bluuebunny/crossref_metadata_2025 huggingface dataset:
Long Term Physical Activity Improves Quality of Life Perception, Healthy Nutrition, and Daily Life Management in Elderly: A Randomized Controlled Trial
Authors: Fiorilli Giovanni , Buonsenso Andrea , Centorbi Marco , Calcagno Giuseppe , Iuliano Enzo , Angiolillo Antonella , Ciccotelli Santina , di Cagno Alessandra , Di Costanzo Alfonso
Published: June 2022

Physical activity (PA) is a key element in the management of successful aging. The aim of this paper was to show the effects of PA on the quality of life perception, nutritional status, and daily life management of 178 older adults (aged 63.87 ± 8.17) randomly assigned to an Experimental Group (EG), which performed moderate-to-high intensity aerobic and strengthening training, and a Control Group (CG) which performed low-impact PA, assessed after 6, 12, and 24 months. The Short-Form Health Survey (SF-36), Mini Nutritional Assessment (MNA), and Physical Activity Scale for the Elderly (PASE) were used for the study. In the SF-36 assessment, EG showed a good quality of life perception maintained after 24 months, while CG showed a worsening in the same period (p = 0.018). The EG reported a significant better nutritional status as compared to pre-intervention assessment (p = 0.003) and to CG (p < 0.001). Regarding the PASE, the EG showed a higher level of weekly activities than the CG after 24 months (p = 0.011), while the CG showed a worsening after 12 months (p = 0.008). The prolonged engagement in moderate-to high-intensity PA allowed the maintenance of a good quality of life perception, a good level of nutritional status, and daily life activities.
Faecal Microbiota Transplantation and Chronic Kidney Disease
Authors: Bian Ji , Liebert Ann , Bicknell Brian , Chen Xin-Ming , Huang Chunling , Pollock Carol A.
Published: June 2022

Faecal microbiota transplantation (FMT) has attracted increasing attention as an intervention in many clinical conditions, including autoimmune, enteroendocrine, gastroenterological, and neurological diseases. For years, FMT has been an effective second-line treatment for Clostridium difficile infection (CDI) with beneficial outcomes. FMT is also promising in improving bowel diseases, such as ulcerative colitis (UC). Pre-clinical and clinical studies suggest that this microbiota-based intervention may influence the development and progression of chronic kidney disease (CKD) via modifying a dysregulated gut–kidney axis. Despite the high morbidity and mortality due to CKD, there are limited options for treatment until end-stage kidney disease occurs, which results in death, dialysis, or kidney transplantation. This imposes a significant financial and health burden on the individual, their families and careers, and the health system. Recent studies have suggested that strategies to reverse gut dysbiosis using FMT are a promising therapy in CKD. This review summarises the preclinical and clinical evidence and postulates the potential therapeutic effect of FMT in the management of CKD.
The New Coronavirus Infection (COVID-19) and Hearing Function in Adults
Authors: Boboshko Maria Y. , Garbaruk Ekaterina S. , Vikhnina Sof’ya M. , Golovanova Larisa E. , Ogorodnikova Elena A. , Rabchevskaya Anna V. , Zhilinskaia Ekaterina V.
Published: June 2022

In this study, we assessed the impact of COVID-19 on the hearing function in adults. A total of 161 subjects were examined, and the results of a previous audiological examination of 24 patients were reviewed. Pure tone audiometry, impedancemetry, speech audiometry in quiet and noise, the Binaural Fusion Test, the dichotic digits test, and a cognitive status examination were performed. A total of 81% of patients complained about hearing disorders, and 43% noted memory impairment. According to pure tone audiometry, 24% of the subjects had normal hearing, while 76% had some degree of hearing loss. No significant changes in hearing thresholds were found in comparison with audiological examinations performed before COVID-19. Disorder of monosyllabic words’ intelligibility in quiet was found in 33% of patients, and in 42% in noise, along with low indicators in the dichotic digits test in 54% of patients. Moreover, 71% of patients had low scores on the MoCA scale that indicated cognitive impairment. Conclusions: The deterioration of speech test scores in patients after COVID-19 can occur due to central auditory processing disorders (CAPD), memory impairment, or changes in cognitive status in general.
Lost in Translation: Exploring microRNA Biogenesis and Messenger RNA Fate in Anoxia-Tolerant Turtles
Authors: Breedon Sarah A. , Storey Kenneth B.
Published: June 2022

Red-eared slider turtles face natural changes in oxygen availability throughout the year. This includes long-term anoxic brumation where they reduce their metabolic rate by ~90% for months at a time, which they survive without apparent tissue damage. This metabolic rate depression (MRD) is underlaid by various regulatory mechanisms, including messenger RNA (mRNA) silencing via microRNA (miRNA), leading to mRNA decay or translational inhibition in processing bodies (P-bodies) and stress granules. Regulation of miRNA biogenesis was assessed in red-eared slider turtle liver and skeletal muscle via immunoblotting. Hepatic miRNA biogenesis was downregulated in early processing steps, while later steps were upregulated. These contradictory findings indicate either overall decreased miRNA biogenesis, or increased biogenesis if sufficient pre-miRNA stores were produced in early anoxia. Conversely, muscle showed clear upregulation of multiple biogenesis steps indicating increased miRNA production. Additionally, immunoblotting indicated that P-bodies may be favoured by the liver for mRNA storage/decay during reoxygenation with a strong suppression of stress granule proteins in anoxia and reoxygenation. Muscle however showed downregulation of P-bodies during anoxia and reoxygenation, and upregulation of stress granules for mRNA storage during reoxygenation. This study advances our understanding of how these champion anaerobes regulate miRNA biogenesis to alter miRNA expression and mRNA fate during prolonged anoxia.
The Role of Acetate Kinase in the Human Parasite Entamoeba histolytica
Authors: Dang Thanh , Angel Matthew , Cho Jin , Nguyen Diana , Ingram-Smith Cheryl
Published: June 2022

