bluuebunny/crossref_metadata_2025 huggingface dataset:
Nationwide Determination of Required Total Lengths of Multiple Borehole Heat Exchangers under Variable Climate and Geology in Japan
Authors: Sakata Yoshitaka , Katsura Takao , Nagano Katsunori
Published: April 2021

This study determined the required lengths of borehole heat exchangers (BHEs) in ground-source heat pump systems for heating/cooling a building (with 300 m2 of floor area) across Japan’s four main islands through a simulation approach. Hourly thermal loads were estimated in 10 km gridded cells based on the outside temperature and humidity. Three-dimensional estimates of ground thermal conductivity from our previous study at the depths of the BHEs were used. A 5-year system operation was simulated in a total of 4059 cells with 81 combinations of individual lengths and total numbers of BHEs to determine the shortest total length required to achieve sustainable use and targeted performance. The optimal combination of individual length and total number varied regionally due to climate conditions and locally among adjacent cells due to geological conditions. The total required lengths ranged widely from 78 to 1782 m. However, the lengths were less than 400 m in 85% of the cells. Additionally, cost-effectiveness in 69% of the cells was shown by reducing the total lengths to half or less of those in the practical method. The reduction could potentially increase the feasibility of heat pump system use in Japan. The total lengths were dependent on the heating/cooling loads approximately as secondary-polynomial functions, but the relations with the ground thermal conductivity were not clear.
CrimeVec—Exploring Spatial-Temporal Based Vector Representations of Urban Crime Types and Crime-Related Urban Regions
Authors: Crivellari Alessandro , Ristea Alina
Published: April 2021

The traditional categorization of crime types relies on a hierarchical structure, from high-level categories to lower-level subtypes. This tree-based classification treats crime types as mutually independent when they do not branch from the same higher-level category, therefore lacking inter-category semantic relations. The issue then extends over crime distribution analysis of urban regions, often reporting statistics based on crime type counts, but neglecting implicit relations between different crime categories. Our study aims to fill this information gap, providing a more complete understanding of urban crime in both qualitative and quantitative terms. Specifically, we propose a vector-based crime type representation, constructed via unsupervised machine learning on temporal and geographic factors. The general idea is to define crime types as “related” if they often occur in the same area at the same time span, regardless of any initial hierarchical categorization. This opens to a new metric of comparison that goes beyond pre-defined structures, revealing hidden relationships between crime types by generating a vector space in a completely data-driven manner. Crime types are represented as points in this space, and their relative distances disclose stronger or weaker semantic relations. A direct application on urban crime distribution analysis stands out in the form of visualization tools for intuitive data investigations and convenient comparison measures on composite vectors of urban regions. Meaningful insights on crime type distributions and a better understanding of urban crime characteristics determine a valuable asset to urban management and development.
Mapping Very-High-Resolution Evapotranspiration from Unmanned Aerial Vehicle (UAV) Imagery
Authors: Park Suyoung , Ryu Dongryeol , Fuentes Sigfredo , Chung Hoam , O’Connell Mark , Kim Junchul
Published: April 2021

There is a growing concern about water scarcity and the associated decline in Australia’s agricultural production. Efficient water use as a natural resource requires more precise and adequate monitoring of crop water use and irrigation scheduling. Therefore, accurate estimations of evapotranspiration (ET) at proper spatial–temporal scales are critical to understand the crop water demand and uptake and to enable optimal irrigation scheduling. Remote sensing (RS)-based ET estimation has been adopted as a method for large-scale applications when the detailed spatial representation of ET is required. This research aimed to estimate instantaneous ET using very-high-resolution (VHR) multispectral and thermal imagery (GSD < 8 cm) collected using a single flight of a UAV over a high-density peach orchard with a discontinuous canopy. The energy balance component estimation was based on the high-resolution mapping of evapotranspiration (HRMET) model. A tree-by-tree ET map was produced using the canopy surface temperature and the leaf area index (LAI) resampled at the corresponding scale via a systematic feature segmentation method based on pure canopy extraction. Results showed a strong linear relationship between the estimated ET and the leaf transpiration (n = 42) measured using a gas exchange sensor, with a coefficient of determination (R2) of 0.89. Daily ET (5.5 mm d−1) derived from the instantaneous ET map was comparable with daily crop ET (6.4 mm d−1) determined by the meteorological approach over the study site. The proposed approach has important implications for mapping tree-by-tree ET over horticultural fields using VHR imagery.
Long-Term Iron Deficiency and Dietary Iron Excess Exacerbate Acute Dextran Sodium Sulphate-Induced Colitis and Are Associated with Significant Dysbiosis
Authors: Mahalhal Awad , Burkitt Michael D. , Duckworth Carrie A. , Hold Georgina L. , Campbell Barry J. , Pritchard David Mark , Probert Chris S.
Published: April 2021

