bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding Deterioration due to Salt and Ice Crystallization in Scandinavian Massive Brick Masonry
Authors: Balksten Kristin , Strandberg-de Bruijn Paulien
Published: February 2021

Extensive durability problems such as weathering and degradation are found in historic Scandinavian brick masonry buildings, especially from the neo-Gothic period. These are largely due to the crystallization of salts and frost action in the bricks and mortars. This article aims to show and illustrate which salts and crystals are found in historic brick masonry buildings and to describe their appearance and behavior. An additional aim is to explore possibilities of preventing salt-related damage on internal masonry wall surfaces, such as using hemp-lime sacrificial plaster beneath the plaster. The objective is to show the mechanisms behind salt-related problems and to perform a case study and a laboratory study on salt-damaged brick masonry containing sodium sulphate. In order to prevent and stop damage to the masonry, it is important to be able to identify the nature of the salt damage and the type of salt that caused the damage. Neo-Gothic brick masonry buildings require well-planned, continuous maintenance of the masonry. It is therefore of the utmost importance to have an understanding of the complex functions of the masonry and of the salts that can cause damage to these historic buildings.
Wnt/β-catenin Pathway-Mediated PPARδ Expression during Embryonic Development Differentiation and Disease
Authors: Sidrat Tabinda , Rehman Zia-Ur , Joo Myeong-Don , Lee Kyeong-Lim , Kong Il-Keun
Published: February 2021

The Wnt/β-catenin signaling pathway plays a crucial role in early embryonic development. Wnt/β-catenin signaling is a major regulator of cell proliferation and keeps embryonic stem cells (ESCs) in the pluripotent state. Dysregulation of Wnt signaling in the early developmental stages causes several hereditary diseases that lead to embryonic abnormalities. Several other signaling molecules are directly or indirectly activated in response to Wnt/β-catenin stimulation. The crosstalk of these signaling factors either synergizes or opposes the transcriptional activation of β-catenin/Tcf4-mediated target gene expression. Recently, the crosstalk between the peroxisome proliferator-activated receptor delta (PPARδ), which belongs to the steroid superfamily, and Wnt/β-catenin signaling has been reported to take place during several aspects of embryonic development. However, numerous questions need to be answered regarding the function and regulation of PPARδ in coordination with the Wnt/β-catenin pathway. Here, we have summarized the functional activation of the PPARδ in co-ordination with the Wnt/β-catenin pathway during the regulation of several aspects of embryonic development, stem cell regulation and maintenance, as well as during the progression of several metabolic disorders.
Hypoxia-Induced Non-Coding RNAs Controlling Cell Viability in Cancer
Authors: Barreca Maria Magdalena , Zichittella Chiara , Alessandro Riccardo , Conigliaro Alice
Published: February 2021

Hypoxia, a characteristic of the tumour microenvironment, plays a crucial role in cancer progression and therapeutic response. The hypoxia-inducible factors (HIF-1α, HIF-2α, and HIF-3α), are the master regulators in response to low oxygen partial pressure, modulating hypoxic gene expression and signalling transduction pathways. HIFs’ activation is sufficient to change the cell phenotype at multiple levels, by modulating several biological activities from metabolism to the cell cycle and providing the cell with new characteristics that make it more aggressive. In the past few decades, growing numbers of studies have revealed the importance of non-coding RNAs (ncRNAs) as molecular mediators in the establishment of hypoxic response, playing important roles in regulating hypoxic gene expression at the transcriptional, post-transcriptional, translational, and posttranslational levels. Here, we review recent findings on the different roles of hypoxia-induced ncRNAs in cancer focusing on the data that revealed their involvement in tumour growth.
CRISPR/Cas9 Mediated Knock Down of δ-ENaC Blunted the TNF-Induced Activation of ENaC in A549 Cells
Authors: Shabbir Waheed , Topcagic Nermina , Aufy Mohammed , Oz Murat
Published: February 2021

Tumor necrosis factor (TNF) is known to activate the epithelial Na+ channel (ENaC) in A549 cells. A549 cells are widely used model for ENaC research. The role of δ-ENaC subunit in TNF-induced activation has not been studied. In this study we hypothesized that δ-ENaC plays a major role in TNF-induced activation of ENaC channel in A549 cells which are widely used model for ENaC research. We used CRISPR/Cas 9 approach to knock down (KD) the δ-ENaC in A549 cells. Western blot and immunofluorescence assays were performed to analyze efficacy of δ-ENaC protein KD. Whole-cell patch clamp technique was used to analyze the TNF-induced activation of ENaC. Overexpression of wild type δ-ENaC in the δ-ENaC KD of A549 cells restored the TNF-induced activation of whole-cell Na+ current. Neither N-linked glycosylation sites nor carboxyl terminus domain of δ-ENaC was necessary for the TNF-induced activation of whole-cell Na+ current in δ-ENaC KD of A549 cells. Our data demonstrated that in A549 cells the δ-ENaC plays a major role in TNF-induced activation of ENaC.
Aspects of Distance Education in Combination with Home Offices
Authors: Rozehnal Petr , Danel Roman
Published: February 2021

