bluuebunny/crossref_metadata_2025 huggingface dataset:
Twenty-four-hour National Institute of Health Stroke Scale predicts short- and long-term outcomes of basilar artery occlusion after endovascular treatment
Authors: Chen Jing , Liu Shuai , Wu Mingchao , Dai Ling , Wang Jie , Xie Weihua , Peng Yuqi , Mu Jinlin , Yang Shunyu , Ran Jinbo , Zhang Jian , Niu Wenshu , Zheng Jingbang , Wu Junxiong , Yuan Guangxiong
Published: October 2022

Background

The present study aimed to evaluate the prognostic value of the 24-h National Institute of Health Stroke Scale (NIHSS) for short- and long-term outcomes of patients with basilar artery occlusion (BAO) after endovascular treatment (EVT) in daily clinical routine.

Methods

Patients with EVT for acute basilar artery occlusion study registry with the 24-h NIHSS, and clinical outcomes documented at 90 days and 1 year were included. The NIHSS admission, 24-h NIHSS, NIHSS delta, and NIHSS percentage change, binary definitions of early neurological improvement [ENI; improvement of 4/(common ENI)/8 (major ENI)/10 (dramatic ENI)] NIHSS points were compared to predict the favorable outcomes and mortality at 90 days and 1 year. The primary outcome was defined as favorable if the modified Rankin Scale (mRS) score was 0–3 at 90 days.

Results

Of the 644 patients treated with EVT, the 24-h NIHSS had the highest discriminative ability for favorable outcome prediction [receiver operator characteristic (ROC)NIHSS 24 h area under the curve (AUC): 0.92 (0.90–0.94)] at 90 days and 1 year [(ROCNIHSS 24 h AUC: 0.91 (0.89–0.94)] in comparison to the NIHSS score at admission [ROCNIHSS admission AUC at 90 days: 0.73 (0.69–0.77); 1 year: 0.74 (0.70–0.78)], NIHSS delta [ROCΔ NIHSS AUC at 90 days: 0.84 (0.81–0.87); 1 year: 0.81 (0.77–0.84)], and NIHSS percentage change [ROC%change AUC at 90 days: 0.85 (0.82–0.89); 1 year: 0.82 (0.78–0.86)].

Conclusion

The 24-h NIHSS with a threshold of ≤23 points was the best surrogate for short- and long-term outcomes after EVT for BAO in the clinical routine.
Multiplex immunohistochemistry reveals cochlear macrophage heterogeneity and local auditory nerve inflammation in cisplatin-induced hearing loss
Authors: Bedeir Mai Mohamed , Ninoyu Yuzuru , Nakamura Takashi , Tsujikawa Takahiro , Hirano Shigeru
Published: October 2022

Inner ear macrophages play a vital role in cochlear homeostasis. Recent studies have demonstrated the existence of macrophages at different sites of the cochlea, with increased cochlear infiltration as an inflammatory response mechanism to injury. However, current methods, such as conventional immunohistochemistry and flow cytometry, provide limited information about the diversity of cochlear macrophages. Recently, multiplex immunohistochemistry (mIHC) successfully identified the heterogeneity of immune cells in cancer tissue and thereby improved our understanding of the disease prognosis. In this study, we modified the mIHC technique for cochlear tissue and utilized it to investigate cochlear macrophage behavior and heterogeneity before and after exposure to ototoxic drugs such as cisplatin. Four-week-old C57BL/6N female mice were intraperitoneally injected with cisplatin at 5 mg/kg/day consecutively for 6 days. Their hearing levels were assessed before and after the injection. Their cochleae were harvested before (day 0) and on days 8 and 15 after the cisplatin injection. Paraffin-embedded sections were sequentially immunostained using macrophage surface markers to identify the different categories of macrophages. Each immunostaining cycle included incubation with primary antibody, incubation with secondary antibody, chromogenic staining, and image scanning. Thereafter, all antibodies were stripped out, and antigen retrieval was performed to prepare the tissue for the next cycle. The results revealed that activated cochlear macrophages were not entirely differentiated into M1 or M2 categories but into multi-marker M1/M2 mixed macrophages. Furthermore, the ratio of these mixed (M1/M2) macrophages to Iba1+ macrophages increased in the auditory nerve after cisplatin exposure, suggesting local auditory nerve inflammation. The increase in the population of activated macrophages in the auditory nerve region was concomitant with the temporary shift of hearing threshold on day 8 post-cisplatin injection. The findings of this study indicate the effectiveness of mIHC in identifying cochlear macrophage heterogeneity both in the resting state and after cisplatin exposure. Therefore, mIHC could be a powerful tool in cochlear immunology research. Our findings may provide new insights into the co-relation between the cochlear macrophage and cisplatin exposure.
Clinically important change on the Unified Dyskinesia Rating Scale among patients with Parkinson's disease experiencing dyskinesia
Authors: Pahwa Rajesh , Fox Susan , Hauser Robert A. , Isaacson Stuart , Lytle Judy , Johnson Reed , Llorens Lily , Formella Andrea E. , Tanner Caroline M.
Published: October 2022

Background

The Unified Dyskinesia Rating Scale (UDysRS) evaluates dyskinesia in patients with Parkinson's disease (PD). A minimal clinically important change (MCIC)—the smallest change in a treatment outcome that a patient considers important—remains undefined for the UDysRS.

Objective

To utilize pivotal amantadine delayed-release/extended-release (DR/ER) trial data to derive MCICs for the UDysRS total score in patients with PD experiencing dyskinesia.

