bluuebunny/crossref_metadata_2025 huggingface dataset:
Rosmarinic Acid and Sodium Citrate Have a Synergistic Bacteriostatic Effect against Vibrio Species by Inhibiting Iron Uptake
Authors: Lu Peng , Sui Miaomiao , Zhang Mimin , Wang Mengyao , Kamiya Takehiro , Okamoto Ken , Itoh Hideaki , Okuda Suguru , Suzuki Michio , Asakura Tomiko , Fujiwara Toru , Nagata Koji
Published: December 2021

Background: New strategies are needed to combat multidrug-resistant bacteria. The restriction of iron uptake by bacteria is a promising way to inhibit their growth. We aimed to suppress the growth of Vibrio bacterial species by inhibiting their ferric ion-binding protein (FbpA) using food components. Methods: Twenty spices were selected for the screening of FbpA inhibitors. The candidate was applied to antibacterial tests, and the mechanism was further studied. Results: An active compound, rosmarinic acid (RA), was screened out. RA binds competitively and more tightly than Fe3+ to VmFbpA, the FbpA from V. metschnikovii, with apparent KD values of 8 μM vs. 17 μM. Moreover, RA can inhibit the growth of V. metschnikovii to one-third of the control at 1000 μM. Interestingly, sodium citrate (SC) enhances the growth inhibition effect of RA, although SC only does not inhibit the growth. The combination of RA/SC completely inhibits the growth of not only V. metschnikovii at 100/100 μM but also the vibriosis-causative pathogens V. vulnificus and V. parahaemolyticus, at 100/100 and 1000/100 μM, respectively. However, RA/SC does not affect the growth of Escherichia coli. Conclusions: RA/SC is a potential bacteriostatic agent against Vibrio species while causing little damage to indigenous gastrointestinal bacteria.
Experimental and Numerical Analysis of a Compressor Stage under Flow Distortion
Authors: Baretter Alberto , Godard Benjamin , Joseph Pierric , Roussette Olivier , Romanò Francesco , Barrier Raphael , Dazin Antoine
Published: December 2021

On many occasions, fan or compressor stages have to face azimuthal flow distortion at inlet, which affects their performance and stability. These flow distortions can be caused by external events or by some particular geometrical features. The aim of this work is to propose a joined numerical and experimental analysis of the flow behavior in a single axial compressor stage under flow distortion. The distortions are generated by different grids that are placed upstream to the rotor. Experimentally, the flow analysis is based on the measurements obtained by a series of unsteady pressure sensors flush-mounted at the casing of the machine rotor. URANS computations are conducted using the elsA software. The flow distortion is simulated by a drop of stagnation pressure ratio at the inlet boundary condition. The study is focusing first on the ability of a pressure drop, imposed as an inlet boundary condition in CFD, to reproduce accurately the effect of a flow distortion. The analysis is conducted using singular value decomposition (SVD) and dynamic mode decomposition (DMD). A special attention is then paid, on the experimental level, to the arising of rotating stall, from the onset of the instability up to completely developed stall cells.
Data Driven Modal Decomposition of the Wake behind an NREL-5MW Wind Turbine
Authors: Cherubini Stefania , De Cillis Giovanni , Semeraro Onofrio , Leonardi Stefano , De Palma Pietro
Published: December 2021

The wake produced by a utility-scale wind turbine invested by a laminar, uniform inflow is analyzed by means of two different modal decompositions, the proper orthogonal decomposition (POD) and the dynamic mode decomposition (DMD), in its sparsity-promoting variant. The turbine considered is the NREL-5MW at tip-speed ratio λ=7 and a diameter-based Reynolds number of the order 108. The flow is simulated through large eddy simulation, where the forces exerted by the blades are modeled using the actuator line method, whereas tower and nacelle are modeled employing the immersed boundary method. The main flow structures identified by both modal decompositions are compared and some differences emerge that can be of great importance for the formulation of a reduced-order model. In particular, a high-frequency mode directly related to the tip vortices is found using both methods, but it is ranked differently. The other dominant modes are composed by large-scale low-frequency structures, but with different frequency content and spatial structure. The most energetic 200 POD modes account for ≈20% only of the flow kinetic energy. While using the same number of DMD modes, it is possible to reconstruct the flow field to within 80% accuracy. Despite the similarities between the set of modes, the comparison between these modal-decomposition techniques points out that an energy-based criterion such as that used in the POD may not be suitable for formulating a reduced-order model of wind turbine wakes, while the sparsity-promoting DMD appears able to perform well in reconstructing the flow field with only a few modes.
Transport of Swirling Entropy Waves through an Axial Turbine Stator
Authors: Notaristefano Andrea , Gaetani Paolo
Published: December 2021

The transport of entropy waves and their impact on the stage aerodynamics are still open questions. This paper shows the results of an experimental campaign that focuses on the swirling entropy waves advection through an axial turbine stator. The research aims at quantifying the aerodynamic impact of the swirling entropy waves on the first nozzle and characterizing their transport. The disturbance is generated by a novel entropy wave generator that ensures a wide set of different injection parameters. The device injects the disturbance axially, four different clocking positions are investigated. Measurements show a severe temperature attenuation of the swirling entropy wave at stator outlet. The high temperature location changes with the injection position as a result of the different interaction with the stator secondary flows. Depending on the injection position, the aerodynamic flow field is strongly perturbed by the injected swirl profile, instead the entropy wave effect is negligible.
Resilience Endangered: The Role of Regional Airports in Remote Areas in Sweden
Authors: Große Christine , Olausson Pär M. , Svensson Bo
Published: December 2021

