bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of In Vivo Nodal Assessment of Solid Malignancies with USPIO-Enhanced MRI: A Workflow Protocol
Authors: Driessen Daphne A. J. J. , de Gouw Didi J. J. M. , Stijns Rutger C. H. , Litjens Geke , Israël Bas , Philips Bart W. J. , Hermans John J. , Dijkema Tim , Klarenbeek Bastiaan R. , van der Post Rachel S. , Nagtegaal Iris D. , van Engen-van Grunsven Adriana C. H. , Brosens Lodewijk A. A. , Veltien Andor , Zámecnik Patrik , Scheenen Tom W. J.
Published: March 2022

Background: In various cancer types, the first step towards extended metastatic disease is the presence of lymph node metastases. Imaging methods with sufficient diagnostic accuracy are required to personalize treatment. Lymph node metastases can be detected with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI), but this method needs validation. Here, a workflow is presented, which is designed to compare MRI-visible lymph nodes on a node-to-node basis with histopathology. Methods: In patients with prostate, rectal, periampullary, esophageal, and head-and-neck cancer, in vivo USPIO-enhanced MRI was performed to detect lymph nodes suspicious of harboring metastases. After lymphadenectomy, but before histopathological assessment, a 7 Tesla preclinical ex vivo MRI of the surgical specimen was performed, and in vivo MR images were radiologically matched to ex vivo MR images. Lymph nodes were annotated on the ex vivo MRI for an MR-guided pathological examination of the specimens. Results: Matching lymph nodes of ex vivo MRI to pathology was feasible in all cancer types. The annotated ex vivo MR images enabled a comparison between USPIO-enhanced in vivo MRI and histopathology, which allowed for analyses on a nodal, or at least on a nodal station, basis. Conclusions: A workflow was developed to validate in vivo USPIO-enhanced MRI with histopathology. Guiding the pathologist towards lymph nodes in the resection specimens during histopathological work-up allowed for the analysis at a nodal basis, or at least nodal station basis, of in vivo suspicious lymph nodes with corresponding histopathology, providing direct information for validation of in vivo USPIO-enhanced, MRI-detected lymph nodes.
Direct RT-qPCR Assay for the Detection of SARS-CoV-2 in Saliva Samples
Authors: Tarantini Francesco Saverio , Wu Siyu , Jenkins Harry , Tellechea Lopez Ana , Tomlin Hannah , Hyde Ralph , Lis-Slimak Katarzyna , Thompson Jamie Louise , Pijuan-Galitó Sara , Scales Danielle , Kaneko Kazuyo , Dey Jayasree , Park Emily , Hill Jack , Lee I-Ning , Doolan Lara , Arendt-Tranholm Asta , Denning Chris , Seedhouse Claire , Benest Andrew V.
Published: March 2022

Since mid-2020 there have been complexities and difficulties in the standardisation and administration of nasopharyngeal swabs. Coupled with the variable and/or poor accuracy of lateral flow devices, this has led to increased societal ‘testing fatigue’ and reduced confidence in test results. Consequently, asymptomatic individuals have developed reluctance towards repeat testing, which remains the best way to monitor COVID-19 cases in the wider population. On the other hand, saliva-based PCR, a non-invasive, highly sensitive, and accurate test suitable for everyone, is gaining momentum as a straightforward and reliable means of detecting SARS-CoV-2 in symptomatic and asymptomatic individuals. Here, we provide an itemised list of the equipment and reagents involved in the process of sample submission, inactivation and analysis, as well as a detailed description of how each of these steps is performed.
Genomic Fishing and Data Processing for Molecular Evolution Research
Authors: Lorente-Martínez Héctor , Agorreta Ainhoa , San Mauro Diego
Published: March 2022

Molecular evolution analyses, such as detection of adaptive/purifying selection or ancestral protein reconstruction, typically require three inputs for a target gene (or gene family) in a particular group of organisms: sequence alignment, model of evolution, and phylogenetic tree. While modern advances in high-throughput sequencing techniques have led to rapid accumulation of genomic-scale data in public repositories and databases, mining such vast amount of information often remains a challenging enterprise. Here, we describe a comprehensive, versatile workflow aimed at the preparation of genome-extracted datasets readily available for molecular evolution research. The workflow involves: (1) fishing (searching and capturing) specific gene sequences of interest from taxonomically diverse genomic data available in databases at variable levels of annotation, (2) processing and depuration of retrieved sequences, (3) production of a multiple sequence alignment, (4) selection of best-fit model of evolution, and (5) solid reconstruction of a phylogenetic tree.
High-Speed Erosion Behavior of Hydrophobic Micro/Nanostructured Titanium Surfaces
Authors: Chen Yong , Zhang Jiguo
Published: March 2022