This article discusses the impact of a lockdown caused by the novel coronavirus disease 2019 on the educational process at a selected faculty of a public university in the Czech Republic focused on economic education. The aim was to capture relevant aspects in the context of impacts on the management of the educational process in the organization. The unique situation brought the possibility of analyzing the flexibility of the organization, its ability to adapt. A questionnaire survey was conducted among academics. We found out how they coped with this situation, their technical equipment, support from the faculty, and whether they encountered any problems. The goal of the article was not to bring an exact evaluation of selected questions, but to show the state of the actual situation, to point out possible problems of users, and to link these things with the approach to the management of the organization. Based on the analysis, we bring suggestions and recommendations for improving the process of transition to online learning as well as distance education management and recommendation to support teaching, regardless of the teacher’s workplace. The basic areas and activities that need to be managed were also identified.
A Safety Analysis Method for Control Software in Coordination with FMEA and FTA
Authors: Takahashi Masakazu , Anang Yunarso , Watanabe Yoshimichi
Published: February 2021

In this study, we proposed a method to improve the safety level of control software (CSW) by managing the CSW’s design information and safety analysis results, and combining failure mode and effects analysis (FMEA) and fault tree analysis (FTA). Here, the CSW is developed using structured analysis and design methodology. In the upper stage of the CSW’s development process, as the input of the preliminary design information (data flow diagrams (DFDs) and control flow diagrams (CFDs)), the causes of undesirable events of the CSW are clarified by FMEA, and the countermeasures are reflected in the preliminary design information. In the lower stage of the CSW’s development process, as the inputs of the detailed design information (DFDs and CFDs in the lower level) and programs, the causes of the specific undesirable event are clarified by FTA, and the countermeasures are reflected in the detailed design specifications and programs. The processes are repeated until the impact of undesirable events become the acceptable safety level. By applying the proposed method to the CSW installed into a communication control equipment on the space system, we clarified several undesirable events and adopted adequate countermeasures. Consequently, a safer CSW is developed by applying the proposed method.
Windows PE Malware Detection Using Ensemble Learning
Authors: Azeez Nureni Ayofe , Odufuwa Oluwanifise Ebunoluwa , Misra Sanjay , Oluranti Jonathan , Damaševičius Robertas
Published: February 2021

In this Internet age, there are increasingly many threats to the security and safety of users daily. One of such threats is malicious software otherwise known as malware (ransomware, Trojans, viruses, etc.). The effect of this threat can lead to loss or malicious replacement of important information (such as bank account details, etc.). Malware creators have been able to bypass traditional methods of malware detection, which can be time-consuming and unreliable for unknown malware. This motivates the need for intelligent ways to detect malware, especially new malware which have not been evaluated or studied before. Machine learning provides an intelligent way to detect malware and comprises two stages: feature extraction and classification. This study suggests an ensemble learning-based method for malware detection. The base stage classification is done by a stacked ensemble of fully-connected and one-dimensional convolutional neural networks (CNNs), whereas the end-stage classification is done by a machine learning algorithm. For a meta-learner, we analyzed and compared 15 machine learning classifiers. For comparison, five machine learning algorithms were used: naïve Bayes, decision tree, random forest, gradient boosting, and AdaBoosting. The results of experiments made on the Windows Portable Executable (PE) malware dataset are presented. The best results were obtained by an ensemble of seven neural networks and the ExtraTrees classifier as a final-stage classifier.
Sexual Competitiveness and Induced Egg Sterility by Aedes aegypti and Aedes albopictus Gamma-Irradiated Males: A Laboratory and Field Study in Mexico
Authors: Bond J. Guillermo , Aguirre-Ibáñez Santiago , Osorio Adriana R. , Marina Carlos F. , Gómez-Simuta Yeudiel , Tamayo-Escobar Rodolfo , Dor Ariane , Liedo Pablo , Carvalho Danilo O. , Williams Trevor
Published: February 2021

The sterile insect technique may prove useful for the suppression of mosquito vectors of medical importance in regions where arboviruses pose a serious public health threat. In the present study, we examined the effects of sterilizing irradiation doses across different ratios of fertile:irradiated males on the mating competitiveness of Ae. aegypti and Ae. albopictus under laboratory and field-cage conditions. For both species, the percentage of females inseminated and the number of eggs laid over two gonotrophic cycles varied significantly in mating treatments involving 1:1, 1:5, and 1:10 fertile:irradiated males compared to controls of entirely fertile or entirely irradiated males but was not generally affected by the irradiation dose. Egg hatching was negatively affected in females exposed to increasing proportions of irradiated males in both laboratory and field cages. Male competitiveness (Fried’s index) values varied from 0.19 to 0.58 in the laboratory and were between 0.09 and 1.0 in field cages, depending on th species. Competitiveness values were negatively affected by th eirradiation dose in both species under field-cage conditions, whereas in the laboratory, Ae. albopictus was sensitive to the dose but Ae. aegypti was not. In general, male competitiveness was similar across all mating regimes. Most importantly, induced egg sterility was positively correlated with the proportion of irradiated males present in the mating treatments, reaching a maximum of 88% under field-cage conditions for both Ae. aegypti and Ae. albopictus males treated with 50 and 40 Gy irradiation, respectively. These results indicate that sterile males produced at our facility are suitable and competitive enough for field pilot SIT projects and provide guidance to decide the optimal sterile:fertile ratios.
Does Ammonia Released from Protein-Based Attractants Modulate the Capture of Anastrepha obliqua (Diptera: Tephritidae)?
Authors: Lasa Rodrigo , Williams Trevor
Published: February 2021

