Clinical features, prognostic stratification, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma: a multi-institutional real-world study.

The present study aimed to investigate the clinical features, prognosis, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma (ENKTCL). This real-world study retrospectively reviewed 56 newly diagnosed advanced-stage non-nasal type ENKTCL patients from two large-scale Chinese cancer centers in the last 10-15 years and screened 139 newly diagnosed advanced-stage nasal type ENKTCLs admitted during the same period for comparison. The non-nasal type ENKTCLs exhibited significantly higher Ki-67 expression levels compared to nasal type disease (P = 0.011). With a median follow-up duration of 75.03 months, the non-nasal group showed slightly inferior survival outcomes without statistically significant differences compared to the nasal group (median overall survival (OS): 14.57 vs. 21.53 months, 5-year OS: 28.0% vs. 38.5%, P = 0.120). Eastern Cooperative Oncology Group (ECOG) score ≥ 2 (hazard ratio (HR) = 2.18, P = 0.039) and lactic dehydrogenase (LDH) elevation (HR = 2.44, P = 0.012) were significantly correlated with worse OS in the non-nasal group. First-line gemcitabine-based chemotherapy regimens showed a trend toward slightly improved efficacy and survival outcomes compared to non-gemcitabine-based ones in the present cohort of non-nasal ENKTCLs (objective response rate: 91.7% vs. 63.6%, P = 0.144; complete response rate: 50.0% vs. 33.3%, P = 0.502; median progression-free survival: 10.43 vs. 3.40 months, P = 0.106; median OS: 25.13 vs. 9.30 months, P = 0.125), which requires further validation in larger sample size studies. Advanced-stage non-nasal type patients could achieve comparable prognosis with nasal cases after rational therapy. The modified nomogram-revised index (including age, ECOG score, and LDH) and modified international prognostic index (including age, ECOG score, LDH, and number of extranodal involvement) functioned effectively for prognostic stratification in non-nasal type ENKTCLs.

Intensive therapy can improve long-term survival in newly diagnosed, advanced-stage extranodal NK/T-cell lymphoma: A multi-institutional, real-world study.

The study investigated the treatment and prognosis of advanced-stage extranodal natural killer/T-cell lymphoma (ENKTL). With a median follow-up of 75.03 months, the median overall survival (mOS) for the 195 newly diagnosed stage III/IV ENKTL patients was 19.43 months, and estimated 1-, 2-, 3- and 5-year OS were 59.5%, 46.3%, 41.8% and 35.1%, respectively. Chemotherapy (CT) + radiotherapy (RT) compared to CT alone (P = .007), and hematopoietic stem cell transplantation (HSCT) compared to non-HSCT (P < .001), both improved OS. For patients ≤60 years and ineligible for HSCT, other therapies with complete remission led to comparable OS (P = .141). Nine patients ever treated with chidamide achieved a median progression-free survival (mPFS) and mOS of 53.63 (range, 3.47-92.33) and 54.80 (range, 5.50-95.70) months, and four with chidamide maintenance therapy (MT) achieved a mPFS and mOS of 55.83 (range, 53.27-92.33) and 60.65 (range, 53.70-95.70) months, possibly providing an alternative option for non-HSCT patients. Non-anthracycline (ANT)- compared to ANT-, asparaginase (Aspa)- compared to non-Aspa- and gemcitabine (Gem)- compared to non-Gem-based regimens, prolonged PFS (P = .031; P = .005; P = .009) and OS (P = .010; P = .086; P = .003), respectively. Multivariate analysis demonstrated that Gem-based regimens improved PFS (HR = 0.691, P = .061) and OS (HR = 0.624, P = .037). Gem + Aspa combinations slightly improved PFS and OS compared to regimens containing Gem or Aspa alone (P > 0.05). First-line "intensive therapy," including CT (particularly Gem + Aspa regimens), RT, HSCT and alternative chidamide MT, was proposed and could improve long-term survival for advanced-stage ENKTLs. Ongoing prospective clinical studies may shed further light on the value of chidamide MT.

Treatment and prognosis of newly diagnosed advanced-stage extranodal natural killer / T cell lymphoma: a single-center real-world study across two decades.