Methods

Pivotal trials included PD patients with ≥1 h daily ON time with troublesome dyskinesia and baseline scores ≥2 on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV, item 4.2. Patients randomized to amantadine DR/ER or placebo completed two consecutive 24-h diaries before each clinic visit and were evaluated during ON time with dyskinesia using the UDysRS, MDS-UPDRS, and Clinician Global Impression of Change (CGI-C). The UDysRS changes from baseline to week 12 were anchored to corresponding changes in MDS-UPDRS item 4.2 scores. A minimal clinically important improvement in the CGI-C and diary-reported ON time with troublesome dyskinesia (≥0.5 h) were supportive anchors. Receiver operating characteristic curves determined the UDysRS change values optimizing sensitivity and specificity to at least minimal improvement on each anchor.

Results

The analyses included 196 patients. Week 12 UDysRS total score reduction of ≥8 points corresponded to at least minimal MDS-UPDRS item 4.2 improvement. UDysRS reduction of ≥9 points corresponded to decreased ON time with troublesome dyskinesia of ≥0.5 h per patient diaries, and UDysRS reduction of ≥10 points corresponded to at least minimal improvement on the CGI-C.

Conclusion

Anchored to the MDS-UPDRS Part IV, item 4.2, an 8-point reduction in the UDysRS total score can be considered an MCIC for PD patients with dyskinesia.
The feasibility and accuracy of machine learning in improving safety and efficiency of thrombolysis for patients with stroke: Literature review and proposed improvements
Authors: Shao Huiling , Chen Xiangyan , Ma Qilin , Shao Zhiyu , Du Heng , Chan Lawrence Wing Chi
Published: October 2022

In the treatment of ischemic stroke, timely and efficient recanalization of occluded brain arteries can successfully salvage the ischemic brain. Thrombolysis is the first-line treatment for ischemic stroke. Machine learning models have the potential to select patients who could benefit the most from thrombolysis. In this study, we identified 29 related previous machine learning models, reviewed the models on the accuracy and feasibility, and proposed corresponding improvements. Regarding accuracy, lack of long-term outcome, treatment option consideration, and advanced radiological features were found in many previous studies in terms of model conceptualization. Regarding interpretability, most of the previous models chose restrictive models for high interpretability and did not mention processing time consideration. In the future, model conceptualization could be improved based on comprehensive neurological domain knowledge and feasibility needs to be achieved by elaborate computer science algorithms to increase the interpretability of flexible algorithms and shorten the processing time of the pipeline interpreting medical images.
The correlation of temporal changes of neutrophil-lymphocyte ratio with seizure severity and the following seizure tendency in patients with epilepsy
Authors: Li Hanli , Yang Yujing , Hu Mingwei , Cao Xiaoyan , Ding Chuhan , Sun Qibing , Li Ran , Liu Ruonan , Xu Xihai , Wang Yu
Published: October 2022

Background

Changes in the neutrophil-lymphocyte ratio (NLR) has been reported to be associated with epilepsy. Here we aim to investigate the correlation of temporal changes of NLR level with seizure severity and the follow-up seizure attacks in patients with epilepsy (PWE).

Methods

We performed a retrospective analysis of the laboratory data including leukocyte count and NLR within 24 h of acute seizure and during the follow-up period of 5–14 days after acute seizure (NLR1, NLR2, respectively) in 115 PWE, and 98 healthy individuals were included as controls in this study. The correlation of laboratory data with seizure types, etiology of epilepsy, anti-seizure drugs (ASDs), seizure severity, and the follow-up seizure attacks in PWE was studied.

Results

Leukocyte count (P < 0.001) and NLR level (P < 0.001) were found significantly different between PWE and controls. On the other hand, a multivariable logistic regression analysis showed that NLR1 level (OR = 2.992, P = 0.001) and admission leukocyte (OR = 2.307, P = 0.002) were both independently associated with acute epileptic seizures. Especially, higher NLR1 level was significantly associated with status epileptics (P = 0.013) and recurrent seizures after admission (P < 0.001). Furthermore, the multivariable logistic regression analysis indicated that higher NLR1 was a predictor for the tendency of the following recurrent seizure attacks (OR = 1.144, P = 0.002). NLR2 was inversely correlated with ASDs taken (P = 0.011). Levels of NLR1 (r = 0.441, P < 0.001) and NLR2 (r = 0.241, P = 0.009) were both positively correlated with seizure severity.

Conclusions

Seizures were correlated with the alterations of systemic inflammation reflected by leukocyte and NLR. NLR1 and admission leukocyte were both independently associated with acute epileptic seizures. Higher NLR1 was associated with status epilepticus and independently predicted the tendency of the following epileptic seizures. NLR2 was significantly associated with ASDs taken. Besides, NLR may be used as a biomarker for seizure severity.
Neurotoxic effects of different sizes of plastics (nano, micro, and macro) on juvenile common carp (Cyprinus carpio)
Authors: Hamed Mohamed , Martyniuk Christopher J. , Naguib Mervat , Lee Jae-Seong , Sayed Alaa El-Din H.
Published: October 2022

Using common carp as a model, we assessed the effects of polyethylene (PE) plastics on the brain. We measured activity of acetylcholinesterase (AChE), monoamine oxidase (MAO), and the content of nitric oxide (NO) in carp brain following exposure to 100 mg/L of either macroplastics (MaP), microplastics (MPs), or nanoplastic (NPs) for 15 days compared to an unexposed group. Following exposure, each biochemical biomarker was reduced 30–40%, with a higher magnitude of change corresponding to the smaller size of the particles (NPs > MPs > MaPs). In the carp tectum, exposure for 15 days to plastic particles caused varying degrees of necrosis, fibrosis, changes in blood capillaries, tissue detachment, edema, degenerated connective tissues, and necrosis in large cerebellar neurons and ganglion cells. In the carp retina, there was evidence for necrosis, degeneration, vacuolation, and curvature in the inner layer. Here we provide evidence that exposure to plastic particles can be associated with neurotoxicity in common carp.
Parallel schedules for MOC sweep in the neutron transport code PANDAS-MOC
Authors: Tao Shunjiang , Xu Yunlin
Published: October 2022

