Search

Purpose This study aims to investigate the clinical and molecular differences between diffuse large B-cell lymphoma (DLBCL) patients with MYD88L265P and MYD88other. Methods DLBCL patients with MYD88 variations were collected from the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CHCAMS), and Suzhou Municipal Hospital from February 6th, 2007 to May 20th, 2022. Clinicopathological parameters and treatment outcomes between MYD88L265P and MYD88other were investigated. Results A total of 132 patients with MYD88 variations from a cohort of 475 DLBCL patients were included, among which, 78 were MYD88L265P, while 54 were MYD88other. MYD88L265P was more common in non-GCB subtype than MYD88other (83% vs. 60%, P = 0.004). Besides, MYD88L265P was significantly related to higher proportion of testicle/ central nervous system involvement (31% vs. 6%, P P P = 0.018), compared with MYD88other. Compared with MYD88L265P, MYD88other were more likely to have higher percentage of advanced stage (60% vs. 42%, P = 0.044), extranodal site ≥ 2 (45% vs. 28%, P = 0.044), elevated LDH (55% vs. 35%, P = 0.033), positive CD10 expression (36% vs. 16%, P = 0.009), BCL-6 translocation (20% vs. 8%, P = 0.033), and NOTCH pathway gene alteration (24% vs. 13%, P = 0.040). In non-GCB DLBCL subtype, patients with MYD88other were significantly associated with worse progression free survival (PFS) than those with MYD88L265P when treated initially with R-CHOP/R-CHOP-like regimen (P = 0.010). Conclusion The findings of this study indicate that DLBCL patients with MYD88L265P and MYD88other are likely to be two subgroups with different clinical and molecular characteristics. The survival of patients with MYD88other is not superior than those with MYD88L265P, even poorer when focusing on the non-GCB subtype.

Objective: This study aimed to observe the diagnostic value of cranial magnetic resonance imaging (MRI) in patients with vascular dementia induced by ischemic stroke. Methods: The experiment was designed according to the randomized control principle. Two hundred and eighty patients with ischemic stroke who were admitted to Gucheng County Hospital between June 2019 and June 2021 were selected as research subjects. Patients without vascular dementia after stroke were included in the control group, and patients with vascular dementia after stroke were included in the observation group. The cranial MRI was performed in both groups. Results: Proportions of patients with large and moderate infarct lesions in brain tissues were significantly higher in the observation group than the control group. The data variation of relevant MRI detection indicators of the observation group was more obvious than that of the control group (P0.05). Patients with changes in brain morphology were more in the observation group than the control group (P

Objective: Limited data about the prognostic significance of BCL2 mutations and BCL2 copy number variations in diffuse large B-cell lymphoma (DLBCL) are available. This study aimed to comprehensively describe BCL2 genetic alterations in DLBCL patients, and examine correlation of BCL2, TP53 and other genetic alterations with outcomes in patients treated with R-CHOP. Methods: Probe capture-based high-resolution sequencing was performed on 191 patients diagnosed with de novo DLBCL. MYC, BCL2, and BCL6 protein expressions were detected by immunohistochemistry. Results: The presence of BCL2 alterations significantly correlated with poor progression-free survival (PFS) (5-year PFS: 13.7% vs. 40.8%; P = 0.003) and overall survival (OS) (5-year OS: 34.0% vs. 70.9%; P = 0.036). Importantly, patients who harbored BCL2 gain/amplifications (BCL2GA/AMP) also had a remarkably inferior 5-year PFS (11.1% vs. 38.3%; P < 0.001) and OS (22.1% vs. 69.6%; P = 0.009). In contrast, neither BCL2 mutations nor BCL2 translocations were significantly prognostic for survival. Multivariable analyses showed that the presence of BCL2 alterations, especially BCL2GA/AMP, TP53 mutations, and International Prognostic Index (IPI) were significantly associated with inferior PFS and OS. Novel prognostic models for OS were constructed based on 3 risk factors, including BCL2 alterations (Model 1) or BCL2GA/AMP (Model 2), TP53 mutations, and IPI, to stratify patients into 4 risk groups with different survival outcomes. Conclusions: This study showed that DLBCL patients treated with R-CHOP, BCL2 alterations, especially BCL2GA/AMP and TP53 mutations were significantly associated with inferior outcomes, which were independent of the IPI. The novel prognostic models we proposed predicted outcomes for DLBCL patients treated with R-CHOP, but further validation of the prognostic models is still warranted.

Inflammation is one of the most crucial mechanism underlying hepatic ischemia-reperfusion injury (HIRI). Several studies have shown that Ac2-26, the active

The COVID-19 pandemic has created an unprecedented crisis all over the world, while it also marks the coming of a new era of opportunities and challenges, especially for higher education. Universities should be more inclusive and innovative in communication and cooperation, promoting opportunities for collaborations in all aspects and reshaping international education.

