Fear of cancer recurrence and associated factors in family caregivers of patients with hematologic malignancy receiving chemotherapy: A latent profile analysis.

Objective: This study identified the potential subgroups of fear of cancer recurrence (FCR) in family caregivers (FCs) of patients with hematologic malignancies receiving chemotherapy, as well as exploring factors associated with subgroups. Methods: This was a cross-sectional study involving 206 pairs of participating patients with hematologic malignancies receiving chemotherapy and their FCs. Using Mplus 8.3 to perform the latent profile analysis of FCs' FCR, the FCs' burden, quality of life, psychological resilience, and anxiety as well as their demographic characteristics were compared between the subgroups, with a logistic regression analysis being applied to examine the factors associated with the FCR subgroups. Results: A total of 206 FCs were classified into two subgroups: "a low level of FCR" (Class 1, 65.4%) and "a high level of FCR" (Class 2, 34.6%). Quality of life, anxiety, and frequency of chemotherapy were significantly associated with the two subgroups. Conclusions: FCs of patients with hematologic malignancy receiving chemotherapy had two FCR subgroups, "a low level of FCR" and "a high level of FCR", in association with quality of life, anxiety, and frequency of chemotherapy. These findings provide the theoretical foundations for screening the FCR factor of FCs and conducting interventions for them.

A genome-wide study of the lipoxygenase gene families in Medicago truncatula and Medicago sativa reveals that MtLOX24 participates in the methyl jasmonate response.

BACKGROUND: Lipoxygenase (LOX) is a multifunctional enzyme that is primarily related to plant organ growth and development, biotic and abiotic stress responses, and production of flavor-associated metabolites. In higher plants, the LOX family encompasses several isozymes with varying expression patterns between tissues and developmental stages. These affect processes including seed germination, seed storage, seedling growth, fruit ripening, and leaf senescence. LOX family genes have multiple functions in response to hormones such as methyl jasmonate (MeJA) and salicylic acid. RESULTS: In this study, we identified 30 and 95 LOX homologs in Medicago truncatula and Medicago sativa, respectively. These genes were characterized with analyses of their basic physical and chemical properties, structures, chromosomal distributions, and phylogenetic relationships to understand structural variations and their physical locations. Phylogenetic analysis was conducted for members of the three LOX subfamilies (9-LOX, type I 13-LOX, and type II 13-LOX) in Arabidopsis thaliana, Glycine max, M. truncatula, and M. sativa. Analysis of predicted promoter elements revealed several relevant cis-acting elements in MtLOX and MsLOX genes, including abscisic acid (ABA) response elements (ABREs), MeJA response elements (CGTCA-motifs), and antioxidant response elements (AREs). Cis-element data combined with transcriptomic data demonstrated that LOX gene family members in these species were most likely related to abiotic stress responses, hormone responses, and plant development. Gene expression patterns were confirmed via quantitative reverse transcription PCR. Several MtLOX genes (namely MtLOX15, MtLOX16, MtLOX20, and MtLOX24) belonging to the type I 13-LOX subfamily and other LOX genes (MtLOX7, MtLOX11, MsLOX23, MsLOX87, MsLOX90, and MsLOX94) showed significantly different expression levels in the flower tissue, suggesting roles in reproductive growth. Type I 13-LOXs (MtLOX16, MtLOX20, MtLOX21, MtLOX24, MsLOX57, MsLOX84, MsLOX85, and MsLOX94) and type II 13-LOXs (MtLOX5, MtLOX6, MtLOX9, MtLOX10, MsLOX18, MsLOX23, and MsLOX30) were MeJA-inducible and were predicted to function in the jasmonic acid signaling pathway. Furthermore, exogenous MtLOX24 expression in Arabidopsis verified that MtLOX24 was involved in MeJA responses, which may be related to insect-induced abiotic stress. CONCLUSIONS: We identified six and four LOX genes specifically expressed in the flowers of M. truncatula and M. sativa, respectively. Eight and seven LOX genes were induced by MeJA in M. truncatula and M. sativa, and the LOX genes identified were mainly distributed in the type I and type II 13-LOX subfamilies. MtLOX24 was up-regulated at 8 h after MeJA induction, and exogenous expression in Arabidopsis demonstrated that MtLOX24 promoted resistance to MeJA-induced stress. This study provides valuable new information regarding the evolutionary history and functions of LOX genes in the genus Medicago.

Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations.

We discuss the clinical characteristics and prognostic significance of adult individuals with PTPN11 mutations who have developed acute myeloid leukemia (AML) (none acute promyelocytic leukemia). Next generation sequencing and Sanger sequencing were used to detect 51 gene mutations, and multiplex-PCR was used to detect 41 fusion genes from 232 de novo adult AML patients retrospectively. About 7.76% patients harbored PTPN11 mutations, 20 PTPN11 alterations were identified, all of which were missense mutations in the N-SH2 (n = 16) and PTP (n = 4) domains located in exon 3. Patients with PTPN11 mut had significantly higher platelet counts and hemoglobin levels (p < 0.001), which were mainly detected in M5 (n = 12, 66.67%, p < 0.001) subtype. Patients with MLL-AF6 positive showed a higher frequency of PTPN11 mut (p = 0.018) in the 118 AML cases. PTPN11 mut were accompanied by other mutations, which were NPM1 (44.44%), DNMT3A (38.89%), FLT3 (38.89%), and NRAS (17.2%). PTPN11 mut had a negative impact on the complete remission rate in M5 subtype patients (p < 0.001). However, no statistically significant effect on overall survival (OS) with PTPN11 mut patients in the whole cohort and age group (p > 0.05) was observed. Further analysis revealed no significant difference in OS among NPM1 mut/PTPN11 mut, NPM1 mut/PTPN11 wt, DNMT3A mut/PTPN11 mut, and DNMT3A mut/PTPN11 wt patients (p > 0.05). Multivariate analysis showed the proportion of bone marrow blasts ≥65.4% was a factor significantly affecting OS in PTPN11 mut patients (p = 0.043).

An Externally Validated Nomogram for Predicting the Overall Survival of Patients With Diffuse Large B-Cell Lymphoma Based on Clinical Characteristics and Systemic Inflammatory Markers.

Background: Systemic inflammatory indicators are clinically significant in guiding diffuse large B-cell lymphoma (DLBCL) prognosis. However, which inflammatory markers are the best predictors of DLBCL prognosis is still unclear. In this study, we aimed to create a nomogram based on the best inflammatory markers and clinical indicators to predict the overall survival of patients with DLBCL. Patients and methods: We analyzed data from 423 DLBCL patients from two institutions and divided them into a training set, an internal validation set, and an external validation set (n = 228, 97, and 98, respectively). The least absolute shrinkage and selection operator and Cox regression analysis were used to develop nomograms. We assessed model fit using the Akaike information criterion and Bayesian information criterion. The concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to assess the nomogram's predictive performance and clinical net benefit and compared with the International Prognostic Index (IPI) and National Comprehensive Cancer Network (NCCN)-IPI. Results: The inclusion variables for the nomogram model were age, Eastern Cooperative Oncology Group performance status, lactate dehydrogenase level, the systemic immune-inflammation index (SII), the prognostic nutritional index (PNI), and ß-2 microglobulin (ß-2 MG) level. In the training cohort, the nomogram showed better goodness of fit than the IPI and NCCN-IPI. The C-index of the nomogram (0.804, 95% CI: 0.751-0.857) outperformed the IPI (0.690, 95% CI: 0.629-0.751) and NCCN-IPI (0.691, 95% CI: 0.632-0.750). The calibration curve, ROC curve, and DCA curve analysis showed that the nomogram has satisfactory predictive power and clinical utility. Similar results were found in the validation cohort. Conclusion: The nomogram integrated with the clinical characteristics and inflammatory markers is beneficial to predict the prognosis of patients with DLBCL.

A Novel and Validated Inflammation-Based Prognosis Score (IBPS) Predicts Outcomes in Patients with Diffuse Large B-Cell Lymphoma.

