bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Breast Cancer Resistance Likelihood and Personalized Treatment Through Integrated Multiomics’
Authors: Mehmood Sabba , Faheem Muhammad , Ismail Hammad , Farhat Syeda Mehpara , Ali Mahwish , Younis Sidra , Asghar Muhammad Nadeem
Published: April 2022

In recent times, enormous progress has been made in improving the diagnosis and therapeutic strategies for breast carcinoma, yet it remains the most prevalent cancer and second highest contributor to cancer-related deaths in women. Breast cancer (BC) affects one in eight females globally. In 2018 alone, 1.4 million cases were identified worldwide in postmenopausal women and 645,000 cases in premenopausal females, and this burden is constantly increasing. This shows that still a lot of efforts are required to discover therapeutic remedies for this disease. One of the major clinical complications associated with the treatment of breast carcinoma is the development of therapeutic resistance. Multidrug resistance (MDR) and consequent relapse on therapy are prevalent issues related to breast carcinoma; it is due to our incomplete understanding of the molecular mechanisms of breast carcinoma disease. Therefore, elucidating the molecular mechanisms involved in drug resistance is critical. For management of breast carcinoma, the treatment decision not only depends on the assessment of prognosis factors but also on the evaluation of pathological and clinical factors. Integrated data assessments of these multiple factors of breast carcinoma through multiomics can provide significant insight and hope for making therapeutic decisions. This omics approach is particularly helpful since it identifies the biomarkers of disease progression and treatment progress by collective characterization and quantification of pools of biological molecules within and among the cancerous cells. The scrupulous understanding of cancer and its treatment at the molecular level led to the concept of a personalized approach, which is one of the most significant advancements in modern oncology. Likewise, there are certain genetic and non-genetic tests available for BC which can help in personalized therapy. Genetically inherited risks can be screened for personal predisposition to BC, and genetic changes or variations (mutations) can also be identified to decide on the best treatment. Ultimately, further understanding of BC at the molecular level (multiomics) will define more precise choices in personalized medicine. In this review, we have summarized therapeutic resistance associated with BC and the techniques used for its management.
A Qualitative Signature to Identify TERT Promoter Mutant High-Risk Tumors in Low-Grade Gliomas
Authors: Zheng Weicheng , Zhang Ruolan , Huang Ziru , Li Jianpeng , Wu Haonan , Zhou Yuwei , Zhu Jinwei , Wang Xianlong
Published: April 2022

Background: Telomerase reverse transcriptase promoter (TERT-p) mutation has been frequently found, but associated with contrary prognosis, in both low-grade gliomas and glioblastomas. For the low-grade gliomas (Grades II-III), TERT-p mutant patients have a better prognosis than the wildtype patients, whereas for the GBMs (Grade IV), TERT-p mutation is related to a poor prognosis. We hypothesize that there exist high-risk patients in LGGs who share GBM-like molecular features, including TERT-p mutation, and need more intensive treatment than other LGGs. A molecular signature is needed to identify these high-risk patients for an accurate and timely treatment.

Methods: Using the within-sample relative expression orderings of gene pairs, we identified the gene pairs with significantly stable REOs, respectively, in both the TERT-p mutant LGGs and GBMs but with opposite directions in the two groups. These reversely stable gene pairs were used as the molecular signature to stratify the LGGs into high-risk and low-risk groups.

Results: A signature consisting of 21 gene pairs was developed, which can classify LGGs into two groups with significantly different overall survival. The high-risk group has a similar genetic mutation profile and a similar survival profile as GBMs, and these high-risk tumors may progress to a more malignant state.

Conclusion: The 21 gene-pair signature based on REOs is capable of identifying high-risk patients in LGGs and guiding the clinical choice for appropriate and timely intervention.
High-Throughput Native Mass Spectrometry Screening in Drug Discovery
Authors: Gavriilidou Agni F. M. , Sokratous Kleitos , Yen Hsin-Yung , De Colibus Luigi
Published: April 2022

The design of new therapeutic molecules can be significantly informed by studying protein-ligand interactions using biophysical approaches directly after purification of the protein-ligand complex. Well-established techniques utilized in drug discovery include isothermal titration calorimetry, surface plasmon resonance, nuclear magnetic resonance spectroscopy, and structure-based drug discovery which mainly rely on protein crystallography and, more recently, cryo-electron microscopy. Protein-ligand complexes are dynamic, heterogeneous, and challenging systems that are best studied with several complementary techniques. Native mass spectrometry (MS) is a versatile method used to study proteins and their non-covalently driven assemblies in a native-like folded state, providing information on binding thermodynamics and stoichiometry as well as insights on ternary and quaternary protein structure. Here, we discuss the basic principles of native mass spectrometry, the field’s recent progress, how native MS is integrated into a drug discovery pipeline, and its future developments in drug discovery.
Alphaviruses in Cancer Therapy
Authors: Lundstrom Kenneth
Published: April 2022

