bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and cortical similarities identified between bipolar disorder I and schizophrenia: A multivariate approach
Authors: Rootes-Murdy Kelly , Edmond Jesse T. , Jiang Wenhao , Rahaman Md A. , Chen Jiayu , Perrone-Bizzozero Nora I. , Calhoun Vince D. , van Erp Theo G. M. , Ehrlich Stefan , Agartz Ingrid , Jönsson Erik G. , Andreassen Ole A. , Westlye Lars T. , Wang Lei , Pearlson Godfrey D. , Glahn David C. , Hong Elliot , Buchanan Robert W. , Kochunov Peter , Voineskos Aristotle , Malhotra Anil , Tamminga Carol A. , Liu Jingyu , Turner Jessica A.
Published: November 2022

Background

Structural neuroimaging studies have identified similarities in the brains of individuals diagnosed with schizophrenia (SZ) and bipolar I disorder (BP), with overlap in regions of gray matter (GM) deficits between the two disorders. Recent studies have also shown that the symptom phenotypes associated with SZ and BP may allow for a more precise categorization than the current diagnostic criteria. In this study, we sought to identify GM alterations that were unique to each disorder and whether those alterations were also related to unique symptom profiles.

Materials and methods

We analyzed the GM patterns and clinical symptom presentations using independent component analysis (ICA), hierarchical clustering, and n-way biclustering in a large (N ∼ 3,000), merged dataset of neuroimaging data from healthy volunteers (HV), and individuals with either SZ or BP.

Results

Component A showed a SZ and BP < HV GM pattern in the bilateral insula and cingulate gyrus. Component B showed a SZ and BP < HV GM pattern in the cerebellum and vermis. There were no significant differences between diagnostic groups in these components. Component C showed a SZ < HV and BP GM pattern bilaterally in the temporal poles. Hierarchical clustering of the PANSS scores and the ICA components did not yield new subgroups. N-way biclustering identified three unique subgroups of individuals within the sample that mapped onto different combinations of ICA components and symptom profiles categorized by the PANSS but no distinct diagnostic group differences.

Conclusion

These multivariate results show that diagnostic boundaries are not clearly related to structural differences or distinct symptom profiles. Our findings add support that (1) BP tend to have less severe symptom profiles when compared to SZ on the PANSS without a clear distinction, and (2) all the gray matter alterations follow the pattern of SZ < BP < HV without a clear distinction between SZ and BP.
Effect of transcranialdirect current stimulation on the right brain temporal area on processing approach and avoidance attitudes with negation
Authors: Nuez Aarón , Padrón Iván , Reyes-Moreno Cristian , Marrero Hipólito
Published: November 2022

Language describes approach/avoidance intentionality by means of attitudinal verbs (e.g., accept vs. reject). The right superior temporal sulcus (rSTS) has been shown to be recruited in processing action goals and approach intentionality in social contexts. In this study, we examine whether transcranial direct current stimulation (tDCS) of this area improves the processing of attitudinal verbs (either of approach or avoidance) in the context of affirmative and negative sentences [e.g., Julio (did not)/included meat on the grocery list]. After being subjected to tDCS, 46 participants were given sentences for passive reading. Sentences were displayed in segments with a fixed time of exposition, and a verb, either the one mentioned in the sentence or an alternative one was displayed 1,500 ms after the sentence (e.g., included vs. excluded, in the example). Participants were told to read them and then press the space bar to continue the experiment. Results showed shorter latencies for approach verbs that were either mentioned in approach sentences or the alternatives in avoidance sentences, both in affirmative and negative versions under anodal conditions compared to sham conditions. Thus, the anodal stimulation of rSTS affected the accessibility of approach verbs that were not modulated either by being mentioned or by sentence polarity. In addition, mentioned verbs had shorter reading times than the alternative ones in negative sentences in the anodal vs. sham condition. This suggests that stimulation caused an effect of negation in the activation of the mentioned verb. Implications are discussed in the context of the role of the rSTS in processing attitudinal verbs and negation to understand better approach and avoidance mediated by language in the framework of the two-step model of negation processing.
Test-retest reliability of time-varying patterns of brain activity across single band and multiband resting-state functional magnetic resonance imaging in healthy older adults
Authors: Cahart Marie-Stephanie , Dell’Acqua Flavio , Giampietro Vincent , Cabral Joana , Timmers Maarten , Streffer Johannes , Einstein Steven , Zelaya Fernando , Williams Steven C. R. , O’Daly Owen
Published: November 2022

Leading Eigenvector Dynamics Analysis (LEiDA) is an analytic approach that characterizes brain activity recorded with functional Magnetic Resonance Imaging (fMRI) as a succession of discrete phase-locking patterns, or states, that consistently recur over time across all participants. LEiDA allows for the extraction of three state-related measures which have previously been key to gaining a better understanding of brain dynamics in both healthy and clinical populations: the probability of occurrence of a given state, its lifetime and the probability of switching from one state to another. The degree to which test-retest reliability of the LEiDA measures may be affected by increasing MRI multiband (MB) factors in comparison with single band sequences is yet to be established. In this study, 24 healthy older adults were scanned over three sessions, on weeks 0, 1, and 4. On each visit, they underwent a conventional single band resting-state fMRI (rs-fMRI) scan and three different MB rs-fMRI scans, with MB factors of 4, with and without in-plane acceleration, and 6 without in-plane acceleration. We found test-retest reliability scores to be significantly higher with MB factor 4 with and without in-plane acceleration for most cortical networks. These findings will inform the choice of acquisition parameters for future studies and clinical trials.
Vascular smooth muscle cell dysfunction in neurodegeneration
Authors: Hayes Genevieve , Pinto Joana , Sparks Sierra N. , Wang Congxiyu , Suri Sana , Bulte Daniel P.
Published: November 2022

