bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the Application of Maximum Radius in Horizontal Curves Using Vehicle Dynamic Simulation
Authors: Sharf Aldeen Asame , Abdi Kordani Ali , Hosseinian Seyed Mohsen , Mehdi Nazar Mehdi
Published: March 2022

Most road design standards recommend using a spiral curve for transitions. The main advantages of using this curve are the gradual increase in the centrifugal force, creating a suitable space for presenting superelevation, and providing a correct perception of the curve for the driver. In this research, vehicle dynamic simulation software CarSim and TruckSim is used to assess the forces imposed on the vehicles. In this regard, 360 scenarios are considered for sedans, SUVs, and trucks, which consist of variations of the road geometry (simple or spiral horizontal curve), curve radius, and type and speed of the vehicle. In addition, the regression analysis is performed to examine the relationships between the lateral acceleration (as a dependent variable) and the vehicle speed, curve radius, and vehicle type (as independent variables). The results indicate that in all cases, safety in the spiral horizontal curve is greater than that in the simple horizontal curve, and the maximum side friction factor, lateral acceleration, roll rate, roll angle, yaw rate, and lateral distance in the simple horizontal curve are higher than those in the spiral horizontal curve. Moreover, the difference percentage of the side friction factor, lateral acceleration, yaw rate, and lateral distance between the simple and spiral horizontal curves is the highest in SUVs, followed by sedans and trucks, while the difference percentage of the roll rate and roll angle is the highest in sedans, followed by SUVs and trucks. The results of regression analysis illustrate that the coefficient of determination (R2) in the proposed model is 0.972, 0.964, and 0.981 for sedans, SUVs, and trucks, respectively, indicating the strong relationships between the dependent and the explanatory variables as well as the capability of the model to cover the data.
Exploration on the Application of New Media Interactive Art to the Protection of Traditional Culture
Authors: Guo Lingling , Zhang Lipeng
Published: March 2022

The background of information age promotes the rapid development of interactive art with new media. The interactive art of new media combines modern photography with the Internet and other technologies. The emergence of new art interacting with media not only reflects the progress and development of media technology but also reflects the tremendous progress of media art, which provides more ways for the development of art and is conducive to improving the diversity of people’s art and cultural activities. This paper summarizes the characteristics of interactive technology and new media and analyzes the application of interactive art of new media in the protection and dissemination of traditional culture. Interactive art is a virtual space that provides artists and engineers with interactive experience through technology platform. Interaction takes place in different areas and guides visitors to create it in different ways. In addition to being applied in many commercial fields of modern society, this art form has also been applied in the field of culture as an important means of communication of traditional culture. Through literature collection, data analysis, and questionnaire survey, it can be concluded that the application of new media interactive art in the protection of traditional culture can not only repair and replicate damaged traditional cultural resources but also display, preserve, and disseminate rare cultural resources.
Simultaneous Determination of Fifteen Polyphenols in Fruit Juice Using Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry Combining Dispersive Liquid-Liquid Microextraction
Authors: Li Yuxiu , He Zengyang , Bao Youmei , Zhu Qingsheng , Ning Yong , Tian Zhenfeng , Zhu Xiaolan
Published: March 2022

Polyphenols are secondary metabolites of plants and used as effective antioxidants in dietary supplements, whose main sources are fruits, vegetables, and grains. To clarify the content and distribution of polyphenols in different fruit species samples accurately, a rapid and sensitive ultrahigh-pressure liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) method combining dispersive liquid-liquid microextraction (DLLME) was developed for quantitative determination of fifteen polyphenol compounds in fruit juice. In this method, the targets were first extracted from 1 g of fruit juice sample using 10 mL of 80% ethanol solution by ultrasonic-assisted extraction (UAE). Then, 1.0 mL of UAE extracted solution, 60 μL of n-octanol and 2.0 mL of H2O were performed in the following DLLME procedure. A C18 reversed-phase column, ZORBAX SB (100 × 4.6 mm, 3.5 μm), was proposed under gradient elution with 0.1% formic acid aqueous solution and methanol mobile phases for the determination of 15 polyphenols, allowing us to obtain polyphenolic profiles in less than 23.0 min. Under the optimum conditions, the enrichment factors ranged from 162 to 194. The results showed that the 15 polyphenols had linear correlation coefficients (R2) more than 0.99. The limits of detection (LODs) were between 18.3 and 103.5 ng/g, and the average recoveries were between 96.9 and 116.3% with interday relative standard deviations (RSDs) ranging from 4.4 to 8.2% in all cases. The method was successfully applied to the analysis of real fruit juice samples and presented itself as a simple, rapid, practical, and environment-friendly technique.
Role of CT Images in the Diagnosis of Common Acute Abdominal Diseases in General Surgery
Authors: Nan Yunguang , Zhang Zuyan , Zhang Jianbo , Jiang Bo , Zhu Yuxi , Zhang Li
Published: March 2022