Ice accretion on aircrafts or their engines can cause serious problems and even accidents. Traditional anti-icing and de-icing systems reduce engine efficiency, which can be improved by the use of hydrophobic/icephobic coatings or surfaces that reduce the amount of bleed air or electric power needed. These hydrophobic/icephobic coatings or surfaces are eroded by high-speed air flow, water droplets, ice crystals, sand, and volcanic ash, resulting in the degradation, material loss, or deterioration of the coating’s waterproof and anti-icing properties. Thus, the durability of hydrophobic micro/nanostructured surfaces is a major concern in aircraft applications. However, the mechanism responsible for material loss in hydrophobic micro/nanostructured surfaces resulting from high-speed erosion remains unclear. In this paper, hydrophobic titanium alloy surfaces with cubic pit arrays are fabricated by photoetching and tested using a high-speed sand erosion rig. Under the same impact conditions, the erosion rates of the micro/nanostructured titanium surfaces were similar to those of smooth titanium alloy, implying that the hydrophobic surface fabricated on the bulk material had erosion-resistant capabilities. The material loss mechanisms of the micro/nanostructures under different impact angles were compared, providing useful information for the future optimization of micro/nanostructures with the goal of improved erosion resistance.
Carbon Nanotube-Modified Nickel Hydroxide as Cathode Materials for High-Performance Li-S Batteries
Authors: Jin Qianwen , Yan Yajing , Hu Chenchen , Zhang Yongguang , Wang Xi , Liang Chunyong
Published: March 2022

The advantages of high energy density and low cost make lithium–sulfur batteries one of the most promising candidates for next-generation energy storage systems. However, the electrical insulativity of sulfur and the serious shuttle effect of lithium polysulfides (LiPSs) still impedes its further development. In this regard, a uniform hollow mesoporous Ni(OH)2@CNT microsphere was developed to address these issues. The SEM images show the Ni(OH)2 delivers an average size of about 5 μm, which is composed of nanosheets. The designed Ni(OH)2@CNT contains transition metal cations and interlayer anions, featuring the unique 3D spheroidal flower structure, decent porosity, and large surface area, which is highly conducive to conversion systems and electrochemical energy storage. As a result, the as-fabricated Li-S battery delivers the reversible capacity of 652 mAh g−1 after 400 cycles, demonstrating excellent capacity retention with a low average capacity loss of only 0.081% per cycle at 1 C. This work has shown that the Ni(OH)2@CNT sulfur host prepared by hydrothermal embraces delivers strong physical absorption as well as chemical affinity.
Impact of Fluorinated Ionic Liquids on Human Phenylalanine Hydroxylase—A Potential Drug Delivery System
Authors: Alves Márcia M. S. , Leandro Paula , Mertens Haydyn D. T. , Pereiro Ana B. , Archer Margarida
Published: March 2022

Phenylketonuria (PKU) is an autosomal recessive disease caused by deficient activity of human phenylalanine hydroxylase (hPAH), which can lead to neurologic impairments in untreated patients. Although some therapies are already available for PKU, these are not without drawbacks. Enzyme-replacement therapy through the delivery of functional hPAH could be a promising strategy. In this work, biophysical methods were used to evaluate the potential of [N1112(OH)][C4F9SO3], a biocompatible fluorinated ionic liquid (FIL), as a delivery system of hPAH. The results herein presented show that [N1112(OH)][C4F9SO3] spontaneously forms micelles in a solution that can encapsulate hPAH. This FIL has no significant effect on the secondary structure of hPAH and is able to increase its enzymatic activity, despite the negative impact on protein thermostability. The influence of [N1112(OH)][C4F9SO3] on the complex oligomerization equilibrium of hPAH was also assessed.
Defect-Rich Monolayer MoS2 as a Universally Enhanced Substrate for Surface-Enhanced Raman Scattering
Authors: Sun Shiyu , Zheng Jingying , Sun Ruihao , Wang Dan , Sun Guanliang , Zhang Xingshuang , Gong Hongyu , Li Yong , Gao Meng , Li Dongwei , Xu Guanchen , Liang Xiu
Published: March 2022

Monolayer 2H-MoS2 has been widely noticed as a typical transition metal dichalcogenides (TMDC) for surface-enhanced Raman scattering (SERS). However, monolayer MoS2 is limited to a narrow range of applications due to poor detection sensitivity caused by the combination of a lower density of states (DOS) near the Fermi energy level as well as a rich fluorescence background. Here, surfaced S and Mo atomic defects are fabricated on a monolayer MoS2 with a perfect lattice. Defects exhibit metallic properties. The presence of defects enhances the interaction between MoS2 and the detection molecule, and it increases the probability of photoinduced charge transfer (PICT), resulting in a significant improvement of Raman enhancement. Defect-containing monolayer MoS2 enables the fluorescence signal of many dyes to be effectively burst, making the SERS spectrum clearer and making the limits of detection (LODs) below 10−8 M. In conclusion, metallic defect-containing monolayer MoS2 becomes a promising and versatile substrate capable of detecting a wide range of dye molecules due to its abundant DOS and effective PICT resonance. In addition, the synergistic effect of surface defects and of the MoS2 main body presents a new perspective for plasma-free SERS based on the chemical mechanism (CM), which provides promising theoretical support for other TMDC studies.
Mechanism of Photocurrent Degradation and Contactless Healing in p-Type Mg-Doped Gallium Nitride Thin Films
Authors: Wu Xiaoyan , Li Wei , Chen Qingrong , Xu Caixia , Wang Jiamian , Wu Lingyuan , Liu Guodong , Wang Weiping , Li Ting , Chen Ping , Xu Long
Published: March 2022

Light-induced degradation (LID) phenomenon is commonly found in optoelectronics devices. Self-healing effect in halide lead perovskite solar cells was investigated since the electrons and holes in the shallow traps could escape easily at room temperature. However, the degradation in the semiconductors could not easily recover at room temperature, and many of them needed annealing at temperatures in the several hundreds, which was not friendly to the integrated optoelectronic semiconductor devices. To solve this problem, in this work, LID effect of photocurrent in p-type Mg-doped gallium nitride thin films was investigated, and deep defect and vacancy traps played a vital role in the LID and healing process. This work provides a contactless way to heal the photocurrent behavior to its initial level, which is desirable in integrated devices.
Polyethylene Oxide Assisted Fish Collagen-Poly-ε-Caprolactone Nanofiber Membranes by Electrospinning
Authors: He Xiaoli , Wang Lei , Lv Kangning , Li Wenjun , Qin Song , Tang Zhihong
Published: March 2022

