bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on Stability of Gray Value of Excited-State Fluorescent Oil Film Based on Variable Light Vector Angle
Authors: Qian Hongjiang , Dong Xiucheng , Zhang Zhengyu
Published: December 2021

In global skin-friction measurement of aircraft, the fluorescent oil film method can characterize the distribution of skin friction well. However, in an actual wind tunnel test, the wing of the aircraft will inevitably produce corresponding vibrations due to the influence of wind, which will change the relative position between fluorescent oil film and UV (ultraviolet) excitation light source (position fixed). This also directly affects gray value imaging of fluorescent oil films. Based on this, a mathematical model is established to judge the stability of the gray value of fluorescent oil film in this vibrational environment; then, the model can be solved to obtain the vibrational range constraint that enables the gray value of fluorescent oil film to be stabilized. In order to simplify the calculation process, the light vector angle is used to describe the constraint, which also makes the results more intuitive. Through experimental analysis and demonstration, the prediction accuracy of this model can reach 95.61%, which has certain practical engineering application significance.
Cognitive Electronic Jamming Decision-Making Method Based on Improved
Q
-Learning Algorithm
Authors: Li Huiqin , Li Yanling , He Chuan , Zhan Jianwei , Zhang Hui
Published: December 2021

In this paper, a cognitive electronic jamming decision-making method based on improved

Q

-learning is proposed to improve the efficiency of radar jamming decision-making. First, the method adopts the simulated annealing (SA) algorithm’s Metropolis criterion to enhance the exploration strategy, balancing the contradictory relationship between exploration and utilization in the algorithm to avoid falling into local optima. At the same time, the idea of stochastic gradient descent with warm restarts (SGDR) is introduced to improve the learning rate of the algorithm, which reduces the oscillation and improves convergence speed at the later stage of the algorithm iteration. Then, a cognitive electronic jamming decision-making model is constructed, and the improved

Q

-learning algorithm’s specific steps are given. The simulation experiment takes a multifunctional radar as an example to analyze the influence of exploration strategy and learning rate on decision-making performance. The results reveal that compared with the traditional

Q

-learning algorithm, the improved

Q

-learning algorithm proposed in this paper can fully explore and efficiently utilize and converge the results to a better solution at a faster speed. The number of iterations can be reduced to more than 50%, which proves the feasibility and effectiveness of the method applied to cognitive electronic jamming decision-making.
Swing Characteristics and Vibration Feature of Tower Cranes under Compound Working Condition
Authors: Liu Fu , Yang Jianwei , Wang Jinhai , Liu Changdong
Published: December 2021

The swing behaviour of tower cranes under compound working conditions is closely related to construction safety and structural health. This paper presents dynamic models and simulated them for parameter analysis to understand tower cranes’ dynamic characteristics and vibration features under compound working conditions. The parameters contain payload mass, rope length, lifting acceleration, slewing acceleration, luffing acceleration, and initial angle. For the lifting‐luffing coupling motion (LLCM) and lifting‐slewing coupling motion (LSCM) of the tower crane, the D’Alembert principle provides a theoretical basis for the derivation of system dynamics equations. The spatial swing angle description of the crane payload includes the time‐domain response and frequency‐domain response, which uses a dynamic model. The result shows that the mass has little effect on the spatial swing angle. The value of the lifting acceleration is stable at 0.004 m/s2 to 0.01 m/s2. Peak value (PV), root mean square value (RMS), root mean square frequency (RMSF), and frequency standard deviation (RVF) present the best sensitivity to changes in the spatial swing angle response. When PV of angles θ and β increases by tens of thousands of times in the LLCM, PV can reflect the phenomenon of angle divergence. The skewness value (SV) increases by 3422% at the severe swing angle performance in the LSCM. The swing angle regularity with the compound working conditions can provide theoretical guidance for eliminating structural vibration.
Some Real‐Life Applications of a Newly Designed Algorithm for Nonlinear Equations and Its Dynamics via Computer Tools
Authors: Naseem Amir , Rehman M. A. , Younis Jihad
Published: December 2021

In this article, we design a novel fourth‐order and derivative free root‐finding algorithm. We construct this algorithm by applying the finite difference scheme on the well‐known Ostrowski’s method. The convergence analysis shows that the newly designed algorithm possesses fourth‐order convergence. To demonstrate the applicability of the designed algorithm, we consider five real‐life engineering problems in the form of nonlinear scalar functions and then solve them via computer tools. The numerical results show that the new algorithm outperforms the other fourth‐order comparable algorithms in the literature in terms of performance, applicability, and efficiency. Finally, we present the dynamics of the designed algorithm via computer tools by examining certain complex polynomials that depict the convergence and other graphical features of the designed algorithm.
Certain Class of Almost
α
-Cosymplectic Manifolds
Authors: Öztürk Sermin , Öztürk Hakan
Published: December 2021

This paper concerned with almost

α

-cosymplectic manifolds satisfying conformally flat condition. Firstly, we investigate Kaehler integral submanifolds of almost

α

-cosymplectic manifolds. Next, we study conformally flat almost

α

-cosymplectic manifolds of dim

≥

5 whose integral submanifolds are Kaehler. Finally, an illustrative example is constructed to verify our result.
Delayed-Onset Neuropathic Pain after Septoplasty
Authors: Koumpa Foteini-Stefania , Ferguson Mark , Saleh Hesham
Published: December 2021