Vascular smooth muscle cells (VSMCs) are the key moderators of cerebrovascular dynamics in response to the brain’s oxygen and nutrient demands. Crucially, VSMCs may provide a sensitive biomarker for neurodegenerative pathologies where vasculature is compromised. An increasing body of research suggests that VSMCs have remarkable plasticity and their pathophysiology may play a key role in the complex process of neurodegeneration. Furthermore, extrinsic risk factors, including environmental conditions and traumatic events can impact vascular function through changes in VSMC morphology. VSMC dysfunction can be characterised at the molecular level both preclinically, and clinically ex vivo. However the identification of VSMC dysfunction in living individuals is important to understand changes in vascular function at the onset and progression of neurological disorders such as dementia, Alzheimer’s disease, and Parkinson’s disease. A promising technique to identify changes in the state of cerebral smooth muscle is cerebrovascular reactivity (CVR) which reflects the intrinsic dynamic response of blood vessels in the brain to vasoactive stimuli in order to modulate regional cerebral blood flow (CBF). In this work, we review the role of VSMCs in the most common neurodegenerative disorders and identify physiological systems that may contribute to VSMC dysfunction. The evidence collected here identifies VSMC dysfunction as a strong candidate for novel therapeutics to combat the development and progression of neurodegeneration, and highlights the need for more research on the role of VSMCs and cerebrovascular dynamics in healthy and diseased states.
Voltage slope guided learning in spiking neural networks
Authors: Hu Lvhui , Liao Xin
Published: November 2022

A thorny problem in machine learning is how to extract useful clues related to delayed feedback signals from the clutter of input activity, known as the temporal credit-assignment problem. The aggregate-label learning algorithms make an explicit representation of this problem by training spiking neurons to assign the aggregate feedback signal to potentially effective clues. However, earlier aggregate-label learning algorithms suffered from inefficiencies due to the large amount of computation, while recent algorithms that have solved this problem may fail to learn due to the inability to find adjustment points. Therefore, we propose a membrane voltage slope guided algorithm (VSG) to further cope with this limitation. Direct dependence on the membrane voltage when finding the key point of weight adjustment makes VSG avoid intensive calculation, but more importantly, the membrane voltage that always exists makes it impossible to lose the adjustment point. Experimental results show that the proposed algorithm can correlate delayed feedback signals with the effective clues embedded in background spiking activity, and also achieves excellent performance on real medical classification datasets and speech classification datasets. The superior performance makes it a meaningful reference for aggregate-label learning on spiking neural networks.
Nuclear localization of alpha-synuclein affects the cognitive and motor behavior of mice by inducing DNA damage and abnormal cell cycle of hippocampal neurons
Authors: Pan Yue , Zong Qinglan , Li Guoxiang , Wu Zhengcun , Du Tingfu , Huang Zhangqiong , Zhang Ying , Ma Kaili
Published: November 2022

Nuclear accumulation of alpha-synuclein (α-syn) in neurons can promote neurotoxicity, which is considered the key factor in the pathogenesis of synucleinopathy. The damage to hippocampus neurons driven by α-syn pathology is also the potential cause of memory impairment in Parkinson’s disease (PD) patients. In this study, we examined the role of α-syn nuclear translocation in the cognition and motor ability of mice by overexpressing α-syn in cell nuclei in the hippocampus. The results showed that the overexpression of α-syn in nuclei was able to cause significant pathological accumulation of α-syn in the hippocampus, and quickly lead to memory and motor impairments in mice. It might be that nuclear overexpression of α-syn may cause DNA damage of hippocampal neurons, thereby leading to activation and abnormal blocking of cell cycle, and further inducing apoptosis of hippocampal neurons and inflammatory reaction. Meanwhile, the inflammatory reaction further aggravated DNA damage and formed a vicious circle. Therefore, the excessive nuclear translocation of α-syn in hippocampal neurons may be one of the main reasons for cognitive decline in mice.
The emerging roles of N6-methyladenosine in osteoarthritis
Authors: Liu Hui , Zheng Yi-Li , Wang Xue-Qiang
Published: November 2022

Finding new biomarkers and molecular targets to guide OA treatment remains a significant challenge. One of the most frequent forms of RNA methylation, N6-methyladenosine (m6A), can affect gene expression and RNA transcription, processing, translation, and metabolism. Osteoarthritis (OA) can cause disability and pain degenerative disease, reduce the quality of life of the elderly, and increase the social and economic burden. Changes in m6A levels are crucial in OA progress. In this review, the discussion will concentrate on the role that m6A plays in OA occurrence and progression. The m6A involved in the OA process mainly includes METTL3 and FTO. Current studies on m6A and OA primarily focus on four signaling pathways, namely, NF-κB, LNCRNAs, ATG7, and Bcl2. m6A participates in these signaling pathways and affects cellular inflammation, apoptosis, senescence, and autophagy, thus controlling the OA process. The modification of m6A affects so many signaling pathways. For the treatment of OA, it may represent a viable new therapeutic target.
Physiological, transcriptomic, and metabolic analyses reveal that mild salinity improves the growth, nutrition, and flavor properties of hydroponic Chinese chive (Allium tuberosum Rottler ex Spr)
Authors: Liu Ning , Hu Manman , Liang Hao , Tong Jing , Xie Long , Wang Baoju , Ji Yanhai , Han Beibei , He Hongju , Liu Mingchi , Wu Zhanhui
Published: November 2022

