bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic Applications of Metal and Metal-Oxide Nanoparticles: Dermato-Cosmetic Perspectives
Authors: Pan Sharadwata , Goudoulas Thomas B. , Jeevanandam Jaison , Tan Kei Xian , Chowdhury Shamik , Danquah Michael K.
Published: August 2021

Invention of novel nanomaterials guaranteeing enhanced biomedical performance in diagnostics and therapeutics, is a perpetual initiative. In this regard, the upsurge and widespread usage of nanoparticles is a ubiquitous phenomenon, focusing predominantly on the application of submicroscopic (< 100 nm) particles. While this is facilitated attributing to their wide range of benefits, a major challenge is to create and maintain a balance, by alleviating the associated toxicity levels. In this minireview, we collate and discuss particularly recent advancements in therapeutic applications of metal and metal oxide nanoparticles in skin and cosmetic applications. On the one hand, we outline the dermatological intrusions, including applications in wound healing. On the other hand, we keep track of the recent trends in the development of cosmeceuticals via nanoparticle engrossments. The dermato-cosmetic applications of metal and metal oxide nanoparticles encompass diverse aspects, including targeted, controlled drug release, and conferring ultraviolet and antimicrobial protections to the skin. Additionally, we deliberate on the critical aspects in comprehending the advantage of rheological assessments, while characterizing the nanoparticulate systems. As an illustration, we single out psoriasis, to capture and comment on the nanodermatology-based curative standpoints. Finally, we lay a broad outlook and examine the imminent prospects.
Tether: A Study on Bubble-Networks
Authors: Rosa Giovanni , Pareschi Remo
Published: August 2021

Tether is a stablecoin, namely a cryptocurrency associated with an underlying security. Tether provides one of the most relevant ways to buy bitcoins and has been the centre of many controversies. In fact, it has been hypothesized that new tethers are issued without the underlying reserves, and that new massive Tether emissions are the basis of strong speculative movements on the Bitcoin, with consequent bubble effects. In the course of this article, we conduct a Social Network Analysis focused on the Tether transaction graph to identify the main actors that play a leading role on the network and characterize the transaction flow between them. From our analysis, we conclude that 1) the Tether transaction network does not enjoy the Smallworld property, with the robustness and reliability it carries with it; 2) cryptopcurrency exchanges are the nodes with the greatest centrality; 3) even Assortativity is not found, as the subjects who move Tether on a large scale do not give continuity to their presence and operations, therefore do not get a chance to consolidate stable links between them; and 4) among the exchanges, Bitfinex, which has co-ownership and co-administration relationships with the Tether issuer, can be mostly associated with the Rich-gets-Richer property.
Reconstruction of the Cytokine Signaling in Lysosomal Storage Diseases by Literature Mining and Network Analysis
Authors: Parolo Silvia , Tomasoni Danilo , Bora Pranami , Ramponi Alan , Kaddi Chanchala , Azer Karim , Domenici Enrico , Neves-Zaph Susana , Lombardo Rosario
Published: August 2021

Lysosomal storage diseases (LSDs) are characterized by the abnormal accumulation of substrates in tissues due to the deficiency of lysosomal proteins. Among the numerous clinical manifestations, chronic inflammation has been consistently reported for several LSDs. However, the molecular mechanisms involved in the inflammatory response are still not completely understood. In this study, we performed text-mining and systems biology analyses to investigate the inflammatory signals in three LSDs characterized by sphingolipid accumulation: Gaucher disease, Acid Sphingomyelinase Deficiency (ASMD), and Fabry Disease. We first identified the cytokines linked to the LSDs, and then built on the extracted knowledge to investigate the inflammatory signals. We found numerous transcription factors that are putative regulators of cytokine expression in a cell-specific context, such as the signaling axes controlled by STAT2, JUN, and NR4A2 as candidate regulators of the monocyte Gaucher disease cytokine network. Overall, our results suggest the presence of a complex inflammatory signaling in LSDs involving many cellular and molecular players that could be further investigated as putative targets of anti-inflammatory therapies.
Fusobacterium nucleatum Acts as a Pro-carcinogenic Bacterium in Colorectal Cancer: From Association to Causality
Authors: Wang Shuang , Liu Yang , Li Jun , Zhao Lei , Yan Wei , Lin Baiqiang , Guo Xiao , Wei Yunwei
Published: August 2021

Colorectal cancer (CRC) is a common cancer worldwide with complex etiology. Fusobacterium nucleatum (F. nucleatum), an oral symbiotic bacterium, has been linked with CRC in the past decade. A series of gut microbiota studies show that CRC patients carry a high abundance of F. nucleatum in the tumor tissue and fecal, and etiological studies have clarified the role of F. nucleatum as a pro-carcinogenic bacterium in various stages of CRC. In this review, we summarize the biological characteristics of F. nucleatum and the epidemiological associations between F. nucleatum and CRC, and then highlight the mechanisms by which F. nucleatum participates in CRC progression, metastasis, and chemoresistance by affecting cancer cells or regulating the tumor microenvironment (TME). We also discuss the research gap in this field and give our perspective for future studies. These findings will pave the way for manipulating gut F. nucleatum to deal with CRC in the future.
The Risk of Type 2 Diabetes and Coronary Artery Disease in Non-obese Patients With Non-alcoholic Fatty Liver Disease: A Cohort Study
Authors: Dai Wen , Zhang Ziyu , Zhao Shuiping
Published: August 2021

Background: Non-alcoholic fatty liver disease (NAFLD) is not uncommon in non-obese subjects, referred to as non-obese NAFLD. It is not fully determined whether non-obese NAFLD is associated with increased risks of type 2 diabetes (T2D) and coronary artery disease (CAD) in Chinese. This study aimed to examine the association between NAFLD and risks of T2D and CAD in a non-obese Chinese population.

