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Acalabrutinib studies have limited Asian participation. This phase 1/2 study (NCT03932331) assessed acalabrutinib in Chinese patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). Primary endpoint was blinded independent central review (BICR)-assessed overall response rate (ORR). Overall, 34 patients were enrolled. Most patients were men (88%); median age was 63 years and 59% had ≥3 prior treatments. Median treatment duration was 14 months (range, 1–24). Any-grade adverse events (AEs) and grade ≥3 AEs occurred in 85.3% and 44.1% of patients, respectively. AEs causing treatment discontinuation were aplastic anemia, thrombocytopenia, and gastrointestinal infection (n = 1 each). Fatal AEs occurred in 2 patients (aplastic anemia and multiple organ dysfunction syndrome [n = 1 each]). BICR-assessed ORR was 82.4% (95% confidence interval [CI]: 65.5, 93.2); 12 (35.3%) patients achieved complete response. Estimated 12-month OS was 84.5% (95% CI: 66.6, 93.3). Acalabrutinib yielded tolerable safety and high response rates in Chinese patients with R/R MCL. [ABSTRACT FROM AUTHOR]

Semantic segmentation is critical in enabling self-driving cars to understand their environment. However, existing real-time segmentation networks are challenged by the loss of target detail information and insufficient segmentation capability for multi-scale targets due to the lightweight requirement of the model. So, we propose a lightweight bilateral cascade feature fusion network to overcome these limitations. In particular, we introduce the feature enhancement module during the feature extraction stage, incorporating dual-dimensional attention within the convolutional layer. This module effectively reduces redundant information and significantly improves the feature extraction capability of the network. Furthermore, the network output employs cross-aggregation to fuse the output features of different branches to improve the missing pixel problem during the fusion process. Experimental evaluations conducted on benchmark datasets such as CityScapes and CamVid demonstrate the superior performance of our approach compared to existing semantic segmentation techniques. Notably, our method remarkably balances segmentation accuracy and processing speed, affirming its efficacy and practicality. Specifically, our model achieves a mean IoU accuracy of 77.8% and 76.3% on the CityScapes and CamVid test datasets. Additionally, it satisfies the real-time demands concerning inference speed. [ABSTRACT FROM AUTHOR]

The presence of haze results in diminished image clarity, the loss of image details, color alterations, and a decline in image visibility. This paper proposes an efficient multi-stage feature fusion defogging network based on the attention mechanism for effective defogging in complex environments. To create a multi-branch defogging network, the model integrates several attention techniques to create various sorts of branching network architectures. The image's spatial details and contextual information are supplemented and merged based on the recovered image feature information of different network branches to increase the effectiveness of the network model. The stage attention fusion mechanism created among several network branches can lessen the loss of image data during feature extraction and improve the effectiveness of the image-defogging operation. The experimental results demonstrate that the proposed algorithm has superior defogging performance in both synthetic and real-world scene datasets and performs more admirably in terms of accuracy compared to other sophisticated algorithms, particularly in the RESIDE and O-Haze datasets. The PSNR metrics on the RESIDE and O-Haze datasets are improved by 1.58 dB and 1.61 dB, respectively, compared to the best-advanced technique suggested in this study, and the SSIM metrics on the O-Haze dataset are improved by 3.4%. [ABSTRACT FROM AUTHOR]

Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, has shown encouraging anti-tumour activity in heavily pre-treated patients with relapsed or refractory peripheral T-cell lymphoma in a phase 1 study (JACKPOT8 Part A). Here, we report the full analysis of a phase 2 study, in which we assessed the anti-tumour activity of golidocitinib in a large multinational cohort of patients. We did a single-arm, multinational, phase 2 trial (JACKPOT8 Part B) in 49 centres in Australia, China, South Korea, and the USA. Eligible patients were adults (aged ≥18 years) with relapsed or refractory peripheral T-cell lymphoma who had received at least one previous line of systemic therapy and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were given oral golidocitinib 150 mg once daily until disease progression or other discontinuation criteria were met. The primary endpoint was the CT-based objective response rate, assessed by an independent review committee (IRC) per Lugano 2014 classification. The activity analysis set included all patients who received at least one dose and whose pathological diagnosis of peripheral T-cell lymphoma had been retrospectively confirmed by a central laboratory and who had at least one measurable lesion at baseline assessed by IRC. The safety analysis set included all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov , NCT04105010 , and is closed to accrual and follow-up is ongoing. Between Feb 26, 2021, and Oct 12, 2022, we assessed 161 patients for eligibility, of whom 104 (65%) were enrolled and received at least one dose of study drug; the activity analysis set included 88 (85%) patients (median age 58 years [IQR 51–67], 57 [65%] of 88 were male, 31 [35%] were female, and 83 [94%] were Asian). As of data cutoff (Aug 31, 2023; median follow-up was 13·3 months [IQR 4·9–18·4]), per IRC assessment, the objective response rate was 44·3% (95% CI 33·7–55·3; 39 of 88 patients, p<0·0001), with 21 (24%) patients having a complete response and 18 (20%) having a partial response. In the safety analysis set, 61 (59%) of 104 patients had grade 3–4 drug-related treatment-emergent adverse events. The most common grade 3–4 drug-related treatment-emergent adverse events were neutrophil count decreased (30 [29%]), white blood cell count decreased (27 [26%]), lymphocyte count decreased (22 [21%]), and platelet count decreased (21 [20%]), which were clinically manageable and reversible. 25 (24%) patients had treatment-related serious adverse events. Deaths due to treatment-emergent adverse events occurred in three (3%) patients: two (2%) due to pneumonia (one case with fungal infection [related to golidocitinib] and another one with COVID-19 infection) and one (1%) due to confusional state. In this phase 2 study, golidocitinib showed a favourable benefit–risk profile in treating relapsed or refractory peripheral T-cell lymphoma. The results of this study warrant further randomised clinical studies to confirm activity and assess efficacy in this population. Dizal Pharmaceutical. [ABSTRACT FROM AUTHOR]

Background The spread of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) among humans and food-producing animals has been widely reported. However, the transmission routes and associated risk factors remain incompletely understood. Methods Here, we used commensal Escherichia coli bacteria strains from faeces of pigs and local citizens [HEG: high exposure group (pig breeders, butchers or restaurant chefs) and LEG: low exposure group (other occupations)] to explore the dynamics of ARB and ARG transmission between animals and humans. Results Most ARGs (96%) present in pigs were shared with humans. Carriage rates of the shared ARGs suggest two transmission patterns among pigs, the HEG and LEG: one pattern was highest in pigs, gradually decreasing in the HEG and LEG (e.g. floR and cmlA1); the other pattern was increasing from pigs to the HEG but then decreasing in the LEG (e.g. mcr-1.1). Carriage rates of the HEG were higher than in the LEG in both patterns, implicating the HEG as a crucial medium in transmitting ARB and ARGs between food-producing animals and humans. Moreover, frequent inter/intragroup transmission via strains, plasmids and/or mobile elements was evident. Carriage of mcr-1.1 on human-gut-prevalent plasmids possibly promoted its enrichment in the HEG. Conclusions The HEG is a crucial factor in transmitting ARB and ARGs between food-producing animals and humans. Rational measures to contain the risks of occupational exposure are urgently needed to keep dissemination of antibiotic resistance in check and safeguard public health. [ABSTRACT FROM AUTHOR]

Targeted therapy with Bruton tyrosine kinase (BTK) inhibitors have revolutionized the treatment of patients with various B-cell malignancies. BTK inhibitors such as ibrutinib, zanubrutinib, orelabrutinib, and acalabrutinib have shown good clinical efficacy and better safety profiles than those of traditional chemotherapy and chemoimmunotherapy regimens. Multiple studies on new BTK inhibitors are ongoing, which may provide more therapeutic options for the treatment of B-cell malignancies. Considering the unmet need of evidence on BTK inhibitors in all clinical settings and to standardize the use of BTK inhibitors available in mainland China, Taiwan, Hong Kong, and Macau regions, this consensus has been formulated for the treatment of various B-cell malignancies based on the clinical practice and available evidences on the use of BTK inhibitors. The recommendations of this consensus will provide guidance to physicians and clinical researchers on the effective treatment of B-cell malignancies with BTK inhibitors. [ABSTRACT FROM AUTHOR]

