Progressive encephalomyelitis with rigidity and myoclonus: a pediatric case report and literature review.

BACKGROUND: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare and life-threatening autoimmune disease of the central nervous system. So far, only ten cases of PERM have been reported in children worldwide, including the one in this study. CASE PRESENTATION: We report a case of an 11-year-old boy with PERM with an initial presentation of abdominal pain, skin itching, dysuria, urinary retention, truncal and limb rigidity, spasms of the trunk and limbs during sleep, deep and peripheral sensory disturbances, and dysphagia. A tissue-based assay using peripheral blood was positive, demonstrated by fluorescent staining of mouse cerebellar sections. He showed gradual and persistent clinical improvement after immunotherapy with intravenous immunoglobulin, steroids, plasmapheresis and rituximab. CONCLUSIONS: We summarized the diagnosis and treatment of a patient with PERM and performed a literature review of pediatric PERM to raise awareness among pediatric neurologists. A better comprehension of this disease is required to improve its early diagnosis, treatment, and prognosis.

The influence of existing piles on station settlement during the construction of a tunnel undercrossing under existing stations.

In the construction of tunnels under existing stations, it is necessary to control their settlement. When there is a pile foundation in the existing station, the pile cutting has a significant impact on the settlement of the existing station. To determine the influence of existing piles on the settlement of subway stations, a reasonable pile-cutting time is proposed. Based on the Chengdu Metro Line 9 underpassing the existing Line 1 hatchery station, the settlement law of the tunnel underpassing the existing Line 1 station is analysed via a numerical simulation. Furthermore, the deformation and stress characteristics of the existing piles, pipe roofs, and tunnel linings and the supporting effect on the existing station are discussed. It is concluded that the cutting of existing piles causes a change in the tunnel bearing system, thus resulting in a certain deformation of the station. The influence of different pile cutting times on the settlement of the existing station is then analysed, and it is clarified that the tunnel support stiffness is significantly enhanced after the construction of the secondary lining. At this time, the settlement of the existing pile station is significantly reduced. Finally, through a field investigation, the effect of surface grouting, pipe shed, and multilayer lining on the settlement control of the existing station while the existing pile foundation exists is determined. This research can provide a reference for the settlement control and foundation underpinning of existing stations at ultra-small distances in underground excavation tunnels.

Insufficient phosphorylation of STAT5 in Tregs inhibits the expression of BLIMP-1 but not IRF4, reduction the proportion of Tregs in pediatric aplastic anemia.

Deficiency in regulatory T cells (Tregs) is an important mechanism underlying the pathogenesis of pediatric aplastic anemia, but its specific mechanism is unclear. In our study, we aimed to investigate whether IL-2/STAT5 can regulate the proliferation of Tregs in aplastic anemia (AA) by regulating their expression of B lymphocyte-induced mature protein-1 (BLIMP-1) or interferon regulatory factor 4 (IRF4). Through clinical research and animal experiments, we found that poor activation of the IL-2/STAT5 signaling pathway may leads to low expression of BLIMP-1 in Tregs of children with AA, which leads to defects in the differentiation and proliferation of Tregs in AA. In AA model mice, treatment with IL-2c reversed the decrease in Treg proportions and reduction in Blimp-1 expression in Tregs by increasing the phosphorylation of Stat5 in Tregs. In AA, deficiency of IRF4 expression in Tregs is closely related to the deficiency of Tregs, but is not regulated by the IL-2/STAT5 pathway.

Case report of pediatric TTMV-related acute promyelocytic leukemia with central nervous system infiltration and rapid accumulation of RARA-LBD mutations.