Methods: The present cohort study included two stages. In the first cross-sectional study, 16,093 non-obese subjects with a body max index (BMI) < 25.0 kg/m2 were enrolled from The Second Xiangya Hospital, China, from 2011 to 2014. Hepatic steatosis was evaluated by ultrasonography examination. Logistic regression analyses were used to examine the association of non-obese NAFLD with T2D and CAD at baseline. In the subsequent 5-year follow-up study, 12,649 subjects free of T2D and CAD at baseline were included, and the incidence of T2D and CAD were observed. Cox proportional hazard regression analyses were performed to determine the risk of incident T2D and CAD with NAFLD.

Results: At baseline, the prevalence of NAFLD, T2D and CAD were 10.7% (1,717/16,093), 3.3% (529/16,093) and 0.7% (113/16,093), respectively. The univariate logistic regression analyses showed NAFLD associated with both T2D and CAD. Moreover, in a multivariate logistic regression model, NAFLD remained independently associated with T2D (OR: 2.7, 95% CI: 2.2–3.3, p < 0.001). However, no significant association was found between NAFLD and CAD by the multivariate logistic regression analyses (OR: 1.1, 95% CI: 0.6–1.8, p = 0.854). During a 5-year follow-up period, 177 (1.4%) patients developed T2D, and 134 (1.1%) developed CAD, respectively. In univariate Cox regression models, NAFLD associated with both T2D and CAD. Moreover, the multivariate Cox regression analysis revealed that NAFLD independently associated with an increased risk of T2D (HR: 2.3, 95% CI: 1.7–3.2, p < 0.001). However, the association between NAFLD and incident CAD was lost in the multivariate Cox regression analysis (HR = 1.5, 95% CI: 1.0–2.4, p = 0.059).

Conclusions: NAFLD was an independent risk factor for T2D in non-obese subjects. However, no significant association was observed between non-obese NAFLD and incident CAD after adjusting other traditional cardiovascular risk factors, suggesting these factors might mediate the increased incidence of CAD in non-obese NAFLD patients.
Use of My Health Record by Clinicians in the Emergency Department: An Analysis of Log Data
Authors: Mullins Alexandra K. , Morris Heather , Enticott Joanne , Ben-Meir Michael , Rankin David , Mantripragada Kumar , Skouteris Helen
Published: August 2021

Objectives: Leverage log data to explore access to My Health Record (MHR), the national electronic health record of Australia, by clinicians in the emergency department.

Materials and Methods: A retrospective analysis was conducted using secondary routinely-collected data. Log data pertaining to all patients who presented to the emergency department between 2019 and 2021 of a not-for-profit hospital (that annually observes 23,000 emergency department presentations) were included in this research. Attendance data and human resources data were linked with MHR log data. The primary outcome was a dichotomous variable that indicated whether the MHR of a patient was accessed. Logistic regression facilitated the exploration of factors (user role, day of the week, and month) associated with access.

Results: My Health Record was accessed by a pharmacist, doctor, or nurse in 19.60% (n = 9,262) of all emergency department presentations. Access was dominated by pharmacists (18.31%, n = 8,656). All users demonstrated a small, yet significant, increase in access every month (odds ratio = 1.07, 95% Confidence interval: 1.06–1.07, p ≤ 0.001).

Discussion: Doctors, pharmacists, and nurses are increasingly accessing MHR. Based on this research, substantially more pharmacists appear to be accessing MHR, compared to other user groups. However, only one in every five patients who present to the emergency department have their MHR accessed, thereby indicating a need to accelerate and encourage the adoption and access of MHR by clinicians.
Feasibility Study of an Earthquake Early Warning System in Eastern Central Italy
Authors: Ladina Chiara , Marzorati Simone , Amato Alessandro , Cattaneo Marco
Published: August 2021

An earthquake early warning system (EEWS) is a monitoring infrastructure that allows alerting strategic points (targets) before the arrival of strong shaking waves during an earthquake. In a region like Central Italy, struck by recent and historical destructive earthquakes, the assessment of implementation of an EEWS is a significant challenge due to the proximity of seismic sources to many potential targets, such as historical towns, industrial plants, and hospitals. In order to understand the feasibility of an EEWS in such an area, we developed an original method of event declaration simulation (EDS), a tool for assessing the effectiveness of an EEWS for existing seismic networks, improving them with new stations, and designing new networks for EEW applications. Values of the time first alert (TFA), blind zone radius (BZ), and lead time (LT) have been estimated with respect to selected targets for different network configurations in the study region. Starting from virtual sources homogeneously arranged on regular mesh grids, the alert response was evaluated for actual and improved seismic networks operating in the area, taking into account the effects of the transmission and acquisition systems. In the procedure, the arrival times of the P wave picks, the association binder, the transmission latencies, and the computation times were used to simulate the configuration of PRESTo EEWS, simulating both real-time and playback elaborations of real earthquakes. The NLLOC software was used to estimate P and S arrival times, with a local velocity model also implemented in the PRESTo EEWS. Our results show that, although Italy’s main seismic sources are located close to urban areas, the lead times calculated with the EDS procedure, applied to actual and to improved seismic networks, encourage the implementation of EEWS in the study area. Considering actual delays due to data transmission and computation time, lead times of 5–10 s were obtained simulating real historical events striking some important targets of the region. We conclude that EEWSs are useful tools that can contribute to protecting people from the harmful effects of earthquakes in Italy.
Mapping Hydrothermal Alteration at the Fentale-Dofan Magmatic Segment of the Main Ethiopian Rift
Authors: Raggiunti Martina , Keir Derek , Pagli Carolina
Published: August 2021