Background: We previously reported results of a pooled analysis of two zanubrutinib studies in relapsed or refractory (R/R) MCL showing better survival outcomes when zanubrutinib is used in second‐line versus later‐line. Here, we present an updated pooled analysis with a longer follow‐up of 35.2 months. Methods: Data were pooled from two studies—BGB‐3111‐AU‐003 (NCT02343120) and BGB‐3111‐206 (NCT03206970) of zanubrutinib in R/R MCL. The patients were divided into two groups based on the treatment line of zanubrutinib: the second‐line and the later‐line group. The inverse propensity score weighting method was used to balance the baseline covariates between the groups. The primary outcome was overall survival (OS). Secondary outcomes included progression‐free survival (PFS), PFS, and OS rates, objective response rate (ORR), duration of response (DOR), and safety. Results: Among 112 pooled patients, 41 (36.6%) patients received zanubrutinib as second‐line and 71 (63.4%) patients as later‐line therapy. After weighting, OS was significantly improved in the second‐line versus later‐line group (HR, 0.459 [95% CI: 0.215, 0.98]; p = 0.044) with median OS not estimable in both groups. The PFS was similar between the two groups (HR, 0.78 [95% CI: 0.443, 1.373]; p = 0.389) but with numerically longer median PFS in the second‐line versus later‐line group (27.8 vs. 22.1 months). ORR was numerically higher in the second‐line versus later‐line (88.6% vs. 85.7%), and DOR was similar between the two groups (25.2 vs. 25.1 months). Zanubrutinib showed a similar safety profile in both groups. Conclusion: Zanubrutinib in second‐line treatment was associated with significantly improved OS compared with later‐line treatment of R/R MCL. This pooled analysis of two studies of zanubrutinib examined its efficacy and safety in the treatment of patients with recurrent/relapsed mantle cell lymphoma (MCL) in two different settings—second‐line and later‐line with long‐term follow‐up.This analysis showed that patients receiving zanubrutinib in the second‐line had significantly better overall survival than those who received it in the later‐line.The finding suggests that earlier use of zanubrutinib in the treatment line may lead to better outcomes in patients with recurrent/relapsed MCL. [ABSTRACT FROM AUTHOR]

Background: Streptococcus pneumoniae is a gram-positive opportunistic pathogen, and infection risks of S. pneumoniae can be profoundly augmented by its acquired multidrug-resistance (MDR). The rapid development of MDR in S. pneumoniae was attributed to the international dissemination of a small number of multidrug-resistant "clones." Clonal complex (CC) 271 is a prevalent MDR CC in the world and the most prevalent CC in China. However, the evolutionary trajectories of multidrug-resistant S. pneumoniae CC271 in China still are largely unknown. Methods: We investigated a collection of 1312 S. pneumoniae isolates collected from 28 tertiary hospitals in China from 2007 to 2020. Recombination prediction and recombination-masked phylogenetic analysis were combined to determine the population structure and mode of evolution of CC271. Data from the Global Pneumococcal Sequencing program (GPS) were combined to understand the global distribution of clones identified in this study. Bayesian analysis were recruited to analysis the evolutionary dynamics of dominant clones within CC271 in China. Results: The phylogenomic analysis resulted in the discovery of two globally distributed clones, ST271-A and ST271-B. ST271-A was a derivative of ST236 and an ancestor of ST271-B and ST320, refining the internal phylogenetic relationship of CC271. ST271-B was the most dominant clone in China, with higher β-lactam resistance especially for cephalosporins comparing to other MDR clones. Bayesian skyline plot showed a rapid expansion of 19F ST271-B from 1995 to 2000, which correlates with the widespread use of cephalosporins in the 1990s in China. 19A ST320, a vaccine-escape clone, is the second largest population in China. The Bayesian skyline plot showed that the 19A ST320 began to expand rapidly around 2001, which appeared to coincide with the prevalence of 19A after application of PCV7 in 2000 in the USA. We also observed frequent transmission of 19A ST320 between countries. It suggests that mass vaccination in some countries could affect the prevalence of clones in unvaccinated countries in the context of high-frequency international transmission. Conclusions: Our results refined the internal phylogenetic relationship of CC271, showing that the 19F ST271-B and 19A ST320 evolved independently from ST271-A, with different histories and driving forces for their evolution and dissemination in China. [ABSTRACT FROM AUTHOR]

This research article investigates the application of Lévy noise to understand the dynamic aspects of measles epidemic modeling and seeks to explain the impact of vaccines on the spread of the disease. After model formulation, the study utilises uniqueness and existence techniques to derive a positive solution to the underlying stochastic model. The Lyapunov function is used to investigate the stability results associated with the proposed stochastic model. The model's dynamic characteristics are analyzed in the vicinity of the infection-free and endemic states of the associated ODEs model. The stochastic threshold R s that ensures disease's extinction whenever R s < 1 is calculated. We utilized data from Pakistan in 2019 to estimate the parameters of the model and conducted simulations to forecast the future behavior of the disease. The results were compared to actual data using standard curve fitting tools. [ABSTRACT FROM AUTHOR]

Summary: This single‐arm, multicentre, phase I study is the first study of zanubrutinib, a potent, specific, irreversible Bruton tyrosine kinase (BTK) inhibitor, in Chinese patients with relapsed/refractory B‐cell malignancies. The objectives were to evaluate safety and preliminary anti‐tumour activity. Forty‐four patients received zanubrutinib 320 mg once daily (QD) (n = 10) or 160 mg twice daily (BID) (n = 34) until disease progression or unacceptable toxicity. 29.5% of patients received zanubrutinib for at least two years. The most common adverse event (AE) and the most common grade 3 or higher AE was neutrophil count decreased (54.5% and 25.0% respectively). Two patients (4.5%) discontinued treatment due to AEs and one treatment‐emergent AE led to death. All haemorrhagic events were grade 1–2 (except for one non‐serious grade 3 purpura). No second primary malignancies, tumour lysis syndrome, or atrial fibrillation/flutter occurred. The overall response rate was 52.3% (complete response rate, 18.2%). Patients with all cancer subtypes benefited from treatment. BTK C481S/R or L528W mutations were found in zanubrutinib‐progressive patients. The safety/efficacy profiles of patients treated with 320 mg QD and 160 mg BID were comparable and similar daily area under the curve (AUC) was achieved. Overall, zanubrutinib was well tolerated and either of these two regimens is clinically practical. Registered at ClinicalTrials.gov (NCT03189524, on 16 June 2017, https://clinicaltrials.gov/ct2/show/NCT03189524). [ABSTRACT FROM AUTHOR]

Background: Jujube is a typical fruit tree species from China. 'Muzao', a cracking-susceptible cultivar, and 'Linhuang No. 1', a cracking-resistant cultivar, were selected in a previous study as contrasting research materials. Whole-genome resequencing and transcriptomic analysis of 'Linhuang No. 1' and 'Muzao' allowed the identification of differentially expressed genes with different gene structures between the two cultivars and could be helpful in explaining the differences and similarities between the two cultivars. Results: Resequencing identified 664,129 polymorphic variable sites between 'Linhuang No. 1' and 'Muzao'. To determine the genetic relationship among 'Linhuang No. 1', 'Muzao' and the jujube genome reference cultivar 'Dongzao', the characteristic polymorphic variable sites were analysed by principal component analysis. The genetic relationship between 'Linhuang No. 1' and 'Muzao' was closer than that of either variety and 'Dongzao'. Nineteen differentially expressed genes were identified by combining transcriptomic analysis with resequencing analysis. LOC107427052 (encoding a nitrite reductase) was identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for further study. The identified insertion was not in the domain region of the LOC107427052 gene coding sequence (CDS) region and was verified by the finding that the insertion did not affect translation of the protein. The LOC107427052 gene expression levels, nitrite reductase activities and nitrite contents of 'Muzao' were significantly higher than the corresponding values of 'Linhuang No. 1' at the young fruit stage. There was no significant difference in the quantity of the product of nitrite reductase, namely, ammonia, between the two cultivars. Conclusions: The present study was the first to explore the differences between different jujube cultivars ('Linhuang No. 1' and 'Muzao') by combining genome resequencing and transcriptomics. LOC107427052 (encoding a nitrite reductase) was characterized by KEGG enrichment analysis. The insertion in the CDS region of the LOC107427052 gene provides a new direction for the study of nitrogen metabolism in jujube. Our study has laid a foundation for the comparative analysis of nitrite metabolism between the jujube cultivars 'Linhuang No. 1' and 'Muzao'. [ABSTRACT FROM AUTHOR]

Lactobacillus delbrueckii ssp. bulgaricus is one of the most commonly used starter cultures for yogurt production. However, how its genetic background affects acid production capacity is unclear. This study investigated the industrial potential of L. delbrueckii ssp. bulgaricus using population genomics and GWAS analysis. To meet our goal, population genetics and functional genomics analyses were performed on 188 newly sequenced L. delbrueckii ssp. bulgaricus strains isolated from naturally fermented dairy products together with 19 genome sequences retrieved from the NCBI database. Four distinct clusters were identified, and they were correlated with the geographical sites where the samples were collected. The GWAS analysis about acidification fermentation results with sucrose-fortified reconstituted skim milk revealed a significant association between l -lactate dehydrogenase (lldD ; Ldb2036) and the bacterial acid production rate. Our study has broadened the understanding of the population structure and genetic diversity of L. delbrueckii ssp. bulgaricus by identifying potential targets for further research, development, and use of lactic acid bacteria in the dairy industry. [ABSTRACT FROM AUTHOR]

