bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Glycosylated Hemoglobin Outcomes Following an Enhanced Medication Therapy Management Service via Telehealth
Authors: Bingham Jennifer M. , Stanislaw Jennifer , Warholak Terri , Scovis Nicole , Axon David R. , Turgeon Jacques , Marupuru Srujitha
Published: June 2021

(1) Background: Regular contact with a medication therapy management (MTM) pharmacist is shown to improve patients’ understanding of their condition; however, continued demonstration of the value of a pharmacist delivered comprehensive medication review (CMR) using enhanced MTM services via telehealth is needed. The study aimed to describe a pilot program designed to improve type 2 diabetes mellitus (T2DM) management through enhanced condition specific MTM services. (2) Methods: This retrospective study included patients with T2DM aged 40–75 years who received a pharmacist-delivered CMR between January and December 2018. An evaluation of glycosylated hemoglobin (HbA1c) values 3 months pre- and post-CMR was performed. Wilcoxon signed-rank and chi-square tests were used. (3) Results: Of 444 eligible patients, a majority were female (58%) with a median age of 70 years. Median HbA1c values post-CMR were lower than pre-CMR (median 7.1% range 4.5–13.6; median 7.4% range 4.5–13.9, respectively; p = 0.009). There were fewer participants with HbA1c >9% post-CMR (n = 66) than pre-CMR (n = 80; p < 0.001) and more with HbA1C <6.5% post-CMR (n = 151) than pre-CMR (n = 130; p < 0.001). (4) Conclusion: This program evaluation highlighted the value of an enhanced condition specific MTM service via telehealth. Patients had improved HbA1c values three months after receiving a single pharmacist delivered CMR.
Screening of Eurasian Tundra Reindeer for Viral Sequences by Next-Generation Sequencing
Authors: Sánchez Romano Javier , Omazic Anna , Leijon Mikael , Hagström Åsa , Tryland Morten , Kantanen Juha , Reilas Tiina , Rockström Ulrika , Fedorov Valery , Albihn Ann
Published: June 2021

Reindeer husbandry is essential for the livelihood and culture of indigenous people in the Arctic. Parts of the herding areas are also used as pastures for farm animals, facilitating potential transmission of viruses between species. Following the Covid-19 pandemic, viruses circulating in the wild are receiving increased attention, since they might pose a potential threat to human health. Climate change will influence the prevalence of infectious diseases of both humans and animals. The aim of this study was to detect known and previously unknown viruses in Eurasian tundra reindeer. In total, 623 nasal and 477 rectal swab samples were collected from reindeer herds in Fennoscandia, Iceland, and Eastern Russia during 2016–2019. Next-generation sequencing analysis and BLAST-homology searches indicated the presence of viruses of domesticated and wild animals, such as bovine viral diarrhea virus, bovine papillomavirus, alcephaline herpesvirus 1 and 2, deer mastadenovirus B, bovine rotavirus, and roe deer picobirnavirus. Several viral species previously found in reindeer and some novel species were detected, although the clinical relevance of these viruses in reindeer is largely unknown. These results indicate that it should be possible to find emerging viruses of relevance for both human and animal health using reindeer as a sentinel species.
Auditory and Language Development Assessment of Newborns Aged One to Four Years Exposed to Gestational Zika Virus Infection: A Case Series
Authors: Gonik Liora , Oliveira Amanda Tupinambá da Fonseca , Chagas Paula Silva de Carvalho , Frônio Jaqueline da Silva
Published: June 2021

The known neurotropism of the Zika virus (ZikV) suggests that auditory organs and their neural pathways may be affected by prenatal Zika infections. Among the possible manifestations are audiological and language disorders, but so far, the data in the literature are inconclusive. Objective: To describe early and late hearing disorders in children with Congenital Zika Virus Infection (CZVI) and evaluate the language development of this population between 14 and 47 months of age and its possible correlation with the alterations found in auditory exams. Methods: Longitudinal, prospective, observational study of newborns born in Juiz de Fora and its macroregion with confirmed diagnosis of ZikV infection during pregnancy. Participants were examined from one to four years of age for hearing using the transient otoacoustic emissions (TOAE) test, immittance testing and brainstem auditory evoked potential (BAEP), and language using the Bayley Scales of Infant Development—Third Edition (Bayley III). Results: 15 participants were included; eight (53.33%) presented alterations in at least one of the hearing tests, one had an early loss (6%) of sensorineural origin, and seven (46.67%) had a poor language performance. In the three (20%) participants whose audiological exams were altered, there was language impairment, and two (13.33%) participants had extensive malformations in the central nervous system (CNS), presented language delay, and hearing exams were within normality. Conclusion: Infants and preschoolers with CZVI may present early neurosensory loss and late hearing loss with fluctuating character. Even if there were no significant association between the audiological exams results and the Bayley III performance, in the present sample, language development was below expectations for the age in the participants who had alterations in the three audiological exams, when there is early hearing loss or extensive lesions to the CNS. The results reinforce the importance of audiological examinations, especially the BAEP morphological and auditory threshold, in monitoring cases of CZVI until at least three years of age.
Modeling Provincial Covid-19 Epidemic Data Using an Adjusted Time-Dependent SIRD Model
Authors: Ferrari Luisa , Gerardi Giuseppe , Manzi Giancarlo , Micheletti Alessandra , Nicolussi Federica , Biganzoli Elia , Salini Silvia
Published: June 2021

