bluuebunny/crossref_metadata_2025 huggingface dataset:
Eosinophilic Granulomatosis Polyangiitis (EGPA) Masquerading as a Mycotic Aneurysm of the Abdominal Aorta: Case Report and Review of Literature
Authors: Kumari Pooja , Pattanaik Debendra , Williamson Claire
Published: September 2021

Introduction. Aortic involvement leading to aortitis in eosinophilic granulomatosis polyangiitis (EGPA) is infrequent, and only 2 cases have been reported so far in the literature. Even more so, aortic aneurysm, secondary to EGPA, has never been reported and remains a diagnostic and therapeutic challenge. Case Presentation. We present a 63-year-old Caucasian male patient with a prior diagnosis of EGPA presenting with abdominal pain, nausea, and loose stools to the emergency department. Physical examination showed periumbilical tenderness. He had no peripheral eosinophilia but had high C-reactive protein and procalcitonin levels. CT abdomen revealed a mycotic aneurysm involving the infrarenal abdominal aorta. The patient declined surgical repair initially and was treated with IV antibiotics only. Unfortunately, 24 hours later, the aneurysm ruptured, leading to emergent axillofemoral bypass surgery. Surgical biopsy showed aortitis, periaortitis, and active necrotizing vasculitis. Conclusion. Abdominal aneurysms should be considered a complication of EGPA, and earlier immunosuppressive therapy should be considered to prevent further complications.
Efficacy and Safety of Single-Session Radiofrequency Ablation in Treating Benign Thyroid Nodules: A Short-Term Prospective Cohort Study
Authors: Nguyen Van Bang , Nguyen Thi Xuan , Nguyen Van Vy Hau , Nguyen Hai Thuy , Nguyen Dinh Toan , Le Chi Van
Published: September 2021

Objective. The aims of this study are to evaluate the safety and efficacy of RFA in the treatment of benign thyroid nodule(s) and to find independent factors related to the volume reduction rate of the nodule(s). Materials and Methods. This short-term prospective study from a single medical center was conducted on 93 benign thyroid nodules in 93 patients treated with RFA. Two basic techniques were used: the trans-isthmic approach and moving-shot technique. Clinical and ultrasonography examinations were performed at 1- and 3-month follow-up after the treatment session. Primary outcomes included volume reduction ratio (VRR) at 1-month and 3-month follow-ups; secondary outcomes were therapeutic success rate and complications. Multiple linear regression analysis was used to determine independent factors associated with VRR. Results. A final sample of 78 patients with 78 nodules, given participant rate 83.8% (including 60 solid nodules, 16 predominantly cystic nodules, and 2 thyroid cysts), was followed up for 3 months. The mean volume reduction ratio was 41.47% and 64.72% after 1-month and 3-month follow-ups, respectively. The therapeutic success rate was 30.8% at 1-month and 84.6% at 3-month follow-ups. Symptom score and cosmetic score improved significantly. There was no change in thyroid function tests. Two minor complications (transient voice change) were found. The multiple linear regression analysis showed that the internal component of the nodules significantly related to the VRR during the 3-month follow-up (β = 23.00; 95%CI (7.59–38.45)). Conclusion. RFA was demonstrated as a safe and effective option for benign thyroid nodules treatment. It can be used as an alternative treatment with encouraging results.
Revisited on the Free Vibration of a Cantilever Beam with an Asymmetrically Attached Tip Mass
Authors: Lei Xiangsheng , Wang Yanfeng , Wang Xinghua , Lin Gang , Shi Shihong
Published: September 2021

Cantilever with an asymmetrically attached tip mass arises in many engineering applications. Both the traditional method of separation of variables and the method of Laplace transform are employed in the present paper to solve the eigenvalue problem of the free vibration of such structures, and the effect of the eccentric distance along the vertical direction and the length direction of the tip mass is considered here. For the traditional method of separation of variables, tip mass only affects to the boundary conditions, and the eigenvalue problem of the free vibration is solved based on the nonhomogeneous boundary conditions. For the method of Laplace transform, the effect of the tip mass is introduced in the governing equation with the Dirac function, and the eigenvalue problem then can be solved through Laplace transform with homogeneous boundary conditions. The computed results with these two methods are compared well with the numerical solution obtained by finite element method and approximate analytical solutions, and the effect of tip mass dimensions on the natural frequencies and corresponding mode shapes is also given.
Analysis on the Influence of Increasing Seismic Fortification Intensity on Seismic Performance of Underground Station
Authors: Zeng Ying , Xu Shiguang , Yin Shiqian
Published: September 2021

China Earthquake Parameter Zoning (2016) has increased the seismic fortification intensity in Chengdu from VII to VIII. It is necessary to conduct in‐depth discussion on the impact of the seismic performance of the built underground station structure. In this paper, a stratum‐structure finite element model is established with a Chengdu subway station as an example. The model boundary adopts viscoelastic boundary, and the ground motion is input in the form of equivalent nodal force. The equivalent linearization method is used to consider the nonlinearity of soil materials. The time‐history analysis of seismic fortification intensity of VII and VIII degrees is carried out, respectively. By comparing the calculation results of the two seismic fortification intensity ground motion conditions, it is concluded that the connection between the side wall and the floor is the weakest position of the station structure under the action of the earthquake; the seismic fortification intensity is increased from VII to VIII to the internal force of the structure. It has a relatively large impact, especially the most obvious impact on the bending moment. The results of the verification of the seismic time‐history analysis show that the increase of fortification intensity will have a more obvious impact on the structural deformation, and the structural design of the station can meet the safety performance requirements of VII and VIII degrees of seismic fortification. The research has certain reference significance for the seismic safety evaluation of the built underground station structure in Chengdu area.
Adversarial Sample Detection with Gaussian Mixture Conditional Generative Adversarial Networks
Authors: Zhang Pengfei , Ju Xiaoming
Published: September 2021