Tephritid fly responses to food-based attractants involve a complex range of food-derived semiochemicals, including ammonia. We performed laboratory and field experiments to compare the attraction of Anastrepha obliqua (Macquart) to ammonia with the attraction to commercial food attractants and torula yeast at a range of pHs. A positive correlation was established between the concentration of ammonia in solution (1.5–150 mM ammonium solution) and gaseous ammonia released by bottle-type traps. This resulted in an asymptotic response in captures of A. obliqua flies in traps that released 99–295 µg ammonia/h. Pairwise comparisons in laboratory cages revealed that traps baited with 150 mM ammonia solution captured similar numbers of A. obliqua as traps baited with Biolure 2C, CeraTrap, and hydrolyzed protein products (Captor, Winner, and Flyral) plus borax, despite the low quantities of ammonia (11–56 µg/h) released from these attractants. Subsequent choice experiment captures in traps containing ammonia solution were similar or higher than those of commercial attractants, with the exception of Winner + borax, but were not correlated with the ammonia released from attractants. Captures of flies in traps containing ammonia solution were increased by the addition of 1% torula yeast or torula yeast alkalized with sodium hydroxide or borax despite differences in the quantities of ammonia released. Fly captures generally increased with increasing alkalization of torula yeast (pH 7.5–9.5). In the field, torula yeast in ammonia solution captured similar numbers of A. obliqua flies as Captor + borax when traps were evaluated after 24 h but not after a 7-day trapping period. Traps baited with ammonia solution or Winner + borax were significantly less attractive than Captor + borax in both field experiments. We conclude that A. obliqua flies are attracted to ammonia solutions of increasing concentration, up to 150 mM, in the absence of other stimuli, whereas attraction to commercial attractants or alkalized torula yeast is not correlated with the release of ammonia.
Process Automation in an IoT–Fog–Cloud Ecosystem: A Survey and Taxonomy
Authors: Chegini Hossein , Naha Ranesh Kumar , Mahanti Aniket , Thulasiraman Parimala
Published: February 2021

The number of IoT sensors and physical objects accommodated on the Internet is increasing day by day, and traditional Cloud Computing would not be able to host IoT data because of its high latency. Being challenged of processing all IoT big data on Cloud facilities, there is not enough study on automating components to deal with the big data and real-time tasks in the IoT–Fog–Cloud ecosystem. For instance, designing automatic data transfer from the fog layer to cloud layer, which contains enormous distributed devices is challenging. Considering fog as the supporting processing layer, dealing with decentralized devices in the IoT and fog layer leads us to think of other automatic mechanisms to manage the existing heterogeneity. The big data and heterogeneity challenges also motivated us to design other automatic components for Fog resiliency, which we address as the third challenge in the ecosystem. Fog resiliency makes the processing of IoT tasks independent to the Cloud layer. This survey aims to review, study, and analyze the automatic functions as a taxonomy to help researchers, who are implementing methods and algorithms for different IoT applications. We demonstrated the automatic functions through our research in accordance to each challenge. The study also discusses and suggests automating the tasks, methods, and processes of the ecosystem that still process the data manually.
From Stripes to a Beating Heart: Early Cardiac Development in Zebrafish
Authors: Kemmler Cassie L. , Riemslagh Fréderike W. , Moran Hannah R. , Mosimann Christian
Published: February 2021

The heart is the first functional organ to form during vertebrate development. Congenital heart defects are the most common type of human birth defect, many originating as anomalies in early heart development. The zebrafish model provides an accessible vertebrate system to study early heart morphogenesis and to gain new insights into the mechanisms of congenital disease. Although composed of only two chambers compared with the four-chambered mammalian heart, the zebrafish heart integrates the core processes and cellular lineages central to cardiac development across vertebrates. The rapid, translucent development of zebrafish is amenable to in vivo imaging and genetic lineage tracing techniques, providing versatile tools to study heart field migration and myocardial progenitor addition and differentiation. Combining transgenic reporters with rapid genome engineering via CRISPR-Cas9 allows for functional testing of candidate genes associated with congenital heart defects and the discovery of molecular causes leading to observed phenotypes. Here, we summarize key insights gained through zebrafish studies into the early patterning of uncommitted lateral plate mesoderm into cardiac progenitors and their regulation. We review the central genetic mechanisms, available tools, and approaches for modeling congenital heart anomalies in the zebrafish as a representative vertebrate model.
Sinus Bradycardia Associated with Remdesivir Treatment in COVID-19: A Case Report and Literature Review
Authors: Barkas Fotios , Styla Chrysoula-Paraskevi , Bechlioulis Aris , Milionis Haralampos , Liberopoulos Evangelos
Published: February 2021

Background: Although remdesivir treatment is widely used during the pandemic coronavirus disease 2019 (COVID-19), there is scarce evidence regarding its cardiac side effects. Case presentation: We report the case of a 36-year-old male hospitalized due to severe COVID-19 symptoms. He presented with a 10-day history of fever (up to 39.7 °C), productive cough, hemoptysis, fatigue, myalgias and hypoxemia. The patient received supplemental oxygen, dexamethasone, remdesivir and empirical antibiotic treatment according to protocol. Asymptomatic sinus bradycardia developed on hospital day 3 (namely, heart rate 39/min compared to 92/min on admission). Secondary causes of bradycardia were excluded based on the absence of relevant evidence from laboratory work-up and echocardiographic examination. The patient’s rhythm restored to normal 9 days after the discontinuation of remdesivir. Conclusions: Considering the frequent use of remdesivir in patients with COVID-19, physicians should be aware of this possible adverse event.
Endorectal Ultrasound and Magnetic Resonance Imaging for Rectal Cancer Staging: A Modern Multimodality Approach
Authors: Reginelli Alfonso , Clemente Alfredo , Sangiovanni Angelo , Nardone Valerio , Selvaggi Francesco , Sciaudone Guido , Ciardiello Fortunato , Martinelli Erika , Grassi Roberto , Cappabianca Salvatore
Published: February 2021