TTMV::RARA is a recently reported fusion gene associated with acute promyelocytic leukemia (APL), caused by the integration of torque teno mini virus (TTMV) genomic fragments into the second intron of the RARA gene. Currently, there have been only six documented cases, with clinical presentations showing significant variability. Although initial responses to all-trans retinoic acid (ATRA) treatment may be observed in patients with TTMV::RARA-APL, the overall prognosis remains unfavorable among infrequent reported cases. This article presents a pediatric case that manifested as PML::RARA-negative APL with central nervous system involvement at onset. The patient experienced both intramedullary and extramedullary relapse one year after undergoing allogeneic hematopoietic stem cell transplantation. Upon identification as TTMV::RARA-APL and subsequent administration of two rounds of ATRA-based treatment, the patient rapidly developed multiple RARA ligand-binding domain mutations and demonstrated extensive resistance to ATRA and various other therapeutic interventions. Additionally, the patient experienced ARID1A mutant clone expansion and progressed MYC-targeted gene activation. This case represents the first documentation of extramedullary involvement at both the initial diagnosis and relapse stages, emphasizing the intricate clinical features and challenges associated with the rapid accumulation of multiple ATRA-resistant mutations in TTMV::RARA-APL, characterizing it as a distinct and complex sub-entity of atypical APL.

Water-stable metal-organic frameworks (MOFs): rational construction and carbon dioxide capture.

Metal-organic frameworks (MOFs) are considered to be a promising porous material due to their excellent porosity and chemical tailorability. However, due to the relatively weak strength of coordination bonds, the stability (e.g., water stability) of MOFs is usually poor, which severely inhibits their practical applications. To prepare water-stable MOFs, several important strategies such as increasing the bonding strength of building units and introducing hydrophobic units have been proposed, and many MOFs with excellent water stability have been prepared. Carbon dioxide not only causes a range of climate and health problems but also is a by-product of some important chemicals (e.g., natural gas). Due to their excellent adsorption performances, MOFs are considered as a promising adsorbent that can capture carbon dioxide efficiently and energetically, and many water-stable MOFs have been used to capture carbon dioxide in various scenarios, including flue gas decarbonization, direct air capture, and purified crude natural gas. In this review, we first introduce the design and synthesis of water-stable MOFs and then describe their applications in carbon dioxide capture, and finally provide some personal comments on the challenges facing these areas.

Assessing wound complications in gastroscopy with Streptomyces protease enzyme combined with Shutai.

Current gastroscopy practices necessitate a balance between procedural efficiency and patient safety. It has been hypothesized that increasing procedure outcomes through the use of Streptomyces protease enzyme and Shutai is possible; however, precise nature of any potential adverse reactions and complications remains unknown. In Zhanjiang, China, 213 patients undergoing gastroscopy participated in this controlled trial. The subjects were allocated at random into two groups: control and treatment. The treatment group was administered topical Streptomyces protease enzyme and intravenous Shutai. Using chi-square and t-tests, information regarding patient demographics, adverse reactions, wound healing, procedure duration, distress levels, and satisfaction was gathered and analysed. The demographic and medical history characteristics of the groups were comparable. There was a greater prevalence of modest immediate reactions in the treatment group (p < 0.05), whereas there were no significant variations observed in delayed reactions and long-term complications (p > 0.05). The treatment group exhibited superior efficiency metrics, including shorter durations for diagnosis, procedure completion and recuperation (p < 0.05). The treatment group exhibited significantly higher patient satisfaction scores (p < 0.05). The incorporation of Streptomyces protease enzyme and Shutai into gastroscopy procedures resulted in significantly enhanced level of procedural efficacy and patient contentment while not introducing an additional risk of long-term complications. The increase in moderate immediate reactions that have been observed requires additional research in order to determine their clinical significance. Although these agents present a possible progression in the field of gastroscopy, their application should be tempered by the immediate adverse reactions that have been documented.

Optimizing Iodine Enrichment through Induced-Fit Transformations in a Flexible Ag(I)-Organic Framework: From Accelerated Adsorption Kinetics to Record-High Storage Density.

Efficient capture and storage of radioactive I2 is a prerequisite for developing nuclear power but remains a challenge. Here, two flexible Ag-MOFs (FJI-H39 and 40) with similar active sites but different pore sizes and flexibility are prepared; both of them can capture I2 with excellent removal efficiencies and high adsorption capacities. Due to the more flexible pores, FJI-H39 not only possesses the record-high I2 storage density among all the reported MOFs but also displays a very fast adsorption kinetic (124 times faster than FJI-H40), while their desorption kinetics are comparable. Mechanistic studies show that FJI-H39 can undergo induced-fit transformations continuously (first contraction then expansion), making the adsorbed iodine species enrich near the Ag(I) nodes quickly and orderly, from discrete I- anion to the dense packing of various iodine species, achieving the very fast adsorption kinetic and the record-high storage density simultaneously. However, no significant structural transformations caused by the adsorbed iodine are observed in FJI-H40. In addition, FJI-H39 has excellent stability/recyclability/obtainability, making it a practical adsorbent for radioactive I2 . This work provides a useful method for synthesizing practical radioactive I2 adsorbents.