It is important to detect adversarial samples in the physical world that are far away from the training data distribution. Some adversarial samples can make a machine learning model generate a highly overconfident distribution in the testing stage. Thus, we proposed a mechanism for detecting adversarial samples based on semisupervised generative adversarial networks (GANs) with an encoder-decoder structure; this mechanism can be applied to any pretrained neural network without changing the network’s structure. The semisupervised GANs also give us insight into the behavior of adversarial samples and their flow through the layers of a deep neural network. In the supervised scenario, the latent feature (or the discriminator’s output score information) of the semi-supervised GAN and the target network's logit information are used as the input of logistic regression classifier to detect the adversarial samples. In the unsupervised scenario, first, we proposed a one-class classier based on the semisupervised Gaussian mixture conditional generative adversarial network (GM-CGAN) to fit the joint feature information of the normal data, and then, we used a discriminator network to detect normal data and adversarial samples. In both supervised scenarios and unsupervised scenarios, experimental results show that our method outperforms latest methods.
Using Convolution Neural Network for Defective Image Classification of Industrial Components
Authors: Wu Hao , Zhou Zhi
Published: September 2021

Computer vision provides effective solutions in many imaging relation problems, including automatic image segmentation and classification. Artificially trained models can be employed to tag images and identify objects spontaneously. In large-scale manufacturing, industrial cameras are utilized to take constant images of components for several reasons. Due to the limitations caused by motion, lens distortion, and noise, some defective images are captured, which are to be identified and separated. One common way to address this problem is by looking into these images manually. However, this solution is not only very time-consuming but is also inaccurate. The paper proposes a deep learning-based artificially intelligent system that can quickly train and identify faulty images. For this purpose, a pretrained convolution neural network based on the PyTorch framework is employed to extract discriminating features from the dataset, which is then used for the classification task. In order to eliminate the chances of overfitting, the proposed model also employed Dropout technology to adjust the network. The experimental study reveals that the system can precisely classify the normal and defective images with an accuracy of over 91%.
VIP Stabilizes the Cytoskeleton of Schlemm’s Canal Endothelia via Reducing Caspase‐3 Mediated ZO‐1 Endolysosomal Degradation
Authors: Lou Xiaotong , Mou Qianxue , Zhao Bowen , Huang Jingqiu , Yao Ke , Luo Zhaoxia , Ye Meng , Hu Yuanyuan , Duan Qiming , Li Xing , Wen Zheng , Chen Zhiqi , Zhang Hong , Zhao Yin
Published: September 2021

Objectives. In glaucomatous eyes, the main aqueous humor (AH) outflow pathway is damaged by accumulated oxidative stress arising from the microenvironment, vascular dysregulation, and aging, which results in increased outflow resistance and ocular hypertension. Schlemm’s canal (SC) serves as the final filtration barrier of the main AH outflow pathway. The present study is aimed at investigating the possible regulation of vasoactive intestinal peptide (VIP) on the cytoskeleton by stabilizing ZO‐1 in SC. Methods. Model of chronic ocular hypertension (COH) induced by episcleral venous cauterization was treated with topical VIP. The ultrastructure of junctions, ZO‐1 levels, and permeability of the SC inner wall to FITC‐dextran (70 kDa) were detected in the COH models. The F‐actin distribution, F/G‐actin ratio, and ZO‐1 degradation pathway in human umbilical vein endothelial cells (HUVECs) and HEK 293 cells were investigated. Results. ZO‐1 in the outer wall of the SC was less than that in the inner wall. COH elicited junction disruption, ZO‐1 reduction, and increased permeability of the SC inner wall to FITC‐dextran in rats. ZO‐1 plays an essential role in maintaining the F/G‐actin ratio and F‐actin distribution. VIP treatment attenuated the downregulation of ZO‐1 associated with COH or H2O2‐induced oxidative damage. In H2O2‐stimulated HUVECs, the caspase‐3 inhibitor prevents ZO‐1 disruption. Caspase‐3 activation promoted endolysosomal degradation of ZO‐1. Furthermore, a decrease in caspase‐3 activation and cytoskeleton redistribution was demonstrated in VIP + H2O2‐treated cells. The knockdown of ZO‐1 or the overexpression of caspase‐3 blocked the effect of VIP on the cytoskeleton. Conclusion. This study provides insights into the role of VIP in stabilizing the interaction between the actin cytoskeleton and cell junctions and may provide a promising targeted strategy for glaucoma treatment.
A Phase I Study of an MPS1 Inhibitor (BAY 1217389) in Combination with Paclitaxel Using a Novel Randomized Continual Reassessment Method for Dose Escalation
Authors: Atrafi Florence , Boix Oliver , Subbiah Vivek , Diamond Jennifer R. , Chawla Sant P. , Tolcher Anthony W. , LoRusso Patricia M. , Eder Joseph P. , Gutierrez Martin , Sankhala Kumar , Rajagopalan Prabhu , Genvresse Isabelle , Langer Simon , Mathijssen Ron H.J. , Verweij Jaap , Bruns Ingmar , Lolkema Martijn P.
Published: September 2021

Purpose:

Monopolar spindle 1 (MPS1) kinase inhibitor, BAY 1217389 (BAY) synergizes with paclitaxel. This phase I study assessed the combination of BAY with paclitaxel using a novel randomized continuous reassessment method (rCRM) to improve dose determination.

