Pediatric-inspired regimen for adolescent and adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia: a prospective study from China.

Several international centers have used and reported pediatric-inspired regimens for adolescent and adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL). However, there is a lack of prospective data on the Chinese population. Herein, we performed a prospective study with a pediatric-inspired regimen (IH-2014 regimen) in treating adolescent and adult Ph- ALL patients in our center. From 2014 to 2021, a total of 415 patients aged between 14 and 65 years (median age, 27) were included in this study. After a median follow-up of 40.8 months, the 5-year overall survival, disease-free survival, and event-free survival rates were 53.8%, 51.1% and 45.0%, respectively. The regimen was generally well tolerated and safe, and the overall chemotherapy-related mortality was 3.6%. Age ≥ 40 years and persistent detectable minimal residual disease (MRD) post-induction were independent prognostic factors. Traditional risk factors for adult patients combined with MRD post-induction exhibit predictive significance for survival and relapse, which is helpful in the selection of subsequent treatment. Patients with high risk factors who can achieve deep MRD response after induction do not derive benefit from allogeneic hematopoietic stem cell transplantation.

Preparation and utilization of carbon dots as a nanoprobe for sensitive detection of tartrazine and palladium (II).

We prepared novel green, eco-friendly carbon dots as a dual-channel probe for highly sensitive and selective detection of tartrazine (Trz) and palladium(II) (Pd(II)) involving, respectively, FRET and electron transfer mechanisms. Furthermore, the successful utilization of the carbon dots for detecting Trz and Pd(II) in actual samples implies its potential application prospects in analysis.

Selective identification of p-nitroaniline by bromine-mediated polarization of carbon dots.

A fluorometric method based on boron, bromide-codoped carbon dots (BBCNs) was developed for the first time for the highly selective detection of p-nitroaniline (PNA) in wastewater samples. It should be noted that the introduction of bromine greatly increases the molecular polarizability of the probe, which can regulate the energy level matching between the probe and PNA, resulting in the interaction between BBCNs and PNA. In the presence of PNA, the fluorescence of BBCNs is obviously quenched and accompanied by a red shift of the fluorescence band, which might be attributed to the formation of aggregates caused by the polar adsorption of BBCNs and PNA. It is beneficial for constructing a highly selective sensing platform for PNA determination compared to its isomers (o-nitroaniline and m-nitroaniline) through atomic bromine-mediated polarization of the BBCNs. With the help of this mechanism, an excellent linear range of 0.5-300 µM with a low detection limit of 0.24 µM toward PNA was obtained. This work further confirms that there is a significant relationship between the nature of doping elements and the optical and physicochemical properties of fluorescent materials.

Slackline training for Paralympic alpine sit skiers: Development of human-device multi-joint coordination.

PURPOSE: Para-alpine sit skiers face unique challenges in balance control due to their disabilities and the use of sit skis. This study assessed their multi-joint coordination before and after slackline training. METHODS: Nine alpine sit skiers (6 M/3 F; 27 ± 8 years; height: 168.3 ± 6.0 cm; body mass: 55.4 ± 6.9 kg) with different disabilities (LW10-LW12) volunteered for the experiment. All subjects performed slackline training for 5 weeks (20 sessions). Joint kinematics were captured by vision-based markerless motion analysis. Root mean square (RMS) amplitude, mean velocity and mean power frequency (MPF) were evaluated. RESULTS: After training, performance improved significantly with an increase in balance time (1041%, p = 0.002), and a decrease in joint angular velocities and RMS amplitude of the sit ski foot (p < 0.05). Joint synergies were developed through in- or anti-phase movements between joint pairs, particularly involving the hip joints (continuous relative phase angles ~0° or 180°, p < 0.001). Multi-joint coordination shifted from large-RMS amplitude of elbows to low-MPF large-RMS amplitude of the hip and shoulders (p < 0.05), with a significant increase of hip weighting (77.61%, p = 0.031) in the principal component analysis. The coordination was maintained with the change of slackline tension (p < 0.05). Athletes with severe trunk disabilities (LW10) had shorter balance time and poorer coordination than athletes with full trunk functions (LW12). CONCLUSIONS: Our findings showed the development of joint coordination involving better control of the hip and sit skis during the challenging slackline training task.