Fish collagen has higher biocompatibility and lower immunogenicity than terrestrial collagen, and is currently one of the important raw materials for preparing biological materials. In this study, PEO was used as a spinning aid to prepare fish skin collagen-PCL nanofiber membranes by electrospinning, and the process was optimized to get smooth nanofibers. The morphological and mechanical properties of collagen-PCL nanofiber membranes were assessed by scanning electron microscopy (SEM). The changes in chemical composition due to the incorporation of collagen into PCL and PEO were determined by Fourier Transform infrared spectroscopy (FTIR). The biocompatibility of the collagen-PCL nanofiber membranes was evaluated in vitro in cultures of mouse fibroblasts and in vivo by subcutaneous implantation studies in rats. It was found that the diameter of the spun fibers became fine and smooth when the ratio of the collagen/PCL increased. The finally obtained nanofiber had good mechanical strength, porosity, and hydrophilicity, and could promote cell adhesion and proliferation. The FC-PCL nanofiber membrane prepared by this route opens a new way to prepare fish collagen biomaterials with electrospinning.
Beneficial In Vitro Effects of a Low Myo-Inositol Dose in the Regulation of Vascular Resistance and Protein Peroxidation under Inflammatory Conditions
Authors: Rolnik Agata , Olas Beata , Szablińska-Piernik Joanna , Lahuta Lesław Bernard , Rynkiewicz Andrzej , Cygański Piotr , Socha Katarzyna , Gromadziński Leszek , Thoene Michael , Majewski Michał
Published: March 2022

Oxidative stress induces functional changes in arteries. Therefore, the effect of myo-inositol, a possible anti-inflammatory/antioxidant agent was studied on human plasma and rat thoracic arteries. Aortic rings from male Wistar rats (3 months of age) were incubated with myo-inositol (1, 10 and 100 μM, 120 min) and analyzed using the gas chromatography (GC) method. In another experiment, aortic rings were protected first with myo-inositol (1 µM, 60 min) and then subjected to a thromboxane receptor agonist (U-46619, 0.1 nM, 60 min). Therefore, these four groups under the following conditions were studied: (i) the control in the vehicle; (ii) myo-inositol; (iii) the vehicle plus U-46619; (iv) myo-inositol plus U-46619. The hemostatic parameters of human plasma and an H2O2/Fe2+ challenge for lipid and protein peroxidation were also performed. Myo-inositol was not absorbed into the pre-incubated aortic rings as measured by the GC method (0.040 µg/mg, p ≥ 0.8688). The effect of myo-inositol was more significant in the impaired arteries due to U-46619 incubation, which resulted in an improved response to acetylcholine (% Emax: 58.47 vs. 86.69), sodium nitroprusside (logEC50: −7.478 vs. −8.076), CORM-2 (% Emax: 44.08 vs. 83.29), pinacidil (logEC50: −6.489 vs. −6.988) and noradrenaline (logEC50: −7.264 vs. −6.525). This was most likely a possible response to increased nitric oxide release (×2.6-fold, p < 0001), and decreased hydrogen peroxide production (×0.7-fold, p = 0.0012). KCl-induced membrane depolarization was not modified (p ≥ 0.4768). Both the plasma protein carbonylation (×0.7-fold, p = 0.0006), and the level of thiol groups (×3.2-fold, p = 0.0462) were also improved, which was not significant for TBARS (×0.8-fold, p = 0.0872). The hemostatic parameters were also not modified (p ≥ 0.8171). A protective effect of myo-inositol was demonstrated against prooxidant damage to human plasma and rat thoracic arteries, suggesting a strong role of this nutraceutical agent on vasculature which may be of benefit against harmful environmental effects.
Short-Term Ingestion of Medium-Chain Triglycerides Could Enhance Postprandial Consumption of Ingested Fat in Individuals with a Body Mass Index from 25 to Less than 30: A Randomized, Placebo-Controlled, Double-Blind Crossover Study
Authors: Nosaka Naohisa , Tsujino Shougo , Kato Kazuhiko
Published: March 2022

The elimination of obesity is essential to maintaining good health. Medium-chain triglycerides (MCTs) inhibit fat accumulation. However, studies examining energy expenditure and fat oxidation with continuous ingestion of MCTs show little association with the elimination of obesity. In this study, we conducted a randomized, double-blind crossover clinical trial to investigate the effects of continuous ingestion of MCTs on postprandial energy expenditure and ingested long-chain triglycerides (LCTs) oxidation. A daily 2 g of MCTs were ingested for two weeks by sedentary participants with a body mass index (BMI) from 25 (kg/m2) to less than 30. Ingestion of a meal containing MCTs and isotopic carbon-13-labeled (13C) LCTs increased energy expenditure and consumption of diet-derived LCTs, as determined by postprandial 13C carbon dioxide excretion, compared to canola oil as the placebo control. These results indicate that continuous ingestion of MCTs could enhance postprandial degradation of diet-derived fat and energy expenditure in sedentary, overweight individuals.
Dietary Sodium and Potassium Intake and Risk of Non-Fatal Cardiovascular Diseases: The Million Veteran Program
Authors: Wang Dong D. , Li Yanping , Nguyen Xuan-Mai T. , Song Rebecca J. , Ho Yuk-Lam , Hu Frank B. , Willett Walter C. , Wilson Peter W. F. , Cho Kelly , Gaziano J. Michael , Djoussé Luc ,   on behalf of the VA Million Veteran Program
Published: March 2022