Method of characteristics (MOC) is a commonly applied technique for solving the Boltzmann form of the neutron transport equation. In the PANDAS-MOC neutron transport code, MOC is used to determine the 2D radial solution. However, in the whole-code OpenMP threading hybrid model (WCP) of PANDAS-MOC, it is found that when using the classic parallelism, the MOC sweeping performance is restricted by the overhead incurred by the unbalanced workload and omp atomic clause. This article describes three parallel algorithms for the MOC sweep in the WCP model: the long-track schedule, equal-segment schedule, and no-atomic schedule. All algorithms are accomplished by updating the partition approach and rearranging the sweeping order of the characteristic rays, and their parallel performances are examined by the C5G7 3D core. The results illustrate that the no-atomic schedule can reach 0.686 parallel efficiency when using 36 threads, which is larger than the parallel efficiency obtained in the MPI-only parallelization model.
Quality changes of duck meat during thermal sterilization processing caused by microwave, stepwise retort, and general retort heating
Authors: Yang Xiaoqi , Li Yan , Wang Peng , Luan Donglei , Sun Jingxin , Huang Ming , Wang Baowei , Zheng Yuandong
Published: October 2022

The quality changes of duck meat during thermal sterilization using microwave, stepwise retort and general retort heating were evaluated. Results showed that compared with stepwise retort and general retort, duck meat subjected to microwave showed significantly higher gumminess, chewiness, cohesiveness and resilience as well as glutamic acid, lysine and total amino acids. Low-field NMR revealed that the relative content of immobilized water after microwave and stepwise retort treatment was significantly higher than that after general retort treatment. The relative content of 1-octen-3-ol with characteristic mushroom aroma was significantly higher with microwave and stepwise retort heating than with general retort heating, while 2-pentyl-furan with poor taste was only detected with general retort heating. The muscle bundles subjected to microwave were neatly arranged, similar to those with no thermal sterilization. Overall, the meat quality after three thermal sterilization treatment was microwave > stepwise retort > general retort.
Pear pomace soluble dietary fiber ameliorates the negative effects of high-fat diet in mice by regulating the gut microbiota and associated metabolites
Authors: Ji Yuehong , Mao Kemin , Gao Jie , Chitrakar Bimal , Sadiq Faizan Ahmed , Wang Zhongxuan , Wu Jiangna , Xu Chao , Sang Yaxin
Published: October 2022

The gut microbiota and related metabolites are positively regulated by soluble dietary fiber (SDF). In this study, we explored the effects of SDF from pear pomace (PP) on the regulation of gut microbiota and metabolism in high-fat-diet-fed (HFD-fed) C57BL/6J male mice. The results showed that PP-SDF was able to maintain the HFD disrupted gut microbiota diversity with a significant increase in Lachnospiraceae_UCG-006, Akkermansia, and Bifidobacterium spp. The negative effects of high-fat diet were ameliorated by PP-SDF by regulating lipid metabolisms with a significant increase in metabolites like isobutyryl carnitine and dioscoretine. Correlation analysis revealed that gut microbiota, such as Akkermansia and Lachnospiraceae_UCG-006 in the PP-SDF intervention groups had strong positive correlations with isobutyryl carnitine and dioscoretin. These findings demonstrated that PP-SDF interfered with the host's gut microbiota and related metabolites to reduce the negative effects caused by a high-fat diet.
Energy efficient drying technologies for sweet potatoes: Operating and drying mechanism, quality-related attributes
Authors: Rashid Muhammad Tayyab , Liu Kunlun , Jatoi Mushtaque Ahmed , Safdar Bushra , Lv Dingyang , Li Qingyun
Published: October 2022

Sweet potatoes (SPs) are a versatile tuberous crop used as subsistence and cash crop in raw and processed forms. The major issue with SPs is post-harvest losses, which result in noticeable quality decline because of inappropriate handling, storage, delayed transit, and sales, as well as microbiological and enzymatic activity. Drying is an excellent strategy for managing short postharvest storage life, preserving nutrients, and maximizing long-term benefits. However, several parameters must be considered before drying SPs, such as relative humidity, temperature, drying duration, size, and shape. The current review looks at the factors influencing SPs' moisture loss, drying kinetics, diverse drying methods, pretreatments, operating conditions, and their efficacy in improving the drying process, functional, and nutritional qualities. An optimal drying process is required to preserve SPs to obtain concentrated nutrients and improve energy efficiency to be ecofriendly. Drying sweet potatoes using traditional methods such as sun or open-air drying was found to be a slow process that could result in a lower quality. Various advanced drying techniques, like vacuum, infrared, freeze drying, and pretreatments such as ultrasound and osmotic dehydration, have been developed and are successfully used globally. The best-fit thin-layer models (Hii, Page, two-term, logarithmic) utilized for drying SPs and appropriate modeling methods for optimizing drying procedures are also discussed.
Microbial succession and its correlation with the dynamics of volatile compounds involved in fermented minced peppers
Authors: Ma Ding , Li Yong , Chen Chengcheng , Fan Shichao , Zhou Yi , Deng Fangming , Zhao Lingyan
Published: October 2022