In this paper, we develop a forecasting model for the spread of COVID-19 infection at a provincial (i.e., EU NUTS-3) level in Italy by using official data from the Italian Ministry of Health integrated with data extracted from daily official press conferences of regional authorities and local newspaper websites. This data integration is needed as COVID-19 death data are not available at the NUTS-3 level from official open data channels. An adjusted time-dependent SIRD model is used to predict the behavior of the epidemic; specifically, the number of susceptible, infected, deceased, recovered people and epidemiological parameters. Predictive model performance is evaluated using comparison with real data.
Measurement of Air Pollution Parameters in Montenegro Using the Ecomar System
Authors: Zaric Nikola , Spalevic Velibor , Bulatovic Nikola , Pavlicevic Nikola , Dudic Branislav
Published: June 2021

Particulate matter air pollution is one of the most dangerous pollutants nowadays and an indirect cause of numerous diseases. A number of these consequences could possibly be avoided if the right information about air pollution were available at a large number of locations, especially in urban areas. Unfortunately, this is not the case today. In the whole of Europe, there are just approximately 3000 automated measuring stations for PM10, and only about 1400 stations equipped for PM2.5 measurement. In order to improve this issue and provide availability of real-time data about air pollution, different low-cost sensor-based solutions are being considered both on-field and in laboratory research. In this paper, we will present the results of PM particle monitoring using a self-developed Ecomar system. Measurements are performed in two cities in Montenegro, at seven different locations during several periods. In total, three Ecomar systems were used during 1107 days of on-field measurements. Measurements performed at two locations near official automated measuring stations during 610 days justified that the Ecomar system performance is satisfying in terms of reliability and measurement precision (NRMSE 0.33 for PM10 and 0.44 for PM2.5) and very high in terms of data validity and operating stability (Ecomar 94.13%–AMS 95.63%). Additionally, five distant urban/rural locations with different traffic, green areas, and nearby industrial objects were utilized to highlight the need for more dense spatial distributions of measuring locations. To our knowledge, this is the most extensive study of low-cost sensor-based air quality measurement systems in terms of the duration of the on-field tests in the Balkan region.
A New Swiss Federal Act on Gambling: From Missed Opportunities towards a Public Health Approach?
Authors: Dickson Cheryl , Jeannot Emilien , Peduzzi Fabio , Savary Jean-Félix , Costes Jean-Michel , Simon Olivier
Published: June 2021

In January 2019, a new Swiss Federal Act on Gambling (Loi federal de jeux d’argent: LJAr) entered into force following a vote by the Swiss electorate. Intended to modernize and harmonize previous law and open the market for online casinos; the new regulations have highlighted the need for a comprehensive monitoring system. The present article outlines work undertaken by experts within the field to identify and elaborate the first steps towards developing such a monitoring system. This work includes the mapping of institutional actors and draft conceptualization of an impact model, including structural (i.e., prevention and intervention-based components), process (means), and outcomes (effect) indicators. Initial estimations of effective access to indicators and their perceived priority for data gathering are also described. Subsequent steps necessary for implementation of this public health approach for gambling are considered including grey areas for future action.
Prevalence of Everyday Discrimination and Relation with Wellbeing among Aboriginal and Torres Strait Islander Adults in Australia
Authors: Thurber Katherine , Colonna Emily , Jones Roxanne , Gee Gilbert , Priest Naomi , Cohen Rubijayne , Williams David , Thandrayen Joanne , Calma Tom , Lovett Raymond ,   on behalf of the Mayi Kuwayu Study Team
Published: June 2021

Discrimination is a fundamental determinant of health and health inequities. However, despite the high prevalence of discrimination exposure, there is limited evidence specific to Indigenous populations on the link between discrimination and health. This study employs a validated measure to quantify experiences of everyday discrimination in a national sample of Aboriginal and Torres Strait Islander (Australia’s Indigenous peoples) adults surveyed from 2018 to 2020 (≥16 years, n = 8108). It quantifies Prevalence Ratios (PRs) and 95% Confidence Intervals (CIs) for wellbeing outcomes by level of discrimination exposure, and tests if associations vary by attribution of discrimination to Indigeneity. Of the participants, 41.5% reported no discrimination, 47.5% low, and 11.0% moderate-high. Discrimination was more commonly reported by younger versus older participants, females versus males, and those living in remote versus urban or regional areas. Discrimination was significantly associated in a dose-response manner, with measures of social and emotional wellbeing, culture and identity, health behaviour, and health outcomes. The strength of the association varied across outcomes, from a 10–20% increased prevalence for some outcomes (e.g., disconnection from culture (PR = 1.08; 95% CI: 1.03, 1.14), and high blood pressure (1.20; 1.09, 1.32)), to a five-fold prevalence of alcohol dependence (4.96; 3.64, 6.76), for those with moderate-high versus no discrimination exposure. The association was of consistent strength and direction whether attributed to Indigeneity or not—with three exceptions. Discrimination is associated with a broad range of poor wellbeing outcomes in this large-scale, national, diverse cohort of Aboriginal and Torres Strait Islander adults. These findings support the vast potential to improve Aboriginal and Torres Strait Islander peoples’ wellbeing, and to reduce Indigenous-non-Indigenous inequities, by reducing exposure to discrimination.
Hopelessness and Post-Traumatic Stress Symptoms among Healthcare Workers during the COVID-19 Pandemic: Any Role for Mediating Variables?
Authors: Aguglia Andrea , Amerio Andrea , Costanza Alessandra , Parodi Nicolò , Copello Francesco , Serafini Gianluca , Amore Mario
Published: June 2021