Environmental stressors such as salinity have pronounced impacts on the growth, productivity, nutrition, and flavor of horticultural crops, though yield loss sometimes is inevitable. In this study, the salinity influences were evaluated using hydroponic Chinese chive (Allium tuberosum) treated with different concentrations of sodium chloride. The results demonstrated that lower salinity could stimulate plant growth and yield. Accordingly, the contents of soluble sugar, ascorbic acid, and soluble protein in leaf tissues increased, following the decrease of the nitrate content, under mild salinity (6.25 or 12.5 mM NaCl). However, a higher level of salinity (25 or 50 mM NaCl) resulted in growth inhibition, yield reduction, and leaf quality deterioration of hydroponic chive plants. Intriguingly, the chive flavor was boosted by the salinity, as evidenced by pungency analysis of salinity-treated leaf tissues. UPLC-MS/MS analysis reveals that mild salinity promoted the accumulation of glutamic acid, serine, glycine, and proline in leaf tissues, and thereby enhanced the umami and sweet flavors of Chinese chive upon salinity stress. Considering the balance between yield and flavor, mild salinity could conduce to hydroponic Chinese chive cultivation. Transcriptome analysis revealed that enhanced pungency could be ascribed to a salt stress-inducible gene, AtuFMO1, associated with the biosynthesis of S-alk(en)yl cysteine sulphoxides (CSOs). Furthermore, correlation analysis suggested that two transcription factors, AtubHLH and AtuB3, were potential regulators of AtuFMO1 expressions under salinity. Thus, these results revealed the molecular mechanism underlying mild salinity-induced CSO biosynthesis, as well as a practical possibility for producing high-quality Chinese chive hydroponically.
Red, white, and processed meat consumption related to inflammatory and metabolic biomarkers among overweight and obese women
Authors: Shiraseb Farideh , Hosseininasab Dorsa , Mirzababaei Atieh , Bagheri Reza , Wong Alexei , Suzuki Katsuhiko , Mirzaei Khadijeh
Published: November 2022

Background

Considering that a high meat intake is directly associated with obesity, it is critical to address the relationship between consuming different types of meat with inflammation and metabolism in overweight and obese cohorts. Thus, we evaluated the association between red, white, and processed meat consumption with inflammatory and metabolic biomarkers in overweight and obese women.

Methods

The current cross-sectional study was conducted on 391 overweight and obese Iranian women. Dietary intake was obtained from a food frequency questionnaire (FFQ) with 147 items. The anthropometric measurements, serum lipid profile, and inflammatory markers were measured by standard protocols. All associations were assessed utilizing one-way analysis of variance (ANOVA), analysis of covariance (ANCOVA), and linear regression models.

Results

In the adjusted model, it was established that higher intake of processed meat had a significant positive association with leptin levels (β: 0.900, 95% CI: 0.031;1.233, p = 0.015). Moreover, after considering the confounders, a significant positive association between processed meat and macrophage inflammatory protein (MCP-1) levels was observed (β: 0.304, 95% CI:0.100;1.596, p = 0.025). Positive significant associations between high-sensitivity C-reactive protein (hs-CRP) (β:0.020, 95% CI:0.000;0.050, P = 0.014) and plasminogen activator inhibitor 1 (PAI-1) (β:0.263, 95% CI:0.112;0.345, p = 0.053) and MCP-1 (β:0.490, 95% CI: 0.175;1.464, p = 0.071) levels with red meat were also shown; while there was a significant negative association between red meat and the homeostasis model assessment of insulin resistance (HOMA-IR) (β: −0.016, 95% CI: −0.022, −0.001, p = 0.033). Furthermore, a significant negative association were established following confounding adjustment between Galectin-3 (Gal-3) (β: −0.110, 95% CI: −0.271;0.000, p = 0.044), MCP-1 (β: −1.933, 95% CI: −3.721;0.192, p = 0.022) and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (β: −0.011, 95% CI: −0.020,0.000, p = 0.070) levels with high adherence of white meat intake. In contrast, a significant marginally positive association between PAI-1 levels and high adherence to white meat intake (β: −0.340, 95% CI: −0.751;0.050, p = 0.070) has been shown.

Conclusions

Higher red and processed meat consumption were positively associated with inflammatory and metabolic markers in overweight and obese women. In contrast, negative relationships between high adherence to white meat and various inflammatory and metabolic parameters were established. Further studies are needed to confirm the causality of these associations and potential mediating pathways.
Zinc agronomic biofortification of staple crops may be a cost-effective strategy to alleviate zinc deficiency in Ethiopia
Authors: Abdu Abdu Oumer , De Groote Hugo , Joy Edward J. M. , Kumssa Diriba B. , Broadley Martin R. , Gashu Dawd
Published: November 2022

Background

Inadequate dietary zinc (Zn) supplies and Zn deficiency (ZnD) are prevalent in Ethiopia, where cereals are major dietary sources, yet low in bioavailable Zn. Zinc agronomic biofortification (ZAB) of staple crops through application of Zn fertilizers may contribute to alleviating ZnD. However, large-scale promotion and adoption of ZAB requires evidence of the feasibility and public health benefits. This paper aimed to quantify the potential cost-effectiveness of ZAB of staple crops for alleviating ZnD in Ethiopia.

