bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal and Spatial Dynamics of Dark Septate Endophytes in the Roots of Lycium ruthenicum in the Desert Region of Northwest China
Authors: Han Li , Shi Jingxin , He Chao , He Xueli
Published: March 2021

With the intensification of desertification in northwest China, drought has become a serious environmental problem restricting plant growth and ecological restoration. Recently, dark septate endophytes (DSEs) have attracted more attention because of their ability to improve plants’ resistance to drought. Here, we investigated DSE colonization and species diversity in roots of Lycium ruthenicum collected from Anxi and Minqin, in northwest China, during July, September, and December 2019. This study aimed to evaluate the influence of seasonality and sampling sites on DSEs. In different seasons, DSE colonization varied with the phenology of L. ruthenicum. At different sites, DSE colonization significantly differed. Four isolates were reported in desert ecosystems for the first time. The results showed microsclerotial colonization was directly affected by changing seasons, while hyphal colonization and species diversity were directly affected by sampling sites. The soil organic carbon, pH, alkaline phosphatase, and alkali-hydrolyzable nitrogen were the main predictors of DSE colonization and species diversity. We conclude that DSE colonization and diversity showed significant spatial–temporal heterogeneity and were closely related to soil factors. This research provides a basis for the further understanding of the ecological functions of DSEs and their application potential for vegetative restoration and agricultural cultivation in drylands.
Management to Promote Flowering Understoreys Benefits Natural Enemy Diversity, Aphid Suppression and Income in an Agroforestry System
Authors: Staton Tom , Walters Richard , Smith Jo , Breeze Tom , Girling Robbie
Published: March 2021

Agroforestry systems, where productive trees are integrated into agricultural land, can deliver benefits to biodiversity, natural pest control, and pollination, but the effects are highly variable. Recent advances in our understanding of flower strips in agricultural systems suggest that the management of the tree row understorey could be an important contributor to this variation. Here, we compare two cutting regimes for an understorey, originally seeded with the same flower mix, in the tree rows of an apple-arable agroforestry system: (i) uncut vegetation to promote a flowering understorey, and (ii) regularly mown vegetation. We recorded the effects of management on invertebrate pests, natural enemies, and pollinators, in both the apple and arable components. Apple trees above flowering understoreys supported significantly: (i) more natural enemies early in the season, (ii) fewer aphid colonies, (iii) fewer aphid-damaged fruits, and (iv) higher pollinator visitation, compared with those above mown understoreys. In the arable crop alleys, both the taxonomic richness and Shannon diversity of ground-based natural enemies were significantly higher adjacent to flowering understoreys, compared with those adjacent to mown understoreys, early in the season. Financial modelling based on aphid damage to apples, mowing costs, and income from Countryside Stewardship grants, indicated that flowering understoreys increased farm income by GBP 231.02 per ha of agroforestry compared with mown understoreys. Our results provide the first empirical evidence that management to promote flowering understoreys in agroforestry systems can be a win-win option to improve invertebrate diversity, associated ecosystem services, and farm income.
Cattle Cleanliness from the View of Swedish Farmers and Official Animal Welfare Inspectors
Authors: Lundmark Hedman Frida , Andersson Maria , Kinch Vanja , Lindholm Amelie , Nordqvist Angelica , Westin Rebecka
Published: March 2021

Dirty cattle have been commonly recorded in official animal welfare inspections in Sweden for years. The relevant authorities have initiated work to better understand the causes of dirty cattle, in order to improve compliance and standardize the grounds for categorizing a farm as non-compliant with welfare legislation when dirty animals are present. This study investigated the occurrence of dirty cattle in official animal welfare controls, on Swedish cattle farms, and examined farmers’ views on the reasons for non-compliance and on key factors in keeping animals clean. The data used were collected by animal welfare inspectors at the county level during the regular official inspections of 371 dairy and beef cattle farms over two weeks in winter 2020. In addition to completing the usual inspection protocol, the inspectors asked farmers a set of questions relating to why their animals were clean or dirty. Dirty cattle were found on 49% of the farms inspected, but only 33% of the farms were categorized as being non-compliant with Swedish welfare legislation. According to inspectors and farmers, dirtiness in cattle depends mainly on management routines, which is a promising result since routines can be improved. The results also revealed a need for better guidance for inspectors and farmers on when dirtiness should be categorized as non-compliance with animal welfare legislation.
Feeding Forage Mixtures of Ryegrass (Lolium spp.) with Clover (Trifolium spp.) Supplemented with Local Feed Diets to Reduce Enteric Methane Emission Efficiency in Small-Scale Dairy Systems: A Simulated Study
Authors: Celis-Alvarez Maria Danaee , López-González Felipe , Arriaga-Jordán Carlos Manuel , Robles-Jiménez Lizbeth E. , González-Ronquillo Manuel
Published: March 2021

