bluuebunny/crossref_metadata_2025 huggingface dataset:
Urban Geological 3D Modeling Based on Papery Borehole Log
Authors: Zhang Xinyu , Zhang Junqiang , Tian Yiping , Li Zhilong , Zhang Yi , Xu Lirui , Wang Song
Published: June 2020

Borehole log is important data for urban geological 3D modeling. Most of the current borehole logs are stored in a papery form. The construction of a smart city puts forward requirements for the automatic and intelligent 3D modeling of urban geology. However, it is difficult to extract the information from the papery borehole log quickly. What is more, it is unreliable to rely entirely on automated algorithms for modeling without artificial participation, but there is no effective way to integrate geological knowledge into 3D geological modeling currently. Therefore, it is necessary to research how to use existing papery borehole logs efficiently. To overcome the above obstacles, we designed a method that combines structural analysis and layout understanding to extract information from the borehole log. Then, the knowledge-driven three-dimensional geological modeling is proposed based on dynamic profiles. With these methods, the papery borehole log can be converted into structured data which can be used for data analysis directly, and geological knowledge can be integrated into the process of 3D geological modeling. The 3D geological modeling of Xinyang City based on a papery borehole log has been taken as an example to verify the feasibility of the method.
RETRACTED: Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 Cells
Authors: Al-Wahaibi Lamya , Al-Saleem Muneera , Ahmed Osama , Fahmy Usama , Alhakamy Nabil , Eid Basma , Abdel-Naim Ashraf , Abdel-Mageed Wael , AlRasheed Maha , Shazly Gamal
Published: June 2020

Accumulating evidence indicates that statins reduce the risk of different cancers and inhibit the proliferation of liver cancer cells. This study aims to explore whether the electrostatic conjugation of optimized fluvastatin (FLV) to human immunodeficiency virus type 1 (HIV-1) trans-activator transcription peptide (TAT) would enhance the anti-proliferative activity against HepG2 cells. FLV–TAT conjugation was optimized to achieve the lowest size with highest zeta potential. Nine formulae were constructed, using a factorial design with three factors—FLV concentration, TAT concentration, and pH of the medium—while the responses were zeta potential and size. The optimized formula showed a particle size of 199.24 nm and 29.14 mV zeta potential. Data indicates that conjugation of FLV to TAT (optimized formula) significantly enhances anti-proliferative activity and uptake by HepG2 cells when compared to raw FLV. Flow cytometry showed significant accumulation of cells in the pre-G phase, which highlights higher apoptotic activity. Annexin V staining indicated a significant increase in total cell death in early and late apoptosis. This was confirmed by significantly elevated caspase 3 in cells exposed to FLV–TAT preparation. In conclusion, the FLV–TAT optimized formula exhibited improved anti-proliferative action against HepG2. This is partially attributed to the enhanced apoptotic effects and cellular uptake of FLV.
Theoretical Insight into the Interaction between Chloramphenicol and Functional Monomer (Methacrylic Acid) in Molecularly Imprinted Polymers
Authors: Xie Lei , Xiao Nan , Li Lu , Xie Xinan , Li Yan
Published: June 2020

Molecular imprinting technology is a promising method for detecting chloramphenicol (CAP), a broad-spectrum antibiotic with potential toxicity to humans, in animal-derived foods. This work aimed to investigate the interactions between the CAP as a template and functional monomers required for synthesizing efficient molecularly imprinted polymers for recognition and isolation of CAP based on density functional theory. The most suitable monomer, methacrylic acid (MAA), was determined based on interaction energies and Gibbs free energy changes. Further, the reaction sites of CAP and MAA was predicted through the frontier molecular orbitals and molecular electrostatic potentials. Atoms in molecules topology analysis and non-covalent interactions reduced density gradient were applied to investigate different types of non-covalent and inter-atomic interactions. The simulation results showed that CAP was the main electron donor, while MAA was the main electron acceptor. Moreover, the CAP–MAA complex simultaneously involved N-H···O and C=O···H double hydrogen bonds, where the strength of the latter was greater than that of the former. The existence of hydrogen bonds was also confirmed by theoretical and experimental hydrogen nuclear magnetic resonance and Fourier transform infrared spectroscopic analyses. This research can act as an important reference for intermolecular interactions and provide strong theoretical guidance regarding CAP in the synthesis of molecularly imprinted polymers.
Genomic and Non-Genomic Mechanisms of Action of Thyroid Hormones and Their Catabolite 3,5-Diiodo-L-Thyronine in Mammals
Authors: Giammanco Marco , Di Liegro Carlo Maria , Schiera Gabriella , Di Liegro Italia
Published: June 2020