This paper examines the role of regional airports in regional and municipal crisis preparedness based on evidence from a case study in Sweden. During the summer of 2018, Sweden experienced some of the most extensive wildfires in modern time. Aerial suppression, for which airports provided the essential preconditions, played an important role in extinguishing these fires. This study includes analyses of public policies that shape the Swedish airport system as well as evidence from interviews and a workshop with stakeholders. The results show that an efficiently operated network of regional airports is critical not only for crisis management but also to ensure important societal services such as health care in sparsely inhabited regions. Moreover, access to quick transportation by air is necessary for the Swedish Prison and Probation Service, tourism industry, public institutions and private businesses. Additionally intensified by effects of both the public debate on flight shame and the COVID-19 pandemic on air-based transportation, the insights arising from this study emphasise that the currently one-sided focus on the number of passengers is an insufficient foundation for the Swedish airport system to construct a resilient base for regional development, crisis management and civil defense.
Public Bus Transportation System Environmental Impact Projections Regarding Different Policy Scenarios—A LCA Study
Authors: Leichter Michelle , Hackenhaar Isadora , Passuello Ana
Published: December 2021

Urban activities, such as transportation, are responsible for a large portion of energy-related CO2 emissions. As the need for sustainable urban development increases, decision-makers embrace Life Cycle Assessment (LCA) as a reliable tool capable of generating scientifically based information on environmental impacts. However, there is still a lack of an analysis standard regarding the particularities of urban systems. Therefore, this research aims to define current and future environmental profiles, considering a case study of the public transport system in Porto Alegre, considering specificities of the urban context and different public policy scenarios through LCA. These results show that, although the transportation system management relies on the municipalities, the higher significance of environmental impacts depend on a national policy for using biodiesel in the diesel sold, which could lead to an increase of, for example, up to 9.4% of CO2 emissions from 2017 (baseline) to 2030. Finally, it is perceivable that to conduct a LCA to support decision-making in public urban services, a detailed approach is needed considering that technological variables interact with the territorial context and policy changes.
Environmental Correlates of Sexual Signaling in the Heteroptera: A Prospective Study
Authors: Gourevitch Eleanor H. Z. , Shuker David M.
Published: December 2021

Sexual selection is a major evolutionary process, shaping organisms in terms of success in competition for access to mates and their gametes. The study of sexual selection has provided rich empirical and theoretical literature addressing the ecological and evolutionary causes and consequences of competition for gametes. However, there remains a bias towards individual, species-specific studies, whilst broader, cross-species comparisons looking for wider-ranging patterns in sexual selection remain uncommon. For instance, we are still some ways from understanding why particular kinds of traits tend to evolve under sexual selection, and under what circumstances. Here we consider sexual selection in the Heteroptera, a sub-order of the Hemiptera, or true bugs. The latter is the largest of the hemimetabolous insect orders, whilst the Heteroptera itself comprises some 40,000-plus described species. We focus on four key sexual signaling modes found in the Heteroptera: chemical signals, acoustic signaling via stridulation, vibrational (substrate) signaling, and finally tactile signaling (antennation). We compare how these modes vary across broad habitat types and provide a review of each type of signal. We ask how we might move towards a more predictive theory of sexual selection, that links mechanisms and targets of sexual selection to various ecologies.
Analysis of Platform Leveling Systems for Tracked Feller-Buncher Machines
Authors: Alexandr Andronov , Ivan Bacherikov , Igor Zverev
Published: December 2021

The study was devoted to the analysis of feller buncher platform leveling systems. The widespread use of these systems in the design of modern feller-buncher machines makes the study relevant to assess operational efficiency. The analysis was conducted in five stages using analytical and stochastic mathematical modeling methods. In the first stage, the existing layouts of alignment systems were analyzed from the position of force on the hydraulic cylinder rods of the platform tilt drive. The three-cylinder layout scheme, where the force on the hydraulic cylinder rod was 50…60% less than that on the two-cylinder layout, appeared to be the most expedient. In the second stage, a mathematical model for determining changes in the position of the center of mass of the feller-buncher depending on the inclination angle of the platform was derived. In the third stage, a mathematical model was derived for determining the limiting angle of slope of the terrain when the feller buncher moved up the slope. For this purpose, two calculation schemes were considered when the machine moved up the slope without and with a tilted platform. Zero support reaction on the front roller was taken as the stability criterion. In the fourth stage, a mathematical model for determining the limiting angle of slope of the terrain during the roll of the feller-buncher machine was obtained. In the fifth stage, the efficiency of the application of leveling systems was evaluated. A graph of the dependence of changes in the terrain slope angle on the platform slope angle was plotted, and a regression dependence for an approximate estimate was obtained. A regression analysis was also carried out, and dependencies were obtained to determine the weight of a feller-buncher with a leveling system and the added pressure on the ground caused by the increase in the weight of the base machine. The analysis of platform leveling systems showed the effectiveness of their application in the designs of feller-buncher machines, as it allows the machines to work on slopes with an inclination of 50…60% more than without them.
Methodology and Tools for Digital Twin Management—The FA3ST Approach
Authors: Stojanovic Ljiljana , Usländer Thomas , Volz Friedrich , Weißenbacher Christian , Müller Jens , Jacoby Michael , Bischoff Tino
Published: December 2021

