bluuebunny/crossref_metadata_2025 huggingface dataset:
A Qualitative Investigation of the Acceptability and Feasibility of a Urinary Tract Infection Patient Information Leaflet for Older Adults and Their Carers
Authors: Jones Leah F. , Williamson Heidi , Downing Petronella , Lecky Donna M. , Harcourt Diana , McNulty Cliodna
Published: January 2021

Urinary tract infections (UTIs) can be life threatening in older adults. The aim of this study was to primarily understand the acceptability and feasibility of using a UTI leaflet for older adults in care homes and the community. Qualitative interviews and focus groups informed by the Theoretical Domains Framework were conducted in 2019 with 93 participants from two English areas where a UTI leaflet for older adults had been introduced to improve self-care advice. Discussions were conducted with care staff (carers and nurses), older adults, general practice staff (GPs, nurses and health care assistants), and other relevant stakeholders and covered experiences of using the leaflet; its implementation; and barriers and facilitators to use. Participants deemed the leaflet an acceptable tool. Clinicians and care staff believed that having information in writing would reinforce their messages to older adults. Care staff reported that some older adults may find the information overwhelming. Where implemented, care staff used the leaflet as an educational guide. Clinicians requested the leaflet in electronic and paper formats to suit preferences. Implementation barriers included lack of awareness of the leaflet, lack of staffing and resource, and weak working relationships between care homes and general practices. It is recommended that regional strategies must include plans for dissemination to care homes, training, promotion and easy access to the leaflet. Improvements to the leaflet consisted of inclusion of antibiotic course length, D-mannose, atrophic vaginitis and replacement of less alarmist terminology such as ‘life threatening’.
Melatonin as an Antitumor Agent against Liver Cancer: An Updated Systematic Review
Authors: Fernández-Palanca Paula , Méndez-Blanco Carolina , Fondevila Flavia , Tuñón María J. , Reiter Russel J. , Mauriz José L. , González-Gallego Javier
Published: January 2021

Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine with antioxidant, chronobiotic and anti-inflammatory properties; reduced levels of this hormone are associated with higher risk of cancer. Several beneficial effects of melatonin have been described in a broad number of tumors, including liver cancers. In this work we systematically reviewed the publications of the last 15 years that assessed the underlying mechanisms of melatonin activities against liver cancers, and its role as coadjuvant in the treatment of these tumors. Literature research was performed employing PubMed, Scopus and Web of Science (WOS) databases and, after screening, 51 articles were included. Results from the selected studies denoted the useful actions of melatonin in preventing carcinogenesis and as a promising treatment option for the primary liver tumors hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), either alone or in combination with other compounds. Different processes were modulated by the indole, such as inhibition of oxidative stress, proliferation, angiogenesis and invasion, promotion of immune system response, cell cycle arrest and apoptosis, as well as recovery of circadian rhythms and autophagy modulation. Taken together, the present systematic review highlights the evidence that document the potential role of melatonin in improving the landscape of liver tumor treatment.
Acoustic and Flow Aspects of Synthetic Jet Actuators with Chevron Orifices
Authors: Smyk Emil , Markowicz Marek
Published: January 2021

The use of a chevron nozzle/orifice is one of the methods of heat transfer enhancement and noise reduction. In the case of synthetic jets, the number of papers on this topic is small. Therefore, a synthetic jet actuator with three different chevron orifices and one circular orifice is investigated. The aim of this study is to find the impact of orifice shape on centerline velocity (measured with a hot-wire anemometer) and determine if the chevron orifice reduces the generated noise. The sound pressure level was strongly dependent on the input actuator’s power, and only one chevron orifice ensured noise reduction for low power (p = 6; 8 W). At real power p = 12 W, the sound pressure level was lower for each chevron orifice actuator than in the case of the circular orifice actuator. It is shown that the application of a chevron nozzle does not have to provide noise reduction. It is important in the case of the design of new actuators that are to operate in places where noise levels should be limited (e.g., offices).
Maintainability Approach: Hydraulic Pump with External Gears Explored with Design for Disassembly and Augmented Reality
Authors: Ritucci Angelica Lucia , Frizziero Leonardo , Liverani Alfredo
Published: January 2021

The work carried out has the purpose of improving and optimizing various industrial technical operations, such as preventive maintenance, taken here as an example of application, using the Design for Disassembly (DfD) technique. Therefore, through four metaheuristic methods that have been chosen among the most widespread in the field (described below) to make a comparison between them, the optimal disassembly sequence is sought, if it exists, in terms of time and then costs in order to extract a target component without damaging the other mechanical parts of the assembly. The hypothesis that has been tested throughout this case study is “a responsible application of DfD, not only from the design process of a product but also during the disassembly procedure, can bring substantial benefits to the company”. Interaction with a hypothetical operator in charge of the work to be performed is implemented with the use of augmented reality. In fact, through an application programmed for an Android device (in this case, a mobile phone, hence a handheld device), the operator can be instructed step-by-step on the disassembly sequence in dynamics as an animation. Finally, two virtual buttons were added in augmented reality with which the operator can start and pause/resume the animation at any time to facilitate the understanding of the different steps established by the sequence.
Design and Applications of GLANCE: GLanceable Alarm Notification for a User Centered Experience
Authors: Tarantino Laura , Angelucci Daniela , Bonomo Alessandra , Cardinali Annalisa , Di Paolo Stefania
Published: January 2021

