bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Value Stream Mapping in Healthcare Services: A Scoping Review
Authors: Marin-Garcia Juan A. , Vidal-Carreras Pilar I. , Garcia-Sabater Julio J.
Published: January 2021

Lean healthcare aims to manage and improve the processes in the healthcare sector by eliminating everything that adds no value by improving quality of services, ensuring patient safety and facilitating health professionals’ work to achieve a flexible and reliable organization. Value Stream Mapping (VSM) is considered the starting point of any lean implementation. Some papers report applications of VSM in healthcare services, but there has been less attention paid to their contribution on sustainability indicators. The purpose of this work is to analyze the role of VSM in this context. To do so, a scoping review of works from recent years (2015 to 2019) was done. The results show that most applications of VSM reported are in the tertiary level of care, and the United States of America (USA) is the country which leads most of the applications published. In relation with the development of VSM, a heterogeneity in the maps and the sustainability indicators is remarkable. Moreover, only operational and social sustainability indicators are commonly included. We can conclude that more standardization is required in the development of the VSM in the healthcare sector, also including the environmental indicators.
Estimation of COVID-19 Epidemiology Curve of the United States Using Genetic Programming Algorithm
Authors: Anđelić Nikola , Šegota Sandi Baressi , Lorencin Ivan , Jurilj Zdravko , Šušteršič Tijana , Blagojević Anđela , Protić Alen , Ćabov Tomislav , Filipović Nenad , Car Zlatan
Published: January 2021

Estimation of the epidemiology curve for the COVID-19 pandemic can be a very computationally challenging task. Thus far, there have been some implementations of artificial intelligence (AI) methods applied to develop epidemiology curve for a specific country. However, most applied AI methods generated models that are almost impossible to translate into a mathematical equation. In this paper, the AI method called genetic programming (GP) algorithm is utilized to develop a symbolic expression (mathematical equation) which can be used for the estimation of the epidemiology curve for the entire U.S. with high accuracy. The GP algorithm is utilized on the publicly available dataset that contains the number of confirmed, deceased and recovered patients for each U.S. state to obtain the symbolic expression for the estimation of the number of the aforementioned patient groups. The dataset consists of the latitude and longitude of the central location for each state and the number of patients in each of the goal groups for each day in the period of 22 January 2020–3 December 2020. The obtained symbolic expressions for each state are summed up to obtain symbolic expressions for estimation of each of the patient groups (confirmed, deceased and recovered). These symbolic expressions are combined to obtain the symbolic expression for the estimation of the epidemiology curve for the entire U.S. The obtained symbolic expressions for the estimation of the number of confirmed, deceased and recovered patients for each state achieved R2 score in the ranges 0.9406–0.9992, 0.9404–0.9998 and 0.9797–0.99955, respectively. These equations are summed up to formulate symbolic expressions for the estimation of the number of confirmed, deceased and recovered patients for the entire U.S. with achieved R2 score of 0.9992, 0.9997 and 0.9996, respectively. Using these symbolic expressions, the equation for the estimation of the epidemiology curve for the entire U.S. is formulated which achieved R2 score of 0.9933. Investigation showed that GP algorithm can produce symbolic expressions for the estimation of the number of confirmed, recovered and deceased patients as well as the epidemiology curve not only for the states but for the entire U.S. with very high accuracy.
Central Attention and a Dual Path Convolutional Neural Network in Real-World Tree Species Recognition
Authors: Chung Yi , Chou Chih-Ang , Li Chih-Yang
Published: January 2021

Identifying plants is not only the job of professionals, but also useful or essential for the plant lover and the general public. Although deep learning approaches for plant recognition are promising, driven by the success of convolutional neural networks (CNN), their performances are still far from the requirements of an in-field scenario. First, we propose a central attention concept that helps focus on the target instead of backgrounds in the image for tree species recognition. It could prevent model training from confused vision by establishing a dual path CNN deep learning framework, in which the central attention model combined with the CNN model based on InceptionV3 were employed to automatically extract the features. These two models were then learned together with a shared classification layer. Experimental results assessed the effectiveness of our proposed approach which outperformed each uni-path alone, and existing methods in the whole plant recognition system. Additionally, we created our own tree image database where each photo contained a wealth of information on the entire tree instead of an individual plant organ. Lastly, we developed a prototype system of an online/offline available tree species identification working on a consumer mobile platform that can identify the tree species not only by image recognition, but also detection and classification in real-time remotely.
Risk of Amyotrophic Lateral Sclerosis and Exposure to Particulate Matter from Vehicular Traffic: A Case-Control Study
Authors: Filippini Tommaso , Mandrioli Jessica , Malagoli Carlotta , Costanzini Sofia , Cherubini Andrea , Maffeis Giuseppe , Vinceti Marco
Published: January 2021

