bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of Significant Coronary Artery Disease Through Advanced Echocardiography: Role of Non-invasive Myocardial Work
Authors: Sabatino Jolanda , De Rosa Salvatore , Leo Isabella , Strangio Antonio , Spaccarotella Carmen , Polimeni Alberto , Sorrentino Sabato , Di Salvo Giovanni , Indolfi Ciro
Published: August 2021

Background: Non-invasive prediction of critical coronary artery stenosis (CAST) in patients with coronary artery disease (CAD) is challenging. Strain parameters can often capture an impairment of regional longitudinal function; however, they are load dependent. A novel non-invasive method to estimate Myocardial Work (MW) has been recently proposed, showing a strong correlation with invasive work measurements. Our aim was to investigate the ability of non-invasive MW to predict the ischaemic risk area underlying a CAST.

Methods and Results: The study population comprises 80 individuals: 50 patients with CAST and 30 controls (CTRL). Echocardiography recordings were obtained before coronary angiography to measure global longitudinal strain (GLS), Myocardial Work Index (MWI), Myocardial Constructive Work (MCW), Myocardial Wasted work (MWW), Myocardial Work Efficiency (MWE). Global MWI (p = 0.048), MWE (p < 0.001), and MCW (p = 0.048) at baseline were significantly reduced in patients with CAST compared to controls (p < 0.05). Regional MWE within the myocardial segments underlying the CAST, but not LS, was significantly reduced compared to non-target segments (p < 0.001). At ROC analysis, the diagnostic performance to predict CAST for regional MWE (AUC = 0.920, p < 0.001) was higher compared to both regional post-systolic shortening index (PSI) (AUC = 0.600, p = 0.129) and regional LS (AUC = 0.546, p = 0.469).

Conclusions: Non-invasive estimation of MW work indices is able to predict a CAST before invasive angiography.
Imaging of Cardiac Device-Related Infection
Authors: Aguilera Jose , Hutt Erika , Jaber Wael A.
Published: August 2021

Cardiac devices are frequently used in different cardiovascular conditions for the purpose of morbidity or mortality prevention. These include cardiac implantable electronic devices (CIED) like permanent pacemakers and implantable cardiac defibrillators, ventricular assistance devices (VADs), left atrial appendage occlusion (LAAO) devices like the Watchman™, atrial and ventricular septal occluders like the Amplatzer™, among others. In the past years, there has been an increase in the development of these devices as a result of a rise in the number of indications for implantation, paired with the aging and more medically complex patient population. This has led to an increase in the incidence of cardiac device-related infections, one of the most feared and serious complications which is associated with significant morbidity, mortality and financial burden. Accurate diagnosis of cardiac device-related infections is essential given the management implications which often involve removal of the infected device, removal of other prosthetic material and long-term antimicrobial therapy. Clinical and laboratory data are useful diagnostic tools but multimodality imaging is often necessary. The recently published 2020 European Heart Rhythm Association International Consensus document, which is endorsed by many expert societies, has recommended the use of multimodality imaging for the diagnosis of CIED infections. (1) This allows better disease characterization by identifying abnormal fluid collections and guiding aspiration for both diagnostic and therapeutic purposes (i.e. soft tissue ultrasound and computed tomography), evaluation for local extent of disease (i.e. transesophageal echocardiogram to evaluate for concomitant infective endocarditis), embolic manifestation of disease (i.e. computed tomography and magnetic resonance imaging) and metabolic tissue characterization (positron emission tomography and tagged white blood cell scan). (2) In addition, computed tomography (CT) allows for pre-procedural planning which has shown to be associated with better procedural outcomes.
A Novel Computed Tomography-Based Imaging Approach for Etiology Evaluation in Patients With Acute Coronary Syndrome and Non-obstructive Coronary Angiography
Authors: Ling Runjianya , Yu Lihua , Lu Zhigang , Li Yuehua , Zhang Jiayin
Published: August 2021

Objective: This study sought to investigate the diagnostic value of dynamic CT myocardial perfusion imaging (CT-MPI) combined with coronary CT angiography (CCTA) in acute coronary syndrome (ACS) patients without obstructive coronary angiography.

Methods: Consecutive ACS patients with normal or non-obstructive coronary angiography findings who had cardiac magnetic resonance (CMR) contraindications or inability to cooperate with CMR examinations were prospectively enrolled and referred for dynamic CT-MPI + CCTA + late iodine enhancement (LIE). ACS etiology was determined according to combined assessment of coronary vasculature by CCTA, quantified myocardial blood flow (MBF) and presence of LIE.

Results: Twenty two patients were included in the final analysis. CCTA revealed two cases of side branch occlusion and one case of intramural hematoma which were overlooked by invasive angiography. High risk plaques were observed in 6 (27.3%) patients whereas myocardial ischemia was presented in 19 (86.4%) patients with varied extent and severity. LIE was positive in 13 (59.1%) patients and microvascular obstruction was presented in three cases with side branch occlusion or spontaneous intramural hematoma. The specific etiology was identified in 20 (90.9%) patients, of which the most common cause was cardiomyopathies (41%), followed by microvascular dysfunction (14%) and plaque disruption (14%).