Fermented minced peppers are a traditional fermented food that has a unique flavor due to various microbial communities involved in fermentation. Understanding the changes in microbial communities and volatile components of fermented minced peppers is particularly important to unveil the formation of unique flavor of fermented peppers. In this study, the microbial communities and volatile compounds in fermented minced pepper was analyzed by high-throughput sequencing and GC-MS, as well as their underlying correlations were also established. Results indicated that 17 genera were identified as dominant microorganisms in the fermentation of minced pepper, accompanied by the detection of 64 volatile compounds. Further hierarchical clustering analysis (HCA) displayed that dynamic change of volatile metabolites were involved in the fermentation process, where alkane volatile components were mainly generated in the early stage (3–5 days), and alcohols volatile components were in the middle stage (7–17 days), while ester volatile components were mainly produced in both the early stage (3–5 days) and last stage (17–20 days). Bidirectional orthogonal partial least squares (O2PLS) analysis revealed that 11 genera were core functional microorganisms of fermented minced pepper. Cladosporium and Hansenpora were significantly correlated with the formation of 9 and 6 volatiles, respectively. These findings provide new insights into aroma profile variation of fermented minced peppers and underlying mechanism of characteristic aroma formation during fermentation.
Effects of different boiling processes on chemical compositions of Lilii Bulbus soup
Authors: He Guowei , Liu Ziying , Chen Hong , Wang Yuhui , Huang Wei , Lu Xiangyang , Tian Yun , Liu Huhu
Published: October 2022

Lilii Bulbus, an edible Chinese herbal medicine, has a long history in medicine. However, research on effectively boiling Lilii Bulbus is rare. To make the more nutritious Lilii Bulbus soup, the optimized boiling process, using an alternate heating mode by decoction pot carrying a mixture of water and Chinese liquor at the ration of 9:1, was established in this study. Compared to the soup prepared by the daily process, the polysaccharide amount improved by 54%, and the total heavy metals decreased by 33.5% using the optimized boiling process. In addition, the total saponins at 34.3 μg/g were determined in the soup prepared by the optimized process. Meanwhile, the colchicine content in the boiled Lilii Bulbus soup was undetectable using the optimized process. This research performs an optimized boiling process for making Lilii Bulbus soup, and provides a reference for generating high commercial value from Lilii Bulbus soup in the future.
Necroptosis-related lncRNAs: Combination of bulk and single-cell sequencing reveals immune landscape alteration and a novel prognosis stratification approach in lung adenocarcinoma
Authors: Yao Yizhu , Gu Liudan , Zuo Ziyi , Wang Dandan , Zhou Tianlin , Xu Xiaomei , Yang Lehe , Huang Xiaoying , Wang Liangxing
Published: October 2022

Necroptosis, which is recently recognized as a form of programmed cell death, plays a critical role in cancer biology, including tumorigenesis and cancer immunology. It was recognized not only to defend against tumor progression by suppressing adaptive immune responses but also to promote tumorigenesis and cancer metastasis after recruiting inflammatory responses. Thus the crucial role of necrosis in tumorigenesis has attracted increasing attention. Due to the heterogeneity of the tumor immune microenvironment (TIME) in lung adenocarcinoma (LUAD), the prognosis and the response to immunotherapy vary distinctly across patients, underscoring the need for a stratification algorithm for clinical practice. Although previous studies have formulated the crucial role of lncRNAs in tumorigenicity, the relationship between necroptosis-related lncRNAs, TIME, and the prognosis of patients with LUAD was still elusive. In the current study, a robust and novel prognostic stratification model based on Necroptosis-related LncRNA Risk Scoring (NecroLRS) and clinicopathological parameters was constructed and systemically validated in both internal and external validation cohorts. The expression profile of four key lncRNAs was further validated by qRT-PCR in 4 human LUAD cell lines. And a novel immune landscape alteration was observed between NecroLRS-High and -Low patients. To further elucidate the mechanism of necroptosis in the prognosis of LUAD from a single-cell perspective, a novel stratification algorithm based on K-means clustering was introduced to extract both malignant and NecroLRS-High subsets from epithelial cells. And the necroptosis-related immune infiltration landscape and developmental trajectory were investigated respectively. Critically, NecroLRS was found to be positively correlated with neutrophil enrichment, inflammatory immune response, and malignant phenotypes of LUAD. In addition, novel ligand-receptor pairs between NecroLRS-High cells and other immunocytes were investigated and optimal therapeutic compounds were screened to provide potential targets for future studies. Taken together, our findings reveal emerging mechanisms of necroptosis-induced immune microenvironment alteration on the deteriorative prognosis and may contribute to improved prognosis and individualized precision therapy for patients with LUAD.
Circulating tumor DNA – A potential aid in the management of chordomas
Authors: Frederico Stephen C. , Darling Corbin , Zhang Xiaoran , Huq Sakibul , Agnihotri Sameer , Gardner Paul A. , Snyderman Carl H. , Wang Eric W. , Zenonos Georgios A.
Published: October 2022

