bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-infiltrating immune cell status predicts successful response to immune checkpoint inhibitors in renal cell carcinoma
Authors: Kazama Akira , Bilim Vladimir , Tasaki Masayuki , Anraku Tsutomu , Kuroki Hiroo , Shirono Yuko , Murata Masaki , Hiruma Kaede , Tomita Yoshihiko 
Published: May 2022

Abstract
Immune checkpoint inhibitors (ICI) have dramatically changed the treatment of metastatic renal cell carcinoma (mRCC). Although many studies have reported biomarkers as predicting the efficacy of ICI in mRCC, they remain controversial and have challenges to apply in real-world practice. We evaluated prognostic significance of multiple molecules associated with tumor immunity in patients treated with ICI. The molecules were detected in tumor tissues by immunohistochemical staining. We identified CD8 positive T cells and CD68 positive macrophages infiltrating into the tumor tissue as a significant favorable prognostic factors for ICI treatment. Conversely, high expression of CD4-positive T cells was associated with poor response to ICI. Furthermore, we demonstrated that scoring for the expression status of these three molecules provides a remarkably accurate biomarker in patients with mRCC. Even the classical approach of immunohistochemistry could predict the outcome of ICI treatment by assessing the combined status of tumor-infiltrating immune cells.
Construction of Remote Patient Perceived Value Satisfaction Model with Online Medical Service for Specialties Based on ACSIM and TAM
Authors: Zhemin Zhang , Alturas Bráulio 
Published: May 2022

Abstract
With the development of medical treatment partnership and “internet + medical service” in China, this study proposes a remote patient perceived value satisfaction model (RPPVSM) with online medical service for specialties from the perspective of patient perceived value. Taking Shanghai Pulmonary Hospital Specialist Alliance (SPHSA) as the research subject, RPPVSM was constructed based on ACSI and TAM. Structural Equation Modeling (SEM) was modified to have a better degree of fitness and validation outcomes of the hypothesis as follows: Perceived ease of use has a significantly positive impact on perceived value with coefficient being 0.248; perceived usefulness has a significantly positive impact on the satisfaction with coefficient being 0.577; perceived value has a significantly positive impact on satisfaction with coefficient being 0.163. Perceived synergy has a significantly positive impact on perceived value with coefficient of 0.547; perceived ease of use will have a significantly positive impact on satisfaction through the perceived value variable with coefficient of mediation being 0.094; perceived synergy has a significant impact on satisfaction through perceived value with mediation coefficient being 0.196. The results suggest that the inclusion of the patient’s perception value index in the medical information platform is conducive to the construction of RPPVSM. Note: This study is not a clinical trial.
Contributions and synaptic basis of diverse cortical neuron responses to task performance
Authors: Froemke Robert , Insanally Michele , Albanna Badr , Toth Jack , DePasquale Brian , Fadaei Saba , Gupta Trisha , Kuchibhotla Kishore , Rajan Kanaka 
Published: May 2022

Abstract

Neuronal responses during behavior are diverse, ranging from highly reliable ‘classical’ responses to irregular or seemingly-random ‘non-classically responsive’ firing. While a continuum of response properties is frequently observed across neural systems, little is known about the synaptic origins and contributions of diverse response profiles to network function, perception, and behavior. Here we use a task-performing, spiking recurrent neural network model incorporating spike-timing-dependent plasticity that captures heterogeneous responses measured from auditory cortex of behaving rodents. Classically responsive and non-classically responsive model units contributed to task performance via output and recurrent connections, respectively. Excitatory and inhibitory plasticity independently shaped spiking responses and task performance. Local patterns of synaptic inputs predicted spiking response properties of network units as well as the responses of auditory cortical neurons from in vivo whole-cell recordings during behavior. Thus a diversity of neural response profiles emerges from synaptic plasticity rules with distinctly important functions for network performance.
Leaf wounding and jasmonic acid act synergistically to enable efficient Agrobacterium-mediated transient transformation of Persea americana
Authors: Salazar-González Jorge , Castro-Medina Manuela , Martínez-Terrazas Eduardo , Casson Stuart Anthony , Urrea-Lopez Rafael 
Published: May 2022

