Management of Anaphylaxis Following Pre-Hospital Epinephrine Use in Children with Food-induced Anaphylaxis.

BACKGROUND: Previous guidelines recommend prompt epinephrine administration, followed by observation in the emergency department (ED). The need for transfer in all cases of anaphylaxis has recently been challenged. OBJECTIVE: We aimed to evaluate the need for additional ED treatment among children with anaphylaxis who received pre-hospital epinephrine. METHODS: Between 2011-2023, data were collected on symptoms, triggers, comorbidities, and pre-hospital and in-hospital management from children (<18 years) with food-induced anaphylaxis who received at least one dose of pre-hospital epinephrine presenting at 7 pediatric EDs. Multivariable logistic regression assessed factors associated with the usage of two or more pre-hospital EAI, epinephrine use in the ED, and hospital admission. RESULTS: Of 1127 children (mean 8.1 +/-5.3 years; 60.6% male) with food-induced anaphylaxis who used at least one EAI pre-hospital, the most common trigger was peanuts (25.3%). 209 (18.5%) received additional epinephrine in the ED, the majority of whom (88.0%) received one dose. 30 (2.7%) patients were admitted to hospital. Among all patients, severe reactions (cardiovascular instability/ cyanosis/ loss of consciousness) (adjusted odds ratio [aOR] 1.22; 95% confidence interval [CI] 1.12-1.33) and reactions to tree nuts (aOR 1.09; 95% CI 1.03-1.16) were associated with increased odds of in-hospital epinephrine use. Pre-hospital inhaled beta-agonists (aOR 1.08; 95% CI 1.01-1.16) use and severe reactions (aOR 1.13; 95% CI 1.05-1.22) were associated with the use of 2 or more EAI pre-hospital. CONCLUSION: A minority of anaphylaxis cases that used pre-hospital EAIs required additional treatment, supporting that shared decision making about transfer to ED works for the vast majority of patients.

Ranking the attribution of high-risk genotypes among women with cervical precancers and cancers: a cross-sectional study in Ningbo, China.

BACKGROUND: The region-specific importance of carcinogenic HPV genotypes is required for optimizing HPV-based screening and promoting appropriate multivalent HPV prophylactic vaccines. This information is lacking for Ningbo, one of the first cities of China's Healthy City Innovation Pilot Program for Cervical Cancer Elimination. Here, we investigated high-risk HPV (HR-HPV) genotype-specific distribution and attribution to biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) before mass vaccination in Ningbo, China. METHODS: A total of 1393 eligible CIN2+ archived blocks (including 161 CIN2, 1107 CIN3, and 125 invasive cervical cancers [ICC]) were collected from 2017 to 2020 in Ningbo. HR-HPV DNA was genotyped using the SPF10-DEIA-LiPA25 version 1 detection system and the SureX HPV 25X Genotyping Kit. Genotype-specific attribution to CIN2+ was estimated using a fractional contribution approach. RESULTS: Ranking by the attributable proportions, HPV16 remained the most important genotype in both cervical precancers and cancers, accounting for 36.8% of CIN2, 53.2% of CIN3, and 73.3% of ICC cases. Among cervical precancers, HPV52 (17.3% in CIN2, 12.7% in CIN3) and HPV58 (13.9%, 14.9%) ranked second and third, while HPV33 (8.3%, 7.9%) and HPV31 (6.5%, 4.1%) ranked fourth and fifth, respectively. However, among ICCs, HPV18 (5.7%) accounted for the second highest proportion, followed by HPV33 (5.4%), HPV58 (4.0%), and HPV45 (3.2%). HPV18/45 together accounted for 46.8% of adenocarcinomas, which was slightly lower than that of HPV16 (47.7%). The remaining HR-HPV genotypes (HPV35/39/51/56/59/66/68) combined accounted for only 6.7% of CIN2, 2.9% of CIN3, and 4.2% of ICC. CONCLUSIONS: With Ningbo's strong medical resources, it will be important to continue HPV16/18 control efforts, and could broaden to HPV31/33/45/52/58 for maximum health benefits. However, different strategies should be proposed for other HR-HPV genotypes based on their lower carcinogenic risks.

DNA domino circuits based on a hairpin exonuclease assistance signal transmission architecture for temporal logic operations.

DNA circuits are important fundamental tools for performing temporal logic operations with complex structures, but they lack sequence orthogonality. Here, we developed a simple and orthogonal hairpin exonuclease assistance signal (H-EAST) architecture to construct DNA domino circuits with time-delay characteristics and temporal logic operations, which has potential applications in biomolecular computing.