In cattle, greenhouse gas (GHG) emissions and nutrient balance are influenced by factors such as diet composition, intake, and digestibility. This study evaluated CH4 emissions and surpluses of crude protein, using five simulated scenarios of supplementation in small-scale dairy systems (SSDS). In addition, two pasture managements (cut-and-carry versus grazing) and two varieties of legumes (red clover vs. white clover) were considered. The diets were tested considering similar milk yield and chemical composition; CH4 emission was estimated using Tier-2 methodology from the Intergovernmental Panel on Climate Change (IPCC), and the data were analyzed in a completely randomized 5 × 2 × 2 factorial design. Differences (p < 0.05) were found in predicted CH4 emissions per kg of milk produced (g kg−1 FCM 3.5%). The lowest predicted CH4 emissions were found for S3 and S4 as well as for pastures containing white clover. Lower dietary surpluses of CP (p < 0.05) were observed for the control diet (1320 g CP/d), followed by S5 (1793 g CP/d), compared with S2 (2175 g CP/d), as well as in cut-and-carry management with red clover. A significant correlation (p < 0.001) was observed between dry matter intake and CH4 emissions (g−1 and per kg of milk produced). It is concluded that the environmental impact of formulating diets from local inputs (S3 and S4) can be reduced by making them more efficient in terms of methane kg−1 of milk in SSDS.
Modified Proximal Interphalangeal Joint Arthrodesis in a Yearling Filly with an Osseous Cyst-Like Lesion in the Proximal Phalanx
Authors: Kol’vek Filip , Krešáková Lenka , Vdoviaková Katarína , Medvecký Ľubomír , Žert Zdeněk
Published: March 2021

After the medial femoral condyle (MFC), the phalanges are the second most common site for osseous cyst-like lesions (OCLLs). Conservative treatment of phalangeal cysts on the convex surface of proximal phalanx presents a technical problem with access to the stoma of the cyst. Surgical therapy options usually aim to avoid cyst enlargement through drilling or screw placement or to encourage lesion filling with osteoconductive material. This paper describes a case of treatment of the OCLL in a yearling Czech warmblood filly with surgical arthrodesis, together with the packing of the OCLL with calcium phosphate biocement (CPB). The filly showed a chronic, moderate to severe, intermittent left hindlimb lameness. Dynamic examination combined with regional anesthesia and radiography confirmed a clinically significant large OCLL on the distal joint surface of the first phalanx. Treatment of the OCLL was performed by surgical arthrodesis of the proximal interphalangeal joint, using two paraxial and one axial crossed lag screw, after curetting of the cyst and filling with CPB.
Clinical and Echocardiographic Findings in an Aged Population of Cavalier King Charles Spaniels
Authors: Prieto Ramos Jorge , Corda Andrea , Swift Simon , Saderi Laura , De La Fuente Oliver Gabriel , Corcoran Brendan , Summers Kim M. , French Anne T.
Published: March 2021

Myxomatous mitral valve disease (MMVD) is the most common cardiac disease in dogs. It varies from dogs without clinical signs to those developing left-sided congestive heart failure, leading to death. Cavalier King Charles Spaniels (CKCSs) are particularly susceptible to MMVD. We hypothesised that within the elderly CKCS population, there is a sub-cohort of MMVD-affected dogs that do not have cardiac remodelling. The objectives of the present study were (i) to determine the prevalence and the degree of cardiac remodelling associated with MMVD; and (ii) assess the effect of age, gender, and body weight on echocardiographic status in a population of aged CKCSs. A total of 126 CKCSs ≥ 8 years old were prospectively included. They all had a physical and echocardiographic examination. A systolic murmur was detected in 89% of dogs; the presence of clinical signs was reported in 19% of them; and echocardiographic evidence of MMVD was described in 100%. Despite the high prevalence, 44.4% of the dogs were clear of echocardiographic signs of cardiac remodelling. Age was significantly associated with the presence and severity of cardiac remodelling and mitral valve prolapse. Our results showed that a proportion of elderly CKCS with confirmed MMVD did not undergo advanced stages of this pathology.
Parent and Clinician Views of Managing Children with Symptoms of a Lower Respiratory Tract Infection and Their Influence upon Decisions to Take Part in a Placebo-Controlled Randomised Control Trial
Authors: Woods Catherine J. , Morrice Zoe , Francis Nick A. , Little Paul , Verheij Theo , Leydon Geraldine M.
Published: March 2021

Children presenting with uncomplicated lower respiratory tract infections (LRTIs) commonly receive antibiotics despite public campaigns on antibiotic resistance. Qualitative interview studies were nested in a placebo-controlled trial of amoxicillin for LRTI in children. Thirty semi-structured telephone interviews were conducted with sixteen parents and fourteen clinicians to explore views of management and decisions to participate in the trial. All interviews were audio-recorded, transcribed and analysed using thematic analysis. Parents found it difficult to interpret symptoms and signs, and commonly used the type of cough (based on sound) to judge severity, highlighting the importance of better information to support parents. Provision of a clinical examination and reassurance regarding illness severity were key motivations for consulting. Many parents now acknowledge that antibiotics should only be used when ‘necessary’, and clinicians reported noticing a shift in parent attitudes with less demand for antibiotics and greater satisfaction with clinical assessment, reassurance and advice. Decisions to take part in the trial were influenced by the perceived risks associated with allocation to a placebo, and concerns about unnecessary use of antibiotics. Clear communication about self-management and safety-netting were identified as important when implementing ‘no antibiotic’ prescribing strategies to reassure parents and to support prescribing decisions.
Early Monitoring Response to Therapy in Patients with Brain Lesions Using the Cumulative SUV Histogram
Authors: Stefano Alessandro , Pisciotta Pietro , Pometti Marco , Comelli Albert , Cosentino Sebastiano , Marletta Francesco , Cicero Salvatore , Sabini Maria G. , Ippolito Massimo , Russo Giorgio
Published: March 2021