Since the realization that the cellular homologs of a gene found in the retrovirus that contributes to erythroblastosis in birds (v-erbA), i.e. the proto-oncogene c-erbA encodes the nuclear receptors for thyroid hormones (THs), most of the interest for THs focalized on their ability to control gene transcription. It was found, indeed, that, by regulating gene expression in many tissues, these hormones could mediate critical events both in development and in adult organisms. Among their effects, much attention was given to their ability to increase energy expenditure, and they were early proposed as anti-obesity drugs. However, their clinical use has been strongly challenged by the concomitant onset of toxic effects, especially on the heart. Notably, it has been clearly demonstrated that, besides their direct action on transcription (genomic effects), THs also have non-genomic effects, mediated by cell membrane and/or mitochondrial binding sites, and sometimes triggered by their endogenous catabolites. Among these latter molecules, 3,5-diiodo-L-thyronine (3,5-T2) has been attracting increasing interest because some of its metabolic effects are similar to those induced by T3, but it seems to be safer. The main target of 3,5-T2 appears to be the mitochondria, and it has been hypothesized that, by acting mainly on mitochondrial function and oxidative stress, 3,5-T2 might prevent and revert tissue damages and hepatic steatosis induced by a hyper-lipid diet, while concomitantly reducing the circulating levels of low density lipoproteins (LDL) and triglycerides. Besides a summary concerning general metabolism of THs, as well as their genomic and non-genomic effects, herein we will discuss resistance to THs and the possible mechanisms of action of 3,5-T2, also in relation to its possible clinical use as a drug.
Profound Nanoscale Structural and Biomechanical Changes in DNA Helix upon Treatment with Anthracycline Drugs
Authors: Kaczorowska Aleksandra , Lamperska Weronika , Frączkowska Kaja , Masajada Jan , Drobczyński Sławomir , Sobas Marta , Wróbel Tomasz , Chybicka Kinga , Tarkowski Radosław , Kraszewski Sebastian , Podbielska Halina , Kałas Wojciech , Kopaczyńska Marta
Published: June 2020

In our study, we describe the outcomes of the intercalation of different anthracycline antibiotics in double-stranded DNA at the nanoscale and single molecule level. Atomic force microscopy analysis revealed that intercalation results in significant elongation and thinning of dsDNA molecules. Additionally, using optical tweezers, we have shown that intercalation decreases the stiffness of DNA molecules, that results in greater susceptibility of dsDNA to break. Using DNA molecules with different GC/AT ratios, we checked whether anthracycline antibiotics show preference for GC-rich or AT-rich DNA fragments. We found that elongation, decrease in height and decrease in stiffness of dsDNA molecules was highest in GC-rich dsDNA, suggesting the preference of anthracycline antibiotics for GC pairs and GC-rich regions of DNA. This is important because such regions of genomes are enriched in DNA regulatory elements. By using three different anthracycline antibiotics, namely doxorubicin (DOX), epirubicin (EPI) and daunorubicin (DAU), we could compare their detrimental effects on DNA. Despite their analogical structure, anthracyclines differ in their effects on DNA molecules and GC-rich region preference. DOX had the strongest overall effect on the DNA topology, causing the largest elongation and decrease in height. On the other hand, EPI has the lowest preference for GC-rich dsDNA. Moreover, we demonstrated that the nanoscale perturbations in dsDNA topology are reflected by changes in the microscale properties of the cell, as even short exposition to doxorubicin resulted in an increase in nuclei stiffness, which can be due to aberration of the chromatin organization, upon intercalation of doxorubicin molecules.
Post-Traumatic Meningitis Is a Diagnostic Challenging Time: A Systematic Review Focusing on Clinical and Pathological Features
Authors: La Russa Raffaele , Maiese Aniello , Di Fazio Nicola , Morano Alessandra , Di Bonaventura Carlo , De Matteis Alessandra , Fazio Valentina , Frati Paola , Fineschi Vittorio
Published: June 2020

Post-traumatic meningitis is a dreadful condition that presents additional challenges, in terms of both diagnosis and management, when compared with community-acquired cases. Post-traumatic meningitis refers to a meningeal infection causally related to a cranio-cerebral trauma, regardless of temporal proximity. The PICO (participants, intervention, control, and outcomes) question was as follows: “Is there an association between traumatic brain injury and post-traumatic meningitis?” The present systematic review was carried out according to the Preferred Reporting Items for Systematic Review (PRISMA) standards. Studies examining post-traumatic meningitis, paying particular attention to victims of traumatic brain injury, were included. Post-traumatic meningitis represents a high mortality disease. Diagnosis may be difficult both because clinical signs are nonspecific and blurred and because of the lack of pathognomonic laboratory markers. Moreover, these markers increase with a rather long latency, thus not allowing a prompt diagnosis, which could improve patients’ outcome. Among all the detectable clinical signs, the appearance of cranial cerebrospinal fluid (CSF) leakage (manifesting as rhinorrhea or otorrhea) should always arouse suspicion of meningitis. On one hand, microbiological exams on cerebrospinal fluid (CSF), which represent the gold standard for the diagnosis, require days to get reliable results. On the other hand, radiological exams, especially CT of the brain, could represent an alternative for early diagnosis. An update on these issues is certainly of interest to focus on possible predictors of survival and useful tools for prompt diagnosis.
Malicious Text Identification: Deep Learning from Public Comments and Emails
Authors: Baccouche Asma , Ahmed Sadaf , Sierra-Sosa Daniel , Elmaghraby Adel
Published: June 2020