(1) Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with still unknown etiology. Some occupational and environmental risk factors have been suggested, including long-term air pollutant exposure. We carried out a pilot case-control study in order to evaluate ALS risk due to particulate matter with a diameter of ≤10 µm (PM10) as a proxy of vehicular traffic exposure. (2) Methods: We recruited ALS patients and controls referred to the Modena Neurology ALS Care Center between 1994 and 2015. Using a geographical information system, we modeled PM10 concentrations due to traffic emissions at the geocoded residence address at the date of case diagnosis. We computed the odds ratio (OR) and 95% confidence interval (CI) of ALS according to increasing PM10 exposure, using an unconditional logistic regression model adjusted for age and sex. (3) Results: For the 132 study participants (52 cases and 80 controls), the average of annual median and maximum PM10 concentrations were 5.2 and 38.6 µg/m3, respectively. Using fixed cutpoints at 5, 10, and 20 of the annual median PM10 levels, and compared with exposure <5 µg/m3, we found no excess ALS risk at 5–10 µg/m3 (OR 0.87, 95% CI 0.39–1.96), 10–20 µg/m3 (0.94, 95% CI 0.24–3.70), and ≥20 µg/m3 (0.87, 95% CI 0.05–15.01). Based on maximum PM10 concentrations, we found a statistically unstable excess ALS risk for subjects exposed at 10–20 µg/m3 (OR 4.27, 95% CI 0.69–26.51) compared with those exposed <10 µg/m3. However, risk decreased at 20–50 µg/m3 (OR 1.49, 95% CI 0.39–5.75) and ≥50 µg/m3 (1.16, 95% CI 0.28–4.82). ALS risk in increasing tertiles of exposure showed a similar null association, while comparison between the highest and the three lowest quartiles lumped together showed little evidence for an excess risk at PM10 concentrations (OR 1.13, 95% CI 0.50–2.55). After restricting the analysis to subjects with stable residence, we found substantially similar results. (4) Conclusions: In this pilot study, we found limited evidence of an increased ALS risk due to long-term exposure at high PM10 concentration, though the high statistical imprecision of the risk estimates, due to the small sample size, particularly in some exposure categories, limited our capacity to detect small increases in risk, and further larger studies are needed to assess this relation.
Bioaccessibility and In Vitro Intestinal Permeability of a Recombinant Lectin from Tepary Bean (Phaseolus acutifolius) Using the Everted Intestine Assay
Authors: Vega-Rojas Lineth Juliana , Luzardo-Ocampo Ivan , Mosqueda Juan , Palmerín-Carreño Dulce María , Escobedo-Reyes Antonio , Blanco-Labra Alejandro , Escobar-García Konisgmar , García-Gasca Teresa
Published: January 2021

Tepary bean (Phaseolus acutifolius) lectins exhibit differential in vitro and in vivo biological effects, but their gastrointestinal interactions and digestion have not yet been assessed. This work aimed to evaluate the changes of a recombinant Tepary bean lectin (rTBL-1) through an in vitro and ex vivo gastrointestinal process. A polyclonal antibody was developed to selectively detect rTBL-1 by Western blot (WB) and immunohistochemical analysis. Everted gut sac viability was confirmed until 60 min, where protein bioaccessibility, apparent permeability coefficient, and efflux ratio showed rTBL-1 partial digestion and absorption. Immunoblot assays suggested rTBL-1 internalization, since the lectin was detected in the digestible fraction. The immunohistochemical assay detected rTBL-1 presence at the apical side of the small intestine, potentially due to the interaction with the intestinal cell membrane. The in silico interactions between rTBL-1 and some saccharides or derivatives showed high binding affinity to sialic acid (−6.70 kcal/mol) and N-acetylglucosamine (−6.10 kcal/mol). The ultra-high-performance liquid chromatography–electron spray ionization–quantitative time-of-flight coupled to mass spectrometry (UHPLC–ESI–QTOF/MS) analysis showed rTBL-1 presence in the gastric content and the non-digestible fraction after intestinal simulation conditions. The results indicated that rTBL-1 partially resisted the digestive conditions and interacted with the intestinal membrane, whereas its digestion allowed the absorption or internalization of the protein or the derivative peptides. Further purification of digestion samples should be conducted to identify intact rTBL-1 protein and digested peptides to assess their physiological effects.
Titanium Wear of Dental Implants from Placement, under Loading and Maintenance Protocols
Authors: Romanos Georgios , Fischer Gerard , Delgado-Ruiz Rafael
Published: January 2021

The objective of this review was to analyze the process of wear of implants leading to the shedding of titanium particles into the peri-implant hard and soft tissues. Titanium is considered highly biocompatible with low corrosion and toxicity, but recent studies indicate that this understanding may be misleading as the properties of the material change drastically when titanium nanoparticles (NPs) are shed from implant surfaces. These NPs are immunogenic and are associated with a macrophage-mediated inflammatory response by the host. The literature discussed in this review indicates that titanium NPs may be shed from implant surfaces at the time of implant placement, under loading conditions, and during implant maintenance procedures. We also discuss the significance of the micro-gap at the implant-abutment interface and the effect of size of the titanium particles on their toxicology. These findings are significant as the titanium particles can have adverse effects on local soft and hard tissues surrounding implants, implant health and prognosis, and even the health of systemic tissues and organs.
Restraint of Human Skin Fibroblast Motility, Migration, and Cell Surface Actin Dynamics, by Pannexin 1 and P2X7 Receptor Signaling
Authors: Flores-Muñoz Carolina , Maripillán Jaime , Vásquez-Navarrete Jacqueline , Novoa-Molina Joel , Ceriani Ricardo , Sánchez Helmuth A. , Abbott Ana C. , Weinstein-Oppenheimer Caroline , Brown Donald I. , Cárdenas Ana María , García Isaac E. , Martínez Agustín D.
Published: January 2021

