Activated interferon response from DNA damage in multiple myeloma cells contributes to the chemotherapeutic effects of anthracyclines.

Introduction: Multiple myeloma (MM) is a malignant plasma cell disease caused by abnormal proliferation of clonal plasma cells in bone marrow. Upfront identification of tumor subgroups with specific biological markers has the potential to improve biologically-driven therapy. Previously, we established a molecular classification by stratifying multiple myeloma into two subtypes with a different prognosis based on a gene module co-expressed with MCL-1 (MCL1-M). Methods: Gene Ontology (GO) analysis with differentially expressed genes was performed to identify signal pathway. Drug sensitivity was analyzed using the OncoPredict algorithm. Drug sensitivity of different myeloma cell lines was detected by CCK8 and flow cytometry. RNA-seq was performed on drug-sensitive cell lines before and after adriamycin treatment. RT-qPCR was used to further verify the sequencing results. The expression of γ-H2AX and dsDNA in sensitive and resistant cell lines was detected by immunofluorescence method. Results: In our study, we demonstrated that MCL1-M low MM were more sensitive to anthracyclines. We treated different myeloma cell lines with doxorubicin in vitro and discovered the association of drug sensitivity with IFN signaling. Herein, we demonstrate that the doxorubicin-sensitive myeloma cell line showed significant DNA damage and up-regulated expression of genes related to the IFN response, which was not observed in drug-insensitive cell lines. Discussion: Our results suggest that the active IFN signaling pathway may serve as a marker for predicting chemotherapy sensitivity in patients with myeloma. With our MCL1-M molecular classification system, we can screen patients with a potentially good response to the interferon signaling pathway and provide individualized treatment for MM. We propose IFN-a as adjuvant therapy for patients with myeloma sensitive to anthracyclines to further improve the therapeutic effect and prolong the survival of patients.

An investigation of idiom processing advantage using translated familiar idioms.

The facilitatory effect shown in native speakers processing idiomatic phrases compared to matched novel phrases may be explained by a dual route model. This postulates that all phrases are processed literally at first, and if a phrase was recognized as familiar during processing, it would then be processed by a faster retrieval-route; if the phrase was not perceived as familiar, it would continue to be processed literally by the slower computation-route. The goals of the current project were to test the dual route model and to decipher the underlying mechanism in retrieval-route activation. English idioms and translated Chinese idioms were presented to both native English speakers and Chinese-English bilinguals in a random order. Participants listened to the idiom up until the last word (e.g., "draw a snake and add"), then saw either the idiom ending (e.g., "feet") or the matched control ending (e.g., "hair"); to which they made lexical decision and reaction times were recorded. We examined the priming effect for idioms compared to controls across the two language groups. The results showed that the two groups processed idioms of different origins differently. Native English speakers' faster responses to English idioms than controls supported a dual route model; however, both native English and bilingual speakers' faster responses to Chinese idioms than controls called for a less straightforward interpretation. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Quantitative Evaluation of Rotator Cuff Tears Based on Non-linear Statistical Analysis of Ultrasound Radiofrequency Signals.

There is increasing clinical requirement for early and accurate ultrasound diagnosis of rotator cuff tears (RCTs). A method based on non-linear statistical analysis was proposed for the detection of RCTs using ultrasound radiofrequency (RF) signals. One hundred fifty-two patients with shoulder pain were first examined with ultrasound and then diagnosed with magnetic resonance imaging (MRI) as the ground truth. By comparison of the region of interest (ROI) with a part of the supraspinatus with no pathologic change part in the same RF signal frame, the relative Pks value (viz., rPks value) was evaluated to quantify the pathophysiologic changes. The results indicated that the rPks values of all RCTs are <0.7, and the accuracy, sensitivity and specificity of the proposed method can reach 97.5%, 100% and 91.4%, respectively. This computer-aided method was found to perform better diagnostic than the results reported by an experienced radiologist (accuracy = 75.7%, sensitivity = 72.6%, and specificity = 85.7%). The high sensitivity advantage of this method indicates that the prospects for its application in the computer-aided diagnosis of RCTs are good.