The human parasite Entamoeba histolytica, which causes approximately 100 million cases of amoebic dysentery each year, relies on glycolysis as the major source of ATP production from glucose as it lacks a citric acid cycle and oxidative phosphorylation. Ethanol and acetate, the two major glycolytic end products for E. histolytica, are produced at a ratio of 2:1 under anaerobic conditions, creating an imbalance between NADH production and utilization. In this study we investigated the role of acetate kinase (ACK) in acetate production during glycolysis in E. histolytica metabolism. Analysis of intracellular and extracellular metabolites demonstrated that acetate levels were unaffected in an ACK RNAi cell line, but acetyl-CoA levels and the NAD+/NADH ratio were significantly elevated. Moreover, we demonstrated that glyceraldehyde 3-phosphate dehydrogenase catalyzes the ACK-dependent conversion of acetaldehyde to acetyl phosphate in E. histolytica. We propose that ACK is not a major contributor to acetate production, but instead provides a mechanism for maintaining the NAD+/NADH balance during ethanol production in the extended glycolytic pathway.
Probe Capture Enrichment Methods for HIV and HCV Genome Sequencing and Drug Resistance Genotyping
Authors: Munyuza Chantal , Ji Hezhao , Lee Emma R.
Published: June 2022

Human immunodeficiency virus (HIV) infections remain a significant public health concern worldwide. Over the years, sophisticated sequencing technologies such as next-generation sequencing (NGS) have emerged and been utilized to monitor the spread of HIV drug resistance (HIVDR), identify HIV drug resistance mutations, and characterize transmission dynamics. Similar applications also apply to the Hepatitis C virus (HCV), another bloodborne viral pathogen with significant intra-host genetic diversity. Several advantages to using NGS over conventional Sanger sequencing include increased data throughput, scalability, cost-effectiveness when batched sample testing is performed, and sensitivity for quantitative detection of minority resistant variants. However, NGS alone may fail to detect genomes from pathogens present in low copy numbers. As with all sequencing platforms, the primary determinant in achieving quality sequencing data is the quality and quantity of the initial template input. Samples containing degraded RNA/DNA and/or low copy number have been a consistent sequencing challenge. To overcome this limitation probe capture enrichment is a method that has recently been employed to target, enrich, and sequence the genome of a pathogen present in low copies, and for compromised specimens that contain poor quality nucleic acids. It involves the hybridization of sequence-specific DNA or RNA probes to a target sequence, which is followed by an enrichment step via PCR to increase the number of copies of the targeted sequences after which the samples are subjected to NGS procedures. This method has been performed on pathogens such as bacteria, fungus, and viruses and allows for the sequencing of complete genomes, with high coverage. Post NGS, data analysis can be performed through various bioinformatics pipelines which can provide information on genetic diversity, genotype, virulence, and drug resistance. This article reviews how probe capture enrichment helps to increase the likelihood of sequencing HIV and HCV samples that contain low viral loads and/or are compromised.
Efficacy of a Fungal Formulation with the Nematophagous Fungus Pochonia chlamydosporia in the Biological Control of Bovine Nematodiosis
Authors: Fonseca Júlia dos Santos , Ferreira Vinícius Monteiro , Freitas Samuel Galvão de , Vieira Ítalo Stoupa , Araújo Jackson Victor de
Published: June 2022

In the control of bovine worms, biological control by nematophagous fungi stands out, especially Pochoniachlamydosporia which causes the destruction of helminth eggs. This study aims to test the effectiveness of a formulation containing the nematophagous fungus Pochonia chlamydosporia isolated for the biological control of bovine nematodiosis. Twelve cattle were divided into two groups: control group (GC) and the group that received the formulation (GT). Feces and pasture samples were collected for the research of gastrointestinal nematodes. Lung worms and trematodes were investigated. The animals were weighed monthly. The averages of temperature and rainfall were recorded. The supply of the fungus Pochonia chlamydosporia was not effective in reducing the eggs per gram of feces of gastrointestinal nematodes (EPG) of the animals, not differing statistically (p > 0.05) between the groups. The mean values of larvae recovered in the pasture did not differ significantly (p > 0.05). The genus Haemonchus sp. was the most prevalent. There was no correlation between the number of larvae with temperature and rainfall (p > 0.05). There was a statistically significant difference (p < 0.05) in the penultimate weighing of the experiment. The formulation containing Pochonia chlamydosporia was not efficient in the biological control of bovine gastrointestinal nematodes.
Red Foxes (Vulpes vulpes) Are Exposed to High Diversity of Borrelia burgdorferi Sensu Lato Species Infecting Fox-Derived Ixodes Ticks in West-Central Poland
Authors: Wodecka Beata , Michalik Jerzy , Grochowalska Renata
Published: June 2022