The trade-off between awareness and interruption is a crucial aspect in network fault notifiers: Low severity alarms should not distract operators from other primary tasks, however it might be crucial that operators promptly react to critical notifications. A notification system should hence determine when a particular interruption is appropriate and how it should be presented. In this direction, this paper presents a multistep design path beginning from the objective of designing a proof-of-concept for a glanceable alarm notification component for telecommunication network management systems based on a peripheral display approach. In particular the goal was a notifier guided by severity-based strategies and offering the information expressiveness of a one-notification-at-the-time perspective while enriching it with overview capabilities to guarantee (possibly subliminal) long-term local and global content comprehension and prompt reaction only when the interruption from the foreground task is dictated by the fault severity. A first design macro-phase led to the simple yet effective GLANCE (GLanceable Alarm Notification for a User Centered Experience) model, based on a visual coding technique oriented to comprehension and reaction, and a transition strategy oriented to interruptions and reaction. A second design macro-phase studied the application of GLANCE to a personal customizable multichannel notification tool and to a service-oriented fault monitor for digital terrestrial television broadcasting networks.
Object-Wise Video Editing
Authors: Siddique Ashraf , Lee Seungkyu
Published: January 2021

Beyond time frame editing in video data, object level video editing is a challenging task; such as object removal in a video or viewpoint changes. These tasks involve dynamic object segmentation, novel view video synthesis and background inpainting. Background inpainting is a task of the reconstruction of unseen regions presented by object removal or viewpoint change. In this paper, we propose a video editing method including foreground object removal background inpainting and novel view video synthesis under challenging conditions such as complex visual pattern, occlusion, overlaid clutter and variation of depth in a moving camera. Our proposed method calculates a weighted confidence score on the basis of normalized difference between observed depth and predicted distance in 3D space. A set of potential points from epipolar lines from neighbor frames are collected, refined, and weighted to select a few number of highly qualified observations to fill the desired region of interest area in the current frame from video. Based on the background inpainting method, novel view video synthesis is conducted with arbitrary viewpoint. Our method is evaluated with both a public dataset and our own video clips and compared with multiple state of the art methods showing a superior performance.
A Local Search Maximum Likelihood Parameter Estimator of Chirp Signal
Authors: Ben Guangli , Zheng Xifeng , Wang Yongcheng , Zhang Ning , Zhang Xin
Published: January 2021

A local search Maximum Likelihood (ML) parameter estimator for mono-component chirp signal in low Signal-to-Noise Ratio (SNR) conditions is proposed in this paper. The approach combines a deep learning denoising method with a two-step parameter estimator. The denoiser utilizes residual learning assisted Denoising Convolutional Neural Network (DnCNN) to recover the structured signal component, which is used to denoise the original observations. Following the denoising step, we employ a coarse parameter estimator, which is based on the Time-Frequency (TF) distribution, to the denoised signal for approximate estimation of parameters. Then around the coarse results, we do a local search by using the ML technique to achieve fine estimation. Numerical results show that the proposed approach outperforms several methods in terms of parameter estimation accuracy and efficiency.
Geostatistical Analysis of the Spatial Correlation between Territorial Anthropization and Flooding Vulnerability: Application to the DANA Phenomenon in a Mediterranean Watershed
Authors: Garcia-Ayllon Salvador , Radke John
Published: January 2021

Climate change is making intense DANA (depresión aislada en niveles altos) type rains a more frequent phenomenon in Mediterranean basins. This trend, combined with the transformation of the territory derived from diffuse anthropization processes, has created an explosive cocktail for many coastal towns due to flooding events. To evaluate this problem and the impact of its main guiding parameters, a geostatistical analysis of the territory based on GIS indicators and an NDVI (Normalized Difference Vegetation Index) analysis is developed. The assessment of the validity of a proposed methodology is applied to the case study of the Campo de Cartagena watershed located around the Mar Menor, a Mediterranean coastal lagoon in Southeastern Spain. This area has suffered three catastrophic floods derived from the DANA phenomenon between 2016 and 2019. The results show that apart from the effects derived from climate change, the real issue that amplifies the damage caused by floods is the diffuse anthropization process in the area, which has caused the loss of the natural hydrographic network that traditionally existed in the basin.
Design and Development of Continuous Passive Motion (CPM) for Fingers and Wrist Grounded-Exoskeleton Rehabilitation System
Authors: Almusawi Husam , Husi Géza
Published: January 2021