Cluster analysis of multiple impairment measures in evidence-based classification for para-alpine sit skiers.

The International Paralympic Committee has been promoting the development of evidence-based classification to reduce the subjectivity in current decision-making systems. The current study aimed to evaluate the validity of the impairment and performance tests for para-alpine sit skiing classification, and whether cluster analysis of the measures would produce a valid classification structure. Thirty-eight para-alpine sit skiers with different disabilities completed seven tests. During these tests, isometric trunk strength, trunk muscle excitation, trunk range of movement (ROM), and simulated skiing performance (board tilt angle) were assessed. Correlations between the measures and the board tilt angle were calculated. To group athletes, K-means cluster analysis was performed according to how much the impairment measures affected the board tilting. There were significant correlations between all measures and the maximal board tilt angle (r = 0.35-0.81, p < 0.05). The cluster analysis revealed that the introduction of ROM and muscle excitation was an effective supplement to strength measures in improving the classification accuracy (53%-79%). It produced four clusters with strong structures (mean silhouette coefficient = 0.81) and large and significant inter-cluster differences in most measures and performance between clusters (p < 0.05). The cluster analysis produced classes comprising athletes with similar degrees of activity limitation. All tests reported can help establish a more transparent classification system for para-alpine sit skiers. This study also provides a reference for evidence-based classification systems in other Para sports.

Configuration Investigation, Structure Design and Deployment Dynamics of Rigid-Reflector Spaceborne Antenna with Deviation-Angle Panel.

Rigid-reflector spaceborne antennas (RRSAs) are well-suited for high-frequency application scenarios due to their high surface accuracy. However, the low stowing efficiency of RRSAs limits the aperture diameters and further deteriorates the electromagnetic (EM) performances in terms of gain, resolution and sensitivity. After conducting systematic feature analysis with respect to several typical RRSAs, we propose a novel type of RRSA to solve the aforementioned problems. Inspired by the pose adjustment process for a higher stowing efficiency of traditional RRSAs, we also propose a new segmentation scheme of a reflective surface consisting of a deviation-angle panel that facilitates a higher stowing efficiency. Based on this scheme, its corresponding folded configuration is implemented by combining Euler's rotation theorem and the idea of parameter identification. In addition, we also compare the stowing efficiency of different schemes to verify the high stowing efficiency of the configuration. Finally, we perform mechanism/structure design and deployment dynamics to demonstrate that the antenna can be successfully deployed and exhibits excellent deployment quality. The results suggest that the proposed antenna possesses higher stowing efficiency than that of the same kind, with a stable deployment and interference-free process.

An eco-friendly fluorometric assay for high-sensitive meloxicam quantitation in biological matrices.

Meloxicam (Mel), as a powerful and effective anti-inflammatory drug, is commonly employed for the treatment of various inflammatory diseases; however, the use of Mel at high doses or for extended periods could cause severe side effects in human visceral organs. Therefore, a simple, rapid, and reliable method is urgently needed to monitor Mel in biological samples. Herein, novel water-soluble luminescent nano-carbon dots (nano-Cdots) with outstanding physicochemical properties were prepared by a one-pot high-temperature hydrothermal process of ellagic acid and guanidine. The nano-Cdots were further used as an optical probe for the sensitive detection of Mel in serum samples through the cooperative mechanisms of the inner filter effect and photoelectron transfer. By employing this sensor, an excellent linear correlation was achieved between the relative luminescent intensity [(PL0 - PL)/PL0] and the concentration of Mel in the range of 0.1 to 200 µM, with a limit of detection of 34.68 nM (3σ/k). This sensor was effectively employed for the analysis of Mel in real serum samples, implying its potential development prospects for the advancement of drug analysis with carbon-based probes.

The prognostic factors in acute myeloid leukaemia with double-mutated CCAAT/enhancer-binding protein alpha (CEBPAdm).

