bluuebunny/crossref_metadata_2025 huggingface dataset:
Graph Co-Attentive Session-based Recommendation
Authors: Pan Zhiqiang , Cai Fei , Chen Wanyu , Chen Honghui
Published: December 2021

Session-based recommendation aims to generate recommendations merely based on the ongoing session, which is a challenging task. Previous methods mainly focus on modeling the sequential signals or the transition relations between items in the current session using RNNs or GNNs to identify user’s intent for recommendation. Such models generally ignore the dynamic connections between the local and global item transition patterns, although the global information is taken into consideration by exploiting the global-level pair-wise item transitions. Moreover, existing methods that mainly adopt the cross-entropy loss with softmax generally face a serious over-fitting problem, harming the recommendation accuracy. Thus, in this article, we propose a Graph Co-Attentive Recommendation Machine (GCARM) for session-based recommendation. In detail, we first design a Graph Co-Attention Network (GCAT) to consider the dynamic correlations between the local and global neighbors of each node during the information propagation. Then, the item-level dynamic connections between the output of the local and global graphs are modeled to generate the final item representations. After that, we produce the prediction scores and design a Max Cross-Entropy (MCE) loss to prevent over-fitting. Extensive experiments are conducted on three benchmark datasets, i.e., Diginetica, Gowalla, and Yoochoose. The experimental results show that GCARM can achieve the state-of-the-art performance in terms of Recall and MRR, especially on boosting the ranking of the target item.
Reinforced Neighborhood Selection Guided Multi-Relational Graph Neural Networks
Authors: Peng Hao , Zhang Ruitong , Dou Yingtong , Yang Renyu , Zhang Jingyi , Yu Philip S.
Published: December 2021

Graph Neural Networks (GNNs) have been widely used for the representation learning of various structured graph data, typically through message passing among nodes by aggregating their neighborhood information via different operations. While promising, most existing GNNs oversimplify the complexity and diversity of the edges in the graph and thus are inefficient to cope with ubiquitous heterogeneous graphs, which are typically in the form of multi-relational graph representations. In this article, we propose
RioGNN
, a novel Reinforced, recursive, and flexible neighborhood selection guided multi-relational Graph Neural Network architecture, to navigate complexity of neural network structures whilst maintaining relation-dependent representations. We first construct a multi-relational graph, according to the practical task, to reflect the heterogeneity of nodes, edges, attributes, and labels. To avoid the embedding over-assimilation among different types of nodes, we employ a label-aware neural similarity measure to ascertain the most similar neighbors based on node attributes. A reinforced relation-aware neighbor selection mechanism is developed to choose the most similar neighbors of a targeting node within a relation before aggregating all neighborhood information from different relations to obtain the eventual node embedding. Particularly, to improve the efficiency of neighbor selecting, we propose a new recursive and scalable reinforcement learning framework with estimable depth and width for different scales of multi-relational graphs.
RioGNN
can learn more discriminative node embedding with enhanced explainability due to the recognition of individual importance of each relation via the filtering threshold mechanism. Comprehensive experiments on real-world graph data and practical tasks demonstrate the advancements of effectiveness, efficiency, and the model explainability, as opposed to other comparative GNN models.
Evaluation of Helium Plasma Surface Modification on Tensile Bond Strength of Denture Base Materials: A Scanning Electron Microscope Study
Authors: Akay Canan , Avukat Esra Nur , Topcu Mirac Berke , Mumcu Emre , Pat Suat
Published: December 2021

The purpose of this study was to compare the effect of helium plasma treatment on tensile bond strength between polymethylmethacrylate and soft liner material. For the tensile test, acrylic samples (30 × 10 × 10 mm3; n = 100) were prepared. Acrylic samples were divided into five surface groups (n = 10/group) and treated by different concentrations of helium plasma: G I: Control group (untreated), G II: 100% Helium plasma-treated group, G III: 90% Helium plasma-treated group, G IV: 85% Helium plasma-treated group, G V: 80% Helium plasma-treated group. After plasma treatment, the soft liner was processed between two acrylic resin blocks according to the manufacturer’s instructions and polymerized. The surface properties were evaluated by scanning electron microscopy and atomic force microscopy. All samples were submitted to a tensile test using a universal testing machine. After failure, the surface properties were evaluated by stereomicroscope. One-way analysis of variance was used to compare the groups. p < 0.05 value was considered statistically significant. While the highest mean tensile bond strength value was obtained with the G III (1.56 ± 0.13 MPa), the lowest value was observed with the G I (0.95 ± 0.2 MPa). In addition, it was observed that the surface roughness increased the most in G III.
GRK2 promotes activation of lung fibroblast cells and contributes to pathogenesis of pulmonary fibrosis through increasing Smad3 expression
Authors: Li Yanhui , Sun Ying , Wu Nan , Ma Haichun
Published: December 2021