Acute abdomen is a clinical emergency disease with acute abdominal pain as the main prominent feature. Through severe disease changes in intra-abdominal, extrapelvic, and retroperitoneal tissues and organs, symptoms and clinical signs led by abdominal pain are formed. This article mainly explores the role of CT imaging diagnosis in common acute abdominal diseases in general surgery. In this paper, the use of computer-aided CT scan imaging technology in pulmonary nodules was firstly investigated, and the image segmentation algorithms based on CT images were given, including the spatial domain fuzzy C-mean clustering separation algorithm and the spatial domain fuzzy clustering level set semiautomatic separation algorithm, then the treatment of acute abdomen under the concept of ERAS was explored, and the treatment of ERAS under CT images of the acute abdomen was analyzed and studied. The empirical research results show that the ERAS's concept is guided by the undergoing national nutritional support with the traditional perioperative management. Compared to 12.9% of complications in traditional CPM groups, the recall rate of complications after ERAS group was only 6.01%, the improvement was obvious and the results were statistically significant (

P
<
0.05

). Postoperative hospitalization time was also 4.62 days from 7.93 days, thus controlling the clinical risks of perioperative periods, providing a benefit to patient life.
The Quality of Counseling for Headache OTC Medications in German Community Pharmacies Using a Simulated Patient Approach: Are There Differences between Self-Purchase and Purchase for a Third Party?
Authors: Langer Bernhard , Kunow Christian
Published: March 2022

Background. In Germany—as worldwide—headache is one of the most frequent causes of self-medication. The dispensing of over-the-counter (OTC) medications may only be carried out by community pharmacies (CPs). In doing so, CPs have to ensure “adequate” counseling, for both self-purchase and purchase for a third party, which also occurs in everyday pharmacy practice. The aim of this study was to evaluate the quality of counseling for headache OTC medications in German CPs and, as the first study worldwide, to analyze whether and to what extent there are differences in counseling between self-purchase and purchase for a third party. Methods. A cross-sectional study was carried out using the covert simulated patient methodology (SPM) in all 42 CPs in the German big city Potsdam. With the help of 8 trained simulated patients (SPs), each CP was visited four times by a different SP. The SPs simulated in each CP two scenarios two times with the demand for an OTC medication against headache, which differed only in whether the demand was for themselves or for their boyfriend/girlfriend. Results. All 168 planned pharmacy visits (84 visits per scenario) were successfully carried out. Overall, the median counseling score was 3.0 out of 9 points (interquartile range [IQR 2.0]). There were no significant differences between the two scenarios (Wilcoxon signed-rank test;

p
=
0.495

, r = 0.053). In a multivariate binary logistic regression analysis, the counseling level and the different scenarios were not significantly associated (adjusted odds ratio [AOR] = 1.635, 95% CI = 0.673–3.972,

p
=
0.278

). Conclusions. Due to the partly considerable deficits in counseling of German CPs, policy-makers and the regional chambers of pharmacists are called upon to take appropriate measures to improve the quality of counseling. It is positive that no differences in counseling between self-purchase and purchase for a third party were found, but further verifying studies with a modified methodology are recommended.
An Empirical Study on the Behavioral Intention of College Students’ Online Ideological and Political Learning
Authors: Ren Miaomiao , Ma Yan , Fan Wenxiang , Li Mingyong , Feng Yuming
Published: March 2022

Based on the integration of the technology acceptance model and the information system success model, this study constructs the structural equation model of college students’ online ideological and political learning behavioral intention; then, a questionnaire survey is conducted among college students from 7 colleges of Chongqing and Hangzhou. The results show that there are group differences in system perception, technology acceptance perception, and behavioral intention among college students with different genders and grades; different dimensions of information system quality have different effects on behavioral intention; perceived ease of use is an important mediating variable, which has a direct positive impact on the use attitude; perceived usefulness and use attitude have positive direct effects on behavioral intention; and perceived usefulness has a higher predictive effect on behavioral intention. Therefore, we put forward four suggestions. First, in the future practice, we should pay attention to the group differences of college students and constantly improve the practice mechanism of network ideological and political education. Second, we propose to take the quality construction of information system as the goal and constantly consolidate the service system of network platform. Third, we believe that we can improve users’ attitude towards the use of the platform by improving their perception of ease of use. Finally, we also suggest that we should focus on improving users’ useful perception of the platform, so as to promote their use behavior.
Geostatistics and Artificial Intelligence Applications for Spatial Evaluation of Bearing Capacity after Dynamic Compaction
Authors: Ewusi-Wilson Rodney , Park Junghee , Yoon Boyoung , Lee Changho
Published: March 2022

This study employs geostatistical and artificial intelligence (AI) methods to estimate the degree of ground improvement after dynamic compaction. We implement artificial neural network (ANN) and random forest (RF) for artificial intelligence spatial interpolation to investigate the efficiency of dynamic compaction considering the spatial distribution of the geotechnical parameters. Data used in this study involve averaged SPTNvalue before dynamic compaction (Nbefore), averaged SPTNvalue after dynamic compaction (Nafter), applied energy (AE), X‐ and Y‐coordinates at each borehole location, and degree of ground improvement (DI). This study uses the data obtained from a total of 42 borehole logs with an average depth of 17 m and testing depth intervals of 1.5 m after dynamic compaction and 26 SPT‐N log data before dynamic compaction. An optimal spatial interpolation tool selected in this study develops a bearing capacity map after dynamic compaction. The model performance is examined using the correlations between SPT‐based and predicted bearing capacity in the context of mean absolute error (MAE), coefficient of determination (r2), and root mean square error (RMSE). The model with the least MAE and RMSE and the highestr2is selected as optimal. The optimal RF (RFVD) model has an RMSE of 15.83 while out of the two geostatistical models considered OK recorded the lower RMSE of 22.62. Results show that RF spatial interpolation techniques outperform traditional geostatistical methods. The artificial neural network model shows good compatibility with physical and intuitive processes pertinent to dynamic compaction. The ANN resulted in a prediction RMSE of 0.11 for DI and anr2of 0.97. This unique approach for evaluating the efficiency of dynamic compaction will be useful to geotechnical engineers when designing site improvement projects, especially dynamic compaction by employing easily obtainable field data for coarse‐grained soils.
Research on Dynamic Spectrum Allocation Algorithm Based on Cyclic Neural Network
Authors: Yu Xiaomo , Cai Yonghua , Li Wenjing , Zhou Xiaomeng , Tang Ling
Published: March 2022