Magnetic resonance imaging findings of carcinoma arising from anal fistula: A retrospective study in a single institution.

BACKGROUND: Magnetic resonance imaging (MRI) is currently the standard investigation for suspected perianal diseases. Carcinoma arising from anal fistula is very rare, and early diagnosis is often difficult. AIM: To describe and summarize the MRI findings of carcinoma arising from anal fistula. METHODS: In this retrospective study, records of ten patients diagnosed with carcinoma arising from anal fistula and confirmed by surgery (n = 7) or biopsy (n = 3) between June 2006 and August 2018 were analyzed. All patients underwent preoperative pelvic MRI. Morphologic features, signal characteristics, fistula between the mass and the anus, contrast enhancement of mass, signal and enhancement of peritumoral areas, and regional lymphadenopathy were assessed. RESULTS: All ten tumors were solitary (8 mucinous adenocarcinomas and 2 adenocarcinomas). The maximum diameter of the tumors ranged from 3.4 cm to 12.4 cm (median: 4.15 cm; mean: 5.68 cm). Eight patients had a fistula between the mass and the anus. Contrast enhancement of the peritumoral areas was noted in three (3/5) patients. Perirectal or inguinal lymphadenopathy was noted in seven patients. Most lesions of mucinous adenocarcinoma were multiloculated and cauliflower-like, with a thin capsule and focally unclear boundary. They were markedly hyperintense on fat-suppressed T2WI, slightly hyperintense with focal hyperintensity on diffusion-weighted imaging (DWI), and hyperintense with focal hypointensity on apparent diffusion coefficient (ADC) map, with progressive mesh-like contrast enhancement. Adenocarcinomas had an infiltrative margin without a capsule and appeared heterogeneously hyperintense or slightly hyperintense on fat-suppressed T2WI, hyperintense on DWI, and hypointense on ADC map, with persistent heterogeneous enhancement. CONCLUSION: Our study highlighted several characteristic and potentially helpful MRI findings to diagnose carcinomas arising from anal fistula.

Cognitive changes in conjunctive rule-based category learning: An ERP approach.

When learning rule-based categories, sufficient cognitive resources are needed to test hypotheses, maintain the currently active rule in working memory, update rules after feedback, and to select a new rule if necessary. Prior research has demonstrated that conjunctive rules are more complex than unidimensional rules and place greater demands on executive functions like working memory. In our study, event-related potentials (ERPs) were recorded while participants performed a conjunctive rule-based category learning task with trial-by-trial feedback. In line with prior research, correct categorization responses resulted in a larger stimulus-locked late positive complex compared to incorrect responses, possibly indexing the updating of rule information in memory. Incorrect trials elicited a pronounced feedback-locked P300 elicited which suggested a disconnect between perception, and the rule-based strategy. We also examined the differential processing of stimuli that were able to be correctly classified by the suboptimal single-dimensional rule ("easy" stimuli) versus those that could only be correctly classified by the optimal, conjunctive rule ("difficult" stimuli). Among strong learners, a larger, late positive slow wave emerged for difficult compared with easy stimuli, suggesting differential processing of category items even though strong learners performed well on the conjunctive category set. Overall, the findings suggest that ERP combined with computational modelling can be used to better understand the cognitive processes involved in rule-based category learning.

Modeling the melting temperature of nanoscaled bimetallic alloys.

The effect of size, composition and dimension on the melting temperature of nanoscaled bimetallic alloys was investigated by considering the interatomic interaction. The established thermodynamics model without any arbitrarily adjustable parameters can be used to predict the melting temperature of nanoscaled bimetallic alloys. It is found that, the melting temperature and interatomic interaction of nanoscaled bimetallic alloys decrease with the decrease in size and the increasing composition of the lower surface energy metal. Moreover, for the nanoscaled bimetallic alloys with the same size and composition, the dependence of the melting temperature on the dimension can be sequenced as follows: nanoparticles > nanowires > thin films. The accuracy of the developed model is verified by the recent experimental and computer simulation results.