Background: Oral iron supplementation causes gastrointestinal side effects. Short-term alterations in dietary iron exacerbate inflammation and alter the gut microbiota, in murine models of colitis. Patients typically take supplements for months. We investigated the impact of long-term changes in dietary iron on colitis and the microbiome in mice. Methods: We fed mice chow containing differing levels of iron, reflecting deficient (100 ppm), normal (200 ppm), and supplemented (400 ppm) intake for up to 9 weeks, both in absence and presence of dextran sodium sulphate (DSS)-induced chronic colitis. We also induced acute colitis in mice taking these diets for 8 weeks. Impact was assessed (i) clinically and histologically, and (ii) by sequencing the V4 region of 16S rRNA. Results: In mice with long-term changes, the iron-deficient diet was associated with greater weight loss and histological inflammation in the acute colitis model. Chronic colitis was not influenced by altering dietary iron however there was a change in the microbiome in DSS-treated mice consuming 100 ppm and 400 ppm iron diets, and control mice consuming the 400 ppm iron diet. Proteobacteria levels increased significantly, and Bacteroidetes levels decreased, in the 400 ppm iron DSS group at day-63 compared to baseline. Conclusions: Long-term dietary iron alterations affect gut microbiota signatures but do not exacerbate chronic colitis, however acute colitis is exacerbated by such dietary changes. More work is needed to understand the impact of iron supplementation on IBD. The change in the microbiome, in patients with colitis, may arise from the increased luminal iron and not simply from colitis.
Insoluble Vascular Amyloid Deposits Trigger Disruption of the Neurovascular Unit in Alzheimer’s Disease Brains
Authors: Soto-Rojas Luis O. , Campa-Córdoba B. Berenice , Harrington Charles R. , Salas-Casas Andrés , Hernandes-Alejandro Mario , Villanueva-Fierro Ignacio , Bravo-Muñoz Marely , Garcés-Ramírez Linda , De La Cruz-López Fidel , Ontiveros-Torres Miguel Ángel , Gevorkian Goar , Pacheco-Herrero Mar , Luna-Muñoz José
Published: April 2021

Alzheimer’s disease (AD) is a neurodegenerative disease, characterized histopathologically by intra-neuronal tau-related lesions and by the accumulation of amyloid β-peptide (Aβ) in the brain parenchyma and around cerebral blood vessels. According to the vascular hypothesis of AD, an alteration in the neurovascular unit (NVU) could lead to Aβ vascular accumulation and promote neuronal dysfunction, accelerating neurodegeneration and dementia. To date, the effects of insoluble vascular Aβ deposits on the NVU and the blood–brain barrier (BBB) are unknown. In this study, we analyze different Aβ species and their association with the cells that make up the NVU. We evaluated post-mortem AD brain tissue. Multiple immunofluorescence assays were performed against different species of Aβ and the main elements that constitute the NVU. Our results showed that there are insoluble vascular deposits of both full-length and truncated Aβ species. Besides, insoluble aggregates are associated with a decrease in the phenotype of the cellular components that constitute the NVU and with BBB disruption. This approach could help identify new therapeutic targets against key molecules and receptors in the NVU that can prevent the accumulation of vascular fibrillar Aβ in AD.
Evaluation of Selective COX-2 Inhibition and In Silico Study of Kuwanon Derivatives Isolated from Morus alba
Authors: Baek Seung-Hwa , Hwang Sungbo , Park Tamina , Kwon Yoon-Ju , Cho Myounglae , Park Daeui
Published: April 2021

Six kuwanon derivatives (A/B/C/E/H/J) extracted from the roots of Morus alba L. were evaluated to determine their cyclooxygenase (COX)-1 and 2 inhibitory effects. Cyclooxygenase (COX) is known as the target enzyme of nonsteroidal anti-inflammatory drugs (NSAIDs), which are the most widely used therapeutic agents for pain and inflammation. Among six kuwanon derivatives, kuwanon A showed selective COX-2 inhibitory activity, almost equivalent to that of celecoxib, a known COX inhibitor. Kuwanon A showed high COX-2 inhibitory activity (IC50 = 14 μM) and a selectivity index (SI) range of >7.1, comparable to celecoxib (SI > 6.3). To understand the mechanisms underlying this effect, we performed docking simulations, fragment molecular orbital (FMO) calculations, and pair interaction energy decomposition analysis (PIEDA) at the quantum-mechanical level. As a result, kuwanon A had the strongest interaction with Arg120 and Tyr355 at the gate of the COX active site (−7.044 kcal/mol) and with Val89 in the membrane-binding domain (−6.599 kcal/mol). In addition, kuwanon A closely bound to Val89, His90, and Ser119, which are residues at the entrance and exit routes of the COX active site (4.329 Å). FMO calculations and PIEDA well supported the COX-2 selective inhibitory action of kuwanon A. It showed that the simulation and modeling results and experimental evidence were consistent.
Germinated Rhynchosia nulubilis Fermented with Lactobacillus pentosus SC65 Reduces Particulate Matter Induced Type II Alveolar Epithelial Apoptotic Cell Death
Authors: Lee Hye-Ji , Park Hye-Jin
Published: April 2021