Gamma Knife treatment is an alternative to traditional brain surgery and whole-brain radiation therapy for treating cancers that are inaccessible via conventional treatments. To assess the effectiveness of Gamma Knife treatments, functional imaging can play a crucial role. The aim of this study is to evaluate new prognostic indices to perform an early assessment of treatment response to therapy using positron emission tomography imaging. The parameters currently used in nuclear medicine assessments can be affected by statistical fluctuation errors and/or cannot provide information on tumor extension and heterogeneity. To overcome these limitations, the Cumulative standardized uptake value (SUV) Histogram (CSH) and Area Under the Curve (AUC) indices were evaluated to obtain additional information on treatment response. For this purpose, the absolute level of [11C]-Methionine (MET) uptake was measured and its heterogeneity distribution within lesions was evaluated by calculating the CSH and AUC indices. CSH and AUC parameters show good agreement with patient outcomes after Gamma Knife treatments. Furthermore, no relevant correlations were found between CSH and AUC indices and those usually used in the nuclear medicine environment. CSH and AUC indices could be a useful tool for assessing patient responses to therapy.
Comparative Effectiveness of a Commercial Mouthwash and an Herbal Infusion in Oral Health Care
Authors: Ciavoi Gabriela , Dobjanschi Luciana , Jurca Tunde , Osser Gyongyi , Scrobota Ioana , Pallag Annamaria , Muresan Mariana Eugenia , Vicaș Laura Gratiela , Marian Eleonora , Bechir Farah , Mihai Laurenta Lelia , Béres Enikő , Iurcov Raluca Ortensia Cristina , Ghitea Timea Claudia , Tohati Adrian
Published: March 2021

Mouthrinse solutions represent a group of products used for maintaining oral hygiene after tooth brushing. Substances contained by plants bring benefits for the whole mouth health. The purpose of this study was to comparatively evaluate the effectiveness of a commercial mouthwash and of an herbal infusion on dental plaque formation and gingival inflammation. The participants in the study (90 patients) were divided into two groups, the CM group, which rinsed with a commercial fluoride-containing mouthwash and the IM group, which used an herbal infusion. The Silness–Loe plaque index (PI) and the Loe–Silness gingival index (GI) were assessed at baseline and in three following monitoring sessions. Both mouthwashes used had good results in reducing plaque index and gingival index values. In all monitoring sessions, the average PI value calculated in the CM group was relatively lower than in the IM group, probably because of the fluoride contained in the commercial mouthwash. The average GI value calculated in the CM group was slightly higher in showing gingival inflammation than that of the IM group, therefore the IM group had a better average result than the CM group in GI value. Herbal mouthwashes are adequate to induce proper oral prevention through the preservation of good oral health.
Preliminary Realization of an Electric-Powered Hydraulic Pump System for a Waste Compactor Truck and a Techno-Economic Analysis
Authors: De Santis Michele , Silvestri Luca , Forcina Antonio , Di Bona Gianpaolo , Di Fazio Anna Rita
Published: March 2021

Most industrial trucks are equipped with hydraulic systems designed for specific operations, for which the required power is supplied by the internal combustion engine (ICE). The largest share of the power consumption is required by the hydraulic system during idling operations, and, consequently, the current literature focuses on energy saving strategies for the hydraulic system rather than making the vehicle traction more efficient. This study presents the preliminary realization of an electric-powered hydraulic pump system (e-HPS) that drives the lifting of the dumpster and the garbage compaction in a waste compactor truck, rather than traditional ICE-driven hydraulic pump systems (ICE-HPSs). The different components of the e-HPS are described and the battery pack was modelled using the kinetic battery model. The end-of-life of the battery pack was determined to assess the economic feasibility of the proposed e-HPS for the truck lifespan, using numerical simulations. The aim was twofold: to provide an implementation method to retrofit the e-HPS to a conventional waste compactor truck and to assess its economic feasibility, investigating fuel savings during the use phase and the consequent reduction of CO2 emissions. Results show that the total lifespan cost saving achieved a value of 65,000 €. Furthermore, total CO2 emissions for the e-HPS were about 80% lower than those of the ICE-HPS, highlighting that the e-HPS can provide significant environmental benefits in an urban context.
Fieldwork and Field Trials in Hospitals: Co-Designing A Robotic Solution to Support Data Collection in Geriatric Assessment
Authors: Lan Hing Ting Karine , Voilmy Dimitri , De Roll Quitterie , Iglesias Ana , Marfil Rebeca
Published: March 2021

Comprehensive geriatric assessment (CGA) is a multidimensional and multidisciplinary diagnostic instrument that helps provide personalized care to older adults by evaluating their state of health. This evaluation is based on extensive data collection in order to develop a coordinated plan to maximize overall health with aging. In the social and economic context of growing ageing populations, medical experts can save time and effort if provided with interactive tools to efficiently assist them in doing CGAs, managing either standardized tests or data collection. Recent research proposes the use of social robots as the central part of this optimization of clinicians’ time and effort. This paper presents the first and last steps of the research made around the design and evaluation of the CLARC robot: fieldwork (analysis of needs and practices concerning clinical data management) and field trials (pilot experiment in real-life conditions in a rehab hospital). Based on an extensive literature review of social robotics applications for health and ageing, it discusses the practical and methodological questions raised around how to design and test assistive social robots for clinical routine, and questions the feasibility of an automated CGA procedure.
Advancing Grid-Connected Renewable Generation Systems
Authors: Liivik Elizaveta , Yang Yongheng , Sangwongwanich Ariya , Blaabjerg Frede
Published: March 2021