Due to the wide application of cognitive wireless network, the network structure is becoming more and more complex. It is difficult to establish the corresponding mathematical model to simulate the high complexity network environment. The algorithm based on recurrent neural network in deep reinforcement learning can effectively solve this problem. In addition, with the rise of deep learning in recent years, the combination of reinforcement learning and deep learning shows excellent ability in dealing with complex problems and data operation. This paper is aimed at studying dynamic spectrum allocation based on cyclic neural network. This paper briefly introduces MATLAB, sets up the network environment of algorithm simulation, then analyzes the overall performance of the improved genetic algorithm, and explores the influence of genetic algorithm-related parameters and network environment-related parameters on the performance of the algorithm. The results show the improved genetic algorithm. The network efficiency can be improved by about 2%, but the spectrum switching frequency can be reduced by 69%. When the number of primary users in the network is large, the network benefit of improving the genetic algorithm is superior to the other two algorithms. In addition, when the crossover probability is 0.6 and 0.1, the fitness value is higher than the crossover probability of 0.9 and 0.5; the interference of authorized users in the network initially has less impact on the secondary user.
Separation of Crystal Violet Dye from Wastewaters by Using Supported Liquid Membrane Technology
Authors: Ashraf M. Waqar , Collins Michael P. , Mir M. Amin , Salam Abdus , Ul-Hamid Anwar
Published: March 2022

The current study enumerates the use of supported liquid membrane (SLM) technology to remove and recover crystal violet dye from wastewaters. The management of textile industry waste effluents is one of the main concerns of environmental health experts due to having excessive concentrations of dyes and resistance to biodegradation. Liquid membranes offer an affordable and green method for the selective removal of dyes from aqueous solutions. To create a liquid membrane, refined and edible vegetable oils were supported on microporous polymeric films of polypropylene (PP1E). Various parameters influencing transport, such as pH range in the feed solution, initial dye concentration, acid concentration in the strip solution, oil viscosities, and membrane lifetime, have been studied. The maximum flux value (

1.7
×

10

−
5

mg/cm2/s) for crystal violet dye was obtained with sunflower oil-supported membrane at a pH of 12 in the feed solution and a concentration of 0.3 M hydrochloric acid in the strip solution. Under ideal conditions, the maximum amount of dye was transported within 6 hours. Studies on membrane stability and morphology revealed that the flux remained constant up to about 24 hours and then decreased gradually. Morphological studies showed that this may be attributed to deformation of pores shape and gradual clogging.
Numerical Study on Flow-Induced Noise of Deflector Jet Servo Valve Based on LES/Lighthill Hybrid Method
Authors: Ren Yukai , Yan Hao , Cai Cunkun
Published: March 2022

The flow-induced noise occurring in the prestage of the deflector jet servo valve (DJV) significantly affects the performance of DJV, which is a critical issue for electrohydraulic servo valves. To capture the root causes of flow-induced noise, DJV is numerically studied using computational aeroacoustics (CAA) methods in this paper. The acoustic field is investigated with Lighthill’s acoustic analogy based on the pulsation data from a large eddy simulation (LES). The flow-induced noise generation mechanism in DJV is revealed by analyzing the sound pressure level and vorticity distribution at different moments. Moreover, a kind of oscillation cavity model based on the Helmholtz oscillator is built, which reveals that the flow-induced noise is caused by self-excited oscillation and vortex. In addition, the result shows that continuous broadband dipole noise with medium- and high-frequency components of 1100 Hz and 2501 Hz dominates the DJV flow field. In order to avoid unexpected resonance, the natural frequency of the prestage should not coincide with the frequency of the flow oscillation frequency. Thus, this work can benefit the design and optimization of the prestage structure.
Dynamic Correlation between Ozone and Volatile Organic Compounds in the Southeastern Coastal Region
Authors: Li Hao , Nie Xing
Published: March 2022

In order to investigate the sources and effects of atmospheric volatile organic compounds (VOCs) in the southeast coastal region and to formulate effective ozone control policies, 96 VOCs were measured in the southeast coastal region from September to October 2016 using an online gas chromatograph-mass spectrometer/flame ionization detector (Online-GC-MS/FID). The composition, daily trends, sources, and contribution to ozone production of 96 VOCs in the southeast coastal region were analyzed. The results of the study showed that the volume mixing ratio of alkanes was the highest, followed by aromatic hydrocarbons; the daily variation trend of alkanes and aromatic hydrocarbons was obvious, with a double-peaked feature; propane, isoprene, and aromatic hydrocarbons in the atmosphere of the southeast coastal region came from liquefied petroleum gas (LPG), natural sources, and industrial emissions, respectively. The analysis of the activity of VOCs shows that aromatic hydrocarbons and alkanes are the most important contributors to OFP in the southeast coastal region, with toluene, m-/paraxylene, and ethylene being the species that contribute the most to OFP. Therefore, the control of VOC emissions from anthropogenic sources is a priority for ozone pollution control in the southeast coastal region in the future.
Clinical Effect of Qili Qiangxin Capsule Combined with Sacubitril-Valsartan in Patients with Chronic Heart Failure
Authors: Yao Jiafang , Liu Dan
Published: March 2022

