bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel ganglioside-related risk signature can reveal the distinct immune landscape of neuroblastoma and predict the immunotherapeutic response
Authors: Yang Jiaxing , Han Lei , Sha Yongliang , Jin Yan , Li Zhongyuan , Gong Baocheng , Li Jie , Liu Yun , Wang Yangyang , Zhao Qiang 
Published: December 2022

IntroductionGangliosides play an essential role in cancer development and progression. However, the involvement of gangliosides in the prognosis and tumor microenvironment (TME) of neuroblastoma is not entirely understood.MethodsConsensus clustering analysis was performed to identify ganglioside-mediated molecular subtypes. LASSO-Cox analysis was conducted to identify independent prognostic genes, and a novel risk signature was constructed. The risk signature was validated internally and externally. We further explored the independent prognosis value, immune landscape, drug susceptibility, and tumor dedifferentiation of the risk signature. The role of the signature gene B3GALT4 in neuroblastoma was explored in vitro.ResultsSeventeen ganglioside-related genes were differentially expressed between INSS stage 4 and other stages, and two ganglioside-related clusters with distinct prognoses were identified. A novel risk signature integrating ten ganglioside-related prognostic genes was established. Across the train set and external validation sets, the risk signature presented high predictive accuracy and discrimination. The risk signature was an independent prognostic factor and constructed a nomogram combining multiple clinical characteristics. In the high-score group, the deficiency in antigen processing and presenting machinery, lack of immune cell infiltration, and escaping NK cells contributed substantially to immune escape. The low-score group was more responsive to immune checkpoint blockade therapy, while the high-score group showed substantial sensitivity to multiple chemotherapeutic drugs. Besides, the risk score was significantly positively correlated with the stemness index and reduced considerably in all-trans retinoic acid-treated neuroblastoma cell lines, indicating high dedifferentiation in the high-score group. Additionally, neuroblastoma cells with downregulation of B3GALT4 present with increased proliferation, invasion, and metastasis abilities in vitro.ConclusionThe novel ganglioside-related risk signature highlights the role of ganglioside in neuroblastoma prognosis and immune landscape and helps optimize chemotherapy and immunotherapy for neuroblastoma.
The HLA class-II immunopeptidomes of AAV capsids proteins
Authors: Brito-Sierra Carlos A. , Lannan Megan B. , Siegel Robert W. , Malherbe Laurent P. 
Published: December 2022

IntroductionGene therapies are using Adeno-associated viruses (AAVs) as vectors, but immune responses against the capsids pose challenges to their efficiency and safety. Helper T cell recognition of capsid-derived peptides bound to human leukocyte antigen (HLA) class II molecules is an essential step in the AAV-specific adaptive immunity.MethodsUsing MHC-associated peptide proteomics, we identified the HLA-DR and HLA-DQ immunopeptidomes of the capsid proteins of three different AAV serotypes (AAV2, AAV6, and AAV9) from a panel of healthy donors selected to represent a majority of allele usage.ResultsThe identified sequences span the capsids of all serotypes, with AAV2 having the highest peptide count. For all the serotypes, multiple promiscuous peptides were identified and displayed by both HLA-DR and -DQ. However, despite high sequence homology, there were few identical peptides among AAV2, AAV6, and AAV9 immunopeptidomes, and none were promiscuous.DiscussionResults from this work represent a comprehensive immunopeptidomics research of potential CD4+ T cell epitopes and provide the basis for immunosurveillance efforts for safer and more efficient AAV-based gene therapies.
Sex differences in the progression of cerebral microbleeds in patients with concomitant cerebral small vessel disease
Authors: Yoon Cindy W. , Rha Joung-Ho , Park Hee-Kwon , Park Soo-Hyun , Kwon Soonwook , Kim Byeong C. , Youn Young Chul , Jeong Jee Hyang , Han Hyun Jeong , Choi Seong Hye 
Published: December 2022