The concept of digital twins (DT) has already been discussed some decades ago. Digital representations of physical assets are key components in industrial applications as they are the basis for decision making. What is new is the conceptual approach to consider DT as well-defined software entities themselves that follow the whole lifecycle of their physical counterparts from the engineering, operation up to the discharge, and hence, have their own type description, identity, and lifecycle. This paper elaborates on this idea and argues the need for systematic DT engineering and management. After a conceptual description of DT, the paper proposes a DT lifecycle model and presents methodologies and tools for DT management, also in the context of Industrie 4.0 concepts, such as the asset administration shell (AAS), the international data spaces (IDS), and IEC standards (such as OPC UA and AML). As a tool example for the support of DT engineering and management, the Fraunhofer-advanced AAS tools for digital twins (FA3ST) are presented in more detail.
The Role of POPDC Proteins in Cardiac Pacemaking and Conduction
Authors: Gruscheski Lena , Brand Thomas
Published: December 2021

The Popeye domain-containing (POPDC) gene family, consisting of Popdc1 (also known as Bves), Popdc2, and Popdc3, encodes transmembrane proteins abundantly expressed in striated muscle. POPDC proteins have recently been identified as cAMP effector proteins and have been proposed to be part of the protein network involved in cAMP signaling. However, their exact biochemical activity is presently poorly understood. Loss-of-function mutations in animal models causes abnormalities in skeletal muscle regeneration, conduction, and heart rate adaptation after stress. Likewise, patients carrying missense or nonsense mutations in POPDC genes have been associated with cardiac arrhythmias and limb-girdle muscular dystrophy. In this review, we introduce the POPDC protein family, and describe their structure function, and role in cAMP signaling. Furthermore, the pathological phenotypes observed in zebrafish and mouse models and the clinical and molecular pathologies in patients carrying POPDC mutations are described.
Cardiovascular Characteristics and Outcomes of Young Patients with COVID-19
Authors: Trimaille Antonin , Ribeyrolles Sophie , Fauvel Charles , Chaumont Corentin , Weizman Orianne , Pommier Thibaut , Cellier Joffrey , Geneste Laura , Panagides Vassili , Marsou Wassima , Deney Antoine , Attou Sabir , Delmotte Thomas , Chemaly Pascale , Karsenty Clément , Giordano Gauthier , Gautier Alexandre , Guilleminot Pierre , Sagnard Audrey , Pastier Julie , Duceau Baptiste , Sutter Willy , Waldmann Victor , Pezel Théo , Mika Delphine , Cohen Ariel , Bonnet Guillaume ,   the Critical COVID-19 France Investigators
Published: December 2021

Although 18–45-year-old (y-o) patients represent a significant proportion of patients hospitalized for COVID-19, data concerning the young population remain scarce. The Critical COVID France (CCF) study was an observational study including consecutive patients hospitalized for COVID-19 in 24 centers between 26 February and 20 April 2020. The primary composite outcome included transfer to the intensive care unit (ICU) or in-hospital death. Secondary outcomes were cardiovascular (CV) complications. Among 2868 patients, 321 (11.2%) patients were in the 18–45-y-o range. In comparison with older patients, young patients were more likely to have class 2 obesity and less likely to have hypertension, diabetes and dyslipidemia. The primary outcome occurred less frequently in 18–45-y-o patients in comparison with patients > 45 years old (y/o) (16.8% vs. 30.7%, p < 0.001). The 18–45-y-o patients presented with pericarditis (2.2% vs. 0.5%, p = 0.003) and myocarditis (2.5% vs. 0.6%, p = 0.002) more frequently than patients >45 y/o. Acute heart failure occurred less frequently in 18–45-y-o patients (0.9% vs. 7.2%, p < 0.001), while thrombotic complications were similar in young and older patients. Whereas both transfer to the ICU and in-hospital death occurred less frequently in young patients, COVID-19 seemed to have a particular CV impact in this population.
Medium- and Long-Term Lead Stability and Echocardiographic Outcomes of Left Bundle Branch Area Pacing Compared to Right Ventricular Pacing
Authors: Zhu Haojie , Wang Zhao , Li Xiaofei , Yao Yan , Liu Zhimin , Fan Xiaohan
Published: December 2021

The long-term lead stability and echocardiographic outcomes of left bundle branch area pacing (LBBAP) are not fully understood. This study aimed to observe the mid-long-term clinical impact of LBBAP compared to right ventricular pacing (RVP). Consecutive bradycardia patients undergoing LBBAP or RVP were enrolled. Pacing and electrophysiological characteristics, echocardiographic measurements, and procedural complications were prospectively recorded at baseline and follow-up. LBBAP was successful in 376 of 406 patients (92.6%), while 313 patients received RVP. During a mean follow-up of 13.6 ± 7.8 months, LBBAP presented with similar pacing parameters and complications to RVP, except a significantly narrower paced QRS duration (115.7 ± 12.3 ms vs. 148.0 ± 18.0 ms, p < 0.001). In 228 patients with ventricular pacing burden >40%, LBBAP at last follow-up resulted in decreased left atrial diameter (LAD) (40.1 ± 8.5 mm vs. 38.5 ± 8.0 mm, p < 0.001) while RVP produced decreased left ventricular ejection fraction (62.7 ± 4.8% vs. 60.5 ± 6.9%, p < 0.001) when compared to baseline. After adjusting for age, the presence of atrial fibrillation, and other clinical factors, LBBAP was still associated with a decrease in LAD (−1.601, 95% CI −3.094–−0.109, p = 0.036). We conclude that LBBAP might result in more preserved echocardiographic outcomes than RVP.
An Automated System for ECG Arrhythmia Detection Using Machine Learning Techniques
Authors: Sraitih Mohamed , Jabrane Younes , Hajjam El Hassani Amir
Published: December 2021