Particulate matter (PM) is a significant environmental pollutant that promotes respiratory diseases, including lung injury and inflammation, by inducing oxidative stress. Rhynchosia nulubilis (black soybean) is traditionally used to prevent chronic respiratory disease via inducing antioxidant and anti-inflammatory effects. To investigate the effects of Lactobacillus pentosus SC65 fermented GR (GR-SC65) and Pediococcus pentosaceus ON81A (GR-ON81A) against PM-induced oxidative stress and cell death in A549 cells, we performed the 2-7-dichlorodihydrofluorescein diacetate and cell counting kit-8 assays, as well as Hoechst 33342 and propidium iodide staining and western blotting. GR-SC65 showed the highest total polyphenolic contents and 1,1-diphenyl-2-picrylidrazil radical scavenging activity among lactic acid bacteria-fermented GRs (p < 0.001 vs. GR). Four soy peptides, β-conglycinin breakdowns (INAENNQRNF, ISSEDKPFN, LAFPGSAQAVEK, and LAFPGSAKDIEN), were detected in GR-SC65, but not in GR. In GR-SC65, PM-induced A549 cell death was less than that observed in GR-ON81A and GR (p < 0.001 vs. PM-treated group). GR-SC65 significantly decreased intracellular reactive oxidative species (ROS) when compared with PM (*** p < 0.001 vs. PM). GR-SC65 decreased the levels of BAX, active caspase-9, -3, and poly ADP-ribose polymerase (PARP) proteins (#p < 0.01, ###p < 0.001 vs. PM), while increasing the level of BCL-2 protein, a mitochondrial anti-apoptotic protein (###p < 0.001 vs. PM). Our findings indicate that GR-SC65 inhibited PM-induced cell death by suppressing the levels of ROS, active caspase-9 and -3, and PARP proteins, while enhancing the level of BCL-2 protein in type II alveolar epithelial A549 cells. Therefore, GR-SC65 might be a potential therapeutic and preventive agent against PM-induced lung injury.
Thrombin Activatable Fibrinolysis Inhibitor (TAFI): An Updated Narrative Review
Authors: Sillen Machteld , Declerck Paul J.
Published: April 2021

Thrombin activatable fibrinolysis inhibitor (TAFI), a proenzyme, is converted to a potent attenuator of the fibrinolytic system upon activation by thrombin, plasmin, or the thrombin/thrombomodulin complex. Since TAFI forms a molecular link between coagulation and fibrinolysis and plays a potential role in venous and arterial thrombotic diseases, much interest has been tied to the development of molecules that antagonize its function. This review aims at providing a general overview on the biochemical properties of TAFI, its (patho)physiologic function, and various strategies to stimulate the fibrinolytic system by interfering with (activated) TAFI functionality.
The Importance of Free Fatty Chain Length on the Lipid Organization in the Long Periodicity Phase
Authors: Beddoes Charlotte M. , Rensen Denise E. , Gooris Gert S. , Malfois Marc , Bouwstra Joke A.
Published: April 2021

The skin’s barrier ability is an essential function for terrestrial survival, which is controlled by intercellular lipids within the stratum corneum (SC) layer. In this barrier, free fatty acids (FFAs) are an important lipid class. As seen in inflammatory skin diseases, when the lipid chain length is reduced, a reduction in the barrier’s performance is observed. In this study, we have investigated the contributing effects of various FFA chain lengths on the lamellar phase, lateral packing. The repeat distance of the lamellar phase increased with FFA chain length (C20–C28), while shorter FFAs (C16 to C18) had the opposite behaviour. While the lateral packing was affected, the orthorhombic to hexagonal to fluid phase transitions were not affected by the FFA chain length. Porcine SC lipid composition mimicking model was then used to investigate the proportional effect of shorter FFA C16, up to 50% content of the total FFA mixture. At this level, no difference in the overall lamellar phases and lateral packing was observed, while a significant increase in the water permeability was detected. Our results demonstrate a FFA C16 threshold that must be exceeded before the structure and barrier function of the long periodicity phase (LPP) is affected. These results are important to understand the lipid behaviour in this unique LPP structure as well as for the understanding, treatment, and development of inflammatory skin conditions.
Dose-Dependent Physiological and Transcriptomic Responses of Lettuce (Lactuca sativa L.) to Copper Oxide Nanoparticles—Insights into the Phytotoxicity Mechanisms
Authors: Xiong Tiantian , Zhang Shasha , Kang Zhuangzhuang , Zhang Ting , Li Shaoshan
Published: April 2021

Understanding the complex mechanisms involved in plant response to nanoparticles (NPs) is indispensable in assessing the environmental impact of nano-pollutants. Plant leaves can directly intercept or absorb NPs deposited on their surface; however, the toxicity mechanisms of NPs to plant leaves are unclear. In this study, lettuce leaves were exposed to copper oxide nanoparticles (CuO-NPs, 0, 100, and 1000 mg/L) for 15 days, then physiological tests and transcriptomic analyses were conducted to evaluate the negative impacts of CuO-NPs. Both physiological and transcriptomic results demonstrated that CuO-NPs adversely affected plant growth, photosynthesis, and enhanced reactive oxygen species (ROS) accumulation and antioxidant system activity. The comparative transcriptome analysis showed that 2270 and 4264 genes were differentially expressed upon exposure to 100 and 1000 mg/L CuO-NPs. Gene expression analysis suggested the ATP-binding cassette (ABC) transporter family, heavy metal-associated isoprenylated plant proteins (HIPPs), endocytosis, and other metal ion binding proteins or channels play significant roles in CuO-NP accumulation by plant leaves. Furthermore, the variation in antioxidant enzyme transcript levels (POD1, MDAR4, APX2, FSDs), flavonoid content, cell wall structure and components, and hormone (auxin) could be essential in regulating CuO-NPs-induced stress. These findings could help understand the toxicity mechanisms of metal NPs on crops, especially NPs resulting from foliar exposure.
Energy Metabolism in the Inner Retina in Health and Glaucoma
Authors: Liu Hanhan , Prokosch Verena
Published: April 2021