Radiopharmaceutical-activated silicon naphthalocyanine nanoparticles towards tumor photodynamic therapy.

Naphthalocyanine-based agents exhibit huge potential in photodynamic therapy, yet their photodynamic performance is restricted by the penetration depth of the external laser. Herein, we employed 18F-FDG as an internal light source to excite silicon naphthalocyanine nanoparticles to simultaneously circumvent radiative transition and boost 1O2 generation for tumor suppression.

Correction: Radiopharmaceutical-activated silicon naphthalocyanine nanoparticles towards tumor photodynamic therapy.

Correction for 'Radiopharmaceutical-activated silicon naphthalocyanine nanoparticles towards tumor photodynamic therapy' by Tingting Wang et al., Chem. Commun., 2024, https://doi.org/10.1039/d4cc03281k.

The role of IL-1 family of cytokines in the pathogenesis and therapy of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive and irreversible neurological condition that occurs with age and poses a significant global public health concern, is distinguished by the degeneration of neurons and synapses in various regions of the brain. While the exact processes behind the neurodegeneration in AD are not completely known, it is now acknowledged that inflammation may have a significant impact on the beginning and advancement of AD neurodegeneration. The severity of many neurological illnesses can be influenced by the equilibrium between pro-inflammatory and anti-inflammatory mediators. The IL-1 family of cytokines is linked to innate immune responses, which are present in both acute inflammation and chronic inflammatory diseases. Research on the role of the IL-1 family in chronic neurological disease has been concentrated on AD. In this context, there is indirect evidence suggesting its involvement in the development of the disease. This review aims to provide a summary of the contribution of every IL-1 family member in AD pathogenesis, current immunotherapies in AD disease, and present treatment possibilities for either targeting or boosting these cytokines.

Burden of digestive system diseases in China and its provinces during 1990-2019: Results of the 2019 Global Disease Burden Study.

BACKGROUND: Evaluating the impact of digestive system diseases is vital for devising effective prevention strategies. However, comprehensive reports on the burden of digestive system diseases in China are lacking. Our study aimed to provide an overview of the burden and trends of digestive system diseases from 1990 to 2019 in China and its provinces. METHODS: This cross-sectional study utilized the Global Disease Burden Study 2019 to estimate the incidence, mortality rate, disability-adjusted life years (DALYs), years of life disability, years of life lost, and changes in the burden of digestive diseases across 31 Chinese provinces from 1990 to 2019. The analysis of disease burden primarily examines the characteristics of sub-disease distribution, time trends, age distribution, and sex distribution. Additionally, we compared provincial age-standardized DALYs for digestive diseases with the expected rates based on the socio-demographic index (SDI). RESULTS: In 2019, there were 499.2 million cases of digestive system diseases in China, resulting in 1,557,310 deaths. Stomach cancer, colon and rectal cancer, and esophageal cancer are the top three diseases associated with mortality and DALY related to digestive system diseases. Meanwhile, cirrhosis and other chronic liver diseases, gastroesophageal reflux disease, and gallbladder and biliary diseases are the top three kinds of diseases with the highest prevalence among digestive system diseases. The risk of gastric cancer sharply increases among men after the age of 40 years, leading to a significant disparity in burden between men and women. As the SDI increased, the DALYs associated with digestive system diseases in China and its provinces showed a downward trend. CONCLUSION: Our study highlights the inverse correlation between DALYs associated with digestive system diseases and the SDI, providing valuable insights that can assist public health officials in the estimation of the disease burden in this area.

Risk Factors for Non-Alcoholic Fatty Liver Disease in Patients with Bipolar Disorder: A Cross-Sectional Retrospective Study.