Pulmonary fibrosis is a chronic, progressive, and irreversible interstitial lung disease. Transforming growth factor-β1 (TGF-β1) plays a major role in lung fibroblast cell differentiation to myofibroblast cells and production of extracellular matrix, which are hallmarks of pulmonary fibrosis. G protein-coupled receptor kinase-2 (GRK2) has been shown to play controversial roles in TGF-β1-induced signal transduction in different cell types; however, the role of GRK2 in TGF-β1-induced activation of lung fibroblast cells and development of pulmonary fibrosis has not been revealed. In this study, we found that GRK2 levels were increased in lungs and isolated fibroblast cells in a murine model of pulmonary fibrosis, as well as TGF-β1-treated lung fibroblasts. GRK2 levels were not changed in lungs in the injury phase of pulmonary fibrosis. Posttreatment with GRK2 inhibitor reduced extracellular matrix (ECM) accumulation in lungs in bleomycin-challenged mice, suggesting that GRK2 activation contributes to the progressive phase of pulmonary fibrosis. Inhibition or downregulation of GRK2 attenuates fibronectin, collagen, and α-smooth muscle actin expression in TGF-β1-induced lung fibroblast cells or myofibroblast cells isolated from patients with pulmonary fibrosis. Furthermore, we showed that GRK2 regulates Smad3 expression, indicating that inhibition of GRK2 attenuates ECM accumulation through downregulation of Smad3 expression. This study reveals that GRK2 is a therapeutic target in treating pulmonary fibrosis and inhibition of GRK2 dampens pulmonary fibrosis by suppression of Smad3 expression, eventually attenuating TGF-β1 signal pathway and ECM accumulation.
The highly packed and dehydrated structure of preformed unexposed human pulmonary surfactant isolated from amniotic fluid
Authors: Castillo-Sánchez José Carlos , Roldán Nuria , García-Álvarez Begoña , Batllori Emma , Galindo Alberto , Cruz Antonio , Pérez-Gil Jesús
Published: December 2021

By coating the alveolar air-liquid interface, lung surfactant overwhelms surface tension forces that, otherwise, would hinder the lifetime effort of breathing. Years of research have provided a picture of how highly hydrophobic and specialized proteins in surfactant promote rapid and efficient formation of phospholipid-based complex three-dimensional films at the respiratory surface, highly stable under the demanding breathing mechanics. However, recent evidence suggests that the structure and performance of surfactant typically isolated from bronchoalveolar lung lavages may be far from that of nascent, still unused, surfactant as freshly secreted by type II pneumocytes into the alveolar airspaces. In the present work, we report the isolation of lung surfactant from human amniotic fluid (amniotic fluid surfactant, AFS) and a detailed description of its composition, structure, and surface activity in comparison to a natural surfactant (NS) purified from porcine bronchoalveolar lavages. We observe that the lipid/protein complexes in AFS exhibit a substantially higher lipid packing and dehydration than in NS. AFS shows melting transitions at higher temperatures than NS and a conspicuous presence of nonlamellar phases. The surface activity of AFS is not only comparable with that of NS under physiologically meaningful conditions but displays significantly higher resistance to inhibition by serum or meconium, agents that inactivate surfactant in the context of severe respiratory pathologies. We propose that AFS may be the optimal model to study the molecular mechanisms sustaining pulmonary surfactant performance in health and disease, and the reference material to develop improved therapeutic surfactant preparations to treat yet unresolved respiratory pathologies.
Short palate, lung, and nasal epithelial clone 1 (SPLUNC1) level determines steroid-resistant airway inflammation in aging
Authors: Jaiswal Anil Kumar , Yadav Jyoti , Makhija Sangeet , Sandey Maninder , Suryawanshi Amol , Mitra Amit Kumar , Mishra Amarjit
Published: December 2021

Asthma and its heterogeneity change with age. Increased airspace neutrophil numbers contribute to severe steroid-resistant asthma exacerbation in the elderly, which correlates with the changes seen in adults with asthma. However, whether that resembles the same disease mechanism and pathophysiology in aged and adults is poorly understood. Here, we sought to address the underlying molecular mechanism of steroid-resistant airway inflammation development and response to corticosteroid (Dex) therapy in aged mice. To study the changes in inflammatory mechanism, we used a clinically relevant treatment model of house-dust mite (HDM)-induced allergic asthma and investigated lung adaptive immune response in adult (20–22 wk old) and aged (80–82 wk old) mice. Our result indicates an age-dependent increase in airway hyperresponsiveness (AHR), mixed granulomatous airway inflammation comprising eosinophils and neutrophils, and Th1/Th17 immune response with progressive decrease in frequencies and numbers of HDM-bearing dendritic cells (DC) accumulation in the draining lymph node (DLn) of aged mice as compared with adult mice. RNA-Seq experiments of the aged lung revealed short palate, lung, and nasal epithelial clone 1 (SPLUNC1) as one of the steroid-responsive genes, which progressively declined with age and further by HDM-induced inflammation. Moreover, we found increased glycolytic reprogramming, maturation/activation of DCs, the proliferation of OT-II cells, and Th2 cytokine secretion with recombinant SPLUNC1 (rSPLUNC1) treatment. Our results indicate a novel immunomodulatory role of SPLUNC1 regulating metabolic adaptation/maturation of DC. An age-dependent decline in the SPLUNC1 level may be involved in developing steroid-resistant airway inflammation and asthma heterogeneity.
Low-dose fentanyl does not alter muscle sympathetic nerve activity, blood pressure, or tolerance during progressive central hypovolemia
Authors: Huang Mu , Watso Joseph C. , Belval Luke N. , Cimino Frank A. , Fischer Mads , Jarrard Caitlin P. , Hendrix Joseph M. , Laborde Carmen Hinojosa , Crandall Craig G.
Published: December 2021

