bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of High Intensity Laser Therapy in the Treatment of Tendon and Ligament Injuries in Performance Horses
Authors: Zielińska Paulina , Nicpoń Jakub , Kiełbowicz Zdzisław , Soroko Maria , Dudek Krzysztof , Zaborski Daniel
Published: August 2020

The aim of this study was to evaluate the effects of high intensity laser therapy (HILT) on tendon and ligament injury treatment in horses. Twenty six horses with tendinopathies were randomly assigned to a HILT treated or to a non-treated group. Each horse was subjected to the same rehabilitation programme. Horses from the treatment group underwent a series of fifteen HILT treatments with the same parameters. Clinical and ultrasound assessments were performed by the same veterinarian and were carried out before (day 0), during (day 13–15) and after treatment (day 38–40). Clinical evaluation included: pain, swelling and lameness of the affected limb. The ultrasound examination evaluated lesion echogenicity and lesion percentage. After the treatment, pain, swelling and lameness were significantly improved by HILT compared with the control group (p = 0.023, 0.008 and 0.044, respectively). No significant changes were found in lesion echogenicity degree between both groups in measurements taken during treatment (p = 0.188) and after treatment (p = 0.070). For lesion percentage reduction, the statistical modelling showed a significant improvement in the HILT group compared with the control group during (p = 0.038) and after treatment (p = 0.019). In conclusion, HILT promoted analgesic and anti-oedema effects, with visual lameness reduction in horses with tendon and ligament injuries, and reduced lesion percentage but did not influence change in lesion echogenicity.
Dietary Phytogenic Combination with Hops and a Mixture of a Free Butyrate Acidifier and Gluconic Acid Maintaining the Health Status of the Gut and Performance in Chickens
Authors: Ząbek Katarzyna , Szkopek Dominika , Michalczuk Monika , Konieczka Paweł
Published: August 2020

Additives with bioactive properties can improve chickens’ gut health. This study investigated the physiological status of the gut, including its morphological structure and microbiome activities in chickens fed diets supplemented with phytogenic ingredients with hops (Anta®Phyt) or a mixture of a free butyrate acidifier and gluconic acid (PreAcid). In this study, 1155 broilers were distributed to three dietary treatments with 5 replicate pens per treatment, 77 birds each. Anta®Phyt was added at 400/300/200/200 mg/kg diet whereas PreAcid was added at 3/2/1/1 g/kg starter/grower I/grower II/finisher diet respectively. Dietary treatments did not compromise body weight in different growth periods. In the birds fed PreAcid-supplemented diet, higher gut concentration of butyric acid was observed, particularly in the early stage of growth, while the profile of the short-chain fatty acids was maintained among the treatments. Neither additive significantly affected cecal bacterial enzyme activities. Feeding the birds with Anta®Phyt and PreAcid had beneficial effects on gut morphostructure indices, including intestinal wall thickness, crypt depth and the villus height to crypt depth ratio, in 35- and 42-day old birds. In conclusion, the feeding Anta®Phyt- or PreAcid-supplemented diet exerted beneficial effects on the indices determining the physiological status of the gut and maintained good performance of birds of different ages.
Binding Sites of Anti-Lcr V Monoclonal Antibodies Are More Critical than the Avidities and Affinities for Passive Protection against Yersinia pestis Infection in a Bubonic Plague Model
Authors: Amemiya Kei , Dankmeyer Jennifer L. , Keasey Sarah L. , Trevino Sylvia R. , Wormald Michael M. , Halasohoris Stephanie A. , Ribot Wilson J. , Fetterer David P. , Cote Christopher K. , Worsham Patricia L. , Adamovicz Jeffrey J. , Ulrich Robert G.
Published: August 2020