Glaucoma, the leading cause of irreversible blindness, is a heterogeneous group of diseases characterized by progressive loss of retinal ganglion cells (RGCs) and their axons and leads to visual loss and blindness. Risk factors for the onset and progression of glaucoma include systemic and ocular factors such as older age, lower ocular perfusion pressure, and intraocular pressure (IOP). Early signs of RGC damage comprise impairment of axonal transport, downregulation of specific genes and metabolic changes. The brain is often cited to be the highest energy-demanding tissue of the human body. The retina is estimated to have equally high demands. RGCs are particularly active in metabolism and vulnerable to energy insufficiency. Understanding the energy metabolism of the inner retina, especially of the RGCs, is pivotal for understanding glaucoma’s pathophysiology. Here we review the key contributors to the high energy demands in the retina and the distinguishing features of energy metabolism of the inner retina. The major features of glaucoma include progressive cell death of retinal ganglions and optic nerve damage. Therefore, this review focuses on the energetic budget of the retinal ganglion cells, optic nerve and the relevant cells that surround them.
Association of Mean and Variability of HbA1c with Heart Failure in Patients with Type 2 Diabetes
Authors: Lin You-Ting , Huang Wei-Lun , Wu Hung-Pin , Chang Man-Ping , Chen Ching-Chu
Published: April 2021

Heart failure (HF) is a common presentation in patients with type 2 diabetes mellitus (T2DM). Previous studies revealed that the HbA1c level is significantly associated with HF. However, little is known about the association between HbA1c variability and HF. We aimed to evaluate the association of mean and variability of HbA1c with HF in patients with T2DM. Using Diabetes Share Care Program data, patients with T2DM who had mean HbA1c (HbA1c-Mean), and HbA1c variability (tertiles of HbA1c-SD and HbA1c-adjSD) within 12–24 months during 2001–2008 were included. The cutoffs of HbA1c-Mean were set at <7%, 7–7.9%, and ≥8%. Hazard ratios (HRs) for HF during 2008–2018 were estimated using Cox proportional hazard models. A total of 3824 patients were included, of whom 315 patients developed HF during the observation period of 11.72 years. The associated risk of HF increased with tertiles of HbA1c variability and cutoffs of HbA1c-Mean. In mutually adjusted models, HbA1c-Mean showed a consistent dose-response association with HF, while the association of HbA1c variability with HF disappeared. Among patients with HbA1c-Mean <7%, the associated risk of HF in patients with HbA1c variability in tertile 3 was comparable to patients with HbA1c-Mean ≥8%. In conclusion, mean HbA1c was an independent predictor of HF and not explained by HbA1c variability. In addition to absolute HbA1c level, targeting on stability of HbA1c in patients with good glycemic control was also important for the development of HF in patients with T2DM.
Fatty Liver Is Associated with Low N-Terminal Pro-B-Type Natriuretic Peptide in a Healthy Population
Authors: Choi Hyo-In , Lee Mi Yeon , Oh Byeong Kil , Lee Seung Jae , Kang Jeong Gyu , Lee Sung Ho , Lee Jong-Young , Kim Byung Jin , Kim Bum Soo , Kang Jin Ho , Sung Ki-Chul
Published: April 2021

Fatty liver (FL), insulin resistance (IR) and obesity often coexist, but data on the independent impacts of these factors on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels are scarce. We examined the impact of FL, IR and obesity on NT-proBNP levels using a large set of cross-sectional data. The associations of FL, IR and obesity with NT-proBNP were analyzed in 39,923 healthy adult participants. IR was estimated using a homeostasis model assessment-estimated insulin resistance (HOMA-IR) index. A multivariable regression model was conducted to identify associations between NT-proBNP and FL on abdominal ultrasound. FL, IR and obesity showed independent inverse associations with NT-proBNP after multiple adjustments for baseline characteristics. In a multivariable regression model adjusting for IR and obesity, FL was independently associated with lower levels of NT-proBNP (estimates, Exp(β) 0.864, 0.849–0.880). The combination of FL and IR was a powerful dual indicator, lowering NT-proBNP levels approximately 25% in the generally healthy study population. In conclusion, FL was independently associated with lower NT-proBNP levels. FL and a high HOMA-IR index are a powerful indicator combination for lower NT-proBNP levels. Further research is needed to elucidate the mechanism underlying the association between FL and NT-proBNP.
Modeling of Various Spatial Patterns of SARS-CoV-2: The Case of Germany
Authors: Mościcka Albina , Araszkiewicz Andrzej , Wabiński Jakub , Kuźma Marta , Kiliszek Damian
Published: April 2021

Among numerous publications about the SARS-CoV-2, many articles present research from the geographic point of view. The cartographic research method used in this area of science can be successfully applied to analyze the spatiotemporal characteristics of the pandemic using limited data and can be useful for a quick and preliminary assessment of the spread of infections. In this paper, research on the spatial differentiation of the structure and homogeneity of the system in which SARS-CoV-2 occurs, as well as spatial concentration of people infected was undertaken. The phenomena were investigated in a period of two infection waves in Germany: in spring and autumn 2020. We applied the potential model, entropy, centrographic method, and Lorenz curve in spatial analysis. The potentials model made it possible to distinguish core regions with a high level of the growth of new infections, along with areas of their impact, and regions with a low level of generation of new infections. The entropy showed the spatial distribution of differentiation of the studied system and the change of these characteristics between spring and autumn. The concentration method allowed for spatial and numerical demonstration of the concentration of infected population in a given area. We wanted to show that it is possible to draw meaningful conclusions about the pandemic characteristics using only basic data about infections, along with proper cartographic methods. The results can be used to designate the zones of the greatest threats, and thus, the areas where the most intense actions should be taken.
What Is Currently the Role of TcPO2 in the Choice of the Amputation Level of Lower Limbs? A Comprehensive Review
Authors: Catella Judith , Long Anne , Mazzolai Lucia
Published: April 2021

