bluuebunny/crossref_metadata_2025 huggingface dataset:
How Do Women Managers Avoid Paying Bribes?
Authors: Clarke George R. G.
Published: February 2021

Previous studies have found that firms where women have greater influence are less likely to pay bribes than other firms. In this study, we ask how these firms avoid paying bribes. Using data from the World Bank’s Enterprise Surveys, we find that firms run by women avoid meeting and interacting with government officials when they can. Female-managed firms, for example, are less likely to apply for construction and import licenses, less likely to meet with tax officials, and less likely to bid for government contracts than male-managed firms. However, female-managed firms are no less likely to say that officials sought bribes when they met with them than male-managed firms. This suggests the main way that firms with women in positions of power avoid paying bribes is by avoiding situations where officials might seek them.
An Experimental Study on D2D Route Selection Mechanism in 5G Scenarios
Authors: Chamran Mohammad Kazem , Yau Kok-Lim Alvin , Noor Rafidah Md. , Wu Celimuge
Published: February 2021

This paper demonstrates a route selection mechanism on a testbed with heterogeneous device-to-device (D2D) wireless communication for a 5G network scenario. The source node receives information about the primary users’ (PUs’) (or licensed users’) activities and available routes from the macrocell base station (or a central controller) and makes a decision to select a multihop route to the destination node. The source node from small cells can either choose: (a) a route with direct communication with the macrocell base station to improve the route performance; or (b) a route with D2D communication among nodes in the small cells to offload traffic from the macrocell to improve spectrum efficiency. The selected D2D route has the least PUs’ activities. The route selection mechanism is investigated on our testbed that helps to improve the accuracy of network performance measurement. In traditional testbeds, each node (e.g., Universal Software Radio Peripheral (USRP) that serves as the front-end communication block) is connected to a single processing unit (e.g., a personal computer) via a switch using cables. In our testbed, each USRP node is connected to a separate processing unit, i.e., raspberry Pi3 B+ (or RP3), which offers three main advantages: (a) control messages and data packets are exchanged via the wireless medium; (b) separate processing units make decisions in a distributed and heterogeneous manner; and (c) the nodes are placed further apart from one another. Therefore, in the investigation of our route selection scheme, the response delay of control message exchange and the packet loss caused by the operating environment (e.g., ambient noise) are implied in our end-to-end delay and packet delivery ratio measurement. Our results show an increase of end-to-end delay and a decrease of packet delivery ratio due to the transmission of control messages and data packets in the wireless medium in the presence of the dynamic PUs’ activities. Furthermore, D2D communication can offload 25% to 75% traffic from macrocell base station to small cells.
Suppressing Voltage Spikes of MOSFET in H-Bridge Inverter Circuit
Authors: Aboadla Ezzidin Hassan , Khan Sheroz , Abdul Kadir Kushsairy , Md Yusof Zulkhairi , Habaebi Mohamed Hadi , Habib Shabana , Islam Muhammad , Hasan Mohammad Kamrul , Hossain Eklas
Published: February 2021

Power electronics devices are made from semiconductor switches such as thyristors, MOSFETs, and diodes, along with passive elements of inductors, capacitors, and resistors, and integrated circuits. They are heavily used in power processing for applications in computing, communication, medical electronics, appliance control, and as converters in high power DC and AC transmission in what is now called harmonized AC/DC networks. A converter’s operation is described as a periodic sequencing of different modes of operation corresponding to different topologies interfaced to filters made of passive elements. The performance of converters has improved considerably using high switching frequency, which leads to a significant improvement in a power converter’s performance. However, the high dv/dt through a fast-switching transient of the MOSFET is associated with parasitic components generating oscillations and voltage spikes having adverse effects on the operation of complementary switches, thereby affecting the safe operation of the power devices. In this paper, the MOSFET gate-driver circuit performance is improved to suppress the H-Bridge inverter’s voltage spikes. The proposed technique is a simple improvement to the gate driver based on the IR2112 driver (IC) by adding a capacitor to attenuate the effect of parasitic components and the freewheeling current, suppressing the negative voltage spikes. This paper’s main contribution is to improve the gate driver circuit’s capability for suppressing the voltage spikes in the H-Bridge inverter. The improved gate driver circuit is validated experimentally and is compared with the conventional gate driver. The experimental results show that the proposed technique can effectively suppress the MOSFET’s voltage spikes and oscillations.
Fusion Chain: A Decentralized Lightweight Blockchain for IoT Security and Privacy
Authors: Na Dongjun , Park Sejin
Published: February 2021