The Main Ethiopian Rift (MER) is characterized by extensional tectonics and volcanism, associated with active hydrothermal systems, hydrothermal alteration and fumarolic deposits. The spatial distribution of these hydrothermal products and their link with faults and rock types provides important clues to what controls fluid flow in the subsurface. However, little is known about this in the East African Rift. We address this issue with a multidisciplinary approach in the Fentale-Dofan magmatic segment of the MER, an area characterized by intense volcanic and tectonic activity and a geothermal prospect. Primarily we conduct mapping of hydrothermal alteration and fumarolic deposits, and rock lithologies using a surface feature classification technique of multispectral satellite images. Then we interpret the map using a new database of faults and active hydrothermal manifestations such as hot-springs and fumaroles. We find that the surface hydrothermal alteration and deposits are mainly focused near Fentale and the Dofan Volcanic Complex (DVC). At DVC the hydrothermal products are focused on rhyolites on the western side of the volcano, in an area of intense NNE striking, rift parallel faults. At Fentale volcano the hydrothermal products are mainly associated with ignimbrite and show a circular pattern around the volcanic edifice, but also in places follow the NNE striking faults. At Fentale, the more complex association of hydrothermal products and active manifestations around the edge of the ignimbrite suggests formation contacts may also localize fluid flow in places. At both volcanoes the association between hydrothermal products with either the rhyolites and ignimbrites is likely due to them being relatively easily altered (in comparison to basalt), and also their brittle nature allows for fracturing through which localized fluid flow can occur (as opposed to the sediments). The general pattern of hydrothermal products suggests a stronger structural influence at the DVC with respect to Fentale. The presence of hydrothermal products and active hydrothermal manifestations, along with other lines of evidence such as locus of subsurface dike intrusion at the volcanic centres, suggest that discrete and localized magma reservoirs beneath Fentale and the DVC are the heat source for hydrothermal circulation. Our study also demonstrates that geology, including hydrothermal deposits, can be successfully mapped using automated remote sensing based classification.
An Energy Efficiency Index Formation and Analysis of Integrated Energy System Based on Exergy Efficiency
Authors: Su Huiling , Huang Qifeng , Wang Zhongdong
Published: August 2021

In the context of the energy crisis and environmental deterioration, the integrated energy system (IES) based on multi-energy complementarity and cascaded utilization of energy is considered as an effective way to solve these problems. Due to the different energy forms and the various characteristics in the IES, the coupling relationships among various energy forms are complicated which enlarges the difficulty of energy efficiency evaluation of the IES. In order to flexibly analyze the energy efficiency of the IES, an operation efficiency evaluation model for the IES is established. First, energy utilization efficiency (EUE) and exergy efficiency (EXE) are proposed based on the first/second law of thermodynamics. Second, the energy efficiency models for five processes and four subsystems of the IES are formed. Lastly, an actual commercial-industrial park with integrated energy is employed to validate the proposed method.
Citizen Science for Quantification of Insect Abundance on Windshields of Cars Across Two Continents
Authors: Møller Anders Pape , Czeszczewik Dorota , Erritzøe Johannes , Flensted-Jensen Einar , Laursen Karsten , Liang Wei , Walankiewicz Wiesław
Published: August 2021

The abundance and the diversity of insects in Europe have declined considerably during recent decades, while it remains unclear whether similar changes may also have occurred elsewhere. Here we used citizen science for quantifying the abundance of flying insects on windshields of cars across Europe and to a smaller extent in China. We used the abundance of insects killed against windshields of cars during 3,530 transects for a total distance of 83,019 km made by 50 observers as estimates of insect abundance. A total of 124,606 insects were recorded, or approximately 1.5 insect per km. The abundance of insects killed against windshields was highly repeatable among days for the same locality, showing consistent estimates of abundance. The main determinants of insect abundance were features of cars (driving speed and car model that can be considered noise of no biological significance), local weather (temperature, cloud cover and wind speed) and variation across the season and the day. We tested for differences in the abundance of flying insects killed on windshields of cars predicting and finding (1) a reduction in insect abundance in areas with ionizing radiation at Chernobyl compared to uncontaminated control sites in the neighborhood, (2) a reduction in the abundance of flying insects in Western compared to Eastern Europe, (3) a reduction in the abundance of flying insects killed on windshields from southern to northern Europe compared to latitudinal samples of insects from southern to northern China, and (4) a difference in abundance of insects killed on windshields of cars in Spain with a significant interaction between Spain and Denmark. Thus a number of abiotic and biotic factors accounted for temporal and spatial heterogeneity in abundance of insects, providing a useful tool for monitoring and studying determinants of spatial and temporal patterns of insect abundance. This also implies that our estimate of insect abundance may be relevant for the study of competition and for interactions at higher trophic levels.
The Role of Distinct Subsets of Macrophages in the Pathogenesis of MS and the Impact of Different Therapeutic Agents on These Populations
Authors: Radandish Maedeh , Khalilian Parvin , Esmaeil Nafiseh
Published: August 2021

Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central nervous system (CNS). Besides the vital role of T cells, other immune cells, including B cells, innate immune cells, and macrophages (MФs), also play a critical role in MS pathogenesis. Tissue-resident MФs in the brain’s parenchyma, known as microglia and monocyte-derived MФs, enter into the CNS following alterations in CNS homeostasis that induce inflammatory responses in MS. Although the neuroprotective and anti-inflammatory actions of monocyte-derived MФs and resident MФs are required to maintain CNS tolerance, they can release inflammatory cytokines and reactivate primed T cells during neuroinflammation. In the CNS of MS patients, elevated myeloid cells and activated MФs have been found and associated with demyelination and axonal loss. Thus, according to the role of MФs in neuroinflammation, they have attracted attention as a therapeutic target. Also, due to their different origin, location, and turnover, other strategies may require to target the various myeloid cell populations. Here we review the role of distinct subsets of MФs in the pathogenesis of MS and different therapeutic agents that target these cells.
Genetic Prioritization, Therapeutic Repositioning and Cross-Disease Comparisons Reveal Inflammatory Targets Tractable for Kidney Stone Disease
Authors: Fang Hai , Jiang Lulu
Published: August 2021

Background

Formation of kidney stones resulting in urological disorders remains a major cause of morbidity in renal diseases and many others. Innate immunity, mainly inflammasome, has demonstrated a key role in the development of kidney stone disease (or “nephrolithiasis”), but a molecular rationale for therapeutic intervention targeting immunity is far from clear. We reason that identifying inflammatory gene networks underlying disease risk would inform immunotherapeutic targets for candidate drug discovery.

Results

We generated an atlas of genetic target prioritization, with the top targets highly enriched for genes involved in the NF-kB regulation, including interaction neighbors of inflammasome genes. We identified a network of highly ranked and interconnecting genes that are of functional relevance to nephrolithiasis and mediate crosstalk between inflammatory pathways. Crosstalk genes can be utilized for therapeutic repositioning, as highlighted by identification of ulixertinib and losmapimod that are both under clinical investigation as inhibitors of inflammatory mediators. Finally, we performed cross-disease comparisons and druggable pocket predictions, identifying inflammatory targets that are specific to and tractable for nephrolithiasis.

Conclusion

Genetic targets and candidate drugs, in silico identified in this study, provide the rich information of how to target innate immune pathways, with the potential of advancing immunotherapeutic strategies for nephrolithiasis.
RETRACTED: Harnessing TRAIL-Induced Apoptosis Pathway for Cancer Immunotherapy and Associated Challenges
Authors: Razeghian Ehsan , Suksatan Wanich , Sulaiman Rahman Heshu , Bokov Dmitry O. , Abdelbasset Walid Kamal , Hassanzadeh Ali , Marofi Faroogh , Yazdanifar Mahboubeh , Jarahian Mostafa
Published: August 2021

The immune cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted rapidly evolving attention as a cancer treatment modality because of its competence to selectively eliminate tumor cells without instigating toxicity in vivo. TRAIL has revealed encouraging promise in preclinical reports in animal models as a cancer treatment option; however, the foremost constraint of the TRAIL therapy is the advancement of TRAIL resistance through a myriad of mechanisms in tumor cells. Investigations have documented that improvement of the expression of anti-apoptotic proteins and survival or proliferation involved signaling pathways concurrently suppressing the expression of pro-apoptotic proteins along with down-regulation of expression of TRAILR1 and TRAILR2, also known as death receptor 4 and 5 (DR4/5) are reliable for tumor cells resistance to TRAIL. Therefore, it seems that the development of a therapeutic approach for overcoming TRAIL resistance is of paramount importance. Studies currently have shown that combined treatment with anti-tumor agents, ranging from synthetic agents to natural products, and TRAIL could result in induction of apoptosis in TRAIL-resistant cells. Also, human mesenchymal stem/stromal cells (MSCs) engineered to generate and deliver TRAIL can provide both targeted and continued delivery of this apoptosis-inducing cytokine. Similarly, nanoparticle (NPs)-based TRAIL delivery offers novel platforms to defeat barricades to TRAIL therapeutic delivery. In the current review, we will focus on underlying mechanisms contributed to inducing resistance to TRAIL in tumor cells, and also discuss recent findings concerning the therapeutic efficacy of combined treatment of TRAIL with other antitumor compounds, and also TRAIL-delivery using human MSCs and NPs to overcome tumor cells resistance to TRAIL.
Immunogenic Cell Death Induction by Ionizing Radiation
Authors: Zhu Mengqin , Yang Mengdie , Zhang Jiajia , Yin Yuzhen , Fan Xin , Zhang Yu , Qin Shanshan , Zhang Han , Yu Fei
Published: August 2021

