bluuebunny/crossref_metadata_2025 huggingface dataset:
The Targeting of Nuclear Factor Kappa B by Drugs Adopted for the Prevention and Treatment of Preeclampsia
Authors: Sakowicz Agata
Published: March 2022

Preeclampsia (PE) is characterised by high levels and activity of the transcription factor Nuclear Factor kappa B (NFĸB) in the maternal blood and placental cells. This factor is responsible for the regulation of over 400 genes known to influence processes related to inflammation, apoptosis and angiogenesis, and cellular responses to oxidative stress and hypoxia. Although high NFĸB activity induces hypoxia and inflammation, which are beneficial for the process of implantation, NFĸB level should be reduced in the later stages of physiological pregnancy to favour maternal immunosuppression and maintain gestation. It is believed that the downregulation of NFĸB activity by pharmacotherapy might be a promising way to treat preeclampsia. Interestingly, many of the drugs adopted for the prevention and treatment of preeclampsia have been found to regulate NFĸB activity. Despite this, further innovation is urgently needed to ensure treatment safety and efficacy. The present article summarizes the current state of knowledge about the drugs recommended by cardiology, obstetrics, and gynaecology societies for the prevention and treatment of preeclampsia with regard to their impact on the cellular regulation of NFĸB pathways.
Effect of Empagliflozin on Sphingolipid Catabolism in Diabetic and Hypertensive Rats
Authors: Pérez-Villavicencio Roxana , Flores-Estrada Javier , Franco Martha , Escalante Bruno , Pérez-Méndez Oscar , Mercado Adriana , Bautista-Pérez Rocio
Published: March 2022

The profile of sphingomyelin and its metabolites shows changes in the plasma, organs, and tissues of patients with cardiovascular, renal, and metabolic diseases. The objective of this study was to investigate the effect of empagliflozin on the levels of sphingomyelin and its metabolites, as well as on the activity of acid and neutral sphingomyelinase (aSMase and nSMase) and neutral ceramidase (nCDase) in the plasma, kidney, heart, and liver of streptozotocin-induced diabetic and Angiotensin II (Ang II)-induced hypertension rats. Empagliflozin treatment decreased hyperglycemia in diabetic rats whereas blood pressure remained elevated in hypertensive rats. In diabetic rats, empagliflozin treatment decreased sphingomyelin in the plasma and liver, ceramide in the heart, sphingosine-1-phosphate (S1P) in the kidney, and nCDase activity in the plasma, heart, and liver. In hypertensive rats, empagliflozin treatment decreased sphingomyelin in the plasma, kidney, and liver; S1P in the plasma and kidney; aSMase in the heart, and nCDase activity in the plasma, kidney, and heart. Our results suggest that empagliflozin downregulates the interaction of the de novo pathway and the catabolic pathway of sphingolipid metabolism in the diabetes, whereas in Ang II-dependent hypertension, it only downregulates the sphingolipid catabolic pathway.
Cosmeceutical Therapy: Engaging the Repercussions of UVR Photoaging on the Skin’s Circadian Rhythm
Authors: Mahendra Camille Keisha , Ser Hooi-Leng , Pusparajah Priyia , Htar Thet Thet , Chuah Lay-Hong , Yap Wei Hsum , Tang Yin-Quan , Zengin Gokhan , Tang Siah Ying , Lee Wai Leng , Liew Kai Bin , Ming Long Chiau , Goh Bey Hing
Published: March 2022

Sunlight is an important factor in regulating the central circadian rhythm, including the modulation of our sleep/wake cycles. Sunlight had also been discovered to have a prominent influence on our skin’s circadian rhythm. Overexposure or prolonged exposure to the sun can cause skin photodamage, such as the formation of irregular pigmentation, collagen degradation, DNA damage, and even skin cancer. Hence, this review will be looking into the detrimental effects of sunlight on our skin, not only at the aspect of photoaging but also at its impact on the skin’s circadian rhythm. The growing market trend of natural-product-based cosmeceuticals as also caused us to question their potential to modulate the skin’s circadian rhythm. Questions about how the skin’s circadian rhythm could counteract photodamage and how best to maximize its biopotential will be discussed in this article. These discoveries regarding the skin’s circadian rhythm have opened up a completely new level of understanding of our skin’s molecular mechanism and may very well aid cosmeceutical companies, in the near future, to develop better products that not only suppress photoaging but remain effective and relevant throughout the day.
Prenatal Hypoxia Affects Foetal Cardiovascular Regulatory Mechanisms in a Sex- and Circadian-Dependent Manner: A Review
Authors: Sutovska Hana , Babarikova Katarina , Zeman Michal , Molcan Lubos
Published: March 2022

Prenatal hypoxia during the prenatal period can interfere with the developmental trajectory and lead to developing hypertension in adulthood. Prenatal hypoxia is often associated with intrauterine growth restriction that interferes with metabolism and can lead to multilevel changes. Therefore, we analysed the effects of prenatal hypoxia predominantly not associated with intrauterine growth restriction using publications up to September 2021. We focused on: (1) The response of cardiovascular regulatory mechanisms, such as the chemoreflex, adenosine, nitric oxide, and angiotensin II on prenatal hypoxia. (2) The role of the placenta in causing and attenuating the effects of hypoxia. (3) Environmental conditions and the mother’s health contribution to the development of prenatal hypoxia. (4) The sex-dependent effects of prenatal hypoxia on cardiovascular regulatory mechanisms and the connection between hypoxia-inducible factors and circadian variability. We identified that the possible relationship between the effects of prenatal hypoxia on the cardiovascular regulatory mechanism may vary depending on circadian variability and phase of the days. In summary, even short-term prenatal hypoxia significantly affects cardiovascular regulatory mechanisms and programs hypertension in adulthood, while prenatal programming effects are not only dependent on the critical period, and sensitivity can change within circadian oscillations.
Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis
Authors: Walker Rashidra R. , Patel Jankiben R. , Gupta Akash , Davidson A. Michael , Williams Christopher C. , Payton-Stewart Florastina , Boué Stephen M. , Burow Matthew E. , Khupse Rahul , Tilghman Syreeta L.
Published: March 2022