If we look at the history of renewable energy sources (RESs), how it all began, and how rapidly they continue to develop, it can be argued that one of the main reasons is due to the rapid improvements in power electronics technology in interfacing the renewable source to the grid [...]
Atmospheric and Ocean Optics: Atmospheric Physics II
Authors: Romanovskii Oleg A. , Matvienko Gennadii G.
Published: March 2021

The Atmosphere Special Issue entitled “Atmospheric and Ocean Optics: Atmospheric Physics II” comprises eight original papers [...]
Contribution of Local and Transboundary Air Pollution to the Urban Air Quality of Fukuoka, Japan
Authors: Yoshino Ayako , Takami Akinori , Hara Keiichiro , Nishita-Hara Chiharu , Hayashi Masahiko , Kaneyasu Naoki
Published: March 2021

Transboundary air pollution (TAP) and local air pollution (LAP) influence the air quality of urban areas. Fukuoka, located on the west side of Japan and affected by TAP from the Asian continent, is a unique example for understanding the contribution of LAP and TAP. Gaseous species and particulate matter (PM) were measured for approximately three weeks in Fukuoka in the winter of 2018. We classified two distinctive periods, LAP and TAP, based on wind speed. The classification was supported by variations in the concentration of gaseous species and by backward trajectories. Most air pollutants, including NOx and PM, were high in the LAP period and low in the TAP period. However, ozone was the exception. Therefore, our findings suggest that reducing local emissions is necessary. Ozone was higher in the TAP period, and the variation in ozone concentration was relatively small, indicating that ozone was produced outside of the city and transported to Fukuoka. Thus, air pollutants must also be reduced at a regional scale, including in China.
Convection and Its Impact on Weather
Authors: Bechtold Peter
Published: March 2021

This Special Issue of Atmosphere is entitled “Convection and its impact on weather comprises seven original papers” [...]
Bombesin-Tethered Reactive Oxygen Species (ROS)-Responsive Nanoparticles for Monomethyl Auristatin F (MMAF) Delivery
Authors: Kim Jihoon , Kim Jee Seon , Min Kyung Hyun , Kim Young-Hwa , Chen Xiaoyuan
Published: March 2021

Dolastatin derivatives, represented by monomethylauristatin E (MMAE), have been translated in clinic with a form of antibody–drug conjugate; however, their potential in nanoparticle systems has not been well established due to the potential risk of immature release of extremely high cytotoxic dolastatin drugs during blood circulation. Herein, we rationally propose monomethylauristatin F (MMAF), a dolastatin-derived, loaded nanoparticle system composed of bombesin (BBN)-tethered ROS-responsive micelle system (BBN-PEG-PPADT) to achieve efficient anticancer therapy with targeted and efficient delivery of MMAF. The developed MMAF-loaded BBN-PEG-PPADT micelles (MMAF@BBN-PEG-PPADT) exhibited improved cellular uptake via interactions between BBN and gastrin-releasing peptide receptors on the cancer cells and the intracellular burst release of MMAF, owing to the ROS-responsive disruption, which allowed the efficient anticancer effects of MMAF in vitro. This study suggests the potential of nanoparticle systems in the delivery of dolastatin drugs.
Glycan Epitopes on 201B7 Human-Induced Pluripotent Stem Cells Using R-10G and R-17F Marker Antibodies
Authors: Nagai Yuko , Nakao Hiromi , Kojima Aya , Komatsubara Yuka , Ohta Yuki , Kawasaki Nana , Kawasaki Nobuko , Toyoda Hidenao , Kawasaki Toshisuke
Published: March 2021

We developed two human-induced pluripotent stem cell (hiPSC)/human embryonic stem cell (hESC)-specific glycan-recognizing mouse antibodies, R-10G and R-17F, using the Tic (JCRB1331) hiPSC line as an antigen. R-10G recognizes a low-sulfate keratan sulfate, and R-17F recognizes lacto-N-fucopentaose-1. To evaluate the general characteristics of stem cell glycans, we investigated the hiPSC line 201B7 (HPS0063), a prototype iPSC line. Using an R-10G affinity column, an R-10G-binding protein was isolated from 201B7 cells. The protein yielded a single but very broad band from 480 to 1236 kDa by blue native gel electrophoresis. After trypsin digestion, the protein was identified as podocalyxin by liquid chromatography/mass spectrometry. According to Western blotting, the protein reacted with R-10G and R-17F. The R-10G-positive band was resistant to digestion with glycan-degrading enzymes, including peptide N-glycanase, but the intensity of the band was decreased significantly by digestion with keratanase, keratanase II, and endo-β-galactosidase, suggesting the R-10G epitope to be a keratan sulfate. These results suggest that keratan sulfate-type epitopes are shared by hiPSCs. However, the keratan sulfate from 201B7 cells contained a polylactosamine disaccharide unit (Galβ1-4GlcNAc) at a significant frequency, whereas that from Tic cells consisted mostly of keratan sulfate disaccharide units (Galβ1-4GlcNAc(6S)). In addition, the abundance of the R-10G epitope was significantly lower in 201B7 cells than in Tic cells.
Dexamethasone Conjugates: Synthetic Approaches and Medical Prospects
Authors: Dubashynskaya Natallia V. , Bokatyi Anton N. , Skorik Yury A.
Published: March 2021