Purpose: We aimed to create a novel prognostic score, the inflammation-based prognosis score (IBPS). In addition, we attempted to establish and validate a nomogram to predict the overall survival (OS) of patients with DLBCL. Patients and Methods: We retrospectively investigated the data of 213 patients with DLBCL diagnosed and treated in the Affiliated Hospital of Jiangnan University and used these data to develop nomograms. At the same time, 89 patients diagnosed and treated in Wuxi People's Hospital Affiliated with Nanjing Medical University from January 2015 to June 2021 were collected as an external validation cohort. We developed IBPS through the least absolute shrinkage and selection operator (LASSO) Cox regression. The univariate and multivariate Cox regression method was used to develop the nomogram. We used the concordance index (C-index), calibration chart, time-dependent receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and the Kaplan-Meier curve were used to assess the nomogram. Results: The systemic immune inflammation index (SII), prognostic nutrition index (PNI), and modified Glasgow prognostic score (mGPS) were used to construct IBPS. The Eastern Cooperative Oncology Group performance status (ECOG PS), IBPS, response to treatment, and whether accept surgery were used to construct the nomogram to predict the OS of DLBCL patients. The C-index in the training and validation cohorts were 0.844 and 0.828, respectively. According to the time-dependent ROC curve and DCA, the nomogram has good predictive accuracy and clinical net benefit. The Kaplan-Meier curve showed that according to the nomogram score, patients in the training and validation cohorts could be classified into three risk groups. Conclusion: In patients with DLBCL, baseline IBPS was a reliable predictor of OS. The survival probability of DLBCL patients can be precisely predicted using the prognosis nomogram based on IBPS.

Fovea-UNet: detection and segmentation of lymph node metastases in colorectal cancer with deep learning.

BACKGROUND: Colorectal cancer is one of the most serious malignant tumors, and lymph node metastasis (LNM) from colorectal cancer is a major factor for patient management and prognosis. Accurate image detection of LNM is an important task to help clinicians diagnose cancer. Recently, the U-Net architecture based on convolutional neural networks (CNNs) has been widely used to segment image to accomplish more precise cancer diagnosis. However, the accurate segmentation of important regions with high diagnostic value is still a great challenge due to the insufficient capability of CNN and codec structure in aggregating the detailed and non-local contextual information. In this work, we propose a high performance and low computation solution. METHODS: Inspired by the working principle of Fovea in visual neuroscience, a novel network framework based on U-Net for cancer segmentation named Fovea-UNet is proposed to adaptively adjust the resolution according to the importance-aware of information and selectively focuses on the region most relevant to colorectal LNM. Specifically, we design an effective adaptively optimized pooling operation called Fovea Pooling (FP), which dynamically aggregate the detailed and non-local contextual information according to the pixel-level feature importance. In addition, the improved lightweight backbone network based on GhostNet is adopted to reduce the computational cost caused by FP. RESULTS: Experimental results show that our proposed framework can achieve higher performance than other state-of-the-art segmentation networks with 79.38% IoU, 88.51% DSC, 92.82% sensitivity and 84.57% precision on the LNM dataset, and the parameter amount is reduced to 23.23 MB. CONCLUSIONS: The proposed framework can provide a valid tool for cancer diagnosis, especially for LNM of colorectal cancer.

Overexpression of the elongation factor MtEF1A1 promotes salt stress tolerance in Arabidopsis thaliana and Medicago truncatula.

BACKGROUND: Elongation factor 1 A (EF1A), an essential regulator for protein synthesis, has been reported to participate in abiotic stress responses and environmental adaption in plants. However, the role of EF1A in abiotic stress response was barely studied in Medicago truncatula. Here, we identified elongation factor (EF) genes of M. truncatula and studied the salt stress response function of MtEF1A1 (MTR_6g021805). RESULTS: A total of 34 EF genes were identified in the M. truncatula genome. Protein domains and motifs of EFs were highly conserved in plants. MtEF1A1 has the highest expression levels in root nodules and roots, followed by the leaves and stems. Transgenic Arabidopsis thaliana overexpressing MtEF1A1 was more resistant to salt stress treatment, with higher germination rate, longer roots, and more lateral roots than wild type plant. In addition, lower levels of H2O2 and malondialdehyde (MDA) were also detected in transgenic Arabidopsis. Similarly, MtEF1A1 overexpressing M. truncatula was more resistant to salt stress and had lower levels of reactive oxygen species (ROS) in leaves. Furthermore, the expression levels of abiotic stress-responsive genes (MtRD22A and MtCOR15A) and calcium-binding genes (MtCaM and MtCBL4) were upregulated in MtEF1A1 overexpressing lines of M. truncatula. CONCLUSION: These results suggested that MtEF1A1 play a positive role in salt stress regulation. MtEF1A1 may realize its function by binding to calmodulin (CaM) or by participating in Ca2+-dependent signaling pathway. This study revealed that MtEF1A1 is an important regulator for salt stress response in M. truncatula, and provided potential strategy for salt-tolerant plant breeding.

