A Chinese verb semantic feature dataset (CVFD).

Language is an advanced cognitive function of humans, and verbs play a crucial role in language. To understand how the human brain represents verbs, it is critical to analyze what knowledge humans have about verbs. Thus, several verb feature datasets have been developed in different languages such as English, Spanish, and German. However, there is still a lack of a dataset of Chinese verbs. In this study, we developed a semantic feature dataset of 1140 Chinese Mandarin verbs (CVFD) with 11 dimensions including verb familiarity, agentive subject, patient, action effector, perceptual modality, instrumentality, emotional valence, action imageability, action complexity, action intensity, and the usage scenario of action. We calculated the semantic features of each verb and the correlation between dimensions. We also compared the difference between action, mental, and other verbs and gave some examples about how to use CVFD to classify verbs according to different dimensions. Finally, we discussed the potential applications of CVFD in the fields of neuroscience, psycholinguistics, cultural differences, and artificial intelligence. All the data can be found at https://osf.io/pv29z/ .

Retrospective memory integration accompanies reconfiguration of neural cell assemblies.

Memory is a dynamic process that is based on and can be altered by experiences. Integrating memories of multiple experiences (memory integration) is the basis of flexible and complex decision-making. However, the mechanism of memory integration in neural networks of the brain remains poorly understood. In this study, we built a recurrent spiking network model and investigated the neural mechanism of memory integration before a decision is made (retrospective memory integration) at the neural circuit level. Our simulations suggest that retrospective memory integration accompanies reconfiguration of neural cell assemblies. Additionally, partially blocking neural network plasticity leads to failure of memory integration. These findings can potentially guide the experimental investigation of the neural mechanism of retrospective memory integration and serve as the basis for developing new artificial intelligence algorithms.

A Chinese Conceptual Semantic Feature Dataset (CCFD).

Memory and language are important high-level cognitive functions of humans, and the study of conceptual representation of the human brain is a key approach to reveal the principles of cognition. However, this research is often constrained by the availability of stimulus materials. The research on concept representation often needs to be based on a standardized and large-scale database of conceptual semantic features. Although Western scholars have established a variety of English conceptual semantic feature datasets, there is still a lack of a comprehensive Chinese version. In the present study, a Chinese Conceptual semantic Feature Dataset (CCFD) was established with 1,410 concepts including their semantic features and the similarity between concepts. The concepts were grouped into 28 subordinate categories and seven superior categories artificially. The results showed that concepts within the same category were closer to each other, while concepts between categories were farther apart. The CCFD proposed in this study can provide stimulation materials and data support for related research fields. All the data and supplementary materials can be found at https://osf.io/ug5dt/ .

Assessment of thyroid cancer risk in more than 334,000 patients with inflammatory bowel disease: a case-control study and a meta-analysis.

BACKGROUND: Potential risk of thyroid cancer in patients with inflammatory bowel disease has not been well investigated. The aim of the study was to reveal the relationship between history of inflammatory bowel disease and risk of thyroid cancer. METHODS: First, 1392 patients with inflammatory bowel disease and 1392 controls were included in a case-control study. All patients did not receive immunosuppressive therapy. A multivariate logistic regression analysis was adopted to determine the relationship between history of inflammatory bowel disease and risk of thyroid cancer. Second, a literature search was performed and eight articles were collected. Pooled odds ratios with 95% confidence intervals were reported for relevant risk estimates in fixed or random effect model. RESULTS: In the case-control study, thyroid cancer was more common in patients with inflammatory bowel disease than in controls (P = 0.032). After Bonferroni correction, association of thyroid cancer risk with history of total inflammatory bowel disease or its two subtypes was not found. In the meta-analysis, patients with total inflammatory bowel disease or ulcerative colitis showed an increased risk of thyroid cancer, but patients with Crohn's disease did not. Furthermore, inflammatory bowel disease patients with immunosuppressive therapy showed an increased risk of the cancer, but patients without immunosuppressive therapy did not have this finding. CONCLUSIONS: Risk of thyroid cancer probably elevates in patients with inflammatory bowel disease. Inflammatory bowel disease (particularly ulcerative colitis) itself and use of immunosuppressant might contribute to the development of the cancer.

Eosinophilia in a patient with aggressive systemic mastocytosis harboring a KIT D816V mutation: A case report.

