A study of ruxolitinib response-based stratified treatment for pediatric hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a lethal disorder characterized by hyperinflammation. Recently, ruxolitinib (RUX), targeting key cytokines in HLH, has shown promise for HLH treatment. However, there is a lack of robust clinical trials evaluating its efficacy, especially its utility as a frontline therapy. In this study (www.chictr.org.cn, ChiCTR2000031702), we designed ruxolitinib as a first-line agent for pediatric HLH and stratified the treatment based on its early response. Fifty-two newly diagnosed patients were enrolled. The overall response rate (ORR) of ruxolitinib monotherapy (day 28) was 69.2% (36/52), with 42.3% (22/52) achieving sustained complete remission (CR). All responders achieved their first response to ruxolitinib within 3 days. The response to ruxolitinib was significantly associated with the underlying etiology at enrollment (P = .009). Epstein-Barr virus (EBV)-HLH patients were most sensitive to ruxolitinib, with an ORR of 87.5% (58.3% in CR). After ruxolitinib therapy, 57.7% (30/52) of the patients entered intensive therapy with additional chemotherapy. Among them, 53.3% (16/30) patients achieved CR, and 46.7% (14/30) patients dominated by chronic active EBV infection-associated HLH (CAEBV-HLH) developed refractory HLH by week 8. The median interval to additional treatment since the first ruxolitinib administration was 6 days (range, 3-25 days). Altogether, 73.1% (38/52) of the enrolled patients achieved CR after treatment overall. The 12-month overall survival (OS) for all patients was 86.4% (95% confidence interval [CI], 77.1% to 95.7%). Ruxolitinib had low toxicity and was well tolerated compared with intensive chemotherapy. Our study provides clinical evidence for ruxolitinib as a frontline agent for pediatric HLH. The efficacy was particularly exemplified with stratified regimens based on the early differential response to ruxolitinib. This study was registered in the Chinese Clinical Trials Registry Platform (http://www.chictr.org.cn/) as ChiCTR2000031702.

Relationship between subtype-specific minimal residual disease level and long-term prognosis in children with acute lymphoblastic leukemia.

Minimal residual disease (MRD) based risk stratification criteria for specific genetic subtypes remained unclear in childhood acute lymphoblastic leukemia (ALL). Among 723 children with newly diagnosed ALL treated with the Chinese Children Leukemia Group CCLG-2008 protocol, MRD was assessed at time point 1 (TP1, at the end of induction) and TP2 (before consolidation treatment) and the MRD levels significantly differed in patients with different fusion genes or immunophenotypes (P all < 0.001). Moreover, the prognostic impact of MRD varied by distinct molecular subtypes. We stratified patients in each molecular subtype into two MRD groups based on the results. For patients carrying BCR::ABL1 or KMT2A rearrangements, we classified patients with MRD < 10-2 at both TP1 and TP2 as the low MRD group and the others as the high MRD group. ETV6::RUNX1+ patients with TP1 MRD < 10-3 and TP2 MRD-negative were classified as the low MRD group and the others as the high MRD group. For T-ALL, We defined children with TP1 MRD ≥ 10-3 as the high MRD group and the others as the low MRD group. The 10-year relapse-free survival of low MRD group was significantly better than that of high MRD group. We verified the prognostic impact of the subtype-specific MRD-based stratification in patients treated with the BCH-ALL2003 protocol. In conclusion, the subtype-specific MRD risk stratification may contribute to the precise treatment of childhood ALL.