Preoperative staging represents a crucial point for the management, type of surgery, and candidacy for neoadjuvant therapy in patient with rectal cancer. The most recent clinical guidelines in oncology recommend an accurate preoperative evaluation in order to address early and advanced tumors to different therapeutic options. In particular, potential pitfalls may occur in the assessment of T3 tumors, which represents the most common stage at diagnosis. The depth of tumor invasion is known to be an important prognostic factor in rectal carcinoma; as a consequence, the T3 imaging classification has a substantial importance for treatment strategy and patient survival. However, the differentiation between tumor invasion of perirectal fat and mesorectal desmoplastic reactions remains a main goal for radiologists. Magnetic resonance imaging (MRI) is actually considered as the best imaging modality for rectal cancer staging. Although the endorectal ultrasound (ERUS) is the preferred staging method for early tumors, it could also be useful in identifying perirectal fat invasion. Moreover, the addiction of diffusion weighted imaging (DWI) improves the diagnostic performance of MRI in rectal cancer staging by adding functional information about rectal tumor and adjacent mesorectal tissues. This study investigated the diagnostic performance of conventional MRI alone, in combination with the DWI technique and ERUS in order to assess the best diagnostic imaging combination for rectal cancer staging.
Updated Review and Meta-Analysis of Probiotics for the Treatment of Clinical Depression: Adjunctive vs. Stand-Alone Treatment
Authors: Nikolova Viktoriya , Cleare Anthony , Young Allan , Stone James
Published: February 2021

Recent years have seen a rapid increase in the use of gut microbiota-targeting interventions, such as probiotics, for the treatment of psychiatric disorders. The objective of this update review was to evaluate all randomised controlled clinical trial evidence on the efficacy of probiotics for clinical depression. Cochrane guidelines for updated reviews were followed. By searching PubMed and Web of Science databases, we identified 546 new records since our previous review. A total of seven studies met selection criteria, capturing 404 people with depression. A random effects meta-analysis using treatment type (stand-alone vs. adjunctive) as subgroup was performed. The results demonstrated that probiotics are effective in reducing depressive symptoms when administered in addition to antidepressants (SMD = 0.83, 95%CI 0.49–1.17), however, they do not seem to offer significant benefits when used as stand-alone treatment (SMD = −0.02, 95%CI −0.34–0.30). Potential mechanisms of action may be via increases in brain-derived neurotrophic factor (BDNF) and decreases in C-reactive protein (CRP), although limited evidence is available at present. This review offers stronger evidence to support the clinical use of probiotics in depressed populations and provides an insight into the mode of administration more likely to yield antidepressant effects.
Mitral Valve Annulus Dimensions Assessment with Three-Dimensional Echocardiography Versus Computed Tomography: Implications for Transcatheter Interventions
Authors: Hirasawa Kensuke , Vo N. Mai , Gegenava Tea , Pio Stephan Milhorini , van Wijngaarden Suzanne E. , Ajmone Marsan Nina , Bax Jeroen J. , Delgado Victoria
Published: February 2021

The aim of this study is to evaluate the agreement between three-dimensional (3D) transesophageal echocardiography (TEE) and multidetector computed tomography (MDCT) for assessing mitral annular (MA) dimensions. A total of 105 patients (79 ± 9 years old, 52% male) who underwent clinically indicated 3D TEE and MDCT feasible for MA geometrical assessment were included. Using dedicated semi-automated postprocessing software, MA geometry, including mitral annular area (MAA), perimeter, septal-lateral (SL) diameter, and inter-trigonal (TT) diameter, was evaluated using 3D TEE and MDCT. Compared to 3D TEE, MAA, perimeter, and SL distance measured on MDCT data were larger (9.9 ± 3.0 vs. 9.3 ± 3.1 cm2 for MAA; 115 ± 18 vs. 108 ± 18 mm for perimeter; and 35 ± 5 vs. 32 ± 5 cm for SL distance, all p < 0.001). By contrast, the TT distance was comparable between MDCT and 3D TEE (26 ± 4 vs. 26 ± 4 cm, p = 0.258). The correlations of all the MA dimensions were good to excellent between the two modalities (R = 0.911 for MAA, 0.890 for perimeter, 0.739 for TT distance, and 0.857 for SL distance, respectively, all p < 0.001). This study showed good agreement between 3D TEE- and MDCT-derived MA measurements although MDCT systematically provided larger MAA, perimeter, and SL distance compared with 3D TEE.
Effect of Excessive Body Weight and Emotional Disorders on the Course of Pregnancy and Well-Being of a Newborn before and during COVID-19 Pandemic
Authors: Wdowiak Artur , Makara-Studzińska Marta , Raczkiewicz Dorota , Janczyk Paula , Słabuszewska-Jóźwiak Aneta , Wdowiak-Filip Anita , Studzińska Noemi
Published: February 2021

