Differential diagnosis of Crohn's disease and intestinal tuberculosis: development and assessment of a nomogram prediction model.

BACKGROUND: China is a region with a high incidence of tuberculosis, and the incidence of IBD has also been rising rapidly in recent years. Differentiating Crohn's disease(CD) from intestinal tuberculosis (ITB) has become a very challenging issue. We aimed to develop and assess a diagnostic nomogram to differentiate between CD and ITB to improve the accuracy and practicability of the model. METHODS: A total of 133 patients (CD 90 and ITB 43) were analyzed retrospectively. Univariate and multivariate logistic regression analysis was included to determine the independent predictive factors and establish the regression equation. On this basis, the nomogram prediction model was constructed. The discrimination, calibration and clinical efficiency of the nomogram were assessed using area under the curve(AUC), C-index, calibration curve, decision curve analysis (DCA) and clinical impact curve. RESULTS: T-SPOT positive, cobblestone appearance, comb sign and granuloma were significant predictors in differentiating CD from ITB. Base on the above independent predictors, a diagnostic nomogram was successfully established. The sensitivity, specificity, accuracy of the prediction model are 94.4%, 93.0%, 94.0% respectively. The AUC and the C-index of the prediction model are both 0.988, which suggest that the model had a good discrimination power. The calibration curve indicated a high calibration degree of the prediction model. The DCA and clinical impact curve indicated a good clinical efficiency of the prediction model which could bring clinical benefits. CONCLUSION: A nomogram prediction model for distinguishing CD from ITB was developed and assessed, with high discrimination, calibration and clinical efficiency. It can be used as an accurate and convenient diagnostic tool to distinguish CD from ITB, facilitating clinical decision-making.

Examining Humans' Problem-Solving Styles in Technology-Rich Environments Using Log File Data.

This study investigated how one's problem-solving style impacts his/her problem-solving performance in technology-rich environments. Drawing upon experiential learning theory, we extracted two behavioral indicators (i.e., planning duration for problem solving and human-computer interaction frequency) to model problem-solving styles in technology-rich environments. We employed an existing data set in which 7516 participants responded to 14 technology-based tasks of the Programme for the International Assessment of Adult Competencies (PIAAC) 2012. Clustering analyses revealed three problem-solving styles: Acting indicates a preference for active explorations; Reflecting represents a tendency to observe; and Shirking shows an inclination toward scarce tryouts and few observations. Explanatory item response modeling analyses disclosed that individuals with the Acting style outperformed those with the Reflecting or the Shirking style, and this superiority persisted across tasks with different difficulties.

Advancing automatic guidance in virtual science inquiry: from ease of use to personalization.

This article is in response to the review entitled "Identifying potential types of guidance for supporting student inquiry when using virtual and remote labs in science: a literature review" (Zacharia et al. in Educ Technol Res Dev 63(2): 257-302). As COVID-19 alerts us to shift science education to digital when in-person schooling is not viable, one approach to facilitate this shift, as reviewed by Zacharia et al. (2015), is to involve students in computer supported inquiry learning (CoSIL) with appropriate guidance. As CoSIL guidance is critical to student success in CoSIL, Zacharia et al. (2015) contribute to our knowledge by systematically reviewing the forms and the efficacy of such guidance tools that are associated with each phase of scientific inquiry. With such knowledge we may develop decent guidance so that students can experience scientific inquiry virtually as they used to do in-person. Zacharia et al. (2015) indicated that the various guidance tools had increased the ease of use of CoSIL but failed in personalizing CoSIL to individual students. I agree with Zacharia et al. that the personalization of CoSIL guidance is vital. Further, I argue that the emergent machine learning may significantly increase the personalization of CoSIL without burdening teachers. I conclude the essay with suggestions to further investigate the cognitive needs of students in CoSIL and integrate the content, CoSIL, and guidance tools, as a way to move forward the personalization of CoSIL.

LINC01585 functions as a regulator of gene expression by the CAMP/CREB signaling pathway in breast cancer.