Hemorrhage is a leading cause of battlefield and civilian trauma deaths. Several pain medications, including fentanyl, are recommended for use in the prehospital (i.e., field setting) for a hemorrhaging solider. However, it is unknown whether fentanyl impairs arterial blood pressure (BP) regulation, which would compromise hemorrhagic tolerance. Thus, the purpose of this study was to test the hypothesis that an analgesic dose of fentanyl impairs hemorrhagic tolerance in conscious humans. Twenty-eight volunteers (13 females) participated in this double-blinded, randomized, placebo-controlled trial. We conducted a presyncopal limited progressive lower body negative pressure test (LBNP; a validated model to simulate hemorrhage) following intravenous administration of fentanyl (75 µg) or placebo (saline). We quantified tolerance as a cumulative stress index (mmHg·min), which was compared between trials using a paired, two-tailed t test. We also compared muscle sympathetic nerve activity (MSNA; microneurography) and beat-to-beat BP (photoplethysmography) during the LBNP test using a mixed effects model [time (LBNP stage) × trial]. LBNP tolerance was not different between trials (fentanyl: 647 ± 386 vs. placebo: 676 ± 295 mmHg·min, P = 0.61, Cohen’s d = 0.08). Increases in MSNA burst frequency (time: P < 0.01, trial: P = 0.29, interaction: P = 0.94) and reductions in mean BP (time: P < 0.01, trial: P = 0.50, interaction: P = 0.16) during LBNP were not different between trials. These data, the first to be obtained in conscious humans, demonstrate that administration of an analgesic dose of fentanyl does not alter MSNA or BP during profound central hypovolemia, nor does it impair tolerance to this simulated hemorrhagic insult.
Small directional treadmill perturbations induce differential gait stability adaptation
Authors: Li Jinfeng , Huang Helen J.
Published: December 2021

Little is known about if and how humans can adapt to small magnitude perturbations experienced on a stride-by-stride basis during walking. Here, we show that even small perturbations disrupted gait stability and that subjects could still adapt their reactive balance control. Depending on the perturbation direction, subjects might prefer adjusting their foot placement over their center of mass and vice versa. These findings could help potentially tune balance training to target specific aspects of balance.
Cloning and Embryo Splitting in Mammalians: Brief History, Methods, and Achievements
Authors: Rahbaran Mohaddeseh , Razeghian Ehsan , Maashi Marwah Suliman , Jalil Abduladheem Turki , Widjaja Gunawan , Thangavelu Lakshmi , Kuznetsova Mariya Yurievna , Nasirmoghadas Pourya , Heidari Farid , Marofi Faroogh , Jarahian Mostafa
Published: December 2021

Embryo splitting is one of the newest developed methods in reproductive biotechnology. In this method, after splitting embryos in 2-, 4-, and even 8-cell stages, every single blastomere can be developed separately, but the embryos are genetically identical. Embryo splitting, as an approach in reproductive cloning, is extensively employed in reproductive medicine studies, such as investigating human diseases, treating sterility, embryo donation, and gene therapy. In the present study, cloning in mammalians and cloning approaches are briefly reviewed. In addition, embryo splitting and the methods commonly used in embryo splitting and recent achievements in this field, as well as the applications of embryo splitting into livestock species, primate animals, and humans, are outlined. Finally, a perspective of embryo splitting is provided as the conclusion.
EZH2 Might Affect Macrophage Chemotaxis and Anti-Inflammatory Factors by Regulating CCL2 in Dental Pulp Inflammation
Authors: Hu Ziqi , Chen Yingyi , He Jie , Liu He , Hui Tianqian
Published: December 2021

Objectives. We aimed to evaluate the effects of Enhancer of Zeste Homolog 2 (EZH2) on regulation of macrophage migration and expression of anti-inflammatory genes in pulpitis. Methods. Dental pulp inflammation was verified by histology in rat pulpitis model induced by lipopolysaccharide (LPS). Immunohistochemistry staining was used to detect changes of the expression of EZH2 and tumor necrosis factor alpha (TNF-α) in dental pulp inflammation. The expression of EZH2, CCL2, and cluster of differentiation 68 (CD68: macrophage surface marker) was measured by immunofluorescence staining. The effect of EZH2 on microphage migration was assessed by cell migration assay. The expressions of anti-inflammatory cytokine interleukins (IL-4 and IL-10) and transforming growth factor-β (TGF-β) in HDPCs which were treated by EZH2 complex, CCL2 complex, and CCL2 antibody were examined by quantitative real-time polymerase chain reaction (q-PCR). Results. The expression of TNF-α gradually increased in dental pulp inflammation. The expression of EZH2 in dental pulp decreased in 8 hours after LPS stimulation. However, the expression of EZH2 gradually increased in dental pulp after 1 day stimulation by LPS. The results of immunofluorescence staining showed that the expressions of EZH2, CCL2, and CD68 were significantly upregulated in dental pulp inflammation of rats. EZH2 could enhance macrophage migration. And the chemotactic activity of macrophages exposed to supernatants of EZH2-treated HDPCs could be inhibited by CCL2 inhibition. In addition, EZH2 suppressed the expression of anti-inflammatory genes, but CCL2 inhibition reversed the downregulation of anti-inflammatory factors, including IL-4 and TGF-β in HDPCs. Conclusions. EZH2 might affect chemotaxis of macrophages and the expression of anti-inflammatory factors by regulating CCL2. EZH2 plays an important role in the development of dental pulp inflammation, and it might be as a target for treatment of pulpitis.
Evaluation of Ischemic Penumbra in Stroke Patients Based on Deep Learning and Multimodal CT
Authors: Liu Changhua , Qin Tao , Liu Liangjin
Published: December 2021

