bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinear Structural Fusion for Multiplex Network
Authors: Ning Nianwen , Long Feiyu , Wang Chunchun , Zhang Youjie , Yang Yilin , Wu Bin
Published: July 2020

Many real-world complex systems have multiple types of relations between their components, and they are popularly modeled as multiplex networks with each type of relation as one layer. Since the fusion analysis of multiplex networks can provide a comprehensive insight, the structural information fusion of multiplex networks has become a crucial issue. However, most of these existing data fusion methods are inappropriate for researchers to apply to complex network analysis directly. The feature-based fusion methods ignore the sharing and complementarity of interlayer structural information. To tackle this problem, we propose a multiplex network structural fusion (MNSF) model, which can construct a network with comprehensive information. It is composed of two modules: the network feature extraction (NFE) module and the network structural fusion (NSF) module. (1) In NFE, MNSF first extracts a low-dimensional vector representation of a node from each layer. Then, we construct a node similarity network based on embedding matrices and K-D tree algorithm. (2) In NSF, we present a nonlinear enhanced iterative fusion (EIF) strategy. EIF can strengthen high-weight edges presented in one (i.e., complementary information) or more (i.e., shared information) networks and weaken low-weight edges (i.e., redundant information). The retention of low-weight edges shared by all layers depends on the tightness of connections of their K-order proximity. The usage of higher-order proximity in EIF alleviates the dependence on the quality of node embedding. Besides, the fused network can be easily exploited by traditional single-layer network analysis methods. Experiments on real-world networks demonstrate that MNSF outperforms the state-of-the-art methods in tasks link prediction and shared community detection.
Magnetic Colloidal Particles in Combinatorial Thin-Film Gradients for Magnetic Resonance Imaging and Hyperthermia
Authors: Khizar Sumera , Ahmad Nasir Mahmood , Saleem Hassan , Hamayun Muhammad Asif , Manzoor Sadia , Lebaz Noureddine , Elaissari Abdelhamid
Published: July 2020

A stable oil-in-water (O/W) magnetic emulsion was prepared by the emulsification of organic ferrofluid in an aqueous media, and its theranostic applications were investigated. The synthesis and characterization of the organic ferrofluid were carried out comprising of superparamagnetic maghemite nanoparticles with oleic acid coating stabilized in octane. Both exhibit spherical morphology with a mean size of 6 nm and 200 nm, respectively, as determined by TEM. Thermogravimetric analysis was carried out to determine the chemical composition of the emulsion. The research work described here is novel and elaborates the fabrication of thin-film gradients with 5, 10, 15, and 20 bilayers by layer-by-layer technique using polydimethyl diallyl ammonium chloride (PDAC) and prepared magnetic colloidal particles. The thin-film gradients were characterized for their roughness, morphology, and wettability. The developed gradient films and colloids were explored in magnetic resonance imaging (MRI) and hyperthermia. T1- and T2-weighted images and their corresponding signal intensities were obtained at 1.5 T. A decreasing trend in signal intensities with an increase in nanoparticle concentration in colloids and along the gradient was observed in T2-weighted images. The hyperthermia capability was also evaluated by measuring temperature rise and calculating specific absorption rates (SAR). The SAR of the colloids at 259 kHz, 327 kHz, and 518 kHz were found to be 156 W/g, 255 W/g, and 336 W/g, respectively. The developed magnetic combinatorial thin-film gradients present a significant potential for the future efficient simultaneous diagnostic and therapeutic bioapplications.
A Neural Network Based Intelligent Support Model for Program Code Completion
Authors: Rahman Md. Mostafizer , Watanobe Yutaka , Nakamura Keita
Published: July 2020

In recent years, millions of source codes are generated in different languages on a daily basis all over the world. A deep neural network-based intelligent support model for source code completion would be a great advantage in software engineering and programming education fields. Vast numbers of syntax, logical, and other critical errors that cannot be detected by normal compilers continue to exist in source codes, and the development of an intelligent evaluation methodology that does not rely on manual compilation has become essential. Even experienced programmers often find it necessary to analyze an entire program in order to find a single error and are thus being forced to waste valuable time debugging their source codes. With this point in mind, we proposed an intelligent model that is based on long short-term memory (LSTM) and combined it with an attention mechanism for source code completion. Thus, the proposed model can detect source code errors with locations and then predict the correct words. In addition, the proposed model can classify the source codes as to whether they are erroneous or not. We trained our proposed model using the source code and then evaluated the performance. All of the data used in our experiments were extracted from Aizu Online Judge (AOJ) system. The experimental results obtained show that the accuracy in terms of error detection and prediction of our proposed model approximately is 62% and source code classification accuracy is approximately 96% which outperformed a standard LSTM and other state-of-the-art models. Moreover, in comparison to state-of-the-art models, our proposed model achieved an interesting level of success in terms of error detection, prediction, and classification when applied to long source code sequences. Overall, these experimental results indicate the usefulness of our proposed model in software engineering and programming education arena.
STW1 and Its Versatile Pharmacological and Clinical Effects in Rheumatic Disorders: A Comprehensive Report
Authors: Gundermann Karl-Josef , Müller Jürgen , Kraft Karin
Published: July 2020