The role of red fox, Vulpes vulpes, and its associated ticks in maintaining Borrelia burgdorferi sensu lato (s.l.) was studied. A total of 1583 ticks were removed from ears of 120 infested animals and were identified as species using a nested PCR targeting the ITS2 and coxI fragments of Ixodes DNA. Ixodes kaiseri prevailed (76%), followed by I. canisuga, I. ricinus, and I. hexagonus. In total, 32.4% of 943 ticks revealed Borrelia DNA and 10 species of B. burgdorferi s.l. complex were identified. Borrelia garinii and B. afzelii comprised 70% of all infections. The other eight species included B. americana, B. bissettiae, B. burgdorferi sensu stricto (s.s.), B. californiensis, B. carolinensis, B. lanei, B. spielmanii, and B. valaisiana. Analysis of tissues from 243 foxes showed that 23.5% were infected with B. burgdorferi s.l. Borrelia garinii was detected in 91% of the infected animals, including 31% of mixed infections with B. afzelii, the second most prevalent species, followed by B. spielmanii. The predominance of B. garinii in PCR-positive animals and infected larval ticks (38.1%), suggests that this spirochete and B. afzelii are preferentially associated with foxes. Although red foxes are exposed to a high diversity of B. burgdorferi s.l. species found in engorged Ixodes ticks, their reservoir competence for most of them appears to be low.
Orbivirus Screening from Imported Captive Oryx in the United Arab Emirates Stresses the Importance of Pre-Import and Transit Measures
Authors: Martinelle Ludovic , Haegeman Andy , Lignereux Louis , Chaber Anne-Lise , Dal Pozzo Fabiana , De Leeuw Ilse , De Clercq Kris , Saegerman Claude
Published: June 2022

From 1975 to 2021, the United Arab Emirates (UAE) imported more than 1300 live Arabian oryxes (AOs) and scimitar-horned oryxes (SHOs) for conservation programs. The objective of this study was to estimate the prevalence of orbiviruses Bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV) in AOs and SHOs from captive herds in the UAE. Between October 2014 and April 2015, 16 AOs and 13 SHOs originating from Texas (USA) and 195 out of about 4000 SHOs from two locations in the UAE were blood sampled to be tested by indirect enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcriptase polymerase chain reaction (RT-qPCR) assays. Eight imported AOs (50% CI [24.7–75.4%]) and eight imported SHOs (61.5% CI [31.6–86.1%]) were found BTV seropositive, in contrast with three out of 195 SHOs (1.5% CI [0.3–4.4%]) from the Emirates. BTV-2 genome was detected in 6/16 of the Arabian Oryx, and amongst those, one out of six was seronegative. None of the tested samples was found positive for EHDV. Our results illustrate the wide local variation regarding BTV seroprevalence in domestic and wild ruminants in the Arabian Peninsula. These results stress the need for pre-import risk assessment when considering translocation of wild ruminant species susceptible to orbiviruses not only in the country of destination but also where transit happens.
Mobile Colistin Resistance (mcr) Genes in Cats and Dogs and Their Zoonotic Transmission Risks
Authors: Hamame Afaf , Davoust Bernard , Cherak Zineb , Rolain Jean-Marc , Diene Seydina M.
Published: June 2022

Background: Pets, especially cats and dogs, represent a great potential for zoonotic transmission, leading to major health problems. The purpose of this systematic review was to present the latest developments concerning colistin resistance through mcr genes in pets. The current study also highlights the health risks of the transmission of colistin resistance between pets and humans. Methods: We conducted a systematic review on mcr-positive bacteria in pets and studies reporting their zoonotic transmission to humans. Bibliographic research queries were performed on the following databases: Google Scholar, PubMed, Scopus, Microsoft Academic, and Web of Science. Articles of interest were selected using the PRISMA guideline principles. Results: The analyzed articles from the investigated databases described the presence of mcr gene variants in pets including mcr-1, mcr-2, mcr-3, mcr-4, mcr-5, mcr-8, mcr-9, and mcr-10. Among these articles, four studies reported potential zoonotic transmission of mcr genes between pets and humans. The epidemiological analysis revealed that dogs and cats can be colonized by mcr genes that are beginning to spread in different countries worldwide. Overall, reported articles on this subject highlight the high risk of zoonotic transmission of colistin resistance genes between pets and their owners. Conclusions: This review demonstrated the spread of mcr genes in pets and their transmission to humans, indicating the need for further measures to control this significant threat to public health. Therefore, we suggest here some strategies against this threat such as avoiding zoonotic transmission.
Cryptococcal Meningitis in Kidney Transplant Recipients: A Two-Decade Cohort Study in France
Authors: Tardieu Laurène , Divard Gillian , Lortholary Olivier , Scemla Anne , Rondeau Éric , Accoceberry Isabelle , Agbonon Rémi , Alanio Alexandre , Angoulvant Adela , Albano Laetitia , Attias Philippe , Bellanger Anne Pauline , Bertrand Dominique , Bonhomme Julie , Botterel Françoise , Bouvier Nicolas , Buchler Matthias , Chouaki Taieb , Crépin Thomas , Durieux Marie-Fleur , Desoubeaux Guillaume , Doppelt Gary , Favennec Loïc , Fekkar Arnaud , Fourdinier Ophélie , Frimat Marie , Gangneux Jean-Pierre , Garandeau Claire , Hasseine Lilia , Hennequin Christophe , Iriart Xavier , Kamar Nassim , Kaminski Hannah , Kormann Raphael , Lachaud Laurence , Legendre Christophe , Le Quintrec Donnette Moglie , Leroy Jordan , Levi Charlène , Machouart Marie , Marx David , Menotti Jean , Moal Valérie , Morio Florent , Mrozek Natacha , Nicolas Muriel , Poirier Philippe , Peraldi Marie-Noelle , Poussot Benjamin , Ranque Stéphane , Rerolle Jean-Philippe , Sendid Boualem , Snanoudj Renaud , Tourret Jérôme , Vasse Marc , Vigneau Cécile , Villard Odile , Mesnard Laurent , Lanternier Fanny , Rafat Cédric
Published: June 2022

Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well as its clinical features and radiological characteristics, have not yet been considered on a large scale in the context of kidney transplantation (KT). We performed a nationwide retrospective study of adult patients diagnosed with cryptococcosis after KT between 2002 and 2020 across 30 clinical centers in France. We sought to describe overall and graft survival based on whether KT patients with cryptococcosis developed CM or not. Clinical indicators of CNS involvement and brain radiological characteristics were assessed. Eighty-eight cases of cryptococcosis were diagnosed during the study period, with 61 (69.3%) cases of CM. Mortality was high (32.8%) at 12 months (M12) but not significantly different whether or not patients presented with CM. Baseline hyponatremia and at least one neurological symptom were independently associated with CM (p < 0.001). Positive serum cryptococcal antigen at diagnosis was also significantly associated with CM (p < 0.001). On magnetic resonance imaging (MRI), three patterns of brain injury were identified: parenchymal, meningeal, and vascular lesions. Although CM does not affect graft function directly, it entails a grim prognosis.
Diagnostic Laboratory Characteristics of COVID-19 Patients Infected by Fomites: COVID-19 Outbreak in a South Korean Public Administrative Facility
Authors: Hwang Se-Min , Jung Yoomi , Seo Haesook
Published: June 2022

There is a paucity of data regarding the differentiating characteristics of patients who were infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by fomites around the world. We conducted an event-based outbreak investigation, involving 795 public officers and 277 assistant staff, in the Ministry of Oceans and Fisheries (MOF) or the same building from March 2 to March 18, 2020. The SARS-CoV-2 patients were found to have more frequently touched fomites and used public toilets than those who were tested negative for the virus (cOR, 24.38; 95% CI, 4.95–120.01). Symptoms such as coughing and loss of taste and smell were more frequently found in the office-cleaner group than in the public-officer group. The SARS-CoV-2 office-cleaner patients were more likely to have a high RdRp(Ct) value of PCR (median: 34.17 vs. 24.99; p = 0.035) and E(Ct) value of PCR (median: 32.30 vs. 24.74; p = 0.045). All office cleaner patients (100%) had a ground glass opacity in both lobes. Regarding segmental lung involvement of CT, two patients (100%) had a lesion in the right middle lobe, which invaded the whole lobe later. This implies that the fomite might be a selective risk factor of SARS-CoV-2 infection.
Sublingual Atropine Administration as a Tool to Decrease Salivary Glands’ PSMA-Ligand Uptake: A Preclinical Proof of Concept Study Using [68Ga]Ga-PSMA-11
Authors: Nail Vincent , Louis Béatrice , Moyon Anaïs , Chabert Adrien , Balasse Laure , Fernandez Samantha , Hache Guillaume , Garrigue Philippe , Taïeb David , Guillet Benjamin
Published: June 2022

Prostate Specific Membrane Antigen (PSMA)-directed radionuclide therapy has gained an important role in the management of advanced castration-resistant prostate cancer. Although extremely promising, the prolongation in survival and amelioration of disease-related symptoms must be balanced against the direct toxicities of the treatment. Xerostomia is amongst the most common and debilitating of these, particularly when using an alpha emitter. It is therefore of main importance to develop new preventive strategies. This preclinical study has evaluated the effect of α-adrenergic and anticholinergic drugs on [99mTc]TcO4− Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) and [68Ga]Ga-PSMA-11 Positron Emission Tomography (PET/CT). Methods: The effects of phenylephrine, scopolamine, atropine, and ipratropium on salivary glands uptake were evaluated in non-tumor-bearing mice by [99mTc]TcO4− microSPECT/CT. The most efficient identified strategy was evaluated in non-tumor-bearing and xenografted mice by [68Ga]Ga-PSMA-11 PET/CT. Results: Scopolamine and atropine showed a significant decrease in the parotid glands’ uptake on SPECT/CT whereas phenylephrine and ipratropium failed. Atropine premedication (sublingual route), which was the most effective strategy, also showed a drastic decrease of [68Ga]Ga-PSMA-11 salivary glands’ uptake in both non-tumor-bearing mice (−51.6% for the parotids, p < 0.0001) and human prostate adenocarcinoma xenografted mice (−26.8% for the parotids, p < 0.0001). Conclusion: Premedication with a local administration of atropine could represent a simple, safe, and efficient approach for reducing salivary glands’ uptake.
Stereomicroscope with Imaging Analysis: A Versatile Tool for Wetting, Gel Formation and Erosion Rate Determinations of Eutectic Effervescent Tablet
Authors: Chaiya Pornsit , Okonogi Siriporn , Phaechamud Thawatchai
Published: June 2022