Some patients still require major amputation for lower extremity peripheral arterial disease treatment. The purpose of pre-operative amputation level selection is to determine the most distal amputation site with the highest healing probability without re-amputation. Transcutaneous oximetry (TcPO2) can detect viable tissue with the highest probability of healing. Several factors affect the accuracy of TcPO2; nevertheless, surgeons rely on TcPO2 values to determine the optimal amputation level. Background about the development of TcPO2, methods of measurement, consequences of lower limb amputation level, and the place of TcPO2 in the choice of the amputation level are reviewed herein. Most of the retrospective studies indicated that calf TcPO2 values greater than 40 mmHg were associated with a high percentage of successful wound healing after below-knee-amputation, whereas values lower than 20 mmHg indicated an increased risk of unsuccessful healing. However, a consensus on the precise cut-off value of TcPO2 necessary to assure healing is missing. Ways of improvement for TcPO2 performance applied to the optimization of the amputation-level are reported herein. Further prospective data are needed to better approach a TcPO2 value that will promise an acceptable risk of re-amputation. Standardized TcPO2 measurement is crucial to ensure quality of data.
The Effect of Tranexamic Acid Administration on Early Endothelial Damage Following Posterior Lumbar Fusion Surgery
Authors: Kim Hye Jin , Lee Bora , Lee Byung Ho , Kim So Yeon , Jun Byongnam , Choi Yong Seon
Published: April 2021

Tranexamic acid (TXA) protects against endothelial glycocalyx injury in vitro. We aimed to evaluate whether TXA could protect against endothelial glycocalyx degradation in patients undergoing posterior lumbar fusion surgery. Patients aged 30–80 years were enrolled. The TXA group was administered a loading dose of 10 mg/kg, followed by a 1 mg/kg/h infusion. Serum syndecan-1 and heparan sulfate concentrations, which are biomarkers of glycocalyx degradation, were measured at preoperative baseline (T0), immediately post-surgery (T1), and 2 h post-surgery (T2). Postoperative complications were assessed, including hypotension, desaturation, and acute kidney injury. Among the 121 patients who completed the study, 60 received TXA. There were no significant differences in the marker concentrations at each time point. However, the postoperative increase in syndecan-1 levels from baseline was significantly attenuated in the TXA group compared with the control group (median (interquartile range); T1 vs. T0: −1.6 (−5.3–2.6) vs. 2.2 (−0.7–4.8), p = 0.001; T2 vs. T0: 0.0 (−3.3–5.5) vs. 3.6 (−0.1–9.3), p = 0.013). Postoperative complications were significantly associated with the magnitude of the change in syndecan-1 levels (for T2 vs. T0: odds ratio: 1.08, 95% confidence interval: 1.02–1.14, p = 0.006). TXA administration was associated with reduced syndecan-1 shedding in patients undergoing posterior lumbar fusion surgery.
Correlation between Hospital Volume of Severely Injured Patients and In-Hospital Mortality of Severely Injured Pediatric Patients in Japan: A Nationwide 5-Year Retrospective Study
Authors: Toida Chiaki , Muguruma Takashi , Gakumazawa Masayasu , Shinohara Mafumi , Abe Takeru , Takeuchi Ichiro , Morimura Naoto
Published: April 2021

Appropriate trauma care systems, suitable for children are needed; thus, this retrospective nationwide study evaluated the correlation between the annual total hospital volume of severely injured patients and in-hospital mortality of severely injured pediatric patients (SIPP) and compared clinical parameters and outcomes per hospital between low- and high-volume hospitals. During the five-year study period, we enrolled 53,088 severely injured patients (Injury Severity Score, ≥16); 2889 (5.4%) were pediatric patients aged <18 years. Significant Spearman correlation analysis was observed between numbers of total patients and SIPP per hospital (p < 0.001), and the number of SIPP per hospital who underwent interhospital transportation and/or urgent treatment was correlated with the total number of severely injured patients per hospital. Actual in-hospital mortality, per hospital, of SIPP patients was significantly correlated with the total number patients per hospital (p < 0.001,). The total number of SIPP, requiring urgent treatment, was higher in the high-volume than in the low-volume hospital group. No significant differences in actual in-hospital morality (p = 0.246, 2.13 (0–8.33) vs. 0 (0–100)) and standardized mortality ratio (SMR) values (p = 0.244, 0.31 (0–0.79) vs. 0 (0–4.87)) were observed between the two groups; however, the 13 high-volume hospitals had an SMR of <1.0. Centralizing severely injured patients, regardless of age, to a higher volume hospital might contribute to survival benefits of SIPP.
Patient-Specific Instrumentation Accuracy Evaluated with 3D Virtual Models
Authors: León-Muñoz Vicente J. , Parrinello Andrea , Manca Silvio , Galloni Gianluca , López-López Mirian , Martínez-Martínez Francisco , Santonja-Medina Fernando
Published: April 2021

