bluuebunny/crossref_metadata_2025 huggingface dataset:
Programmed Death Ligand-1 (PD-L1) Is an Independent Negative Prognosticator in Western-World Gallbladder Cancer
Authors: Albrecht Thomas , Brinkmann Fritz , Albrecht Michael , Lonsdorf Anke S. , Mehrabi Arianeb , Hoffmann Katrin , Kulu Yakup , Charbel Alphonse , Vogel Monika N. , Rupp Christian , Köhler Bruno , Springfeld Christoph , Schirmacher Peter , Roessler Stephanie , Goeppert Benjamin
Published: April 2021

Inhibition of the programmed cell death protein-1/ligand-1 (PD-1/PD-L1) axis has opened a new era in the treatment of solid cancers. However, there is no data on the expression and relevance of PD-L1 in Western gallbladder cancer (GBC). We assessed PD-L1 immunohistochemically in 131 GBC patients as Tumor Proportion Score (TPS), Immune Cell Score (IC) and Combined Positivity Score (CPS). Tumor cells expressed PD-L1 in a subset of 14.7% GBC patients at a TPS cut-off of 1%. Higher PD-L1 levels above 10% and 25% TPS were reached in 4.7% and 3.1% of GBC cases, respectively. At a 10% cut-off, TPS was associated with distinct histomorphological subtypes and correlated with poor tumor differentiation. Survival analysis revealed a TPS above 10% to be a highly significant and independent negative prognosticator in GBC. PD-L1 expression was associated with increased CD4+, CD8+ and PD-1+ immune cell densities. In 14.8% of the cases, scattered immune cells expressed T-cell immunoreceptor with Ig and ITIM domains (TIGIT), which was correlated to tumoral expression of its ligand CD155. We here show that a high PD-L1 expression confers a negative prognostic value in Western-world GBC and highlight the TIGIT/CD155 immune checkpoint as a potential new target for GBC immunotherapy.
Infection Complications after Lymphodepletion and Dosing of Chimeric Antigen Receptor T (CAR-T) Cell Therapy in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia or B Cell Non-Hodgkin Lymphoma
Authors: Korell Felix , Schubert Maria-Luisa , Sauer Tim , Schmitt Anita , Derigs Patrick , Weber Tim Frederik , Schnitzler Paul , Müller-Tidow Carsten , Dreger Peter , Schmitt Michael
Published: April 2021

Chimeric antigen receptor T (CAR-T) cell therapy has proven to be very effective in patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). However, infections—related either due to lymphodepletion or the CAR-T cell therapy itself—can result in severe and potentially life-threatening complications, while side effects such as cytokine release syndrome (CRS) might complicate differential diagnosis. Sixty-seven dosings of CAR-T cells in sixty adult patients with NHL (85%) and ALL (15%) receiving CAR-T cell therapy were assessed for infectious complications. Almost two-thirds of patients (61%) developed fever following lymphodepletion and CAR-T cell dosing. Microbiological or radiological findings were observed in 25% of all cases (bacterial 12%, viral 5%, fungal 8%). Inpatient infections were associated with more lines of therapy and more severe CRS. However, overall serious complications were rare after CAR-T therapy, with one patient dying of infection. Pathogen detection after inpatient stay was infrequent and mostly occurred in the first 90 days after dosing. Infections in CAR-T cell treated patents are common. Fast and suitable identification and treatment are crucial in these heavily pretreated and immunocompromised patients. In most cases infectious complications are manageable. Nonetheless, standardized anti-infective prophylaxis and supportive therapy are mandatory to reduce morbidity and mortality in CAR-T cell therapy.
Emerging Therapeutic Strategies to Overcome Drug Resistance in Multiple Myeloma
Authors: Davis Lorraine N. , Sherbenou Daniel W.
Published: April 2021

Multiple myeloma is a malignant plasma cell neoplasm that remains incurable and is ultimately fatal when patients acquire multi-drug resistance. Thus, advancing our understanding of the mechanisms behind drug resistance in multi-relapsed patients is critical for developing better strategies to extend their lifespan. Here, we review the understanding of resistance to the three key drug classes approved for multiple myeloma treatment: immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies. We consider how the complex, heterogenous biology of multiple myeloma may influence the acquisition of drug resistance and reflect on the gaps in knowledge where additional research is needed to improve our treatment approaches. Fortunately, many agents are currently being evaluated preclinically and in clinical trials that have the potential to overcome or delay drug resistance, including next-generation immunomodulatory drugs and proteasome inhibitors, novel small molecule drugs, chimeric antigen receptor T cells, antibody-drug conjugates, and bispecific antibodies. For each class, we discuss the potential of these strategies to overcome resistance through modifying agents within each class or new classes without cross-resistance to currently available drugs.
Margin Assessment in Soft Tissue Sarcomas: Review of the Literature
Authors: Sambri Andrea , Caldari Emilia , Fiore Michele , Zucchini Riccardo , Giannini Claudio , Pirini Maria Giulia , Spinnato Paolo , Cappelli Alberta , Donati Davide Maria , De Paolis Massimiliano
Published: April 2021