Postoperative pain following a septoplasty is expected to be mild and limited to a few days after the operation. Chronic pain following the procedure is rare. No cases of delayed-onset neuropathic pain or allodynia have been described in the literature. This paper presents a case of delayed-onset neuropathic pain after septoplasty in a previously pain-free asthmatic patient that was successfully managed by administration of intranasal local anaesthesia. Physical examination and imaging excluded any other cause of neuralgia. A literature review revealed reports of chronic pain in patients following septoplasty if there were nasal contact or compression points or nasal tumours. Separately, acute postseptoplasty allodynia is documented in iatrogenic maxillary nerve damage. However, delayed-onset neuralgic pain, exacerbated by certain environmental triggers, has not been previously described. Facial pain can be debilitating; successfully managing this neuralgic pain with administration of intranasal local anaesthetic had a substantial effect on the patient’s quality of life.
Immunomodulation of T- and NK-cell Responses by a Bispecific Antibody Targeting CD28 Homolog and PD-L1
Authors: Ramaswamy Madhu , Kim Taeil , Jones Des C. , Ghadially Hormas , Mahmoud Tamer I. , Garcia Andrew , Browne Gareth , Zenonos Zenon , Puplampu-Dove Yvonne , Riggs Jeffrey M. , Bhat Geetha K. , Herbst Ronald , Schofield Darren J. , Carlesso Gianluca
Published: December 2021

Checkpoint blockade therapies targeting PD-1/PD-L1 and CTLA-4 are clinically successful but also evoke adverse events due to systemic T-cell activation. We engineered a bispecific, mAb targeting CD28 homolog (CD28H), a newly identified B7 family receptor that is constitutively expressed on T and natural killer (NK) cells, with a PD-L1 antibody to potentiate tumor-specific immune responses. The bispecific antibody led to T-cell costimulation, induced NK-cell cytotoxicity of PD-L1–expressing tumor cells, and activated tissue-resident memory CD8+ T cells. Mechanistically, the CD28H agonistic arm of the bispecific antibody reduced PD-L1/PD-1–induced SHP2 phosphorylation while simultaneously augmenting T-cell receptor signaling by activating the MAPK and AKT pathways. This bispecific approach could be used to target multiple immune cells, including CD8+ T cells, tissue-resident memory T cells, and NK cells, in a tumor-specific manner that may lead to induction of durable, therapeutic antitumor responses.
Spatial Organization and Prognostic Significance of NK and NKT-like Cells via Multimarker Analysis of the Colorectal Cancer Microenvironment
Authors: Väyrynen Juha P. , Haruki Koichiro , Lau Mai Chan , Väyrynen Sara A. , Ugai Tomotaka , Akimoto Naohiko , Zhong Rong , Zhao Melissa , Dias Costa Andressa , Borowsky Jennifer , Bell Phoenix , Takashima Yasutoshi , Fujiyoshi Kenji , Arima Kota , Kishikawa Junko , Shi Shan-shan , Twombly Tyler S. , Song Mingyang , Wu Kana , Chan Andrew T. , Zhang Xuehong , Fuchs Charles S. , Meyerhardt Jeffrey A. , Giannakis Marios , Ogino Shuji , Nowak Jonathan A.
Published: December 2021

Although tumor-infiltrating T cells hold a beneficial prognostic role in colorectal cancer, other lymphocytic populations are less characterized. We developed a multiplexed immunofluorescence assay coupled with digital image analysis and machine learning to identify natural killer (NK) cells (NCAM1+CD3−), natural killer T-like (NKT-like) cells (NCAM1+CD3+), and T cells (NCAM1−CD3+) within the PTPRC+ (CD45+) cell population and to measure their granzyme B (GZMB; cytotoxicity marker) and FCGR3A (CD16a; NK-cell maturity marker) expression. We evaluated immune cell densities and spatial configuration in 907 incident colorectal carcinoma cases within two prospective cohort studies. We found that T cells were approximately 100 times more abundant than NK and NKT-like cells. Overall, NK cells showed high GZMB expression and were located closer to tumor cells than T and NKT-like cells. In T and NKT-like cells, GZMB expression was enriched in cells in closer proximity to tumor cells. Higher densities of both T and NKT-like cells associated with longer cancer-specific survival, independent of potential confounders (Ptrend < 0.0007). Higher stromal GZMB+ and FCGR3A+ NK-cell densities associated with longer cancer-specific survival (Ptrend < 0.003). For T and NKT-like cells, greater proximity to tumor cells associated with longer cancer-specific survival (Ptrend < 0.0001). These findings indicate that cytotoxic NCAM1+CD3−GZMB+ NK cells and NCAM1+CD3+ NKT-like cells are relatively rare lymphocytic populations within the colorectal cancer microenvironment and show distinct spatial configuration and associations with patient outcome. The results highlight the utility of a quantitative multimarker assay for in situ, single-cell immune biomarker evaluation and underscore the importance of spatial context for tumor microenvironment characterization.
Vascular Smooth Muscle Cells Mechanosensitive Regulators and Vascular Remodeling
Authors: Liu Shangmin , Lin Zhanyi
Published: December 2021