Alphaviruses have been engineered as expression vectors for different strategies of cancer therapy including immunotherapy and cancer vaccine development. Administration of recombinant virus particles, RNA replicons and plasmid DNA-based replicons provide great flexibility for alphavirus applications. Immunization and delivery studies have demonstrated therapeutic efficacy in the form of reduced tumor growth, tumor regression and eradication of established tumors in different animal models for cancers such as brain, breast, colon, cervical, lung, ovarian, pancreas, prostate cancers, and melanoma. Furthermore, vaccinated animals have showed protection against challenges with tumor cells. A limited number of clinical trials in the area of brain, breast, cervical, colon prostate cancers and melanoma vaccines has been conducted. Particularly, immunization of cervical cancer patients elicited immune responses and therapeutic activity in all patients included in a phase I clinical trial. Moreover, stable disease and partial responses were observed in breast cancer patients and prolonged survival was achieved in colon cancer patients.
Associations of Polygenic Risk Score for Late-Onset Alzheimer's Disease With Biomarkers
Authors: Li Qiaojun , Lv Xingping , Jin Fei , Liao Kun , Gao Liyuan , Xu Jiayuan
Published: April 2022

Late-onset Alzheimer's disease (LOAD) is a common irreversible neurodegenerative disease with heterogeneous genetic characteristics. Identifying the biological biomarkers with the potential to predict the conversion from normal controls to LOAD is clinically important for early interventions of LOAD and clinical treatment. The polygenic risk score for LOAD (AD-PRS) has been reported the potential possibility for reliably identifying individuals with risk of developing LOAD recently. To investigate the external phenotype changes resulting from LOAD and the underlying etiology, we summarize the comprehensive associations of AD-PRS with multiple biomarkers, including neuroimaging, cerebrospinal fluid and plasma biomarkers, cardiovascular risk factors, cognitive behavior, and mental health. This systematic review helps improve the understanding of the biomarkers with potential predictive value for LOAD and further optimizing the prediction and accurate treatment of LOAD.
Situated Neural Representations: Solving the Problems of Content
Authors: Piccinini Gualtiero
Published: April 2022

Situated approaches to cognition maintain that cognition is embodied, embedded, enactive, and affective (and extended, but that is not relevant here). Situated approaches are often pitched as alternatives to computational and representational approaches, according to which cognition is computation over representations. I argue that, far from being opposites, situatedness and neural representation are more deeply intertwined than anyone suspected. To show this, I introduce a neurocomputational account of cognition that relies on neural representations. I argue not only that this account is compatible with (non-question-begging) situated approaches, but also that itrequiresembodiment, embeddedness, enaction, and affect at its very core. That is, constructing neural representations and their semantic content, and learning computational processes appropriate for their content, requires a tight dynamic interaction between nervous system, body, and environment. Most importantly, I argue that situatedness is needed to give a satisfactory account of neural representation: neurocognitive systems that are embodied, embedded, affective, dynamically interact with their environment, and use feedback from their interaction to shape their own representations and computations (1) can construct neural representations with original semantic content, (2) their neural vehicles and the way they are processed are automatically coordinated with their content, (3) such content is causally efficacious, (4) is determinate enough for the system's purposes, (5) represents the distal stimulus, and (6) can misrepresent. This proposal hints at what is needed to build artifacts with some of the basic cognitive capacities possessed by neurocognitive systems.
Ca2+ Dyshomeostasis Links Risk Factors to Neurodegeneration in Parkinson’s Disease
Authors: Xu Jianjun , Minobe Etsuko , Kameyama Masaki
Published: April 2022

Parkinson’s disease (PD), a common neurodegenerative disease characterized by motor dysfunction, results from the death of dopaminergic neurons in the substantia nigra pars compacta (SNc). Although the precise causes of PD are still unknown, several risk factors for PD have been determined, including aging, genetic mutations, environmental factors, and gender. Currently, the molecular mechanisms underlying risk factor-related neurodegeneration in PD remain elusive. Endoplasmic reticulum stress, excessive reactive oxygen species production, and impaired autophagy have been implicated in neuronal death in the SNc in PD. Considering that these pathological processes are tightly associated with intracellular Ca2+, it is reasonable to hypothesize that dysregulation of Ca2+ handling may mediate risk factors-related PD pathogenesis. We review the recent findings on how risk factors cause Ca2+ dyshomeostasis and how aberrant Ca2+ handling triggers dopaminergic neurodegeneration in the SNc in PD, thus putting forward the possibility that manipulation of specific Ca2+ handling proteins and subcellular Ca2+ homeostasis may lead to new promising strategies for PD treatment.
Janus Kinase-2 V617F Mutation and Antiphospholipid Syndrome in Cerebral Sinus Venous Thrombosis: Natural History and Retrospective Bicenter Analysis
Authors: Orion David , Itsekson-Hayosh Ze'ev , Peretz Shlomi , Mendel Rom , Yaniv Gal , Attia Moshe , Grizim-Merkel Drorit
Published: April 2022

Background

Cerebral sinus venous thrombosis (CSVT) is a rare neurovascular entity, usually associated with acquired or genetic hypercoagulable states. In up to 30% of the cases it remains idiopathic. Bone marrow proliferation disorders that are associated with Janus Kinase 2 V617F mutation (JAK-2) are known causes of the systemic and cerebral thrombosis—at times despite normal blood counts—for which hematologic treatment exists. However, JAK-2 prevalence in the CSVT cases is not clear.

Methods

In this retrospective analysis, data of 236 patients with CSVT admitted to two tertiary centers between 2010 and 2020 were analyzed, with emphasis on laboratory and imaging data and clinical and interventional outcomes.

Results

A total of 236 patients were included in the analysis. The patients' median age was 42 years and the average age was 44 years (±19 years), with 59% female patients. JAK-2 positivity rate was 18% (among 77 patients tested for the mutation). Patients with normal blood counts on presentation comprised 36% of the JAK-2 positive cases. Other hypercoagulability states were also investigated, with the antiphospholipid syndrome (APLA) showing the highest prevalence (11%) followed by other etiologies including oral contraceptive use, Factor V Leiden, prothrombin mutation, and malignancy. Selected JAK-2, APLA, and prothrombin mutation cases showed a more severe clinical course.