Adequacy of margins must take into consideration both the resection margin width (quantity) and anatomic barrier (quality). There are several classification schemes for reporting surgical resection margin status for soft tissue sarcomas (STS). Most of the studies regarding treatment outcomes in STS included all histologic grades and histological subtypes, which include infiltrative and non-infiltrative subtypes and are very heterogeneous in terms of both histologic characteristics and treatment modalities (adjuvant treatments or not). This lack of consistency makes it difficult to compare results from study to study. Therefore, there is a great need for evidence-based standardization concerning the width of resection margins. The aim of this narrative review is to provide a comprehensive assessment of the literature on margins, and to highlight the need for a uniform description of the margin status for patients with STS. Patient cases should be discussed at multidisciplinary tumor boards and treatments should be individualized to clinical and demographic characteristics, which must include also a deep knowledge of specific histotypes behaviors, particularly infiltrative ones.
Search for the Microwave Nonthermal Effect in Microwave Chemistry: Synthesis of the Heptyl Butanoate Ester with Microwave Selective Heating of a Sulfonated Activated Carbon Catalyst
Authors: Sakemi Daisuke , Serpone Nick , Horikoshi Satoshi
Published: April 2021

The heptyl butanoate ester was synthesized from butanoic acid and heptanol in a heterogeneous medium in the presence of sulfonated activated carbon (AC-SO3H) catalyst particles subjected to microwave irradiation, which led to higher conversion yields (greater product yields) than conventional heating with an oil bath. The advantage of the microwaves appeared only when the moisture content in the butanoic acid batch(es) was high, suggesting that, unlike conventional heating, the reverse reaction caused by the moisture content and/or by the byproduct water was suppressed by the microwaves. This contrasted with the results that were found when carrying out the reaction in a homogeneous medium in the presence of the 2,4,6-trimethylpyridinium-p-toluene sulfonate (TMP-PTS) catalyst, as product yields were not improved by microwave heating relative to conventional heating. The removal of moisture/water content in the reaction solution was more pronounced when the reactor was cooled, as the reaction yields were enhanced via selective heating of the heterogeneous catalyst. A coupled electromagnetic field/heat transfer analysis gave credence to the selective heating of the AC-SO3H catalyst, which was further enhanced by cooling the reactor. It was deduced that unforeseen impurities and local high-temperature fields generated on the surface of small fine catalyst particles may have had an effect on the microwave chemistry such that the associated phenomena could be mistaken as originating from a nonthermal effect of the microwaves. Accordingly, it is highly recommended that impurities and selective heating be taken into consideration when examining and concluding the occurrence of a microwave nonthermal effect.
Acanthocyte Sedimentation Rate as a Diagnostic Biomarker for Neuroacanthocytosis Syndromes: Experimental Evidence and Physical Justification
Authors: Darras Alexis , Peikert Kevin , Rabe Antonia , Yaya François , Simionato Greta , John Thomas , Dasanna Anil Kumar , Buvalyy Semen , Geisel Jürgen , Hermann Andreas , Fedosov Dmitry A. , Danek Adrian , Wagner Christian , Kaestner Lars
Published: April 2021

(1) Background: Chorea-acanthocytosis and McLeod syndrome are the core diseases among the group of rare neurodegenerative disorders called neuroacanthocytosis syndromes (NASs). NAS patients have a variable number of irregularly spiky erythrocytes, so-called acanthocytes. Their detection is a crucial but error-prone parameter in the diagnosis of NASs, often leading to misdiagnoses. (2) Methods: We measured the standard Westergren erythrocyte sedimentation rate (ESR) of various blood samples from NAS patients and healthy controls. Furthermore, we manipulated the ESR by swapping the erythrocytes and plasma of different individuals, as well as replacing plasma with dextran. These measurements were complemented by clinical laboratory data and single-cell adhesion force measurements. Additionally, we followed theoretical modeling approaches. (3) Results: We show that the acanthocyte sedimentation rate (ASR) with a two-hour read-out is significantly prolonged in chorea-acanthocytosis and McLeod syndrome without overlap compared to the ESR of the controls. Mechanistically, through modern colloidal physics, we show that acanthocyte aggregation and plasma fibrinogen levels slow down the sedimentation. Moreover, the inverse of ASR correlates with the number of acanthocytes (R2=0.61, p=0.004). (4) Conclusions: The ASR/ESR is a clear, robust and easily obtainable diagnostic marker. Independently of NASs, we also regard this study as a hallmark of the physical view of erythrocyte sedimentation by describing anticoagulated blood in stasis as a percolating gel, allowing the application of colloidal physics theory.
Additional Inhibition of Wnt/β-Catenin Signaling by Metformin in DAA Treatments as a Novel Therapeutic Strategy for HCV-Infected Patients
Authors: Lin Dong , Reddy Venu , Osman Hanadi , Lopez Adriana , Koksal Ali Riza , Rhadhi Sadeq Mutlab , Dash Srikanta , Aydin Yucel
Published: April 2021