Background and purposeSex differences in cerebral microbleeds (CMBs) are not well-known. We aimed to assess the impact of sex on the progression of CMBs.MethodsThe CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Out of 256 subjects, 189 participants with a follow-up brain scan were included in the analysis. The linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between men and women.ResultsA total of 65 men and 124 women were analyzed. There were no significant differences in the prevalence (70.8 vs. 71.8%; P = 1.000) and the median [interquartile range (IQR)] number of total CMBs [1 (0–7) vs. 2 (0–7); P = 0.810] at baseline between men and women. The median (IQR) increase over 2 years in the number of CMBs was statistically higher in women than in men [1 (0–2) vs. 0 (0–1), P = 0.026]. The multivariate linear mixed-effects model showed that women had a significantly greater increase in the number of total, deep, and lobar CMBs compared to men after adjusting for age and the baseline number of CMBs [estimated log-transformed mean of difference between women and men: 0.040 (P = 0.028) for total CMBs, 0.037 (P = 0.047) for deep CMBs, and 0.047 (P = 0.009) for lobar CMBs].ConclusionThe progression of CMB over 2 years was significantly greater in women than in men.
Multiparametric magnetic resonance imaging-derived deep learning network to determine ferroptosis-related gene signatures in gliomas
Authors: Zuo Zhichao , Liu Wen , Zeng Ying , Fan Xiaohong , Li Li , Chen Jing , Zhou Xiao , Jiang Yihong , Yang Xiuqi , Feng Yujie , Lu Yixin 
Published: December 2022

IntroductionFerroptosis-related gene (FRG) signature is important for assessing novel therapeutic approaches and prognosis in glioma. We trained a deep learning network for determining FRG signatures using multiparametric magnetic resonance imaging (MRI).MethodsFRGs of patients with glioma were acquired from public databases. FRG-related risk score stratifying prognosis was developed from The Cancer Genome Atlas (TCGA) and validated using the Chinese Glioma Genome Atlas. Multiparametric MRI-derived glioma images and the corresponding genomic information were obtained for 122 cases from TCGA and The Cancer Imaging Archive. The deep learning network was trained using 3D-Resnet, and threefold cross-validation was performed to evaluate the predictive performance.ResultsThe FRG-related risk score was associated with poor clinicopathological features and had a high predictive value for glioma prognosis. Based on the FRG-related risk score, patients with glioma were successfully classified into two subgroups (28 and 94 in the high- and low-risk groups, respectively). The deep learning networks TC (enhancing tumor and non-enhancing portion of the tumor core) mask achieved an average cross-validation accuracy of 0.842 and an average AUC of 0.781, while the deep learning networks WT (whole tumor and peritumoral edema) mask achieved an average cross-validation accuracy of 0.825 and an average AUC of 0.781.DiscussionOur findings indicate that FRG signature is a prognostic indicator of glioma. In addition, we developed a deep learning network that has high classification accuracy in automatically determining FRG signatures, which may be an important step toward the clinical translation of novel therapeutic approaches and prognosis of glioma.
A multicenter randomized trials to compare the bioequivalence and safety of a generic doxorubicin hydrochloride liposome injection with Caelyx ® in advanced breast cancer
Authors: Li Yinjuan , Qi Lu , Wang Yu , Li Yan , Lei Chunpu , Zhang Yingjuan , Cheng Xiaoqiang , Liu Ju , Bai HaiHong , Zhao Xia , Lv Shuzhen , Xiong Bingjun , Liu Juan , Shi Yehui , Zhou Huan , Li Hongtao , Liu Lihong , Jiang Hongchuan , Ouyang Weiwei , Li Xiaowen , Li Yanping , Wang Xinghe 
Published: December 2022