Aromatase inhibitors (AIs) are standard treatment for estrogen-dependent postmenopausal breast tumors; however, resistance develops leading to tumor relapse and metastasis. We previously demonstrated that glyceollin inhibits proliferation, survival, and migration of hormone-independent letrozole-resistant breast cancer. Since many AI-resistant tumors remain hormone-dependent, identifying distinctions between estrogen-receptor-positive (ER+) and ER-negative (ER-) AI-resistant tumor response to therapy is critical. We hypothesize that treating ER+ letrozole-resistant T47D breast cancer cells (T47DaromLR) with a combination of 10 μM glyceollin and 0.5 μM lapatinib (a dual EGFR/HER2 inhibitor) will decrease cell proliferation through induction of apoptosis. The T47DaromLR cells were found to overexpress HER2 and MAPK while maintaining aromatase and ER levels compared to their letrozole-sensitive (T47Darom) counterparts. In the absence of estrogen stimulation, glyceollin ± lapatinib had no effect on the proliferation of the T47Darom cells, while glyceollin treatment caused 46% reduction in the proliferation of T47DaromLR cells, which was further diminished when combined with lapatinib. While neither agent influenced cell migration, glyceollin and lapatinib reduced S and G2/M phase cell entry and exclusively induced apoptosis by 1.29-fold in the T47DaromLR cells. Taken together, these results suggest that glyceollins and lapatinib may have potential as a novel combination therapeutic approach for hormone-dependent, letrozole-resistant tumors.
Molecular Hydrogen Enhances Proliferation of Cancer Cells That Exhibit Potent Mitochondrial Unfolded Protein Response
Authors: Hasegawa Tomoya , Ito Mikako , Hasegawa Satoru , Teranishi Masaki , Takeda Koki , Negishi Shuto , Nishiwaki Hiroshi , Takeda Jun-ichi , LeBaron Tyler W. , Ohno Kinji
Published: March 2022

Molecular hydrogen ameliorates pathological states in a variety of human diseases, animal models, and cell models, but the effects of hydrogen on cancer have been rarely reported. In addition, the molecular mechanisms underlying the effects of hydrogen remain mostly unelucidated. We found that hydrogen enhances proliferation of four out of seven human cancer cell lines (the responders). The proliferation-promoting effects were not correlated with basal levels of cellular reactive oxygen species. Expression profiling of the seven cells showed that the responders have higher gene expression of mitochondrial electron transport chain (ETC) molecules than the non-responders. In addition, the responders have higher mitochondrial mass, higher mitochondrial superoxide, higher mitochondrial membrane potential, and higher mitochondrial spare respiratory capacity than the non-responders. In the responders, hydrogen provoked mitochondrial unfolded protein response (mtUPR). Suppression of cell proliferation by rotenone, an inhibitor of mitochondrial ETC complex I, was rescued by hydrogen in the responders. Hydrogen triggers mtUPR and induces cell proliferation in cancer cells that have high basal and spare mitochondrial ETC activities.
Key Soybean Seedlings Drought-Responsive Genes and Pathways Revealed by Comparative Transcriptome Analyses of Two Cultivars
Authors: Xuan Huidong , Huang Yanzhong , Zhou Li , Deng Sushuang , Wang Congcong , Xu Jianyu , Wang Haitang , Zhao Jinming , Guo Na , Xing Han
Published: March 2022

Seedling drought stress is one of the most important constraints affecting soybean yield and quality. To unravel the molecular mechanisms under soybean drought tolerance, we conducted comprehensive comparative transcriptome analyses of drought-tolerant genotype Jindou 21 (JD) and drought-sensitive genotype Tianlong No.1 (N1) seedlings that had been exposed to drought treatment. A total of 6038 and 4112 differentially expressed genes (DEGs) were identified in drought-tolerant JD and drought-sensitive N1, respectively. Subsequent KEGG pathway analyses showed that numerous DEGs in JD are predominately involved in signal transduction pathways, including plant hormone signaling pathway, calcium signaling pathway, and MAPK signaling pathway. Interestingly, JA and BR plant hormone signal transduction pathways were found specifically participating in drought-tolerant JD. Meanwhile, the differentially expressed CPKs, CIPKs, MAPKs, and MAP3Ks of calcium and MAPK signaling pathway were only identified in JD. The number of DEGs involved in transcription factors (TFs) is larger in JD than that of in N1. Moreover, some differently expressed transcriptional factor genes were only identified in drought-tolerant JD, including FAR1, RAV, LSD1, EIL, and HB-PHD. In addition, this study suggested that JD could respond to drought stress by regulating the cell wall remodeling and stress-related protein genes such as EXPs, CALSs, CBPs, BBXs, and RD22s. JD is more drought tolerant than N1 owing to more DEGs being involved in multiple signal transduction pathways (JA, BR, calcium, MAPK signaling pathway), stress-related TFs, and proteins. The above valuable genes and pathways will deepen the understanding of the molecular mechanisms under drought stress in soybean.
Insight into the Phylogeny and Binding Ability of WRKY Transcription Factors
Authors: Hsin Kuan-Ting , Hsieh Min-Che , Lee Yu-Hsuan , Lin Kai-Chun , Cheng Yi-Sheng
Published: March 2022

