential to salt and drought tolerance.

Folates are essential to the maintenance of normal life activities in almost all organisms. Proton-coupled folate transporter (PCFT), belonging to the major facilitator superfamily, is one of the three major folate transporter types widely studied in mammals. However, information about plant PCFTs is limited. Here, a genome-wide identification of maize PCFTs was performed, and two PCFTs, ZmMFS_1-62 and ZmMFS_1-73, were functionally investigated. Both proteins contained the typical 12 transmembrane helixes with N- and C-termini located in the cytoplasm, and were localized in the plasma membrane. Molecular docking analysis indicated their binding activity with folates via hydrogen bonding. Interference with ZmMFS_1-62 and ZmMFS_1-73 in maize seedlings through virus-induced gene silencing disrupted folate homeostasis, mainly in the roots, and reduced tolerance to drought and salt stresses. Moreover, a molecular chaperone protein, ZmHSP20, was found to interact with ZmMFS_1-62 and ZmMFS_1-73, and interference with ZmHSP20 in maize seedlings also led to folate disruption and increased sensitivity to drought and salt stresses. Overall, this is the first report of functional identification of maize PCFTs, which play essential roles in salt and drought stress tolerance, thereby linking folate metabolism with abiotic stress responses in maize.

An abdominal vibration combined with walking exercise (AVCWE) program for older patients with constipation: Development and feasibility study.

BACKGROUND: Older patients with constipation are at higher risk for inadequate bowel preparation, but there are currently no targeted strategies. This study aims to develop an abdominal vibration combined with walking exercise (AVCWE) program and assess its feasibility among older patients with constipation. METHODS: Phase I: Using the Delphi technique, eight experts across three professional fields were consulted to develop the AVCWE program. The experts evaluated and provided recommendations on demonstration videos and detailed descriptions of the preliminary protocol. Phase II: A single-arm feasibility study of the AVCWE program was conducted on 30 older patients with constipation undergoing colonoscopy at a tertiary hospital in China. A 10-point exercise program evaluation form and several open-ended questions were used to gather feedback from participants regarding the program. In both phases, content analysis was used to critically analyze and summarize qualitative suggestions for protocol modifications. RESULTS: Based on feedback from the expert panel, the AVCWE program developed in Phase I included two procedures during laxative ingestion: at least 5,500 steps of walking exercise and two cycles of moderate-intensity abdominal vibration (each cycle consisted of 10 min of vibration and 10 min of rest). The feasibility study in Phase II showed high positive patient feedback scores for the program, ranging from 9.07 ± 0.74 to 9.73 ± 0.52. CONCLUSION: The AVCWE program was developed by eight multidisciplinary experts and was well accepted by 30 older patients with constipation. Study participants believed that this program was simple, safe, appropriate, and helpful for their bowel preparation. The findings of this study may provide valuable information for optimizing bowel preparation in older patients with constipation.

[Energy-saving and Emission Reduction Path for Road Traffic in Key Coastal Cities of Guangdong, Fujian and Zhejiang].