INTRODUCTION: Although there is now a consensus on asparaginase-based chemotherapy regimens in treatment of advanced-stage extranodal natural killer / T cell lymphomas (ENKTCLs), patient survival in the real-world setting is still not optimistic according to previous literature reports, and the optimal chemotherapeutic regimens and integration of different therapeutic methods under the concept of combined-modality treatment still need to be further explored and verified. METHODS: Newly diagnosed stage Ⅲ / Ⅳ ENKTCL patients from Chinese National Cancer Center in the last two decades were retrospectively collected and analyzed. Overall survival (OS) and progression-free survival (PFS) were determined as primary endpoints. Log-rank tests and Cox proportional hazard models were performed to test for survival differences between subgroups and examine the univariable and multivariable associations. RESULTS: The study included 83 newly diagnosed stage Ⅲ / Ⅳ ENKTCL patients and reported a median OS of 26.07 months and an estimated 5-year OS of 41.3% with a median follow-up of 82.13 months. First-line asparaginase- compared to non-asparaginase-based regimens significantly prolonged PFS (P=0.007; HR=0.48, P=0.020) and showed a tendency to improve OS (P=0.064; HR=0.74, P=0.359). Gemcitabine-based regimens also exhibited a trend towards improved PFS (P=0.048; HR=0.59, P=0.164) and OS (P=0.008; HR=0.67, P=0.282) compared to non-gemcitabine-based ones. The asparaginase and gemcitabine combinations yielded a 5-year OS of 55.0% and led to significantly superior PFS (P=0.020; HR=0.40, P=0.022) and slightly better OS (P=0.054; HR=0.79, P=0.495) compared to the remaining regimens. First-line combined-modality treatment integrating chemotherapy and radiotherapy improved PFS (P=0.051) and OS (P=0.036) compared to chemotherapy alone. Four autologous hematopoietic stem cell transplantation recipients reached a median OS of 58.34 months. CONCLUSION: Asparaginase and gemcitabine alone brought favorable impact on PFS and OS; and the asparaginase and gemcitabine combination chemotherapy yielded the optimal efficacy, response duration and survival outcomes. Combined-modality treatment including potent chemotherapy supplemented by radiotherapy and/or consolidative transplantation could improve prognosis in newly diagnosed advanced-stage ENKTCLs.

Receiving sensitivity improvement by wide-spectrum OAM with OTDM and polarization multiplexing in weak atmospheric turbulence.

In this paper, a wide-spectrum orbital angular momentum (OAM) system with a polarization and optical time division multiplexing (OTDM) free-space transmission system is experimentally demonstrated. To enhance the system transmission performance in atmospheric turbulent channel, a wide-spectrum laser and an OAM beam are used. The wide-spectrum laser can be generated by utilizing pumped laser to pump nonlinear fiber, and OAM can be generated with a special light modulator. Furthermore, OTDM and polarization multiplexing methods are used to enhance the communication rate from 4 Gbit/s to 32 Gbit/s. With the use of the wide-spectrum laser and the OAM beam, the receiving scintillation index (SI) can be reduced, and detection sensitivity can be improved. It is the first time a wide-spectrum OAM communication system performance has been studied. It is shown that under weak atmospheric turbulence condition, the SI can be reduced by 38% and the receiving sensitivity can be improved by 3.18 dB via wide-spectrum OAM beams.

CMSA: a heterogeneous CPU/GPU computing system for multiple similar RNA/DNA sequence alignment.

