bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Hot Air, Microwave, and Infrared Drying of Hawthorn Fruit: Effects of Ultrasonic Pretreatment on Drying Time, Energy, Qualitative, and Bioactive Compounds’ Properties
Authors: Abbaspour-Gilandeh Yousef , Kaveh Mohammad , Fatemi Hamideh , Aziz Muhammad
Published: May 2021

The present study aimed to examine the effect of ultrasonic pretreatment and hot air, microwave–hot-air, infrared–hot air, and freeze-drying on the drying time, specific energy (SE), qualitative properties (i.e., color, shrinkage, and rehydration ratio), and bioactive compounds’ properties (i.e., antioxidant activity, phenolic, and flavonoid contents) of hawthorn fruit. Drying of hawthorn was conducted from 45 min for the ultrasonic + microwave–hot-air drying to 1280 min for the freeze-drying method. The lowest amount of SE was obtained using the ultrasonic-microwave–hot-air drying method, which was 47.57 MJ/kg. The lowest values in color changes (12.25) and shrinkage (17.21%) were recorded for the freeze-drying method, while the highest amounts for these traits were 45.57% and 66.75% in the HA drying, respectively. In general, the use of different drying methods reduces the antioxidant capacity (AC), total phenolic content (TPC), and total flavonoid content (TFC) during processing compared to fresh samples. The highest values for AC, TPC, TFC, and the rehydration ratio were 30.69%, 73.07 mg-GAE/gdw, 65.93 mg-QE/gdw, and 2.02 for the freeze-drying method, respectively.
Imputation and Reanalysis of ExomeChip Data Identifies Novel, Conditional and Joint Genetic Effects on Parkinson’s Disease Risk
Authors: Rodrigo Linduni M. , Nyholt Dale R.
Published: May 2021

Given that improved imputation software and high-coverage whole genome sequence (WGS)-based haplotype reference panels now enable inexpensive approximation of WGS genotype data, we hypothesised that WGS-based imputation and analysis of existing ExomeChip-based genome-wide association (GWA) data will identify novel intronic and intergenic single nucleotide polymorphism (SNP) effects associated with complex disease risk. In this study, we reanalysed a Parkinson’s disease (PD) dataset comprising 5540 cases and 5862 controls genotyped using the ExomeChip-based NeuroX array. After genotype imputation and extensive quality control, GWA analysis was performed using PLINK and a recently developed machine learning approach (GenEpi), to identify novel, conditional and joint genetic effects associated with PD. In addition to improved validation of previously reported loci, we identified five novel genome-wide significant loci associated with PD: three (rs137887044, rs78837976 and rs117672332) with 0.01 < MAF < 0.05, and two (rs187989831 and rs12100172) with MAF < 0.01. Conditional analysis within genome-wide significant loci revealed four loci (p < 1 × 10−5) with multiple independent risk variants, while GenEpi analysis identified SNP–SNP interactions in seven genes. In addition to identifying novel risk loci for PD, these results demonstrate that WGS-based imputation and analysis of existing exome genotype data can identify novel intronic and intergenic SNP effects associated with complex disease risk.
Determinants Impacting User Behavior towards Emergency Use Intentions of m-Health Services in Taiwan
Authors: Lee Wan-I , Fu Hsin-Pin , Mendoza Nelio , Liu Tzu-Yu
Published: May 2021

Emergency usage intention and behavior are crucial to business service success for m-Health providers and patient healthcare service. This study aimed to identify the factors that influence m-Health acceptance and the effect of emergency use intentions on usage behavior among Taiwanese m-Health users by adopting and extending the Unified Theory of Acceptance and Use of Technology (UTAUT). This study also examines the moderating role of gender and age in the effects of the independent variables on satisfaction with m-Health services. An online questionnaire was used to collect data from 371 participants. The results revealed that performance expectancy, facilitating conditions, and trust had positive effects on user satisfaction. Additionally, m-Health knowledge and user satisfaction had positive effects on emergency use intentions. However, social influence and effort expectancy did not have a significant effect on satisfaction. Moreover, age and gender significantly moderated the effects of some predictors.
Out-of-Pocket Health Expenditure and Poverty: Evidence from a Dynamic Panel Threshold Analysis
Authors: Sirag Abdalla , Mohamed Nor Norashidah
Published: May 2021

The current study investigated the association between out-of-pocket health expenditure and poverty using macroeconomic data from a sample of 145 countries from 2000 to 2017. In particular, it was examined whether the relationship between out-of-pocket health expenditure and poverty was contingent on a certain threshold level of out-of-pocket health spending. The dynamic panel threshold method, which allows for the endogeneity of the threshold regressor (out-of-pocket health expenditure), was used. Three indicators were adopted as poverty measures, namely the poverty headcount ratio, the poverty gap index, and the poverty gap squared index. At the same time, out-of-pocket health expenditure was measured as a percentage of total health expenditure. The results showed the validity of the estimated threshold models, indicating that only beyond the turning point, which was about 29 percent, that out-of-pocket health spending led to increased poverty. When heterogeneity was controlled for in the sample, using the World Bank income classification, the findings showed variations in the estimated threshold, with higher values for the low- and lower-middle-income groups, as compared to the high-income group. For the lower-income groups, below the threshold for out-of-pocket health expenditure, it had a positive or insignificant effect on poverty reduction, while it led to higher poverty above the threshold. Further, the sampled countries were divided into regions, according to the World Health Organization. Generally, improving health care systems through tolerable levels of out-of-pocket health expenditure is an inevitable step toward better health coverage and poverty reduction in many developing countries.
Effects of a Home-Based Pulmonary Rehabilitation Program in Patients with Chronic Obstructive Pulmonary Disease in GOLD B Group: A Pilot Study
Authors: Vilarinho Rui , Serra Lúcia , Coxo Ricardo , Carvalho João , Esteves Cátia , Montes António Mesquita , Caneiras Cátia
Published: May 2021