OBJECTIVE: Breast cancer is the leading cause of cancer death among women. Nowadays, long non-coding RNAs (lncRNAs) have been identified and emerged as critical bio-markers in breast cancer tumorigenesis and progression. However, only a handful of lncRNAs which are implicated in BC have been characterized. The underlying molecular mechanisms are still largely unknown. METHODS: In this study, we explored 12 nominated lncRNAs at breast cancer susceptibility loci identified by genome-wide association studies to contribute to the risk and effects of breast cancer. We then analyzed these lncRNAs in a total of 132 pairs of breast cancer tissues and surrounding non-tumor tissues from southern China population. RESULTS: Here, we report a novel lncRNA, LINC01585, is aberrantly down regulated during breast cancer (BC). Next, to explore the molecular mechanisms underlying the biological activity of LINC01585, we identified LINC01585 binding protein by RNA pull-down experiments. Functionally, we found that LINC01585 overexpression inhibited breast cancer proliferation and growth by prototypical experiments. Mechanistically, LINC01585 was located in nuclear and binding with NONO protein. Interestingly, when LINC01585 was down-expressed, NONO separated from LINC01585 and then interacted with CRTC. The complex promotes CAMP/CREB target gene transcription and thus promotes the growth of breast cancer. CONCLUSIONS: A series of discoveries suggest to us that LINC01585 has a potential value in anti-carcinoma therapy and deserves further investigation.

Prognostic Value of Serum Lactate Dehydrogenase in Patients with Nasopharyngeal Carcinoma: a Meta-Analysis.

BACKGROUND: Serum-lactate dehydrogenase (S-LDH) is reported to be associated with poor survival in patients with nasopharyngeal carcinoma (NPC); however, the results are inconsistent. The aim of the study was to perform a meta-analysis to evaluate the prognostic value of S-LDH in patients with NPC. METHODS: PubMed and Web of Science were searched for relevant studies, and the fixed-effects model was employed to pool the hazard risks (HRs) from individual studies when no substantial heterogeneity was detected; otherwise, the random-effects model was used. Heterogeneity and publication bias were also analyzed. RESULTS: A total of 18 studies involving 13,789 patients were included in the meta-analysis, serum LDH level was associated with worse outcome in NPC patients. The combined HR for overall survival (OS) was 1.86 (95% confidence interval [CI]: 1.66 - 2.08; p < 0.01), and the pooled HRs for disease-free survival (DFS), distant metastasisfree survival (DMFS), and distant local relapse-free survival (LRFS) were 1.64 (95% CI: 1.45 - 1.86), 2.64 (95% CI: 2.15 - 3.25), and 2.59 (95% CI: 1.74 - 3.87), respectively. CONCLUSIONS: Our results suggest that higher serum LDH level is associated with worse survival in patients with NPC, which is helpful for a personalized treatment strategy for NPC patients.

Significance of XRCC1 Codon399 polymorphisms in Chinese patients with locally advanced nasopharyngeal carcinoma treated with radiation therapy.

AIM: Little is known about the relationship between XRCC1 Codon399 polymorphisms and radiotherapy (RT) outcomes in patients with nasopharyngeal carcinoma (NPC). We aimed to investigate whether XRCC1 Codon399 polymorphisms were correlated to treatment efficacy and normal tissue toxicity in Chinese patients with locally advanced NPC after RT. METHODS: Sixty eligible patients with NPC stage III-IVa were recruited. Patients received definitive RT, 66-76 Gy. One cycle neoadjuvant chemotherapy with docetaxel and cisplatin regimen was used before RT, two or three cycles for concurrent chemo-RT followed by two to four cycles adjuvant chemotherapy with the same regimen. Before the treatment, XRCC1 Codon399 polymorphisms were determined by polymerase chain reaction based ligase detection reaction methods. RESULTS: Six of 60 NPC patients were homozygous for XRCC1 Codon399 Gln/Gln and 35% were heterozygous. The expressions of genotypes were unrelated to gender, age, clinical stage, T stage or N stage. Codon399 Gln/Gln allele correlated with a higher medium-term tumor regression ratio after RT for primary nasopharyngeal neoplasm and metastatic lymph nodes (>80% vs 40-60%, P < 0.01). Compared with other two genotypes, patients with XRCC1 Codon399 Gln/Gln allele were more likely to obtain complete remission of tumor (100% vs 76 and 67%, P > 0.05). No correlation between XRCC1 Codon399 polymorphisms and acute or late radiation-induced injury of normal tissues was observed. CONCLUSIONS: The XRCC1 Codon399 Gln/Gln allele may be associated with better tumor regression, and is suggested as a promising predictive factor for outcome for locally advanced NPC. Further study with larger samples and long-time follow-up is needed for accurate assessment.

Prognostic value of phospho-Akt in patients with non-small cell lung carcinoma: a meta-analysis.