Conclusion: Dynamic CT-MPI + CCTA was able to reveal the potential etiologies in majority of patients with ACS and non-obstructive coronary angiography. It may be a useful alternative to CMR for accurate etiology evaluation.
Operating an eHealth System for Prehospital and Emergency Health Care Support in Light of Covid-19
Authors: Kyriacou Efthyvoulos , Antoniou Zinonas , Hadjichristofi George , Fragkos Prokopios , Kronis Chris , Theodosiou Theodosis , Constantinou Riana
Published: August 2021

Introduction: The support of prehospital and emergency call handling and the impact of Covid-19 is discussed throughout this study. The initial purpose was to create an electronic system (eEmergency system) in order to support, improve, and help the procedure of handling emergency calls. This system was expanded to facilitate needed operation changes for Covid-19.

Materials and Methods: An effort to reform the procedures followed for emergency call handling and Ambulance dispatch started on the Island of Cyprus in 2016; along that direction, a central call centre was created. The electronic system presented in this work was designed for this call centre and the new organization of the ambulance services. The main features are the support for ambulance fleet handling, the support for emergency call evaluation and triage procedure, and the improvement of communication between the call centre and the ambulance vehicles. This system started regular operation at the end of 2018. One year later, when Covid-19 period started, we expanded it with the addition of several new features in order to support the handling of patients infected with the new virus.

Results: This system has handled 112,414 cases during the last 25 months out of which 4,254 were Covid-19 cases. These cases include the transfer of patients from their house to the reference hospital, or the transfer of critical patients from the reference hospital to another hospital with an intensive care unit or transfer of patients from one hospital to another one for other reasons, like the number of admissions.

Conclusion: The main purpose of this study was to create an electronic system (eEmergency system) in order to support, improve, and help the procedure of handling emergency calls. The main components and the architecture of this system are outlined in this paper. This system is being successfully used for 25 months and has been a useful tool from the beginning of the pandemic period of Covid-19.
Hydrochemical and Isotopic Difference of Spring Water Depending on Flow Type in a Stratigraphically Complex Karst Area of South Korea
Authors: Yu Soonyoung , Chae Gitak , Oh Junseop , Kim Se-Hoon , Kim Dong-Il , Yun Seong-Taek
Published: August 2021

Characterizing the subsurface flow in karstic areas is challenging due to distinct flow paths coexisting, and lithologic heterogeneity makes it more difficult. A combined use of hydrochemical, environmental isotopic, and hydrograph separation study was performed to understand the subsurface flow in a karst terrain where Ordovician carbonate rocks overlie Jurassic sandstone and shale along thrusts. Spring water collected was divided into Type Ⅰ (n= 11) and Ⅱ (n= 30) based on flow patterns (i.e., low and high discharge, respectively). In addition, groundwater (n= 20) was examined for comparison. Three Type Ⅱ springs were additionally collected during a storm event to construct hydrographs using δ18O and δD. As a result, Type Ⅱ had higher electrical conductivity, Mg2+, HCO3−, and Ca2+/(Na++ K+) than Type Ⅰ and was mostly saturated with calcite, similar to deep groundwater. The hydrochemical difference between Types Ⅰ and Ⅱ was opposite to the expectation that Type Ⅱ would be undersaturated given fast flow and small storage, which could be explained by the distinct geology and water sources. Most Type Ⅱ springs and deep groundwater occurred in carbonate rocks, whereas Type Ⅰ and shallow groundwater occurred in various geological settings. The carbonate rocks seemed to provide conduit flow paths for Type Ⅱ given high solubility and faults, resulting in 1) relatively high tritium and NO3−and Cl−viashort-circuiting flow paths and 2) the similar hydrochemistry and δ18O and δD to deep groundwaterviaupwelling from deep flow paths. The deep groundwater contributed to 83–87% of the discharge at three Type Ⅱ springs in the dry season. In contrast, Type Ⅰ showed low Ca2++ Mg2+and Ca2+/(Na++ K+) discharging diffuse sources passing through shallow depths in a matrix in mountain areas. Delayed responses to rainfall and the increased concentrations of contaminants (e.g., NO3−) during a typhoon at Type Ⅱ implied storage in the vadose zone. This study shows that hydrochemical and isotopic investigations are effective to characterize flow paths, when combined with hydrograph separation because the heterogenous geology affects both flow paths and the hydrochemistry of spring water passing through each pathway.
A Novel Shale Gas Production Prediction Model Based on Machine Learning and Its Application in Optimization of Multistage Fractured Horizontal Wells
Authors: Wang Huijun , Qiao Lu , Lu Shuangfang , Chen Fangwen , Fang Zhixiong , He Xipeng , Zhang Jun , He Taohua
Published: August 2021