This study aimed to evaluate whether excessive body weight and the COVID-19 pandemic affect depression, and subsequently whether depression, excessive body weight, and the COVID-19 pandemic affect the course of pregnancy, as well as the well-being of a newborn. The research material included data retrieved from the medical records of 280 pregnant women who were provided with care by medical facilities in Lublin (100 women with normal weight, 100 overweight women, 50 with Class I and 30 with Class II obesity). They completed a Beck depression inventory (BDI) in pregnancy twice, in order to assess the risk of occurrence of postpartum depression. Pre-pregnancy BMI positively correlated with the severity of depression, both at 10–13 weeks of pregnancy (p < 0.001), and at 32 weeks of pregnancy (p < 0.001). The higher the pre-pregnancy BMI, on average the higher the severity of depression. The severity of depression was significantly higher during the pandemic than before it in women with normal body weight before pregnancy (p < 0.001), as well as in those overweight (p < 0.001) and with Class II obesity (p = 0.015). Excessive body weight before pregnancy leads to depressive disorders during pregnancy, increases the risk of preterm delivery, and exerts a negative effect on the state of a newborn. Depressive symptoms among pregnant, overweight and obese women intensified during the COVID-19 pandemic.
Risk of Hospital Readmission among Older Patients Discharged from the Rehabilitation Unit in a Rural Community Hospital: A Retrospective Cohort Study
Authors: Ohta Ryuichi , Sano Chiaki
Published: February 2021

Rehabilitation for hospitalized older people can improve their independence for performing activities of daily living (ADL), but determining its appropriateness can be challenging because of inherent limitations in their ADL and short life expectancy. Thus, we aimed to clarify the benefit of rehabilitation among older Japanese patients. We retrospectively evaluated consecutive older patients (age > 65 years) admitted to the rehabilitation unit of a rural community hospital between 1 April 2016 and 31 March 2020. The primary outcome measure was readmission for acute conditions. Of the 732 patients evaluated, 311 patients (42.5%) were readmitted. Readmission was significantly associated with body mass index (BMI) (p < 0.001), dependent condition (p < 0.001), higher cognitive domain scores in the functional independence measure (FIM) (p = 0.019), and polypharmacy (p = 0.026). The most frequent cause of readmission was pyelonephritis (11.9%), followed by pneumonia (10.9%), compression fracture (10.6%), heat stroke (8.4%), and cerebral stroke (8.0%). In conclusion, older Japanese patients discharged from rehabilitation units have lower readmission rates than those previously reported. Thus, better nutritional control, a multidisciplinary approach to the management of cognitive dysfunction, and a decrease in polypharmacy could be associated with improved outcomes among discharged older patients.
Serum TARC Levels in Patients with Systemic Sclerosis: Clinical Association with Interstitial Lung Disease
Authors: Kuzumi Ai , Yoshizaki Ayumi , Ebata Satoshi , Fukasawa Takemichi , Yoshizaki-Ogawa Asako , Asano Yoshihide , Oba Koji , Sato Shinichi
Published: February 2021

Systemic sclerosis (SSc) is a multisystem fibrotic disorder with autoimmune background. Accumulating evidence has highlighted the importance of T helper (Th) 2 cells in the pathogenesis of SSc and its complications. Because thymus and activation-regulated chemokine (TARC) is a potent chemoattractant for Th2 cells, we measured serum TARC levels in SSc patients and analyzed their correlation with interstitial lung disease (ILD), a major complication of SSc. Serum TARC levels were significantly elevated in patients with SSc, especially in those with the diffuse subtype, compared with healthy controls. In particular, dcSSc patients with SSc-associated ILD (SSc-ILD) showed higher TARC levels than those without SSc-ILD. However, there was no significant correlation between serum TARC levels and pulmonary function in SSc patients. Serum TARC levels did not correlate with serum levels of interleukin-13, an important Th2 cytokine, either. Furthermore, in the longitudinal study, serum TARC levels did not predict the onset or progression of SSc-ILD in patients with SSc. These results were in contrast with those of KL-6 and surfactant protein D, which correlated well with the onset, severity, and progression of SSc-ILD. Overall, these results suggest that serum TARC levels are not suitable for monitoring the disease activity of SSc-ILD.
Same Day Discharge versus Inpatient Surgery for Robot-Assisted Radical Prostatectomy: A Comparative Study
Authors: Rahota Razvan George , Salin Ambroise , Gautier Jean Romain , Almeras Christophe , Loison Guillaume , Tollon Christophe , Beauval Jean Baptiste , Ploussard Guillaume
Published: February 2021