The new advances in multiple types of devices and machine learning models provide opportunities for practical automatic computer-aided diagnosis (CAD) systems for ECG classification methods to be practicable in an actual clinical environment. This imposes the requirements for the ECG arrhythmia classification methods that are inter-patient. We aim in this paper to design and investigate an automatic classification system using a new comprehensive ECG database inter-patient paradigm separation to improve the minority arrhythmical classes detection without performing any features extraction. We investigated four supervised machine learning models: support vector machine (SVM), k-nearest neighbors (KNN), Random Forest (RF), and the ensemble of these three methods. We test the performance of these techniques in classifying: Normal beat (NOR), Left Bundle Branch Block Beat (LBBB), Right Bundle Branch Block Beat (RBBB), Premature Atrial Contraction (PAC), and Premature Ventricular Contraction (PVC), using inter-patient real ECG records from MIT-DB after segmentation and normalization of the data, and measuring four metrics: accuracy, precision, recall, and f1-score. The experimental results emphasized that with applying no complicated data pre-processing or feature engineering methods, the SVM classifier outperforms the other methods using our proposed inter-patient paradigm, in terms of all metrics used in experiments, achieving an accuracy of 0.83 and in terms of computational cost, which remains a very important factor in implementing classification models for ECG arrhythmia. This method is more realistic in a clinical environment, where varieties of ECG signals are collected from different patients.
Clinical Outcomes in Older Patients Aged over 75 Years Who Underwent Early Surgical Treatment for Pyogenic Vertebral Osteomyelitis
Authors: Lee Jeong Hwan , Kim Jihye , Kim Tae-Hwan
Published: December 2021

Older patients with pyogenic vertebral osteomyelitis (PVO) usually have more medical comorbidities compared with younger patients, and present with advanced infections from different causative organisms. To aid surgical decision-making, we compared surgical outcomes of older patients with PVO to those who underwent nonoperative treatment. We identified the risk factors for adverse post-operative outcomes, and analyzed the clinical risks from further spinal instrumentation. This retrospective comparative study included 439 patients aged ≥75 years with PVO. Multivariable analysis was performed to compare treatment outcomes among three groups: 194, 130, and 115 patients in the non-operative, non-instrumented, and instrumented groups, respectively. The risk factors for adverse outcomes after surgical treatment were evaluated using a logistic regression model, and the estimates of the multivariable models were internally validated using bootstrap samples. Recurrence and mortality of these patients were closely associated with neurologic deficits, and increased surgical invasiveness, resulting from additional spinal instrumentation, did not increase the risk of recurrence or mortality. We propose that surgical treatment for these patients should focus on improving neurologic deficits through immediate and sufficient removal of abscesses. Spinal instrumentation can be performed if indicated, within reasonable clinical risk.
Multi-Parametric Diagnostic Approach and Potential Markers of Early Onset Subclinical Cardiovascular Disease in a Cohort of Children, Adolescents and Young Adults Vertically Infected with HIV on cART
Authors: Castaldi Biagio , Lanzoni Gloria , Rampon Osvalda , Donà Daniele , Di Candia Angela , Milanesi Ornella , Giaquinto Carlo , Di Salvo Giovanni
Published: December 2021

Background: HIV infection and lifelong cART are responsible of an increase in cardiovascular risk. The aim of this study was to describe the subclinical cardiovascular disease and to identify early markers of cardiovascular damage in adolescents and young adults vertically infected with HIV on cART, through an innovative multi-parametric approach. Methods: We enrolled 52 patients vertically infected with HIV. Demographic records, traditional cardiovascular risk factors, laboratory findings and echocardiographic measurements were collected in a one-year routine follow up. The echocardiographic examination included measurements of the 2D and 3D ejection fraction (EF), E/A ratio, E/E′ ratio, carotid intima media thickness (cIMT), flow-mediated dilation (FMD) and global longitudinal strain (GLS). Results: At the time of enrolment, all the patients were on cART therapy. The viral load was suppressed in 95% of them. EF was normal in 94.2% of patients (66 ± 7.2%), and GLS (mean value: −20.0 ± 2.5%) was reduced in 29% of patients. The cIMT mean value was higher than the 95th centile for sex and age in 73%, and FMD was impaired in 45% of patients. Clinically evident disease was found in three patients: dilative cardiomyopathy in one, thoracic-abdominal aneurysm Crawford type II with a bilateral carotid dilation in one and carotid plaque with 30% of stenosis in a third patient. Conclusions: This study confirms the presence of clinical and subclinical cardiovascular disease in a very young population vertically infected with HIV, underlining the importance of an early, multi-parametric cardiovascular follow up.
Pregnancy as a Risk Factor of Severe COVID-19
Authors: Celewicz Aleksander , Celewicz Marta , Michalczyk Michał , Woźniakowska-Gondek Paula , Krejczy Kamila , Misiek Marcin , Rzepka Rafał
Published: December 2021