Purpose: The co-morbidity of non-alcoholic fatty liver disease (NAFLD) in patients with bipolar disorder (BD) has a negative impact on patient treatment and prognosis. This study aimed to identify the prevalence of NAFLD in patients with BD and investigate the risk factors of NAFLD. Patients and Methods: A total of 678 patients with BD were included in the study. Clinical data were obtained from the hospital's electronic health record system. Data included fasting blood glucose, alanine aminotransferase, triglycerides, aspartate aminotransferase, high-density lipoprotein cholesterol (HDL), alkaline phosphatase, total cholesterol, glutamine transpeptidase, uric acid, apolipoprotein A1, apolipoprotein B, and liver ultrasound findings. Results: The prevalence of NAFLD was 43.66% in patients with BD. Significant differences in body mass index (BMI), mean age, diabetes prevalence, course of BD, fasting blood glucose, alanine aminotransferase, HDL, alkaline phosphatase, triglycerides, aspartate aminotransferase, uric acid, glutamine transpeptidase, apolipoprotein B, total cholesterol, and apolipoprotein A1 were seen between the groups (all P<0.01). Male sex, age, BMI, course of BD, alanine aminotransferase, fasting blood glucose, aspartate aminotransferase, diabetes, glutamine transpeptidase, total cholesterol, alkaline phosphatase, triglycerides, uric acid, apolipoprotein B, HDL, and apolipoprotein A1 levels were correlated with NAFLD (all P<0.05). In patients with BD, diabetes (OR=6.412, 95% CI=1.049-39.21), BMI (OR=1.398, 95% CI=1.306-1.497), triglycerides (OR=1.456, 95% CI=1.036-2.045), and apolipoprotein A1 (OR=0.272, 95% CI=0.110-0.672) were risk factors for NAFLD (all P<0.05). Conclusion: Risk factors for NAFLD in patients with BD include diabetes, BMI, course of BD, and a low level of apolipoprotein A1. A proactive approach to disease management, such as appropriate physical activity and adoption of a healthy diet, and regular monitoring of changes in patient markers should be adopted to reduce the prevalence of NAFLD.

Fractional-order state space reconstruction: a new frontier in multivariate complex time series.

This paper presents a novel approach to the phase space reconstruction technique, fractional-order phase space reconstruction (FOSS), which generalizes the traditional integer-order derivative-based method. By leveraging fractional derivatives, FOSS offers a novel perspective for understanding complex time series, revealing unique properties not captured by conventional methods. We further develop the multi-span transition entropy component method (MTECM-FOSS), an advanced complexity measurement technique that builds upon FOSS. MTECM-FOSS decomposes complexity into intra-sample and inter-sample components, providing a more comprehensive understanding of the dynamics in multivariate data. In simulated data, we observe that lower fractional orders can effectively filter out random noise. Time series with diverse long- and short-term memory patterns exhibit distinct extremities at different fractional orders. In practical applications, MTECM-FOSS exhibits competitive or superior classification performance compared to state-of-the-art algorithms when using fewer features, indicating its potential for engineering tasks.

Abnormal large-scale brain functional network dynamics in social anxiety disorder.

AIMS: Although static abnormalities of functional brain networks have been observed in patients with social anxiety disorder (SAD), the brain connectome dynamics at the macroscale network level remain obscure. We therefore used a multivariate data-driven method to search for dynamic functional network connectivity (dFNC) alterations in SAD. METHODS: We conducted spatial independent component analysis, and used a sliding-window approach with a k-means clustering algorithm, to characterize the recurring states of brain resting-state networks; then state transition metrics and FNC strength in the different states were compared between SAD patients and healthy controls (HC), and the relationship to SAD clinical characteristics was explored. RESULTS: Four distinct recurring states were identified. Compared with HC, SAD patients demonstrated higher fractional windows and mean dwelling time in the highest-frequency State 3, representing "widely weaker" FNC, but lower in States 2 and 4, representing "locally stronger" and "widely stronger" FNC, respectively. In State 1, representing "widely moderate" FNC, SAD patients showed decreased FNC mainly between the default mode network and the attention and perceptual networks. Some aberrant dFNC signatures correlated with illness duration. CONCLUSION: These aberrant patterns of brain functional synchronization dynamics among large-scale resting-state networks may provide new insights into the neuro-functional underpinnings of SAD.

Development and Validation of a Comprehensive Analysis of the Competing Endogenous circRNA/miRNA/mRNA Network for the Identification of Immune-Related Targets in Esophageal Squamous Cell Carcinoma.

Immunotherapy for esophageal squamous cell carcinoma (ESCC) exhibits notable variability in efficacy. Concurrently, recent research emphasizes circRNAs' impact on the ESCC tumor microenvironment. To further explore the relationship, we leveraged circRNA, microRNA, and mRNA sequence datasets to construct a comprehensive immune-related circRNA-microRNA-mRNA network, revealing competing endogenous RNA (ceRNA) roles in ESCC. The network comprises 16 circular RNAs, 13 microRNAs, and 1,560 mRNAs. Weighted gene co-expression analysis identified immune-related modules, notably cancer-associated fibroblast (CAF) and myeloid-derived suppressor cell modules, correlating significantly with immune and stemness scores. Among them, the CAF module plays a crucial role in extracellular matrix function and effectively discriminates ESCC patients. Four hub collagen family genes within CAF correlated robustly with CAF, macrophage infiltration, and T-cell exclusion. In-house sequencing and RT-qPCR validated their elevated expression. We also identified CAF module-targeting drugs as potential ESCC treatments. In summary, we established an immune-related circRNA-miRNA-mRNA network that not only illuminates ceRNA functionality but also highlights circRNAs' involvement in the CAF through collagen gene targeting. These findings hold promise to predict ESCC immune landscapes and therapy responses, ultimately aiding in more personalized and effective clinical decision-making.