Immunogenic cell death (ICD) is a form of regulated cell death (RCD) induced by various stresses and produces antitumor immunity via damage-associated molecular patterns (DAMPs) release or exposure, mainly including high mobility group box 1 (HMGB1), calreticulin (CRT), adenosine triphosphate (ATP), and heat shock proteins (HSPs). Emerging evidence has suggested that ionizing radiation (IR) can induce ICD, and the dose, type, and fractionation of irradiation influence the induction of ICD. At present, IR-induced ICD is mainly verified in vitro in mice and there is few clinical evidence about it. To boost the induction of ICD by IR, some strategies have shown synergy with IR to enhance antitumor immune response, such as hyperthermia, nanoparticles, and chemotherapy. In this review, we focus on the molecular mechanisms of ICD, ICD-promoting factors associated with irradiation, the clinical evidence of ICD, and immunogenic forms of cell death. Finally, we summarize various methods of improving ICD induced by IR.
Defining a Methylation Signature Associated With Operational Tolerance in Kidney Transplant Recipients
Authors: Rodriguez Ramon M. , Hernández-Fuentes María P. , Corte-Iglesias Viviana , Saiz María Laura , Lozano Juan José , Cortazar Ana R. , Mendizabal Isabel , Suarez-Fernandez María Luisa , Coto Eliecer , López-Vázquez Antonio , Díaz-Corte Carmen , Aransay Ana M. , López-Larrea Carlos , Suarez-Álvarez Beatriz
Published: August 2021

Operational tolerance after kidney transplantation is defined as stable graft acceptance without the need for immunosuppression therapy. However, it is not clear which cellular and molecular pathways are driving tolerance in these patients. We performed genome-wide analysis of DNA methylation in peripheral blood mononuclear cells from kidney transplant recipients with chronic rejection and operational tolerance from the Genetic Analysis of Molecular Biomarkers of Immunological Tolerance (GAMBIT) study. Our results showed that both clinical stages diverge in 2737 genes, indicating that each one has a specific methylation signature associated with transplant outcome. We also observed that tolerance is associated with demethylation in genes involved in immune function, including B and T cell activation and Th17 differentiation, while in chronic rejection it is associated with intracellular signaling and ubiquitination pathways. Using co-expression network analysis, we selected 12 genomic regions that are specifically hypomethylated or hypermethylated in tolerant patients. Analysis of these genes in transplanted patients with low dose of steroids showed that these have a similar methylation signature to that of tolerant recipients. Overall, these results demonstrate that methylation analysis can mirror the immune status associated with transplant outcome and provides a starting point for understanding the epigenetic mechanisms associated with tolerance.
Comparison of Neutralizing Dengue Virus B Cell Epitopes and Protective T Cell Epitopes With Those in Three Main Dengue Virus Vaccines
Authors: Pinheiro Josilene Ramos , Camilo dos Reis Esther , Souza Rayane da Silva Oliveira , Rocha Ana Luíza Silva , Suesdek Lincoln , Azevedo Vasco , Tiwari Sandeep , Rocha Beatriz Gonçalves Silva , Birbrair Alexander , Méndez Erick Carvalho , Luiz Wilson Barros , Amorim Jaime Henrique
Published: August 2021

The four serotypes of Dengue virus (DENV1-4) are arboviruses (arthropod-borne viruses) that belong to the Flavivirus genus, Flaviviridae family. They are the causative agents of an infectious disease called dengue, an important global public health problem with significant social-economic impact. Thus, the development of safe and effective dengue vaccines is a priority according to the World Health Organization. Only one anti-dengue vaccine has already been licensed in endemic countries and two formulations are under phase III clinical trials. In this study, we aimed to compare the main anti-dengue virus vaccines, DENGVAXIA®, LAV-TDV, and TAK-003, regarding their antigens and potential to protect. We studied the conservation of both, B and T cell epitopes involved in immunological control of DENV infection along with vaccine viruses and viral isolates. In addition, we assessed the population coverage of epitope sets contained in each vaccine formulation with regard to different human populations. As main results, we found that all three vaccines contain the main B cell epitopes involved in viral neutralization. Similarly, LAV-TDV and TAK-003 contain most of T cell epitopes involved in immunological protection, a finding not observed in DENGVAXIA®, which explains main limitations of the only licensed dengue vaccine. In summary, the levels of presence and absence of epitopes that are target for protective immune response in the three main anti-dengue virus vaccines are shown in this study. Our results suggest that investing in vaccines that contain the majority of epitopes involved in protective immunity (cellular and humoral arms) is an important issue to be considered.
The Weekend Drug; Recreational Use of Sildenafil Citrate and Concomitant Factors: A Cross-Sectional Study
Authors: Atsbeha Berhanemeskel Weldegerima , Kebede Beza Tefera , Birhanu Biruktawit Shewafera , Yimenu Dawit Kumilachew , Belay Wudneh Simegn , Demeke Chilot Abiyu
Published: August 2021

Background: Men who use erectile dysfunction medications for recreational purposes may be at increased risk of becoming psychologically dependent, which in turn could lead to psychogenic-based erectile dysfunction symptoms. Sildenafil has become one of the most commonly prescribed and abused drugs available today.

Objectives: This study aimed to describe the utilization pattern and associated factors of sildenafil citrate among its users visiting community pharmacies in Gondar, Ethiopia.

Methods: A facility-based cross-sectional study was conducted from March 20, 2017 to May 10, 2017, among male clients who visited community pharmacies in Gondar town, North West Ethiopia. A self-administered, structured questionnaire was used to collect data from Sildenafil users older than 18 years, that started using the drug (Sildenafil) for at least 6 months before the data collection period. A regression analysis was conducted to determine the association between study variables, and a P-value of <0.05 was considered to declare statistical significance.