Shale gas production prediction and horizontal well parameter optimization are significant for shale gas development. However, conventional reservoir numerical simulation requires extensive resources in terms of labor, time, and computations, and so the optimization problem still remains a challenge. Therefore, we propose, for the first time, a new gas production prediction methodology based on Gaussian Process Regression (GPR) and Convolution Neural Network (CNN) to complement the numerical simulation model and achieve rapid optimization. Specifically, through sensitivity analysis, porosity, permeability, fracture half-length, and horizontal well length were selected as influencing factors. Second, the n-factorial experimental design was applied to design the initial experiment and the dataset was constructed by combining the simulation results with the case parameters. Subsequently, the gas production model was built by GPR, CNN, and SVM based on the dataset. Finally, the optimal model was combined with the optimization algorithm to maximize the Net Present Value (NPV) and obtain the optimal fracture half-length and horizontal well length. Experimental results demonstrated the GPR model had prominent modeling capabilities compared with CNN and Support Vector Machine (SVM) and achieved the satisfactory prediction performance. The fracture half-length and well length optimized by the GPR model and reservoir numerical simulation model converged to almost the same values. Compared with the field reference case, the optimized NPV increased by US$ 7.43 million. Additionally, the time required to optimize the GPR model was 1/720 of that of numerical simulation. This work enriches the knowledge of shale gas development technology and lays the foundation for realizing the scale-benefit development for shale gas, so as to realize the integration of geological engineering.
Realizing Stretchable Aqueous Zn–Based Batteries by Material and Structural Designs
Authors: Hang Lifeng , Jiang Guihua
Published: August 2021

The increasing demands on stretchable power supply for wearable electronics accelerate the development of stretchable batteries. Zn-based batteries are promising to be applied in wearable electronics due to their outstanding performance, intrinsic safety, low cost, and environmental friendliness. Recently, stretchable Zn-based batteries are designed to demonstrate the capability of delivering excellent electrochemical performance, meanwhile maintaining their mechanical stability. This review provides an overview of different strategies and designs to realize stretchability in different Zn-based battery components. The general strategies to realize stretchability are first introduced, followed by the specific designs on the cathode, anode, and electrolytes of Zn batteries. Moreover, current issues and possible strategies are also highlighted.
Evolutionary Diversity Peaks at Mid-Elevations Along an Amazon-to-Andes Elevation Gradient
Authors: Griffiths Andy R. , Silman Miles R. , Farfan-Rios William , Feeley Kenneth J. , Cabrera Karina García , Meir Patrick , Salinas Norma , Segovia Ricardo A. , Dexter Kyle G.
Published: August 2021

Elevation gradients present enigmatic diversity patterns, with trends often dependent on the dimension of diversity considered. However, focus is often on patterns of taxonomic diversity and interactions between diversity gradients and evolutionary factors, such as lineage age, are poorly understood. We combine forest census data with a genus level phylogeny representing tree ferns, gymnosperms, angiosperms, and an evolutionary depth of 382 million years, to investigate taxonomic and evolutionary diversity patterns across a long tropical montane forest elevation gradient on the Amazonian flank of the Peruvian Andes. We find that evolutionary diversity peaks at mid-elevations and contrasts with taxonomic richness, which is invariant from low to mid-elevation, but then decreases with elevation. We suggest that this trend interacts with variation in the evolutionary ages of lineages across elevation, with contrasting distribution trends between younger and older lineages. For example, while 53% of young lineages (originated by 10 million years ago) occur only below ∼1,750 m asl, just 13% of old lineages (originated by 110 million years ago) are restricted to below ∼1,750 m asl. Overall our results support an Environmental Crossroads hypothesis, whereby a mid-gradient mingling of distinct floras creates an evolutionary diversity in mid-elevation Andean forests that rivals that of the Amazonian lowlands.
AI: UBI Income Portfolio Adjustment to Technological Transformation
Authors: Przegalinska Alexandra K. , Wright Robert E.
Published: August 2021

Positive and normative claims that artificial intelligence (AI) will or should lead to adoption of a universal basic income policy (UBI) remain insufficiently empirically grounded to merit serious consideration. Long-term trends in individual/familial income portfolio adjustment (IPA) to business, economic, and technological change (BETC) point to continued incremental changes in the ways that individuals/families achieve life goals, not a fundamental structural break necessitating radical policy changes that may not be desirable in any event. Moreover, if AI proves a more rapid disruptor than anticipated, UBI-like payments can be made quickly, as recent bailouts and fiscal stimuli demonstrate.
Enhanced CXCR4 Expression of Human CD8Low T Lymphocytes Is Driven by S1P4
Authors: Burkard Tobias , Dreis Caroline , Herrero San Juan Martina , Huhn Meik , Weigert Andreas , Pfeilschifter Josef M. , Radeke Heinfried H.
Published: August 2021

Although the human immune response to cancer is naturally potent, it can be severely disrupted as a result of an immunosuppressive tumor microenvironment. Infiltrating regulatory T lymphocytes contribute to this immunosuppression by inhibiting proliferation of cytotoxic CD8+ T lymphocytes, which are key to an effective anti-cancer immune response. Other important contributory factors are thought to include metabolic stress caused by the local nutrient deprivation common to many solid tumors. Interleukin-33 (IL-33), an alarmin released in reaction to cell damage, and sphingosine-1-phosphate (S1P) are known to control cell positioning and differentiation of T lymphocytes. In an in vitro model of nutrient deprivation, we investigated the influence of IL-33 and S1P receptor 4 (S1P4) on the differentiation and migration of human CD8+ T lymphocytes. Serum starvation of CD8+ T lymphocytes induced a subset of CD8Low and IL-33 receptor-positive (ST2L+) cells characterized by enhanced expression of the regulatory T cell markers CD38 and CD39. Both S1P1 and S1P4 were transcriptionally regulated after stimulation with IL-33. Moreover, expression of the chemokine receptor CXCR4 was increased in CD8+ T lymphocytes treated with the selective S1P4 receptor agonist CYM50308. We conclude that nutrient deprivation promotes CD8Low T lymphocytes, contributing to an immunosuppressive microenvironment and a poor anti-cancer immune response by limiting cytotoxic effector functions. Our results suggest that S1P4 signaling modulation may be a promising target for anti-CXCR4 cancer immunotherapy.
Case Report: Complete Response of Primary Massive Hepatocellular Carcinoma to Anti-Programmed Death Ligand-1 Antibody Following Progression on Anti-Programmed Death-1 Antibody
Authors: Liu Gang , Zhou Wenxuan , Li Xiaoli , Guo Lijie , He Tingting , Zhao Juan , Gong Liansheng
Published: August 2021