The clinical effect of Qili Qiangxin capsule combined with sacubitril-valsartan on patients with chronic heart failure was studied. We selected 108 patients with chronic heart failure in our hospital from March 2016 to January 2020 and divided them into a control group and a study group according to the random table method, with 54 cases in each. The control group took sacubitril and valsartan orally, and the study group took Qili Qiangxin pill on the basis of sacubitril and valsartan. The course of the treatment for 2 groups is 4 weeks. We compared the total effective rate of the treatment of the 2 groups for 4 weeks, cardiac function (left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF)) before and after 4 weeks of treatment, 6 min walking distance (6MWT), changes in cTnI and NT-proBNP levels, and adverse reactions. The total effective rate in the study group (90.74%) is higher than that in the control group (72.22%) (

P

＜0.05). After 4 weeks of treatment, the study group LVESV (45.23 ± 2.98 mm) and LVEDV (43.38 ± 4.01 mm) are lower than those of the control group ((49.98 ± 2.56 mm) and (50.75 ± 3.49 mm), respectively), while LVEF (47.38 ± 2.78%) is higher than that in the control group (42.08 ± 3.24%) (

P

 ＜ 0.05). After 4 weeks of treatment, the study group 6MWT (476.58 ± 31.25 m) of patients with chronic heart failure is higher than that of the control group (396.52 ± 24.52 m) (P ＜0.05). After 4 weeks of treatment, the study group serum cTnI (0.36 ± 0.12 μg/L) and NT-proBNP (276.91 ± 30.12 pg/ml) of patients with chronic heart failure are lower than those in the control group (0.87 ± 0.25 μg/L) and (367.48 ± 48.57 pg/ml) (

P

＜0.05). There is no significant difference between the adverse reactions in the two groups (

P

 ＞ 0.05). Conclusion: Xinbao pills combined with sacubitril and valsartan have a good effect on patients with chronic heart failure, which can improve the heart function and exercise endurance and reduce serum cTnI and NT-proBNP levels.
The Effect of Edible Mushroom on Health and Their Biochemistry
Authors: Assemie Anmut , Abaya Galana
Published: March 2022

Edible mushrooms are fungi that can be seen with the naked eye and are relatively easy to gather by hand. This review article highlights the health benefit and the biochemistry of several mushroom species. Agaricus bisporus, Pleurotus species. Lentinus edodes, and Volvariella species are the most acceptable varieties among the cultivated mushroom. Various biochemical methods such as methanol, ethanol, and water extract of different parts of the edible mushroom in the laboratory have been applied to determine and/or quantify the presence and effectiveness of their chemical compounds, food value, and medicinal properties. They contain varying amounts of carbohydrates, proteins, nucleic acids, lipids, minerals, terpenoids, phenolic compounds, steroids, and lectins and vitamins, as well as lowering cholesterol levels in the body. Due to the presence of those vital nutrients, mushrooms are the best food item with high nutritional value. These compounds have a wide range of therapeutic effects and can act as immunomodulatory, anticarcinogenic, antiviral, antioxidant, and anti-inflammatory agents. Routine consumption of edible mushrooms would give adequate protection due to the presence of all the necessary nutrients from them. Therefore, edible mushrooms are herbal antibiotics to many diseases as well as various cancers of humans.
Validation of Balance Map Analysis of Walking at Different Speeds
Authors: Kagawa Takahiro
Published: March 2022

Walking balance about falling in the forward direction is associated with the body’s center of mass and placement of the swing foot during the swing phase. Balance map analysis evaluates walking balance based on the prediction of the reachability of an appropriate foot placement using a simple biomechanical model during the swing phase without active joint torque (ballistic walking model). The ballistic walking model can be justified in terms of the preferred walking speed because the metabolic energy consumption associated with muscle activity in faster and slower walking is higher than that in preferred speed walking. Therefore, the assumption that the active joint torque is sufficiently small during the swing phase may not hold in faster or slower walking, which can be a significant limitation of balance map analysis. In this study, it was hypothesized that steady-state walking at various walking speeds would be evaluated as stable for validation of the balance map analysis, and the gait patterns for three types of walking speeds (slow, normal, and fast) were examined. The results showed that the trajectories during the swing phase were within stable regions for all conditions, with a sufficient margin from the forward balance loss region. In addition, the margin from forward balance was reduced with an increase in walking velocity. The decrease in the margin during fast walking resulted from an increase in the forward velocity of the body’s center of mass in relation to the velocity of the swing leg. These results suggest that balance map analysis effectively measures walking balance at various speeds.
Cross-Site Concordance Evaluation of Tumor DNA and RNA Sequencing Platforms for the CIMAC-CIDC Network
Authors: Zeng Zexian , Fu Jingxin , Cibulskis Carrie , Jhaveri Aashna , Gumbs Curtis , Das Biswajit , Sanchez-Espiridion Beatriz , Janssens Sylvie , Taing Len , Wang Jin , Lindsay James , Vilimas Tomas , Zhang Jianhua , Tokheim Collin , Sahu Avinash , Jiang Peng , Yan Chunhua , Duose Dzifa Yawa , Cerami Ethan , Chen Li , Cohen David , Chen Qingrong , Enos Rebecca , Huang Xin , Lee Jack J. , Liu Yang , Neuberg Donna S. , Nguyen Cu , Patterson Candace , Sarkar Sharmistha , Shukla Sachet , Tang Ming , Tsuji Junko , Uduman Mohamed , Wang Xiaoman , Weirather Jason L. , Yu Jijun , Yu Joyce , Zhang Jianjun , Zhang Jiexin , Meerzaman Daoud , Thurin Magdalena , Futreal Andrew , Karlovich Chris , Gabriel Stacey B. , Wistuba Ignacio Ivan , Liu X. Shirley , Wu Catherine J.
Published: March 2022