Patients with chronic obstructive pulmonary disease (COPD) in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) B group can be included in pulmonary rehabilitation (PR) settings outside the hospitals. This study aimed to explore the feasibility of a home-based pulmonary rehabilitation (HBPR) program and assess its impact on patients with COPD in the GOLD B group. A real-world, pre–post intervention study was conducted with 12 weeks of HBPR (presential home visits and phone calls) using the self-management program Living Well with COPD. The 1-min sit-to-stand test (1MSTS), modified Medical Research Council Questionnaire (mMRC), COPD Assessment Test (CAT), Hospital Anxiety and Depression Scale (HADS), and London Chest Activity of Daily Living (LCADL) were used to assess the impact. Pre–post differences and correlations between changes in outcomes were calculated. In 30 patients (71.6 years, FEV1 (%) 52.8), significant improvements (p < 0.05) were observed on 1MSTS (Pre 17.2, Post 21.2), mMRC (Pre 2.0, Post 1.0), CAT (Pre 16.3, Post 9.9), HADS (Pre 14.4, Post 9.6), and LCADL (Pre 21.0, Post 15.8), with no adverse events reported. When significant, correlations between changes in outcomes were moderate or strong (0.48 ≤ ρ ≤ 0.66). HBPR can be feasible and safe, and it shows the potential to significantly improve outcomes of patients with COPD in the GOLD B group.
Ultrasound-Guided Percutaneous Neuromodulation in Patients with Chronic Lateral Epicondylalgia: A Pilot Randomized Clinical Trial
Authors: De-la-Cruz-Torres Blanca , Abuín-Porras Vanesa , Navarro-Flores Emmanuel , Calvo-Lobo César , Romero-Morales Carlos
Published: May 2021

Objective: The aim was to analyze effects of a percutaneous neuromodulation (PNM) treatment on the radial nerve, regarding pain, functionality, electrophysiologic excitability, and morphology, in patients with chronic lateral epicondylalgia (LE). Methods: Twenty-four patients with chronic unilateral elbow pain were recruited for this preliminary study and were divided into two groups: control (n = 12) and PNM group (n = 12). The subjects in the PNM group received percutaneous peripheral neurostimulation with an acupuncture needle that was located next to the nerve with ultrasound guidance. Pain using a numerical rating scale (NRS), functional ability using patient-rated tennis elbow evaluation (PRTEE), radial nerve cross-sectional area measured by ultrasound, and chronaxie and accommodation index (AI) measured by the strength–duration curve were evaluated. Results: Both groups showed no differences in the baseline measurements (all p = 0.001). However, at the end of the treatment, there were significant differences between groups since only the PNM group significantly improved their values compared to their baseline values: level of pain and cross-sectional area (CSA) values showed a significant decrease while the PRTEE scores showed a significant improvement. Then, regarding AI, the PNM group showed significant improvement for the electrophysiologic nerve excitability pattern, reporting normal function in all radial nerves after treatment (p = 0.001). However, chronaxie values always reported similar values with no differences between groups (p >0.05); Conclusion: Ultrasound-PNM technique may be an interesting therapeutic tool for the treatment of chronic LE due to the improvement in the level of pain, functionality, nerve morphology, and excitability in this population.
Co-Circulation of Bovine Leukemia Virus Haplotypes among Humans, Animals, and Food Products: New Insights of Its Zoonotic Potential
Authors: Corredor-Figueroa Adriana P. , Olaya-Galán Nury N. , Velandia-Álvarez Sebastian , Muñoz Marina , Salas-Cárdenas Sandra P. , Ibáñez-Pinilla Milcíades , Patarroyo Manuel A. , Gutiérrez Maria F.
Published: May 2021

Bovine leukemia virus (BLV) is the causative agent of leukemia/lymphoma in cattle. It has been found in humans and cattle-derived food products. In humans, it is described as a potential risk factor for breast cancer development. However, the transmission path remains unclear. Here, a molecular epidemiology analysis was performed to identify signatures of genetic flux of BLV among humans, animals, and food products. Sequences obtained from these sources in Colombia were used (n = 183) and compared with reference sequences available in GenBank. Phylogenetic reconstruction was performed in IQ-TREE software with the maximum likelihood algorithm. Haplotype (hap) distribution among the population was carried out with a median-joining model in Network5.0. Recombination events were inferred using SplitsTree4 software. In the phylogenetic analysis, no specific branches were identified for the Colombian sequences or for the different sources. A total of 31 haps were found, with Hap 1, 4, 5 and 7 being shared among the three sources of the study. Reticulation events among the different sources were also detected during the recombination analysis. These results show new insights about the zoonotic potential of BLV, showing evidence of genetic flux between cattle and humans. Prevention and control strategies should be considered to avoid viral dissemination as part of the One Health program policies.
Manufacturing and Application of 3D Printed Photo Fenton Reactors for Wastewater Treatment
Authors: Nasr Esfahani Kourosh , Zandi Mohammad Damous , Travieso-Rodriguez J. Antonio , Graells Moisès , Pérez-Moya Montserrat
Published: May 2021