The plasma-soluble CSF1R level is a promising prognostic indicator for pediatric Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare hematologic neoplasm characterized by the clonal proliferation of Langerhans-like cells. Colony-stimulating factor 1 receptor (CSF1R) is a membrane-bound receptor that is highly expressed in LCH cells and tumor-associated macrophages. In this study, a soluble form of CSF1R protein (sCSF1R) was identified by plasma proteome profiling, and its role in evaluating LCH prognosis was explored. We prospectively measured plasma sCSF1R levels in 104 LCH patients and 10 healthy children using ELISA. Plasma sCSF1R levels were greater in LCH patients than in healthy controls (p < .001) and significantly differed among the three disease extents, with the highest level in MS RO+ LCH patients (p < .001). Accordingly, immunofluorescence showed the highest level of membrane-bound CSF1R in MS RO+ patients. Furthermore, the plasma sCSF1R concentration at diagnosis could efficiently predict the prognosis of LCH patients treated with standard first-line treatment (AUC = 0.782, p < .001). Notably, dynamic monitoring of sCSF1R levels could predict relapse early in patients receiving BRAF inhibitor treatment. In vitro drug sensitivity data showed that sCSF1R increased resistance to Ara-C in THP-1 cells expressing ectopic BRAF-V600E. Overall, the plasma sCSF1R level at diagnosis and during follow-up is of great clinical importance in pediatric LCH patients.

BRAF-V600E mutations in plasma and peripheral blood mononuclear cells correlate with prognosis of pediatric Langerhans cell histiocytosis treated with first-line therapy.

BACKGROUND: The clinical relevance of BRAF-V600E alleles in peripheral blood mononuclear cells (PBMCs) and the prognostic impact of the mutants in cell-free (cf) and PBMC DNAs of Langerhans cell histiocytosis (LCH) have not been fully clarified in pediatric LCH. METHODS: We retrospectively determined the levels of BRAF-V600E mutation in paired plasma and PBMC samples at the time of diagnosis of LCH. Subsequently, we performed a separate or combined analysis of the clinical and prognostic impact of the mutants. RESULTS: We assessed BRAF-V600E mutation in peripheral blood from 94 patients of childhood LCH. Our data showed that cfBRAF-V600E was related to young age, multiple-system (MS) disease, involvements of organs with high risk, increased risk of relapse, and worse progression-free survival (PFS) of patients. We also observed that the presence of BRAF-V600E in PBMCs at baseline was significantly associated with MS LCH with risk organ involvement, younger age, and disease progression or relapse. The coexisting of plasma(+)/PBMC(+) identified 36.2% of the patients with the worst outcome, and the hazard ratio was more significant than either of the two alone or neither, indicating that combined analysis of the mutation in plasma and PBMCs was more accurate to predict relapse than evaluation of either one. CONCLUSIONS: Concurrent assessment of BRAF-V600E mutation in plasma and PBMCs significantly impacted the prognosis of children with LCH. Further prospective studies with larger cohorts need to validate the results of this study.

Chiral Two-Dimensional Hybrid Organic-Inorganic Perovskites for Piezoelectric Ultrasound Detection.

Hybrid organic-inorganic perovskites (HOIPs) have exhibited striking application potential in piezoelectric energy harvesting and sensing due to their high piezoelectricity, light weight, and solution processability. However, to date, the application of piezoelectric HOIPs in ultrasound detection has not yet been explored. Here, we report the synthesis of a pair of chiral two-dimensional piezoelectric HOIPs, R-(4-bromo-2-butylammonium)2PbBr4 and S-(4-bromo-2-butylammonium)2PbBr4 [R-(BrBA)2PbBr4 and S-(BrBA)2PbBr4], which show low mechanical strength and significant piezoelectric strain coefficients that are advantageous for mechanoelectrical energy conversion. Benefiting from these virtues, the R-(BrBA)2PbBr4@PBAT and S-(BrBA)2PbBr4@PBAT [PBAT = poly(butyleneadipate-co-terephthalate)] composite films show prominent underwater ultrasound detection performance with a transmission effectivity of 12.0% using a 10.0 MHz probe, comparable with that of a polyvinylidene fluoride (PVDF) device fabricated in the same conditions. Density functional theory calculations reveal that R-(BrBA)2PbBr4 and S-(BrBA)2PbBr4 have a beneficial acoustic impedance (5.07-6.76 MRayl) compatible with that of water (1.5 MRayl), which is responsible for the facile ultrasound-induced electricity generation. These encouraging results open up new possibilities for applying piezoelectric HOIPs in underwater ultrasound detection and imaging technologies.