The Coronavirus-19 (COVID-19) pandemic has many psychological consequences for the population, ranging from anxious-depressive symptoms and insomnia to complex post-traumatic syndromes. This study aimed to evaluate the impact of the Covid-19 pandemic on the mental well-being of healthcare workers, focusing on the association between hopelessness, death anxiety, and post-traumatic symptomatology. Eight hundred forty-two healthcare workers were recruited between 21 March 2020 and 15 May 2020. A specific questionnaire was administered to assess socio-demographic and clinical characteristics, together with psychometric scales: Beck Hopelessness Scale, Death Anxiety Scale (DAS), and Davidson Trauma Scale (DTS). Respondents with hopelessness scored higher in the DAS and DTS than respondents without hopelessness. Furthermore, death anxiety was identified as a potential mediator of the significant association between hopelessness and post-traumatic symptomatology. The impact of death anxiety should be recognized in vulnerable populations, such as frontline healthcare workers. Therefore, pharmacological and non-pharmacological strategies could be useful to attenuate the negative psychological consequences and reduce the burden worldwide.
Removal of Heavy Metal Ions from Wastewater Using Hydroxyethyl Methacrylate-Modified Cellulose Nanofibers: Kinetic, Equilibrium, and Thermodynamic Analysis
Authors: Gouda Mohamed , Aljaafari Abdullah
Published: June 2021

The objective of this work was to fabricate modified cellulose nanofibers (CNFs) for the removal of heavy metal ions (Cd2+ and Pb2+) from wastewater. Cellulose was modified with 2-hydroxyethyl methacrylate (HEMA) via grafting copolymerization using the microwave-assisted technique in the presence of ceric ammonium nitrate (CAN) as an initiator. Prepared cellulose-graft-(2-hydroxyethyl methacrylate) (HEMA/C) copolymers were characterized using Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). Different factors affecting the graft yield, such as irradiation time, monomer concentrations, and initiator concentrations, were investigated. Furthermore, cellulose-graft-(2-hydroxyethyl methacrylate) copolymer nanofibers (HEMA/CNF) were fabricated by electrospinning using N,N-dimethylacetamide-LiCl as a solvent. Electrospun nanofiber copolymers were characterized using SEM and thermogravimetric analysis (TGA). Operating parameters, including time, starting metal concentrations, and adsorbent concentration, were analyzed at a pH of 5.6 for the two metal ions. The best-fit model of adsorption energy was the pseudo-second-order model, and adsorption isotherms at equilibrium were well described by the Langmuir and Freundlich models. The negative values of ΔG and positive values of ΔH and ΔS suggest that the adsorption of Cd2+ and Pb2+ ions onto electrospun HEMA/CNF is a spontaneous, endothermic, and favorable reaction.
Suicide among Older Adults with Dementia: Effects of Korea’s Long-Term Care Insurance System
Authors: Moon Sungje , Choi Mankyu , Sohn Minsung
Published: June 2021

South Korea recently expanded its coverage rate of long-term care insurance (LTCI) by adding a “dementia special grade” in 2014 to improve care service accessibility and extend health life for older adults with dementia. In this study, we propose a multifaceted policy to reduce the suicide risk among older adults with dementia by evaluating the effectiveness of using the long-term care services (LTCS). A sample of 62,282 older adults was selected from the “Older Adults Cohort DB” of the National Health Insurance Service. We conducted Kaplan–Meier and Cox regression to represent the yearly survival curve from 2002 to 2015 according to the individual characteristics. Difference-in-difference estimation was conducted to identify the effect of LTCS on suicide rates by using LTCS before and after 2014. The suicide risk of older adults using LTCS was about 0.256-times lower than those who did not use it (OR = 0.296, 95% CI = 0.183–0.478), whereas it increased after the expansion of the dementia grading (OR = 2.131, 95% CI = 1.061–4.280). To prevent the risk of suicide among older adults with dementia, not only did the mortality rate vary depending on the sex, activities of daily living (ADL), and type of caregiver at the individual level but appropriate national intervention and management, such as improving the accessibility of LTCS, are also needed.
Risk Factors of Early Adolescence in the Criminal Career of Polish Offenders in the Light of Life Course Theory
Authors: Pękala Krzysztof , Kacprzak Andrzej , Pękala-Wojciechowska Anna , Chomczyński Piotr , Olszewski Michał , Marczak Michał , Kozłowski Remigiusz , Timler Dariusz , Zakonnik Łukasz , Sienkiewicz Kamila , Kozłowska Elżbieta , Rasmus Paweł
Published: June 2021

Life course theory (LCT) diagnoses childhood and adolescent factors that determine an individual’s involvement in crime in the future. Farrington lists eight key correlates identified by empirical analyses of criminal careers. In this paper, we seek to discuss the inconsistencies with LCT that we observed in our three empirical studies of the criminal careers of Polish offenders. During 12 years of qualitative research, we conducted direct observations and in-depth interviews in juvenile correction institutions (21) and prisons (8) across the country. We gained access to incarcerated (102) and released (30) juvenile offenders, as well as to incarcerated (68) and released (28) adult offenders. We also conducted in-depth interviews (92) with experts working with young and adult offenders. We similarly accessed some offenders’ criminal records and psychological opinions. Our study revealed the strong presence of family and neighborhood influences on early criminality. Contrary to LCT assumptions, state-dependent institutions (military, work, family) were not strong enough determinants of delinquency. Polish offenders generally experience criminal onset later than LCT-oriented criminologists indicate. Based on our data, we also agree with the thesis that the onset of crime should be discussed as different age-related periods rather than just a general onset.
Alpha-Synuclein as a Prominent Actor in the Inflammatory Synaptopathy of Parkinson’s Disease
Authors: Cardinale Antonella , Calabrese Valeria , de Iure Antonio , Picconi Barbara
Published: June 2021