Plague is a zoonotic disease that is caused by Yersinia pestis. Monoclonal antibodies (mAbs) that bind to the V-antigen, a virulence factor that is produced by Y. pestis, can passively protect mice from plague. An analysis of protective mAbs that bind to V-antigen was made to assess binding sites, avidities, and affinities. Anti-V mAbs were screened for their efficacy in a murine model of plague. Antigen-binding sites of protective V mAbs were determined with a linear peptide library, V-antigen fragment, competitive binding, and surface plasmon resonance. The avidities to the V-antigen was determined by ELISA, and affinities of the mAbs to the V-antigen were determined by surface plasmon resonance. The most protective mAb 7.3 bound to a unique conformational site on the V-antigen, while a less protective mAb bound to a different conformational site located on the same V-antigen fragment as mAb 7.3. The avidity of mAb 7.3 for the V-antigen was neither the strongest overall nor did it have the highest affinity for the V-antigen. The binding site of the most protective mAb was critical in its ability to protect against a lethal plague challenge.
Squalene: More than a Step toward Sterols
Authors: Micera Marco , Botto Alfonso , Geddo Federica , Antoniotti Susanna , Bertea Cinzia Margherita , Levi Renzo , Gallo Maria Pia , Querio Giulia
Published: August 2020

Squalene (SQ) is a natural triterpene widely distributed in nature. It is a metabolic intermediate of the sterol biosynthetic pathway and represents a possible target in different metabolic and oxidative stress-related disorders. Growing interest has been focused on SQ’s antioxidant properties, derived from its chemical structure. Strong evidence provided by ex vivo models underline its scavenging activity towards free radicals, whereas only a few studies have highlighted its effect in cellular models of oxidative stress. Given the role of unbalanced free radicals in both the onset and progression of several cardiovascular diseases, an in depth evaluation of SQ’s contribution to antioxidant defense mechanisms could represent a strategic approach in dealing with these pathological conditions. At present experimental results overall show a double-edged sword role of squalene in cardiovascular diseases and its function has to be better elucidated in order to establish intervention lines focused on its features. This review aims to summarize current knowledge about endogenous and exogenous sources of SQ and to point out the controversial role of SQ in cardiovascular physiology.
Effect of Nanoconfinement of Polyphenolic Extract from Grape Pomace into Functionalized Mesoporous Silica on Its Biocompatibility and Radical Scavenging Activity
Authors: Brezoiu Ana-Maria , Bajenaru Laura , Berger Daniela , Mitran Raul-Augustin , Deaconu Mihaela , Lincu Daniel , Stoica Guzun Anicuta , Matei Cristian , Moisescu Mihaela Georgeta , Negreanu-Pirjol Ticuta
Published: August 2020

The aim of this paper is to assess the properties of Mamaia (MM) grape pomace polyphenolic extract loaded onto pristine and functionalized MCM-41 mesoporous silica as potential ingredients for nutraceuticals or cosmetics. The chemical profile of hydroalcoholic polyphenolic extracts, prepared either by conventional extraction or microwave-assisted method, was analyzed by reverse-phase high-performance liquid chromatography with photodiode array detector (HPLC-PDA) analysis, while their radical scavenger activity (RSA) was evaluated using DPPH (2,2-diphenyl-1-picrylhydrazyl radical) and ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) assays. The extract-loaded materials were characterized by Fourier transform infrared (FTIR) spectroscopy, N2 adsorption-desorption isotherms, thermogravimetric analysis, as well as RSA (DPPH and ABTS assays). The polyphenols release profiles from pristine and functionalized (with mercaptopropyl, propyl sulfonic acid, cyanoethyl and propionic acid moieties) MCM-41-type supports were determined in phosphate buffer solution (PBS) pH 5.7. For selected materials containing embedded phytochemicals, cellular viability, and oxidative stress level on immortalized mouse embryonic fibroblast cell line (NIH3T3) were evaluated. A more acidic functional groups linked on silica pore walls determined a higher amount of phytochemicals released in PBS. The extract-loaded materials showed a good cytocompatibility on tested concentrations. The embedded extract preserved better the RSA over time than the free extract. The polyphenols-loaded MCM-41-type silica materials, especially MM@MCM-COOH material, demonstrated a good in vitro antioxidant effect on NIH3T3 cells, being potential candidates for nutraceutical or cosmetic formulations.
Polyphenols as Potential Agents in the Management of Temporomandibular Disorders
Authors: Moccia Stefania , Nucci Ludovica , Spagnuolo Carmela , d’Apuzzo Fabrizia , Piancino Maria Grazia , Minervini Giuseppe
Published: August 2020