A fluorescent sensing strategy was developed for rapid, highly sensitive and specific detection of lead (II) ion (Pb2+) on the basis of Pb2+ DNAzyme-controlled tetrahedral DNA nanostructure (TDN)-mediated hyper-branched hybridization chain reaction (hHCR). In this strategy, DNA hairpins used for HCR amplification are modified on the four vertexes of TDN, which are then used to perform rapid TDN-hHCR in the presence of an initiator strand, producing large-sized cross-linked reaction products and thus giving greatly improved fluorescence resonance energy transfer (FRET) signal output. Pb2+ DNAzyme catalyzes the cleavage of the initiator strand, inhibiting the initiation of TDN-hHCR and giving decreased FRET signal. Synergetic signal amplification of Pb2+ DNAzyme-catalyzed cleavage reaction and subsequent TDN-hHCR confers the sensing platform with ultrahigh sensitivity. As low as 0.25 pM Pb2+ can be detected by using either signal “turn-on” or “turn-off” mode. The whole detection process can be finished within 20 min. Strong anti-interference capacity of FRET-based ratiometric detection and high specificity of Pb2+ DNAzyme endow the sensing platform with great practical application potential, which was demonstrated by the accurate detection of Pb2+ in real river water, fruit, vegetable and grain samples.

Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous malignancy. Following front-line immunochemotherapy, 30–40% of DLBCL patients develop relapsed or refractory (r/r) disease, which can be treated with ibrutinib. It has been previously reported that MYD88MUT affects the response to ibrutinib in patients with r/r DLBCL. Here, we aimed to gather understanding of MYD88MUT in r/r DLBCL patients and to evaluate its influence on response to ibrutinib. In this study, tissue samples from DLBCL patients (n = 212) were retrospectively collected and sequenced by target-capturing panels of either 413 or 112 genes that are frequently mutated in non-Hodgkin’s lymphoma. Sixty patients with MYD88 mutations and available clinical information were included for further analysis. Seven MYD88MUT variants were identified, L265P (65.0%, n = 39), S219C (13.3%, n = 8), S243N (8.3%, n = 5), P258L (6.7%, n = 4), F283V (1.7%, n = 1), P141R (1.7%, n = 1), and V217F (1.7%, n = 1). One patient had MYD88 amplification. In addition, mutations in PIM1 (67%, n = 40), IGH fusion (48%, n = 29), CD79B (43%, n = 26), KMT2D (30%, n = 18), and TP53 (27%, n = 17) were identified. For patients with L265P, IRF4 (p = 0.011) was frequently mutated. Otherwise, TET2 (p = 0.016), NOTCH2 (p = 0.044), MET (p = 0.037), SOCS1 (p = 0.011), TNFRSF14 (p = 0.011), EZH2 (p = 0.037), and BCL6 (p

We propose an effective method for manufacturing human anatomical specimens in response to the shortage of cadaver specimens and the poor simulation results of anatomical specimen substitutes. Digital human data with high precision were used to create digital models and corresponding mapped textures. Different materials were chosen to print the digital models with full-color and multimaterial 3D-printing technology based on the histological characteristics of the anatomical structures. Anatomy experts and surgeons were then invited to compare the 3D printed models with authentic anatomical specimens in terms of morphological appearance, anatomical detail, and textural properties. The skull, brain, hand muscles, blood vessels and nerves of the hand, and the deep structure of the head and face were printed. The skull model used hard material, and the brain and hand muscles models used flexible and hard materials combined. The blood vessels, nerves of the hand, and the superficial and deep structure of the head and face used transparent materials, revealing the small vessels and nerves in the interior. In all the models, there were no significant differences from anatomical specimens in morphological appearance and anatomical detail. They also affected vision and touch in the same way as authentic specimens in the textural properties of color, roughness, smoothness, and fineness. Full-color and multi-material 3D printed anatomical models have the same visual and tactile properties as anatomical specimens and could serve to complement or supplement them in anatomy teaching to compensate for the shortage of cadavers.