Wound healing is a dynamic process required to maintain skin integrity and which relies on the precise migration of different cell types. A key molecule that regulates this process is ATP. However, the mechanisms involved in extracellular ATP management are poorly understood, particularly in the human dermis. Here, we explore the role, in human fibroblast migration during wound healing, of Pannexin 1 channels and their relationship with purinergic signals and in vivo cell surface filamentous actin dynamics. Using siRNA against Panx isoforms and different Panx1 channel inhibitors, we demonstrate in cultured human dermal fibroblasts that the absence or inhibition of Panx1 channels accelerates cell migration, increases single-cell motility, and promotes actin redistribution. These changes occur through a mechanism that involves the release of ATP to the extracellular space through a Panx1-dependent mechanism and the activation of the purinergic receptor P2X7. Together, these findings point to a pivotal role of Panx1 channels in skin fibroblast migration and suggest that these channels could be a useful pharmacological target to promote damaged skin healing.
Machine Learning Analysis of Longevity-Associated Gene Expression Landscapes in Mammals
Authors: Kulaga Anton Y. , Ursu Eugen , Toren Dmitri , Tyshchenko Vladyslava , Guinea Rodrigo , Pushkova Malvina , Fraifeld Vadim E. , Tacutu Robi
Published: January 2021

One of the important questions in aging research is how differences in transcriptomics are associated with the longevity of various species. Unfortunately, at the level of individual genes, the links between expression in different organs and maximum lifespan (MLS) are yet to be fully understood. Analyses are complicated further by the fact that MLS is highly associated with other confounding factors (metabolic rate, gestation period, body mass, etc.) and that linear models may be limiting. Using gene expression from 41 mammalian species, across five organs, we constructed gene-centric regression models associating gene expression with MLS and other species traits. Additionally, we used SHapley Additive exPlanations and Bayesian networks to investigate the non-linear nature of the interrelations between the genes predicted to be determinants of species MLS. Our results revealed that expression patterns correlate with MLS, some across organs, and others in an organ-specific manner. The combination of methods employed revealed gene signatures formed by only a few genes that are highly predictive towards MLS, which could be used to identify novel longevity regulator candidates in mammals.
A Novel Epigenetic Machine Learning Model to Define Risk of Progression for Hepatocellular Carcinoma Patients
Authors: Bedon Luca , Dal Bo Michele , Mossenta Monica , Busato Davide , Toffoli Giuseppe , Polano Maurizio
Published: January 2021

Although extensive advancements have been made in treatment against hepatocellular carcinoma (HCC), the prognosis of HCC patients remains unsatisfied. It is now clearly established that extensive epigenetic changes act as a driver in human tumors. This study exploits HCC epigenetic deregulation to define a novel prognostic model for monitoring the progression of HCC. We analyzed the genome-wide DNA methylation profile of 374 primary tumor specimens using the Illumina 450 K array data from The Cancer Genome Atlas. We initially used a novel combination of Machine Learning algorithms (Recursive Features Selection, Boruta) to capture early tumor progression features. The subsets of probes obtained were used to train and validate Random Forest models to predict a Progression Free Survival greater or less than 6 months. The model based on 34 epigenetic probes showed the best performance, scoring 0.80 accuracy and 0.51 Matthews Correlation Coefficient on testset. Then, we generated and validated a progression signature based on 4 methylation probes capable of stratifying HCC patients at high and low risk of progression. Survival analysis showed that high risk patients are characterized by a poorer progression free survival compared to low risk patients. Moreover, decision curve analysis confirmed the strength of this predictive tool over conventional clinical parameters. Functional enrichment analysis highlighted that high risk patients differentiated themselves by the upregulation of proliferative pathways. Ultimately, we propose the oncogenic MCM2 gene as a methylation-driven gene of which the representative epigenetic markers could serve both as predictive and prognostic markers. Briefly, our work provides several potential HCC progression epigenetic biomarkers as well as a new signature that may enhance patients surveillance and advances in personalized treatment.
Natriuretic Peptide Expression and Function in GH3 Somatolactotropes and Feline Somatotrope Pituitary Tumours
Authors: Mirczuk Samantha M. , Scudder Christopher J. , Read Jordan E. , Crossley Victoria J. , Regan Jacob T. , Richardson Karen M. , Simbi Bigboy , McArdle Craig A. , Church David B. , Fenn Joseph , Kenny Patrick J. , Volk Holger A. , Wheeler-Jones Caroline P. , Korbonits Márta , Niessen Stijn J. , McGonnell Imelda M. , Fowkes Robert C.
Published: January 2021

Patients harbouring mutations in genes encoding C-type natriuretic peptide (CNP; NPPC) or its receptor guanylyl cyclase B (GC-B, NPR2) suffer from severe growth phenotypes; loss-of-function mutations cause achondroplasia, whereas gain-of-function mutations cause skeletal overgrowth. Although most of the effects of CNP/GC-B on growth are mediated directly on bone, evidence suggests the natriuretic peptides may also affect anterior pituitary control of growth. Our previous studies described the expression of NPPC and NPR2 in a range of human pituitary tumours, normal human pituitary, and normal fetal human pituitary. However, the natriuretic peptide system in somatotropes has not been extensively explored. Here, we examine the expression and function of the CNP/GC-B system in rat GH3 somatolactotrope cell line and pituitary tumours from a cohort of feline hypersomatotropism (HST; acromegaly) patients. Using multiplex RT-qPCR, all three natriuretic peptides and their receptors were detected in GH3 cells. The expression of Nppc was significantly enhanced following treatment with either 100 nM TRH or 10 µM forskolin, yet only Npr1 expression was sensitive to forskolin stimulation; the effects of forskolin and TRH on Nppc expression were PKA- and MAPK-dependent, respectively. CNP stimulation of GH3 somatolactotropes significantly inhibited Esr1, Insr and Lepr expression, but dramatically enhanced cFos expression at the same time point. Oestrogen treatment significantly enhanced expression of Nppa, Nppc, Npr1, and Npr2 in GH3 somatolactotropes, but inhibited CNP-stimulated cGMP accumulation. Finally, transcripts for all three natriuretic peptides and receptors were expressed in feline pituitary tumours from patients with HST. NPPC expression was negatively correlated with pituitary tumour volume and SSTR5 expression, but positively correlated with D2R and GHR expression. Collectively, these data provide mechanisms that control expression and function of CNP in somatolactotrope cells, and identify putative transcriptional targets for CNP action in somatotropes.
Diversified Biomineralization Roles of Pteria penguin Pearl Shell Lectins as Matrix Proteins
Authors: Ogawa Tomohisa , Sato Rie , Naganuma Takako , Liu Kayeu , Sato Saho , Sakaue Shizuka , Osada Makoto , Yoshimi Kyosuke , Muramoto Koji
Published: January 2021