Patients and Methods:

Patients with solid tumors were randomized to receive oral BAY (twice daily 2-days-on/5-days-off) with weekly paclitaxel (90 mg/m2) or paclitaxel monotherapy in cycle 1. Dose escalation was guided by CRM modeling. Primary objectives were to assess safety, establish the MTD of BAY, and to evaluate the pharmacokinetic profiles for both compounds. Simulations were performed to determine the contribution of the rCRM for dose determination.

Results:

In total, 75 patients were enrolled. The main dose-limiting toxicities were hematologic toxicities (55.6%). The MTD of BAY was established at 64 mg twice daily with paclitaxel. Inclusion of a control arm enabled the definitive attribution of grade ≥3 neutropenia to higher BAY exposure [AUC0–12 (P< 0.001)]. After determining the MTD, we included 19 patients with breast cancer at this dose for dose expansion. Other common toxicities were nausea (45.3%), fatigue (41.3%), and diarrhea (40.0%). Overall confirmed responses were seen in 31.6% of evaluable patients. Simulations showed that rCRM outperforms traditional designs in determining the true MTD.

Conclusions:

The combination of BAY with paclitaxel was associated with considerable toxicity without a therapeutic window. However, the use of the rCRM design enabled us to determine the exposure–toxicity relation for BAY. Therefore, we propose that the rCRM could improve dose determination in phase I trials that combine agents with overlapping toxicities.
FLT3L Release by Natural Killer Cells Enhances Response to Radioimmunotherapy in Preclinical Models of HNSCC
Authors: Bickett Thomas E. , Knitz Michael , Darragh Laurel B. , Bhatia Shilpa , Van Court Benjamin , Gadwa Jacob , Bhuvane Shiv , Piper Miles , Nguyen Diemmy , Tu Hua , Lenz Laurel , Clambey Eric T. , Barry Kevin , Karam Sana D.
Published: September 2021

Purpose:

Natural killer (NK) cells are type I innate lymphoid cells that are known for their role in killing virally infected cells or cancer cells through direct cytotoxicity. In addition to direct tumor cell killing, NK cells are known to play fundamental roles in the tumor microenvironment through secretion of key cytokines, such as FMS-like tyrosine kinase 3 ligand (FLT3L). Although radiotherapy is the mainstay treatment in most cancers, the role of radiotherapy on NK cells is not well characterized.

Experimental Design:

This study combines radiation, immunotherapies, genetic mouse models, and antibody depletion experiments to identify the role of NK cells in overcoming resistance to radiotherapy in orthotopic models of head and neck squamous cell carcinoma.

Results:

We have found that NK cells are a crucial component in the development of an antitumor response, as depleting them removes efficacy of the previously successful combination treatment of radiotherapy, anti-CD25, and anti-CD137. However, in the absence of NK cells, the effect can be rescued through treatment with FLT3L. But neither radiotherapy with FLT3L therapy alone nor radiotherapy with anti-NKG2A yields any meaningful tumor growth delay. We also identify a role for IL2 in activating NK cells to secrete FLT3L. This activity, we show, is mediated through CD122, the intermediate affinity IL2 receptor, and can be targeted with anti-CD25 therapy.

Conclusions:

These findings highlight the complexity of using radio-immunotherapies to activate NK cells within the tumor microenvironment, and the importance of NK cells in activating dendritic cells for increased tumor surveillance.
Spatial Mapping and Immunomodulatory Role of the OX40/OX40L Pathway in Human Non–Small Cell Lung Cancer
Authors: Porciuncula Angelo , Morgado Micaela , Gupta Richa , Syrigos Kostas , Meehan Robert , Zacharek Sima J. , Frederick Joshua P. , Schalper Kurt A.
Published: September 2021

Purpose:

To evaluate the tissue distribution and clinical significance of OX40 and OX40L in human non–small cell lung cancer (NSCLC).

Experimental Design:

Using multiplexed quantitative immunofluorescence, we conducted simultaneous and localized measurements of OX40 and OX40L proteins, major T-cell subsets, and conventional type 1 dendritic cells (cDC1) in 614 primary NSCLCs from three independent cohorts represented in tissue microarrays. We also measured OX40L protein in samples from a phase I clinical trial of intratumor administration of a lipid nanoparticle encapsulated mRNA encoding OX40L (mRNA-2416) in human solid tumors. Finally, we studied the OX40 pathway in 212 uterine/ovarian serous carcinomas.

Results:

OX40 protein was expressed in approximately 90% of NSCLCs, and OX40L was detected in approximately 10% of cases. Increased expression of OX40 was associated with higher CD4+ and CD8+ T lymphocytes, as well as cDC1s. Elevated expression of OX40L was consistently associated with increased CD4+ tumor-infiltrating lymphocytes and longer overall survival. No association was found between OX40 or OX40L levels and oncogenic driver mutations in EGFR and KRAS in lung adenocarcinomas. Delivering OX40L mRNA using intratumor mRNA-2416 injection mediated increased local OX40L protein levels that was most prominent in a patient with ovarian serous carcinoma. Detectable OX40L protein levels were observed in 15% of primary uterine/ovarian serous malignancies and associated with longer survival.