Aim. To review the published and unpublished experimental and clinical studies about the efficacy and tolerability of STW1 and to compare the results to the efficacy and tolerability of investigated NSAIDs in parallel. Content. STW1 (Phytodolor®) contains a fixed combination of extracts from aspen leaves and bark (Populus tremula), common ash bark (Fraxinus excelsior), and goldenrod herb (Solidago virgaurea). It belongs to the group of anti‐inflammatory and antirheumatic drugs, and it is authorized for the treatment of painful disorders of degenerative and inflammatory rheumatic diseases. The individual components have complementary effects. Its multifocal mode of action includes antiphlogistic, analgesic, antiexudative, antioxidative, antipyretic, and antiproliferative properties. The effects of both STW1 and its components have been verified in comprehensive pharmacological investigations. Open and randomized, placebo‐ and verum‐controlled, and single‐blind (sb) or double‐blind (db) clinical trials, performed in different subtypes of rheumatic diseases confirm the pharmacological evidence. Its efficacy is comparable to a range of standard nonsteroidal anti‐inflammatory drugs (NSAIDs) studied in parallel, but it has a superior safety profile. Conclusion. STW1 is a reasonable alternative to NSAIDs with comparable efficacy and a superior safety profile. It is also suitable to reduce the intake of NSAIDs.
Comparison of In Vitro Antibacterial Activity of Epaltes divaricata and Vetiveria zizanioides against Methicillin-Resistant Staphylococcus aureus
Authors: Rathnayake Hasanga , De Zoysa Manikkuwadura Hasara Nethmini , Hewawasam Ruwani Punyakanthi , Gaya Bandara Wijayaratne Weerasinghe Mudiyanselage Dilip
Published: July 2020

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital- and community-acquired infections worldwide. Therefore, this study was conducted to explore the antibacterial activity of the two medicinal plants Epaltes divaricata and Vetiveria zizanioides against strains of MRSA which were isolated from patients with skin and soft tissue infections. Hexane, ethanol, and water extracts of E. divaricata (whole plant) and V. zizanioides (roots) were prepared. Clinical isolates of MRSA strains (n = 20) were used for the study. Bacterial susceptibility was tested using a disc diffusion assay. Minimum inhibitory concentration (MIC) was determined by a broth microdilution method. Vancomycin was used as the positive control. Hexane, ethanol, and water extracts of E. divaricata showed inhibitory zones against MRSA. Except for water extract, both hexane and ethanol extracts of V. zizanioides showed inhibitory zones. MIC ranges of hexane, ethanol, and water extracts in E. divaricata were 0.012–0.32 mg/mL, 0.019–2.4 mg/mL, and 0.019–0.48 mg/mL, respectively. Respective MIC ranges of hexane and ethanol extracts of V. zizanioides were 0.003–0.032 mg/mL and 0.019–2.4 mg/mL. The hexane extract of V. zizanioides inhibited 55% of the selected MRSA strains at a relatively low MIC value of 0.012 mg/mL. The hexane extract of both plants demonstrated inhibition of 75% of MRSA strains at a MIC value of 0.064 mg/mL. Ethanol extract of V. zizanioides and E. divaricata, respectively, inhibited 70% and 45% of MRSA strains at the MIC of 0.096 mg/mL, whereas water extract of E. divaricata inhibited 80% of MRSA strains at the same MIC. Both E. divaricata and V. zizanioides were equally effective against MRSA at a MIC of 0.064 mg/mL. But V. zizanioides was more effective since the hexane extract inhibited more than 50% of MRSA strains at significantly a lower MIC value of 0.012 mg/mL. Fractionation, purification, and identification of active compounds will warrant further evaluation of the therapeutic potential of both plant extracts.
Patterns and Prevalence of Germline BRCA1 and BRCA2 Mutations among High-Risk Breast Cancer Patients in Jordan: A Study of 500 Patients
Authors: Abdel-Razeq Hikmat , Abujamous Lama , Jadaan Dima
Published: July 2020

Purpose. Knowledge of BRCA1 and BRCA2 mutations has a significant clinical impact on the management and prevention of breast cancer. In this study, we evaluate the pattern and prevalence of germline mutations in BRCA1 and BRCA2 among high-risk Jordanian breast cancer patients selected as per international guidelines. Methods. BRCA1 and BRCA2 testing were performed at a reference genetic lab. Mutations were classified as pathogenic/likely pathogenic and variant of uncertain significance (VUS). Results. A total of 517 patients, median age: 39 (range: 19–78) years, were enrolled. Among the whole group, 72 (13.9%) patients had pathogenic or likely pathogenic BRCA1 (n = 24, 4.6%) or BRCA2 (n = 48, 9.3%) mutations, while 53 (10.3%) others had VUS. Among 333 younger (≤40 years) patients, mutations were observed in 44 (13.2%). Positive mutations were found in 40 (16.5%) patients with one or more close relatives with breast cancer and in 20 (35.1%) of the 57 patients with triple-negative disease. Multivariate analysis showed that a triple-negative status, history of two or more close relatives with breast cancer, and history of one or more close relatives with invasive ovarian cancer were associated with significant high odds ratios (OR) of carrying a pathogenic variant, with an OR (95% CI) of 5.08 (2.66–9.67), 3.24 (1.78–5.89), and 2.97 (1.04–8.52), respectively. Conclusions. BRCA1 and BRCA2 mutations are not uncommon among Jordanian patients. Young age has the weakest association with positive mutations, while patients with triple-negative disease, especially those with an additional positive family history, have the highest mutation rate.
Minor Squirt in Unconsolidated Sands versus Strong Squirt in Compressed Glass Beads
Authors: Li Guangquan , Wang Yuchao , Li Xiang
Published: July 2020