Identifying internet spam has been a challenging problem for decades. Several solutions have succeeded to detect spam comments in social media or fraudulent emails. However, an adequate strategy for filtering messages is difficult to achieve, as these messages resemble real communications. From the Natural Language Processing (NLP) perspective, Deep Learning models are a good alternative for classifying text after being preprocessed. In particular, Long Short-Term Memory (LSTM) networks are one of the models that perform well for the binary and multi-label text classification problems. In this paper, an approach merging two different data sources, one intended for Spam in social media posts and the other for Fraud classification in emails, is presented. We designed a multi-label LSTM model and trained it on the joint datasets including text with common bigrams, extracted from each independent dataset. The experiment results show that our proposed model is capable of identifying malicious text regardless of the source. The LSTM model trained with the merged dataset outperforms the models trained independently on each dataset.
Clinical Relevance and Characteristics of Aspergillus calidoustus and Other Aspergillus Species of Section Usti
Authors: Glampedakis Emmanouil , Erard Véronique , Lamoth Frederic
Published: June 2020

The Aspergilli of section Usti (group ustus) are represented by over 20 species, of which Aspergillus calidoustus is the most relevant human pathogen. Invasive aspergillosis (IA) caused by these fungi is rare but could represent an emerging issue among the expanding population of patients with long-term immunosuppression receiving antifungal prophylaxis. Clinicians should be aware of this unusual type of IA, which often exhibits distinct clinical features, such as an insidious and prolonged course and a high occurrence of extra-pulmonary manifestations, such as skin/soft tissue or brain lesions. Moreover, these Aspergillus spp. pose a therapeutic challenge because of their decreased susceptibility to azole drugs. In this review, we outline the microbiological and clinical characteristics of IA due to Aspergillus spp. of section Usti and discuss the therapeutic options.
Landscape-Ecological Approach to Spatial Planning as a Tool to Minimize Socio-Ecological Conflicts: Case Study of Agrolandscape in the Taiga Zone of Russia
Authors: Khoroshev Alexander
Published: June 2020

Landscape heterogeneity generates significant influences on economic activity. Present-day publications in landscape planning focus more and more on a participatory approach and a communication process. By contrast, we focus on nature-based criteria aimed at proper adaptation of planning decisions to natural landscape patterns. The paper proposes the framework aimed at considering geographical context, matter flows, and dynamic processes in projecting ecological network and perfect sites for various land use types as well as for choosing appropriate technologies. We use the example of a river basin in the taiga zone of European Russia, partially used for forestry and traditional agriculture. A landscape map, space images, and geochemical data are used to provide rationales for the necessary emergent effects resulting from proper proportions, neighborhoods, buffers, and shapes for lands use units. The proposed spatial arrangement of land use types and technologies ensures the coordination of socio-economic and ecological interests and preserves zonal background conditions, including runoff, soils, migration routes, and biodiversity. The allocation of arable lands and cutovers is aimed at minimizing undesirable matter flows that could cause qualitative changes in the geochemical environment.
Quantifying the Economic Value of Ecosystem Services in Oil Palm Dominated Landscapes in Riau Province in Sumatra, Indonesia
Authors: Aulia Ando , Sandhu Harpinder , Millington Andrew
Published: June 2020

Ecosystem services in oil palm plantations owned by smallholders in four villages in the Riau Province, Indonesia were identified and valued. Nine provisioning, three regulating and maintenance, one cultural ecosystem service, and a single ecosystem dis-service, were identified from interviews with 62 farming households. Direct and indirect market valuation methods were used to estimate the total economic value (TEV) of these services, which averaged USD 6520 ha−1 year−1 (range = USD 2970–7729 ha−1 year−1). The values of provisioning services were USD 4331 ha−1 year−1 (range = USD 2263–5489 ha−1 year−1), regulating and maintenance services were valued at USD 1880 ha−1 year−1 (range of USD 707–3110 ha−1 year−1), and cultural services were USD 309 ha−1 year−1. We conclude that identifying and valuing ecosystem services offers an opportunity to improve the environmental and economic sustainability of smallholders in oil palm landscapes in Indonesia.
Neuroprotection or Neurotoxicity of Illicit Drugs on Parkinson’s Disease
Authors: Ferreira Carla , Almeida Catarina , Tenreiro Sandra , Quintas Alexandre
Published: June 2020

Parkinson’s Disease (PD) is currently the most rapid growing neurodegenerative disease and over the past generation, its global burden has more than doubled. The onset of PD can arise due to environmental, sporadic or genetic factors. Nevertheless, most PD cases have an unknown etiology. Chemicals, such as the anthropogenic pollutant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amphetamine-type stimulants, have been associated with the onset of PD. Conversely, cannabinoids have been associated with the treatment of the symptoms’. PD and medical cannabis is currently under the spotlight, and research to find its benefits on PD is on-going worldwide. However, the described clinical applications and safety of pharmacotherapy with cannabis products are yet to be fully supported by scientific evidence. Furthermore, the novel psychoactive substances are currently a popular alternative to classical drugs of abuse, representing an unknown health hazard for young adults who may develop PD later in their lifetime. This review addresses the neurotoxic and neuroprotective impact of illicit substance consumption in PD, presenting clinical evidence and molecular and cellular mechanisms of this association. This research area is utterly important for contemporary society since illicit drugs’ legalization is under discussion which may have consequences both for the onset of PD and for the treatment of its symptoms.
Secondary Metabolites of the Genus Didemnum: A Comprehensive Review of Chemical Diversity and Pharmacological Properties
Authors: Youssef Diaa T. A. , Almagthali Hadeel , Shaala Lamiaa A. , Schmidt Eric W.
Published: June 2020