Limited data about the prognostic significance ofProbe capture-based high-resolution sequencing was performed on 191 patients diagnosed withThe presence ofThis study showed that DLBCL patients treated with R-CHOP

Herein, a fluorescence sensing strategy for ultrasensitive and highly selective detection of adenosine triphosphate (ATP) was presented by taking advantage of the exponential amplification efficiency of branched rolling circle amplification (BRCA) and the extreme specificity of T4 DNA ligase toward ATP. In this strategy, T4 DNA ligase is used to catalyze the cyclization of the template for the subsequent BRCA reaction. And the targeted ATP is the key component to activate the enzyme. The obtained products can then be probed with SYBR Green I (SG I), a kind of DNA duplex specific indicator, giving a dramatically increased fluorescence signal. The experimental results showed that the fluorescence enhancement is highly ATP concentration-dependent, thus making the label-free detection of ATP possible. By using the proposed method, sensitive ATP quantitation with a detection limit of 30 pM was achieved. Since the activity of T4 DNA ligase is highly specific ATP dependent, such a method successfully overcomes the drawback of poor selectivity faced by traditional aptamer-based ATP assays. Moreover, the proposed sensing platform was demonstrated to work well for real sample analysis, suggesting that it has promising potential in practical applications in clinical diagnosis and biochemical research.

During its development in recent decades, DNAzyme has become a promising candidate for application in biosensor field. However, it still suffers from the problem of thermodynamic and biological instability such as nuclease digestion, which limits its applications in complex samples. Here we have presented a simple and common strategy to resolve this problem by engineering the linear DNAzyme into a circular shape DNAzyme based on the integration of substrate and enzyme parts into one single-stranded sequence. This circular DNAzyme system is indeed endowed with excellent stability due to the stable intramolecular double-stranded formation and extraordinary resistance to nuclease digestion due to the closed structure. We demonstrated that this circular DNAzyme system gained excellent stability and could active under conditions across a broader range of temperature, salt concentrations, and pH. Depending on this circular DNAzyme, combing with Terminal deoxynucleotidyl transferase (TdT)-generated G-quadruplexes, a label free colorimetric sensing platform for Pb

A fluorescent sensing strategy was developed for rapid, highly sensitive and specific detection of lead (II) ion (Pb

In the history of cultural exchange between China and the West, it’s a deed praised far and wide that the Chinese paintings Eight Views of Xiao Xiang had exerted great influence on Ezra Pound’s poetic work “Seven Lakes Canto” or “Canto 49.” By exploring the details of the paintings and tracing the influence of the paintings on the creation of the poem, this paper reveals that the etymological and compositional use of Chinese ideograms had an enormous impact on Pound’s thinking about poetry and cultural matters, and on the writing of The Cantos. Pound, by adopting the images of China in Eight Views of Xiao Xiang, finds another paradise, so the Chinese cultural elements enabled him to create a new entity in its own right: the Poundian poem. Discussion of Pound’s “Seven Lakes Canto” from his poetic and translation theories certifies that the poem can actually be perceived as a unique way of interpreting and displaying China. Resumo: Na história das trocas culturais entre a China e o Ocidente, é um feito amplamente louvado que as pinturas chinesas Oito Vistas de Xiao Xiang tenham exercido grande influência na obra poética de Ezra Pound “Seven Lakes Canto” ou “Canto 49”. Ao explorar os detalhes das pinturas e traçar a influência das pinturas na criação do poema, este artigo revela que o uso etimológico e composicional dos ideogramas chineses teve um enorme impacto no pensamento de Pound sobre poesia e assuntos culturais, e na escrita dos Cantos. Pound, ao adotar as imagens da China em Oito Vistas de Xiao Xiang, encontra outro paraíso, de modo que os elementos culturais chineses lhe possibilitaram criar uma nova entidade em seus próprios termos: o poema poundiano. A discussão de “Seven Lakes Canto”, de Pound, a partir de suas teorias poéticas e tradutórias, comprova que o poema pode de fato ser percebido como um modo único de interpretar e apresentar a China.

Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous malignancy. Following front-line immunochemotherapy, 30-40% of DLBCL patients develop relapsed or refractory (r/r) disease, which can be treated with ibrutinib. It has been previously reported that MYD88Here, we aimed to gather understanding of MYD88In this study, tissue samples from DLBCL patients (n = 212) were retrospectively collected and sequenced by target-capturing panels of either 413 or 112 genes that are frequently mutated in non-Hodgkin's lymphoma. Sixty patients with MYD88 mutations and available clinical information were included for further analysis.Seven MYD88This study adds clinical observations with MYD88

Ligase and polynucleotide kinase (PNK) play important roles in DNA repair process. In this work, a simple, convenient and ultrasensitive fluorescence biosensor for label-free detection of ligase and PNK was proposed on the basis of target-triggered hyper-branched rolling circle amplification (HRCA). In the presence of PNK and ligase, the 5′-OH end of a linear Padlock DNA strand could be phosphorylated by PNK and then be converted by ligase into a circular template to trigger subsequent exponential HRCA reaction, producing amounts of double-stranded DNA (dsDNA) fragments, accompanied by the significant fluorescence increase of dsDNA-intercalating dye–SYBR Green I (SG I). In the absence of ligase or PNK, however, HRCA primer and uncyclized Padlock strands were completely digested by exonucleases, thus providing a low background for the sensing system. Therefore, by recording the fluorescence change of SG I, ligase and PNK activity could be facilely determined. The proposed biosensor exhibited excellent detection sensitivity for ligase and PNK activity with the detection limits of 3.4 × 10−4 U/mL and 3.8 × 10−4 U/mL, respectively. Such a sensing strategy could be easily extended to studies on inhibitors of these two enzymes, thus might offer a promising tool in clinical molecular diagnostics and cancer therapy.