WRKY transcription factors (TFs), which make up one of the largest families of TFs in the plant kingdom, are key players in modulating gene expression relating to embryogenesis, senescence, pathogen resistance, and abiotic stress responses. However, the phylogeny and grouping of WRKY TFs and how their binding ability is affected by the flanking regions of W-box sequences remain unclear. In this study, we reconstructed the phylogeny of WRKY across the plant kingdom and characterized the DNA-binding profile of Arabidopsis thaliana WRKY (WRKY54) based on its W-box recognition sequence. We found that WRKY TFs could be separated into five clades, and that the functional zinc-finger motif at the C-terminal of WRKY appeared after several nucleotide substitutions had occurred at the 3′-end of the zinc-finger region in chlorophytes. In addition, we found that W-box flanking regions affect the binding ability of WRKY54 based on the results of a fluorescence-based electrophoretic mobility shift assay (fEMSA) and quartz crystal microbalance (QCM) analysis. The great abundance of WRKY TFs in plants implicates their involvement in diverse molecular regulatory networks, and the flanking regions of W-box sequences may contribute to their molecular recognition mechanism. This phylogeny and our findings on the molecular recognition mechanism of WRKY TFs should be helpful for further research in this area.
Corrosion Resistance and Electrical Conductivity of Hybrid Coatings Obtained from Polysiloxane and Carbon Nanotubes by Electrophoretic Co-Deposition
Authors: Bezkosty Patryk , Długoń Elżbieta , Sowa Maciej , Nizioł Jacek , Jeleń Piotr , Marchewka Jakub , Błażewicz Marta , Sitarz Maciej
Published: March 2022

Nanocomposites developed based on siloxanes modified with carbon nanoforms are materials with great application potential in the electronics industry, medicine and environmental protection. This follows from the fact that such nanocomposites can be endowed with biocompatibility characteristics, electric conductivity and a high mechanical durability. Moreover, their surface, depending on the type and the amount of carbon nanoparticles, may exhibit antifouling properties, as well as those that limit bacterial adhesion. The paper reports on the properties of polysiloxane (PS) and carbon nanotubes (CNT) nanocomposite coatings on metal surfaces produced by the electrophoretic deposition (EPD). A comparison with coatings made of pure PS or pure CNT on the same substrates using the same deposition method (EPD) is provided. The coatings were examined for morphology and elemental composition (SEM, EDS), structural characteristics (confocal Raman spectroscopy), electrical conductivity and were tested for corrosion (electrochemical impedance spectroscopy-EIS, potentiodynamic polarization-PDP). The results obtained in this study clearly evidenced that such hybrid coatings conduct electricity and protect the metal from corrosion. However, their corrosion resistance differs slightly from that of a pure polymeric coating.
Generation of a Dystrophin Mutant in Dog by Nuclear Transfer Using CRISPR/Cas9-Mediated Somatic Cells: A Preliminary Study
Authors: Oh Hyun Ju , Chung Eugene , Kim Jaehwan , Kim Min Jung , Kim Geon A. , Lee Seok Hee , Ra Kihae , Eom Kidong , Park Soojin , Chae Jong-Hee , Kim Jin-Soo , Lee Byeong Chun
Published: March 2022

Dystrophinopathy is caused by mutations in the dystrophin gene, which lead to progressive muscle degeneration, necrosis, and finally, death. Recently, golden retrievers have been suggested as a useful animal model for studying human dystrophinopathy, but the model has limitations due to difficulty in maintaining the genetic background using conventional breeding. In this study, we successfully generated a dystrophin mutant dog using the CRISPR/Cas9 system and somatic cell nuclear transfer. The dystrophin mutant dog displayed phenotypes such as elevated serum creatine kinase, dystrophin deficiency, skeletal muscle defects, an abnormal electrocardiogram, and avoidance of ambulation. These results indicate that donor cells with CRISPR/Cas9 for a specific gene combined with the somatic cell nuclear transfer technique can efficiently produce a dystrophin mutant dog, which will help in the successful development of gene therapy drugs for dogs and humans.
Role of Nuclear-Receptor-Related 1 in the Synergistic Neuroprotective Effect of Umbilical Cord Blood and Erythropoietin Combination Therapy in Hypoxic Ischemic Encephalopathy
Authors: Choi Joo-Wan , Kang Su Jung , Choi Jee In , Kwack KyuBum , Kim MinYoung
Published: March 2022