Chronic hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC). Although HCV clearance has been improved by the advent of direct-acting antiviral agents (DAA), retrospective studies have shown that the risk of subsequent HCC, while considerably decreased compared with active HCV infection, persists after DAA regimens. However, either the mechanisms of how chronic HCV infection causes HCC or the factors responsible for HCC development after viral eradication in patients with DAA treatments remain elusive. We reported an in vitro model of chronic HCV infection and determined Wnt/β-catenin signaling activation due to the inhibition of GSK-3β activity via serine 9 phosphorylation (p-ser9-GSK-3β) leading to stable non-phosphorylated β-catenin. Immunohistochemical staining demonstrated the upregulation of both β-catenin and p-Ser9-GSK-3β in HCV-induced HCC tissues. Chronic HCV infection increased proliferation and colony-forming ability, but knockdown of β-catenin decreased proliferation and increased apoptosis. Unexpectedly, Wnt/β-catenin signaling remained activated in chronic HCV-infected cells after HCV eradication by DAA, but metformin reversed it through PKA/GSK-3β-mediated β-catenin degradation, inhibited colony-forming ability and proliferation, and increased apoptosis, suggesting that DAA therapy in combination with metformin may be a novel therapy to treat HCV-associated HCC where metformin suppresses Wnt/β-catenin signaling for HCV-infected patients.
Succinate Injection Rescues Vasculature and Improves Functional Recovery Following Acute Peripheral Ischemia in Rodents: A Multimodal Imaging Study
Authors: Moyon Anaïs , Garrigue Philippe , Balasse Laure , Fernandez Samantha , Brige Pauline , Bouhlel Ahlem , Hache Guillaume , Dignat-George Françoise , Taïeb David , Guillet Benjamin
Published: April 2021

Succinate influences angiogenesis and neovascularization via a hormonelike effect on G-protein-coupled receptor 91 (GPR91). This effect has been demonstrated in the pathophysiology of diabetic retinopathy and rheumatoid arthritis. To evaluate whether succinate can play a role in acute peripheral ischemia, a preclinical study was conducted with ischemic mice treated with succinate or PBS and evaluated by imaging. Acute ischemia was followed by an increased in GPR91 expression in the ischemic muscle. As assessed with LASER-Doppler, succinate treatment resulted in an earlier and more intense reperfusion of the ischemic hindlimb compared to the control group (* p = 0.0189). A microPET study using a radiolabeled integrin ligand ([68Ga]Ga-RGD2) showed an earlier angiogenic activation in the succinate arm compared to control mice (* p = 0.020) with a prolonged effect. Additionally, clinical recovery following ischemia was better in the succinate group. In conclusion, succinate injection promotes earlier angiogenesis after ischemia, resulting in a more effective revascularization and subsequently a better functional recovery.
Cells with Many Talents: Lymphatic Endothelial Cells in the Brain Meninges
Authors: Suárez Irina , Schulte-Merker Stefan
Published: April 2021

The lymphatic system serves key functions in maintaining fluid homeostasis, the uptake of dietary fats in the small intestine, and the trafficking of immune cells. Almost all vascularized peripheral tissues and organs contain lymphatic vessels. The brain parenchyma, however, is considered immune privileged and devoid of lymphatic structures. This contrasts with the notion that the brain is metabolically extremely active, produces large amounts of waste and metabolites that need to be cleared, and is especially sensitive to edema formation. Recently, meningeal lymphatic vessels in mammals and zebrafish have been (re-)discovered, but how they contribute to fluid drainage is still not fully understood. Here, we discuss these meningeal vessel systems as well as a newly described cell population in the zebrafish and mouse meninges. These cells, termed brain lymphatic endothelial cells/Fluorescent Granular Perithelial cells/meningeal mural lymphatic endothelial cells in fish, and Leptomeningeal Lymphatic Endothelial Cells in mice, exhibit remarkable features. They have a typical lymphatic endothelial gene expression signature but do not form vessels and rather constitute a meshwork of single cells, covering the brain surface.
A ROS-Based Energy Management System for a Prototype Fuel Cell Hybrid Vehicle
Authors: Piperidis Savvas , Chrysomallis Iason , Georgakopoulos Stavros , Ghionis Nikolaos , Doitsidis Lefteris , Tsourveloudis Nikos
Published: April 2021

The automotive industry has been rapidly transforming and moving further from internal combustion engines, towards hybrid or electric vehicles. A key component for the successful adoption of the aforementioned approach is their Energy Management Systems (EMSs). In the proposed work, we describe in detail a custom EMS, with unique characteristics, which was developed and installed in a hydrogen-powered prototype vehicle. The development of the EMS was based on off-the-shelf components and the adoption of a Robot Operating System (ROS), a meta-operating system developed for robotic-oriented applications. Our approach offers soft real-time control and the ability to organize the controller of the EMS as a straightforward and comprehensive message system that provides the necessary inter-process communication at the core of the EMS control procedure. We describe in detail the software-based implementation and validate our approach through experimental results obtained while the prototype was racing in a low-energy consumption competition.
Business and Energy Efficiency in the Age of Industry 4.0: The Hulten, Broweus and Van Dijk Sensory Marketing Model Applied to Spanish Textile Stores during the COVID-19 Crisis
Authors: Jiménez-Marín Gloria , Elías Zambrano Rodrigo , Galiano-Coronil Araceli , Ravina-Ripoll Rafael
Published: April 2021