Objective: To examine the association between intakes of sodium and potassium and the ratio of sodium to potassium and incident myocardial infarction and stroke. Design, Setting and Participants: Prospective cohort study of 180,156 Veterans aged 19 to 107 years with plausible dietary intake measured by food frequency questionnaire (FFQ) who were free of cardiovascular disease (CVD) and cancer at baseline in the VA Million Veteran Program (MVP). Main outcome measures: CVD defined as non-fatal myocardial infarction (MI) or acute ischemic stroke (AIS) ascertained using high-throughput phenotyping algorithms applied to electronic health records. Results: During up to 8 years of follow-up, we documented 4090 CVD cases (2499 MI and 1712 AIS). After adjustment for confounding factors, a higher sodium intake was associated with a higher risk of CVD, whereas potassium intake was inversely associated with the risk of CVD [hazard ratio (HR) comparing extreme quintiles, 95% confidence interval (CI): 1.09 (95% CI: 0.99–1.21, p trend = 0.01) for sodium and 0.87 (95% CI: 0.79–0.96, p trend = 0.005) for potassium]. In addition, the ratio of sodium to potassium (Na/K ratio) was positively associated with the risk of CVD (HR comparing extreme quintiles = 1.26, 95% CI: 1.14–1.39, p trend < 0.0001). The associations of Na/K ratio were consistent for two subtypes of CVD; one standard deviation increment in the ratio was associated with HRs (95% CI) of 1.12 (1.06–1.19) for MI and 1.11 (1.03–1.19) for AIS. In secondary analyses, the observed associations were consistent across race and status for diabetes, hypertension, and high cholesterol at baseline. Associations appeared to be more pronounced among participants with poor dietary quality. Conclusions: A high sodium intake and a low potassium intake were associated with a higher risk of CVD in this large population of US veterans.
First Trimester Maternal Homocysteine and Embryonic and Fetal Growth: The Rotterdam Periconception Cohort
Authors: Rubini Eleonora , Snoek Katinka M. , Schoenmakers Sam , Willemsen Sten P. , Sinclair Kevin D. , Rousian Melek , Steegers-Theunissen Régine P. M.
Published: March 2022

Homocysteine is a marker for derangements in one-carbon metabolism. Elevated homocysteine may represent a causal link between poor maternal nutrition and impaired embryonic and fetal development. We sought to investigate associations between reference range maternal homocysteine and embryonic and fetal growth. We enrolled 1060 singleton pregnancies (555 natural and 505 in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancies) from November 2010 to December 2020. Embryonic and fetal body and head growth was assessed throughout pregnancy using three-dimensional ultrasound scans and virtual reality techniques. Homocysteine was negatively associated with first trimester embryonic growth in the included population (crown-rump length B −0.023 mm, 95% CI −0.038,−0.007, p = 0.004, embryonic volume B −0.011 cm3, 95% CI −0.018,−0.004, p = 0.003). After stratification for conception mode, this association remained in IVF/ICSI pregnancies with frozen embryo transfer (crown-rump length B −0.051 mm, 95% CI −0.081,−0.023, p < 0.001, embryonic volume B −0.024 cm3, 95% CI −0.039,−0.009, p = 0.001), but not in IVF/ICSI pregnancies with fresh embryo transfer and natural pregnancies. Homocysteine was not associated with longitudinal measurements of head growth in first trimester, nor with second and third trimester fetal growth. Homocysteine in the highest quartile (7.3–14.9 µmol/L) as opposed to the lowest (2.5–5.2 µmol/L) was associated with reduced birth weight in natural pregnancies only (B −51.98 g, 95% CI −88.13,−15.84, p = 0.005). In conclusion, high maternal homocysteine within the reference range is negatively associated with first trimester embryonic growth and birth weight, and the effects of homocysteine are dependent on conception mode.
Recent Advances in Clinical Nutrition in Stroke Rehabilitation
Authors: Yoshimura Yoshihiro
Published: March 2022

Stroke is a common cause of death and disability worldwide [...]
Exosomal FZD-7 Expression Is Modulated by Different Lifestyle Interventions in Patients with NAFLD
Authors: Scavo Maria , Depalo Nicoletta , Rizzi Federica , Carrieri Livianna , Serino Grazia , Franco Isabella , Bonfiglio Caterina , Pesole Pasqua , Cozzolongo Raffaele , Gianuzzi Vito , Curri Maria , Osella Alberto , Giannelli Gianluigi
Published: March 2022