Wettability, gel formation and erosion behaviors could influence the drug release pattern of solid dosage forms. Typically, these parameters are evaluated using a variety of techniques. Nonetheless, there has been no previous research on versatile tool development for evaluating several tablet characteristics with a single tool. The aim of this study was to develop the versatile tool for measuring various physical properties of eutectic effervescent tablets and also investigate the relationship between these parameters with parameters from drug dissolution. Ibuprofen (IBU)-poloxamer 407 (P407) eutectic effervescent tablets were fabricated with a direct compression method. Their wetting properties, gel formation and erosion behaviors were investigated using a stereomicroscope with imaging analysis in terms of the liquid penetration distance, gel thickness and erosion boundary diameter, respectively. In addition, the dissolution rate (k) and disintegration time of eutectic effervescent tablets in 0.1 N HCl buffer pH 1.2 were also determined. Incorporation of P407 into the IBU tablet improved the tablet wetting properties with increasing liquid penetration distance under stereoscope. CO2 liberation from effervescent agents promoted tablet surface roughness from matrix erosion. The relationship between observed physical properties and disintegration and dissolution parameters suggested that the combination of erosion by effervescent agents and gel formation by P407 had a potential influence on dissolution enhancement of the formulation. Therefore, a developed stereomicroscope with an imaging analysis technique was exhibited as an alternative versatile tool for determining the wetting properties, gel formation and erosion behaviors of pharmaceutical solid dosage forms.
Pre-Clinical Evaluation of Tenofovir and Tenofovir Alafenamide for HIV-1 Pre-Exposure Prophylaxis in Foreskin Tissue
Authors: Else Laura , Penchala Sujan D. , Pillay Azure-Dee , Seiphetlo Thabiso B. , Lebina Limakatso , Callebaut Christian , Minhas Suks , Morley Roland , Rashid Tina , Martinson Neil , Fox Julie , Khoo Saye , Herrera Carolina
Published: June 2022

Background: HIV-1 pre-exposure prophylaxis (PrEP) has focused predominantly on protective efficacy in receptive sex, with limited research on the dosing requirements for insertive sex. We pre-clinically assessed the ex vivo pharmacokinetic–pharmacodynamic (PK–PD) profile of tenofovir (TFV) and tenofovir alafenamide (TAF) in foreskin tissue. Methods: Inner and outer foreskin explants were exposed to serial dilutions of TFV or TAF prior to addition of HIV-1BaL at a high (HVT) or a low viral titer (LVT). Infection was assessed by measurement of p24 in foreskin culture supernatants. TFV, TAF and TFV–diphosphate (TFV–DP) concentrations were measured in tissues, culture supernatants and dosing and washing solutions. Results: Dose–response curves were obtained for both drugs, with greater potency observed against LVT. Inhibitory equivalency mimicking oral dosing was defined between 1 mg/mL of TFV and 15 µg/mL of TAF against HVT challenge. Concentrations of TFV–DP in foreskin explants were approximately six-fold higher after ex vivo dosing with TAF than with TFV. Statistically significant negative linear correlations were observed between explant levels of TFV or TFV–DP and p24 concentrations following HVT. Conclusions: Pre-clinical evaluation of TAF in foreskin explants revealed greater potency than TFV against penile HIV transmission. Clinical evaluation is underway to support this finding.
Novel In Situ-Cross-Linked Electrospun Gelatin/Hydroxyapatite Nonwoven Scaffolds Prove Suitable for Periodontal Tissue Engineering
Authors: Dieterle Martin Philipp , Steinberg Thorsten , Tomakidi Pascal , Nohava Jiri , Vach Kirstin , Schulz Simon Daniel , Hellwig Elmar , Proksch Susanne
Published: June 2022

Periodontal diseases affect millions of people worldwide and can result in tooth loss. Regenerative treatment options for clinical use are thus needed. We aimed at developing new nonwoven-based scaffolds for periodontal tissue engineering. Nonwovens of 16% gelatin/5% hydroxyapatite were produced by electrospinning and in situ glyoxal cross-linking. In a subset of scaffolds, additional porosity was incorporated via extractable polyethylene glycol fibers. Cell colonization and penetration by human mesenchymal stem cells (hMSCs), periodontal ligament fibroblasts (PDLFs), or cocultures of both were visualized by scanning electron microscopy and 4′,6-diamidin-2-phenylindole (DAPI) staining. Metabolic activity was assessed via Alamar Blue® staining. Cell type and differentiation were analyzed by immunocytochemical staining of Oct4, osteopontin, and periostin. The electrospun nonwovens were efficiently populated by both hMSCs and PDLFs, while scaffolds with additional porosity harbored significantly more cells. The metabolic activity was higher for cocultures of hMSCs and PDLFs, or for PDLF-seeded scaffolds. Periostin and osteopontin expression was more pronounced in cocultures of hMSCs and PDLFs, whereas Oct4 staining was limited to hMSCs. These novel in situ-cross-linked electrospun nonwoven scaffolds allow for efficient adhesion and survival of hMSCs and PDLFs. Coordinated expression of differentiation markers was observed, which rendered this platform an interesting candidate for periodontal tissue engineering.
Pharmacogenetic Analysis of Voriconazole Treatment in Children
Authors: Tilen Romy , Paioni Paolo , Goetschi Aljoscha N. , Goers Roland , Seibert Isabell , Müller Daniel , Bielicki Julia A. , Berger Christoph , Krämer Stefanie D. , Meyer zu Schwabedissen Henriette E.
Published: June 2022

Voriconazole is among the first-line antifungal drugs to treat invasive fungal infections in children and known for its pronounced inter- and intraindividual pharmacokinetic variability. Polymorphisms in genes involved in the metabolism and transport of voriconazole are thought to influence serum concentrations and eventually the therapeutic outcome. To investigate the impact of these genetic variants and other covariates on voriconazole trough concentrations, we performed a retrospective data analysis, where we used medication data from 36 children suffering from invasive fungal infections treated with voriconazole. Data were extracted from clinical information systems with the new infrastructure SwissPKcdw, and linear mixed effects modelling was performed using R. Samples from 23 children were available for DNA extraction, from which 12 selected polymorphism were genotyped by real-time PCR. 192 (49.1%) of 391 trough serum concentrations measured were outside the recommended range. Voriconazole trough concentrations were influenced by polymorphisms within the metabolizing enzymes CYP2C19 and CYP3A4, and within the drug transporters ABCC2 and ABCG2, as well as by the co-medications ciprofloxacin, levetiracetam, and propranolol. In order to prescribe an optimal drug dosage, pre-emptive pharmacogenetic testing and careful consideration of co-medications in addition to therapeutic drug monitoring might improve voriconazole treatment outcome of children with invasive fungal infections.
Biomaterials in Skin Wound Healing and Tissue Regenerations—An Overview
Authors: Konop Marek
Published: June 2022

