bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiepileptic Effects of Cicadae Periostracum on Mice and Its Antiapoptotic Effects in H2O2‐Stimulated PC12 Cells via Regulation of PI3K/Akt/Nrf2 Signaling Pathways
Authors: Zhang Qing , Li Ruo-Lan , Tao Ting , Sun Jia-Yi , Liu Jia , Zhang Ting , Peng Wei , Wu Chun-Jie
Published: July 2021

Cicadae Periostracum (CPM), a commonly used animal traditional Chinese medicine (TCM), possesses antifebrile, spasmolytic, antiasthmatic, and antiphlogistic effects. In our present paper, we aimed to systemically investigate the antiepileptic effects of CPM in epileptic mice and explore the related molecular mechanism. Pentylenetetrazole‐ (PTZ) and strychnine‐induced convulsion mice were established, and the results showed CPM could prolong the latency of convulsion and death and improve the neuronal damage in the hippocampus of PTZ‐induced mice. Furthermore, the H2O2‐treated PC12 cells were prepared to explore the possible mechanisms for the antiepileptic effects of CPM. CCK‐8 results showed that CPM significantly improved the cell viability of H2O2‐treated PC12 cells. Results of the acridine orange‐ (AO‐) ethidium bromide (EB) staining, cell mitochondrial membrane potential (MOMP) analysis, and flow cytometry analysis showed that CPM significantly suppressed the H2O2‐induced apoptosis in PC12 cells. In addition, CPM also downregulated the proapoptosis proteins, including Bax, cleaved‐ (C‐) caspase‐3, and C‐caspase‐9, and upregulated Bcl‐2. Furthermore, CPM reduced the reactive oxygen species (ROS) levels via increasing antioxidative enzyme activities, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH‐Px). Importantly, CPM could increase the phosphorylation of phosphoinositide 3‐kinase (PI3K) and protein kinase B (Akt) in H2O2‐induced PC12 cells and can promote the nuclear transfer of the nuclear factor E2‐related factor 2 (Nrf2) and increase the expression of heme oxygenase‐1 (HO‐1) in the cytoplasm. In conclusion, our present study suggested CPM possessed antiepileptic effects through antiapoptosis of neuron cells via regulation of the PI3K/Akt/Nrf2 signaling pathway.
Study on the Effect of Precrack on Specimen Failure Characteristics under Static and Dynamic Loads by Brazilian Split Test
Authors: Liu Enyan , Liu Fuchun , Xiong Youwei , Lei Xianquan , Wang Shiming
Published: July 2021

To analyse the dynamic failure characteristics of the rock with a crack in rock engineering, the Brazilian split tests were conducted on the split Hopkinson pressure bar (SHPB) using precrack specimens under dynamic loads. In the study, five groups of different precrack angles are selected; they are 0°, 30°, 45°, 60°, and 90°, respectively. The results show that the static failure load of the specimen as a whole decreases to increase with the growth of the loading angle, and the DIF linear increases with the increase of the loading rate; the failure load of the specimen with an angle of 45° precrack is the most sensitive to the loading rate, followed by 0°, 60°, 30°, and 90°. The crack initiation time of specimen with 30°, 45°, and 60°precrack decreases with the loading rate, while it has no obvious change with the loading rate with 0° and 90°precrack. The failure mode of the specimen was controlled by the stress concentration at the crack tip; the main cracks all point from the crack tip to the loading end. When the precrack and the loading direction are at a certain angle, the failure process will produce secondary cracks; it would be particularly obvious under dynamic load splitting. Once the precrack and the loading direction are at a certain inclination angle, type-II secondary cracks will develop under dynamic load splitting.
Robust Visual Relationship Detection towards Sparse Images in Internet‐of‐Things
Authors: He Yang , Duan Guiduo , Luo Guangchun , Liu Xin
Published: July 2021

Visual relationship can capture essential information for images, like the interactions between pairs of objects. Such relationships have become one prominent component of knowledge within sparse image data collected by multimedia sensing devices. Both the latent information and potential privacy can be included in the relationships. However, due to the high combinatorial complexity in modeling all potential relation triplets, previous studies on visual relationship detection have used the mixed visual and semantic features separately for each object, which is incapable for sparse data in IoT systems. Therefore, this paper proposes a new deep learning model for visual relationship detection, which is a novel attempt for cooperating computational intelligence (CI) methods with IoTs. The model imports the knowledge graph and adopts features for both entities and connections among them as extra information. It maps the visual features extracted from images into the knowledge‐based embedding vector space, so as to benefit from information in the background knowledge domain and alleviate the impacts of data sparsity. This is the first time that visual features are projected and combined with prior knowledge for visual relationship detection. Moreover, the complexity of the network is reduced by avoiding the learning of redundant features from images. Finally, we show the superiority of our model by evaluating on two datasets.
[Retracted] Changes in Expressions of HSP27, HSP70, and Soluble Glycoprotein in Heart Failure Rats Complicated with Pulmonary Edema and Correlations with Cardiopulmonary Functions
Authors: Hong Yingcai , Wang Zheng , Rao Zhanpeng , Wan Jun , Ling Xie’an , Zheng Qijun
Published: July 2021