Results: A total of 65 men participated in the study. Of the total study participants, 33.8% were aged 25–34 years and about 40% of them had multiple sexual partners. The use of sildenafil for recreational purposes was 66.2% and was found to be higher than its use for medical purposes 33.8%. Use of the drug for <1-year duration (AOR = 34.086, 95% CI [2.90, 401.37]) and 2 years duration (AOR = 21.42: 95% CI [2.10, 218.82]) were significantly associated with its use for recreational purpose. Non-recreational use of sildenafil includes erectile problems associated with diabetes mellitus (27.1%), heart disease (9.2%), hyperlipidemia (4.2%), and relationship problems due to stress and poor communication (3.1%).

Conclusion: Most men who use sildenafil citrate do so for recreational purposes, and use of sildenafil citrate for 2 years or less was associated with recreational use. There should be a collaborative effort among pharmacists, health professionals, and policymakers to improve the rational use of sildenafil.
Role of Dermoscopy in the Assessment of Basal Cell Carcinoma
Authors: Ungureanu Loredana , Cosgarea Ioana , Şenilǎ Simona , Vasilovici Alina
Published: August 2021

Basal cell carcinoma is one of the most common cancers in white people, with a continuous increase worldwide. Dermoscopy, a non-invasive technique, allows early diagnosis based on the presence of typical vascular structures, pigmented structures, and ulceration and the absence of specific melanocytic structures. Moreover, dermoscopy is useful in basal cell carcinoma management, enabling the differentiation between multiple histological subtypes, between pigmented and non-pigmented variants and allowing a more accurate assessment of surgical margins. After non-ablative therapies, dermoscopy allows the accurate detection of residual disease. The purpose of this review is to highlight the dermoscopic features encountered in basal cell carcinoma and to outline the role of dermoscopy for diagnosis and therapeutic response in this cancer.
Coagulation Dysfunction in Acute Respiratory Distress Syndrome and Its Potential Impact in Inflammatory Subphenotypes
Authors: Livingstone Samantha A. , Wildi Karin S. , Dalton Heidi J. , Usman Asad , Ki Katrina K. , Passmore Margaret R. , Li Bassi Gianluigi , Suen Jacky Y. , Fraser John F.
Published: August 2021

The Acute Respiratory Distress Syndrome (ARDS) has caused innumerable deaths worldwide since its initial description over five decades ago. Population-based estimates of ARDS vary from 1 to 86 cases per 100,000, with the highest rates reported in Australia and the United States. This syndrome is characterised by a breakdown of the pulmonary alveolo-epithelial barrier with subsequent severe hypoxaemia and disturbances in pulmonary mechanics. The underlying pathophysiology of this syndrome is a severe inflammatory reaction and associated local and systemic coagulation dysfunction that leads to pulmonary and systemic damage, ultimately causing death in up to 40% of patients. Since inflammation and coagulation are inextricably linked throughout evolution, it is biological folly to assess the two systems in isolation when investigating the underlying molecular mechanisms of coagulation dysfunction in ARDS. Although the body possesses potent endogenous systems to regulate coagulation, these become dysregulated and no longer optimally functional during the acute phase of ARDS, further perpetuating coagulation, inflammation and cell damage. The inflammatory ARDS subphenotypes address inflammatory differences but neglect the equally important coagulation pathway. A holistic understanding of this syndrome and its subphenotypes will improve our understanding of underlying mechanisms that then drive translation into diagnostic testing, treatments, and improve patient outcomes.
Severe SARS-CoV-2 Breakthrough Reinfection With Delta Variant After Recovery From Breakthrough Infection by Alpha Variant in a Fully Vaccinated Health Worker
Authors: Shastri Jayanthi , Parikh Swapneil , Aggarwal Veena , Agrawal Sachee , Chatterjee Nirjhar , Shah Rajit , Devi Priti , Mehta Priyanka , Pandey Rajesh
Published: August 2021

Background: Post infection immunity and post vaccination immunity both confer protection against COVID-19. However, there have been many whole genome sequencing proven reinfections and breakthrough infections. Both are most often mild and caused by Variants of Concern (VOC).

Methods: The patient in our study underwent serial COVID-19 RT-PCR, blood tests for serology, acute phase reactants, and chest imaging as part of clinical care. We interviewed the patient for clinical history and retrieved reports and case papers. We retrieved stored RT-PCR positive samples for whole genome sequencing (WGS) of SARS-CoV-2 from the patient's breakthrough infections and the presumed index case.

Findings: The patient had three RT-PCR confirmed SARS-CoV-2 infections. Two breakthrough infections occurred in quick succession with the first over 3 weeks after complete vaccination with COVISHIELD and despite post-vaccination seroconversion. The first breakthrough infection was due to the Alpha variant and the second due to the Delta variant. The Delta variant infection resulted in hypoxia, hospitalization, and illness lasting seven weeks. Serial serology, acute phase reactants, and chest imaging supported WGS in establishing distinct episodes of infection. WGS established a fully vaccinated family member as the index case.