Methods

Current burden of ZnD among children in Ethiopia was quantified using a disability-adjusted life years (DALYs) framework. Evidence on baseline dietary Zn intake, cereal consumption, and fertilizer response ratio was compiled from existing literature and secondary data sources. Reduction in the burden of ZnD attributable to ZAB of three staple cereals (maize, teff, and wheat) via granular and foliar Zn fertilizer applications was calculated under optimistic and pessimistic scenarios. The associated costs for fertilizer, labor, and equipment were estimated in proportion to the cropping area and compared against DALYs saved and the national Gross Domestic Product capita–1.

Results

An estimated 0.55 million DALYs are lost annually due to ZnD, mainly due to ZnD-related mortality (91%). The ZAB of staple cereals via granular Zn fertilizer could reduce the burden of ZnD by 29 and 38% under pessimistic and optimistic scenarios, respectively; the respective values for ZAB via foliar application were 32 and 40%. The ZAB of staple cereals via granular fertilizer costs US$502 and US$505 to avert each DALY lost under optimistic and pessimistic scenarios, respectively; the respective values for ZAB via foliar application were US$226 and US$ 496. Foliar Zn application in combination with existing pesticide use could reduce costs to US$260–353 for each DALY saved. Overall, ZAB of teff and wheat were found to be more cost-effective in addressing ZnD compared to maize, which is less responsive to Zn fertilizer.

Conclusion

ZAB of staple crops via granular or foliar applications could be a cost-effective strategy to address ZnD, which can be integrated with the existing fertilizer scheme and pesticide use to minimize the associated costs.
Bibliometric and visual analysis in the field of ketogenic diet on cancer from 2012 to 2021
Authors: Li Rongrong , Huang Qingcheng , Ye Chenxiao , Wu Changhong , Luo Ning , Lu Yi , Fang Jianqiao , Wang Yun
Published: November 2022

Increasing evidence demonstrated that the ketogenic diet (KD) played a positive effect on cancer treatment. However, no systematic review and bibliometric analysis were conducted in this field. This study aimed to explore the current status, and reveal the potential trends and hotspots to provide a reference for future research. Publications were extracted from the Web of Science Core Collection. CiteSpace (5.6.R3) software and the website of bibliometrics were used for visual analysis. A total of 500 publications with 334 articles and 166 reviews were included, with the timespan of 2012 to 2021. The United States was the most productive country. Majority of the top 10 institutions were from the United States, and Harvard University was the top-contributing institution. The most prolific author and the co-cited author was Thomas N Seyfried from Boston College. The highest cited reference was published in PLoS ONE, authored by Abdelwahab Mohammed G, with 161 citations. Glioma and breast cancer were the most common types of cancer in this field, while hepatocellular carcinoma and pancreatic cancer were the new hotspots. The anti-tumor mechanism of KD mainly focused on regulating metabolism, decanoic acid, oxidative stress, fatty acid oxidation, and cell apoptosis. Additionally, the presence of “chemotherapy” and “radiotherapy” in the keywords indicated that KD combined with anti-tumor research was a topic, while “immunotherapy” has became a recent frontiers. Notably, as a metabolic therapy, KD was deserved more attention in the treatment of hepatocellular carcinoma and pancreatic cancer, and KD combined with immunotherapy was the new hotspot and frontier. Additionally, more molecular studies and high-quality uniformly, randomized, controlled clinical trials are urgently warranted to evaluate the effect of KD in multiple cancers.
Intrahepatic biliary cystadenoma: Confusion, experience, and lessons learned from our center
Authors: Yang Yongguang , Chen Weihuang , Cen Haiqiang , Li Zuobiao , Di Xiaoqing , Wu Yongjun , Liu Lijuan
Published: November 2022

Background

Intrahepatic biliary cystadenoma (IBC) is a rare benign cystic tumor of the liver. So far, it has not been comprehensively understood, which causes incorrect diagnosis, treatment confusion, and even inappropriate treatment. Here, we reviewed clinical data of IBC patients in our center, shared our experiences and lessons learned, and improved the level of diagnosis and treatment.

Methods

The clinical data of 10 patients with pathologically diagnosed IBC, admitted to the Department of Hepatobiliary Surgery of the Affiliated Hospital of Guangdong Medical University from January, 2007, to January, 2022 were retrospectively analyzed.

Results

10 patients underwent surgery and were discharged successfully. Cyst morphology: multiple cysts: 6 cases (6/10), monocular cyst: four cases(4/10). Six patients (6/10) were diagnosed as IBC preoperatively and received hepatectomy. Four patients with monocular cyst IBC underwent intraoperative frozen section examination, except one case showed IBC; the rest were misdiagnosed as simple liver cyst. In three misdiagnosed patients, one underwent open left hepatectomy seven days after the initial operation. The other patient refused to undergo reoperation and required follow-up observation. The last patient could not tolerate hepatectomy due to insufficient residual liver volume and chose follow-up observation

Conclusion

For IBC, especially monocular IBC, it is easy to be misdiagnosed as simple hepatic cyst, which brings great confusion to clinical treatment. We propose strengthening communication with pathologists to deepen understanding of IBC. Attention should be paid to the cyst wall’s shape and the cyst fluid’s properties during the operation to avoid the missed diagnosis, misdiagnosis, or even improper operation. For suspicious cases, directly choose hepatectomy to avoid reoperation after thoroughly evaluating the patient’s condition.
Targeting the MDM2-p53 pathway in dedifferentiated liposarcoma
Authors: Traweek Raymond S. , Cope Brandon M. , Roland Christina L. , Keung Emily Z. , Nassif Elise F. , Erstad Derek J.
Published: November 2022