Squirt driven by local pressure imbalance between contact of grains (or throat) and the main pore space is a mechanism of P-wave attenuation in consolidated rocks. In this paper, we investigate squirt in unconsolidated and consolidated porous media (represented by Toyoura sands and compressed glass beads, respectively). The former sample has very small bulk modulus and shear modulus, manifested by relatively free/mobile grains. As such, solid stress on the surface tends to be uniform and squirt should be minor. Biot’s theory improved with dynamic permeability successfully predicts the ultrasonic velocity and quality factor of P wave measured in the unconsolidated sands, confirming the aforementioned judgment. Dynamic permeability inverted at a high frequency is far lower than Darcy permeability. However, the improved model remains to be incapable of predicting velocity and attenuation measured in the latter sample; the reason is that the compressed beads allows a high pressure at compliant throat which drives strong squirt between throat and the main pore space.
Reviews and Thoughts on the Relevance between Qualitative Chinese Medicinal Properties and Quantitative Material Components
Authors: Hou Zheng-Kun , Hu Wen , Liu Feng-bin , Liang Ying-yu , Huang Zhong-yu , Huang Zhi-bang
Published: July 2020

Objective. Chinese Medicinal Properties (CMP) play a vital role in theoretical research and clinical practice. However, the traditional CMP system is subjective, qualitative, fixed, inconsistent, and obscured. Nowadays, quantifying CMP research achieved a notable progress. This study aims to review and reflect the relevance between qualitative CMP and quantitative material components. Methods. A raw literature search was performed firstly in CNKI and Pubmed database to get a rough idea on the general advances in measuring CMP. Then, a strict literature search and data extraction from two dependent research studies were performed to analyze the relevance and discrimination between CMP and material components. Results. The quantitative CMP research mainly focused on the microelements and chemical compositions. The largest microelements research listed 747 Chinese Materia Medica (CMM) (6780 flavors) and 120,000 element data. The measurement of chemical composition of CMM has risen rapidly in the 1990s and continues till the present. Thirty‐seven articles were finally identified for the relevance analysis of CMP and material components. Of these, 18 and 19 articles correspondingly focused on the chemical compositions and microelements, and 26 and 11 articles correspondingly focused on their correlation and discrimination relationship. The most commonly used method for correlation analysis is intuitive analysis. The support vector machine maybe highly efficient and would act as the preferred method in discriminant analysis. Twelve (67%) and 5 (26%) articles’ data came from the literature search in chemical compositions and microelement research studies. Four studies indicated that the research objects are the basic substances and material basis of CMP, 15 articles claimed that the chemical compositions were significantly related to CMP, 12 research studies concluded that the regularity and causality were identified between the research objects and CMP, and 9 research studies successfully established discriminant models for CMP basing on the detected substances. Conclusions. The relevance research between qualitative CMP and quantitative material components achieved a positive progress, though it is weak and defective. Standardizing the qualitative CMP system, establishing series comprehensive databases for the material components, innovating statistical and data mining methods, and integrating doctors’ experiences are important and feasible for future research.
An Efficient Searchable Public-Key Authenticated Encryption for Cloud-Assisted Medical Internet of Things
Authors: Chi Tianyu , Qin Baodong , Zheng Dong
Published: July 2020

In recent years, it has become popular to upload patients’ medical data to a third-party cloud server (TCS) for storage through medical Internet of things. It can reduce the local maintenance burden of the medical data and importantly improve accuracy in the medical treatment. As remote TCS cannot be fully trusted, medical data should be encrypted before uploading, to protect patients’ privacy. However, encryption makes search capabilities difficult for patients and doctors. To address this issue, Huang et al. recently put forward the notion of Public-key Authenticated Encryption with Keyword Search (PAEKS) against inside keyword guessing attacks. However, the existing PAEKS schemes rely on time-consuming computation of parings. Moreover, some PAEKS schemes still have security issues in a multiuser setting. In this paper, we propose a new and efficient PAEKS scheme, which uses the idea of Diffie-Hellman key agreement to generate a shared secret key between each sender and receiver. The shared key will be used to encrypt keywords by the sender and to generate search trapdoors by the receiver. We prove that our scheme is semantically secure against inside keyword guessing attacks in a multiuser setting, under the oracle Diffie-Hellman assumption. Experimental results demonstrate that our PAEKS scheme is more efficient than that of previous ones, especially in terms of keyword searching time.
A Luenberger-Like Observer for Multistable Kapitaniak Chaotic System
Authors: Pérez-Cruz J. Humberto , Allende Peña Jacobo Marcos , Nwachioma Christian , Rubio Jose de Jesus , Pacheco Jaime , Meda-Campaña Jesus Alberto , Ávila-González David , Guevara Galindo Olivia , Adrian Romero Ignacio , Belmonte Jiménez Salvador Isidro
Published: July 2020

The objective of this paper is to estimate the unmeasurable variables of a multistable chaotic system using a Luenberger-like observer. First, the observability of the chaotic system is analyzed. Next, a Lipschitz constant is determined on the attractor of this system. Then, the methodology proposed by Raghavan and the result proposed by Thau are used to try to find an observer. Both attempts are unsuccessful. In spite of this, a Luenberger-like observer can still be used based on a proposed gain. The performance of this observer is tested by numerical simulation showing the convergence to zero of the estimation error. Finally, the chaotic system and its observer are implemented using 32-bit microcontrollers. The experimental results confirm good agreement between the responses of the implemented and simulated observers.
Combinatorial ETS1-Dependent Control of Oncogenic NOTCH1 Enhancers in T-cell Leukemia
Authors: McCarter Anna C. , Della Gatta Giusy , Melnick Ashley , Kim Erin , Sha Cher , Wang Qing , Nalamolu Jahnavi K. , Liu Yiran , Keeley Theresa M. , Yan Ran , Sun Mengxi , Kodgule Rohan , Kunnath Nicholas , Ambesi-Impiombato Alberto , Kuick Rork , Rao Arvind , Ryan Russell J.H. , Kee Barbara L. , Samuelson Linda C. , Ostrowski Michael C. , Ferrando Adolfo A. , Chiang Mark Y.
Published: July 2020