Conclusions:

The OX40 pathway is expressed in a fraction of NSCLCs and is associated with a favorable immune contexture. Although OX40L is uncommonly expressed in NSCLC and serous malignancies, it is associated with better prognosis and can be introduced using exogenous mRNA.
Surface Free Energy, Interaction, and Adsorption of Calcium and Phosphate to Enamel Treated with Trimetaphosphate and Glycerophosphate
Authors: Nalin Emanuelle Karine Prado , Danelon Marcelle , da Silva Emanuel Soares , Hosida Thayse Yumi , Pessan Juliano Pelim , Delbem Alberto Carlos Botazzo
Published: September 2021

This study aimed to evaluate the surface (γs) and interaction (ΔGiwi) free energy and calcium (Ca2+) and phosphate (PO43−) adsorption to dental enamel treated with sodium trimetaphosphate (TMP) or calcium glycerophosphate (CaGP) that had or had not been exposed to CaPO4-containing solutions. Bovine enamel blocks (n = 192; 24 blocks/group) were treated (2 mL/block; 2 min) with TMP (0%, 1%, 3%, and 9%) and CaGP (0, 0.25, 0.5, and 1%) or exposed to a CaPO4-containing solution. The adsorption of these compounds by enamel was assessed before and after treatment. γs and ΔGiwi and their apolar (γsLW and ΔGiwiLW) and polar (γsAB and ΔGiwiAB) components and acid-base interactions (γs+/γs−) were determined by the contact angles. The data were subjected to ANOVA, followed by the Student-Newman-Keuls test (p < 0.05). The adsorption of TMP was dose dependent (p < 0.001), and it reduced γs and γsAB and increased ΔGiwiAB (ΔGiwi > 0) and γs− when compared with the group without TMP (p < 0.001). The immersion in CaPO4-containing solution increased γs and γsAB and reduced ΔGiwiAB (ΔGiwi > 0) and γs− (p < 0.001). There was a correlation between the adsorption of TMP and Ca2+ (r = 0.916; p < 0.001) and PO43− (r = 0.899; p < 0.001). The adsorption of CaGP on the enamel was dose dependent (p < 0.001), reducing γs, ΔGiwiAB (ΔGiwi < 0), γsLW, and γs− when compared to the group without CaGP (p < 0.001). When exposed to the CaPO4-containing solution, there was an increase in ΔGiwiAB (ΔGiwi > 0), γsLW, and γs− and a decrease in γsAB (p < 0.001) without adsorption of Ca2+ by enamel. It may be concluded that TMP and CaGP were adsorbed onto the enamel, producing hydrophilic and hydrophobic surfaces, respectively. TMP produces electron donor sites that induce Ca2+ adsorption, while CaGP releases Ca2+ into the medium.
Macrophage MST1/2 Disruption Impairs Post-Infarction Cardiac Repair via LTB4
Authors: Liu Mingming , Yan Meng , He Jinlong , Lv Huizhen , Chen Zhipeng , Peng Liyuan , Cai Wenbin , Yao Fang , Chen Chen , Shi Lei , Zhang Kai , Zhang Xu , Wang Dao-Wen , Wang Li , Zhu Yi , Ai Ding
Published: September 2021

Rationale:

Timely inhibition of inflammation and initiation of resolution are important to repair injured tissues. MST1/2 (mammalian STE20-like protein kinase 1/2) acts as a regulator of macrophage-associated immune responses to bacterial infections. However, the role of MST1/2 in regulating macrophage phenotype and function in myocardial infarction (MI) remains unclear.

Objective:

To determine the function and underlying mechanism of macrophage MST1/2 in cardiac repair post-MI.

Methods and Results:

Using
LysMCre
-mediated
Mst1/2
-deficient mice, we found that MST1 deficiency exacerbated cardiac dysfunction after MI. Single-cell RNA sequencing assay indicated that the effect was attributed to a shift of macrophage subtypes from those expressing
Cxcl2
and
Cd163
toward
Ccl2
and
Ccl4
expression. Mass spectrometry identified LTB4 (leukotriene B4) as the lipid mediator that was upregulated in the absence of MST1. We found that MST1 phosphorylated 5-LOX (5-lipoxygenase) at its T218 residue, disrupting the interaction between 5-LOX and 5-LOX-activating protein, resulting in a reduction of LTB4 production. In contrast, a 5-LOX
T218A
variant showed no response to MST1. Moreover, treatment of peritoneal macrophages with LTB4 or medium conditioned by
Mst1
-deficient macrophages resulted in high
Ccl2
and
Ccl4
expression and low
Cxcl2
and
Cd163
expression, except when the cells were co-treated with the BLT1 (LTB4 receptor 1) antagonist CP105696. Furthermore, CP105696 ameliorated cardiac dysfunction in
LysMCre
-mediated
Mst1/2
-deficient mice and enhanced cardiac repair in wild-type mice treated with XMU-MP-1 (4-((5,10-dimethyl-6-oxo-6,10-dihydro-5H-pyrimido[5,4-b]thieno[3,2-e][1,4]diazepin-2-yl)amino)benzenesulfonamide) after MI.

Conclusions:

Taken together, our results demonstrate that inhibition of MST1/2 impaired post-MI repair through activating macrophage 5-LOX–LTB4–BLT1 axis.
Historical and Recent Changes in Maternal Mortality Due to Hypertensive Disorders in the United States, 1979 to 2018
Authors: Ananth Cande V. , Brandt Justin S. , Hill Jennifer , Graham Hillary L. , Grover Sonal , Schuster Meike , Patrick Haylea S. , Joseph K.S.
Published: September 2021