BACKGROUND: The multiple sequence alignment (MSA) is a classic and powerful technique for sequence analysis in bioinformatics. With the rapid growth of biological datasets, MSA parallelization becomes necessary to keep its running time in an acceptable level. Although there are a lot of work on MSA problems, their approaches are either insufficient or contain some implicit assumptions that limit the generality of usage. First, the information of users' sequences, including the sizes of datasets and the lengths of sequences, can be of arbitrary values and are generally unknown before submitted, which are unfortunately ignored by previous work. Second, the center star strategy is suited for aligning similar sequences. But its first stage, center sequence selection, is highly time-consuming and requires further optimization. Moreover, given the heterogeneous CPU/GPU platform, prior studies consider the MSA parallelization on GPU devices only, making the CPUs idle during the computation. Co-run computation, however, can maximize the utilization of the computing resources by enabling the workload computation on both CPU and GPU simultaneously. RESULTS: This paper presents CMSA, a robust and efficient MSA system for large-scale datasets on the heterogeneous CPU/GPU platform. It performs and optimizes multiple sequence alignment automatically for users' submitted sequences without any assumptions. CMSA adopts the co-run computation model so that both CPU and GPU devices are fully utilized. Moreover, CMSA proposes an improved center star strategy that reduces the time complexity of its center sequence selection process from O(mn 2) to O(mn). The experimental results show that CMSA achieves an up to 11× speedup and outperforms the state-of-the-art software. CONCLUSION: CMSA focuses on the multiple similar RNA/DNA sequence alignment and proposes a novel bitmap based algorithm to improve the center star strategy. We can conclude that harvesting the high performance of modern GPU is a promising approach to accelerate multiple sequence alignment. Besides, adopting the co-run computation model can maximize the entire system utilization significantly. The source code is available at https://github.com/wangvsa/CMSA .

[Comparison of controlled pressure belt -allowing mobility to sandbags after percutaneous coronary intervention: pilot study]. / Perkütan koroner girisim sonrasi -mobiliteye izin veren- kontrollü baski kemerinin kum torbasiyla karsilastirilmasi: Pilot çalisma.

OBJECTIVES: We aimed to investigate the efficacy and safety of a belt mechanism (anjiobelt), which we developed recently and patented, which allows mobility after coronary operations and the application of adjustable pressure to the femoral artery. STUDY DESIGN: Between October 2012 and April 2013, 189 consecutive patients undergoing percutaneous coronary intervention electively or due to acute coronary syndrome were enrolled. There were 96 patients in the sandbag group and 93 patients in anjiobelt group. Manual compression was applied to the femoral artery until reaching primary homeostasis. Then, a 4-5 kilogram sandbag or anjiobelt was placed. Mobilization was allowed in case of need in the anjiobelt group. Twenty-four hours after the procedure, superficial bruising in the femoral region, hematoma, pseudo-aneurysm, and arteriovenous fistula, as femoral artery complications, were noted using Doppler ultrasound. RESULTS: Hematoma occurred more frequently in the sandbag group. Hematoma of <1 cm developed in 52 patients with sandbag and in 25 patients with anjiobelt (p<0.0001), while hematoma of 1-5 cm developed in 5 patients with sandbag and in 3 patients with anjiobelt (p<0.0001). Femoral artery pseudoaneurysm was seen in 4 patients (2 with anjiobelt, 2 with sandbag; p=0.975). CONCLUSION: Anjiobelt significantly reduces the incidence of hematoma in comparison to conventional sandbag in patients undergoing percutaneous coronary intervention. Other complications of the femoral region in terms of efficiency and safety appear to be similar to those observed with sandbag. The main problems occurring in these patients due to absolute immobilization have been eliminated with the anjiobelt.

ARIMA Model and Few-Shot Learning for Vehicle Speed Time Series Analysis and Prediction.

In the fields of traffic management, traffic health, and vehicle safety, vehicle speed prediction is an important research topic. The greater the difference between vehicle speed and average vehicle speed, or the more discrete the vehicle speed distribution, the higher the accident rate. This paper proposes a vehicle speed prediction method based on adaptive KF (Kalman filtering) in the ARMA (Autoregressive Moving Average) environment to address the problem of high-speed moving vehicle speed prediction. The ARMA theory is used to model the prediction of speed time series. The contribution rate of each coefficient representing the original time series is different after fitting the original time series with the ARMA model, so each coefficient must be given a certain weight. Multisource traffic data fusion and interval speed prediction are carried out on the basis of few-shot data preprocessing and traffic state division, according to different traffic states. The speed prediction accuracy is very high, according to the algorithm verification results.