Notch activation is highly prevalent among cancers, in particular T-cell acute lymphoblastic leukemia (T-ALL). However, the use of pan-Notch inhibitors to treat cancers has been hampered by adverse effects, particularly intestinal toxicities. To circumvent this barrier in T-ALL, we aimed to inhibit ETS1, a developmentally important T-cell transcription factor previously shown to cobind Notch response elements. Using complementary genetic approaches in mouse models, we show that ablation of Ets1 leads to strong Notch-mediated suppressive effects on T-cell development and leukemogenesis but milder intestinal effects than pan-Notch inhibitors. Mechanistically, genome-wide chromatin profiling studies demonstrate that Ets1 inactivation impairs recruitment of multiple Notch-associated factors and Notch-dependent activation of transcriptional elements controlling major Notch-driven oncogenic effector pathways. These results uncover previously unrecognized hierarchical heterogeneity of Notch-controlled genes and point to Ets1-mediated enucleation of Notch–Rbpj transcriptional complexes as a target for developing specific anti-Notch therapies in T-ALL that circumvent the barriers of pan-Notch inhibition.

Significance:

Notch signaling controls developmentally important and tissue-specific activities, raising barriers for developing anti-Notch therapies. Pivoting away from pan-Notch inhibitors, we show antileukemic but less toxic effects of targeting ETS1, a T-cell NOTCH1 cofactor. These results demonstrate the feasibility of context-dependent suppression of NOTCH1 programs for the treatment of T-ALL.

This article is highlighted in the In This Issue feature, p. 127
Resensitization to Nivolumab after Intratumoral Chemotherapy in Recurrent Head and Neck Squamous Cell Cancer: A Report of 2 Cases
Authors: Houessinon Aline , Moreira Aurélie , Bettoni Jérèmie , Schoonaker Marine , Sauzay Chloé , Galmiche Antoine , Coutte Alexandre , Biet Aurélie , Krzisch Claude , Chauffert Bruno
Published: July 2020

The survival of patients with head and neck squamous cancer with locoregional recurrence is short if salvage surgery or radiation cannot be performed. Systemic chemotherapy based on platinum salts and cetuximab produces only partial and transient responses. Immune checkpoint inhibitors (i.e., nivolumab) lead to a low complete response rate of only about 10%, but in some cases the effects can be long-lasting. Intratumoral chemotherapy (ITC) has been proposed for patients with local recurrence of head and neck squamous cell carcinoma with an objective response rate of 27–50%. However, it often leads to peritumoral tissue necrosis, and the duration of local control is limited. Here, we present 2 patients with head and neck squamous cell cancer whose local recurrences were refractory to intravenous chemotherapy and nivolumab. ITC using nonnecrotizing molecules, associated with nivolumab, led to complete stable local and distant response. ITC seems to trigger tumor resensitization to previously ineffective immunotherapy. This combination deserves an evaluation in the framework of a prospective trial.
A Case of Pulmonary Tumor Thrombotic Microangiopathy Suggested by the Presence of Tumor Cells in Peripheral Blood
Authors: Kawanaka Yusuke , Kawakami Hisato , Shimizu Shigeki , Yoshida Takeshi , Hayashi Hidetoshi , Nishio Kazuto , Satou Takao , Nakagawa Kazuhiko
Published: July 2020

Pulmonary tumor thrombotic microangiopathy (PTTM) is characterized by tumor cell microemboli with occlusive fibrointimal remodeling in small pulmonary vessels. Platelet-derived growth factor (PDGF) has been implicated in the development of PTTM, and fibroblast growth factor (FGF) promotes PDGF signaling via PDGF receptor β. We here describe a cancer patient who presented with dyspnea of uncertain etiology and whose condition worsened rapidly. A 68-year-old man with hypopharyngeal squamous cell carcinoma (cT4aN2bM0, stage IVA) was treated with surgery followed by radiation. Two years later, a lung metastatic lesion was surgically removed on the basis of suspected primary lung cancer. The patient was thereafter monitored without chemotherapy. Two months later, he had third-degree burns and received conservative therapy including debridement and application of trafermin (FGF2) spray. Two weeks later, he was hospitalized with complaints of fever and dyspnea. Pneumonia and pulmonary embolism were ruled out by chest computed tomography with pulmonary arterio­graphy, whereas intravascular lymphoma was excluded by laboratory testing. Malignant cells were detected in his peripheral blood on hospital day 8, and their number increased gradually thereafter. His respiratory symptoms worsened, and the patient died on hospital day 10. We concluded that the cause of death was PTTM, with the clinical course suggesting a possible relation to trafermin. This suggestion was supported by the detection of FGF receptor 2 overexpression in the primary tumor by immunostaining.
Prescriptive Reference Standards of Third-Trimester Cerebroplacental Ratio and Its Physiological Determinants
Authors: Rial-Crestelo Marta , Garcia-Otero Laura , Cancemi Annalisa , Giannone Mariella , Escazzocchio Elena , Biterna Alex , Ferriols Elena , Hernandez Jose Luis , Lubusky Marek , Kolarova Veronika , Krofta Ladislav , Vojtêch Jiri , Zohav Eyal , Krajden Karina , Cruz-Martinez Rogelio , Cruz-Lemini Monica , Parra-Cordero Mauro , Socias Pamela , Crispi Fàtima , Lopez Marta , Gratacós Eduard , Figueras Francesc ,   on behalf of the Ratio 37 study group
Published: July 2020