PurposeTo compare the pharmacokinetic (PK) bioequivalence (BE) and safety of a generic pegylated liposomal doxorubicin (PLD) formulation with the reference product Caelyx®.MethodsA multicenter, single-dose, open-label, randomized, two-way crossover study was conducted in patients with breast cancer. For each period, the patients were administered with the test or the reference PLD intravenously at a dose of 50 mg/m2. Cmax, AUC0−t and AUC0−∞ for free, and encapsulated doxorubicin (doxorubicin) and partial AUC (AUC0−48h, AUC48h−t) for encapsulated doxorubicin were evaluated in 17 blood samples taken predose, and increasing time intervals over the following 14 days in each period. A washout period of 28-35 days was observed before crossing over.Results48 patients were enrolled and randomised, of which 44 were included and analysed in bioequivalence set (BES). The 90% confidence intervals (CIs) of the geometric mean ratio (GMR) of Cmax, AUC0−t and AUC0−∞ for free doxorubicin and encapsulated doxorubicin all fall within the bioequivalent range of 80% to 125%. The 90% CIs of GMR of partial AUC (AUC0−48h, AUC48h−t) for encapsulated doxorubicin also fall within the bioequivalent range. 48 patients were all included in the safety set (SS). The incidence of treatment-emergent adverse events (TEAEs) related to T and R was 95.8% (46/48) and 97.8% (45/46) respectively. The highest incidence of TEAEs was various laboratory abnormalities. 2 patients withdrew due to T-drug-related AEs. Only one patient experienced serious adverse events and no death occurred in this study. There were no significant differences between the safety profiles of the generic formulation and Caelyx®.ConclusionsBioequivalence between the test and the reference products was established for free and encapsulated doxorubicin.Clinical trial registrationhttp://www.chinadrugtrials.org.cn, identifier [CTR20210375].
Risk factors and prediction model of level II lymph node metastasis in papillary thyroid carcinoma
Authors: Huang Chun , Hu Daixing , Zhuang Yuchen , Su Xinliang 
Published: December 2022

IntroductionSurgical management of lateral lymph nodes in papillary thyroid carcinoma, especially at level II, remains controversial. This study aimed to investigate the risk factors for level II lymph node metastasis in patients with papillary thyroid carcinoma and establish a prediction model to estimate the metastatic risk.Materials and methodsA total of 768 patients with papillary thyroid carcinoma underwent thyroidectomy and central plus lateral lymph node dissection, including levels VI, II, III, and IV, at the First Affiliated Hospital of Chongqing Medical University from January 2016 to December 2018. Data on the clinicopathological characteristics were collected and analyzed. Univariate and multivariate analyses were performed to identify risk factors for level II lymph node metastasis. Subsequently, a predictive model was established based on the results of the multivariate analyses.ResultsThe level II lymph node metastatic rate was 34.11% with the following features: largest tumor diameter &gt;20 mm (Odds ratio=1.629, P=0.026), located in the upper pole (Odds ratio=4.970, P&lt;0.001), clinical lymph node-positive (clinical central lymph node-positive: Odds ratio=1.797; clinical lateral lymph node-positive: Odds ratio=1.805, P=0.008), vascular invasion (Odds ratio=6.759, P=0.012), and rate of central lymph node metastasis (Odds ratio=2.498, P&lt;0.001). Level III lymph node metastasis (Odds ratio=2.749, P&lt;0.001) and level IV lymph node metastasis (Odds ratio=1.732, P=0.007) were independent of level II lymph node metastasis predictors. The prediction model’s areas under the receiver operating characteristic curve were 0.815 and 0.804, based on bootstrapping validation. Level II lymph node metastasis was associated with the tumor-free survival rate of patients with papillary thyroid carcinoma (P&lt;0.001).ConclusionsLargest tumor diameter &gt;20 mm, located in the upper pole, clinical lymph node-positive, vascular invasion, rate of central lymph node metastasis, and levels III and IV lymph node metastases were independent level II lymph node metastasis predictors. We developed a prediction model for level II lymph node metastasis. Overall, level II lymph node metastasis dissection should be individualized according to clinicopathological data both preoperatively and intraoperatively.
A heterogeneous integrated self-powered IoT system of an LiNbO3 device and CMOS readout circuit
Authors: Wang Xiuyu , Kang Min , Zhao Yang , Su Yue , Zhang Xu , Mao Xurui 
Published: December 2022

A self-powered IoT system with high integration, robust performance, and adaptability to complex environments is one of the current research hotspots. Piezoelectric materials have been widely used in pressure sensing and energy harvesting due to their stable output electrical properties. In this paper, a heterogeneous integrated self-powered IoT system based on a lithium niobate (LiNbO3) piezoelectric device and CMOS readout circuit is proposed. The piezoelectric sensor is fabricated by depositing electrodes on the surface of the 36°Y-cut LiNbO3 piezoelectric material. The sensitivity of the fabricated sensor is 17.5 mV/kPa. Based on the CSMC 0.18 μm BCD process, a ring voltage-controlled oscillator (VCO) based on the current starvation delay element is designed as a wireless data transmission unit. The oscillator has two tuning terminals, which can realize frequency alignment and voltage threshold judgment. Using photolithography, wire bonding technology, etc., the heterogeneous integration of the Si-based chip and LiNbO3 piezoelectric device is realized. The experimental results show that below 1.8 V supply voltage, the oscillation frequency of the chip increases with the increase in the control terminal voltage, which provides an idea for solving the energy supply problem of an IoT system. This system has great application potential in the field of self-powered sensing.
Developing an in vitro validated 3D in silico internal carotid artery sidewall aneurysm model
Authors: Yi Hang , Yang Zifeng , Johnson Mark , Bramlage Luke , Ludwig Bryan 
Published: December 2022