Dexamethasone (DEX) is the most commonly prescribed glucocorticoid (GC) and has a wide spectrum of pharmacological activity. However, steroid drugs like DEX can have severe side effects on non-target organs. One strategy to reduce these side effects is to develop targeted systems with the controlled release by conjugation to polymeric carriers. This review describes the methods available for the synthesis of DEX conjugates (carbodiimide chemistry, solid-phase synthesis, reversible addition fragmentation-chain transfer [RAFT] polymerization, click reactions, and 2-iminothiolane chemistry) and perspectives for their medical application as GC drug or gene delivery systems for anti-tumor therapy. Additionally, the review focuses on the development of DEX conjugates with different physical-chemical properties as successful delivery systems in the target organs such as eye, joint, kidney, and others. Finally, polymer conjugates with improved transfection activity in which DEX is used as a vector for gene delivery in the cell nucleus have been described.
Involvement of microRNA in Solid Cancer: Role and Regulatory Mechanisms
Authors: Lin Ying-Chin , Chen Tso-Hsiao , Huang Yu-Min , Wei Po-Li , Lin Jung-Chun
Published: March 2021

MicroRNAs (miRNAs) function as the post-transcriptional factor that finetunes the gene expression by targeting to the specific candidate. Mis-regulated expression of miRNAs consequently disturbs gene expression profile, which serves as the pivotal mechanism involved in initiation or progression of human malignancy. Cancer-relevant miRNA is potentially considered the therapeutic target or biomarker toward the precise treatment of cancer. Nevertheless, the regulatory mechanism underlying the altered expression of miRNA in cancer is largely uncovered. Detailed knowledge regarding the influence of miRNAs on solid cancer is critical for exploring its potential of clinical application. Herein, we elucidate the regulatory mechanism regarding how miRNA expression is manipulated and its impact on the pathogenesis of distinct solid cancer.
The Effect of FGF21 and Its Genetic Variants on Food and Drug Cravings, Adipokines and Metabolic Traits
Authors: Epperlein Sarah , Gebhardt Claudia , Rohde Kerstin , Chakaroun Rima , Patt Marie , Schamarek Imke , Kralisch Susan , Heiker John T. , Scholz Markus , Stumvoll Michael , Kovacs Peter , Breitfeld Jana , Tönjes Anke
Published: March 2021

Fibroblast growth factor 21 (FGF21) is a regulator of addictive behavior. Increasing evidence suggests an impact of FGF21 on eating behavior, food and drug cravings and on other adipokines like insulin-like growth factor 1 (IGF-1) or adiponectin. We investigated the association of serum FGF21 and genetic variants with aspects of food and drug craving and obesity related metabolic parameters including serum adipokine levels. Standardized questionnaires, blood samples and anthropometric data of the Sorbs cohort (n = 1046) were analyzed using SPSS. For genetic analyses, the FGF21-locus ±10 kb was genotyped and analyzed using PLINK. Validation was conducted in a second independent cohort (n = 704). FGF21 was significantly associated with alcohol and coffee consumption, smoking and eating behavior (disinhibition). We confirmed correlations of FGF21 serum levels with IGF-1, adiponectin, pro-enkephalin, adipocyte fatty-acid-binding protein, chemerin and progranulin. FGF21 genetic variants were associated with anthropometric and metabolic parameters, adipokines, food and drug craving while strongest evidence was seen with low-density lipoprotein cholesterol (LDL-C). We highlight the potential role of FGF21 in food and drug cravings and provide new insights regarding the link of FGF21 with other adipokines as well as with metabolic traits, in particular those related to lipid metabolism (LDL-C).
Multi-Functionalized Nanomaterials and Nanoparticles for Diagnosis and Treatment of Retinoblastoma
Authors: Arshad Rabia , Barani Mahmood , Rahdar Abbas , Sargazi Saman , Cucchiarini Magali , Pandey Sadanand , Kang Misook
Published: March 2021

Retinoblastoma is a rare type of cancer, and its treatment, as well as diagnosis, is challenging, owing to mutations in the tumor-suppressor genes and lack of targeted, efficient, cost-effective therapy, exhibiting a significant need for novel approaches to address these concerns. For this purpose, nanotechnology has revolutionized the field of medicine with versatile potential capabilities for both the diagnosis, as well as the treatment, of retinoblastoma via the targeted and controlled delivery of anticancer drugs via binding to the overexpressed retinoblastoma gene. Nanotechnology has also generated massive advancements in the treatment of retinoblastoma based on the use of surface-tailored multi-functionalized nanocarriers; overexpressed receptor-based nanocarriers ligands (folate, galactose, and hyaluronic acid); lipid-based nanocarriers; and metallic nanocarriers. These nanocarriers seem to benchmark in mitigating a plethora of malignant retinoblastoma via targeted delivery at a specified site, resulting in programmed apoptosis in cancer cells. The effectiveness of these nanoplatforms in diagnosing and treating intraocular cancers such as retinoblastoma has not been properly discussed, despite the increasing significance of nanomedicine in cancer management. This article reviewed the recent milestones and future development areas in the field of intraocular drug delivery and diagnostic platforms focused on nanotechnology.
Clock/Sleep-Dependent Learning and Memory in Male 3xTg-AD Mice at Advanced Disease Stages and Extrinsic Effects of Huprine X and the Novel Multitarget Agent AVCRI104P3
Authors: Giménez-Llort Lydia , Santana-Santana Mikel , Ratia Míriam , Pérez Belén , Camps Pelayo , Muñoz-Torrero Diego , Badia Albert , Clos Maria Victòria
Published: March 2021