During its development in recent decades, DNAzyme has become a promising candidate for application in biosensor field. However, it still suffers from the problem of thermodynamic and biological instability such as nuclease digestion, which limits its applications in complex samples. Here we have presented a simple and common strategy to resolve this problem by engineering the linear DNAzyme into a circular shape DNAzyme based on the integration of substrate and enzyme parts into one single-stranded sequence. This circular DNAzyme system is indeed endowed with excellent stability due to the stable intramolecular double-stranded formation and extraordinary resistance to nuclease digestion due to the closed structure. We demonstrated that this circular DNAzyme system gained excellent stability and could active under conditions across a broader range of temperature, salt concentrations, and pH. Depending on this circular DNAzyme, combing with Terminal deoxynucleotidyl transferase (TdT)-generated G-quadruplexes, a label free colorimetric sensing platform for Pb2+ quantitation was developed, and a detection limit of 0.085 nM was achieved. Then the enzyme digestion cycle amplification was introduced to further improve the sensitivity of the sensing system, an ultralow detection limit of 0.0015 nM for this fluorescence method was achieved. Based on the two sensing platforms, ultrasensitive analysis of Pb2+ in environmental water and food samples was successfully realized. It is anticipated that this stable circular DNAzyme design will be helpful for trace detection in complex samples.

Diffuse large B-cell lymphoma (DLBCL) is a clinically aggressive and heterogenous disease. Although most patients can be cured by immunochemotherapy, 30% to 40% patient will ultimately develop relapsed or refractory disease. Here, we investigated the molecular landscapes of patients with diverse responses to R-CHOP. We performed capture-based targeted sequencing on baseline samples of 105 DLBCL patients using a panel consisting of 112 lymphoma-related genes. Subsequently, 81 treatment-naive patients with measurable disease and followed for over 1 year were included for survival analysis. Collectively, the most commonly seen mutations included IGH fusion (69%), PIM1(33%), MYD88 (29%), BCL2 (29%), TP53 (29%), CD79B (25%) and KMT2D (24%). Patients with TP53 mutations were more likely to have primary refractory disease (87.0% vs 50.0%, P = .009). For those with TP53 disruptive mutations, 91.7% patients were in the primary refractory group. Interestingly, BCL-2 somatic hypermutation was only seen in patients without primary refractory disease (P = .014). In multivariate analysis, BCL-2 amplification (hazard ratio [HR] = 2.94, P = .022), B2M mutation (HR = 2.99, P = .017) and TP53 mutation (HR = 3.19, P < .001) were independently associated with shorter time to progression (TTP). Furthermore, TP53 mutations was correlated with worse overall survival (P = .049). Next, we investigated mutation landscape in patients with wild-type (WT) TP53 (n = 58) and found that patients harboring MYD88 L265P had significantly inferior TTP than those with WT or non-265P (P = .046). Our study reveals the mutation spectrum of treatment-naive Chinese DLBCL patients. It also confirms the clinical significance of TP53 mutations and indicates the prognostic value of MYD88 L265P in TP53 WT patients.

The role of mediastinal radiotherapy (RT) in primary mediastinal large B cell lymphoma is controversial. We used the Surveillance, Epidemiology and End Results program 18 database to identify the role after rituximab approval. Among 474 patients included, 65.8% were 18-39 years old and 34.2% were 40-59 years old; 45.8% received RT. Univariate analysis showed that disease stage and race could affect survival. After adjusting for stage and race, RT was correlated with prognosis in patients aged 40-59 years (none/unknown vs. RT, hazard ratio = 2.898