Additive manufacturing (AM) or 3D printing offers a new paradigm for designing and developing chemical reactors, in particular, prototypes. The use of 3D printers has been increasing, their performance has been improving, and their price has been reducing. While the general trend is clear, particular applications need to be assessed for their practicality. This study develops and follows a systematic approach to the prototyping of Advanced Oxidation Processes (AOP) reactors. Specifically, this work evaluates and discusses different printable materials in terms of mechanical and chemical resistance to photo-Fenton reactants. Metallic and ceramic materials are shown to be impracticable due to their high printing cost. Polymeric and composite materials are sieved according to criteria such as biodegradability, chemical, thermal, and mechanical resistance. Finally, 3D-printed prototypes are produced and tested in terms of leakage and resistance to the photo-Fenton reacting environment. Polylactic acid (PLA) and wood–PLA composite (Timberfill®) were selected, and lab-scale raceway pond reactors (RPR) were printed accordingly. They were next exposed to H2O2/Fe(II) solutions at pH = 3 ± 0.2 and UV radiation. After 48 h reaction tests, results revealed that the Timberfill® reactor produced higher Total Organic Carbon (TOC) concentrations (9.6 mg·L−1) than that obtained for the PLA reactor (5.5 mg·L−1) and Pyrex® reactor (5.2 mg·L−1), which suggests the interference of Timberfill® with the reaction. The work also considers and discusses further chemical and mechanical criteria that also favor PLA for 3D-printing Fenton and photo-Fenton reactors. Finally, the work also provides a detailed explanation of the printing parameters used and guidelines for preparing prototypes.
Sudden Changes and Their Associations with Quality of Life during COVID-19 Lockdown: A Cross-Sectional Study in the French-Speaking Part of Switzerland
Authors: Duay Manon , Morgiève Margot , Niculita-Hirzel Hélène
Published: May 2021

The lockdown due to the COVID-19 pandemic has led to various sudden changes in a large number of individuals. In response, the question of how individuals from different social and economic strata cope with those changes has arisen, as well as how much they have affected their mental well-being. Choosing strategies that cope with both the pandemic and the well-being of the population has also been a challenge for different governments. While a large number of studies have investigated the mental health of people from different populations during the COVID-19 pandemic, few have explored the number and type of changes experienced during lockdown by the general population, alongside their relationships with health-related quality of life (HRQoL). To fill this research gap, an observational cross-sectional study on those associations was conducted in the French-speaking part of the Swiss general population. Data were collected from 431 participants during the first four weeks of lockdown due to COVID-19. Multivariate regressions were used to identify the sociodemographic profile of the population that experienced different types and numbers of changes during this period, the association of those changes with the HRQoL—mental and physical—and infection beliefs, and the perception of the governmental measures. We show that the more changes people experienced, the lower their mental HRQoL; however, adherence to governmental measures has helped people to cope with the imposed changes, even though the number of unexpected and unwished changes have strained their mental HRQoL. The low-income population experienced financial difficulties and changes in their food intake more frequently, while dual-citizenship or non-Swiss individuals declared conflictual situations more frequently. Sport practice had a positive association with mental HRQoL; nevertheless, a decrease in sport practice was frequently reported, which correlated with a lower mental HRQoL. Risk perception of COVID-19 increased with lower physical HRQoL score, which supports the efficiency of governmental communication regarding the pandemic. Our results support that government measures should be accompanied by effective and targeted communication about the risk of infection, in order to encourage all strata of the general population to follow such measures and adapt to the changes without unduly affecting their mental health. The usage of such tools might help to reduce the impact of policy-imposed changes on the mental HRQoL of the general population, by inducing voluntary changes in informed and engaged populations.
Significantly Reduced Alanine Aminotransferase Level Increases All-Cause Mortality Rate in the Elderly after Ischemic Stroke
Authors: An Sang Joon , Yang Yun-Jung , Jeon Na-mo , Hong Yeon-Pyo , Kim Yeong In , Kim Doo-Young
Published: May 2021

(1) Background: A significantly reduced alanine aminotransferase (ALT) level is being recognized as a risk factor of increasing mortality in the elderly in relation to frailty. In the elderly, both frailty and ischemic stroke are not only common, but are also associated with mortality. The aim of this research was to investigate whether a significantly reduced ALT level increases the all-cause mortality rate in the elderly with ischemic stroke. (2) Methods: Between February 2014 and April 2019, a retrospective study of 901 patients with ischemic stroke admitted to a university-affiliated hospital was conducted. Cox proportional hazard regression was used to determine whether a significantly reduced ALT level is an independent risk factor for mortality in elderly patients after an ischemic stroke. (3) Results: This study enrolled 323 older adults (age ≥ 65 years) who were first diagnosed with ischemic stroke. The mean age of the participants was 76.5 ± 6.6 years, the mean survival time was 37.1 ± 20.4 months, and the number of deaths was 96 (29.7%). Our results showed that reduced ALT level (less than 10 U/L) increased the risk of all-cause mortality in the elderly after ischemic stroke (adjusted HR: 3.24, 95% CI: 1.95–5.41; p < 0.001). (4) Conclusions: A significantly reduced ALT level at the time of diagnosis (less than 10 U/L) is an independent risk factor that increases the mortality rate in the elderly after ischemic stroke.
Assessing Influential Factors on Inland Property Damage from Gulf of Mexico Tropical Cyclones in the United States
Authors: Rifat Shaikh Abdullah Al , Senkbeil Jason C. , Liu Weibo
Published: May 2021