Blood vessels are subjected to mechanical loads of pressure and flow, inducing smooth muscle circumferential and endothelial shear stresses. The perception and response of vascular tissue and living cells to these stresses and the microenvironment they are exposed to are critical to their function and survival. These mechanical stimuli not only cause morphological changes in cells and vessel walls but also can interfere with biochemical homeostasis, leading to vascular remodeling and dysfunction. However, the mechanisms underlying how these stimuli affect tissue and cellular function, including mechanical stimulation-induced biochemical signaling and mechanical transduction that relies on cytoskeletal integrity, are unclear. This review focuses on signaling pathways that regulate multiple biochemical processes in vascular mesangial smooth muscle cells in response to circumferential stress and are involved in mechanosensitive regulatory molecules in response to mechanotransduction, including ion channels, membrane receptors, integrins, cytoskeletal proteins, nuclear structures, and cascades. Mechanoactivation of these signaling pathways is closely associated with vascular remodeling in physiological or pathophysiological states.
A Quality Improvement Project to Minimize COVID-19 Infections in Patients Receiving Haemodialysis and the Role of Routine Surveillance Using Nose and Throat Swabs for SARS-CoV-2 rRT-PCR and Serum Antibody Testing
Authors: Poulikakos Dimitrios , Chinnadurai Rajkumar , Mcgee Yvonne , Gray Simon , Clough Toni , Clarke Nicola , Murphy Tracey , Wickens Olivia , Mitchell Carol , Darby Denise , Paul Joel , Chadwick Paul , Sethi Su , Sinha Smeeta , Kalra Philip A. , Donne Rosie
Published: December 2021

Background: Patients receiving in-centre haemodialysis (ICHD) are highly vulnerable to COVID-19. Objective: We created a quality improvement (QI) project aimed to eliminate outbreaks of COVID-19 in haemodialysis units and evaluated the utility of surveillance rRT-PCR test and SARS-CoV-2 serum antibodies for prompt identification of patients infected with COVID-19. Methods: A multifaceted QI programme including a bundle of infection prevention control (IPC) measures was implemented across 5 ICHD units following the first wave of the pandemic in June 2020. Primary outcomes evaluated before and after QI implementation were incidence of outbreaks and severe COVID-19 illness defined as COVID-19-related death or hospitalization. Secondary outcomes included the proportion of patients identified in the pre-symptomatic/asymptomatic phase on surveillance rRT-PCR screening and the incidence and longevity of SARS-CoV-2 antibody response. Results: Following the implementation of the QI project, there were no further outbreaks. Pre- and post-implementation comparison showed a significant reduction in COVID-19-related mortality and hospitalization (26 vs. 13 events, respectively, p < 0.001). Surveillance rRT-PCR screening identified 39 asymptomatic or pre-symptomatic cases out of a total of 59 rRT-PCR-positive patients (39/59, 66%). SARS-CoV-2 antibody levels were detected in 72/74 (97%) rRT-PCR-positive patients. Amongst rRT-PCR-positive patients diagnosed before August 2020, 96% had detectable antibodies until January 2021 (days from the rRT-PCR test to last antibody testing, 245–280). Conclusions: Systematic implementation of a bundle of IPC measures using QI methodology and surveillance rRT-PCR eliminated outbreaks in HD facilities. Most HD patients mount and sustain antibody response to COVID-19 for over 8 months.
Late-Onset, Noninfectious Pulmonary Complications following Allogeneic Hematopoietic Stem Cell Transplantation: A Nationwide Cohort Study of Long-Term Survivors
Authors: Myrdal Ole Henrik , Aaløkken Trond Mogens , Diep Phoi Phoi , Ruud Ellen , Brinch Lorentz , Fosså Kristian , Mangseth Henrik , Kongerud Johny , Sikkeland Liv Ingunn , Lund May B.
Published: December 2021

Background: Survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk for pulmonary adverse events. Data on late-onset noninfectious pulmonary complications in long-term adult survivors of allo-HSCT are limited and incomplete. Objectives: This study aimed (1) to determine occurrence and degree of pulmonary sequelae in adult survivors of allo-HSCT and (2) to identify associations between pulmonary function, high-resolution CT (HRCT), and clinical characteristics. Method: In a nationwide, single-center cross-sectional study, 103 survivors (aged median [range] 35 [17–58] years, 53% females) were examined 17 (6–32) years after allo-HSCT and compared with healthy controls (n = 105). Methods included pulmonary function tests and HRCT. Results: Chronic graft-versus-host disease was diagnosed in 33% of survivors, including 12% with bronchiolitis obliterans syndrome (BOS). Mean lung volumes (TLC, FVC, and FEV1) and gas diffusing capacity were >80% of predicted for the survivors as a group, but significantly lower than in healthy controls. Pathological HRCT findings were detected in 48% of the survivors (71% airways disease, 35% interstitial lung disease, and 24% apical subpleural interstitial thickening). Air trapping (%) on HRCT correlated with % predicted FEV1, p < 0.001. In a multiple logistic regression model, both BOS and pathological findings on HRCT were associated with chemotherapy prior to allo-HSCT, p < 0.05. Conclusions: Long-term allo-HSCT survivors had significantly lower pulmonary function than age- and gender-matched healthy controls and nearly half had pathological findings on HRCT. Longitudinal data will determine if pulmonary sequelae will remain stable or progress. We recommend lifelong monitoring of pulmonary function in allo-HSCT survivors. HRCT provides additional information, but is not suited for surveillance.
Differential Internalization of Thrombin-Derived Host Defense Peptides into Monocytes and Macrophages
Authors: Hansen Finja C. , Nadeem Aftab , Browning Kathryn L. , Campana Mario , Schmidtchen Artur , van der Plas Mariena J.A.
Published: December 2021