Since first being identified in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an etiological agent behind Coronavirus disease 19 (COVID-19), has caused three waves of a global pandemic, with a fourth in progress. Despite its high percentage of asymptomatic and low-symptomatic courses of illness, the SARS-CoV-2 pandemic has claimed a higher death toll than the SARS-CoV and MERS-CoV epidemics because of its high infectivity when compared to the other coronaviruses. High COVID-19 mortality is associated with age and other coexisting morbidities, as well as healthcare quality. According to several studies, pregnant women are at a higher risk of severe COVID-19 infection and adverse pregnancy outcomes (caesarean delivery, pre-term birth, low birth weight, preeclampsia, ICU admission, and need for mechanical ventilation). In our review of recent literature, we focused on the effects of COVID-19 in pregnant women, emphasizing the subcellular pathophysiology of SARS-CoV-2. In this paper, we concentrate on the pathophysiology of sub-cellular changes in COVID-19 and endeavor to highlight the aspects that manifest in physiological pregnancy and potentially create a higher risk of SARS-CoV-2 infection and acute COVID-19 symptoms. Understanding how pregnancy-associated changes can cause a synergistic effect with COVID-19 may point us in the right direction for future prophylaxis and treatment for women undergoing COVID-19 during pregnancy.
Quantitative Detection of Disseminated Melanoma Cells by Trp-1 Transcript Analysis Reveals Stochastic Distribution of Pulmonary Metastases
Authors: Kyjacova Lenka , Saup Rafael , Rothley Melanie , Schmaus Anja , Wagner Tabea , Boßerhoff Anja , Garvalov Boyan K. , Thiele Wilko , Sleeman Jonathan P.
Published: December 2021

A better understanding of the process of melanoma metastasis is required to underpin the development of novel therapies that will improve patient outcomes. The use of appropriate animal models is indispensable for investigating the mechanisms of melanoma metastasis. However, reliable and practicable quantification of metastases in experimental mice remains a challenge, particularly if the metastatic burden is low. Here, we describe a qRT-PCR-based protocol that employs the melanocytic marker Trp-1 for the sensitive quantification of melanoma metastases in the murine lung. Using this protocol, we were able to detect the presence of as few as 100 disseminated melanoma cells in lung tissue. This allowed us to quantify metastatic burden in a spontaneous syngeneic B16-F10 metastasis model, even in the absence of visible metastases, as well as in the autochthonous Tg(Grm1)/Cyld−/− melanoma model. Importantly, we also observed an uneven distribution of disseminated melanoma cells amongst the five lobes of the murine lung, which varied considerably from animal to animal. Together, our findings demonstrate that the qRT-PCR-based detection of Trp-1 allows the quantification of low pulmonary metastatic burden in both transplantable and autochthonous murine melanoma models, and show that the analysis of lung metastasis in such models needs to take into account the stochastic distribution of metastatic lesions amongst the lung lobes.
Algorithms for Automated Calibration of Transcutaneous Spinal Cord Stimulation to Facilitate Clinical Applications
Authors: Salchow-Hömmen Christina , Schauer Thomas , Müller Philipp , Kühn Andrea A. , Hofstoetter Ursula S. , Wenger Nikolaus
Published: December 2021

Transcutaneous spinal cord stimulation (tSCS) is a promising intervention that can benefit spasticity control and augment voluntary movement in spinal cord injury (SCI) and multiple sclerosis. Current applications require expert knowledge and rely on the thorough visual analysis of electromyographic (EMG) responses from lower-limb muscles to optimize attainable treatment effects. Here, we devised an automated tSCS setup by combining an electrode array placed over low-thoracic to mid-lumbar vertebrae, synchronized EMG recordings, and a self-operating stimulation protocol to systematically test various stimulation sites and amplitudes. A built-in calibration procedure classifies the evoked responses as reflexes or direct motor responses and identifies stimulation thresholds as recommendations for tSCS therapy. We tested our setup in 15 individuals (five neurologically intact, five SCI, and five Parkinson’s disease) and validated the results against blinded ratings from two clinical experts. Congruent results were obtained in 13 cases for electrode positions and in eight for tSCS amplitudes, with deviations of a maximum of one position and 5 to 10 mA in amplitude in the remaining cases. Despite these minor deviations, the calibration found clinically suitable tSCS settings in 13 individuals. In the remaining two cases, the automatic setup and both experts agreed that no reflex responses could be detected. The presented technological developments may facilitate the dissemination of tSCS into non-academic environments and broaden its use for diagnostic and therapeutic purposes.
New Time-Related Insights into an Old Laboratory Parameter: Early CRP Discovered by IBM Watson Trauma Pathway Explorer© as a Predictor for Sepsis in Polytrauma Patients
Authors: Mica Ladislav , Pape Hans-Christoph , Niggli Philipp , Vomela Jindřich , Niggli Cédric
Published: December 2021