The Gulf and southeast coastal communities in the United States are particularly vulnerable to tropical cyclones. Coastal areas generally receive the greatest economic losses from tropical cyclones; however, research suggests that losses in the inland zone can occasionally be higher than the coastal zone. Previous research assessing the inland impacts from tropical cyclones was limited to the areas that are adjacent to the coastal zone only, where losses are usually higher. In this study, we assessed the spatial distribution of inland property damage caused by tropical cyclones. We included all the inland counties that fall within the inland zone in the states of Louisiana, Mississippi, and Alabama. Additionally, different factors, including meteorological storm characteristics (tropical cyclone wind and rain), elevation, and county social-economic vulnerability (county social vulnerability index and GDP) were assessed to measure their influence on property damage, using both ordinary least squares (OLS) and geographically weighted regression (GWR) models. GWR performs better than the OLS, signifying the importance of considering spatial variations in the explanation of inland property damage. Results from the tristate region suggest that wind was the strongest predictor of property damage in OLS and one of the major contributing factors of property damage in the GWR model. These results could be beneficial for emergency managers and policymakers when considering the inland impacts of tropical cyclones.
Surveying Reality (SurReal): Software to Simulate Surveying in Virtual Reality
Authors: Bolkas Dimitrios , Chiampi Jeffrey , Fioti Joseph , Gaffney Donovan
Published: May 2021

Experiential learning through outdoor labs is an integral component of surveying education. Cancelled labs as a result of weather, the inability to visit a wide variety of terrain location, recent distance education requirements create significant instructional challenges. In this paper, we present a software solution called surveying reality (SurReal); this software allows for students to conduct immersive and interactive virtual reality labs. This paper discusses the development of a virtual differential leveling lab. The developed software faithfully replicates major steps followed in the field and any skills learned in virtual reality are transferable in the physical world. Furthermore, this paper presents a novel technique for leveling multi-legged objects like a tripod on variable terrain. This method relies solely on geometric modeling and does not require physical simulation of the tripod. This increases efficiency and ensures that the user experiences at least 60 frames per second, thus reducing lagging and creating a pleasant experience for the user. We conduct two leveling examples, a three-benchmark loop and a point-to-point leveling line. Both surveys had a misclosure of 1 mm due to observational random errors, which demonstrated that leveling can be conducted with mm-level precision, much like in the physical world.
A Progressive and Combined Building Simplification Approach with Local Structure Classification and Backtracking Strategy
Authors: Wei Zhiwei , Liu Yang , Cheng Lu , Ding Su
Published: May 2021

Several algorithms have been developed to simplify buildings based on their local structure in past decades. However, different local structures are defined for certain purposes, and no algorithm can appropriately simplify all buildings. We propose a combined building simplification approach based on local structure classification and backtracking strategy. In this approach, local structures are classified and their based operations are defined by considering the buildings’ orthogonal and non-orthogonal features. Each building is simplified to target scale with a selected local-structure-based operation progressively scale-by-scale. Rules are built to support the selection of local-structure-based operations with a binary decision tree, and a backtracking strategy is used when an invalid operation is applied. When the building is too small or the evaluation shows that it cannot be simplified based on local structures, template matching or enlargement algorithms are applied to simplify the building. A dataset (1:10k) collected from the Ordnance Survey was used for the experiment and simplified scale of 1:25k. Results satisfied legibility constraints and the change in area, orientation and position of simplified buildings are controlled within certain range by comparing with the results generated based on other four simplification algorithms. Possible use of our approach for continuous scale transformation of buildings is also discussed.
Crowdsourcing of Popular Toponyms: How to Collect and Preserve Toponyms in Spoken Use
Authors: Vrbík Daniel , Lábus Václav
Published: May 2021

The article presents a process of collecting unstandardized toponyms, in particular urbanonyms (place names denoting objects located in the cadastre of the city), within the territory of two municipalities in the Czech Republic. The collecting process was performed in two phases by crowdsourcing, using a web map application created especially for this purpose. In the first phase (October 2019–September 2020) it was collecting as many unstandardized toponyms as possible. In the second phase (October 2020–January 2021) we focused on the degree of the knowledge of these toponyms among the population living within the studied territory. The interest on the side of the general public was surprising in both phases. In the first phase, over five hundred respondents submitted more than two and a half thousand place names, most of them during the first two weeks. More than nine hundred respondents actively participated in the second phase, thanks to which we received an average of 200 responses for each place name. As regards the motivation of the public, it was most often altruism, patriotism, and curiosity that stimulated them; in the second phase, the element of gamification, embedded into the map application, also had a positive effect. The collected data can be used, for instance, in the activities of local authorities in the process of standardization of place names or as reference data for maps used within the integrated rescue system.
Radiation-Induced Senescence Reprograms Secretory and Metabolic Pathways in Colon Cancer HCT-116 Cells
Authors: Nagineni Chandrasekharam N. , Naz Sarwat , Choudhuri Rajani , Chandramouli Gadisetti V. R. , Krishna Murali C. , Brender Jeffrey R. , Cook John A. , Mitchell James B.
Published: May 2021