Conclusion

JAK-2 mutation is underdiagnosed and its screening may be warranted in the cases of idiopathic CSVT, even despite normal blood counts, to allow disease-modifying treatment and blood cell count monitoring. JAK-2, APLA, and prothrombin mutation may be associated with a more complicated clinical course.
Predictors of Functional School Outcome in Children With Pediatric Acquired Brain Injury
Authors: Stubberud Jan , Hypher Ruth , Brandt Anne E. , Finnanger Torun G. , Skovlund Eva , Andersson Stein , Risnes Kari , Rø Torstein B.
Published: April 2022

Objective

Among the variety of domains that may be impacted after pediatric acquired brain injury (pABI) are functional school outcomes. The purpose of this study was to identify demographic, medical, and psychological factors associated with impairments in functional school outcomes, defined as school absence, need of educational and psychological services, quality of life (QoL) in the school setting, and academic performance in children with pABI, with a specific emphasis on the significance of fatigue.

Materials and Method

We used baseline data from a randomized controlled trial. The sample consisted of seventy-six children aged 10 to 17 (M = 13 yrs) with pABI in the chronic phase (>1 year). All completed assessments of school-related QoL, academic performance, global functioning, fatigue, IQ, behavioral problems, and executive function.

Results

Fatigue, IQ, global functioning, behavioral problems, and sex emerged as potential predictors for functional school outcomes. Of note, overall fatigue emerged as the strongest potential predictor for parent-reported QoL in school (β = 0.548; p < 0.001) and self-reported QoL in school (β = 0.532; p < 0.001).

Conclusions

Following pABI, specific psychological, medical, and demographic factors are associated with functional school outcomes. Neither of the injury-related variables age at insult and time since insult were associated with functional school outcomes. Overall, our findings may suggest that a reintroduction to school with personalized accommodations tailored to the child's specific function and symptoms, such as fatigue, is recommended.
Effects of Sub-threshold Transcutaneous Auricular Vagus Nerve Stimulation on Cingulate Cortex and Insula Resting-state Functional Connectivity
Authors: Mao Yixiang , Chen Conan , Falahpour Maryam , MacNiven Kelly H. , Heit Gary , Sharma Vivek , Alataris Konstantinos , Liu Thomas T.
Published: April 2022

Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive alternative to vagus nerve stimulation (VNS) with implantable devices, has shown promise in treating disorders such as depression, migraine, and insomnia. Studies of these disorders with resting-state functional magnetic resonance imaging (MRI) (rsfMRI) have found sustained changes in resting-state functional connectivity (rsFC) in patients treated with low frequency (1–20 Hz) taVNS. A recent study has reported reductions in pain scores in patients with rheumatoid arthritis after a 12-week treatment of high-frequency (20 kHz) sub-threshold taVNS. However, no studies to date have examined the effects of high-frequency sub-threshold taVNS on rsFC. The objective of this study was to determine whether high-frequency sub-threshold taVNS induces changes in rsFC using seed regions from the cingulate cortex and insula, brain regions that play a key role in interoception and processing of pain. With a single-blind placebo-controlled repeated measures experimental design, rsfMRI scans were acquired before and after 15 min of either sub-threshold taVNS treatment or a sham control. Significant taVNS-related changes in functional connections to the cingulate cortex were detected between the anterior cingulate cortex and right superior temporal gyrus and between the midcingulate cortex and right inferior parietal lobule. In addition, significant changes in functional connections to the insula were detected between the posterior insula and right precuneus and between the anterior insula and right cuneus gyrus. These results suggest that high-frequency sub-threshold taVNS can lead to sustained effects on the rsFC of brain regions involved in interoception and processing of pain in a cohort of healthy subjects. This study lays the foundation for future rsfMRI studies of high-frequency sub-threshold taVNS in clinical populations.
Benefits of Endogenous Spatial Attention During Visual Double-Training in Cortically-Blinded Fields
Authors: Cavanaugh Matthew R. , Tadin Duje , Carrasco Marisa , Huxlin Krystel R.
Published: April 2022

Recovery of visual discrimination thresholds inside cortically-blinded (CB) fields is most commonly attained at a single, trained location at a time, with iterative progress deeper into the blind field as performance improves over several months. As such, training is slow, inefficient, burdensome, and often frustrating for patients. Here, we investigated whether double-location training, coupled with a covert spatial-attention (SA) pre-cue, could improve the efficiency of training. Nine CB participants completed a randomized, training assignment with either a spatial attention or neutral pre-cue. All trained for a similar length of time on a fine direction discrimination task at two blind field locations simultaneously. Training stimuli and tasks for both cohorts were identical, save for the presence of a central pre-cue, to manipulate endogenous (voluntary) SA, or a Neutral pre-cue. Participants in the SA training cohort demonstrated marked improvements in direction discrimination thresholds, albeit not to normal/intact-field levels; participants in the Neutral training cohort remained impaired. Thus, double-training within cortically blind fields, when coupled with SA pre-cues can significantly improve direction discrimination thresholds at two locations simultaneously, offering a new method to improve performance and reduce the training burden for CB patients. Double-training without SA pre-cues revealed a hitherto unrecognized limitation of cortically-blind visual systems’ ability to improve while processing two stimuli simultaneously. These data could potentially explain why exposure to the typically complex visual environments encountered in everyday life is insufficient to induce visual recovery in CB patients. It is hoped that these new insights will direct both research and therapeutic developments toward methods that can attain better, faster recovery of vision in CB fields.
Identification of Functional CircRNA–miRNA–mRNA Regulatory Network in Dorsolateral Prefrontal Cortex Neurons of Patients With Cocaine Use Disorder
Authors: Chen Yun , Li Xianfeng , Meng Shiqiu , Huang Shihao , Chang Suhua , Shi Jie
Published: April 2022