The study is aimed at investigating the changes in expressions of heat shock protein 27 (HSP27), HSP70, and soluble glycoprotein (SGP) in heart failure (HF) rats complicated with pulmonary edema and exploring their potential correlations with cardiopulmonary functions. The rat model of HF was established, and the rats were divided into HF model group (model group, n = 15) and normal group (n = 15). After successful modeling, MRI and ECG were applied to detect the cardiac function indexes of the rats. The myocardial function indexes were determined, the injury of myocardial tissues was observed via hematoxylin and eosin (HE) staining, and the content of myeloperoxidase (MPO), matrix metalloproteinase‐9 (MMP‐9), and tumor necrosis factor‐alpha (TNF‐α) in the blood was measured. The partial pressure of oxygen (PaO2) and oxygenation index (OI) were observed, and the airway resistance and lung compliance were examined. Moreover, quantitative polymerase chain reaction (qPCR) and Western blotting assay were performed to detect the gene and protein expression levels of HSP27, HSP70, and SGP130. The levels of serum creatine kinase (CK), creatine (Cr), and blood urea nitrogen (BUN) were increased markedly in model group (p < 0.05). Model group had notably decreased fractional shortening (FS) and ejection fraction (EF) compared with normal group (p < 0.05), while the opposite results of left ventricular end‐diastolic diameter (LVEDD) and left ventricular end‐systolic diameter (LVESD) were detected. In model group, the content of serum MPO, MMP‐9, and TNF‐α was raised remarkably (p < 0.05), OI and PaO2 were reduced notably (p < 0.05), the airway resistance was increased (p < 0.05), and the lung compliance was decreased (p < 0.05). Obviously elevated gene and protein expression levels of HSP27, HSP70, and SGP130 were detected in model group (p < 0.05). The expressions of HSP27, HSP70, and SGP130 are increased in HF rats complicated with pulmonary edema, seriously affecting the cardiopulmonary functions of the rats.
Correlation Analysis of External Environment Risk Factors for High-Speed Railway Derailment Based on Unstructured Data
Authors: Wang Haixing , Tian Yuanlanduo , Yin Hong
Published: July 2021

In railway operation, unsafe events such as faults may occur, and a large number of unsafe event records are generated in the process of unsafe events’ recording and reporting. Unsafe events have been described in unstructured natural language, which often has inconsistent structure and complex sources, involving multiple railway specialties, with multisource, heterogeneous, and unstructured characteristics. In practical application, the efficiency of processing is extremely low, leading to potentially unsafe management utilization. Based on the data on unsafe events, this paper utilizes big data processing technology, conducts association rules mining and association degree analysis, extracts the word segmentation, and obtains the feature vector of unsafe fault event data. At the same time, the unsafe event data analysis model is constructed in combination with regular expression and pattern matching technology. This paper establishes the matching model of high-speed railway derailment-based external environment risk factors and applies it to the occurrence of unsafe events. This model could be utilized to analyze and excavate the link between external environment risk factors and the occurrence of unsafe events and carry out the automatic extraction of characteristic information such as risk possibility and consequence severity; hence, it has potential for identifying, with enhanced accuracy, high-risk factors that may lead to high-speed railway derailment. Based on this study, we could make full use of the unsafe event data, forecast the risk trend, and discover the law of high-speed railway derailment. This study introduces a viable approach to analyzing the unsafe event data, forecasting risk trend, and conceptualizing high-speed railway derailment. It could also enforce the accurate quantification of high-speed railway safety situation, refine the risk index and conduct in-depth analysis combined with the model, and effectively support the digitalization and intellectualization of high-speed railway operation safety.
Solving Misclassification of the Credit Card Imbalance Problem Using Near Miss
Authors: Mqadi Nhlakanipho Michael , Naicker Nalindren , Adeliyi Timothy
Published: July 2021

In ordinary credit card datasets, there are far fewer fraudulent transactions than ordinary transactions. In dealing with the credit card imbalance problem, the ideal solution must have low bias and low variance. The paper aims to provide an in-depth experimental investigation of the effect of using a hybrid data-point approach to resolve the class misclassification problem in imbalanced credit card datasets. The goal of the research was to use a novel technique to manage unbalanced datasets to improve the effectiveness of machine learning algorithms in detecting fraud or anomalous patterns in huge volumes of financial transaction records where the class distribution was imbalanced. The paper proposed using random forest and a hybrid data-point approach combining feature selection with Near Miss-based undersampling technique. We assessed the proposed method on two imbalanced credit card datasets, namely, the European Credit Card dataset and the UCI Credit Card dataset. The experimental results were reported using performance matrices. We compared the classification results of logistic regression, support vector machine, decision tree, and random forest before and after using our approach. The findings showed that the proposed approach improved the predictive accuracy of the logistic regression, support vector machine, decision tree, and random forest algorithms in credit card datasets. Furthermore, we found that, out of the four algorithms, the random forest produced the best results.
Predictive Value of Red Blood Cell Distribution Width in Poststroke Depression
Authors: Dai Ming , Wei Qiyao , Zhang Yuxin , Fang Chuanqin , Qu Ping , Cao Lei
Published: July 2021