Hepatocellular carcinoma (HCC) is an aggressive liver tumor that occurs due to chronic liver disease, and it has a high mortality rate and limited treatment options. Immune checkpoint inhibitors have been successfully introduced and used in cancer therapy, among which inhibitors of programmed death ligand-1 (PD-L1) and its receptor programmed death-1 (PD-1) are commonly administered for HCC as combination therapy, including combined anti-angiogenic and immunotherapy combination therapy. We report a case of a primary massive HCC patient with portal hepatic vein tumor thrombus who had a good response to atezolizumab in combination with bevacizumab, following progression of disease on combined immunotherapy with pembrolizumab and lenvatinib. This case demonstrates for the first time that an HCC patient who is resistant to anti-PD-1 antibody immunotherapy can benefit from anti-PD-L1 antibody immunotherapy, providing a potentially promising strategy for the treatment of HCC.
Emerging Biomarkers and Therapeutic Strategies for Refractory Bullous Pemphigoid
Authors: Zhou Tong , Peng Bin , Geng Songmei
Published: August 2021

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disorder in the elderly. Systemic and topical use of glucocorticoids and immunosuppressants has been shown to be effective in most patients. However, refractory BP patients are challenged to clinicians with severe clinical symptoms, resistance to treatment, and high relapse rate. How to predict and assess the refractory and severity of bullous pemphigoid is the key issue in clinical practice, and the urgent need for precision medicine in refractory patients is driving the search for biomarkers and biologics. Recently, some biomarkers, such as the level of specific autoantibodies and released cytokines, have been proposed as the potential parameters to reflect the disease severity and predict the treatment response and relapse of refractory BP. Moreover, new biologics targeting pathogenic antibodies, complement, Th2 axis, eosinophils, and Th17 axis have shown potent efficacy on refractory BP. Here, we review the literature and give an overview of emerging biomarkers and therapeutic strategies for refractory bullous pemphigoid to improve the prognosis of the patient.
Alterations in Saliva and Plasma Cytokine Concentrations During Long-Duration Spaceflight
Authors: Krieger Stephanie S. , Zwart Sara R. , Mehta Satish , Wu Honglu , Simpson Richard J. , Smith Scott M. , Crucian Brian
Published: August 2021

Long-duration spaceflight is known to cause immune dysregulation in astronauts. Biomarkers of immune system function are needed to determine both the need for and effectiveness of potential immune countermeasures for astronauts. Whereas plasma cytokine concentrations are a well-established biomarker of immune status, salivary cytokine concentrations are emerging as a sensitive indicator of stress and inflammation. For this study, to aid in characterizing immune dysregulation during spaceflight, plasma and saliva cytokines were monitored in astronauts before, during and after long-duration spaceflight onboard the International Space Station. Blood was collected from 13 astronauts at 3 timepoints before, 5 timepoints during and 3 timepoints after spaceflight. Saliva was collected from 6 astronauts at 2 timepoints before spaceflight, 2 timepoints during and 3 timepoints following spaceflight. Samples were analyzed using multiplex array technology. Significant increases in the plasma concentration of IL-3, IL-15, IL-12p40, IFN-α2, and IL-7 were observed during spaceflight compared to before flight baseline. Significant decreases in saliva GM-CSF, IL-12p70, IL-10 and IL-13 were also observed during spaceflight as compared to compared to before flight baseline concentrations. Additionally, plasma TGFβ1 and TGFβ2 concentrations tended to be consistently higher during spaceflight, although these did not reach statistical significance. Overall, the findings confirm anin-vivohormonal dysregulation of immunity, appearing pro-inflammatory and Th1 in nature, persists during long-duration orbital spaceflight. These biomarkers may therefore have utility for monitoring the effectiveness of biomedical countermeasures for astronauts, with potential application in terrestrial research and medicine.
Measuring the Impact of the COVID-19 Shutdown on Great Lakes Water Quality Using Remote Sensing
Authors: Bosse Karl R. , Sayers Michael J. , Shuchman Robert A. , Lekki John , Tokars Roger
Published: August 2021

