bluuebunny/crossref_metadata_2025 huggingface dataset:
New Double Bifurcation of Nilpotent Focus
Authors: Li Feng , Li Hongwei , Liu Yuanyuan
Published: April 2021

In this paper, a new bifurcation phenomenon of nilpotent singular point is analyzed. A nilpotent focus or center of the planar systems with 3-multiplicity can be broken into two complex singular points and a second order elementary weak focus. Then, two more limit cycles enclosing the second order elementary weak focus can bifurcate through the multiple Hopf bifurcation.
AGE-BASED ANALYSIS OF HEART RATE VARIABILITY (HRV) FOR PATIENTS WITH CONGESTIVE HEART FAILURE
Authors: NAMAZI HAMIDREZA , BALEANU DUMITRU , KREJCAR ONDREJ
Published: April 2021

It is known that heart activity changes during aging. In this paper, we evaluated alterations of heart activity from the complexity point of view. We analyzed the variations of heart rate of patients with congestive heart failure that are categorized into four different age groups, namely 30–39, 50–59, 60–69, and 70–79 years old. For this purpose, we employed three complexity measures that include fractal dimension, sample entropy, and approximate entropy. The results showed that the trend of increment of subjects’ age is reflected in the trend of increment of the complexity of heart rate variability (HRV) since the values of fractal dimension, approximate entropy, and sample entropy increase as subjects get older. The analysis of the complexity of other physiological signals can be further considered to investigate the variations of activity of other organs due to aging.
Dynamic Graph Learning Convolutional Networks for Semi-supervised Classification
Authors: Fu Sichao , Liu Weifeng , Guan Weili , Zhou Yicong , Tao Dapeng , Xu Changsheng
Published: April 2021

Over the past few years, graph representation learning (GRL) has received widespread attention on the feature representations of the non-Euclidean data. As a typical model of GRL, graph convolutional networks (GCN) fuse the graph Laplacian-based static sample structural information. GCN thus generalizes convolutional neural networks to acquire the sample representations with the variously high-order structures. However, most of existing GCN-based variants depend on the static data structural relationships. It will result in the extracted data features lacking of representativeness during the convolution process. To solve this problem, dynamic graph learning convolutional networks (DGLCN) on the application of semi-supervised classification are proposed. First, we introduce a definition of dynamic spectral graph convolution operation. It constantly optimizes the high-order structural relationships between data points according to the loss values of the loss function, and then fits the local geometry information of data exactly. After optimizing our proposed definition with the one-order Chebyshev polynomial, we can obtain a single-layer convolution rule of DGLCN. Due to the fusion of the optimized structural information in the learning process, multi-layer DGLCN can extract richer sample features to improve classification performance. Substantial experiments are conducted on citation network datasets to prove the effectiveness of DGLCN. Experiment results demonstrate that the proposed DGLCN obtains a superior classification performance compared to several existing semi-supervised classification models.
Mechanistic Insights into Catalytic Reduction of N2O by CO over Cu-Embedded Graphene: A Density Functional Theory Perspective
Authors: Akça Aykan , Karaman Onur , Karaman Ceren
Published: April 2021

In this study, the mechanism of N2O reduction by CO over Cu-embedded graphene(CuG) surface was examined through Density Functional Theory(DFT) with Grimme-D2 dispersion correction. Cu-embedded graphene networks can be synthesized experimentally, and are less costly than plain graphene by virtue of the limited use of Cu atoms. Cu atoms strongly bond to defective structures and make the structure more stable. The binding energy between the defective graphene structure and the Cu atom was calculated as −3.92 eV. The Bader analysis was performed for CuG surface characteristics, and adsorption geometries of N2O and electron density difference maps were created. The results showed that the charge density of Cu atoms provided a high catalytic activity for reduction reactions. O* atom adsorbed to the surface renders O transfer easier. The results indicated that there were 0.16 ∣e∣ and 0.02 ∣e∣ electron were transferred from the surface to the N-terminated and O-terminated N2O molecule, respectively. The calculations proved that the surface possessed a high catalytic activity on O∗+N2O → N2 + O2 and CO + N2O → CO2 + N2 reduction reactions. This study paves the way for tailoring a high-performance electrocatalyst for NO2 reduction reaction by considering the high electrocatalytic activity and superior physicochemical properties of Cu-embedded graphene.
Some Inequalities Related to Interval-Valued

η

h

-Convex Functions
Authors: Chen Lei , Saleem Muhammad Shoaib , Zahoor Muhammad Sajid , Bano Rahat
Published: April 2021

Convexity plays an important role in many areas of mathematics, especially in the study of optimization problems where they are distinguished by a number of convenient properties. Our aim is to introduce a more extended version of convexity. In this paper, we introduced interval-valued generalized

η

h

convex function and proved Hermite–Hadamard-, Jensen-, and Ostrowski-type inequalities in this generalization. The presented results are generalizations of many existing results of literature.
Identification of a Gene Prognostic Signature for Oral Squamous Cell Carcinoma by RNA Sequencing and Bioinformatics
Authors: Zhang Yang-Yang , Mao Ming-Hui , Han Zheng-Xue
Published: April 2021