Purpose. Red blood cell distribution width (RDW) is increased in a variety of inflammatory-related diseases. However, there is no report of its clinical significance in poststroke depression (PSD). This study explores the clinical significance of RDW in PSD patients. Methods. A total of 185 patients with first-ever acute ischaemic stroke (AIS) in the Second Hospital of Anhui Medical University were chosen as subjects. A retrospective observational study was conducted from February 2019 to February 2020. PSD patients were diagnosed at 6 months after stroke based on the Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Clinical and laboratory data were obtained from all patients. Coefficient of Variation (RDW-CV) and standard deviation (RDW-SD) were used to statistically report the performance of red blood cell distribution width. Results. At the 6-month follow-up, 46 patients were diagnosed with PSD. Compared with non-PSD patients, PSD patients exhibited an increase in RDW-CV and RDW-SD, which positively correlated with serum interleukin 6 (IL-6) concentrations. In PSD patients, only RDW-SD demonstrated a consistent positive association with the Hamilton Rating Scale for Depression (HAM-D) scores at 6 months after admission. RDW-CV, RDW-SD, and IL-6 were recognized as independent predictors of PSD. The area under the receiver operating characteristic (ROC) curve (AUC) of RDW-SD was 0.796 (95% CI: 0.731-0.852) for the prediction of PSD, which was superior to that of RDW-CV. The specificity for predicting PSD was 60.43%, and the sensitivity was 91.30% if RDW-SD was higher than 43.80 fL. Conclusions. RDW-SD is a simple, inexpensive, rapid, and easily accessible parameter that can be used to predict PSD in patients with stroke.
Fast Synergetic Control for Chaotic Oscillation in the Power System Based on Input-Output Feedback Linearization
Authors: Liu Ling , Wang Jiangbin , Liu Chongxin
Published: July 2021

This paper presents a fast synergetic control scheme for chaotic oscillation in a three-bus power system model. First, the coupling dynamic model of a controlled power system with the current source converter-based STATCOM device and energy storage device is established. Then, the input-output linearization process for the controlled power system is derived step by step, the control problem for the complex nonlinear power system model is completely transformed into the control of linear systems, and a fast synergetic control scheme is proposed for these linear systems. Since the designed control inputs contain complex system functions which are very difficult to obtain and reduce the engineering practicability of the designed controllers, the assumption that system functions are bounded is introduced into the controller design process, and the controllers are redesigned. The remarkable advantages of the proposed control method are that it improves the rapidity of traditional synergetic control and avoids complex system functions in control inputs. Finally, the effectiveness and the superiority of the control scheme are verified by simulation results.
Aeroengine High-Attitude/Low Mach Number Oscillations: Mechanism and Prevention Design
Authors: Wang Jiqiang
Published: July 2021

The issue of aeroengine oscillations over high-attitude and low-speed flight envelope has been an unsolved problem due to their classified nature and hard reproduction in simulated altitude test stand. Efforts have been sought for either structural integrity or component damage. However, it is rarely realized that the oscillations can be an inherent property of the engine itself. Consequently, a dynamical system approach is proposed in this paper to demonstrate that engine oscillations are recurring over high-attitude and low-speed flight envelope, yet they can be suppressed through appropriate control designs. However, the resulting design can be compromised with the conventional high-gain control where the transient and steady-state performance must be balanced with disturbance attenuation performance. Examples are given to illustrate and validate the claims made through the en route analysis.
Rational Wave Solutions and Dynamics Properties of the Generalized (
2
+
1
)-Dimensional Calogero-Bogoyavlenskii-Schiff Equation by Using Bilinear Method
Authors: Han Lihui , Bilige Sudao , Wang Xiaomin , Li Meiyu , Zhang Runfa
Published: July 2021

Through symbolic computation with Maple, fifty-seven sets of rational wave solutions to the generalized Calogero-Bogoyavlenskii-Schiff equation are presented by employing the generalized bilinear operator when the parameter

p
=
2

. Via the three-dimensional plots and contour plots with the help of Maple, the dynamics of these solutions are described very well. These solutions have greatly enriched the exact solutions of the generalized Calogero-Bogoyavlenskii-Schiff equation on the existing literature. The result will be widely used to describe many nonlinear scientific phenomena.
Increment of Heterogeneous Knowledge in Enterprise Innovation Ecosystem: An Agent‐Based Simulation Framework
Authors: Wu Rong , Wang Zhiqiang , Shi Qinfen
Published: July 2021

How can enterprises acquire knowledge resources quickly to maintain a competitive advantage in the market has become the focus of attention among academic circles and enterprises in the era of the knowledge economy. Based on the ecology theory, this paper analyzed the characteristics of the innovation subject and the rules of the heterogeneous knowledge interaction between innovation subjects. Then, this paper proposed a multiagent‐based model of EIE (enterprise innovation ecosystem) heterogeneous knowledge increment to simulate the interactions between innovation subjects. By combining the biotic factors (government and service institutions) and abiotic factors (economical, social, and cultural), this paper designs eight different innovation environment scenarios to explore the dynamic impacts of these factors on EIE heterogeneous knowledge increment. The research findings were as follows: (1) In the introduction stage of innovation collaboration between innovation subjects, the same investment of the innovation elements in academic institutes is more beneficial to increasing system heterogeneous knowledge than investment in enterprises. (2) The cultivation of innovative biotic factors in service institutions is conducive to the rapid interaction of heterogeneous knowledge among the innovation subjects. Still, it is not suitable for areas with higher homogeneous knowledge because high homogeneous environment can easily lead to intensified market competition. (3) The cultivation of the abiotic innovation environment is conducive to maintain stable high‐speed growth of EIE heterogeneous knowledge increment over a long period. (4) Without considering the cost of environmental cultivation, cultivating biotic and abiotic environments at the same time is the most beneficial choice to EIE heterogeneous knowledge increment.
Study of Hardness of Superhard Crystals by Topological Indices
Authors: Zhang Xiujun , Naeem Muhammad , Baig Abdul Qudair , Zahid Manzoor Ahmad
Published: July 2021