Proteolytic cleavage of thrombin generates C-terminal host defense peptides exerting multiple immunomodulatory effects in response to bacterial stimuli. Previously, we reported that thrombin-derived C-terminal peptides (TCPs) are internalized in monocytes and macrophages in a time- and temperature-dependent manner. In this study, we investigated which endocytosis pathways are responsible for the internalization of TCPs. Using confocal microscopy and flow cytometry, we show that both clathrin-dependent and clathrin-independent pathways are involved in the internalization of the prototypic TCP GKY25 in RAW264.7 and human monocyte-derived M1 macrophages, whereas the uptake of GKY25 in monocytic THP-1 cells is mainly dynamin-dependent. Internalized GKY25 was transported to endosomes and finally lysosomes, where it remained detectable for up to 10 h. Comparison of GKY25 uptake with that of the natural occurring TCPs HVF18 and FYT21 indicates that the pathway of TCP endocytosis is not only cell type-dependent but also depends on the length and composition of the peptide as well as the presence of LPS and bacteria. Finally, using neutron reflectometry, we show that the observed differences between HVF18 and the other 2 TCPs may be explained partially by differences in membrane insertion. Taken together, we show that TCPs are differentially internalized into monocytes and macrophages.
Exosome miR-23a-3p from Osteoblast Alleviates Spinal Cord Ischemia/Reperfusion Injury by Down-Regulating KLF3-Activated CCNL2 Transcription
Authors: Wu Cheng , Zhu Qinghua , Yao Yi , Shi Zhaoyang , Jin Chaojie , Chen Leilei
Published: December 2021

Background: Spinal cord ischemia/reperfusion injury (SCIRI) is usually caused by spinal surgery or aortic aneurysm surgery and can eventually lead to paralysis or paraplegia and neurological dysfunction. Exosomes are considered as one of the most promising therapeutic strategies for SCIRI as they can pass the blood-spinal barrier. Previous studies have proved that exosomes secreted by osteocytes have a certain slowing effect on SCIRI. Aim: We aimed to explore the effect of osteoblast secreted exosomes on SCIRI. Methods: First, neurons and osteoblasts were co-cultured under different conditions. GEO database was utilized to detect the expression of miR-23a-3p in osteoblast exosomes. SCIRI cells were treated with exosomes, and the detection was taken to prove whether miR-23a-3p could slow the progression of SCIRI. Downstream gene and the potential regulatory mechanism were explored through database and functional experiments. Results: MiR-23a-3p was highly expressed in exosomes and it slowed down the process of SCIRI. Downstream mRNA KLF3 could bind to miR-23a-3p and was highly expressed in IRI. Moreover, CCNL2 was regulated by KLF3 and was highly expressed in IRI. Rescue experiments verified that miR-23a-3p suppressed the transcription of CCNL2 by targeting KLF3. Conclusion: Exosome miR-23a-3p from osteoblast alleviates SCIRI by down-regulating KLF3-activated CCNL2 transcription.
The Effect of Various Fluoride Products on Dentine Lesions during pH-Cycling
Authors: Alhothali Marwa M. , Exterkate Rob A.M. , Lagerweij Maxim D. , van Strijp A.J.P. , Buijs Mark J. , van Loveren Cor
Published: December 2021

This study compared the effect of topically applied fluoride products on dentine lesions in an in vitro experiment. Demineralized bovine dentine specimens were treated once with either SDF solution (35,400 ppm F), NaF varnish (22,600 ppm F), TiF4 solution (9,200 ppm F), SnF2 gel (1,000 ppm F), no treatment (control), or preserved as baseline lesions. After the application and subsequent removal of the fluoride products, the specimens were subjected to pH-cycling. Calcium loss and uptake in the de- and remineralization buffers were assessed daily. Fluoride release into the buffers was analyzed on days 1, 2, 3, 5, 8, and 13. After the pH-cycling period, mineral distribution throughout the lesion depth was analyzed using transversal microradiography (TMR). X-ray energy-dispersive spectroscopy (EDS) examined the deposition of silver, titanium, and tin after application of SDF, TiF4, and SnF2, respectively. Overall, calcium loss and uptake analysis in the de- and remineralization buffers revealed that the SDF product was the most effective in inhibiting lesion progression, followed by the TiF4, NaF, and SnF2 products. Fluoride analysis disclosed a steep reduction of the amount of fluoride released into de- and remineralization buffers with time. The fluoride effects on de- and remineralization continued beyond the days that fluoride was released into the buffers. TMR analysis showed significant remineralization in the outer zone of the dentine lesions for all fluoride products, with SDF giving hypermineralization in this zone. In the inner zone, lesions developed in all fluoride groups, with the smallest in the SDF group. EDS showed silver and titanium deposition in depth up to 85 μm and 8 μm, respectively, while no tin deposition was observed. The silver in the dentine lesions did not contribute significantly to the density of the TMR profiles in the SDF group. In conclusion, all topical fluoride products protected the dentine lesions against lesion progression, but at different degrees. SDF showed a superior effect in protection against further demineralization and enhancement of remineralization. This was probably attributed to its fluoride concentration that was the highest among the fluoride products.
Crosslinked Layered Surfaces of Heparin and Poly(L-Lysine) Enhance Mesenchymal Stromal Cell Behavior in the Presence of Soluble Interferon Gamma
Authors: Haseli Mahsa , Pinzon-Herrera Luis , Almodovar Jorge
Published: December 2021