Parkinson’s disease (PD) is considered the most common disorder of synucleinopathy, which is characterised by intracellular inclusions of aggregated and misfolded α-synuclein (α-syn) protein in various brain regions, and the loss of dopaminergic neurons. During the early prodromal phase of PD, synaptic alterations happen before cell death, which is linked to the synaptic accumulation of toxic α-syn specifically in the presynaptic terminals, affecting neurotransmitter release. The oligomers and protofibrils of α-syn are the most toxic species, and their overexpression impairs the distribution and activation of synaptic proteins, such as the SNARE complex, preventing neurotransmitter exocytosis and neuronal synaptic communication. In the last few years, the role of the immune system in PD has been increasingly considered. Microglial and astrocyte activation, the gene expression of proinflammatory factors, and the infiltration of immune cells from the periphery to the central nervous system (CNS) represent the main features of the inflammatory response. One of the actors of these processes is α-syn accumulation. In light of this, here, we provide a systematic review of PD-related α-syn and inflammation inter-players.
The Exon Junction Complex Core Represses Cancer-Specific Mature mRNA Re-splicing: A Potential Key Role in Terminating Splicing
Authors: Otani Yuta , Fujita Ken-ichi , Kameyama Toshiki , Mayeda Akila
Published: June 2021

Using TSG101 pre-mRNA, we previously discovered cancer-specific re-splicing of mature mRNA that generates aberrant transcripts/proteins. The fact that mRNA is aberrantly re-spliced in various cancer cells implies there must be an important mechanism to prevent deleterious re-splicing on the spliced mRNA in normal cells. We thus postulated that mRNA re-splicing is controlled by specific repressors, and we searched for repressor candidates by siRNA-based screening for mRNA re-splicing activity. We found that knock-down of EIF4A3, which is a core component of the exon junction complex (EJC), significantly promoted mRNA re-splicing. Remarkably, we could recapitulate cancer-specific mRNA re-splicing in normal cells by knock-down of any of the core EJC proteins, EIF4A3, MAGOH, or RBM8A (Y14), implicating the EJC core as the repressor of mRNA re-splicing often observed in cancer cells. We propose that the EJC core is a critical mRNA quality control factor to prevent over-splicing of mature mRNA.
Retinal Stem Cell ‘Retirement Plans’: Growth, Regulation and Species Adaptations in the Retinal Ciliary Marginal Zone
Authors: Miles Amanda , Tropepe Vincent
Published: June 2021

The vertebrate retina develops from a specified group of precursor cells that adopt distinct identities and generate lineages of either the neural retina, retinal pigmented epithelium, or ciliary body. In some species, including teleost fish and amphibians, proliferative cells with stem-cell-like properties capable of continuously supplying new retinal cells post-embryonically have been characterized and extensively studied. This region, termed the ciliary or circumferential marginal zone (CMZ), possibly represents a conserved retinal stem cell niche. In this review, we highlight the research characterizing similar CMZ-like regions, or stem-like cells located at the peripheral margin, across multiple different species. We discuss the proliferative parameters, multipotency and growth mechanisms of these cells to understand how they behave in vivo and how different molecular factors and signalling networks converge at the CMZ niche to regulate their activity. The evidence suggests that the mature retina may have a conserved propensity for homeostatic growth and plasticity and that dysfunction in the regulation of CMZ activity may partially account for dystrophic eye growth diseases such as myopia and hyperopia. A better understanding of the properties of CMZ cells will enable important insight into how an endogenous generative tissue compartment can adapt to altered retinal physiology and potentially even restore vision loss caused by retinal degenerative conditions.
Methylglyoxal-Derived Advanced Glycation End Product (AGE4)-Induced Apoptosis Leads to Mitochondrial Dysfunction and Endoplasmic Reticulum Stress through the RAGE/JNK Pathway in Kidney Cells
Authors: Jeong So-Ra , Lee Kwang-Won
Published: June 2021

Advanced glycation end products (AGEs) are formed via nonenzymatic reactions between reducing sugars and proteins. Recent studies have shown that methylglyoxal, a potent precursor for AGEs, causes a variety of biological dysfunctions, including diabetes, inflammation, renal failure, and cancer. However, little is known about the function of methylglyoxal-derived AGEs (AGE4) in kidney cells. Therefore, we verified the expression of endoplasmic reticulum (ER) stress-related genes and apoptosis markers to determine the effects of AGE4 on human proximal epithelial cells (HK-2). Moreover, our results showed that AGE4 induced the expression of apoptosis markers, such as Bax, p53, and kidney injury molecule-1, but downregulated Bcl-2 and cyclin D1 levels. AGE4 also promoted the expression of NF-κB, serving as a transcription factor, and the phosphorylation of c-Jun NH2-terminal kinase (JNK), which induced cell apoptosis and ER stress mediated by the JNK inhibitor. Furthermore, AGE4 induced mitochondrial dysfunction by inducing the permeabilization of the mitochondrial membrane and ATP synthesis. Through in vitro and in vivo experiments, this study provides a new perspective on renal dysfunction with regard to the AGE4-induced RAGE /JNK signaling pathway, which leads to renal cell apoptosis via the imbalance of mitochondrial function and ER stress in kidney damage.
The Journey of DDR1 and DDR2 Kinase Inhibitors as Rising Stars in the Fight Against Cancer
Authors: Elkamhawy Ahmed , Lu Qili , Nada Hossam , Woo Jiyu , Quan Guofeng , Lee Kyeong
Published: June 2021