Strategic and tactical factors come into play in shop competitiveness where, in addition to the products sold, other marketing mix variables must also be considered. There are also subjective factors, such as perceptions through the senses. This became even more important when, as a result of the COVID-19 crisis and the forced closure of certain establishments with physical sales, it was necessary to increase profitability and efficiency. The aim of this study was to determine the exact role of sensory marketing in shop efficiency and profitability, based on the guiding principles of technology, innovation, and respect for the environment. We conducted an exploratory and experimental study consisting of the creation of a sensory strategy through the adaptation of the Hulten, Broweus and Van Dijk model on a specific establishment in the current era of Industry 4.0. The results indicate an increase in sales as well as customer satisfaction and happiness after implementing the relevant strategies. The conclusions show that this model is valid and reliable for physical retail establishments, and that these business strategies can significantly contribute to the optimisation of energy resources.
Combustion Characteristics of Small Laminar Flames in an Upward Decreasing Magnetic Field
Authors: Xie Yu , Wei Zhilong , Zhou Teng , Zhen Haishen , Liu Zihao , Huang Zuohuang
Published: April 2021

The combustion characteristics of laminar biogas premixed and diffusion flames in the presence of upward decreasing magnetic fields have been investigated in this study. The mechanism of magnet–flame interaction in the literature, in which magnetic fields change the behaviors of laminar flames due to the paramagnetic and diamagnetic properties of the constituent gases, is examined and the results are as follows. The magnetic field has no noticeable effect on premixed flames due to low oxygen concentration of the mixed gas at the injection and the relatively high flow momentum. However, due to the diffusion nature of diffusion flames and paramagnetic property of oxygen in ambient air, oxygen distributions are subjected to the gradient of magnetic flux, thus shortening the height of diffusion flames. Results also show that the flame volume is more strongly varied than flame height. Altered oxygen distributions result in improved combustion and higher flame temperature. In the case of current magnet–flame interaction, the magnetic driving force is combined with gravitational force, and a modified gravity g* as well as gravity modification factor G are derived to characterize the paramagnetism theory of oxygen.
Green Building Adoption on Office Markets in Europe: An Empirical Investigation into LEED Certification
Authors: Gluszak Michal , Malkowska Agnieszka , Marona Bartłomiej
Published: April 2021

The goal of the paper is to evaluate the impact of selected factors on the adoption of LEED (Leadership in Energy and Environmental Design) green building certification in Europe. In the empirical part of the paper we track the fraction of LEED-registered office space in selected European cities, and assess the impact of selected socioeconomic and environmental factors on the certification adoption rate. This research contributes to the ongoing debate about the adoption of green buildings in commercial property markets. In this paper, we investigate factors affecting the adoption of LEED certification using the Arellano and Bond generalized method-of-moments estimator. Compared to prior studies, which relied on cross-sectional data, our research uses a panel approach to investigate the changes in green building adoption rates in selected European cities. Among the cities that are quickly adopting LEED are Frankfurt, Warsaw, Stockholm, and Dublin. The adoption process was not equally fast in Brussels and Copenhagen. Using the dynamic panel model approach, we found that the adoption of green building certification is linked to overall innovativeness in the economy and the perceived greenness of the city. Contrary to some previous studies we did not observe links between the size of the office market and the LEED adoption rate.
Optimization of Window-to-Wall Ratio for Buildings Located in Different Climates: An IDA-Indoor Climate and Energy Simulation Study
Authors: Sayadi Sana , Hayati Abolfazl , Salmanzadeh Mazyar
Published: April 2021

This study investigates different cases to obtain optimal Window-to-Wall ratio (WWR) in seven different climate conditions based on the Köppen–Geiger climate classification. The optimal WWR was decided based on the minimum amount of total energy use (total of cooling, heating, and lighting energy use) of a building model during a complete year. The impact of overhang and automatic blinds were assessed on the optimization of WWR for a building with integrated automatic lighting control. Moreover, three different windows with different U-values and features were employed in order to analyze their effect on the energy use and WWR of the building. IDA-Indoor Climate and Energy (IDA-ICE) was used to carry out the simulations. The software has been validated based on ASHRAE Standard 140. Based on each climate condition, orientation, employed window type, and comfort conditions, an optimal range with a specific combination of window with blind, overhang, or neither was found.
An Improved and Integrated Design of Segmented Dynamic Wireless Power Transfer for Electric Vehicles
Authors: Wang Heshou , Cheng Ka Wai Eric
Published: April 2021

This paper describes improvements in a segmented dynamic wireless power transfer (DWPT) system for electric vehicles (EVs), and aims to offer a stable charging method for high-power applications. An integrated design is presented, including the modified switching sequence, the size of segmented transmitters, and parallel inverter technology for high-power applications. Three consecutive transmitters mounted on the rail track are energized according to the position of the pickups. This three-consecutive-transmitter group is comprised of a Q-shaped coil, a DD-shaped coil, and a Q-shaped coil again (QDDQ). QDDQ is used as an elementary energized group to optimize the number of energized transmitters and mitigate the output voltage variation. The entire DWPT system is designed with finite element analysis (FEA) and studied with circuit topologies. Overall, an experimental prototype for dynamic charging is built to verify the overall performance, which shows a great agreement with the theoretical analysis. In this prototype, there are five transmitters and one receiver. All dimensions are 500 mm × 500 mm. The proposed system has been validated to realize 500 V constant output voltage with approximately 85% dc-dc efficiency from the 100 Ω to 200 Ω load conditions. A 2.5 kW maximum output power occurs at the 100 Ω load condition.
Flame Stabilization and Blow-Off of Ultra-Lean H2-Air Premixed Flames
Authors: Vance Faizan Habib , Shoshin Yuriy , de Goey Philip , van Oijen Jeroen
Published: April 2021