Human mesenchymal stromal cells (hMSCs) are multipotent cells that have been proposed for the treatment of immune-mediated diseases. Culturing hMSCs on tissue culture plastic reduces their therapeutic potential in part due to the lack of extracellular matrix components. The aim of this study is to evaluate multilayers of heparin and poly(L-lysine) (HEP/PLL) as a bioactive surface for hMSCs stimulated with soluble interferon gamma (IFN-γ). Multilayers were formed, via layer-by-layer assembly, with HEP as the final layer and supplemented with IFN-γ in the culture medium. Multilayer construction and chemistry were confirmed using Azure A staining, quartz crystal microbalance, and X-ray photoelectron spectroscopy. hMSCs adhesion, viability, and differentiation, were assessed. Results showed that (HEP/PLL) multilayer coatings were poorly adhesive for hMSCs. However, performing chemical crosslinking using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide significantly enhanced hMSCs adhesion and viability. The immunosuppressive properties of hMSCs cultured on crosslinked (HEP/PLL) multilayers were confirmed by measuring indoleamine 2,3-dioxygenase activity. Lastly, hMSCs cultured on crosslinked (HEP/PLL) multilayers in the presence of soluble IFN- γ successfully differentiated towards the osteogenic and adipogenic lineages as confirmed by Alizarin red, and oil-red O staining, as well as alkaline phosphatase activity. This study suggests that crosslinked (HEP/PLL) films can modulate hMSCs response to soluble factors, which may improve hMSCs-based therapies aimed at treating several immune diseases.
Report of Dirofilaria immitis infection with acute cardiopulmonary complications in a cat from Northeastern Brazil
Authors: Moraes Marcela Figuerêdo Duarte , Pollo Andressa de Souza , Marques Kayana Cunha , Góis Rayr César de Souza , Ferreira Mirlla Baracho , Silva Alessandra Moreira da , Lucena Rivaldo Bruno Medeiros de , Batista Jael Soares , Filgueira Kilder , Sellera Fábio Parra , Reche-Júnior Archivaldo , Hoppe Estevam Guilherme Lux
Published: December 2021

Dirofilariasis is a zoonotic disease caused by Dirofilaria immitis, a nematode found mainly in the pulmonary artery and right chambers of the heart, lungs, and large vessels of dogs. This parasitism also occasionally occurs in cats, causing an amicrofilaremic and asymptomatic infection, resulting in severe illness and rapid death. In this case report, it was described acute clinical signs and histopathological alterations in a domestic cat with heartworm disease from the city of Mossoró, the Rio Grande do Norte, Brazil. The nematode species, D. immitis, was confirmed by morphological and molecular analyses. This is the first documented and full report of feline heartworm disease in northeastern Brazil.
Association Between Age and Outcomes of Catheter Ablation Versus Medical Therapy for Atrial Fibrillation: Results From the CABANA Trial
Authors: Bahnson Tristram D. , Giczewska Anna , Mark Daniel B. , Russo Andrea M. , Monahan Kristi H. , Al-Khalidi Hussein R. , Silverstein Adam P. , Poole Jeanne E. , Lee Kerry L. , Packer Douglas L. ,   for the CABANA Investigators
Published: December 2021

Background:

Observational data suggest that catheter ablation may be safe and effective to treat younger and older patients with atrial fibrillation. No large, randomized trial has examined this issue. This report describes outcomes according to age at entry in the CABANA trial (Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation).

Methods:

Patients with atrial fibrillation ≥65 years of age, or <65 with ≥1 risk factor for stroke, were randomly assigned to catheter ablation versus drug therapy. The primary outcome was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Secondary outcomes included all-cause mortality, the composite of mortality or cardiovascular hospitalization, and recurrence of atrial fibrillation. Treatment effect estimates were adjusted for baseline covariables using proportional hazards regression models.

Results:

Of 2204 patients randomly assigned in CABANA, 766 (34.8%) were <65 years of age, 1130 (51.3%) were 65 to 74 years of age, and 308 (14.0%) were ≥75 years of age. Catheter ablation was associated with a 43% reduction in the primary outcome for patients <65 years of age (adjusted hazard ratio [aHR], 0.57 [95% CI, 0.30–1.09]), a 21% reduction for 65 to 74 years of age (aHR, 0.79 [95% CI, 0.54–1.16]), and an indeterminate effect for age ≥75 years of age (aHR, 1.39 [95% CI, 0.75–2.58]). Four-year event rates for ablation versus drug therapy across age groups, respectively, were 3.2% versus 7.8%, 7.8% versus 9.6%, and 14.8% versus 9.0%. For every 10-year increase in age, the primary outcome aHR increased (ie, less favorable to ablation) an average of 27% (interaction
P
value=0.215). A similar pattern was seen with all-cause mortality: for every 10-year increase in age, the aHR increased an average of 46% (interaction
P
value=0.111). Atrial fibrillation recurrence rates were lower with ablation than with drug therapy across age subgroups (aHR 0.47, 0.58, and 0.49, respectively). Treatment-related complications were infrequent for both arms (<3%) regardless of age.

Conclusions:

We found age-based variations in clinical outcomes for catheter ablation compared with drug therapy, with the largest relative and absolute benefits of catheter ablation in younger patients. No prognostic benefits for ablation were seen in the oldest patients. No differences were found by age in treatment-related complications or in the relative effectiveness of catheter ablation in preventing recurrent atrial arrhythmias.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT00911508.
Impact of a Patient’s Baseline Risk on the Relative Benefit and Harm of a Preventive Treatment Strategy: Applying Trial Results in Clinical Decision Making
Authors: de Vries Tamar I. , Stam‐Slob Manon C. , Peters Ron J. G. , van der Graaf Yolanda , Westerink Jan , Visseren Frank L. J.
Published: December 2021

Background

For translating an overall trial result into an individual patient’s expected absolute treatment effect, differences in relative treatment effect between patients need to be taken into account. The aim of this study was to evaluate whether relative treatment effects of medication in 2 large contemporary trials are influenced by multivariable baseline risk of an individual patient.