The rapid development of society and economy has resulted in a substantial increase in energy consumption, consequently exacerbating pollution issues. Current research predominantly focuses on energy-saving and emission reduction in road transportation within individual cities or the three major economic regions of China:the Yangtze River Delta, the Pearl River Delta, and the Beijing-Tianjin-Hebei Region. However, there is a dearth of studies addressing the southeastern coastal economic region. Located at the heart of China's southeastern coastal economic development, the provinces of Guangdong, Fujian, and Zhejiang unavoidably face challenges associated with energy consumption and emissions while pursuing economic growth. To address these challenges, this study employed a LEAP model to construct various scenarios for road transportation in the key coastal cities of Guangdong, Fujian, and Zhejiang from 2015 to 2035. These scenarios included a baseline scenario (BAU), an existing policy scenario (EPS), and an improved policy scenario (MPS). The MPS and EPS encompassed vehicle structure optimization (VSO), improved fuel economy (IFE), and reduced annual average mileage (RDM). By simulating and evaluating these scenarios, the energy-saving and emission reduction potentials of road transportation in the key coastal cities were assessed. The results indicated that, in the primary scenario, the MPS exhibited the most significant improvements in energy-saving, carbon reduction, and pollutant reduction effects. By 2035, the MPS achieved a remarkable 75% energy-saving rate compared to that in the baseline scenario, accompanied by reductions of 68%, 59%, 66%, 70%, and 64% in CO2, CO, NOx, PM2.5, and SO2 emissions, respectively. In the secondary scenario, the improved scenario of enhancing fuel economy achieved a notable 30% reduction in energy consumption. Additionally, the scenarios involving vehicle structure adjustment (yielding reductions of 36%, 30%, 36%, 26%, and 40%) and annual average mileage reduction (resulting in reductions of 37%, 37%, 36%, 37%, and 36%) demonstrated significant reductions in CO2, CO, NOx, PM2.5, and SO2 emissions.

Enhanced protein-metabolite correlation analysis: To investigate the association between Staphylococcus aureus mastitis and metabolic immune pathways.

Mastitis is a disease characterized by congestion, swelling, and inflammation of the mammary gland and usually caused by infection with pathogenic microorganisms. Furthermore, the development of mastitis is closely linked to the exogenous pathway of the gastrointestinal tract. However, the regulatory mechanisms governing the gut-metabolism-mammary axis remain incompletely understood. The present study revealed alterations in the gut microbiota of mastitis rats characterized by an increased abundance of the Proteobacteria phylum. Plasma analysis revealed significantly higher levels of L-isoleucine and cholic acid along with 7-ketodeoxycholic acid. Mammary tissue showed elevated levels of arachidonic acid metabolites and norlithocholic acid. Proteomic analysis showed increased levels of IFIH1, Tnfaip8l2, IRGM, and IRF5 in mastitis rats, which suggests that mastitis triggers an inflammatory response and immune stress. Follistatin (Fst) and progesterone receptor (Pgr) were significantly downregulated, raising the risk of breast cancer. Extracellular matrix (ECM) receptors and focal adhesion signaling pathways were downregulated, while blood-milk barrier integrity was disrupted. Analysis of protein-metabolic network regulation revealed that necroptosis, protein digestion and absorption, and arachidonic acid metabolism were the principal regulatory pathways involved in the development of mastitis. In short, the onset of mastitis leads to changes in the microbiota and alterations in the metabolic profiles of various biological samples, including colonic contents, plasma, and mammary tissue. Key manifestations include disturbances in bile acid metabolism, amino acid metabolism, and arachidonic acid metabolism. At the same time, the integrity of the blood-milk barrier is compromised while inflammation is promoted, thereby reducing cell adhesion in the mammary glands. These findings contribute to a more comprehensive understanding of the metabolic status of mastitis and provide new insights into its impact on the immune system.

Transcriptomic responses of rabbits to infections by precocious line and wild-type Eimeria media: revealing molecular signatures and pathway differences in liver and duodenum during the peak and terminal phases of oocyst production.

Eimeria media is a principal pathogen responsible for rabbit coccidiosis, targeting the rabbit's intestinal epithelial cells. This parasitism damages the intestinal mucosal barrier, initiating a systemic immune and inflammatory response that jeopardizes the sustainable growth of rabbit farming. To understand the implications of infection on the host's immune and metabolic responses, we employed RNA-Seq to analyze RNA from the liver and duodenum tissues of post-infected rabbits infected with both the precocious line and wild-type strain of E.media. Comprehensive transcriptomic analysis revealed that the two parasites exhibit divergent transcriptomic imprints on host tissues. While the precocious line predominantly modulates immune-centric pathways with significant differential gene enrichment, wild-type strain favors pathways that affect metabolism. In addition, our study pinpointed a set of genes that undergo significant modifications in response to these effects. These revelations grant a fresh avenue to probe deeper into the symbiotic intricacies of the E.media and its rabbit host.