As the use of internet of things (IoT) devices increases, the importance of security has increased, because personal and private data such as biometrics, images, photos, and voices can be collected. However, there is a possibility of data leakage or manipulation by monopolizing the authority of the data, since such data are stored in a central server by the centralized structure of IoT devices. Furthermore, such a structure has a potential security problem, caused by an attack on the server due to single point vulnerability. Blockchain’s, through their decentralized structure, effectively solve the single point vulnerability, and their consensus algorithm allows network participants to verify data without any monopolizing. Therefore, blockchain technology becomes an effective solution for solving the security problem of the IoT’s centralized method. However, current blockchain technology is not suitable for IoT devices. Blockchain technology requires large storage space for the endless append-only block storing, and high CPU processing power for performing consensus algorithms, while its opened block access policy exposes private data to the public. In this paper, we propose a decentralized lightweight blockchain, named Fusion Chain, to support IoT devices. First, it solves the storage size issue of the blockchain by using the interplanetary file system (IPFS). Second, it does not require high computational power by using the practical Byzantine fault tolerance (PBFT) consensus algorithm. Third, data privacy is ensured by allowing only authorized users to access data through public key encryption using PKI. Fusion Chain was implemented from scratch written using Node.js and golang. The results show that the proposed Fusion Chain is suitable for IoT devices. According to our experiments, the size of the blockchain dramatically decreased, and only 6% of CPU on an ARM core, and 49 MB of memory, is used on average for the consensus process. It also effectively protects privacy data by using a public key infrastructure (PKI).
Voltage Control Strategy for Energy Storage System in Sustainable Distribution System Operation
Authors: Zhang Yue , Srivastava Anurag
Published: February 2021

Due to the increasing penetration of distributed energy resources (DERs) required for the sustainable distribution system, new voltage control strategy is needed by utilities. Traditional voltage control strategy can not support the increasing number of DERs in a coordinated and scalable manner to meet the operational voltage regulation requirement. Supported by the power electronics converter, the energy storage system can provide fast, smooth, and flexible voltage control services. In this paper, an effective and easy to implement sensitivity-based voltage control strategy is developed for the energy storage system. The developed control strategy is validated using an industrial feeder data in Northwest Washington. The proposed strategy can mitigate the voltage unbalance issue, improve the voltage profile, and correct power factors while supporting sustainable distribution system operation.
Problems of Innovative Development of Oil Companies: Actual State, Forecast and Directions for Overcoming the Prolonged Innovation Pause
Authors: Matkovskaya Yana , Vechkinzova Elena , Petrenko Yelena , Steblyakova Larissa
Published: February 2021

The study of the rates of innovative development of various sectors of the modern economy makes it possible to determine the existence of a scientific and practical problem, eliciting the need for urgent identification of the reasons for non-innovative development of Oil and Gas Companies and development of the directions for innovation development. Based on a number of methods, including methods of graphical analysis, time series forecasting, construction of linear trends, correlation analysis and scenario forecasting, the authors stated the fact of the serious depth of the problem of innovative insufficiency in the oil sector in comparison with other sectors and they built six scenarios for the development of these companies. The applied methods made it possible to not only come to the conclusion that with the current level of investment in R&D in the oil and gas sector, Oil Companies may find themselves in difficult conditions, especially if breakthrough technologies show themselves in the non-hydrocarbon energy of the future, but also made it possible to determine the most important directions for the development of Oil Companies, including the formation and development of the oil and gas industry 4.0, marketing strategic management of the activities of these companies.
Digital Communication Tools and Knowledge Creation Processes for Enriched Intellectual Outcome—Experience of Short-Term E-Learning Courses during Pandemic
Authors: Pokrovskaia Nadezhda N. , Leontyeva Veronika L. , Ababkova Marianna Yu. , Cappelli Lucio , D’Ascenzo Fabrizio
Published: February 2021

Social isolation during the pandemic contributed to the transition of educational processes to e-learning. A short-term e-marketing education program for a variety of students was introduced in May 2020 and is taught entirely online. A survey was conducted regularly in the last week of training using Google Forms, and three cohorts were surveyed in July, September, and December 2020. A high level of satisfaction indicates an interest in the content and a positive assessment of the level of comfort of an organization adapted to the needs of students; this positive result contrasted with the negative opinion of the remote learning in Russia since March 2020, and this surprising satisfaction of students has motivated the study to try to explain its reasons. This result was compared with the short-term course taught through the educational pedagogical platform of a university. The students of traditional short- and long-term university programs were asked to assess their satisfaction with different digital communication tools used for e-learning. They showed low satisfaction with the pedagogical platform and a positive reaction to the e-communication tools (messengers, social media, short surveys, video conferences, etc.). The qualitative responses helped to better understand the real problems of the cognitive process and the triple structure of intellectual production during e-learning, including interest in the intellectual outcome, the need for emotional and motivational elements of cooperation and competition between students, and smooth behavioral enrichment, which requires special efforts from students and their leading from teachers. The main conclusion concerns a practical decision to continue the implementation of the educational program in the form of an online course with the use of the mixed digital communication tools of social media, messengers, and video conferences, which most likely meets the expectations and capabilities of students.
Qualitative and Nutritional Improvement of Cereal-Based Foods and Beverages
Authors: Pasqualone Antonella , Summo Carmine
Published: February 2021