Impairments of fingers, wrist, and hand forearm result in significant hand movement deficiencies and daily task performance. Most of the existing rehabilitation assistive robots mainly focus on either the wrist training or fingers, and they are limiting the natural motion; many mechanical parts associated with the patient’s arms, heavy and expensive. This paper presented the design and development of a new, cost-efficient Finger and wrist rehabilitation mechatronics system (FWRMS) suitable for either hand right or left. The proposed machine aimed to present a solution to guide individuals with severe difficulties in their everyday routines for people suffering from a stroke or other motor diseases by actuating seven joints motions and providing them repeatable Continuous Passive Motion (CPM). FWRMS approach uses a combination of; grounded-exoskeleton structure to provide the desired displacement to the hand’s four fingers flexion/extension (F/E) driven by an indirect feed drive mechanism by adopting a leading screw and nut transmission; and an end-effector structure to provide angular velocity to the wrist flexion/ extension (F/E), wrist radial/ulnar deviation (R/U), and forearm supination/pronation (S/P) driven by a rotational motion mechanism. We employed a single dual-sided actuator to power both mechanisms. Additionally, this article presents the implementation of a portable embedded controller. Moreover, this paper addressed preliminary experimental testing and evaluation process. The conducted test results of the FWRMS robot achieved the required design characteristics and executed the motion needed for the continuous passive motion rehabilitation and provide stable trajectories guidance by following the natural range of motion (ROM) and a functional workspace of the targeted joints comfortably for all trainable movements by FWRMS.
Review of Adaptive Shock Control Systems
Authors: Künnecke Sven Christian , Vasista Srinivas , Riemenschneider Johannes , Keimer Ralf , Kintscher Markus
Published: January 2021

Drag reduction plays a major role in future aircraft design in order to lower emissions in aviation. In transonic flight, the transonic shock induces wave drag and thus increases the overall aircraft drag and hence emissions. In the past decades, shock control has been investigated intensively from an aerodynamic point of view and has proven its efficacy in terms of reducing wave drag. Furthermore, a number of concepts for shock control bumps (SCBs) that can adapt their position and height have been introduced. The implementation of adaptive SCBs requires a trade-off between aerodynamic benefits, system complexity and overall robustness. The challenge is to find a system with low complexity which still generates sufficient aerodynamic improvement to attain an overall system benefit. The objectives of this paper are to summarize adaptive concepts for shock control, and to evaluate and compare them in terms of their advantages and challenges of their system integrity so as to offer a basis for robust comparisons. The investigated concepts include different actuation systems as conventional spoiler actuators, shape memory alloys (SMAs) or pressurized elements. Near-term applications are seen for spoiler actuator concepts while highest controllability is identified for concepts several with smaller actuators such as SMAs.
3D Kinematics and Decision Trees to Predict the Impact of a Physical Exercise Program on Knee Osteoarthritis Patients
Authors: Mezghani Marwa , Hagemeister Nicola , Ouakrim Youssef , Cagnin Alix , Fuentes Alexandre , Mezghani Neila
Published: January 2021

Measuring knee biomechanics provides valuable clinical information for defining patient-specific treatment options, including patient-oriented physical exercise programs. It can be done by a knee kinesiography test measuring the three-dimensional rotation angles (3D kinematics) during walking, thus providing objective knowledge about knee function in dynamic and weight-bearing conditions. The purpose of this study was to assess whether 3D kinematics can be efficiently used to predict the impact of a physical exercise program on the condition of knee osteoarthritis (OA) patients. The prediction was based on 3D knee kinematic data, namely flexion/extension, adduction/abduction and external/internal rotation angles collected during a treadmill walking session at baseline. These measurements are quantifiable information suitable to develop automatic and objective methods for personalized computer-aided treatment systems. The dataset included 221 patients who followed a personalized therapeutic physical exercise program for 6 months and were then assigned to one of two classes, Improved condition (I) and not-Improved condition (nI). A 10% improvement in pain was needed at the 6-month follow-up compared to baseline to be in the improved group. The developed model was able to predict I and nI with 84.4% accuracy for men and 75.5% for women using a decision tree classifier trained with 3D knee kinematic data taken at baseline and a 10-fold validation procedure. The models showed that men with an impaired control of their varus thrust and a higher pain level at baseline, and women with a greater amplitude of internal tibia rotation were more likely to report improvements in their pain level after 6 months of exercises. Results support the effectiveness of decision trees and the relevance of 3D kinematic data to objectively predict knee OA patients’ response to a treatment consisting of a physical exercise program.
Temporal Variability of Equivalent Black Carbon Components in Atmospheric Air in Southern Poland
Authors: Zioła Natalia , Błaszczak Barbara , Klejnowski Krzysztof
Published: January 2021

This study assesses the air quality in Zabrze (southern Poland) based on the ambient concentrations of equivalent black carbon (eBC). eBC measurement campaigns were carried out from April 2019 to March 2020 using a modern AE33 Aethalometer, accompanied by parallel measurements of gaseous pollutants, PM10 and meteorological parameters. The use of the two-component AE33 model allows for the determination of the eBC from fossil fuel combustion (eBCff) and biomass burning (eBCbb). The obtained results showed a clear seasonal variability of eBC concentrations, with higher average levels in the heating season (4.70 µg·m−3) compared to the non-heating one (1.79 µg·m−3). In both seasons, the eBCff component had a dominant share in total eBC, which indicates significant emissions from the combustion of fossil fuels for heating purposes and from local traffic sources. The obtained results showed high correlation coefficients with gaseous and particulate pollutants, with the strongest relationship for eBC and carbon monoxide (CO). During the non-heating and heating period, both anticyclone and cyclone systems played an important role in shaping eBC, eBCff and eBCbb concentrations. High concentrations of all components occurred with a significant decrease in air temperature and solar radiation in winter.
The Vascular Effects of Isolated Isoflavones—A Focus on the Determinants of Blood Pressure Regulation
Authors: Silva Henrique
Published: January 2021