Objective: To construct valid reference standards reflecting optimal cerebroplacental ratio and to explore its physiological determinants. Methods: A cohort of 391 low-risk pregnancies of singleton pregnancies of nonmalformed fetuses without maternal medical conditions and with normal perinatal outcomes was created. Doppler measurements of the middle cerebral artery and umbilical artery were performed at 24–42 weeks. Reference standards were produced, and the influence of physiological determinants was explored by nonparametric quantile regression. The derived standards were validated in a cohort of 200 low-risk pregnancies. Results: Maternal body mass index was significantly associated with the 5th centile of the cerebroplacental ratio. For each additional unit of body mass index, the 5th centile was on average 0.014 lower. The derived 5th, 10th, and 50th centiles selected in the validation cohort were 5, 9.5, and 51% of the measurements. Conclusions: This study provides methodologically sound prescriptive standards and suggests that maternal body mass index is a determinant of a cutoff commonly used for decision-making.
Systemische Sklerose: Den prognostischen Wert von kardiopulmonalen Belastungstests erkennen
Authors: Krüger Stefan
Published: July 2020

Background: Systemic sclerosis (SSc) is a severe rheumatic disease of the interstitial tissue, in which heart and lung involvement can lead to disease-specific mortality. Our study tests the hypothesis that in addition to established prognostic factors, cardiopulmonary exercise testing (CPET) parameters, particularly peak oxygen uptake (peakVO2) and ventilation/carbon dioxide (VE/VCO2)-slope, can predict survival in patients with SSc. Subjects and methods: We retrospectively assessed 210 patients (80.9% female) in 6 centres over 10 years with pulmonary testing and CPET. Survival was analysed with Cox regression analysis (adjusted for age and gender) by age, comorbidity (Charlson-Index), body weight, body-mass index, extensive interstitial lung disease, pulmonary artery pressure (measured by echocardiography and invasively), and haemodynamic, pulmonary and CPET parameters. Results: Five- and ten-year survival of SSc patients was 93.8 and 86.9%, respectively. There was no difference in survival between patients with diffuse (dcSSc) and limited cutaneous manifestation (lcSSc; p = 0.3). Pulmonary and CPET parameters were significantly impaired. Prognosis was worst for patients with pulmonary hypertension (p = 0.007), 6-min walking distance < 413m (p = 0.003), peakVO2 < 15.6 mL•kg− 1•min− 1, and VE/VCO2-slope > 35. Age (hazard ratio HR = 1.23; 95% confidence interval CI: 1.14;1.41), VE/VCO2-slope (HR = 0.9; CI 0.82;0.98), diffusion capacity (Krogh factor, HR = 0.92; CI 0.86;0.98), forced vital capacity (FVC, HR = 0.91; CI 0.86;0.96), and peakVO2 (HR = 0.87; CI 0.81;0.94) were significantly linked to survival in multivariate analyses (Harrell’s C = 0.95). Summary: This is the first large study with SSc patients that demonstrates the prognostic value of peakVO2 < 15.6 mL•kg− 1•min− 1 (< 64.5% of predicted peakVO2) and VE/VCO2-slope > 35.
Moderne Aspekte der Immuntherapie mit Checkpoint-Inhibitoren bei Melanom
Authors: Petrova Vera , Arkhypov Ihor , Weber Rebekka , Groth Christopher  , Altevogt Peter , Utikal Jochen , Umansky Viktor
Published: July 2020

Das Melanom gehört zu den am stärksten immunogenen Tumoren. Dennoch ist es in der Lage, sich einer antitumoralen Immunantwort zu entziehen, indem es Toleranzmechanismen, einschließlich negativer Immuncheckpoint-Moleküle, nutzt. Die am umfassendsten untersuchten Immuncheckpoints sind CTLA-4 (cytotoxic T lymphocyte-associated protein-4) und PD-1 (programmed cell death protein 1). Immuncheckpoint-Inhibitoren (ICI), die in den vergangenen 10 Jahren häufig zur Behandlung von Melanomen eingesetzt wurden, können antitumorale Immunreaktionen auslösen und eine Rückbildung des Melanoms bewirken. Patienten, die auf die ICI-Behandlung ansprachen, erreichten eine langanhaltende Remission oder einen Zustand der Krankheitskontrolle. Eine große Gruppe von Patienten sprach dagegen nicht auf diese Therapie an, was darauf hindeutet, dass es zu einer Entwicklung von Resistenzmechanismen kommt, darunter intrinsische Eigenschaften des Tumors, Funktionsstörungen der Effektorzellen und die Entstehung eines immunsuppressiven Tumormikromilieus (tumor microenvironment, TME). In der vorliegenden Übersichtsarbeit werden die Erfolge der ICI-Therapie bei Melanom, die Gründe für ein Therapieversagen und vielversprechende Ansätze zur Überwindung der Resistenz erörtert. Letztere umfassen die Kombination verschiedener ICI, Strategien zur Neutralisierung des immunsuppressiven Tumormikromilieus und die Kombination von ICI mit anderen antitumoralen Therapien wie Bestrahlung, onkolytische Viren oder zielgerichtete Therapien. Darüber hinaus werden neue therapeutische Ansätze, die gegen andere Immuncheckpoint-Moleküle gerichtet sind, ebenfalls besprochen.
Acute Kidney Injury and Special Considerations during Renal Replacement Therapy in Children with Coronavirus Disease-19: Perspective from the Critical Care Nephrology Section of the European Society of Paediatric and Neonatal Intensive Care
Authors: Deep Akash , Bansal Mehak , Ricci Zaccaria
Published: July 2020