Objectives. Oral squamous cell carcinoma (OSCC) is the most common oral cancer and has a poor prognosis. We aimed to identify new biomarkers or potential therapeutic targets for OSCC. Materials and Methods. Four pairs of tumor and adjacent normal tissues were collected from OSCC patients, and differentially expressed genes (DEGs) were screened via high‐throughput RNA sequencing (RNA‐seq). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to analyze the DEGs. A protein‐protein interaction (PPI) network was established with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and Cytoscape, and two significant clusters were found. Candidate genes were screened by analyzing head and neck squamous cell carcinoma (HNSCC) data from The Cancer Genome Atlas (TCGA). A DEG‐based risk model was established to predict the overall survival (OS) of OSCC patients via Kaplan‐Meier analysis and the log‐rank test. Furthermore, univariate Cox regression analysis was applied to assess associations between potential biomarkers and the overall survival rate. Results. Of 720 total DEGs, fifty‐two DEGs in the two subclusters of the PPI network analysis were selected. A risk model was established, and five candidate genes (SPRR2E, ICOS, CTLA4, HTR1D, and CCR4) were identified as biomarkers of OS in OSCC patients. Conclusions. We successfully constructed a prognostic signature to predict prognosis and identified five candidate genes associated with the OS of OSCC patients that are potential tumor biomarkers and targets in OSCC.
Hybrid Trajectory Optimization Method and Tracking Guidance for Variable-Sweep Missiles
Authors: Wei Zhifang , Cheng Yang , Guo Xiangxiang , Liu Senlin
Published: April 2021

In this paper, an offline hybrid trajectory optimization approach is proposed for variable-sweep missiles to explore the superiority in the diving phase. Aiming at the maximal terminal velocity with the impact angle constraint, the trajectory optimization model is formulated under multiple constraints, and the aerodynamic analysis in different sweep angles is discussed. Unlike only the attack angle used for the optimization process traditionally, the two-variable optimization scheme on both the attack angle and sweep angle is investigated for variable-sweep missiles. Then, the trajectory optimization problem is transformed into the nonlinear programming problem via a hybrid optimization strategy combining the Gauss pseudospectral method and direct shooting method to obtain the high precision and fast convergence solution. Finally, to verify the feasibility of the optimal trajectory under uncertainties, the tracking guidance law is designed on basis of the gain scheduled linear quadratic regulator control. Numerical simulation results reveal not only of the proposed hybrid optimization strategy but also of the superiority of variable-sweep missiles compared with traditional missiles.
Risk of Uterine Rupture with Vaginal Birth after Cesarean in Twin Gestations
Authors: Baradaran Kimya
Published: April 2021

Background. Women with a previous cesarean delivery may attempt a subsequent vaginal birth or repeat cesarean. Vaginal birth after cesarean carries a greater risk of uterine rupture, defined as the disruption of all uterine layers, resulting in maternal-fetal morbidity or mortality. It is unclear how the risk of uterine rupture compares in patients with twin gestations who undergo different delivery methods. Objective. The purpose of this systematic review is to determine if there is an increased risk of uterine rupture in patients with twin gestations attempting vaginal birth after cesarean (VBAC) versus planned repeat cesarean delivery (PRCD). Study Design. PubMed, Cochrane Library, and CINAHL were searched systematically. Eligible studies were prospective and retrospective studies that evaluated the incidence of uterine rupture in twin pregnancies that attempted VBAC or PRCD. Data were manually extracted from these studies, and the number of events in each group was used to calculate an odds ratio (OR) and 95% confidence interval (CI). Results. 4 retrospective studies were included with a total of 7699 participants, 2305 of whom attempted VBAC and 5394 underwent PRCD. The absolute risk of uterine rupture in the VBAC and PRCD groups was 0.87% and 0.09%, respectively. The rate of uterine rupture was significantly higher in the VBAC group than in the PRCD group (OR: 9.43; CI: 3.54–25.17). Conclusion. Although VBAC is associated with higher rates of uterine rupture in twin pregnancies when compared with PRCD, the absolute risk of uterine rupture is low in both groups. Depending on individual risk factors, vaginal birth may be offered as a safe option to women with twin pregnancies and a history of cesarean delivery.
Functional Analysis of DNMT1 SNPs (rs2228611 and rs2114724) Associated with Schizophrenia
Authors: Saxena Sonal , Maroju Pranay Amruth , Choudhury Sumana , Voina Vidhya Chitta , Naik Poonam , Gowdhaman Kavitha , Kkani Poornima , Chennoju Kiranmai , Ganesh Kumar S. , Ramasubramanian C. , Prasad Rao G. , Jamma Trinath , Narayan Kumar Pranav , Mohan K. Naga
Published: April 2021

A recent study showed the association of minor alleles of rs2228611 (T allele) and rs2114724 (T allele) of DNMT1 with schizophrenia (SZ) and suggested their effects on splicing of the transcripts. We performed a replication study using 310 controls and 304 SZ patients and confirmed the association of the homozygous minor allele genotypes with SZ (

P

 = 0.04 for rs2114724 and

P

 = 0.007 for rs2228611). This significant association persisted after Bonferroni correction when the previously published data of 301 controls and 325 patients were also considered (

P

 ≤ 0.0002). In addition, we found that the proportion of male patients with homozygous minor alleles at rs2114724 was significantly higher than that of females (

P

 = 0.002). When haplotype analysis of both loci was performed, we observed a significant association of T/T–T/T and T/T–C/T (