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition characterized from hypertriglyceridemia and hepatic fat accumulation, in the absence of alcohol intake. NAFLD starts as steatosis (NAFL), and the continued injury relative to the toxic fat induces inflammation, steatohepatitis (NASH), and HCC. One of the factors determining liver degeneration during the evolution of NAFLD is a modification of Wnt/Frizzled (FZD) signaling. In particular, an inhibition of Wnt signaling and an overexpression of a specific FZD receptor protein, namely, the FZD7, have been observed in NAFLD. Actually, the prognosis and the follow-up of NAFLD is not easy, and the liver biopsy is the gold standard for an accurate detection of liver fibrosis. In this study, the modulation of the FZD7 expression levels in plasma-derived exosomes of NAFLD-affected patients, before and after specific lifestyle interventions, were experimentally evaluated by Western blotting analysis. The experimental data were analyzed by an accurate statistical study that indicated, in the exosomes derived from plasma of NAFLD patients with moderate or severe steatosis, an average expression level of FZD7 that was significantly higher than healthy subjects at baseline; conversely, the values were normalized after 90 days of specific lifestyle interventions. The overall results suggested that the FZD7 delivered by exosomes represents a good candidate as a new and effective biomarker for diagnosis and prognosis of NAFLD.
Characterization of Vitamin D Status in Older Persons with Cognitive Impairment
Authors: Arosio Beatrice , Rossi Paolo Dionigi , Ferri Evelyn , Cesari Matteo , Vitale Giovanni
Published: March 2022

Vitamin D exerts a role in the maintenance of cognitive abilities and in frailty. Although several studies evaluated the interactions between vitamin D and cognitive impairment, results were conflicting. In a cohort of community-dwelling older persons, we described the association between vitamin D levels and cognitive decline and all-cause dementia evaluating frailty’s contribution. Our cohort included 509 adults, aged 64–92 years: 176 patients with mild cognitive impairment (MCI), 59 with Alzheimer’s Disease (AD), 26 with idiopathic Normal Pressure Hydrocephalus (iNPH), 133 with mixed dementia (MD) and 115 without cognitive decline. Frailty was measured by frailty index, and serum 25-hydroxyvitamin D concentrations through electrochemiluminescence immunoassays. We found a significant association between vitamin D levels and Mini Mental State Examination independently of cognitive impairment, age, sex and frailty. The patients with dementia (AD and MD) showed the lowest vitamin D levels, while MCI patients showed higher levels than the other groups. The most severe deficiency was observed in MD patients, the most aged as well as cognitively and functionally impaired. In conclusion, in our community-dwelling older persons investigated for a suspected cognitive impairment, we observed an association between vitamin D levels and cognitive decline, regardless of the frailty status.
Review of Dietary Recommendations for Twin Pregnancy: Does Nutrition Science Keep Up with the Growing Incidence of Multiple Gestations?
Authors: Wierzejska Regina Ewa
Published: March 2022

Recommendations for nutrition and the use of dietary supplements for pregnant women are updated on regular basis but it remains to be seen to what extent they may be applicable in twin pregnancies. The aim of this narrative review is to present the current state of knowledge about the energy and nutrient demand in twin pregnancy. There is general consensus in literature that the energy demand is higher than in a singleton pregnancy, but there is a lack of position statements from scientific societies on specific energy intake that is required. In turn, recommended maternal weight gain, which favors the normal weight of the neonate, has been determined. There is even a larger knowledge gap when it comes to vitamins and minerals, the body stores of which are theoretically used up faster. The greatest number of studies so far focused on vitamin D, and most of them concluded that its concentration in maternal blood is lower in twin as compared to singleton pregnancy. Few randomized studies focus on iron supplementation and there are no other studies that would assess dietary interventions. In light of a growing incidence of multiple pregnancies, more studies are necessary to establish the nutritional demands of the mother and the course of action for adequate supplementation.
Efficacy of Vitamin D Supplements in Treatment of Acute Respiratory Infection: A Meta-Analysis for Randomized Controlled Trials
Authors: Cho Herim , Myung Seung-Kwon , Cho Hae-Eun
Published: March 2022

Background: Recent randomized controlled trials (RCTs) have reported inconsistent findings regarding the efficacy of vitamin D supplementation in the treatment of acute respiratory infections (ARIs). This study aimed to investigate the efficacy of vitamin D supplementation in the treatment of ARIs using a meta-analysis of RCTs. Methods: PubMed, EMBASE, and the Cochrane Library were searched for relevant articles in June 2021. Two of the authors independently assessed the eligibility of the trials. Results: Out of 390 articles retrieved from the databases, we included 18 RCTs, which involved 3648 participants, with 1838 in an intervention group and 1810 in a control group in the final analysis. In the meta-analysis of all the trials, vitamin D supplements had a beneficial effect in the treatment of ARIs (relative risk (RR) = 1.07; 95% confidence interval (CI), 1.01–1.13; I2 = 66.9%). Publication bias was observed in the funnel plot. In the subgroup meta-analysis of high-quality RCTs, no significant efficacy of vitamin D supplements was found (RR = 1.02; 95% CI, 0.98–1.06; I2 = 24.0%). Although statistically significant changes of 7% in the treatment effects were observed, they are not considered as clinically substantial ones. Conclusions: The current meta-analysis suggests that vitamin D supplements are not clinically effective in the treatment of ARIs.
Anisakis, Something Is Moving inside the Fish
Authors: Audicana María Teresa
Published: March 2022