Understanding the global metabolic changes during the senescence of tumor cells can have implications for developing effective anti-cancer treatment strategies. Ionizing radiation (IR) was used to induce senescence in a human colon cancer cell line HCT-116 to examine secretome and metabolome profiles. Control proliferating and senescent cancer cells (SCC) exhibited distinct morphological differences and expression of senescent markers. Enhanced secretion of pro-inflammatory chemokines and IL-1, anti-inflammatory IL-27, and TGF-β1 was observed in SCC. Significantly reduced levels of VEGF-A indicated anti-angiogenic activities of SCC. Elevated levels of tissue inhibitors of matrix metalloproteinases from SCC support the maintenance of the extracellular matrix. Adenylate and guanylate energy charge levels and redox components NAD and NADP and glutathione were maintained at near optimal levels indicating the viability of SCC. Significant accumulation of pyruvate, lactate, and suppression of the TCA cycle in SCC indicated aerobic glycolysis as the predominant energy source for SCC. Levels of several key amino acids decreased significantly, suggesting augmented utilization for protein synthesis and for use as intermediates for energy metabolism in SCC. These observations may provide a better understanding of cellular senescence basic mechanisms in tumor tissues and provide opportunities to improve cancer treatment.
Posttranslational Modification of Waxy to Genetically Improve Starch Quality in Rice Grain
Authors: Adegoke Tosin Victor , Wang Yifeng , Chen Lijuan , Wang Huimei , Liu Wanning , Liu Xingyong , Cheng Yi-Chen , Tong Xiaohong , Ying Jiezheng , Zhang Jian
Published: May 2021

The waxy (Wx) gene, encoding the granule-bound starch synthase (GBSS), is responsible for amylose biosynthesis and plays a crucial role in defining eating and cooking quality. The waxy locus controls both the non-waxy and waxy rice phenotypes. Rice starch can be altered into various forms by either reducing or increasing the amylose content, depending on consumer preference and region. Low-amylose rice is preferred by consumers because of its softness and sticky appearance. A better way of improving crops other than downregulation and overexpression of a gene or genes may be achieved through the posttranslational modification of sites or regulatory enzymes that regulate them because of their significance. The impact of posttranslational GBSSI modifications on extra-long unit chains (ELCs) remains largely unknown. Numerous studies have been reported on different crops, such as wheat, maize, and barley, but the rice starch granule proteome remains largely unknown. There is a need to improve the yield of low-amylose rice by employing posttranslational modification of Wx, since the market demand is increasing every day in order to meet the market demand for low-amylose rice in the regional area that prefers low-amylose rice, particularly in China. In this review, we have conducted an in-depth review of waxy rice, starch properties, starch biosynthesis, and posttranslational modification of waxy protein to genetically improve starch quality in rice grains.
Tuning Anti-Biofilm Activity of Manganese(II) Complexes: Linking Biological Effectiveness of Heteroaromatic Complexes of Alcohol, Aldehyde, Ketone, and Carboxylic Acid with Structural Effects and Redox Activity
Authors: Jabłońska-Wawrzycka Agnieszka , Rogala Patrycja , Czerwonka Grzegorz , Michałkiewicz Sławomir , Hodorowicz Maciej , Gałczyńska Katarzyna , Cieślak Beata , Kowalczyk Paweł
Published: May 2021

The constantly growing resistance of bacteria to antibiotics and other antibacterial substances has led us to an era in which alternative antimicrobial therapies are urgently required. One promising approach is to target bacterial pathogens using metal complexes. Therefore, we investigated the possibility of utilizing series of manganese(II) complexes with heteroaromatic ligands: Alcohol, aldehyde, ketone, and carboxylic acid as inhibitors for biofilm formation of Pseudomonas aeruginosa. To complete the series mentioned above, Mn-dipyCO-NO3 with dipyridin-2-ylmethanone (dipyCO) was isolated, and then structurally (single-crystal X-ray analysis) and physicochemically characterized (FT-IR, TG, CV, magnetic susceptibility). The antibacterial activity of the compounds against representative Gram-negative and Gram-positive bacteria was also evaluated. It is worth highlighting that the results of the cytotoxicity assays performed (MTT, DHI HoloMonitorM4) indicate high cell viability of the human fibroblast (VH10) in the presence of the Mn(II) complexes. Additionally, the inhibition effect of catalase activity by the complexes was studied. This paper focused on such aspects as studying different types of intermolecular interactions in the crystals of the Mn(II) complexes as well as their possible effect on anti-biofilm activity, the structure–activity relationship of the Mn(II) complexes, and regularity between the electrochemical properties of the Mn(II) complexes and anti-biofilm activity.
A Proteomic Approach for Systematic Mapping of Substrates of Human Deubiquitinating Enzymes
Authors: Ramirez Juanma , Prieto Gorka , Olazabal-Herrero Anne , Borràs Eva , Fernandez-Vigo Elvira , Alduntzin Unai , Osinalde Nerea , Beaskoetxea Javier , Lectez Benoit , Aloria Kerman , Rodriguez Jose Antonio , Paradela Alberto , Sabidó Eduard , Muñoz Javier , Corrales Fernando , Arizmendi Jesus M. , Mayor Ugo
Published: May 2021