A new hypothesis highlights sleep-dependent learning/memory consolidation and regards the sleep-wake cycle as a modulator of β-amyloid and tau Alzheimer’s disease (AD) pathologies. Sundowning behavior is a common neuropsychiatric symptom (NPS) associated with dementia. Sleep fragmentation resulting from disturbances in sleep and circadian rhythms in AD may have important consequences on memory processes and exacerbate the other AD-NPS. The present work studied the effect of training time schedules on 12-month-old male 3xTg-AD mice modeling advanced disease stages. Their performance in two paradigms of the Morris water maze for spatial-reference and visual-perceptual learning and memory were found impaired at midday, after 4 h of non-active phase. In contrast, early-morning trained littermates, slowing down from their active phase, exhibited better performance and used goal-directed strategies and non-search navigation described for normal aging. The novel multitarget anticholinesterasic compound AVCRI104P3 (0.6 µmol·kg−1, 21 days i.p.) exerted stronger cognitive benefits than its in vitro equipotent dose of AChEI huprine X (0.12 μmol·kg−1, 21 days i.p.). Both compounds showed streamlined drug effectiveness, independently of the schedule. Their effects on anxiety-like behaviors were moderate. The results open a question of how time schedules modulate the capacity to respond to task demands and to assess/elucidate new drug effectiveness.
Simulating Expansion of the Intracranial Space to Accommodate Brain Swelling after Decompressive Craniectomy: Volumetric Quantification in a 3D CAD Skull Model with Contour Elevation
Authors: Kung Woon-Man , Wang Yao-Chin , Tzeng I-Shiang , Chen Yu-Te , Lin Muh-Shi
Published: March 2021

Background: Decompressive craniectomy (DC) can be used to augment intracranial space and halt brainstem compromise. However, a widely adopted recommendation for optimal surgical extent of the DC procedure is lacking. In the current study, we utilized three-dimensional (3D) computer-assisted design (CAD) skull models with defect contour elevation for quantitative assessment. Methods: DC was performed for 15 consecutive patients, and 3D CAD models of defective skulls with contour elevations (0–50 mm) were reconstructed using commercial software. Quantitative assessments were conducted in these CAD subjects to analyze the effects of volumetric augmentation when elevating the length of the contour and the skull defect size. The final positive results were mathematically verified using a computerized system for numerical integration with the rectangle method. Results: Defect areas of the skull CAD models ranged from 55.7–168.8 cm2, with a mean of 132.3 ± 29.7 cm2. As the contour was elevated outward for 6 mm or above, statistical significance was detected in the volume and the volume-increasing rate, when compared to the results obtained from the regular CAD model. The volume and the volume-increasing rate increased by 3.665 cm3, 0.285% (p < 0.001) per 1 mm of contour elevation), and 0.034% (p < 0.001) per 1 cm2 of increase of defect area, respectively. Moreover, a 1 mm elevation of the contour in Groups 2 (defect area 125–150 cm2) and 3 (defect area >150 cm2, as a proxy for an extremely large skull defect) was shown to augment the volume and the volume-increasing rate by 1.553 cm3, 0.101% (p < 0.001) and 1.126 cm3, 0.072% (p < 0.001), respectively, when compared to those in Group 1 (defect area <125 cm2). The volumetric augmentation achieved by contour elevation for an extremely large skull defect was smaller than that achieved for a large skull defect. Conclusions: The 3D CAD skull model contour elevation method can be effectively used to simulate the extent of a space-occupying swollen brain and to quantitatively assess the extent of brainstem protection in terms of volume augmentation and volume-increasing rate following DC. As the tangential diameter (representing the degree of DC) exceeded the plateau value, volumetric augmentation was attenuated. However, an increasing volumetric augmentation was detected before the plateau value was reached.
Public Engagement and Neurology: An Update
Authors: Lavorgna Luigi , Brigo Francesco , Esposito Sabrina , Abbadessa Gianmarco , Sparaco Maddalena , Lanzillo Roberta , Moccia Marcello , Inglese Matilde , Bonfanti Luca , Trojsi Francesca , Spina Emanuele , Russo Antonio , De Micco Pasquale , Clerico Marinella , Tedeschi Gioacchino , Bonavita Simona
Published: March 2021

Background: Public engagement (PE) is defined as the involvement of “specialists who listen, develop their understanding, and interact with non-specialists in non-profit activities of educational, cultural, and social nature to engage the public in science-related matters”. The public health relevance of PE consists in building up a scientifically literate society, able to participate in and support scientific and technological developments and their implications for educational settings. Neurological disorders account for 35% of all diseases. PE could have a positive impact on the lives of people affected by neurological diseases. Method: This review evaluates the role of PE in dementia, stroke, epilepsy, multiple sclerosis, Parkinson’s disease, migraine, neurogenetics, and amyotrophic lateral sclerosis. Results and Conclusions: PE can provide accessible information, support research activities and prevention through appropriate lifestyles, and increase knowledge and awareness of neurological disorders, improving their diagnosis and treatment.
Transcranial Magnetic Stimulation as a Tool to Investigate Motor Cortex Excitability in Sport
Authors: Moscatelli Fiorenzo , Messina Antonietta , Valenzano Anna , Monda Vincenzo , Salerno Monica , Sessa Francesco , La Torre Ester , Tafuri Domenico , Scarinci Alessia , Perrella Michela , Marsala Gabriella , Monda Marcellino , Cibelli Giuseppe , Porro Chiara , Messina Giovanni
Published: March 2021