Purpose:

Whole-exome (WES) and RNA sequencing (RNA-seq) are key components of cancer immunogenomic analyses. To evaluate the consistency of tumor WES and RNA-seq profiling platforms across different centers, the Cancer Immune Monitoring and Analysis Centers (CIMAC) and the Cancer Immunologic Data Commons (CIDC) conducted a systematic harmonization study.

Experimental Design:

DNA and RNA were centrally extracted from fresh frozen and formalin-fixed paraffin-embedded non–small cell lung carcinoma tumors and distributed to three centers for WES and RNA-seq profiling. In addition, two 10-plex HapMap cell line pools with known mutations were used to evaluate the accuracy of the WES platforms.

Results:

The WES platforms achieved high precision (> 0.98) and recall (> 0.87) on the HapMap pools when evaluated on loci using > 50× common coverage. Nonsynonymous mutations clustered by tumor sample, achieving an index of specific agreement above 0.67 among replicates, centers, and sample processing. A DV200 > 24% for RNA, as a putative presequencing RNA quality control (QC) metric, was found to be a reliable threshold for generating consistent expression readouts in RNA-seq and NanoString data. MedTIN > 30 was likewise assessed as a reliable RNA-seq QC metric, above which samples from the same tumor across replicates, centers, and sample processing runs could be robustly clustered and HLA typing, immune infiltration, and immune repertoire inference could be performed.

Conclusions:

The CIMAC collaborating laboratory platforms effectively generated consistent WES and RNA-seq data and enable robust cross-trial comparisons and meta-analyses of highly complex immuno-oncology biomarker data across the NCI CIMAC-CIDC Network.
Systematic Evaluation of the Immune Environment of Small Intestinal Neuroendocrine Tumors
Authors: Vesely Clare , Wong Yien Ning Sophia , Childs Alexa , Akarca Ayse U. , Dhami Pawan , Vaikkinen Heli , Conde Lucia , Herrero Javier , Ogunbiyi Olagunju , Gander Amir , Luong Tu Vinh , Thirlwell Chrissie , Caplin Martyn , Toumpanakis Christos , Peggs Karl , Quezada Sergio A. , Marafioti Teresa , Meyer Tim
Published: March 2022

Purpose:

The immune tumor microenvironment and the potential therapeutic opportunities for immunotherapy in small intestinal neuroendocrine tumors (siNET) have not been fully defined.

Experimental Design:

Herein, we studied 40 patients with primary and synchronous metastatic siNETs, and matched blood and normal tissue obtained during surgery. We interrogated the immune checkpoint landscape using multi-parametric flow cytometry. In addition, matched FFPE tissue was obtained for multi-parametric IHC to determine the relative abundance and distribution of T-cell infiltrate. Tumor mutational burden (TMB) was also assessed and correlated with immune infiltration.

Results:

Effector tumor-infiltrating lymphocytes (TIL) had a higher expression of PD-1 in the tumor microenvironment compared with the periphery. In addition, CD8+ TILs had a significantly higher co-expression of PD-1/ICOS and PD-1/CTLA-4 (cytotoxic T lymphocyte antigen-4) and higher levels of PD-1 expression compared with normal tissue. IHC revealed that the majority of cases have ≤10% intra-tumoral T cells but a higher number of peri-tumoral T cells, demonstrating an “exclusion” phenotype. Finally, we confirmed that siNETs have a low TMB compared with other tumor types in the TCGA database but did not find a correlation between TMB and CD8/Treg ratio.

Conclusions:

Taken together, these results suggest that a combination therapy approach will be required to enhance the immune response, using PD-1 as a checkpoint immunomodulator backbone in combination with other checkpoint targeting molecules (CTLA-4 or ICOS), or with drugs targeting other pathways to recruit “excluded” T cells into the tumor microenvironment to treat patients with siNETs.
One Size Does Not Fit All: Breast Cancer in Young Women
Authors: Yehia Lamis , Eng Charis
Published: March 2022

Breast cancers occurring in young women remain poorly characterized. Through studying a series of very young women with breast cancer compared with older women with breast cancer, distinct biological features were identified, with important implications for the personalized genomics-driven management of these cancers.