In order to investigate the value of multimodal CT for quantitative assessment of collateral circulation, ischemic semidark zone, core infarct volume in patients with acute ischemic stroke (AIS), and prognosis assessment in intravenous thrombolytic therapy, segmentation model which is based on the self-attention mechanism is prone to generate attention coefficient maps with incorrect regions of interest. Moreover, the stroke lesion is not clearly characterized, and lesion boundary is poorly differentiated from normal brain tissue, thus affecting the segmentation performance. To address this problem, a primary and secondary path attention compensation network structure is proposed, which is based on the improved global attention upsampling U-Net model. The main path network is responsible for performing accurate lesion segmentation and outputting segmentation results. Likewise, the auxiliary path network generates loose auxiliary attention compensation coefficients, which compensate for possible attention coefficient errors in the main path network. Two hybrid loss functions are proposed to realize the respective functions of main and auxiliary path networks. It is experimentally demonstrated that both the improved global attention upsampling U-Net and the proposed primary and secondary path attention compensation networks show significant improvement in segmentation performance. Moreover, patients with good collateral circulation have a small final infarct area volume and a good clinical prognosis after intravenous thrombolysis. Quantitative assessment of collateral circulation and ischemic semidark zone by multimodal CT can better predict the clinical prognosis of intravenous thrombolysis.
Prediction and Analysis of Length of Stay Based on Nonlinear Weighted XGBoost Algorithm in Hospital
Authors: Chen Yong
Published: December 2021

An improved nonlinear weighted extreme gradient boosting (XGBoost) technique is developed to forecast length of stay for patients with imbalance data. The algorithm first chooses an effective technique for fitting the duration of stay and determining the distribution law and then optimizes the negative log likelihood loss function using a heuristic nonlinear weighting method based on sample percentage. Theoretical and practical results reveal that, when compared to existing algorithms, the XGBoost method based on nonlinear weighting may achieve higher classification accuracy and better prediction performance, which is beneficial in treating more patients with fewer hospital beds.
Research on Improved Droop Control Strategy of Microsource Inverter Based on Internet of Things
Authors: Bai Di , Zhang Tieyan , Yang Zheng
Published: December 2021

Microgrid connects the distributed power supply with the assistance of power electronic devices. Power electronic devices, especially in the inversion link, play a crucial role in the access of distributed power to microgrid. Whether in grid-connected mode or island mode, the control method of inverters is related to the stable operation of distributed power supply and plays an important role in the control strategy of microgrid. In this paper, by adding the drop control of controllable virtual impedance, the power coupling problem caused by resistive line impedance is reduced, and virtual impedance key points such as voltage feedback and frequency compensation are added. By optimizing the power reference value, the parallel operation stability of the control strategy is improved. The experimental results show that the proposed method improves not only the stability of the system and the power quality but also the accuracy of reactive power distribution.
Research on the Risk Measurement Algorithm of Supply Chain Order Financing Based on Insurance Actuarial
Authors: Li Gushuo , Yin Menglin
Published: December 2021

In today’s globalized economy, all the links of supply chain are interlinked. Most of the upstream raw material manufacturers or producers in the said chain are small- and medium-sized enterprises (SMEs) that provide the basis for the efficient operation of the whole supply chain. However, SMEs in China, especially those playing a pivotal role in China’s export-oriented economy at this stage, do not have access to the corresponding financial treatment. Supply chain finance provides a new perspective to solve this contradiction. Henceforth, this paper introduces modern financial engineering risk measurement tools to measure the financial risk in supply chain finance, specifically while evaluating the single financing business. Moreover, the chief objective of this paper will be the analysis of the characteristics and connotations of order financing business model. In addition, the focus will be to analyze the risk of order financing from the perspective of banks and other financial institutions. Additionally, this paper will use the CreditRisk + model based on insurance actuarial principles to manage credit risk in order financing business based on foreign currency settlement, in conjunction with the characteristics of supply chain finance and multinational supply chain. Furthermore, a risk measurement method for the application of order financing in multinational supply chains will be provided. Ultimately, the experiments show that the solution of this paper defines and analyzes the financial risks brought by order financing business to bank financing.
Prognostic Role of TIGIT Expression in Patients with Solid Tumors: A Meta-Analysis
Authors: Xiao Kunmin , Xiao Kunlin , Li Kexin , Xue Peng , Zhu Shijie
Published: December 2021

Background. T cell immunoglobulin and ITIM domain (TIGIT) is a recently identified immunosuppressive receptor. The expression levels of TIGIT affect the prognosis of patients with solid tumors. To fully comprehend the role of TIGIT on the prognosis of patients with solid tumors, we conducted a meta-analysis. Methods. We performed an online search of PubMed, Embase, Web of Science (WOS), and MEDLINE databases for literature published till March 31, 2021. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the literature, and Stata 16.0 and Engauge Digitizer 4.1 software were used for data analysis. Results. Our literature search identified eight papers comprising 1426 patients with solid tumors. Increased expression of TIGIT was associated with poor prognosis. High expression of TIGIT was a risk factor for overall survival (OS) {

hazard
 
ratio
 

HR

=
1.66

, 95% confidence interval (CI) [1.26, 2.20],

P
<
0.001

} and progression-free survival (PFS) (

HR
=
1.44

, 95% CI [1.15, 1.81],

P
=
0.01

). We performed subgroup analysis to explore the source of heterogeneity, colorectal cancer (