(1) Background: no study has compared outcomes of same day discharge (SDD) versus inpatient robot-assisted radical prostatectomy (RARP) in homogenous cohorts. Our aim was to compare perioperative outcomes and urinary continence recovery between SDD and inpatient RARP in contemporary, comparable patients. (2) Methods: we included consecutive patients undergoing RARP between 2018 and 2020 (n = 376). Only patients eligible for SDD (no oral anticoagulant, distance home-hospital <150 km) and having >6-month follow-up were included (n = 180). All patients underwent RARP with or without lymph node dissection. Comparisons were performed between SDD (n = 42) and inpatient RARP (n = 138). Primary outcomes were 90-day complication and readmission rates and continence rates at 1 and 6 months. (3) Results: median patient age was 66.7 years. Median duration of surgery and blood loss was 134 min and 200 mL, respectively. Lymph node dissection and nerve-sparing procedures were performed in 76.7% and 82.2% of cases, respectively. Median follow-up was 19.5 months. No difference was seen regarding patient features, peri-operative outcomes, and pathology parameters between both groups. The proportion of SDD RARP was stable over time (23.5%). The 90-day unplanned visits, readmission and complication rates were 9.5%, 7.1%, and 19.0% in SDD patients versus 14.5% (p = 0.407), 10.1% (p = 0.560), 28.3% (p = 0.234) for inpatient RARP, respectively. Trends favoring SDD were not statistically significant. Continence rates at 1-(p = 0.589) and 6-months (p = 0.674) were comparable between SDD and inpatient RARP. The main limitation was the lack of randomization. (4) Conclusions: this multi-surgeon comparative study confirms the safety of routine SDD RARP in terms of perioperative and functional outcomes. Trends favoring SDD in terms of complications, emergency visits and readmission have to be confirmed.
Curiosity or Underdiagnosed? Injuries to Thoracolumbar Spine with Concomitant Trauma to Pancreas
Authors: Hax Jakob , Halvachizadeh Sascha , Jensen Kai Oliver , Berk Till , Teuber Henrik , Di Primio Teresa , Lefering Rolf , Pape Hans-Christoph , Sprengel Kai ,   TraumaRegister DGU
Published: February 2021

The pancreas is at risk of damage as a consequence of thoracolumbar spine injury. However, there are no studies providing prevalence data to support this assumption. Data from European hospitals documented in the TraumaRegister DGU® (TR-DGU) between 2008–2017 were analyzed to estimate the prevalence of this correlation and to determine the impact on clinical outcome. A total of 44,279 patients with significant thoracolumbar trauma, defined on Abbreviated Injury Scale (AIS) as ≥2, were included. Patients transferred to another hospital within 48 h were excluded to prevent double counting. A total of 135,567 patients without thoracolumbar injuries (AIS ≤ 1) were used as control group. Four-hundred patients with thoracolumbar trauma had a pancreatic injury. Pancreatic injuries were more common after thoracolumbar trauma (0.90% versus (vs.) 0.51%, odds ratio (OR) 1.78; 95% confidence intervals (CI), 1.57–2.01). Patients with pancreatic injuries were more likely to be male (68%) and had a higher mean Injury Severity Score (ISS) than those without (35.7 ± 16.0 vs. 23.8 ± 12.4). Mean length of stay (LOS) in intensive care unit (ICU) and hospital was longer with pancreatic injury. In-hospital mortality was 17.5% with and 9.7% without pancreatic injury, respectively. Although uncommon, concurrent pancreatic injury in the setting of thoracolumbar trauma can portend a much more serious injury.
Update on New Aspects of the Renin-Angiotensin System in Hepatic Fibrosis and Portal Hypertension: Implications for Novel Therapeutic Options
Authors: Rajapaksha Indu G. , Gunarathne Lakmie S. , Angus Peter W. , Herath Chandana B.
Published: February 2021

There is considerable experimental evidence that the renin angiotensin system (RAS) plays a central role in both hepatic fibrogenesis and portal hypertension. Angiotensin converting enzyme (ACE), a key enzyme of the classical RAS, converts angiotensin I (Ang I) to angiotensin II (Ang II), which acts via the Ang II type 1 receptor (AT1R) to stimulate hepatic fibrosis and increase intrahepatic vascular tone and portal pressure. Inhibitors of the classical RAS, drugs which are widely used in clinical practice in patients with hypertension, have been shown to inhibit liver fibrosis in animal models but their efficacy in human liver disease is yet to be tested in adequately powered clinical trials. Small trials in cirrhotic patients have demonstrated that these drugs may lower portal pressure but produce off-target complications such as systemic hypotension and renal failure. More recently, the alternate RAS, comprising its key enzyme, ACE2, the effector peptide angiotensin-(1–7) (Ang-(1–7)) which mediates its effects via the putative receptor Mas (MasR), has also been implicated in the pathogenesis of liver fibrosis and portal hypertension. This system is activated in both preclinical animal models and human chronic liver disease and it is now well established that the alternate RAS counter-regulates many of the deleterious effects of the ACE-dependent classical RAS. Work from our laboratory has demonstrated that liver-specific ACE2 overexpression reduces hepatic fibrosis and liver perfusion pressure without producing off-target effects. In addition, recent studies suggest that the blockers of the receptors of alternate RAS, such as the MasR and Mas related G protein-coupled receptor type-D (MrgD), increase splanchnic vascular resistance in cirrhotic animals, and thus drugs targeting the alternate RAS may be useful in the treatment of portal hypertension. This review outlines the role of the RAS in liver fibrosis and portal hypertension with a special emphasis on the possible new therapeutic approaches targeting the ACE2-driven alternate RAS.
Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes
Authors: Lee Byung-Chul , Kang Insung , Yu Kyung-Rok
Published: February 2021

Identification of the immunomodulatory and regenerative properties of mesenchymal stem cells (MSCs) have made them an attractive alternative therapeutic option for diseases with no effective treatment options. Numerous clinical trials have followed; however, issues such as infusional toxicity and cellular rejection have been reported. To address these problems associated with cell-based therapy, MSC exosome therapy was developed and has shown promising clinical outcomes. MSC exosomes are nanosized vesicles secreted from MSCs and represent a non-cellular therapeutic agent. MSC exosomes retain therapeutic features of the cells from which they originated including genetic material, lipids, and proteins. Similar to MSCs, exosomes can induce cell differentiation, immunoregulation, angiogenesis, and tumor suppression. MSC exosomes have therefore been employed in several experimental models and clinical studies. Here, we review the therapeutic potential of MSC-derived exosomes and summarize currently ongoing clinical trials according to disease type. In addition, we propose several functional enhancement strategies for the effective clinical application of MSC exosome therapy.
Clinical and Laboratory Predictors for the Development of Low Cardiac Output Syndrome in Infants Undergoing Cardiopulmonary Bypass: A Pilot Study
Authors: Drennan Sarah E. , Burge Kathryn Y. , Szyld Edgardo G. , Eckert Jeffrey V. , Mir Arshid M. , Gormley Andrew K. , Schwartz Randall M. , Daves Suanne M. , Thompson Jess L. , Burkhart Harold M. , Chaaban Hala
Published: February 2021