Background: Limited information is available regarding the patient safety culture in Chinese hospitals. This study aims to assess the patient safety culture in Peking University Cancer Hospital and to identify opportunities for improving the organization's safety culture.Methods: A cross-sectional study was conducted in April 2018 and 2019, respectively. Data on patient safety culture were collected from clinical and administrative staffs using the Hospital Survey on Patient Safety Culture (HSOPSC).Results: Twelve composite dimension variables were hierarchically clustered. Three highest positive response dimensions include 'Organizational Learning and continuous improvement' (92.9%), 'Teamwork within units' (89.7%), and 'Hospital management support for patient safety' (83.7%), while 3 lowest positive response dimensions included 'Frequency of events reported' (43.9%), 'Non-punitive response to error' (51.1%), 'Communication openness' (52.2%), and 'Staffing' (53.7%). Compared to the average scores of the United States, the scores of the Peking University Cancer Hospital was significantly lower on 'Communication openness' and 'Frequency of events reported'. After targeted continuous improvement based on results in 2018, all 12 dimensions surprisingly increased in the safety culture conducted in 2019.Conclusion: Inadequate feedback and communications about error and lack of communication openness are key challenges for patient safety in the delivery of care in this hospital. Results of this baseline survey indicate the need for a modified approach and attention to context when designing interventions aimed at improving the safety culture in this organization. [ABSTRACT FROM AUTHOR]

Background: Classical Hodgkin lymphoma (cHL) is a highly curable disease, while novel therapy is needed for refractory or relapsed (R/R) patients. This phase II trial aimed to evaluate the role of camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in R/R cHL patients. Methods: Transplant-eligible patients with R/R cHL were enrolled and received two 14-day cycles of camrelizumab 200 mg intravenously (IV) and two 28-day cycles of camrelizumab 200 mg IV, gemcitabine 1000 mg/m2 IV, and oxaliplatin 100 mg/m2 IV on days 1 and 15. Patients with partial response (PR) or stable disease received an additional cycle of combination therapy. Those who achieved complete response (CR) or PR proceeded to autologous stem cell transplantation (ASCT). The primary endpoint was the CR rate at the end of protocol therapy before ASCT. Results: Forty-two patients were enrolled. At the end of protocol therapy, the objective response rate and CR rate were 94.9% (37/39) and 69.2% (27/39) in the evaluable set, and 88.1% (37/42) and 64.3% (27/42) in the full analysis set, respectively. Twenty-nine patients (69.0%) proceeded to ASCT, and 4 of 5 patients with PR achieved CR after ASCT. After a median follow-up of 20.7 months, the 12-month progression-free survival rate was 96.6% and the 12-month overall survival rate was 100%. Grade 3 or higher treatment emergent adverse events occurred in 28.6% of patients (12/42), mainly hematological toxicity. Conclusions: Camrelizumab combined with GEMOX constitutes an effective salvage therapy for R/R cHL, proving to be relatively well-tolerated and facilitating ASCT in most patients, thus promoting sustained remission. Trial registration: ClinicalTrials.gov NCT04239170. Registered on January 1, 2020. [ABSTRACT FROM AUTHOR]

During the development of the jujube fruit, cracking can occur. This is due to physiological disease and can cause huge economic losses. Analyzing changes in the cuticular membrane (CM) and mechanical properties during the jujube fruit development can clarify the relationship between the characteristics of the CM and cracking. This study used Hupingzao ( Ziziphus jujuba Mill. ‘Hupingzao’) to examine the development of CM and the biomechanical properties of the fruit through enzymatic hydrolysis and a puncture test. The results showed that the mass of the CM per unit fruit surface area gradually increased and CM mass per unit area in the shoulder region was always higher during the fruit development process. After the white-ripe period, cracks appeared in the waxy layer on the surface of the pericarp and the shoulders mainly had transverse cracks. And the cuticle structure was loose. Pericarp break force, pericarp break distance and pericarp toughness showed a negative correlation to the CM mass per unit area. The pericarp break force, pericarp toughness and pericarp brittleness stopped decreasing and started increasing in the white-ripe period. The differences in the biomechanical properties among the three regions of the fruit increased during the coloring period. In the coloring period, the pericarp break force and pericarp brittleness were significantly lower in the fruit shoulder and top regions than in the fruit cheek region. However, the pericarp break distance was significantly higher in the fruit shoulder and top regions than in the fruit cheek region. [ABSTRACT FROM AUTHOR]

Extranodal natural killer (NK)/T cell lymphoma-associated hemophagocytic syndrome (HPS) (NK/T-LAHS) is a heterogeneous and life-threatening disease, which warrants investigation of its risk factors and clinical features. We retrospectively analyzed the clinical records of 202 patients with extranodal NK/T cell lymphoma and compared the characteristics and survival of extranodal NK/T cell lymphoma patients with and without HPS. The cumulative incidence of NK/T-LAHS was 11.4 % (23/202). In a multivariate logistic regression model, younger age (p = 0.012), bone marrow involvement (p = 0.012), and reduced serum albumin (p < 0.001) were independent risk factors for developing HPS in patients with extranodal NK/T cell lymphoma. The survival of extranodal NK/T cell lymphoma patients was aggravated when complicated with HPS, with an overall 2-year survival of 72.1 and 30.4 %, respectively (p < 0.001). Six patients with HPS onset at lymphoma diagnosis tended to have a poor performance status (p = 0.040), while the rate of elevated bilirubin was significantly higher in 17 patients with HPS onset at lymphoma relapse (p = 0.045). After HPS onset, treatment response was poor (response rate, 17.4 %) and survival was dismal with a median of 26 days. Univariate analysis showed that patients with lactate dehydrogenase >1000 U/L (p = 0.048) and disseminated intravascular coagulation (p = 0.004) had shorter survival time. Extranodal NK/T cell lymphoma was frequently complicated with HPS, and survival was discouraging in this circumstance. Intensive chemotherapy regimens including L-asparaginase or pegaspargase and allogeneic stem cell transplantation should be investigated. [ABSTRACT FROM AUTHOR]

Air pollution is a serious environmental issue that has been long recognized. Whereas government policies attempt to reduce air pollution by controlling various pollution sources, research on risk perception of air pollution tends to treat air pollution as a single unified risk and neglects the complication of the polluting sources. Previous research consistently demonstrates that lay people have an inaccurate understanding of air pollution and are unwilling to change their behaviors to decrease pollution. However, these findings can hardly be employed in policy-making because researchers and policy-makers treat air pollution differently. The aim of the present study is to obtain a nuanced understanding of people's risk perception of air pollution from different sources. Moreover, we propose a new risk dimension, Self-Relevancy, and try to understand people's reluctance to change their behaviors to reduce pollution. Three main findings emerged. First, we demonstrated that people perceived each air pollution source differently. Second, factor analysis of risk characteristics showed that ratings of Self-Relevancy questions mainly loaded on the same factor, which indicates the robustness of the Self-Relevancy risk dimension. Finally, we found that people's ratings of Self-Relevancy positively predicted their perceived risk for some of the pollution sources. These findings highlight the importance of investigating sub-categories of risks and exploring the risk dimension of Self-Relevancy in future risk perception research to provide detailed and informative data for policy-makers. [ABSTRACT FROM AUTHOR]

Grassland ecological migration project is implemented in Northwest China as an attempt to restore the deteriorative ecosystems. People are relocated from uninhabitable areas to immigrant areas, resulting in land use changes, which would significantly impact the ecological environment. Therefore, it urgently needs quantitative evaluation and analysis of the trends of ecological change in these immigrant areas. We selected Luanjingtan, which is the largest ecological immigrant area in Alxa, Inner Mongolia, as our case. In this case, we chose ecological carrying capacity (EC) and ecosystem services value as indicators to evaluate the ecological changes from 1992 to 2011. Due to the expansion of cropland and grassland, the total EC increased from 320.0 gha in 1992 to 86,214.6 gha in 2011, and the total ecosystem services value increased from 570.0 million yuan in 1992 to 963.1 million yuan in 2011. The expansions of cropland and grassland were closely related to agricultural development and a project for returning grazing land to pasture in Luanjigntan. These measures provided a livelihood as well as alleviated the grazing pressure. Therefore, creating a sustainable long-term industry to address the conflict between environmental protection and the needs of those affected by the plan is one of the most important considerations in a grassland ecological migration project. [ABSTRACT FROM PUBLISHER]

Summary Wetland restoration in floodplains is an ecological solution that can address basin-wide flooding issues and minimize flooding and damages to riverine and downstream areas. High population densities, large economic outputs, and heavy reliance on water resources make flood retention and management pressing issues in China. To balance flood control and sustainable development economically, socially, and politically, flood retention areas have been established to increase watershed flood storage capacities and enhance the public welfare for the populace living in the areas. However, conflicts between flood storage functions and human habitation appear irreconcilable. We developed a site-specific methodology for identifying potential sites and functional zones for wetland restoration in a flood retention area in middle and eastern China, optimizing the spatial distribution and functional zones to maximize flood control and human and regional development. This methodology was applied to Mengwa, one of 21 flood retention areas in China’s Huaihe River Basin, using nine scenarios that reflected different flood, climatic, and hydraulic conditions. The results demonstrated improved flood retention and ecological functions, as well as increased economic benefits. [ABSTRACT FROM AUTHOR]