Dedifferentiated liposarcoma (DDLPS) is an aggressive adipogenic cancer with poor prognosis. DDLPS tumors are only modestly sensitive to chemotherapy and radiation, and there is a need for more effective therapies. Genetically, DDLPS is characterized by a low tumor mutational burden and frequent chromosomal structural abnormalities including amplification of the 12q13-15 chromosomal region and the MDM2 gene, which are defining features of DDLPS. The MDM2 protein is an E3 ubiquitin ligase that targets the tumor suppressor, p53, for proteasomal degradation. MDM2 amplification or overexpression in human malignancies is associated with cell-cycle progression and worse prognosis. The MDM2–p53 interaction has thus garnered interest as a therapeutic target for DDLPS and other malignancies. MDM2 binds p53 via a hydrophobic protein interaction that is easily accessible with synthetic analogues. Multiple agents have been developed, including Nutlins such as RG7112 and small molecular inhibitors including SAR405838 and HDM201. Preclinical in vitro and animal models have shown promising results with MDM2 inhibition, resulting in robust p53 reactivation and cancer cell death. However, multiple early-phase clinical trials have failed to show a benefit with MDM2 pathway inhibition for DDLPS. Mechanisms of resistance are being elucidated, and novel inhibitors and combination therapies are currently under investigation. This review provides an overview of these strategies for targeting MDM2 in DDLPS.
Expanding the molecular spectrum of tenosynovial giant cell tumors
Authors: Gauduchon Thibault , Vanacker Helene , Pissaloux Daniel , Cassier Philippe , Dufresne Armelle , Karanian Marie , Meurgey Alexandra , Bouhamama Amine , Gouin François , Ray-Coquard Isabelle , Blay Jean-Yves , Tirode Franck , Brahmi Mehdi
Published: November 2022

Background

While great advances in clinical and pathological description of tenosynovial giant cell tumors (TGCT) have been made, TGCT molecular heterogeneity represents an ongoing challenge. The canonical oncogenic fusion CSF1::COL6A3 is not systematically observed, suggesting that other oncogenic mechanisms are involved in tumorigenesis. This study aims to explore by RNA sequencing a retrospective series of tumors diagnosed as TGCT, in order to provide a better description of their molecular landscape and to correlate molecular features with clinical data.

Methods

We analyzed clinicopathological data and performed whole-exome RNA sequencing on 41 TGCT samples.

Results

RNAseq analysis showed significant higher CSF1 and CSF1-R expression than a control panel of 2642 solid tumors. RNA sequencing revealed fusion transcripts in 14 patients including 6 not involving CSF1 and some previously unreported fusions. Unsupervised clustering on the expression profiles issued from this series suggested two distinct subgroups: one composed of various molecular subtypes including CSF1 and FN1 rearranged samples and one composed of four tumors harboring an HMGA2::NCOR2 fusion, suggesting distinct tumor entities. Overall, 15 patients received at least one systemic anti-CSF1R treatment and clinical improvement was observed in 11 patients, including patients from both clusters.

Discussion

This study reported molecular heterogeneity in TGCT, contrasting with the clinical and pathological homogeneity and the ubiquitous high CSF1 and CSF1R expression levels. Whether molecular diversity may impact the efficacy of systemic treatments needs to be further investigated.
Different expression patterns of VISTA concurrent with PD-1, Tim-3, and TIGIT on T cell subsets in peripheral blood and bone marrow from patients with multiple myeloma
Authors: Huang Shuxin , Zhao Yujie , Liao Pengjun , Wang Jinghua , Li Zhiyan , Tan Jiaxiong , Zha Xianfeng , Chen Shaohua , Li Yangqiu , Zhong Liye
Published: November 2022

V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA) is considered as an immunosuppressive factor and potential therapeutic target for anticancer therapy. However, little is known about VISTA expression and its role in immunosuppression in multiple myeloma (MM). In this study, VISTA expression and co-expression with programmed cell death receptor-1 (PD-1), T cell immunoglobulin mucin-domain-containing-3 (Tim-3), and T cell immunoglobulin and ITIM domain (TIGIT) in CD3+, CD4+, CD8+, and regulatory T (Treg) cells were analyzed in patients with MM by multi-color fluorescent flow cytometry of peripheral blood (PB) and bone marrow (BM) samples from 36 patients with MM and compared to 36 PB samples and 10 BM samples from healthy individuals (HIs), which served as controls. The results demonstrated a significant increased percentage of VISTA co-expression with PD-1, Tim-3, and TIGIT in CD3+, CD4+, CD8+, and Treg cells in PB from MM patients compared with HIs. A similar trend for VISTA+CD8+ T cells was found in BM. Moreover, a trend of a high percentage on VISTA expression and co-expression in PB rather than BM was found. Furthermore, significant positive correlations existed for VISTA expression concurrent with PD-1, Tim-3, and TIGIT in T cell subsets and clinical indicators, including Revised International Staging System (R-ISS) staging of multiple myeloma, Eastern Cooperative Oncology Group (ECOG) score, and beta-2-microglobulin (β2-MG). In conclusion, higher VISTA expression concurrent with PD-1, Tim-3, and TIGIT on T cells, particularly in the PB of patients with MM, may result in T cell exhaustion and dysfunction and be closely associated with disease progression and clinical indicators. Thus, VISTA may be considered a potential target for reversing T cell exhaustion and improving T cell function in MM.
Prediction of radiation-induced acute skin toxicity in breast cancer patients using data encapsulation screening and dose-gradient-based multi-region radiomics technique: A multicenter study
Authors: Feng Huichun , Wang Hui , Xu Lixia , Ren Yao , Ni Qianxi , Yang Zhen , Ma Shenglin , Deng Qinghua , Chen Xueqin , Xia Bing , Kuang Yu , Li Xiadong
Published: November 2022