Wound healing is a complex biological process [...]
Ruthenium(II)–Cyclopentadienyl-Derived Complexes as New Emerging Anti-Colorectal Cancer Drugs
Authors: Teixeira-Guedes Catarina , Brás Ana Rita , Teixeira Ricardo G. , Valente Andreia , Preto Ana
Published: June 2022

Colorectal cancer (CRC) is one of the most common malignancies and one of the leading causes of cancer-related death worldwide, urging the need for new and more efficient therapeutic approaches. Ruthenium complexes have emerged as attractive alternatives to traditional platinum-based compounds in the treatment of CRC. This work aims to evaluate anti-CRC properties, as well as to identify the mechanisms of action of ruthenium complexes with the general formula [Ru(η5-C5H4R)(PPh3)(4,4′-R′-2,2′-bipyridine)][CF3SO3], where R = CH3, CHO or CH2OH and R′ = H, CH3, CH2OH, or dibiotin ester. The complexes (Ru 1–7) displayed high bioactivity, as shown by low IC50 concentrations against CRC cells, namely, RKO and SW480. Four of the most promising ruthenium complexes (Ru 2, 5–7) were phenotypically characterized and were shown to inhibit cell viability by decreasing cell proliferation, inducing cell cycle arrest, and increasing apoptosis. These findings were in accordance with the inhibition of MEK/ERK and PI3K/AKT signaling pathways. Ruthenium complexes also led to a decrease in cellular clonogenic ability and cell migration, which was associated with the disruption of F-actin cytoskeleton integrity. Here, we demonstrated that ruthenium complexes, especially Ru7, have a high anticancer effect against CRC cells and are promising drugs to be used as a new therapeutical strategy for CRC treatment.
Toxicity Assessment of Resveratrol Liposomes-in-Hydrogel Delivery System by EpiVaginalTM Tissue Model
Authors: Jøraholmen May Wenche , Damdimopoulou Pauliina , Acharya Ganesh , Škalko-Basnet Nataša
Published: June 2022

The natural polyphenol resveratrol (RES) has shown great potential as an antimicrobial, including against microbes associated with vaginal infections. To fully exploit the activities of RES, an all-natural ingredients formulation for RES delivery at vaginal site has been developed, namely liposomes loaded with RES, incorporated into a chitosan hydrogel as secondary vehicle. Although considered non-toxic and safe on their own, the compatibility of the final formulation must be evaluated for its biocompatibility and non-irritancy to the vaginal mucosa. As a preclinical safety assessment, the impact of RES formulation on the tissue viability, the effect on barrier function and cell monolayer integrity, and cytotoxicity were evaluated using the cell-based vaginal tissue model, the EpiVaginal™ tissue. RES liposomes-in-hydrogel formulations neither affected the mitochondrial activity, nor the integrity of the cell monolayer in RES concentration up to 60 µg/mL. Moreover, the barrier function was maintained to a greater extent by RES in formulation, emphasizing the benefits of the delivery system. Additionally, none of the tested formulations expressed an increase in lactate dehydrogenase activity compared to the non-treated tissues. The evaluation of the RES delivery system suggests that it is non-irritant and biocompatible with vaginal tissue in vitro in the RES concentrations considered as therapeutic.
Ontology and Attention: Addressing the Challenge of the Amoralist through Merleau-Ponty’s Phenomenology and Care Ethics
Authors: Daly Anya
Published: June 2022

This paper addresses the persistent philosophical problem posed by the amoralist—one who eschews moral values—by drawing on complementary resources within phenomenology and care ethics. How is it that the amoralist can reject ethical injunctions that serve the general good and be unpersuaded by ethical intuitions that for most would require neither explanation nor justification? And more generally, what is the basis for ethical motivation? Why is it that we can care for others? What are the underpinning ontological structures that are able to support an ethics of care? To respond to these questions, I draw on the work of Merleau-Ponty, focusing specifically on his analyses of perceptual attention. What is the nature and quality of perceptual attention that underwrite our capacities or incapacities for care? I proceed in dialogue with a range of philosophers attuned to the compelling nature of care, some who have also drawn on Merleau-Ponty and others who have examined the roots of an ethics of care inspired or incited by other thinkers.
Spectrum-Entropy-Minimized Routing and Spectrum Allocation in IP over Mixed-Fixed/Flex-Grid Optical Networks
Authors: Yu Xiaosong , Lu Lu , Zhu Qingcheng , Zhao Yongli , Nag Avishek , Zhang Jie
Published: June 2022