P

 = 0.04) haplotypes with SZ. To gain insights into the functional effects of the two SNPs on the levels of DNMT1 transcripts, quantitative real-time PCR experiments were performed using peripheral blood monocytes from 10 individuals each with T/T–T/T (homozygous minor allele), C/T–C/T (heterozygous), and C/C–C/C (homozygous major allele) haplotypes. Independently, the levels of DNMT1 protein were also compared in three individuals each by immunofluorescence. These results suggest that neither DNMT1 transcript nor the protein levels were significantly different in the peripheral blood monocytes among the individuals studied for the three groups. Taken together, our results confirm that the two minor alleles in homozygosity are associated with SZ but with no discernible effects on transcript or protein levels of DNMT1 in the peripheral blood monocytes of the small number of samples tested.
Mechanical Mechanism and Propagation Law of Fissure‐Tip Cracks of Large‐Size Rock Specimens with Two Precut Fissures
Authors: Yin Liming , Li Ming , Sun Wenbin , Chen Juntao , Liu Bin , Wang Ziqi
Published: April 2021

The rock is a kind of geological medium with damages of different degrees including fissures, faults, joints, and other structural defects. Many underground rock engineering projects, such as mining and tunnel excavation, can break the three‐dimensional stress balance state of rock mass and make it subject to two‐dimensional or even one‐dimensional stress, thus inducing stress concentration which leads to rapid failure. In order to investigate the failure law of the rock mass with such defects under two‐dimensional stress, based on the similarity theory, we first prepared rocklike specimens with fissures featuring actual mechanical properties and then systematically analyzed the fissure‐tip crack propagation and specimen failure law and mechanical mechanism under two‐dimensional stress in view of the stress field theory. The results demonstrate that with the increase of load, the microcracks developed and propagated gradually, during which a number of branch paths were generated from the fissure tips of the specimens; the upper and lower cracks were connected first due to the main crack propagation, forming a sliding surface which caused the failure of the specimens, and the strengths of the specimens also fluctuated according to the different combinations of the fissure dip angles and rock bridge dip angles. In view of acoustic emission (AE), we calculated and obtained the spatial positions of stress peaks in each direction at the fissure tips; through comparison and analysis, the angle corresponding to the negative angle peak of the maximum circumferential tensile stress and the maximum radial tensile stress is basically the same as the angle of the main crack propagation direction generated from the preexisting fissure; it can be inferred that the tensile stress is the main stress inducing crack initiation and specimen failure, which is consistent with the physical characteristics of rock (resistant to compression but not tension). This may serve as a guidance for judging the direction along which new cracks are generated in a rock mass with double structural planes.
Nanoemulsified Butenafine for Enhanced Performance against Experimental Cutaneous Leishmaniasis
Authors: Bezerra-Souza Adriana , Jesus Jéssica A. , Laurenti Márcia D. , Lalatsa Aikaterini , Serrano Dolores R. , Passero Luiz Felipe D.
Published: April 2021

The production of ergosterol lipid involves the activity of different enzymes and is a crucial event for the Leishmania membrane homeostasis. Such enzymes can be blocked by azoles and allylamines drugs, such as the antifungal butenafine chloride. This drug was active on parasites that cause cutaneous and visceral leishmaniasis. Based on the leishmanicidal activity of butenafine chloride and considering the absence of reports about the therapeutic potential of this drug in cutaneous leishmaniasis, the present work is aimed at analyzing the efficacy of butenafine formulated in two different topical delivery systems, the self-nanoemulsifying drug delivery systems (BUT-SNEDDS) and in a SNEDDS-based nanogel (BUT-SNEDDS gel) as well as in the free form in experimental cutaneous leishmaniasis. Physical studies showed that both formulations were below 300 nm with low polydispersity (<0.5) and good colloidal stability (around -25 mV). Increased steady-state flux was reported for nanoenabled butenafine formulations with reduced lag time in Franz cell diffusion assays across Strat-M membranes. No toxic or inflammatory reactions were detected in animals treated with BUT-SNEDDS, BUT-SNEDDS gel, or butenafine. Animals topically treated with butenafine (free or nanoformulated) showed small dermal lesions and low tissue parasitism. Furthermore, BUT-SNEDD gel and butenafine presented similar efficacy than the standard drug Glucantime given by the intralesional route. Increased levels of IFN-γ were observed in animals treated with BUT-SNEDDS gel or butenafine. Based on these data, the antifungal drug butenafine chloride can be considered an interesting repurposed drug for the treatment of cutaneous leishmaniasis.
18F‐FDG‐PET/CT Whole‐Body Imaging Lung Tumor Diagnostic Model: An Ensemble E‐ResNet‐NRC with Divided Sample Space
Authors: Tao Zhou , Bing-qiang Huo , Huiling Lu , Hongbin Shi , Pengfei Yang , Hongsheng Ding
Published: April 2021