Children seem to be less severely affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) as compared to adults. Little is known about the prevalence and pathogenesis of acute kidney injury (AKI) in children affected by SARS-CoV-2. Dehydration seems to be the most common trigger factor, and meticulous attention to fluid status is imperative. The principles of initiation, prescription, and complications related to renal replacement therapy are the same for coronavirus disease (COVID) patients as for non-COVID patients. Continuous renal replacement therapy (CRRT) remains the most common modality of treatment. When to initiate and what modality to use are dependent on the available resources. Though children are less often and less severely affected, diversion of all hospital resources to manage the adult surge might lead to limited CRRT resources. We describe how these shortages might be mitigated. Where machines are limited, one CRRT machine can be used for multiple patients, providing a limited number of hours of CRRT per day. In this case, increased exchange rates can be used to compensate for the decreased duration of CRRT. If consumables are limited, lower doses of CRRT (15–20 mL/kg/h) for 24 h may be feasible. Hypercoagulability leading to frequent filter clotting is an important issue in these children. Increased doses of unfractionated heparin, combination of heparin and regional citrate anticoagulation, or combination of prostacyclin and heparin might be used. If infusion pumps to deliver anticoagulants are limited, the administration of low-molecular-weight heparin might be considered. Alternatively in children, acute peritoneal dialysis can successfully control both fluid and metabolic disturbances. Intermittent hemodialysis can also be used in patients who are hemodynamically stable. The keys to successfully managing pediatric AKI in a pandemic are flexible use of resources, good understanding of dialysis techniques, and teamwork.
ТОПІЧНА ДІАГНОСТИКА СТУПЕНЯ УРАЖЕННЯ ЛИЦЬОВОГО НЕРВА
Authors: Davybida N. , Berezyak I.
Published: July 2020

Неврит лицьового нерва – це запалення нервів, що відповідають за контроль над рухами лицьових мʼязів. 98 % випадків невриту супроводжуються явною лицьовою асиметрією, помітною в стані спокою і різко посиленою при мімічних рухах. Одужання настає протягом двох-трьох тижнів, але в деяких випадках повне відновлення міміки може тривати до року. Тому важливо розпочинати лікування якомога раніше, щоб не допустити ускладнень. Повне одужання спостерігають у 75 % пацієнтів.
ПРОФІЛАКТИЧНА РОБОТА СЕРЕД НАСЕЛЕННЯ – ПОТРЕБА ЧИ НЕОБХІДНІСТЬ ДЛЯ СУЧАСНОЇ ЛЮДИНИ
Authors: Zhavrichenko K. V.
Published: July 2020

У статті проаналізовано необхідність проведення медичними сестрами профілактичної роботи серед населення.
Adhesive systems modified with antimicrobial agents: a literature review
Authors: Aguiar Juliana Dias , Youssef Michel Nicolau , Medeiros Igor Studart
Published: July 2020

Secondary caries is the primary cause of restoration failure. Thus, the development of adhesives with antimicrobial action is an advantageous option for their inhibition. However, this effect must be proven, as well as that the additional benefit does not interfere with material mechanical properties or biocompatibility. We analyzed adhesives with antimicrobial action by microbiological tests, bond strength, degree of conversion, and cytotoxicity. We analyzed 32 studies with commercially available antimicrobial adhesives (Clearfil™ SE Protect Bond/ MDPB, Gluma 2Bond/ glutaraldehyde, Peak Universal Bond/chlorhexidine), and experimental materials or commercial adhesives modified with antimicrobial agents, including materials with quaternary ammonium methacrylate (QAM) [dimethylaminododecyl methacrylate (DMADDM) and dimethylaminohexadecyl methacrylate (DMAHDM)], nanoparticles [silver (NAg), titanium dioxide (TiO2), zinc oxide (ZnO)], silver or zinc doped bioactive active glass (BAG), titanium, copper iodide, and compounds such as triclosan, quercetin, grape seed extract, among others. The use of antimicrobial agents is a favorable perspective for the functionalization of adhesive systems to inhibit secondary caries. However, more clinical studies need to prove the efficacy of these materials.
Efficacy of an Adjunctive Electrophysiological Test–Guided Left Atrial Posterior Wall Isolation in Persistent Atrial Fibrillation Without a Left Atrial Low-Voltage Area
Authors: Yamaji Hirosuke , Higashiya Shunichi , Murakami Takashi , Hina Kazuyoshi , Kawamura Hiroshi , Murakami Masaaki , Kamikawa Shigeshi , Hirohata Satoshi , Kusachi Shozo
Published: July 2020

Background:

Electrical remodeling precedes structural remodeling. In adjunctive left atrial (LA) low-voltage area (LVA) ablation to pulmonary vein isolation of atrial fibrillation (AF), LA areas without LVA have not been targeted for ablation. We studied the effect of adjunctive LA posterior wall isolation (PWI) on persistent AF without LA-LVA according to electrophysiological testing (EP test).

Methods:

We examined consecutive patients with persistent AF with (n=33) and without (n=111) LA-LVA. Patients without LA-LVA were randomly assigned to EP test–guided (n=57) and control (n=54) groups. In the EP test–guided group, an adjunctive PWI was performed in those with positive results (PWI subgroup; n=24), but not in those with negative results (n=33). The criteria for positive EP tests were an effective refractory period ≤180 ms, effective refractory period>20 ms shorter than the other sites, and/or induction of AF/atrial tachycardia (AT) during measurements. LVA ablation was performed in the patients with LA-LVA.

Results:

During the follow-up period (62±33 weeks), the EP test–guided group had significantly lower recurrence rates (19%,11/57 versus 41%, 22/54,
P
=0.012) and higher Kaplan-Meier AF/AT–free survival curve rates than the control group (
P
=0.01). No significant differences in the recurrence and AF/AT–free survival curve rates between the PWI (positive EP test) and non-PWI (negative EP test) subgroups were observed. Therefore, PWI for positive EP tests reduced the AF/AT recurrence in the EP test–guided group. A stepwise Cox proportional hazard analyses identified EP test–guided ablation as a factor reducing the recurrence rate. The recurrence rates in the LA-LVA ablation group and EP test–guided group were similar.