The human genome contains nearly 100 deubiquitinating enzymes (DUBs) responsible for removing ubiquitin moieties from a large variety of substrates. Which DUBs are responsible for targeting which substrates remain mostly unknown. Here we implement the bioUb approach to identify DUB substrates in a systematic manner, combining gene silencing and proteomics analyses. Silencing of individual DUB enzymes is used to reduce their ubiquitin deconjugating activity, leading to an increase of the ubiquitination of their substrates, which can then be isolated and identified. We report here quantitative proteomic data of the putative substrates of 5 human DUBs. Furthermore, we have built a novel interactive database of DUB substrates to provide easy access to our data and collect DUB proteome data from other groups as a reference resource in the DUB substrates research field.
Testing EGFR with Idylla on Cytological Specimens of Lung Cancer: A Review
Authors: Caputo Alessandro , D’Ardia Angela , Sabbatino Francesco , Picariello Caterina , Ciaparrone Chiara , Zeppa Pio , D’Antonio Antonio
Published: May 2021

The current standard of care for advanced non-small-cell lung cancer is based on detecting actionable mutations that can benefit from targeted therapy. Comprehensive genetic tests can have long turn-around times, and because EGFR mutations are the most prevalent actionable mutation, a quick detection would enable a prompt initiation of targeted therapy. Furthermore, the scarcity of diagnostic material means that sometimes only cytologic material is available. The Idylla™ EGFR assay is a real-time PCR–based method able to detect 51 EGFR mutations in 2.5 h. Idylla is validated for use only on FFPE sections, but some researchers described their experiences with cytological material. We reviewed the relevant literature, finding four articles describing 471 cases and many types of cytological input material: smears, cell-block sections, suspensions, and extracted DNA. The sensitivity, specificity, and limit of detection appear comparable to those obtained with histological input material, with one exception: the usage of scraped stained smears as input may reduce the accuracy of the test. In conclusion, usage of cytological material as input to the Idylla EGFR test is possible. A workflow where common mutations are tested first and fast, leaving rarer mutations for subsequent comprehensive profiling, seems the most effective approach.
Amelioration of Cognitive and Behavioral Deficits after Traumatic Brain Injury in Coagulation Factor XII Deficient Mice
Authors: Stetter Christian , Lopez-Caperuchipi Simon , Hopp-Krämer Sarah , Bieber Michael , Kleinschnitz Christoph , Sirén Anna-Leena , Albert-Weißenberger Christiane
Published: May 2021

Based on recent findings that show that depletion of factor XII (FXII) leads to better posttraumatic neurological recovery, we studied the effect of FXII-deficiency on post-traumatic cognitive and behavioral outcomes in female and male mice. In agreement with our previous findings, neurological deficits on day 7 after weight-drop traumatic brain injury (TBI) were significantly reduced in FXII−/− mice compared to wild type (WT) mice. Also, glycoprotein Ib (GPIb)-positive platelet aggregates were more frequent in brain microvasculature of WT than FXII−/− mice 3 months after TBI. Six weeks after TBI, memory for novel object was significantly reduced in both female and male WT but not in FXII−/− mice compared to sham-operated mice. In the setting of automated home-cage monitoring of socially housed mice in IntelliCages, female WT mice but not FXII−/− mice showed decreased exploration and reacted negatively to reward extinction one month after TBI. Since neuroendocrine stress after TBI might contribute to trauma-induced cognitive dysfunction and negative emotional contrast reactions, we measured peripheral corticosterone levels and the ration of heart, lung, and spleen weight to bodyweight. Three months after TBI, plasma corticosterone levels were significantly suppressed in both female and male WT but not in FXII−/− mice, while the relative heart weight increased in males but not in females of both phenotypes when compared to sham-operated mice. Our results indicate that FXII deficiency is associated with efficient post-traumatic behavioral and neuroendocrine recovery.
The (Poly)Pharmacology of Cannabidiol in Neurological and Neuropsychiatric Disorders: Molecular Mechanisms and Targets
Authors: Vitale Rosa Maria , Iannotti Fabio Arturo , Amodeo Pietro
Published: May 2021

Cannabidiol (CBD), the major nonpsychoactive Cannabis constituent, has been proposed for the treatment of a wide panel of neurological and neuropsychiatric disorders, including anxiety, schizophrenia, epilepsy and drug addiction due to the ability of its versatile scaffold to interact with diverse molecular targets that are not restricted to the endocannabinoid system. Albeit the molecular mechanisms responsible for the therapeutic effects of CBD have yet to be fully elucidated, many efforts have been devoted in the last decades to shed light on its complex pharmacological profile. In particular, an ever-increasing number of molecular targets linked to those disorders have been identified for this phytocannabinoid, along with the modulatory effects of CBD on their cascade signaling. In this view, here we will try to provide a comprehensive and up-to-date overview of the molecular basis underlying the therapeutic effects of CBD involved in the treatment of neurological and neuropsychiatric disorders.
Botulinum Toxin: From Poison to Possible Treatment for Spasticity in Spinal Cord Injury
Authors: Palazón-García Ramiro , Benavente-Valdepeñas Ana María
Published: May 2021