There have been remarkable advances in knee replacement surgery over the last few decades. One of the concerns continues to be the accuracy in achieving the desired alignment. Patient-specific instrumentation (PSI) was developed to increase component placement accuracy, but the available evidence is not conclusive. Our study aimed to determine a PSI system’s three-dimensional accuracy on 3D virtual models obtained by post-operative computed tomography. We compared the angular placement values of 35 total knee arthroplasties (TKAs) operated within a year obtained with the planned ones, and we analyzed the possible relationships between alignment and patient-reported outcomes. The mean (SD) discrepancies measured by two experienced engineers to the planned values observed were 1.64° (1.3°) for the hip–knee–ankle angle, 1.45° (1.06°) for the supplementary angle of the femoral lateral distal angle, 1.44° (0.97°) for the proximal medial tibial angle, 2.28° (1.78°) for tibial slope, 0.64° (1.09°) for femoral sagittal flexion, and 1.42° (1.06°) for femoral rotation. Neither variables related to post-operative alignment nor the proportion of change between pre-and post-operative alignment influenced the patient-reported outcomes. The evaluated PSI system’s three-dimensional alignment analysis showed a statistically significant difference between the angular values planned and those obtained. However, we did not find a relevant effect size, and this slight discrepancy did not impact the clinical outcome.
De Novo Cancer Incidence after Cholecystectomy in Korean Population
Authors: Jung Yun Kyung , Yoon Junghyun , Lee Kyeong Geun , Kim Han Joon , Park Boyoung , Choi Dongho
Published: April 2021

Background: Cancer development after cholecystectomy remains debatable. We estimated the major cancer incidence rates after cholecystectomy stratified by age and sex. Methods: The records of 408,769 subjects aged >20 years were extracted from the National Health Insurance database from 2008 to 2016. The risks of major cancers were compared between the cholecystectomy and general populations using standardised incidence ratios (SIR). Results: The overall cancer incidence was comparable between cholecystectomy patients and the general population. However, patients aged <65 years who underwent cholecystectomy had a higher cancer risk than those aged ≥65 years and the general population (SIR 2.62; 95% confidence interval [CI] 2.15–3.08; SIR 1.36, 95% CI 1.32–1.40; and SIR 0.90, 95% CI 0.87–0.92 in men and SIR 1.91; 95% CI 1.71–2.10; SIR 1.07; 95% CI 1.03–1.10; and SIR 0.90; 95% CI 0.87–0.94 in women aged 20–34, 35–64, and ≥65 years at cholecystectomy). Colorectal and liver cancer incidences after cholecystectomy were higher than those in the general population regardless of age group and sex (SIR, 1.55 for colorectal cancer in men and women; SIR, 1.25 and 1.51 for liver cancer in men and women, respectively). However, for other major cancers, the risk was higher in patients who underwent cholecystectomy at a younger age than in those who underwent cholecystectomy at an age ≥65 years. Conclusion: Patients with cholecystectomy, especially those undergoing cholecystectomy at a younger age, need preventive strategies based on the cancer type.
Are Differences in Presentation of Early Lyme Borreliosis in Europe and North America a Consequence of a More Frequent Spirochetemia in American Patients?
Authors: Maraspin Vera , Bogovič Petra , Ogrinc Katarina , Rojko Tereza , Ružić-Sabljić Eva , Kastrin Andrej , Strle Klemen , Wormser Gary P. , Strle Franc
Published: April 2021

To assess whether differences in presentation between US and European patients with early Lyme borreliosis are due to the lower rate of spirochetemia in Europe, we compared multiple variables for patients with erythema migrans (EM), restricting the analysis to subjects with a positive blood culture at the time of presentation: 93 US patients infected with Borrelia burgdorferi versus 183 European patients infected with Borrelia afzelii (No = 144) or Borrelia garinii (No = 39). Compared to spirochetemic Slovenian EM patients infected with B. afzelii, US patients with a positive blood culture significantly less often recalled a preceding tick bite at the site of the EM skin lesion, had a shorter duration of EM prior to diagnosis and more often had multiple EM lesions, regional lymphadenopathy, constitutional symptoms, an increased ESR value, a low blood lymphocyte count and detectable borrelia antibodies in acute and convalescent phase blood samples. Similar differences were observed when US patients were compared to Slovenian patients with B. garinii infection, but not all reached statistical significance. The findings are comparable to those previously reported for the corresponding skin culture positive patients and do not support the hypothesis that a higher frequency of spirochetemia at the time of presentation in US patients with EM, compared with European EM patients, is the reason for the observed differences.
A Retrospective Case Series of Thiamine Deficiency in Non-Alcoholic Hospitalized Veterans: An Important Cause of Delirium and Falling?
Authors: Mates Elisabeth , Alluri Deepti , Artis Tailer , Riddle Mark S.
Published: April 2021

Thiamine deficiency (TD) in non-alcoholic hospitalized patients causes a variety of non-specific symptoms. Studies suggest it is not rare in acutely and chronically ill individuals in high income countries and is underdiagnosed. Our aim is to demonstrate data which help define the risk factors and constellation of symptoms of TD in this population. We describe 36 cases of TD in hospitalized non-alcoholic veterans over 5 years. Clinical and laboratory data were extracted by chart review +/− 4 weeks of plasma thiamine level 7 nmol/L or less. Ninety-seven percent had two or more chronic inflammatory conditions (CICs) and 83% had one or more acute inflammatory conditions (AICs). Of possible etiologies of TD 97% had two or more of: insufficient intake, inflammatory stress, or increased losses. Seventy-five percent experienced 5% or more weight loss. Ninety-two percent had symptoms with the most common being weakness or falling (75%) followed by neuropsychiatric manifestations (72%), gastrointestinal dysfunction (53%), and ataxia (42%). We conclude that TD is underdiagnosed in this population with consequent morbidity and mortality. TD likely develops because of inflammatory stress from CIC’s compounded by AIC’s combined with decreased energy intake or increased nutrient losses.
Replication of Previous Findings? Comparing Gray Matter Volumes in Transgender Individuals with Gender Incongruence and Cisgender Individuals
Authors: Clemens Benjamin , Votinov Mikhail , Puiu Andrei Alexandru , Schüppen Andre , Hüpen Philippa , Neulen Josef , Derntl Birgit , Habel Ute
Published: April 2021