Methods and Results

In 9361 patients from SPRINT (Systolic Blood Pressure Intervention Trial), risk of major adverse cardiovascular events was assessed using a newly derived risk model. In 18 133 patients from the RE‐LY (Randomized Evaluation of Long‐Term Anticoagulant Therapy) trial, risk of stroke or systemic embolism and major bleeding was assessed using the Global Anticoagulant Registry in the Field–Atrial Fibrillation risk model. Heterogeneity of trial treatment effect was assessed using Cox models of trial allocation, model linear predictor, and their interaction. There was no significant interaction between baseline risk and relative treatment effect from intensive blood pressure lowering in SPRINT (
P
=0.92) or from dabigatran compared with warfarin for stroke or systemic embolism in the RE‐LY trial (
P
=0.71). There was significant interaction between baseline risk and treatment effect from dabigatran versus warfarin in the RE‐LY trial (
P
<0.001) for major bleeding. Quartile‐specific hazard ratios for bleeding ranged from 0.40 (95% CI, 0.26–0.61) to 1.04 (95% CI, 0.83–1.03) for dabigatran, 110 mg, and from 0.61 (95% CI, 0.42–0.88) to 1.20 (95% CI, 0.97–1.50) for dabigatran, 150 mg, compared with warfarin.

Conclusions

Effect modification of relative treatment effect by individual baseline event risk should be assessed systematically in randomized clinical trials using multivariate risk prediction, not only in terms of treatment efficacy but also for important treatment harms, as a prespecified analysis.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01206062.
Registry for Acute Coronary Events in Nigeria (RACE‐Nigeria): Clinical Characterization, Management, and Outcome
Authors: Isezuo Simeon , Sani Mahmoud Umar , Talle Abdullahi , Johnson Adeyemi , Adeoye Abiodun‐Moshood , Ulgen Mehmet S. , Mbakwem Amam , Ogah Okechukwu , Edafe Emmanuel , Kolo Philip , Nagabea Murtala , Adebayo Rasaaq , Nwafor Eze , Daniel Folasade , Zagga Muiyawa , Umar Hayatu , Oboirien Isa , Sulaiman Balarabe A. , Abdullahi Umar , Mijinyawa Muhammad Sani , Buba Farouk , Aje Akinyemi , Okolie Henry , Shehu Muhammad Nazir , Adamu Umar , Olusegun‐Joseph Akinsanya , Familoni Ranti , Chibuzor Nwuriku , Olunuga Taiwo Olabisi , Ejim Emmanuel , Rasheed Olaide Awodun , Ojji Dike , Sanni Bushra , Ajuluchukwu Jane N. , Balogun Michael O. , Omotoso Ayodele B. , Ajit Mullasari , Falase Ayodele O. ,   RACE‐Nigeria Registry Investigators
Published: December 2021

Background

Coronary artery disease was hitherto a rarity in Africa. Acute coronary syndrome (ACS) accounts for coronary artery disease–related morbidity and mortality. Reports on ACS in Africa are few.

Methods and Results

We enrolled 1072 indigenous Nigerian people 59.2±12.4 years old (men, 66.8%) with ACS in an observational multicentered national registry (2013–2018). Outcome measures included incidence, intervention times, reperfusion rates, and 1‐year mortality. The incidence of ACS was 59.1 people per 100 000 hospitalized adults per year, and comprised ST‐segment–elevation myocardial infarction (48.7%), non–ST‐segment–elevation myocardial infarction (24.5%), and unstable angina (26.8%). ACS frequency peaked 10 years earlier in men than women. Patients were predominantly from urban settings (87.3%). Median time from onset of symptoms to first medical contact (patients with ST‐segment–elevation myocardial infarction) was 6 hours (interquartile range, 20.1 hours), and only 11.9% presented within a 12‐hour time window. Traditional risk factors of coronary artery disease were observed. The coronary angiography rate was 42.4%. Reperfusion therapies included thrombolysis (17.1%), percutaneous coronary intervention (28.6%), and coronary artery bypass graft (11.2%). Guideline‐based pharmacotherapy was adequate. Major adverse cardiac events were 30.8%, and in‐hospital mortality was 8.1%. Mortality rates at 30 days, 3 months, 6 months, and 1 year were 8.7%, 9.9%, 10.9%, and 13.3%, respectively. Predictors of mortality included resuscitated cardiac arrest (odds ratio [OR], 50.0; 95% CI, 0.010–0.081), nonreperfusion (OR, 34.5; 95% CI, 0.004–0.221), pulmonary edema (OR, 11.1; 95% CI, 0.020–0.363), left ventricular diastolic dysfunction (OR, 4.1; 95% CI, 0.091–0.570), and left ventricular systolic dysfunction (OR, 2.1; 95% CI, 1.302–3.367).

Conclusions

ACS burden is rising in Nigeria, and patients are relatively young and from an urban setting. The system of care is evolving and is characterized by lack of capacity and low patient eligibility for reperfusion. We recommend preventive strategies and health care infrastructure‐appropriate management guidelines.
Validation of Specific and Reliable Genetic Tools to Identify, Label, and Target Cardiac Pericytes in Mice
Authors: Alex Linda , Tuleta Izabela , Harikrishnan Venugopal , Frangogiannis Nikolaos G.
Published: December 2021

Background

In the myocardium, pericytes are often confused with other interstitial cell types, such as fibroblasts. The lack of well‐characterized and specific tools for identification, lineage tracing, and conditional targeting of myocardial pericytes has hampered studies on their role in heart disease. In the current study, we characterize and validate specific and reliable strategies for labeling and targeting of cardiac pericytes.