Neonatal hypoxic–ischemic encephalopathy (HIE) results in neurological impairments; cell-based therapy has been suggested as a therapeutic avenue. Previous research has demonstrated the synergistically potentiated therapeutic efficacy of human umbilical cord blood (UCB) by combining recombinant human erythropoietin (EPO) treatment for recovery from HIE. However, its molecular mechanism is not entirely understood. In the present study, we analyzed the mechanisms underlying the effect of combination treatment with EPO and UCB by transcriptomic analysis, followed by gene enrichment analysis. Mouse HIE model of the neonate was prepared and randomly divided into five groups: sham, HIE, and UCB, EPO, and UCB+EPO treatments after HIE. A total of 376 genes were differentially expressed when |log2FC| ≥ 1-fold change expression values were considered to be differentially expressed between UCB+EPO and HIE. Further assessment through qRT-PCR and gene enrichment analysis confirmed the expression and correlation of its potential target, Nurr1, as an essential gene involved in the synergistic effect of the UCB+EPO combination. The results indicated the remarkable activation of Wnt/β-catenin signaling by reducing the infarct size by UCB+EPO treatment, accompanied by Nurr1 activity. In conclusion, these findings suggest that the regulation of Nurr1 through the Wnt/β-catenin pathway exerts a synergistic neuroprotective effect in UCB and EPO combination treatment.
Targeting Myotonic Dystrophy Type 1 with Metformin
Authors: García-Puga Mikel , Saenz-Antoñanzas Ander , Matheu Ander , López de Munain Adolfo
Published: March 2022

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder of genetic origin. Progressive muscular weakness, atrophy and myotonia are its most prominent neuromuscular features, while additional clinical manifestations in multiple organs are also common. Overall, DM1 features resemble accelerated aging. There is currently no cure or specific treatment for myotonic dystrophy patients. However, in recent years a great effort has been made to identify potential new therapeutic strategies for DM1 patients. Metformin is a biguanide antidiabetic drug, with potential to delay aging at cellular and organismal levels. In DM1, different studies revealed that metformin rescues multiple phenotypes of the disease. This review provides an overview of recent findings describing metformin as a novel therapy to combat DM1 and their link with aging.
The Dynamics of Minority versus Majority Behaviors: A Case Study of the Mafia Game
Authors: Ri Hong , Kang Xiaohan , Khalid Mohd Nor Akmal , Iida Hiroyuki
Published: March 2022

The game ‘Mafia’ is a logic puzzle that has been a top-rated party game played worldwide. Many studies have been dedicated to determining the best character combination to keep players engaged while analyzing the overall death toll. Although it has only two-sided plays, there are multiple combinations of characters in which each character’s rules are different. This paper explores the game’s sophistication using the game refinement theory and motion in mind model while measuring the entertainment of each character’s actions. It then focuses on the dynamics of minority versus majority behaviors during the game process. Computer simulations were conducted to collect the data of each character and assess the entertainment impacts. Moreover, the energy value of each character was computed based on the motion in mind model. The results show that when the number of ‘Mafia’ and the number of ‘Sheriffs’ are equal, the sophistication of each character is maximized. In addition, the data indicates the player engagement in the following order: Mafia>Sheriff>Citizen. Thus, it can be concluded that the actions of the Mafia character are the most complicated and significantly impact the game. It is expected that the results in this study enable game designers to improve each character’s perspective and examine possible enhancements from the viewpoint of entertainment.
An Explainable Fake News Detector Based on Named Entity Recognition and Stance Classification Applied to COVID-19
Authors: De Magistris Giorgio , Russo Samuele , Roma Paolo , Starczewski Janusz T. , Napoli Christian
Published: March 2022

Over the last few years, the phenomenon of fake news has become an important issue, especially during the worldwide COVID-19 pandemic, and also a serious risk for the public health. Due to the huge amount of information that is produced by the social media such as Facebook and Twitter it is becoming difficult to check the produced contents manually. This study proposes an automatic fake news detection system that supports or disproves the dubious claims while returning a set of documents from verified sources. The system is composed of multiple modules and it makes use of different techniques from machine learning, deep learning and natural language processing. Such techniques are used for the selection of relevant documents, to find among those, the ones that are similar to the tested claim and their stances. The proposed system will be used to check medical news and, in particular, the trustworthiness of posts related to the COVID-19 pandemic, vaccine and cure.
Multiple-Attribute Decision Making Based on Interval-Valued Intuitionistic Fuzzy Generalized Weighted Heronian Mean
Authors: Hu Ximei , Yang Shuxia , Zhu Ya-Ru
Published: March 2022

Due to the complexity and uncertainty of objective things, interval-valued intuitionistic fuzzy (I-VIF) numbers are often used to describe the attribute values in multiple-attribute decision making (MADM). Sometimes, there are correlations between the attributes. In order to make the decision-making result more objective and reasonable, it is often necessary to take the correlation factors into account. Therefore, the study of MADM based on the correlations between attributes in the I-VIF environment has important theoretical and practical significance. Thus, in this paper, we propose new operators (AOs) for I-VIF information that are able to reflect the completeness of the information, attribute relevance, and the risk preference of decision makers (DMs). Firstly, we propose some new AOs for I-VIF information, including I-VIF generalized Heronian mean (I-VIFGHM), I-VIF generalized weighted Heronian mean (I-VIFGWHM), and I-VIF three-parameter generalized weighted Heronian mean (I-VIFTPGWHM). The properties of the obtained operators, including their idempotency, monotonicity, and boundedness are studied. Furthermore, an MADM method based on the I-VIFGWHM operator is provided. Finally, an example is provided to explain the rationality and feasibility of the proposed method.
Atmospheric Propagation Modelling for Terrestrial Radio Frequency Communication Links in a Tropical Wet and Dry Savanna Climate
Authors: Isabona Joseph , Imoize Agbotiname Lucky , Ojo Stephen , Lee Cheng-Chi , Li Chun-Ta
Published: March 2022