Topological indices give immense information about a molecular structure or chemical structure. The hardness of materials for the indentation can be defined microscopically as the total resistance and effect of chemical bonds in the respective materials. The aim of this paper is to study the hardness of some superhard

B

C

x

crystals by means of topological indices, specifically Randić index and atom-bond connectivity index.
Dynamic Characteristics of the Rotating Penetrating Missile for Attacking Warship Vertically
Authors: Qin Dong-ze , Li Pei-hang
Published: July 2021

The paper aimed to analyze the dynamic response of a new type penetrating missile in rotary attacking warship. The dynamic response characteristics of the penetrator become more complex when attacking the ship target due to the special materials of the deck such as stiffeners. Therefore, different from attacking other targets, the article reveals the design rules of precession penetration ammunition and fuze. A physical model of the missile target is established to study the numerical simulation of the penetration process of rotating projectile into a stiffened target based on finite element analysis (FEA) software. We studied the dynamic response characteristics of different projectile positions, rotational speeds, and positions that act in precession penetration. As experimental results show, the residual velocity of the precession penetrator decreases with the distance between the projectile point and stiffener. When the projectile penetrates the second target plate, the acceleration is greater than that in the first layer. It is proved that the deflection angle of the shell body is affected by comprehensive factors. The rotational speed in the projectile has less contribution to precession penetration ammunition. In addition, the change of acceleration in the missile’s central section can be significantly perceived in the direction perpendicular to the penetration direction.
The Development and Usability Assessment of an mHealth Application to Encourage Self-Care in Pregnant Women against COVID-19
Authors: Moulaei Khadijeh , Sheikhtaheri Abbas , Ghafaripour Zahra , Bahaadinbeigy Kambiz
Published: July 2021

The coronavirus disease 2019 (COVID-19) pandemic has caused serious concerns in pregnant women. Self-care mHealth applications can provide helpful guidelines for COVID-19 prevention or management in case of infection. This study aimed to develop and then assess a self-care smartphone-based application to provide self-care for pregnant women against COVID-19. The present study was conducted in two phases. First, a needs assessment was performed based on the opinions of 30 obstetricians and pregnant women. Then, relying on the results, a smartphone-based application was prototyped and assessed in terms of its usability and user satisfaction. To assess the application, 36 pregnant women (11 infected with COVID-19) were asked to use the application for a week. The QUIS questionnaire 5.5 was used for assessment, and the results were analyzed via descriptive statistics in SPSS 23. According to the obstetricians and pregnant women, of the 41 information requirements, 35 data elements were noted to be essential in the needs assessment. Features of the application were placed in four categories of User’s Profile, Lifestyle, Disease Management and Control, and Application Functions (e.g., introducing high-risk places in terms of COVID-19 prevalence in each city, introducing specialized COVID-19 medical centers to pregnant women to receive services, medication management, stress management and control, nutrition and diet management, sleep management, contacting physicians, doctor’s appointment reminder, searching the available educational materials, and making application adjustments such as text font, size, and color). With an average score of 7.94 (out of 9), pregnant women rated the application at a good level. The application can be used to reduce anxiety and stress about COVID-19 in mothers, provide access to reliable information to answer possible questions, identify high-risk locations, and provide pregnant women with instant access to healthcare facilities and information related to COVID-19 self-care processes.
The Liver–Immunity Nexus and Cancer Immunotherapy
Authors: Lee James C. , Green Michael D. , Huppert Laura A. , Chow Christine , Pierce Robert H. , Daud Adil I.
Published: July 2021

The impact of liver metastases on immune checkpoint-inhibitor effectiveness in patients with solid-tumor malignancies has been the focus of several recent clinical and translational studies. We review the literature describing the immune functions of the liver and particularly the mechanistic observations in these studies. The initial clinical observation was that pembrolizumab appeared to be much less effective in melanoma and non–small cell lung cancer (NSCLC) patients with liver metastasis. Subsequently other clinical studies have extended and reported similar findings with programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitors in many cancers. Two recent translational studies in animal models have dissected the mechanism of this systemic immune suppression. In both studies CD11b+ suppressive macrophages generated by liver metastasis in a two-site MC38 model appear to delete CD8+ T cells in a FasL-dependent manner. In addition, regulatory T-cell (Treg) activation was observed and contributed to the distal immunosuppression. Finally, we discuss some of the interventions reported to address liver immune suppression, such as radiation therapy, combination checkpoint blockade, and Treg depletion.
A Phase I Dose-Escalation and Expansion Study of Telaglenastat in Patients with Advanced or Metastatic Solid Tumors
Authors: Harding James J. , Telli Melinda , Munster Pamela , Voss Martin H. , Infante Jeffrey R. , DeMichele Angela , Dunphy Mark , Le Mai H. , Molineaux Chris , Orford Keith , Parlati Frank , Whiting Sam H. , Bennett Mark K. , Tannir Nizar M. , Meric-Bernstam Funda
Published: July 2021

Purpose:

Glutamine is a critical fuel for solid tumors. Interference with glutamine metabolism is deleterious to neoplasia in preclinical models. A phase I study of the oral, first-in-class, glutaminase (GLS) inhibitor telaglenastat was conducted in treatment-refractory solid tumor patients to define recommended phase II dose (RP2D) and evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity.

