Background: The second revision of the International Staging System (R2-ISS) is a new and simple tool to risk stratify newly diagnosed multiple myeloma (NDMM) patients. Our aim in this study was to ...evaluate the utility of R2-ISS in NDMM patients who received upfront autologous hematopoietic stem cell transplantation (auto-HCT).
Methods: We conducted a retrospective analysis of all NDMM patients who underwent upfront auto-HCT between 1988 and 2021 at MD Anderson Cancer Center and had available data for calculation of R2-ISS, including albumin, β-2 microglobulin, LDH, and fluorescence in-situ hybridization (FISH) analysis at diagnosis. High-risk cytogenetic abnormalities (HRCA) were t(4;14), del(17p), and 1q21 gain or amplification, as detected by FISH. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoint was hematological response after auto-HCT.
Results: A total of 1291 patients were included, with a median age of 62 years (range 29 - 83) and 60% were male. Four hundred-and-nineteen patients (32%) had HRCA. Most patients received either bortezomib, lenalidomide, and dexamethasone (VRD) (34%) or carfilzomib, lenalidomide, and dexamethasone (KRD) (25%) induction regimens, and most patients (95%) received melphalan based conditioning. The distribution of R2-ISS stages in our cohort was as follows: 123 (10%) stage I, 471 (36%) stage II, 566 (44%) stage III, and 131 (10%) stage IV. A total of 1027 (80%) patients received post auto-HCT maintenance, mostly lenalidomide with or without dexamethasone (n = 785, 61%) (Table 1).
With a median follow-up of 42.2 months (range 0.3 - 181.0) for the entire cohort, the median PFS was 73.0, 65.2, 44.0, and 24.8 months ( P < .001) and the median OS was 130.8, 128.5, 94.2, and 61.4 months ( P < .001) for patients with R2-ISS stages I, II, III, and IV, respectively (Figure 1). On multivariable analysis (MVA) for PFS, using R2-ISS stage I as the reference group, there was no significant difference for R2-ISS stage II (hazard ratio 95% CI, 1.11 0.76-1.63; P = .59), but there was a significant worsening in PFS for R2-ISS stage III (1.55 1.05-2.29; P = .028) and R2-ISS stage IV (2.04 1.24-3.36; P = .005). On MVA for OS, again using R2-ISS stage I as the reference group, there was no significant difference for R2-ISS stage II (1.33 0.74-2.40; P = .34) or R2-ISS stage III (1.75 0.97-3.17; P = .06), but there was a significant worsening in OS for R2-ISS stage IV (2.43 1.18-5.01; P = .017).
On MVA, other measures significantly associated with worsening PFS were year of auto-HCT < 2010, lambda light chain disease subtype, presence of HRCA, prior MRD/response other than negative/≥CR, and not achieving MRD negative/≥ CR post auto-HCT. For OS, other measures significantly associated with worsening survival on MVA were presence of HRCA, HCT-CI > 3, having at least one bone lesion, not achieving CR at best response, and not receiving post auto-HCT maintenance therapy.
Conclusion: Our study demonstrates that R2-ISS is a reliable prognostic tool for NDMM in a large cohort of patients who received standard anti-myeloma treatment, including modern induction regimens, upfront auto-HCT, and post-transplant maintenance.
Understanding the spatial distribution and pollution characteristics of heavy metals in lake sediment is crucial for studying deposition and migration processes, assessing lake conditions, and ...determining the extent of remediation dredging. The present work is a case study of heavy metal pollution in Shitang Lake in Anhui province, China. Heavy metal concentrations were determined in sediment at locations across the lake to a depth of 100 cm, and pollution levels were assessed on the basis of the Geoaccumulation Index (Igeo) and Potential Ecological Risk Index (RI). Hg and Cd were the predominant heavy metals in the sediment, and the Igeo and RI indicated high pollution levels in the northern and southern zones of the lake. These findings can be used to guide the prioritization of dredging operations.
