bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibitory Effects of the Bioactive Thermorubin Isolated from the Fungus Thermoactinomyces Antibioticus on Melanogenesis
Authors: Goenka Shilpi , R. Simon Sanford
Published: July 2020

Skin hyperpigmentation disorders arise due to aberrant regulation of melanin synthesis and export. Current treatments include natural compounds like kojic acid and hydroquinone, which suffer from limitations due to adverse reactions. Thermorubin (TR) is a secondary metabolite derived from the fungus Thermoactinomyces antibioticus and has previously demonstrated to possess anti-inflammatory properties by inhibition of matrix metalloproteinases (MMPs), as well as antimicrobial activity. In the current study, we explored whether TR might be a used as a candidate for the treatment of skin hyperpigmentation disorders by studying its effects on melanin synthesis and melanin export in B16F10 mouse melanoma cells and primary human melanocytes derived from darkly-pigmented (DP) skin. Non-toxic doses of TR were first identified in B16F10 mouse melanoma cells. These doses were subsequently tested for their effects on both extracellular and intracellular melanin levels under conditions of basal and hormone-stimulated melanogenesis. Our results demonstrated that TR at 25 µM inhibited total melanin levels with selective inhibition of extracellular melanin in B16F10 cells under both basal and hormone-stimulated conditions. The mechanisms of inhibition did not include tyrosinase inhibition, either in cellular lysates or cell-free system. However, TR potently inhibited activity of α-glucosidase enzyme in vitro and exhibited antioxidant activity. Furthermore, our results with primary human melanocytes from DP skin showed that TR at 10 µM significantly suppressed dendricity along with an increase in accumulation of intracellular melanin. These findings point to a mechanism of action of TR as an exclusive inhibitor of melanosome export. Taken together, our preliminary results demonstrate that TR might offer a novel ingredient as a skin depigmenting agent for inclusion in cosmetic formulations. Further studies delineating molecular mechanisms of hypopigmentation of TR and testing in human skin tissue-equivalents are warranted.
Non-Small-Cell Lung Cancer-Sensitive Detection of the p.Thr790Met EGFR Alteration by Preamplification before PNA-Mediated PCR Clamping and Pyrosequencing
Authors: Billaud Amandine , Verriele Veronique , Dauvé Jonathan , Chevalier Louise-Marie , Morel Alain
Published: July 2020

Targeted therapies and, more precisely, EGFR tyrosine kinase inhibitors (TKIs) have been a major improvement in the therapeutic management of EGFR-mutated non-small-cell lung cancers (NSCLCs). Earlier administration of these TKIs throughout tumor progression is imperative to improve patient outcomes. Consequently, studies have focused on refining the characterization of biomarkers, especially concerning the resistance mutation p.Thr790Met of EGFR. Herein, we developed peptide nucleic acid (PNA)-mediated PCR clamping followed by pyrosequencing, favoring enrichment of the mutated fraction. A preamplification step was first added to increase the amplifiable DNA fraction. Throughout the application of our method on DNA extracted from FFPE samples of 46 patients with NSCLC who had relapsed under first-generation EGFR TKI, we evaluated a sensitivity of 93.3% and a specificity of 100%. All 19 patients who were positive for the p.Thr790Met mutation with NGS were also found to be positive with our protocol. The only discordant case was a sample with no mutation detected with NGS, but which was positive with PNA. This protocol allows for the detection of the p.Thr790Met mutation with a sensitivity of 0.5% which will permit earlier detection and an improvement of therapeutic management.
Risk-Neutrality of RND and Option Pricing within an Entropy Framework
Authors: Yu Xisheng
Published: July 2020

This article constructs an entropy pricing framework by incorporating a set of informative risk-neutral moments (RNMs) extracted from the market-available options as constraints. Within the RNM-constrained entropic framework, a unique distribution close enough to the correct one is obtained, and its risk-neutrality is deeply verified based on simulations. Using this resultant risk-neutral distribution (RND), a sample of risk-neutral paths of the underlying price is generated and ultimately the European option’s prices are computed. The pricing performance and analysis in simulations demonstrate that this proposed valuation is comparable to the benchmarks and can produce fairly accurate prices for options.
On the Use of a New Class of Simplified Multi-Window Iris Notch in the Design of Ultra-Compact High-Rejection Waveguide Filters for Satellite Links
Authors: Cano Juan Luis , Mediavilla Angel , Tazon Antonio
Published: July 2020

This work introduces a simplified multi-aperture iris notch suitable for designing waveguide filters having an extremely improved compactness/rejection ratio, regarding available solutions, and adequate pass-band performances. The proposed iris architecture, analyzed for the first time, exhibits a unique transmission zero in the waveguide mono-mode bandwidth which can be easily located below or above the pass-band. The frequency of this transmission zero is evaluated in terms of the iris dimensions thus providing useful guidelines for designing filters with suitable responses. As a consequence of this simplified topology, any designed filter can be easily manufactured by cutting along its E-field symmetry plane. This strategy greatly improves the filter’s insertion loss regarding classical implementations based on more complicated arrangements with piled thin metallic sheets. Two exemplary filters have been designed and tested to be used in a high-performance X-band SATCOM terminal with an 80% size reduction with respect to the existing systems. Both filters covering the Rx (7.25–75 GHz) and Tx (7.9–8.4 GHz) sub-bands show a reflection of −25 dB with insertion losses below 1 dB in the pass-band, whereas they present a very sharp out-of-band rejection of at least 90 dB, that is, a 600 dB/GHz slope at X band.
Center-Articulated Hydrostatic Cotton Harvesting Rover Using Visual-Servoing Control and a Finite State Machine
Authors: Fue Kadeghe , Porter Wesley , Barnes Edward , Li Changying , Rains Glen
Published: July 2020