Overexpression of Mtr-miR319a Contributes to Leaf Curl and Salt Stress Adaptation in Arabidopsis thaliana and Medicago truncatula.

Salt stress is a worldwide agronomic issue that limits crop yield and quality. Improving salt stress tolerance via genetic modification is the most efficient method to conquer soil salinization problems in crops. Crop miRNAs have been declared to be tightly associated with responding and adapting to salt stress and are advantageous for salt tolerance modification. However, very few studies have validated vital salt tolerance miRNAs and coupled potent target genes in Medicago species, the most economically important forage legume species. In this study, Mtr-miR319a, a miRNA that was identified from the previous next-generation sequencing assay of salt-treated Medicago truncatula, was overexpressed in M. truncatula and Arabidopsis thaliana, inducing the curly leaves and salt stress tolerance phenotypes. Combining the elevated expression level of Mtr-miR319a in the M. truncatula overexpression lines under normal and salt-treatment conditions, the regulatory roles of Mtr-miR319a in leaf development and salt stress adaptation were demonstrated. Several predicted target genes of Mtr-miR319a were also regulated by Mtr-miR319a and were associated with the aforementioned phenotypes in M. truncatula plants, most notably MtTCP4. Our study clarified the functional role of Mtr-miR319a and its target genes in regulating leaf development and defending salt stress, which can help to inform crop breeding efforts for improving salt tolerance via genetic engineering.

Spike-sorting analysis of neural electrical signals evoked by acupuncture based on model.

Acupuncturing the Zusanli (ST 36) point with different types of manual acupuncture manipulations (MAs) and different frequencies can evoke a lot of neural response activities in spinal dorsal root neurons. The action potential is the basic unit of communication in the neural response process. With the rapid development of the electrode acquisition technology, we can simultaneously obtain neural electrical signals of multiple neurons in the target area. So it is crucial to extract spike trains of each neuron from raw recorded data. To solve the problem of variability of the spike waveform, this paper adopts a optimization algorithm based on model to improve the wave-cluster algorithm, which can provide higher accuracy and reliability. Further, through this optimization algorithm, we make a statistical analysis on spike events evoked by different MAs. Results suggest that numbers of response spikes under reinforcing manipulations are far more than reducing manipulations, which mainly embody in synchronous spike activities.

Spiking Correlation Analysis of Synchronous Spikes Evoked by Acupuncture Mechanical Stimulus.

Acupuncturing the ST36 acupoint can evoke the response of the sensory nervous system, which is translated into output electrical signals in the spinal dorsal root. Neural response activities, especially synchronous spike events, evoked by different acupuncture manipulations have remarkable differences. In order to identify these network collaborative activities, we analyze the underlying spike correlation in the synchronous spike event. In this paper, we adopt a log-linear model to describe network response activities evoked by different acupuncture manipulations. Then the state-space model and Bayesian theory are used to estimate network spike correlations. Two sets of simulation data are used to test the effectiveness of the estimation algorithm and the model goodness-of-fit. In addition, simulation data are also used to analyze the relationship between spike correlations and synchronous spike events. Finally, we use this method to identify network spike correlations evoked by four different acupuncture manipulations. Results show that reinforcing manipulations (twirling reinforcing and lifting-thrusting reinforcing) can evoke the third-order spike correlation but reducing manipulations (twirling reducing and lifting-thrusting reducing) does not. This is the main reason why synchronous spikes evoked by reinforcing manipulations are more abundant than reducing manipulations.