Atmospheric impairment-induced attenuation is the prominent source of signal degradation in radio wave communication channels. The computation-based modeling of radio wave attenuation over the atmosphere is the stepwise application of relevant radio propagation models, data, and procedures to effectively and prognostically estimate the losses of the propagated radio signals that have been induced by atmospheric constituents. This contribution aims to perform a detailed prognostic evaluation of radio wave propagation attenuation due to rain, free space, gases, and cloud over the atmosphere at the ultra-high frequency band. This aim has been achieved by employing relevant empirical atmospheric data and suitable propagation models for robust prognostic modeling using experimental measurements. Additionally, the extrapolative attenuation estimation results and the performance analysis were accomplished by engaging different stepwise propagation models and computation parameters often utilized in Earth–satellite and terrestrial communications. Results indicate that steady attenuation loss levels rise with increasing signal carrier frequency where free space is more dominant. The attenuation levels attained due to rain, cloud, atmospheric gases, and free space are also dependent on droplet depths, sizes, composition, and statistical distribution. While moderate and heavy rain depths achieved 3 dB and 4 dB attenuations, the attenuation due to light rainfall attained a 2.5 dB level. The results also revealed that attenuation intensity levels induced by atmospheric gases and cloud effects are less than that of rain. The prognostic-based empirical attenuation modeling results can provide first-hand information to radio transmission engineers on link budgets concerning various atmospheric impairment effects during radio frequency network design, deployment, and management, essentially at the ultra-high frequency band.
A Hypothesis on How the Azolla Symbiosis Mitigates Nitrous Oxide Based on In Silico Analyses
Authors: Gunawardana Dilantha , Herath Venura
Published: March 2022

Nitrous oxide is a long-lived greenhouse gas that exists for 114 years in the atmosphere and is 298-fold more potent than carbon dioxide in its global warming potential. Two recent studies showcased the utility of Azolla plants for a lesser footprint in nitrous oxide production from urea and other supplements to the irrigated ecosystem, which mandates exploration since there is still no clear solution to nitrous oxide in paddy fields or in other ecosystems. Here, we propose a solution based on the evolution of a single cytochrome oxidase subunit II protein (WP_013192178.1) from the cyanobiont Trichormus azollae that we hypothesize to be able to quench nitrous oxide. First, we draw attention to a domain in the candidate protein that is emerging as a sensory periplasmic Y_Y_Y domain that is inferred to bind nitrous oxide. Secondly, we draw the phylogeny of the candidate protein showcasing the poor bootstrap support of its position in the wider clade showcasing its deviation from the core function. Thirdly, we show that the NtcA protein, the apical N-effecting transcription factor, can putatively bind to a promoter sequence of the gene coding for the candidate protein (WP_013192178.1), suggesting a function associated with heterocysts and N-metabolism. Our fourth point involves a string of histidines at the C-terminal extremity of the WP_013192178.1 protein that is missing on all other T. azollae cytochrome oxidase subunit II counterparts, suggesting that such histidines are perhaps involved in forming a Cu center. As the fifth point, we showcase a unique glycine-183 in a lengthy linker region containing multiple glycines that is absent in all proximal Nostocales cyanobacteria, which we predict to be a DNA binding residue. We propose a mechanism of action for the WP_013192178.1 protein based on our in silico analyses. In total, we hypothesize the incomplete and rapid conversion of a likely heterocystous cytochrome oxidase subunit II protein to an emerging nitrous oxide sensing/quenching subunit based on bioinformatics analyses and past literature, which can have repercussions to climate change and consequently, future human life.
Glucose Counteracts Isoprenaline Effects on Ion Channel Functions in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Qiao Lin , Fan Xuehui , Yang Zhen , El-Battrawy Ibrahim , Zhou Xiaobo , Akin Ibrahim
Published: March 2022

Recent studies indicate that the disorder of glucose metabolism in myocardial tissue is involved in the development of Takotsubo syndrome (TTS). This study investigated the effects of a high level of glucose on the pathogenesis of TTS, focusing on the electrophysiological mechanisms. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were treated with toxic concentration of isoprenaline (Iso, 1 mM) and a high level of glucose (22 mM) to mimic the setting of TTS and diabetes mellitus (DM). Iso prolonged action potential duration (APD) through enhancing the late sodium channel current and suppressing the transient outward potassium current (Ito). However, a high level of glucose prevented the APD prolongation and the change in Ito. High-level glucose reduced the expression levels of PI3K/Akt, β1-adrenoceptors, Gs-protein, and PKA, suggesting their involvement in the protective effects of high-level glucose against toxic effects of catecholamine. High glucose level did not influence Iso-induced ROS-generation, suggesting that the protective effects of high-level glucose against Iso did not result from changes in ROS generation. High-level glucose may protect cardiomyocytes from the toxic effects of catecholamine excess through suppressing β1-adrenoceptor-Gs-PKA signaling. DM may reduce the risk for occurrence of arrhythmias due to QT prolongation in TTS patients.
Imaging Features of Pediatric Left Ventricular Noncompaction Cardiomyopathy in Echocardiography and Cardiovascular Magnetic Resonance
Authors: Paszkowska Agata , Sarnecki Jędrzej , Mirecka-Rola Alicja , Kowalczyk-Domagała Monika , Mazurkiewicz Łukasz , Ziółkowska Lidia
Published: March 2022