Multiple small rovers can repeatedly pick cotton as bolls begin to open until the end of the season. Several of these rovers can move between rows of cotton, and when bolls are detected, use a manipulator to pick the bolls. To develop such a multi-agent cotton-harvesting system, each cotton-harvesting rover would need to accomplish three motions: the rover must move forward/backward, turn left/right, and the robotic manipulator must move to harvest cotton bolls. Controlling these actions can involve several complex states and transitions. However, using the robot operating system (ROS)-independent finite state machine (SMACH), adaptive and optimal control can be achieved. SMACH provides task level capability for deploying multiple tasks to the rover and manipulator. In this study, a center-articulated hydrostatic cotton-harvesting rover, using a stereo camera to locate end-effector and pick cotton bolls, was developed. The robot harvested the bolls by using a 2D manipulator that moves linearly horizontally and vertically perpendicular to the direction of the rover’s movement. We demonstrate preliminary results in an environment simulating direct sunlight, as well as in an actual cotton field. This study contributes to cotton engineering by presenting a robotic system that operates in the real field. The designed robot demonstrates that it is possible to use a Cartesian manipulator for the robotic harvesting of cotton; however, to reach commercial viability, the speed of harvest and successful removal of bolls (Action Success Ratio (ASR)) must be improved.
Multilevel Switching Characteristics of Si3N4-Based Nano-Wedge Resistive Switching Memory and Array Simulation for In-Memory Computing Application
Authors: Lee Dong Keun , Kim Min-Hwi , Bang Suhyun , Kim Tae-Hyeon , Kim Sungjun , Cho Seongjae , Park Byung-Gook
Published: July 2020

In this research, nano-wedge resistive switching random-access memory (ReRAM) based on a Si3N4 switching layer and silicon bottom electrode was fabricated, and its multilevel switching characteristics were investigated. The wedge bottom electrode was formed by a tetramethyl ammonium hydroxide (TMAH) wet-etching process. The nano-wedge ReRAM was demonstrated to have different reset current levels by varying the compliance currents. To explain the effect of modulating the compliance currents, the switching characteristics of both the SET and RESET behaviors were shown. After measuring the device under four different compliance currents, it was proved to have different current levels due to an inhibited resistive state after a SET switching process. Furthermore, SPICE circuit simulation was carried out to show the effect of line resistance on current summation for the array sizes of 8 × 8 and 16 × 16. These results indicate the importance of minimizing the line resistance for successful implementation as a hardware-based neural network.
Rapid Recent Deforestation Incursion in a Vulnerable Indigenous Land in the Brazilian Amazon and Fire-Driven Emissions of Fine Particulate Aerosol Pollutants
Authors: de Oliveira Gabriel , Chen Jing M. , Mataveli Guilherme A. V. , Chaves Michel E. D. , Seixas Hugo T. , Cardozo Francielle da S. , Shimabukuro Yosio E. , He Liming , Stark Scott C. , dos Santos Carlos A. C.
Published: July 2020

Deforestation in the Brazilian Amazon is related to the use of fire to remove natural vegetation and install crop cultures or pastures. In this study, we evaluated the relation between deforestation, land-use and land-cover (LULC) drivers and fire emissions in the Apyterewa Indigenous Land, Eastern Brazilian Amazon. In addition to the official Brazilian deforestation data, we used a geographic object-based image analysis (GEOBIA) approach to perform the LULC mapping in the Apyterewa Indigenous Land, and the Brazilian biomass burning emission model with fire radiative power (3BEM_FRP) to estimate emitted particulate matter with a diameter less than 2.5 µm (PM2.5), a primary human health risk. The GEOBIA approach showed a remarkable advancement of deforestation, agreeing with the official deforestation data, and, consequently, the conversion of primary forests to agriculture within the Apyterewa Indigenous Land in the past three years (200 km2), which is clearly associated with an increase in the PM2.5 emissions from fire. Between 2004 and 2016 the annual average emission of PM2.5 was estimated to be 3594 ton year−1, while the most recent interval of 2017–2019 had an average of 6258 ton year−1. This represented an increase of 58% in the annual average of PM2.5 associated with fires for the study period, contributing to respiratory health risks and the air quality crisis in Brazil in late 2019. These results expose an ongoing critical situation of intensifying forest degradation and potential forest collapse, including those due to a savannization forest-climate feedback, within “protected areas” in the Brazilian Amazon. To reverse this scenario, the implementation of sustainable agricultural practices and development of conservation policies to promote forest regrowth in degraded preserves are essential.
Extraction and Characterization of Antioxidant Peptides from Fruit Residues
Authors: Olivares-Galván Saúl , Marina María Luisa , García María Concepción
Published: July 2020