Tunicates (ascidians) are common marine invertebrates that are an exceptionally important source of natural products with biomedical and pharmaceutical applications, including compounds that are used clinically in cancers. Among tunicates, the genus Didemnum is important because it includes the most species, and it belongs to the most speciose family (Didemnidae). The genus Didemnum includes the species D. molle, D. chartaceum, D. albopunctatum, and D. obscurum, as well as others, which are well known for their chemically diverse secondary metabolites. To date, investigators have reported secondary metabolites, usually including bioactivity data, for at least 69 members of the genus Didemnum, leading to isolation of 212 compounds. Many of these compounds exhibit valuable biological activities in assays targeting cancers, bacteria, fungi, viruses, protozoans, and the central nervous system. This review highlights compounds isolated from genus Didemnum through December 2019. Chemical diversity, pharmacological activities, geographical locations, and applied chemical methods are described.
Recent Developments and Trends in Sheet Metal Forming
Authors: Trzepieciński Tomasz
Published: June 2020

Sheet metal forming (SMF) is one of the most popular technologies for obtaining finished products in almost every sector of industrial production, especially in the aircraft, automotive, food and home appliance industries. Parallel to the development of new forming techniques, numerical and empirical approaches are being developed to improve existing and develop new methods of sheet metal forming. Many innovative numerical algorithms, experimental methods and theoretical contributions have recently been proposed for SMF by researchers and business research centers. These methods are mainly focused on the improvement of the formability of materials, production of complex-shaped parts with good surface quality, speeding up of the production cycle, reduction in the number of operations and the environmental performance of manufacturing. This study is intended to summarize recent development trends in both the numerical and experimental fields of conventional deep-drawing, spinning, flexible-die forming, electromagnetic forming and computer-controlled forming methods like incremental sheet forming. The review is limited to the considerable changes that have occurred in the SMF sector in the last decade, with special attention given to the 2015–2020 period. The progress observed in the last decade in the area of SMF mainly concerns the development nonconventional methods of forming difficult-to-form lightweight materials for automotive and aircraft applications. In evaluating the ecological convenience of SMF processes, the tribological aspects have also become the subject of great attention.
Magnetic Nanohydrometallurgy Applied to Lanthanide Separation
Authors: de Melo Fernando , Almeida Sabrina , Toma Henrique
Published: June 2020

Lanthanides play an important role in modern technology because of their outstanding optical, electronic, and magnetic properties. Their current hydrometallurgical processing involves lixiviation, leading to concentrates of elements whose separation requires exhaustive procedures because of their similar chemical properties. In this sense, a new nanotechnological approach is here discussed, involving the use of iron oxide nanoparticles functionalized with complexing agents, such as diethylenetriaminepentaacetic acid (DTPA), for carrying out the magnetic extraction and separation of the lanthanide ions in aqueous solution. This strategy, also known as magnetic nanohydrometallurgy (MNHM), was first introduced in 2011 for dealing with transition metal recovery in the laboratory, and has been recently extended to the lanthanide series. This technology is based on lanthanide complexation and depends on the chemical equilibrium involved. It has been better described in terms of Langmuir isotherms, considering a uniform distribution of the metal ions over the nanoparticles surface, as evidenced by high angle annular dark field microscopy. The observed affinity parameters correlate with the lanthanide ion contraction series, and the process dynamics have been studied by monitoring the nanoparticles migration under an applied magnetic field (magnetophoresis). The elements can be reversibly captured and released from the magnetically confined nanoparticles, allowing their separation by a simple acid-base treatment. It can operate in a circular scheme, facilitated by the easy magnetic recovery of the extracting agents, without using organic solvents and ionic exchange columns. MNHM has been successfully tested for the separation of the lanthanide elements from monazite mineral, and seems a promising green nanotechnology, particularly suitable for urban mining.
Facile Chemical Synthesis of Doped ZnO Nanocrystals Exploiting Oleic Acid
Authors: Barui Sugata , Gerbaldo Roberto , Garino Nadia , Brescia Rosaria , Laviano Francesco , Cauda Valentina
Published: June 2020

Zinc oxide nanocrystals (ZnO-NCs) doped with transition metal elements or rare earth elements can be probed for magnetic resonance imaging to be used as a molecular imaging technique for accurate diagnosis of various diseases. Herein, we use Mn as a candidate of transition metal elements and Gd as a presenter of rare earth elements. We report an easy and fast coprecipitation method exploiting oleic acid to synthesize spherical-shaped, small-sized doped ZnO-NCs. We show the improved colloidal stability of oleate-stabilized doped ZnO-NCs compared to the doped ZnO-NCs synthesized by conventional sol–gel synthesis method, i.e., without a stabilizing agent, especially for the Mn dopant. We also analyze their structural, morphological, optical, and magnetic properties. We are able to characterize the persistence of the crystalline properties (wurtzite structure) of ZnO in the doped structure and exclude the formation of undesired oxides by doping elements. Importantly, we determine the room-temperature ferromagnetism of the doped ZnO-NCs. This oleate-stabilized coprecipitation method can be subjected as a standard procedure to synthesize doped and also co-doped ZnO-NCs with any transition metal elements or rare earth elements. In the future, oleate-stabilized Gd/Mn-doped ZnO-NCs can be exploited as magnetic resonance imaging (MRI) contrast agents and possibly increase the signal intensity on T1-weighted images or reduce the signal intensity on T2-weighted images.
Can Probiotics and Diet Promote Beneficial Immune Modulation and Purine Control in Coronavirus Infection?
Authors: Morais Ana H. A. , Passos Thais S. , Maciel Bruna L. L. , da Silva-Maia Juliana K.
Published: June 2020