The main directions of research aimed at nutritional improvement have to face either excesses or deficiencies in the diet. To this end, different strategies may be adopted, such as the reformulation of products, the introduction of functional ingredients, and the application of biotechnology to increase the bioavailability of bioactive compounds. These interventions, however, can alter the physico-chemical and sensory properties of the final products, making it necessary to achieve a balance between nutritional and quality modification. This Special Issue offers readers information on innovative ways to improve the cereal-based foods and beverages, useful for researchers and for industry operators.
Non-Linear First-Order Differential Boundary Problems with Multipoint and Integral Conditions
Authors: Mardanov Misir J. , Sharifov Yagub A. , Gasimov Yusif S. , Cattani Carlo
Published: February 2021

This paper considers boundary value problem (BVP) for nonlinear first-order differential problems with multipoint and integral boundary conditions. A suitable Green function was constructed for the first time in order to reduce this problem into a corresponding integral equation. So that by using the Banach contraction mapping principle (BCMP) and Schaefer’s fixed point theorem (SFPT) on the integral equation, we can show that the solution of the multipoint problem exists and it is unique.
Integrated Full-Length Transcriptome and RNA-Seq to Identify Immune System Genes from the Skin of Sperm Whale (Physeter macrocephalus)
Authors: Wang Daling , Li Ying , Aierken Reyilamu , Kang Qi , Wang Xianyan , Zeng Qianhui , Fan Zhichang , Zhen Yu , Zhao Liyuan
Published: February 2021

Cetaceans are a group of secondary aquatic mammals whose ancestors returned to the ocean from land, and during evolution, their immune systems adapted to the aquatic environment. Their skin, as the primary barrier to environmental pathogens, supposedly evolved to adapt to a new living environment. However, the immune system in the skin of cetaceans and the associated molecular mechanisms are still largely unknown. To better understand the immune system, we extracted RNA from the sperm whale’s (Physeter macrocephalus) skin and performed PacBio full-length sequencing and RNA-seq sequencing. We obtained a total of 96,350 full-length transcripts with an average length of 1705 bp and detected 5150 genes that were associated with 21 immune-related pathways by gene annotation enrichment analysis. Moreover, we found 89 encoding genes corresponding to 33 proteins were annotated in the NOD-like receptor (NLR)-signaling pathway, including NOD1, NOD2, RIP2, and NF-κB genes, which were discussed in detail and predicted to play essential roles in the immune system of the sperm whale. Furthermore, NOD1 was highly conservative during evolution by the sequence comparison and phylogenetic tree. These results provide new information about the immune system in the skin of cetaceans, as well as the evolution of immune-related genes.
Experiences of Living with Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
Authors: Strassheim Victoria , Newton Julia L. , Collins Tracy
Published: February 2021

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a rare disease with no known etiology. It affects 0.4% of the population, 25% of which experience the severe and very severe categories; these are defined as being wheelchair-, house-, and bed-bound. Currently, the absence of biomarkers necessitates a diagnosis by exclusion, which can create stigma around the illness. Very little research has been conducted with the partly defined severe and very severe categories of CFS/ME. This is in part because the significant health burdens experienced by these people create difficulties engaging in research and healthcare provision as it is currently delivered. This qualitative study explores the experiences of five individuals living with CFS/ME in its most severe form through semi-structured interviews. A six-phase themed analysis was performed using interview transcripts, which included identifying, analysing, and reporting patterns amongst the interviews. Inductive analysis was performed, coding the data without trying to fit it into a pre-existing framework or pre-conception, allowing the personal experiences of the five individuals to be expressed freely. Overarching themes of ‘Lived Experience’, ‘Challenges to daily life’, and ‘Management of the condition’ were identified. These themes highlight factors that place people at greater risk of experiencing the more severe presentation of CFS/ME. It is hoped that these insights will allow research and clinical communities to engage more effectively with the severely affected CFS/ME population.
The Glucocorticoid Receptor Gene (NR3C1) 9β SNP Is Associated with Posttraumatic Stress Disorder
Authors: Castro-Vale Ivone , Durães Cecília , van Rossum Elisabeth F. C. , Staufenbiel Sabine M. , Severo Milton , Lemos Manuel C. , Carvalho Davide
Published: February 2021

Posttraumatic stress disorder (PTSD) has been associated with glucocorticoid (GC) hypersensitivity. Although genetic factors account for 30–46% of the variance in PTSD, no associations have been found between single nucleotide polymorphisms (SNPs) of the GC receptor (GR) gene (NR3C1) and risk for this disorder. We studied the association of five SNPs in the GR gene (rs10052957, rs6189/rs6190, rs6195, rs41423247, and rs6198) and haplotypes with PTSD, in a group of Portuguese male war veterans (33 with lifetime PTSD, 28 without). To determine whether the 9β SNP (rs6198) was associated with chronically altered cortisol levels, we evaluated hair cortisol concentrations (HCC) in a sample of 69 veterans’ offspring. The 9β variant (G allele) was significantly associated with lifetime PTSD under a dominant model of inheritance. The 9β variant was also significantly associated with severity of current PTSD symptoms. The haplotype analysis revealed an association between a common haplotype comprising the 9β risk allele and lifetime PTSD. Carriers of the 9β risk allele had significantly lower HCC than non-carriers. We found the 9β risk allele and a haplotype comprising the 9β risk allele of the GR gene to be associated with PTSD in veterans. This 9β risk allele was also associated with lower HCC in their offspring.
Treatment, Persistent Symptoms, and Depression in People Infected with COVID-19 in Bangladesh
Authors: Islam Md. Saiful , Ferdous Most. Zannatul , Islam Ummay Soumayia , Mosaddek Abu Syed Md. , Potenza Marc N. , Pardhan Shahina
Published: February 2021