Patients and Methods:

Dose escalation by 3 + 3 design was followed by exploratory tumor-/biomarker-specific cohorts.

Results:

Among 120 patients, fatigue (23%) and nausea (19%) were the most common toxicity. Maximum tolerated dose was not reached. Correlative analysis indicated >90% GLS inhibition in platelets at plasma exposures >300 nmol/L, >75% tumoral GLS inhibition, and significant increase in circulating glutamine. RP2D was defined at 800 mg twice-daily. Disease control rate (DCR) was 43% across expansion cohorts (overall response rate 5%, DCR 50% in renal cell carcinoma).

Conclusions:

Telaglenastat is safe, with a favorable PK/PD profile and signal of antitumor activity, supporting further clinical development.
Opportunities for Utilization of DNA Repair Inhibitors in Homologous Recombination Repair-Deficient and Proficient Pancreatic Adenocarcinoma
Authors: Cleary James M. , Wolpin Brian M. , Dougan Stephanie K. , Raghavan Srivatsan , Singh Harshabad , Huffman Brandon , Sethi Nilay S. , Nowak Jonathan A. , Shapiro Geoffrey I. , Aguirre Andrew J. , D'Andrea Alan D.
Published: July 2021

Pancreatic cancer is rapidly progressive and notoriously difficult to treat with cytotoxic chemotherapy and targeted agents. Recent demonstration of the efficacy of maintenance PARP inhibition in germline BRCA mutated pancreatic cancer has raised hopes that increased understanding of the DNA damage response pathway will lead to new therapies in both homologous recombination (HR) repair-deficient and proficient pancreatic cancer. Here, we review the potential mechanisms of exploiting HR deficiency, replicative stress, and DNA damage-mediated immune activation through targeted inhibition of DNA repair regulatory proteins.
Establishment of a Plasticity-Associated Risk Model Based on a SOX2- and SOX9-Related Gene Set in Head and Neck Squamous Cell Carcinoma
Authors: Khorani Karam , Schwaerzler Julia , Burkart Sebastian , Kurth Ina , Holzinger Dana , Flechtenmacher Christa , Plinkert Peter K. , Zaoui Karim , Hess Jochen
Published: July 2021

Recent studies highlighted SOX2 and SOX9 as key determinants for cancer-cell plasticity and demonstrated that cisplatin-induced adaptation in oral squamous cell carcinoma (SCC) is acquired by an inverse regulation of both transcription factors. However, the association between SOX2/SOX9-related genetic programs with risk factors and genetic or epigenetic alterations in primary head and neck SCC (HNSCC), and their prognostic value is largely unknown.

Here, we identified differentially-expressed genes (DEG) related to SOX2 and SOX9 transcription in The Cancer Genome Atlas (TCGA)-HNSC, which enable clustering of patients into groups with distinct clinical features and survival. A prognostic risk model was established by LASSO Cox regression based on expression patterns of DEGs in TCGA-HNSC (training cohort), and was confirmed in independent HNSCC validation cohorts as well as other cancer cohorts from TCGA. Differences in the mutational landscape among risk groups of TCGA-HNSC demonstrated an enrichment of truncating NSD1 mutations for the low-risk group and elucidated DNA methylation as modulator of SOX2 expression. Gene set variation analysis (GSVA) revealed differences in several oncogenic pathways among risk groups, including upregulation of gene sets related to oncogenic KRAS signaling for the high-risk group. Finally, in silico drug screen analysis revealed numerous compounds targeting EGFR signaling with significantly lower efficacy for cancer cell lines with a higher risk phenotype, but also indicated potential vulnerabilities.

Implications:

The established risk model identifies patients with primary HNSCC, but also other cancers at a higher risk for treatment failure, who might benefit from a therapy targeting SOX2/SOX9-related gene regulatory and signaling networks.
Lower Urinary Tract Symptoms in Myasthenia Gravis
Authors: Tateno Fuyuki , Sakakibara Ryuji , Aiba Yosuke
Published: July 2021

It remains uncertain to what extent lower urinary tract (LUT) symptom (LUTS) is a comorbidity of myasthenia gravis (MG). We prospectively administered a LUTS questionnaire devised for detecting neurogenic pelvic organ dysfunction (not validated) in an MG group and a healthy control group and compared the results. The MG group comprised 21 patients: 15 women and 6 men, with age range 22–73 (mean 47) years, illness duration range 0.2–8 (mean 3.5) years, median Myasthenia Gravis Foundation of America (MGFA) grade 2, all walking independently. Therapies included thymectomy in 17, predonisolone 5–20 mg/day in 10, and pyridostigmine bromide 60–180 mg/day in 9 patients. The control group, who were undergoing an annual health survey, comprised 235 consecutive subjects: 120 women and 115 men, with age range 30–69 (mean 48) years. The questionnaire had 9 questions. Each question was scored from 0 (none) to 3 (severe) with an additional quality of life (QOL) index scored from 0 (satisfied) to 3 (extremely dissatisfied). Statistical analysis was made using Student’s t test. Compared with the control subjects, the frequency of LUTSs in the MG patients was significantly higher for daytime frequency (43%; p < 0.01), nocturia (24%; p < 0.01), and urinary incontinence (43%; p < 0.05). The LUTS-related QOL index for the MG patients was significantly higher for MG patients as a whole than that for all control patients (29%) (p < 0.05). In conclusion, our study results showed that MG patients had significantly more LUTSs (overactive bladder) than healthy control subjects and had worse LUTS-related QOL; therefore, amelioration of LUTS in MG is important.
Pustular Rash in Crohn’s Patient on Ustekinumab Raises Concern for Drug-Induced Paradoxical Psoriasis
Authors: Barahimi Mitra , Lee Scott , Clark-Snustad Kindra
Published: July 2021