Temporomandibular disorders (TMD) consist of multifactorial musculoskeletal disorders associated with the muscles of mastication, temporomandibular joint (TMJ), and annexed structures. This clinical condition is characterized by temporomandibular pain, restricted mandibular movement, and TMJ synovial inflammation, resulting in reduced quality of life of affected people. Commonly, TMD management aims to reduce pain and inflammation by using pharmacologic therapies that show efficacy in pain relief but their long-term use is frequently associated with adverse effects. For this reason, the use of natural compounds as an effective alternative to conventional drugs appears extremely interesting. Indeed, polyphenols could represent a potential therapeutic strategy, related to their ability to modulate the inflammatory responses involved in TMD. The present work reviews the mechanisms underlying inflammation-related TMD, highlighting the potential role of polyphenols as a promising approach to develop innovative management of temporomandibular diseases.
The Potential of Non-Ionic Surfactants for Extraction of Lactic Acid from Aqueous Solution
Authors: Aguda Remil , LeBoeuf Shayla , Stelly Cody , Bonilla Samantha , LeBlanc Brandon , Holmes William , Hernandez Rafael , Zappi Mark E. , Revellame Emmanuel D.
Published: August 2020

Lactic acid, an important commodity chemical for various applications, is mainly produced through fermentation. In this study, the potential of non-ionic surfactants (an alcohol ethoxylate (AE) and two alcohol alkoxylates (AAs)) as solvents for the extraction of lactic acid from aqueous solutions is reported for the first time. Ternary mixtures containing lactic acid, water, and surfactants were prepared for the assessment. The results indicated that for all the systems, the water–surfactant binary pair exhibits partial immiscibility. Furthermore, the results suggested that with respect to the size of the two-phase region and stability of phases developed, the AE is the suitable solvent for the targeted extraction process. Thus, tie-lines for the system lactic acid + water + AE were then determined to establish the phase diagram of the system at 308.15 K. From the tie-lines, distribution coefficients and separation factors were estimated, which indicated that a compromise between the size and number of extraction units is necessary if AE is to be used as a solvent for lactic acid extraction. The extraction efficiency was estimated to be only about 37–48%. Nevertheless, the biodegradability and non-toxicity of AE makes it a viable solvent for the development of the extractive lactic acid fermentation process.
Upper Limb Bionic Orthoses: General Overview and Forecasting Changes
Authors: Rzyman Gustaw , Szkopek Jacek , Redlarski Grzegorz , Palkowski Aleksander
Published: August 2020

Using robotics in modern medicine is slowly becoming a common practice. However, there are still important life science fields which are currently devoid of such advanced technology. A noteworthy example of a life sciences field which would benefit from process automation and advanced robotic technology is rehabilitation of the upper limb with the use of an orthosis. Here, we present the state-of-the-art and prospects for development of mechanical design, actuator technology, control systems, sensor systems, and machine learning methods in rehabilitation engineering. Moreover, current technical solutions, as well as forecasts on improvement, for exoskeletons are presented and reviewed. The overview presented might be the cornerstone for future research on advanced rehabilitation engineering technology, such as an upper limb bionic orthosis.
Hybrid Data Hiding Based on AMBTC Using Enhanced Hamming Code
Authors: Kim Cheonshik , Shin Dong-Kyoo , Yang Ching-Nung , Leng Lu
Published: August 2020