Eosinophilia may result from three main causes: secondary (reactive), primary (clonal), and/or idiopathic. The diagnosis of idiopathic eosinophilia must be made based on excluding all reactive or clonal causes. However, some causes may be very rare so as to be misdiagnosed as idiopathic. We present the case of eosinophilia caused by aggressive systemic mastocytosis, originally recognized as idiopathic. Lymphadenopathy, dysmyelopoiesis, and hepatosplenomegaly gradually appeared and deteriorated with increasing eosinophils. This case carried KIT D816V mutation. The BCR::ABL fusion gene and the mutations in JAK2 V617F, PDGFRα, and PDGFRß in bone marrow were all negative. PHF6, PPM1D, and TET2 mutations were demonstrable. The patient was prescribed to avapritinib. The condition was effectively controlled. However, the patient discontinued medication for economic reasons 5 months later. Disease progression happened and died 10 months after diagnosis. Our study indicates that gene mutation detection at diagnosis is helpful for patient accurate diagnosis and targeted therapy of such patients.

Case Report: Pathogenesis With a Rare RHOA A161E Mutation in a Patient With Angioimmunoblastic T-Cell Lymphoma.

Angioimmunoblastic T-cell lymphoma (AITL) genomic abnormalities are highly disease-specific, and the ras homology family member A (RHOA) gene is one of the most recurrent mutated genes, especially for RHOA G17V mutation site. Here, we identified a rare RHOA A161E mutation in an AITL patient through gene sequencing platforms. The patient presented with persistent hypereosinophilia, asymptomatic or symptomatic mildly for over 3 years. At diagnosis, this patient manifested night sweats, weight loss, multiple lymphadenopathies, and enlargement of the liver and spleen. We performed a retrospective genetic mutation analysis by whole-exome sequencing (WES) and droplet digital PCR (ddPCR) on serial gastric, intestinal, and lymph node specimens. The genetic mutation testing result demonstrated that a rare RHOA A161E mutation was found, which was elevated significantly on diagnosis related to AITL pathogenesis. Our case confirms that genetic mutation testing is helpful for diagnostic classification in AITL and dynamic monitoring of gene mutations at multiple time points may facilitate early detection of disease diagnosis.

Disruption of REC8 in Meiosis I led to watermelon seedless.

In triploid watermelon (Citrullus lanatus), the homologous chromosomes of germ cells are disorder during meiosis, resulting in the failure of seeds formation and producing seedless fruit. Therefore, mutating the genes specifically functioning in meiosis may be an alternative way to achieve seedless watermelon. REC8, as a key component of the cohesin complex in meiosis, is dramatically essential for sister chromatid cohesion and chromosome segregation. However, the role of REC8 in meiosis has not yet been characterized in watermelon. Here, we identified ClREC8 as a member of RAD21/REC8 family with a high expression in male and female flowers of watermelon. In situ hybridization analysis showed that ClREC8 was highly expressed at the early stage of meiosis during pollen formation. Knocking out ClREC8 in watermelon led to decline of pollen vitality. After pollinating with foreign normal pollen, the ovaries of ClREC8 knockout lines could inflate normally but failed to form seeds. We further compared the meiosis chromosomes of pollen mother cells in different stages between the knockout lines and the corresponding wild type. The results indicated that ClREC8 was required for the monopolar orientation of the sister kinetochores in Meiosis I. Additionally, transcriptome sequencing (RNA-seq) analysis between WT and the knockout lines revealed that the disruption of ClREC8 caused the expression levels of mitosis-related genes and meiosis-related genes to decrease. Our results demonstrated ClREC8 has a specific role in Meiosis I of watermelon germ cells, and loss-of-function of the ClREC8 led to seedless fruit, which may provide an alternative strategy to breed cultivars with seedless watermelon.

A Novel Prognostic Scoring Model for Myelodysplastic Syndrome Patients With SF3B1 Mutation.

The outcomes of myelodysplastic syndrome (MDS) patients with SF3B1 mutation, despite identified as a favorable prognostic biomarker, are variable. To comprehend the heterogeneity in clinical characteristics and outcomes, we reviewed 140 MDS patients with SF3B1 mutation in Zhejiang province of China. Seventy-three (52.1%) patients diagnosed as MDS with ring sideroblasts (MDS-RS) following the 2016 World Health Organization (WHO) classification and 118 (84.3%) patients belonged to lower risk following the revised International Prognostic Scoring System (IPSS-R). Although clonal hematopoiesis-associated mutations containing TET2, ASXL1 and DNMT3A were the most frequent co-mutant genes in these patients, RUNX1, EZH2, NF1 and KRAS/NRAS mutations had significant effects on overall survival (OS). Based on that we developed a risk scoring model as IPSS-R×0.4+RUNX1×1.1+EZH2×0.6+RAS×0.9+NF1×1.6. Patients were categorized into two subgroups: low-risk (L-R, score <= 1.4) group and high risk (H-R, score > 1.4) group. The 3-year OS for the L-R and H-R groups was 91.88% (95% CI, 83.27%-100%) and 38.14% (95% CI, 24.08%-60.40%), respectively (P<0.001). This proposed model distinctly outperformed the widely used IPSS-R. In summary, we constructed and validated a personalized prediction model of MDS patients with SF3B1 mutation that can better predict the survival of these patients.