Comparison of Ba-Hao burn ointment gauze and petrolatum gauze in split graft donor site healing: A randomized, prospective, and self-control study.

Background and Aims: To assess patient comfort, wound healing, and scarring at the 6-month follow-up of split-skin graft donor sites treated with Ba-Hao burn ointment (BHBO) gauze, a compound preparation of traditional Chinese medicine since 1970s, compared with petrolatum gauze. Methods: Thirty patients admitted to the Department of Burns of the First Affiliated Hospital of Anhui Medical University between September 2021 and September 2022 participated in this randomized, prospective, self-control clinical study. After harvesting the split skin, donor sites were divided into two parts along the midline. BHBO gauze was applied to half of the donor wounds, and petrolatum gauze was applied to the other half. The wound healing time, pain scores on the postoperative Days 3, 6, and 9, and Vancouver Scar Scale (VSS) score at the 6-month follow-up were assessed. Results: The wound healing time was significantly shorter in the BHBO group than in the control group (10.07 ± 1.48 days vs. 11.50 ± 1.74 days, p < 0.001). On postoperative Days 3 and 6, the pain scores quantified by visual analog scores were significantly lower in the BHBO group than in the control group (5.33 ± 1.54 and 4.17 ± 1.51, respectively vs. 7.57 ± 1.41 and 5.20 ± 1.47, respectively). The difference in the visual analog scale score on postoperative Day 9 between the groups was not significant (p > 0.05). Microbiological assessment revealed the absence of bacterial contamination in both groups. At the 6-month follow up, the VSS score was significantly lower in the BHBO group (6.67 ± 1.92) than in the control group (9.57 ± 1.55). Conclusion: BHBO resulted in faster donor-site healing, reduced postoperative pain, and improved scar quality at the 6-month follow-up than petrolatum gauze alone.

Development and evaluation of a text analytics algorithm for automated application of national COVID-19 shielding criteria in rheumatology patients.

INTRODUCTION: At the beginning of the COVID-19 pandemic, the UK's Scientific Committee issued extreme social distancing measures, termed 'shielding', aimed at a subpopulation deemed extremely clinically vulnerable to infection. National guidance for risk stratification was based on patients' age, comorbidities and immunosuppressive therapies, including biologics that are not captured in primary care records. This process required considerable clinician time to manually review outpatient letters. Our aim was to develop and evaluate an automated shielding algorithm by text-mining outpatient letter diagnoses and medications, reducing the need for future manual review. METHODS: Rheumatology outpatient letters from a large UK foundation trust were retrieved. Free-text diagnoses were processed using Intelligent Medical Objects software (Concept Tagger), which used interface terminology for each condition mapped to Systematized Medical Nomenclature for Medicine-Clinical Terminology (SNOMED-CT) codes. We developed the Medication Concept Recognition tool (Named Entity Recognition) to retrieve medications' type, dose, duration and status (active/past) at the time of the letter. Age, diagnosis and medication variables were then combined to calculate a shielding score based on the most recent letter. The algorithm's performance was evaluated using clinical review as the gold standard. The time taken to deploy the developed algorithm on a larger patient subset was measured. RESULTS: In total, 5942 free-text diagnoses were extracted and mapped to SNOMED-CT, with 13 665 free-text medications (n=803 patients). The automated algorithm demonstrated a sensitivity of 80% (95% CI: 75%, 85%) and specificity of 92% (95% CI: 90%, 94%). Positive likelihood ratio was 10 (95% CI: 8, 14), negative likelihood ratio was 0.21 (95% CI: 0.16, 0.28) and F1 score was 0.81. Evaluation of mismatches revealed that the algorithm performed correctly against the gold standard in most cases. The developed algorithm was then deployed on records from an additional 15 865 patients, which took 18 hours for data extraction and 1 hour to deploy. DISCUSSION: An automated algorithm for risk stratification has several advantages including reducing clinician time for manual review to allow more time for direct care, improving efficiency and increasing transparency in individual patient communication. It has the potential to be adapted for future public health initiatives that require prompt automated review of hospital outpatient letters.