Efficacy of ruxolitinib for HAVCR2 mutation-associated hemophagocytic lymphohistiocytosis and panniculitis manifestations in children.

Frequent germline mutations of HAVCR2, recently identified in subcutaneous panniculitis-like T-cell lymphoma (SPTCL), are associated with an increased risk of hemophagocytic lymphohistiocytosis (HLH). However, SPTCL-HLH represents a challenge because of the difficulties in treatment with poor survival. Its malignant nature, specifically harbouring HAVCR2 mutations, has also been questioned. To better understand its pathology and treatment, we analysed the clinical data of six patients diagnosed at our centre. The median age at onset was 10.5 years (range, 0.8-12.4). Five patients presented with skin lesions of subcutaneous nodules/plaques and/or ulceration. All patients developed HLH; notably, one infant only had HLH without skin involvement. Histopathologically, only two patients were diagnosed with SPTCL and three were reported as panniculitis with no sufficient evidence of lymphoma. Genetically, germline homozygous mutation of HAVCR2 (p.Y82C) was identified in all patients, with a median diagnosis time of 4.6 months. All patients initially received corticosteroids, immunosuppressants or chemotherapy, achieving unfavourable responses. Strikingly, they responded well to ruxolitinib targeting inflammatory cytokines, allowing rapid disease resolution and/or long-term maintenance of remission. The excellent efficacy of ruxolitinib highlights this disease as an inflammatory condition instead of neoplastic nature and indicates novel agents targeting key inflammatory pathways as an encouraging approach for this disease entity.

PES1 reduces CD8+ T cell infiltration and immunotherapy sensitivity via interrupting ILF3-IL15 complex in esophageal squamous cell carcinoma.

BACKGROUND: Although immune checkpoint blockade (ICB) therapy has brought survival benefits to patients with specific cancer types, most of cancer patients remain refractory to the ICB therapy, which is largely attributed to the immunosuppressive tumor microenvironment. Thereby, it is urgent to profile key molecules and signal pathways responsible for modification of tumor microenvironment. METHODS: Multiple databases of esophageal squamous cell carcinoma (ESCC) were integratively analyzed to screen candidate genes responsible for infiltration of CD8+ T cells. Expression of pescadillo ribosomal biogenesis factor 1 (PES1) in clinical ESCC samples was examined by qRT-PCR, western blotting, and immunohistochemistry. The mechanisms of PES1 were investigated via RNA sequencing and mass spectrometry followed by immunoprecipitation and proximity ligation assay. The clinical and therapeutic significance of PES1 in ESCC was comprehensively investigated using ESCC cells and mouse model. RESULTS: PES1 was significantly upregulated and correlated with poor prognosis in ESCC patients. PES1 knockdown decreased ESCC cell growth in vitro and in vivo and enhanced the efficacy of ICB therapy in mouse model, which was established through subcutaneous inoculation with ESCC cells. Analyses on RNA sequencing and mass spectrometry suggested that PES1 expression was negatively correlated with IL15 and ILF3 was one of the PES1-associated proteins. It has been known that ILF3 interacts with and stabilizes IL15 mRNA to increase IL15 protein level. Our data further indicated that PES1 interfered with the interaction between ILF3 and IL15 mRNA and impaired ILF3-mediated stabilization of IL15 mRNA, which eventually reduced the protein level of IL15. Interestingly, the inhibitory effect of ICB therapy boosted by PES1 knockdown dramatically antagonized by knockdown of IL15, which suppressed the tumor-infiltrated CD8+ T cells in ESCC. Finally, we confirmed the relationships among PES1, IL15, and CD8+ T cell infiltration in 10 locally advanced ESCC patients receiving ICB neoadjuvant therapy and demonstrated that ICB therapy would be more effective in those with low expression of PES1. CONCLUSIONS: Altogether, our findings herein provided novel insights on biological function and clinical significance of PES1 and suggested that high expression of PES1 could suppress ILF3-IL15 axis-mediated immunosurveillance and promote resistance to ICB through restraining tumor-infiltrated CD8+ T cells.