HR
=
2.07

, 95% CI [0.23, 18.82],

P
=
0.518

), lung cancer (

HR
=
1.29

, 95% CI [0.96, 1.72],

P
=
0.094

), esophageal cancer (

HR
=
1.70

, 95% CI [1.20, 2.40],

P
=
0.003

), and other cancers (

HR
=
1.83

, 95% CI [1.25, 2.68],

P
=
0.002

). In addition to cancer type, expression location, sample size, and different statistical analysis methods are also considered the possible causes of heterogeneity between studies. Funnel plots suggested no publication bias for OS (

P
=
0.902

), and Egger’s test supported this conclusion (

P
=
0.537

). Conclusion. TIGIT expression was associated with OS and PFS in patients with solid tumors. Patients with elevated TIGIT expression have a shorter OS and PFS, and TIGIT expression could be a novel biomarker for prognosis prediction and a valuable therapeutic target for solid tumors.
Correlation of Impaired NF-kB Activation in Sepsis-Induced Acute Lung Injury (ALI) in Diabetic Rats
Authors: Chen Xiaoying , Sun Zhangping , Zhang Huanran , Wang Lei
Published: December 2021

Background. The allergic lung inflammation is reduced in the diabetic rats which can be restored by treating it with insulin. As observed in multiple studies, the diabetic patients are more vulnerable to infections and their inflammatory reactions. There are confirmations on insulin and its effects control the inflammatory reactions. Objective. This study was performed to understand the correlation of impaired NF-kB activation in sepsis-induced acute lung injury (ALI) in diabetic rats. Material and Methods. Streptozotocin was used for induction of diabetes and sepsis was induced by colon ligation puncture surgery. Post 6 hours of CLP, the lungs in the groups were analyzed for cell infiltration using broncho-alveolar lavage. The lungs were removed for histopathological analysis at the end of study where the bronchioles, alveoli, and edema were analyzed and compared. Cell expressions quantified by the help of antibodies and inflammatory events were analyzed. Results. Diabetic rats developed mild acute lung injury due to the suppression of activation of NF-kB in alveolar macrophages. Conclusion. Even the diabetic rats were more susceptible to sepsis in comparison to the nondiabetic rats, but the NF-kB suppression has a major role to play in the faint symptoms of ALI.
GRHL3 Promotes Tumor Growth and Metastasis via the MEK Pathway in Colorectal Cancer
Authors: Tan Lin , Qu Weiming , Wu Dajun , Liu Minji , Wang Qian , Ai Qiongjia , Hu Hongsai , Chen Min , Chen Weishun , Zhou Hongbing
Published: December 2021

GRHL3 is a factor associated with a tumor, of which the molecular mechanism remains a further investigation. We explored the underlying mechanism of tumor-promoting effect of GRHL3 in colorectal cancer (CRC), which is involved in the MEK1/2 pathway. The expression of GRHL3 was measured in CRC and adjacent normal tissue using qPCR and immunohistochemical staining. Lentivirus-mediated knockdown expression of GRHL3 was performed in the CRC cell line HT29. Cell proliferation and metastasis were assayed in vitro, and tumorigenicity was investigated in vivo. We found higher GRHL3 expression in colorectal cancer, which was negatively correlated with patients’ prognosis. Results from studies in vitro and in vivo indicated that downregulation of GRHL3 expression inhibited tumor growth and metastasis and inhibited the activation of the MEK1/2 pathway. The effect of GRHL3 downexpression was the same as that of MEK1/2 antagonists on suppression of tumor growth and metastasis. Our results suggested that GRHL3 may act as an oncogene to promote tumor growth and metastasis via the MEK pathway in colorectal cancer.
Gene Editing in Pluripotent Stem Cells and Their Derived Organoids
Authors: Zhou Hang , Wang Yun , Liu Li-Ping , Li Yu-Mei , Zheng Yun-Wen
Published: December 2021

With the rapid rise in gene-editing technology, pluripotent stem cells (PSCs) and their derived organoids have increasingly broader and practical applications in regenerative medicine. Gene-editing technologies, from large-scale nucleic acid endonucleases to CRISPR, have ignited a global research and development boom with significant implications in regenerative medicine. The development of regenerative medicine technologies, regardless of whether it is PSCs or gene editing, is consistently met with controversy. Are the tools for rewriting the code of life a boon to humanity or a Pandora’s box? These technologies raise concerns regarding ethical issues, unexpected mutations, viral infection, etc. These concerns remain even as new treatments emerge. However, the potential negatives cannot obscure the virtues of PSC gene editing, which have, and will continue to, benefit mankind at an unprecedented rate. Here, we briefly introduce current gene-editing technology and its application in PSCs and their derived organoids, while addressing ethical concerns and safety risks and discussing the latest progress in PSC gene editing. Gene editing in PSCs creates visualized in vitro models, providing opportunities for examining mechanisms of known and unknown mutations and offering new possibilities for the treatment of cancer, genetic diseases, and other serious or refractory disorders. From model construction to treatment exploration, the important role of PSCs combined with gene editing in basic and clinical medicine studies is illustrated. The applications, characteristics, and existing challenges are summarized in combination with our lab experiences in this field in an effort to help gene-editing technology better serve humans in a regulated manner. Current preclinical and clinical trials have demonstrated initial safety and efficacy of PSC gene editing; however, for better application in clinical settings, additional investigation is warranted.
Surfactant Stock Optimization for Cost Minimization in Neonatal Intensive Care Units
Authors: Narli Müfide , Kokangül Ali
Published: December 2021