Discoidin domain receptor (DDR) is a collagen-activated receptor tyrosine kinase that plays critical roles in regulating essential cellular processes such as morphogenesis, differentiation, proliferation, adhesion, migration, invasion, and matrix remodeling. As a result, DDR dysregulation has been attributed to a variety of human cancer disorders, for instance, non-small-cell lung carcinoma (NSCLC), ovarian cancer, glioblastoma, and breast cancer, in addition to some inflammatory and neurodegenerative disorders. Since the target identification in the early 1990s to date, a lot of efforts have been devoted to the development of DDR inhibitors. From a medicinal chemistry perspective, we attempted to reveal the progress in the development of the most promising DDR1 and DDR2 small molecule inhibitors covering their design approaches, structure-activity relationship (SAR), biological activity, and selectivity.
Nanotechnology of Tyrosine Kinase Inhibitors in Cancer Therapy: A Perspective
Authors: Russo Eleonora , Spallarossa Andrea , Tasso Bruno , Villa Carla , Brullo Chiara
Published: June 2021

Nanotechnology is an important application in modern cancer therapy. In comparison with conventional drug formulations, nanoparticles ensure better penetration into the tumor mass by exploiting the enhanced permeability and retention effect, longer blood circulation times by a reduced renal excretion and a decrease in side effects and drug accumulation in healthy tissues. The most significant classes of nanoparticles (i.e., liposomes, inorganic and organic nanoparticles) are here discussed with a particular focus on their use as delivery systems for small molecule tyrosine kinase inhibitors (TKIs). A number of these new compounds (e.g., Imatinib, Dasatinib, Ponatinib) have been approved as first-line therapy in different cancer types but their clinical use is limited by poor solubility and oral bioavailability. Consequently, new nanoparticle systems are necessary to ameliorate formulations and reduce toxicity. In this review, some of the most important TKIs are reported, focusing on ongoing clinical studies, and the recent drug delivery systems for these molecules are investigated.
The Efficacy of Black Chokeberry Fruits against Cardiovascular Diseases
Authors: Kasprzak-Drozd Kamila , Oniszczuk Tomasz , Soja Jakub , Gancarz Marek , Wojtunik-Kulesza Karolina , Markut-Miotła Ewa , Oniszczuk Anna
Published: June 2021

Epidemiological studies have emphasized the association between a diet rich in fruits and vegetables and a lower frequency of occurrence of inflammatory-related disorders. Black chokeberry (Aronia melanocarpa L.) is a valuable source of biologically active compounds that have been widely investigated for their role in health promotion and cardiovascular disease prevention. Many in vitro and in vivo studies have demonstrated that consumption of these fruits is associated with significant improvements in hypertension, LDL oxidation, lipid peroxidation, total plasma antioxidant capacity and dyslipidemia. The mechanisms for these beneficial effects include upregulation of endothelial nitric oxide synthase, decreased oxidative stress, and inhibition of inflammatory gene expression. Collected findings support the recommendation of such berries as an essential fruit group in a heart-healthy diet. The aim of this review was to summarize the reports on the impact of black chokeberry fruits and extracts against several cardiovascular diseases, e.g., hyperlipidemia, hypercholesterolemia, hypertension, as well as to provide an analysis of the antioxidant and anti-inflammatory effect of these fruits in the abovementioned disorders.
Nanoparticles Functionalised with Re(I) Tricarbonyl Complexes for Cancer Theranostics
Authors: Mkhatshwa Marcus , Moremi Joshua Mamolatelo , Makgopa Katlego , Manicum Amanda-Lee Ezra
Published: June 2021

Globally, cancer is the second (to cardiovascular diseases) leading cause of death. Regardless of various efforts (i.e., finance, research, and workforce) to advance novel cancer theranostics (diagnosis and therapy), there have been few successful attempts towards ongoing clinical treatment options as a result of the complications posed by cancerous tumors. In recent years, the application of magnetic nanomedicine as theranostic devices has garnered enormous attention in cancer treatment research. Magnetic nanoparticles (MNPs) are capable of tuning the magnetic field in their environment, which positively impacts theranostic applications in nanomedicine significantly. MNPs are utilized as contrasting agents for cancer diagnosis, molecular imaging, hyperfusion region visualization, and T cell-based radiotherapy because of their interesting features of small size, high reactive surface area, target ability to cells, and functionalization capability. Radiolabelling of NPs is a powerful diagnostic approach in nuclear medicine imaging and therapy. The use of luminescent radioactive rhenium(I), 188/186Re, tricarbonyl complexes functionalised with magnetite Fe3O4 NPs in nanomedicine has improved the diagnosis and therapy of cancer tumors. This is because the combination of Re(I) with MNPs can improve low distribution and cell penetration into deeper tissues.
Circulating Non-Coding RNAs as a Signature of Autism Spectrum Disorder Symptomatology
Authors: Salloum-Asfar Salam , Elsayed Ahmed K. , Elhag Saba F. , Abdulla Sara A.
Published: June 2021