The image-based data hiding method is a technology used to transmit confidential information secretly. Since images (e.g., grayscale images) usually have sufficient redundancy information, they are a very suitable medium for hiding data. Absolute Moment Block Truncation Coding (AMBTC) is one of several compression methods and is appropriate for embedding data due to its very low complexity and acceptable distortion. However, since there is not enough redundant data compared to grayscale images, the research to embed data in the compressed image is a very challenging topic. That is the motivation and challenge of this research. Meanwhile, the Hamming codes are used to embed secret bits, as well as a block code that can detect up to two simultaneous bit errors and correct single bit errors. In this paper, we propose an effective data hiding method for two quantization levels of each block of AMBTC using Hamming codes. Bai and Chang introduced a method of applying Hamming (7,4) to two quantization levels; however, the scheme is ineffective, and the image distortion error is relatively large. To solve the problem with the image distortion errors, this paper introduces a way of optimizing codewords and reducing pixel distortion by utilizing Hamming (7,4) and lookup tables. In the experiments, when concealing 150,000 bits in the Lena image, the averages of the Normalized Cross-Correlation (NCC) and Mean-Squared Error (MSE) of our proposed method were 0.9952 and 37.9460, respectively, which were the highest. The sufficient experiments confirmed that the performance of the proposed method is satisfactory in terms of image embedding capacity and quality.
Visuo-Haptic Mixed Reality Simulation Using Unbound Handheld Tools
Authors: Aygün Mehmet Murat , Öğüt Yusuf Çağrı , Baysal Hulusi , Taşcıoğlu Yiğit
Published: August 2020

Visuo-haptic mixed reality (VHMR) adds virtual objects to a real scene and enables users to see and also touch them via a see-through display and a haptic device. Most studies with kinesthetic feedback use general-purpose haptic devices, which require the user to continuously hold an attached stylus. This approach constrains users to the mechanical limits of the device even when it is not needed. In this paper, we propose a novel VHMR concept with an encountered-type haptic display (ETHD), which consists of a precision hexapod positioner and a six-axis force/torque transducer. The main contribution is that the users work with unbound real-life tools with tracking markers. ETHD’s end-effector remains inside the virtual object and follows the tooltip to engage only during an interaction. We have developed a simulation setup and experimentally evaluated the relative accuracy and synchronization of the three major processes, namely tool tracking, haptic rendering, and visual rendering. The experiments successfully build-up to a simple simulation scenario where a tennis ball with a fixed center is deformed by the user.
Women Architects in Portugal: Working in Colonial Africa before the Carnation Revolution (1950–1974)
Authors: Vaz Milheiro Ana , Fiúza Filipa
Published: August 2020

How did women architects shape a modern world in the late period of Portuguese colonial Africa, just before the Carnation Revolution? The specific role of women in Portugal working in colonial African architectural culture has now started to be addressed by Portuguese and Lusophone-African historiography. During the 1950s, the presence of women in the metropolitan schools of architecture was reduced. Of those who could graduate, few actually worked as architects. Most were absorbed by the commonly feminine roles, resulting from marriage and from the ideal of family promoted by the Estado Novo dictatorship. To the ones that risked prosecution for working outside the family, the option of jobs associated with the feminine universe, such as teaching, was privileged. Among those who were emancipated from this pattern, the majority worked in familiar partnerships, regarded as an extension of marriage. The women architects that follow the husbands in their African emigration often ended up having the opportunities to work in their professional field partly due to the lack of qualified technicians, and to the high demand of commissions. This paper not only seeks to outline a perspective on these women, but also tries to understand the context of their work by presenting two case-studies in the late in the late period of Portuguese Colonisation: Maria Carlota Quintanilha and Maria Emilia Caria.
Updated Assessment of Temperature Extremes over the Middle East–North Africa (MENA) Region from Observational and CMIP5 Data
Authors: Ntoumos Athanasios , Hadjinicolaou Panos , Zittis George , Lelieveld Jos
Published: August 2020

The objective of this analysis is to provide an up-to-date observation-based assessment of the evolution of temperature extremes in the Middle East–North Africa (MENA) region and evaluate the performance of global climate model simulations of the past four decades. A list of indices of temperature extremes, based on absolute level, threshold, percentile and duration is used, as defined by the Expert Team on Climate Change Detection and Indices (ETCCDI). We use daily near-surface air temperature (Tmax and Tmin) to derive the indices of extremes for the period 1980–2018 from: (i) re-analyses (ERA-Interim, MERRA-2) and gridded observational data (Berkeley Earth) and (ii) 18 CMIP5 model results combining historical (1950–2005) and scenario runs (2006–2018 under RCP 2.6, RCP 4.5 and RCP 8.5). The CMIP5 results show domain-wide strong, statistically significant warming, while the observation based ones are more spatially variable. The CMIP5 models capture the climatology of the hottest areas in the western parts of northern Africa and the Gulf region with the thewarmest day (TXx) > 46 °C and warmest night (TNx) > 33 °C. For these indices, the observed trends are about 0.3–0.4 °C/decade while they are 0.1–0.2 °C/decade stronger in the CMIP5 results. Overall, the modeled climate warming up to 2018, as reflected in the indices of temperature extremes is confirmed by re-analysis and observational data.
Correction: Yu, L., et al. Evaluation of Moist Static Energy in a Simulated Tropical Cyclone. Atmosphere 2019, 10, 319/doi:10.3390/atmos10060319
Authors: Yu Lijun , Wu Shuhui , Ma Zhanhong
Published: August 2020