Background: Left ventricular noncompaction (LVNC) is a distinct cardiomyopathy characterized by the presence of a two-layer myocardium with prominent trabeculation and deep intertrabecular recesses. The diagnosis of LVNC can be challenging because the diagnostic criteria are not uniform. The aim of our study was to evaluate echocardiographic and CMR findings in a group of children with isolated LVNC. Methods: From February 2008 to July 2021, pediatric patients under 18 years of age at the time of diagnosis with echocardiographic evidence of isolated LVNC were prospectively enrolled. The patients underwent echocardiography and contrast-enhanced cardiovascular magnetic resonance (CMR) with late gadolinium enhancement to assess myocardial noncompaction, ventricular size, and function. Results: A total of 34 patients, with a median age of 11.9 years, were recruited. The patients were followed prospectively for a median of 5.1 years. Of the 31 patients who met Jenni’s criteria in echocardiography, CMR was performed on 27 (79%). Further comprehensive analysis was performed in the group of 25 patients who met the echocardiographic and CMR criteria for LVNC. In echocardiography, the median NC/C ratio in systole was 2.60 and in diastole 3.40. In 25 out of 27 children (93%), LVNC was confirmed by CMR, according to Petersen’s criteria, with a median NC/C ratio of 3.27. Conclusions: (1) Echocardiography precisely identifies patients with LVNC. (2) Echocardiography is a good method for monitoring LV systolic function, but CMR is indicated for the precise assessment of LV remodeling and RV size and function, as well as for the detection of myocardial fibrosis.
Lymph-Venous Anastomosis for Breast Cancer-Related Lymphoedema after Docetaxel-Based Chemotherapy
Authors: Fuse Yuma , Karakawa Ryo , Yano Tomoyuki , Yoshimatsu Hidehiko
Published: March 2022

Docetaxel-based chemotherapy, which is administered before or after axillary lymph node dissection (ALND) in breast cancer patients with positive axillary lymph nodes, is reported as an independent risk factor for development of breast cancer-related lymphoedema (BCRL). Severe hardening of the soft tissue, which is a typical manifestation of BCRL with a history of docetaxel-based chemotherapy, has been considered a contraindication for lymph-venous anastomosis (LVA). This study aimed to evaluate the efficacy of LVA for BCRL with a history of the use of docetaxel. Twenty-six consecutive BCRL patients who underwent LVA were reviewed retrospectively. All patients underwent ALND. Amongst 23 patients who had chemotherapy for breast cancer, docetaxel-based chemotherapy was administered in 12 patients. The postoperative change of the limb circumferences and the improvement of subjective symptoms were assessed. Overall, patients showed improvements of the limb circumferences at the wrist, the elbow, and 5 cm above and below the elbow. There were no statistical differences of the postoperative changes of the circumferences between the docetaxel-administered and non-administered groups (0.25% vs. 2.8% at 5 cm above the elbow (p = 0.23), −0.4% vs. 0.7% at 5 cm below the elbow (p = 0.56), and 2.5% vs. 2.5 % at the wrist (p = 0.82)). LVA is comparably effective for lymphedematous patients who had undergone docetaxel-based chemotherapy before or after ALND.
Association between Long-Term Change in Arterial Stiffness and Cardiovascular Outcomes in Kidney Transplant Recipients: Insights from the TRANSARTE Study
Authors: Salib Madonna , Simon Arnaud , Girerd Nicolas , Kearney-Schwartz Anna , Rossignol Patrick , Benetos Athanase , Frimat Luc , Girerd Sophie
Published: March 2022

(1) Background: Increased arterial stiffness is associated with cardiovascular (CV) diseases in end-stage renal disease (ESRD) patients, and CV mortality remains higher in kidney transplantation (KT) recipients compared to in the general population. KT is associated with an improvement in arterial stiffness in the early post-transplant period, followed by a potential re-worsening in the late period. In a cohort of KT patients, we evaluated the associations of pulse-wave velocity (PWV) measured at different time-points (pre-transplant, and early and late post-transplant periods) with CV morbi-mortality, as well as the evolution between these measurements with CV morbi-mortality. (2) Methods: Forty KT recipients with a 10-year follow-up were included. The association of PWV with CV events was assessed with multivariable cox analysis. Backward linear regressions were conducted to identify the determinants of PWV at 1 year and those of the long-term evolution of PWV after KT (delta PWV at 1 year—latest PWV). (3) Results: The absence of arterial stiffening during the long-term follow-up after KT is associated with a lower CV outcome rate (HR for the delta PWV = 0.76 (0.58–0.98), p = 0.036). Age at KT is associated with the worsening of arterial stiffness in the late post-transplantation period (β for the delta PWV = −0.104, p = 0.031). A high PWV at 1 year was associated with a potential for recovery during follow-up (β = 0.744, p < 0.0001). (4) Conclusions: The absence of PWV worsening in the late post-transplantation period was significantly associated with a lower risk of CV events, whereas early changes in PWV were not. Finding an intervention capable of reducing long-term PWV could improve the prognosis of KT recipients.
Comparative Impact of Pharmacological Therapies on Cluster Headache Management: A Systematic Review and Network Meta-Analysis
Authors: Kwon Jae-Hee , Han Ja-Young , Choi Ji-Woong , Park Hye-Rim , Lee Heeyoung
Published: March 2022