Increasing evidence has indicated that circular RNAs (circRNAs) act as competing endogenous RNAs (ceRNAs) regulatory network to regulate the expression of target genes by sponging microRNAs (miRNAs), and therefore play an essential role in many neuropsychiatric disorders, including cocaine use disorder. However, the functional roles and regulatory mechanisms of circRNAs as ceRNAs in dorsolateral prefrontal cortex (dlPFC) of patients with cocaine use disorder remain to be determined. In this study, an expression profiling for dlPFC in 19 patients with cocaine use disorder and 17 controls from Gene Expression Omnibus datasets was used for the differentially expressed circRNAs analysis and the differentially expressed mRNAs analysis. Several tools were used to predict the miRNAs targeted by the circRNAs and the miRNAs targeted mRNAs, which then overlapped with the cocaine-associated differentially expressed mRNAs to determine the functional roles of circRNAs. Functional analysis for the obtained mRNAs was performed via Gene Ontology (GO) in Metascape database. Integrated bioinformatics analysis was conducted to further characterize the circRNA–miRNA–mRNA regulatory network and identify the functions of distinct circRNAs. We found a total of 41 differentially expressed circRNAs, and 98 miRNAs were targeted by these circRNAs. The overlapped mRNAs targeted by the miRNAs and the differentially expressed mRNAs constructed a circRNA–miRNA–mRNA regulation network including 24 circRNAs, 43 miRNAs, and 82 mRNAs in the dlPFC of patients with cocaine use disorder. Functional analysis indicated the regulation network mainly participated in cell response-related, receptor signaling-related, protein modification-related and axonogenesis-related pathways, which might be involved with cocaine use disorder. Additionally, we determined four hub genes (HSP90AA1, HSPA1B, YWHAG, and RAB8A) from the protein–protein interaction network and constructed a circRNA–miRNA-hub gene subnetwork based on the four hub genes. In conclusion, our findings provide a deeper understanding of the circRNAs-related ceRNAs regulatory mechanisms in the pathogenesis of cocaine use disorder.
Predictive Model for Oral Status in Elderly People in a Taiwanese Nursing Home Using a High-Protein Black Soybean Koji Food
Authors: Liao Kai-Wei , Lo Wen-Liang , Hsu Chien-Yeh , Chiu Wan-Chun , Wu Chieh-Hsi , Chen Yi-Wen , Hsu Po-Chi , Huang Hui-Yu
Published: April 2022

With increased age, the appetite, chewing, swallowing, and digestive ability gradually decrease. Previous studies have shown that poor oral health is associated with an inadequate intake of macro and micronutrients and malnutrition. Therefore, improving the diet of elderly people and promoting nutrient absorption will help to improve the quality of life for elderly people. However, few studies have predicted their oral ability based on different food textures and other factors. The purpose of this study was to explore the correlation between oral assessment and texture parameters of high-protein black soybean koji products in elderly people in a nursing home. We used cross-sectional study design for seventy-nine residents aged 65 years and older were recruited. Three different texture of cookies, including normal cookie hardness (1.4 × 105 N/m2), minced cookie hardness (4.4 × 104 N/m2), and pureed cookie hardness (1.4 × 104 N/m2) were provided to participants to test the oral status. An oral assessment scale was used by a dentist to evaluate the oral status of the elderly participants. Different cookie textures showed a significant positive correlation with pronunciation (r = 0.237, p < 0.05), face (r = 0.371, p < 0.01), tongue (r = 0.362, p < 0.01), pharynx (r = 0.256, p < 0.05), swallowing (r = 0.272, p < 0.05), breathing (r = 0.315, p < 0.01), and the total oral score (r = 0.339, p < 0.01). We also used the high-protein black soybean koji products combined with elderly people’s comprehensions in a predictive model that had a moderately high correlation to predict the oral status in the elderly group (r = 0.612). We concluded that the high-protein black soybean koji product was associated with the oral ability of elderly people in a nursing home in Taiwan. Our findings indicated that elderly people could immediately understand the correct food texture.
Preparation, Characterization, and Cytoprotective Effects on HUVECs of Fourteen Novel Angiotensin-I-Converting Enzyme Inhibitory Peptides From Protein Hydrolysate of Tuna Processing By-Products
Authors: Qiao Qian-Qian , Luo Qian-Bin , Suo Shi-Kun , Zhao Yu-Qin , Chi Chang-Feng , Wang Bin
Published: April 2022