Isoflavones are phytoestrogen compounds with important biological activities, including improvement of cardiovascular health. This activity is most evident in populations with a high isoflavone dietary intake, essentially from soybean-based products. The major isoflavones known to display the most important cardiovascular effects are genistein, daidzein, glycitein, formononetin, and biochanin A, although the closely related metabolite equol is also relevant. Most clinical studies have been focused on the impact of dietary intake or supplementation with mixtures of compounds, with only a few addressing the effect of isolated compounds. This paper reviews the main actions of isolated isoflavones on the vasculature, with particular focus given to their effect on the determinants of blood pressure regulation. Isoflavones exert vasorelaxation due to a multitude of pathways in different vascular beds. They can act in the endothelium to potentiate the release of NO and endothelium-derived hyperpolarization factors. In the vascular smooth muscle, isoflavones modulate calcium and potassium channels, leading to hyperpolarization and relaxation. Some of these effects are influenced by the binding of isoflavones to estrogen receptors and to the inhibition of specific kinase enzymes. The vasorelaxation effects of isoflavones are mostly obtained with plasma concentrations in the micromolar range, which are only attained through supplementation. This paper highlights isolated isoflavones as potentially suitable alternatives to soy-based foodstuffs and supplements and which could enlarge the current therapeutic arsenal. Nonetheless, more studies are needed to better establish their safety profile and elect the most useful applications.
Review of Venoms of Non-Polydnavirus Carrying Ichneumonoid Wasps
Authors: Quicke Donald L. J. , Butcher Buntika A.
Published: January 2021

Parasitoids are predominantly insects that develop as larvae on or inside their host, also usually another insect, ultimately killing it after various periods of parasitism when both parasitoid larva and host are alive. The very large wasp superfamily Ichneumonoidea is composed of parasitoids of other insects and comprises a minimum of 100,000 species. The superfamily is dominated by two similarly sized families, Braconidae and Ichneumonidae, which are collectively divided into approximately 80 subfamilies. Of these, six have been shown to release DNA-containing virus-like particles, encoded within the wasp genome, classified in the virus family Polydnaviridae. Polydnaviruses infect and have profound effects on host physiology in conjunction with various venom and ovarial secretions, and have attracted an immense amount of research interest. Physiological interactions between the remaining ichneumonoids and their hosts result from adult venom gland secretions and in some cases, ovarian or larval secretions. Here we review the literature on the relatively few studies on the effects and chemistry of these ichneumonoid venoms and make suggestions for interesting future research areas. In particular, we highlight relatively or potentially easily culturable systems with features largely lacking in currently studied systems and whose study may lead to new insights into the roles of venom chemistry in host-parasitoid relationships as well as their evolution.
Plasticity-Related Activity in the Hippocampus, Anterior Cingulate, Orbitofrontal, and Prefrontal Cortex Following a Repeated Treatment with D2/D3 Agonist Quinpirole
Authors: Brozka Hana , Alexova Daniela , Radostova Dominika , Janikova Martina , Krajcovic Branislav , Kubík Štěpán , Svoboda Jan , Stuchlik Ales
Published: January 2021

Quinpirole (QNP) sensitization is a well-established model of stereotypical checking relevant to obsessive-compulsive disorder. Previously, we found that QNP-treated rats display deficits in hippocampus-dependent tasks. The present study explores the expression of immediate early genes (IEG) during QNP-induced stereotypical checking in the hippocampus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and medial prefrontal cortex (mPFC). Adult male rats were injected with QNP (0.5 mg/mL/kg; n = 15) or saline (n = 14) daily for 10 days and exposed to an arena enriched with two objects. Visits to the objects and the corners of the arena were recorded. QNP-treated rats developed an idiosyncratic pattern of visits that persisted across experimental days. On day 11, rats were exposed to the arena twice for 5 min and sacrificed. The expression of IEGs Arc and Homer1a was determined using cellular compartment analysis of temporal activity by fluorescence in situ hybridization. IEG-positive nuclei were counted in the CA1 area of the hippocampus, ACC, OFC, and mPFC. We found significantly fewer IEG-positive nuclei in the CA1 in QNP-treated rats compared to controls. The overlap between IEG expressing neurons was comparable between the groups. We did not observe significant differences in IEG expression between QNP treated and control rats in ACC, OFC, and mPFC. In conclusion, treatment of rats with quinpirole decreases plasticity-related activity in the hippocampus during stereotypical checking.
Non-Canonical Functions of the ARF Tumor Suppressor in Development and Tumorigenesis
Authors: Lagopati Nefeli , Belogiannis Konstantinos , Angelopoulou Andriani , Papaspyropoulos Angelos , Gorgoulis Vassilis
Published: January 2021