Cellulose-based carbon ribbons with a right-handed helical/torsional morphology were directly obtained by facile carbonization of microcrystalline cellulose. The right-handed helical carbon ribbons ...are about 50 μm in length and less than 10 μm in diameter. The thermal behavior of cellulose at low-temperature pyrolysis was investigated by thermogravimetry, mass spectrum, Fourier transform infrared, nuclear magnetic resonance, X-ray photon spectroscopy, and electron spin resonance, and the formation mechanism of the right-handed helical morphology was analyzed. It indicated that the inter- and intramolecular hydrogen bond breaking was the initially triggered factor of helical morphology formation of the cellulose-based carbon, enabling torsion freedom of cellulose molecular chains. Subsequent elimination reaction on C-2 and C-3 resulted in regular vacancies in the cellulose molecular chain, accelerating the formation of helical morphology. After carbonization, abundant “S-like space” lattice finger spaces were originated in the right-handed helical cellulose-based carbon matrix. It showed a certain enantioseparation performance for racemic tartaric acid owing to high adsorption capacity for l-tartaric acid. Moreover, the chiral selectivity of resultant cellulose-based carbon was promoted by a fast heating rate during carbonization. This work presented a feasible strategy to design novel enantioselective carbon materials with potential application in chiral separation.
Inflammation plays an important role in polycystic kidney disease (PKD). Cordyceps sinensis, a prized -Chinese medicinal herb, exerts anti-tumor, anti-inflammatory and anti-metastatic effects and ...benefits patients with kidney diseases. The aim of this study was to test the efficacy of FTY720, an immunosuppressant derived from C. sinensis, in a rat cystic kidney disease model, and explore its underlining mechanism.
Male wild type and Cy/+ Han:SPRD rats were treated with FTY720 at 3 and 10 mg/kg/day for 5 weeks and 12 weeks by gavage. Blood and kidney were collected for functional, morphological, RNA, and protein analysis.
Inflammation is activated in Cy/+ Han:SPRD rats. Inflammatory cytokines including interleukin 6 and tumor necrosis factor alpha were upregulated and inflammation-related pathways were activated, such as nuclear factor κB and signal transducer and activator of transcription 3 (STAT3) pathways. Furthermore, the bioactive sphingolipid mediator sphingosine-1-phosphate (S1P), a regulator of inflammation, was accumulated in the Cy/+ Han:SPRD rats. FTY720 significantly reduced cyst growth and delayed disease progression by reducing the accumulation of S1P, thereby inhibiting inflammatory responses.
FTY720 treatment reduced the expression of inflammatory cytokines and attenuated the activation of NK-κB and STAT3 pathways in Cy/+ Han:SPRD rats. It suggests that FTY720 may serve as a therapeutic agent for clinical autosomal dominant PKD treatment.
Cervical hyperextension injury is very frequent with anterior longitudinal ligament (ALL) injury, and the ligament damage has a remarkable effect on whether and what type of operation should be ...performed. This study aims to establish a new scoring system for the accurate diagnosis of ALL damage.
The imaging data of the consecutive patients was measured and scored by four radiologists. Intraoperative exploration was performed by three surgeons. The crude and adjusted odds ratios (cOR and aOR) and receiver operating characteristic curve (ROC) were constructed to assess the diagnostic accuracy of the scoring system.
A total of 255 patients with cervical spine trauma were included in this study. There was no statistical difference in the relationship between demographics and ALL injuries (P > 0.05). Thickness of prevertebral soft tissue (aOR = 11.922, P = 0.004), intervertebral disk angle (aOR = 13.21, P = 0.002), avulsion fracture of the anterior edge of the vertebral body (aOR = 13.844, P = 0.029), ALL disrupted in T1-weighted sequence (aOR = 18.349, P < 0.001), and high signal area in T2-weighted sequence (aOR = 20.898, P = 0.002) had significantly higher diagnostic accuracy. The scoring system's sensitivity and specificity were 94.0% and 88.1%, respectively, and the accuracy was 90.8%.
The study established a new scoring system for ALL injuries based on the analysis of a series of clinical data and statistics. A total of five scoring items, a total score of 7 points, and an ALL injury may be diagnosed when the score is not less than 3 points. This scoring system enables an efficient and accurate diagnosis of all injuries.