Based on the prognosis model of immunogenes, the prognosis model was constructed to predict the invasion of immune genes and immune cells related to primary liver cancer and its experimental validation.

Background: Primary liver cancer (PLC) is a prevalent malignancy of the digestive system characterized by insidious symptom onset and a generally poor prognosis. Recent studies have highlighted a significant correlation between the initiation and prognosis of liver cancer and the immune function of PLC patients. Purpose: Revealing the expression of PLC-related immune genes and the characteristics of immune cell infiltration provides assistance for the analysis of clinical pathological parameters and prognosis of PLC patients. Methods: PLC-related differentially expressed genes (DEGs) with a median absolute deviation (MAD > 0.5) were identified from TCGA and GEO databases. These DEGs were intersected with immune-related genes (IRGs) from the ImmPort database to obtain PLC-related IRGs. The method of constructing a prognostic model through immune-related gene pairs (IRGPs) is used to obtain IRGPs and conduct the selection of central immune genes. The central immune genes obtained from the selection of IRGPs are validated in PLC. Subsequently, the relative proportions of 22 types of immune cells in different immune risk groups are evaluated, and the differential characteristics of PLC-related immune cells are verified through animal experiments. Results: Through database screening and the construction of an IRGP prognosis model, 84 pairs of IRGPs (P < 0.001) were ultimately obtained. Analysis of these 84 IRGPs revealed 11 central immune genes related to PLC, showing differential expression in liver cancer tissues compared to normal liver tissues. Results from the CiberSort platform indicate differential expression of immune cells such as naive B cells, macrophages, and neutrophils in different immune risk groups. Animal experiments demonstrated altered immune cell proportions in H22 tumor-bearing mice, validating findings from peripheral blood and spleen homogenate analyses. Conclusion: Our study successfully predicted and validated PLC-related IRGs and immune cells, suggesting their potential as prognostic indicators and therapeutic targets for PLC.

Morus alba L. (Sangzhi) alkaloids mitigate atherosclerosis by regulating M1/M2 macrophage polarization.

BACKGROUND: Atherosclerosis (AS) is an important cause of cardiovascular disease, posing a substantial health risk. Recognized as a chronic inflammatory disorder, AS hinges on the pivotal involvement of macrophages in arterial inflammation, participating in its formation and progression. Sangzhi alkaloid (SZ-A) is a novel natural alkaloid extracted from the mulberry branches, has extensive pharmacological effects and stable pharmacokinetic characteristics. However, the effects and mechanisms of SZ-A on AS remain unclear. PURPOSE: To explore the effect and underlying mechanisms of SZ-A on inflammation mediated by macrophages and its role in AS development. METHODS: Atherosclerosis was induced in vivo in apolipoprotein E-deficient mice through a high-fat and high-choline diet. We utilized macrophages and vascular endothelial cells to investigate the effects of SZ-A on macrophage polarization and its anti-inflammatory properties on endothelial cells in vitro. The transcriptomic analyses were used to investigate the major molecule that mediates cell-cell interactions and the antiatherogenic mechanisms of SZ-A based on AS, subsequently validated in vivo and in vitro. RESULTS: SZ-A demonstrated a significant inhibition in vascular inflammation and alleviation of AS severity by mitigating macrophage infiltration and modulating M1/M2 macrophage polarization in vitro and in vivo. Moreover, SZ-A effectively reduced the release of the proinflammatory mediator C-X-C motif chemokine ligand (CXCL)-10, predominantly secreted by M1 macrophages. This reduction in CXCL-10 contributed to improved endothelial cell function, reduced recruitment of additional macrophages, and inhibited the inflammatory amplification effect. This ultimately led to the suppression of atherogenesis. CONCLUSION: SZ-A exhibited potent anti-inflammatory effects by inhibiting macrophage-mediated inflammation, providing a new therapeutic avenue against AS. This is the first study demonstrating the efficacy of SZ-A in alleviating AS severity and offers novel insights into its anti-inflammatory mechanism.