Purpose

Radiation-induced dermatitis is one of the most common side effects for breast cancer patients treated with radiation therapy (RT). Acute complications can have a considerable impact on tumor control and quality of life for breast cancer patients. In this study, we aimed to develop a novel quantitative high-accuracy machine learning tool for prediction of radiation-induced dermatitis (grade ≥ 2) (RD 2+) before RT by using data encapsulation screening and multi-region dose-gradient-based radiomics techniques, based on the pre-treatment planning computed tomography (CT) images, clinical and dosimetric information of breast cancer patients.

Methods and Materials

214 patients with breast cancer who underwent RT between 2018 and 2021 were retrospectively collected from 3 cancer centers in China. The CT images, as well as the clinical and dosimetric information of patients were retrieved from the medical records. 3 PTV dose related ROIs, including irradiation volume covered by 100%, 105%, and 108% of prescribed dose, combined with 3 skin dose-related ROIs, including irradiation volume covered by 20-Gy, 30-Gy, 40-Gy isodose lines within skin, were contoured for radiomics feature extraction. A total of 4280 radiomics features were extracted from all 6 ROIs. Meanwhile, 29 clinical and dosimetric characteristics were included in the data analysis. A data encapsulation screening algorithm was applied for data cleaning. Multiple-variable logistic regression and 5-fold-cross-validation gradient boosting decision tree (GBDT) were employed for modeling training and validation, which was evaluated by using receiver operating characteristic analysis.

Results

The best predictors for symptomatic RD 2+ were the combination of 20 radiomics features, 8 clinical and dosimetric variables, achieving an area under the curve (AUC) of 0.998 [95% CI: 0.996-1.0] and an AUC of 0.911 [95% CI: 0.838-0.983] in the training and validation dataset, respectively, in the 5-fold-cross-validation GBDT model. Meanwhile, the top 12 most important characteristics as well as their corresponding importance measures for RD 2+ prediction in the GBDT machine learning process were identified and calculated.

Conclusions

A novel multi-region dose-gradient-based GBDT machine learning framework with a random forest based data encapsulation screening method integrated can achieve a high-accuracy prediction of acute RD 2+ in breast cancer patients.
Mutational patterns along different evolution paths of follicular lymphoma
Authors: Michaeli Miri , Carlotti Emanuela , Hazanov Helena , Gribben John G. , Mehr Ramit
Published: November 2022

Follicular lymphoma (FL) is an indolent disease, characterized by a median life expectancy of 18-20 years and by intermittent periods of relapse and remission. FL frequently transforms into the more aggressive diffuse large B cell lymphoma (t-FL). In previous studies, the analysis of immunoglobulin heavy chain variable region (IgHV) genes in sequential biopsies from the same patient revealed two different patterns of tumor clonal evolution: direct evolution, through acquisition of additional IgHV mutations over time, or divergent evolution, in which lymphoma clones from serial biopsies independently develop from a less-mutated common progenitor cell (CPC). Our goal in this study was to characterize the somatic hypermutation (SHM) patterns of IgHV genes in sequential FL samples from the same patients, and address the question of whether the mutation mechanisms (SHM targeting, DNA repair or both), or selection forces acting on the tumor clones, were different in FL samples compared to healthy control samples, or in late relapsed/transformed FL samples compared to earlier ones. Our analysis revealed differences in the distribution of mutations from each of the nucleotides when tumor and non-tumor clones were compared, while FL and transformed FL (t-FL) tumor clones displayed similar mutation distributions. Lineage tree measurements suggested that either initial clone affinity or selection thresholds were lower in FL samples compared to controls, but similar between FL and t-FL samples. Finally, we observed that both FL and t-FL tumor clones tend to accumulate larger numbers of potential N-glycosylation sites due to the introduction of new SHM. Taken together, these results suggest that transformation into t-FL, in contrast to initial FL development, is not associated with any major changes in DNA targeting or repair, or the selection threshold of the tumor clone.
SKA1/2/3 is a biomarker of poor prognosis in human hepatocellular carcinoma
Authors: Song Guo-Qiang , He Tian-Li , Ji Ke-Jie , Duan Yi-Meng , Zhang Jia-Wen , Hu Guo-Qiang
Published: November 2022

Background

Spindle and kinetochore-associated complex subunits 1–3 (SKA1–3) stabilize the kinetochore-attached spindle microtubules in metaphase. Due to the dysregulation in multiple cancers, SKA1–3 is considered a predictor for the prognosis of the patients. However, the potential clinical applications of SKA1–3, particularly in hepatocellular carcinoma (HCC) prognosis and progression, have completely unknown yet.

Methods

For the analysis of SKA1–3 expression and applications in clinics in HCC patients, several databases, such as STRING, UALCAN, GEO, and TCGA, were searched. In addition, the underlying mechanisms of SKA for the regulation of HCC occurrence, development, and progression were also explored.