A Simplified Plasticity Model Based on Synaptic Tagging and Capture Theory: Simplified STC.

The formation and consolidation of memory play a vital role for survival in an ever-changing environment. In the brain, the change and stabilization of potentiated and depressed synapses are the neural basis of memory formation and maintenance. These changes can be induced by rather short stimuli (only a few seconds or even less) but should then be stable for months or years. Recently, the neural mechanism of conversion from rapid change during the early phase of synaptic plasticity into a stable memory trace in the late phase of synaptic plasticity is more and more clear at the protein and molecular levels, among which synaptic tagging and capture (STC) theory is one of the most popular theories. According to the STC theory, the change and stabilization of synaptic efficiency mainly depend on three processes related to calcium concentration, including synaptic tagging, synthesis of plasticity-related product (PRP), and the capture of PRP by tagged synapse. Based on the STC theory, several computational models are proposed. However, these models hardly take simplicity and biological interpretability into account simultaneously. Here, we propose a simplified STC (SM-STC) model to address this issue. In the SM-STC model, the concentration of calcium ion in each neuronal compartment and synapse is first calculated, and then the tag state of synapse and PRP are updated, and the coupling effect of tagged synapse and PRP is further considered to determine the plasticity state of the synapse, either potentiation or depression. We simulated the Schaffer collaterals pathway of the hippocampus targeting a multicompartment CA1 neuron for several hours of biological time. The results show that the SM-STC model can produce a broad range of experimental phenomena known in the physiological experiments, including long-term potentiation induced by high-frequency stimuli, long-term depression induced by low-frequency stimuli, and cross-capture with two stimuli separated by a delay. Thus, the SM-STC model proposed in this study provides an effective learning rule for brain-like computation on the premise of ensuring biological plausibility and computational efficiency.

Predicting Spike Features of Hodgkin-Huxley-Type Neurons With Simple Artificial Neural Network.

Hodgkin-Huxley (HH)-type model is the most famous computational model for simulating neural activity. It shows the highest accuracy in capturing neuronal spikes, and its model parameters have definite physiological meanings. However, HH-type models are computationally expensive. To address this problem, a previous study proposed a spike prediction module (SPM) to predict whether a spike will take place 1 ms later based on three voltage values with intervals of 1 ms. Although SPM does well, it fails to evaluate the informative features of the spike. In this study, the feature prediction module (FPM) based on simple artificial neural network (ANN) was proposed to predict spike features including maximum voltage, minimum voltage, and dropping interval. Nine different HH-type models were adopted whose firing patterns cover most of the firing behaviors observed in the brain. Voltage and spike feature samples under constant external input current were collected for training and testing. Experiment results illustrated that the combination of SPM and FPM can accurately predict the spiking part of different HH-type models and can generalize to unseen types of input current. The combination of SPM and FPM may offer a possible way to simulate the action potentials of biological neurons with high accuracy and efficiency.

Early Death and Survival of Patients With Acute Promyelocytic Leukemia in ATRA Plus Arsenic Era: A Population-Based Study.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

CAG regimen for refractory or relapsed adult T-cell acute lymphoblastic leukemia: A retrospective, multicenter, cohort study.

Adult patients with relapsed or refractory T-cell acute lymphoblastic leukemia (R/R-T-ALL) have extremely poor prognosis, representing an urgent unmet medical need. Finding an optimal salvage regimen to bridge transplantation is a priority. The CAG (cytarabine, aclarubicin, and G-CSF) regimen was initially used by one group in China, showing unexpectedly promising results in 11 R/R-T-ALL patients. Here, we report the multicenter results of 41 patients who received the CAG regimen as salvage therapy. After one cycle of the CAG regimen, complete remission and partial remission were achieved in 33 (80.5%) and two (4.9%) patients, respectively. Failure to respond was observed in six patients (14.6%). Early T-cell precursor (ETP) (n = 26) and non-ETP (n = 15) patients had a similar CR rate (80.8% vs 80.0%, P = .95). Among 41 patients, allo-HSCT was successfully performed in 27 (66%) patients (22 in CR and 5 in non-CR). With a median follow-up time of 12 months, the estimated 2-year overall survival and event-free survival were 68.8% (95% CI, 47.3%-83.0%) and 56.5% (95% CI, 37.1%-71.9%), respectively. The CAG regimen was well-tolerated, and no early death occurred. Our multicenter results show that the CAG regimen is highly effective and safe, representing a novel choice for adult patients with R/R-T-ALL and providing a better bridge to transplantation.