The University Hospital Zurich together with IBM® invented an outcome prediction tool based on the IBM Watson technology, the Watson Trauma Pathway Explorer®. This tool is an artificial intelligence to predict three outcome scenarios in polytrauma patients: the Systemic Inflammatory Response Syndrome (SIRS) and sepsis within 21 days as well as death within 72 h. The knowledge of a patient’s future under standardized trauma treatment might be of utmost importance. Here, new time-related insights on the C-reactive protein (CRP) and sepsis are presented. Meanwhile, the validated IBM Watson Trauma Pathway Explorer® offers a time-related insight into the most frequent laboratory parameters. In total, 3653 patients were included in the databank used by the application, and ongoing admissions are constantly implemented. The patients were grouped according to sepsis, and the CRP was analyzed according to the point of time at which the value was acquired (1, 2, 3, 4, 6, 8, 12, 24, and 48 h and 3, 4, 5, 7, 10, 14, and 21 days). The differences were analyzed using the Mann–Whitney U-Test; binary logistic regression was used to determine the dependency of prediction, and the Closest Top-left Threshold Method presented time-specific thresholds at which CRP is predictive for sepsis. The data were considered as significant at p < 0.05, all analyses were performed in R. The differences in the CRP value of the non-sepsis and sepsis groups are starting to be significant between 6 and 8 h (p < 0.05) after admission inclusive of post hoc analysis, and the binary logistic regression depicts a similar picture. The level of significance is reached between 6 and 8 h (p < 0.05) after admission. The knowledge of the outcome reflected by the CRP in polytrauma patients improves the surgeon’s tactical position to indicate operations to reduce antigenic load and avoid an infectious adverse outcome.
The (Still Unknown) Hypothetical Protective Role of COVID-19 Therapy in Bladder Cancer
Authors: Di Gianfrancesco Luca
Published: December 2021

The COVID-19 pandemic continues to put a strain on the entire world population. The common features of bladder cancer (BCa) and COVID infection have been widely reported and discussion may continue regarding treatment as well. We have highlighted how COVID-19 therapy has many implications with BCa therapy, in particular with potential protective role.
Multiple Approaches at Admission Based on Lung Ultrasound and Biomarkers Improves Risk Identification in COVID-19 Patients
Authors: Rubio-Gracia Jorge , Sánchez-Marteles Marta , Garcés-Horna Vanesa , Martínez-Lostao Luis , Ruiz-Laiglesia Fernando , Crespo-Aznarez Silvia , Peña-Fresneda Natacha , Gracia-Tello Borja , Cebollada Alberto , Carrera-Lasfuentes Patricia , Pérez-Calvo Juan , Giménez-López Ignacio
Published: December 2021

Background: Risk stratification of COVID-19 patients is fundamental to improving prognosis and selecting the right treatment. We hypothesized that a combination of lung ultrasound (LUZ-score), biomarkers (sST2), and clinical models (PANDEMYC score) could be useful to improve risk stratification. Methods: This was a prospective cohort study designed to analyze the prognostic value of lung ultrasound, sST2, and PANDEMYC score in COVID-19 patients. The primary endpoint was in-hospital death and/or admission to the intensive care unit. The total length of hospital stay, increase of oxygen flow, or escalated medical treatment during the first 72 h were secondary endpoints. Results: a total of 144 patients were included; the mean age was 57.5 ± 12.78 years. The median PANDEMYC score was 243 (52), the median LUZ-score was 21 (10), and the median sST2 was 53.1 ng/mL (30.9). Soluble ST2 showed the best predictive capacity for the primary endpoint (AUC = 0.764 (0.658–0.871); p = 0.001), towards the PANDEMYC score (AUC = 0.762 (0.655–0.870); p = 0.001) and LUZ-score (AUC = 0.749 (0.596–0.901); p = 0.002). Taken together, these three tools significantly improved the risk capacity (AUC = 0.840 (0.727–0.953); p ≤ 0.001). Conclusions: The PANDEMYC score, lung ultrasound, and sST2 concentrations upon admission for COVID-19 are independent predictors of intra-hospital death and/or the need for admission to the ICU for mechanical ventilation. The combination of these predictive tools improves the predictive power compared to each one separately. The use of decision trees, based on multivariate models, could be useful in clinical practice.
Lactoferrin: Cytokine Modulation and Application in Clinical Practice
Authors: Presti Santiago , Manti Sara , Parisi Giuseppe Fabio , Papale Maria , Barbagallo Ignazio Alberto , Li Volti Giovanni , Leonardi Salvatore
Published: December 2021

Multiple properties of lactoferrin have been reported in the literature so far. Decades of in vitro and in vivo studies have demonstrated the important antimicrobial, anti-inflammatory, anti-oxidant, and immunomodulating properties. It suggests the use of lactoferrin as an effective and safe option for the treatment of several common disorders. Herein, we show the applications of lactoferrin in clinical practice, highlighting its evidence-based capacities for the treatment of heterogeneous disorders, such as allergic, gastrointestinal, and respiratory diseases, and hematologic, oncologic, gynecologic, dermatologic, and dental disorders. Moreover, the widespread use of lactoferrin in neonatology is summarized here. As a result of its antiviral properties, lactoferrin has also been proposed as a valid option for the treatment for COVID-19 patients. Here, the uses of lactoferrin in clinical practice as a new, safe, and evidence-based treatment for many types of disorders are summarized.
Increased Geriatric Treatment Frequency Improves Mobility and Secondary Fracture Prevention in Older Adult Hip Fracture Patients—An Observational Cohort Study of 23,828 Patients from the Registry for Geriatric Trauma (ATR-DGU)
Authors: Gleich Johannes , Fleischhacker Evi , Rascher Katherine , Friess Thomas , Kammerlander Christian , Böcker Wolfgang , Bücking Benjamin , Liener Ulrich , Drey Michael , Höfer Christine , Neuerburg Carl
Published: December 2021