Infection caused by the SARS-CoV-2 coronavirus worldwide has led the World Health Organization to declare a COVID-19 pandemic. Because there is no cure or treatment for this virus, it is emergingly urgent to find effective and validated methods to prevent and treat COVID-19 infection. In this context, alternatives related to nutritional therapy might help to control the infection. This narrative review proposes the importance and role of probiotics and diet as adjunct alternatives among the therapies available for the treatment of this new coronavirus. This review discusses the relationship between intestinal purine metabolism and the use of Lactobacillus gasseri and low-purine diets, particularly in individuals with hyperuricemia, as adjuvant nutritional therapies to improve the immune system and weaken viral replication, assisting in the treatment of COVID-19. These might be promising alternatives, in addition to many others that involve adequate intake of vitamins, minerals and bioactive compounds from food.
Red Bull Increases Heart Rate at Near Sea Level and Pulmonary Shunt Fraction at High Altitude in a Porcine Model
Authors: Treml Benedikt , Schöpf Elisabeth , Geiger Ralf , Niederwanger Christian , Löckinger Alexander , Kleinsasser Axel , Bachler Mirjam
Published: June 2020

Red Bull energy drink is popular among athletes, students and drivers for stimulating effects or enhancing physical performance. In previous work, Red Bull has been shown to exert manifold cardiovascular effects at rest and during exercise. Red Bull with caffeine as the main ingredient increases blood pressure in resting individuals, probably due to an increased release of (nor)-epinephrine. Red Bull has been shown to alter heart rate or leaving it unchanged. Little is known about possible effects of caffeinated energy drinks on pulmonary ventilation/perfusion distribution at sea level or at altitude. Here, we hypothesized a possible alteration of pulmonary blood flow in ambient air and in hypoxia after Red Bull consumption. We subjected eight anesthetized piglets in normoxia (FiO2 = 0.21) and in hypoxia (FiO2 = 0.13), respectively, to 10 mL/kg Red Bull ingestion. Another eight animals served as controls receiving an equivalent amount of saline. In addition to cardiovascular data, ventilation/perfusion distribution of the lung was assessed by using the multiple inert gas elimination technique (MIGET). Heart rate increased in normoxic conditions but was not different from controls in acute short-term hypoxia after oral Red Bull ingestion in piglets. For the first time, we demonstrate an increased fraction of pulmonary shunt with unchanged distribution of pulmonary blood flow after Red Bull administration in acute short-term hypoxia. In summary, these findings do not oppose moderate consumption of caffeinated energy drinks even at altitude at rest and during exercise.
Anticancer Activity of Rosmarinus officinalis L.: Mechanisms of Action and Therapeutic Potentials
Authors: Allegra Alessandro , Tonacci Alessandro , Pioggia Giovanni , Musolino Caterina , Gangemi Sebastiano
Published: June 2020

Alternative treatments for neoplastic diseases with new drugs are necessary because the clinical effectiveness of chemotherapy is often reduced by collateral effects. Several natural substances of plant origin have been demonstrated to be successful in the prevention and treatment of numerous tumors. Rosmarinus officinalis L. is a herb that is cultivated in diverse areas of the world. There is increasing attention being directed towards the pharmaceutical capacities of rosemary, utilized for its anti-inflammatory, anti-infective or anticancer action. The antitumor effect of rosemary has been related to diverse mechanisms, such as the antioxidant effect, antiangiogenic properties, epigenetic actions, regulation of the immune response and anti-inflammatory response, modification of specific metabolic pathways, and increased expression of onco-suppressor genes. In this review, we aim to report the results of preclinical studies dealing with the anticancer effects of rosemary, the molecular mechanisms related to these actions, and the interactions between rosemary and anticancer drugs. The prospect of utilizing rosemary as an agent in the treatment of different neoplastic diseases is discussed. However, although the use of rosemary in the therapy of neoplasms constitutes a fascinating field of study, large and controlled studies must be conducted to definitively clarify the real impact of this substance in clinical practice.
In “High-Risk” Infants with Sufficient Vitamin D Status at Birth, Infant Vitamin D Supplementation Had No Effect on Allergy Outcomes: A Randomized Controlled Trial
Authors: Rueter Kristina , Jones Anderson P. , Siafarikas Aris , Lim Ee-Mun , Prescott Susan L. , Palmer Debra J.
Published: June 2020