• A combination of transcriptome and genome re-sequencing was used to explore one of the main factors leading to fruit cracking in jujube, namely the difference in wax metabolism between jujube cultivars ('Linhuang No. 1' and 'Muzao') with different cracking sensitivity. • The wax form of the 'Muzao' fruit was fissured during the mature period. The fatty acid content of 'Linhuang No. 1' was always significantly greater than that of 'Muzao' under control (CK) or hormone treatments. The proportion of total fatty acids with fewer than 16 C atoms in 'Linhuang No. 1' was less than in 'Muzao'. All of these are due to the loss of 107 bases in the promoter region of the LOC107415896 in 'Muzao', which encodes the protein of biotin carboxyl carrier protein of acetyl-CoA carboxylase 2, chloroplastic (BCCP2). • This research could be helpful in explaining divergence/similarity of wax metabolism-related genes between the two cultivars and their possible role in fruit cracking. The fruit pericarp wax of jujube accessions with different cracking resistance show differences in morphology and wax chemical content. In this study, transcriptome and genome re-sequencing were used to analyze the differences in wax metabolism between jujube cultivars with different cracking resistance characteristics. The results showed that 431 differentially expressed genes were identified through transcriptome screening between the cracking-resistant cultivar 'Linhuang No. 1' and the cracking-susceptible cultivar 'Muzao' during the mature stage of fruit development. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis annotated three wax metabolism pathways (involving eight wax metabolism-related genes). Information on gene sequence variation in the eight genes was obtained from genome resequencing, with sequence variation between the two cultivars found in the promoter region of the LOC107415896 gene, which encodes the biotin carboxyl carrier protein of acetyl-CoA carboxylase 2, chloroplastic (BCCP2) protein, where 107 bases were inserted in 'Linhuang No.1'. As a result, the fatty acid concentration in the wax of 'Muzao' was lower than that of 'Linhuang No. 1', with the proportion of fatty acids with fewer than 16 C atoms in 'Muzao' accounting for a greater proportion of the total fatty acids. This indicated that the expression of the 'Muzao' LOC107415896 gene was affected. Our research has laid the foundation for further analysis of the function of jujube wax metabolism in the cracking-resistant fruit phenomenon. [ABSTRACT FROM AUTHOR]

This study aimed to explore the distribution, characteristics and prognostic value of baseline peripheral blood lymphocyte subsets in patients with extranodal NK/T-cell lymphoma (NKTCL). We conducted this cross-sectional study of 205 newly-diagnosed NKTCL patients receiving first-line chemotherapy and radiation at our institute between 2010 and 2020. Baseline peripheral blood lymphocytes were detected using flow cytometry, and the clinical value was analyzed. Compared with healthy controls, patients with NKTCL presented with a distinct peripheral immunity with higher levels of cytotoxic CD8+ T cells (33.230 ± 12.090% vs. 27.060 ± 4.010%, p < 0.001) and NKT cells (7.697 ± 7.219% vs. 3.550 ± 2.088%, p < 0.001) but lower proportions of suppressive regulatory T cells (Treg, 2.999 ± 1.949% vs. 3.420 ± 1.051%, p = 0.003) and CD4+ helper T cells (Th, 33.084 ± 11.361% vs. 37.650 ± 3.153%, p < 0.001). Peripheral lymphocytes were differentially distributed according to age, stage, and primary site in patients with NKTCL. The proportion of Th cells/lymphocytes was associated with tumor burden reflected by stage (p = 0.037), serum lactate dehydrogenase (p = 0.0420), primary tumor invasion (p = 0.025), and prognostic index for NK/T-cell lymphoma (PINK) score (p = 0.041). Furthermore, elevated proportions of T cells (58.9% vs. 76.4%, p = 0.005), Th cells (56.3% vs. 68.8%, p = 0.047), or Treg cells (49.5% vs. 68.9%, p = 0.040) were associated with inferior 5-year progression-free survivals (PFS) via univariable survival analysis. Multivariate cox regression revealed elevated Th cells as an independent predictor for unfavorable PFS (HR = 2.333, 95% CI, 1.030–5.288, p = 0.042) in NKTCL. These results suggested the proportion of Th cells positively correlated with tumor burden and was a potential non-invasive biomarker for inferior survival for patients with NKTCL. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) and salicylic acid (SA) are essential signaling molecules in plant cells that participate in responses to biotic and abiotic stresses. Changes in ROS and SA signals during interactions between pear and the pear scab pathogen Venturia nashicola remain unclear. Herein, we analyzed the roles of ROS in the signal transduction pathway of pear scab resistance using the highly resistant Huangguan and susceptible Xuehua cultivars of pear (Pyrus bretschneideri Rehd). Protoplasts, calluses, and leaves were obtained from 14-year-old pear trees and treated with V. nashicola for different periods. The results showed that ROS rapidly accumulated in protoplasts of both cultivars within a 120-min treatment period, but the fluorescence intensity of ROS differed between cultivars. The H2O2 content in fruit-derived calluses of Huangguan peaked at 48 h post-infection at levels 1.85 times higher than those in Xuehua. Induction of H2O2 by V. nashicola in Huangguan was more intense than in Xuehua over a 96-h treatment period. At 96 h post-infection, the malondialdehyde content in leaves of Huangguan was significantly lower than in Xuehua, while the activities of superoxide dismutase, peroxidase, and catalase, and the relative expression levels of PbMnSOD, PbPOD, and PbCAT genes were higher in Huangguan than Xuehua. V. nashicola infection also caused a continuous increase in the leaf SA content of Huangguan, which was 6.76 times higher than in Xuehua at 96 h post-infection, and V. nashicola exposure upregulated the expression of PbPAL, PbICS, PbPR1, and PbPR5. In summary, both ROS and SA participated in the responses of pear trees to V. nashicola infection and played vital roles in the signal transduction pathway of pear scab resistance. [ABSTRACT FROM AUTHOR]

This study explored the changes in the photosynthetic characteristics of the Fengdan peony under high-temperature stress to provide a reference for understanding the tolerance of peony plants under heat stress. In this study, the effects of high-temperature stress (40 °C) on the photosynthetic characteristics of the Fengdan leaves were studied. At 25 °C, the net photosynthetic rate (Pn), stomatal conductance (Gs), and transpiration rate (Tr) of the leaves decreased gradually with the increase in heat stress time, and intercellular CO2 concentration (Ci) decreased first and then increased. High-temperature stress reduced the light energy absorption (ABS/RC) and capture (TRO/RC), light energy for electron transport (ETO/RC), and heat dissipation (DIO/RC) per unit leaf area. The maximum photochemical efficiency (FV/FM), leaf photochemical performance index (PIabs), the probability that captured excitons can transfer electrons to other electron acceptors in the electron transport chain beyond QA (ψO), and the quantum yield for electron transport (φEo), decreased gradually. The results showed that high temperatures damaged the photosynthetic capacity of the peony leaves and destroyed the photosynthetic apparatus of leaves. This study provides a reference for understanding the photosynthetic characteristics and tolerance of peony plants under heat stress. [ABSTRACT FROM AUTHOR]

The incorporation of real-world data (RWD) into medical product development and evaluation has exhibited consistent growth. However, there is no universally adopted method of how much information to borrow from external data. This paper proposes a study design methodology called Tree-based Monte Carlo (TMC) that dynamically integrates patients from various RWD sources to calculate the treatment effect based on the similarity between clinical trial and RWD. Initially, a propensity score is developed to gauge the resemblance between clinical trial data and each real-world dataset. Utilizing this similarity metric, we construct a hierarchical clustering tree that delineates varying degrees of similarity between each RWD source and the clinical trial data. Ultimately, a Gaussian process methodology is employed across this hierarchical clustering framework to synthesize the projected treatment effects of the external group. Simulation result shows that our clustering tree could successfully identify similarity. Data sources exhibiting greater similarity with clinical trial are accorded higher weights in treatment estimation process, while less congruent sources receive comparatively lower emphasis. Compared with another Bayesian method, meta-analytic predictive prior (MAP), our proposed method’s estimator is closer to the true value and has smaller bias. [ABSTRACT FROM AUTHOR]

YY-20394, an oral phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor, was investigated in a first-in-human study of patients with relapsed or refractory B-cell malignancies. During dose escalation, 25 patients received 20–200 mg of YY-20394 daily. The primary outcome measures were tolerability and dose-limiting toxicity (DLT). The secondary outcomes were pharmacokinetic parameters, progression-free survival (PFS) and the objective response rate (ORR). Since no patients experienced DLT, the maximum tolerated dose (MTD) was not reached. The majority (≥ 5%) of drug-related adverse events were ≥ grade III, being neutropenia (44.0%), pneumonia (16.0%), hyperuricemia (12.0%), lymphocythemia (8.0%), leukopenia (8.0%) and pneumonitis (8.0%). The overall ORR was 64.0% (95% confidence interval (CI): 45.2, 82.8%) including 5 patients with complete remission (CR), 11 with partial remission (PR), 2 with stable disease (SD) and 7 with progressive disease (PD), while the disease control rate (DCR) was 72.0% (95% CI: 54.4, 89.6%). The ORR of 10 patients with follicular lymphoma was 90%. The median PFS time was 255 days. One PR patient with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who received 40 mg q.d. had a durable response of around 36 months. The median PFS time of 10 patients with follicular lymphoma was 300 days. A recommended phase 2 dose of 80 mg q.d. was established. Considering that YY-20394 was well-tolerated with promising preliminary efficacy, further development is warranted. Trial registration clinicaltrials.gov, NCT03757000, retrospectively registered, November 28, 2018, https://clinicaltrials.gov/ct2/show/NCT03757000?term=NCT03757000&draw=2&rank=1. [ABSTRACT FROM AUTHOR]