Previously, we isolated jacalin-related lectins termed PPL2, PPL3 (PPL3A, 3B and 3C) and PPL4 from the mantle secretory fluid of Pteria penguin (Mabe) pearl shell. They showed the sequence homology with the plant lectin family, jacalin-related β-prism fold lectins (JRLs). While PPL3s and PPL4 shared only 35%–50% homology to PPL2A, respectively, they exhibited unique carbohydrate binding properties based on the multiple glycan-binding profiling data sets from frontal affinity chromatography analysis. In this paper, we investigated biomineralization properties of these lectins and compared their biomineral functions. It was found that these lectins showed different effects on CaCO3 crystalization, respectively, although PPL3 and PPL2A showed similar carbohydrate binding specificities. PPL3 suppressed the crystal growth of CaCO3 calcite, while PPL2A increased the number of contact polycrystalline calcite composed of more than one crystal with various orientations. Furthermore, PPL4 alone showed no effect on CaCO3 crystalization; however, PPL4 regulated the size of crystals collaborated with N-acetyl-D-glucosamine and chitin oligomer, which are specific in recognizing carbohydrates for PPL4. These observations highlight the unique functions and molecular evolution of this lectin family involved in the mollusk shell formation.
Investigation of Receptor Heteromers Using NanoBRET Ligand Binding
Authors: Johnstone Elizabeth K. M. , See Heng B. , Abhayawardana Rekhati S. , Song Angela , Rosengren K. Johan , Hill Stephen J. , Pfleger Kevin D. G.
Published: January 2021

Receptor heteromerization is the formation of a complex involving at least two different receptors with pharmacology that is distinct from that exhibited by its constituent receptor units. Detection of these complexes and monitoring their pharmacology is crucial for understanding how receptors function. The Receptor-Heteromer Investigation Technology (Receptor-HIT) utilizes ligand-dependent modulation of interactions between receptors and specific biomolecules for the detection and profiling of heteromer complexes. Previously, the interacting biomolecules used in Receptor-HIT assays have been intracellular proteins, however in this study we have for the first time used bioluminescence resonance energy transfer (BRET) with fluorescently-labeled ligands to investigate heteromerization of receptors on the cell surface. Using the Receptor-HIT ligand binding assay with NanoBRET, we have successfully investigated heteromers between the angiotensin II type 1 (AT1) receptor and the β2 adrenergic receptor (AT1-β2AR heteromer), as well as between the AT1 and angiotensin II type 2 receptor (AT1-AT2 heteromer).
Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel GSN Variant p.Glu580Lys
Authors: Potrč Maja , Volk Marija , de Rosa Matteo , Pižem Jože , Teran Nataša , Jaklič Helena , Maver Aleš , Drnovšek-Olup Brigita , Bollati Michela , Vogelnik Katarina , Hočevar Alojzija , Gornik Ana , Pfeifer Vladimir , Peterlin Borut , Hawlina Marko , Fakin Ana
Published: January 2021

Gelsolin amyloidosis typically presents with corneal lattice dystrophy and is most frequently associated with pathogenic GSN variant p.Asp214Asn. Here we report clinical and histopathological features of gelsolin amyloidosis associated with a novel GSN variant p.Glu580Lys. We studied DNA samples of seven members of a two-generation family. Exome sequencing was performed in the proband, and targeted Sanger sequencing in the others. The heterozygous GSN variant p.Glu580Lys was identified in six patients. The patients exhibited corneal dystrophy (5/6), loose skin (5/6) and/or heart arrhythmia (3/6) and one presented with bilateral optic neuropathy. The impact of the mutation on the protein structure was evaluated in silico. The substitution is located in the fifth domain of gelsolin protein, homologous to the second domain harboring the most common pathogenic variant p.Asp214Asn. Structural investigation revealed that the mutation might affect protein folding. Histopathological analysis showed amyloid deposits in the skin. The p.Glu580Lys is associated with corneal dystrophy, strengthening the association of the fifth domain of gelsolin protein with the typical amyloidosis phenotype. Furthermore, optic neuropathy may be related to the disease and is essential to identify before discussing corneal transplantation.
Neurodegenerative Proteinopathies in the Proteoform Spectrum—Tools and Challenges
Authors: Noor Aneeqa , Zafar Saima , Zerr Inga
Published: January 2021