Lower vitamin D status at birth and during infancy has been associated with increased incidence of eczema and food allergies. The aim of this study was to investigate the effect of early infancy vitamin D supplementation on allergic disease outcomes in infants at “hereditary risk” of allergic disease, but who had sufficient vitamin D levels at birth. Here, we report the early childhood follow-up to 2.5 years of age of “high-risk” infants who participated in a double-blinded, randomized controlled trial. For inclusion in this trial, late gestation (36–40 weeks) maternal 25-hydroxyvitamin D levels needed to be ≥50 nmol/L. Infants were randomized to either oral vitamin D supplementation of 400 IU/day (n = 97) or a placebo (n = 98) for the first six months of life. Vitamin D levels and allergic disease outcomes were followed up. There were no statistically significant differences in incidence of any medically diagnosed allergic disease outcomes or allergen sensitization rates between the vitamin D-supplemented and placebo groups at either 1 year or at 2.5 years of age. In conclusion, for “allergy high-risk” infants who had sufficient vitamin D status at birth, early infancy oral vitamin D supplementation does not appear to reduce the development of early childhood allergic disease.
Microbiota Composition of Breast Milk from Women of Different Ethnicity from the Manawatu—Wanganui Region of New Zealand
Authors: Butts Christine A. , Paturi Gunaranjan , Blatchford Paul , Bentley-Hewitt Kerry L. , Hedderley Duncan I. , Martell Sheridan , Dinnan Hannah , Eady Sarah L. , Wallace Alison J. , Glyn-Jones Sarah , Wiens Frank , Stahl Bernd , Gopal Pramod
Published: June 2020

Human breastmilk components, the microbiota and immune modulatory proteins have vital roles in infant gut and immune development. In a population of breastfeeding women (n = 78) of different ethnicities (Asian, Māori and Pacific Island, New Zealand European) and their infants living in the Manawatu–Wanganui region of New Zealand, we examined the microbiota and immune modulatory proteins in the breast milk, and the fecal microbiota of mothers and infants. Breast milk and fecal samples were collected over a one-week period during the six to eight weeks postpartum. Breast milk microbiota differed between the ethnic groups. However, these differences had no influence on the infant’s gut microbiota composition. Based on the body mass index (BMI) classifications, the mother’s breast milk and fecal microbiota compositions were similar between normal, overweight and obese individuals, and their infant’s fecal microbiota composition also did not differ. The relative abundance of bacteria belonging to the Bacteroidetes phylum was higher in feces of infants born through vaginal delivery. However, the bacterial abundance of this phylum in the mother’s breast milk or feces was similar between women who delivered vaginally or by cesarean section. Several immune modulatory proteins including cytokines, growth factors, and immunoglobulin differed between the BMI and ethnicity groups. Transforming growth factor beta 1 and 2 (TGFβ1, TGFβ2) were present in higher concentrations in the milk from overweight mothers compared to those of normal weight. The TGFβ1 and soluble cluster of differentiation 14 (sCD14) concentrations were significantly higher in the breast milk from Māori and Pacific Island women compared with women from Asian and NZ European ethnicities. This study explores the relationship between ethnicity, body mass index, mode of baby delivery and the microbiota of infants and their mothers and their potential impact on infant health.
Prevalence and Epitope Recognition of Anti-Trypanosoma cruzi Antibodies in Two Procyonid Species: Implications for Host Resistance
Authors: Villalobos Guiehdani , Muñoz-García Claudia I. , Rodríguez-Cabo-Mercado Roberto , Mendoza-Bazán Nancy , Hernández-Ortiz Adrián , Villanueva-García Claudia , Martínez-Hernández Fernando , Rendón-Franco Emilio
Published: June 2020

More than 180 mammalian species have been found naturally infected with Trypanosoma cruzi. Many of them play an important role in the maintenance of this parasite. In particular, new studies have appeared which indicate that some species of Procyonidae family may play a role as T. cruzi hosts, however, more data are needed to evaluate their long-term physiological response to parasite infection, especially for specific antibodies. In this study, antibodies to T. cruzi were detected and prevalence and epitope recognition were assessed by ELISA (using discrete typing unit (DTU) I as antigen) and WB (using DTU I and DTU II as antigens) and sera from two procyonid species obtained through five-year follow-up of two semicaptive populations living in the same habitat. Marked heterogeneity in antigens recognition between species and differences in seroprevalence (p = 0.0002) between white-nosed coatis (Nasua narica), 51.8% (115/222), and common raccoons (Procyon lotor), 28.3% (23/81), were found. Antigens with high molecular weight when DTU-I was used were the most recognized, while a greater antigen diversity recognition was observed with DTU-II; for white-nosed coatis, low-molecular-weight antigens were mainly recognized, while for common raccoons proteins with molecular weights greater than 80 kDa were recognized most. These divergent humoral immune responses could be related to an alleged pattern of recognition receptors and major histocompatibility complex molecules difference in the procyonids species.
Non-Nucleoside Reverse Transcriptase Inhibitors Join Forces with Integrase Inhibitors to Combat HIV
Authors: Himmel Daniel M. , Arnold Eddy
Published: June 2020