The workloads of routine repair， maintenance， and abnormality detection of hydropower units are heavy. Therefore， traditional manual monitoring may leave out or misjudge abnormalities. Deep learning ...algorithms are used for data modeling and monitoring abnormalities to reduce costs and improve safety and reliability. With the help of the Transformer neural networks， the efficient and accurate modeling capacity of long-term sequences and the GAN （generative adversarial network） architecture data are used to generate a training strategy. A TransGAN model is used for generative modeling of the measured data of hydropower units and proactively detects abnormal data points. The TransGAN model achieves a detection accuracy rate of 97.76% and a recall rate of 99.23% in hydropower data measurement. The anomaly detection delay is less than 0.1 s. The real-time high-precision anomaly monitoring function is realized.
Gastric cancer (GC) is a major health problem worldwide, with high prevalence and mortality. The present GC staging system provides inadequate prognostic information and does not reflect the ...chemotherapy benefit of GC.
Two hundred fifty-five patients who underwent surgical resection were enrolled in our study (training cohort = 212, internal validation cohort = 43). Nine clinicopathologic features were obtained to construct an support vector machine (SVM) model. The cohorts from 4 domestic centres and The Cancer Genome Atlas (TCGA) were used for external validation.
In the training cohort, the AUCs were 0.773 (95% CI 0.708-0.838) for 5-year overall survival (OS) and 0.751 (95% CI 0.683-0.820) for 5-year disease-free survival (DFS); in the domestic validation cohort, the AUCs were 0.852 (95% CI 0.810-0.894) and 0.837 (95% CI 0.792-0.882), respectively. The model performed better than the TNM staging system according to the receiver operator characteristic(ROC) curve. GC patients were significantly divided into low, moderate and high risk based on the SVM. High-risk TNM stage Ⅱ and Ⅲ patients were more likely to benefit from adjuvant chemotherapy than low-risk patients.
The SVM-based model may be used to predict OS and DFS in GC patients and the benefit of adjuvant chemotherapy in TNM stage Ⅱ and Ⅲ GC patients.
Data collected from the previous studies show that the tidal current along the mouth of Jiaozhou Bay (JZB) appears to have weakened, whereas the spatial asymmetry (stronger flooding in the north ...region and stronger ebbing in the south region) has remained nearly unchanged during the past several decades of large‐scale land reclamation. This study is conducted to explain the underlying dynamics for this phenomenon. The analytic evaluation of the tidal motion indicates that the tidal current in a small coastal bay such as the JZB is linearly proportional to its length (L), if L is far less than one‐quarter of the tidal wave length. This relation suggests that the decrease in tidal current speed in JZB mouth results from the land reclamation within the Bay. Also, the relationship between bay areas and tidal current along the JZB mouth can be derived. The results of this simple theoretical method for predicting the change in mean tidal current amplitude after the land reclamation largely agree with previous three‐dimensional (3‐D) modeling studies. It is also found that the spatial asymmetry of the tidal current along the JZB mouth is controlled by the sharp headland (the local factor). The unchanged shoreline around the headland leads to the stable spatial asymmetry of the tidal current. The weaker tidal current can explain the weaker residual current, and the unchanged asymmetry of the tidal current explains the unaltered pattern of inflow over the north region and outflow over the south region for the tidally induced residual current along the JZB mouth.
Key Points:
Decrease in tidal current speed in JZB mouth is owing to land reclamation
Spatial asymmetry of the tidal current is controlled by the sharp headland
Tidal residual current changes with the change in tidal current accordingly
Femtosecond laser microsurgery has become an advanced method for clinical procedures and biological research. The tissue treated by femtosecond laser can become highly fluorescent, indicating the ...formation of new fluorescent compounds that can naturally label the treated tissue site. We systematically characterized the fluorescence signals produced by femtosecond laser ablation in biological tissues
. Our findings showed that they possess unique fluorescence properties and can be clearly differentiated from endogenous signals and major fluorescent proteins. We further demonstrated that the new fluorescent compounds can be used as
labelling agent for biological imaging and guided laser microsurgery.
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