Scalable Production of Thin and Durable Practical Li Metal Anode for High-Energy-Density Batteries.

Utilization of thin Li metal is the ultimate pathway to achieving practical high-energy-density Li metal batteries (LMBs), but its practical implementation has been significantly impeded by formidable challenges of poor thinning processability, severe interphase instability and notorious dendritic Li growth. Here we report a practical thin (10-40 µm) Li/Mo/Li2Se with concurrently modulated interphase and mechanical properties, achieved via a scalable mechanical rolling process. The in-situ generated Li2Se and Mo not only enhance the mechanical strength enabling the scalable fabrication of thin Li metal, but also promote homogenous Li electrodeposition. Significantly, the Li/Mo/Li2Se demonstrates ultrahigh-rate performance (15 mA cm-2) and ultralong-lifespan cycling sustainability (2700 cycles) with exceptional anti-pulverization capability. The Li|LiFePO4 cells show substantially prolonged cyclability over 1200 cycles with an ultralow decay rate of ~0.01% per cycle. Moreover, the Li|LiNi0.8Co0.1Mn0.1O2 pouch cells deliver enhanced cycling stability even under the extremely harsh conditions of low negative-to-positive-capacity (N/P) ratio of ~1.2 and lean electrolyte of ~0.95 g Ah-1, showing an exceptional energy density of 329.2 Wh kg-1. This work sheds light on facile pathway for scalable production of durable thin Li metal anode toward reliable practicability.

Microbiota-gut-brain axis: interplay between microbiota, barrier function and lymphatic system.

The human gastrointestinal tract, boasting the most diverse microbial community, harbors approximately 100 trillion microorganisms comprising viruses, bacteria, fungi, and archaea. The profound genetic and metabolic capabilities of the gut microbiome underlie its involvement in nearly every facet of human biology, from health maintenance and development to aging and disease. Recent recognition of microbiota - gut - brain axis, referring to the bidirectional communication network between gut microbes and their host, has led to a surge in interdisciplinary research. This review begins with an overview of the current understandings regarding the influence of gut microbes on intestinal and blood-brain barrier integrity. Subsequently, we discuss the mechanisms of the microbiota - gut - brain axis, examining the role of gut microbiota-related neural transmission, metabolites, gut hormones and immunity. We propose the concept of microbiota-mediated multi-barrier modulation in the potential treatment in gastrointestinal and neurological disorders. Furthermore, the role of lymphatic network in the development and maintenance of barrier function is discussed, providing insights into lesser-known conduits of communication between the microbial ecosystem within the gut and the brain. In the final section, we conclude by describing the ongoing frontiers in understanding of the microbiota - gut - brain axis's impact on human health and disease.

Morphological characteristics and phylogenetic analyses revealed four new wood inhabiting fungi (Agaricomycetes, Basidiomycota) in Xizang Autonomous Region, China.

Four new fungi from Xizang in southwest China, Caloceraramaria, Ceraceomycesrhizomorphus, Leptosporomyceslinzhiensis, and Ramariaxizangensis are described and illustrated based on the morphological and molecular evidence. Caloceraramaria is characterized by the ramal and bright orange basidiomata, a monomitic hyphal system with simple septa generative hyphae, usually 4-septate basidiospores; Ceraceomycesrhizomorphus is characterized by the cream to yellowish basidiomata with rhizomorphs, cylindrical basidiospores; Leptosporomyceslinzhiensis is characterized by white with pink basidiomata, cylindrical to oblong ellipsoid basidiospores; Ramariaxizangensis is characterized by flesh pink basidiomata, branched dichotomously in 4-5 ranks, a monomitic hyphal system with clamped generative hyphae, ellipsoid to cylindrical and densely warted basidiospores.

Randomized Phase II Trial of Immunotherapy-Based Total Neoadjuvant Therapy for Proficient Mismatch Repair or Microsatellite Stable Locally Advanced Rectal Cancer (TORCH).

PURPOSE: To assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). PATIENTS AND METHODS: We conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT. RESULTS: Of the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis (P < .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and remained disease free. The most frequent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. Patients in group A had higher rate of cCR (43.5% v 35.6%) at restaging and lower rate of grade 3 to 4 thrombocytopenia (24.2% v 33.9%) during neoadjuvant treatment. CONCLUSION: The iTNT regimens remarkably improved CR rates in pMMR/MSS LARC compared with historical benchmark with acceptable toxicity. Up-front SCRT followed by immunochemotherapy was selected for future definitive study.