In the treatment of acquired immune deficiency syndrome (AIDS), the diarylpyrimidine (DAPY) analogs etravirine (ETR) and rilpivirine (RPV) have been widely effective against human immunodeficiency virus (HIV) variants that are resistant to other non-nucleoside reverse transcriptase inhibitors (NNRTIs). With non-inferior or improved efficacy, better safety profiles, and lower doses or pill burdens than other NNRTIs in the clinic, combination therapies including either of these two drugs have led to higher adherence than other NNRTI-containing treatments. In a separate development, HIV integrase strand transfer inhibitors (INSTIs) have shown efficacy in treating AIDS, including raltegravir (RAL), elvitegravir (EVG), cabotegravir (CAB), bictegravir (BIC), and dolutegravir (DTG). Of these, DTG and BIC perform better against a wide range of resistance mutations than other INSTIs. Nevertheless, drug-resistant combinations of mutations have begun to emerge against all DAPYs and INSTIs, attributable in part to non-adherence. New dual therapies that may promote better adherence combine ETR or RPV with an INSTI and have been safer and non-inferior to more traditional triple-drug treatments. Long-acting dual- and triple-therapies combining ETR or RPV with INSTIs are under study and may further improve adherence. Here, highly resistant emergent mutations and efficacy data on these novel treatments are reviewed. Overall, ETR or RPV, in combination with INSTIs, may be treatments of choice as long-term maintenance therapies that optimize efficacy, adherence, and safety.
Providing Digital Infrastructure for Audio-Visual Linguistic Research Data with Diverse Usage Scenarios: Lessons Learnt
Authors: Hedeland Hanna
Published: June 2020

This article describes the development of the digital infrastructure at a research data centre for audio-visual linguistic research data, the Hamburg Centre for Language Corpora (HZSK) at the University of Hamburg in Germany, over the past ten years. The typical resource hosted in the HZSK Repository, the core component of the infrastructure, is a collection of recordings with time-aligned transcripts and additional contextual data, a spoken language corpus. Since the centre has a thematic focus on multilingualism and linguistic diversity and provides its service to researchers within linguistics and other disciplines, the development of the infrastructure was driven by diverse usage scenarios and user needs on the one hand, and by the common technical requirements for certified service centres of the CLARIN infrastructure on the other. Beyond the technical details, the article also aims to be a contribution to the discussion on responsibilities and services within emerging digital research data infrastructures and the fundamental issues in sustainability of research software engineering, concluding that in order to truly cater to user needs across the research data lifecycle, we still need to bridge the gap between discipline-specific research methods in the process of digitalisation and generic digital research data management approaches.
Introduction to Special Issue on “Exploring New Assemblages of Islamic Expert Education in Western Europe”
Authors: Groeninck Mieke , Boender Welmoet
Published: June 2020

What constitutes ‘relevant’ and ‘apt’ Islamic knowledge and expert education of future Islamic authorities in Western Europe? This central point of departure of this Special Issue is a burdened question in the current public and political debate in Western Europe. In the last decades, higher education on Islam in Europe has predominantly taken place in two domains: in the publicly funded university context as Islamic Studies, and in the privately funded context of mosques, madrasa’s and teaching institutes, often with strong links to Muslim countries of origin. In recent years, however, different answers have been formulated to this question; alternative initiatives have been taken—or are in the making—to train Islamic experts who are preparing for professional and academic careers in Europe. Publicly funded universities have started to organize imam training or Islamic theology programs, notably in Germany, Belgium, The Netherlands and the Scandinavian countries. Furthermore, private confessional Muslim institutes are now recruiting lecturers who also graduated from Western Islamic Studies university programs. This Special Issue focuses both theoretically and empirically on these new aspirations, initiatives, debates and practices of those various actors who navigate between and beyond. To understand these developments, we need a theoretical framework that is able to deconstruct the power related epistemological narratives constituting these dichotomies. Therefore, we will use this introductory editorial article to elaborate on how these spaces/places of departure are not absolute or analytically stable, but per definition uncertain, blurry and constantly ‘in the making’, constituted by what David Scott has called ‘a problem-space’. Moreover, in addition to thinking only in terms of ‘interstices’ in order to overcome these dichotomies by way of ‘bonding or bridging’, but which often seems to presume an essential character to both ends, we suggest to consider these alternative initiatives in terms of ‘assemblages’.
A Multi-State Approach to Modelling Intermediate Events and Multiple Mortgage Loan Outcomes
Authors: Chamboko Richard , Bravo Jorge Miguel
Published: June 2020

This paper proposes a novel system-wide multi-state framework to model state occupations and the transitions among current, delinquency, default, prepayment, repurchase, short sale and foreclosure on mortgage loans. The approach allows for the modelling of the progression of borrowers from one state to another to fully understand the risks of a cohort of borrowers over time. We use a multi-state Markov model to model the transitions to and from various states. The key factors affecting the transition into various loan outcomes are the ability to pay as measured by debt-to-income ratio, equity as marked by loan-to-value ratio, interest rates and the property type. Our findings have broader policy implications for better decision-making on granting loans and the design of debt relief and mortgage modification policies.
Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19)
Authors: Yuan Shuofeng , Chan Chris Chun-Yiu , Chik Kenn Ka-Heng , Tsang Jessica Oi-Ling , Liang Ronghui , Cao Jianli , Tang Kaiming , Cai Jian-Piao , Ye Zi-Wei , Yin Feifei , To Kelvin Kai-Wang , Chu Hin , Jin Dong-Yan , Hung Ivan Fan-Ngai , Yuen Kwok-Yung , Chan Jasper Fuk-Woo
Published: June 2020