See related article by Waks et al., p. 2339
The Role of ARID1A in the Nonestrogenic Modulation of IGF-1 Signaling
Authors: Jdeed Sham , Erdős Edina , Bálint Bálint L. , Uray Iván P.
Published: March 2022

Gaining pharmacologic access to the potential of ARID1A, a tumor suppressor protein, to mediate transcriptional control over cancer gene expression is an unresolved challenge. Retinoid X receptor ligands are pleiotropic, incompletely understood tools that regulate breast epithelial cell proliferation and differentiation. We found that low-dose bexarotene (Bex) combined with the nonselective beta-blocker carvedilol (Carv) reduces proliferation of MCF10DCIS.com cells and markedly suppresses ARID1A levels. Similarly, Carv synergized with Bex in MCF-7 cells to suppress cell growth. Chromatin immunoprecipitation sequencing analysis revealed that under nonestrogenic conditions Bex + Carv alters the concerted genomic distribution of the chromatin remodeler ARID1A and acetylated histone H3K27, at sites related to insulin-like growth factor (IGF) signaling. Several distinct sites of ARID1A enrichment were identified in the IGF-1 receptor and IRS1 genes, associated with a suppression of both proteins. The knock-down of ARID1A increased IGF-1R levels, prevented IGF-1R and IRS1 suppression upon Bex + Carv, and stimulated proliferation. In vitro IGF-1 receptor neutralizing antibody suppressed cell growth, while elevated IGF-1R or IRS1 expression was associated with poor survival of patients with ER-negative breast cancer. Our study demonstrates direct impact of ARID1A redistribution on the expression and growth regulation of IGF-1–related genes, induced by repurposed clinical drugs under nonestrogenic conditions.

Implications:

This study underscores the possibility of the pharmacologic modulation of the ARID1A factor to downregulate protumorigenic IGF-1 activity in patients with postmenopausal breast cancer undergoing aromatase inhibitor treatment.
The Capsule of Acinetobacter baumannii Protects against the Innate Immune Response
Authors: Akoolo Lavoisier , Pires Silvia , Kim Jisun , Parker Dane
Published: March 2022

Acinetobacter baumannii is an opportunistic pathogen that has recently emerged as a global threat associated with high morbidity, mortality, and antibiotic resistance. We determined the role of type I interferon (IFN) signaling in A. baumannii infection. We report that A. baumannii can induce a type I IFN response that is dependent upon TLR4-TRIF-IRF3 and phagocytosis of the bacterium. Phase variants of A. baumannii that have a reduced capsule, lead to enhanced TLR4-dependent type I IFN induction. This was also observed in a capsule-deficient strain. However, we did not observe a role for this pathway in vivo. The enhanced signaling could be accounted for by increased phagocytosis in capsule-deficient strains that also lead to enhanced host cell-mediated killing. The increased cytokine response in the absence of the capsule was not exclusive to type I IFN signaling. Several cytokines, including the proinflammatory IL-6, were increased in cells stimulated with the capsule-deficient strain, also observed in vivo. After 4 h in our acute pneumonia model, the burden of a capsule-null strain was significantly reduced, yet we observed increases in innate immune cells and inflammatory markers compared to wild-type A. baumannii. This study underscores the role of phase variation in the modulation of host immune responses and indicates that the capsule of A. baumannii plays an important role in protection against host cell killing and evasion from activation of the innate immune response.
A Community-Based Education Program for Overactive Bladder in a Predominantly Minority Older Female Population: A Pilot Study
Authors: Martinez Díaz Susana , Pierce Hudson , Lee John Richard , Asfaw Tirsit , Abram Andrew , Bhojani Naeem , Elterman Dean , Zorn Kevin , Chughtai Bilal
Published: March 2022

Introduction: Knowledge gaps regarding available treatment and social stigmatization are barriers to care in patients with overactive bladder (OAB). We assessed the feasibility of an OAB education program targeting older community-dwelling females. Methods: Community-dwelling women over 55 years old were recruited. Eligible participants underwent an education program covering continence-promotion strategies. The Overactive Bladder Questionnaire-Short Form and Short Form-12 were completed at baseline, 1 week, 3 months, and 6 months post-intervention to measure symptom bother and condition-specific and general quality of life (QoL). Data were analyzed using a linear mixed-effects model for repeated measures. Results: Thirty-seven female patients with OAB symptoms at baseline were assessed with the majority from Latino/Hispanic or Black/African American ethnic/racial backgrounds. For our youngest subgroup (≤68 years old), significant improvements were observed at 3 and 6 months compared to 1 week post-intervention for symptom bother (3 months, −22.75, p = 0.006; 6 months, −25.76; p = 0.001) and condition-specific and health-related QoL subscale scores for concern (3 months, +23.76, p = 0.006; 6 months, +22.15, p = 0.011) and social interaction (3 months, +21.11, p = 0.017; 6 months, +20.51; p = 0.021). For all age subgroups, improvements in general QoL measures for mental health were seen at 3 and 6 months compared to baseline (3 months, +7.57, p = 0.02; 6 months, +6.70; p = 0.048). Conclusions: Statistically significant improvements in symptom bother, condition-specific, and general QoL measures were observed following an OAB education program pilot study in a predominantly minority female population. Further studies are needed to support efficacy and optimize program design.
Gene Therapy With the N-Terminus of Junctophilin-2 Improves Heart Failure in Mice
Authors: Wang Jinxi , Shi Qian , Wang Yihui , Dawson Logan W. , Ciampa Grace , Zhao Weiyang , Zhang Guangqin , Chen Biyi , Weiss Robert M. , Grueter Chad E. , Hall Duane D. , Song Long-Sheng
Published: March 2022

Background:

Transcriptional remodeling is known to contribute to heart failure (HF). Targeting stress-dependent gene expression mechanisms may represent a clinically relevant gene therapy option. We recently uncovered a salutary mechanism in the heart whereby JP2 (junctophilin-2), an essential component of the excitation-contraction coupling apparatus, is site-specifically cleaved and releases an N-terminal fragment (JP2NT [N-terminal fragment of JP2]) that translocates into the nucleus and functions as a transcriptional repressor of HF-related genes. This study aims to determine whether JP2NT can be leveraged by gene therapy techniques for attenuating HF progression in a preclinical pressure overload model.