The manner in which an ultra-lean hydrogen flame stabilizes and blows off is crucial for the understanding and design of safe and efficient combustion devices. In this study, we use experiments and numerical simulations for pure H2-air flames stabilized behind a cylindrical bluff body to reveal the underlying physics that make such flames stable and eventually blow-off. Results from CFD simulations are used to investigate the role of stretch and preferential diffusion after a qualitative validation with experiments. It is found that the flame displacement speed of flames stabilized beyond the lean flammability limit of a flat stretchless flame (ϕ=0.3) can be scaled with a relevant tubular flame displacement speed. This result is crucial as no scaling reference is available for such flames. We also confirm our previous hypothesis regarding lean limit blow-off for flames with a neck formation that such flames are quenched due to excessive local stretching. After extinction at the flame neck, flames with closed flame fronts are found to be stabilized inside a recirculation zone.
A Comparison of Integrated Filtering and Prediction Methods for Smart Grids
Authors: Escobar-Avalos Emmanuel , Rodríguez-Licea Martín A. , Rostro-González Horacio , Soriano-Sánchez Allan G. , Pérez-Pinal Francisco J.
Published: April 2021

The intelligent use of green and renewable energies requires reliable and preferably anticipated information regarding their availability and the behavior of meteorological variables in a scenario of natural intermittency. Examples of this are the smart grids, which can incorporate, among others, a charging system for electric vehicles and modern and predictive management techniques. However, some issues associated with such procedures are data captured by sensors and transducers with noise in their signals and low information repeatability under the same reading conditions. To tackle such problems, numerous filtering and data fitting techniques and various prediction methods have been developed, but an appropriate selection can be cumbersome. Also, some filtering techniques, such as RANdom SAmple Consensus (RANSAC) appear not to have been used in prediction scenarios for smart grids, to the authors’ knowledge. In this regard, this paper aims to present a comparison in terms of average error, determination coefficient, and cross validation that can be expected under prediction schemes as Multiple Linear Regression, Vector Support Machines and a Multilayer Perceptron Regression Neural Network (MLPRNN), with filtering/scaling methods such as Maximum and Minimum, L2 Norm, Standard Scale, and RANSAC. Cross validation allows to flag problems like overfitting or selection bias, and this comparison is another novelty for smart grid scenarios, to the authors’ knowledge. Although many combinations were analyzed, RANSAC, with L2 Norm filtering and an MLPRNN for prediction, generate the best results. RANSAC algorithm with L2 Norm is a novelty for filtering and predicting in smart grids, and through an MLPRNN, the R2 error can be reduced to 0.8843, the MSE to 0.8960, and the cross validation accuracy can be increased to 0.44 (±0.2).
Water Budget Analysis Considering Surface Water–Groundwater Interactions in the Exploitation of Seasonally Varying Agricultural Groundwater
Authors: Chang Sun Woo , Chung Il-Moon
Published: April 2021

In South Korea, groundwater intended for use in greenhouse cultivation is collected from shallow riverside aquifers as part of agricultural activities during the winter season. This study quantified the effects of intensive groundwater intake on aquifers during the winter and examined the roles of nearby rivers in this process. Observation data were collected for approximately two years from six wells and two river-level observation points on the study site. Furthermore, the river water levels before and after the weir structures were examined in detail, because they are determined by artificial structures in the river. The structures have significant impacts on the inflow and outflow from the river to the groundwater reservoirs. As a result, a decline in groundwater levels owing to groundwater depletion was observed during the water curtain cultivation (WCC) period in the winter season. In addition, we found that the groundwater level increased owing to groundwater recharge due to rainfall and induced recharge by rivers during the spring–summer period after the end of the WCC period. MODFLOW, a three-dimensional difference model, was used to simulate the groundwater level decreases and increases around the WCC area in Cheongwon-gun. Time-variable recharge data provided by the soil and water assessment tool model, SWAT for watershed hydrology, was used to determine the amount of groundwater recharge that was input to the groundwater model. The groundwater level time series observations collected from observation wells during the two-year simulation period (2012 to 2014) were compared with the simulation values. In addition, to determine the groundwater depletion of the entire demonstration area and the sustainability of the WCC, the quantitative water budget was analyzed using integrated hydrologic analysis. The result indicated that a 2.5 cm groundwater decline occurred on average every year at the study site. Furthermore, an analysis method that reflects the stratification and boundary conditions of underground aquifers, hydrogeologic properties, hydrological factors, and artificial recharge scenarios was established and simulated with injection amounts of 20%, 40%, and 60%. This study suggested a proper artificial recharge method of injecting water by wells using riverside groundwater in the study area.
Exploring COVID-19 Daily Records of Diagnosed Cases and Fatalities Based on Simple Nonparametric Methods
Authors: Diebner Hans H. , Timmesfeld Nina
Published: April 2021