The score-goldilocks design for phase 3 clinical trials.

In this paper, we propose a new Bayesian adaptive design, score-goldilocks design, which has the same algorithmic idea as goldilocks design. The score-goldilocks design leads to a uniform formula for calculating the probability of trial success for different endpoint trials by using the normal approximation. The simulation results show that the score-goldilocks design is not only very similar to the goldilocks design in terms of operating characteristics such as type 1 error, power, average sample size, probability of stop for futility, and probability of early stop for success, but also greatly saves the calculation time and improves the operation efficiency.

Modular Synthesis of High Performance Energetic Biocidal Bicyclic Compounds Derivated from Iodopyrazoles.

Modular synthesis can combine different functional module to flexibly regulate comprehensive properties and study the diversity of compounds. This study established a modular bicyclic synthesis strategy of combining polynitro energetic module with iodine-containing biocidal module. Compounds 1-6 with high iodine content (48.72-69.56%) and high thermal stability (Td: 172-304 ˚C) were synthesized and exhaustively identified. By modular synthesis, the detonation properties and gas-production of 3-6 improved greatly expanding their biocidal efficacy and maintained the iodine atomic utilization of iodine-containing module. Notably, 4,5-diiodo-3,4',5'-trinitro-1,3'-bipyrazole (5) and 3,5-diiodo-4,4',5'-trinitro-1,3'-bipyrazole (6) exhibit high detonation velocities (D: 5903 m s-1, 5769 m s-1, respectively) and highest gas production of 212.85 L mol-1 and 217.66 L mol-1 after decomposition. This study diversifies polyiodio-nitro compounds, and also inspire the implementation of similar synthesis strategies to provide family-level synthetic solutions to energetic biocidal materials.

Membrane protein MHZ3 regulates the on-off switch of ethylene signaling in rice.

Ethylene regulates plant growth, development, and stress adaptation. However, the early signaling events following ethylene perception, particularly in the regulation of ethylene receptor/CTRs (CONSTITUTIVE TRIPLE RESPONSE) complex, remains less understood. Here, utilizing the rapid phospho-shift of rice OsCTR2 in response to ethylene as a sensitive readout for signal activation, we revealed that MHZ3, previously identified as a stabilizer of ETHYLENE INSENSITIVE 2 (OsEIN2), is crucial for maintaining OsCTR2 phosphorylation. Genetically, both functional MHZ3 and ethylene receptors prove essential for OsCTR2 phosphorylation. MHZ3 physically interacts with both subfamily I and II ethylene receptors, e.g., OsERS2 and OsETR2 respectively, stabilizing their association with OsCTR2 and thereby maintaining OsCTR2 activity. Ethylene treatment disrupts the interactions within the protein complex MHZ3/receptors/OsCTR2, reducing OsCTR2 phosphorylation and initiating downstream signaling. Our study unveils the dual role of MHZ3 in fine-tuning ethylene signaling activation, providing insights into the initial stages of the ethylene signaling cascade.

ABL1-mediated phosphorylation promotes FOXM1-related tumorigenicity by Increasing FOXM1 stability.

The transcription factor FOXM1, which plays critical roles in cell cycle progression and tumorigenesis, is highly expressed in rapidly proliferating cells and various tumor tissues, and high FOXM1 expression is related to a poor prognosis. However, the mechanism responsible for FOXM1 dysregulation is not fully understood. Here, we show that ABL1, a nonreceptor tyrosine kinase, contributes to the high expression of FOXM1 and FOXM1-dependent tumor development. Mechanistically, ABL1 directly binds FOXM1 and mediates FOXM1 phosphorylation at multiple tyrosine (Y) residues. Among these phospho-Y sites, pY575 is indispensable for FOXM1 stability as phosphorylation at this site protects FOXM1 from ubiquitin-proteasomal degradation. The interaction of FOXM1 with CDH1, a coactivator of the E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C), which is responsible for FOXM1 degradation, is significantly inhibited by Y575 phosphorylation. The phospho-deficient FOXM1(Y575F) mutant exhibited increased ubiquitination, a shortened half-life, and consequently a substantially decreased abundance. Compared to wild-type cells, a homozygous Cr-Y575F cell line expressing endogenous FOXM1(Y575F) that was generated by CRISPR/Cas9 showed obviously delayed mitosis progression, impeded colony formation and inhibited xenotransplanted tumor growth. Overall, our study demonstrates that ABL1 kinase is involved in high FOXM1 expression, providing clear evidence that ABL1 may act as a therapeutic target for the treatment of tumors with high FOXM1 expression.