Renal pelvis sarcomatoid carcinoma with renal vein tumor thrombus: A case report and literature review.

BACKGROUND: Renal pelvis sarcomatoid carcinoma (RPSC) is a rare and aggressive malignancy whose diagnosis is difficult because radiological imaging results can lead to misclassification as a more common type of renal tumor. In addition, clinical management of patients with RPSC is difficult because of the limited efficacy of available treatments. In this study, we present a comprehensive description of a patient who presented with RPSC and a simultaneous renal vein tumor thrombus. CASE SUMMARY: During April, 2020, a 64-year-old female presented with an isolated episode of hematuria accompanied by abdominal pain. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a lesion in the right renal pelvis. We therefore performed a radical nephrectomy of the right kidney. The subsequent histopathological and immunological results verified the diagnosis of RPSC. Despite administration of 6 cycles of a gemcitabine-cisplatin regimen, the patient's condition progressively deteriorated, and she died about 15 mo after the nephrectomy. CONCLUSION: We performed a comprehensive analysis of a patient with RPSC that included CT, MRI, immunohistochemistry, and genetic testing. The insights from our detailed analysis of this patient and our concomitant review of the literature may assist clinicians in their diagnosis and treatment of RPSC.

Age-dependent seasonal growth cessation in Populus.

In temperate and boreal regions, perennial plants adapt their annual growth cycle to the change of seasons. In natural forests, juvenile seedlings usually display longer growth seasons compared to adult trees to ensure their establishment and survival under canopy shade. However, how trees adjust their annual growth according to their age is not known. In this study, we show that age-dependent seasonal growth cessation is genetically controlled and found that the miR156-SPL3/5 module, a key regulon of vegetative phase change (VPC), also triggers age-dependent growth cessation in Populus trees. We show that miR156 promotes shoot elongation during vegetative growth, and its targets SPL3/5s function in the same pathway but as repressors. We find that the miR156-SPL3/5s regulon controls growth cessation in both leaves and shoot apices and through multiple pathways, but with a different mechanism compared to how the miR156-SPL regulon controls VPC in annual plants. Taken together, our results reveal an age-dependent genetic network in mediating seasonal growth cessation, a key phenological process in the climate adaptation of perennial trees.

The effect of reactive oxygen species (ROS) in immunity and WSSV infection of Scylla paramamosain.

Reactive oxygen species (ROS) are typically regarded as being generated by the cellular respiratory chain or by cells under pathological damage, which play a crucial role as signaling molecules in promoting hemocytes circulation and normal cellular physiological functions. In this study, the antioxidant N-acetylcysteine (NAC) was used to reduce ROS in vivo and in vitro, which to analyze the effect of ROS on innate immunity and viral infection of mud crab. The total hemocyte count (THC), phenoloxidase (PO), superoxide dismutase (SOD) activity, immune-relative genes were analyzed, respectively. Moreover, the effect of ROS on WSSV infection was analyzed by THC and hemocytes apoptosis. The data showed that NAC could effectively remove and inhibit intracellular ROS. The THC of NAC group was reduced at 12 h and 24 h compared with that of control. And the inhibition of ROS by NAC could increase the SOD activity with control group, while increased the PO activity caused by early WSSV infection. And NAC could up-regulate the expression of MCM7, JAK, TLR and proPO significantly, while down-regulate the expression of Astakine, proPO, caspase and p53. Similarly, NAC could inhibit WSSV-induced apoptosis of S. paramamosain hemocytes. The data illustrated that ROS participates in the interaction between hemocytes and virus infection by regulating innate immunity. Especially, after NAC inhibited ROS, the expression of hemocytes proliferation gene Astakine was also inhibited, which may indicate that ROS is related to the process of hemocytes proliferation. The data will show a preliminary exploration on the regulatory role of ROS in crustacean immune system.