Under the background of 18F‐FDG‐PET/CT multimodal whole‐body imaging for lung tumor diagnosis, for the problems of network degradation and high dimension features during convolutional neural network (CNN) training, beginning with the perspective of dividing sample space, an E‐ResNet‐NRC (ensemble ResNet nonnegative representation classifier) model is proposed in this paper. The model includes the following steps: (1) Parameters of a pretrained ResNet model are initialized using transfer learning. (2) Samples are divided into three different sample spaces (CT, PET, and PET/CT) based on the differences in multimodal medical images PET/CT, and ROI of the lesion was extracted. (3) The ResNet neural network was used to extract ROI features and obtain feature vectors. (4) Individual classifier ResNet‐NRC was constructed with nonnegative representation NRC at a fully connected layer. (5) Ensemble classifier E‐ResNet‐NRC was constructed using the “relative majority voting method.” Finally, two network models, AlexNet and ResNet‐50, and three classification algorithms, nearest neighbor classification algorithm (NNC), softmax, and nonnegative representation classification algorithm (NRC), were combined to compare with the E‐ResNet‐NRC model in this paper. The experimental results show that the overall classification performance of the Ensemble E‐ResNet‐NRC model is better than the individual ResNet‐NRC, and specificity and sensitivity are more higher; the E‐ResNet‐NRC has better robustness and generalization ability.
The Complex Integration of T-cell Metabolism and Immunotherapy
Authors: Madden Matthew Z. , Rathmell Jeffrey C.
Published: April 2021

Immune oncology approaches of adoptive cell therapy and immune checkpoint blockade aim to activate T cells to eliminate tumors. Normal stimulation of resting T cells induces metabolic reprogramming from catabolic and oxidative metabolism to aerobic glycolysis in effector T cells, and back to oxidative metabolism in long-lived memory cells. These metabolic reprogramming events are now appreciated to be essential aspects of T-cell function and fate. Here, we review these transitions, how they are disrupted by T-cell interactions with tumors and the tumor microenvironment, and how they can inform immune oncology to enhance T-cell function against tumors.

Significance:

T-cell metabolism plays a central role in T-cell fate yet is altered in cancer in ways that can suppress antitumor immunity. Here, we discuss challenges and opportunities to stimulate effector T-cell metabolism and improve cancer immunotherapy.
Gut Microbiota and Antitumor Immunity: Potential Mechanisms for Clinical Effect
Authors: Baruch Erez N. , Wang Jingjing , Wargo Jennifer A.
Published: April 2021

Several landmark preclinical studies have shown an association between the gut microbiota and the effectiveness of immunotherapy for cancer. These studies have sparked clinical trials aimed at modulating the gut microbiota in order to improve clinical response rates to immunotherapy. Despite this, the mechanisms through which the gut microbiota influences the effectiveness of immunotherapy are still incompletely characterized. Preclinical and preliminary clinical findings from numerous types of gut microbiota modulation studies, including fecal transplantation, probiotics, consortia, and diet, demonstrate that favorable microbiota modulation is associated with increased intratumoral infiltration of CD8+ effector T cells. This CD8+ T-cell infiltration is often associated with enhanced intratumoral activity of T-helper type 1 cells and dendritic cells and a lower density of immunosuppressive cells. Herein, we discuss how gut microbiota may affect the activity of immune cells by at least three interlacing mechanisms: activation of pattern recognition receptors, molecular mimicry, and impact of metabolites. We also discuss the therapeutic potential and limitations of the different gut microbiota modulation techniques and their putative mechanisms of immune activation.
Topical Tofacitinib: A Janus Kinase Inhibitor for the Treatment of Vitiligo in an Adolescent Patient
Authors: Berbert Ferreira Sineida , Berbert Ferreira Rachel , Neves Neto Afonso Cesar , Assef Silvana Martins Caparroz , Scheinberg Morton
Published: April 2021

Vitiligo is an autoimmune skin disease presenting with areas of depigmentation. Recent reports suggest that Janus kinase (JAK) inhibitors may be an effective therapy. In this case report, we show our experience with an adolescent patient with a long history of generalized and refractory vitiligo, for which treatment with topical tofacitinib, a JAK inhibitor, associated with phototherapy for 9 months, resulted in near complete repigmentation.
MiR-22-3p Suppresses Vascular Remodeling and Oxidative Stress by Targeting CHD9 during the Development of Hypertension
Authors: Chen Hanqing , Xu Xiru , Liu Zhengqing , Wu Yong
Published: April 2021

Hypertension is considered a risk factor for a series of systematic diseases. Known factors including genetic predisposition, age, and diet habits are strongly associated with the initiation of hypertension. The current study aimed to investigate the role of miR-22-3p in hypertension. In this study, we discovered that the miR-22-3p level was significantly decreased in the thoracic aortic vascular tissues and aortic smooth muscle cells (ASMCs) of spontaneously hypertensive rats. Functionally, the overexpression of miR-22-3p facilitated the switch of ASMCs from the synthetic to contractile phenotype. To investigate the underlying mechanism, we predicted 11 potential target mRNAs for miR-22-3p. After screening, chromodomain helicase DNA-binding 9 (CHD9) was validated to bind with miR-22-3p. Rescue assays showed that the co-overexpression of miR-22-3p and CHD9 reversed the inhibitory effect of miR-22-3p mimics on cell proliferation, migration, and oxidative stress in ASMCs. Finally, miR-22-3p suppressed vascular remodeling and oxidative stress in vivo. Overall, miR-22-3p regulated ASMC phenotype switch by targeting CHD9. This new discovery provides a potential insight into hypertension treatment.
An Optical Method for Immediate Evaluation of Microfoam Stability in Foam Sclerotherapy
Authors: Bai Taoping , Jiang Wentao , Liang Lin , Li Yalan , Fan Yubo
Published: April 2021