Chordomas are a locally invasive, low-grade, CNS malignancy that are primarily found in the skull base, spine, and sacrum. They are thought to be derived from notochordal remnants and remain a significant clinical challenge due to their local invasiveness, resistance to chemoradiation, and difficulty in achieving a complete resection. Adjuvant therapy such as proton beam therapy is critical in preventing recurrence in patients who are at high risk, however this treatment is associated with increased risk of complication. Currently, intraoperative observation and imaging findings are used to determine recurrence and success of gross total resection. These methods can be unreliable due to limited operative view, bony and soft tissue involvement, and complex post-operative changes on MRI. Earlier detection of incomplete resection or recurrence will allow for earlier ability to intervene and potentially improve patient outcomes. Circulating-tumor DNA (ctDNA) is cell-free DNA that is released by tumor cells as they undergo cellular turn-over. Monitoring ctDNA has been shown to be more sensitive at predicting residual tumor than imaging in numerous solid malignancies. Furthermore, ctDNA could be detected earlier in peripheral blood as opposed to imaging changes, allowing for earlier intervention. In this review, we intend to give a brief overview of the current state of molecular diagnosis for skull base chordomas. We will then discuss current advances in the utilization of ctDNA for the management of CNS pathologies such as glioblastoma (GBM) and brain metastases. We will also discuss the role ctDNA has in the management of non-CNS pathologies such as osteosarcoma and Ewing sarcoma (EWS). Finally, we will discuss potential implications of ctDNA monitoring for chordoma management.
Fatty acid metabolism predicts prognosis and NK cell immunosurveillance of acute myeloid leukemia patients
Authors: Ye Zhitao , Li Yishan , Tian Xiaobin , Wei Yan , Yu Yanhui , Lai Kaibin , Yang Keyue , Qiu Zixuan , Lin Jianqing , Zhao Meng , Lin Dongjun , Xu Xiaojun
Published: October 2022

Background

Cell metabolic reprogramming is a hallmark of tumor prognosis, and fatty acid metabolism (FAM) plays a crucial role in the tumor microenvironment (TME). However, the relationship between FAM, TME, and prognosis of acute myeloid leukemia (AML) patients remains elusive.

Methods

We extracted the single-cell RNA sequencing (scRNA-Seq) and bulk transcriptome data of AML patients from the TCGA and GEO databases and assessed the relationship between FAM, TME, and AML patient prognosis. We also performed functional enrichment (FE) assay to evaluate the significance of FAM in anti-AML immunosurveillance.

Results

Our scRNA-Seq analysis revealed that the leukemic stem cell (LSC)-enriched population exhibited elevated levels of FAM-related genes. Using these FAM-related genes, we developed a prognostic model that accurately estimated AML patient outcome. FE analysis showed that FAM was strongly related to alterations of TME-based immunosurveillance in AML patients. More importantly, we demonstrated that FAM inhibition via pharmaceutical targeting of PLA2G4A, a highly expressed FAM gene in AML patients with poor prognosis, enhanced the NK cell-mediated immunosurveillance in leukemia cells.

Conclusions

Leukemic stem cell (LSC)-enriched population exhibited elevated levels of FAM-related genes. We have successfully established the FAM formula that predicts AML patient prognosis and alterations in the TME-based immunosurveillance. We also found that PLA2G4A was a highly expressed FAM gene in AML patients with poor prognoses. Pharmaceutical targeting of PLA2G4A increased the expression of NKG2DL in leukemia cells in vitro and thus enhanced the NK cell-mediated immunosurveillance.
Investigation of chemoresistance to first-line chemotherapy and its possible association with autophagy in high-risk neuroblastoma
Authors: Chen Tingting , Zeng Chenggong , Li Zhuoran , Wang Juan , Sun Feifei , Huang Junting , Lu Suying , Zhu Jia , Zhang Yizhuo , Sun Xiaofei , Zhen Zijun
Published: October 2022

High-risk neuroblastoma (NB) is sensitive to chemotherapy but susceptible to chemoresistance. In this study, we aimed to analyze the incidence of chemoresistance in high-risk NB patients and to explore the role of autophagy in NB chemoresistance. We retrospectively analyzed the incidence of changing the chemotherapy regimen due to disease stabilization or disease progression during induction chemotherapy in high-risk NB patients, which was expressed as the chemoresistance rate. The autophagy levels were probed in tumor cells exposed to first-line chemotherapy agents. The sensitivity of tumor cells to chemotherapy agents and apoptosis rate were observed after inhibiting autophagy by transfection of shRNA or chloroquine (CQ). This study included 247 patients with high-risk NB. The chemoresistance rates of patients treated with cyclophosphamide + adriamycin + vincristine (CAV) alternating with etoposide + cisplatin (EP) (Group 1) and CAV alternating with etoposide + ifosfamide + cisplatin (VIP) (Group 2) was 61.5% and 39.9% (P = 0.0009), respectively. Group 2 had better survival rates than group 1. After exposure to cisplatin, cyclophosphamide, and etoposide, the autophagy-related proteins LC3-I, LC3-II, and Beclin-1 were upregulated, and the incidence of autophagy vesicle formation and the expression of P62 were increased. Chemotherapeutic agents combined with CQ significantly increased the chemotherapeutic sensitivity of tumor cells and increased the cell apoptosis. The downregulated expression of Beclin-1 increased the sensitivity of tumor cells to chemotherapeutics. Our results suggest that increasing the chemotherapy intensity can overcome resistance to NB. Inhibition of autophagy is beneficial to increase the sensitivity of NB to chemotherapy agents.
A novel 10-gene ferroptosis-related prognostic signature in acute myeloid leukemia
Authors: Zhu Kai , Lang Zhichao , Zhan Yating , Tao Qiqi , Yu Zhijie , Chen Lili , Fan Congcong , Jin Yan , Yu Kang , Zhu Bihan , Gao Yuxiang , Wang Chengchi , Jiang Songfu , Shi Yifen
Published: October 2022

Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies and exhibits a high rate of relapse and unfavorable outcomes. Ferroptosis, a relatively recently described type of cell death, has been reported to be involved in cancer development. However, the prognostic value of ferroptosis-related genes (FRGs) in AML remains unclear. In this study, we found 54 differentially expressed ferroptosis-related genes (DEFRGs) between AML and normal marrow tissues. 18 of 54 DEFRGs were correlated with overall survival (OS) (P<0.05). Using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis, we selected 10 DEFRGs that were associated with OS to build a prognostic signature. Data from AML patients from the International Cancer Genome Consortium (ICGC) cohort as well as the First Affiliated Hospital of Wenzhou Medical University (FAHWMU) cohort were used for validation. Notably, the prognostic survival analyses of this signature passed with a significant margin, and the riskscore was identified as an independent prognostic marker using Cox regression analyses. Then we used a machine learning method (SHAP) to judge the importance of each feature in this 10-gene signature. Riskscore was shown to have the highest correlation with this 10-gene signature compared with each gene in this signature. Further studies showed that AML was significantly associated with immune cell infiltration. In addition, drug-sensitive analysis showed that 8 drugs may be beneficial for treatment of AML. Finally, the expressions of 10 genes in this signature were verified by real-time quantitative polymerase chain reaction. In conclusion, our study establishes a novel 10-gene prognostic risk signature based on ferroptosis-related genes for AML patients and FRGs may be novel therapeutic targets for AML.
Preclinical evaluation and first in human study of Al18F radiolabeled ODAP-urea-based PSMA targeting ligand for PET imaging of prostate cancer
Authors: Ren Ya’nan , Liu Chen , Liu Teli , Duan Xiaojiang , Zhang Qian , Liu Jiayue , Wang Pei , Guo Qian , Yang Xing , Du Peng , Zhu Hua , Yang Zhi
Published: October 2022

Purpose

This study aimed to introduce a novel [18F]AlF-labeled ODAP-Urea-based Prostate-specific membrane antigen (PSMA) probe, named [18F]AlF-PSMA-137, which was derived from the successful modification of glutamate-like functional group. The preclinically physical and biological characteristics of the probe were analyzed. Polit clinical PET/CT translation was performed to analyze its feasibility in clinical diagnosis of prostate cancer.

Methods

[18F]AlF-PSMA-137 was maturely labeled with the [18F]AlF2+ labeling technique. It was analyzed by radio-HPLC for radiochemical purity and stability analysis in vitro and in vivo. The PSMA specificity was investigated in PSMA-positive (LNCaP) and PSMA-negative (PC3) cells, and the binding affinity was evaluated in LNCaP cells. Micro-PET/CT imaging was performed in mice bearing LNCaP or PC3 tumors. Thirteen patients with newly diagnosed prostate cancer were included for [18F]AlF-PSMA-137 PET/CT imaging. Physiologic biodistribution and tumor burden were semi-quantitatively evaluated and the radiation dosimetry of [18F]AlF-PSMA-137 was estimated.

Results

The radiochemical yield of [18F]AlF-PSMA-137 was 54.2 ± 10.7% (n = 16) with the radiochemical purity over 99% and the specific activity of 26.36 ± 7.33 GBq/μmol. The binding affinity to PSMA was 2.11 ± 0.63 nM. [18F]AlF-PSMA-137 showed high cell/tumor uptake which can be specifically blocked by PSMA inhibitor. According to the biodistribution in patients, [18F]AlF-PSMA-137 was mainly accumulated in kidneys, lacrimal glands, parotid glands, submandibular glands and liver which was similar to the extensive Glu-Ureas based probes. A total of 81 lesions were detected in PET/CT imaging and over 91% of lesions increased between 1 h p.i. (SUVmean: 10.98 ± 18.12) and 2 h p.i. (SUVmean: 14.25 ± 21.28) (p < 0.001). Additionally, the probe showed intensive accumulation in lesions which provided excellent imaging contrast with the high tumor-to-muscle ratio of 15.57 ± 27.21 at 1 h p.i. and 25.42 ± 36.60 at 2 h p.i. (p < 0.001), respectively. The effective dose of [18F]AlF-PSMA-137 was estimated as 0.0119 ± 0.0009 mSv/MBq.

Conclusion

An ODAP-Urea-based PSMA probe [18F]AlF-PSMA-137 was successfully prepared with high specificity and binding affinity to PSMA. Micro-PET/CT imaging study demonstrated its feasibility for prostate cancer imaging. Pilot clinical study showed its potential for delay-imaging and prostate cancer detection.
Laparoscopy for evaluating mesenteric lymphangiomatosis: A case report
Authors: Yin Yefeng , Wang Rongdi , Wang Xishan
Published: October 2022

Background

Lymphangiomatosis is an extremely rare disease with potential soft tissue, bone, and spleen involvement, which can be characterized by lymphangioma. Only a few cases of colon and mesenteric lymphangiomatosis have been reported. We report a case presenting with fatigue, periumbilical pain, and intermittent bloody stools. This patient underwent a series of examinations. Exploratory laparoscopy, in particular, yielded very valuable images and videos for this disease, which can provide evidence for the diagnosis of this disease.

Case summary

The current patient had fatigue, periumbilical pain, and intermittent bloody stools. Colonoscopy indicated numerous variable-sized hyaline cysts in the colon. Submucosal puncture was performed during colonoscopy. The patient was readmitted to the hospital due to periumbilical pain. B-ultrasound and abdominal CT showed multiple hypoechoic nodules in the mesenteric area. Exploratory laparoscopy was performed, and histopathology revealed that D2-40 was positive. Based on auxiliary examination and laparoscopic biopsy, surgeons and pathologists reached the diagnosis of mesenteric lymphangiomatosis.

Conclusion

Clinicians need to comprehensively improve their knowledge of lymphangiomatosis, and the combination of clinical symptoms, histological characteristics, and colonoscopy biopsy findings should be considered to improve lymphangiomatosis diagnosis, thereby reducing misdiagnosis.