Background: Coronavirus disease (COVID-19) has affected people’s lives globally. While important research has been conducted, much remains to be known. In Bangladesh, initial treatment (self-administered, hospitalized), persistent COVID-19 symptoms (“long COVID-19”), and whether COVID-19 leads to changes in mental state, such as depressive symptoms, of people are not known. This study aimed to examine treatment, persistent symptoms, and depression in people who had been infected with COVID-19 in Bangladesh. Methods: A cross-sectional survey was conducted on 1002 individuals infected with COVID-19 (60% male; mean age = 34.7 ± 13.9; age range = 18–81 years), with data taken over a one-month period (11 September 2020 to 13 October 2020). A self-reported online questionnaire was used to collect data on socio-demographics, lifestyle, COVID-19 symptoms (during and beyond COVID-19), medication (over-the-counter or doctor-prescribed), and depression (assessed using the Patient Health Questionnaire (PHQ-9)). Results: Twenty-four percent of participants self-medicated with over-the-counter medicine when they were first diagnosed with COVID-19. Self-medication was higher among female vs. male respondents (29.6% vs. 20.2%, respectively, p = 0.002). A minority (20%) reported that they experienced persistent COVID-like symptoms after recovering from COVID-19. The most reported persistent symptoms were diarrhea (12.7%) and fatigue (11.5%). Forty-eight percent of participants were categorized as having moderate to severe depression. Based on multivariate regression analysis, depression during COVID-19 was positively associated with lower family income, poor health status, sleep disturbance, lack of physical activity, hypertension, asthma/respiratory problems, fear of COVID-19 re-infection, and persistent COVID-19 symptoms. Conclusions: The findings suggest a need for appropriate interventions for COVID-19 patients to promote physical and mental wellbeing.
Non-Pharmacological Approaches to Headaches: Non-Invasive Neuromodulation, Nutraceuticals, and Behavioral Approaches
Authors: Grazzi Licia , Toppo Claudia , D’Amico Domenico , Leonardi Matilde , Martelletti Paolo , Raggi Alberto , Guastafierro Erika
Published: February 2021

Significant side effects or drug interactions can make pharmacological management of headache disorders very difficult. Non-conventional and non-pharmacological treatments are becoming increasingly used to overcome these issues. In particular, non-invasive neuromodulation, nutraceuticals, and behavioral approaches are well tolerated and indicated for specific patient categories such as adolescents and pregnant women. This paper aims to present the main approaches reported in the literature in the management of headache disorders. We therefore reviewed the available literature published between 2010 and 2020 and performed a narrative presentation for each of the three categories (non-invasive neuromodulation, nutraceuticals, and behavioral therapies). Regarding non-invasive neuromodulation, we selected transcranial magnetic stimulation, supraorbital nerve stimulation, transcranial direct current stimulation, non-invasive vagal nerve stimulation, and caloric vestibular stimulation. For nutraceuticals, we selected Feverfew, Butterbur, Riboflavin, Magnesium, and Coenzyme Q10. Finally, for behavioral approaches, we selected biofeedback, cognitive behavioral therapy, relaxation techniques, mindfulness-based therapy, and acceptance and commitment therapy. These approaches are increasingly seen as a valid treatment option in headache management, especially for patients with medication overuse or contraindications to drug treatment. However, further investigations are needed to consider the effectiveness of these approaches also with respect to the long-term effects.
Adverse Drug Reaction Reporting by Patients in 12 European Countries
Authors: Valinciute-Jankauskiene Agne , Kubiliene Loreta
Published: February 2021

Patients who report suspected adverse drug reactions (ADRs) help minimize drug safety risks and bolster the pharmacovigilance system. The aim of this study was to examine the contribution of patients to pharmacovigilance and compare the tools used to promote patient reporting in European countries that implemented this reporting type in 2012–2013. A web-based questionnaire was sent to the national competent authorities (NCAs) of the European countries. The received answers were systematized and compared using statistical analysis. The performed statistical analysis demonstrated that changes in the number of received ADR reports increased significantly in each country during the analyzed period. These changes were significantly different in Ireland and Finland from those in the other reviewed countries. The common source of information on direct patient reporting was the country’s NCA website. Other sources used were social media pages, leaflets, and posters. This is the first study on patient reporting schemes implemented after the significant reform of the European regulatory system for pharmacovigilance. However, some countries did not actively promote their patient reporting schemes. Our findings indicate that countries with minimal experience in pharmacovigilance systems that include direct patient reporting should organize comprehensive campaigns on ADR reporting.
Work-Time Compositions of Physical Behaviors and Trajectories of Sick Leave Due to Musculoskeletal Pain
Authors: Hallman David M. , Gupta Nidhi , Bergamin Januario Leticia , Holtermann Andreas
Published: February 2021