To effectively utilize skipjack tuna (Katsuwonus pelamis) processing by-products to prepare peptides with high angiotensin-I-converting enzyme (ACE) inhibitory (ACEi) activity, Neutrase was selected from five kinds of protease for hydrolyzing skipjack tuna dark muscle, and its best hydrolysis conditions were optimized as enzyme dose of 1.6%, pH 6.7, and temperature of 50°C using single factor and response surface experiments. Subsequently, 14 novel ACEi peptides were prepared from the high ACEi protein hydrolysate and identified as TE, AG, MWN, MEKS, VK, MQR, MKKS, VKRT, IPK, YNY, LPRS, FEK, IRR, and WERGE. MWN, MEKS, MKKS, and LPRS displayed significantly ACEi activity with IC50 values of 0.328 ± 0.035, 0.527 ± 0.030, 0.269 ± 0.006, and 0.495 ± 0.024 mg/mL, respectively. Furthermore, LPRS showed the highest increasing ability on nitric oxide (NO) production among four ACEi peptides combining the direct increase and reversing the negative influence of norepinephrine (NE), and MKKS showed the highest ability on directly decreasing and reversing the side effects of NE on the secretion level of endothelin-1 (ET-1) among four ACEi peptides. These findings demonstrate that seafood by-product proteins are potential ACEi peptide sources and prepared ACEi peptides from skipjack tuna dark muscle, which are beneficial components for functional food against hypertension and cardiovascular diseases.
Assessment of Variations in Round Green Tea Volatile Metabolites During Manufacturing and Effect of Second-Drying Temperature via Nontargeted Metabolomic Analysis
Authors: Wang Huajie , Yu Yaya , Ouyang Wen , Jiang Yongwen , Wang Jinjin , Hua Jinjie , Yuan Haibo
Published: April 2022

Round green tea (RGT) is widely distributed and presents a high yield in China. The quality of RGT can be determined by its aroma; however, the transformation and formation of volatile metabolites during RGT processing remain unclear. In this study, 173 volatile compounds (nine categories) were identified totally from RGT via gas chromatography-mass spectrometry with infrared-assisted headspace-solid phase microextraction. These substances exhibited different changing trends during various procedures, with the most intense transformation occurring during fixation, followed by pan-frying and second drying; moreover, 51 substances were screened, mainly containing fatty acid-derived volatiles (i.e., (E)-2-hexen-1-ol, Hexanal, pentanal, hexanal) and glycoside-derived volatiles (i.e., linalool, geraniol, benzyl alcohol, benzaldehyde), and their evolution during processing was clarified. Furthermore, the effect of the second-drying temperature on volatile compound metabolism was clarified, and 90°C was the best temperature for RGT aroma. This research lays a foundation for in-depth quality control and the aroma formation mechanism of RGT.
LAG3-PD-1 Combo Overcome the Disadvantage of Drug Resistance
Authors: Wei Yiming , Li Zhaoming
Published: April 2022

Although PD-1 blockade therapy has been promising in cancer treatment, only 4% (pancreatic cancer) to 70% (melanoma) of patients have a positive response to this blockade therapy, which is one of its important disadvantages. Therefore, it is important to seek out new targets for cancer immunotherapy to improve the overall response rate in patients. Lymphocyte activation gene-3 (LAG-3), an immune checkpoint receptor, is mainly expressed in activated immune cells. LAG-3 maintains the body’s immune homeostasis under physiological conditions while mediating tumour immune escape. Several preclinical and clinical examinations have shown that LAG-3 blockade effectively alleviates the patient’s tolerance to PD-1 immune checkpoint inhibitors. Moreover, the combination of LAG-3 and PD-1 blockade has good clinical efficacy in cancers. Hence, synchronous LAG-3 and PD-1 inhibition may be a potential new strategy for tumour immunotherapy.
Application of Convolutional Neural Network in the Diagnosis of Cavernous Sinus Invasion in Pituitary Adenoma
Authors: Fang Yi , Wang He , Feng Ming , Chen Hongjie , Zhang Wentai , Wei Liangfeng , Pei Zhijie , Wang Renzhi , Wang Shousen
Published: April 2022

Objectives

Convolutional neural network (CNN) is a deep-learning method for image classification and recognition based on a multi-layer NN. In this study, CNN was used to accurately assess cavernous sinus invasion (CSI) in pituitary adenoma (PA).

Methods

A total of 371 patients with PA were enrolled in the retrospective study. The cohort was divided into the invasive (n = 102) and non-invasive groups (n = 269) based on surgically confirmed CSI. Images were selected on the T1-enhanced imaging on MR scans. The cohort underwent a fivefold division of randomized datasets for cross-validation. Then, a tenfold augmented dataset (horizontal flip and rotation) of the training set was enrolled in the pre-trained Resnet50 model for transfer learning. The testing set was imported into the trained model for evaluation. Gradient-weighted class activation mapping (Grad-CAM) was used to obtain the occlusion map. The diagnostic values were compared with different dichotomizations of the Knosp grading system (grades 0-1/2-4, 0-2/3a-4, and 0-3a/3b-4).

Results

Based on Knosp grades, 20 cases of grade 0, 107 cases of grade 1, 82 cases of grade 2, 104 cases of grade 3a, 22 cases of grade 3b, and 36 cases of grade 4 were recorded. The CSI rates were 0%, 3.7%, 18.3%, 37.5%, 54.5%, and 88.9%. The predicted accuracies of the three dichotomies were 60%, 74%, and 81%. The area under the receiver operating characteristic (AUC-ROC) of Knosp grade for CSI prediction was 0.84; the cutoff was 2.5 with a Youden value of 0.62. The accuracies of the CNN model ranged from 0.80 to 0.96, with AUC-ROC values ranging from 0.89 to 0.98. The Grad-CAM saliency maps confirmed that the region of interest of the model was around the sellar region.