We evaluated the contributions of maternal age, year of death (period), and year of birth (cohort) on trends in hypertension-related maternal deaths in the United States. We undertook a sequential time series analysis of 155 710 441 live births and 3287 hypertension-related maternal deaths in the United States, 1979 to 2018. Trends in pregnancy-related mortality rate (maternal mortality rate [MMR]) due to chronic hypertension, gestational hypertension, and preeclampsia/eclampsia, were examined. MMR was defined as death during pregnancy or within 42 days postpartum due to hypertension. Trends in overall and race-specific hypertension-related MMR based on age, period, and birth cohort were evaluated based on weighted Poisson models. Trends were also adjusted for secular changes in obesity rates and corrected for potential death misclassification. During the 40-year period, the overall hypertension-related MMR was 2.1 per 100 000 live births, with MMR being almost 4-fold higher among Black compared with White women (5.4 [n=1396] versus 1.4 [n=1747] per 100 000 live births). Advancing age was associated with a sharp increase in MMR at ≥15 years among Black women and at ≥25 years among White women. Birth cohort was also associated with increasing MMR. Preeclampsia/eclampsia-related MMR declined annually by 2.6% (95% CI, 2.2–2.9), but chronic hypertension–related MMR increased annually by 9.2% (95% CI, 7.9–10.6). The decline in MMR was attenuated when adjusted for increasing obesity rates. The temporal burden of hypertension-related MMR in the United States has increased substantially for chronic hypertension–associated MMR and decreased for preeclampsia/eclampsia-associated MMR. Nevertheless, deaths from hypertension continue to contribute substantially to maternal deaths.
Sodium‐Glucose Cotransporter 2 Inhibitors, All‐Cause Mortality, and Cardiovascular Outcomes in Adults with Type 2 Diabetes: A Bayesian Meta‐Analysis and Meta‐Regression
Authors: Odutayo Ayodele , da Costa Bruno R. , Pereira Tiago V. , Garg Vinay , Iskander Samir , Roble Fatimah , Lalji Rahim , Hincapié Cesar A. , Akingbade Aquila , Rodrigues Myanca , Agarwal Arnav , Lawendy Bishoy , Saadat Pakeezah , Udell Jacob A. , Cosentino Francesco , Grant Peter J. , Verma Subodh , Jüni Peter
Published: September 2021

Background

This study aimed to assess the effectiveness of sodium‐glucose cotransporter 2 inhibitors in reducing the incidence of mortality and cardiovascular outcomes in adults with type 2 diabetes.

Methods and Results

We conducted a Bayesian meta‐analysis of randomized controlled trials comparing sodium‐glucose cotransporter 2 inhibitors with placebo. We used meta‐regression to examine the association between treatment effects and control group event rates as measures of cardiovascular baseline risk. Fifty‐three randomized controlled trials were included in our synthesis. Empagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all‐cause mortality (empagliflozin: rate ratio [RR], 0.79; 95% credibility interval [CrI], 0.63–0.97; canagliflozin: RR, 0.86; 95% CrI, 0.69–1.05; dapagliflozin: RR, 0.86; 95% CrI, 0.72–1.01) and cardiovascular mortality (empagliflozin: RR, 0.78; 95% CrI, 0.61–1.00; canagliflozin: RR, 0.83; 95% CrI, 0.63–1.05; dapagliflozin: RR, 0.88; 95% CrI, 0.71–1.08), with a 90.1% to 98.7% probability for the true RR to be <1.00 for both outcomes. There was little evidence for ertugliflozin and sotagliflozin versus placebo for reducing all‐cause and cardiovascular mortality. There was no association between treatment effects for all‐cause and cardiovascular mortality and the control group event rates. There was evidence for a reduction in the incidence of heart failure for empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin versus placebo (probability RR <1.00 of ≥99.3%) and weaker, albeit positive, evidence for acute myocardial infarction for the first 3 agents (probability RR <1.00 of 89.0%–95.2%). There was little evidence of any agent except canagliflozin for reducing the incidence of stroke.

Conclusions

Empagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all‐cause and cardiovascular mortality versus placebo. Treatment effects of sodium‐glucose cotransporter 2 inhibitors versus placebo do not vary by baseline risk.
Disrupted Blood‐Brain Barrier and Mitochondrial Impairment by Autotaxin–Lysophosphatidic Acid Axis in Postischemic Stroke
Authors: Bhattarai Susmita , Sharma Sudha , Ara Hosne , Subedi Utsab , Sun Grace , Li Chun , Bhuiyan Md. Shenuarin , Kevil Christopher , Armstrong William P. , Minvielle Miles T. , Miriyala Sumitra , Panchatcharam Manikandan
Published: September 2021

Background

The loss of endothelial integrity increases the risk of intracerebral hemorrhage during ischemic stroke. Adjunct therapeutic targets for reperfusion in ischemic stroke are in need to prevent blood‐brain barrier disruption. Recently, we have shown that endothelial permeability is mediated by lysophosphatidic acid (LPA), but the role of autotaxin, which produces LPA, remains unclear in stroke. We investigate whether autotaxin/LPA axis regulates blood‐brain barrier integrity after cerebral ischemia.

Methods and Results

Ischemic stroke was induced in mice by middle cerebral artery occlusion for 90 minutes, followed by 24‐hour reperfusion. The therapeutic efficacy of autotaxin/LPA receptor blockade was evaluated using triphenyl tetrazolium chloride staining, Evans blue permeability, infrared imaging, mass spectrometry, and XF24 analyzer to evaluate blood‐brain barrier integrity, autotaxin activity, and mitochondrial bioenergetics. In our mouse model of ischemic stroke, the mRNA levels of autotaxin were elevated 1.7‐fold following the cerebral ischemia and reperfusion (I/R) group compared with the sham. The enzymatic activity of autotaxin was augmented by 4‐fold in the I/R group compared with the sham. Plasma and brain tissues in I/R group showed elevated LPA levels. The I/R group also demonstrated mitochondrial dysfunction, as evidenced by decreased (
P
<0.01) basal oxygen consumption rate, mitochondrial ATP production, and spare respiratory capacity. Treatment with autotaxin inhibitors (HA130 or PF8380) or autotaxin/LPA receptor inhibitor (BrP‐LPA) rescued endothelial permeability and mitochondrial dysfunction in I/R group.