Introduction: Direct quantification of hemodynamic factors applied to a cerebral aneurysm (CA) remains inaccessible due to the lack of technologies to measure the flow field within an aneurysm precisely. This study aimed to develop an in vitro validated 3D in silico patient-specific internal carotid artery sidewall aneurysm (ICASA) model which can be used to investigate hemodynamic factors on the CA pathophysiology.Methods: The validated ICASA model was developed by quantifying and comparing the flow field using particle image velocimetry (PIV) measurements and computational fluid dynamics (CFD) simulations. Specifically, the flow field characteristics, i.e., blood flowrates, normalized velocity profiles, flow streamlines, and vortex locations, have been compared at representative time instants in a cardiac pulsatile period in two designated regions of the ICASA model, respectively. One region is in the internal carotid artery (ICA) inlet close to the aneurysm sac, the other is across the middle of the aneurysmal sac.Results and Discussion: The results indicated that the developed computational fluid dynamics model presents good agreements with the results from the parallel particle image velocimetry and flowrate measurements, with relative differences smaller than 0.33% in volumetric flow rate in the ICA and relative errors smaller than 9.52% in averaged velocities in the complex aneurysmal sac. However, small differences between CFD and PIV in the near wall regions were observed due to the factors of slight differences in the 3D printed model, light reflection and refraction near arterial walls, and flow waveform uncertainties. The validated model not only can be further employed to investigate hemodynamic factors on the cerebral aneurysm pathophysiology statistically, but also provides a typical model and guidance for other professionals to evaluate the hemodynamic effects on cerebral aneurysms.
Dose-response relationship of Ralstonia solanacearum and potato in greenhouse and in vitro experiments
Authors: Eisfeld Carina , Schijven Jack F. , Kastelein Pieter , van Breukelen Boris M. , Medema Gertjan , Velstra Jouke , Teunis Peter F. M. , van der Wolf Jan M. 
Published: December 2022

Ralstonia solanacearum is the causative agent of bacterial wilt of potato and other vegetable crops. Contaminated irrigation water contributes to the dissemination of this pathogen but the exact concentration or biological threshold to cause an infection is unknown. In two greenhouse experiments, potted potato plants (Solanum tuberosum) were exposed to a single irrigation with 50 mL water (non-invasive soil-soak inoculation) containing no or 102 – 108 CFU/mL R. solanacearum. The disease response of two cultivars, Kondor and HB, were compared. Disease development was monitored over a three-month period after which stems, roots and tubers of asymptomatic plants were analyzed for latent infections. First wilting symptoms were observed 15 days post inoculation in a plant inoculated with 5x109 CFU and a mean disease index was used to monitor disease development over time. An inoculum of 5x105 CFU per pot (1.3x102 CFU/g soil) was the minimum dose required to cause wilting symptoms, while one latent infection was detected at the lowest dose of 5x102 CFU per pot (0.13 CFU/g). In a second set of experiments, stem-inoculated potato plants grown in vitro were used to investigate the dose-response relationship under optimal conditions for pathogen growth and disease development. Plants were inoculated with doses between 0.5 and 5x105 CFU/plant which resulted in visible symptoms at all doses. The results led to a dose-response model describing the relationship between R. solanacearum exposure and probability of infection or illness of potato plants. Cultivar Kondor was more susceptible to brown-rot infections than HB in greenhouse experiments while there was no significant difference between the dose-response models of both cultivars in in vitro experiments. The ED50 for infection of cv Kondor was 1.1x107 CFU. Results can be used in management strategies aimed to reduce or eliminate the risk of bacterial wilt infection when using treated water in irrigation.
A study of the factors which influence digital transformation in Kibs companies
Authors: Marino-Romero Jorge Alberto , Palos-Sanchez Pedro Ramiro , Velicia-Martin Félix Antonio , Rodrigues Ricardo Gouveia 
Published: December 2022