The prognostic factors to stratify acute myeloid leukaemia (AML) with double-mutated CCAAT/enhancer-binding protein alpha (CEBPAdm) into different risk groups remains to be determined. In this retrospective study, we evaluated 171 consecutive patients with newly diagnosed AML with CEBPAdm by a Cox proportional hazards regression model. In univariate analyses, colony stimulating factor 3 receptor (CSF3R) and Wilms tumour 1 (WT1) mutations were associated with poor relapse-free survival (RFS). The induction regimens including homoharringtonine (omacetaxine mepesuccinate) or intermediate-dose cytarabine was associated with favourable RFS and overall survival (OS). The induction regimen including both homoharringtonine and intermediate-dose cytarabine was associated with the most favourable RFS (3-year RFS 84.7%) and OS (3-year OS 92.8%) compared to the conventional cytarabine and daunorubicin regimen (3-year RFS 27.7%, hazard ratio [HR] 0.126, 95% confidence interval [CI] 0.051-0.313, Wald p < 0.001; and 3-year OS 56.4%, HR 0.179, 95% CI 0.055-0.586, Wald p = 0.005). In multivariate analyses, the induction regimen including intermediate-dose cytarabine (HR 0.364, 95% CI 0.205-0.646, Wald p < 0.001) and CSF3R mutations (HR 2.667, 95% CI 1.276-5.572, Wald p = 0.009) were independently associated with RFS. Taken together, we found that induction regimen and CSF3R mutations were independent prognostic factors for AML with CEBPAdm.

CD19 CAR-T cell treatment conferred sustained remission in B-ALL patients with minimal residual disease.

The persistence or recurrence of minimal residual disease (MRD) after chemotherapy predicts relapse of B-cell acute lymphoblastic leukemia (B-ALL). CD19-directed chimeric antigen receptor T (CD19 CAR-T) cells have shown promising responses in B-ALL. However, their role in chemotherapy-refractory MRD-positive B-ALL remains unclear. Here we aimed to assess the effectiveness and safety of CD19 CAR-T cells in MRD-positive B-ALL patients. From January 2018, a total of 14 MRD-positive B-ALL patients received one or more infusions of autogenous CD19 CAR-T cells. Among them, 12 patients achieved MRD-negative remission after one cycle of CAR-T infusion. At a median follow-up time of 647 days (range 172-945 days), the 2-year event-free survival rate in MRD-positive patients was 61.2% ± 14.0% and the 2-year overall survival was 78.6 ± 11.0%, which were significantly higher than patients with active disease (blasts ≥ 5% or with extramedullary disease). Moreover, patients with MRD had a lower grade of cytokine release syndrome (CRS) than patients with active disease. However, the peak expansion of CAR-T cells in MRD positive patients showed no statistical difference compared to patients with active disease. Five patients received two or more CAR-T cell infusions and these patients showed a decreased peak expansion of CAR-T cell in subsequent infusions. In conclusion, pre-emptive CD19 CAR-T cell treatment is an effective and safe approach and may confer sustained remission in B-ALL patients with chemotherapy-refractory MRD. The trials were registered at www.chictr.org.cn as ChiCTR-ONN-16009862 (November 14, 2016) and ChiCTR1800015164 (March 11, 2018).

Nilotinib combined with multi-agent chemotherapy in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a single-center prospective study with long-term follow-up.

The aim of this study is to investigate the efficacy and safety of nilotinib combined with multi-agent chemotherapy in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Thirty patients with Ph+ ALL were recruited. Standard induction chemotherapy was given for 4 weeks. Nilotinib was administered beginning on day 15 of induction. After achieving hematologic complete remission (HCR), patients received either seven courses of consolidation or hematopoietic cell transplantation (HCT). Nilotinib was continued 2 years after achieving HCR or before stem cell transplantation conditioning. HCR and molecular complete response (MCR), overall survival (OS), hematologic relapse-free survival (HRFS), molecular relapse-free survival (MRFS), toxicity, and nilotinib levels in the serum and cerebrospinal fluid were evaluated. All patients achieved HCR, and cumulative MCR rate was 83.3%. The median HRFS and OS were 18 and 47.5 months, respectively. Four-year HRFS and OS rates were 54% and 45%, respectively. The median MRFS and 4-year MRFS for the patients with MCR were 19 months and 45%, respectively. The molecular response of patients after induction cycle had no impact on HRFS, MRFS, or OS. The patients who achieved MCR after 3 and 6 months had superior HRFS. The HCT cohort in the first HCR had significantly lower rates of relapse and longer MRFS, HRFS, and OS. Most adverse events were reversible with dose reduction or transient interruption of nilotinib therapy. Only traces of nilotinib were detected in cerebrospinal fluid. Nilotinib combined with cytotoxic chemotherapy was effective and translated to a high HCR and MCR for patients with Ph+ ALL. It should be noted that nilotinib cannot cross the blood-brain barrier.