The first case of human infection by a species of the Anisakidae family was reported more than 60 years ago. Over the last 20 years, Anisakis has become a highly studied parasite, not only for its parasitism, but also for its role as an inducer of allergic reactions. Several studies have indicated that the pathological changes occurring within the gastrointestinal tract during infection with Anisakis simplex are the combined result of the direct action of the larvae invading the tissue and the complex interaction between the host’s immune system and the parasite. Although the most commonly described pathologies are digestive, urticaria/angioedema and anaphylaxis, occupational asthma and arthritis have been seldom described. This paper is a narrative of the immune-mediated reaction induced by this parasite over the course of the last two decades.
Integrated Management Strategies for Viral Nervous Necrosis (VNN) Disease Control in Marine Fish Farming in the Mediterranean
Authors: Padrós Francesc , Caggiano Massimo , Toffan Anna , Constenla Maria , Zarza Carlos , Ciulli Sara
Published: March 2022

Viral nervous necrosis (VNN) is the most important viral disease affecting farmed fish in the Mediterranean. VNN can affect multiple fish species in all production phases (broodstock, hatchery, nursery and ongrowing) and sizes, but it is especially severe in larvae and juvenile stages, where can it cause up to 100% mortalities. European sea bass has been and is still the most affected species, and VNN in gilthead sea bream has become an emerging problem in recent years affecting larvae and juveniles and associated to the presence of new nervous necrosis virus (NNV) reassortants. The relevance of this disease as one of the main biological hazards for Mediterranean finfish farming has been particularly addressed in two recent H2020 projects: PerformFISH and MedAID. The presence of the virus in the environment and in the farming systems poses a serious menace for the development of the Mediterranean finfish aquaculture. Several risks associated to the VNN development in farms have been identified in the different phases of the farming system. The main risks concerning VNN affecting gilthead seabream and European seabass have been identified as restocking from wild fish in broodstock facilities, the origin of eggs and juveniles, quality water supply and live food in hatcheries and nurseries, and infected juveniles and location of farms in endemic areas for on-growing sites. Due to the potential severe impact, a holistic integrated management approach is the best strategy to control VNN in marine fish farms. This approach should include continuous surveillance and early and accurate diagnosis, essential for an early intervention when an outbreak occurs, the implementation of biosecurity and disinfection procedures in the production sites and systematic vaccination with effective vaccines. Outbreak management practices, clinical aspects, diagnostic techniques, and disinfections methods are reviewed in detail in this paper. Additionally, new strategies are becoming more relevant, such as the use of genetic resistant lines and boosting the fish immune system though nutrition.
Pyrazolo[4,3-c]pyridine Sulfonamides as Carbonic Anhydrase Inhibitors: Synthesis, Biological and In Silico Studies
Authors: Angeli Andrea , Kartsev Victor , Petrou Anthi , Lichitsky Boris , Komogortsev Andrey , Pinteala Mariana , Geronikaki Athina , Supuran Claudiu T.
Published: March 2022

Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the essential reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho-/physiological conditions. A series of chromene-based sulfonamides were synthesized and tested as possible CA inhibitors. On the other hand, in microorganisms, the β- and γ- classes are expressed in addition to the α- class, showing substantial structural differences to the human isoforms. In this scenario, not only human but also bacterial CAs are of particular interest as new antibacterial agents with an alternative mechanism of action for fighting the emerging problem of extensive drug resistance afflicting most countries worldwide. Pyrazolo[4,3-c]pyridine sulfonamides were synthesized using methods of organic chemistry. Their inhibitory activity, assessed against the cytosolic human isoforms hCA I and hCA II, the transmembrane hCA IX and XII, and β- and γ-CAs from three different bacterial strains, was evaluated by a stopped-flow CO2 hydrase assay. Several of the investigated derivatives showed interesting inhibition activity towards the cytosolic associate isoforms hCA I and hCA II, as well as the 3β- and 3γ-CAs. Furthermore, computational procedures were used to investigate the binding mode of this class of compounds within the active site of hCA IX. Four compounds (1f, 1g, 1h and 1k) were more potent than AAZ against hCA I. Furthermore, compound 1f also showed better activity than AAZ against the hCA II isoform. Moreover, ten compounds out of eleven appeared to be very potent against the γ-CA from E.coli, with a Ki much lower than that of the reference drug. Most of the compounds showed better activity than AAZ against hCA I as well as the γ-CA from E.coli and the β-CA from Burkholderia pseudomallei (BpsCAβ). Compounds 1f and 1k showed a good selectivity index against hCA I and hCA XII, while 1b was selective against all 3β-CA isoforms from E.coli, BpsCA, and VhCA and all 3γ-CA isoforms from E.coli, BpsCA and PgiCA.
From Biomedical Applications of Alginate towards CVD Implications Linked to COVID-19
Authors: Spoială Angela , Ilie Cornelia-Ioana , Ficai Denisa , Ficai Anton , Andronescu Ecaterina
Published: March 2022

In the past year, researchers have focused their attention on developing new strategies for understanding how the coronavirus affects human health and developing novel biomaterials to help patients with cardiovascular disease, which greatly increases the risk of complications from the virus. Natural biopolymers have been investigated, and it has been proven that alginate-based materials have important features. This review presents an overview of alginate-based materials used for developing innovative biomaterial platforms for biomedical applications to mitigate the effects of the coronavirus. As presented in this review, COVID-19 affects the cardiovascular system, not only the lungs. The first part of the review presents an introduction to cardiovascular diseases and describes how they have become an important problem worldwide. In the second part of the review, the origin and unique properties of the alginate biopolymer are presented. Among the properties of alginate, the most important are its biocompatibility, biodegradability, low cost, nontoxicity, unique structure, and interesting features after chemical modification. The third section of the review illustrates some of the functions of alginate in biomedical, pharmaceutical, and drug delivery applications. Researchers are using alginate to develop new devices and materials for repairing heart tissues that have been damaged by the coronavirus. Further, insights regarding how cardiovascular disease affects COVID-19 patients are also discussed. Finally, we conclude the review by presenting a summary of the impacts of COVID-19 on cardiovascular patients, their implications, and several hypothetical alginate-based treatments for infected patients.
Small Molecule Induced FLT3 Degradation
Authors: Han Sun-Young
Published: March 2022