Conclusions:

This pilot study proposed that an EP test–guided adjunctive PWI of persistent AF without LA-LVA potentially reduced AF/AT recurrences. The results suggest that there is an AF substrate in the LA with altered electrophysiological function even when there is no LA-LVA.

Graphic Abstract:

A
graphic abstract
is available for this article.
Association of Body Mass Index With Coronary Artery Calcium and Subsequent Cardiovascular Mortality
Authors: Jensen Joseph C. , Dardari Zeina A. , Blaha Michael J. , White Susan , Shaw Leslee J. , Rumberger John , Rozanski Alan , Berman Daniel S. , Budoff Matthew J. , Nasir Khurram , Miedema Michael D.
Published: July 2020

Background:

Obesity is associated with higher risk for coronary artery calcium (CAC), but the relationship between body mass index (BMI) and mortality is complex and frequently paradoxical.

Methods:

We analyzed BMI, CAC, and subsequent mortality using data from the CAC Consortium, a multi-centered cohort of individuals free of established cardiovascular disease (CVD) who underwent CAC testing. Mortality was assessed through linkage to the Social Security Death Index and cause of death from the National Death Index. Multivariable logistic regression was used to determine odds ratios for the association of clinically relevant BMI categories and prevalent CAC. Cox proportional hazards regression modeling was used to determine hazard ratios for coronary heart disease, CVD, and all-cause mortality according to categories of BMI and CAC.

Results:

Our sample included 36 509 individuals, mean age 54.1 (10.3) years, 34.4% female, median BMI 26.6 (interquartile range, 24.1–30.1), 46.6% had zero CAC, and 10.5% had CAC ≥400. Compared with individuals with normal BMI, the multivariable adjusted odds of CAC >0 were increased in those overweight (odds ratio, 1.13 [95% CI, 1.1–1.2]) and obese (odds ratio, 1.5 [95% CI, 1.4–1.6]). Over a median follow-up of 11.4 years, there were 1550 deaths (4.3%). Compared with normal BMI, obese individuals had a higher risk of coronary heart disease, CVD, and all-cause mortality while overweight individuals, despite a higher odds of CAC, showed no significant increase in mortality. In a sex-stratified analysis, the increase in coronary heart disease, CVD, and all-cause mortality in obese individuals appeared largely limited to men, and there was a lower risk of all-cause mortality in overweight women (hazard ratio, 0.79 [95% CI, 0.63–0.98]).

Conclusions:

In a large sample undergoing CAC scoring, obesity was associated with a higher risk of CAC and subsequent coronary heart disease, CVD, and all-cause mortality. However, overweight individuals did not have a higher risk of mortality despite a higher risk for CAC.
Ticagrelor is Not Superior to Clopidogrel in Patients With Acute Coronary Syndromes Undergoing PCI: A Report from Swedish Coronary Angiography and Angioplasty Registry
Authors: Völz Sebastian , Petursson Petur , Odenstedt Jacob , Ioanes Dan , Haraldsson Inger , Angerås Oskar , Dworeck Christian , Hirlekar Geir , Myredal Anna , Albertsson Per , Råmunddal Truls , Redfors Björn , Omerovic Elmir
Published: July 2020

Background

Ticagrelor reduces ischaemic end points in acute coronary syndromes. However, outcomes of ticagrelor versus clopidogrel in real‐world patients with acute coronary syndromes treated with percutaneous coronary intervention (PCI) remain unclear. We sought to examine whether treatment with ticagrelor is superior to clopidogrel in unselected patients with acute coronary syndromes treated with PCI.

Methods and Results

We used data from SCAAR (Swedish Coronary Angiography and Angioplasty Registry) for PCI performed in Västra Götaland County, Sweden. The database contains information about all PCI performed at 5 hospitals (∼20% of all data in SCAAR). All procedures between January 2005 and January 2015 for unstable angina/non‒ST‐segment‒elevation myocardial infarction and ST‐segment‒elevation myocardial infarction were included. We used instrumental variable 2‐stage least squares regression to adjust for confounders. The primary combined end point was mortality or stent thrombosis at 30 days, secondary end points were mortality at 30 days and 1‐year, stent thrombosis at 30 days, in‐hospital bleeding, in‐hospital neurologic complications and long‐term mortality. A total of 15 097 patients were included in the study of which 2929 (19.4%) were treated with ticagrelor. Treatment with ticagrelor was not associated with a lower risk for the primary end point (adjusted odds ratio [aOR], 1.20; 95% CI, 0.87–1.61;
P
=0.250). Estimated risk of death at 30 days (aOR, 1.18; 95% CI, 0.88–1.64;
P
=0.287) and at 1‐year (aOR, 1.28; 95% CI, 0.86–1.64;
P
=0.556) was not different between the groups. The risk of in‐hospital bleeding was higher with ticagrelor (aOR, 2.88; 95% CI, 1.53–5.44;
P
=0.001).

Conclusions

In this observational study, treatment with ticagrelor was not superior to clopidogrel in patients with acute coronary syndromes treated with PCI.
One‐Year Mortality After Intensification of Outpatient Diuretic Therapy
Authors: Madelaire Christian , Gustafsson Finn , Stevenson Lynne Warner , Kristensen Søren Lund , Køber Lars , Andersen Julie , D'Souza Maria , Biering‐Sørensen Tor , Andersson Charlotte , Torp‐Pedersen Christian , Gislason Gunnar , Schou Morten
Published: July 2020

Background

Mortality is increased following a hospitalization for decompensated heart failure (
HF
), during which diuretics are usually intensified. It is unclear how risk is affected after outpatient intensification of diuretic therapy for
HF
.