Objectives: The objective of our study was to develop an optical method that instantly evaluates the stability of sclerosing foam, which would enable early predictions of the clinical performance of the foam and reduce the occurrence of clinical side effects. Methods: Based on the principle of light scattering, we developed a method to optically test foam stability and verified it experimentally using sodium morrhuate (2 mL; 0.05 g/mL) and carbon dioxide. A self-made foam preparation instrument was used to achieve a preparation speed of 275 mm/s. The liquid-gas ratios were considered as 1:3, 1:4, and 1:5. Curves of illuminance with respect to the drainage rate and decay time were obtained. By fitting the curve, the relationship between foam half-life time (FHT) and foam decay was obtained. Thus, foam stability was evaluated using the initial illuminance value; the foam transfer time was approximately 3 s. Results: The experimental FHT varies between 205 and 232 s. Illuminance is exponentially related to drainage rate and linearly related with time. FHT can be expressed by the initial illuminance and illuminance curve fitting coefficients. The half-life of the foam decreases as the initial illuminance value increases, for the same sclerosing drug. The suitability of foam stability is determined by the position of the initial value in the chart. Conclusion: Optical methods are feasible for evaluating foam stability over a short period of time. Clinically predicting the stability of freshly prepared foam can reduce number of incidences of further complications. This will promote the development of foam sclerotherapy and provide a basic understanding of the internal mechanical properties of foam.
New-Onset Perioperative Atrial Fibrillation Is Associated with Increased All-Cause Mortality in Elderly Patients Undergoing Total Knee and Hip Replacements
Authors: Varon Ben , Kandel Leonid , Rivkin Gurion , Leibowitz David
Published: April 2021

Introduction: Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are common surgeries performed in elderly patients with osteoarthritis. Limited data address the clinical significance of perioperative atrial fibrillation (AF) in these patients. This study aimed to determine whether preexisting or new-onset AF is associated with increased 1-year all-cause mortality rates in the elderly population. Methods: 280 patients over the age of 60 undergoing THA or TKA with perioperative AF and 280 control-matched patients were retrospectively identified, and their files reviewed. The primary end point was 1-year all-cause mortality from the date of the surgery. Results: Of the 280 patients with perioperative AF, 37 had new-onset AF with a 1-year all-cause mortality rate of 10.8%. This mortality was significantly higher in patients with new-onset AF compared to patients without AF or patients with previous AF (10.8% vs. 1.1% and 2.5%, respectively; p = 0.005). On multivariate analysis, this difference remained significant after adjustment for risk factors associated with all-cause mortality. Conclusions: One-year all-cause mortality in elderly patients undergoing TKA or THA is significantly increased in the patients that develop new postoperative AF. These patients warrant increased clinical surveillance following surgery.
Flexible Stoichiometry: Implications for KCNQ2- and KCNQ3-Associated Neurodevelopmental Disorders
Authors: Springer Kristen , Varghese Nissi , Tzingounis Anastasios V.
Published: April 2021

KCNQ2 and KCNQ3 pathogenic channel variants have been associated with a spectrum of developmentally regulated diseases that vary in age of onset, severity, and whether it is transient (i.e., benign familial neonatal seizures) or long-lasting (i.e., developmental and epileptic encephalopathy). KCNQ2 and KCNQ3 channels have also emerged as a target for novel antiepileptic drugs as their activation could reduce epileptic activity. Consequently, a great effort has taken place over the last 2 decades to understand the mechanisms that control the assembly, gating, and modulation of KCNQ2 and KCNQ3 channels. The current view that KCNQ2 and KCNQ3 channels assemble as heteromeric channels (KCNQ2/3) forms the basis of our understanding of KCNQ2 and KCNQ3 channelopathies and drug design. Here, we review the evidence that supports the formation of KCNQ2/3 heteromers in neurons. We also highlight functional and transcriptomic studies that suggest channel composition might not be necessarily fixed in the nervous system, but rather is dynamic and flexible, allowing some neurons to express KCNQ2 and KCNQ3 homomers. We propose that to fully understand KCNQ2 and KCNQ3 channelopathies, we need to adopt a more flexible view of KCNQ2 and KCNQ3 channel stoichiometry, which might differ across development, brain regions, cell types, and disease states.
The Bracketing of Presence: Dematerialization and Disembodiment in Times of Pandemic and of Social Distancing Biopolitics
Authors: Stanghellini Giovanni , Sass Louis
Published: April 2021

The purpose of this paper is to help us understand how and why the COVID pandemic, and its associated biopolitics of social distancing, may have affected our relationships with our own bodies and other persons, thus helping to accelerate what might be termed a bracketing of presence that was already well underway in our modern and contemporary social practices. We focus on 3 historical vectors, all rooted in specific technologies, that have profound implications at the levels of our social imaginary and prereflective ways of being: architecture, social media, and medicine. Architecture has progressively eliminated “porosity” between spaces by establishing clear borders between public and private spaces (also within the private ones), thereby contributing to our drive for social distancing. Social media have provided apparatuses that replace intercorporeal encounters with disembodied, virtual interactions mediated by images. Visual experiences that are more embodied, participatory, and “immersed” are replaced by passive forms of “seeing”: the other becomes an image for me, and I for the other. The object of medicine has also recently dematerialized with the advent of the new “optical” and “digital” machines of modern medicine, which can operate remotely thanks to an increasingly powerful interface reliant on computational power and the resources of artificial intelligence, thereby dispensing with body-to-body interactions. We offer these reflections as routes to a better understanding of changes that have occurred and are occurring on the planes of both culture and individual psychological existence.
Correlation of Endoscopic Ultrasonography Features with the Mitotic Index in 2- to 5-cm Gastric Gastrointestinal Stromal Tumors
Authors: Seven Gulseren , Arici Dilek Sema , Senturk Hakan
Published: April 2021