Clinical outcomes and prognostic risk factors of Langerhans cell histiocytosis in children: Results from the BCH-LCH 2014 protocol study.

Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm mainly affecting young children. This study aimed to evaluate the outcomes of 449 pediatric patients enrolled in the BCH-LCH 2014 study. 52.6% of patients were classified with single-system (SS) LCH, 28.1% with multisystem (MS) risk organ negative (RO-) LCH, and 19.4% with MS RO+ LCH. Three hundred ninety-six patients (88.2%) were initially treated with first-line therapy based on the vindesine-prednisone combination. One hundred thirty-nine patients who lacked a response to initial treatment were shifted to second-line therapy, 72 to intensive treatment Arm S1 (a combination of cytarabine, cladribine, vindesine, and dexamethasone), and 67 to Arm S2 (without cladribine). The 5-year overall survival (OS), progression-free survival (PFS), and relapse rates were 98.2% (median: 97.6 months), 54.6% (median: 58.3 months), and 29.9%, respectively. MS RO+ patients had the worst prognosis among the three clinical subtypes. For the patients initially treated with first-line therapy, the 5-year OS, PFS, and relapse rates were 99.2%, 54.5%, and 29.3%, respectively. Patients in Arm S1 had a significantly better prognosis than patients in Arm S2 (5-year PFS: 69.2% vs. 46.5%, p = .042; relapse rate: 23.4% vs. 44.2%, p = .031). Multivariate analysis revealed that early treatment response, the involvement of RO, skin, and oral mucosa, as well as laboratory parameters, including CRP and γ-GT, were independent risk factors for the PFS of LCH. Thus, the prognosis of LCH in children has been improved significantly with stratified chemotherapy, and progression and relapse remained the challenges, especially for RO+ patients.

Interaction of E2F3a and CASP8AP2 Regulates Histone Expression and Chemosensitivity of Leukemic Cells.

Low expression levels of E2F3a and caspase 8-associated protein 2 (CASP8AP2) are associated with poor outcomes in children with acute lymphoblastic leukemia. Our previous study showed that a combined assessment of E2F3a and CASP8AP2 expression was more accurate in predicting relapse in children with acute lymphoblastic leukemia. However, the underlying mechanism remains unclear. In this study, the interaction between E2F3a and CASP8AP2 and its role in the regulation of histone expression, cell proliferation, the cell cycle, and chemosensitivity were investigated. Exogenous E2F3a-GST was coprecipitated with CASP8AP2-FLAG in HEK-293T cells. E2F3a was colocalized with CASP8AP2-GFP in the nucleus. The replication-dependent histones H2A and H2B were significantly upregulated when E2F3a or CASP8AP2 was overexpressed in HEK-293T or 697 cells and downregulated by E2F3a or CASP8AP2 knockdown. E2F3a and CASP8AP2 could collaboratively enhance the transcriptional activity of HIST1H2AG and HIST1H2BK . Both CASP8AP2 and E2F3a are involved in S phase progression. E2F3a and CASP8AP2 also affected the sensitivity of leukemic cells to daunorubicin. Therefore, CASP8AP2 and E2F3a collaboratively regulated replication-dependent histone expression, cell cycle progression, and chemosensitivity of leukemic cells.

Development and global validation of a 1-week-old piglet head finite element model for impact simulations.