Conclusions

We constructed a CNN model with a high proficiency at CSI diagnosis. A more accurate CSI identification was achieved with the constructed CNN than the Knosp grading system.
Lucanthone Targets Lysosomes to Perturb Glioma Proliferation, Chemoresistance and Stemness, and Slows Tumor Growth In Vivo
Authors: Radin Daniel P. , Smith Gregory , Moushiaveshi Victoria , Wolf Alexandra , Bases Robert , Tsirka Stella E.
Published: April 2022

Glioblastoma is the most common and aggressive primary brain tumor in adults. Median survival time remains at 16-20 months despite multimodal treatment with surgical resection, radiation, temozolomide and tumor-treating fields therapy. After genotoxic stress glioma cells initiate cytoprotective autophagy, which contributes to treatment resistance, limiting the efficacy of these therapies and providing an avenue for glioma recurrence. Antagonism of autophagy steps has recently gained attention as it may enhance the efficacy of classical chemotherapies and newer immune-stimulating therapies. The modulation of autophagy in the clinic is limited by the low potency of common autophagy inhibitors and the inability of newer ones to cross the blood-brain barrier. Herein, we leverage lucanthone, an anti-schistosomal agent which crosses the blood-brain barrier and was recently reported to act as an autophagy inhibitor in breast cancer cells. Our studies show that lucanthone was toxic to glioma cells by inhibiting autophagy. It enhanced anti-glioma temozolomide (TMZ) efficacy at sub-cytotoxic concentrations, and suppressed the growth of stem-like glioma cells and temozolomide-resistant glioma stem cells. In vivo lucanthone slowed tumor growth: reduced numbers of Olig2+ glioma cells, normalized tumor vasculature, and reduced tumor hypoxia. We propose that lucanthone may serve to perturb a mechanism of temozolomide resistance and allow for successful treatment of TMZ-resistant glioblastoma.
Transfer Learning-Based Autosegmentation of Primary Tumor Volumes of Glioblastomas Using Preoperative MRI for Radiotherapy Treatment
Authors: Tian Suqing , Wang Cuiying , Zhang Ruiping , Dai Zhuojie , Jia Lecheng , Zhang Wei , Wang Junjie , Liu Yinglong
Published: April 2022

Objectives

Glioblastoma is the most common primary malignant brain tumor in adults and can be treated with radiation therapy. However, tumor target contouring for head radiation therapy is labor-intensive and highly dependent on the experience of the radiation oncologist. Recently, autosegmentation of the tumor target has been playing an increasingly important role in the development of radiotherapy plans. Therefore, we established a deep learning model and improved its performance in autosegmenting and contouring the primary gross tumor volume (GTV) of glioblastomas through transfer learning.

Methods

The preoperative MRI data of 20 patients with glioblastomas were collected from our department (ST) and split into a training set and testing set. We fine-tuned a deep learning model for autosegmentation of the hippocampus on separate MRI scans (RZ) through transfer learning and trained this deep learning model directly using the training set. Finally, we evaluated the performance of both trained models in autosegmenting glioblastomas using the testing set.

Results

The fine-tuned model converged within 20 epochs, compared to over 50 epochs for the model trained directly by the same training set, and demonstrated better autosegmentation performance [Dice similarity coefficient (DSC) 0.9404 ± 0.0117, 95% Hausdorff distance (95HD) 1.8107 mm ±0.3964mm, average surface distance (ASD) 0.6003 mm ±0.1287mm] than the model trained directly (DSC 0.9158±0.0178, 95HD 2.5761 mm ± 0.5365mm, ASD 0.7579 mm ± 0.1468mm) with the same test set. The DSC, 95HD, and ASD values of the two models were significantly different (P<0.05).

Conclusion

A model developed with semisupervised transfer learning and trained on independent data achieved good performance in autosegmenting glioblastoma. The autosegmented volume of glioblastomas is sufficiently accurate for radiotherapy treatment, which could have a positive impact on tumor control and patient survival.
Application Value of Radiomic Nomogram in the Differential Diagnosis of Prostate Cancer and Hyperplasia
Authors: Gui Shaogao , Lan Min , Wang Chaoxiong , Nie Si , Fan Bing
Published: April 2022

Objective

Prostate cancer and hyperplasia require different treatment strategies and have completely different outcomes; thus, preoperative identification of prostate cancer and hyperplasia is very important. The purpose of this study was to evaluate the application value of magnetic resonance imaging (MRI)-derived radiomic nomogram based on T2-weighted images (T2WI) in differentiating prostate cancer and hyperplasia.

Materials and Methods

One hundred forty-six patients (66 cases of prostate cancer and 80 cases of prostate hyperplasia) who were confirmed by surgical pathology between September 2019 and September 2019 were selected. We manually delineated T2WI of all patients using ITK-SNAP software and radiomic analysis using Analysis Kit (AK) software. A total of 396 tumor texture features were extracted. Subsequently, the effective features were selected using the LASSO algorithm, and the radiomic feature model was constructed. Next, combined with independent clinical risk factors, a multivariate Logistic regression model was used to establish a radiomic nomogram. The receiver operator characteristic (ROC) curve was used to evaluate the prediction performance of the radiomic nomogram. Finally, the clinical application value of the nomogram was evaluated by decision curve analysis.