Mixed-Fixed/Flex-Grid Optical Networks (MFGONs) are a new paradigm that emerged during the brown-field migration from fixed-grid Wavelength Division Multiplexing (WDM) optical networks to flex-grid Elastic Optical Networks (EONs). Based on the flex-grid, we can accommodate IP traffic directly to the optical layer by configuration. Considering the different granularities of spectrum resources and complex constraints in MFGONs, it is difficult to apply Routing and Wavelength/Spectrum Allocation (RWA/RSA) algorithms proposed in either fixed-grid or flex-grid optical networks. This paper first proposes two concepts, i.e., Link Spectrum Compactness (LSC) and Radiancy of Nodes (RoNs), to evaluate different scenarios of candidate paths for the end-to-end requests in MFGONs. Then, based on these two concepts, a Spectrum Entropy (SE) model is proposed in MFGONs. Here, the SE is the metric that combines LSC and RoNs to judge the fragmentation of network resources, and the value of SE is treated as the cost of candidate paths during the RSA operation. Finally, an SE-minimized RSA algorithm in MFGONs is designed. Simulation results prove that the proposed algorithm can effectively reduce the Bandwidth Blocking Ratio (BBR) and increase the revenues for upgrading the nodes compared to the state-of-the-art RSA algorithm. Particularly, the performance improvement is more obvious for highly connected networks.
Raman-Guided Bronchoscopy: Feasibility and Detection Depth Studies Using Ex Vivo Lung Tissues and SERS Nanoparticle Tags
Authors: Wu Zongyu , Wang Ziwen , Xie Haoqiang , Wang Yiming , He Haoqi , Nie Shuming , Ye Jian , Lin Li
Published: June 2022

Image-guided and robotic bronchoscopy is currently under intense research and development for a broad range of clinical applications, especially for minimally invasive biopsy and surgery of peripheral pulmonary nodules or lesions that are frequently discovered by CT or MRI scans. Optical imaging and spectroscopic modalities at the near-infrared (NIR) window hold great promise for bronchoscopic navigation and guidance because of their high detection sensitivity and molecular/cellular specificity. However, light scattering and background interference are two major factors limiting the depth of tissue penetration of photons, and diseased lesions such as small tumors buried under the tissue surface often cannot be detected. Here we report the use of a miniaturized Raman device that is inserted into one of the bronchoscope channels for sensitive detection of “phantom” tumors using fresh pig lung tissues and surface-enhanced Raman scattering (SERS) nanoparticle tags. The ex vivo results demonstrate not only the feasibility of using Raman spectroscopy for endoscopic guidance, but also show that ultrabright SERS nanoparticles allow detection through a bronchial wall of 0.85 mm in thickness and a 5 mm-thick layer of lung tissue (approaching the fourth-generation airway). This work highlights the prospects and potential of Raman-guided bronchoscopy for minimally invasive imaging and detection of lung lesions.
Shell Model Applications in Nuclear Astrophysics
Authors: Martínez-Pinedo Gabriel , Langanke Karlheinz
Published: June 2022

In recent years, shell model studies have significantly contributed in improving the nuclear input, required in simulations of the dynamics of astrophysical objects and their associated nucleosynthesis. This review highlights a few examples such as electron capture rates and neutrino-nucleus cross sections, important for the evolution and nucleosynthesis of supernovae. For simulations of rapid neutron-capture (r-process) nucleosynthesis, shell model studies have contributed to an improved understanding of half lives of neutron-rich nuclei with magic neutron numbers and of the nuclear level densities and γ-strength functions that are both relevant for neutron capture rates.
From Innate Immunity to Inflammation: A Primer on Multiple Facets of NF-κB Signaling in COVID-19
Authors: Pandey Ashutosh , Mishra Abhinava K.
Published: June 2022

Nuclear factor-kappa B (NF-κB) induces the expression of many pro-inflammatory genes, including cytokines and chemokines. In the past decades, a wealth of clinical as well as animal model-based studies have demonstrated the association of the deregulated NF-κB signaling pathway with the progression of various inflammatory diseases, including inflammatory bowel disease (IBD), multiple sclerosis (MS), and chronic obstructive pulmonary disease (COPD). Given the conserved role of the NF-κB pathway as the pivotal regulator of pro-inflammatory gene expression, different components of the NF-κB pathway are proposed as major therapeutic targets against these diseases. The ongoing coronavirus disease of 2019 (COVID-19) has posed a significant public health crisis regarding inflammation-related diseases. A robust inflammatory response is associated with COVID-19-infection-related complications, including muti-organ failure and death. This review summarizes the past and current state of knowledge on the role of the NF-κB signaling pathway in the innate immune response and inflammatory diseases with the objective of potential therapeutic use in developing effective treatment options for COVID-19.
Poorly Investigated Ecuadorian Medicinal Plants
Authors: Armijos Chabaco , Ramírez Jorge , Vidari Giovanni
Published: June 2022

Ecuador has, in proportion of its size, one of the richest floras of Latin America and the world; the country also has an immense cultural heritage due to the presence of different ethnic groups that have implemented the use of many wild and cultivated plants, mainly as medicinal remedies. In a recent publication, we have summarized the results of research activities recently carried out on about 120 plants native to Ecuador, which includes the structures of non-volatile isolated compounds, as well as the chemical composition of essential oils (EOs) and the in vitro tested biological activity data. For the sake of completeness, we have collected in this paper the main information obtained from recent ethnobotanical investigations on other important Ecuadorian medicinal plants for which phytochemical, pharmacological, and toxicological studies are, however, still largely lacking. Thus, one of the objectives of this paper is to preserve the traditional knowledge of Ecuadorian Indigenous communities which, being transmitted orally, is in danger of becoming lost. Moreover, it is our intention to stimulate more extensive studies on the rich medicinal flora of the country, which can provide economic and social benefits, especially to the people who traditionally cultivate or collect the plants.
Biostimulants as an Alternative to Improve the Wine Quality from Vitis vinifera (cv. Tempranillo) in La Rioja
Authors: Olavarrieta Cristina E. , Sampedro Maria Carmen , Vallejo Asier , Štefelová Nikola , Barrio Ramón J. , De Diego Nuria
Published: June 2022