Results

Compared to the normal controls, HCC patients showed dramatically elevated SKA1–3 expression at the mRNA level, and the values of the area under the curve (AUC) were 0.982, 0.887, and 0.973, respectively. Increased SKA1–3 expression levels were associated with the clinical stage, age, body mass index, tumor grade, tissue subtype, and Tp53 mutation status in HCC patients. The analyses of Kyoto Encyclopedia of Genes and Genome (KEGG) and Gene ontology (GO) demonstrated that SKA1–3 are enriched mainly in the Fanconi anemia, homologous recombination, spliceosome, DNA replication, and cell cycle signaling pathways. The hub genes, such as CDK1, CCNB1, CCNA2, TOP2A, BUB1, AURKB, CCNB2, BUB1B, NCAPG, and KIF11, were identified in protein–protein interactions (PPIs). The expression levels of hub genes were increased in HCC patients and predictive of a poor prognosis. Finally, the expression levels of SKA1–3 were determined using the GEO database.

Conclusions

SKA1–3 are potential prognostic biomarkers of and targets for HCC. In addition, SKA1–3 may affect HCC prognosis via the Fanconi anemia pathway, homologous recombination, spliceosome, DNA replication, and cell cycle signaling pathway.
Case report: Almonertinib in combination with bevacizumab for leptomeningeal metastases from epidermal growth factor receptor-mutation non-small cell lung cancer: Case series
Authors: Zhang Yuhai , Zhang Meilin , Cheng Wanwan , Fang Shencun
Published: November 2022

Leptomeningeal metastasis (LM) is a lethal complication of advanced non-small cell lung cancer (NSCLC) with rapid deterioration and poor prognosis. It has no standard treatment for epidermal growth factor receptor mutation (EGFRm) NSCLC, and improving the clinical outcomes for patients with LM has become an urgent problem in clinical treatment. Both almonertinib and bevacizumab are capable of crossing the blood–brain barrier with comparable central nervous system effectiveness. To date, the almonertinib treatment in combination with bevacizumab in EGFRm NSCLC with LM has not been studied. We herein present five cases to further evaluate the effectiveness and tolerability of almonertinib in combination with bevacizumab for patients with EGFRm NSCLC and LM. For the first time, we report that almonertinib plus bevacizumab can not only effectively improve the neurological symptoms caused by LM but also prolong the survival time of patients with limited and controllable side effects, which provided a novel therapeutic approach for LM from EGFRm NSCLC.
A novel prognostic model for prostate cancer based on androgen biosynthetic and catabolic pathways
Authors: Fan Aoyu , Zhang Yunyan , Cheng Jiangting , Li Yunpeng , Chen Wei
Published: November 2022

Prostate cancer (PCa) is one of the most common malignancies in males globally, and its pathogenesis is significantly related to androgen. As one of the important treatments for prostate cancer, androgen deprivation therapy (ADT) inhibits tumor proliferation by controlling androgen levels, either surgically or pharmacologically. However, patients treated with ADT inevitably develop biochemical recurrence and advance to castration-resistant prostate cancer which has been reported to be associated with androgen biosynthetic and catabolic pathways. Thus, gene expression profiles and clinical information of PCa patients were collected from TCGA, MSKCC, and GEO databases for consensus clustering based on androgen biosynthetic and catabolic pathways. Subsequently, a novel prognostic model containing 13 genes (AFF3, B4GALNT4, CD38, CHRNA2, CST2, ADGRF5, KLK14, LRRC31, MT1F, MT1G, SFTPA2, SLC7A4, TDRD1) was constructed by univariate cox regression, lasso regression, and multivariate cox regression. Patients were divided into two groups based on their risk scores: high risk (HS) and low risk (LS), and survival analysis was used to determine the difference in biochemical recurrence-free time between the two. The results were validated on the MSKCC dataset and the GEO dataset. Functional enrichment analysis revealed some pivotal pathways that may have an impact on the prognosis of patients including the CDK-RB-E2F axis, G2M checkpoint, and KRAS signaling. In addition, somatic mutation, immune infiltration, and drug sensitivity analyses were performed to further explore the characteristics of HS and LS groups. Besides, two potential therapeutic targets, BIRC5 and RHOC, were identified by us in prostate cancer. These results indicate that the prognostic model may serve as a predictive tool to guide clinical treatment and provide new insight into the basic research in prostate cancer.
CRISPR Cas9-mediated ablation of pyruvate carboxylase gene in colon cancer cell line HT-29 inhibits growth and migration, induces apoptosis and increases sensitivity to 5-fluorouracil and glutaminase inhibitor
Authors: Ngamkham Jarunya , Siritutsoontorn Siraprapa , Saisomboon Saowaluk , Vaeteewoottacharn Kulthida , Jitrapakdee Sarawut
Published: November 2022