The states of Michigan and Ohio issued shutdown orders in mid-March 2020 in an attempt to slow the spread of the coronavirus (COVID-19), resulting in widespread disruption to economic and human activity. This study, which was commissioned by NASA headquarters, utilized satellite remote sensing data from the Visible Infrared Imaging Radiometer Suite sensor onboard the Suomi National Polar-orbiting Partnership satellite to investigate whether these changes in activity led to any short-term changes in water quality in the Great Lakes region by comparing 2020 data to a historic baseline. The water quality parameters examined included chlorophyll-a (CHL) and total suspended solids (TSS) concentrations, water clarity, and harmful algal bloom (HAB) extent. These parameters were investigated in two Great Lakes basins which experience significant anthropogenic pressure: the western basin of Lake Erie (WBLE) and Saginaw Bay in Lake Huron (SBLH). TSS concentrations in April 2020 were below the historic baseline in both basins, and largely remained low until September. SBLH also experienced elevated CHL concentrations in April which persisted through the summer. Additionally, the WBLE HAB extent was down in 2020 after an early end to the growing season. However, this investigation found that the COVID-19 shutdowns were likely not a direct driver of these short-term anomalies. Instead, recent trends in the indicators and co-occurring anomalies in hydrological and meteorological conditions (e.g., lake temperature, river discharge, and wind speed) appeared to be more responsible for the detected water quality changes. Future work will investigate whether the shutdowns have a long-term or delayed impact on Great Lakes water quality.
Assessing the Impact of a Winter Storm on the Beach and Dune Systems and Erosion Mitigation by Plants
Authors: Maximiliano-Cordova Carmelo , Martínez M. Luisa , Silva Rodolfo , Hesp Patrick A. , Guevara Roger , Landgrave Rosario
Published: August 2021

The impact of storms on coastal dunes and beaches and the effects they induce in topography and plant communities are natural processes that contribute to maintaining natural coastal dynamics. However, because coasts are often densely populated, these phenomena are perceived as major threats to human property. To protect human assets sustainably, nature-based defenses have emerged as an option. Coastal dunes act as natural buffers that mitigate the extent of erosion and inland flooding, and their resistance depends on the biogeomorphological feedback between the plants and the dunes. This study aimed to evaluate the effect of one winter storm on beach and dune topography and the plant communities, and to explore the effect of plants in mitigating erosion on beaches with different geomorphological features. The effects on plant communities were evaluated by comparing diversity and plant cover before and after the storm. Later, the role of plants in conferring dune resistance against erosion was examined by measuring erosion on the exposed face of the dunes considering plant cover and plant richness. The results did not show significant differences in plant diversity and plant cover between pre-and post-storm conditions, but turnover of species was recorded. The dune building species were not affected but inland species disappeared. Erosion was reduced when the dunes were higher and, furthermore, plant cover was negatively correlated with erosion on these dunes. The results showed a reduced impact of the storm on the plant communities, which is important as it facilitates the recovery of dunes by the dune-building species and protects them in a subsequent storm. The novelty of this study is that: (a) it demonstrates the species-specific role of plants in mitigating dune erosion in field conditions; (b) it shows the interaction between plant-related features and geomorphological variables in promoting dune resistance to erosion, and (c) it explores the immediate effect of a winter storm on the plant community and dune-building species.
Immunomodulatory Effects of Heme Oxygenase-1 in Kidney Disease
Authors: Li Yunlong , Ma Kuai , Han Zhongyu , Chi Mingxuan , Sai Xiyalatu , Zhu Ping , Ding Zhaolun , Song Linjiang , Liu Chi
Published: August 2021

Kidney disease is a general term for heterogeneous damage that affects the function and the structure of the kidneys. The rising incidence of kidney diseases represents a considerable burden on the healthcare system, so the development of new drugs and the identification of novel therapeutic targets are urgently needed. The pathophysiology of kidney diseases is complex and involves multiple processes, including inflammation, autophagy, cell-cycle progression, and oxidative stress. Heme oxygenase-1 (HO-1), an enzyme involved in the process of heme degradation, has attracted widespread attention in recent years due to its cytoprotective properties. As an enzyme with known anti-oxidative functions, HO-1 plays an indispensable role in the regulation of oxidative stress and is involved in the pathogenesis of several kidney diseases. Moreover, current studies have revealed that HO-1 can affect cell proliferation, cell maturation, and other metabolic processes, thereby altering the function of immune cells. Many strategies, such as the administration of HO-1-overexpressing macrophages, use of phytochemicals, and carbon monoxide-based therapies, have been developed to target HO-1 in a variety of nephropathological animal models, indicating that HO-1 is a promising protein for the treatment of kidney diseases. Here, we briefly review the effects of HO-1 induction on specific immune cell populations with the aim of exploring the potential therapeutic roles of HO-1 and designing HO-1-based therapeutic strategies for the treatment of kidney diseases.
Case Report: Two Cases of Subacute Thyroiditis Following SARS-CoV-2 Vaccination
Authors: Bornemann Catherine , Woyk Katharina , Bouter Caroline
Published: August 2021

Subacute thyroiditis is an inflammatory thyroid disorder associated with viral infections. Rare cases of subacute thyroiditis have also been described following vaccination. Recently, a few cases of subacute thyroiditis following SARS-CoV-2 vaccination have also been reported. Here, we present two cases of cytological proven subacute thyroiditis after receiving the first dose of a SARS-CoV-2 vaccination. We describe clinical, laboratory, imaging and cytological findings in two cases of subacute thyroiditis that presented in our department 2 weeks after SARS-CoV-2 vaccination with Spikevax (Moderna Biotech, Spain) and Vaxzevria (AstraZeneca; Sweden). Both cases did not have a previous history of thyroid disorders and presented with anterior and lateral neck pain. Clinical test results as well as cytological findings were consistent with subacute thyroiditis. Subacute thyroiditis may develop following a SARS-CoV-2 vaccination and should be considered as a possible side effect in cases that present with thyroid pain.
Dietary Exposure of Pacific Oyster (Crassostrea gigas) Larvae to Compromised Microalgae Results in Impaired Fitness and Microbiome Shift
Authors: Vignier Julien , Laroche Olivier , Rolton Anne , Wadsworth Pandora , Kumanan Karthiga , Trochel Branwen , Pochon Xavier , King Nick
Published: August 2021