PURPOSE: Child head injury under impact scenarios (e.g. falls, vehicle crashes, etc.) is an important topic in the field of injury biomechanics. The head of piglet was commonly used as the surrogate to investigate the biomechanical response and mechanisms of pediatric head injuries because of the similar cellular structures and material properties. However, up to date, piglet head models with accurate geometry and material properties, which have been validated by impact experiments, are seldom. We aim to develop such a model for future research. METHODS: In this study, first, the detailed anatomical structures of the piglet head, including the skull, suture, brain, pia mater, dura mater, cerebrospinal fluid, scalp and soft tissue, were constructed based on CT scans. Then, a structured butterfly method was adopted to mesh the complex geometries of the piglet head to generate high-quality elements and each component was assigned corresponding constitutive material models. Finally, the guided drop tower tests were conducted and the force-time histories were ectracted to validate the piglet head finite element model. RESULTS: Simulations were conducted on the developed finite element model under impact conditions and the simulation results were compared with the experimental data from the guided drop tower tests and the published literature. The average peak force and duration of the guide drop tower test were similar to that of the simulation, with an error below 10%. The inaccuracy was below 20%. The average peak force and duration reported in the literature were comparable to those of the simulation, with the exception of the duration for an impact energy of 11 J. The results showed that the model was capable to capture the response of the pig head. CONCLUSION: This study can provide an effective tool for investigating child head injury mechanisms and protection strategies under impact loading conditions.

Metabonomics Analysis of Brain Stem Tissue in Rats with Primary Brain Stem Injury Caused Death.

OBJECTIVES: To explore the potential biomarkers for the diagnosis of primary brain stem injury (PBSI) by using metabonomics method to observe the changes of metabolites in rats with PBSI caused death. METHODS: PBSI, non-brain stem brain injury and decapitation rat models were established, and metabolic maps of brain stem were obtained by LC-MS metabonomics method and annotated to the HMDB database. Partial least square-discriminant analysis (PLS-DA) and random forest methods were used to screen potential biomarkers associated with PBSI diagnosis. RESULTS: Eighty-six potential metabolic markers associated with PBSI were screened by PLS-DA. They were modeled and predicted by random forest algorithm with an accuracy rate of 83.3%. The 818 metabolic markers annotated to HMDB database were used for random forest modeling and prediction, and the accuracy rate was 88.9%. According to the importance in the identification of cause of death, the most important metabolic markers that were significantly up-regulated in PBSI group were HMDB0038126 (genipinic acid, GA), HMDB0013272 (N-lauroylglycine), HMDB0005199 [(R)-salsolinol] and HMDB0013645 (N,N-dimethylsphingosine). CONCLUSIONS: GA, N-lauroylglycine, (R)-salsolinol and N,N-dimethylsphingosine are expected to be important metabolite indicators in the diagnosis of PBSI caused death, thus providing clues for forensic medicine practice.

Pressure-Tuned Multicolor Emission of 2D Lead Halide Perovskites with Ultrahigh Color Purity.

The chemical diversity and structural flexibility of lead halide perovskites (LHPs) offer tremendous opportunities to tune their optical properties through internal molecular engineering and external stimuli. Herein, we report the wide-range and ultrapure photoluminescence emissions in a family of homologous 2D LHPs, [MeOPEA]2 PbBr4-4x I4x (MeOPEA=4-methoxyphenethylammonium; x=0, 0.2, 0.425, 0.575, 1) enabled through internal chemical pressure and external hydrostatic pressure. The chemical pressure, induced by the C-H⋅⋅⋅π interactions and halogen doping/substitution strengthens the structural rigidity to give sustained narrow emissions, and regulates the emission energy, respectively. Further manipulation of physical pressure leads to wide-range emission tuning from 412 to 647 nm in a continuous and reversible manner. This work could open up new pathways for developing 2D LHP emitters with ultra-wide color gamut and high color purity which are highly useful for pressure sensing.

Origin of Ferroelectricity in Two Prototypical Hybrid Organic-Inorganic Perovskites.