The brain structural changes related to gender incongruence (GI) are still poorly understood. Previous studies comparing gray matter volumes (GMV) between cisgender and transgender individuals with GI revealed conflicting results. Leveraging a comprehensive sample of transmen (n = 33), transwomen (n = 33), cismen (n = 24), and ciswomen (n = 25), we employ a region-of-interest (ROI) approach to examine the most frequently reported brain regions showing GMV differences between trans- and cisgender individuals. The primary aim is to replicate previous findings and identify anatomical regions which differ between transgender individuals with GI and cisgender individuals. On the basis of a comprehensive literature search, we selected a set of ROIs (thalamus, putamen, cerebellum, angular gyrus, precentral gyrus) for which differences between cis- and transgender groups have been previously observed. The putamen was the only region showing significant GMV differences between cis- and transgender, across previous studies and the present study. We observed increased GMV in the putamen for transwomen compared to both transmen and ciswomen and for all transgender participants compared to all cisgender participants. Such a pattern of neuroanatomical differences corroborates the large majority of previous studies. This potential replication of previous findings and the known involvement of the putamen in cognitive processes related to body representations and the creation of the own body image indicate the relevance of this region for GI and its potential as a structural biomarker for GI.
A Small Molecule Targeting Human MEK1/2 Enhances ERK and p38 Phosphorylation under Oxidative Stress or with Phenothiazines
Authors: Otręba Michał , Sjölander Johanna Johansson , Grøtli Morten , Sunnerhagen Per
Published: April 2021

Small molecules are routinely used to inhibit protein kinases, but modulators capable of enhancing kinase activity are rare. We have previously shown that the small molecule INR119, designed as an inhibitor of MEK1/2, will enhance the activity of its fission yeast homologue, Wis1, under oxidative stress. To investigate the generality of these findings, we now study the effect of INR119 in human cells under similar conditions. Cells of the established breast cancer line MCF-7 were exposed to H2O2 or phenothiazines, alone or combined with INR119. In line with the previous results in fission yeast, the phosphorylation of the MAPKs ERK and p38 increased substantially more with the combination treatment than by H2O2 or phenothiazines, whereas INR119 alone did not affect phosphorylation. We also measured the mRNA levels of TP53 and BAX, known to be affected by ERK and p38 activity. Similarly, the combination of INR119 and phenothiazines increased both mRNAs to higher levels than for phenothiazines alone. In conclusion, the mechanism of action of INR119 on its target protein kinase may be conserved between yeast and humans.
Previous Humoral Immunity to the Endemic Seasonal Alphacoronaviruses NL63 and 229E Is Associated with Worse Clinical Outcome in COVID-19 and Suggests Original Antigenic Sin
Authors: Focosi Daniele , Genoni Angelo , Lucenteforte Ersilia , Tillati Silvia , Tamborini Antonio , Spezia Pietro Giorgio , Azzi Lorenzo , Baj Andreina , Maggi Fabrizio
Published: April 2021

Antibody-dependent enhancement (ADE) of severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) infection has been hypothesized. However, to date, there has been no in vitro or in vivo evidence supporting this. Cross-reactivity exists between SARS CoV-2 and other Coronaviridae for both cellular and humoral immunity. We show here that IgG against nucleocapsid protein of alphacoronavirus NL63 and 229E correlate with the World Health Organization’s (WHO) clinical severity score ≥ 5 (incidence rate ratios was 1.87 and 1.80, respectively, and 1.94 for the combination). These laboratory findings suggest possible ADE of SARS CoV-2 infection by previous alphacoronavirus immunity.
Multipotent Stromal Cell Extracellular Vesicle Distribution in Distant Organs after Introduction into a Bone Tissue Defect of a Limb
Authors: Maiborodin Igor , Shevela Aleksandr , Toder Michael , Marchukov Sergey , Tursunova Natalya , Klinnikova Marina , Maiborodina Vitalina , Lushnikova Elena , Shevela Andrew
Published: April 2021

When administered intravenously, extracellular vesicles derived from multipotent stromal cells (MSC EVs) immediately pass through the lungs along with the blood and regularly spread to all organs. When administered intraperitoneally, they are absorbed either into the blood or into the lymph and are quickly disseminated throughout the body. The possibility of generalized spread of MSC EVs to distant organs in case of local intratissular administration remains unexplored. However, it is impossible to exclude MSC EV influence on tissues distant from the injection site due to the active or passive migration of these injected nanoparticles through the vessels. The research is based on findings obtained when studying the samples of lungs, heart, spleen, and liver of outbred rabbits of both sexes weighing 3–4 kg at various times after the injection of EVs derived from MSCs of bone marrow origin and labeled by PKH26 into an artificially created defect of the proximal condyle of the tibia. MSC EVs were isolated by serial ultracentrifugation and characterized by transmission electron microscopy and flow cytometry. After the introduction of MSC EVs into the damaged proximal condyle of the tibia of rabbits, these MSC EVs can be found most frequently in the lungs, myocardium, liver, and spleen. MSC EVs enter all of these organs with the blood flow. The lungs contained the maximum number of labeled MSC EVs; moreover, they were often associated with detritus and were located in the lumen of the alveoli. In the capillary network of various organs except the myocardium, MSC EVs are adsorbed by paravasal phagocytes; in some cases, specifically labeled small dust-like objects can be detected throughout the entire experiment—up to ten days of observation. Therefore, we can conclude that the entire body, including distant organs, is effected both by antigenic detritus, which appeared in the bloodstream after extensive surgery, and MSC EVs introduced from the outside.
Novel Red Light-Absorbing Organic Dyes Based on Indolo[3,2-b]carbazole as the Donor Applied in Co-Sensitizer-Free Dye-Sensitized Solar Cells
Authors: Xiao Zhanhai , Chen Bing , Cheng Xudong
Published: April 2021