The Pacific oyster Crassostrea gigas is the world’s most cultivated oyster and seed supply is heavily reliant on hatchery production where recurring mass mortality events are a major constraint. Outbreaks of bacterial infection via microalgal feed are frequently implicated in these mortalities. This study assessed the effects of feeding compromised microalgae to developing oyster larvae. Intentionally ‘stressed’ (high pH) or non-stressed microalgae were fed to 11 day-old oyster larvae at two feeding rations for 96 h, followed by a recovery period. Biological endpoints of larval performance were measured following the 96 h exposure and subsequent recovery. Bacterial communities associated with the microalgae feed, rearing seawater, and the oyster larvae, were characterized and correlated with effects on oyster fitness parameters. Feeding stressed algae to oyster larvae for 96 h increased the occurrence of deformities (>70% vs. 20% in control), reduced feeding and swimming ability, and slowed development. Following the recovery period, fewer larvae reached pediveliger stage (2.7% vs. 36% in control) and became spat (1.5% vs. 6.6% in control). The quantity of stressed algae supplied to oyster larvae also influenced overall larval performance, with high feeding rations generally causing greater impairment than low rations. Bacterial profiling using 16S rRNA showed that most bacterial families characterized in larval tissue were also present in larval rearing seawater and in the microalgae feed (98%). The rearing seawater showed the highest bacterial richness compared to the larval and the microalgal compartments, regardless of feeding regime. In larval tissue, bacterial richness was highest in stressed and high-feed treatments, and negatively correlated with larval fitness parameters. These results suggest significant dysbiosis induced by compromised feed and/or increased feed ration. Several bacterial genera (e.g., Halomonas, Marinomonas) were strongly associated with impaired larval performance while the presence of genera in larvae including Vibrio was closely associated with overfeeding. Our research demonstrated that metabarcoding can be effectively used to identify microbiota features associated with larval fitness.
Metagenomic Analysis of Antibiotic Resistance Genes in Untreated Wastewater From Three Different Hospitals
Authors: Guo Xiurong , Tang Nan , Lei Hui , Fang Qi , Liu Li , Zhou Quan , Song Can
Published: August 2021

Controlling antibiotic resistance genes (ARGs) is a worldwide intervention to ensure global health. Hospital wastewater is the main pollution source of antibiotic-resistant bacteria and ARGs in the environment. Expanding our knowledge on the bacterial composition of hospital wastewater could help us to control infections in hospitals and decrease pathogen release into the environment. In this study, a high-throughput sequencing-based metagenomic approach was applied to investigate the community composition of bacteria and ARGs in untreated wastewater from three different types of hospitals [the general hospital, traditional Chinese medicine (TCM) hospital, and stomatology hospital]. In total, 130 phyla and 2,554 genera were identified from the microbiota of the wastewaters, with significantly different bacterial community compositions among the three hospitals. Total ARG analysis using the Antibiotic Resistance Genes Database (ARDB) and Comprehensive Antibiotic Resistance Database (CARD) revealed that the microbiota in the wastewaters from the three hospitals harbored different types and percentage of ARGs, and their composition was specific to the hospital type based on the correlation analysis between species and ARG abundance, some ARGs contributed to different bacterial genera with various relationships in different hospitals. In summary, our findings demonstrated a widespread occurrence of ARGs and ARG-harboring microbiota in untreated wastewaters of different hospitals, suggesting that protection measures should be applied to prevent human infections. Concurrently, hospital wastewater should be treated more specifically for the removal of pathogens before its discharge into the urban sewage system.
Epigenetic Therapy Promotes the Ratio of Th1/Th17 Lineage to Reverse Immune Evasion and Treat Leukemia Relapse Post-allogeneic Stem Cell Transplantation in Non-APL AML Patients
Authors: Xi Yang , Jingying Dai , Chenglong Li , Hong Zheng , Rong Zhang , Xiaodong Wang , Chunsen Wang , Xiaobing Huang
Published: August 2021

To reverse the early-stage relapse post-hematopoietic stem cell transplantation, we investigated the safety and efficacy of a new epigenetic regimen (chidamide and decitabine plus thymalfasin simultaneously) on acute myeloid leukemia patients (excluding acute promyelocytic leukemia). Twenty-four patients were enrolled in this observational study during April 2015 to May 2018. The most common adverse event was reversible CTCAE grade 2 thrombocytopenia (20/24). Strikingly, all 24 patients had response to this epigenetic regimen accompanied with decreased measurable residual disease. The overall survival rate is 79.2% (19/24), with a relapse-free survival rate of 79.2% (19/24). During this regimen treatment, Th1 cells and CD3+CD4-CD8+T cells increased, and Th17 cells decreased gradually. The status of high Th1 and low Th17 cells was still observed on the 3rd month after discontinuation of this regimen. Interestingly, the significantly elevated ratio of Th1/Th17 seemed to reflect the treatment-related immune effect, which may be a valuable marker to be monitored in the early-relapse stage for evaluating the efficacy and prognosis.
Role of Copper on Mitochondrial Function and Metabolism
Authors: Ruiz Lina M. , Libedinsky Allan , Elorza Alvaro A.
Published: August 2021