Abstract
Avocado, Persea americana Mill, is one of the most traded tropical fruits in the international market. Here, we report transient transformation of avocado leaves via agroinfiltration with the LBA4404 strain of Agrobacterium tumefaciens and constructs encoding the synthetic betalain gene biosynthesis cassette, RUBY, or GFP. The efficiency of transformation was dependent on leaf age, whilst microwounding and jasmonic acid treatments significantly enhanced transformation, acting synergistically to improve avocado transformation. This is the first report on Agrobacterium-mediated transient transformation on avocado leaves. It provides a useful tool in plant molecular and cellular biology research and has the potential to facilitate new capabilities to the genomics research community of this ancestral angiosperm.
Determination of 20 neonicotinoid insecticides and their metabolites in infant foods by a modified QuEChERS method combined with HPLC-MS/MS
Authors: Guo Liqiang , Li Kai , Zhang Jinling , Tian Guoning , Ke Wang , Li Yajing 
Published: May 2022

Abstract
A rapid, effective, and reliable method for the simultaneous detection of 20 neonicotinoids and their metabolites in infant foods has been developed using liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). To improve the accuracy and precision of the method, different extraction solvents, extraction methods, and adsorbents were evaluated to achieve a better recovery and clean-up effect. Under optimized conditions, the samples were extracted with acetic acid acidified acetonitrile/ethyl acetate by ultrasonication, and then were cleaned with reduced graphene oxide@Fe3O4 (rGO@Fe3O4) and primary and secondary amine (PSA) through a QuEChERS step. A matrix-matched calibration method was applied for quantification. In three different food matrixes (vegetable & fruit cookies, grain rice cereals, and vegetable purees), all the target compounds showed good linearity, both with values of r2 > 0.99. The average recovery of all neonicotinoids ranges from 68.0%~106.5% (vegetable & fruit cookies), 70.4%~105.4% (grain rice cereals), and 71.9%~107.4% (vegetable purees). Relative standard deviations were all < 15% for intraday and interday precision. The values of limit of detection and limit of quantification were, respectively, ranging from 0.02–0.35 µg kg− 1 and 0.1-1.0 µg kg− 1. The presented method was applied to the analysis of real samples.
Dietary tryptophan catabolite released by intratumoral Lactobacillus reuteri facilitates αPD-L1 therapy
Authors: Bender Mackenzie , McPherson Alex , Phelps Catherine , Rana Mohit , Pandey Surya , Shapira Jake , Gocher Angela , Mullett Steven , Wendell Stacy , Davar Diwakar , Hinterleitner Reinhard , Vignali Dario , Joglekar Alok , Zarour Hassane , Meisel Marlies 
Published: May 2022

Abstract
The gut microbiome has been identified as a critical factor influencing cancer patient responses to immune checkpoint inhibitor (ICI) therapy; however, the underlying mechanisms of how gut microbes modulate ICI therapy efficacy remain enigmatic. Here, we show that gut-commensal Lactobacillus reuteri (L. reuteri) translocates to melanoma tumors where it mediates antitumor interferon-γ-producing CD8 T cell (Tc1 cell) immunity and facilitates ICI therapy via its released aryl hydrocarbon receptor (AhR) ligand, indole-3-aldehyde (I3A). This dietary tryptophan (Trp) catabolite is necessary and sufficient for antitumor immunity, and AhR signaling within CD8 T cells is required for L. reuteri to suppress melanoma growth. Further, a Trp-enriched diet potentiated L. reuteri- and ICI-induced antitumor immunity. Finally, we uncovered a role of I3A in promoting ICI therapy responses and survival in advanced melanoma patients. Collectively, our findings elucidate a novel crosstalk within the tumor microenvironment between the microbial metabolite I3A and CD8 T cells that facilitates ICI therapy efficacy, paving the way for dietary- and probiotic-based cancer therapeutics.
Effect of the addition of sweet red pepper (Capsicum annuum) oleoresin and yellow tree tomato (Solanum betaceum Cav.) juice on quality parameters and shelf life of margarines
Authors: Martínez-Girón Jader 
Published: May 2022