The prevalence of non-suicidal self-injurious (NSSI) in adolescents is high. However, few studies exist to predict NSSI in this population. This study employed a machine learning algorithm to develop a predictive model, aiming to more accurately assess the risk of NSSI in Chinese adolescents. Sociodemographic, psychological data were collected in 50 schools in western China. We constructed eXtreme Gradient Boosting (XGBoost) model and multivariate logistic regression model to predict the risk of NSSI and nomograms are plotted. Data from 13,304 adolescents were used for model development, with an average age of 13.00 ± 2.17 years; 617 individuals (4.6 %) reported non-suicidal self-injury (NSSI) behaviors. The results of the XGBoost model showed that depression and anxiety were the top two predictors of NSSI in adolescents. The results of the multivariate logistic regression model showed that the risk factors for adolescent NSSI behaviors include: gender (being female), Age, Living with whom (father), History of psychiatric consultation, Stress, Depression, Anxiety, Tolerance, Emotion abreaction. The XGBoost prediction and multivariate logistic regression model showed good predictive ability. Nomograms can serve as clinical tools to assist in intervention measures, helping adolescents reduce NSSI behaviors and improve their mental and physical well-being. • Few studies exist to predict non-suicidal self-injury (NSSI) in this population. • This study employed a machine learning algorithm to develop a predictive model. • The study found some risk predictors for NSSI in adolescents. • Our predictive model showed good predictive ability. • Our nomograms can serve as clinical tools to assist in intervention measures. [ABSTRACT FROM AUTHOR]

Background: Patients with lymphoma and chronic hepatitis B virus infection need to be treated with both chemotherapy and nucleotide analogue (NA) therapy. However, dynamic changes in HBV DNA loads with increasing chemotherapy cycles are lacking. It is unknown whether HBV replication markers, namely, the quantitative hepatitis B core antibody (qAnti-HBc), HBV RNA, and the hepatitis B virus core-related antigen (HBcrAg), are also markers for predicting HBV reactivation (HBVr). Methods: From 29 June 2010 to 6 December 2021, the data of patients with single-site diffuse large B-cell lymphoma and HBV infection (HBsAg+ and HBsAg−/anti-HBc+) were collected from a hospital medical record system, retrospectively. Serum HBV DNA loads (using real-time fluorescent quantitative PCR tests), qAnti-HBc levels (using a newly developed chemiluminescent particle immunoassay), HBV RNA levels (using the simultaneous amplification testing method based on real-time fluorescence detection), and HBcrAg levels (using a Lumipulse G HBcrAg assay) were tested, and factors related to HBVr were analyzed. Results: Under NAs, the HBV DNA loads of 69 HBsAg+ lymphoma patients declined from 3.15 (2.13–4.73) lg IU/mL to 1.00 (1.00–1.75) lg IU/mL, and further declined to 1.00 (1.00–1.04) lg IU/mL at the end of a 24-month follow-up. The qAnti-HBc levels decreased gradually during chemotherapy in HBsAg+ lymphoma patients (F = 7.090, p = 0.009). The HBV RNA and HBcrAg levels remained stable. A multivariate analysis revealed that higher qAnti-HBc levels (1.97 ± 1.20 vs. 1.12 ± 0.84 lg IU/mL, OR = 6.369, [95% CI: 1.523–26.641], p = 0.011) and higher HBV RNA levels (1.00 ± 1.13 vs. 0.37 ± 0.80 lg copies/mL, OR = 3.299, [95% CI: 1.229–8.854], p = 0.018) were related to HBVr in HBsAg−/anti-HBc+ lymphoma patients. Conclusions: HBV DNA loads declined under NAs during chemotherapy in lymphoma patients. In HBsAg−/anti-HBc+ lymphoma patients, a higher level of baseline serum qAnti-HBc and HBV RNA levels can predict the likelihood of HBVr during chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The treatment outcomes and prognosis of lymphoma are affected by various factors such as hospital types. This study was to describe the temporal trend in the survival of lymphoma in an academic center in China. Methods: A total of 3840 consecutive patients with lymphoma diagnosed between 1996 and 2015 were reviewed. Eighty patients were excluded, and finally, 3760 patients were analyzed in this study. The cohort was divided into four groups according to calendar periods at diagnosis: 1996‐2000, 2001‐2005, 2006‐2010, and 2010‐2015. The overall survival (OS) rates among the four groups were compared. Results: The 5‐ and 10‐year OS for the whole cohort were 62% and 52%, respectively. The 5‐year OS of patient with classic Hodgkin lymphoma (cHL), mature B‐cell lymphoma (BCL), and peripheral T‐cell lymphoma (PTCL) were 79%, 63%, and 50%, respectively. Among mature BCL, the 5‐year OS was highest in follicular lymphoma (77.8%), followed by Burkitt lymphoma (76.5%), marginal zone lymphoma (74.1%), diffuse large B‐cell lymphoma (61.5%), small lymphocytic lymphoma/chronic lymphocytic leukemia (55.1%), and mantle cell lymphoma (44.3%). Among PTCL, the 5‐year OS was highest in ALK+anaplastic large cell lymphoma (79.0%), followed by ALK−anaplastic large cell lymphoma (63.1%), natural killer/T‐cell lymphoma (57.7%), angioimmunoblastic T‐cell lymphoma (34.9%, and peripheral T‐cell lymphoma not otherwise specified (27.6%). Significant improvement in the survival of lymphoma was observed, with the 5‐year OS increasing from 48% in 1996‐2000 to 65% in 2011‐2015 (P <.001). The 5‐year OS of patients with cHL, mature BCL, and PTCL changed from 55%, 49%, and 41% in 1996‐2000 to 79%, 65%, and 51% in 2011‐2015, respectively (P values were.014,.002, and.592, respectively). Conclusion: The survival of most types of lymphoma such as cHL and mature BCL, rather than PTCL, was improved significantly during the past two decades. [ABSTRACT FROM AUTHOR]

Objectives: The advanced extra‐nodal NK/T‐cell lymphoma (ENKTL) is highly aggressive and lacks effective treatment with a poor prognosis. This study aimed to investigate the effectiveness and safety of autologous hematopoietic stem cell transplantation (ASCT) in CR1. Methods: Forty of 121 patients with advanced ENKTL from four Chinese hospitals between January 2006 to December 2021 who achieved first complete remission (CR1) and received at least 4 cycles chemotherapy, were enrolled for analysis. Twenty patients received ASCT as up‐front consolidation therapy (Group A), and 20 patients only received chemotherapy (Group B). Clinical features, treatment and follow‐up information were collected. Results: With a median follow‐up of 27 months (range, 4–188 months), the 2‐year overall survival (OS) in Group A, 61% (95% CI 37%–85%), was better than that in Group B, 26% (95% CI 2%–50%), p =.018. The 2‐year progression‐free survival (PFS) was 56% (95% CI 32%–80%) in Group A, 26% (95% CI 2%–50%) in Group B, p =.026. III–IV grade hematological toxicity was the most common adverse event. No treatment‐related deaths were observed in both groups. Conclusion: Up‐front ASCT could improve survival of advanced ENKTL patients in first complete remission, but need be confirmed by a prospective clinical trial. [ABSTRACT FROM AUTHOR]

The RELIANCE study has demonstrated the activity and safety of relmacabtagene autoleucel (relma-cel) (JW Therapeutics [Shanghai] Co, Ltd, Shanghai, China), a CD19-targeted chimeric antigen receptor T-cell product, in patients with heavily pre-treated relapsed/refractory large B-cell lymphoma (r/r LBCL). This study aimed to report the updated 2-year data of the RELIANCE study. The RELIANCE study (NCT04089215) was an open-label, multi-center, randomized, phase 1/2 registrational clinical trial conducted at 10 clinical sites in China. Adult patients with heavily pre-treated r/r LBCL were enrolled and received lymphodepletion chemotherapy followed by infusion of 100 × 106 or 150 × 106 relma-cel. The primary endpoint was objective response rate (ORR) at 3 months, as assessed by investigators. Secondary endpoints were duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety profiles. From November 2017 to January 2022, a total of 68 patients were enrolled, and 59 patients received relma-cel infusion. As of March 29, 2022, a total of 59 patients had a median follow-up of 17.9 months (range, 0.3–25.6). ORR was 77.59% (95% confidence interval [CI], 64.73–87.49) and complete response rate was 53.45% (95% CI, 39.87–66.66). Median DoR was 20.3 months (95% CI, 4.86–not reached [NR]) and median PFS was 7.0 months (95% CI, 4.76–24.15). Median OS was NR and 1-year and 2-year OS rates were 75.0% and 69.3%, respectively. Three (5.1%) patients experienced grade ≥3 cytokine release syndrome and two (3.4%) patients had grade ≥3 neurotoxicity. The updated data of the RELIANCE study demonstrate durable response with and manageable safety profile of relma-cel in patients with heavily pre-treated r/r LBCL. [ABSTRACT FROM AUTHOR]