Proteinopathy refers to a group of disorders defined by depositions of amyloids within living tissue. Neurodegenerative proteinopathies, including Alzheimer’s disease, Parkinson’s disease, Creutzfeldt–Jakob disease, and others, constitute a large fraction of these disorders. Amyloids are highly insoluble, ordered, stable, beta-sheet rich proteins. The emerging theory about the pathophysiology of neurodegenerative proteinopathies suggests that the primary amyloid-forming proteins, also known as the prion-like proteins, may exist as multiple proteoforms that contribute differentially towards the disease prognosis. It is therefore necessary to resolve these disorders on the level of proteoforms rather than the proteome. The transient and hydrophobic nature of amyloid-forming proteins and the minor post-translational alterations that lead to the formation of proteoforms require the use of highly sensitive and specialized techniques. Several conventional techniques, like gel electrophoresis and conventional mass spectrometry, have been modified to accommodate the proteoform theory and prion-like proteins. Several new ones, like imaging mass spectrometry, have also emerged. This review aims to discuss the proteoform theory of neurodegenerative disorders along with the utility of these proteomic techniques for the study of highly insoluble proteins and their associated proteoforms.
Changing Functional Signatures of Microglia along the Axis of Brain Aging
Authors: Brawek Bianca , Skok Maryna , Garaschuk Olga
Published: January 2021

Microglia, the innate immune cells of the brain, are commonly perceived as resident macrophages of the central nervous system (CNS). This definition, however, requires further specification, as under healthy homeostatic conditions, neither morphological nor functional properties of microglia mirror those of classical macrophages. Indeed, microglia adapt exceptionally well to their microenvironment, becoming a legitimate member of the cellular brain architecture. The ramified or surveillant microglia in the young adult brain are characterized by specific morphology (small cell body and long, thin motile processes) and physiology (a unique pattern of Ca2+ signaling, responsiveness to various neurotransmitters and hormones, in addition to classic “immune” stimuli). Their numerous physiological functions far exceed and complement their immune capabilities. As the brain ages, the respective changes in the microglial microenvironment impact the functional properties of microglia, triggering further rounds of adaptation. In this review, we discuss the recent data showing how functional properties of microglia adapt to age-related changes in brain parenchyma in a sex-specific manner, with a specific focus on early changes occurring at middle age as well as some strategies counteracting the aging of microglia.
Retinoid Regulation of Ocular Surface Innate Inflammation
Authors: Alam Jehan , Yu Zhiyuan , de Paiva Cintia S. , Pflugfelder Stephen C.
Published: January 2021

Corneal and conjunctival inflammation and dry eye develop in systemic vitamin A deficiency (VAD). The objective of this study was to investigate the lacrimal ocular surface retinoid axis, particularly immunomodulatory effects of retinoic acid (RA) and change in conjunctival myeloid cell number and phenotype in VAD. We discovered that ocular surface epithelial and myeloid cells express retinoid receptors. Both all trans- and 9-cis-RA suppressed production of dry eye relevant inflammatory mediators [interleukin(IL)-1β, IL-12, regulated upon activation, normal T cell expressed and secreted (RANTES)] by myeloid cells. Systemic VAD was associated with significant goblet cell loss and an increased number of CD45+ immune cells in the conjunctiva. MHCII−CD11b+ classical monocytes were significantly increased in the conjunctiva of VAD C57BL/6 and RXR-α mutated Pinkie strains. RNA seq revealed significantly increased expression of innate immune/inflammatory genes in the Pinkie conjunctiva. These findings indicate that retinoids are essential for maintaining a healthy, well-lubricated ocular surface and have immunomodulatory effects in the conjunctiva that are mediated in part via RXR-α signaling. Perturbation of the homeostatic retinoid axis could potentiate inflammation on the ocular surface.
Development of 3D Printed Bruch’s Membrane-Mimetic Substance for the Maturation of Retinal Pigment Epithelial Cells
Authors: Kim Jongmin , Park Ju Young , Kong Jeong Sik , Lee Hyungseok , Won Jae Yon , Cho Dong Woo
Published: January 2021

Retinal pigment epithelium (RPE) is a monolayer of the pigmented cells that lies on the thin extracellular matrix called Bruch’s membrane. This monolayer is the main component of the outer blood–retinal barrier (BRB), which plays a multifunctional role. Due to their crucial roles, the damage of this epithelium causes a wide range of diseases related to retinal degeneration including age-related macular degeneration, retinitis pigmentosa, and Stargardt disease. Unfortunately, there is presently no cure for these diseases. Clinically implantable RPE for humans is under development, and there is no practical examination platform for drug development. Here, we developed porcine Bruch’s membrane-derived bioink (BM-ECM). Compared to conventional laminin, the RPE cells on BM-ECM showed enhanced functionality of RPE. Furthermore, we developed the Bruch’s membrane-mimetic substrate (BMS) via the integration of BM-ECM and 3D printing technology, which revealed structure and extracellular matrix components similar to those of natural Bruch’s membrane. The developed BMS facilitated the appropriate functions of RPE, including barrier and clearance functions, the secretion of anti-angiogenic growth factors, and enzyme formation for phototransduction. Moreover, it could be used as a basement frame for RPE transplantation. We established BMS using 3D printing technology to grow RPE cells with functions that could be used for an in vitro model and RPE transplantation.
Evaluation of Nanotargeted 111In-Cyclic RGDfK-Liposome in a Human Melanoma Xenotransplantation Model
Authors: Liu Si-Yen , Lo Sheng-Nan , Lee Wan-Chi , Hsu Wei-Chuan , Lee Te-Wei , Chang Chih-Hsien
Published: January 2021