Methods:

We intraventricularly injected adeno-associated virus (AAV) (2/9) vectors expressing eGFP (enhanced green fluorescent protein), JP2NT, or DNA-binding deficient JP2NT (JP2NT
ΔbNLS/ARR
) into neonatal mice and induced cardiac stress by transaortic constriction (TAC) 9 weeks later. We also treated mice with established moderate HF from TAC stress with either AAV-JP2NT or AAV-eGFP. RNA-sequencing analysis was used to reveal changes in hypertrophic and HF-related gene transcription by JP2NT gene therapy after TAC. Echocardiography, confocal imaging, and histology were performed to evaluate heart function and pathological myocardial remodeling following stress.

Results:

Mice preinjected with AAV-JP2NT exhibited ameliorated cardiac remodeling following TAC. The JP2NT DNA-binding domain is required for cardioprotection as its deletion within the AAV-JP2NT vector prevented improvement in TAC-induced cardiac dysfunction. Functional and histological data suggest that JP2NT gene therapy after the onset of cardiac dysfunction is effective at slowing the progression of HF. RNA-sequencing analysis further revealed a broad reversal of hypertrophic and HF-related gene transcription by JP2NT overexpression after TAC.

Conclusions:

Our prevention- and intervention-based approaches here demonstrated that AAV-mediated delivery of JP2NT into the myocardium can attenuate stress-induced transcriptional remodeling and the development of HF when administered either before or after cardiac stress initiation. Our data indicate that JP2NT gene therapy holds great potential as a novel therapeutic for treating hypertrophy and HF.
Novel CaMKII-δ Inhibitor Hesperadin Exerts Dual Functions to Ameliorate Cardiac Ischemia/Reperfusion Injury and Inhibit Tumor Growth
Authors: Zhang Junxia , Liang Ruqi , Wang Kai , Zhang Wenjia , Zhang Mao , Jin Li , Xie Peng , Zheng Wen , Shang Haibao , Hu Qingmei , Li Jiayi , Chen Gengjia , Wu Fujian , Lan Feng , Wang Lipeng , Wang Shi-Qiang , Li Yongfeng , Zhang Yong , Liu Jinghao , Lv Fengxiang , Hu Xinli , Xiao Rui-Ping , Lei Xiaoguang , Zhang Yan
Published: March 2022

Background:

Cardiac ischemia/reperfusion (I/R) injury has emerged as an important therapeutic target for ischemic heart disease, the leading cause of morbidity and mortality worldwide. At present, there is no effective therapy for reducing cardiac I/R injury. CaMKII (Ca
2+
/calmodulin-dependent kinase II) plays a pivotal role in the pathogenesis of severe heart conditions, including I/R injury. Pharmacological inhibition of CaMKII is an important strategy in the protection against myocardial damage and cardiac diseases. To date, there is no drug targeting CaMKII for the clinical therapy of heart disease. Furthermore, at present, there is no selective inhibitor of CaMKII-δ, the major CaMKII isoform in the heart.

Methods:

A small-molecule kinase inhibitor library and a high-throughput screening system for the kinase activity assay of CaMKII-δ9 (the most abundant CaMKII-δ splice variant in human heart) were used to screen for CaMKII-δ inhibitors. Using cultured neonatal rat ventricular myocytes, human embryonic stem cell–derived cardiomyocytes, and in vivo mouse models, in conjunction with myocardial injury induced by I/R (or hypoxia/reoxygenation) and CaMKII-δ9 overexpression, we sought to investigate the protection of hesperadin against cardiomyocyte death and cardiac diseases. BALB/c nude mice with xenografted tumors of human cancer cells were used to evaluate the in vivo antitumor effect of hesperadin.

Results:

Based on the small-molecule kinase inhibitor library and screening system, we found that hesperadin, an Aurora B kinase inhibitor with antitumor activity in vitro, directly bound to CaMKII-δ and specifically blocked its activation in an ATP-competitive manner. Hesperadin functionally ameliorated both I/R- and overexpressed CaMKII-δ9–induced cardiomyocyte death, myocardial damage, and heart failure in both rodents and human embryonic stem cell–derived cardiomyocytes. In addition, in an in vivo BALB/c nude mouse model with xenografted tumors of human cancer cells, hesperadin delayed tumor growth without inducing cardiomyocyte death or cardiac injury.