Previous studies have been inconsistent with respect to the reported associations between phospho-Akt (p-Akt) overexpression and lung cancer prognosis. In this study, we conducted a systematic review and meta-analysis to assess the prognostic value of p-Akt in patients with non-small cell lung carcinoma (NSCLC). Relevant articles were identified by searching MEDLINE. Hazard risks (HRs) from individual studies were calculated and pooled by using a random-effect model, and heterogeneity and publication bias analyses were also performed. Finally, 18 studies comprising 2,353 patients were included in the meta-analysis. p-Akt overexpression was associated with worse survival in NSCLC patients, and the pooled HRs for all the studies was 1.38 (95% confidence interval [CI]: 1.11-1.70; p<0.01). After subgroup analysis, the association was strengthened in the surgery treatment group, with an HR of 1.44 (95% CI: 1.19-1.75; p<0.01), while in the tyrosine kinase inhibitors treatment group, the statistical significance disappeared (HR: 1.22, 95% CI: 0.70-2.14; p=0.48). The HR in cases of early stage disease (I-III) was 1.35 (95% CI: 1.08-1.69; p=0.04); however, in cases of late stage disease (III-IV), the association became non-significant (HR: 1.22, 95% CI: 0.64-2.33; p=0.54). Our results suggest that there was a significantly inverse association between p-Akt overexpression and the prognosis of NSCLC patients, and that this association appeared to be limited in early-stage patients who underwent surgery.

Inhibition of LDH-A by oxamate induces G2/M arrest, apoptosis and increases radiosensitivity in nasopharyngeal carcinoma cells.

An elevated rate of glucose consumption and the dependency on aerobic glycolysis for ATP generation have long been observed in cancer cells, a phenomenon known as the Warburg effect. the altered energy metabolism in cancer cells provides an attractive opportunity for developing novel cancer therapeutic strategies. Lactate dehydrogenase (LDH), which catalyzes the transformation of pyruvate to lactate, plays a vital role in the process of glycolysis. It has been reported that the level of LDH-A expression is increased both in head and neck cancer cells and in the blood serum of nasopharyngeal carcinoma (NPC) patients, and is associated with poor prognosis. However, the effect of LDH-A inhibition on NPC cells remains unknown. Here, in the present study, we found that oxamate, a classical inhibitor of LDH-A, suppressed cell proliferation in a dose- and time-dependent manner both in CNE-1 and CNE-2 cells, two NPC cancer cell lines. LDH inhibition by oxamate induced G2/M cell cycle arrest via downregulation of the CDK1/cyclin B1 pathway and promoted apoptosis through enhancement of mitochondrial ROS generation. N-acetylcysteine, a specific scavenger of ROS, significantly blocked the growth inhibition effect induced by oxamate. We also identified that oxamate increased sensitivity to ionizing radiation in the two NPC cancer cell lines. Furthermore, we verified similar results in tumor xenograft models. collectively, these results suggest that LDH-A may serve as a promising therapeutic target for NPC treatment.

[Comparison of two regimens of postoperative concurrent chemoradiotherapy in adult patients with grade III-IV cerebral gliomas].

OBJECTIVE: To compare the therapeutic efficacy of two regimens of postoperative radiotherapy with concurrent chemotherapy using temozolomide (TMZ) and teniposide (VM-26) plus semustine (Me-CCNU) in adult patients with grade III-IV cerebral gliomas. METHODS: Ninety-six adult postoperative patients with grade III-IV cerebral gliomas were randomized into two groups (n=48) to receive 60 Gy radiotherapy with concurrent TMZ treatment (TMZ-RT group) and radiotherapy with VM-26 plus Me-CCNU treatments (VM-RT group). The adverse effects of marrow depression, gastrointestinal toxicity and acute radiation-induced brain injury were observed. The immediate effect and survival outcome of the patients were compared between the two groups. RESULTS: No adverse effects beyond grade III were observed in the two groups. TMZ-RT group showed a significantly lower incidence of grade I-II adverse effects than VM-RT group (P<0.05). The median survival time and 1-, 2-, and 3-year survival rates of the patients in TMZ-RT group were 28 months, 72.9%, 54.2% and 31.3%, respectively, showing significant differences from those in VM-RT group (16 months, 62.5%, 33.3% and 16.7%, respectively, P<0.05). CONCLUSION: Radiotherapy with concurrent TMZ chemotherapy is an effective regimen with mild toxicities for treatment of adult malignant cerebral glioma.