Fast Dynamic Vehicle Detection in Road Scenarios Based on Pose Estimation with Convex-Hull Model.

Dynamic vehicle detection is of great significance for the safety of autonomous vehicles and the formulation of subsequent driving strategies. A pose-estimation algorithm, namely, the pose estimation with convex-hull model (PE-CHM), is proposed in this paper, and introduced in the dynamic vehicle detection system. In PE-CHM, the convex hull of the object's point-clouds is first extracted and the most fitted bounding box is determined by a multifactor objective function. Next, the center position of the target is inferred according to the location and direction of the target. With the obtained bounding box and the position inference, the pose of the target is determined, which reduces the interference of the missing contour on pose estimation. Finally, three experiments were performed to validate the performance of the proposed PE-CHM method. Compared with several typical model-based methods, PE-CHM can implement dynamic vehicle detection faster, which reduces the amount of calculation on the basis of ensuring detection efficiency.

Flow cytometric analysis of cerebrospinal fluid in adult patients with acute lymphoblastic leukemia during follow-up.

OBJECTIVE: To explore the value of flow cytometric (FCM) analysis of cerebrospinal fluid (CSF) in the diagnosis of central nervous system involvement in adult patients with acute lymphoblastic leukemia (ALL) during follow-up. METHODS: A total of 2871 CSF samples from 357 adult patients with newly diagnosed ALL between the year of 2009 and 2015 were analyzed retrospectively. These patients were divided into 3 groups according to CSF results, FCM+/conventional cytology (CC)+ group, FCM+/CC- group, and FCM-/CC- group, respectively. The overall survival (OS) of the three groups was analyzed. RESULTS: Fifteen (4.2%) and 26 (7.3%) patients' CSF samples were FCM+/CC+ and FCM+/CC-, respectively. The remaining 316 (88.5%) patients' samples were FCM-/CC-. The 2-year OS for the FCM+/CC+, FCM+/CC-, and FCM-/CC- groups was 40.0%, 20.6%, and 64.2%, respectively (P < .001). There was no statistically significant difference in OS between FCM+/CC+ and FCM+/CC- patients (P = .195). In multivariate analysis, a high WBC count and LDH level were independent risk factors for central nervous system involvement in adult patients with ALL. CONCLUSIONS: FCM demonstrated a superior sensitivity over conventional cytology in the diagnosis of central nervous system involvement in adult patients with ALL. FCM+/CC- patients showed a similar survival with FCM+/CC+ patients, suggesting that an isolated FCM-positive status holds clinical significance.

An analysis of 97 previously diagnosed de novo adult acute erythroid leukemia patients following the 2016 revision to World Health Organization classification.