Background: Autologous stem cell transplantation (ASCT) is the standard treatment strategy for refractory or relapsed classical Hodgkin lymphoma (R/R cHL). However, a single transplantation is insufficient to cure the disease because of unfavorable risk factors. Herein, we evaluated the outcomes of single or tandem ASCT in patients with R/R cHL, especially in high‐risk patients. Methods: We retrospectively analyzed R/R cHL patients who underwent single or tandem ASCT between April 2000 and June 2021 at the Beijing Cancer Hospital and Peking University International Hospital. Results: A total of 134 patients were enrolled. Patients were allocated to a favorable‐risk group (group A, n = 33), an unfavorable‐risk group (group B, n = 81) that underwent single ASCT, and an unfavorable‐risk group that underwent tandem ASCT (group C, n = 20). The median follow‐up time was 99 months (range, 91–107 months), and no treatment‐related deaths occurred after single or tandem ASCT. However, 27 patients (2 in group C) died during the follow‐up period. The groups A, B, and C had 5‐year progression‐free survival (PFS) rates of 77.05%, 45%, and 74.67%, respectively (p = 0.0014), and 5‐year overall survival (OS) rates of 89.85%, 76.06%, and 95%, respectively (p = 0.18). Neither the median PFS rates of groups A and C nor the OS rates of all groups were reached. Conclusions: Our study discusses the advantages of tandem transplantation for high‐risk patients with R/R cHL. [ABSTRACT FROM AUTHOR]

Background: To our knowledge, the different situations of identifying second primary malignant tumors (SPMTs) in lymphoma patients with synchronous solid tumors remain to be comprehensively investigated. Methods: We retrospectively collected information pertaining to lymphoma patients with synchronous solid tumors (diagnosed within 6 months) at Peking University Cancer Hospital & Institute between 2009 and 2019. The non‐parametric Aalen–Johansen estimator was applied to calculate cumulative incidence function in the competing risk model. Furthermore, propensity score‐matched analysis was performed to compare survival differences in lymphoma patients with or without synchronous solid tumors. Results: Thirty‐eight patients were enrolled. There were three situations of identifying SPMTs. First, in 15 patients (39.5%), SPMTs were identified before the initiation of any treatment. Among them, priority was given to anti‐lymphoma treatment in case of only three patients. Second, in 17 patients (44.7%), SPMTs were unexpectedly detected on surgical specimen assessment; of them, 13 received anti‐lymphoma treatment after surgery. Third, in six patients (15.8%), SPMTs were identified after the outset of treatment for the primary tumor; in this population, three of four patients with lymphoma switched toward the treatment plan for SPMTs. The 5‐year overall survival was 58.7%. The cumulative incidence function within 5 years was 26.6% for lymphoma and 14.7% for other solid tumors. The early identification of SPMTs was associated with better outcomes (p = 0.048). After balancing the baseline characteristics, no differences in survival were observed between lymphoma patients with and without synchronous solid tumors (p = 0.664). Conclusions: This is the first study to present the different situations of identifying SPMTs in lymphoma patients with synchronous solid tumors. In only <50% patients, SPMTs were identifiable at baseline. SPMT identification at different situations may make it difficult to choose the optimal therapeutic option, which may consequently impact patient survival. [ABSTRACT FROM AUTHOR]

As important lactic acid bacteria, Enterococcus species are widely used in the production of fermented food. However, as some strains of Enterococcus are opportunistic pathogens, their safety has not been generally accepted. In recent years, a large number of new species have been described and classified within the genus Enterococcus , so a better understanding of the genetic relationships and evolution of Enterococcus species is needed. In this study, the genomes of 29 type strains of Enterococcus species were sequenced. In combination with eight complete genome sequences from the Genbank database, the whole genomes of 37 strains of Enterococcus were comparatively analyzed. The average length of Enterococcus genomes was 3.20 Mb and the average GC content was 37.99%. The core- and pan- genomes were defined based on the genomes of the 37 strains of Enterococcus . The core-genome contained 605 genes, a large proportion of which were associated with carbohydrate metabolism, protein metabolism, DNA and RNA metabolism. The phylogenetic tree showed that habitat is very important in the evolution of Enterococcus . The genetic relationships were closer in strains that come from similar habitats. According to the topology of the time tree, we found that humans and mammals may be the original hosts of Enterococcus , and then species from humans and mammals made a host-shift to plants, birds, food and other environments. However, it was just an evolutionary scenario, and more data and efforts were needed to prove this postulation. The comparative genomic analysis provided a snapshot of the evolution and genetic diversity of the genus Enterococcus , which paves the way for follow-up studies on its taxonomy and functional genomics. [ABSTRACT FROM AUTHOR]

Information on Hodgkin lymphoma (HL) is mostly limited to Europe and North America. This real-world, retrospective study assessed treatment pathways and clinical outcomes in adults with stage IIB–IV classical HL receiving frontline treatment (n = 1598) or relapsed/refractory HL (RRHL, n = 426) in regions outside Europe and North America between January 2010 and December 2013. The primary endpoint was progression-free survival (PFS) in the RRHL group. Among patients with RRHL, 89.0% received salvage chemotherapy; most common regimen was etoposide, methylprednisolone, cytarabine, cisplatin (ESHAP; 26.3%). Median PFS in the RRHL group was 13.2 months (95% confidence interval [CI]: 9.9–20.2) and was longer in patients with vs. without stem cell transplantation (SCT; 20.6 vs. 7.5 months; p = 0.0071). This large-scale study identified a lower PFS for RRHL in the rest of the world compared with Europe and North America, highlighting the need for novel targeted therapies and SCT earlier in the treatment continuum. Clinical trial registration: NCT03327571. [ABSTRACT FROM AUTHOR]

: A primary breast lymphomais a rare form of extranodal lymphoma type. We aimed to analyze prognosticriskfactors and explore relapse factors in primary breast diffuse large B cell lymphoma (PB-DLBCL). : From November 2003 to September 2020, sixty-three patients from two medical centers newly diagnosed with PB-DLBCL patients were analyzed retrospectively. : The median age was 52, and >50% of patients were post-menopausal. The international prognostics index (IPI) (0–1) was mainlyin the low-risk group (84%), and there were four patients with stage IV (6%) who had bilateral breast involvement. With a median follow-up time of 4.92 years (3.17–8.00), five-year overall survival (OS) and progression-free survival (PFS) were 78.9% and 67.1%, respectively. Univariate and multivariate analyses showed that elevated erythrocyte sedimentation rate (ESR) and B symptoms were independent adverse prognostic risk factors for OS, whereas bilateral breast involvement was unfavorable for PFS. Disease recurrence and relapse occurred in 40% (25/63) patients, mainly in the breast, followed by the central nervous system (CNS) and skin/soft tissue. : This is the first study to explore the prognostic risk factors and relapse factorsof PB-DLBCL in a relatively large Chinese PBL cohort. Local breast and CNS recurrence after standard R-CHOP treatment were the main issues we are facing now. [ABSTRACT FROM AUTHOR]

Background: Circulating tumor DNA (ctDNA) has been proven to be a promising tumor-specific biomarker in solid tumors, but its clinical utility in risk stratification and early prediction of relapse for diffuse large B cell lymphoma (DLBCL) has not been well explored.Methods: Here, using a lymphoma-specific sequencing panel, we assessed the prognostic and predictive utilities of ctDNA measurements before, during, and after first-line therapy in 73 Chinese DLBCL patients.Results: The pretreatment ctDNA level serving as an independent prognostic factor for both progression-free survival (PFS, adjusted HR 2.47; p = 0.004) and overall survival (OS, adjusted HR 2.49; p = 0.011) was confirmed in our cohort. Furthermore, the patients classified as molecular responders who presented a larger decrease in ctDNA levels after the initial two treatment cycles had more favorable PFS (unreached vs. 6.25 months; HR 5.348; p = 0.0015) and OS (unreached vs. 25.87; HR 4.0; p = 0.028) than non-responders. In addition, interim ctDNA clearance may be an alternative noninvasive method of positron emission tomography and computed tomography (PET-CT) for predicting better PFS (HR 3.65; p = 0.0033) and OS (HR 3.536; p = 0.016). We also demonstrated that posttreatment ctDNA was a sensitive indicator for detecting minimal residual disease (MRD) in patients with a high risk of recurrence (HR 6.471; p = 0.014), who were otherwise claimed to achieve radiographic CR (complete remission).Conclusions: CtDNA is a promising noninvasive tool for prognosis prediction, response assessment, and early relapse prediction of first-line treatment in DLBCL patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This study, for the first time, provided both in-vitro and clinical evidence that established a connection between the presence of residual malignant B cells and the clonal diversity of the resulting BCR repertoire. Lymphoma cells cultured with human germinal center B cells suppressed the normal increase of diversity. In a special setting of stem cell transplant, the retarded growth rate of a patient's peripheral B cell diversity is of great prognostic potential for future relapse. Germinal center (GC) is the vital locus for the evolution of naïve B cells into memory B and plasma cells, but also a hotbed for the proliferation of malignant B cells. We hypothesized that malignant B cells may locally or globally impact GCs to produce peripheral B cell receptor immune repertoire (BCR IR) with reduced clonal diversity. In this study, we first validated our hypothesis in a novel human in-vitro GC (hiGC) model. The addition of the diffuse large B cell lymphoma (DLBCL) cells to the hiGC culture attenuated the rate of diversity growth. For clinical validation, we collected samples from 17 DLBCL patients at various points during high-dose therapy and autologous stem cell rescue. The elimination and reestablishment of the patients' lymphatic pool allowed us to unambiguously monitor the impact of tumor cells on the replenishment of the peripheral BCR IR. Compared to the nine patients who did not relapse after treatment, relapsed patients tended to have a slower rate of recovery regarding the clonal diversity of their peripheral BCR IR. Our results suggest a mechanistic and clinical connection between residual tumor cells and abnormal peripheral BCR IR, which may corelate with treatment efficacy in B cell lymphomas. [ABSTRACT FROM AUTHOR]