Background: Predicting the malignancy potential of gastrointestinal stromal tumor (GIST) before resection could improve patient management strategies as gastric GISTs with a low malignancy potential can be safely treated endoscopically, but surgical resection is required for those tumors with a high malignancy potential. This study aimed to evaluate endoscopic ultrasound (EUS) features of 2- to 5-cm gastric GISTs that might be used to predict their mitotic index using surgical specimens as the gold standard. Patients and Methods: Forty-nine patients (30 females and 19 males; mean age 55.1 ± 12.7 years) who underwent EUS examinations, followed by surgical resections of 2- to 5-cm gastric GISTs, were retrospectively reviewed. Results: The mean tumor size was 3.44 ± 0.97 (range 2.1–5.0) cm. A univariate analysis revealed no significant differences in age, sex, and tumor location in the low mitotic index and high mitotic index groups (all p > 0.05). In terms of EUS features, there were no significant differences in the mitotic indexes with respect to the shape, surface lobulation, border regularity, echogenicity, homogeneity, growth patterns, presence of mucosal ulceration, hyperechogenic foci, anechoic spaces, and hypoechoic halos (all p > 0.05). However, the tumor size was larger in the high mitotic index group than that in the low mitotic index group (3.97 ± 1.05 vs. 3.27 ± 0.9 cm, p = 0.03). Conclusion: Conventional EUS features are not reliable for predicting the mitotic index of 2- to 5-cm gastric GISTs. Further modalities for predicting the mitotic index are needed to prevent unnecessary surgical resections in patients with a low risk of malignancy.
HSP25 Vaccination Attenuates Atherogenesis via Upregulation of LDLR Expression, Lowering of PCSK9 Levels and Curbing of Inflammation
Authors: Chen Yong-Xiang , Shi Chunhua , Deng Jingti , Diao Catherine , Maarouf Nadia , Rosin Matthew , Shrivastava Vipul , Hu Angie A. , Bharadwa Sonya , Adijiang Ayinuer , Ulke-Lemee Annegret , Gwilym Brenig , Hellmich Alexandria , Malozzi Christopher , Batulan Zarah , Dean Jonathan L.E. , Ramirez F. Daniel , Liu Jingwen , Gerthoffer William T. , O’Brien Edward R.
Published: April 2021

Objective:

Elevated HSP27 (heat shock protein 27) levels predict relative freedom from cardiovascular events. Over-expression or twice daily subcutaneous injections of human HSP27 in
ApoE
−/−
mice reduces blood and plaque cholesterol levels, as well as inflammation and atherosclerotic plaque burden. Antibodies to HSP27 are present in human blood, and the purpose of the current studies is to explore their role.

Approach and Results:

Blood levels of both HSP27 and anti-HSP27 IgG antibodies are elevated in healthy controls compared with patients with cardiovascular disease.
ApoE
−/−
mice fed a high-fat diet and vaccinated with recombinant HSP25 (rHSP25, murine ortholog) show increased levels of anti-HSP25 IgG antibodies and reductions in plasma cholesterol and atherogenesis. Moreover, rHSP25 vaccination markedly lowered serum amyloid A levels as well as hepatic macrophage abundance and inflammatory cytokine expression. The effects of the HPS25 vaccination on cholesterol metabolism are divergent: increased hepatic LDLR (low-density lipoprotein receptor) mRNA and protein expression and reduced plasma PCSK9 (proprotein convertase subtilisin/kexin type 9) levels—despite no effect on PCSK9 expression. In vitro, the HSP27 immune complex upregulates hepatocyte LDLR mRNA and protein expression independent of intracellular cholesterol levels and increases LDLR promoter activity. The increase in LDLR expression by the HSP27 immune complex is dependent upon activation of the NF-κB (nuclear factor κ light chain enhancer of activated B cells) pathway. Hepatocyte PCSK9 protein levels are reduced after HSP27 immune complex treatment in vitro despite only minor transient effects on gene expression.

Conclusions:

HSP27 immunotherapy represents a novel means of lowering cholesterol and PCSK9 levels, primarily due to augmentation of LDLR expression and is associated with marked reductions in inflammation.
Hypertension in Low- and Middle-Income Countries
Authors: Schutte Aletta E. , Srinivasapura Venkateshmurthy Nikhil , Mohan Sailesh , Prabhakaran Dorairaj
Published: April 2021