We aimed to investigate the association between work-time compositions of physical behavior and sick leave trajectories due to musculoskeletal pain over one year. We conducted a secondary analysis using the data of 981 workers in a Danish prospective cohort (DPHACTO 2012–2014). At baseline, we assessed physical behaviors (sitting, standing, light physical activity (LIPA), and moderate-to-vigorous physical activity (MVPA)) at work and during leisure, using accelerometers. Over 1 year follow-up, workers reported sick-leave days due to musculoskeletal pain at 4-week intervals. Four distinct trajectories of sick leave were previously identified in this cohort (“no sick leave”, “few days—increasing trajectory”, “some days—decreasing trajectory”, “some days—increasing trajectory”), and used as an outcome in multinomial regression models with work-time compositions as predictors, adjusted for compositions of behavior during leisure, age, sex, body mass index, and smoking habits. More time spent sitting relative to the other behaviors was negatively associated with the trajectory of few days—increasing sick leave (p = 0.004), while time in LIPA was positively associated with the trajectory of some days—increasing sick leave (p = 0.009). Standing and MVPA were not significantly associated with sick leave trajectories. In conclusion, work-time compositions with more sitting relative to the other behaviors had lower risk for an increasing trajectory of sick leave due to pain, while compositions with more LIPA had higher risk. This may have implications for prevention of pain-related sick leave in blue-collar workers.
Implementation of the Use of Ethnomedicinal Plants for Curing Diseases in the Indian Himalayas and Its Role in Sustainability of Livelihoods and Socioeconomic Development
Authors: Kumar Munesh , Rawat Sushma , Nagar Bhuvnesh , Kumar Amit , Pala Nazir A. , Bhat Jahangeer A. , Bussmann Rainer W. , Cabral-Pinto Marina , Kunwar Ripu
Published: February 2021

In recent times, the use of traditional herbal medicines in healthcare has declined, particularly amongst the rural population. This implies a risk of losing vital information from previous generations regarding plants and their use in traditional medicine. The objective of this study is to catalog the ways employed by inhabitants of the Garhwal Himalayas as part of their traditional approaches to healthcare. Information was gathered through snowball sampling using a questionnaire combined with informal interviews. This was supplemented by discussions with peers and practitioners prominent in this healing technique. The homogeneity within ethnomedicinal knowledge of these rural residents was tested using the informant consensus factor (Fic). The calculation of the fidelity value (FL) and the cultural importance index (CI) were made regarding the population’s dependency on plants. A total of 88 plant species from 44 families and 80 genera were identified as medicines for various complaints. Leaves were the most frequently used plant part followed by fruits, seeds, roots, bark, and flowers/buds. The largest number of taxa (15 species) were used for treatment of skin ailments (with Fic score of 0.85) followed by wounds, coughs, and digestive problems. There was a significant relationship observed between the medicinal plants used and distance (time of access) and family income. The present study will provide baseline information to be established for future research. The available information could help to discover new drugs for the pharmaceutical industry. Thus, the study revealed that the plants that have high scores of FL and CI can be used to discover new drug extraction in the future for further studies.
Climate Change Impacts and Workforce Development Needs in Federal Region X: A Qualitative Study of Occupational Health and Safety Professionals’ Perceptions
Authors: Pedersen Katherine M. , Busch Isaksen Tania M. , Baker Marissa G. , Seixas Noah , Errett Nicole A.
Published: February 2021

Climate change is considered one of the top health threats in the United States. This research sought to (1) to understand the perceptions of occupational health and safety (OHS) professionals regarding the impacts of climate-related hazards on OHS in Region X, and (2) to explore the ideas of these OHS professionals regarding the content of future training programs that would better prepare OHS professionals to identify and mitigate climate-related hazards in Region X. Key informant (KI) interviews with 17 OHS professionals familiar with the climate-related hazards and impacts to OHS in Region X were coded and thematically analyzed. Climate hazards, social and economic impacts from climate-related hazards, and sector-specific worker and workplace impacts from climate-related hazards were described as having interacting relationships that influenced worker health and safety impacts. KIs further described how workplace controls could be used to mitigate OHS impacts of climate-related hazards, and how training of the OHS workforce could influence the ability to successfully implement such controls. Our findings suggest that OHS impacts are sector-specific, influenced by social and economic factors, and can be mitigated through workplace controls designed and implemented by a trained OHS workforce. The findings from this work should inform future educational and training programming and additional research and translation activities in the region, while our approach can inform other regions as they develop regionally specific OHS climate change training and programming.
Access to Nature in a Post Covid-19 World: Opportunities for Green Infrastructure Financing, Distribution and Equitability in Urban Planning
Authors: Mell Ian , Whitten Meredith
Published: February 2021