BACKGROUND: The incidence of acute erythroid leukemia subtype (AEL) is rare, accounting for 5% of cases of acute myeloid leukemia (AML), and the outcome is dismal. However, in 2016 revision to the WHO classification, the subcategory of AEL has been removed. Myeloblasts are redefined as the percentage of total marrow cells, not non-erythroid cells. Therefore, the previously diagnosed AEL cases are currently diagnosed as AML or myelodyspalstic syndrome (MDS) according to new criteria. METHODS: We respectively reviewed cases of 97 de novo previously diagnosed AEL and all the patients were diagnosed as AML or MDS according to the new classification scheme, and then the clinical characteristics of these two subtypes were compared. Statistical analyses were performed by SPSS software version 18.0. RESULTS: The median age was 37 years-old, the two-thirds of previous AEL cases were diagnosed as MDS, and there was no obvious difference between two subtypes except for male/female ratio and age. Cytogenetic, rather than MDS/AML subtypes, can better represent the prognostic factor of previously diagnosed AEL patients. When the cytogenetic risk of patients belonged to MRC intermediate category and age were below 40 years-old in previous AEL cases, the patients who received induction chemotherapy without transplantation had a similar survival compared with the patients who underwent transplantation (3-year OS: 67.2% vs 68.5%). CONCLUSIONS: Cytogenetic, rather than MDS/AML subtypes, can better represent the prognostic factor of previously diagnosed AEL patients. Transplantation was a better choice for those whose cytogenetic category was unfavorable.

[A clinical study of acute lymphoblastic leukemia in adolescents: a single center experience].

OBJECTIVE: To explore the clinical and laboratory characteristics, treatment, prognostic factors of acute lymphoblastic leukemia (ALL) in adolescents. METHODS: Adolescents de novo ALL patients in Blood Disease Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences from September 1999 to September 2013 were enrolled in this study. Clinical data, therapeutic effect and prognostic factors were retrospectively analyzed. RESULTS: Of all 94 patients, 91 patients were treated in our center. The overall complete remission (CR) rate was 96.7% (88/91), CR rate after one cycle was 91.2%(83/91). The median follow-up time was 18 months. In all patients, the 6-year anticipated overall survival (OS) rate and disease free survival (DFS) rate were (47.6 ± 6.7)% and (45.4 ± 6.0)% respectively. In standard risk ALL patients , 6-year anticipated OS rate and DFS rate were (65.7 ± 8.1)% and (65.3 ± 7.4)%. Hyperleukocytosis (white blood cell count ≥30 × 10(9)/L in B-ALL; ≥100 × 10(9)/L in T-ALL), Ph(+) , MLL(+) , hypodiploid were risk factors associated with poor clinical outcome. CONCLUSIONS: The therapeutic effect and clinical outcome in adolescents with ALL are relatively favorable, especially in standard risk group. In high risk ALL patients, allogeneic hematopoietic stem cell transplantation may improve therapeutic efficacy.

Influence of Amputation on Kinetic Chain Musculature Activity During Basic and Modified Core Exercises.

PURPOSE: Core strength is vital for athletic performance, and many more exercises that involve the kinetic chain have been designed for able-bodied athletes. Disabilities that impair the kinetic chain can reduce the effectiveness of strength training. However, the impact of amputation on core strength training of people with disabilities and its underlying mechanism remains unclear. This study aimed to evaluate the muscle activation patterns and levels in athletes with amputation during 4 basic and modified weight-bearing core strength-training exercises. METHODS: Fifteen elite athletes with unilateral amputation (170.6 [7.3] cm; 63.9 [11.9] kg; 25.9 [5.3] y) volunteered for this study. Surface electromyography was used to measure the muscle activity mainly in the lumbopelvic-hip complex-stabilizing muscles during 4 kinetic chain trunk exercises with and without modifications. RESULTS: The significance level was set at α = .05. The results showed a significant difference in muscle activation between different body sides (P < .05). Specifically, amputation on the support position resulted in a diagonal pattern of muscle activation, and amputation on the free distal segments resulted in a unilateral dominant pattern with higher activation in muscles on the nonamputated side (P < .05). Modifications led to significant decreases in muscle activation asymmetry index (P < .05). CONCLUSIONS: Amputation caused muscle activation asymmetry and 2 activation patterns. Modifications by enhancing proximal stability and adjusting distal loading effectively reduced the asymmetry of muscle activation. Coaches and clinicians can use these results to tailor exercises for athletes with disabilities in training and rehabilitation.

Adverse effects of unilateral transfemoral amputation on para-alpine sit skiers and mitigation methods.