Nanotargeted liposomes may be modified with targeting peptide on the surface of a prepared liposome to endow specificity and elevate targeting efficiency. The aim of this study was to develop a radioactive targeted nanoparticle, the 111In-cyclic RGDfK-liposome, and its advantage of recognizing the αVβ3 integrin was examined. The cyclic RGDfK modified liposomes were demonstrated the ability to bind the αVβ3 integrin expressed on the surface of human melanoma cell in vitro and in vivo. The effects of the cyclic RGDfK-liposome on the functioning of phagocytes was also examined, showing no considerable negative effects on the engulfment of bacteria and the generation of reactive oxygen species. Based upon these findings, the cyclic RGDfK- liposome is said to be a promising agent for tumor imaging.
Role of Aiolos and Ikaros in the Antitumor and Immunomodulatory Activity of IMiDs in Multiple Myeloma: Better to Lose Than to Find Them
Authors: Cippitelli Marco , Stabile Helena , Kosta Andrea , Petillo Sara , Gismondi Angela , Santoni Angela , Fionda Cinzia
Published: January 2021

The Ikaros zing-finger family transcription factors (IKZF TFs) are important regulators of lymphocyte development and differentiation and are also highly expressed in B cell malignancies, including Multiple Myeloma (MM), where they are required for cancer cell growth and survival. Moreover, IKZF TFs negatively control the functional properties of many immune cells. Thus, the targeting of these proteins has relevant therapeutic implications in cancer. Indeed, accumulating evidence demonstrated that downregulation of Ikaros and Aiolos, two members of the IKZF family, in malignant plasma cells as well as in adaptative and innate lymphocytes, is key for the anti-myeloma activity of Immunomodulatory drugs (IMiDs). This review is focused on IKZF TF-related pathways in MM. In particular, we will address how the depletion of IKZF TFs exerts cytotoxic effects on MM cells, by reducing their survival and proliferation, and concomitantly potentiates the antitumor immune response, thus contributing to therapeutic efficacy of IMiDs, a cornerstone in the treatment of this neoplasia.
Short-Term Electricity Load Forecasting with Machine Learning
Authors: Aguilar Madrid Ernesto , Antonio Nuno
Published: January 2021

An accurate short-term load forecasting (STLF) is one of the most critical inputs for power plant units’ planning commitment. STLF reduces the overall planning uncertainty added by the intermittent production of renewable sources; thus, it helps to minimize the hydrothermal electricity production costs in a power grid. Although there is some research in the field and even several research applications, there is a continual need to improve forecasts. This research proposes a set of machine learning (ML) models to improve the accuracy of 168 h forecasts. The developed models employ features from multiple sources, such as historical load, weather, and holidays. Of the five ML models developed and tested in various load profile contexts, the Extreme Gradient Boosting Regressor (XGBoost) algorithm showed the best results, surpassing previous historical weekly predictions based on neural networks. Additionally, because XGBoost models are based on an ensemble of decision trees, it facilitated the model’s interpretation, which provided a relevant additional result, the features’ importance in the forecasting.
Detection and Characterization of Phosphorylation, Glycosylation, and Fatty Acid Bound to Fetuin A in Human Blood
Authors: Kovářová Markéta , Kalbacher Hubert , Peter Andreas , Häring Hans-Ulrich , Didangelos Triantafyllos , Stefan Norbert , Birkenfeld Andreas , Schleicher Erwin , Kantartzis Konstantinos
Published: January 2021

The hepatokine fetuin A (Fet A) has been associated with diverse pathological states such as insulin resistance, type 2 diabetes, macrovascular disease, and systemic ectopic and vascular calcification. Fet A may also play a role in tumor growth and metastasis. The biological activity of Fet A may be affected by various modifications, including phosphorylation, O- and N-glycosylation and fatty acid binding. We developed an antibody-based assay for the detection of Fet A phosphorylated at serine 312. Fatty acid pattern was determined by gas chromatography. Using the antibody, we found that the phosphorylation was stable in human plasma or serum at room temperature for 8 h. We observed that Fet A is present in several glycosylation forms in human plasma, but the extent of Ser312 phosphorylation was not associated with glycosylation. The phosphorylation pattern did not change during an oral glucose tolerance test (0–120 min). We further found that human Fet A binds preferentially saturated fatty acids (>90%) at the expense of mono- and poly-unsaturated fatty acids. Our results indicate that different molecular species of Fet A are present in human plasma and that these different modifications may determine the different biological effects of Fet A.
Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers on Acute Kidney Injury in Emergency Medical Admissions
Authors: Feidakis Athanasios , Panagiotou Maria-Rosa , Tsoukakis Emmanouil , Bacharaki Dimitra , Gounari Paraskevi , Nikolopoulos Petros , Marathias Katerina P. , Lionaki Sophia , Vlahakos Demetrios
Published: January 2021