Covid-19 changed the way many people viewed and interacted with the natural environment. In the UK, a series of national lockdowns limited the number of places that individuals could use to support their mental and physical health. Parks, gardens, canals and other “green infrastructure” (GI) resources remained open and were repositioned as “essential infrastructure” supporting well-being. However, the quality, functionality and location of GI in urban areas illustrated a disparity in distribution that meant that in many cases communities with higher ethnic diversity, lower income and greater health inequality suffered from insufficient access. This paper provides commentary on these issues, reflecting on how planners, urban designers and environmental organizations are positioning GI in decision-making to address inequality. Through a discussion of access and quality in an era of austerity funding, this paper proposes potential pathways to equitable environmental planning that address historical and contemporary disenfranchisement with the natural environment in urban areas.
Characterization and Reconstitution of Human Lipoyl Synthase (LIAS) Supports ISCA2 and ISCU as Primary Cluster Donors and an Ordered Mechanism of Cluster Assembly
Authors: Hendricks Amber L. , Wachnowsky Christine , Fries Brian , Fidai Insiya , Cowan James A.
Published: February 2021

Lipoyl synthase (LIAS) is an iron–sulfur cluster protein and a member of the radical S-adenosylmethionine (SAM) superfamily that catalyzes the final step of lipoic acid biosynthesis. The enzyme contains two [4Fe–4S] centers (reducing and auxiliary clusters) that promote radical formation and sulfur transfer, respectively. Most information concerning LIAS and its mechanism has been determined from prokaryotic enzymes. Herein, we detail the expression, isolation, and characterization of human LIAS, its reactivity, and evaluation of natural iron–sulfur (Fe–S) cluster reconstitution mechanisms. Cluster donation by a number of possible cluster donor proteins and heterodimeric complexes has been evaluated. [2Fe–2S]-cluster-bound forms of human ISCU and ISCA2 were found capable of reconstituting human LIAS, such that complete product turnover was enabled for LIAS, as monitored via a liquid chromatography–mass spectrometry (LC–MS) assay. Electron paramagnetic resonance (EPR) studies of native LIAS and substituted derivatives that lacked the ability to bind one or the other of LIAS’s two [4Fe–4S] clusters revealed a likely order of cluster addition, with the auxiliary cluster preceding the reducing [4Fe–4S] center. These results detail the trafficking of Fe–S clusters in human cells and highlight differences with respect to bacterial LIAS analogs. Likely in vivo Fe–S cluster donors to LIAS are identified, with possible connections to human disease states, and a mechanistic ordering of [4Fe–4S] cluster reconstitution is evident.
Contribution of Hypothyroidism to Cognitive Impairment and Hippocampal Synaptic Plasticity Regulation in an Animal Model of Depression
Authors: Głombik Katarzyna , Detka Jan , Bobula Bartosz , Bąk Joanna , Kusek Magdalena , Tokarski Krzysztof , Budziszewska Bogusława
Published: February 2021

The role that thyroid hormone deficiency plays in depression and synaptic plasticity in adults has only begun to be elucidated. This paper analyzes the possible link between depression and hypothyroidism in cognitive function alterations, using Wistar–Kyoto (WKY—an animal model of depression) rats and control Wistar rats under standard and thyroid hormone deficiency conditions (propylthiouracil administration—PTU). A weakening of memory processes in the WKY rats is shown behaviorally, and in the reduction of long-term potentiation (LTP) in the dentate gyrus (DG) and CA1 hippocampal regions. PTU administration decreased LTP and increased basal excitatory transmission in the DG in Wistar rats. A decrease in short-term synaptic plasticity is shown by the paired-pulse ratio measurement, occurring during hypothyroidism in DG and CA1 in WKY rats. Differences between the strains may result from decreases in the p-CaMKII, p-AKT, and the level of acetylcholine, while in the case of the co-occurrence of depression and hypothyroidism, an increase in the p-ERK1-MAP seemed to be important. Obtained results show that thyroid hormones are less involved in the inhibition of glutamate release and/or excitability of the postsynaptic neurons in WKY rats, which may indicate a lower sensitivity of the hippocampus to the action of thyroid hormones in depression.
Factor XIII and Fibrin Clot Properties in Acute Venous Thromboembolism
Authors: Ząbczyk Michał , Natorska Joanna , Undas Anetta
Published: February 2021

Coagulation factor XIII (FXIII) is converted by thrombin into its active form, FXIIIa, which crosslinks fibrin fibers, rendering clots more stable and resistant to degradation. FXIII affects fibrin clot structure and function leading to a more prothrombotic phenotype with denser networks, characterizing patients at risk of venous thromboembolism (VTE). Mechanisms regulating FXIII activation and its impact on fibrin structure in patients with acute VTE encompassing pulmonary embolism (PE) or deep vein thrombosis (DVT) are poorly elucidated. Reduced circulating FXIII levels in acute PE were reported over 20 years ago. Similar observations indicating decreased FXIII plasma activity and antigen levels have been made in acute PE and DVT with their subsequent increase after several weeks since the index event. Plasma fibrin clot proteome analysis confirms that clot-bound FXIII amounts associated with plasma FXIII activity are decreased in acute VTE. Reduced FXIII activity has been associated with impaired clot permeability and hypofibrinolysis in acute PE. The current review presents available studies on the role of FXIII in the modulation of fibrin clot properties during acute PE or DVT and following these events. Better understanding of FXIII’s involvement in the pathophysiology of acute VTE might help to improve current therapeutic strategies in patients with acute VTE.
Targeting for Success: Demonstrating Proof-of-Concept with Mechanistic Early Phase Clinical Pharmacology Studies for Disease-Modification in Neurodegenerative Disorders
Authors: Vissers Maurits F. J. M. , Heuberger Jules A. A. C. , Groeneveld Geert Jan
Published: February 2021