Results

The PSA and the selected imaging features were significantly correlated with the differential diagnosis of prostate cancer and hyperplasia. The radiomic model had good discrimination efficiency for prostate cancer and hyperplasia. The training set (AUC = 0.85; 95% CI: 0.77–0.92) and testing set (AUC = 0.84; 95% CI: 0.72–0.96) were effective. The radiomic nomogram, combined with the radiomic characteristics of MRI and independent clinical risk factors, showed better differentiation efficiency in the training set (AUC = 0.91; 95% CI: 0.85–0.97) and testing set (AUC = 0.90; 95% CI: 0.81–0.99). The decision curve showed the clinical application value of the radiomic nomogram.

Conclusion

The radiomic nomogram of T2-MRI combined with clinical risk factors can easily identify prostate cancer and hyperplasia. It also provides suggestions for further clinical events.
YY1-Targeted RBM15B Promotes Hepatocellular Carcinoma Cell Proliferation and Sorafenib Resistance by Promoting TRAM2 Expression in an m6A-Dependent Manner
Authors: Tan Chunzhong , Xia Peng , Zhang Hao , Xu Kequan , Liu Pengpeng , Guo Deliang , Liu Zhisu
Published: April 2022

As one of the most common internal modifications in eukaryotic mRNA, N6-methyladenosine (m6A) modification is involved in the pathogenesis of many diseases, including hepatocellular carcinoma (HCC). In this study, we explored the prognostic significance of the expression of RNA binding motif protein 15B (RBM15B) in HCC, by studying specimens collected from clinical subjects. RBM15B is highly expressed in HCC patients and indicates a poor prognosis. Functionally, overexpression of RBM15B promotes HCC cell proliferation and invasion and induces sorafenib resistance in HCC cells. Mechanistically, we confirmed that RBM15B is transcriptionally activated by YY1 and regulates the stability of TRAM2 mRNA in an m6A-dependent manner. Overall, our results reveal a YY1-RBM15B-TRAM2 regulatory axis and highlight the critical role of RBM15B and m6A modifications in HCC. These findings may provide a novel mechanism and therapeutic targets for the treatment of HCC.
Evaluation of Amide Proton Transfer-Weighted Imaging for Risk Factors in Stage I Endometrial Cancer: A Comparison With Diffusion-Weighted Imaging and Diffusion Kurtosis Imaging
Authors: Jin Xingxing , Yan Ruifang , Li Zhong , Zhang Gaiyun , Liu Wenling , Wang Hongxia , Zhang Meng , Guo Jinxia , Wang Kaiyu , Han Dongming
Published: April 2022

Background

Endometrial cancer (EC) is one of the most common gynecologic malignancies in clinical practice. This study aimed to compare the value of diffusion-weighted imaging (DWI), diffusion kurtosis imaging (DKI), and amide proton transfer-weighted imaging (APTWI) in the assessment of risk stratification factors for stage I EC including histological subtype, grade, stage, and lymphovascular space invasion (LVSI).

Methods

A total of 72 patients with stage I EC underwent pelvic MRI. The apparent diffusion coefficient (ADC), mean diffusivity (MD), mean kurtosis (MK), and magnetization transfer ratio asymmetry (MTRasym at 3.5 ppm) were calculated and compared in risk groups with the Mann–Whitney U test or independent samples t-test. Spearman’s rank correlation was applied to depict the correlation of each parameter with risk stratification. The diagnostic efficacy was evaluated with receiver operating characteristic (ROC) curve analysis and compared using the DeLong test. A multivariate logistic regression was conducted to explore the optimal model for risk prediction.

Results

There were significantly greater MTRasym (3.5 ppm) and MK and significantly lower ADC and MD in the non-adenocarcinoma, stage IB, LVSI-positive, high-grade, and non-low-risk groups (all p < 0.05). The MK and MTRasym (3.5 ppm) were moderately positively correlated with risk stratification as assessed by the European Society for Medical Oncology (EMSO) clinical practice guidelines (r = 0.640 and 0.502, respectively), while ADC and MD were mildly negatively correlated with risk stratification (r = −0.358 and −0.438, respectively). MTRasym (3.5 ppm), MD, and MK were identified as independent risk predictors in stage I EC, and optimal predictive performance was obtained with their combinations (AUC = 0.906, sensitivity = 70.97%, specificity = 92.68%). The results of the validation model were consistent with the above results, and the calibration curve showed good accuracy and consistency.

Conclusions

Although similar performance was obtained with each individual parameter of APTWI, DWI, and DKI for the noninvasive assessment of aggressive behavior in stage I EC, the combination of MD, MK, and MTRasym (3.5 ppm) provided improved predictive power for non-low-risk stage I EC and may serve as a superior imaging marker.
Reproducibility for Hepatocellular Carcinoma CT Radiomic Features: Influence of Delineation Variability Based on 3D-CT, 4D-CT and Multiple-Parameter MR Images
Authors: Duan Jinghao , Qiu Qingtao , Zhu Jian , Shang Dongping , Dou Xue , Sun Tao , Yin Yong , Meng Xiangjuan
Published: April 2022

Purpose

Accurate lesion segmentation is a prerequisite for radiomic feature extraction. It helps to reduce the features variability so as to improve the reporting quality of radiomics study. In this research, we aimed to conduct a radiomic feature reproducibility test of inter-/intra-observer delineation variability in hepatocellular carcinoma using 3D-CT images, 4D-CT images and multiple-parameter MR images.