We report the case of a 51-year-old male with Crohn’s disease (CD) who developed a reproducible pustular rash after ustekinumab (UST) administration. The patient first presented with a pustular rash on his hands, body, extremities, and scalp starting 5 weeks after his initial weight-based UST induction. The rash resolved spontaneously, then recurred 4 weeks after his first subcutaneous maintenance dose of UST 90 mg. Biopsy of the affected area demonstrated subcorneal pustular dermatosis (SPD). UST was discontinued and the rash resolved. Unfortunately, the patient experienced clinical recurrence of CD, and given prior failure of multiple CD medications, UST was restarted with premedication. Two weeks after UST re-induction, the rash recurred, though less severe. Given improvement in CD symptoms, UST was continued and the rash managed with topical corticosteroids. This is the first case of drug-induced SPD associated with UST. One case report has previously described de novo pustular psoriasis associated with UST in a patient with CD and enteropathic arthritis. Notably, SPD and pustular psoriasis can be histologically indistinguishable. The development of a paradoxical psoriasiform rash is thought to be one of the few dose and duration dependent side effects of TNF-antagonist therapy but has not previously been established as a side effect of UST. This case demonstrates a new potential side effect of UST.
Association of Body Mass Index with Mortality in Patients with Cardiogenic Shock following Acute Myocardial Infarction: A Contemporary Danish Cohort Analysis
Authors: Hermansen Gustav Fridolf , Junker Udesen Nanna Louise , Josiassen Jakob , Lerche Helgestad Ole Kristian , Møller Emilie Eifer , Povlsen Amalie Ling , Ravn Hanne Berg , Jensen Lisette Okkels , Holmvang Lene , Schmidt Henrik , Hassager Christian , Møller Jacob Eifer
Published: July 2021

Aims: The obesity paradox suggests a better prognosis in overweight or obese patients with heart failure and acute myocardial infarction (AMI) than patients with normal weight. Few studies have investigated the association between BMI and mortality in patients with AMI complicated by cardiogenic shock (AMICS). The aim of this study was to evaluate the association between BMI and 30-day mortality in patients with AMICS. Methods and Results: A retrospective study of 1,716 patients with AMICS treated at 2 tertiary centers in south-eastern Denmark between 2010 and 2017. Patients undergoing revascularization and who were admitted to the intensive care unit were included (n = 1,216). BMI was available in 1,017 patients (83.6%). Patients were divided according to the WHO classification as normal weight BMI <24.9 kg/m2 (n = 453), overweight BMI 25–29.9 kg/m2 (n = 391), obese class 1 BMI 30–34.9 kg/m2 (n = 131), and obese class 2 + 3 BMI >35 kg/m2 (n = 42). Differences in baseline characteristics, in-hospital treatment, and the primary outcome of all-cause mortality at 30 days were examined. Obese patients had more comorbidities such as diabetes, hypertension, and dyslipidemia than patients with normal weight. Need for renal replacement therapy was higher among obese patients (normal weight, 19% vs. obese class 2 + 3, 35%, p = 0.02); otherwise, no difference in management was found. No difference in 30-day mortality was observed between groups (normal weight 44%, overweight 38%, obese class 1 41%, and obese class 2 + 3 45% at 30 days; ns). Conclusions: Thirty-day mortality in patients with AMICS was not associated with the BMI category. Thus, evidence of an “obesity paradox” was not observed in this contemporary cohort of patients with AMICS in Denmark.
Polysubstance Use Is Positively Associated with Gaming Disorder Symptom Severity: A Latent Class Analytical Study
Authors: Horváth Zsolt , Király Orsolya , Demetrovics Zsolt , Németh Ágnes , Várnai Dóra , Urbán Róbert
Published: July 2021

Introduction: The link between gaming disorder (GD) and substance use amongst adolescents is not clear. Some studies reported positive associations, whereas others suggested that alcohol and illicit drug use are not related to GD severity. Objectives: The present study aimed to identify empirically based latent classes of alcohol and illicit drug use amongst adolescents and explore their associations with GD symptom severity and whether endorsement of specific criteria of GD is linked to the membership of latent classes of alcohol and illicit drug use. Methods: Data of the national sample of Hungarian adolescents from the Health Behaviour in School-aged Children survey (N = 2,768; females: 52.08%; mean age: 16.73 years) were analysed. Measures for frequency of alcohol and illicit drug use, gaming, GD symptom severity, and life satisfaction were included in the analyses. Results: Latent class analysis discriminated 4 subgroups of alcohol and illicit drug use: polysubstance users, high-risk alcohol users, moderate alcohol users, and infrequent substance users. Polysubstance users presented significantly higher levels of GD symptom severity and higher odds for endorsement of criteria of “giving up other activities” and “negative consequences.” Conclusions: Positive associations were shown between higher GD severity and the polysubstance using class. The roles of criteria of “giving up other activities” and “negative consequences” were highlighted in more severe substance use patterns. However, GD severity and criteria did not differ as a function of the level of alcohol use. These findings may imply common roots of GD and illicit drug use in adolescents.
Quantitative Analysis of the RPC Vessel Density and the RNFL Thickness in Patients with Type 2 Diabetes Mellitus by Using OCT Angiography
Authors: Zhang Min , Jia Fan , Li Na , Song Chunyuan , Yang Jin , Yang Kaili , Li Yan , Wang Shuna
Published: July 2021