Copper is essential for life processes like energy metabolism, reactive oxygen species detoxification, iron uptake, and signaling in eukaryotic organisms. Mitochondria gather copper for the assembly of cuproenzymes such as the respiratory complex IV, cytochrome c oxidase, and the antioxidant enzyme superoxide dismutase 1. In this regard, copper plays a role in mitochondrial function and signaling involving bioenergetics, dynamics, and mitophagy, which affect cell fate by means of metabolic reprogramming. In mammals, copper homeostasis is tightly regulated by the liver. However, cellular copper levels are tissue specific. Copper imbalances, either overload or deficiency, have been associated with many diseases, including anemia, neutropenia, and thrombocytopenia, as well as tumor development and cancer aggressivity. Consistently, new pharmacological developments have been addressed to reduce or exacerbate copper levels as potential cancer therapies. This review goes over the copper source, distribution, cellular uptake, and its role in mitochondrial function, metabolic reprograming, and cancer biology, linking copper metabolism with the field of regenerative medicine and cancer.
Green Strategy–Based Synthesis of Silver Nanoparticles for Antibacterial Applications
Authors: Ssekatawa Kenneth , Byarugaba Denis K. , Kato Charles D. , Wampande Eddie M. , Ejobi Francis , Nakavuma Jesca L. , Maaza Malik , Sackey Juliet , Nxumalo Edward , Kirabira John Baptist
Published: August 2021

Antibiotics have been the nucleus of chemotherapy since their discovery and introduction into the healthcare system in the 1940s. They are routinely used to treat bacterial infections and to prevent infections in patients with compromised immune systems and enhancing growth in livestock. However, resistance to last-resort antibiotics used in the treatment of multidrug-resistant infections has been reported worldwide. Therefore, this study aimed to evaluate green synthesized nanomaterials such as silver nanoparticles (AgNPs) as alternatives to antibiotics. UV-vis spectroscopy surface plasmon resonance peaks for AgNPs were obtained between 417 and 475 nm. An X-ray diffraction analysis generated four peaks for bothPrunus africanaextract (PAE) andCamellia sinensisextract (CSE) biosynthesized AgNPs positioned at 2θ angles of 38.2°, 44.4°, 64.5°, and 77.4° corresponding to crystal planes (111), (200), (220), and (311), respectively. A dynamic light-scattering analysis registered the mean zeta potential of +6.3 mV and +0.9 mV for PAE and CSE biosynthesized nanoparticles, respectively. Fourier transform infrared spectroscopy spectra exhibited bands corresponding to different organic functional groups confirming the capping of AgNPs by PAE and CSE phytochemicals. Field emission scanning electron microscopy imaging showed that AgNPs were spherical with average size distribution ranging from 10 to 19 nm. Biosynthesized AgNPs exhibited maximum growth inhibitory zones of 21 mm with minimum inhibitory concentration and minimum bactericidal concentration of 125 and 250 μg/ml, respectively, against carbapenem-resistant bacteria.
Novel Visualization Methods Assisted Transurethral Resection for Bladder Cancer: An Updated Survival-Based Systematic Review and Meta-Analysis
Authors: Li Honglin , Cao Yubin , Ma Pingchuan , Ma Zhongkai , Li Chunjie , Yang Wenbin , Zhou Lingyun
Published: August 2021

Background

Photodynamic diagnosis and narrow-band imaging could help improve the detection rate in transurethral resection (TUR) of bladder cancer. It remained controversial that the novel visualization method assisted transurethral resection (VA-TUR) could elongate patients’ survival compared to traditional TUR.

Methods

We performed electronic and manual searching until December 2020 to identify randomized controlled trials comparing VA-TUR with traditional TUR, which reported patients’ survival data. Two reviewers independently selected eligible studies, extracted data, assessed the risk of bias. Meta-analysis was conducted according to subgroups of types of visualization methods (A) and clinical stage of participants. Publication bias was detected.

Results

We included 20 studies (reported in 28 articles) in this review. A total of 6,062 participants were randomized, and 5,217 participants were included in the analysis. Only two studies were assessed at low risk of bias. VA-TURB could significantly improve the recurrence-free survival (RFS) (HR = 0.72, 95% CI: 0.66 to 0.79, P <0.00001, I2 = 42%) and progression-free survival (PFS) (HR = 0.62, 95% CI: 0.46 to 0.82, P <0.0008, I2 = 0%) compared with TUR under white light. The results remain stable whatever the type of visualization method. The difference could be observed in the non-muscle-invasive bladder cancer (NMIBC) population (P <0.05) but not in the mixed population with muscle-invasive bladder cancer (MIBC) participants (P >0.05).