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signals an urgent need for an expansion in treatment options. In this study, we investigated the anti-SARS-CoV-2 activities of 22 antiviral agents with known broad-spectrum antiviral activities against coronaviruses and/or other viruses. They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. Betaferon (interferon-β1b) exhibited the most potent anti-SARS-CoV-2 activity in viral antigen expression, viral load reduction, and plaque reduction assays among the recombinant interferons. The lipogenesis modulators 25-hydroxycholesterol and AM580 exhibited EC50 at low micromolar levels and selectivity indices of >10.0. Combinational use of these host-based antiviral agents with virus-based antivirals to target different processes of the SARS-CoV-2 replication cycle should be evaluated in animal models and/or clinical trials.
Epidemiology and Clinical Symptoms Related to Seasonal Coronavirus Identified in Patients with Acute Respiratory Infections Consulting in Primary Care over Six Influenza Seasons (2014–2020) in France
Authors: Masse Shirley , Capai Lisandru , Villechenaud Natacha , Blanchon Thierry , Charrel Rémi , Falchi Alessandra
Published: June 2020

There is currently debate about human coronavirus (HCoV) seasonality and pathogenicity, as epidemiological data are scarce. Here, we provide epidemiological and clinical features of HCoV patients with acute respiratory infection (ARI) examined in primary care general practice. We also describe HCoV seasonality over six influenza surveillance seasons (week 40 to 15 of each season) from the period 2014/2015 to 2019/2020 in Corsica (France). A sample of patients of all ages presenting for consultation for influenza-like illness (ILI) or ARI was included by physicians of the French Sentinelles Network during this period. Nasopharyngeal samples were tested for the presence of 21 respiratory pathogens by real-time RT-PCR. Among the 1389 ILI/ARI patients, 105 were positive for at least one HCoV (7.5%). On an annual basis, HCoVs circulated from week 48 (November) to weeks 14–15 (May) and peaked in week 6 (February). Overall, among the HCoV-positive patients detected in this study, HCoV-OC43 was the most commonly detected virus, followed by HCoV-NL63, HCoV-HKU1, and HCoV-229E. The HCoV detection rates varied significantly with age (p = 0.00005), with the age group 0–14 years accounting for 28.6% (n = 30) of HCoV-positive patients. Fever and malaise were less frequent in HCoV patients than in influenza patients, while sore throat, dyspnoea, rhinorrhoea, and conjunctivitis were more associated with HCoV positivity. In conclusion, this study demonstrates that HCoV subtypes appear in ARI/ILI patients seen in general practice, with characteristic outbreak patterns primarily in winter. This study also identified symptoms associated with HCoVs in patients with ARI/ILI. Further studies with representative samples should be conducted to provide additional insights into the epidemiology and clinical features of HCoVs.
High-Throughput Sequencing is a Crucial Tool to Investigate the Contribution of Human Endogenous Retroviruses (HERVs) to Human Biology and Development
Authors: Pisano Maria Paola , Grandi Nicole , Tramontano Enzo
Published: June 2020

Human Endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that represent a large fraction of our genome. Their transcriptional activity is finely regulated in early developmental stages and their expression is modulated in different cell types and tissues. Such activity has an impact on human physiology and pathology that is only partially understood up to date. Novel high-throughput sequencing tools have recently allowed for a great advancement in elucidating the various HERV expression patterns in different tissues as well as the mechanisms controlling their transcription, and overall, have helped in gaining better insights in an all-inclusive understanding of the impact of HERVs in biology of the host.
Daxx Inhibits HIV-1 Reverse Transcription and Uncoating in a SUMO-Dependent Manner
Authors: Maillet Sarah , Fernandez Juliette , Decourcelle Mathilde , El Koulali Khadija , Blanchet Fabien P. , Arhel Nathalie J. , Maarifi Ghizlane , Nisole Sébastien
Published: June 2020

Death domain-associated protein 6 (Daxx) is a multifunctional, ubiquitously expressed and highly conserved chaperone protein involved in numerous cellular processes, including apoptosis, transcriptional repression, and carcinogenesis. In 2015, we identified Daxx as an antiretroviral factor that interfered with HIV-1 replication by inhibiting the reverse transcription step. In the present study, we sought to unravel the molecular mechanism of Daxx-mediated restriction and, in particular, to identify the protein(s) that Daxx targets in order to achieve its antiviral activity. First, we show that the SUMO-interacting motif (SIM) located at the C-terminus of the protein is strictly required for Daxx to inhibit HIV-1 reverse transcription. By performing a quantitative proteomic screen combined with classical biochemical analyses, we found that Daxx associated with incoming HIV-1 cores through a SIM-dependent interaction with cyclophilin A (CypA) and capsid (CA). Daxx was found to reside within a multiprotein complex associated with viral capsids, also containing TNPO3, TRIM5α, and TRIM34. Given the well-known influence of these cellular factors on the stability of HIV-1 cores, we investigated the effect of Daxx on the cytoplasmic fate of incoming cores and found that Daxx prevented HIV-1 uncoating in a SIM-dependent manner. Altogether, our findings suggest that, by recruiting TNPO3, TRIM5α, and TRIM34 and possibly other proteins onto incoming HIV-1 cores through a SIM-dependent interaction with CA-bound CypA, Daxx increases their stability, thus preventing uncoating and reverse transcription. Our study uncovers a previously unknown function of Daxx in the early steps of HIV-1 infection and further illustrates how reverse transcription and uncoating are two tightly interdependent processes.