Background: Acute kidney injury (AKI) has been observed in up to 20% of adult hospital admissions. Sepsis, diarrhea and heart failure, all causing reduced effective volume, are considered risk factors for AKI, especially among patients treated with medications that block the Renin-Angiotensin System (RAS), such as angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB). We aimed to determine the incidence of acute kidney injury (AKI) in emergency medical admissions in relation to the use and dosage of ACEi/ARB. Methods: A single-center observational study conducted in 577 consecutive medical admissions via the Emergency Room (ER) at a University General Hospital in Athens, Greece, between June and July 2018. Patients with incomplete medical records, discharged within 24 h, maintained on chronic renal replacement therapy, admitted to the Cardiology Department or the ICU were excluded. Thus, a total of 309 patients were finally included in this analysis. Results: We compared 86 (28%) patients who presented in the ER with AKI (AKIGroup) with 223 (72%) patients without AKI (non-AKI Group) at the time of admission. Patients in the AKI Group were more frequently male (58% vs. 46%, p = 0.06), with a higher frequency of diarrhea (16% vs. 6%, p = 0.006), edema (15% vs. 6%, p = 0.014) and lower systolic blood pressure (120 (107–135) vs. 126 (113–140), p = 0.007) at presentation, despite higher prevalence of hypertension (64% vs. 47%, p = 0.006). Overall, ACEi/ARB were more likely to have been prescribed in the AKI Group than in the non-AKI Group (49% vs. 28%, p = 0.001). Interestingly, AKI was more frequently observed in patients treated with the target or above target dosage of ACEi/ARB, but not in those receiving lower than the recommended dosage. Conclusion: The risk of AKI in emergency medical admissions is higher among users of ACEIs/ARB at target or above target dosages. Physicians should adjust RAS blockade according to estimated Glomerular Filtration Rate (eGFR) and advise their patients to withhold ACEi/ARB in cases of acute illness.
Impact of Surgical Management of Endometrioma on AMH Levels and Pregnancy Rates: A Review of Recent Literature
Authors: Pais Ana Sofia , Flagothier Clara , Tebache Linda , Almeida Santos Teresa , Nisolle Michelle
Published: January 2021

Ovarian endometrioma are found in up to 40% of women with endometriosis and 50% of infertile women. The best surgical approach for endometrioma and its impact on pregnancy rates is still controversial. Therefore, we conducted a literature review on surgical management of ovarian endometrioma and its impact on pregnancy rates and ovarian reserve, assessed by anti-Müllerian hormone (AMH) serum levels. Ovarian cystectomy is the preferred technique, as it is associated with lower recurrence and higher spontaneous pregnancy rate. However, ablative approaches and combined techniques are becoming more popular as ovarian reserve is less affected and there are slightly higher pregnancy rates. Preoperative AMH level might be useful to predict the occurrence of pregnancy. In conclusion, AMH should be included in the preoperative evaluation of reproductive aged women with endometriosis. The surgical options for ovarian endometrioma should be individualized. The endometrioma ablation procedure seems to be the most promising treatment.
Carotid Beta Stiffness Association with Thyroid Function
Authors: Delitala Alessandro P. , Scuteri Angelo , Fiorillo Edoardo , Orrù Valeria , Lakatta Edward G. , Schlessinger David , Cucca Francesco
Published: January 2021

Background: Thyroid hormone modulation of cardiovascular function has been associated with cardiovascular disease. Recent evidence suggests that free thyroxine (FT4) levels are associated with an increase in systemic arterial stiffness, but little is known about the effects of FT4 at the local level of the common carotid artery. β-stiffness index is a local elastic parameter usually determined by carotid ultrasound imaging. Methods: We conducted a cross-sectional analysis in the ProgeNIA cohort, including 4846 subjects across a broad age range. For the purpose of this study, we excluded subjects with increased thyrotropin (TSH) levels and those treated with levothyroxine or thyrostatic. We assessed β stiffness, strain, wall–lumen ratio, carotid cross-sectional area (CSA), and stress and flow in the right common carotid artery. We tested whether FT4, heart rate, and their interactions were associated with carotid parameters. Results: FT4 was positively and independently associated with β stiffness index (β = 0.026, p = 0.041), and had a negative association with strain (β = −0.025, p = 0.009). After adding heart rate and the interaction between FT4 and heart rate to the model, FT4 was still associated with the β stiffness index (β = 0.186, p = 0.06), heart rate was positively associated with the stiffness index (β = 0.389, p < 0.001) as well as their interaction (β = 0.271, p = 0.007). Conclusion: This study suggests that higher FT4 levels increase arterial stiffness at the common carotid level, consistent with a detrimental effect on elastic arteries. The effect of FT4 is likely to be primarily attributable to its effect on heart rate.
Oral Health-Related Quality of Life, Oral Conditions, and Risk of Malnutrition in Older German People in Need of Care—A Cross-Sectional Study
Authors: Schmalz Gerhard , Denkler Clara Rosa , Kottmann Tanja , Rinke Sven , Ziebolz Dirk
Published: January 2021