Hybrid organic-inorganic perovskite (HOIP) ferroelectrics are attracting considerable interest because of their high performance, ease of synthesis, and lightweight. However, the intrinsic thermodynamic origins of their ferroelectric transitions remain insufficiently understood. Here, we identify the nature of the ferroelectric phase transitions in displacive [(CH3)2NH2][Mn(N3)3] and order-disorder type [(CH3)2NH2][Mn(HCOO)3] via spatially resolved structural analysis and ab initio lattice dynamics calculations. Our results demonstrate that the vibrational entropy change of the extended perovskite lattice drives the ferroelectric transition in the former and also contributes importantly to that of the latter along with the rotational entropy change of the A-site. This finding not only reveals the delicate atomic dynamics in ferroelectric HOIPs but also highlights that both the local and extended fluctuation of the hybrid perovskite lattice can be manipulated for creating ferroelectricity by taking advantages of their abundant atomic, electronic, and phononic degrees of freedom.

Chemically Stable Guanidinium Covalent Organic Framework for the Efficient Capture of Low-Concentration Iodine at High Temperatures.

The capture of radioactive I2 vapor from nuclear waste under industrial operating conditions remains a challenging task, as the practical industrial conditions of high temperature (≥150 °C) and low I2 concentration (∼150 ppmv) are unfavorable for I2 adsorption. We report a novel guanidinium-based covalent organic framework (COF), termed TGDM, which can efficiently capture I2 under industrial operating conditions. At 150 °C and 150 ppmv I2, TGDM exhibits an I2 uptake of ∼30 wt %, which is significantly higher than that of the industrial silver-based adsorbents such as Ag@MOR (17 wt %) currently used in the nuclear fuel reprocessing industry. Characterization and theoretical calculations indicate that among the multiple types of adsorption sites in TGDM, only ionic sites can bond to I2 through strong Coulomb interactions under harsh conditions. The abundant ionic groups of TGDM account for its superior I2 capture performance compared to various benchmark adsorbents. In addition, TGDM exhibits exceptionally high chemical and thermal stabilities that fully meet the requirements of practical radioactive I2 capture (high-temperature, humid, and acidic environment) and differentiate it from other ionic COFs. Furthermore, TGDM has excellent recyclability and low cost, which are unavailable for the current industrial silver-based adsorbents. These advantages make TGDM a promising candidate for capturing I2 vapor during nuclear fuel reprocessing. This strategy of incorporating chemically stable ionic guanidine moieties in COF would stimulate the development of new adsorbents for I2 capture and related applications.

A New Hybrid Lead-Free Metal Halide Piezoelectric for Energy Harvesting and Human Motion Sensing.

Hybrid organic-inorganic piezoelectrics have attracted attention due to their simple synthesis, mechanical flexibility, and designability, which have promising application potential in flexible sensing and self-powered energy harvesting devices. Although some hybrid piezoelectrics are discovered, most of their structures are limited by the perovskite-type and often contain lead. Herein, the synthesis, structure, and piezoelectric properties of a new hybrid lead-free metal halide, (BTMA)2 CoBr4 (BTMA = benzyltrimethylammonium) are reported. The experimental and theoretical results demonstrate that this material simply composed of [CoBr4 ]2- tetrahedra and BTMA+ cations exhibits significant piezoelectricity (d22 = 5.14, d25 = 12.40 pC N-1 ), low Young's and shear moduli (4.11-17.56 GPa; 1.86-7.91 GPa). Moreover, the (BTMA)2 CoBr4 /PDMS (PDMS = polydimethylsiloxane) composite thin films are fabricated and optimized. The 10% (BTMA)2 CoBr4 /PDMS-based flexible devices show attractive performance in energy harvesting with an open-circuit voltage of 19.70 V, short-circuit current of 4.24 µA, and powder density of 11.72 µW cm-2 , catching up with those of piezoelectric ceramic composites. Meanwhile, these film devices show excellent capability in accurately sensing human body motions, such as finger bending and tapping. This work demonstrates that (BTMA)2 CoBr4 and related piezoelectric lead-free halides can be promising molecular materials in modern energy and sensing applications.