Cardiac surgery employing cardiopulmonary bypass exposes infants to a high risk of morbidity and mortality. The objective of this study was to assess the utility of clinical and laboratory variables to predict the development of low cardiac output syndrome, a frequent complication following cardiac surgery in infants. We performed a prospective observational study in the pediatric cardiovascular ICU in an academic children’s hospital. Thirty-one patients with congenital heart disease were included. Serum levels of nucleosomes and a panel of 20 cytokines were measured at six time points in the perioperative period. Cardiopulmonary bypass patients were characterized by increased levels of interleukin-10, -6, and -1α upon admission to the ICU compared to non-bypass cardiac patients. Patients developing low cardiac output syndrome endured longer aortic cross-clamp time and required greater inotropic support at 12 h postoperatively compared to bypass patients not developing the condition. Higher preoperative interleukin-10 levels and 24 h postoperative interleukin-8 levels were associated with low cardiac output syndrome. Receiver operating characteristic curve analysis demonstrated a moderate capability of aortic cross-clamp duration to predict low cardiac output syndrome but not IL-8. In conclusion, low cardiac output syndrome was best predicted in our patient population by the surgical metric of aortic cross-clamp duration.
Factors Affecting Metabolic Outcomes Post Bariatric Surgery: Role of Adipose Tissue
Authors: Keshavjee Sara H. , Schwenger Katherine J. P. , Yadav Jitender , Jackson Timothy D. , Okrainec Allan , Allard Johane P.
Published: February 2021

Obesity is an ever-growing public health crisis, and bariatric surgery (BS) has become a valuable tool in ameliorating obesity, along with comorbid conditions such as diabetes, dyslipidemia and hypertension. BS techniques have come a long way, leading to impressive improvements in the health of the majority of patients. Unfortunately, not every patient responds optimally to BS and there is no method that is sufficient to pre-operatively predict who will receive maximum benefit from this surgical intervention. This review focuses on the adipose tissue characteristics and related parameters that may affect outcomes, as well as the potential influences of insulin resistance, BMI, age, psychologic and genetic factors. Understanding the role of these factors may help predict who will benefit the most from BS.
Positive Airway Pressure Therapy Adherence with Mask Resupply: A Propensity-Matched Analysis
Authors: Benjafield Adam , Oldstone Liesl , Willes Leslee , Kelly Colleen , Nunez Carlos , Malhotra Atul ,   on behalf of the medXcloud Group
Published: February 2021

There are currently few data on the impact of mask resupply on longer-term adherence to positive airway pressure (PAP) therapy. This retrospective analysis investigated the effects of mask/mask cushion resupply on the adherence to PAP versus no resupply. Deidentified patient billing data for PAP supply items were merged with telemonitoring data from Cloud-connected AirSense 10/AirCurve 10 devices via AirViewTM (ResMed). Eligible patients started PAP between 1 July 2014 and 17 June 2016, had ≥360 days of PAP device data, and achieved initial U.S. Medicare adherence criteria. Patients who received a resupply of mask systems/cushions (resupply group) were propensity-score-matched with those not receiving any mask/cushion resupply (control group). A total of 100,370 patients were included. From days 91 to 360, the mean device usage was 5.6 and 4.5 h/night in the resupply and control groups, respectively (p < 0.0001). The proportion of patients with a mean device usage ≥4 h/night was significantly higher in the resupply group versus the control group (77% vs. 59%; p < 0.0001). The therapy termination rate was significantly lower in the resupply group versus the control group (14.7% vs. 31.9%; p < 0.0001); there was a trend toward lower therapy termination rates as the number of resupplies increased. The replacement of mask interface components was associated with better longer-term adherence to PAP therapy versus no resupply.
Cardiac Arrhythmias in Muscular Dystrophies Associated with Emerinopathy and Laminopathy: A Cohort Study
Authors: Marchel Michał , Madej-Pilarczyk Agnieszka , Tymińska Agata , Steckiewicz Roman , Ostrowska Ewa , Wysińska Julia , Russo Vincenzo , Grabowski Marcin , Opolski Grzegorz
Published: February 2021