Background: Hepatic Ischemia-reperfusion injury (HIRI) is a complex process during liver resection and transplantation.The purpose of this study was to investigate whether N-acetyl-L-tryptophan (L-NAT) could protect hepatocytes against acute hepatic ischemia-reperfusion injury through the Toll-Like Receptor 4(TLR4)/nuclear transcription factor-κB (NF-κB) signaling pathway and its possible mechanisms. Methods: The expression of SP and NK-1R were detected in rat models of hepatic ischemia-reperfusion injury. The activity of NF-κB and TLR4 were detected in H2O2-induced by the BRL oxidative damage model. Results: (1) Immunohistochemical staining showed that the expression of substanceP (SP) and Neuroknin 1 Receptor (NK-1R) increased after hepatic ischemia-reperfusion injury (HIRI). (2)L-NAT pretreatment could inhibit the expression of nuclear transcription factor Kappa-B (NF-κB) and toll-like receptor 4 (TLR4) induced by HIRI. Conclusion: Taken together, the increased of SP and NK-1R after HIRI revealing that neurogenic inflammatory responsewas involved inHIRI. The results that L-NATsignificantly decreased the increasing of NF-κB and TLR4induced byHIRI implies that L-NAT protects liver against hepatic ischemia-reperfusion injury through TLR4/NF-κB signaling pathway.

e19549 Background: Unlike BCL2 translocation ( BCL2TR), limited data about the prognostic significance of BCL2 mutations ( BCL2MUT) and BCL2 copy number variations in diffuse large B-cell lymphoma (DLBCL) is available, especially in the era of immunochemotherapy. Predicting outcomes at the time of diagnosis is of extreme importance. Methods: In this study, we performed probe capture-based high resolution sequencing on 191 Chinese patients with de novo DLBCL, attempting to comprehensively describe BCL2 genetic alterations and several other genes. We also examined correlation between genetic alterations and outcomes in 164 patients treated with R-CHOP. BCL2, MYC and BCL6 protein was determined by immunochemistry. Results: Of all the 191 patients, BCL2 gain/amplificatio n ( BCL2GA/AMP) and BCL2MUT occurred in 9.4% and 8.9% of patients, respectively, and only 4.2% of cases harbored BCL2TR. As a result, BCL2 alteration, comprised of the above three genetic alterations, was observed in 18.3% of patients. Compared to patients with the absence of BCL2 alteration, the 5-year progression-free survival (PFS) (13.7% vs 40.8%, P= 0.003) and overall survival (OS) (34.0% vs 70.9%, P= 0.036) were significantly inferior in cases that harbored BCL2 alteration. Importantly, patients who harbored BCL2GA/AMP also had remarkably inferior PFS (5-year PFS, 11.1% vs 38.3%, P< 0.001) and OS (5-year OS, 22.1% vs 69.6%, P= 0.009) compared to those without BCL2GA/AMP. By contrast, neither BCL2MUT nor BCL2TR were significantly prognostic for survival. Multivariate analysis showed that the presence of BCL2 alterations, especially BCL2GA/AMP, TP53 mutation and International Prognostic Index (IPI) were significantly associated with inferior PFS and OS. Novel prognostic models were constructed based on 3 risk factors, including BCL2 alteration (Model 1) or BCL2GA/AMP (Model 2), TP53 mutation and IPI, stratifying patients into three risk groups with different outcomes. According to Model 1, the 5-year PFS were 65.9%, 25.9%, and 12.9% ( P< 0.001), and 5-year OS were 89.4%, 65.0% and 16.4% ( P< 0.001), respectively, for the low-risk, intermediate-risk and high-risk groups. In Model 2, the 5-year PFS was 56.9% for the low-risk, 24.1% for the intermediate-risk and 14.3% for the high-risk group ( P< 0.001), and 5-year OS were 86.6%, 60.9% and 16.9% for the three risk groups ( P< 0.001), respectively. Conclusions: This study demonstrated that, in patients treated with R-CHOP, the presence of BCL2 alteration, especially BCL2GA/AMP, and TP53 mutation were significantly associated with inferior outcomes independent of IPI. The novel prognostic models we proposed could aid in individual risk prediction for DLBCL patients treated with R-CHOP. Further validation of this prognostic model is warranted.

Germ cell cancer (GCC) is a group of neoplasms with heterogeneity. Predominant in young adults, GCC potentially mitigates a high number of productive years of life lost. Indeed, long-term side effects have arisen as a problem in GCC survivors, especially in adolescent and young adult (AYA) subgroup. The objective of this study is to delineate survival and second primary malignancies (SPMs) in AYA patients with GCC.We used US population-based Surveillance, Epidemiology and End Results (SEER) 18 Regs Custom Data (1976-2016 varying) and SEER 9 Regs Research Data, November 2019 Sub (1975-2017) for survival analysis and SPM analysis, respectively.Overall, 5-, 10- and 20-year overall survival rates for AYA patients with GCC were 93%, 91.3%, and 86.9%, respectively. Compared with the general population, a significantly higher risk of SPMs was observed in multiple sites, especially stomach, (standardized incidence ratio [SIR] = 2.94), pancreas (SIR = 3.72), intrahepatic bile duct (SIR = 3.12), soft tissue including heart (SIR = 4.65), leukemia (SIR = 3.70), and testis (SIR = 562.18). The excess risks to develop leukemia were even higher in those with primary mediastinal GCC (SIR = 69.50, P0.05, 95% confidence interval = 30.00-136.94). Multivariate analysis indicated age of diagnosis, primary site, race, receipt of radiotherapy, and histological subtype independently correlated with risk of SPMs.The present study provides risk factors of SPM in AYA patients with GCC, which could facilitate the individualization of long-term surveillance in this population.