Autism spectrum disorder (ASD) is a multifaced neurodevelopmental disorder that becomes apparent during early childhood development. The complexity of ASD makes clinically diagnosing the condition difficult. Consequently, by identifying the biomarkers associated with ASD severity and combining them with clinical diagnosis, one may better factionalize within the spectrum and devise more targeted therapeutic strategies. Currently, there are no reliable biomarkers that can be used for precise ASD diagnosis. Consequently, our pilot experimental cohort was subdivided into three groups: healthy controls, individuals those that express severe symptoms of ASD, and individuals that exhibit mild symptoms of ASD. Using next-generation sequencing, we were able to identify several circulating non-coding RNAs (cir-ncRNAs) in plasma. To the best of our knowledge, this study is the first to show that miRNAs, piRNAs, snoRNAs, Y-RNAs, tRNAs, and lncRNAs are stably expressed in plasma. Our data identify cir-ncRNAs that are specific to ASD. Furthermore, several of the identified cir-ncRNAs were explicitly associated with either the severe or mild groups. Hence, our findings suggest that cir-ncRNAs have the potential to be utilized as objective diagnostic biomarkers and clinical targets.
Role of Anesthetics and Their Adjuvants in Neurovascular Protection in Secondary Brain Injury after Aneurysmal Subarachnoid Hemorrhage
Authors: Athiraman Umeshkumar , Zipfel Gregory J.
Published: June 2021

Aneurysmal rupture accounts for the majority of subarachnoid hemorrhage and is responsible for most cerebrovascular deaths with high mortality and morbidity. Initial hemorrhage severity and secondary brain injury due to early brain injury and delayed cerebral ischemia are the major determinants of outcomes after aneurysmal subarachnoid hemorrhage. Several therapies have been explored to prevent these secondary brain injury processes after aneurysmal subarachnoid hemorrhage with limited clinical success. Experimental and clinical studies have shown a neuroprotective role of certain anesthetics in cerebrovascular disorders including aneurysmal subarachnoid hemorrhage. The vast majority of aneurysmal subarachnoid hemorrhage patients require general anesthesia for surgical or endovascular repair of their aneurysm. Given the potential impact certain anesthetics have on secondary brain injury after SAH, appropriate selection of anesthetics may prove impactful on overall outcome of these patients. This narrative review focuses on the available evidence of anesthetics and their adjuvants in neurovascular protection in aneurysmal subarachnoid hemorrhage and discusses current impact on clinical care and future investigative directions.
Estrogen Receptor Modulators in Viral Infections Such as SARS−CoV−2: Therapeutic Consequences
Authors: Abramenko Nikita , Vellieux Fréderic , Tesařová Petra , Kejík Zdeněk , Kaplánek Robert , Lacina Lukáš , Dvořánková Barbora , Rösel Daniel , Brábek Jan , Tesař Adam , Jakubek Milan , Smetana Karel
Published: June 2021

COVID-19 is a pandemic respiratory disease caused by the SARS−CoV−2 coronavirus. The worldwide epidemiologic data showed higher mortality in males compared to females, suggesting a hypothesis about the protective effect of estrogens against severe disease progression with the ultimate end being patient’s death. This article summarizes the current knowledge regarding the potential effect of estrogens and other modulators of estrogen receptors on COVID-19. While estrogen receptor activation shows complex effects on the patient’s organism, such as an influence on the cardiovascular/pulmonary/immune system which includes lower production of cytokines responsible for the cytokine storm, the receptor-independent effects directly inhibits viral replication. Furthermore, it inhibits the interaction of IL-6 with its receptor complex. Interestingly, in addition to natural hormones, phytestrogens and even synthetic molecules are able to interact with the estrogen receptor and exhibit some anti-COVID-19 activity. From this point of view, estrogen receptor modulators have the potential to be included in the anti-COVID-19 therapeutic arsenal.
Modified Hyaluronic Acid-Laminin-Hydrogel as Luminal Filler for Clinically Approved Hollow Nerve Guides in a Rat Critical Defect Size Model
Authors: Huang Zhong , Kankowski Svenja , Ertekin Ella , Almog Mara , Nevo Zvi , Rochkind Shimon , Haastert-Talini Kirsten
Published: June 2021

Hollow nerve guidance conduits are approved for clinical use for defect lengths of up to 3 cm. This is because also in pre-clinical evaluation they are less effective in the support of nerve regeneration over critical defect lengths. Hydrogel luminal fillers are thought to improve the regeneration outcome by providing an optimized matrix inside bioartificial nerve grafts. We evaluated here a modified hyaluronic acid-laminin-hydrogel (M-HAL) as luminal filler for two clinically approved hollow nerve guides. Collagen-based and chitosan-based nerve guides were filled with M-HAL in two different concentrations and the regeneration outcome comprehensively studied in the acute repair rat sciatic nerve 15 mm critical defect size model. Autologous nerve graft (ANG) repair served as gold-standard control. At 120 days post-surgery, all ANG rats demonstrated electrodiagnostically detectable motor recovery. Both concentrations of the hydrogel luminal filler induced improved regeneration outcome over empty nerve guides. However, neither combination with collagen- nor chitosan-based nerve guides resulted in functional recovery comparable to the ANG repair. In contrast to our previous studies, we demonstrate here that M-HAL slightly improved the overall performance of either empty nerve guide type in the critical defect size model.
Genome-Wide Identification of Soybean ABC Transporters Relate to Aluminum Toxicity
Authors: Huang Junjun , Li Xiaoyu , Chen Xin , Guo Yaru , Liang Weihong , Wang Huahua
Published: June 2021