Fruit residues with high protein contents are generated during the processing of some fruits. These sustainable sources of proteins are usually discarded and, in all cases, underused. In addition to proteins, these residues can also be sources of peptides with protective effects against oxidative damage. The revalorization of these residues, as sources of antioxidant peptides, requires the development of suitable methodologies for their extraction and the application of analytical techniques for their characterization. The exploitation of these residues involves two main steps: the extraction and purification of proteins and their hydrolysis to release peptides. The extraction of proteins is mainly carried out under alkaline conditions and, in some cases, denaturing reagents are also employed to improve protein solubilization. Alternatively, more sustainable strategies based on the use of high-intensity focused ultrasounds, microwaves, pressurized liquids, electric fields, or discharges, as well as deep eutectic solvents, are being implemented for the extraction of proteins. The scarce selectivity of these extraction methods usually makes the subsequent purification of proteins necessary. The purification of proteins based on their precipitation or the use of ultrafiltration has been the usual procedure, but new strategies based on nanomaterials are also being explored. The release of potential antioxidant peptides from proteins is the next step. Microbial fermentation and, especially, digestion with enzymes such as Alcalase, thermolysin, or flavourzyme have been the most common. Released peptides are next characterized by the evaluation of their antioxidant properties and the application of proteomic tools to identify their sequences.
Dairy by-Products Concentrated by Ultrafiltration Used as Ingredients in the Production of Reduced Fat Washed Curd Cheese
Authors: Borges Ana Raquel , Pires Arona Figueiroa , Marnotes Natalí Garcia , Gomes David Gama , Henriques Marta Fernandes , Pereira Carlos Dias
Published: July 2020

In the following study, three different dairy by-products, previously concentrated by ultrafiltration (UF), were used as ingredients in the production of reduced-fat (RF) washed curd cheeses in order to improve their characteristics. Conventional full-fat (FF) cheeses (45% fat, dry basis (db)) and RF cheeses (20–30% fat, db) were compared to RF cheeses produced with the incorporation of 5% concentrated whey (RF + CW), buttermilk (RF + CB) or sheep second cheese whey (RF + CS). Protein-to-fat ratios were lower than 1 in the FF cheeses, while RF cheeses ranged from 1.8 to 2.8. The tested by-products performed differently when added to the milk used for cheese production. The FF cheese showed a more pronounced yellow colour after 60 and 90 days of ripening, indicating that fat plays an important role regarding this parameter. As far as the texture parameters are concerned, after 60 days of ripening, RF cheeses with buttermilk presented similar results to FF cheeses for hardness (5.0–7.5 N) and chewiness (ca. 400). These were lower than the ones recorded for RF cheeses with added UF concentrated whey (RF + CW) and second cheese whey (RF + CS), which presented lower adhesiveness values. RF cheeses with 5% incorporation of buttermilk concentrated by UF presented the best results concerning both texture and sensory evaluation.
Dramatic Increase in Content of Diverse Flavonoids Accompanied with Down-Regulation of F-Box Genes in a Chrysanthemum (Chrysanthemum × morifolium (Ramat.) Hemsl.) Mutant Cultivar Producing Dark-Purple Ray Florets
Authors: Jo Yeong Deuk , Ryu Jaihyunk , Kim Ye-Sol , Kang Kyung-Yun , Hong Min Jeong , Choi Hong-Il , Lim Gah-Hyun , Kim Jin-Baek , Kim Sang Hoon
Published: July 2020

Anthocyanins (a subclass of flavonoids) and flavonoids are crucial determinants of flower color and substances of pharmacological efficacy, respectively, in chrysanthemum. However, metabolic and transcriptomic profiling regarding flavonoid accumulation has not been performed simultaneously, thus the understanding of mechanisms gained has been limited. We performed HPLC-DAD-ESI-MS (high-performance liquid chromatography coupled with photodiode array detection and electrospray ionization mass spectrometry) and transcriptome analyses using “ARTI-Dark Chocolate” (AD), which is a chrysanthemum mutant cultivar producing dark-purple ray florets, and the parental cultivar “Noble Wine” for metabolic characterization and elucidation of the genetic mechanism determining flavonoid content. Among 26 phenolic compounds identified, three cyanidins and eight other flavonoids were detected only in AD. The total amounts of diverse flavonoids were 8.0 to 10.3 times higher in AD. Transcriptome analysis showed that genes in the flavonoid biosynthetic pathway were not up-regulated in AD at the early flower stage, implying that the transcriptional regulation of the pathway did not cause flavonoid accumulation. However, genes encoding post-translational regulation-related proteins, especially F-box genes in the mutated gene, were enriched among down-regulated genes in AD. From the combination of metabolic and transcriptomic data, we suggest that the suppression of post-translational regulation is a possible mechanism for flavonoid accumulation in AD. These results will contribute to research on the regulation and manipulation of flavonoid biosynthesis in chrysanthemum.
Comparison of Applications to Evaluate Groundwater Recharge at Lower Kelantan River Basin, Malaysia
Authors: Hussin Nur Hayati , Yusoff Ismail , Raksmey May
Published: July 2020

Groundwater has supported 70% of the water supply at the Lower Kelantan River Basin (LKRB) since the 1930s and demand for groundwater increases annually. Groundwater has been abstracted from shallow and deep aquifers. However, a comprehensive study on groundwater recharge estimation has never been reported. This study evaluated various methods to quantify recharge rate using chloride mass balance (CMB), water table fluctuation (WTF), temperature–depth profiles (TDP), and groundwater modelling coupled with water balance (GM(WB)). Recharge estimation using CMB, WTF, TDP, and GM(WB) showed high variability within 8% to 68% of annual rainfall. CMB is range from 16% to 68%, WTF 11% to 19%, TDP 8% to 11%, and GM(WB) 7% to 12% of annual rainfall, respectively. At 11%, recharge from GM(WB) was the best method for estimation because the model was constructed and calibrated using locally derived input parameters. GM(WB) is the only method involved with calibration and validation process to reduce the uncertainty. The WTF method based on long-term hydrological records gives a reasonable recharge value, in good agreement with GM(WB) and these methods can be paired to ensure the reliability of recharge value approximation in the same ranges. Applying various methods has given insight into methods selection to quantify recharge at LKRB and it is recommended that a lysimeter is installed as a direct method to estimate recharge.
Enhancing Privacy and Data Security across Healthcare Applications Using Blockchain and Distributed Ledger Concepts
Authors: Liu Haibing , Crespo Rubén González , Martínez Oscar Sanjuán
Published: July 2020