Optimizing Sieving Effect for CO2 Capture from Humid Air Using an Adaptive Ultramicroporous Framework.

Excessive CO2 in the air can not only lead to serious climate problems but also cause serious damage to humans in confined spaces. Here, a novel metal-organic framework (FJI-H38) with adaptive ultramicropores and multiple active sites is prepared. It can sieve CO2 from air with the very high adsorption capacity/selectivity but the lowest adsorption enthalpy among the reported physical adsorbents. Such excellent adsorption performances can be retained even at high humidity. Mechanistic studies show that the polar ultramicropore is very suitable for molecular sieving of CO2 from N2 , and the distinguishable adsorption sites for H2 O and CO2 enable them to be co-adsorbed. Notably, the adsorbed-CO2 -driven pore shrinkage can further promote CO2 capture while the adsorbed-H2 O-induced phase transitions in turn inhibit H2 O adsorption. Moreover, FJI-H38 has excellent stability and recyclability and can be synthesized on a large scale, making it a practical trace CO2 adsorbent. This will provide a new strategy for developing practical adsorbents for CO2 capture from the air.

What drives academic peer effects in middle school classrooms in China: Peer composition or peer performance?

This quasi-experimental study estimates academic peer effects in China's middle school (7th-9th grade) classrooms, using data from a large-scale nationally representative survey of middle schoolers in China. Our study design circumvents endogenous sorting by focusing on 52 schools that randomly assigned incoming 7th graders to different 7th-grade classes. Further, reverse causality is addressed by regressing students' 8th-grade test scores on their (randomly assigned) classmates' average 7th-grade test scores. Our analysis reals that all else equal, a one-standard-deviation increase in (8th-grade) classmates' average 7th-grade test scores raises an individual student's 8th-grade mathematics and English test scores, respectively, by 0.13-0.18 and 0.11-0.17 standard deviations. These estimates remain stable when peer characteristics examined in related peer-effect studies are included in the model. Further analysis reveals that peer effects work through raising individual students' time spent studying per week and their confidence in learning. Finally, classroom peer effects are found to be heterogeneous across subgroups: larger for boys, academically stronger students, students attending better schools (i.e., schools with smaller classes and urban schools), and students with relatively disadvantaged family backgrounds (e.g., lower levels of parental education and family wealth).

Genetic basis of STEM occupational choice and regional economic performance: a UK biobank genome-wide association study.

BACKGROUND: Science, technology, engineering, and mathematics (STEM) professionals are regarded as the highly skilled labor force that fosters economic productivity, enterprise innovation, and international competitiveness of a country. This study aims to understand the genetic predisposition to STEM occupations and investigate its associations with regional economic performance. We conducted a genome-wide association study on the occupational choice of STEM jobs based on a sample of 178,976 participants from the UK Biobank database. RESULTS: We identified two genetic loci significantly associated with participants' STEM job choices: rs10048736 on chromosome 2 and rs12903858 on chromosome 15. The SNP heritability of STEM occupations was estimated to be 4.2%. We also found phenotypic and genetic evidence of assortative mating in STEM occupations. At the local authority level, we found that the average polygenic score of STEM is significantly and robustly associated with several metrics of regional economic performance. CONCLUSIONS: The current study expands our knowledge of the genetic basis of occupational choice and potential regional disparities in socioeconomic developments.

Sp1 promotes tumour progression by remodelling the mitochondrial network in cervical cancer.