Conclusions

Autotaxin‐LPA signaling blockade attenuates blood‐brain barrier disruption and mitochondrial function following I/R, suggesting targeting this axis could be a new therapeutic approach toward treating ischemic stroke.
Ten‐Year Trends in Coronary Bifurcation Percutaneous Coronary Intervention: Prognostic Effects of Patient and Lesion Characteristics, Devices, and Techniques
Authors: Lee Joo Myung , Lee Seung Hun , Kim Juwon , Choi Ki Hong , Park Taek Kyu , Yang Jeong Hoon , Song Young Bin , Hahn Joo‐Yong , Choi Jin‐Ho , Choi Seung‐Hyuk , Kim Hyo‐Soo , Chun Woo Jung , Nam Chang‐Wook , Hur Seung‐Ho , Han Seung Hwan , Rha Seung‐Woon , Chae In‐Ho , Jeong Jin‐Ok , Heo Jung Ho , Yoon Junghan , Lim Do‐Sun , Park Jong‐Seon , Hong Myeong‐Ki , Doh Joon‐Hyung , Cha Kwang Soo , Kim Doo‐Il , Lee Sang Yeub , Chang Kiyuk , Hwang Byung‐Hee , Choi So‐Yeon , Jeong Myung Ho , Hong Soon‐Jun , Koo Bon‐Kwon , Gwon Hyeon‐Cheol
Published: September 2021

Background

Despite advances in devices and techniques, coronary bifurcation lesion remains a challenging lesion subset in the field of percutaneous coronary intervention (PCI). We evaluate 10‐year trends in bifurcation PCI and their effects on patient outcomes.

Methods and Results

We analyzed 10‐year trends in patient/lesion characteristics, devices, PCI strategy, stent optimization techniques, and clinical outcomes using data from 5498 patients who underwent bifurcation PCI from 2004 to 2015. Clinical outcomes 2 years after the index procedure were evaluated in terms of target vessel failure (a composite of cardiac death, myocardial infarction, and target vessel revascularization) and a patient‐oriented composite outcome (a composite of all‐cause death, myocardial infarction, and any revascularization). During the 10‐year study period, patient and lesion complexity, such as multivessel disease, diabetes mellitus, chronic kidney disease, and left main bifurcation, increased continuously (all
P
<0.001). The risk of target vessel failure or patient‐oriented composite outcome decreased continuously from 2004 to 2015 (target vessel failure: from 12.3% to 6.9%, log‐rank
P
<0.001; patient‐oriented composite outcome: from 13.6% to 9.3%, log‐rank
P
<0.001). The use of a second‐generation drug‐eluting stent and decreased target vessel failure risk in true bifurcation lesions were the major contributors to improved patient prognosis (interaction
P
values were <0.001 and 0.013, respectively).

Conclusions

During the past decade of bifurcation PCI, patient and lesion characteristics, devices, PCI techniques, and patient prognosis have all significantly changed. Despite increased patient and lesion complexity, clinical outcomes after bifurcation PCI have improved, mainly because of better devices and more widespread adoption of procedural optimization techniques and appropriate treatment strategies.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifiers: NCT01642992 and NCT03068494.
Collagen‐Targeted Peptides for Molecular Imaging of Diffuse Cardiac Fibrosis
Authors: Ezeani Martin , Noor Asif , Alt Karen , Lal Sean , Donnelly Paul S. , Hagemeyer Christoph E. , Niego Be’eri
Published: September 2021

Background

Cardiac fibrosis is the excessive deposition of extracellular matrix in the heart, triggered by a cardiac insult, aging, genetics, or environmental factors. Molecular imaging of the cardiac extracellular matrix with targeted probes could improve diagnosis and treatment of heart disease. However, although this technology has been used to demonstrate focal scarring arising from myocardial infarction, its capacity to demonstrate extracellular matrix expansion and diffuse cardiac fibrosis has not been assessed.

Methods and Results

Here, we report the use of collagen‐targeted peptides labeled with near‐infrared fluorophores for the detection of diffuse cardiac fibrosis in the β2‐AR (β‐2‐adrenergic receptor) overexpressing mouse model and in ischemic human hearts. Two approaches were evaluated, the first based on a T peptide that binds matrix metalloproteinase‐2‐proteolyzed collagen IV, and the second on the cyclic peptide EP‐3533, which targets collagen I. The systemic and cardiac uptakes of both peptides (intravenously administered) were quantified ex vivo by near‐infrared imaging of whole organs, tissue sections, and heart lysates. The peptide accumulation profiles corresponded to an immunohistochemically‐validated increase in collagen types I and IV in hearts of transgenic mice versus littermate controls. The T peptide could encouragingly demonstrate both the intermediate (7 months old) and severe (11 months old) cardiomyopathic phenotypes. Co‐immunostainings of fluorescent peptides and collagens, as well as reduced collagen binding of a control peptide, confirmed the collagen specificity of the tracers. Qualitative analysis of heart samples from patients with ischemic cardiomyopathy compared with nondiseased donors supported the collagen‐enhancement capabilities of these peptides also in the clinical settings.