Primary central nervous system lymphoma (PCNSL) is a type of central nervous system restricted non-Hodgkin lymphoma, whose histopathological diagnosis is majorly large B cell lymphoma. To provide specific, evidence-based recommendations for medical professionals and to promote more standardized, effective and safe treatment for patients with PCNSL, a panel of experts from the Chinese Neurosurgical Society of the Chinese Medical Association and the Society of Hematological Malignancies of the Chinese Anti-Cancer Association jointly developed an evidence-based consensus. After comprehensively searching literature and conducting systematic reviews, two rounds of Delphi were conducted to reach consensus on the recommendations as follows: The histopathological specimens of PCNSL patients should be obtained as safely and comprehensively as possible by multimodal tomography-guided biopsy or minimally invasive surgery. Corticosteroids should be withdrawn from, or not be administered to, patients with suspected PCNSL before biopsy if the patient's status permits. MRI (enhanced and DWI) should be performed for diagnosing and evaluating PCNSL patients where whole-body PET-CT be used at necessary time points. Mini-mental status examination can be used to assess cognitive function in the clinical management. Newly diagnosed PCNSL patients should be treated with combined high-dose methotrexate-based regimen and can be treated with a rituximab-inclusive regimen at induction therapy. Autologous stem cell transplantation can be used as a consolidation therapy. Refractory or relapsed PCNSL patients can be treated with ibrutinib with or without high-dose chemotherapy as re-induction therapy. Stereotactic radiosurgery can be used for PCNSL patients with a limited recurrent lesion who were refractory to chemotherapy and have previously received whole-brain radiotherapy. Patients with suspected primary vitreoretinal lymphoma (PVRL) should be diagnosed by vitreous biopsy. PVRL or PCNSL patients with concurrent VRL can be treated with combined systemic and local therapy. [ABSTRACT FROM AUTHOR]

The present study investigated the efficacy and toxicity profile of first-line asparaginase (ASP)-based versus non-ASP-based regimens in treating early-stage extranodal NK/T-cell lymphoma (ENKTCL) in non-anthracycline therapy era. This multi-center, real-world retrospective study consisted 305 newly diagnosed localized ENKTCL patients who were treated with sequential chemoradiation between 2010 and 2020 in China: 190 cases received ASP-based regimens and 115 cases received non-ASP-based regimens. Propensity score matching and multivariable analyses were used to compare survivals and toxicities between the two treatment groups. Non-ASP-based regimens achieved comparable survivals compared with ASP-based regimens in the entire cohort. The 5-year overall survival (OS), progression-free survival (PFS) rates were 84.7% and 73.5% for non-ASP-based regimens, and 87.7% (P=0.464) and 74.6% (P=0.702) for ASP-based regimens. The non-inferior survivals of non-ASP-based regimens were consistent after adjustment using PSM and multivariable analyses. However, survival benefits of ASP varied in different treatment modalities. Among patients receiving sequential chemotherapy and radiation (CT+RT±CT), ASP-based regimens achieved higher complete remission rate (54.3 vs. 34.5%, P=0.047) and more favorable survivals compared with non-ASP-based regimens (5-year OS, 87.0 vs. 69.0%, P=0.028). However, for patients receiving sequential radiation and chemotherapy (RT+CT), non-ASP-based regimens achieved comparable favorable survivals as ASP-based regimens. Besides, liver injury, malnutrition, and coagulative dysfunction were significantly more commonly documented in ASP-based regimens. These findings suggested that ASP was an effective agent in treating ENKTCL, especially among those receiving induction CT and RT. For patients who received upfront RT, non-ASP-based regimens might be a comparably effective and more tolerable treatment option. [ABSTRACT FROM AUTHOR]

What is known and objective: Anti‐CD19 CAR‐T cell therapy is effective in B‐cell lymphoma. However, it is rarely used in lymphoma combined with other malignant tumours. Case description: A relapsed/refractory follicular lymphoma (r/r FL) patient underwent anti‐CD19 CAR‐T cell therapy and achieved complete response to lymphoma. However, gastric adenocarcinoma (GAC) was diagnosed during the cellular therapy. After infusion of CAR‐T cells, he received curative treatment for GAC, and maitained complete response in both r/r FL and GAC after the treatment. What is new and conclusion: Anti‐CD19 CAR‐T therapy is an effective treatment for r/r FL, also provided opportunity for the sequential therapy of GAC, and remained significant quality of life afterwards. [ABSTRACT FROM AUTHOR]

Purpose: Copanlisib, a pan-PI3K inhibitor, has previously shown clinical efficacy and a tolerable safety profile in patients with indolent non-Hodgkin lymphoma. However, the pharmacokinetics, safety, tolerability, and efficacy of copanlisib in Chinese patients have not been reported. Methods: This was a single-arm, open-label, phase I study of copanlisib in Chinese patients with relapsed or refractory indolent non-Hodgkin lymphoma (iNHL). Patients received a single intravenous 60 mg infusion of copanlisib over 1 h on days 1, 8, and 15 of a 28-day cycle, with 1 week of rest. Safety was monitored throughout the study, and plasma copanlisib levels were measured for pharmacokinetic analysis. Tumor response was determined by independent central radiologic review. Results: Sixteen patients were enrolled and 13 were treated with 60 mg of copanlisib for a median of 15.0 weeks. With a Cmax of 566 μg/L and a AUC (0–24) of 1880 μg·h/L following single intravenous infusion, the pharmacokinetic parameters of copanlisib were consistent with that in previous studies, and no accumulation in plasma was observed. Treatment-emergent adverse events were reported for all 13 patients, the most common of which were hyperglycemia (100.0%), hypertension (76.9%), decreased neutrophil count (76.9%), and decreased white blood cell count (69.2%). Seven out of 12 evaluated patients achieved partial response, resulting in an overall response rate of 58.3% Conclusions: Copanlisib was well tolerated in Chinese patients with relapsed or refractory iNHL at the dose of 60 mg and demonstrated encouraging disease control, thus warranting further clinical investigation. Clinical trial registration number: NCT03498430 (April 13, 2018). [ABSTRACT FROM AUTHOR]

Angioimmunoblastic T-cell lymphoma (AITL) is a unique sub-type of peripheral T-cell lymphoma (PTCL). We aimed to evaluate treatment programs and prognostic factors of 121 newly diagnosed patients with AITL in China from January 2001 to December 2018. The median age was 58 years with male predominance. Bone marrow involvement appeared in only 8.3% of patients, which was different from the previously published literature. The 5-year progression-free survival (PFS) and 5-year overall survival (OS) were 29.7% and 44.0%, respectively. Univariate and multivariate analyses showed that involvement of >5 nodal areas, age and Beta-2 microglubulin were highly predictive of OS but only the involvement of fewer than five nodal areas was significant for PFS. We identified a novel prognostic model including the three factors that may be applied in clinical practice and offer an alternative to IPI and PIT. [ABSTRACT FROM AUTHOR]