P14ARF (ARF; Alternative Reading Frame) is an extensively characterized tumor suppressor which, in response to oncogenic stimuli, mediates cell cycle arrest and apoptosis via p53-dependent and independent routes. ARF has been shown to be frequently lost through CpG island promoter methylation in a wide spectrum of human malignancies, such as colorectal, prostate, breast, and gastric cancers, while point mutations and deletions in the p14ARF locus have been linked with various forms of melanomas and glioblastomas. Although ARF has been mostly studied in the context of tumorigenesis, it has been also implicated in purely developmental processes, such as spermatogenesis, and mammary gland and ocular development, while it has been additionally involved in the regulation of angiogenesis. Moreover, ARF has been found to hold important roles in stem cell self-renewal and differentiation. As is often the case with tumor suppressors, ARF functions as a pleiotropic protein regulating a number of different mechanisms at the crossroad of development and tumorigenesis. Here, we provide an overview of the non-canonical functions of ARF in cancer and developmental biology, by dissecting the crosstalk of ARF signaling with key oncogenic and developmental pathways.
Strawberry-Derived Exosome-Like Nanoparticles Prevent Oxidative Stress in Human Mesenchymal Stromal Cells
Authors: Perut Francesca , Roncuzzi Laura , Avnet Sofia , Massa Annamaria , Zini Nicoletta , Sabbadini Silvia , Giampieri Francesca , Mezzetti Bruno , Baldini Nicola
Published: January 2021

Plant-derived exosome-like nanovesicles (EPDENs) have recently been isolated and evaluated as potential bioactive nutraceutical biomolecules. It has been hypothesized that EPDENs may exert their activity on mammalian cells through their specific cargo. In this study, we isolated and purified EPDENs from the strawberry juice of Fragaria x ananassa (cv. Romina), a new cultivar characterized by a high content of anthocyanins, folic acid, flavonols, and vitamin C and an elevated antioxidant capacity. Fragaria-derived EPDENs were purified by a series of centrifugation and filtration steps. EPDENs showed size and morphology similar to mammalian extracellular nanovesicles. The internalization of Fragaria-derived EPDENs by human mesenchymal stromal cells (MSCs) did not negatively affect their viability, and the pretreatment of MSCs with Fragaria-derived EPDENs prevented oxidative stress in a dose-dependent manner. This is possibly due to the presence of vitamin C inside the nanovesicle membrane. The analysis of EPDEN cargo also revealed the presence of small RNAs and miRNAs. These findings suggest that Fragaria-derived EPDENs may be considered nanoshuttles contained in food, with potential health-promoting activity.
Kartogenin Enhances Chondrogenic Differentiation of MSCs in 3D Tri-Copolymer Scaffolds and the Self-Designed Bioreactor System
Authors: Chen Ching-Yun , Li Chunching , Ke Cherng-Jyh , Sun Jui-Sheng , Lin Feng-Huei
Published: January 2021

Human cartilage has relatively slow metabolism compared to other normal tissues. Cartilage damage is of great clinical consequence since cartilage has limited intrinsic healing potential. Cartilage tissue engineering is a rapidly emerging field that holds great promise for tissue function repair and artificial/engineered tissue substitutes. However, current clinical therapies for cartilage repair are less than satisfactory and rarely recover full function or return the diseased tissue to its native healthy state. Kartogenin (KGN), a small molecule, can promote chondrocyte differentiation both in vitro and in vivo. The purpose of this research is to optimize the chondrogenic process in mesenchymal stem cell (MSC)-based chondrogenic constructs with KGN for potential use in cartilage tissue engineering. In this study, we demonstrate that KGN treatment can promote MSC condensation and cell cluster formation within a tri-copolymer scaffold. Expression of Acan, Sox9, and Col2a1 was significantly up-regulated in three-dimensional (3D) culture conditions. The lacuna-like structure showed active deposition of type II collagen and aggrecan deposition. We expect these results will open new avenues for the use of small molecules in chondrogenic differentiation protocols in combination with scaffolds, which may yield better strategies for cartilage tissue engineering.
Immune Monitoring upon Treatment with Biologics in Sjögren’s Syndrome: The What, Where, When, and How
Authors: van Beers Joyce J.B.C. , Damoiseaux Jan G.M.C.
Published: January 2021

Over the years, a wide variety of therapeutic antibodies has been successfully introduced in the auto-immunology clinic, and many more are on the way. Many of these treatments address either a pathogenic circulating molecule or a cell-bound molecule. Whereas addressing the former target results in neutralization of the soluble factor and binding to the latter target either inhibits cellular function or induces selective cell death. If this targeted molecule or cell is part of the immune system, this therapy evokes a state of immunodeficiency with infections as a possible consequence. Therefore, immune monitoring is needed to prevent such adverse side effects of immunotherapy. In this paper, different immunotherapies used in Sjögren’s syndrome, as well as different approaches to monitoring the immune system, are discussed.
Zebra-Fishing for Regenerative Awakening in Mammals
Authors: Massoz Laura , Dupont Marie Alice , Manfroid Isabelle
Published: January 2021

Regeneration is defined as the ability to regrow an organ or a tissue destroyed by degeneration or injury. Many human degenerative diseases and pathologies, currently incurable, could be cured if functional tissues or cells could be restored. Unfortunately, humans and more generally mammals have limited regenerative capabilities, capacities that are even further declining with age, contrary to simpler organisms. Initially thought to be lost during evolution, several studies have revealed that regenerative mechanisms are still present in mammals but are latent and thus they could be stimulated. To do so there is a pressing need to identify the fundamental mechanisms of regeneration in species able to efficiently regenerate. Thanks to its ability to regenerate most of its organs and tissues, the zebrafish has become a powerful model organism in regenerative biology and has recently engendered a number of studies attesting the validity of awakening the regenerative potential in mammals. In this review we highlight studies, particularly in the liver, pancreas, retina, heart, brain and spinal cord, which have identified conserved regenerative molecular events that proved to be beneficial to restore murine and even human cells and which helped clarify the real clinical translation potential of zebrafish research to mammals.
Current Limitations and Recent Progress in Nanomedicine for Clinically Available Photodynamic Therapy
Authors: Park Jooho , Lee Yong-Kyu , Park In-Kyu , Hwang Seung Rim
Published: January 2021