BACKGROUND: Cervical cancer remains one of the most prevalent cancers worldwide. Accumulating evidence suggests that specificity protein 1 (Sp1) plays a pivotal role in tumour progression. The underlying role and mechanism of Sp1 in tumour progression remain unclear. METHODS: The protein level of Sp1 in tumour tissues was determined by immunohistochemistry. The effect of Sp1 expression on the biological characteristics of cervical cancer cells was assessed by colony, wound healing, transwell formation, EdU, and TUNEL assays. Finally, the underlying mechanisms and effects of Sp1 on the mitochondrial network and metabolism of cervical cancer were analysed both in vitro and in vivo. RESULTS: Sp1 expression was upregulated in cervical cancer. Sp1 knockdown suppressed cell proliferation both in vitro and in vivo, while overexpression of Sp1 had the opposite effects. Mechanistically, Sp1 facilitated mitochondrial remodelling by regulating mitofusin 1/2 (Mfn1/2), OPA1 mitochondrial dynamin-like GTPase (Opa1), and dynamin 1-like (Drp1). Additionally, the Sp1-mediated reprogramming of glucose metabolism played a critical role in the progression of cervical cancer cells. CONCLUSIONS: Our study demonstrates that Sp1 plays a vital role in cervical tumorigenesis by regulating the mitochondrial network and reprogramming glucose metabolism. Targeting Sp1 could be an effective strategy for the treatment of cervical cancer.

The impact of echinococcosis interventions on economic outcomes in Qinghai Province of China: Evidence from county-level panel data.

Introduction: Echinococcosis can incur substantial economic losses for the livestock industry by causing organ condemnation, delayed growth, and reduced meat and wool output and quality in sheep and cattle, as well as increased surgery costs, hospital care, and decreased productivity in humans. Yet echinococcosis could be prevented and controlled by interventions, such as dog management and deworming, lamb vaccination, slaughter management, and training and public education. Methods: Exploiting temporal and spatial variations in the number of intervention measures implemented in 39 counties in Qinghai province of China in 2015-2020, this study assesses the economic impact of echinococcosis interventions using a dynamic difference-in-differences model. Results: The results suggest that echinococcosis interventions brought about substantial economic gains measured by per capita net income of rural residents and per capita gross output of animal husbandry. These economic gains are greater in non-pastoral counties (with a gain in per capita net income of rural residents of 3,308 yuan and a gain per capita gross output of animal husbandry of 1,035 yuan) than in pastoral counties (with a gain in per capita net income of rural residents of 1,372 yuan and a gain per capita gross output of animal husbandry of 913 yuan). They are also greater in counties with echinococcosis infection level-2 (with a human infection rate of 0.1-1% or a dog infection rate of 1-5%) than infection level-1 counties (with a human prevalence rate ≥1% or a dog infection rate ≥5%). Discussion: Not only will these economic gains encourage livestock farmers to strengthen their echinococcosis prevention and control practices, but they will also inform public policy on zoonotic disease prevention and control in China and other countries alike.

Application of EEG in migraine.

Migraine is a common disease of the nervous system that seriously affects the quality of life of patients and constitutes a growing global health crisis. However, many limitations and challenges exist in migraine research, including the unclear etiology and the lack of specific biomarkers for diagnosis and treatment. Electroencephalography (EEG) is a neurophysiological technique for measuring brain activity. With the updating of data processing and analysis methods in recent years, EEG offers the possibility to explore altered brain functional patterns and brain network characteristics of migraines in depth. In this paper, we provide an overview of the methodology that can be applied to EEG data processing and analysis and a narrative review of EEG-based migraine-related research. To better understand the neural changes of migraine or to provide a new idea for the clinical diagnosis and treatment of migraine in the future, we discussed the study of EEG and evoked potential in migraine, compared the relevant research methods, and put forwards suggestions for future migraine EEG studies.

Galectin-9 blockade synergizes with ATM inhibition to induce potent anti-tumor immunity.