The authors wish to make the following corrections to this paper: [...]
Atmospheric Responses to Mesoscale Oceanic Eddies in the Winter and Summer North Pacific Subtropical Countercurrent Region
Authors: Sun Jianxiang , Zhang Suping , Nowotarski Christopher J. , Jiang Yuxi
Published: August 2020

In the winter and summer North Pacific Subtropical Countercurrent region, the atmospheric responses to 20,000+ mesoscale oceanic eddies (MOEs) are examined using satellite and reanalysis data from 1999 to 2013. The composite results indicate that surface wind speed, cloud, and precipitation anomalies are positively correlated with sea surface temperature anomalies in both seasons. The surface wind speed anomalies and convective precipitation anomalies show dipolar structures centering on MOEs in winter and on unipolar structures in summer. In both seasons, the vertical mixing mechanism plays an obvious role in the atmospheric responses to MOEs. In addition, the distributions of sea level pressure anomalies in winter reflects the effects of the pressure adjustment mechanism. Due to the seasonal variations in the atmospheric background state and the MOEs, the sensitivities of surface wind speeds, clouds, and precipitation responses to MOEs in summer are over 30% higher than those in winter.
On Laser-Modified Rutherford Scattering
Authors: Zaytsev Sergey A. , Zaytsev Alexander S. , Ancarani Lorenzo U. , Kouzakov Konstantin A.
Published: August 2020

We present a theoretical analysis of a charged-particle scattering by a Coulomb potential in the presence of laser radiation. The effect of a laser field is studied using our recently developed nonperturbative parabolic quasi-Sturmian approach for solving the system of coupled Lippmann–Schwinger–Floquet equations in the Kramers–Henneberger frame. We calculate the ratio of multiphoton differential cross sections to the Rutherford cross section in the case of a laser-assisted electron-proton scattering process. Our results are compared with predictions of the Bunkin–Fedorov, Kroll–Watson, and Coulomb–Volkov analytical approximations: marked discrepancies are found for different net numbers of exchanged photons and different orientations of the laser-field polarization vector. Our findings clearly demonstrate deficiencies of those well-known approximations for describing laser-modified Rutherford scattering processes.
Reduction of Homogeneous Pseudo-Kähler Structures by One-Dimensional Fibers
Authors: Carmona Jiménez José Luis , Castrillón López Marco
Published: August 2020

We study the reduction procedure applied to pseudo-Kähler manifolds by a one dimensional Lie group acting by isometries and preserving the complex tensor. We endow the quotient manifold with an almost contact metric structure. We use this fact to connect pseudo-Kähler homogeneous structures with almost contact metric homogeneous structures. This relation will have consequences in the class of the almost contact manifold. Indeed, if we choose a pseudo-Kähler homogeneous structure of linear type, then the reduced, almost contact homogeneous structure is of linear type and the reduced manifold is of type C5⊕C6⊕C12 of Chinea-González classification.
Impact of Copper Fungicide Use in Hop Production on the Total Metal Content and Stability of Wort and Dry-Hopped Beer
Authors: Chrisfield Benjamin J. , Hopfer Helene , Elias Ryan J.
Published: August 2020