Botulism has been known for about three centuries, and since its discovery, botulinum toxin has been considered one of the most powerful toxins. However, throughout the 20th century, several medical applications have been discovered, among which the treatment of spasticity stands out. Botulinum toxin is the only pharmacological treatment recommended for spasticity of strokes and cerebral palsy. Although its use as an adjuvant treatment against spasticity in spinal cord injuries is not even approved, botulinum toxin is being used against such injuries. This article describes the advances that have been made throughout history leading to the therapeutic use of botulinum toxin and, in particular, its application to the treatment of spasticity in spinal cord injury.
Long Non-Coding RNAs as Functional Codes for Oral Cancer: Translational Potential, Progress and Promises
Authors: Lei Cing-Syuan , Kung Hsing-Jien , Shih Jing-Wen
Published: May 2021

Oral cancer is one of the leading malignant tumors worldwide. Despite the advent of multidisciplinary approaches, the overall prognosis of patients with oral cancer is poor, mainly due to late diagnosis. There is an urgent need to develop valid biomarkers for early detection and effective therapies. Long non-coding RNAs (lncRNAs) are recognized as key elements of gene regulation, with pivotal roles in various physiological and pathological processes, including cancer. Over the past few years, an exponentially growing number of lncRNAs have been identified and linked to tumorigenesis and prognosis outcomes in oral cancer, illustrating their emerging roles in oral cancer progression and the associated signaling pathways. Herein, we aim to summarize the most recent advances made concerning oral cancer-associated lncRNA, and their expression, involvement, and potential clinical impact, reported to date, with a specific focus on the lncRNA-mediated molecular regulation in oncogenic signaling cascades and oral malignant progression, while exploring their potential, and challenges, for clinical applications as biomarkers or therapeutic targets for oral cancer.
Short-Stay Hospitalizations for Patients with COVID-19: A Retrospective Cohort Study
Authors: Kilaru Austin S. , Lee Kathleen , Grossman Lindsay , Mankoff Zachary , Snider Christopher K. , Bressman Eric , Porges Stefanie B. , Hemmert Keith C. , Greysen Scott R. , Asch David A. , Delgado Mucio K.
Published: May 2021

Objective: Patients requiring hospital care for COVID-19 may be stable for discharge soon after admission. This study sought to describe patient characteristics associated with short-stay hospitalization for COVID-19. Methods: We performed a retrospective cohort study of patients with COVID-19 admitted to five United States hospitals from March to December 2020. We used multivariable logistic regression to identify patient characteristics associated with short hospital length-of-stay. Results: Of 3103 patients, 648 (20.9%) were hospitalized for less than 48 h. These patients were significantly less likely to have an age greater than 60, diabetes, chronic kidney disease; emergency department vital sign abnormalities, or abnormal initial diagnostic testing. For patients with no significant risk factors, the adjusted probability of short-stay hospitalization was 62.4% (95% CI 58.9–69.6). Conclusion: Identification of candidates for early hospital discharge may allow hospitals to streamline throughput using protocols that optimize the efficiency of hospital care and coordinate post-discharge monitoring.
Surgical Diagnosis of Malignant Pleural Mesothelioma: 20 Years’ Experience at a High-Volume Referral Center
Authors: Iaffaldano Amedeo , Charrier Thomas , Lococo Filippo , Damotte Diane , Bobbio Antonio , Alifano Marco , Fournel Ludovic
Published: May 2021

Despite advances, malignant pleural mesothelioma (MPM) remains a challenging disease in terms of diagnosis, treatment, and overall management. Herein, we analyzed, in a large-scale single-center cohort, the characteristics and perioperative course of patients undergoing surgical diagnosis of MPM. We identified a total of 514 consecutive patients, 71.4% male and 28.6% female, with mean age 71.3 +/− 13.6 years. Most exhibited pleural, respiratory, or general symptoms and American Society of Anesthesiologists (ASA) score was ≥3 in 68.3% of cases. Thoracoscopy was the most frequent approach (92.0%) and short open thoracotomy was performed in the remaining patients. Pleurodesis was simultaneously performed in 74.3% of cases. Diagnostic failure led to redo surgery in 3.7% of patients. Non-epithelioid histology was found in 19.5% of MPMs and was significantly more frequent in right-sided MPM (p = 0.04), and in patients without history of cancer (p = 0.03), or pleural nodules at thoracoscopy (p = 0.01). Minor only or major complications occurred in respectively 7.8% and 3.6% of cases. They were more frequent in patients ≥ 70 years (p = 0.05) and Performance Status > 2 (p = 0.05). The mean hospital stay was 7.5 days. The 30-day and 90-day early mortality rates were 2.3% and 6.4%, respectively. Surgical diagnosis of MPM is a reliable procedure but is associated with significant morbidity and hospital-stay duration.
Identification of Potential Bisphenol A (BPA) Exposure Biomarkers in Ovarian Cancer
Authors: Zahra Aeman , Dong Qiduo , Hall Marcia , Jeyaneethi Jeyarooban , Silva Elisabete , Karteris Emmanouil , Sisu Cristina
Published: May 2021