Conclusions

Together, these observations demonstrate the feasibility and translation potential of molecular imaging with collagen‐binding peptides for noninvasive imaging of diffuse cardiac fibrosis.
The backbone network of dynamic functional connectivity
Authors: Asadi Nima , Olson Ingrid R. , Obradovic Zoran
Published: September 2021

Temporal networks have become increasingly pervasive in many real-world applications, including the functional connectivity analysis of spatially separated regions of the brain. A major challenge in analysis of such networks is the identification of noise confounds, which introduce temporal ties that are nonessential, or links that are formed by chance due to local properties of the nodes. Several approaches have been suggested in the past for static networks or temporal networks with binary weights for extracting significant ties whose likelihood cannot be reduced to the local properties of the nodes. In this work, we propose a data-driven procedure to reveal the irreducible ties in dynamic functional connectivity of resting-state fMRI data with continuous weights. This framework includes a null model that estimates the latent characteristics of the distributions of temporal links through optimization, followed by a statistical test to filter the links whose formation can be reduced to the activities and local properties of their interacting nodes. We demonstrate the benefits of this approach by applying it to a resting-state fMRI dataset, and provide further discussion on various aspects and advantages of it.
Typification and homotypic synonymy of the names published in Kalanchoe (Crassulaceae subfam. Kalanchooideae) by Raymond-Hamet and Henri Perrier de la Bâthie in the 1910s and in 1948
Authors: SMITH GIDEON F. , SHTEIN RONEN
Published: September 2021

The 25 names, mostly at the rank of species, which were jointly published by Raymond-Hamet (1890–1972) and Henri Perrier de la Bâthie (1873–1958) in Kalanchoe (Crassulaceae subfam. Kalanchooideae) between 1912 and 1915, with a final name appearing in 1948, are catalogued. The current taxonomic status of the taxa, to which these names are applied, is provided and where necessary the names are typified or previous typifications are corrected or superseded if these were not effective.
Illustrated key to the genera and catalogue of Mymaridae (Hymenoptera) in the Afrotropical region
Authors: HUBER JOHN T. , READ JENNIFER D. , TRIAPITSYN SERGUEI V.
Published: September 2021

Separate identification keys for females, and for males where known, of the 40 genera of Mymaridae (Hymenoptera: Chalcidoidea) in the Afrotropical region are given. The subgenera of four genera are also included in the key to females. The genera are illustrated with over 300 photographs. The 122 named, valid species reported from the region are catalogued. Reliable host records are reported for 6 genera and 11 species from rearings undertaken in the region. An appendix lists the 27 species from northern Africa and offshore islands (Canary Islands, Madeira) but not recorded in the Afrotropical region as defined in this publication. Camptoptera (Zemicamptoptera) Ogloblin & Annecke, syn. n. is synonymized with Camptoptera (Camptoptera) Foerster. Eofoersteria Mathot, syn. n. is synonymized with Camptoptera Foerster and is treated as subgenus C. (Eofoersteria) Mathot, stat. n.; its type species Eofoersteria camptopteroides Mathot is transferred to Camptoptera as C. (Eofoersteria) camptopteroides (Mathot), comb. n. Polynema megacephala (Risbec) is transferred to Lymaenon as L. megacephala (Risbec), comb. n. Limacis opuntiae Risbec is transferred to Encarsia Foerster (Hymenoptera: Aphelinidae) as E. opuntiae (Risbec), comb. n. A few corrections to Huber et al. (2020) are given.
Atmospheric Convection as an Unstable Predator–Prey Process with Memory
Authors: Colin Maxime , Sherwood Steven C.
Published: September 2021

Heuristic models and observational analyses of atmospheric convection often assume that convective activity, for example, rain rate, approaches some given value for any given large-scale (“macrostate”) environmental conditions, such as static stability and humidity. We present novel convection-resolving simulations in which the convective activity evolves in a fixed equilibrium mean state (“macrostate”). In this case, convective activity is unstable, diverging quasi exponentially away from equilibrium either to extreme or zero rain rate. Thus, almost any rain rate can coexist with an equilibrium profile: the model rain rate also depends on convective history. We then present a two-variable, predator–prey model motivated by this behavior, wherein small-scale (“microstate”) variability is produced by but also promotes convective precipitation, while macrostate properties such as CAPE promote but are consumed by convective precipitation. In this model, convection is influenced as much by its own history (via persistent microstate variability) as by its current environment. This model reproduces the simulated instability found above and could account for several lag relationships in simulated and observed convection, including its afternoon maximum over land and the well-known “quasi-equilibrium” balance at synoptic time scales between the forcing and response of key variables. These results point to a strong role for convective memory and suggest that basic strategies for observing, modeling, and parameterizing convective processes should pay closer attention to persistent variability on scales smaller than that of the grid box.
Evaluating Operational and Experimental HRRR Model Forecasts of Atmospheric River Events in California
Authors: English Jason M. , Turner David D. , Alcott Trevor I. , Moninger William R. , Bytheway Janice L. , Cifelli Robert , Marquis Melinda
Published: September 2021

Improved forecasts of atmospheric river (AR) events, which provide up to half the annual precipitation in California, may reduce impacts to water supply, lives, and property. We evaluate quantitative precipitation forecasts (QPF) from the High-Resolution Rapid Refresh model version 3 (HRRRv3) and version 4 (HRRRv4) for five AR events that occurred in February–March 2019 and compare them to quantitative precipitation estimates (QPE) from Stage IV and Mesonet products. Both HRRR versions forecast spatial patterns of precipitation reasonably well, but are drier than QPE products in the Bay Area and wetter in the Sierra Nevada range. The HRRR dry bias in the Bay Area may be related to biases in the model temperature profile, while integrated water vapor (IWV), wind speed, and wind direction compare reasonably well. In the Sierra Nevada range, QPE and QPF agree well at temperatures above freezing. Below freezing, the discrepancies are due in part to errors in the QPE products, which are known to underestimate frozen precipitation in mountainous terrain. HRRR frozen QPF accuracy is difficult to quantify, but the model does have wind speed and wind direction biases near the Sierra Nevada range. HRRRv4 is overall more accurate than HRRRv3, likely due to data assimilation improvements, and possibly physics improvements. Applying a neighborhood maximum method impacted performance metrics, but did not alter general conclusions, suggesting closest gridbox evaluations may be adequate for these types of events. Improvements to QPF in the Bay Area and QPE/QPF in the Sierra Nevada range would be particularly useful to provide better understanding of AR events.
Categorical Distinctions and Claims-Making: Opportunity, Agency, and Returns from Wage Negotiations
Authors: Sauer Carsten , Valet Peter , Shams Safi , Tomaskovic-Devey Donald
Published: September 2021