Photodynamic therapy (PDT) using oxygen, light, and photosensitizers has been receiving great attention, because it has potential for making up for the weakness of the existing therapies such as surgery, radiation therapy, and chemotherapy. It has been mainly used to treat cancer, and clinical tests for second-generation photosensitizers with improved physicochemical properties, pharmacokinetic profiles, or singlet oxygen quantum yield have been conducted. Progress is also being made in cancer theranostics by using fluorescent signals generated by photosensitizers. In order to obtain the effective cytotoxic effects on the target cells and prevent off-target side effects, photosensitizers need to be localized to the target tissue. The use of nanocarriers combined with photosensitizers can enhance accumulation of photosensitizers in the tumor site, owing to preferential extravasation of nanoparticles into the tumor vasculature by the enhanced permeability and retention effect. Self-assembly of amphiphilic polymers provide good loading efficiency and sustained release of hydrophobic photosensitizers. In addition, prodrug nanomedicines for PDT can be activated by stimuli in the tumor site. In this review, we introduce current limitations and recent progress in nanomedicine for PDT and discuss the expected future direction of research.
Identifying Diurnal Variability of Brain Connectivity Patterns Using Graph Theory
Authors: V. Farahani Farzad , Fafrowicz Magdalena , Karwowski Waldemar , Bohaterewicz Bartosz , Sobczak Anna Maria , Ceglarek Anna , Zyrkowska Aleksandra , Ostrogorska Monika , Sikora-Wachowicz Barbara , Lewandowska Koryna , Oginska Halszka , Beres Anna , Hubalewska-Mazgaj Magdalena , Marek Tadeusz
Published: January 2021

Significant differences exist in human brain functions affected by time of day and by people’s diurnal preferences (chronotypes) that are rarely considered in brain studies. In the current study, using network neuroscience and resting-state functional MRI (rs-fMRI) data, we examined the effect of both time of day and the individual’s chronotype on whole-brain network organization. In this regard, 62 participants (39 women; mean age: 23.97 ± 3.26 years; half morning- versus half evening-type) were scanned about 1 and 10 h after wake-up time for morning and evening sessions, respectively. We found evidence for a time-of-day effect on connectivity profiles but not for the effect of chronotype. Compared with the morning session, we found relatively higher small-worldness (an index that represents more efficient network organization) in the evening session, which suggests the dominance of sleep inertia over the circadian and homeostatic processes in the first hours after waking. Furthermore, local graph measures were changed, predominantly across the left hemisphere, in areas such as the precentral gyrus, putamen, inferior frontal gyrus (orbital part), inferior temporal gyrus, as well as the bilateral cerebellum. These findings show the variability of the functional neural network architecture during the day and improve our understanding of the role of time of day in resting-state functional networks.
Investigating the Impact of Actual and Modeled Occupant Behavior Information Input to Building Performance Simulation
Authors: Jia Mengda , Srinivasan Ravi , Ries Robert , Bharathy Gnana , Weyer Nathan
Published: January 2021

Occupant behaviors are one of the most dominant factors that influence building energy use. Understanding the influences from building occupants can promote the development of energy–efficient buildings. This paper quantifies the impact of different occupant behavior information on building energy model (BEM) from multiple perspectives. For this purpose, an occupant behavior model that uses agent–based modeling (ABM) approach is implemented via co-simulation with a BEM of an existing commercial building. Then, actual occupant behavior data in correspondence to ABM output, including operations on window, door, and blinds in selected thermal zones of the building are recorded using survey logs. A simulation experiment is conducted by creating three BEMs with constant, actual, and modeled occupant behavioral inputs. The analysis of the simulation results among these scenarios helps us gain an in–depth understanding of how occupant behaviors influence building performance. This study aims to facilitate robust building design and operation with human–in–the–loop system optimization.
Haploinsufficiency Interactions of RALBP1 and TP53 in Carcinogenesis
Authors: Awasthi Sanjay
Published: January 2021

Mutagenic environmental chemical or radiant stresses directly damage DNA and amplify the formation of potent endogenous mutagens from lipid peroxidation, leading to cancers that cause millions of deaths and impose enormous financial and social burdens [...]
Gain/Amplification of Chromosome Arm 1q21 in Multiple Myeloma
Authors: Hanamura Ichiro
Published: January 2021