Salvage haploidentical transplantation for graft failure after first haploidentical allogeneic stem cell transplantation: an updated experience.

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9-140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation.

Cannabidiol Inhibits Epithelial Ovarian Cancer: Role of Gut Microbiome.

Epithelial ovarian cancer is among the deadliest gynecological tumors worldwide. Clinical treatment usually consists of surgery and adjuvant chemo- and radiotherapies. Due to the high rate of recurrence and rapid development of drug resistance, the current focus of research is on finding effective natural products with minimal toxic side effects for treating epithelial ovarian tumors. Cannabidiol is among the most abundant cannabinoids and has a non-psychoactive effect compared to tetrahydrocannabinol, which is a key advantage for clinical application. Studies have shown that cannabidiol has antiproliferative, pro-apoptotic, cytotoxic, antiangiogenic, anti-inflammatory, and immunomodulatory properties. However, its therapeutic value for epithelial ovarian tumors remains unclear. This study aims to investigate the effects of cannabidiol on epithelial ovarian tumors and to elucidate the underlying mechanisms. The results showed that cannabidiol has a significant inhibitory effect on epithelial ovarian tumors. In vivo experiments demonstrated that cannabidiol could inhibit tumor growth by modulating the intestinal microbiome and increasing the abundance of beneficial bacteria. Western blot assays showed that cannabidiol bound to EGFR/AKT/MMPs proteins and suppressed EGFR/AKT/MMPs expression in a dose-dependent manner. Network pharmacology and molecular docking results suggested that cannabidiol could affect the EGFR/AKT/MMPs signaling pathway.

An AI-based approach for modeling the synergy between radiotherapy and immunotherapy.

Personalized, ultra-fractionated stereotactic adaptive radiotherapy (PULSAR) is designed to administer tumoricidal doses in a pulsed mode with extended intervals, spanning weeks or months. This approach leverages longer intervals to adapt the treatment plan based on tumor changes and enhance immune-modulated effects. In this investigation, we seek to elucidate the potential synergy between combined PULSAR and PD-L1 blockade immunotherapy using experimental data from a Lewis Lung Carcinoma (LLC) syngeneic murine cancer model. Employing a long short-term memory (LSTM) recurrent neural network (RNN) model, we simulated the treatment response by treating irradiation and anti-PD-L1 as external stimuli occurring in a temporal sequence. Our findings demonstrate that: (1) The model can simulate tumor growth by integrating various parameters such as timing and dose, and (2) The model provides mechanistic interpretations of a "causal relationship" in combined treatment, offering a completely novel perspective. The model can be utilized for in-silico modeling, facilitating exploration of innovative treatment combinations to optimize therapeutic outcomes. Advanced modeling techniques, coupled with additional efforts in biomarker identification, may deepen our understanding of the biological mechanisms underlying the combined treatment.

Temporal and Within-Sporophyte Variations in Triphenyltin Chloride (TPTCL) and Its Degradation Products in Cultivated Undaria pinnatifida.