In this article, we examine wage negotiations as a specific instance of claims-making, predicting that the capacity to make a claim is first a function of the position, rather than the person, and that lower-status actors—women, migrants, fixed-term, part-time, and unskilled workers—are all more likely to be in positions where negotiation is not possible. At the same time, subordinate-status actors may be less likely to make claims even where negotiation is possible, and when they do make wage claims they may receive lower or no returns to negotiation. Analyses of wage negotiations by more than 2,400 German employees largely confirm these theoretical expectations, although the patterns of opportunity, agency, and economic returns vary by categorical status. All low-status actors are more likely to be in jobs where negotiation is not possible. Women, people in lower-class jobs, and people with temporary contracts are less likely to negotiate even when given the opportunity. Regarding returns, agency in wage claims does not seem to improve the wages of women, migrants, or working-class individuals. The advice to “lean-in” will not substantially lower wage inequalities for everyone, although men who lean in do benefit relative to men who do not.
Structured inequalities and authors’ positionalities in academic publishing: The case of Philippine international migration scholarship
Authors: Arnado Janet M
Published: September 2021

This article examines structured inequalities and authors’ positionalities in the academic publishing field. It uses Bourdieu’s insights in explaining the reproduction of publishing inequality and mobility through cultural capital and habitus modification. The article elaborates ‘positionality’ to constitute structure and agency through position and positioning, and situates academics in varying positionalities (insider, outsider, hybrid) in the global publishing field. Focusing on Filipino international migration scholarship, the article examines 392 journal articles from 1989 to 2018, and tracks the first authors’ ethnicity, institutional affiliation, and university where they received their PhD. The findings show that authors institutionally affiliated in the Global North (insiders) dominate the field (publication count and citations), while homeland-based Filipino scholars are in the periphery (outsiders). With their insider-leaning hybrid positionality, overseas Filipino scholars in the Global North accrue network-mediated benefits. They have respectable representation in publication count and are the most frequently cited authors. Positionality is examined as cultural capital accumulation and adoption of the dominant habitus that enable academics to shift positionality from outsider to insider and derive benefits in research and publishing. The article contributes to the literature on positionality-based inequalities in knowledge production and a periphery standpoint in the discourse on academic publishing inequality.
Identifying Problematic Item Characteristics With Small Samples Using Mokken Scale Analysis
Authors: Wind Stefanie A.
Published: September 2021

Researchers frequently use Mokken scale analysis (MSA), which is a nonparametric approach to item response theory, when they have relatively small samples of examinees. Researchers have provided some guidance regarding the minimum sample size for applications of MSA under various conditions. However, these studies have not focused on item-level measurement problems, such as violations of monotonicity or invariant item ordering (IIO). Moreover, these studies have focused on problems that occur for a complete sample of examinees. The current study uses a simulation study to consider the sensitivity of MSA item analysis procedures to problematic item characteristics that occur within limited ranges of the latent variable. Results generally support the use of MSA with small samples ( N around 100 examinees) as long as multiple indicators of item quality are considered.
A Multilevel Mixture IRT Framework for Modeling Response Times as Predictors or Indicators of Response Engagement in IRT Models
Authors: Nagy Gabriel , Ulitzsch Esther
Published: September 2021

Disengaged item responses pose a threat to the validity of the results provided by large-scale assessments. Several procedures for identifying disengaged responses on the basis of observed response times have been suggested, and item response theory (IRT) models for response engagement have been proposed. We outline that response time-based procedures for classifying response engagement and IRT models for response engagement are based on common ideas, and we propose the distinction between independent and dependent latent class IRT models. In all IRT models considered, response engagement is represented by an item-level latent class variable, but the models assume that response times either reflect or predict engagement. We summarize existing IRT models that belong to each group and extend them to increase their flexibility. Furthermore, we propose a flexible multilevel mixture IRT framework in which all IRT models can be estimated by means of marginal maximum likelihood. The framework is based on the widespread Mplus software, thereby making the procedure accessible to a broad audience. The procedures are illustrated on the basis of publicly available large-scale data. Our results show that the different IRT models for response engagement provided slightly different adjustments of item parameters of individuals’ proficiency estimates relative to a conventional IRT model.
Quantitative Analysis of Classroom Communication Environments for Learners With Deaf blindness
Authors: Brady L. Beth
Published: September 2021

Classroom environments were analyzed to better understand adult language modeling rates and whether teacher certification practices contributed to differences with learners with deafblindness (DB). Student characteristics were also examined in relation to communication rates. When there is a dual sensory loss, access to tactile and visual communication forms (i.e., multimodal) in addition to verbal communication is needed. Data were collected from 15 teacher–student dyads from four states through behavioral coding of videotaped language samples, teacher surveys, and the Communication Matrix assessment. Overall, teachers used verbal communication significantly more than additional classroom staff. Teachers in a state that required a severe/profound certification had significantly higher rates of overall communication and visual communication, and they had students with higher communication levels.