Introduction: This study aims to compare the structural differences in the optic disc blood perfusion and the peripapillary retinal nerve fibre layer (pRNFL) thickness in age-matched healthy subjects and patients with type 2 diabetes mellitus (DM) by using quantitative analysis with optical coherence tomography angiography (OCTA). Methods: A cross-sectional cohort study on patients with type 2 DM with or without diabetic retinopathy (DR) and healthy subjects was conducted. The 4.5-mm scanning angio-disc pattern of the OCTA system was used to assess the optic disc. The analysed indices included radial peripapillary capillary (RPC) vessel density and pRNFL thickness. Results: A total of 78 eyes from 78 patients with type 2 DM, including 27 without clinical DR (NDR), 26 with non-proliferative DR (NPDR), and 25 with proliferative DR (PDR), and 28 age-matched healthy subjects were enrolled. The average RPC vessel density of the whole (p < 0.001) and the peripapillary (p < 0.001) regions was significantly different in different groups, whereas the pRNFL was not statistically significant (p = 0.764). Compared with that in healthy subjects, the RPC vessel densities in 4, 5, and 8 peripapillary sectors in NDR (all p < 0.05), NPDR (all p < 0.05), and PDR (all p < 0.05) groups, respectively, were reduced. Compared with that in healthy subjects, the pRNFL thickness significantly decreased in the inferior nasal sector (p = 0.001) in NDR but significantly increased in the 2 sectors (all p < 0.01) in PDR. The DR severity was negatively correlated with the peripapillary RPC vessel density (r = −0.583, p < 0.001) but had no correlation with the pRNFL thickness (r = −0.045, p = 0.648). The positive correlation between the peripapillary RPC vessel density and the pRNFL thickness was statistically significant in the control (r = 0.531, p = 0.004), NDR (r = 0.528, p = 0.004), and NPDR (r = 0.405, p = 0.040) groups but not in the PDR group (r = 0.394, p = 0.05). Conclusions: The peripapillary RPC perfusion decreased with DR aggravation, which may be considered as a useful indicator of DR severity. However, the pRNFL thickness had little diagnostic power in differentiating healthy and DM eyes.
Endovascular Treatment in Acute Ischemic Stroke Adoption and Practice: A Single-Center Indonesian Experience
Authors: Mesiano Taufik , Kurniawan Mohammad , Saputri Kevin M. , Hidayat Rakhmad , Permana Affan P. , Rasyid Al , Harris Salim
Published: July 2021

Indonesia is facing increasing stroke prevalence in the past 5 years. Ischemic stroke imposes economic and productivity burden if it is not addressed properly. Endovascular treatment studies are conducted in developed countries where facilities and cost do not count in therapy consideration if it is indicated. Developing countries like Indonesia should work hard to provide the best hyperacute stroke care with protocol deviation and limitation. This is the first review on endovascular treatment practice in a top single-center hospital in Indonesia. Further improvement is needed to catch up with state-of-the-art hyperacute ischemic stroke treatment.
A Systematic Review and Meta-Analysis: Hyponatremia Predicted All-Cause and Cardiovascular Mortality in Dialysis Population
Authors: Li Jin’e , Song Panai , Yang Dong , Liu Yinghong
Published: July 2021

Background: Hyponatremia is one of the most common disorders of electrolytes. Some research studies reported that hyponatremia was closely associated with mortality in patients with dialysis. However, this viewpoint remains controversial. Objective: We aimed to do a systematic review and meta-analysis to assess the influence of hyponatremia on mortality in patients with dialysis. Methods: We identified the eligible studies that investigated the association between hyponatremia and mortality risk in patients under dialysis by searching systematically a series of databases including PubMed, Embase, Cochrane, Web of science, and Ovid from January 2011 to June 2020. Adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) were pooled. Results: From 1,116 records identified, 12 studies including prospective and retrospective cohort studies met our inclusion criteria. We found hyponatremia both at baseline (HR: 1.50 and 95% CI: 1.41–1.59) and in time-varying (HR: 1.63 and 95% CI: 1.44–1.84) were significantly correlated to all-cause mortality after multivariable adjusted. By the subgroup analysis, the same results were presented in hemodialysis (HR: 1.48 and 95% CI: 1.38–1.59) or peritoneal dialysis patients (HR: 1.52 and 95% CI: 1.37–1.70). We also observed that lower serum sodium was independently associated with cardiovascular death. Conclusions: Hyponatremia was independently associated with all-cause and cardiovascular mortality, and it might predict adverse outcomes of patients under dialysis.
Performance of a Novel Research-Use-Only Secretoneurin ELISA in Patients with Suspected Acute Coronary Syndrome: Comparison with an Established Secretoneurin Radioimmunoassay
Authors: Myhre Peder L. , Ottesen Anett H. , Faaren Arne L. , Tveit Sjur H. , Springett Jon , Pyylampi Johanna , Stridsberg Mats , Christensen Geir , Høiseth Arne Didrik , Omland Torbjørn , Røsjø Helge
Published: July 2021