Background: The present cross-sectional study assessed oral health, nutritional condition, and oral health-related quality of life (OHRQoL) in older German people in need of care. Methods: The participants were recruited from eight nursing homes (including three nursing homes with assisted living) and one mobile nursing service. Oral health, including dental status (decayed, missing and filled teeth (DMF-T), root caries), periodontal treatment needs, and prosthetic conditions, was recorded. Nutritional status was assessed using the screening of the “Mini Nutritional Assessment” (MNA). The OHRQoL was measured using the German short-form of the Oral Health Impact Profile (OHIP-G14) and summarized as a total sum score as well as the four dimensions “oral function”, “psychosocial impact”, “pain” and “orofacial appearance”. Statistics: Linear logistic regression analyses. Results: A total of 151 participants (age: 84.17 ± 7.8 years) were included. Most participants (60.3%) were nursing home residents. Nearly half of the individuals (47%) were edentulous and 75.4% of the dentate subjects required periodontal treatment. A total of 115 of the subjects had at least one denture. According to the MNA screening, 107 (70.9%) older people were at risk of malnutrition or already suffered from malnutrition. The median OHIP-G14 sum score was 3 (mean 5.7 ± 7.67). Regression analysis revealed MNA to be influenced by DMF-T, D-T, M-T and OHIP G14 sum score and root caries (pi < 0.01). Within the regression model, missing teeth (β: −11.9, CI95: −6.4–−1.9; p < 0.01) were the strongest influential factor on MNA, followed by DMF-T (β: 5.1, CI95: 1.7–6.2; p < 0.01). Conclusions: Older people in nursing settings show a high prevalence of oral diseases, risk of malnutrition and nearly unimpaired OHRQoL. Dental care should be fostered in these individuals, whereby OHRQoL might be a further hint for increased risk of malnutrition.
Acknowledgment to Reviewers of Journal of Functional Morphology and Kinesiology in 2020
Authors:   Journal of Functional Morphology Kinesiology Editorial Office
Published: January 2021

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that JFMK maintains its standards for the high quality of its published papers [...]
Performance and Regeneration of Methane Oxidation Catalyst for LNG Ships
Authors: Lehtoranta Kati , Koponen Päivi , Vesala Hannu , Kallinen Kauko , Maunula Teuvo
Published: January 2021

Liquefied natural gas (LNG) use as marine fuel is increasing. Switching diesel to LNG in ships significantly reduces air pollutants but the methane slip from gas engines can in the worst case outweigh the CO2 decrease with an unintended effect on climate. In this study, a methane oxidation catalyst (MOC) is investigated with engine experiments in lean-burn conditions. Since the highly efficient catalyst needed to oxidize methane is very sensitive to sulfur poisoning a regeneration using stoichiometric conditions was studied to reactivate the catalyst. In addition, the effect of a special sulfur trap to protect the MOC and ensure long-term performance for methane oxidation was studied. MOC was found to decrease the methane emission up to 70–80% at the exhaust temperature of 550 degrees. This efficiency decreased within time, but the regeneration done once a day was found to recover the efficiency. Moreover, the sulfur trap studied with MOC was shown to protect the MOC against sulfur poisoning to some extent. These results give indication of the possible use of MOC in LNG ships to control methane slip emissions.
The Host Immune Response to Scedosporium/Lomentospora
Authors: Buldain Idoia , Martin-Souto Leire , Antoran Aitziber , Areitio Maialen , Aparicio-Fernandez Leire , Rementeria Aitor , Hernando Fernando L. , Ramirez-Garcia Andoni
Published: January 2021

Infections caused by the opportunistic pathogens Scedosporium/Lomentospora are on the rise. This causes problems in the clinic due to the difficulty in diagnosing and treating them. This review collates information published on immune response against these fungi, since an understanding of the mechanisms involved is of great interest in developing more effective strategies against them. Scedosporium/Lomentospora cell wall components, including peptidorhamnomannans (PRMs), α-glucans and glucosylceramides, are important immune response activators following their recognition by TLR2, TLR4 and Dectin-1 and through receptors that are yet unknown. After recognition, cytokine synthesis and antifungal activity of different phagocytes and epithelial cells is species-specific, highlighting the poor response by microglial cells against L. prolificans. Moreover, a great number of Scedosporium/Lomentospora antigens have been identified, most notably catalase, PRM and Hsp70 for their potential medical applicability. Against host immune response, these fungi contain evasion mechanisms, inducing host non-protective response, masking fungal molecular patterns, destructing host defense proteins and decreasing oxidative killing. In conclusion, although many advances have been made, many aspects remain to be elucidated and more research is necessary to shed light on the immune response to Scedosporium/Lomentospora.
Unraveling the Diversity of Trajectories and Drivers of Global Agricultural Land Abandonment
Authors: Prishchepov Alexander V. , Schierhorn Florian , Löw Fabian
Published: January 2021

The world is facing a looming scarcity of land necessary to secure the production of agricultural commodities and experiencing competition from other land uses [...]
Using Fuzzy Logic to Analyze the Spatial Distribution of Pottery in Unstratified Archaeological Sites: The Case of the Pobedim Hillfort (Slovakia)
Authors: Tirpáková Anna , Vojteková Jana , Vojtek Matej , Vlkolinská Ivona
Published: January 2021

The aim of this article is to analyze the spatial clustering of pottery finds based on their occurrence at different depths in the Pobedim hillfort archaeological site (Western Slovakia), without reference to stratigraphic data. Two fuzzy sets methods (fuzzy linear function and fuzzy gamma operator) were used to analyze the distribution of Slavic pottery from the 9th century AD at six sectors (I–VI) located at the acropolis of the Pobedim hillfort in terms of their occurrence at different depths, their quantity at different depths, and the number of excavation pits. Using the mentioned fuzzy set methods, significant clusters of pottery were found in two sectors of the Pobedim site (sectors I and II). The results were compared with those obtained in previous research at this site, where the method of spatial autocorrelation was used. It was found that the most significant squares identified with the use of fuzzy set theory coincide with 14 squares where autocorrelation also found significant concentrations of pottery. However, the most significant squares identified by fuzzy methods (in the range 0.7–1) in all sectors of the Pobedim hillfort were 16% less than those identified by the positive spatial autocorrelation.