Undaria pinnatifida can effectively deal with organotin pollution through its excellent accumulation and degradation capabilities found under laboratory conditions. However, nothing is known regarding its accumulation, degradation performance, and related impact factors in the wild farming area. In this study, we monitored triphenyltin chloride (TPTCL) contents and degradation products in different algal parts (blades, stipes, sporophylls, and holdfasts) of cultivated U. pinnatifida from December 2018 to May 2019. Our results showed that sporophytes had an accumulation and degradation capacity for TPTCL. The TPTCL contents and degradation products varied with the algal growth stages and algal parts. TPTCL accumulated in the blades at the growth stage and the blades, stipes, sporophylls, and holdfasts at the mature stage. The TPTCL content among algal parts was blades (74.92 ± 2.52 µg kg-1) > holdfasts (62.59 ± 1.42 µg kg-1) > sporophylls (47.24 ± 1.41 µg kg-1) > stipes (35.53 ± 0.55 µg kg-1). The primary degradation product DPTCL accumulated only in the blades at any stage, with a concentration of 69.30 ± 3.89 µg kg-1. The secondary degradation product MPTCL accumulated in the blades at the growth stage and in the blades, stipe, and sporophyll at the mature stage. The MPTCL content among algal parts was blades (52.80 ± 3.48 µg kg-1) > sporophylls (31.08 ± 1.53 µg kg-1) > stipes (20.44 ± 0.85 µg kg-1). The accumulation pattern of TPTCL and its degradation products seems closely related to nutrient allocation in U. pinnatifida. These results provide the basis for applying cultivated U. pinnatifida in the bioremediation of organotin pollution and the food safety evaluation of edible algae.

Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs.

BACKGROUND: Enhancer RNAs (eRNAs) play a crucial role in transcriptional regulation. While significant progress has been made in understanding epigenetic regulation mediated by eRNAs, research on the construction of eRNA-mediated gene regulatory networks (eGRN) and the identification of critical network components that influence complex traits is lacking. RESULTS: Here, employing the pig as a model, we conducted a comprehensive study using H3K27ac histone ChIP-seq and RNA-seq data to construct eRNA expression profiles from multiple tissues of two distinct pig breeds, namely Enshi Black (ES) and Duroc. In addition to revealing the regulatory landscape of eRNAs at the tissue level, we developed an innovative network construction and refinement method by integrating RNA-seq, ChIP-seq, genome-wide association study (GWAS) signals and enhancer-modulating effects of single nucleotide polymorphisms (SNPs) measured by self-transcribing active regulatory region sequencing (STARR-seq) experiments. Using this approach, we unraveled eGRN that significantly influence the growth and development of muscle and fat tissues, and identified several novel genes that affect adipocyte differentiation in a cell line model. CONCLUSIONS: Our work not only provides novel insights into the genetic basis of economic pig traits, but also offers a generalizable approach to elucidate the eRNA-mediated transcriptional regulation underlying a wide spectrum of complex traits for diverse organisms.

Extracellular CIRP co-stimulated T cells through IL6R/STAT3 in pediatric IgA vasculitis.

Immunoglobulin A vasculitis (IgAV) is the most common vasculitis of childhood. Disordered immune responses play important roles in its pathogenesis, but the comprehensive immune profile of the disease and the underlying mechanisms are still largely unknown. Here we found a potential disease biomarker cold inducible RNA binding protein (CIRP) in our pediatric IgAV cohort. Serum CIRP level in these patients were elevated and positively correlated with the increased early memory (CD45RA+CD62L+CD95+) T cells revealed using multicolor flow cytometry. Immune phenotyping of the patients showed they had more activated T cells with higher IL6Ra expression. T cell culture experiment showed CIRP further activated both human CD4+ and CD8+ T cells as indicated by increased perforin secretion and phosphorylation of STAT3. Blockade of IL6Rα attenuated CIRP-induced T cell toxicity in vitro. RNA-sequencing data further supported CIRP stimulation promoted human T cell activation and migration, fueled inflammation through the JAK-STAT signaling pathway. Therefore, IL6Ra-mediated T cell activation by extracellular CIRP may contribute to pathogenesis of IgAV in children, both CIRP and IL6Ra could be new therapeutic targets for IgAV.

Perception, practice, and barriers toward research among pediatric undergraduates: a cross-sectional questionnaire-based survey.