It is important to find effective and safe pharmacological options for managing cluster headache (CH) because there is limited evidence from studies supporting the general efficacy and safety of pharmacological therapies. This systematic review and network meta-analysis (NMA) analyzed published randomized controlled trials (RCTs) to evaluate the efficacy and safety of pharmacological treatments in patients with CH. The PubMed and Embase databases were searched to identify RCTs that evaluated the efficacy and safety of pharmacological treatments for CH. Efficacy outcomes included frequency and duration of attacks, pain-free rate, and the use of rescue agents. Safety outcomes were evaluated based on the number of patients who experienced adverse events. A total of 23 studies were included in the analysis. The frequency of attacks was reduced (mean difference (MD) = −1.05, 95% confidence interval (CI) = −1.62 to −0.47; p = 0.0004), and the pain-free rate was increased (odds ratio (OR) = 3.89, 95% CI = 2.76–5.48; p < 0.00001) in the pharmacological treatment group, with a lower frequency of rescue agent use than the placebo group. Preventive, acute, and triptan or non-triptan therapies did not show significant differences in efficacy (p > 0.05). In the NMA, different results were shown among the interventions; for example, zolmitriptan 5 mg was more effective than zolmitriptan 10 mg in the pain-free outcome (OR = 0.40, 95% CI = 0.19–0.82; p < 0.05). Pharmacological treatment was shown to be more effective than placebo to manage CH with differences among types of therapies and individual interventions, and it was consistently shown to be associated with the development of adverse events. Thus, individualized therapy approaches should be applied to treat CH in real-world practice.
Growth Trajectories during the First 6 Years in Survivors Born at Less Than 25 Weeks of Gestation Compared with Those between 25 and 29 Weeks
Authors: Shoji Hiromichi , Murano Yayoi , Nojiri Shuko , Arai Yoshiteru , Awata Kentaro , Ikeda Naho , Ohkawa Natsuki , Nishizaki Naoto , Suganuma Hiroki , Hisata Ken , Kantake Masato , Obinata Kaoru , Shimizu Toshiaki
Published: March 2022

We aimed to determine the differences in the growth trajectories of the youngest gestational survivors (<25 weeks’ gestation) up to 6 years of age compared to those of older gestational ages. Preterm infants were divided into two groups: 22–24 weeks’ gestation (male (M) 16, female (F) 28) and 25–29 weeks’ gestation (M 84, F 59). Z-scores of body weight (BW), body length (BL), and body mass index (BMI) were derived from Japanese standards at 1, 1.5, 3, and 6 years of corrected age. Comparisons between the two groups by sex were made using the Wilcoxon test and linear regression analysis to examine the longitudinal and time-point associations of anthropometric z-scores, the presence of small for gestational age (SGA), and the two gestational groups. BW, BL, BMI, and z-scores were significantly lower in the 22–24 weeks group at almost all assessment points. However, there were no significant differences in BW, BL, BMI, and z-scores between the two female groups after 3 years. BMI z-scores were significantly associated with the youngest gestational age and the presence of SGA at all ages in males, but not in females. The youngest gestational age had a greater influence in males on the z-score of anthropometric parameters up to 6 years of age.
Epidemiological Trends in Patients Undergoing Mitral Valve Transcatheter Edge-to-Edge Repair over the Last Decade: Functional vs. Structural Mitral Regurgitation
Authors: Schneider Leonhard , Nita Nicoleta , Dahme Tilman , Markovic Sinisa , Keßler Mirjam , Rottbauer Wolfang , Tadic Marijana
Published: March 2022

Objective: We aimed to investigate the demographic, clinical and hemodynamic characteristics of patients who underwent percutaneous mitral valve (MV) repair over the last decade, as well as to determine the potential changes in trends of these parameters among patients with structural and functional MR (SMR and FMR). Methodology: We analyzed all patients who underwent interventional MV repair in our institution between January 2010 and March 2021. Our study included both SMR and FMR patients. All data were obtained from a local registry. Results: Nine hundred and seventeen patients (357 SMR patients and 563 FMR patients) were involved in this study. We did not find significant differences in demographical, clinical and hemodynamic characteristics among SMR and FMR patients. Left ventricular remodeling and systolic dysfunction were more pronounced in FMR patients. Systemic vascular resistance was the only hemodynamic parameter that differed between SMR and FMR patients; it was higher in SMR group. An evaluation of the trend between the first and last five years of our experience revealed that the number of patients treated with this technique is constantly increasing, but that this is more pronounced in SMR patients. It was also found that the operative risk of SMR and FMR patients was significantly higher in the first five years. Additionally, our results showed change in medical therapy in MR patients over the last decade in terms of increased use of angiotensin II receptor blockers and the introduction of angiotensin receptor II blocker-neprilysin inhibitor. Conclusion: SMR and FMR patients who underwent interventional MV repair have similar clinical and hemodynamic characteristics. The percentage of SMR patients increased more significantly than FMR patients over the last five years.
Time Trends (2012–2020), Sex Differences and Predictors for Influenza Vaccination Uptake among Individuals with Chronic Obstructive Pulmonary Disease in Spain
Authors: Fuentes-Alonso Marta , Jimenez-Garcia Rodrigo , Lopez-de-Andres Ana , Zamorano-Leon Jose , Carabantes-Alarcon David , Jimenez-Trujillo Isabel , Sanz-Rojo Sara , de Miguel-Diez Javier
Published: March 2022