Multiple myeloma (MM), a plasma cell neoplasm, is an incurable hematological malignancy characterized by complex genetic and prognostic heterogeneity. Gain or amplification of chromosome arm 1q21 (1q21+) is the most frequent adverse chromosomal aberration in MM, occurring in 40% of patients at diagnosis. It occurs in a subclone of the tumor as a secondary genomic event and is more amplified as the tumor progresses and a risk factor for the progression from smoldering multiple myeloma to MM. It can be divided into either 1q21 gain (3 copies) or 1q21 amplification (≥4 copies), and it has been suggested that the prognosis is worse in cases of amplification than gain. Trisomy of chromosome 1, jumping whole-arm translocations of chromosome1q, and tandem duplications lead to 1q21+ suggesting that its occurrence is not consistent at the genomic level. Many studies have reported that genes associated with the malignant phenotype of MM are situated on the 1q21 amplicon, including CKS1B, PSMD4, MCL1, ANP32E, and others. In this paper, we review the current knowledge regarding the clinical features, prognostic implications, and the speculated pathology of 1q21+ in MM, which can provide clues for an effective treatment approach to MM patients with 1q21+.
Biomarkers for Precision Urothelial Carcinoma Diagnosis: Current Approaches and the Application of Single-Cell Technologies
Authors: Hong Michelle , He George , Goh Siting , Low Alvin Wei Xiang , Tay Kae Jack , Lim Tony Kiat Hon , Yeong Joe , Khor Li Yan , Lim Tong Seng
Published: January 2021

Urothelial carcinoma (UC) is the most frequent malignancy of the urinary system and is ranked the sixth most diagnosed cancer in men worldwide. Around 70–75% of newly diagnosed UC manifests as the non-muscle invasive bladder cancer (NMIBC) subtype, which can be treated by a transurethral resection of the tumor. However, patients require life-long monitoring due to its high rate of recurrence. The current gold standard for UC diagnosis, prognosis, and disease surveillance relies on a combination of cytology and cystoscopy, which is invasive, costly, and associated with comorbidities. Hence, there is considerable interest in the development of highly specific and sensitive urinary biomarkers for the non-invasive early detection of UC. In this review, we assess the performance of current diagnostic assays for UC and highlight some of the most promising biomarkers investigated to date. We also highlight some of the recent advances in single-cell technologies that may offer a paradigm shift in the field of UC biomarker discovery and precision diagnostics.
‘Educated’ Osteoblasts Reduce Osteoclastogenesis in a Bone-Tumor Mimetic Microenvironment
Authors: Kolb Alexus D. , Dai Jinlu , Keller Evan T. , Bussard Karen M.
Published: January 2021

Breast cancer (BC) metastases to bone disrupt the balance between osteoblasts and osteoclasts, leading to excessive bone resorption. We identified a novel subpopulation of osteoblasts with tumor-inhibitory properties, called educated osteoblasts (EOs). Here we sought to examine the effect of EOs on osteoclastogenesis during tumor progression. We hypothesized that EOs affect osteoclast development in the bone-tumor niche, leading to suppressed pre-osteoclast fusion and bone resorption. Conditioned media (CM) was analyzed for protein expression of osteoclast factors receptor activator of nuclear factor kappa-β ligand (RANKL), osteoprotegerin (OPG), and tumor necrosis factor alpha (TNFα) via ELISA. EOs were co-cultured with pre-osteoclasts on a bone mimetic matrix to assess osteoclast resorption. Pre-osteoclasts were tri-cultured with EOs plus metastatic BC cells and assessed for tartrate-resistance acid phosphatase (TRAP)-positive, multinucleated (≥3 nuclei), mature osteoclasts. Tumor-bearing murine tibias were stained for TRAP to determine osteoclast number in-vivo. EO CM expressed reduced amounts of soluble TNFα and OPG compared to naïve osteoblast CM. Osteoclasts formed in the presence of EOs were smaller and less in number. Upon co-culture on a mimetic bone matrix, a 50% reduction in the number of TRAP-positive osteoclasts formed in the presence of EOs was observed. The tibia of mice inoculated with BC cells had less osteoclasts per bone surface in bones with increased numbers of EO cells. These data suggest EOs reduce osteoclastogenesis and bone resorption. The data imply EOs provide a protective effect against bone resorption in bone metastatic BC.
Sex Differences in Overall Survival and the Effect of Radiotherapy in Merkel Cell Carcinoma—A Retrospective Analysis of A Swedish Cohort
Authors: Björn Andtback Hannah , Björnhagen-Säfwenberg Viveca , Shi Hao , Lui Weng-Onn , Masucci Giuseppe V. , Villabona Lisa
Published: January 2021

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer where Merkel cell Polyomavirus (MCPyV) contributes to the pathogenesis. In an adjuvant setting, radiotherapy (RT) is believed to give a survival benefit. The prognostic impact of sex related to MCPyV-status and adjuvant RT were analyzed in patients referred to Karolinska University Hospital. Data were collected from 113 patients’ hospital records and MCPyV analyses were made in 54 patients (48%). We found a significantly better overall survival (OS) for women compared to men and a significant difference in OS in patients receiving adjuvant RT. Furthermore, we found that men with virus negative MCC have an increased risk for earlier death (HR 3.6). This indicates that MCPyV positive and negative MCC act as two different diseases, and it might be due to different mechanism in the immune response between male and female patients. This could have significance in tailoring treatment and follow-up in MCC patients in the future.
Prevalence and Predictive Factors for Upfront Dose Reduction of the First Cycle of First-Line Chemotherapy in Older Adults with Metastatic Solid Cancer: Korean Cancer Study Group (KCSG) Multicenter Study
Authors: Hwang In Gyu , Kwon Minsuk , Kim Jin Won , Kim Se Hyun , Lee Yun-Gyoo , Kim Jin Young , Koh Su-Jin , Ko Yoon Ho , Shin Seong Hoon , Hong Soojung , Kim Tae-Yong , Kim Sun Young , Kim Hyun Jung , Kim Hyo Jung , Lee Myung Ah , Kwon Jung Hye , Hong Yong Sang , Lee Kyung Hee , Bae Sung Hwa , Koo Dong-Hoe , Kim Jee Hyun , Woo In Sook
Published: January 2021