BACKGROUND: Scientific research activities are crucial for the development of clinician-scientists. However, few people pay attention to the current situation of medical research in pediatric medical students in China. This study aims to assess the perceptions, practices and barriers toward medical research of pediatric undergraduates. METHODS: This cross-sectional study was conducted among third-year, fourth-year and fifth-year pediatric students from Zhejiang University School of Medicine in China via an anonymous online questionnaire. The questionnaires were also received from fifth-year students majoring in other medicine programs [clinical medicine ("5 + 3") and clinical medicine (5-year)]. RESULTS: The response rate of pediatric undergraduates was 88.3% (68/77). The total sample of students enrolled in the study was 124, including 36 students majoring in clinical medicine ("5 + 3") and 20 students majoring in clinical medicine (5-year). Most students from pediatrics ("5 + 3") recognized that research was important. Practices in scientific research activities are not satisfactory. A total of 51.5%, 35.3% and 36.8% of the pediatric students participated in research training, research projects and scientific article writing, respectively. Only 4.4% of the pediatric students contributed to publishing a scientific article, and 14.7% had attended medical congresses. None of them had given a presentation at a congress. When compared with fifth-year students in the other medicine program, the frequency of practices toward research projects and training was lower in the pediatric fifth-year students. Lack of time, lack of guidance and lack of training were perceived as the main barriers to scientific work. Limited English was another obvious barrier for pediatric undergraduates. Pediatric undergraduates preferred to participate in clinical research (80.9%) rather than basic research. CONCLUSIONS: Although pediatric undergraduates recognized the importance of medical research, interest and practices in research still require improvement. Lack of time, lack of guidance, lack of training and limited English were the common barriers to scientific work. Therefore, research training and English improvement were recommended for pediatric undergraduates.

Adapt-On-Demand: A Novel Strategy for Personalized Adaptive Radiotherapy for Locally Advance Lung Cancer.

PURPOSE: Real time adaptation of thoracic radiation plans is compelling because offline adaptive experiences show that tumor volumes and lung anatomy can change during therapy. We present and analyze a novel adaptive-on-demand (AOD) workflow combining online adaptive radiotherapy (ART) on the ETHOS system with image-guided radiotherapy (IGRT) delivery on a Halcyon unit for conventional fractionated radiotherapy of locally advanced lung cancer (LALC). METHOD: We analyzed 26 LALC patients treated with the AOD workflow, adapting weekly. We timed segments of the workflow to evaluate efficiency in a real world clinic. Target coverage and OAR doses were compared between adapted plans (ADP) and scheduled plans without adaptation (SCH). Planning robustness was evaluated by the frequency of preplanning goals being achieved in ADP plans, stratified by tumor volume change. RESULTS: The AOD workflow was achievable within 30 min for most radiation fractions. Over the course of therapy we observed an average 26.6% ± 23.3% reduction in ITV volumes. Despite these changes, with online adaptive radiation therapy (o-ART), ITV and PTV coverage (V100%) was 99.2% and 93.9% for all members of the cohort. This represented a 2.9% and 6.8% improvement over non-adapted plans (p<0.05). For tumors that grew > 10%, V100% was 93.1% for o-ART, while it was 76.4% for non-adaptive plans, representing a median 17.2% improvement in the PTV coverage (p < 0.05). In these plans, critical OAR constraints were met 94.1% of the time, whereas in non-adapted plans it was 81.9%. This represented reductions of 1.32 Gy, 1.34 Gy, or 1.75 Gy in heart, esophagus, and lung, respectively. The effect was larger when tumors had shrunk more than 10%. Regardless of tumor volume alterations, the PTV/ITV coverage was achieved for all adaptive plans. Exceptional cases, where dose constraints were not met, were due to large initial tumor volumes or tumor growth. CONCLUSION: The AOD workflow is efficient and robust in responding to anatomical changes in LALC patients, providing dosimetric advantages over standard therapy. Weekly adaptation was adequate to keep pace with changes. This approach is a feasible alternative to conventional offline replanning workflows for managing anatomy changes in LALC radiotherapy.