Abstract
The objective of this study was to evaluate different quality parameters and the oxidative stability of a vegetable margarine made with different concentrations of sweet red pepper (Capsicum annuum) oleoresin and yellow tree tomato (Solanum betaceum Cav.) juice using ultrasound technology. Oleoresin was added as an enriching agent in the fat phase at different concentrations: 100, 200 and 300 ppm, and tree tomato juice was added as an enriching agent in the aqueous phase at 5, 10 and 15%. Physicochemical, microbiological, sensory and oxidative stability tests were carried out. The results showed that sweet red pepper oleoresin is a significant source of total carotenoids 1473 ± 10.24 mg/100 g, total phenolic compounds 1158 ± 8.65 mg GAE/100 g, flavonoids 814 ± 7.63 mg CE/100 g and ASTA color 765 ± 3.51, additionally tree tomato juice is a source of vitamin C 22.34 ± 1.51 mg AA/100 g. The addition of these two natural extracts improved notably the antioxidant activity, peroxides index and p-anisidine during storage of the developed margarine formulations. The results of the physicochemical and microbiological tests showed that the vegetable margarine developed met the quality standards established for a commercial margarine. The qualification of the sensory analysis indicated that the evaluated attributes were acceptable in all the formulations, being the margarine elaborated with the addition of 200 ppm of sweet red pepper oleoresin and 10% of tree tomato juice, the one that presented the best sensory qualification.
Global Research Trends on Surgery in Uterine Cervical Neoplasms: A Bibliometric Analysis via CiteSpace
Authors: Haibier Kadierguli , Xu Jinbin , Sun Ciming , Dai Fuyang , Liang Kangni , Zhu Qin , Haibier Kailibinuer , Wubuli Reziwanguli 
Published: May 2022

Abstract
Objectives: To identify the cooperation of authors, countries, institutions and explore the hot topics’ prospects regarding research of surgical procedure in uterine cervical neoplasms.Methods: Publications on research of surgical treatment of uterine cervical neoplasms were retrieved from the Web of Science Core Collection (WoSCC). Bibliometric analysis were performed by CiteSpace software. Visualized network maps were performed to evaluate the collaborations between different authors, countries, institutions, and keywords.Results: A total of 1381 articles related to study were identified. An increasing number of publications were observed from 2006 to 2022, and the number of publications were over 100 in 2020 and 2021. Gynecologic Oncology (715 times) was the most co-cited journal. Active collaborations among the top authors were observed. Scambia G(17 papers) was the top most productive authors and Ramirez PT with the largest numbers of citations (155 co-citations) in this field during the past decades. The USA was the leading contributor in this field with 342papers. Active cooperation between countries and between institutions was observed. The main hot topics in the last three years included matters related to uterine cervical neoplasms, quality of life (QoL), guideline, and gynecologic surgical procedure.Conclusion: This study provides a comprehensive overview of surgery in uterine cervical neoplasms, allowing relevant authors and research teams to recognize the current research status in this field and provide a reference for formulating future research directions as well.
Down-regulation of circular RNA C3 in hepatocellular carcinoma and its potential clinical implication
Authors: Zuhua Li , Min Luo , Yidou Shi , Keqin Qing , Hongxia Li , Weiyang He 
Published: May 2022

Abstract
Background
Hepatocellular carcinoma (HCC) is a common primary malignant tumor with an increasing incidence worldwide. Circular RNAs (circRNAs) have been demonstrated in playing significant roles in the processes of physiology and pathology. However, the expression patterns and function of circRNAs in HCC remain unclear.
Methods
The expression of circular RNA C3 (circC3) in HCC tissues, para-cancer tissues and normal liver tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and their associations with clinicopathological features and prognosis were analyzed. Using in vitro models, the role of circC3 in HCC proliferation, apoptosis and glycolysis was evaluated.
Results
Compared with para-carcinoma tissues and normal tissues, CircC3 expression was significantly reduced in HCC tissues. The downregulation of CircC3 levels in HCC was significantly correlated with tumor number (p < 0.001), tumor size (p < 0.001), tumor invasion (p = 0.026) and TNM stage (p = 0.024). Cell experiments revealed that overexpression of circC3 resulted in inhibited proliferation, increased apoptosis and downregulated the expression of GLUT1 and LDHA. Lower expression of circC3 was significantly associated with poor prognosis. ROC curves showed that the circC3 and circSOX5 serve as a biomarker to distinguish HCC from para-carcinoma tissues.
Conclusions
Our study revealed that circC3 could inhibit HCC progress by promoting apoptosis, inhibiting proliferation and glycolysis. CircC3 may serve as a potential diagnosis and prediction biomarker for HCC.
A Novel Tensor Decomposition Networks for Recommender Systems via Adaptive Moment Estimation Method
Authors: Xia Xunpeng , Zhang Rongfu , Yao Xufeng , Huang Gang , Tang Tiequn 
Published: May 2022