The clinical failure rate for disease-modifying treatments (DMTs) that slow or stop disease progression has been nearly 100% for the major neurodegenerative disorders (NDDs), with many compounds failing in expensive and time-consuming phase 2 and 3 trials for lack of efficacy. Here, we critically review the use of pharmacological and mechanistic biomarkers in early phase clinical trials of DMTs in NDDs, and propose a roadmap for providing early proof-of-concept to increase R&D productivity in this field of high unmet medical need. A literature search was performed on published early phase clinical trials aimed at the evaluation of NDD DMT compounds using MESH terms in PubMed. Publications were selected that reported an early phase clinical trial with NDD DMT compounds between 2010 and November 2020. Attention was given to the reported use of pharmacodynamic (mechanistic and physiological response) biomarkers. A total of 121 early phase clinical trials were identified, of which 89 trials (74%) incorporated one or multiple pharmacodynamic biomarkers. However, only 65 trials (54%) used mechanistic (target occupancy or activation) biomarkers to demonstrate target engagement in humans. The most important categories of early phase mechanistic and response biomarkers are discussed and a roadmap for incorporation of a robust biomarker strategy for early phase NDD DMT clinical trials is proposed. As our understanding of NDDs is improving, there is a rise in potentially disease-modifying treatments being brought to the clinic. Further increasing the rational use of mechanistic biomarkers in early phase trials for these (targeted) therapies can increase R&D productivity with a quick win/fast fail approach in an area that has seen a nearly 100% failure rate to date.
Immunohistochemical Analysis of DNA Repair- and Drug-Efflux-Associated Molecules in Tumor and Peritumor Areas of Glioblastoma
Authors: Angelucci Cristiana , D’Alessio Alessio , Sorrentino Silvia , Biamonte Filippo , Moscato Umberto , Mangiola Annunziato , Sica Gigliola , Iacopino Fortunata
Published: February 2021

Glioblastoma (GBM), the most commonly occurring primary tumor arising within the central nervous system, is characterized by high invasiveness and poor prognosis. In spite of the improvement in surgical techniques, along with the administration of chemo- and radiation therapy and the incessant investigation in search of prospective therapeutic targets, the local recurrence that frequently occurs within the peritumoral brain tissue makes GBM the most malignant and terminal type of astrocytoma. In the current study, we investigated both GBM and peritumoral tissues obtained from 55 hospitalized patients and the expression of three molecules involved in the onset of resistance/unresponsiveness to chemotherapy: O6-methylguanine methyltransferase (MGMT), breast cancer resistance protein (BCRP1), and A2B5. We propose that the expression of these molecules in the peritumoral tissue might be crucial to promoting the development of early tumorigenic events in the tissue surrounding GBM as well as responsible for the recurrence originating in this apparently normal area and, accordingly, for the resistance to treatment with the standard chemotherapeutic regimen. Notably, the inverse correlation found between MGMT expression in peritumoral tissue and patients’ survival suggests a prognostic role for this protein.
Molecular Control of Oil Metabolism in the Endosperm of Seeds
Authors: Miray Romane , Kazaz Sami , To Alexandra , Baud Sébastien
Published: February 2021

In angiosperm seeds, the endosperm develops to varying degrees and accumulates different types of storage compounds remobilized by the seedling during early post-germinative growth. Whereas the molecular mechanisms controlling the metabolism of starch and seed-storage proteins in the endosperm of cereal grains are relatively well characterized, the regulation of oil metabolism in the endosperm of developing and germinating oilseeds has received particular attention only more recently, thanks to the emergence and continuous improvement of analytical techniques allowing the evaluation, within a spatial context, of gene activity on one side, and lipid metabolism on the other side. These studies represent a fundamental step toward the elucidation of the molecular mechanisms governing oil metabolism in this particular tissue. In particular, they highlight the importance of endosperm-specific transcriptional controls for determining original oil compositions usually observed in this tissue. In the light of this research, the biological functions of oils stored in the endosperm of seeds then appear to be more diverse than simply constituting a source of carbon made available for the germinating seedling.
Impact of Microbial Metabolites on Microbiota–Gut–Brain Axis in Inflammatory Bowel Disease
Authors: Banfi Davide , Moro Elisabetta , Bosi Annalisa , Bistoletti Michela , Cerantola Silvia , Crema Francesca , Maggi Fabrizio , Giron Maria Cecilia , Giaroni Cristina , Baj Andreina
Published: February 2021