Although current cancer immunotherapies that target PD-1/PD-L1 immune checkpoint to reinvigorate exhausted T cells have achieved impressive clinical outcomes, only a small proportion of patients respond. New therapeutic targets are therefore needed to be identified to further unleash the anti-tumor potential of T cells and benefit more patients. Galectin-9 (Gal-9), initially identified as a ligand for TIM-3 to induce T cell death, acts as an immunosuppressive regulator in the tumor microenvironment (TME) but its potential as a therapeutic target remains largely elusive. Here we show that antibody neutralization of Gal-9, in combination with inhibition of Ataxia telangiectasia mutated (ATM), a kinase essential for DNA damage response (DDR), is a promising modality for cancer immunotherapy. Genetic depletion of ATM in tumors markedly potentiated anti-Gal-9 therapy in a syngeneic mouse model. Mechanistically, ATM inhibition greatly upregulated Gal-9 expression and secretion in a variety of human and murine tumor cells via the cGAS-STING-interferon ß (IFNß) innate immune pathway. Combination of Gal-9 inhibition with AZD1390, a selective ATM inhibitor currently evaluated in clinical trials, significantly suppressed tumor growth and prolonged survival in multiple syngeneic mouse models, including the poorly-immunogenic LLC lung tumors that do not respond to PD-1/PD-L1 blockade, concomitant with increased T cell infiltration. These results reveal Gal-9 induction via STING/IFNß signaling as an important mechanism mediating tumor immune escape that could be targeted for cancer immunotherapies, and unveil a novel anti-Gal-9-based combination strategy for cancer immunotherapies in a wide variety of malignancies, including those resistant to PD-1/PD-L1 blockade.

DNTT activation, TdT-aided gene length mutation, and better prognosis in ATG-based regimen allo-HSCT in AML.

This study aimed to investigate the relationship between anomalous DNA nucleotidylexotransferase (DNTT) activation and the mutagenesis of gene length mutations (LMs) in acute myeloid leukemia (AML), and the relevance of their prognosis in antithymocyte globulin (ATG)-based regimen allogeneic hematopoietic stem cell transplantation (allo-HSCT). A cohort of 578 AML cases was enrolled. Next-generation sequencing was performed to screen mutations of 86 leukemia driver genes. RNA-seq was used to analyze gene expression. Prognostic analysis was investigated in 239 AML cases who underwent ATG-based regimen allo-HSCT. We report a refined subtyping algorithm of LMs (type I-IV) based on sequence anatomy considering the TdT-aided mutagenesis mechanism. GC content adjacent to LM junctions, inserted nontemplate nucleotide bases, and DNTT expression analysis supported the DNTT activation and TdT-aided mutagenesis in type II/III LMs in the total AML cohort. Both single-variate and multivariate analyses showed a better overall survival of FLT3 type III compared to type I in a subset of ATG-based regimen allo-HSCT cases. The novel LM subtyping algorithm not only deciphers the etiology of the mutagenesis of LMs but also helps to fine-tune prognosis differentiation in AML. The possible prognostic versatility of this novel LM subtyping algorithm in terms of chemotherapy, targeted therapy, and allo-HSCT merits further investigation.

The quality disparity of stroke care over time: An analysis based on the national dataset from 2011 to 2017.

BACKGROUND: Adherence to evidence-based hospital stroke care is variable and may change over time. It is important to determine which process measures are associated with variation in outcome. In a large dataset, we analyzed the association between process and outcome and the fluctuations of indicators over time, and identified quality indicators (QIs) that should be prioritized for improving the quality of stroke care. METHODS: We analyzed data from 123,259 patients diagnosed with acute ischemic stroke (AIS) who were treated at 109 large tertiary hospitals in China between January 2011 and May 2017. In total, 12 stroke treatment indicators were selected to calculate the hospital process composite performance (HPCP). Hospitals were divided into subgroups according to the time trend of HPCP estimated by the Group-Based Model. We analyzed the influence of hospital subgroups on the patient outcomes using a multi-level model and explored the QIs that led to variation. RESULTS: The HPCP trends for stroke indicators of 109 hospitals over 7 years were divided into two groups (Group 1, low-HPCP; Group 2, high-HPCP). After adjusting for patient age, medical insurance, comorbidities, patterns of admission, and NIHSS-scores, patients in the high-HPCP group presented higher rate of independence and longer length of stay compared to the low-HPCP group. The multi-level model showed that there was a statistically significant difference in the utilization rate between the two groups, with most marked differences seen in emergency assessment and function evaluation indicators. CONCLUSION: Variation in the quality of stroke care exists across hospitals, and better adherence to guideline-based care is associated with improved outcomes. We found that QIs related to emergency examination and functional assessment were the main factors differing between good and poor adherers to stroke indicators, suggesting that quality improvement in stroke care could prioritize these QIs.