Expression of hypoxia-inducible factor-1a predicts benefit from rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in diffuse large B-cell lymphoma.

Hypoxia-inducible factor-1α (HIF-1α) has been identified as an unfavorable prognostic factor in most solid tumors. However, HIF-1α was suggested to predict improved survival in Western patients with diffuse large B-cell lymphoma (DLBCL) under rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment. We studied HIF-1α protein expression by immunohistochemical staining of 155 paraffin-embedded specimens from Chinese patients with DLBCL treated with R-CHOP or CHOP. Results were correlated with patient outcome. HIF-1α expression had no impact on survival for the patients treated with CHOP. In the R-CHOP-treated group, however, HIF-1α expression was significantly correlated with superior OS and EFS (P = 0.048 and 0.040, respectively). Moreover, HIF-1α expression maintained independent prognostic value for OS (RR, 0.41; 95% CI, 0.19-0.92; P = 0.030) and EFS (RR, 0.53; 95% CI, 0.31-0.90; P = 0.020) when it was adjusted by IPI stratification. Therefore, HIF-1α expression benefits from R-CHOP in DLBCL.

Modulation of neuronal dynamic range using two different adaptation mechanisms.

The capability of neurons to discriminate between intensity of external stimulus is measured by its dynamic range. A larger dynamic range indicates a greater probability of neuronal survival. In this study, the potential roles of adaptation mechanisms (ion currents) in modulating neuronal dynamic range were numerically investigated. Based on the adaptive exponential integrate-and-fire model, which includes two different adaptation mechanisms, i.e. subthreshold and suprathreshold (spike-triggered) adaptation, our results reveal that the two adaptation mechanisms exhibit rather different roles in regulating neuronal dynamic range. Specifically, subthreshold adaptation acts as a negative factor that observably decreases the neuronal dynamic range, while suprathreshold adaptation has little influence on the neuronal dynamic range. Moreover, when stochastic noise was introduced into the adaptation mechanisms, the dynamic range was apparently enhanced, regardless of what state the neuron was in, e.g. adaptive or non-adaptive. Our model results suggested that the neuronal dynamic range can be differentially modulated by different adaptation mechanisms. Additionally, noise was a non-ignorable factor, which could effectively modulate the neuronal dynamic range.

Can the upper inner side of the thigh become a new option for insulin injection?

OBJECTIVE: Sites for subcutaneous insulin injections include the upper arms, abdomen, buttocks and outer sides of the thigh. No similar study has explored the feasibility of using the inner side of the thigh for insulin injection, since the 4 mm pen needles were introduced for clinical use. This study aimed to determine whether the inner side of the thigh is suitable for insulin injection. RESEARCH DESIGN AND METHODS: Seventy-five patients with diabetes under insulin therapy from the Inpatient Department of Endocrinology were recruited for this non-blinded, non-randomized observational study. Subcutaneous adipose layer thicknesses of the upper, middle and lower area of the inner and outer thighs of 35 patients were measured by ultrasound, distance from the skin surface to the femoral deep vessels in 20 patients was measured, and insulin was injected at the upper inner and outer sides of the thigh in 20 patients. Pain perception, bleeding or bruising, leakage at the injection sites, blood glucose changes after insulin injection, and preferred ratings of the patients were measured. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02307968. RESULTS: Subcutaneous adipose layer thicknesses at both the upper inner and outer thighs were more than 4 mm and the minimum distance was 10 mm. Among the 100 injections at the upper inner thigh, only three incidents of perceived pain occurred. No bleeding or bruising and leakage were observed from the inner or outer sides. Furthermore, the difference in blood glucose control between insulin injections at the inner side and outer sides was not statistically significant. Patient ratings for injections at the inner side were similar to injections at the outer side. The key limitation of this study was the small sample size of adult patients as well as the non-randomized controlled design of this study. CONCLUSION: The upper inner thigh might be a new option for insulin injection rotation.

Systemic lupus erythematous and malignancy risk: a meta-analysis.