Abstract
The tag, text, and other multiple auxiliary information are acquired in the social networks. The multi-source auxiliary information is heterogeneous information. A large amount of heterogeneous information would result in extremely difficult to analyze. This paper proposes a deep learning network for multi-heterogeneous information processing. The main idea of the our deep learning network is threefold: (1) using tensor decomposition algorithms to process standard encoded data; (2) mining potential factor from heterogeneous data using multi-layer learning networks. Symmetric non-negative potential factor optimization algorithm can effectively predict the missing values of high dimensional sparse data; (3) adaptive moment estimation optimization algorithm is used to replace the traditional first-order optimization algorithm for stochastic gradient descent(SGD) process. The aggregation of heterogeneous data is essentially a minimization problem of multiple parameters. The rate of the model convergence can be improved by adaptive moment estimation in the training $ Fully documented templates are available in the elsarticle package on CTAN. stage. Simultaneously, it can solve the problem of parameter optimization of large-scale data and processing of non-stationary targets. Finally, experimental results on public vaildation datasets are given to verigy the effectiveness of our proposed blend network.
The outcome of more than 3 decades of orphan drug development in alpha-1-antitypsin deficiency – a cross sectional analysis of the FDA Orphan Drug Product designation database
Authors: Trudzinski Franziska C , Presotto Maria Ada , Buck Emanuel , Herth Felix J. , Ries Markus 
Published: May 2022

Abstract
Introduction Alpha-1 antitrypsin deficiency (AATD, OMIM #613490) is a rare metabolic disorder affecting lungs and liver. The purpose of this study is to assess the impact of the US orphan drug act on AATD by providing a quantitative clinical-regulatory insight into the status of FDA orphan drug approvals and designations for compounds intended to treat AATD.Methods: Cross-sectional analysis of the FDA database for orphan drug designations. Primary endpoint: orphan drug approvals. Secondary endpoint: orphan drug designations by the FDA. Close of database: 16 July 2021. STROBE criteria were respected.Results Primary: one compound, alpha-1-proteinase inhibitor (human) was approved as an orphan drug in 1987 with market exclusivity until 1994.Secondary: sixteen compounds received FDA orphan drug designation including protein, anti-inflammatory, mucolytic, gene, or cell therapy.Conclusion: Drug development activities in the field were comparable to other rare conditions and led to the FDA-approval of one compound, based on a relatively simple technological platform. The current unmet medical need is to fill the gap of missing agents for therapy of extrapulmonary manifestations of AATD. Orphan drug development is actually focusing on (1) diversified recombinant AAT production platforms, and (2) innovative gene therapies, which may, encompass a more holistic therapeutic approach.
Machine Learning approach for Numerical technique for classifying Cysts and Malignant Tumors in Breast
Authors: Makrariya Akshara , Musheer Rabia 
Published: May 2022

Abstract
Tumor is an abnormal tissue which can be appeared at any part of the body. It can be classified to either benign or malignant. One of the most common women's tumors that infest the breast. Various benign disorders like development of cysts in woman’s breast occur due to hormonal changes and are at the risk of becoming malignant. A number of thermal models are reported to differentiate between normal and malignant tissues of breast. But no thermal model is reported in study the effect of benign disorders on the literature to distinguish between benign and malignant disorders in woman’s breast. An attempt has been made in this paper to study the thermal disturbances caused by cysts and malignant tumors in the fat tissues of woman’s breast. The model is developed for a two-dimensional steady state case using penne’s bio heat equation and incorporating parameters like thermal conductivity, blood mass flow rate and self-controlled metabolic heat generation. The appropriate adiabatic boundary conditions have been framed for various environmental conditions. The finite element method has been employed to obtain the solution. The results have been obtained for different sizes of spherical shaped cysts and different depth of tissues in hemispherical shaped woman’s breast. The relation of size and position of the cysts have been studied with the thermal distribution in various tissues layers of the woman’s breast. The comparison of thermal profiles for cysts and malignant tumors in woman’s breast has been performed. A contrast in thermal behavior of cyst and malignant tumor in woman’s breast is observed which can be useful to distinguish between the malignant tumor and cyst in woman’s breast to prevent false positive test for malignant tumor. Accordingly, this study found that there are various factors that could affect the cancer classification and prediction. Therefore in this study, Breast cancer data classification have been done using three classification techniques which are Artifical Neural Network (ANN), Support Vector Machine (SVM), and Random Forest (RF) in order to improve the performance of the model trained the model with selected features according to the analysis done.
Deletion of PLD2 Alleviates LPS Induced Acute Lung Injury by Inhibiting STAT3 Phosphorylation and Regulating Endothelial Tight Junctions
Authors: Qian Tiantian , Qi Boyang , Fei Yuxin , Li Jun , Luo Liqing , Song Yutong , Sheng Shurui , Lv Bingjie , Huang Xiao , Wang Xiaozhi 
Published: May 2022