Interdisciplinary orthogeriatric care of older adult hip fracture patients is of growing importance due to an ageing population, yet there is ongoing disagreement about the most effective model of care. This study aimed to compare different forms of orthogeriatric treatment, with focus on their impact on postoperative mobilization, mobility and secondary fracture prevention. In this observational cohort study, patients aged 70 years and older with a proximal femur fracture requiring surgery, were included from 1 January 2016 to 31 December 2019. Data were recorded from hospital stay to 120-day follow-up in the Registry for Geriatric Trauma (ATR-DGU), a specific designed registry for older adult hip fracture patients. Of 23,828 included patients from 95 different hospitals, 72% were female, median age was 85 (IQR 80–89) years. Increased involvement of geriatricians had a significant impact on mobilization on the first day (OR 1.1, CI 1.1–1.2) and mobility seven days after surgery (OR 1.1, CI 1.1–1.2), initiation of an osteoporosis treatment during in-hospital stay (OR 2.5, CI 2.4–2.7) and of an early complex geriatric rehabilitation treatment (OR 1.3, CI 1.2–1.4). These findings were persistent after 120 days of follow-up. Interdisciplinary treatment of orthogeriatric patients is beneficial and especially during in-patient stay increased involvement of geriatricians is decisive for early mobilization, mobility and initiation of osteoporosis treatment. Standardized treatment pathways in certified geriatric trauma departments with structured data collection in specific registries improve outcome monitoring and interpretation.
Multimodality Treatment in Metastatic Gastric Cancer: Working Together to Tailor the Continuum of Care
Authors: Petrillo Angelica
Published: December 2021

Gastric cancer (GC) represents one of the most frequent and lethal tumors worldwide today, finding itself in fifth place in terms of incidence and third in terms of mortality [...]
Retinal Diseases Regulated by Hypoxia—Basic and Clinical Perspectives: A Comprehensive Review
Authors: Shinojima Ari , Lee Deokho , Tsubota Kazuo , Negishi Kazuno , Kurihara Toshihide
Published: December 2021

In recent years, the number of patients with age-related macular degeneration (AMD) is increasing worldwide along with increased life expectancy. Currently, the standard treatment for wet-AMD is intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs. The upstream of VEGF is hypoxia-inducible factor (HIF), a master regulator of hypoxia-responsive genes responsive to acute and chronic hypoxia. HIF activation induces various pathological pro-angiogenic gene expressions including VEGF under retinal hypoxia, ultimately leading to the development of ocular ischemic neovascular diseases. In this regard, HIF is considered as a promising therapeutic target in ocular ischemic diseases. In clinical ophthalmology, abnormal hypofluorescent areas have been detected in the late-phase of indocyanine green angiography, which are thought to be lipid deposits at the level of Bruch’s membrane to choriocapillaris in vitreoretinal diseases. These deposits may interfere with the oxygen and nutrients that should be supplied to the retinal pigment epithelium, and that HIF/VEGF is highly suspected to be expressed in the hypoxic retinal pigment epithelium, leading to neovascularization. In this review, we comprehensively summarize pathophysiology of AMD-related ocular diseases with the HIF/VEGF pathway from basic and clinic researches with recent findings.
Prognostic Role of Subcutaneous and Visceral Adiposity in Hospitalized Octogenarians with COVID-19
Authors: Scheffler Max , Genton Laurence , Graf Christophe E. , Remuinan Jorge , Gold Gabriel , Zekry Dina , Serratrice Christine , Herrmann François R. , Mendes Aline
Published: December 2021

Background: We investigated the prognostic significance of visceral and subcutaneous adiposity in octogenarians with COVID-19. Methods: This paper presents a monocentric retrospective study that was conducted in acute geriatric wards with 64 hospitalized patients aged 80+ who had a diagnosis of COVID-19 and who underwent a chest CT scan. A quantification of the subcutaneous, visceral, and total fat areas was performed after segmentations on the first abdominal slice caudal to the deepest pleural recess on a soft-tissue window setting. Logistic regression models were applied to investigate the association with in-hospital mortality and the extent of COVID-19 pneumonia. Results: The patients had a mean age of 86.4 ± 6.0 years, and 46.9% were male, with a mean BMI of 24.1 ± 4.4Kg/m2 and mortality rate of 32.8%. A higher subcutaneous fat area had a protective effect against mortality (OR 0.416; 0.183–0.944 95% CI; p = 0.036), which remained significant after adjustments for age, sex, and BMI (OR 0.231; 0.071–0.751 95% CI; p = 0.015). Inversely, higher abdominal circumference, total fat area, subcutaneous fat area, and visceral fat were associated with worse COVID-19 pneumonia, with the latter presenting the strongest association after adjustments for age, sex, and BMI (OR 2.862; 1.523–5.379 95% CI; p = 0.001). Conclusion: Subcutaneous and visceral fat areas measured on chest CT scans were associated with prognosis in octogenarians with COVID-19.
Prenatal Anxiety and Exercise. Systematic Review and Meta-Analysis
Authors: Sánchez-Polán Miguel , Silva-Jose Cristina , Franco Evelia , Nagpal Taniya S. , Gil-Ares Javier , Lili Qin , Barakat Rubén , Refoyo Ignacio
Published: December 2021