Methods and Results

From nationwide administrative registers, we identified all Danish patients who were diagnosed with
HF
from 2001 to 2016 and received angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker and β blocker within 120 days. Subsequent follow‐up tracked progressive events of diuretic intensification and
HF
hospitalization. Intensification events were defined as new addition or doubling of loop diuretic or addition of thiazide to loop diuretic. These events were included in multivariable Cox regression models, calculating 1‐year mortality hazard after each year since inclusion. Patients with an intensification event or hospitalization were risk set matched to 2 nonworsened
HF
controls and absolute 1‐year mortality risks were calculated using Kaplan‐Meier estimates. We included 74 990 patients, their median age was 71 years, and 36% were women. Intensification events were associated with significantly increased mortality at all times during follow‐up. One‐year mortality was 18.0% after an intensification event, 22.6% after
HF
hospitalization, and 10.4% for matched controls with neither. In a multivariable Cox model adjusted for age, sex, ischemic heart disease, atrial fibrillation, chronic obstructive pulmonary disease, and diabetes mellitus, the hazard ratio for 1‐year death after an intensification event was 1.75 (95%
CI
, 1.66–1.85), and it was 2.28 (95%
CI
, 2.16–2.41) after
HF
hospitalization.

Conclusions

In a nationwide cohort of patients with
HF
, outpatient intensification events were associated with almost 2‐fold risk of mortality during the next year. Although
HF
hospitalization was associated with a higher risk, the need to intensify diuretics in the outpatient setting is a signal to review and intensify efforts to improve
HF
outcomes.
Predicting the Risk of Adverse Events in Pregnant Women With Congenital Heart Disease
Authors: Chu Ran , Chen Wei , Song Guangmin , Yao Shu , Xie Lin , Song Li , Zhang Yue , Chen Lijun , Zhang Xiangli , Ma Yuyan , Luo Xia , Liu Yuan , Sun Ping , Zhang Shuquan , Fang Yan , Dong Taotao , Zhang Qing , Peng Jin , Zhang Lu , Wei Yuan , Zhang Wenxia , Su Xuantao , Qiao Xu , Song Kun , Yang Xingsheng , Kong Beihua
Published: July 2020

Background

Women with congenital heart disease are considered at high risk for adverse events. Therefore, we aim to establish 2 prediction models for mothers and their offspring, which can predict the risk of adverse events occurred in pregnant women with congenital heart disease.

Methods and Results

A total of 318 pregnant women with congenital heart disease were included; 213 women were divided into the development cohort, and 105 women were divided into the validation cohort. Least absolute shrinkage and selection operator was used for predictor selection. After validation, multivariate logistic regression analysis was used to develop the model. Machine learning algorithms (support vector machine, random forest, AdaBoost, decision tree, k‐nearest neighbor, naïve Bayes, and multilayer perceptron) were used to further verify the predictive ability of the model. Forty‐one (12.9%) women experienced adverse maternal events, and 93 (29.2%) neonates experienced adverse neonatal events. Seven high‐risk factors were discovered in the maternal model, including New York Heart Association class, Eisenmenger syndrome, pulmonary hypertension, left ventricular ejection fraction, sinus tachycardia, arterial blood oxygen saturation, and pregnancy duration. The machine learning–based algorithms showed that the maternal model had an accuracy of 0.76 to 0.86 (area under the receiver operating characteristic curve=0.74–0.87) in the development cohort, and 0.72 to 0.86 (area under the receiver operating characteristic curve=0.68–0.80) in the validation cohort. Three high‐risk factors were discovered in the neonatal model, including Eisenmenger syndrome, preeclampsia, and arterial blood oxygen saturation. The machine learning–based algorithms showed that the neonatal model had an accuracy of 0.75 to 0.80 (area under the receiver operating characteristic curve=0.71–0.77) in the development cohort, and 0.72 to 0.79 (area under the receiver operating characteristic curve=0.69–0.76) in the validation cohort.

Conclusions

Two prenatal risk assessment models for both adverse maternal and neonatal events were established, which might assist clinicians in tailoring precise management and therapy in pregnant women with congenital heart disease.
Accent-induced Modulation of Neural and Movement Patterns during Spontaneous Synchronization to Auditory Rhythms
Authors: Bouvet Cécile J. , Bardy Benoît G. , Keller Peter E. , Dalla Bella Simone , Nozaradan Sylvie , Varlet Manuel
Published: July 2020

Human rhythmic movements spontaneously synchronize with auditory rhythms at various frequency ratios. The emergence of more complex relationships—for instance, frequency ratios of 1:2 and 1:3—is enhanced by adding a congruent accentuation pattern (binary for 1:2 and ternary for 1:3), resulting in a 1:1 movement–accentuation relationship. However, this benefit of accentuation on movement synchronization appears to be stronger for the ternary pattern than for the binary pattern. Here, we investigated whether this difference in accent-induced movement synchronization may be related to a difference in the neural tracking of these accentuation profiles. Accented and control unaccented auditory sequences were presented to participants who concurrently produced finger taps at their preferred frequency, and spontaneous movement synchronization was measured. EEG was recorded during passive listening to each auditory sequence. The results revealed that enhanced movement synchronization with ternary accentuation was accompanied by enhanced neural tracking of this pattern. Larger EEG responses at the accentuation frequency were found for the ternary pattern compared with the binary pattern. Moreover, the amplitude of accent-induced EEG responses was positively correlated with the magnitude of accent-induced movement synchronization across participants. Altogether, these findings show that the dynamics of spontaneous auditory–motor synchronization is strongly driven by the multi-time-scale sensory processing of auditory rhythms, highlighting the importance of considering neural responses to rhythmic sequences for understanding and enhancing synchronization performance.