Pyruvate carboxylase (PC) is an important anaplerotic enzyme that replenishes the tricarboxylic acid cycle (TCA) intermediates. It prevents the collapse of the TCA cycle upon its intermediates are removed during high anabolic demand. We have recently shown that overexpression of PC protein was associated with staging, metastasis and poor survival of colorectal cancer patients. Herein, we generated the PC knockout (PC KO) colon cancer cell lines, HT-29, by CRISPR-Cas9 technique, as a model to understand the role of this enzyme in colorectal cancer. The PC KO HT-29 cell lines had no detectable PC protein and did not show abnormal cellular or nuclear structures. However, PC KO HT-29 cells showed a 50-60% reduction in their growth rate and a 60-70% reduction in migration. The deficient growth phenotype of PC KO HT-29 cells was associated with apoptotic induction with no apparent cell cycle disruption following five days of growth. Down-regulation of key lipogenic enzymes, including acetyl-CoA carboxylase-1 and fatty acid synthase, was also associated with growth inhibition, suggesting that the de novo lipogenesis is impaired. Furthermore, PC KO HT-29 cells were 50% and 60% more sensitive to 5-fluorouracil and glutaminase inhibitor, CB-839, at their IC50 concentrations, respectively, following 48 h exposure. The increased cytotoxicity of CB-839 to PC KO HT-29 cells was associated with increased poly (ADP-ribose) polymerase cleavage. However, this was not observed with PC KO cells exposed to 5-fluorouracil, suggesting that PC KO HT-29 cells were prone to CB-839-induced apoptosis. Collectively, these findings indicate that ablation of PC expression in HT-29 cells disrupts the metabolic homeostasis of cells and inhibits proliferation and migration, accompanied by apoptotic induction. This study highlights the crucial role of PC in supporting the survival of HT-29 cells during exposure to chemotherapeutic drugs.
Measurable residual disease in hairy cell leukemia: Technical considerations and clinical significance
Authors: Robak Tadeusz , Robak Paweł
Published: November 2022

Hairy cell leukemia (HCL) is a rare type of chronic lymphoid leukemia originating from a mature B lymphocyte. A diagnosis of HCL is based on cytology, confirmed by multiparametric flow cytometry (MFC) studies using anti-B-cell monoclonal antibodies, together with a panel of antibodies more specific to HCL, such as CD11c, CD25, CD103 and CD123. Recently, the BRAF V600E mutation has been described as a disease-defining genetic event. Measurable residual disease (MRD) is defined as the lowest level of HCL cells that can be detected accurately and reproducibly using validated methods; as MRD negativity is associated with high rates of durable complete response, by clearing MRD, the long-term outcome may be improved in patients with advanced HCL. MRD is typically detected using bone marrow, and in some cases, peripheral blood; however, in HCL, discrepancies frequently exist between MRD results obtained from blood, bone marrow aspirate and core biopsy. Among the methods used for MRD detection, MFC appears to be a more sensitive technique than immunohistochemistry. Molecular tests are also used, such as real-time quantitative PCR for unique immunoglobulin heavy chain (IgH) gene rearrangements and PCR techniques with clone specificity for BRAF V600E. Clone-specific PCR (spPCR) is able to detect one HCL cell in 106 normal cells, and is particularly suitable for patients found to be negative for MRD by MFC. Recently, the Hairy Cell Leukemia Consortium created a platform to work on a definition for MRD, and establish the optimal time point, tissue type and method for measuring MRD. This
Prognostic values of the gross volume of metastatic lymph nodes in patients with esophageal squamous cell carcinoma treated with definitive concurrent chemoradiotherapy
Authors: Li Yang , Li Yanqi , Huang Hui , Guo Zhoubo , Zhang Kunning , Zhang Wencheng , Pang Qingsong , Wang Ping
Published: November 2022

Purpose

We aim to explore whether the gross volume of metastatic lymph nodes (GTVnd) and the gross volume of primary tumor (GTVp) could be prognostic factors for esophageal squamous cell carcinoma (ESCC) patients treated with definitive concurrent chemoradiotherapy (dCCRT).

Methods

We retrospectively analyzed 252 ESCC patients treated with dCCRT in the era of intensity-modulated radiation therapy (IMRT) at our institution. The cut-off value for the GTVnd derived from the restricted cubic splines (RCS) was determined. Univariate and multivariate Cox proportional hazard models were performed to determine the association between GTVnd and prognosis. we performed recursive partitioning analysis (RPA) method using GTVnd to develop a new risk stratification (TGTVndM). Moreover, the linear trend χ2, likelihood ratio χ2, and akaike information criterion (AIC) were used to determine the prognostic value between the TNM and TGTVndM staging systems.

Results

The five-year overall survival (OS) rate was 30.6%, with a median follow-up of 38 months. The cut-off value of GTVnd determined by the RCS was 4.35 cm3. GTVnd≥4.35 cm3 was an independent and significant negative prognostic factor for OS (HR=1.949, P<0.001), progression free survival (PFS) (HR=1.425, P=0.048), and distance metastasis free survival (DMFS) (HR=2.548, P=0.001). In multivariable analysis, gender, clinical T stage, and GTVnd were independently associated with OS. RPA segregated patients into 3 prognostic groups: high risk (T1-4 GTVnd≥4.35, n=126, III stage), intermediate risk (T4 GTVnd<4.35,n=38,II stage), and low risk(T1-3GTVnd<4.35, n=88, I stage). The 5-year OS(P<0.001), PFS (P=0.002), and DMFS (P=0.001) were significantly worse in high-risk group in comparison with the intermediate and low risk groups. Compared with the TNM staging system, the clinical T stage combined with GTVnd (TGTVndM) had a higher linear trend χ2 (26.38 versus 25.77), higher likelihood ratio χ2 (24.39 versus 20.69), and lower AIC (1255.07 versus 1260.06).

Conclusions

GTVnd may serve as a good prognostic factor in predicting distant metastasis and death for ESCC patients treated with dCCRT. The TGTVndM staging system demonstrated superior accuracy for predicting OS and could serve as a more effective prognostic guidance for unresectable ESCC patients.