Abstract
Background: Acute respiratory distress syndrome (ARDS) is the leading cause of acute respiratory failure. Endothelial cell damage and increased permeability are critical in developing acute lung injury (ALI). Phospholipase D2 (PLD2) and its metabolite phosphatidic acid (PA) regulate many physiological activities in cells, such as intracellular vesicle transport and cytoskeletal protein recombination, disrupting cell barrier integrity. However, the exact mechanism remains unexplored. Therefore, we elucidated the role and action mechanism of PLD2 in lipopolysaccharide (LPS)-induced endothelial cell integrity.Methods: We used wild-type (WT) and PLD2 knockout (PLD2-/-) mouse models of LPS-induced ALI. Altered pulmonary endothelial permeability were assessed using histopathological analysis and measuring the lung wet/dry weight ratio. The relative permeability of human umbilical vein endothelial cells (HUVECs), a pulmonary vascular endothelial cell culture model, was assessed using transwell chamber assays for FITC-dextran and TEER transcellular resistance. The PA content, a downstream product of PLD2, was detected using ELISA, and the mRNA expression of tight junction proteins was detected by real-time quantitative polymerase chain reaction (RT-PCR). Changes in tight junction protein levels and STAT3 pathway phosphorylation, a critical endothelial barrier component, were assessed using immunofluorescence and western blotting analyses in vivo and in vitro.Results: PLD2-/- could significantly improve the histopathological changes, lung wet-dry ratio, and endothelial cell permeability in LPS-induced ALI mice. Simultaneously, PLD2-/- could reduce PA-induced STAT3 phosphorylation, resulting in reduced endothelial tight junction degradation.Conclusion: Loss or inhibition of PLD2 significantly inhibits tight junction injury and alleviates lung injury. LPS-induced PA production leads to STAT3 pathway phosphorylation and tight junction protein targeting, resulting in increased barrier permeability. Collectively, PA is crucial in ARDS pathogenesis.
Polymeric microneedle-based platform enables simultaneous delivery of cancer immunomodulatory drugs and detection of biomarkers in the skin
Authors: Dosta Pere , Puigmal Núria , Cryer Alexander M. , Rodríguez Alma Lorena , Scott Ella , Weissleder Ralph , Miller Miles A. , Artzi Natalie 
Published: May 2022

Abstract

Background
Intratumorally injected immune-modulating therapies have advanced to clinical trials over the last few years. Despite some reports on efficacy of different approaches, there remains a need for improved delivery strategies and non-invasive monitoring of anti-tumor effects.
Methods
This work reports a microneedle (MN) platform capable of simultaneous delivery of immune activators and collection of sample fluids to monitor therapeutic responses. While either approach has shown promise, the combination of the two into one theranostic platform has been previously untested. MNs were synthesized out of hyaluronic acid (HA) and loaded with a model immunomodulatory drug, CpG nanoparticles (TLR9 agonist), for cancer therapy. The therapeutic response was monitored by temporal analysis of entrapped immune cells in the MNs following their retrieval and digestion.
Results
Transdermal delivery of CpG-NPs induced anti-tumor immune responses in multiple syngeneic mouse cancer models. CpG-loaded MN stimulated innate immune cells and reduced tumor growth. Intravital microscopy showed spatiotemporal co-localization and sustained deposition of CpG-NPs delivered with MN in tumors. Analysis of sampled cells within the MNs revealed similar immune signature to that seen in the bulk tumor homogenate. In addition, immune surveillance using MNs showed an increase in the infiltrates of effector T cells after treatment.
Conclusions
We validated the theranostic potential of our hydrogel-based MNs in dually supporting transdermal drug delivery and temporal monitoring of tumor immune composition in a minimally invasive manner. This platform has the potential to deliver a range of combination therapies while detecting biomarkers.