Surfactant deficiency in newborns is a result of a respiratory insufficiency condition, which is a major cause of illness and death. In terms of maintaining vital functions that require emergency intervention, it is crucial that surfactant is available for treatment upon request. The unknown times between patient arrivals and the patients’ stochastic weight changes in the hospital cause difficulties in determining the surfactant doses needed. The surfactant dose treatment for patients must be calculated according to the patient’s weight. In this study, a mathematical model that minimizes the purchase, order, holding, and waste costs of the surfactant has been developed while finding the optimum vial by considering random variables such as the time between a patient’s arrival and weight changes. With cost and demand affecting each other, the model uses a continuous inventory control policy, including calculating how much each preparation and vial should be used for, the reorder point, and the optimum order quantity. Also, the validity of the optimum values obtained with the mathematical model of a 66-bed neonatal intensive care unit in a hospital was tested with real data.
Exploration on the Teaching Reform Measure for Machine Learning Course System of Artificial Intelligence Specialty
Authors: Jiang Yizhang , Li Bo
Published: December 2021

Due to the particularity of the artificial intelligence major and the machine learning courses learned, the traditional course teaching model is not suitable for artificial intelligence major machine learning courses. Based on this background, this article proposes a new system based on machine learning curriculum teaching reform. It mainly includes the reform of curriculum teaching mode, curriculum practice reform, and teaching process reform. In order to verify the effect of the proposed new model on the teaching quality of machine learning courses, this article also proposes an evaluation method based on intelligent technology. Firstly, the feasibility of evaluation based on intelligent technology is described. Secondly, it lists the application details of the existing teaching evaluation based on intelligent technology. Finally, a novel teaching quality evaluation system based on intelligent technology is proposed. The system collects student facial expression data and uses classification algorithms to make classification decisions on the data. The result of the decision can give feedback on the quality of classroom teaching. The comparison of experiments based on different intelligent technologies shows that the teaching quality evaluation system proposed in this article is feasible and effective.
Prostate Cancer Risk Stratification via Nondestructive 3D Pathology with Deep Learning–Assisted Gland Analysis
Authors: Xie Weisi , Reder Nicholas P. , Koyuncu Can , Leo Patrick , Hawley Sarah , Huang Hongyi , Mao Chenyi , Postupna Nadia , Kang Soyoung , Serafin Robert , Gao Gan , Han Qinghua , Bishop Kevin W. , Barner Lindsey A. , Fu Pingfu , Wright Jonathan L. , Keene C. Dirk , Vaughan Joshua C. , Janowczyk Andrew , Glaser Adam K. , Madabhushi Anant , True Lawrence D. , Liu Jonathan T.C.
Published: December 2021

Prostate cancer treatment planning is largely dependent upon examination of core-needle biopsies. The microscopic architecture of the prostate glands forms the basis for prognostic grading by pathologists. Interpretation of these convoluted three-dimensional (3D) glandular structures via visual inspection of a limited number of two-dimensional (2D) histology sections is often unreliable, which contributes to the under- and overtreatment of patients. To improve risk assessment and treatment decisions, we have developed a workflow for nondestructive 3D pathology and computational analysis of whole prostate biopsies labeled with a rapid and inexpensive fluorescent analogue of standard hematoxylin and eosin (H&E) staining. This analysis is based on interpretable glandular features and is facilitated by the development of image translation–assisted segmentation in 3D (ITAS3D). ITAS3D is a generalizable deep learning–based strategy that enables tissue microstructures to be volumetrically segmented in an annotation-free and objective (biomarker-based) manner without requiring immunolabeling. As a preliminary demonstration of the translational value of a computational 3D versus a computational 2D pathology approach, we imaged 300 ex vivo biopsies extracted from 50 archived radical prostatectomy specimens, of which, 118 biopsies contained cancer. The 3D glandular features in cancer biopsies were superior to corresponding 2D features for risk stratification of patients with low- to intermediate-risk prostate cancer based on their clinical biochemical recurrence outcomes. The results of this study support the use of computational 3D pathology for guiding the clinical management of prostate cancer.

Significance:

An end-to-end pipeline for deep learning–assisted computational 3D histology analysis of whole prostate biopsies shows that nondestructive 3D pathology has the potential to enable superior prognostic stratification of patients with prostate cancer.
Asian American/Pacific Islander and Hispanic Ethnic Enclaves, Neighborhood Socioeconomic Status, and Hepatocellular Carcinoma Incidence in California: An Update
Authors: Sangaramoorthy Meera , Yang Juan , Guan Alice , DeRouen Mindy C. , Tana Michele M. , Somsouk Ma , Thompson Caroline A. , Gibbons Joseph , Ho Chanda , Chu Janet N. , Cheng Iona , Gomez Scarlett Lin , Shariff-Marco Salma
Published: December 2021

Background:

Using more recent cancer registry data, we analyzed disparities in hepatocellular carcinoma (HCC) incidence by ethnic enclave and neighborhood socioeconomic status (nSES) among Asian American/Pacific Islander (AAPI) and Hispanic populations in California.

Methods:

Primary, invasive HCC cases were identified from the California Cancer Registry during 1988–1992, 1998–2002, and 2008–2012. Age-adjusted incidence rates (per 100,000 population), incidence rate ratios, and corresponding 95% confidence intervals were calculated for AAPI or Hispanic enclave, nSES, and the joint effects of ethnic enclave and nSES by time period (and the combination of the three periods), sex, and race/ethnicity.