In recent decades low- and middle-income countries (LMICs) have been witnessing a significant shift toward raised blood pressure; yet in LMICs, only 1 in 3 are aware of their hypertension status, and ≈8% have their blood pressure controlled. This rising burden widens the inequality gap, contributes to massive economic hardships of patients and carers, and increases costs to the health system, facing challenges such as low physician-to-patient ratios and lack of access to medicines. Established risk factors include unhealthy diet (high salt and low fruit and vegetable intake), physical inactivity, tobacco and alcohol use, and obesity. Emerging risk factors include pollution (air, water, noise, and light), urbanization, and a loss of green space. Risk factors that require further in-depth research are low birth weight and social and commercial determinants of health. Global actions include the HEARTS technical package and the push for universal health care. Promising research efforts highlight that successful interventions are feasible in LMICs. These include creation of health-promoting environments by introducing salt-reduction policies and sugar and alcohol tax; implementing cost-effective screening and simplified treatment protocols to mitigate treatment inertia; pooled procurement of low-cost single-pill combination therapy to improve adherence; increasing access to telehealth and mHealth (mobile health); and training health care staff, including community health workers, to strengthen team-based care. As the blood pressure trajectory continues creeping upward in LMICs, contextual research on effective, safe, and cost-effective interventions is urgent. New emergent risk factors require novel solutions. Lowering blood pressure in LMICs requires urgent global political and scientific priority and action.
Vascular Stress Signaling in Hypertension
Authors: Cicalese Stephanie M. , da Silva Josiane Fernandes , Priviero Fernanda , Webb R. Clinton , Eguchi Satoru , Tostes Rita C.
Published: April 2021

Cells respond to stress by activating a variety of defense signaling pathways, including cell survival and cell death pathways. Although cell survival signaling helps the cell to recover from acute insults, cell death or senescence pathways induced by chronic insults can lead to unresolved pathologies. Arterial hypertension results from chronic physiological maladaptation against various stressors represented by abnormal circulating or local neurohormonal factors, mechanical stress, intracellular accumulation of toxic molecules, and dysfunctional organelles. Hypertension and aging share common mechanisms that mediate or prolong chronic cell stress, such as endoplasmic reticulum stress and accumulation of protein aggregates, oxidative stress, metabolic mitochondrial stress, DNA damage, stress-induced senescence, and proinflammatory processes. This review discusses common adaptive signaling mechanisms against these stresses including unfolded protein responses, antioxidant response element signaling, autophagy, mitophagy, and mitochondrial fission/fusion, STING (signaling effector stimulator of interferon genes)-mediated responses, and activation of pattern recognition receptors. The main molecular mechanisms by which the vasculature copes with hypertensive and aging stressors are presented and recent advancements in stress-adaptive signaling mechanisms as well as potential therapeutic targets are discussed.
Device Therapy of Hypertension
Authors: Mahfoud Felix , Schlaich Markus P. , Lobo Melvin D.
Published: April 2021

In the past decade, efforts to improve blood pressure control have looked beyond conventional approaches of lifestyle modification and drug therapy to embrace interventional therapies. Based upon animal and human studies clearly demonstrating a key role for the sympathetic nervous system in the etiology of hypertension, the newer technologies that have emerged are predominantly aimed at neuromodulation of peripheral nervous system targets. These include renal denervation, baroreflex activation therapy, endovascular baroreflex amplification therapy, carotid body ablation, and pacemaker-mediated programmable hypertension control. Of these, renal denervation is the most mature, and with a recent series of proof-of-concept trials demonstrating the safety and efficacy of radiofrequency and more recently ultrasound-based renal denervation, this technology is poised to become available as a viable treatment option for hypertension in the foreseeable future. With regard to baroreflex activation therapy, endovascular baroreflex amplification, carotid body ablation, and programmable hypertension control, these are developing technologies for which more human data are required. Importantly, central nervous system control of the circulation remains a poorly understood yet vital component of the hypertension pathway and mandates further investigation. Technology to improve blood pressure control through deep brain stimulation of key cardiovascular control territories is, therefore, of interest. Furthermore, alternative nonsympathomodulatory intervention targeting the hemodynamics of the circulation may also be worth exploring for patients in whom sympathetic drive is less relevant to hypertension perpetuation. Herein, we review the aforementioned technologies with an emphasis on the preclinical data that underpin their rationale and the human evidence that supports their use.
Harnessing Mobile Health Technology for Secondary Cardiovascular Disease Prevention in Older Adults: A Scientific Statement From the American Heart Association
Authors: Schorr Erica N. , Gepner Adam D. , Dolansky Mary A. , Forman Daniel E. , Park Linda G. , Petersen Kristina S. , Still Carolyn H. , Wang Tracy Y. , Wenger Nanette K. ,   On behalf of the American Heart Association Cardiovascular Disease in Older Populations Committee of the Council on Clinical Cardiology and Council on Cardiovascular and Stroke Nursing; Council on Arteriosclerosis, Thrombosis and Vascular Biology; and Council on Lifestyle and Cardiometabolic Health
Published: April 2021

Secondary prevention of cardiovascular disease (CVD), the leading cause of morbidity and mortality, is critical to improving health outcomes and quality of life in our aging population. As mobile health (mHealth) technology gains universal leverage and popularity, it is becoming more user-friendly for older adults and an adjunct to manage CVD risk and improve overall cardiovascular health. With the rapid advances in mHealth technology and increasing technological engagement of older adults, a comprehensive understanding of the current literature and knowledge of gaps and barriers surrounding the impact of mHealth on secondary CVD prevention is essential. After a systematic review of the literature, 26 studies that used mHealth for secondary CVD prevention focusing on lifestyle behavior change and medication adherence in cohorts with a mean age of ≥60 years were identified. Improvements in health behaviors and medication adherence were observed, particularly when there was a short message service (ie, texting) component involved. Although mobile technologies are becoming more mainstream and are starting to blend more seamlessly with standard health care, there are still distinct barriers that limit implementation particularly in older adults, including affordability, usability, privacy, and security issues. Furthermore, studies on the type of mHealth that is the most effective for older adults with longer study duration are essential as the field continues to grow. As our population ages, identifying and implementing effective, widely accepted, cost-effective, and time-efficient mHealth interventions to improve CVD health in a vulnerable demographic group should be a top health priority.
Is the World Redeemable? Anarchic Cosmopolitanism and Nation States in Franz Rosenzweig’s Messianism
Authors: Kajon Irene
Published: April 2021