ATP-binding cassette (ABC) transporter proteins are a gene super-family in plants and play vital roles in growth, development, and response to abiotic and biotic stresses. The ABC transporters have been identified in crop plants such as rice and buckwheat, but little is known about them in soybean. Soybean is an important oil crop and is one of the five major crops in the world. In this study, 255 ABC genes that putatively encode ABC transporters were identified from soybean through bioinformatics and then categorized into eight subfamilies, including 7 ABCAs, 52 ABCBs, 48 ABCCs, 5 ABCDs, 1 ABCEs, 10 ABCFs, 111 ABCGs, and 21 ABCIs. Their phylogenetic relationships, gene structure, and gene expression profiles were characterized. Segmental duplication was the main reason for the expansion of the GmABC genes. Ka/Ks analysis suggested that intense purifying selection was accompanied by the evolution of GmABC genes. The genome-wide collinearity of soybean with other species showed that GmABCs were relatively conserved and that collinear ABCs between species may have originated from the same ancestor. Gene expression analysis of GmABCs revealed the distinct expression pattern in different tissues and diverse developmental stages. The candidate genes GmABCB23, GmABCB25, GmABCB48, GmABCB52, GmABCI1, GmABCI5, and GmABCI13 were responsive to Al toxicity. This work on the GmABC gene family provides useful information for future studies on ABC transporters in soybean and potential targets for the cultivation of new germplasm resources of aluminum-tolerant soybean.
Is the Jaw Bone Micro-Structure Altered in Response to Osteoporosis and Bisphosphonate Treatment? A Micro-CT Analysis
Authors: Chatterjee Marissa , Faot Fernanda , Correa Cassia , Kerckhofs Jente , Vandamme Katleen
Published: June 2021

The aim of the study was to quantify the micro-architectural changes of the jaw bone in response to ovariectomy, exposed or not to bisphosphonate treatment. A total of 47 Wistar rats were ovariectomized (OVX) or sham-operated (shOVX) and exposed to osteoporosis preventive treatment for eight weeks either with bisphosphonates (alendronate, ALN; group OVX-ALN) three days/week at a dose of 2 mg/kg or with saline solution (untreated control condition; group OVX). The bone morphometric parameters of the trabecular jaw bone were assessed using ex vivo micro-computed tomography. The regions of interest investigated in the maxilla were the inter-radicular septum of the second molar and the tuber. The regions quantified in the mandible included the three molar regions and the condyle. A one-way analysis of variance followed by pairwise comparison using Tukey’s HSD and the Games–Howell test was conducted to explore significant differences between the groups. In the maxilla, OVX decreased the bone volume in the inter-radicular septum of the second molar. Bisphosphonate treatment was able to prevent this deterioration of the jaw bone. The other investigated maxillary regions were not affected by (un)treated ovariectomy. In the mandible, OVX had a significant negative impact on the jaw bone in the buccal region of the first molar and the inter-radicular region of the third molar. Treatment with ALN was able to prevent this jaw bone loss. At the condyle site, OVX significantly deteriorated the trabecular connectivity and shape, whereas preventive bisphosphonate treatment showed a positive effect on this trabecular bone region. No significant results between the groups were observed for the remaining regions of interest. In summary, our results showed that the effects of ovariectomy-induced osteoporosis are manifested at selected jaw bone regions and that bisphosphonate treatment is capable to prevent these oral bone changes.
Aberrations in Lipid Expression and Metabolism in Psoriasis
Authors: Nowowiejska Julia , Baran Anna , Flisiak Iwona
Published: June 2021

Psoriasis (PSO) is a common skin disease that affects about 1%–3% of the general population. It is a great medical, social and economic burden since PSO is associated with many comorbidities, of which the most common are cardiometabolic disorders. Psoriatic patients suffer more frequently from obesity, dyslipidemia, atherosclerosis, and nonalcoholic fatty liver disease. Research shows that lipid expression and metabolism disorders are present more often in such patients. This review focuses on a variety of aberrations in lipids in the skin, blood, and adipose tissue in psoriatic patients and their multifactorial impact on the pathogenesis of psoriasis.
Paracrine Kynurenic Pathway Activation in the Bone of Young Uremic Rats Can Antagonize Anabolic Effects of PTH on Bone Turnover and Strength through the Disruption of PTH-Dependent Molecular Signaling
Authors: Pawlak Krystyna , Sieklucka Beata , Pawlak Dariusz
Published: June 2021