Conclusions:

Here, we identified hesperadin as a specific small-molecule inhibitor of CaMKII-δ with dual functions of cardioprotective and antitumor effects. These findings not only suggest that hesperadin is a promising leading compound for clinical therapy of cardiac I/R injury and heart failure, but also provide a strategy for the joint therapy of cancer and cardiovascular disease caused by anticancer treatment.
The Charism of Care of the Order of St John and Female Monasticism
Authors: Dulska Anna Katarzyna
Published: March 2022

The charism of care inspired the foundation of various medieval religious orders, the Order of St John of Jerusalem being the most renowned of these. This article uses a case study of a female Hospitaller convent in Bargota in the kingdom of Navarre, to examine to what extent the charism of hospitality influenced the Order’s decision-making. By identifying the factors lying behind the foundation of the convent in the early fourteenth century and its dissolution a century later, it contributes to the discussion on the relevance of female Hospitaller monasticism in the Late Middle Ages and argues that the Order sustained the convent as long as the women’s care-worthiness outweighed the burden of cura monialium.
Sufism, Miracles and Oceanic Fatwas: The Beloved of North Jakarta
Authors: Sevea Teren
Published: March 2022

This article examines stories, hagiographies, fatwas, and treatises related to the grave of a sayyid miracle worker (keramat) buried in North Jakarta. It is a product of research that began in 2008 when I first visited the Sufi shrine of the eminent keramat, Habib Hussein al-ʿAydarus (d. 1169/1756), in the village of Luar Batang. Herefrom, I enjoyed access to a series of documents, oral traditions and miracle stories, along with invaluable information via conversations with Sufi elders, devotees, and Habib Hussein’s kinsmen. This article begins by introducing the Luar Batang shrine and stories of the keramat’s apparitions that continue to be told in the village. It discusses a twenty-first century moment when the keramat was seen by some to resist urban redevelopment and collude with controversial Islamists and Sunni vigilantes. His apparitions and miracle stories reminded votaries of his immortal history of resisting colonialism, secularism, Islamophobia and ‘Christianisation’. From this contemporary moment, the article turns its attention towards hagiographies produced in twentieth-century Java by the historians of Sufi networks, before analysing fatwas on the keramat produced in the late nineteenth century by Islamic scholars (ulama) from Yemen, Mecca, Medina and Java concerning revenue, inheritance, and the legality of customs at the Luar Batang shrine. The article works backwards from a contemporary moment in order to introduce readers to the keramat, village and grave and his historical and peripatetic life in Gujarat, Hadramaut and Java, before highlighting how the shrine of a seemingly peripheral village in Jakarta has been a key concern for authorities across the Islamic world and an Indian Ocean-wide devotional community. Miracle stories and hagiographies praising the keramat as the exemplar of Sunnism and Shafiʿism, as well as fatwas defending the customs of his shrine as being inviolable ones, encourage us to discard the still-regnant academic divisions of Sharia/Custom and Sufis/Ulama. Together, they tell a story of miraculous narratives, devotional cultures, social memories and sacral places that are often pushed to the margins of religious studies but refuse to fade into oblivion.
«The Matter Present in Sensibles but not qua Sensibles». Aristotle’s Account of Intelligible Matter as the Matter of Mathematical Objects
Authors: Michetti Beatrice
Published: March 2022

Aristotle explicitly speaks of intelligible matter in three passages only, all from theMetaphysics, in the context of the analysis of definition as the formula that expresses the essence:Metaph.Z10, 1036 a8-11;Metaph.Z11, 1037 a5;Metaph.H6, 1045 a34-36 and 45 b1. In the case of the occurrences of Z10 and Z11, there is almost unanimous consensus that Aristotle uses the expression in a technical way, to indicate the matter of that particular type of objects that are intelligible compounds, of which mathematical objects are paradigmatic instances. By contrast, there is no agreement on how to understand the expression in the case of H6. Here, ‘intelligible matter’ would denote, as stated by some interpreters, the generic element of the definition. The aim of this paper is to show that ὕλη νοητή has the same technical meaning in all the three explicit occurrences in theMetaphisics. Contrary to the interpretation that there is a shift in meaning from Z10-11 to H6, my goal is to illustrate that in both contexts, Aristotle uses the expression ‘intelligible matter’ to designate the matter of mathematical objects insofar as they are paradigmatic intelligible compounds.
Dialectic and Sophisms: The Sceptical Dissolution of Dogmatic Logic
Authors: Spinelli Emidio
Published: March 2022

This paper aims to examine a very specific passage of Sextus Empiricus’s work: the final section of the second book of the Outlines of Pyrrhonism (=ph ii, 229–259). Here Sextus concentrates his attention on a very limited yet crucial topic, namely the question of the validity or invalidity and ‘pragmatic dissolution’ of an allegedly strong tool such as sophisms and their dialectical structure. Indeed, Pyrrhonists do not wander about aimlessly nor lack effective tools through which to dismantle the logical industry of sophisms; their reference point is completely different, since they agree about some evident facts and live their life in accordance with κοινὸς βίος.
Calvariomorphus—a new genus of marsh beetles (Coleoptera: Scirtidae) with remarkable elytral excitators
Authors: RUTA RAFAŁ , YOSHITOMI HIROYUKI
Published: March 2022

A new genus of marsh beetles (Coleoptera: Scirtidae: Scirtinae) from Southeast Asia is described to accommodate Contacyphon peterseni (Klausnitzer, 1973) from Bismarck Archipelago and three newly described species: Calvariomorphus malayanus sp. nov. (type species of the genus), C. sakaii sp. nov., and C. palauensis sp. nov. Morphology and relationships between Calvarium-like taxa, defined on the basis of several common morphological features (compact body, very narrow clypeus, deep subantennal fossae) are discussed.