Eighteen interviews were used in this research to inductively conceptualize the factors that influence digital transformation (DT) in Kibs companies that provide multidisciplinary Knowledge Intensive Business Services. Two main groups were identified: factors of DT and use in the new digital environment. Using the findings obtained, a comparison was made with the existing literature and the most relevant aspects of DT as a disruptive phenomenon which can generate intra-organizational competitive advantage are exposed.ObjectiveTo identify the factors of innovation-oriented organizational management, generated by the collaboration of the professional grouping of Kibs companies through the systematization of knowledge, which serve to conceptually delimit the DT phenomenon. Ultimately, it is expected to establish recommendations for this type of companies based on providing services with high knowledge value that strive to digitally transform their businesses.Originalitythe paper contributes to advancing the conceptual understanding of DT through the study of Kibs companies, which remain understudied. Likewise, there is no known study that analyzes the factors that give rise to DT in a professional grouping of small Kibs companies. It is clear that this union of small companies generates a strong internal capacity for knowledge absorption, through daily interactions with clients and public administrations, which favors the process of implementing certain technological and strategic components that are beneficial for the development of professional activity and increases the propensity to innovate.Methodologyqualitative content was analysed using a grounded theory methodology including interviews with experts and the managers of the Kibs companies in the professional sector to obtain a solid basis that can be used to identify the most relevant factors of DT.Findings/resultsas DT is a multidimensional phenomenon of individual companies, this study presents a conceptual framework for the term with the strategic requirements of the market, organizations, public institutions and technological infrastructures of the professional sector. By considering the disruptive factors of digital development in this macroenvironment, conclusions can be made about the basic principles and effects of DT.
Genome-Wide Identification and Phylogenetic Analysis of TRP Gene Family Members in Saurian
Authors: Zhang Lin , Li Ning , Dayananda Buddhi , Wang Lihu , Chen Huimin , Cao Yunpeng 
Published: December 2022

The transient receptor potential plays a critical role in the sensory nervous systems of vertebrates in response to various mechanisms and stimuli, such as environmental temperature. We studied the physiological adaptive evolution of the TRP gene in the saurian family and performed a comprehensive analysis to identify the evolution of the thermo-TRPs channels. All 251 putative TRPs were divided into 6 subfamilies, except TRPN, from the 8 saurian genomes. Multiple characteristics of these genes were analyzed. The results showed that the most conserved proteins of TRP box 1 were located in motif 1, and those of TRP box 2 were located in motif 10. The TRPA and TRPV in saurian tend to be one cluster, as a sister cluster with TRPC, and the TRPM is the root of group I. The TRPM, TRPV, and TRPP were clustered into two clades, and TRPP were organized into TRP PKD1-like and PKD2-like. Segmental duplications mainly occurred in the TRPM subfamily, and tandem duplications only occurred in the TRPV subfamily. There were 15 sites to be under positive selection for TRPA1 and TRPV2 genes. In summary, gene structure, chromosomal location, gene duplication, synteny analysis, and selective pressure at the molecular level provided some new evidence for genetic adaptation to the environment. This result provides a basis for identifying and classifying TRP genes and contributes to further elucidating their potential function in thermal sensors.
Quadratic Admissibility for a Class of LTI Uncertain Singular Fractional-Order Systems with 0 < α < 2
Authors: Wang Yuying , Zhang Xuefeng , Boutat Driss , Shi Peng 
Published: December 2022

This paper provides a unified framework for the admissibility of a class of singular fractional-order systems with a given fractional order in the interval (0, 2). These necessary and sufficient conditions are derived in terms of linear matrix inequalities (LMIs). The considered fractional orders range from 0 to 2 without separating the ranges into (0, 1) and [1, 2) to discuss the admissibility. Moreover, the uncertain system with the fractional order in the interval (0, 2) is norm-bounded. The quadratic admissibility and general quadratic stability of the system are analyzed, and the equivalence between the two is proved. All the above can be expressed in terms of strict LMIs to avoid any singularity problem in the solution. Finally, the effectiveness of the method is illustrated by three numerical examples.