Nowadays, blockchain is developing as a secure and trustworthy platform for secure information sharing in areas of application like banking, supply chain management, food industry, energy, the Internet, and medical services. Besides, the blockchain can be described in a decentralized manner as an immutable ledger for recording data entries. Furthermore, this new technology has been developed to interrupt a variety of data-driven fields, including the health sector. However, blockchain refers to the distributed ledger technology, which constitutes an innovation in the information recording and sharing without a trusted third party. In this paper, blockchain and Distributed Ledger-based Improved Biomedical Security system (BDL-IBS) has been proposed to enhance the privacy and data security across healthcare applications. Further, our goal is to make it possible for patients to use the data to support their care and to provide strong consent systems for sharing data among different organizations and applications, since this includes managing and accessing a high amount of medical information, and this technology can maintain data to ensure reliability. Finally, results show that new blockchain-based digital platforms allow for fast, easy, and seamless interactions between data suppliers to enhance privacy and data security, including for patients themselves.
Effect of an Integrated Healthcare Program for Korean Rural Older Adults: A Quasi-Experimental Study
Authors: Kim Hyuk Joon , Kim Hye Young , Yang Youngran , Ko Eun
Published: July 2020

Studies have been conducted on the development of healthcare programs for older adults in rural areas, not only in Asia but also in Europe and the United States. However, these reports have been limited by largely non-comprehensive results, lack of demand surveys, or programs with no systematic development. The purpose of this study was to develop an integrated healthcare program for rural older adults and investigate the effects of the program. A nonequivalent control group pretest–posttest design was used. Subjects were aged over 65 and lived in the rural community. The integrated healthcare program involved 12 three-hour sessions over 12 weeks. Compared with the control group, the experimental group demonstrated significant differences in both upper extremities strengths (t = 2.74, p = 0.008; t = 2.03, p = 0.047), static balance (z = −2.38, p = 0.017), dynamic balance (t = −4.82, p < 0.001), loneliness (t = −3.02, p = 0.003), and role self-efficacy (t = 2.39, p = 0.020), but no differences for ego integration (t = 1.51, p = 0.137). To improve physical, mental, and social health of the rural older adults, we developed an integrated healthcare program. The program improved physical functions, loneliness, and role self-efficiency of the rural older adults. Therefore, it is recommended that healthcare professionals actively apply this program in primary healthcare institutes and elsewhere.
Short- and Long-Term Mortality Trends in STEMI-Cardiogenic Shock over Three Decades (1989–2018): The Ruti-STEMI-Shock Registry
Authors: García-García Cosme , Oliveras Teresa , El Ouaddi Nabil , Rueda Ferran , Serra Jordi , Labata Carlos , Ferrer Marc , Cediel German , Montero Santiago , Martínez Maria Jose , Resta Helena , de Diego Oriol , Vila Joan , Dégano Irene R , Elosua Roberto , Lupón Josep , Bayes-Genis Antoni
Published: July 2020

Aims: Cardiogenic shock (CS) is an ominous complication of ST-elevation myocardial infarction (STEMI), despite the recent widespread use of reperfusion and invasive management. The Ruti-STEMI-Shock registry analysed the prevalence of and 30-day and 1-year mortality rates in ST-elevation myocardial infarction (STEMI) complicated by CS (STEMI-CS) over the last three decades. Methods and Results: From February 1989 to December 2018, 493 STEMI-CS patients were consecutively admitted in a well-defined geographical area of ~850,000 inhabitants. Patients were classified into six five-year periods based on their year of admission. STEMI-CS mortality trends were analysed at 30 days and 1 year across the six strata. Cox regression analyses were performed for comparisons. Mean age was 67.5 ± 11.7 years; 69.4% were men. STEMI-CS prevalence did not decline from period 1 to 6 (7.1 vs. 6.2%, p = 0.218). Reperfusion therapy increased from 22.5% in 1989–1993 to 85.4% in 2014–2018. Thirty-day all-cause mortality declined from period 1 to 6 (65% vs. 50.5%, p < 0.001), with a 9% reduction after multivariable adjustment (HR: 0.91; 95% CI: 0.84–0.99; p = 0.024). One-year all-cause mortality declined from period 1 to 6 (67.5% vs. 57.3%, p = 0.001), with an 8% reduction after multivariable adjustment (HR: 0.92; 95% CI: 0.85–0.99; p = 0.030). Short- and long-term mortality trends in patients aged ≥ 75 years remained ~75%. Conclusions: Short- and long-term STEMI-CS-related mortality declined over the last 30 years, to ~50% of all patients. We have failed to achieve any mortality benefit in STEMI-CS patients over 75 years of age.
A Cell-Based Reporter Assay for Screening Inhibitors of MERS Coronavirus RNA-Dependent RNA Polymerase Activity
Authors: Min Jung Sun , Kim Geon-Woo , Kwon Sunoh , Jin Young-Hee
Published: July 2020

Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19) are emerging zoonotic diseases caused by coronavirus (CoV) infections. The viral RNA-dependent RNA polymerase (RdRp) has been suggested as a valuable target for antiviral therapeutics because the sequence homology of CoV RdRp is highly conserved. We established a cell-based reporter assay for MERS-CoV RdRp activity to test viral polymerase inhibitors. The cell-based reporter system was composed of the bicistronic reporter construct and the MERS-CoV nsp12 plasmid construct. Among the tested nine viral polymerase inhibitors, ribavirin, sofosbuvir, favipiravir, lamivudine, zidovudine, valacyclovir, vidarabine, dasabuvir, and remdesivir, only remdesivir exhibited a dose-dependent inhibition. Meanwhile, the Z-factor and Z′-factor of this assay for screening inhibitors of MERS-CoV RdRp activity were 0.778 and 0.782, respectively. Ribavirin and favipiravir did not inhibit the MERS-CoV RdRp activity, and non-nucleoside HCV RdRp inhibitor, dasabuvir, partially inhibited MERS-CoV RdRp activity. Taken together, the cell-based reporter assay for MERS-CoV RdRp activity confirmed remdesivir as a direct inhibitor of MERS-CoV RdRp in cells. A cell-based MERS-CoV RdRp activity reporter assay is reliable and accurate for screening MERS-CoV RdRp-specific inhibitors. It may provide a valuable platform for developing antiviral drugs for emerging CoV infections.
High Intensity Training to Treat Chronic Nonspecific Low Back Pain: Effectiveness of Various Exercise Modes
Authors: Verbrugghe Jonas , Agten Anouk , Stevens Sjoerd , Hansen Dominique , Demoulin Christophe , Eijnde Bert O. , Vandenabeele Frank , Timmermans Annick
Published: July 2020

High-intensity training (HIT) improves rehabilitation outcomes such as functional disability and physical performance in several chronic disorders. Promising results were also found in chronic nonspecific low back pain (CNSLBP). However, the impact of different exercise modes on HIT effectiveness in CNSLBP remains unclear. Therefore, this study evaluated the effectiveness of various HIT exercise modes and compared differences between these modes, on pain intensity, disability, and physical performance, as a therapeutic intervention for persons with CNSLBP. In a randomized comparative trial, consisting of a 12-week program, persons with CNSLBP were divided into four HIT groups, i.e., cardiorespiratory interval training coupled with either general resistance training, core strength training, combined general resistance and core strength training, or mobility exercises. Before and after the program, the Numeric Pain Rating Scale (NPRS), Modified Oswestry Disability Index (MODI), and Patient Specific Functioning Scale (PSFS) were recorded, and a cardiopulmonary exercise test (VO2max, cycling time) and isometric trunk strength test (maximum muscle torque) were performed. Eighty participants (mean age: 44.0 y, 34 males) were included. Improvements were found within all groups after the HIT programs and ranged from −39 to −57% on the NPRS, +27 to +64% on the MODI, +38 to +89% on the PSFS, +7 to +14% on VO2max, and +11 to +18% on cycling time. No differences between groups were found. High-intensity cardiorespiratory interval training improves CNSLBP rehabilitation outcomes when performed with other HIT exercise modes or mobility exercises. Hence, when setting up an exercise therapy program in CNSLBP rehabilitation, various HIT modes can be considered as therapy modalities.
Lighting Up the Tumor—Fluorescein-Guided Resection of Gangliogliomas
Authors: Höhne Julius , Acerbi Francesco , Falco Jacopo , Akçakaya Mehmet Osman , Schmidt Nils Ole , Kiris Talat , de Laurentis Camilla , Ferroli Paolo , Broggi Morgan , Schebesch Karl-Michael
Published: July 2020

(1) Background: Gangliogliomas comprise a small number of brain tumors. They usually present as World Health Organization (WHO) grade I, and they delineate on gadolinium-enhanced MRI; the surgical goal is wide radical resection, and the course thereafter is usually benign. Fluorescein sodium (FL) tends to accumulate in areas with altered blood–brain barrier (BBB). Thus far, the results provided by prospective and retrospective studies show that the utilization of this fluorophore may be associated with better visualization and improvement of resection for several tumors of the central nervous system. In this study, we retrospectively studied the effect of fluorescein sodium on visualization and resection of gangliogliomas. (2) Methods: Surgical databases in three neurosurgical departments (Regensburg University Hospital; Besta Institute, Milano, Italy; and Liv Hospital, Istanbul, Turkey), with approval by the local ethics committee, were retrospectively reviewed to find gangliogliomas surgically removed by a fluorescein-guided technique by the aid of a dedicated filter on the surgical microscope from April 2014 to February 2020. Eighteen patients (13 women, 5 men; mean age 22.9 years, range 3 to 78 years) underwent surgical treatment for gangliogliomas during 19 operations. Fluorescein was intravenously injected (5 mg/kg) after general anesthesia induction. Tumors were removed using a microsurgical technique with the YELLOW 560 Filter (YE560) (KINEVO/PENTERO 900, Carl Zeiss Meditec, Oberkochen, Germany). (3) Results: No side effects related to fluorescein occurred. In all tumors, contrast enhancement on preoperative MRI correlated with bright yellow fluorescence during the surgical procedure (17 gangliogliomas WHO grade I, 1 ganglioglioma WHO grade II). Fluorescein was considered helpful by the operating surgeon in distinguishing tumors from viable tissue in all cases (100%). Biopsy was intended in two operations, and subtotal resection was intended in one operation. In all other operations considered preoperatively eligible, gross total resection (GTR) was achieved in 12 out of 16 (75%) instances. (4) Conclusions: The use of FL and YE560 is a readily available method for safe fluorescence-guided tumor resection, possibly visualizing tumor margins intraoperatively similar to contrast enhancement in T1-weighted MRI. Our data suggested a positive effect of fluorescein-guided surgery on intraoperative visualization and extent of resection during resection of gangliogliomas.
Sodium Hypochlorite Reduces Postoperative Discomfort and Painful Early Failure after Carious Exposure and Direct Pulp Capping—Initial Findings of a Randomized Controlled Trial
Authors: Ballal Nidambur Vasudev , Duncan Henry F. , Rai Namith , Jalan Prateek , Zehnder Matthias
Published: July 2020