Secondary hyperparathyroidism and abnormalities in tryptophan (TRP) metabolism are commonly observed in chronic kidney disease (CKD). The present study aimed to establish potential interactions between endogenous parathyroid hormone (PTH) and activation of the bone kynurenine (KYN) pathway in relation to bone turnover and strength in young rats after one month (CKD-1) and three months (CKD-3) of experimental CKD. TRP, KYN, KYN/TRP ratio and bone turnover markers (BTMs) were measured in trabecular and cortical bone tissue. Expression of aryl hydrocarbon receptor (AhR) and the genes involved in osteogenesis was determined in femoral bone. Biomechanical testing of femoral diaphysis and femoral neck was also performed. Activation of the KYN pathway in trabecular bone during CKD development intensified the expression of genes related to osteogenesis, which led to a decrease in cyclic adenosine monophosphate (cAMP) and BTMs levels, resulting in a stiffer and mechanically weaker femoral neck. In contrast, reduction of the KYN pathway in cortical bone allowed to unblock the PTH-dependent anabolic activating transcription factor 4/parathyroid hormone 1 receptor (PTH1R/ATF4) axis, led to cAMP accumulation, better bone turnover and strength in the course of CKD development. In summary, the paracrine KYN pathway in bone can interfere with the anabolic effects of PTH on bone through disrupting PTH-dependent molecular signaling.
The Influence of Strontium on Bone Tissue Metabolism and Its Application in Osteoporosis Treatment
Authors: Kołodziejska Barbara , Stępień Natalia , Kolmas Joanna
Published: June 2021

Osteoporosis is a chronic disease characterized by low bone mass caused by increased bone turnover and impaired bone microarchitecture. In treatment, we use antiresorptive or anabolic drugs, which usually have a unidirectional effect, i.e., they inhibit the activity of osteoclasts or stimulate the effect of osteoblasts. Strontium ranelate is an anti-osteoporosis drug with a unique mechanism of action (used primarily in postmenopausal women). Unlike other medicines, it has a multidirectional effect on bone tissue, intensifying osteoblastogenesis while inhibiting osteoclastogenesis. It turns out that this effect is demonstrated by strontium ions, an element showing physical and chemical similarity to calcium, the basic element that builds the mineral fraction of bone. As a result, strontium acts through the calcium-sensing receptor (CaSR) receptor in bone tissue cells. In recent years, there has been a significant increase in interest in the introduction of strontium ions in place of calcium ions in ceramics used as bone replacement materials for the treatment of bone fractures and defects caused by osteoporosis. The aim of this study was to summarize current knowledge about the role of strontium in the treatment of osteoporosis, its effects (in various forms), and the ways in which it is administered.
MUC1: Structure, Function, and Clinic Application in Epithelial Cancers
Authors: Chen Wenqing , Zhang Zhu , Zhang Shiqing , Zhu Peili , Ko Joshua Ka-Shun , Yung Ken Kin-Lam
Published: June 2021

The transmembrane glycoprotein mucin 1 (MUC1) is a mucin family member that has different functions in normal and cancer cells. Owing to its structural and biochemical properties, MUC1 can act as a lubricant, moisturizer, and physical barrier in normal cells. However, in cancer cells, MUC1 often undergoes aberrant glycosylation and overexpression. It is involved in cancer invasion, metastasis, angiogenesis, and apoptosis by virtue of its participation in intracellular signaling processes and the regulation of related biomolecules. This review introduces the biological structure and different roles of MUC1 in normal and cancer cells and the regulatory mechanisms governing these roles. It also evaluates current research progress and the clinical applications of MUC1 in cancer therapy based on its characteristics.
Molecular Evolution of Phototransduction Pathway Genes in Nocturnal and Diurnal Fireflies (Coleoptera: Lampyridae)
Authors: Martin Gavin J. , Lower Sarah E. , Suvorov Anton , Bybee Seth M.
Published: June 2021

Most organisms are dependent on sensory cues from their environment for survival and reproduction. Fireflies (Coleoptera: Lampyridae) represent an ideal system for studying sensory niche adaptation due to many species relying on bioluminescent communication; as well as a diversity of ecologies. Here; using transcriptomics; we examine the phototransduction pathway in this non-model organism; and provide some of the first evidence for positive selection in the phototransduction pathway beyond opsins in beetles. Evidence for gene duplications within Lampyridae are found in inactivation no afterpotential C and inactivation no afterpotential D. We also find strong support for positive selection in arrestin-2; inactivation no afterpotential D; and transient receptor potential-like; with weak support for positive selection in guanine nucleotide-binding protein G(q) subunit alpha and neither inactivation nor afterpotential C. Taken with other recent work in flies; butterflies; and moths; this represents an exciting new avenue of study as we seek to further understand diversification and constraint on the phototransduction pathway in light of organism ecology.
Polycystic Ovary Syndrome Susceptibility Loci Inform Disease Etiological Heterogeneity
Authors: Zhang Yanfei , Movva Vani C. , Williams Marc S. , Lee Ming Ta Michael
Published: June 2021

Polycystic ovary syndrome (PCOS) is a complex disorder with heterogenous phenotypes and unclear etiology. A recent phenotypic clustering study identified metabolic and reproductive subtypes of PCOS. We hypothesize that the heterogeneity of PCOS manifestations reflects different mechanistic pathways and can be identified using a genetic approach. We applied k-means clustering to categorize the genome-wide significant PCOS variants into clusters based on their associations with selected quantitative traits that likely reflect PCOS etiological pathways. We evaluated the association of each cluster with PCOS-related traits and disease outcomes. We then applied Mendelian randomization to estimate the causal effects between the traits and PCOS. Three categories of variants were identified: adiposity, insulin resistant, and reproductive. Significant associations were observed for variants in the adiposity cluster with body mass index (BMI), waist circumference and breast cancer, and variants in the insulin-resistant cluster with fasting insulin, glucose values, and homeostatic model assessment of insulin resistance (HOMA-IR). Sex hormone binding globulin (SHBG) has strong association with all three clusters. Mendelian randomization suggested a causal role of BMI and SHBG on PCOS. No causal associations were observed for PCOS on disease outcomes.