GLS-010, a novel engineered fully human immunoglobin G4 monoclonal antibody, can specially block the PD-1/PD-L1/2 axis and reactivate the antitumor immunity. This phase Ia/Ib study was carried out to evaluate the safety, recommended phase II dose (R2PD), and primary antitumor effects of GLS-010 in patients with advanced, refractory lymphoma and solid tumors. In phase Ia study, patients with refractory solid tumors and lymphoma enrolled and received GLS-010 at a dose of 1, 4, or 10 mg/kg Q2W; 240 mg Q3W or Q2W. The primary objective was to assess the dose-limiting toxicity (DLT). In phase Ib study, doses were expanded in 9 specific tumors to ensure the R2PD and explore the efficacy. Tumor mutation burden level and PD-L1 expression were also assessed with whole-exome sequencing and immunohistochemistry (SP263), respectively. Up to April 18, 2020, a total of 289 patients (n = 24, phase Ia; n = 265, phase Ib) were enrolled. DLT was not observed in phase Ia part. The T 1/2 , CL ss , and V d were similar among all dose groups and different tumors. The most common treatment-emergent adverse events (TEAEs) were anemia, leukopenia, elevated alanine aminotransaminase/asparate aminotransferase (ALT/AST), and elevated bilirubin. And hypothyroidism was the most common immune-related adverse event (irAE). The incidence of grade ≥3 TEAE was 39.8%, while grade ≥3 irAE was only 4.5%. Based on safety studies, pharmacokinetics/pharmacodynamics, and preclinical data, 240-mg Q2W was recommended as the expansion dose. The overall objective response rate was 23.6%, with 10 patients achieving complete response. Patients with a high PD-L1 expression level (31.3% Versus. 13.7%, p = 0.012) or t-issue tumor mutation burden level (31.3% Versus. 5.6%, p = 0.009) showed a significantly better response. GLS-010 showed acceptable safety profile and favorable clinical response. The dose of 240 mg Q2W was an optimal recommended dose as monotherapy. • The PK, PD, and immunogenicity characteristics of GLS-010 were described. • DLT and MTD of GLS-010 were not found. The RP2D was 240 mg Q2w. • Anemia, leukopenia, and elevated alanine aminotransaminase/aspartate aminotransferase/bilirubin were commonly reported TEAEs. • GLS-010 showed considerable efficacy (ORR 23.6%), especially in Hodgkin lymphoma. [ABSTRACT FROM AUTHOR]

Background: The unprecedented efficacy of chimeric antigen receptor T (CAR-T) cell immunotherapy of CD19+ B-cell malignancies has opened a new and useful way for the treatment of malignant tumors. Nonetheless, there are still formidable challenges in the field of CAR-T cell therapy, such as the biodistribution of CAR-T cells in vivo.Methods: NALM-6, a human B-cell acute lymphoblastic leukemia (B-ALL) cell line, was used as target cells. CAR-T cells were injected into a mice model with or without target cells. Then we measured the distribution of CAR-T cells in mice. In addition, an exploratory clinical trial was conducted in 13 r/r B-cell non-Hodgkin lymphoma (B-NHL) patients, who received CAR-T cell infusion. The dynamic changes in patient blood parameters over time after infusion were detected by qPCR and flow cytometry.Results: CAR-T cells still proliferated over time after being infused into the mice without target cells within 2 weeks. However, CAR-T cells did not increase significantly in the presence of target cells within 2 weeks after infusion, but expanded at week 6. In the clinical trial, we found that CAR-T cells peaked at 7-21 days after infusion and lasted for 420 days in peripheral blood of patients. Simultaneously, mild side effects were observed, which could be effectively controlled within 2 months in these patients.Conclusions: CAR-T cells can expand themselves with or without target cells in mice, and persist for a long time in NHL patients without serious side effects.Trial Registration: The registration date of the clinical trial is May 17, 2018 and the trial registration numbers is NCT03528421 . [ABSTRACT FROM AUTHOR]

Background: Natural killer/T-cell lymphoma (NKTCL) is a disease with limited treatment options and poor outcomes. Daratumumab monotherapy demonstrated clinical activity in a single-patient case report. We present data from the primary analysis of a phase 2 study of daratumumab monotherapy in relapsed or refractory (R/R) NKTCL. Methods: This phase 2 study with Simon's two-stage design evaluated daratumumab in patients with histologically confirmed extranodal NKTCL, nasal type, per WHO classification that was refractory to or relapsed after ≥ 1 line of chemotherapy, who were not candidates for other treatment modalities. All patients received daratumumab 16 mg/kg intravenously once weekly for Cycles 1 and 2, every other week for Cycles 3 through 6, and every 4 weeks thereafter until progression or unacceptable toxicity; all cycles were 28 days. The primary end point was objective response rate (ORR) based on blinded independent central review per Revised Criteria for Response Assessment of Hodgkin and non-Hodgkin Lymphoma (Lugano classification). Results: In total, 32 Asian patients received daratumumab. The ORR was 25.0% (95% confidence interval [CI] 11.5–43.4); all 8 responders had a partial response; and the median duration of response was 55.0 days (95% CI 29–339). At 10.2 months of median follow-up, median progression-free survival (PFS) was 53.0 days (95% CI 43–106); the 4-month PFS rate was 13.0%. Median overall survival (OS) was 141.0 days (95% CI 94–438); the 6-month OS rate was 42.9%. Nineteen (59.4%) patients had grade 3/4 treatment-emergent adverse events (TEAEs); the most common was thrombocytopenia (25.0%; n = 8). TEAEs leading to death occurred in 4 patients (death, respiratory failure, septic shock, and pneumonia); all were unrelated to daratumumab. Conclusions: In patients with R/R NKTCL, daratumumab monotherapy was well tolerated with no new safety concerns and achieved an ORR of 25.0%. However, no patients achieved complete response, and duration of response was short. Trial registration ClinicalTrials.gov, NCT02927925. Registered 7 October 2016. [ABSTRACT FROM AUTHOR]

Objective: To explore the correlation of mutation landscape with clinical outcomes in patients with peripheral T-cell lymphoma (PTCL). Methods: We retrospectively analyzed the clinicopathological and prognosis data of 53 patients with PTCL from November 2011 to December 2017. Targeted next-generation sequencing of a 659-gene panel was performed for tissues from 53 patients with PTCLs. The correlation of mutation landscape with clinical outcomes was analyzed. Results: TET2 was the most frequently mutated gene (64%), followed by RHOA (43%), PCLO (23%), DNMT3A (19%), IDH2 (17%), PIEZO1 (17%) and TP53 (15%). When mutated genes were categorized into functional groups, the most common mutations were those involved in epigenetic/chromatin modification (75%), T-cell activation (74%), and the DNA repair/TP53 pathway (64%). TET2/TP53 mutations were significantly associated with positive B symptoms (P = 0.045), and elevated lactate dehydrogenase (LDH) level (P = 0.011). Moreover, TET2/TP53 mutation was a risk factor for PTCL patient survival (HR 3.574, 95% CI 1.069 − 11.941, P = 0.039). The occurrence of JAK/STAT pathway mutations in angioimmunoblastic T-cell lymphoma (AITL) patients conferred a worse progression-free survival (HR 2.366, 95% CI 0.9130–6.129, P = 0.0334). Conclusions: Heterogeneous gene mutations occur in PTCL, some of which have a negative impact on the survival outcome. [ABSTRACT FROM AUTHOR]

Background: Despite numerous chimeric antigen receptor T‐cell (CAR‐T) trials conducted in China, no CAR‐T has been registered in the country. Furthermore, China law and regulations restrict the export of patient material for CAR‐T manufacture abroad. Relma‐cel (JWCAR029), an anti‐CD19 product produced with a commercial‐ready process in China, was evaluated in the first prospective, single‐arm, multicenter, pivotal study of CAR‐T therapy conducted under Chinese IND to support an NMPA‐accepted BLA submission in relapsed/refractory (r/r) LBCL (NCT04089215). Methods: Patients were randomized to receive either 100 × 106 (low dose, n = 27) or 150 × 106 (high dose, n = 32) CAR+ T‐cells as a single infusion following lymphodepleting chemotherapy (fludarabine 25 mg/m2 and cyclophosphamide 250 mg/m2 daily × 3), and then, monitored for efficacy and safety outcomes and pharmacokinetics. The primary endpoint was ORR at 3 months, as assessed by the investigators. Secondary endpoints included DOR, PFS, OS, and adverse event frequency/severity and cell expansion kinetics. Results: As of the data cutoff on 17 June 2020, 68 patients were enrolled, and 59 were treated. Among the 58 efficacy‐evaluable patients, the primary endpoint of 3 month ORR was 60.3% (95% CI, 46.6–73.0), excluding the null hypothesis rate of 20%. Any grade and severe grade CRS occurred in 47.5% and 5.1%, respectively, and any grade and severe grade neurotoxicity events occurred in 20.3% and 5.1%. Conclusions: Relma‐cel met the primary endpoint analysis and demonstrated a high rate of durable responses and low rate of CAR‐T‐associated toxicities in patients with r/r LBCL in a multicenter trial supporting regulatory submission in China. [ABSTRACT FROM AUTHOR]

Little is known regarding the outcome of lymphoma patients undergoing autologous hematopoietic stem cell transplantation (AHSCT) using inadequate hematopoietic stem cell (HSC) doses. Fifty-six patients were enrolled in the study, and the cohort was subdivided into two groups according to the infusion dose: < 1 × 106/kg (poor HSC group) and 1–2 × 106/kg (unfavorable HSC group). Compared with the unfavorable group, the poor HSC group had a longer median time to neutrophil (13 vs. 11 days, p =.007) and platelet engraftment (17 vs. 13 days, p =.024). CD34+ cell infusion dose of < 1 × 106/kg was the only risk factor for neutrophil and platelet engraftment. The expected 3-year progression-free survival and overall survival rates for the whole cohort were 53% and 66%, and no statistical difference was observed between two groups. In conclusion, inadequate HSC infusion dose did not negatively impact AHSCT patient survival but significantly prolonged the time to hematopoietic engraftment. [ABSTRACT FROM AUTHOR]