In this randomized controlled single-center clinical trial on 96 adult patients with parallel experimental groups (n = 48), the effects of washing a dentin/pulp wound in non-symptomatic teeth with extremely deep caries and pulpal exposure were compared between a 2.5% sodium hypochlorite (NaOCl) solution and a chemically-inert physiological saline control solution. After the allocated wound lavage, the pulps were capped with a mineral trioxide aggregate, covered by a glass-ionomer/resin liner, and the teeth were immediately restored with a resin-bonded-composite. In this first report, the early events were analyzed: postoperative discomfort (on an NRS-11 scale) at day-3 and -7 after intervention, and the occurrence of unbearable pain causing patients to contact the principal investigator to perform a root canal treatment (pulpectomy) during the first three months. The NaOCl solution caused a highly significant reduction in post-operative discomfort (p = 0.0010 day 3; p = 0.0007 day 7) and early painful failures (p = 0.0008) compared with the control. These novel findings highlight the importance of infection control in teeth with extremely deep carious lesions. Based on these observations, the use of an NaOCl solution to wash the exposed dentin/pulp wound in the vital pulp treatment is highly recommended in order to reduce pain and early failure.
Main Fetal Predictors of Adverse Neonatal Outcomes in Pregnancies with Gestational Diabetes Mellitus
Authors: Antoniou Maria-Christina , Gilbert Leah , Gross Justine , Rossel Jean-Benoît , Fumeaux Céline Julie Fischer , Vial Yvan , Puder Jardena Jacqueline
Published: July 2020

The objectives of this study were to (a) assess the utility of fetal anthropometric variables to predict the most relevant adverse neonatal outcomes in a treated population with gestational diabetes mellitus (GDM) beyond the known impact of maternal anthropometric and metabolic parameters and (b) to identify the most important fetal predictors. A total of 189 patients with GDM were included. The fetal predictors included sonographically assessed fetal weight centile (FWC), FWC > 90% and <10%, and fetal abdominal circumference centile (FACC), FACC > 90% and < 10%, at 29 0/7 to 35 6/7 weeks. Neonatal outcomes comprising neonatal weight centile (NWC), large and small for gestational age (LGA, SGA), hypoglycemia, prematurity, hospitalization for neonatal complication, and (emergency) cesarean section were evaluated. Regression analyses were conducted. Fetal variables predicted anthropometric neonatal outcomes, prematurity, cesarean section and emergency cesarean section. These associations were independent of maternal anthropometric and metabolic predictors, with the exception of cesarean section. FWC was the most significant predictor for NWC, LGA and SGA, while FACC was the most significant predictor for prematurity and FACC > 90% for emergency cesarean section. In women with GDM, third-trimester fetal anthropometric parameters have an important role in predicting adverse neonatal outcomes beyond the impact of maternal predictors.
Association between Hyperacusis and Tinnitus
Authors: Cederroth Christopher , Lugo Alessandra , Edvall Niklas , Lazar Andra , Lopez-Escamez Jose-Antonio , Bulla Jan , Uhlen Inger , Hoare Derek , Baguley David , Canlon Barbara , Gallus Silvano
Published: July 2020

Many individuals with tinnitus report experiencing hyperacusis (enhanced sensitivity to sounds). However, estimates of the association between hyperacusis and tinnitus is lacking. Here, we investigate this relationship in a Swedish study. A total of 3645 participants (1984 with tinnitus and 1661 without tinnitus) were enrolled via LifeGene, a study from the general Swedish population, aged 18–90 years, and provided information on socio-demographic characteristics, as well as presence of hyperacusis and its severity. Tinnitus presence and severity were self-reported or assessed using the Tinnitus Handicap Inventory (THI). Phenotypes of tinnitus with (n = 1388) or without (n = 1044) hyperacusis were also compared. Of 1661 participants without tinnitus, 1098 (66.1%) were women and 563 were men (33.9%), and the mean (SD) age was 45.1 (12.9). Of 1984 participants with tinnitus, 1034 (52.1%) were women and 950 (47.9%) were men, and the mean (SD) age was 47.7 (14.0) years. Hyperacusis was associated with any tinnitus [Odds ratio (OR) 3.51, 95% confidence interval (CI) 2.99–4.13], self-reported severe tinnitus (OR 7.43, 95% CI 5.06–10.9), and THI ≥ 58 (OR 12.1, 95% CI 7.06–20.6). The association with THI ≥ 58 was greater with increasing severity of hyperacusis, the ORs being 8.15 (95% CI 4.68–14.2) for moderate and 77.4 (95% CI 35.0–171.3) for severe hyperacusis. No difference between sexes was observed in the association between hyperacusis and tinnitus. The occurrence of hyperacusis in severe tinnitus is as high as 80%, showing a very tight relationship. Discriminating the pathophysiological mechanisms between the two conditions in cases of severe tinnitus will be challenging, and optimized study designs are necessary to better understand the mechanisms behind the strong relationship between hyperacusis and tinnitus.
Epidemiological Features of the Bladder Neck Rest Position and Mobility
Authors: Horosz Edyta , Pomian Andrzej , Zwierzchowska Aneta , Lisik Wojciech , Majkusiak Wojciech , Tomasik Paweł , Rutkowska Beata , Skalska Joana , Siemion Małgorzata , Banasiuk Dominika , Barcz Ewa
Published: July 2020