Methods and Results

Using the neuron‐glial antigen 2 (NG2)
DsRed
reporter line, we identified a large population of NG2+ periendothelial cells in mouse atria, ventricles, and valves. To examine possible overlap of NG2+ mural cells with fibroblasts, we generated NG2
DsRed
; platelet‐derived growth factor receptor (PDGFR) α
EGFP
pericyte/fibroblast dual reporter mice. Myocardial NG2+ pericytes and PDGFRα+ fibroblasts were identified as nonoverlapping cellular populations with distinct transcriptional signatures. PDGFRα+ fibroblasts expressed high levels of fibrillar collagens, matrix metalloproteinases, tissue inhibitor of metalloproteinases, and genes encoding matricellular proteins, whereas NG2+ pericytes expressed high levels of
Pdgfrb
,
Adamts1
, and
Vtn
. To validate the specificity of pericyte Cre drivers, we crossed these lines with PDGFRα
EGFP
fibroblast reporter mice. The constitutive NG2
Cre
driver did not specifically track mural cells, labeling many cardiomyocytes. However, the inducible NG2
CreER
driver specifically traced vascular mural cells in the ventricle and in the aorta, without significant labeling of PDGFRα+ fibroblasts. In contrast, the inducible PDGFRβ
CreER
line labeled not only mural cells but also the majority of cardiac and aortic fibroblasts.

Conclusions

Fibroblasts and pericytes are topographically and transcriptomically distinct populations of cardiac interstitial cells. The inducible NG2
CreER
driver optimally targets cardiac pericytes; in contrast, the inducible PDGFRβ
CreER
line lacks specificity.
Differences Between Anticoagulated Patients With Ischemic Stroke Versus Intracerebral Hemorrhage
Authors: Schaub Fabian , Polymeris Alexandros A. , Schaedelin Sabine , Hert Lisa , Meya Louisa , Thilemann Sebastian , Traenka Christopher , Wagner Benjamin , Seiffge David , Gensicke Henrik , De Marchis Gian Marco , Bonati Leo , Engelter Stefan T. , Peters Nils , Lyrer Philippe
Published: December 2021

Background

Data on the relative contribution of clinical and neuroimaging risk factors to acute ischemic stroke (AIS) versus intracerebral hemorrhage (ICH) occurring on oral anticoagulant treatment are scarce.

Methods and Results

Cross‐sectional study was done on consecutive oral anticoagulant–treated patients presenting with AIS, transient ischemic attack (TIA), or ICH from the prospective observational NOACISP (Novel‐Oral‐Anticoagulants‐In‐Stroke‐Patients)‐Acute registry. We compared clinical and neuroimaging characteristics (small vessel disease markers and atherosclerosis) in ICH versus AIS/TIA (reference) using logistic regression. Among 734 patients presenting with stroke on oral anticoagulant treatment (404 [55%] direct oral anticoagulants, 330 [45%] vitamin K antagonists), 605 patients (82%) had AIS/TIA and 129 (18%) had ICH. Prior AIS/TIA, coronary artery disease, dyslipidemia, and worse renal function were associated with AIS/TIA (adjusted odds ratio [aOR] [95% CI] 0.51 [0.32–0.82], 0.48 [0.26–0.86], 0.55 [0.34–0.89], and 0.82 [0.75–0.90] per 10 mL/min). Prior ICH, older age, higher admission blood pressure, and statin treatment were associated with ICH (aOR [95% CI] 6.33 [2.87–14.04], 1.37 [1.04–1.81] per 10 years, 1.19 [1.10–1.29] per 10 mm Hg, and 1.81 [1.09–3.03]). Cerebral microbleeds and moderate‐to‐severe white matter hyperintensities contributed more to ICH (aOR [95% CI] 2.77 [1.34–6.18], and 2.62 [1.28–5.63]). Aortic arch, common and internal carotid artery atherosclerosis, and internal carotid artery stenosis ≥50% contributed more to AIS/TIA (aOR [95% CI] 0.54 [0.31–0.90], 0.29 [0.05–0.97], 0.48 [0.30–0.76], and 0.32 [0.13–0.67]).

Conclusions

In patients presenting with stroke on oral anticoagulant, AIS/TIA was 5 times more common than ICH. A high atherosclerotic burden (indicated by cardiovascular comorbidities and extracranial atherosclerosis) and prior AIS/TIA contributed more to AIS/TIA, while small vessel disease markers and prior ICH were stronger determinants for ICH.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02353585.
Abstract 1122‐000005: Plasminogen Activator Inhibitor‐1 5G/5G Polymorphism – Do We Know All About It?
Authors: Karim Nurose , Johnson Mark
Published: December 2021

Introduction
: The etiology of ischemic stroke is heterogeneous, and it has been proposed that different stroke subtypes might have different genetic architecture 1,2. The plasminogen activator inhibitor‐1 (PAI‐1) has been of particular interest due to its role in thrombotic diseases. Several polymorphisms have been found for this gene, with some having protective effect while others increase the risk of ischemic and hemorrhagic strokes 3,4. The protective role appears to be due to the role of PAI‐1 in fibrinolytic cascade and that PAI‐1 also inhibit plasmin‐dependent metalloproteinases activation. We hereby, present a case of ischemic stroke in young adult and its association with our gene of interest.