Increasing knowledge on the hallmark characteristics of cancer and tumor pharmacology has promoted the introduction of phytochemicals, such as traditional Chinese medicine (TCM) in cancer therapy, which modulate numerous molecular targets and exert anticancer activities. β-elemene, an active and non-toxic compound isolated from the Chinese medicinal herb Rhizoma Zedoariae, has been explored as a potent anti-cancer agent against multiple cancers in extensive clinical trials and experimental research in vivo and in vitro. β-elemene exerts therapeutic potential via modulation of core hallmark capabilities of cancer by suppressing proliferative signaling, such as MAPK and PI3K/Akt/mTOR pathway, inducing cell death, up-regulating growth suppressors, deactivating invasion and metastasis and interacting replicative immortality and attenuating angiogenesis. Recent studies have significantly improved our understanding of anti-cancer activities and underlying molecular mechanisms of this Chinese medicine. This review presents these novel findings regarding the unique properties of β-elemene as an agent for cancer treatment, with an emphasis on multi-targeting biological and molecular regulation.

Previously, studies have shown increased risks of second primary malignancies (SPM) after Hodgkin lymphoma and non-Hodgkin lymphoma. Nevertheless, investigation quantifying risks of SPM in patients with diffuse large B-cell lymphoma (DLBCL) remains scarce.We used the US population-based SEER 9 Regs Custom Data, Nov 2016 Sub to analyze the risks of SPM in patients with DLBCL. The standardized incidence ratio (SIR), absolute excess risk (AER), and 95% confidence intervals (CIs) were calculated.Among patients with DLBCL as a primary malignancy, 3751 patients had second cancer episodes identified, with a SIR of 1.19 (95% CI: 1.16-1.23, P0.05). There was a significantly higher risk of tumors/malignancies in the following sites of patients with DLBCL compared with the general population: Oral cavity and pharynx, hepatobiliary system, head and neck, thorax, bone and soft tissue, skin, breasts, urinary tract, and endocrine system. Additionally, leukemia, myeloma and lymphoma, and Kaposi sarcoma occurred more frequently in patients with DLBCL than in the general population. Risk for a subsequent colon/rectum/anus cancer, bone and joint malignancy, and melanoma were significantly elevated in DLBCL patients received beam radiation, while the risk for these malignancies was not significantly increased in those without a radiation record. Notably, for patients under 45 years of age, the risk for SPM was higher than their counterparts in other age groups.Our results offer insight into the occurrence of SPM among patients with DLBCL, suggesting awareness of the increased risk of subsequent malignancies is crucial for DLBCL survivors as well as for their physicians.

A new public high-amylose maize line, GEMS-0067, has been developed by USDA-ARS Germplasm Enhancement of Maize (GEM) Project. GEMS-0067 maize line is a homozygous mutant of amylose-extender (ae) gene and high-amylose modifier (HAM) gene(s). GEMS0067 starches consist of 83.1-85.6% apparent amylose and 39.4%-43.2% resistant starch (RS), which are larger than the ae single-mutant starches (61.7-67.7% and 11.5%-19.1%, respectively) and normal maize starch (~30% and

The physicochemical, functional and pasting properties of whole flours from pinto bean, lima bean, red kidney bean, black bean, navy bean, small red bean, black eye bean, mung bean, lentil and chickpea were investigated. Significant differences in physicochemical characteristics and functional properties were observed ( P Phaseolu s legume flour exhibited higher water absorption capacity, oil absorption capacity, emulsion activity, and emulsion stability compared with other kinds of legume flour. Pasting properties were significantly different ( P