Characteristics and Treatment Outcomes of Pediatric Langerhans Cell Histiocytosis with Thymic Involvement.

OBJECTIVE: To evaluate the characteristics and treatment outcomes of patients with pediatric Langerhans cell histiocytosis (LCH) with thymic involvement. STUDY DESIGN: We retrospectively described the clinical, biological, and imaging characteristics of a series of 19 patients with pediatric LCH with thymic involvement in our center between September 2016 and December 2019. We further analyzed the treatment response and outcomes of patients treated with chemotherapy or targeted therapy. RESULTS: Thymic involvement was found in 4.4% of a 433-consecutive pediatric LCH cohort; all LCH-thymic involvement presented with multisystem disease. Patients with thymic involvement were typically younger, harboring more lung and thyroid involvement and less bone involvement than those without thymic involvement. Most patients with thymic involvement had alteration of immunocompetence with decreased numbers of T-lymphocyte subsets and immunoglobulin G levels. Overall, 47.1% of patients demonstrated a response after 6 weeks of induction therapy, and 92.3% of the patients who did not respond to the first-line treatment had resolution of thymus after the second-line and/or targeted therapy. The progression/relapse rate showed no difference between patients who shifted to second-line therapy and those to dabrafenib (33.3% vs 25%, P = 1.000). The survival for patients with thymic involvement did not differ from those without thymic involvement. More patients treated with second-line chemotherapy had severe adverse events than those given dabrafenib (88.9% vs 0, P < .001). CONCLUSIONS: Thymic involvement was observed rarely in LCH and had specific clinical characteristics. Chemotherapy could resolve most thymic lesions, and BRAF inhibitors might provide a promising treatment option with less toxicity for infants with BRAF-V600E mutation. TRIAL REGISTRATION: http://www.chictr.org.cn, identifier: ChiCTR2000030457 (BCH-LCH 2014 study); ChiCTR2000032844 (dabrafenib study).

Significance of serum Th1/Th2 cytokine levels in underlying disease classification of childhood HLH.

OBJECT: Goal of this research was to investigate values of serum cytokines in childhood HLH with different triggers, with the expectation to find secretion spectrum of 5 main types of underlying diseases. METHOD: 118 newly diagnosed HLH were included, and serum concentrations of 6 cytokines were tested before treatment began. Absolute cytokine levels and ratios between them were then studied in the HLH groups collectively and separately RESULTS: In general, IFN-γ, IL-10 and IL-6 showed differences among 5 HLH groups. Specifically, relative levels of these three cytokines to each other were meaningful in distinguishing 4 types of HLH. Level of IL-6 was higher than those of IFN-γ or IL-10 in HLH driven by Systemic auto-inflammatory disorders (SAIDs) or Langerhans Cell Histiocytosis (LCH), while primary HLH and EBV-HLH shared elevated ratio of IL-10 to IL-6. Although more than one distinctive ratios were found in 3 HLH groups, combination of these parameters didn't offer optimal balance between sensitivity and specificity. CONCLUSION: As a group of easily gained laboratory findings, cytokine levels were reliable in the procedure of roughly classifying HLH cases with the help of patients' clinical phenotype. However, adequate data is still needed to explore the significance of these indicators in identifying one particular underlying disease accurately.

Interaction between CASP8AP2 and ZEB2-CtBP2 Regulates the Expression of LEF1.