Transition metals, including copper, iron, and manganese, are known to catalyze the generation of reactive oxygen species (ROS) in beer leading to reduced product stability. Metals in beer are generally derived from raw ingredients. The present study aims to evaluate the impact of brewing and dry-hopping using hops treated with copper-based fungicides (CBFs) on the final transition metal content of model buffer solutions and pilot-scale systems of wort and beer. Copper levels in model wort and beer solutions were elevated (105.6% and 230.4% increase, respectively) when CBF-treated hops were used. In laboratory-prepared wort, elevated copper concentrations were not observed when CBF-treated hops were used for boiling. Dry hopping of beer using CBF-treated hops led to significant increases in total copper content (ca. 75 µg/kg vs. ca. 40–50 µg/kg in the control-hopped beer) when yeast was absent from the treated beer, but not when yeast was present. It was observed that manganese levels were significantly elevated in all hopped beers (ca. 495–550 µg/kg vs. 90–125 µg/kg in the unhopped control), regardless of hop treatment. A hop varietal thiol, 4-Mercapto-4-methylpentan-2-one, was spiked into treated beers, and the rate of oxidative loss was monitored during aging. Rates of thiol loss in treated beer samples did not differ across CBF treatments but were significantly lower in unhopped controls in the absence of yeast (p < 0.0001) and correlated significantly with total manganese content of the beers (R2 = 0.4228, p = 0.0006). The rate of staling in hopped beers as measured by the rate of 1-hydroxyethyl radical generation did not differ among hop treatments, suggesting that excess copper content contributed from the hops does not negatively impact the oxidative stability of the beers. These findings suggest that brewers can use CBF-treated hops without any negative implications for the shelf stability of their beers and do not contraindicate the use of CBF in hops production when necessary.
A Brief History of Whiskey Adulteration and the Role of Spectroscopy Combined with Chemometrics in the Detection of Modern Whiskey Fraud
Authors: Power Aoife C. , Néill Caoimhe Ní , Geoghegan Sive , Currivan Sinéad , Deasy Mary , Cozzolino Daniel
Published: August 2020

Food fraud and adulteration is a major concern in terms of economic and public health. Multivariate methods combined with spectroscopic techniques have shown promise as a novel analytical strategy for addressing issues related to food fraud that cannot be solved by the analysis of one variable, particularly in complex matrices such distilled beverages. This review describes and discusses different aspects of whisky production, and recent developments of laboratory, in field and high throughput analysis. In particular, recent applications detailing the use of vibrational spectroscopy techniques combined with data analytical methods used to not only distinguish between brand and origin of whisky but to also detect adulteration are presented.
Heparin Administered to Anopheles in Membrane Feeding Assays Blocks Plasmodium Development in the Mosquito
Authors: Lantero Elena , Fernandes Jessica , Aláez-Versón Carlos Raúl , Gomes Joana , Silveira Henrique , Nogueira Fatima , Fernàndez-Busquets Xavier
Published: August 2020

Innovative antimalarial strategies are urgently needed given the alarming evolution of resistance to every single drug developed against Plasmodium parasites. The sulfated glycosaminoglycan heparin has been delivered in membrane feeding assays together with Plasmodium berghei-infected blood to Anopheles stephensi mosquitoes. The transition between ookinete and oocyst pathogen stages in the mosquito has been studied in vivo through oocyst counting in dissected insect midguts, whereas ookinete interactions with heparin have been followed ex vivo by flow cytometry. Heparin interferes with the parasite’s ookinete–oocyst transition by binding ookinetes, but it does not affect fertilization. Hypersulfated heparin is a more efficient blocker of ookinete development than native heparin, significantly reducing the number of oocysts per midgut when offered to mosquitoes at 5 µg/mL in membrane feeding assays. Direct delivery of heparin to mosquitoes might represent a new antimalarial strategy of rapid implementation, since it would not require clinical trials for its immediate deployment.
Viral Ubiquitin and Ubiquitin-Like Deconjugases—Swiss Army Knives for Infection
Authors: Masucci Maria Grazia
Published: August 2020