Methods
: Case: We present a case of 43‐year‐old woman with past medical history significant for Acetylcholine Receptor (AChR) antibody positive Myasthenia Gravis diagnosed in 1993 status post thymectomy (1994), currently on prednisone and intravenous immunoglobulin every two weeks (failed cyclosporine and mycophenolate mofetil). She had two events in 2018 where she reported episodic right sided numbness and weakness that lasted for few hours. Stroke workup was done, and she was found to have focal moderate to severe stenosis of the left middle cerebral artery (MCA) on CT angiography (figure 1) with very subtle left hypoperfusion in the MCA on the brain single‐photon emission computerized tomography scan. She underwent catheter angiogram (figure 1) showing severe stenosis involving the mid and distal M1 segment of the left MCA and nondominant proximal A1 segment left anterior cerebral artery (ACA). There were robust leptomeningeal collaterals from the left anterior and left posterior cerebral arteries. She also reported history of two miscarriages in the first trimester. Hypercoagulable workup was done and all of those were negative including: SLE profile, Lupus anticoagulant, ANA comprehensive panel, Cryoglobulin, Anticardiolipin antibody, Antithrombin III, Antithrombin antigen, protein C, protein S, Factor VIII activity, Factor V Leiden. She also had rheumatoid arthritis factor, Homocysteine, sedimentation rate, and C‐reactive protein done which were unremarkable. Genetic workup showed that she is PAI‐1 5G/5G homozygous. She has been stable since 2018 without new focal neurological events and is on Aspirin monotherapy and Statin.

Results
: The genetics for stroke disease are very complicated and yet to be discovered fully. The association between PA‐1 5G/5G and intracranial stenosis has not been reported previously. New genetic associations will need to be increasingly considered as we assess our cerebrovascular diseases and stroke patients

Conclusions
: • With the current knowledge, ischemic stroke have polygenic basis but no single common “stroke gene” has been identified yet.

• Here we present a case suggesting that PAI‐1 5G/5G genotype is may be associated with an independent risk of intracranial atherosclerosis.
Abstract 1122‐000008: Neurological Patterns in Covid ‐19 – A Hospital Based Study
Authors: Ahmad Saima
Published: December 2021

Introduction
: COVID‐19 infection can show various manifestations, including neurologic manifestations, such as meningoencephalitis, cerebral vascular thrombosis, transverse myelitis, ischemic and hemorrhagic stroke, Guillain‐Barre syndrome, posterior reversible encephalopathy syndrome, reversible cerebral vasoconstriction syndrome, and many more. The study aims to briefly touch upon and identify the neurologic manifestations in the COVID‐19 infection in Pakistan during its third wave of SARS –Cov ‐2 (Kent or alpha) variant strain.

Methods
: We conducted a prospective study of all patients diagnosed with SARS‐CoV‐2 infection either by RT‐PCR or by COVID Index at our institution, from the beginning of the third wave from March 2021 to June 2021. A total of 2,808 patients with Covid were identified at our institution, 26 of whom were diagnosed with neurological diseases.

Results
: A total of 26 cases of COVID ‐19 manifested with neurological diseases. The patients were of all ages ranging from 18 years to 84 years. There were 17 males in the study. hemorrhage. Five patients had Subarachnoid hemorrhaging. Four patients presented with post‐COVID ‐19 mucormycotic. Sixteen cases reported confirmed COVID‐19, confirmation by positive swab test using the real‐time RT‐PCR method, neurological disorder, or syndrome on presentation or found during the hospital stay. The rest were diagnosed based on COVID Index; all markers were raised with COVID ‐19 symptoms. In seventeen cases, the patients recovered fully, while the others all expired.

Conclusions
: It is not commonly known, but COVID‐19 also affects the brain, resulting in a global and focal neurologic manifestation. Currently, it is difficult to distinguish whether the neurological complications of COVID‐19 are a consequence of direct or indirect effects of viral infections—therefore, emphasis on finding the concomitant cause of neurological infection in COVID ‐19. Further, healthcare providers treating a patient with a COVID‐19 infection should also be aware of neurologic manifestation associated with a COVID‐19 infection to improve patient outcomes.
Abstract 1122‐000013: Spinal Dural Arterio‐Venous Fistula: A Masquerade as a Longitudinal Myelitis
Authors: Saund Amardeep , Mawed Saleem Al , Subei Adnan , Mehta Brijesh
Published: December 2021

Introduction
: SDAVF are rare and frequently misdiagnosed due to their nonspecific symptomatology and delay of presentation on imaging. Spinal digital subtraction angiogram is the gold standard diagnostic test. Delayed diagnosis and treatment of SDAVF can lead to irreversible neurologic damage.

Methods
: None

Results
: Two female patients, 69 and 74 years old, each developed recurrent episodes of subacute worsening myelopathy and urinary retention. The subacute onset of symptoms and longitudinal appearance on cord imaging raised concern for inflammatory myelitis. Despite a negative CSF analysis, and the absence of serum inflammatory, metabolic and infectious markers, the working diagnosis was seronegative neuromyelitis optica spectrum disorder. In accordance, both patients were treated with plasma exchange and IV rituximab, initially displaying stabilization on imaging. However, further worsening and extension of the myelopathy alongside the presence of flow voids in one patient’s repeat MRI nine months post‐presentation raised the question of an alternate etiology. A spinal angiogram was ordered for the patient, revealing SDAVF. Subsequently, the patient underwent complete Onyx embolization of the right L2 feeder and surgical clipping of the right L1 feeder. This resulted in stabilization and improvement of symptoms. Although the second patient did not display flow voids in their MRI, they were ordered a spinal angiogram due to their similar clinical course, indeed confirming SDAVF. The patient underwent successful complete embolization of the L3 segmental artery on the right resulting in improvement of symptoms.

Conclusions
: Clinicians should have a high index of suspicion for SDAVF when a patient presents with a longitudinally extensive transverse myelitis negative for inflammatory markers and is unresponsive to treatment. While the appearance of flow voids on imaging is a helpful diagnostic feature, these may not be present in patients.