Background: Circulating secretoneurin (SN) concentrations, as measured by established radioimmunoassay (RIA), risk stratify patients with cardiovascular disease. We now report data for a recently developed research-use-only SN enzyme-linked immunosorbent assay (ELISA) in patients with suspected acute coronary syndrome (ACS). Methods: SN ELISA was developed according to industry standards and tested in 401 unselected chest pain patients. Blood samples were drawn <24 h from admission, and we adjudicated all hospitalizations as ACS or non-ACS. The mean follow-up was 6.2 years. Results: SN ELISA with 2 monoclonal sheep anti-SN antibodies has a measuring range of 10–250 pmol/L and demonstrates excellent analytical precision and accuracy across the range of SN concentrations. SN measured by ELISA and RIA correlated in the chest pain patients: rho = 0.39, p < 0.001. SN concentrations were higher in ACS patients (n = 161 [40%]) than in non-ACS patients (n = 240) for both assays, with an area under the curve (AUC) of 0.66 (95% CI: 0.61–0.71) for ELISA and 0.59 (0.54–0.65) for RIA. SN concentrations were also higher in nonsurvivors (n = 65 [16%]) than survivors, with an AUC of 0.72 (0.65–0.79) for ELISA versus 0.64 (0.56–0.72) for RIA, p = 0.007, for difference between assays. Adjusting for age, sex, blood pressure, previous myocardial infarction, atrial fibrillation, and heart failure in multivariable analysis, SN concentrations as measured by ELISA, but not RIA, remained associated with mortality, with a hazard ratio of 1.71 (1.03–2.84), p = 0.038. Conclusions: The novel SN ELISA has excellent performance, higher AUC for diagnosis, and superior prognostic accuracy compared to the established RIA in chest pain patients.
Effectiveness of Self-Help Plus in Preventing Mental Disorders in Refugees and Asylum Seekers in Western Europe: A Multinational Randomized Controlled Trial
Authors: Purgato Marianna , Carswell Kenneth , Tedeschi Federico , Acarturk Ceren , Anttila Minna , Au Teresa , Bajbouj Malek , Baumgartner Josef , Biondi Massimo , Churchill Rachel , Cuijpers Pim , Koesters Markus , Gastaldon Chiara , Ilkkursun Zeynep , Lantta Tella , Nosè Michela , Ostuzzi Giovanni , Papola Davide , Popa Mariana , Roselli Valentina , Sijbrandij Marit , Tarsitani Lorenzo , Turrini Giulia , Välimäki Maritta , Walker Lauren , Wancata Johannes , Zanini Elisa , White Ross , van Ommeren Mark , Barbui Corrado
Published: July 2021

Introduction: Self-Help Plus (SH+) is a group-based psychological intervention developed by the World Health Organization for managing stress. Objective: To assess the effectiveness of SH+ in preventing mental disorders in refugees and asylum seekers in Western Europe. Methods: We conducted a randomized controlled trial in 5 European countries. Refugees and asylum seekers with psychological distress (General Health Questionnaire score ≥3), but without a Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) or ICD/10 diagnosis of mental disorder, as assessed with the Mini International Neuropsychiatric Interview (MINI), were randomized to SH+ or enhanced treatment as usual (ETAU). The primary outcome was the frequency of mental disorders with the MINI at 6 months. Secondary outcomes included the frequency of mental disorders at postintervention, self-identified problems, psychological symptoms, and other outcomes. Results: Four hundred fifty-nine individuals were randomly assigned to SH+ or ETAU. For the primary outcome, we found no difference in the frequency of mental disorders at 6 months (Cramer V = 0.007, p = 0.90, RR = 0.96; 95% CI 0.52–1.78), while the difference significantly favored SH+ at after the intervention (secondary outcome, measured within 2 weeks from the last session; Cramer V = 0.13, p = 0.01, RR = 0.50; 95% CI 0.29–0.87). Conclusions: This is the first randomized indicated prevention study with the aim of preventing the onset of mental disorders in asylum seekers and refugees in Western Europe. As a prevention effect of SH+ was not observed at 6 months, but rather after the intervention only, modalities to maintain its beneficial effect in the long term need to be identified.
Novel Roles of Necroptosis Mediator Receptor-Interacting Protein Kinase 3 in Kidney Injury
Authors: Uni Rie , Choi Mary E.
Published: July 2021

Necroptosis is a programmed cell death that is characterized by regulated necrosis resulting in plasma membrane rupture and subsequent release of damage-associated molecular patterns (DAMPs). Receptor-interacting protein kinase 3 (RIPK3) is a key mediator of this pathway. Accumulating evidence supports a critical role of RIPK3 and the necroptosis pathway in various human diseases. In this review, we discuss recent investigations that have uncovered pathogenic roles of RIPK3 in both acute kidney injury (AKI) and kidney fibrosis. RIPK3 promotes kidney tubular injury via a mechanism involving mitochondrial dysfunction. Additionally, extracellular mitochondrial DNA, which is one of the necroptotic DAMPs, released from damaged mitochondria correlates with kidney tubular injury and represents a potential novel biomarker. RIPK3 also induces kidney fibrogenesis through AKT-dependent activation of the metabolic enzyme ATP citrate lyase. Thus, the RIPK3-mediated necroptosis pathway may serve as a promising new therapeutic target in AKI and kidney fibrosis.