Although in a sense a follower of both Isaiah and Machiavelli, Rosenzweig did not share their perception of a conflict between idealism and realism in human experience. His Star of Redemption advances a theory of the redemption of the world inspired by both Isaiah and Machiavelli, and at the same time critical of both of them – a theory in which ethics and politics are strongly connected but where ethics renounces the opposition to history and historical laws, and politics renounces the opposition to ethical ideas.
Is the World Redeemable? Contra Redemption
Authors: Mendes-Flohr Paul
Published: April 2021

At this juncture in history what is urgently needed, to state it rather paradoxically, is redemption from visions of redemption. In my brief reflections, I appeal for a studied, indeed resolute retreat from the very concept of redemption, in particular from its contemporary theological and secular iterations.
Is the Human Being Redeemable? A Meditation on Rosenzweig’s Claim That Death Is Very Good
Authors: Bielik-Robson Agata
Published: April 2021

In this article I claim there is no contradiction involved in Franz Rosenzweig’s love of life and his apology for death: what he loves and wants us to love is the finite life, life offered in its finitude which should in the end appear as enough – that is, sufficient and fit for everything we could want from life, redemption included. The beyond toward which death as the end gestures is not a promise of immortality, offering a transcendence in temporal terms infinitely prolonged. The will “to stay, to live,” of which Rosenzweig speaks in the opening paragraph of The Star of Redemption, is the drive characteristic of another finitude: desiring and investing in life, without, at the same time, wishing to prolong itself into infinity.
Is the Human Being Redeemable? A Self-Defeating Question
Authors: Liska Vivian
Published: April 2021

Rosenzweig’s pathos with respect to an ultimate redemption raises the question of the desirability of a state in which so much has to be undone in order to retain nothing but the One, the All, the Eternal, and the True. Similar doubts arise concerning Rosenzweig’s portrayal of the ways that this state of redemption is anticipated in life: through prayer, love of neighbor, the communal hymn of the We. How accessible are these to “the human being” as such? Rather than arguing against what appears as a grand remnant of the urge for totality, I invoke here two figures whose concepts of redemption partly resemble Rosenzweig’s, but depart from him in ways that make all the difference: Benjamin and Kafka.
Evolution and Development Strategy of Collaborative Innovation Network among Cities in the Yangtze River Delta-Based on Urban Innovation Index Data
Authors: Li Yan , Ye Mingque
Published: April 2021

The gravity model is applied to construct a collaborative innovation network between cities in the Yangtze River Delta, analyzes its structural characteristics and evolution from a network perspective, and proposes development strategies. This will help optimize the network structure of collaborative innovation among cities in the Yangtze River Delta, improve the efficiency of collaborative innovation, and promote their innovation level together. Based on the data of urban innovation indexes in 2006, 2011 and 2016, this paper reveals the structural characteristics and evolution of the collaborative innovation network between cities in the Yangtze River Delta, and puts forward corresponding development strategies. The findings are as follows: (1) The overall innovation capability of cities in the Yangtze River Delta has been continuously improved, and the strength of collaborative innovation links between cities has slowly increased. (2) The innovation development of cities in the Yangtze River Delta is unbalanced and asymmetrical. The network presents a significant “core-periphery” spatial structure and a “multi-center, multi-level” pattern, and central cities drive the development of surrounding cities. (3) A reasonable regional innovation community should be constructed from the perspectives of spatial coordination, innovation industry chain integration and resource sharing, and the collaborative innovation network should be optimized.
Negotiating Freedom: Mostašār od-Doule’s Yek kalame and the Iranian Constitutional Experience
Authors: Faridzadeh Ghazaleh , Faridzadeh Raed
Published: April 2021

Innumerable modernization measures were implemented in nineteenth-century Iran, in what might be called a process of translation. In the course of translating new ideas into the Iranian context by means of applying old expressions, Iranian legal language underwent sequences of change. To gain a better understanding of current struggles over the proper interpretation of some basic concepts, the paper seeks to explain how the concept of freedom was modified, by reference to Koselleck’s “space of experience” and the “horizon of expectation”. The analysis is based on Mostašār od-Doule’s treatise Yek kalame (“One word”), one of the most important nineteenth-century Iranian source texts, which greatly influenced the further development of the Iranian freedom movement.
Man, Land and Sea: Local Populations in Territorial and Maritime Disputes before the International Court of Justice
Authors: Suedi Yusra
Published: April 2021

The International Court of Justice routinely resolves territorial and maritime boundary disputes between States. Such disputes often carry repercussions for the lives and livelihoods of local populations living on the territories of the State litigants. This analysis seeks to examine the extent to which State litigants’ concerns for the impact of maritime disputes or territorial disputes on their local populations are factored into the Court’s decision-making process. It also seeks to identify reasons for the Court’s approach in such disputes, and to explore the potential role of the principle of equity in such contexts.