Low expression of CTBP2 and CASP8AP2 correlated with poor outcome and predicted risk of relapse in pediatric B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to investigate the molecular mechanism by which CASP8AP2 regulates LEF1 expression by interacting with CtBP2 and ZEB2 in Acute lymphoblastic lymphoma (ALL). There was an interaction between CASP8AP2, ZEB2, and CtBP2, and then the interaction between CtBP2 and ZEB2 was observed after downregulating the expression of CASP8AP2. The wild type (containing the ZEB2 binding site) or mutant (containing a mutant binding site) LEF1 gene promoter sequence was inserted into the pGL3-basic plasmid, and a dual-luciferase reporter gene detection system was used to observe how CASP8AP2, ZEB2, and CtBP2 regulate the transcription of the LEF1 gene. We conclude that CASP8AP2, CtBP2, and ZEB2 can all bind to the LEF1 gene promoter region and reduce the luciferase activity of the LEF1 promoter. Meanwhile, the interaction of ZEB2 and the LEF1 promoter was significantly weakened after downregulation of CASP8AP2. Knockdown of CASP8AP2 in the 697 cell lines resulted in the significant upregulation of the mRNA expression levels of the stemness-related genes CD44, JAG1, and SALL4. In conclusion, CASP8AP2 is vital for the interaction between CtBP2 and ZEB2, inhibiting LEF1 and stemness-related genes expression ALL.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2022.2033369 .

Recognition of Upper Limb Action Intention Based on IMU.

Using motion information of the upper limb to control the prosthetic hand has become a hotspot of current research. The operation of the prosthetic hand must also be coordinated with the user's intention. Therefore, identifying action intention of the upper limb based on motion information of the upper limb is key to controlling the prosthetic hand. Since a wearable inertial sensor bears the advantages of small size, low cost, and little external environment interference, we employ an inertial sensor to collect angle and angular velocity data during movement of the upper limb. Aiming at the action classification for putting on socks, putting on shoes and tying shoelaces, this paper proposes a recognition model based on the Dynamic Time Warping (DTW) algorithm of the motion unit. Based on whether the upper limb is moving, the complete motion data are divided into several motion units. Considering the delay associated with controlling the prosthetic hand, this paper only performs feature extraction on the first motion unit and the second motion unit, and recognizes action on different classifiers. The experimental results reveal that the DTW algorithm based on motion unit bears a higher recognition rate and lower running time. The recognition rate reaches as high as 99.46%, and the average running time measures 8.027 ms. In order to enable the prosthetic hand to understand the grasping intention of the upper limb, this paper proposes a Generalized Regression Neural Network (GRNN) model based on 10-fold cross-validation. The motion state of the upper limb is subdivided, and the static state is used as the sign of controlling the prosthetic hand. This paper applies a 10-fold cross-validation method to train the neural network model to find the optimal smoothing parameter. In addition, the recognition performance of different neural networks is compared. The experimental results show that the GRNN model based on 10-fold cross-validation exhibits a high accuracy rate, capable of reaching 98.28%. Finally, the two algorithms proposed in this paper are implemented in an experiment of using the prosthetic hand to reproduce an action, and the feasibility and practicability of the algorithm are verified by experiment.

Temperature-Responsive Photoluminescence and Elastic Properties of 1D Lead Halide Perovskites R- and S-(Methylbenzylamine)PbBr3.

Low-dimensional metal halide perovskites (MHPs) have received much attention due to their striking semiconducting properties tunable at a molecular level, which hold great potential in the development of next-generation optoelectronic devices. However, the insufficient understanding of their stimulus-responsiveness and elastic properties hinders future practical applications. Here, the thermally responsive emissions and elastic properties of one-dimensional lead halide perovskites R- and S-MBAPbBr3 (MBA+ = methylbenzylamine) were systematically investigated via temperature-dependent photoluminescence (PL) experiments and first-principles calculations. The PL peak positions of both perovskites were redshifted by about 20 nm, and the corresponding full width at half maximum was reduced by about 40 nm, from ambient temperature to about 150 K. This kind of temperature-responsive self-trapped exciton emission could be attributed to the synergistic effect of electron-phonon coupling and thermal expansion due to the alteration of hydrogen bonding. Moreover, the elastic properties of S-MBAPbBr3 were calculated using density functional theory, revealing that its Young's and shear moduli are in the range of 6.5-33.2 and 2.8-19.5 GPa, respectively, even smaller than those of two-dimensional MHPs. Our work demonstrates that the temperature-responsive emissions and low elastic moduli of these 1D MHPs could find use in flexible devices.