Transcranial magnetic stimulation, since its introduction in 1985, has brought important innovations to the study of cortical excitability as it is a non-invasive method and, therefore, can be used both in healthy and sick subjects. Since the introduction of this cortical stimulation technique, it has been possible to deepen the neurophysiological aspects of motor activation and control. In this narrative review, we want to provide a brief overview regarding TMS as a tool to investigate changes in cortex excitability in athletes and highlight how this tool can be used to investigate the acute and chronic responses of the motor cortex in sport science. The parameters that could be used for the evaluation of cortical excitability and the relative relationship with motor coordination and muscle fatigue, will be also analyzed. Repetitive physical training is generally considered as a principal strategy for acquiring a motor skill, and this process can elicit cortical motor representational changes referred to as use-dependent plasticity. In training settings, physical practice combined with the observation of target movements can enhance cortical excitability and facilitate the process of learning. The data to date suggest that TMS is a valid technique to investigate the changes in motor cortex excitability in trained and untrained subjects. Recently, interest in the possible ergogenic effect of non-invasive brain stimulation in sport is growing and therefore in the future it could be useful to conduct new experiments to evaluate the impact on learning and motor performance of these techniques.
Effects of Early Rehydration on Brain Perfusion and Infarct Core after Middle Cerebral Artery Occlusion in Rats
Authors: Tsai Yuan-Hsiung , Su Chia-Hao , Lee I-Neng , Yang Jen-Tsung , Lin Leng-Chieh , Huang Yen-Chu , Yang Jenq-Lin
Published: March 2021

Imaging evidence for the effect of rehydration on cerebral perfusion and brain ischemia has never been proposed in the literature. This study aimed to test the hypothesis that early rehydration treatment can improve cerebral perfusion and decrease infarct volume, consequently reducing mortality of dehydrated stroke animals. Methods: Thirty dehydrated experimental rats were randomly assigned to either a rehydration or control group after middle cerebral artery occlusion (MCAO). Diffusion-weighted imaging and dynamic contrast enhancement perfusion imaging were performed at 30 min and 6 h after MCAO using a 9.4T MR imaging scanner to measure the infarct volume and brain perfusion. Results: The survival rates after the first MRI scan were 91.7% for the rehydration group and 58.3% for the control group (p = 0.059). The survival rates after the second MRI scan were 66.7% for the rehydration group, and 8.3% of the control group survived (p = 0.003). The infarct volume of the rehydration group was significantly smaller than control group at 30 min after MCAO (p = 0.007). The delay time and time to maximum were significantly shorter in the rehydration group at 30 min (p = 0.004 and 0.035, respectively). Conclusions: The findings suggest that early rehydration therapy can decrease the infarct volume, shorten the delay time of cerebral perfusion, and increase survival of dehydrated ischemic-stroke rats. This preliminary study provided imaging evidence that more intensive early hydration therapies and reperfusion strategies may be necessary for acute stroke patients with dehydrated status.
A Threshold Line for Safe Geologic CO2 Storage Based on Field Measurement of Soil CO2 Flux
Authors: Kuriyama Takashi , Quoc Huy Phung , Salmawati Salmawati , Sasaki Kyuro
Published: March 2021

Carbon capture and storage (CCS) is an established and verified technology that can implement zero emissions on a large enough scale to limit temperature rise to below 2 °C, as stipulated in the Paris Agreement. However, leakage from CCS sites must be monitored to ensure containment performance. Surface monitoring of carbon dioxide (CO2) concentrations at onshore CCS sites is one method to locate and quantify CCS site leakage. Employing soil accumulation chambers, we have established baseline data for the natural flux of CO2 as a threshold alert to detect CO2 leakage flux to ensure the safety of onshore CCS sites. Within this context, we conducted on-site CO2 measurements at three different locations (A, B, and C) on the INAS test field at the Ito campus, Kyushu University (Japan). Furthermore, we developed a specific measurement system based on the closed-chamber method to continuously measure CO2 flux from soil and to investigate the correlation between CO2 flux from the soil surface and various parameters, including environmental factors and soil sample characteristics. In addition, gas permeability and the effect of different locations on soil CO2 flux are discussed in this study. Finally, we present an equation for estimating the soil CO2 flux used in the INAS field site that includes environmental factors and soil characteristics. This equation assists in defining the threshold line for an alert condition related to CO2 leakage at onshore CCS sites.
A Review on van der Waals Boron Nitride Quantum Dots
Authors: Acharya Amit , Sharma Sambhawana , Liu Xiuling , Zhang Dongyan , Yap Yoke Khin
Published: March 2021

Boron nitride quantum dots (BNQDs) have gained increasing attention for their versatile fluorescent, optoelectronic, chemical, and biochemical properties. During the past few years, significant progress has been demonstrated, started from theoretical modeling to actual application. Many interesting properties and applications have been reported, such as excitation-dependent emission (and, in some cases, non-excitation dependent), chemical functionalization, bioimaging, phototherapy, photocatalysis, chemical, and biological sensing. An overview of this early-stage research development of BNQDs is presented in this article. We have prepared un-bias assessments on various synthesis methods, property analysis, and applications of BNQDs here, and provided our perspective on the development of these emerging nanomaterials for years to come.
Pulsed-Focused Ultrasound Slows B16 Melanoma and 4T1 Breast Tumor Growth through Differential Tumor Microenvironmental Changes
Authors: Cohen Gadi , Chandran Parwathy , Lorsung Rebecca M. , Aydin Omer , Tomlinson Lauren E. , Rosenblatt Robert B. , Burks Scott R. , Frank Joseph A.
Published: March 2021