The complex bidirectional communication system existing between the gastrointestinal tract and the brain initially termed the “gut–brain axis” and renamed the “microbiota–gut–brain axis”, considering the pivotal role of gut microbiota in sustaining local and systemic homeostasis, has a fundamental role in the pathogenesis of Inflammatory Bowel Disease (IBD). The integration of signals deriving from the host neuronal, immune, and endocrine systems with signals deriving from the microbiota may influence the development of the local inflammatory injury and impacts also more distal brain regions, underlying the psychophysiological vulnerability of IBD patients. Mood disorders and increased response to stress are frequently associated with IBD and may affect the disease recurrence and severity, thus requiring an appropriate therapeutic approach in addition to conventional anti-inflammatory treatments. This review highlights the more recent evidence suggesting that alterations of the microbiota–gut–brain bidirectional communication axis may concur to IBD pathogenesis and sustain the development of both local and CNS symptoms. The participation of the main microbial-derived metabolites, also defined as “postbiotics”, such as bile acids, short-chain fatty acids, and tryptophan metabolites in the development of IBD-associated gut and brain dysfunction will be discussed. The last section covers a critical evaluation of the main clinical evidence pointing to the microbiome-based therapeutic approaches for the treatment of IBD-related gastrointestinal and neuropsychiatric symptoms.
Post-Quantum Cryptosystems for Internet-of-Things: A Survey on Lattice-Based Algorithms
Authors: Asif Rameez
Published: February 2021

The latest quantum computers have the ability to solve incredibly complex classical cryptography equations particularly to decode the secret encrypted keys and making the network vulnerable to hacking. They can solve complex mathematical problems almost instantaneously compared to the billions of years of computation needed by traditional computing machines. Researchers advocate the development of novel strategies to include data encryption in the post-quantum era. Lattices have been widely used in cryptography, somewhat peculiarly, and these algorithms have been used in both; (a) cryptoanalysis by using lattice approximation to break cryptosystems; and (b) cryptography by using computationally hard lattice problems (non-deterministic polynomial time hardness) to construct stable cryptographic functions. Most of the dominant features of lattice-based cryptography (LBC), which holds it ahead in the post-quantum league, include resistance to quantum attack vectors, high concurrent performance, parallelism, security under worst-case intractability assumptions, and solutions to long-standing open problems in cryptography. While these methods offer possible security for classical cryptosytems in theory and experimentation, their implementation in energy-restricted Internet-of-Things (IoT) devices requires careful study of regular lattice-based implantation and its simplification in lightweight lattice-based cryptography (LW-LBC). This streamlined post-quantum algorithm is ideal for levelled IoT device security. The key aim of this survey was to provide the scientific community with comprehensive information on elementary mathematical facts, as well as to address real-time implementation, hardware architecture, open problems, attack vectors, and the significance for the IoT networks.
Dynamic Susceptibility Perfusion Imaging for Differentiating Progressive Disease from Pseudoprogression in Diffuse Glioma Molecular Subtypes
Authors: Richter Vivien , Klose Uwe , Bender Benjamin , Rabehl Katharina , Skardelly Marco , Schittenhelm Jens , Tabatabai Ghazaleh , Hempel Johann-Martin , Ernemann Ulrike , Brendle Cornelia
Published: February 2021

Rationale and Objectives: Advanced adjuvant therapy of diffuse gliomas can result in equivocal findings in follow-up imaging. We aimed to assess the additional value of dynamic susceptibility perfusion imaging in the differentiation of progressive disease (PD) from pseudoprogression (PsP) in different molecular glioma subtypes. Materials and Methods: 89 patients with treated diffuse glioma with different molecular subtypes (IDH wild type (Astro-IDHwt), IDH mutant astrocytomas (Astro-IDHmut) and oligodendrogliomas), and tumor-suspect lesions on post-treatment follow-up imaging were classified into two outcome groups (PD or PsP) retrospectively by histopathology or clinical follow-up. The relative cerebral blood volume (rCBV) was assessed in the tumor-suspect FLAIR and contrast-enhancing (CE) lesions. We analyzed how a multilevel classification using a molecular subtype, the presence of a CE lesion, and two rCBV histogram parameters performed for PD prediction compared with a decision tree model (DTM) using additional rCBV parameters. Results: The PD rate was 69% in the whole cohort, 86% in Astro-IDHwt, 52% in Astro-IDHmut, and 55% in oligodendrogliomas. In the presence of a CE lesion, the PD rate was higher with 82%, 94%, 59%, and 88%, respectively; if there was no CE lesion, however, the PD rate was only 44%, 60%, 40%, and 33%, respectively. The additional use of the rCBV parameters in the DTM yielded a prediction accuracy for PD of 99%, 100%, 93%, and 95%, respectively. Conclusion: Utilizing combined information about the molecular tumor type, the presence or absence of CE lesions and rCBV parameters increases PD prediction accuracy in diffuse glioma.