Containment strategies to combat epidemics such as SARS-CoV-2/COVID-19 require the availability of epidemiological parameters, e.g., the effective reproduction number. Parametric models such as the commonly used susceptible-infected-removed (SIR) compartment models fitted to observed incidence time series have limitations due to the time-dependency of the parameters. Furthermore, fatalities are delayed with respect to the counts of new cases, and the reproduction cycle leads to periodic patterns in incidence time series. Therefore, based on comprehensible nonparametric methods including time-delay correlation analyses, estimates of crucial parameters that characterise the COVID-19 pandemic with a focus on the German epidemic are presented using publicly available time-series data on prevalence and fatalities. The estimates for Germany are compared with the results for seven other countries (France, Italy, the United States of America, the United Kingdom, Spain, Switzerland, and Brazil). The duration from diagnosis to death resulting from delay-time correlations turns out to be 13 days with high accuracy for Germany and Switzerland. For the other countries, the time-to-death durations have wider confidence intervals. With respect to the German data, the two time series of new cases and fatalities exhibit a strong coherence. Based on the time lag between diagnoses and deaths, properly delayed asymptotic as well as instantaneous fatality–case ratios are calculated. The temporal median of the instantaneous fatality–case ratio with time lag of 13 days between cases and deaths for Germany turns out to be 0.02. Time courses of asymptotic fatality–case ratios are presented for other countries, which substantially differ during the first half of the pandemic but converge to a narrow range with standard deviation 0.0057 and mean 0.024. Similar results are obtained from comparing time courses of instantaneous fatality–case ratios with optimal delay for the 8 exemplarily chosen countries. The basic reproduction number, R0, for Germany is estimated to be between 2.4 and 3.4 depending on the generation time, which is estimated based on a delay autocorrelation analysis. Resonances at about 4 days and 7 days are observed, partially attributable to weekly periodicity of sampling. The instantaneous (time-dependent) reproduction number is estimated from the incident (counts of new) cases, thus allowing us to infer the temporal behaviour of the reproduction number during the epidemic course. The time course of the reproduction number turns out to be consistent with the time-dependent per capita growth.
Postural Sensorimotor Control on Anorectal Pressures and Pelvic Floor Muscle Tone and Strength: Effects of a Single 5P® LOGSURF Session. A Cross-Sectional Preliminary Study
Authors: Fuentes-Aparicio Laura , Arranz-Martín Beatriz , Navarro-Brazález Beatriz , Bailón-Cerezo Javier , Sánchez-Sánchez Beatriz , Torres-Lacomba María
Published: April 2021

Pelvic floor dysfunction (PFD) is a functional condition present most frequently in women. Despite pelvic floor muscle training being considered by the International Continence Society (ICS) as the first-line treatment in uncomplicated urinary incontinence, other more comprehensive postural methods as 5P® LOGSURF have emerged. This preliminary cross-sectional study explores the effects of a single 5P® LOGSURF session on pelvic floor muscle (PFM) tone and strength (MVC), resting anal tone, intrarectal pressure, and deep abdominal muscles activation. Thirty women were included (11 without PFD and 19 with PFD). Primary outcome measures were PFM tone, PFM MVC and resting anal tone and secondary measures outcomes were intrarectal pressure and deep abdominal activation. All outcome measures were collected before, throughout and after a single 30′ 5P® LOGSURF session. The findings from this study suggest that PFM tone (PFD group: p = 0.09, d = 0.72; non-PFD group: p = 0.003, d = 0.49) and PFM MVC (PFD group: p = 0.016; non-PFD group: p = 0.005) decreased in both groups after a single 5P® LOGSURF session, with a medium effect size for women with PFD. Contrarily, deep abdominal muscle MVC increased (PFD group: p < 0.001; non-PFD group: p = 0.03). Intrarectal pressure and resting anal tone decreased in both groups throughout the session. These results suggest that 5P® LOGSURF method may be interesting if is performed by women with mild symptoms of PFD or healthy women to achieve a decrease in PFM tone in women who manifested pain to intracavitary techniques or practices. Further research with higher sample sizes and long-term are necessary for generalizing.
Primary Care Records of Chronic-Disease Patient Adherence to Treatment
Authors: Massot Mesquida Mireia , de la Fuente Josep Anton , Andrés Lorca Anna María , Arteaga Pillasagua Ingrid , Balboa Blanco Edelmiro , Gracia Vidal Sonia , Pablo Reyes Sara , Gómez Iparraguirre Paula , Seda Gombau Gemma , Torán-Monserrat Pere
Published: April 2021

The goal of managing adherence (AD) is to achieve better medication use by patients in order to maximize benefits and reduce risks. With the aim of improving treatment adherence by patients, we carried out a descriptive study to obtain information related to adherence management in primary care. Inclusion criteria were as follows: patients that had at least one record of any treatment adherence assessment variable. For those that had more than one recorded variable, we analyzed consistency across test results. For the comparative analysis of adherence records, patients were categorized into three groups on the basis of the healthcare unit that recorded the data: case management (CM), home care (HC), and primary care team (PCT). A total of 32,137 subjects met inclusion criteria; 79.56% of subjects were older than 65. As for the analysis of assessment records across care units, 69.73% of CM patients, 67.17% of HC patients, and 2.33% of PCT patients had adherence assessment records. CM units made a significantly greater number of records than HC units. We observed low adherence at a rate of 49.3% in the CM group, 31.91% in the HC group, and 17.58% in the PCT group. When more than one adherence variable was recorded, analysis revealed inconsistent test results or recorded variables in 9.06% of PCT cases, 14.83% of HC cases, and 20.47% of CM cases. The inconsistencies observed in records of adherence assessment and management across different care units reveal the huge variability that exists in managing and selecting a tool to assess adherence.
Changes in the Trunk and Lower Extremity Kinematics Due to Fatigue Can Predispose to Chronic Injuries in Cycling
Authors: Galindo-Martínez Alberto , López-Valenciano Alejandro , Albaladejo-García Carlos , Vallés-González Juan M. , Elvira Jose L. L.
Published: April 2021