Materials and Methods

For this retrospective study, 19 HCC patients undergoing 3D-CT, 4D-CT and multiple-parameter MR scans were included in this study. The gross tumor volume (GTV) was independently delineated twice by two observers based on contrast-enhanced computed tomography (CECT), maximum intensity projection (MIP), LAVA-Flex, T2W FRFSE and DWI-EPI images. We also delineated the peritumoral region, which was defined as 0 to 5 mm radius surrounding the GTV. 107 radiomic features were automatically extracted from CECT images using 3D-Slicer software. Quartile coefficient of dispersion (QCD) and intraclass correlation coefficient (ICC) were applied to assess the variability of each radiomic feature. QCD<10% and ICC≥0.75 were considered small variations and excellent reliability. Finally, the principal component analysis (PCA) was used to test the feasibility of dimensionality reduction.

Results

For tumor tissues, the numbers of radiomic features with QCD<10% indicated no obvious inter-/intra-observer differences or discrepancies in 3D-CT, 4D-CT and multiple-parameter MR delineation. However, the number of radiomic features (mean 89) with ICC≥0.75 was the highest in the multiple-parameter MR group, followed by the 3DCT group (mean 77) and the MIP group (mean 73). The peritumor tissues also showed similar results. A total of 15 and 7 radiomic features presented excellent reproducibility and small variation in tumor and peritumoral tissues, respectively. Two robust features showed excellent reproducibility and small variation in tumor and peritumoral tissues. In addition, the values of the two features both represented statistically significant differences among tumor and peritumoral tissues (P<0.05). The PCA results indicated that the first seven principal components could preserve at least 90% of the variance of the original set of features.

Conclusion

Delineation on multiple-parameter MR images could help to improve the reproducibility of the HCC CT radiomic features and weaken the inter-/intra-observer influence.
Hidden Infection in Asymptomatic Congenital Lung Malformations—A Decade Retrospective Study
Authors: Liu Chenyu , Yu Xuejiao , Cheng Kaisheng , Luo Dengke , Yuan Miao , He Taozhen , Xu Chang
Published: April 2022

Background

Whether to operate on asymptomatic patients with congenital lung malformations (CLMs) remains controversial. Our study intended to find out the proportion of hidden infection in CLMs and its effect on surgery, to provide help for the management of asymptomatic CLMs patients.

Methods

A retrospective review of the medical records of patients with asymptomatic CLMs from January 2011 to December 2020 was performed in our center. Selected asymptomatic patients were divided into a non-hidden infection group (NHI) and a hidden infection group (HI).

Results

A total of 581 asymptomatic CLMs patients were included in this study. Thirty-two percent of asymptomatic CLMs patients had hidden infection in the lesion. Among various CLMs diseases, intralobular pulmonary sequestration had the highest percentage of hidden infection (48.8%). With age, the proportion of HI gradually increased. Patients in the HI and NHI groups were 223 and 121. The incidence of pleural adhesion and focal abscess in the HI group were 14.9 and 7.4%. Statistical significances were shown between the two groups in intraoperative blood loss (p = 0.002), operation time (p = 0.045), chest tube drainage time (p < 0.001), postoperative hospital stay (p < 0.001), and air leak (p = 0.012).

Conclusion

The proportion of HI detected by postoperative pathological results was high and they could increase the difficulty and risk of surgery. Therefore, early surgery may be a more appropriate choice for the management of asymptomatic CLMs patients.
The Efficacy and Safety of Bivalirudin Versus Heparin in the Anticoagulation Therapy of Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis
Authors: Ma Min , Liang Shichu , Zhu Jingbo , Dai Manyu , Jia Zhuoran , Huang He , He Yong
Published: April 2022

Background:Bivalirudin is a direct thrombin inhibitor (DTI) that can be an alternative to unfractionated heparin (UFH). The efficacy and safety of bivalirudin in anticoagulation therapy in extracorporeal membrane oxygenation (ECMO) remain unknown.

Methods:This study followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A systematic literature search was performed in PubMed, EMBASE, and The Cochrane Library databases to identify all relevant original studies estimating bivalirudin’s efficacy and safety versus UFH as anticoagulation therapy in ECMO. The time limit for searching is from the search beginning to June 2021. Two researchers independently screened the literature, extracted data and evaluated the risk of bias of the included studies. The meta-analysis (CRD42020214713) was performedviathe RevMan version 5.3.5 Software and STATA version 15.1 Software.

Results:Ten articles with 847 patients were included for the quantitative analysis. Bivalirudin can significantly reduce the incidence of major bleeding in children (I2= 48%,p= 0.01, odd ratio (OR) = 0.17, 95% confidence interval (CI): 0.04–0.66), patient thrombosis (I2= 0%,p= 0.02, OR = 0.58, 95% CI: 0.37–0.93), in-circuit thrombosis/interventions (I2= 0%,p= 0.0005, OR = 0.40, 95% CI: 0.24–0.68), and in-hospital mortality (I2= 0%,p= 0.007, OR = 0.64, 95% CI: 0.46–0.88). Also, comparable clinical outcomes were observed in the incidence of major bleeding in adults (I2= 48%,p= 0.65, OR = 0.87, 95% CI: 0.46–1.62), 30-day mortality (I2= 0%,p= 0.61, OR = 0.83, 95% CI: 0.41–1.68), and ECMO duration in adults (I2= 41%,p= 0.75, mean difference (MD) = −3.19, 95% CI: −23.01–16.63) and children (I2= 76%,p= 0.65, MD = 40.33, 95% CI:−135.45–216.12).

Conclusions:Compared with UFH, bivalirudin can be a safe and feasible alternative anticoagulant option to UFH as anticoagulation therapy in ECMO, especially for heparin resistance (HR) and heparin-induced thrombocytopenia (HIT) cases.