First-Line Chemoradiation With or Without Chidamide (Tucidinostat) in Patients With Intermediate- and High-Risk Early-Stage Extranodal Nasal-Type Natural Killer/T-Cell Lymphoma: A Randomized Phase 2 Study in China.

PURPOSE: We investigated the safety and efficacy profile of intensity-modulated radiation therapy (IMRT) followed by gemcitabine, dexamethasone, cisplatin (GDP), plus chidamide in the first-line setting for intermediate- and high-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTCL). METHODS: This was an open-label, randomized phase 2 trial performed at 2 centers in China. Patients were eligible if they were newly-diagnosed with intermediate- and high-risk early-stage ENKTCL with at least one risk factor based on a nomogram-revised risk index: >60 years old, elevated serum lactate dehydrogenase, invasion of the primary tumor, stage II or Eastern Cooperative Oncology Group performance status >1 or stage II disease. Patients were treated with IMRT followed by GDP, with or without chidamide, in the first-line setting. Two-year progression-free survival (PFS) comprised the primary endpoint. Toxicities, the 2-year overall survival (OS), and the response rate comprised the secondary endpoints. RESULTS: Eligible patients (N = 74) were enrolled between May 2015 and December 2019. Among them, 37 patients were treated with IMRT + GDP + chidamide (chidamide group), whereas 37 cases were treated with IMRT + GDP (control group). Follow-up comprised a median of 43.4 months (range, 1.0-74.6 months). The objective response rate was 86.5% in the chidamide group and 78.4% in the control group (P = .359) at the end of treatment completion. The 2 year OS and PFS rates were 89.2% and 75.2% in the chidamide group versus 83.8% (P = .388) and 70.2% (P = .821) in the control group. The main adverse events were hematological toxicities and mucositis, with similar rates in the 2 groups (P > .05). CONCLUSIONS: The addition of chidamide to IMRT + GDP as first-line treatment achieved similar treatment outcomes and tolerable toxicities compared with IMRT + GDP in patients with intermediate- and high-risk early-stage ENKTCL.

Mutations in the TSGA14 gene in families with autism spectrum disorders.

Linkage to 7q has been the most robust genetic finding in familial autism. A previous scan of multiplex families with autism spectrum disorders found a linkage signal of genome-wide significance at D7S530 on 7q32. We searched a candidate imprinted region at this location for genetic variants in families with positive linkage scores. Using exon resequencing, we identified three rare potentially pathogenic variants in the TSGA14 gene, which encodes a centrosomal protein. Two variants were missense mutations (c.664C>G; p.P206A and c.766T>G; p.C240G) that changed conserved residues in the same protein domain; the third variant (c.192+5G>A) altered splicing, which resulted in a protein with an internal deletion of 16 residues and a G33D substitution. These rare TSGA14 variants are enriched in the affected subjects (6/348 patients versus 2/670 controls, Fisher's exact two tailed P = 0.022). This is the first report of a possible link of a gene with a centrosomal function with familial autism.

Photogenerated charge separation and recombination path modification in monocline Lu2WO6via lattice transition and Bi-O antibonding states.

Monoclinic Lu2WO6 undergoes diphase-to-perovskite BiLuWO6 transition via selective occupancy of Bi in three Lu sites. The transformation mechanism, process, and structure stabilities are revealed by variable cell nudged elastic band method, video, and phonon spectrum. Lattice transition brings about photogenerated charge separation in BiLuWO6. This is verified by indirect band gap transition, high electron migration rate, weak exciton binding energy, large photocurrent response, and small impedance. The electron-hole life time is elongated to produce abundant superoxide and hydroxyl radicals for the degradation of rhodamine B and phenol molecules. Bi-O antibonding states serve as immediate energy levels to change the recombination path, inducing 340 nm excitation band and 510 nm green light emission of Lu2WO6. Furthermore, multicolor emission of 1 at% Bi3+ + RE3+ (RE = Sm/Eu/Dy)-codoped Lu2WO6 is acquired via synergistic modification of the Bi-O antibonding state and RE3+ 4f states. Thus, the photogenerated charge motion in Lu2WO6 is tuned to expand application fields.

Variants regulating ZBTB4 are associated with age-at-onset of Alzheimer's disease.