Core tip

Colon and mesenteric lymphangiomatosis is an extremely uncommon benign condition of unknown etiology and pathogenesis in adult patients. We report a case of mesenteric lymphangiomatosis in a 37-year-old woman who presented with fatigue, periumbilical pain, and intermittent bloody stools, as well as lesions in the kidney, spleen, and bones. This case provides new insights into the diagnosis and treatment of this disease.
Case report: complete remission with crizotinib in ROS1 fusion-positive sinonasal mucosal melanoma
Authors: Cao Jun , Yu Yaner , Zhou Yangkun , Ji Qing , Qian Wenkang , Jia Dongdong , Jin Gu , Qi Yajun , Li Xin , Li Ningning , Li Tao , Fang Meiyu , Jin Hongchuan
Published: October 2022

Introduction

Sinonasal mucosal melanoma (SNMM) originates from melanocytes. Currently, the main treatment methods, including surgery, radiotherapy and chemotherapy, have little effect on the recurrence and metastasis of SNMM. However, targeted therapy may be a breakthrough in treating SNMM.

Methods

A SNMM patient with ROS1 fusion received 250mg Crizotinib capsule (2 times a day, 1 tablet each time) therapy.

Results

The patient achieved partial remission after 4 months of treatment and complete remission after 8 months of treatment.

Conclusion

Our findings suggest that crizotinib can be an option to improve overall survival and quality of life of patients with metastatic ROS1-fusion SNMM. We believe that our report will provide insights for the application of crizotini in the treatment of melanoma.
ERCC1 is a potential biomarker for predicting prognosis, immunotherapy, chemotherapy efficacy, and expression validation in HER2 over-expressing breast cancer
Authors: Li Yilun , Liao Xiaomei , Ma Li
Published: October 2022

Objective

To investigate the relationship between Excision repair cross-complementation 1 (ERCC1) expression, clinicopathological features, and breast cancer prognosis in patients treated with trastuzumab. Further, we aim to explore the immune status of ERCC1 in breast cancer.

Methods

The data were retrieved from publicly available databases like the Cancer Genome Atlas, Therapeutically Applicable Research to Generate Effective Treatments, and the Genotype-Tissue Expression. The data was used to perform differential expression analyses between tumor and normal tissues in pan-cancers, immune-related analysis, homologous recombination deficiency (HRD), tumor mutation burden, and microsatellite instability. A total of 210 patients with HER2 over-expressing breast cancer from the Fourth Hospital of Hebei Medical University between January 2013 to December 2015 were enrolled in the study. Ten adjacent normal tissues were used to study the expression pattern of ERCC1 in normal tissues. Immunohistochemistry was performed to study ERCC1 expression and immune cell infiltration in different status of ERCC1 expression. Further, the correlation between ERCC1 expression, immune cell infiltration clinicopathological features, and the prognosis of patients with breast cancer was analyzed.

Results

The immune analysis revealed a significant correlation between CD8+ T cell, CD4+ T cell, T helper cell, macrophages, mast cells, and ERCC1 expression. Spearman analysis show that ERCC1 expression is related to macrophages and T cells. A close correlation was observed between increased ERCC1 expression and high tumor immune dysfunction and exclusion (TIDE) score as well as HRD. The results revealed a significant correlation among ERCC1, chemotherapy and estrogen receptor (ER; P < 0.05) expression. Univariate survival analysis revealed a significant correlation (P < 0.05) between that ERCC1 and ER expression, blood vessel invasion, and disease-free survival (DFS). ERCC1 and ER expression, tumor size, blood vessel invasion, pathological type, and lymph node metastases significantly correlated (P < 0.05) with overall survival in patients. Multivariate regression analysis revealed that ERCC1 expression and chemotherapy were independent factors that influence DFS. ERCC1 expression and vascular tumor thrombus were independent influencing factors that influence OS.

Conclusion

A correlation was observed between high ERCC1 expression and poor patient prognosis. High ERCC1 expression also influences the efficacy of immunotherapy and chemotherapy.
Cancer-specific survival and metastasis in pancreatic mucinous cystadenocarcinoma: A SEER-based cohort study
Authors: Wang Ruobing , Su Dan , Liu Yueze , Qiu Jiangdong , Cao Zhe , Yang Gang , Luo Wenhao , Tao Jinxin , Zhang Taiping
Published: October 2022

Aims

This study aimed to investigate the prognostic value of clinical features for cancer-specific survival (CSS) and metastasis in patients with pancreatic mucinous cystadenocarcinoma (MCAC). We further constructed and validated an effective nomogram to predict CSS.

Methods

We screened patients diagnosed with pancreatic MCAC from Surveillance Epidemiology and End Results (SEER) database. Kaplan-Meier curves were used to determine the CSS time. Univariate and multivariate Cox and logistic regression analyses were conducted to identify the prognostic factors for CSS and metastasis. The nomogram was constructed to predict the prognosis of pancreatic MCAC based on the results from the multivariate analysis. We used the concordance index (C-index), the area under the curve (AUC), and the calibration plots to determine the predictive accuracy and discriminability of the nomogram.

Results

Multivariate Cox analysis revealed that age, primary site, grade, and radiotherapy were independent prognostic factors associated with CSS. Multivariate logistic regression analysis revealed that surgery and grade were independent risk factors associated with metastasis. The independent risk factors were included to construct a prognosis prediction model for predicting CSS in patients with pancreatic MCAC. The concordance index (C-index), receiver operating characteristic (ROC) curves, and calibration plots of the training cohort and the validation cohort showed that the nomogram had an acceptable predictive performance.