OBJECTIVES: This study aimed to evaluate the adverse effects of unilateral transfemoral amputation on neuromuscular and kinematic parameters in alpine sit skiers, and to determine if additional restraints on the human-bucket interface could help mitigate the effects. DESIGN: Cross-sectional, repeated measures study. METHODS: Simulated skiing tests were conducted indoors involving 10 skiers with unilateral transfemoral amputation and 10 able-bodied participants. A Paralympic silver medalist performed slalom skiing tests on snow. These tests were conducted with and without additional strapping on the residual limb. Surface electromyography of trunk muscles and athletic performance was measured, and the asymmetry index was calculated. RESULTS: Athletes were significantly dependent on muscle activation on the dominant side (asymmetry index = 7.8 %-28.3 %, p < 0.05). Worse athletic performance to the dominant side was found based on inclination angles of the indoor board (asymmetry index = -9.8 %, p = 0.014) and outdoor sit ski (-11.1 %, p = 0.006), and distance to the gate poles during skiing turns (18.6 %, p < 0.001). After using additional restraints, the above asymmetry index declined significantly (asymmetry index < 4.5 %, p < 0.05). Furthermore, athletic performance was significantly improved on both body sides by 11.1 %-30.7 % (p < 0.05). CONCLUSIONS: Unilateral transfemoral amputation caused the dependence on the trunk muscles of the dominant side and the corresponding unilateral poor performance in athletes. Adjusting restraints in the human-equipment interface by additional strapping could mitigate the asymmetry issues and improve athletic performance.

A Large-Scale Network Construction and Lightweighting Method for Point Cloud Semantic Segmentation.

To significantly enhance the performance of point cloud semantic segmentation, this manuscript presents a novel method for constructing large-scale networks and offers an effective lightweighting technique. First, a latent point feature processing (LPFP) module is utilized to interconnect base networks such as PointNet++ and Point Transformer. This intermediate module serves both as a feature information transfer and a ground truth supervision function. Furthermore, in order to alleviate the increase in computational costs brought by constructing large-scale networks and better adapt to the demand for terminal deployment, a novel point cloud lightweighting method for semantic segmentation network (PCLN) is proposed to compress the network by transferring multidimensional feature information of large-scale networks. Specifically, at different stages of the large-scale network, the structure and attention information of the point features are selectively transferred to guide the compressed network to train in the direction of the large-scale network. This paper also solves the problem of representing global structure information of large-scale point clouds through feature sampling and aggregation. Extensive experiments on public datasets and real-world data demonstrate that the proposed method can significantly improve the performance of different base networks and outperform the state-of-the-art.

The RTK-RAS signaling pathway is enriched in patients with rare acute myeloid leukemia harboring t(16;21)(p11;q22)/FUS::ERG.

Acute myeloid leukemia (AML) with t(16;21)(p11;q22)/FUS::ERG is a rare AML subtype associated with poor prognosis. However, its clinical and molecular features remain poorly defined. We determined the clinicopathological, genomic, and transcriptomic characteristics and outcomes of patients with AML harboring FUS::ERG at our center. Thirty-six AML patients harboring FUS::ERG were identified, with an incidence rate of 0.3%. These patients were characterized by high lactate dehydrogenase levels (median: 838.5 U/L), elevated bone marrow blast counts (median: 71.5%), and a CD56-positive immunophenotype (94.3%). Notably, we found that RTK-RAS GTPase (RAS) pathway genes, including NRAS (33%) and PTPN11 (24%), were frequently mutated in this subtype. Transcriptome analysis revealed enrichment of the phosphatidylinositol-3-kinase-Akt (PI3K-Akt), mitogen-activated protein kinase (MAPK), and RAS signaling pathways and upregulation of BCL2, the target of venetoclax, in FUS::ERG AML compared to RUNX1::RUNX1T1 AML, a more common AML subtype with good prognosis. The median event-free survival in patients with FUS::ERG AML was 11.9 (95% confidence interval [CI]: 9.0-not available [NA]) months and the median overall survival was 18.2 (95% CI: 12.4-NA) months. Allogeneic hematopoietic stem cell transplantation failed to improve outcomes. Overall, the high incidence of RTK-RAS pathway mutations and high expression of BCL2 may indicate promising therapeutic targets in this high-risk AML subset.