Kinematic analysis of the cycling position is a determining factor in injury prevention and optimal performance. Fatigue caused by high volume training can alter the kinematics of the lower body and spinal structures, thus increasing the risk of chronic injury. However, very few studies have established relationships between fatigue and postural change, being these in 2D analysis or incremental intensity protocols. Therefore, this study aimed to perform a 3D kinematic analysis of pedaling technique in a stable power fatigue protocol 23 amateur cyclists (28.3 ± 8.4 years) participated in this study. For this purpose, 3D kinematics in hip, knee, ankle, and lumbar joints, and thorax and pelvis were collected at three separate times during the protocol. Kinematic differences at the beginning, middle, and end of the protocol were analyzed for all joints using one-dimensional statistical parametric mapping. Significant differences (p < 0.05) were found in all the joints studied, but not all of them occur in the same planes or the same phase of the cycle. Some of the changes produced, such as greater lumbar and thoracic flexion, greater thoracic and pelvic tilt, or greater hip adduction, could lead to chronic knee and lumbar injuries. Therefore, bike fitting protocols should be carried out in fatigue situations to detect risk factor situations.
Developing a Culturally Sensitive ICF-Based Tool to Describe Functioning of Children with Autism Spectrum Disorder: TEA-CIFunciona Version 1.0 Pilot Study
Authors: Napoli Silvana B. , Vitale María Paula , Cafiero Pablo J. , Micheletti María Belén , Bradichansky Paula Pedernera , Lejarraga Celina , Urinovsky Maria Gabriela , Escalante Anabella , Rodriguez Estela , Schiariti Verónica
Published: April 2021

Background: Autism spectrum disorder (ASD) affects the daily functioning of children and their families; however, in Argentina, there are no standardized tools to guide the description, evaluation, and follow-up of functioning and disability of children with ASD. To fill this gap, the overarching purpose of this study was to create a novel tool guided by the International Classification of Functioning, Disability, and Health (ICF) Core Sets for ASD for clinical practice. Methods: A multistep methodology was used to identify the most relevant ICF categories for an Argentinian clinical setting. The content of this ICF-based shortlist was piloted and revised according to the results. Subsequently, a toolbox of measures was proposed to operationalize each ICF category. Finally, profiles of the functioning of 100 children with ASD were created. Results: An ICF-based tool called TEA-CIFunciona was created, consisting of 32 ICF categories (10 body functions, 15 activities and participation, 7 environmental factors categories). The application of TEA-CIFunciona incorporated a family-centered approach in ASD evaluations and helped identify functional needs. Conclusions: TEA-CIFunciona is the first ICF-based instrument that guides the description of functioning of children with ASD in Argentina. TEA-CIFunciona standardizes collaborative assessments in pediatric ASD populations in Latin American contexts.
Analysis of High-Risk Sexual Behavior among Polish University Students
Authors: Stokłosa Iga , Stokłosa Maciej , Porwolik Mateusz , Bugajski Maciej , Więckiewicz Gniewko , Piegza Magdalena , Męcik-Kronenberg Tomasz , Gorczyca Piotr
Published: April 2021

High-risk sexual behavior consists of activities and habits that put a person at increased risk of sexually transmitted infections (STIs) or unplanned pregnancy. Poland is currently experiencing a problem with increased STI rates, largely due to poor sexual education. Our exploratory study aims to evaluate the sexual behavior of students attending universities across Poland. The study covered 7678 students from 50 different faculties and universities across the country. The authors created an original questionnaire which consists of 31 questions which, among others, included demographic factors, sexual initiation, high-risk sexual behavior, STI’s and religious beliefs. 78% of students have participated in sexual activity, among them 19% of students had ‘casual sex’ consisting of intercourse without the use of a condom, 27% had participated in sexual intercourse after the consumption of alcohol. Our study found that students who are influenced by religious belief tend to engage in sexual activity into their later years. The groups most exposed to the consequences of risky sexual behavior are mostly homosexual men, bisexual women, art students, and military students. Alcohol consumption is a strong factor contributing to risky sexual behavior. Sexual education in Poland should be improved.
Molecular Biomechanics Controls Protein Mixing and Segregation in Adherent Membranes
Authors: Li Long , Stumpf Bernd , Smith Ana-Sunčana
Published: April 2021