BACKGROUND: Pilot studies have estimated cancer incidence in patients with systemic lupus erythematous (SLE). However, the results have been inconclusive. To ascertain the correlation between SLE and malignancy more comprehensively and precisely, we conducted a meta-analysis. METHODS: PubMed, the Cochrane Library and Embase databases through June 2014, were searched to identify observational studies evaluating the association between SLE and malignancy. The outcomes from these studies were measured as relative risks (RRs). A random or fixed effects model was chosen to calculate the pooled RR according to heterogeneity test. Between-study heterogeneity was assessed by estimating I2 index. Publication bias was assessed by Egger's test. RESULTS: A total of 16 papers, including 59,662 SLE patients, were suitable for the meta-analysis. Of these papers, 15 reported RRs for overall malignancy, 12 for non-Hodgkin lymphoma (NHL) and lung cancer, 7 for bladder cancer, 6 for Hodgkin lymphoma (HL) and leukemia, 5 for skin melanoma, and liver and thyroid cancers, 4 for multiple myeloma (MM), and esophageal and vaginal/vulvar cancers and 3 for laryngeal and non-melanoma skin cancers. The pooled RRs were 1.28 (95% CI, 1.17-1.41) for overall cancer, 5.40 (95% CI, 3.75-7.77) for NHL, 3.26(95% CI, 2.17-4.88) for HL, 2.01(95% CI, 1.61-2.52) for leukemia, 1.45(95% CI, 1.04-2.03) for MM, 4.19(95% CI, 1.98-8.87) for laryngeal cancer, 1.59 (95% CI, 1.44-1.76) for lung cancer, 1.86(95% CI, 1.21-2.88) for esophageal cancer, 3.21(95% CI, 1.70-6.05) for liver cancer, 3.67(95% CI, 2.80-4.81) for vaginal/vulvar cancer, 2.11(95% CI, 1.12-3.99) for bladder cancer, 1.51(95% CI, 1.12-2.03) for non-melanoma skin cancer, 1.78(95% CI, 1.35-2.33) for thyroid cancer, and 0.65(95% CI, 0.50-0.85) for skin melanoma. Only the meta-analyses of overall malignancy, NHL, and liver and bladder cancers produced substantial heterogeneity (I2, 57.6% vs 74.3% vs 67.7% vs 82.3%). No apparent publication bias was detected except for NHL studies. CONCLUSIONS: Our data support an association between SLE and malignancy, not only demonstrating an increased risk for NHL, HL, leukemia, and some non-hematologic malignancies, including laryngeal, lung, liver, vaginal/vulvar, and thyroid malignancies, but also a reduced risk for skin melanoma. Although an increased risk of MM, and esophageal, bladder and non-melanoma skin cancers was identified from the accumulated data in these studies, this observation requires confirmation.

The risk of hepatitis B virus reactivation and the role of antiviral prophylaxis in hepatitis B surface antigen negative/hepatitis B core antibody positive patients with diffuse large B-cell lymphoma receiving rituximab-based chemotherapy.

The risk factors and the role of prophylactic antiviral therapy of hepatitis B virus (HBV) reactivation in patients with hepatitis B surface antigen (HBsAg) negative/hepatitis B core antibody (HBcAb) positive disease remain controversial. We reviewed 629 patients with diffuse large B-cell lymphoma (DLBCL). Among 629 patients, 150 of 246 patients with resolved HBV (HBsAg negative and HBcAb positive) were treated with rituximab-combined therapy. Among these 150 patients, none of 104 patients (0.0%) who were hepatitis B surface antibody (HBsAb) positive experienced HBV reactivation versus four of 46 patients (8.7%) who were HBsAb negative (p = 0.008). One of 113 patients (0.9%) with International Prognostic Index (IPI) 0-2 suffered HBV reactivation versus three of the remaining 37 patients (8.1%) with IPI 3-5 (p = 0.047). HBsAb and IPI are potential risk factors for HBV reactivation. The use of prophylactic agents may not be recommended for these patients until the occurrence of HBV reactivation.

[Expression and activity of membrane surface tissue factor in peripheral blood cells of patients with cerebral infarction].

This study was aimed to investigate the expression and activity of membrane surface tissue factor (TF) of monocytes and platelets in peripheral blood cells from patients with cerebral infarction and their clinical significance. The TF expressions in monocytes and platelets from 25 patients with cerebral infarction were detected by flow cytometry, the TF activity was detected by chromogenic reaction method, and compared with 24 normal people used as control. The results showed that the TF expressions of monocytes and platelets in peripheral blood cells from patients with cerebral infarction were significantly higher than that in normal controls (p<0.01), and TF activity was also higher in patients than that in controls (p<0.01). In conclusion, the expression and activity of membrane surface in patients with cerebral infarction were enhanced, the hematocyte-derived tissue factor as a trigger in coagulation pathway is involved in pathological thrombosis in patients with cerebral infarction.