Target protein degrader is a new paradigm in the small molecule drug discovery field and relates to the term ‘event-driven pharmacology’. Fms-like tyrosine kinase 3 (FLT3) is a significant target for treating acute myeloid leukemia (AML). A few FLT3 kinase inhibitors are currently used in the clinic for AML patients. However, resistance to current FLT3 inhibitors has emerged, and strategies to overcome this resistance are required. Small molecules downregulating FLT3 protein level are reported, exhibiting antileukemic effects against AML cell lines. Small molecules with various mechanisms such as Hsp90 inhibition, proteasome inhibition, RET inhibition, and USP10 inhibition are explained. In addition, reports of FLT3 as a client of Hsp90, current knowledge of the ubiquitin proteasome system for FLT3 degradation, the relationship with FLT3 phosphorylation status and susceptibility of FLT3 degradation are discussed.
COVID-19 and Seasonal Influenza Vaccination: Cross-Protection, Co-Administration, Combination Vaccines, and Hesitancy
Authors: Domnich Alexander , Orsi Andrea , Trombetta Carlo-Simone , Guarona Giulia , Panatto Donatella , Icardi Giancarlo
Published: March 2022

SARS-CoV-2 and influenza are the main respiratory viruses for which effective vaccines are currently available. Strategies in which COVID-19 and influenza vaccines are administered simultaneously or combined into a single preparation are advantageous and may increase vaccination uptake. Here, we comprehensively review the available evidence on COVID-19/influenza vaccine co-administration and combination vaccine candidates from the standpoints of safety, immunogenicity, efficacy, policy and public acceptance. While several observational studies have shown that the trained immunity induced by influenza vaccines can protect against some COVID-19-related endpoints, it is not yet understood whether co-administration or combination vaccines can exert additive effects on relevant outcomes. In randomized controlled trials, co-administration has proved safe, with a reactogenicity profile similar to that of either vaccine administered alone. From the immunogenicity standpoint, the immune response towards four influenza strains and the SARS-CoV-2 spike protein in co-administration groups is generally non-inferior to that seen in groups receiving either vaccine alone. Several public health authorities have advocated co-administration. Different combination vaccine candidates are in (pre)-clinical development. The hesitancy towards vaccine co-administration or combination vaccines is a multifaceted phenomenon and may be higher than the acceptance of either vaccine administered separately. Public health implications are discussed.
Identifying Human PTP1B Enzyme Inhibitors from Marine Natural Products: Perspectives for Developing of Novel Insulin-Mimetic Drugs
Authors: Casertano Marcello , Genovese Massimo , Piazza Lucia , Balestri Francesco , Del Corso Antonella , Vito Alessio , Paoli Paolo , Santi Alice , Imperatore Concetta , Menna Marialuisa
Published: March 2022

Diabetes mellitus (DM) represents a complex and multifactorial disease that causes metabolic disorders with acute and long-term serious complications. The onset of DM, with over 90% of cases of diabetes classified as type 2, implies several metabolic dysfunctions leading to consider DM a worldwide health problem. In this frame, protein tyrosine phosphatase 1B (PTP1B) and aldose reductase (AR) are two emerging targets involved in the development of type 2 diabetes mellitus (T2DM) and its chronic complications. Herein, we employed a marine-derived dual type inhibitor of these enzymes, phosphoeleganin, as chemical starting point to perform a fragment-based process in search for new inhibitors. Phosphoeleganin was both disassembled by its oxidative cleavage and used as model structure for the synthesis of a small library of functionalized derivatives as rationally designed analogues. Pharmacological screening supported by in silico docking analysis outlined the mechanism of action against PTP1B exerted by a phosphorylated fragment and a synthetic simplified analogue, which represent the most potent inhibitors in the library.
Plastid Phylogenomic Analysis of Tordylieae Tribe (Apiaceae, Apioideae)
Authors: Samigullin Tahir , Logacheva Maria , Terentieva Elena , Degtjareva Galina , Pimenov Michael , Valiejo-Roman Carmen
Published: March 2022

Based on the nrDNA ITS sequence data, the Tordylieae tribe is recognized as monophyletic with three major lineages: the subtribe Tordyliinae, the Cymbocarpum clade, and the Lefebvrea clade. Recent phylogenomic investigations showed incongruence between the nuclear and plastid genome evolution in the tribe. To assess phylogenetic relations and structure evolution of plastomes in Tordylieae, we generated eleven complete plastome sequences using the genome skimming approach and compared them with the available data from this tribe and close relatives. Newly assembled plastomes had lengths ranging from 141,148 to 150,103 base pairs and contained 122–127 genes, including 79–82 protein-coding genes, 35–37 tRNAs, and 8 rRNAs. We observed substantial differences in the inverted repeat length and gene content, accompanied by a complex picture of multiple JLA and JLB shifts. In concatenated phylogenetic analyses, Tordylieae plastomes formed at least three not closely related lineages with plastomes of the Lefebvrea clade as a sister group to plastomes from the Selineae tribe. The newly obtained data have increased our knowledge on the range of plastome variability in Apiaceae.
The Impact of Different Weed Management Systems on Weed Flora and Dry Biomass Production of Barley Grown under Various Barley-Based Cropping Systems
Authors: Naeem Muhammad , Farooq Shahid , Hussain Mubshar
Published: March 2022