Introduction: Cardiac involvement in patients with muscular dystrophy associated with Lamin A/C mutations (LMNA) is characterized by atrioventricular conduction abnormalities and life-threatening cardiac arrhythmias. Little is known about cardiac involvement in patients with emerin mutation (EMD). The aim of our study was to describe and compare the prevalence and time distribution of cardiac arrhythmias at extended follow-up. Patients and methods: 45 consecutive patients affected by muscular dystrophy associated to laminopathy or emerinopathy were examined. All patients underwent clinical evaluation, 12-lead surface electrocardiogram (ECG), 24 h electrocardiographic monitoring, and cardiac implanted device interrogation. Results: At the end of 11 (5.0–16.6) years of follow-up, 89% of the patients showed cardiac arrhythmias. The most prevalent was atrial standstill (AS) (31%), followed by atrial fibrillation/flutter (AF/Afl) (29%) and ventricular tachycardia (22%). EMD patients presented more frequently AF/AFl compared to LMNA (50% vs. 20%, p = 0.06). Half of the EMD patients presented with AS, whilst there was no occurrence of such in the LMNA (p = 0.001). Ventricular arrhythmias were found in 60% of patients with laminopathy compared to 3% in patients with emerinopathy (p < 0.001). The age of AVB occurrence was higher in the LMNA group (32.8 +/− 10.6 vs. 25.1 +/− 9.1, p = 0.03). Conclusions: Atrial arrhythmias are common findings in patients with muscular dystrophy associated with EMD/LMNA mutations; however, they occurred earlier in EMD patients. Ventricular arrhythmias were very common (60%) in LMNA and occurred definitely earlier compared to the EMD group.
Percutaneous Mitral Valve Repair: Outcome Improvement with Operator Experience and a Second-Generation Device
Authors: Freixa Xavier , Estévez-Loureiro Rodrigo , Carrasco-Chinchilla Fernando , Millán Xavier , Amat-Santos Ignacio , Regueiro Ander , Nombela-Franco Luis , Pascual Isaac , Cid Belen , López-Mínguez José Ramón , Hernández-Antolín Rosa Ana , Cruz-González Ignacio , Andraka Leire , Goicolea Javier , Ruíz-Quevedo Valeriano , Díez Jose Luís , Berenguer Alberto , Baz José Antonio , Pan Manuel , Benito-González Tomas , Briales Juan H. Alonso , Li Chi Hion , Sanchis Laura , Serrador Ana , Jiménez-Quevedo Pilar , Avanzas Pablo , Salido Luisa , Fernández-Vázquez Felipe , Hernández-García José Maria , Arzamendi Dabit
Published: February 2021

Background and aim: Recent randomized data comparing percutaneous mitral valve repair (PMVR) versus optimal medical treatment in patients with functional MR (FMR) seemed to highlight the importance of the learning curve not only for procedural outcomes but also for patient selection. The aim of the study was to compare a contemporary series of patients undergoing PMVR using a second-generation Mitraclip device (Mitraclip NT) with previous cohorts treated with a first-generation system. Methods: This multicenter study collected individual data from 18 centers between 2012 and 2017. The cohort was divided into three groups according to the use of the first-generation Mitraclip during the first (control-1) or second half (control-2) or the Mitraclip NT system. Results: A total of 545 consecutive patients were included in the study. Among all, 182 (33.3%), 183 (33.3%), and 180 (33.3%) patients underwent mitral repair in the control-1, control-2, and NT cohorts, respectively. Procedural success was achieved in 93.3% of patients without differences between groups. Major adverse events did not statistically differ among groups, but there was a higher rate of pericardial effusion in the control-1 group (4.3%, 0.6%, and 2.6%, respectively; p = 0.025). The composite endpoint of death, surgery, and admission for congestive heart failure (CHF) at 12 months was lower in the NT group (23.5% in control-1, 22.5% in control-2, and 8.3% in the NT group; p = 0.032). Conclusions: The present paper shows that contemporary clinical outcomes of patients undergoing PMVR with the Mitraclip system have improved over time.
SP-D Serum Levels Reveal Distinct Epithelial Damage in Direct Human ARDS
Authors: Peukert Konrad , Seeliger Benjamin , Fox Mario , Feuerborn Caroline , Sauer Andrea , Schuss Patrick , Schneider Matthias , David Sascha , Welte Tobias , Putensen Christian , Wilhelm Christoph , Steinhagen Folkert , Bode Christian
Published: February 2021

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome with multiple underlying diseases. Particularly epithelial damage results from direct (e.g., pneumonia) rather than indirect lung injury (e.g., nonpulmonary sepsis), which is more likely associated with endothelial damage. Hence, targeting ARDS patients based on their molecular phenotypes is a promising approach to improve outcome. With regard to distinct inflammatory responses and subsequent lung damage in direct ARDS due to the causing pathogen, we quantified markers of epithelial and endothelial damage and pro-inflammatory cytokines in patients with ARDS triggered by bacterial, viral, and atypical pathogen pneumonia or indirect ARDS. The serum levels of interleukin-6 (IL-6) and interleukin-8 (IL-8), lung epithelial injury markers surfactant protein D (SP-D), and soluble receptor for advanced glycation end-products (sRAGE) as well as endothelial injury marker angiopoietin-2 (Ang-2) from 49 patients with distinct types of ARDS were analyzed by multiplex immunoassay. Epithelial damage marker SP-D was significantly higher in direct ARDS caused by viral and atypical pathogens in contrast to ARDS caused by typical bacterial pneumonia and nonpulmonary sepsis. In contrast, sRAGE levels did not differ due to the causing pathogen. Patients with atypical pathogen pneumonia related ARDS showed significantly lower Ang-2 levels compared to patients with viral and indirect ARDS. Patients with viral and atypical pneumonia related ARDS possessed significantly lower serum IL-6 levels compared to bacterial pneumonia related ARDS and IL-6 levels in atypical pneumonia related ARDS were significantly lower than in indirect ARDS. Current findings report a potential difference in ARDS biomarkers due to the underlying disease and pathogen.