Old age alone does not reflect an intolerability to chemotherapy. However, upfront dose reduction (UDR) of the first cycle of first-line palliative chemotherapy has sometimes been chosen by physicians for older adults with metastatic cancer due to concerns regarding adverse events. The development of predictive factors for UDR of palliative chemotherapy would be helpful for treatment planning among older adults. This was a secondary analysis of a study on predicting adverse events of first-line palliative chemotherapy in 296 patients (≥70 years) with solid cancer. We assessed the prevalence of UDR of the first cycle of first-line chemotherapy and the association of UDR with the variables of geriatric assessment (GA) and chemotherapy compliance. Among the 296 patients, 177 (59.8%) patients were treated with UDR. The mean percentage of UDR for the total patient group was 19.2% (range: 4–47%) of the standard dose. In a multivariate analysis, poor performance status (PS) and living without a spouse were independent predictive factors of UDR of first-line palliative chemotherapy in older adults. Patients with UDR showed fewer grade 3–5 adverse events versus the standard dose group. Study completion as planned was significantly higher in the UDR group versus the standard dose group. Older adults with UDR better tolerated chemotherapy than patients with a standard dose.
Identification of Cathepsin D as a Plasma Biomarker for Alzheimer’s Disease
Authors: Kim Jae-Whan , Jung Soon-Young , Kim Youngbin , Heo Hansol , Hong Chang-Hyung , Seo Sang-Won , Choi Seong-Hye , Son Sang-Joon , Lee Seongju , Chang Jaerak
Published: January 2021

Although Alzheimer’s disease (AD) is the most common neurodegenerative disease, there are still no drugs available to treat or prevent AD effectively. Here, we examined changes in levels of selected proteins implicated in the pathogenesis of AD using plasma samples of control subjects and patients with cognition impairment. To precisely categorize the disease, fifty-six participants were examined with clinical cognitive tests, amyloid positron emission tomography (PET) scan, and white matter hyperintensities scored by magnetic resonance imaging. Plasma cathepsin D levels of the subjects were examined by immunoblotting and enzyme-linked immunosorbent assay (ELISA). Correlation of plasma cathepsin D levels with AD-related factors and clinical characteristics were examined by statistical analysis. By analyzing quantitative immunoblot and ELISA, we found that the plasma level of cathepsin D, a major lysosomal protease, was decreased in the group with amyloid plaque deposition at the brain compared to the control group. The level of plasma cathepsin D was negatively correlated with clinical dementia rating scale sum of boxes (CDR-SB) scores. In addition, our integrated multivariable logistic regression model suggests the high performance of plasma cathepsin D level for discriminating AD from non-AD. These results suggest that the plasma cathepsin D level could be developed as a diagnostic biomarker candidate for AD.
The Predictive Value of miR-16, -29a and -134 for Early Identification of Gestational Diabetes: A Nested Analysis of the DALI Cohort
Authors: Sørensen Anja , van Poppel Mireille , Desoye Gernot , Damm Peter , Simmons David , Jensen Dorte , Dalgaard Louise ,   The DALI Core Investigator Group
Published: January 2021

Early identification of gestational diabetes mellitus (GDM) aims to reduce the risk of adverse maternal and perinatal outcomes. Currently, no circulating biomarker has proven clinically useful for accurate prediction of GDM. In this study, we tested if a panel of small non-coding circulating RNAs could improve early prediction of GDM. We performed a nested case-control study of participants from the European multicenter ‘Vitamin D and lifestyle intervention for GDM prevention (DALI)’ trial using serum samples from obese pregnant women (BMI ≥ 29 kg/m2) entailing 82 GDM cases (early- and late- GDM), and 41 age- and BMI-matched women with normal glucose tolerance (NGT) throughout pregnancy (controls). Anthropometric, clinical and biochemical characteristics were obtained at baseline (<20 weeks of gestation) and throughout gestation. Baseline serum microRNAs (miRNAs) were measured using quantitative real time PCR (qPCR). Elevated miR-16-5p, -29a-3p, and -134-5p levels were observed in women, who were NGT at baseline and later developed GDM, compared with controls who remained NGT. A combination of the three miRNAs could distinguish later GDM from NGT cases (AUC 0.717, p = 0.001, compared with fasting plasma glucose (AUC 0.687, p = 0.004)) as evaluated by area under the curves (AUCs) using Receiver Operator Characteristics (ROC) analysis. Elevated levels of individual miRNAs or a combination hereof were associated with higher odds ratios of GDM. Conclusively, circulating miRNAs early in pregnancy could serve as valuable predictive biomarkers of GDM.