Results:

In the combined time period, HCC risk increased 25% for highest versus lowest quintile of AAPI enclave among AAPI males. HCC risk increased 22% and 56% for lowest versus highest quintile of nSES among AAPI females and males, respectively. In joint analysis, AAPI males living in low nSES areas irrespective of enclave status were at 17% to 43% increased HCC risk compared with AAPI males living in areas of nonenclave/high nSES. HCC risk increased by 22% for Hispanic females living in areas of low nSES irrespective of enclave status and by 19% for Hispanic males living in areas of nonenclave/low nSES compared with their counterparts living in areas of nonenclave/high nSES.

Conclusions:

We found significant variation in HCC incidence by ethnic enclave and nSES among AAPI and Hispanic populations in California by sex and time period.

Impact:

Future studies should explore how specific attributes of enclaves and nSES impact HCC risk for AAPI and Hispanic populations.
Rare Sequences Make Sense of CAR T-cell Therapy Outcomes
Authors: Ghorashian Sara , Bartram Jack
Published: December 2021

In this issue, Pulsipher and colleagues used next-generation sequencing to detect leukemia-specific sequences following tisagenlecleucel therapy of acute lymphoblastic leukemia. A challenge for the field currently is to identify which patients will have therapy failure and to do so early enough to allow planning for further treatment, for example, stem cell transplantation. Detection of disease below the standard detection level for this technique (less than one per million cells) at day 28 was associated with poorer outcomes and potentially therefore could be used to identify those that might benefit from adjunctive therapies.

See related article by Pulsipher et al. p. 66.
Differences between Atrial Fibrillation Detected before and after Stroke and TIA: A Systematic Review and Meta-Analysis
Authors: Fridman Sebastian , Jimenez-Ruiz Amado , Vargas-Gonzalez Juan Camilo , Sposato Luciano A.
Published: December 2021

Background: Preliminary evidence suggests that patients with atrial fibrillation (AF) detected after stroke (AFDAS) may have a lower prevalence of cardiovascular comorbidities and lower risk of stroke recurrence than AF known before stroke (KAF). Objective: We performed a systematic search and meta-analysis to compare the characteristics of AFDAS and KAF. Methods: We searched PubMed, Scopus, and EMBASE for articles reporting differences between AFDAS and KAF until June 30, 2021. We performed random- or fixed-effects meta-analyses to evaluate differences between AFDAS and KAF in demographic factors, vascular risk factors, prevalent vascular comorbidities, structural heart disease, stroke severity, insular cortex involvement, stroke recurrence, and death. Results: In 21 studies including 22,566 patients with ischemic stroke or transient ischemic attack, the prevalence of coronary artery disease, congestive heart failure, prior myocardial infarction, and a history of cerebrovascular events was significantly lower in AFDAS than KAF. Left atrial size was smaller, and left ventricular ejection fraction was higher in AFDAS than KAF. The risk of recurrent stroke was 26% lower in AFDAS than in KAF. There were no differences in age, sex, stroke severity, or death rates between AFDAS and KAF. There were not enough studies to report differences in insular cortex involvement between AF types. Conclusions: We found significant differences in the prevalence of vascular comorbidities, structural heart disease, and stroke recurrence rates between AFDAS and KAF, suggesting that they constitute different clinical entities within the AF spectrum. PROSPERO registration number is CRD42020202622.
Rethinking ‘active participation’ after a pandemic
Authors: Salisbury Matthew
Published: December 2021

This article argues that the reimagining of Christian worship during the coronavirus pandemic beginning in 2020 calls for a consequent repositioning of the term ‘active participation’ in worship. It argues that the various gifts and capacities of a dispersed worshipping community point to kinds of participation in typical ‘in-person’ worship that are often overlooked. Reference is made to Paul’s theology of the members of the body of Christ and to the practice of music.
Diagnostic accuracy of point-of-care knee ultrasound for evaluation of meniscus and collateral ligaments pathology in comparison with MRI
Authors: Elshimy Ahmed , Osman Ahmed M , Awad Mohamed El Sayed , Abdel Aziz Mohamed M
Published: December 2021

Background

Although magnetic resonance imaging (MRI) is often the “gold standard” for diagnosing knee problems, it has many limitations. Therefore, ultrasonography has been suggested as an effective rapid alternative in many knee abnormalities, especially after injuries of the meniscus and collateral ligaments.

Purpose

To determine the diagnostic accuracy of point-of-care ultrasound (POCUS) in detecting injuries of the meniscus and collateral ligament compared to MRI.

Material and Methods

An observational cross-sectional blinded study was conducted of 60 patients with clinically suspicious meniscus and collateral ligament injuries who were planned for an arthroscopy and or operative procedure. These patients underwent both blinded POCUS and MRI of the knees before the intervention procedure and results of both imaging modalities were compared according to the operative and arthroscopic findings.

Results

The preoperative reliability of POCUS compared to MRI for the assessment of meniscus injuries was sensitivity (92.9% vs. 90.5%), specificity (88.9% vs. 83.3%), positive predictive value (PPV; 95.1% vs. 92.7%), negative predictive value (NPV; 84.2% vs. 79%), and overall accuracy (91.7% vs. 88.3%). However, for diagnosing collateral ligament injures, POCUS versus MRI assessed sensitivity (92.3% vs. 88.5%), specificity (100% vs. 97.1%), PPV (100% vs. 95.8%), NPV (94.4% vs. 91.7%), and overall accuracy (96.7% vs. 93.3%).