The identification of novel genetic modifiers of age-at-onset (AAO) of Alzheimer's disease (AD) could advance our understanding of AD and provide novel therapeutic targets. A previous genome scan for modifiers of AAO among families affected by early-onset AD caused by the PSEN2 N141I variant identified 2 loci with significant evidence for linkage: 1q23.3 and 17p13.2. Here, we describe the fine-mapping of these 2 linkage regions, and test for replication in 6 independent datasets. By fine-mapping these linkage signals in a single large family, we reduced the linkage regions to 11% their original size and nominated 54 candidate variants. Among the 11 variants associated with AAO of AD in a larger sample of Germans from Russia, the strongest evidence implicated promoter variants influencing NCSTN on 1q23.3 and ZBTB4 on 17p13.2. The association between ZBTB4 and AAO of AD was replicated by multiple variants in independent, trans-ethnic datasets. Our results show association between AAO of AD and both ZBTB4 and NCSTN. ZBTB4 is a transcriptional repressor that regulates the cell cycle, including the apoptotic response to amyloid beta, while NCSTN is part of the gamma secretase complex, known to influence amyloid beta production. These genes therefore suggest important roles for amyloid beta and cell cycle pathways in AAO of AD.

A neural network approach to predict survival/death and growth/no-growth interfaces for Escherichia coli O157:H7.

An artificial neural network (ANN) model was developed to predict survival/death and growth/no-growth interfaces for Escherichia coli O157:H7 in a mayonnaise-type system. Temperature, pH, acetic acid, sucrose and salt were the inputs to a three-layer back-propagation neural network. The ANN model was trained using the data-set of McKellar et al. [2002. A probability model describing the interface between survival and death of E. coli O157:H7 in a mayonnaise model system. Food Microbiol. 19, 235-247] that consisted of 1,820 treatment combinations from controlled experiments with a cocktail of five strains of E. coli O157:H7. After training, the model correctly predicted the growth/no-growth in 1,810 combinations (99.5%) with 8 false positives and 2 false negatives, and survival/death in 1,804 combinations (99.1%) with 13 false positives and 3 false negatives. Classification accuracy was validated using additional literature data-sets for growth of E. coli O157:H7 under various environmental conditions. The ANN model accurately predicted the survival/death in 27 of 30 cases (90%) in experimental mayonnaise inoculated with E. coli O157:H7, with 3 fail-positive predictions and all observed growth (100%). Simulations were used to estimate the influence of incubation temperature on survival and growth for specific combinations of acetic acid, salt, pH and sucrose. The ANN model is recommended as an alternative tool for classification of survival and growth conditions in predictive microbiology.

Evidence for multiple loci from a genome scan of autism kindreds.

We performed a genome-wide linkage scan using highly polymorphic microsatellite markers. To minimize genetic heterogeneity, we focused on sibpairs meeting the strict diagnosis of autism. In our primary analyses, we observed a strong linkage signal (P=0.0006, 133.16 cM) on chromosome 7q at a location coincident with other linkage studies. When a more relaxed diagnostic criteria was used, linkage evidence at this location was weaker (P=0.01). The sample was stratified into families with only male affected subjects (MO) and families with at least one female affected subject (FC). The strongest signal unique to the MO group was on chromosome 11 (P=0.0009, 83.82 cM), and for the FC group on chromosome 4 (P=0.002, 111.41 cM). We also divided the sample into regression positive and regression negative families. The regression-positive group showed modest linkage signals on chromosomes 10 (P=0.003, 0 cM) and 14 (P=0.005, 104.2 cM). More significant peaks were seen in the regression negative group on chromosomes 3 (P=0.0002, 140.06 cM) and 4 (P=0.0005, 111.41 cM). Finally, we used language acquisition data as a quantitative trait in our linkage analysis and observed a chromosome 9 signal (149.01 cM) of P=0.00006 and an empirical P-value of 0.0008 at the same location. Our work provides strong conformation for an autism locus on 7q and suggestive evidence for several other chromosomal locations. Diagnostic specificity and detailed analysis of the autism phenotype is critical for identifying autism loci.