Background Diffuse large B-cell lymphoma (DLBCL) is heterogenous morphologically, clinically and genetically. Although half of patients could be cured by frontline R-CHOP, approximately 10%-15% are refractory or relapse within the 1st year. Here, we investigated the molecular landscapes of patients with diverse responses to R-CHOP. Methods Targeted sequencing was performed on baseline samples of 105 DLBCL patients. After a median follow-up of 67 months, 63 (60.0%) patients had refractory or relapsed disease. All patients received R-CHOP(-like) regimen as the first-line treatment. After excluding double-hit and primary central system lymphoma, 81 patients with measurable disease before initial treatment and followed over 1 year were included for survival analysis. Patients who received less than a partial remission in the first-line setting or those relapsed within the first 12 months since the initiation of the treatment were defined as having primary refractory. Results Collectively, we identified 1162 mutations spanning 103 genes from this cohort. The most commonly seen mutations included PIM1(33%), MYD88 (29%), BCL2 (29%), TP53 (29%), CD79B (25%) and KMT2D (24%). Patients with TP53 mutations were more likely to have primary refractory disease (41.7% vs 7.4%, p = 0.002). For those with TP53 disruptive mutations, primary refractory is also more common (22.9% vs. 0%, p = 0.006). Interestingly, BCL-2 somatic hypermutation (SHM) was only seen in patients without primary refractory disease (p = 0.014). The International prognostic index (IPI) score and other clinical characteristics were comparable between the 2 groups. Furthermore, TP53 mutations were correlated with shorter PFS (p = 0.001) and OS (p = 0.049). Next, we investigated mutation landscape in patients with WT TP53 (n = 58) and found that patients harboring MYD88 L265P had significantly inferior PFS than those with WT or non-265P (p = 0.046). Conclusions We revealed that patients with TP53 mutation are more likely to have primary refractory to standard R-CHOP. This study also showed the prognostic potential of MYD88 L265P in those with WT TP53 and indicated that distinct subgroups could be identified by TP53 and MYD88 L265P mutations. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Although Permanent Magnet Synchronous Generator (PMSG) wind turbines (WTs) mitigate gearbox impacts, they requires high reliability of generators and converters. Statistical analysis shows that the failure rate of direct-drive PMSG wind turbines’ generators and inverters are high. Intelligent fault diagnosis algorithms to detect inverters faults is a premise for the condition monitoring system aimed at improving wind turbines’ reliability and availability. The influences of random wind speed and diversified control strategies lead to challenges for developing intelligent fault diagnosis algorithms for converters. This paper studies open-circuit fault features of wind turbine converters in variable wind speed situations through systematic simulation and experiment. A new fault diagnosis algorithm named Wind Speed Based Normalized Current Trajectory is proposed and used to accurately detect and locate faulted IGBT in the circuit arms. It is compared to direct current monitoring and current vector trajectory pattern approaches. The results show that the proposed method has advantages in the accuracy of fault diagnosis and has superior anti-noise capability in variable wind speed situations. The impact of the control strategy is also identified. Experimental results demonstrate its applicability on practical WT condition monitoring system which is used to improve wind turbine reliability and reduce their maintenance cost.

Native starches from twenty-six botanical sources were determined for their structural features and stability against freeze–thaw treatments. Starch gels (5%, w/w) were prepared and repeatedly freeze–thawed up to five cycles by storing at −18 °C for 21 h and then at 30 °C for 3 h. Water release (syneresis) from the thawed gel after the 1st, 3rd and 5th cycle was measured gravimetrically, and evaluated in relation to apparent amylose content (AAC) and distribution of amylopectin branch chains with degree of polymerization 6–12 (APC ratio). Syneresis was not observed for starch gels of cassava, normal and waxy japonica rice up to the 1st, 3rd and 5th cycle, respectively. On the other hand, syneresis rapidly occurred for starch gels of elephant yam, new cocoyam, potato, edible canna, and water yam. Optimal multiple linear regression models were generated to predict individual effect of AAC and APC ratio on syneresis of starch gels. The prediction models illustrated the positive unit-contribution of AAC and negative unit-contribution of APC ratio to syneresis (P

Structural changes from the octenylsuccinylation of high-amylose maize starch were investigated by FT-IR and differential scanning calorimetry (DSC), with observations made on the distribution of octenyl succinate (OS) groups using confocal laser scanning microscopy (CLSM). Results of the octenylsuccinylation on in vitro digestion property (uncooked and cooked) were also determined. DSC data revealed a broad gelatinization endothermic peak ranged from 72.5 °C to 96.4 °C for the native starch, and a downward trend for products of increasing degree of substitution (DS). The OS groups appeared to be distributed throughout the OS-starch granules, especially on the surface. Octenylsuccinylation decreased the slowly digestible starch content of low DS OS-starch after cooking, while increased the resistant starch (RS) level in uncooked OS-starch. Even though uncooked OS-starch (DS ≈ 0.04) has 86.3% RS content, its RS content was reduced to 7.5% after cooking.