Interpretation: The patient had an Alpha variant breakthrough infection despite past infection, complete vaccination, and seroconversion. Despite boosting after this infection, the patient subsequently had a severe Delta variant breakthrough infection. This was also a WGS proven reinfection and, therefore, a case of breakthrough reinfection. The patient acquired the infection from a fully vaccinated family member.
Pseudomonas palmensis sp. nov., a Novel Bacterium Isolated From Nicotiana glauca Microbiome: Draft Genome Analysis and Biological Potential for Agriculture
Authors: Gutierrez-Albanchez Enrique , García-Villaraco Ana , Lucas José A. , Horche Ignacio , Ramos-Solano Beatriz , Gutierrez-Mañero F. J.
Published: August 2021

A novel Pseudomonas, designated strain BBB001T, an aerobic, rod-shaped bacterium, was isolated from the rhizosphere of Nicotiana glauca in Las Palmas Gran Canaria, Spain. Genomic analysis revealed that it could not be assigned to any known species of Pseudomonas, so the name Pseudomonas palmensis sp. nov. was proposed. A 16S rRNA gene phylogenetic analysis suggested affiliation to the Pseudomonas brassicae group, being P. brassicae MAFF212427 T the closest related type strain. Upon genomic comparisons of both strains, all values were below thresholds established for differentiation: average nucleotide identity (ANI, 88.29%), average amino acid identity (AAI, 84.53%), digital DNA-DNA hybridization (dDDH, 35.4%), and TETRA values (0.98). When comparing complete genomes, a total of 96 genes present exclusively in BBB001T were identified, 80 of which appear associated with specific subsystems. Phenotypic analysis has shown its ability to assimilate glucose, potassium gluconate, capric acid malate, trisodium citrate, and phenylacetic acid; it was oxidase positive. It is able to produce auxins and siderophores in vitro; its metabolic profile based on BIOLOG Eco has shown a high catabolic capacity. The major fatty acids accounting for 81.17% of the total fatty acids were as follows: C16:0 (33.29%), summed feature 3 (22.80%) comprising C16:1 ω7c and C16:1 ω6c, summed feature 8 (13.66%) comprising C18:1 ω7c, and C18:1ω6c and C17:0 cyclo (11.42%). The ability of this strain to improve plant fitness was tested on tomato and olive trees, demonstrating a great potential for agriculture as it is able to trigger herbaceous and woody species. First, it was able to improve iron nutrition and growth on iron-starved tomatoes, demonstrating its nutrient mobilization capacity; this effect is related to its unique genes related to iron metabolism. Second, it increased olive and oil yield up to 30% on intensive olive orchards under water-limiting conditions, demonstrating its capacity to improve adaptation to adverse conditions. Results from genomic analysis together with differences in phenotypic features and chemotaxonomic analysis support the proposal of strain BBB001T (=LMG 31775T = NCTC 14418T) as the type strain of a novel species for which the name P. palmensis sp. nov is proposed.
Pan-Genome-Wide Analysis of Pantoea ananatis Identified Genes Linked to Pathogenicity in Onion
Authors: Agarwal Gaurav , Choudhary Divya , Stice Shaun P. , Myers Brendon K. , Gitaitis Ronald D. , Venter Stephanus N. , Kvitko Brian H. , Dutta Bhabesh
Published: August 2021

Pantoea ananatis, a gram negative and facultative anaerobic bacterium is a member of aPantoeaspp. complex that causes center rot of onion, which significantly affects onion yield and quality. This pathogen does not have typical virulence factors like type II or type III secretion systems but appears to require a biosynthetic gene-cluster, HiVir/PASVIL (located chromosomally comprised of 14 genes), for a phosphonate secondary metabolite, and the ‘alt’ gene cluster (located in plasmid and comprised of 11 genes) that aids in bacterial colonization in onion bulbs by imparting tolerance to thiosulfinates. We conducted a deep pan-genome-wide association study (pan-GWAS) to predict additional genes associated with pathogenicity inP. ananatisusing a panel of diverse strains (n= 81). We utilized a red-onion scale necrosis assay as an indicator of pathogenicity. Based on this assay, we differentiated pathogenic (n= 51)- vs. non-pathogenic (n= 30)-strains phenotypically. Pan-genome analysis revealed a large core genome of 3,153 genes and a flexible accessory genome. Pan-GWAS using the presence and absence variants (PAVs) predicted 42 genes, including 14 from the previously identified HiVir/PASVIL cluster associated with pathogenicity, and 28 novel genes that were not previously associated with pathogenicity in onion. Of the 28 novel genes identified, eight have annotated functions of site-specific tyrosine kinase, N-acetylmuramoyl-L-alanine amidase, conjugal transfer, and HTH-type transcriptional regulator. The remaining 20 genes are currently hypothetical. Further, a core-genome SNPs-based phylogeny and horizontal gene transfer (HGT) studies were also conducted to assess the extent of lateral gene transfer among diverseP. ananatisstrains. Phylogenetic analysis based on PAVs and whole genome multi locus sequence typing (wgMLST) rather than core-genome SNPs distinguished red-scale necrosis inducing (pathogenic) strains from non-scale necrosis inducing (non-pathogenic) strains ofP. ananatis. A total of 1182 HGT events including the HiVir/PASVIL andaltcluster genes were identified. These events could be regarded as a major contributing factor to the diversification, niche-adaptation and potential acquisition of pathogenicity/virulence genes inP. ananatis.
Deciphering the Shifts in Microbial Community Diversity From Material Pretreatment to Saccharification Process of Fuyu-Flavor Baijiu
Authors: Kang Jiamu , Hu Yunan , Ding Ziyuan , Ye Li , Li Haoran , Cheng Jun , Fan Lin , Zhao Hu , Han Beizhong , Zheng Xiaowei
Published: August 2021