The data concerning epidemiological determinants of the bladder neck (BN) mobility are scarce. The aim of the study was to determine epidemiological features and identify factors influencing BN position at rest and BN mobility in patients without pelvic organ prolapse (POP). Seven hundred and ninety-six patients that attended two outpatient clinics were enrolled in the study. Position and mobility of the BN were measured with the use of pelvic floor ultrasound. Demographic and functional factors that were hypothesized to influence BN mobility were assessed. Vaginal deliveries (VDs) and age ≥65 were associated with lower BN position at rest. Higher BN mobility was observed in women with stress urinary incontinence (SUI). In obese women, higher BN position and lower BN mobility was observed compared to non-obese women, and it was correlated with longer urethras in this group of patients. VDs and their number were associated with increased BN mobility, independently of body mass index (BMI). To conclude, obesity, VDs, and age are factors associated with changes in bladder neck position at rest and its mobility. Higher BMI correlates with restricted BN mobility, and, therefore, the incidence of SUI in obese patients is probably not connected to BN hypermobility.
Association between Bone Metabolism and Vestibular Problems in the Modified Romberg Test: Data from the 2009–2010 Korean National Health and Nutrition Examination Survey
Authors: Kim So Young , Cho Yang-Sun , Kim Ji-Soo , Koo Ja-Won
Published: July 2020

Osteoporosis contributes to the occurrence of falling and vestibular problems, particularly in elderly patients. This study aimed to investigate the association between bone metabolism with vestibular problems and falling. A total of 4054 participants of the Korean National Health and Nutrition Examination Survey (KNHANES) from 2009 to 2010 aged ≥50 years old were surveyed on their history of falling, vestibular problems evaluated by the modified Romberg test, variables involving bone metabolism, and serum levels of vitamin D and alkaline phosphatase. They also underwent dual energy X-ray absorptiometry. The crude (simple) and adjusted odd ratios (ORs) of variables involving bone metabolism for vestibular problems in the modified Romberg test and falling were analyzed using a logistic regression model. A subgroup analysis was performed according to sex and the presence of menopause in females. Vestibular problems in the modified Romberg test group but not the falling group were associated with decreased serum vitamin D levels (p < 0.001; odds ratio (OR) = 0.951; 95% confidence interval (CI), 0.926–0.976). In subgroup analysis according to sex, the post-menopause group showed a higher rate of vestibular problems in the modified Romberg test compared to the pre-menopause group (4.5% vs. 0.7%, p = 0.019). In the post-menopause group, osteoporosis was positively associated with vestibular problems in the modified Romberg test (p = 0.001, OR = 10.971, 95% CI = 2.650–45.414). On the other hand, a history of hormone replacement therapy was negatively related with vestibular problems in this subgroup (p = 0.035; OR = 0.473; 95% CI = 0.239–0.948). A decrease in serum vitamin D levels may impact the vestibular system through neural signaling or by osteoporotic changes of the otic capsule, as well as otolith particles. Decreased estrogen levels in postmenopausal women may make them more prone to osteoporotic changes, which were associated with vestibular problems in the modified Romberg test. Because this is a cross-sectional study, the causal relationship of bone metabolism with vestibular function needs to be investigated.
Allogeneic Stem Cell Transplantation for Adult T-Cell Leukemia/Lymphoma—Romanian Experience
Authors: Tanase Alina D. , Colita Andrei , Craciun Oana G. , Lipan Lavinia , Varady Zsofia , Stefan Laura , Ranete Adela , Pasca Sergiu , Bumbea Horia , Andreescu Mihaela , Popov Viola , Bardas Alexandru , Coriu Daniel , Lupu Anca Roxana , Tomuleasa Ciprian , Colita Anca , Hermine Olivier
Published: July 2020

Adult T-cell leukemia/lymphoma (ATLL) is a rare and aggressive mature T-cell malignancy caused by the human T lymphoma virus I (HTLV-I) affecting 3–5% of HTLV-1 carriers and is usually diagnosed in endemic regions. Romania is a region with high prevalence of HTLV-1 infection and ATLL and with low median age at diagnosis for aggressive types. We performed a retrospective analysis of post-transplant outcome in the first Romanian patients with ATLL receiving hematopoietic stem cell allotransplant. The study population included eight patients (three males, five females), with median age of 39.5 (range 26–57), with acute (one case) and lymphoma type (seven cases) that received peripheral stem cells (PBSC) from matched related (MRD) and unrelated donors (MUD) after reduced intensity conditioning. Graft versus host disease (GVHD) developed in six patients. Relapse occurred in four cases (50%) at a median time of 5-months post-transplant. Six patients died: four cases with disease-related deaths and two patients with GVHD-related deaths. The median survival post-transplant was 19.5 months (range 2.3–44.2 months). The post-transplant survival at 1-year was 62.5%, at 2-years 50%, and at 3-years 37.5%. In our opinion allogeneic transplant improves outcome in aggressive type ATLL.
Dynamics of Platelet Counts in Major Trauma: The Impact of Haemostatic Resuscitation and Effects of Platelet Transfusion—A Sub-Study of the Randomized Controlled RETIC Trial
Authors: Tauber Helmuth , Innerhofer Nicole , von Langen Daniel , Ströhle Mathias , Fries Dietmar , Mittermayr Markus , Hell Tobias , Oswald Elgar , Innerhofer Petra
Published: July 2020