The objective of this study was to understand the crystalline structures of maize ae-mutant starches by analyzing the structures and properties of their Naegeli dextrins. After an exhaustive acid hydrolysis of the starch granules with sulfuric acid (15.3%, v/v) at 38 °C for up to 102 days, the maize ae-mutant starches produced 18.3–39.5% Naegeli dextrins. The Naegeli dextrins showed the B-type polymorph and displayed similar onset (45.1–51.4 °C), peak (113.9–122.2 °C), and conclusion (148.0–160.0 °C) gelatinization-temperatures and large enthalpy changes (21.8–31.3 J/g) and percentage crystallinity (77.0–79.2%). The Naegeli dextrins showed unimodal molecular-size distributions with the peak molecular-size at degree of polymerization (DP) 16. The molecular-size distributions of the Naegeli dextrins did not significantly change after debranching with isoamylase, indicating predominantly linear molecules. The isoamylase-treated Naegeli dextrins had average chain lengths of DP 23.8–27.5 and large proportions of long chains (DP ≥ 25, 36.7–52.7%), resulting from hydrolysis of amylose double helices.

GEMS-0067 maize starch contains up to 32% elongated starch granules, much higher than amyloseextender (ae) single-mutant maize starch (7%) and normal (non-mutant) maize starch (0%). These elongated granules are highly resistant to enzymatic hydrolysis at 95–100 C, which function as resistant starch. The structure and formation of these elongated starch granules, however, were not known. In this study, light, confocal laser-scanning, scanning electron, and transmission electron microscopy were used to reveal the structure and formation of these elongated starch granules. The transmission electron micrographs showed fusion through amylose interaction between adjacent small granules in the amyloplast at the early stage of granule development. A mechanistic model for the formation of elongated starch granules is proposed.

GEMS-0067 maize ae -line starches developed by the Germplasm Enhancement of Maize (GEM) project consist of 39.4–43.2% resistant starch (RS), which is larger than the existing ae -line starches of H99 ae , OH43 ae , B89 ae , and B84 ae (11.5–19.1%) as reported in part I of the study. The objective of this study was to understand the mechanism of the RS formation in the GEMS-0067 ae -line starch. In the current study, we analyzed the structures and properties of the RS residues that remained after enzymatic hydrolysis of the ae -line starches at 95–100 °C. The RS residues consisted of two major components: large starch molecules of average degrees of polymerization (DP) 840–951 with a few branches and small starch molecules (average DP 59–74) with mostly linear chains. All the RS residues had a semi-crystalline structure with the B-type polymorph and displayed high onset (100.7–107.7 °C), peak (118.6–121.4 °C), and conclusion (139.7–158.8 °C) gelatinization temperatures. After the maize ae -mutant starches were defatted with methanol, the RS contents decreased to 27.8–28.9% for the GEMS-0067 ae -line starches and 9.0–11.0% for the existing ae -line starches. The RS residues were attributed to the presence of long-chain double-helical crystallites derived from amylose and the intermediate component (IC). These crystallites present in native ae -line starches had gelatinization temperatures above 100 °C and maintained the semi-crystalline structures after enzymatic hydrolysis at 95–100 °C.

Endosperm starches were isolated from kernels of seven maize amylose-extender ( ae ) lines: three new ae -lines, derived from a Guatemalan breeding cross with pedigrees of GUAT209:S13 × (OH43 ae × H99 ae ) B-B-4-1-2-1-1, GUAT209:S13 × (OH43 ae × H99 ae ) B-B-4-4-2-1-1, and GUAT209:S13 × (OH43 ae × H99 ae ) B-B-4-4-2-1-2, designated as GSOH1, GSOH2, and GSOH3, respectively, were developed by the USDA-ARS Germplasm Enhancement of Maize (GEM) Project, and four existing inbred lines, H99 ae, OH43 ae , B89 ae , and B84 ae . The resistant starch (RS) contents, measured using AOAC method 991.43 for total dietary fiber, showed that the three new-line starches had larger RS contents (39.4–43.2%) than the four inbred lines (11.5–19.1%). This study was conducted to understand relationship between the RS content and molecular structure of the maize ae-mutant starch. Analytical results showed that the three new-line starches had larger apparent (83.1–85.6%) and absolute amylose-contents (57.4–62.6%) than the starches of the inbred ae -lines (61.7–67.7% and 35.5–44.7%, respectively). The RS content of the ae -mutant starch was positively correlated with both the apparent and absolute amylose-contents of the starch with correlation coefficients of 0.99 and 0.96, respectively. Gel permeation chromatograms revealed that all seven ae starches contained large proportions of intermediate components (IC), 22.4%–52.0%. All seven ae starches displayed similar onset gelatinization temperatures (64.5–65.8 °C), but the three new-line starches displayed higher conclusion temperatures (122.0–130.0 °C) than the four inbred-line starches (100.5–105.3 °C). These results indicated that the crystalline structure of the three new ae- line starches was retained after boiling at ∼100 °C. The crystalline structure was resistant to enzyme hydrolysis and resulted in greater RS contents.