The microbiota of the pretreatment phase is crucial to the assembly of the microbial community in the saccharification of fuyu-flavor baijiu. This study investigates the shifts in microbial community diversity from the pretreatment of raw materials to the end of saccharification. High-throughput sequencing reveals that Lactobacillus, Weissella, and Bacillus in the bacterial community and Rhizopus, Candida, Pichia, and Aspergillus in the fungal community are predominant during raw material pretreatment and saccharification processes. Also, 11 bacterial genera, including Bacillus, Lactobacillus, Leuconostoc, Weissella, Lactococcus, and Acetobacter, and eight yeast genera, including Candida, Pichia, Saccharomyces, and Wickerhamomyces, were isolated from the initial saccharification stage by culture-dependent approaches. Sourcetracker analysis indicates that the cooling grains and rice husks were the main contributors to the bacterial community composition of the saccharification process, and Qu was the main contributor to the shaping of the fungal community structure during the saccharification process. Abundance variation of the predictive functional profiles of microbial communities encoding for key enzymes involved in pyruvate metabolism, starch and sucrose metabolism, and glycolysis/gluconeogenesis during the pretreatment and saccharification phases were inferred by PICRUSt2 analysis. The results of this study will be utilized to produce consistently high-quality fuyu-flavor baijiu via better controlling the shaping of microbial community structures during the pretreatment and fermentation processes.
Establishing an Efficient Genetic Manipulation System for Sulfated Echinocandin Producing Fungus Coleophoma empetri
Authors: Men Ping , Wang Min , Li Jinda , Geng Ce , Huang Xuenian , Lu Xuefeng
Published: August 2021

Micafungin is an important echinocandin antifungal agent for the treatment of invasive fungal infections. In industry, micafungin is derived from the natural product FR901379, which is a non-ribosomal cyclic hexapeptide produced by the filamentous fungus Coleophoma empetri. The difficulty of genetic manipulation in C. empetri restricts the clarification of FR901379 biosynthetic mechanism. In this work, we developed an efficient genetic manipulation system in the industrial FR901379-producing strain C. empetri MEFC009. Firstly, a convenient protoplast-mediated transformation (PMT) method was developed. Secondly, with this transformation method, the essential genetic elements were verified. Selectable markers hph, neo, and nat can be used for the transformation, and promotors Ppgk, PgpdA, and PgpdAt are functional in C. empetri MEFC009. Thirdly, the frequency of homologous recombination was improved from 4 to 100% by deleting the ku80 gene, resulting in an excellent chassis cell for gene-targeting. Additionally, the advantage of this genetic manipulation system was demonstrated in the identification of the polyketide synthase (PKS) responsible for the biosynthesis of dihydroxynapthalene (DHN)-melanin. This genetic manipulation system will be a useful platform for the research of FR901379 and further genome mining of secondary metabolites in C. empetri.
Prospective Memory and Regional Functional Connectivity in Subcortical Ischemic Vascular Disease
Authors: Zhuang Xuan-Miao , Kuo Li-Wei , Lin Shih-Yen , Yang Jir-Jei , Tu Min-Chien , Hsu Yen-Hsuan
Published: August 2021

Objectives: Patients with subcortical ischemic vascular disease (SIVD) often have prominent frontal dysfunction. However, it remains unclear how SIVD affects prospective memory (PM), which strongly relies on the frontoparietal network. The present study aimed to investigate PM performance in patients with early stage SIVD as compared to those with Alzheimer's disease (AD) and to older adults with normal cognition, and to explore the neural correlates of PM deficits.

Method: Patients with very-mild to mild dementia due to SIVD or AD and normal controls (NC) aged above 60 years were recruited. Seventy-three participants (20 SIVD, 22 AD, and 31 NC) underwent structural magnetic resonance imaging (MRI), cognitive screening tests, and a computerized PM test. Sixty-five of these participants (19 SIVD, 20 AD, and 26 NC) also received resting-state functional MRI.

Results: The group with SIVD had significantly fewer PM hits than the control group on both time-based and non-focal event-based PM tasks. Among patients in the very early stage, only those with SIVD but not AD performed significantly worse than the controls. Correlational analyses showed that non-focal event-based PM in SIVD was positively correlated with regional homogeneity in bilateral superior and middle frontal gyri, while time-based PM was not significantly associated with regional homogeneity in any of the regions of interest within the dorsal frontoparietal regions.

Conclusions: The findings of this study highlight the vulnerability of non-focal event-based PM to the disruption of regional functional connectivity in bilateral superior and middle frontal gyri in patients with SIVD.
N-Truncated Aβ Starting at Position Four—Biochemical Features, Preclinical Models, and Potential as Drug Target in Alzheimer’s Disease
Authors: Bayer Thomas A.
Published: August 2021

The discussion of whether amyloid plaque Aβ is a valid drug target to fight Alzheimer’s disease (AD) has been a matter of scientific dispute for decades. This question can only be settled by successful clinical trials and the approval of disease-modifying drugs. However, many clinical trials with antibodies against different regions of the amyloid Aβ peptide have been discontinued, as they did not meet the clinical endpoints required. Recently, passive immunization of AD patients with Donanemab, an antibody directed against the N-terminus of pyroglutamate Aβ, showed beneficial effects in a phase II trial, supporting the concept that N-truncated Aβ is a relevant target for AD therapy. There is long-standing evidence that N-truncated Aβ variants are the main variants found in amyloid plaques besides full-length Aβ1–42, t, therefore their role in triggering AD pathology and as targets for drug development are of interest. While the contribution of pyroglutamate Aβ3–42 to AD pathology has been well studied in the past, the potential role of Aβ4–42 has been largely neglected. The present review will therefore focus on Aβ4–42 as a possible drug target based on human and mouse pathology, in vitro and in vivo toxicity, and anti-Aβ4-X therapeutic effects in preclinical models.