(1) Background: To analyze time trends, sex differences, and factors associated with influenza vaccination uptake among individuals with COPD in Spain, 2012–2020. (2) Methods: A cross-sectional study based on data from the European Health Surveys for Spain, 2020 (EHSS2020) and 2014 and from the Spanish National Health Interview Surveys for 2017 and 2012. (3) Results: The study included 65,447 participants. Prevalence of COPD was 5.9% (n = 3855). Overall, the influenza vaccination uptake among COPD patients was 57.8% versus 28.6% for those without COPD (p < 0.001). Men with COPD reported higher uptake than women in all the surveys studied. Neither the crude nor the multivariable analysis showed a significant variation change overtime for people with COPD. However, among those aged <65 years, crude uptake decreased from 2012 to 2020 (39.4% vs. 33.3%; p = 0.039). Over the entire period, men were vaccinated significantly more than women (OR 1.28; 95% CI 1.12–1.47). Among COPD participants, included in the EHSS2020, independent predictors of vaccine uptake included being male, higher age, reporting no current smoking and suffering cancer or heart disease. (4) Conclusions: In COPD patients, the influenza vaccination uptake is below desirable levels and did not improve from 2012 to 2020. Sex differences are found, with consistent and constant lower uptake among women with COPD. The observed lower uptake among COPD women and patients with unhealthy lifestyle requires increased attention.
Opioids and Ocular Surface Pathology: A Literature Review of New Treatments Horizons
Authors: García-López Celia , Gómez-Huertas Carmen , Sánchez-González José-María , Borroni Davide , Rodríguez-Calvo-de-Mora Marina , Romano Vito , Rachwani-Anil Rahul , Ramos-López Juan-Francisco , Ortiz-Pérez Santiago , Rocha-de-Lossada Carlos
Published: March 2022

This review discusses the role of opioids in the corneal surface and the different pathways and therapeutic methods of management. A literature review was performed using PubMed database. For the database search, the main searching words “opioid” and “topical opioid treatment” were used with the descriptors “cornea”, “ocular surface”, “neuropathic corneal pain”, “corneal sensitivity” and “naltrexone”; original scientific articles and reviews were included to achieve the purpose of the review. The endogenous opioid system has relevant functions in the organism, and in daily use, opioids are used as painkillers. However, these drugs may be employed for other indications as opioid pathways have a wide spectrum. The corneal surface for topical treatment is easily accessible, hence sparing the side effects of systemic opioids. Instillation of opioid antagonist substances, such as naltrexone, increases corneal healing rates and stimulates the division of corneal epithelium cells without deleterious effects. The natural modulation of endogenous opioids controls different forms of pain, including inflammatory and neuropathic pain, both in the ocular surface and in the central nervous system. There are diverse methods in controlling pain using opioids, especially in refractory forms. This review attempts to collect the literature about corneal surface and opioid pathways to provide an overview image and a possible direction of the news treatments.
Predisposing Factors and Neurologic Outcomes of Patients with Elevated Serum Amylase and/or Lipase after Out-of-Hospital Cardiac Arrest: A Retrospective Cohort Study
Authors: Park Shin Young , Kim Min Joung , Park Incheol , Kim Ha Yan , Lee Myeongjee , Park Yoo Seok , Chung Sung Phil
Published: March 2022

This study investigated the patient outcomes, incidence, and predisposing factors of elevated pancreatic enzyme levels after OHCA. We conducted a retrospective cohort study of patients treated with targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA). Elevation of pancreatic enzyme levels was defined as serum amylase or lipase levels that were at least three times the upper limit of normal. The factors associated with elevated pancreatic enzyme levels and their association with neurologic outcomes and mortality 28 days after OHCA were analyzed. Among the 355 patients, 166 (46.8%) patients developed elevated pancreatic enzyme levels. In the multivariable analysis (odds ratio, 95% confidence interval), initial shockable rhythm (0.62, 0.39–0.98, p = 0.04), time from collapse to return of spontaneous circulation (1.02, 1.01–1.04, p < 0.001), and history of coronary artery disease (1.7, 1.01–2.87, p = 0.046) were associated with elevated pancreatic enzyme levels. After adjusting for confounding factors, elevated pancreatic enzyme levels were associated with neurologic outcomes (5.44, 3.35–8.83, p < 0.001) and mortality (3.74, 2.39–5.86, p < 0.001). Increased pancreatic enzyme levels are common in patients treated with TTM after OHCA and are associated with unfavorable neurologic outcomes and mortality at 28 days after OHCA.
Importance of the Immune Microenvironment in the Spontaneous Regression of Cervical Squamous Intraepithelial Lesions (cSIL) and Implications for Immunotherapy
Authors: Muntinga Caroline L. P. , de Vos van Steenwijk Peggy J. , Bekkers Ruud L. M. , van Esch Edith M. G.
Published: March 2022

Cervical high-grade squamous intraepithelial lesions (cHSILs) develop as a result of a persistent high-risk human papilloma virus (hrHPV) infection. The natural course of cHSIL is hard to predict, depending on a multitude of viral, clinical, and immunological factors. Local immunity is pivotal in the pathogenesis, spontaneous regression, and progression of cervical dysplasia; however, the underlying mechanisms are unknown. The aim of this review is to outline the changes in the immune microenvironment in spontaneous regression, persistence, and responses to (immuno)therapy. In lesion persistence and progression, the immune microenvironment of cHSIL is characterized by a lack of intraepithelial CD3+, CD4+, and CD8+ T cell infiltrates and Langerhans cells compared to the normal epithelium and by an increased number of CD25+FoxP3+ regulatory T cells (Tregs) and CD163+ M2 macrophages. Spontaneous regression is characterized by low numbers of Tregs, more intraepithelial CD8+ T cells, and a high CD4+/CD25+ T cell ratio. A ‘hot’ immune microenvironment appears to be essential for spontaneous regression of cHSIL. Moreover, immunotherapy, such as imiquimod and therapeutic HPV vaccination, may enhance a preexisting pro-inflammatory immune environment contributing to lesion regression. The preexisting immune composition may reflect the potential for lesion regression, leading to a possible immune biomarker for immunotherapy in cHSILs.