Three novel organic dyes (D6, D7 and D8), based on indolo[3,2-b]carbazole as the donor and different types of electron-withdrawing groups as the acceptors, were synthesized and successfully applied in dye-sensitized solar cells (DSSCs). Their molecular structures were fully characterized by 1H NMR, 13C NMR and mass spectroscopy. The density functional theory (DFT) calculations, electrochemical impedance spectroscopy analysis, UV–Vis absorption characterization and tests of the solar cells were used to investigate the photophysical/electrochemical properties as well as DSSCs’ performances based on the dyes. Dye D8 showed the broadest light-response range (300–770 nm) in the incident monochromatic photo-to-electron conversion efficiency (IPCE) curve, due to its narrow bandgap (1.95 eV). However, dye D6 exhibited the best device performance among the three dyes, with power conversion efficiency of 5.41%, Jsc of 12.55 mA cm−2, Voc of 745 mV and fill factor (FF) of 0.59. We also found that dye aggregation was efficiently suppressed by the introduction of alkylated indolo[3,2-b]carbazole, and, hence, better power conversion efficiencies were observed for all the three dyes, compared to the devices of co-sensitization with chenodeoxycholic acid (CDCA). It was unnecessary to add adsorbents to suppress the dye aggregation.
Bayesian Regularized Artificial Neural Network Model to Predict Strength Characteristics of Fly-Ash and Bottom-Ash Based Geopolymer Concrete
Authors: Aneja Sakshi , Sharma Ashutosh , Gupta Rishi , Yoo Doo-Yeol
Published: April 2021

Geopolymer concrete (GPC) offers a potential solution for sustainable construction by utilizing waste materials. However, the production and testing procedures for GPC are quite cumbersome and expensive, which can slow down the development of mix design and the implementation of GPC. The basic characteristics of GPC depend on numerous factors such as type of precursor material, type of alkali activators and their concentration, and liquid to solid (precursor material) ratio. To optimize time and cost, Artificial Neural Network (ANN) can be a lucrative technique for exploring and predicting GPC characteristics. In this study, the compressive strength of fly-ash based GPC with bottom ash as a replacement of fine aggregates, as well as fly ash, is predicted using a machine learning-based ANN model. The data inputs are taken from the literature as well as in-house lab scale testing of GPC. The specifications of GPC specimens act as input features of the ANN model to predict compressive strength as the output, while minimizing error. Fourteen ANN models are designed which differ in backpropagation training algorithm, number of hidden layers, and neurons in each layer. The performance analysis and comparison of these models in terms of mean squared error (MSE) and coefficient of correlation (R) resulted in a Bayesian regularized ANN (BRANN) model for effective prediction of compressive strength of fly-ash and bottom-ash based geopolymer concrete.
Structures and Dissolution Behaviors of Quaternary CaO-SrO-P2O5-TiO2 Glasses
Authors: Lee Sungho , Nagata Fukue , Kato Katsuya , Nakano Takayoshi , Kasuga Toshihiro
Published: April 2021

Calcium phosphate glasses have a high potential for use as biomaterials because their composition is similar to that of the mineral phase of bone. Phosphate glasses can dissolve completely in aqueous solution and can contain various elements owing to their acidity. Thus, the glass can be a candidate for therapeutic ion carriers. Recently, we focused on the effect of strontium ions for bone formation, which exhibited dual effects of stimulating bone formation and inhibiting bone resorption. However, large amounts of strontium ions may induce a cytotoxic effect, and there is a need to control their releasing amount. This work reports fundamental data for designing quaternary CaO-SrO-P2O5-TiO2 glasses with pyro- and meta-phosphate compositions to control strontium ion-releasing behavior. The glasses were prepared by substituting CaO by SrO using the melt-quenching method. The SrO/CaO mixed composition exhibited a mixed cation effect on the glassification degree and ion-releasing behavior, which showed non-linear properties with mixed cation compositions of the glasses. Sr2+ ions have smaller field strength than Ca2+ ions, and the glass network structure may be weakened by the substitution of CaO by SrO. However, glassification degree and chemical durability of pyro- and meta-phosphate glasses increased with substituted all CaO by SrO. This is because titanium groups in the glasses are closely related to their glass network structure by SrO substitution. The P-O-Ti bonds in pyrophosphate glass series and TiO4 tetrahedra in metaphosphate glass series increased with substitution by SrO. The titanium groups in the glasses were crosslink and/or coordinate phosphate groups to improve glassification degree and chemical durability. Sr2+ ion releasing amount of pyrophosphate glasses with >83% SrO substitution was larger than 0.1 mM at day seven, an amount that reported enhanced bone formation by stimulation of osteogenic markers.