Weeds are among the major issues responsible for reduction in yield and profit in any crop production system. Herbicides are the easiest and quickest solution of weeds; however, their frequent use exert negative consequences on environment, human health, and results in the evolution of herbicide-resistant weed species. Due to these reasons, alternative weed management methods that are less harmful to environment and human health are needed. This two-year study evaluated the impact of different weed management options, i.e., false seedbed (FS), allelopathic water extracts (AWE), chemical control (CC), weed-free (WF) weedy-check (WC) on weed spectrum in various barley-based cropping systems, i.e., fallow-barley (FB), maize-barley (MB), cotton-barley (CB), mungbean-barley (M*B), and sorghum-barley (SB). Data relating to density, diversity, and biomass production of weed species prevailing in the studied cropping systems were recorded. Interactive effect of weed management methods and barley-based cropping systems significantly altered weed diversity, and densities of individual, broadleaved, and grassy weeds. A total 13 weed species (ten broadleaved and three grass) were recorded during both years of study. The highest dry biomass, diversity, and density of individual, broadleaved, and grassy weeds were noted in WC treatment, whereas WF treatment resulted in the lowest values of these traits. Chemical control resulted in the highest suppression of weed flora and improved dry biomass production of barley followed by AWE. The SB cropping system with CC or AWE resulted in the least weed flora. The M*B cropping system with CC or AWE produced the highest dry biomass of barley. It is concluded that including sorghum crop in rotation and applying AWE could suppress weeds comparable to herbicides. Similarly, including mungbean in rotation and applying AWE could increase dry biomass production of barley. In conclusion, herbicides can be replaced with an eco-friendly approach, i.e., allelopathy and inclusion of sorghum crop could be helpful in suppressing weed flora.
A Survey of Main Pepper Crop Viruses in Different Cultivation Systems for the Selection of the Most Appropriate Resistance Genes in Sensitive Local Cultivars in Northern Spain
Authors: Ojinaga Mikel , Guirao Pedro , Larregla Santiago
Published: March 2022

Viral diseases have become one of the main phytosanitary problems for pepper growers in the Basque Country (northern Spain). In 2014, a survey was carried out to determine the prevalence of the most common viruses found in Gernika pepper and Ibarra chili pepper landraces. A total of 97 plots were surveyed and classified according to the crop system. Within these plots, 1107 plants were sampled and tested for tobacco mosaic virus (TMV), tomato mosaic virus (ToMV), tobacco mild green mosaic virus (TMGMV), pepper mild mottle virus (PMMoV), paprika mild mottle virus (PaMMV), potato virus Y (PVY) and tomato spotted wilt virus (TSWV) applying a DAS-ELISA test. PaMMV was verified by the non-radioactive molecular hybridization technique and it was found to be negative. All viruses were detected, but the most prevalent viruses were PVY and TMGMV (19.8% and 10.6% of tested plants, respectively). Differences among cultivation systems were found for most of the tested viruses. PVY had a higher level of infection under open field conditions (27.3%) than under greenhouse conditions (12.3%). Inversely, the viruses belonging to the Tobamovirus genus and TSWV prevailed under greenhouse conditions (28.9% and 5.2%) when compared to open field (11.2% and 1.1%), respectively. Single (28%) and multiple infections (8.9%) were found. All PMMoV isolates were classified as pathotype P1.2. Survey results indicated that tobamovirus and PVY resistance genes would be the most appropriate to be included in breeding programs with these sensitive pepper landraces.
Auxin-Producing Bacteria from Duckweeds Have Different Colonization Patterns and Effects on Plant Morphology
Authors: Gilbert Sarah , Poulev Alexander , Chrisler William , Acosta Kenneth , Orr Galya , Lebeis Sarah , Lam Eric
Published: March 2022

The role of auxin in plant–microbe interaction has primarily been studied using indole-3-acetic acid (IAA)-producing pathogenic or plant-growth-promoting bacteria. However, the IAA biosynthesis pathway in bacteria involves indole-related compounds (IRCs) and intermediates with less known functions. Here, we seek to understand changes in plant response to multiple plant-associated bacteria taxa and strains that differ in their ability to produce IRCs. We had previously studied 47 bacterial strains isolated from several duckweed species and determined that 79% of these strains produced IRCs in culture, such as IAA, indole lactic acid (ILA), and indole. Using Arabidopsis thaliana as our model plant with excellent genetic tools, we performed binary association assays on a subset of these strains to evaluate morphological responses in the plant host and the mode of bacterial colonization. Of the 21 tested strains, only four high-quantity IAA-producing Microbacterium strains caused an auxin root phenotype. Compared to the commonly used colorimetric Salkowski assay, auxin concentration determined by LC–MS was a superior indicator of a bacteria’s ability to cause an auxin root phenotype. Studies with the auxin response mutant axr1-3 provided further genetic support for the role of auxin signaling in mediating the root morphology response to IAA-producing bacteria strains. Interestingly, our microscopy results also revealed new evidence for the role of the conserved AXR1 gene in endophytic colonization of IAA-producing Azospirillum baldaniorum Sp245 via the guard cells.