Conclusion

Ultrasonography is a useful screening tool for the initial diagnosis of meniscal and collateral ligament pathology compared to or even with potential advantages over MRI, especially when MRI is unavailable or contraindicated. As newly advanced portable ultrasonography becomes available, it could be considered as a point-of-injury diagnostic modality.
Is 2D SWE sufficient as clinical diagnosis in patients with plantar fasciitis?
Authors: Beydoğan Engin , Yalçın Atilla
Published: December 2021

Background

The use of shear wave elastography (SWE) seems to be an important imaging method in the diagnosis of plantar fasciitis (PF).

Purpose

To compare patients diagnosed with PF with similar and young healthy control groups in terms of B-mode ultrasound (US) and SWE results and to evaluate the elasticity of the plantar fascia.

Material and Methods

A total of 140 feet of 70 participants were evaluated, including 30 patients and 40 healthy individuals as the control. Clinical, B-mode US, and SWE evaluations were performed for each patient. In addition, American Orthopedic Foot and Ankle Score (AOFAS) was calculated to evaluate pain and foot function in both groups.

Results

Of the patients in the PF group, 40 (88%) were women and the healthy control groups had similar sex distributions ( P = 0.23). The AOFAS score was lower in feet with PF compared to the other groups ( P < 0.001). Of 30 patients with PF, 15 (50%) had bilateral PF and 15 (50%) unilateral PF. In addition, ≥4 mm thickness measurement, which was used as a diagnostic criterion for PF as a US finding, could be shown in 11 (73.3%) patients with unilateral PF and 6 (40%) patients with bilateral PF.

Conclusion

In conclusion, the evaluation of the diagnosis of PF with clinical findings and regular follow-up of measurements with SWE can provide measurement results with higher sensitivity in the diagnosis of PF.
Outbreak of postoperative endophthalmitis caused by Pseudomonas aeruginosa: a case report and brief literature review
Authors: Cheraqpour Kasra , Ahmadraji Aliasghar , Tabatabaei Seyed Ali , Bohrani Sefidan Bahram , Soleimani Mohammad , Shahriari Mansoor , Ramezani Bahareh
Published: December 2021

Endophthalmitis is the most serious complication of cataract surgery. A cluster of endophthalmitis is a devastating event for surgeons. Pseudomonas aeruginosa is the main causative pathogen of Gram-negative endophthalmitis, which can be suggestive of the occurrence of an outbreak.

Ten patients diagnosed with endophthalmitis after cataract surgery performed by one surgeon were analyzed in this study. At presentation, five patients had obvious clinical findings of endophthalmitis with visual acuity of light perception, two patients had poor light perception/no light perception of vision complicated by concomitant keratitis, and three patients had earlier signs of infection (e.g., a lower degree of anterior chamber and vitreous cells, better presenting visual acuity, and greater visibility of the fundus). Investigations revealed that the source of infection was growth of P. aeruginosa on the phaco probe. All of the surgeries had been performed by the same contaminated probe without sterilization between surgeries. This finding emphasizes the importance of strict adherence to sterility protocols during high-risk surgeries such as intraocular surgeries. Additionally, this report aims to emphasize to surgeons that negligence of simple but vital steps of sterility for any reason, such as limitations in time or equipment, can lead to catastrophic events.
Vitritis and retinal vasculitis caused by pseudorabies virus
Authors: Ying Manman , Hu Xin , Wang Mengli , Cheng Xiangshu , Zhao Bo , Tao Yong
Published: December 2021

Pseudorabies virus (PRV) is a herpesvirus of swine. PRV is also called suid herpesvirus 1 and is a member of the Alphaherpesvirinae subfamily within the family Herpesviridae. The number of PRV cases worldwide is small, but in susceptible individuals, infection with this virus has a poor prognosis. Therefore, it is urgent to improve our understanding of this disease in clinical practice to avoid misdiagnosis and to identify optimal treatments. We report a patient with PRV infection who was admitted to hospital with viral encephalitis and subsequently developed intraocular infection. Because to the lack of relevant clinical experience in the treatment of this disease, we carried out experimental treatment with good therapeutic effect. This case provides a basis for clinical diagnosis and treatment of patients with PRV.
Association between serum lipids and breast cancer risk in premenopausal women: systematic review and meta-analysis
Authors: Wu Jing , Lei Xun , Pan Xianjun , Zeng Xiaohua , Li Wei
Published: December 2021

Objective

Associations between serum lipids and their individual components with premenopausal breast cancer risk are unclear. This meta-analysis summarized the literature on serum lipids and premenopausal breast cancer risk to elucidate their relationship.

Methods

Eligible studies were identified by searching the PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases until 31 December 2020. Standardized mean difference (SMD) scores with 95% confidence intervals (95%CIs) were used to assess the impact of serum lipids on premenopausal breast cancer risk. The I2 statistic was calculated to measure the percentage of heterogeneity, and Egger’s test was performed to measure publication bias.

Results

Thirteen studies were included. The SMD scores of triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) were 12.90 (95%CI: 7.19–18.61) and 31.43 (95%CI: 8.72–54.15), respectively. The SMD scores of total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) were not significantly different between the groups. The included studies were highly heterogeneous. There were no publication biases found in TC, LDL-C, or HDL-C analyses, whereas publication bias was present in the TG analysis.

Conclusions

TG and LDL-C were higher in premenopausal breast cancer patients than in women without breast cancer. However, no significant differences were found in TC or HDL-C levels.