Although platelets play a central role in haemostasis, the dynamics of platelet counts during haemostatic resuscitation, the response to platelet transfusion, and effects on clinical outcome are poorly described for trauma patients. As a sub-study of the already published randomized controlled RETIC Study “Reversal of Trauma-induced Coagulopathy using First-line Coagulation Factor Concentrates or Fresh-Frozen Plasma” trial, we here analysed whether the type of first-line haemostatic resuscitation influences the frequency of platelet transfusion and determined the effects of platelet transfusion in coagulopathic patients with major trauma. Patients randomly received first-line plasma (FFP) or coagulation factor concentrates (CFC), mainly fibrinogen concentrate. In both groups, platelets were transfused to maintain platelet counts between 50 and 100 × 109/L. Transfusion rates were significantly higher in the FFP (n = 44) vs. CFC (n = 50) group (FFP 47.7% vs. CFC 26%); p = 0.0335. Logistic regression analysis adjusted for the stratification variables injury severity score (ISS) and brain injury confirmed that first-line FFP therapy increases the odds for platelet transfusion (odds ratio (OR) 5.79 (1.89 to 20.62), p = 0.0036) and this effect was larger than a 16-point increase in ISS (OR 4.33 (2.17 to 9.74), p = 0.0001). In conclusion, early fibrinogen supplementation exerted a platelet-saving effect while platelet transfusions did not substantially improve platelet count and might contribute to poor clinical outcome.
Sex-Specific Prognostic Implications in Dilated Cardiomyopathy After Left Ventricular Reverse Remodeling
Authors: Cannata Antonio , Manca Paolo , Nuzzi Vincenzo , Gregorio Caterina , Artico Jessica , Gentile Piero , Pio Loco Carola , Ramani Federica , Barbati Giulia , Merlo Marco , Sinagra Gianfranco
Published: July 2020

Background. Women affected by Dilated Cardiomyopathy (DCM) experience better outcomes compared to men. Whether a more pronounced Left Ventricular Reverse Remodelling (LVRR) might explain this is still unknown. Aim. We investigated the relationship between LVRR and sex and its long-term outcomes. Methods. A cohort of 605 DCM patients with available follow-up data was consecutively enrolled. LVRR was defined, at 24-month follow-up evaluation, as an increase in left ventricular ejection fraction (LVEF) ≥ 10% or a LVEF > 50% and a decrease ≥ 10% in indexed left ventricular end-diastolic diameter (LVEDDi) or an LVEDDi ≤ 33 mm/m2. Outcome measures were a composite of all-cause mortality/heart transplantation (HTx) or ventricular assist device (VAD) and a composite of Sudden Cardiac Death (SCD) or Major Ventricular Arrhythmias (MVA). Results. 181 patients (30%) experienced LVRR. The cumulative incidence of LVRR at 24-months evaluation was comparable between sexes (33% vs. 29%; p = 0.26). During a median follow-up of 149 months, women experiencing LVRR had the lowest rate of main outcome measure (global p = 0.03) with a 71% relative risk reduction compared to men with LVRR, without significant difference between women without LVRR and males. A trend towards the same results was found regarding SCD/MVA (global p = 0.06). Applying a multi-state model, male sex emerged as an independent adverse prognostic factor even after LVRR completion. Conclusions. Although the rate of LVRR was comparable between sexes, females experiencing LVRR showed the best outcomes in the long term follow up compared to males and females without LVRR. Further studies are advocated to explain this difference in outcomes between sexes.
Impact of Lymphadenectomy on Survival of Patients with Serous Advanced Ovarian Cancer After Neoadjuvant Chemotherapy: A French National Multicenter Study (FRANCOGYN)
Authors: Bund Virginie , Lecointre Lise , Velten Michel , Ouldamer Lobna , Bendifallah Sofiane , Koskas Martin , Bolze Pierre-Adrien , Collinet Pierre , Canlorbe Geoffroy , Touboul Cyril , Huchon Cyrille , Coutant Charles , Faller Emilie , Boisramé Thomas , Gantzer Justine , Demarchi Martin , Baldauf Jean-Jacques , Ballester Marcos , Lavoué Vincent , Akladios Chérif
Published: July 2020

Background: The population of interest to this study comprised individuals with advanced-stage ovarian carcinoma who were exposed to neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS). Those who had not received systematic lymphadenectomy (SL; Group 1) were compared to those who had received SL (Group 2). Outcome measures included progression-free survival (PFS), overall survival (OS), and surgical complications. Methods: This was a retrospective, multicenter cohort study in nine referral centers of France between January 2000 and June 2017. OS analysis using the multivariate Cox regression model was performed. PFS and surgery-related morbidity were analyzed. Results: Of the 255 patients included, 100 were in Group 1 and 155 in Group 2. Patient majority was, on average, younger and less comorbid, with predominant R0 surgery in Group 2. Dindo–Clavien score was similar between the two groups (p = 0.15). Median OS was 26.8 months in Group 2 and 27.6 months in Group 1. SL was not statistically significant on OS (p = 0.7). Median PFS was 18.3 months in Group 2 and 16.6 months in Group 1. SL had positive impact on PFS (p = 0.005). Conclusions: patients who had received SL (Group 2) had significantly higher PFS regardless of node-positivity status when compared to those who had not received SL (Group 1).