Conclusion

VA-TUR could improve RFS and PFS in NMIBC patients. No significant difference is found among different types of VA-TUR. VA-TUR may be not indicated to MIBC patients.
Cystatin-B Negatively Regulates the Malignant Characteristics of Oral Squamous Cell Carcinoma Possibly Via the Epithelium Proliferation/Differentiation Program
Authors: Xu Tian-Tian , Zeng Xiao-Wen , Wang Xin-Hong , Yang Lu-Xi , Luo Gang , Yu Ting
Published: August 2021

Disturbance in the proteolytic process is one of the malignant signs of tumors. Proteolysis is highly orchestrated by cysteine cathepsin and its inhibitors. Cystatin-B (CSTB) is a general cysteine cathepsin inhibitor that prevents cysteine cathepsin from leaking from lysosomes and causing inappropriate proteolysis. Our study found that CSTB was downregulated in both oral squamous cell carcinoma (OSCC) tissues and cells compared with normal controls. Immunohistochemical analysis showed that CSTB was mainly distributed in the epithelial structure of OSCC tissues, and its expression intensity was related to the grade classification. A correlation analysis between CSTB and clinical prognosis was performed using gene expression data and clinical information acquired from The Cancer Genome Atlas (TCGA) database. Patients with lower expression levels of CSTB had shorter disease-free survival times and poorer clinicopathological features (e.g., lymph node metastases, perineural invasion, low degree of differentiation, and advanced tumor stage). OSCC cell models overexpressing CSTB were constructed to assess the effects of CSTB on malignant biological behaviors and upregulation of CSTB inhibited cell proliferation, migration, and invasion in vitro. Weighted gene correlation network analysis (WGCNA) and gene set enrichment analysis (GSEA) were performed based on the TCGA data to explore potential mechanisms, and CSTB appeared to correlate with squamous epithelial proliferation-differentiation processes, such as epidermal cell differentiation and keratinization. Moreover, in WGCNA, the gene module most associated with CSTB expression (i.e., the brown module) was also the one most associated with grade classification. Upregulation of CSTB promoted the expression levels of markers (LOR, IVL, KRT5/14, and KRT1/10), reflecting a tendency for differentiation and keratinization in vitro. Gene expression profile data of the overexpressed CSTB cell line were obtained by RNA sequencing (RNA-seq) technology. By comparing the GSEA enrichment results of RNA-seq data (from the OSCC models overexpressing CSTB) and existing public database data, three gene sets (i.e., apical junction, G2/M checkpoint, etc.) and six pathways (e.g., NOTCH signaling pathway, glycosaminoglycan degradation, mismatch repair, etc.) were enriched in the data from both sources. Overall, our study shows that CSTB is downregulated in OSCC and might regulate the malignant characteristics of OSCC via the epithelial proliferation/differentiation program.
Association of Serum Anti-PCSK9 Antibody Levels with Favorable Postoperative Prognosis in Esophageal Cancer
Authors: Ito Masaaki , Hiwasa Takaki , Oshima Yoko , Yajima Satoshi , Suzuki Takashi , Nanami Tatsuki , Sumazaki Makoto , Shiratori Fumiaki , Funahashi Kimihiko , Li Shu-Yang , Iwadate Yasuo , Yamagata Hiroki , Jambaljav Byambasteren , Takemoto Minoru , Yokote Koutaro , Takizawa Hirotaka , Shimada Hideaki
Published: August 2021

Background

Esophageal cancer often appears as postoperative metastasis or recurrence after radical surgery. Although we had previously reported that serum programmed cell death ligand 1 (PD-L1) level correlated with the prognosis of esophageal cancer, further novel biomarkers are required for more precise prediction of the prognosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with the cholesterol metabolism. But there was no report of relationship between serum PCSK9 antibody and cancer. Therefore, we investigated whether anti-PCSK9 antibodies could be a novel biomarker for solid cancer.

Methods

Serum levels of anti-PCSK9 antibodies and antigens in patients with solid cancer were analyzed using amplified luminescence proximity homogeneous assay-linked immunosorbent assay (AlphaLISA). The reactivity of serum antibodies against recombinant PCSK9 protein was investigated by Western blotting, and the expression of PCSK9 antigens in esophageal cancer tissues was examined by immunohistochemical staining.

Results

AlphaLISA showed that serum anti-PCSK9 antibody (s-PCSK9-Ab) levels were significantly higher in patients with esophageal cancer, gastric cancer, colorectal cancer, lung cancer, and breast cancer than in healthy donors, and patients with esophageal cancer had the highest levels. The presence of serum antibody in patients was confirmed by Western blotting. There was no apparent correlation between s-PCSK9-Ab and PCSK9 antigen levels. Immunohistochemical staining demonstrated the expression of PCSK9 antigen in both the cytoplasm and nuclear compartments of esophageal squamous cell carcinoma tissue but not in normal tissue. Compared with patients with low s-PCSK9-Ab levels, those with high s-PCSK9-Ab levels had a favorable postoperative prognosis after radical surgery for esophageal cancer. In the multivariate analysis, tumor depth and s-PCSK9-Ab level were identified as independent prognostic factors. In the univariate analysis of clinicopathological features, high PCSK9 antibody levels were not associated with sex, age, location, tumor depth, lymph node status, squamous cell carcinoma antigen, or p53-Ab, whereas they correlated significantly with PD-L1 levels, which were associated with unfavorable prognosis. Correlation between s-PCSK9-Ab and PD-L1 levels was also confirmed in the logistic regression analysis; therefore, low s-PCSK9-Ab levels could discriminate another poor prognosis group other than high-PD-L1 group.

Conclusions

Patients with solid cancer had higher s-PCSK9-Ab levels than healthy donors. High s-PCSK9-Ab levels indicated better prognosis for overall survival after surgery in patients with esophageal cancer.