Focused ultrasound (FUS) has shown promise as a non-invasive treatment modality for solid malignancies. FUS targeting to tumors has been shown to initiate pro-inflammatory immune responses within the tumor microenvironment. Pulsed FUS (pFUS) can alter the expression of cytokines, chemokines, trophic factors, cell adhesion molecules, and immune cell phenotypes within tissues. Here, we investigated the molecular and immune cell effects of pFUS on murine B16 melanoma and 4T1 breast cancer flank tumors. Temporal changes following sonication were evaluated by proteomics, RNA-seq, flow-cytometry, and histological analyses. Proteomic profiling revealed molecular changes occurring over 24 h post-pFUS that were consistent with a shift toward inflamed tumor microenvironment. Over 5 days post-pFUS, tumor growth rates were significantly decreased while flow cytometric analysis revealed differences in the temporal migration of immune cells. Transcriptomic analyses following sonication identified differences in gene expression patterns between the two tumor types. Histological analyses further demonstrated reduction of proliferation marker, Ki-67 in 4T1, but not in B16 tumors, and activated cleaved-caspase 3 for apoptosis remained elevated up to 3 days post-pFUS in both tumor types. This study revealed diverse biological mechanisms following pFUS treatment and supports its use as a possible adjuvant to ablative tumor treatment to elicit enhanced anti-tumor responses and slow tumor growth.
Pineal Gland Tumors: A Review
Authors: Favero Gaia , Bonomini Francesca , Rezzani Rita
Published: March 2021

The pineal gland is a small, pinecone-shaped endocrine gland that participates in the biological rhythm regulation of vertebrates. The recognized major product of the pineal gland is melatonin—a multifunctional endogenous indoleamine. Accumulating evidence suggests that the pineal gland is important for preserving ideal health conditions in vertebrate. Tumors of the pineal region account for approximately 3–11% of pediatric brain neoplasms but fewer than 1% of brain neoplasms in adults. It is fundamental to expand advanced imaging techniques together with both clinical and laboratory knowledge, to help to differentiate among pineal neoplasms and thus facilitate accurate primary diagnoses and proper therapeutic interventions. In this review, we report the gross anatomy of the pineal gland and its functional significance and discuss the clinical relevance of pineal gland tumors, underlining the importance of identifying the leading causes of pineal region masses.
Correlation of Clinical Parameters with Intracranial Outcome in Non-Small Cell Lung Cancer Patients with Brain Metastases Treated with Pd-1/Pd-L1 Inhibitors as Monotherapy
Authors: Rounis Konstantinos , Skribek Marcus , Makrakis Dimitrios , De Petris Luigi , Agelaki Sofia , Ekman Simon , Tsakonas Georgios
Published: March 2021

There is a paucity of biomarkers for the prediction of intracranial (IC) outcome in immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients (pts) with brain metastases (BM). We identified 280 NSCLC pts treated with ICIs at Karolinska University Hospital, Sweden, and University Hospital of Heraklion, Greece. The inclusion criteria for response assessment were brain metastases (BM) prior to ICI administration, radiological evaluation with CT or MRI for IC response assessment, PD-1/PD-L1 inhibitors as monotherapy, and no local central nervous system (CNS) treatment modalities for ≥3 months before ICI initiation. In the IC response analysis, 33 pts were included. Non-primary (BM not present at diagnosis) BM, odds ratio (OR): 13.33 (95% CI: 1.424–124.880, p = 0.023); no previous brain radiation therapy (RT), OR: 5.49 (95% CI: 1.210–25.000, p = 0.027); and age ≥70 years, OR: 6.19 (95% CI: 1.27–30.170, p = 0.024) were associated with increased probability of IC disease progression. Two prognostic groups (immunotherapy (I-O) CNS score) were created based on the abovementioned parameters. The I-O CNS poor prognostic group B exhibited a higher probability for IC disease progression, OR: 27.50 (95% CI: 2.88–262.34, p = 0.004). Age, CNS radiotherapy before the start of ICI treatment, and primary brain metastatic disease can potentially affect the IC outcome of NSCLC pts with BM.
Individualized Prediction of Breast Cancer Survival Using Flexible Parametric Survival Modeling: Analysis of a Hospital-Based National Clinical Cancer Registry
Authors: Pongnikorn Donsuk , Phinyo Phichayut , Patumanond Jayanton , Daoprasert Karnchana , Phothong Pachaya , Siribumrungwong Boonying
Published: March 2021

Prognostic models for breast cancer developed from Western countries performed less accurately in the Asian population. We aimed to develop a survival prediction model for overall survival (OS) and disease-free survival (DFS) for Thai patients with breast cancer. We conducted a prognostic model research using a multicenter hospital-based cancer clinical registry from the Network of National Cancer Institutes of Thailand. All women diagnosed with breast cancer who underwent surgery between 1 January 2010 and 31 December 2011 were included in the analysis. A flexible parametric survival model was used for developing the prognostic model for OS and DFS prediction. During the study period, 2021 patients were included. Of these, 1386 patients with 590 events were available for a complete-case analysis. The newly derived individualized prediction of breast cancer survival or the IPBS model consists of twelve routinely available predictors. The C-statistics from the OS and the DFS model were 0.72 and 0.70, respectively. The model showed good calibration for the prediction of five-year OS and DFS. The IPBS model provides good performance for the prediction of OS and PFS for breast cancer patients. A further external validation study is required before clinical implementation.