The application of biostimulants appears to be an environmentally friendly, innovative, and sustainable agronomical tool to mitigate the negative effects induced by adverse climatology in traditional grape-growing regions such as La Rioja (Spain). However, their mechanism of action in grapevines is still unclear. We evaluated how commercial substances (two from Ascophyllum nodosum extraction and one amino acids-based biostimulant) and the non-proteinogenic amino acid β-aminobutyric acid (BABA) affect the quality and quantity of musts and grapes in Vitis vinifera L. cv. Tempranillo from a semi-arid region of La Rioja during two seasons. We hypothesized an enhancement in organic metabolites in berries and leaves in response to these treatments, changing the organoleptic characteristics of the final products. The treatments altered the primary metabolites such as carbohydrates, organic acids (AcOrg), and free amino acids, first in the leaves as the effect of the foliar application and second in grapes and musts. As the main result, the biostimulant efficiency depended on the climatology and vineyard location to improve the final yield. Whereas biostimulant application enhanced the yield in 2018 (less dry year), it did not help production in 2019 (dry year). BABA was the most efficient biostimulant, enhancing plant production. Regarding yield quality, the biostimulant application improved the musts mainly by enhancing the fumaric acid content and by reducing carbohydrates, except in BABA-treated plants, where they were accumulated. These results corroborate biostimulants as an exciting approach in wine production, especially for improving wine quality.
Haploid Induction in Tomato (Solanum lycopersicum L.) via Gynogenesis
Authors: Marin-Montes Ivan Maryn , Rodríguez-Pérez Juan Enrique , Robledo-Paz Alejandrina , de la Cruz-Torres Eulogio , Peña-Lomelí Aureliano , Sahagún-Castellanos Jaime
Published: June 2022

The generation of new hybrid varieties of tomato (Solanum lycopersicum L.) is the most widely used breeding method for this species and requires at least seven self-fertilization cycles to generate stable parent lines. The development of doubled haploids aims at obtaining completely homozygous lines in a single generation, although, to date, routine commercial application has not been possible in this species. In contrast, obtaining doubled haploid lines via gynogenesis has been successfully implemented in recalcitrant crops such as melon, cucumber, pumpkin, loquat and walnut. This review provides an overview of the requirements and advantages of gynogenesis as an inducer of haploidy in different agricultural crops, with the purpose of assessing the potential for its application in tomato breeding. Successful cases of gynogenesis variants involving in vitro culture of unfertilized ovules, use of 60Co-irradiated pollen, in vivo haploid inducers and wide hybridization are presented, suggesting that these methodologies could be implemented in tomato breeding programs to obtain doubled haploids.
Ethnobotanical Uses, Phytochemical Composition, Biosynthesis, and Pharmacological Activities of Carpesium abrotanoides L. (Asteraceae)
Authors: Ibrahim Sabrin R. M. , Fadil Sana A. , Fadil Haifa A. , Hareeri Rawan H. , Abdallah Hossam M. , Mohamed Gamal A.
Published: June 2022

Carpesium abrotanoides L. (Asteraceae) is a medicinal plant with immense therapeutic importance and bioactivities. It is commonly encountered in various Asian regions. It has numerous ethnomedicinal uses for curing diverse ailments such as toothache, stomach ulcer, boils, tonsillitis, bronchitis, bacterial infection, bruises, swelling, virus infection, fever, and amygdalitis, as well as an anthelmintic versus round-, tape-, hook-, and pinworms. Different classes of phytoconstituents such as sesquiterpenes, sesquiterpene dimers, monoterpenes, and nitrogenous compounds have been reported from this plant. These phytoconstituents have proved to possess anti-inflammatory, cytotoxic, antimicrobial, and insecticidal capacities. The present review aims to summarize all published data on C. abrotanoides including traditional uses, phytoconstituents, bioactivities, and toxicological aspects, as well as the synthesis and biosynthesis of its metabolites through an extensive survey on various databases and various publishers. These reported data could draw the attention of various natural-metabolite-interested researchers and medicinal chemists towards the development of this plant and/or its metabolites into medicine for the prevention and treatment of certain illnesses. Despite the diverse traditional uses of C. abrotanoides, there is a need for scientific evidence to support these claims. Clinical trials are also required to further assure these data and validate this plant utilization in treating several diseases.
Therapeutic Potential of Ranunculus Species (Ranunculaceae): A Literature Review on Traditional Medicinal Herbs
Authors: Goo Youn-Kyoung
Published: June 2022

The genus Ranunculus includes approximately 600 species and is distributed worldwide. To date, several researchers have investigated the chemical and biological activities of Ranunculus species, and my research team has found them to have antimalarial effects. This review is based on the available information on the traditional uses and pharmacological studies of Ranunculus species. The present paper covers online literature, particularly from 2010 to 2021, and books on the ethnopharmacology and botany of Ranunculus species. Previous studies on the biological activity of crude or purified compounds from Ranunculus species, including R. sceleratus Linn., R. japonicus Thunb., R. muricatus Linn., R. ternatus Thunb., R. arvensis Linn., R. diffusus DC., R. sardous Crantz, R. ficaria Linn., R. hyperboreus Rotlb., and R. pedatus Waldst. & Kit., have provided new insights into their activities, such as antibacterial and antiprotozoal effects as well as antioxidant, immunomodulatory, and anticarcinogenic properties. In addition, the anti-inflammatory and analgesic effects of plants used in traditional medicine applications have been confirmed. Therefore, there is a need for more diverse studies on the chemical and pharmacological activities of highly purified molecules from Ranunculus species extracts to understand the mechanisms underlying their activities and identify novel drug candidates.