The prevalence of prenatal anxiety has increased during the COVID-19 pandemic. Anxiety is associated with other cardiovascular, physiological, and mental illnesses, resulting in adverse health effects for the mother and foetus. The purpose of this study was to evaluate the effects of physical activity (PA) during pregnancy on the prevalence of prenatal anxiety or symptoms of anxiety. A systematic review and two meta-analyses were performed (Registration No. CRD42021275333). Peer-reviewed articles reporting the effect of a PA intervention on anxiety during pregnancy were included. The first meta-analysis (MA) included 10 studies reporting final scores of prenatal anxiety. A negative association between moderate PA during pregnancy and prenatal anxiety was found in this analysis (z = −2.62, p < 0.01; ES = −0.46, 95% CI = −0.80, −12, I2 = 84%, Pheterogeneity = 0.001). The second MA included eight studies in which measures both before and after a PA intervention were reported. The findings of this analysis revealed a positive association between exercise practice during pregnancy and a decrease in prenatal anxiety scores (z = −3.39, p < 0.001; ES = −0.48, 95% CI = −0.76, −0.20, I2 = 71%, Pheterogeneity = 0.001). Supervised PA during pregnancy could prevent and reduce prenatal anxiety and anxiety symptoms.
Impact of Bariatric Surgery on Adipose Tissue Biology
Authors: Osorio-Conles Óscar , Vidal Josep , de Hollanda Ana
Published: December 2021

Bariatric surgery (BS) procedures are actually the most effective intervention to help subjects with severe obesity achieve significant and sustained weight loss. White adipose tissue (WAT) is increasingly recognized as the largest endocrine organ. Unhealthy WAT expansion through adipocyte hypertrophy has pleiotropic effects on adipocyte function and promotes obesity-associated metabolic complications. WAT dysfunction in obesity encompasses an altered adipokine secretome, unresolved inflammation, dysregulated autophagy, inappropriate extracellular matrix remodeling and insufficient angiogenic potential. In the last 10 years, accumulating evidence suggests that BS can improve the WAT function beyond reducing the fat depot sizes. The causal relationships between improved WAT function and the health benefits of BS merits further investigation. This review summarizes the current knowledge on the short-, medium- and long-term outcomes of BS on the WAT composition and function.
Prevalence of Pain within Limb Girdle Muscular Dystrophy R9 and Implications for Other Degenerative Diseases
Authors: Richardson Mark , Mayhew Anna , Muni-Lofra Robert , Murphy Lindsay B. , Straub Volker
Published: December 2021

Our primary aim was to establish the prevalence of pain within limb girdle muscular dystrophy R9 (LGMDR9). As part of the Global FKRP Registry, patients are asked to complete the Short Form McGill Pain Questionnaire (SF-MPQ) annually. We used the results of this questionnaire to determine individuals’ maximum pain score and total pain score and examined overall pain intensity and associations between pain intensity and LGMDR9 genotypes, age, and ambulatory status. We also considered the pain descriptors used and pain progression over time. Of the 502 patients, 87% reported current pain and 25% reported severe current pain. We found no associations in pain severity between the different genotypes of LGMDR9. However, we did find statistically significant associations between pain severity and ambulatory status and between our paediatric and adult populations. We found pain descriptors to be more common words that one may associate with non-neural pain, and we found that a significant number of individuals (69%) reported a fluctuating pain pattern over time. We concluded that pain should be considered a significant issue among individuals with LGMDR9 requiring management. Implications regarding assessment of pain for other degenerative diseases are discussed.
Reasons for Utilizing Telemedicine during and after the COVID-19 Pandemic: An Internet-Based International Study
Authors: Benis Arriel , Banker Maxim , Pinkasovich David , Kirin Mark , Yoshai Bat-el , Benchoam-Ravid Raquel , Ashkenazi Shai , Seidmann Abraham
Published: December 2021

The COVID-19 pandemic challenges healthcare services. Concomitantly, this pandemic had a stimulating effect on technological expansions related to telehealth and telemedicine. We sought to elucidate the principal patients’ reasons for using telemedicine during the COVID-19 pandemic and the propensity to use it thereafter. Our primary objective was to identify the reasons of the survey participants’ disparate attitudes toward the use of telemedicine. We performed an online, multilingual 30-question survey for 14 days during March–April 2021, focusing on the perception and usage of telemedicine and their intent to use it after the pandemic. We analyzed the data to identify the attributes influencing the intent to use telemedicine and built decision trees to highlight the most important related variables. We examined 473 answers: 272 from Israel, 87 from Uruguay, and 114 worldwide. Most participants were women (64.6%), married (63.8%) with 1–2 children (52.9%), and living in urban areas (84.6%). Only a third of the participants intended to continue using telemedicine after the COVID-19 pandemic. Our main findings are that an expected substitution effect, technical proficiency, reduced queueing times, and peer experience are the four major factors in the overall adoption of telemedicine. Specifically, (1) for most participants, the major factor influencing their telemedicine usage is the implicit expectation that such a visit will be a full substitute for an in-person appointment; (2) another factor affecting telemedicine usage by patients is their overall technical proficiency and comfort level in the use of common web-based tools, such as social media, while seeking relevant medical information; (3) time saving as telemedicine can allow for asynchronous communications, thereby reducing physical travel and queuing times at the clinic; and finally (4) some participants have also indicated that telemedicine seems more attractive to them after watching family and friends (peer experience) use it successfully.