Cells interact with their environment by forming complex structures involving a multitude of proteins within assemblies in the plasma membrane. Despite the omnipresence of these assemblies, a number of questions about the correlations between the organisation of domains and the biomechanical properties of the involved proteins, namely their length, flexibility and affinity, as well as about the coupling to the elastic, fluctuating membrane, remain open. Here we address these issues by developing an effective Kinetic Monte Carlo simulation to model membrane adhesion. We apply this model to a typical experiment in which a cell binds to a functionalized solid supported bilayer and use two ligand-receptor pairs to study these couplings. We find that differences in affinity and length of proteins forming adhesive contacts result in several characteristic features in the calculated phase diagrams. One such feature is mixed states occurring even with proteins with length differences of 10 nm. Another feature are stable nanodomains with segregated proteins appearing on time scales of cell experiments, and for biologically relevant parameters. Furthermore, we show that macroscopic ring-like patterns can spontaneously form as a consequence of emergent protein fluxes. The capacity to form domains is captured by an order parameter that is founded on the virial coefficients for the membrane mediated interactions between bonds, which allow us to collapse all the data. These findings show that taking into account the role of the membrane allows us to recover a number of experimentally observed patterns. This is an important perspective in the context of explicit biological systems, which can now be studied in significant detail.
The Effect of Oxidized Dopamine on the Structure and Molecular Chaperone Function of the Small Heat-Shock Proteins, αB-Crystallin and Hsp27
Authors: Hayashi Junna , Ton Jennifer , Negi Sparsh , Stephens Daniel E. K. M. , Pountney Dean L. , Preiss Thomas , Carver John A.
Published: April 2021

Oxidation of the neurotransmitter, dopamine (DA), is a pathological hallmark of Parkinson’s disease (PD). Oxidized DA forms adducts with proteins which can alter their functionality. αB-crystallin and Hsp27 are intracellular, small heat-shock molecular chaperone proteins (sHsps) which form the first line of defense to prevent protein aggregation under conditions of cellular stress. In vitro, the effects of oxidized DA on the structure and function of αB-crystallin and Hsp27 were investigated. Oxidized DA promoted the cross-linking of αB-crystallin and Hsp27 to form well-defined dimer, trimer, tetramer, etc., species, as monitored by SDS-PAGE. Lysine residues were involved in the cross-links. The secondary structure of the sHsps was not altered significantly upon cross-linking with oxidized DA but their oligomeric size was increased. When modified with a molar equivalent of DA, sHsp chaperone functionality was largely retained in preventing both amorphous and amyloid fibrillar aggregation, including fibril formation of mutant (A53T) α-synuclein, a protein whose aggregation is associated with autosomal PD. In the main, higher levels of sHsp modification with DA led to a reduction in chaperone effectiveness. In vivo, DA is sequestered into acidic vesicles to prevent its oxidation and, intracellularly, oxidation is minimized by mM levels of the antioxidant, glutathione. In vitro, acidic pH and glutathione prevented the formation of oxidized DA-induced cross-linking of the sHsps. Oxidized DA-modified αB-crystallin and Hsp27 were not cytotoxic. In a cellular context, retention of significant chaperone functionality by mildly oxidized DA-modified sHsps would contribute to proteostasis by preventing protein aggregation (particularly of α-synuclein) that is associated with PD.
Targeting Protein Kinases in Blood Cancer: Focusing on CK1α and CK2
Authors: Spinello Zaira , Fregnani Anna , Quotti Tubi Laura , Trentin Livio , Piazza Francesco , Manni Sabrina
Published: April 2021

Disturbance of protein kinase activity may result in dramatic consequences that often lead to cancer development and progression. In tumors of blood origin, both tyrosine kinases and serine/threonine kinases are altered by different types of mutations, critically regulating cancer hallmarks. CK1α and CK2 are highly conserved, ubiquitously expressed and constitutively active pleiotropic kinases, which participate in multiple biological processes. The involvement of these kinases in solid and blood cancers is well documented. CK1α and CK2 are overactive in multiple myeloma, leukemias and lymphomas. Intriguingly, they are not required to the same degree for the viability of normal cells, corroborating the idea of “druggable” kinases. Different to other kinases, mutations on the gene encoding CK1α and CK2 are rare or not reported. Actually, these two kinases are outside the paradigm of oncogene addiction, since cancer cells’ dependency on these proteins resembles the phenomenon of “non-oncogene” addiction. In this review, we will summarize the general features of CK1α and CK2 and the most relevant oncogenic and stress-related signaling nodes, regulated by kinase phosphorylation, that may lead to tumor progression. Finally, we will report the current data, which support the positioning of these two kinases in the therapeutic scene of hematological cancers.
Identifying Methylation Patterns in Dental Pulp Aging: Application to Age-at-Death Estimation in Forensic Anthropology
Authors: C. Zapico Sara , Gauthier Quentin , Antevska Aleksandra , McCord Bruce R.
Published: April 2021

Age-at-death estimation constitutes one of the key parameters for identification of human remains in forensic investigations. However, for applications in forensic anthropology, many current methods are not sufficiently accurate for adult individuals, leading to chronological age estimates erring by ±10 years. Based on recent trends in aging studies, DNA methylation has great potential as a solution to this problem. However, there are only a few studies that have been published utilizing DNA methylation to determine age from human remains. The aim of the present study was to expand the range of this work by analyzing DNA methylation in dental pulp from adult individuals. Healthy erupted third molars were extracted from individuals aged 22–70. DNA from pulp was isolated and bisulfite converted. Pyrosequencing was the chosen technique to assess DNA methylation. As noted in previous studies, we found that ELOVL2 and FHL2 CpGs played a role in age estimation. In addition, three new markers were evaluated—NPTX2, KLF14, and SCGN. A set of CpGs from these five loci was used in four different multivariate regression models, providing a Mean Absolute Error (MAE) between predicted and chronological age of 1.5–2.13 years. The findings from this research can improve age estimation, increasing the accuracy of identification in forensic anthropology.