Endocrine-disrupting chemicals (EDCs) can exert multiple deleterious effects and have been implicated in carcinogenesis. The xenoestrogen Bisphenol A (BPA) that is found in various consumer products has been involved in the dysregulation of numerous signalling pathways. In this paper, we present the analysis of a set of 94 genes that have been shown to be dysregulated in presence of BPA in ovarian cancer cell lines since we hypothesised that these genes might be of biomarker potential. This study sought to identify biomarkers of disease and biomarkers of disease-associated exposure. In silico analyses took place using gene expression data extracted from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Differential expression was further validated at protein level using immunohistochemistry on an ovarian cancer tissue microarray. We found that 14 out of 94 genes are solely dysregulated in the presence of BPA, while the remaining 80 genes are already dysregulated (p-value < 0.05) in their expression pattern as a consequence of the disease. We also found that seven genes have prognostic power for the overall survival in OC in relation to their expression levels. Out of these seven genes, Keratin 4 (KRT4) appears to be a biomarker of exposure-associated ovarian cancer, whereas Guanylate Binding Protein 5 (GBP5), long intergenic non-protein coding RNA 707 (LINC00707) and Solute Carrier Family 4 Member 11 (SLC4A11) are biomarkers of disease. BPA can exert a plethora of effects that can be tissue- or cancer-specific. Our in silico findings generate a hypothesis around biomarkers of disease and exposure that could potentially inform regulation and policy making.
Undiagnosed Diabetes and Prediabetes in Patients with Chronic Coronary Syndromes—An Alarming Public Health Issue
Authors: Drobek Natalia , Sowa Paweł , Jankowski Piotr , Haberka Maciej , Gąsior Zbigniew , Kosior Dariusz , Czarnecka Danuta , Pająk Andrzej , Szostak-Janiak Karolina , Krzykwa Agnieszka , Setny Małgorzata , Kozieł Paweł , Paniczko Marlena , Jamiołkowski Jacek , Kowalska Irina , Kamiński Karol
Published: May 2021

Dysglycemia is a public health challenge for the coming decades, especially in patients with chronic coronary syndromes (CCS). We want to assess the prevalence of undiagnosed diabetes mellitus (DM) and prediabetes, as well as identify factors associated with the development of dysglycaemia in patients with CCS. In total, 1233 study participants (mean age 69 ± 9 years), who, between 6 and 18 months earlier were hospitalized for acute coronary syndrome or elective revascularization, were examined (71.4% men). The diagnosis of DM, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) have been made according to World Health Organization (WHO) criteria. Based on the oral glucose tolerance test (OGTT) results, DM has been newly diagnosed in 28 (5.1%, mean age 69.9 ± 8.4 years) patients, 75% were male (n = 21). Prediabetes has been observed in 395 (72.3%) cases. IFG was found in 234 (42.9%) subjects, 161 (29.5%) individuals had IGT. According to multinomial logistic regression, body mass index (BMI) and high-density lipoprotein cholesterol (HDL-C) should be considered when assessing risk of development of dysglycaemia after discharge from the hospital. Among people with previously diagnosed DM, a significantly higher percentage were willing to change their lifestyles after the index event compared to other patients. Patients with chronic coronary syndromes suffer a very high frequency of dysglycaemia. Most patients with chronic coronary syndromes, especially those with high BMI or low HDL-C, should be considered for screening for dysglycemia using OGTT within the first year after hospitalization. A higher percentage of patients who were aware of their diabetic status changed their lifestyles, which added the benefit of timely diagnosis and treatment of diabetes.
Estimation of Potassium Changes Following Potassium Supplements in Hypokalemic Critically Ill Adult Patients–A Patient Personalized Practical Treatment Formula
Authors: Frenkel Amit , Hassan Lior , Segal Adi , Israeli Adir , Binyamin Yair , Zlotnik Alexander , Novack Victor , Klein Moti
Published: May 2021

Hypokalemia is common among critically ill patients. Parenteral correction of hyperkalemia depends on dosages and patient characteristics. Our aims were to assess changes in potassium levels following parenteral administration, and to derive a formula for predicting rises in serum potassium based on patient characteristics. We conducted a population-based retrospective cohort study of adults hospitalized in a general intensive care unit for 24 h or more between December 2006 and December 2017, with hypokalemia. The primary exposures were absolute cumulative intravenous doses of 20, 40, 60 or 80 mEq potassium supplement. Adjusted linear mixed models were used to estimate changes in serum potassium. Of 683 patients, 422 had mild and 261 moderate hypokalemia (serum potassium 3.0–3.5 mEq/L and 2.5–2.99 mEq, respectively). Following doses of 20–80 mEq potassium, serum potassium levels rose by a mean 0.27 (±0.4) mEq/L and 0.45 (±0.54) mEq/L in patients with mild and moderate hypokalemia, respectively. Changes were associated with creatinine level, and the use of mechanical ventilation and vasopressors. Among critically ill patients with mild to moderate hypokalemia, increases in serum potassium after intravenous potassium supplement are influenced by several clinical parameters. We generated a formula to predict the expected rise in serum potassium based on clinical parameters.