Conclusion

We established a nomogram that could determine the 3- and 5-year CSS, which could evaluate individual clinical outcomes and provide individualized clinical decisions.
Chromosome instability in neuroblastoma: A pathway to aggressive disease
Authors: Paolini Lucia , Hussain Sajjad , Galardy Paul J.
Published: October 2022

For over 100-years, genomic instability has been investigated as a central player in the pathogenesis of human cancer. Conceptually, genomic instability includes an array of alterations from small deletions/insertions to whole chromosome alterations, referred to as chromosome instability. Chromosome instability has a paradoxical impact in cancer. In most instances, the introduction of chromosome instability has a negative impact on cellular fitness whereas in cancer it is usually associated with a worse prognosis. One exception is the case of neuroblastoma, the most common solid tumor outside of the brain in children. Neuroblastoma tumors have two distinct patterns of genome instability: whole-chromosome aneuploidy, which is associated with a better prognosis, or segmental chromosomal alterations, which is a potent negative prognostic factor. Through a computational screen, we found that low levels of the de- ubiquitinating enzyme USP24 have a highly significant negative impact on survival in neuroblastoma. At the molecular level, USP24 loss leads to destabilization of the microtubule assembly factor CRMP2 - producing mitotic errors and leading to chromosome missegregation and whole-chromosome aneuploidy. This apparent paradox may be reconciled through a model in which whole chromosome aneuploidy leads to the subsequent development of segmental chromosome alterations. Here we review the mechanisms behind chromosome instability and the evidence for the progressive development of segmental alterations from existing numerical aneuploidy in support of a multi-step model of neuroblastoma progression.
Human clinical trial using diagnostic ultrasound and microbubbles to enhance neoadjuvant chemotherapy in HER2- negative breast cancer
Authors: Zhou Biqiang , Lian Qingshu , Jin Chunchun , Lu Jianghao , Xu Lifeng , Gong Xuehao , Zhou Peng
Published: October 2022

Background

In vivo and in vitro experiments have demonstrated that diagnostic ultrasound combined with microbubbles (USMB) can enhance tumor chemotherapy, but few clinical studies have explored the effect of USMB in human HER2-negative breast cancer. We aimed to compare USMB combined with neoadjuvant chemotherapy (NAC) with NAC alone in the treatment of human HER2-negative breast cancer.

Methods

Patients (n=10) enrolled in the study were treated with TAC (taxane – (docetaxel), anthracycline – (epirubicin or doxorubicin liposomes), and cyclophosphamide) and ultrasound using a commercial clinical ultrasound scanner for 20 min after each chemotherapy session, followed by intermittent injections of SonoVue® to induce sonoporation and enhance therapeutic efficacy. Contrast-enhanced ultrasound (CEUS) was used to record tumor perfusion before and after ultrasound treatment.

Results

After completion of chemotherapy, the maximum tumor diameter of patients in the combined treatment group (n=10) was significantly smaller than that in the control group (n=16) (p=0.017). Although the combined treatment group had higher overall response and clinical benefit rates than those in the control group, there was no statistically significant difference in RECIST between the combined treatment group and the control groups (p=0.590). More patients in the combination therapy group achieved pathologic complete response than in the control group (p=0.014). For combined treatment, CEUS revealed that the peak intensity, mean transit time, and area under the curve were higher after treatment than before treatment (p<0.001, p<0.001, p=0.003, respectively). Combined therapy did not cause additional toxicity or increase side effects.

Conclusion

USMB and chemotherapy can be combined in a clinical setting using commercially available equipment, without additional toxicity, and may improve the efficacy of NAC in HER2-negative breast cancer.
Predicting anaplastic lymphoma kinase rearrangement status in patients with non-small cell lung cancer using a machine learning algorithm that combines clinical features and CT images
Authors: Hao Peng , Deng Bo-Yu , Huang Chan-Tao , Xu Jun , Zhou Fang , Liu Zhe-Xing , Zhou Wu , Xu Yi-Kai
Published: October 2022

Purpose

To develop an appropriate machine learning model for predicting anaplastic lymphoma kinase (ALK) rearrangement status in non-small cell lung cancer (NSCLC) patients using computed tomography (CT) images and clinical features.

Method and materials

This study included 193 patients with NSCLC (154 in the training cohort, 39 in the validation cohort), 68 of whom tested positive for ALK rearrangements and 125 of whom tested negative. From the nonenhanced CT scans, 157 radiomic characteristics were extracted, and 8 clinical features were collected. Five machine learning (ML) models were assessed to find the best classification model for predicting ALK rearrangement status. A radiomic signature was developed using the least absolute shrinkage and selection operator (LASSO) algorithm. The predictive performance of the models based on radiomic features, clinical features, and their combination was assessed by receiver operating characteristic (ROC) curves.

Results

The support vector machine (SVM) model had the highest AUC of 0.914 for classification. The clinical features model had an AUC=0.805 (95% CI 0.731–0.877) and an AUC=0.735 (95% CI 0.566–0.863) in the training and validation cohorts, respectively. The CT image-based ML model had an AUC=0.953 (95% CI 0.913–1.0) in the training cohort and an AUC=0.890 (95% CI 0.778–0.971) in the validation cohort. For predicting ALK rearrangement status, the ML model based on CT images and clinical features performed better than the model based on only clinical information or CT images, with an AUC of 0.965 (95% CI 0.826–0.882) in the primary cohort and an AUC of 0.914 (95% CI 0.804–0.893) in the validation cohort.

Conclusion

Our findings revealed that ALK rearrangement status could be accurately predicted using an ML-based classification model based on CT images and clinical data.