Posttranslational modifications of cellular proteins by covalent conjugation of ubiquitin and ubiquitin-like polypeptides regulate numerous cellular processes that are captured by viruses to promote infection, replication, and spreading. The importance of these protein modifications for the viral life cycle is underscored by the discovery that many viruses encode deconjugases that reverse their functions. The structural and functional characterization of these viral enzymes and the identification of their viral and cellular substrates is providing valuable insights into the biology of viral infections and the host’s antiviral defense. Given the growing body of evidence demonstrating their key contribution to pathogenesis, the viral deconjugases are now recognized as attractive targets for the design of novel antiviral therapeutics.
Extracellular Vesicles (EVs) and Pancreatic Cancer: From the Role of EVs to the Interference with EV-Mediated Reciprocal Communication
Authors: Moeng Sokviseth , Son Seung Wan , Lee Jong Sun , Lee Han Yeoung , Kim Tae Hee , Choi Soo Young , Kuh Hyo Jeong , Park Jong Kook
Published: August 2020

Pancreatic cancer is malignant and the seventh leading cause of cancer-related deaths worldwide. However, chemotherapy and radiotherapy are—at most—moderately effective, indicating the need for new and different kinds of therapies to manage this disease. It has been proposed that the biologic properties of pancreatic cancer cells are finely tuned by the dynamic microenvironment, which includes extracellular matrix, cancer-associated cells, and diverse immune cells. Accumulating evidence has demonstrated that extracellular vesicles (EVs) play an essential role in communication between heterogeneous subpopulations of cells by transmitting multiplex biomolecules. EV-mediated cell–cell communication ultimately contributes to several aspects of pancreatic cancer, such as growth, angiogenesis, metastasis and therapeutic resistance. In this review, we discuss the role of extracellular vesicles and their cargo molecules in pancreatic cancer. We also present the feasibility of the inhibition of extracellular biosynthesis and their itinerary (release and uptake) for a new attractive therapeutic strategy against pancreatic cancer.
The Effectiveness of Multi-Session FMT Treatment in Active Ulcerative Colitis Patients: A Pilot Study
Authors: Mańkowska-Wierzbicka Dorota , Stelmach-Mardas Marta , Gabryel Marcin , Tomczak Hanna , Skrzypczak-Zielińska Marzena , Zakerska-Banaszak Oliwia , Sowińska Anna , Mahadea Dagmara , Baturo Alina , Wolko Łukasz , Słomski Ryszard , Dobrowolska Agnieszka
Published: August 2020

The modification of the microbiome through fecal microbiota transplantation (FMT) is becoming a very promising therapeutic option for inflammatory bowel disease (IBD) patients. Our pilot study aimed to assess the effectiveness of multi-session FMT treatment in active ulcerative colitis (UC) patients. Ten patients with UC were treated with multi-session FMT (200 mL) from healthy donors, via colonoscopy/gastroscopy. Patients were evaluated as follows: at baseline, at week 7, and after 6 months, routine blood tests (including C reactive protein (CRP) and calprotectin) were performed. 16S rRNA gene (V3V4) sequencing was used for metagenomic analysis. The severity of UC was classified based on the Truelove–Witts index. The assessment of microbial diversity showed significant differences between recipients and healthy donors. FMT contributed to long-term, significant clinical and biochemical improvement. Metagenomic analysis revealed an increase in the amount of Lactobacillaceaea, Micrococcaceae, Prevotellaceae, and TM7 phylumsp.oral clone EW055 during FMT, whereas Staphylococcaceae and Bacillaceae declined significantly. A positive increase in the proportion of the genera Bifidobacterium, Lactobacillus, Rothia, Streptococcus, and Veillonella and a decrease in Bacillus, Bacteroides, and Staphylococcus were observed based on the correlation between calprotectin and Bacillus and Staphylococcus; ferritin and Lactobacillus, Veillonella, and Bifidobacterium abundance was indicated. A positive change in the abundance of Firmicutes was observed during FMT and after 6 months. The application of multi-session FMT led to the restoration of recipients’ microbiota and resulted in the remission of patients with active UC.
Method Standardization for Conducting Innate Color Preference Studies in Different Zebrafish Strains
Authors: Siregar Petrus , Juniardi Stevhen , Audira Gilbert , Lai Yu-Heng , Huang Jong-Chin , Chen Kelvin H.-C. , Chen Jung-Ren , Hsiao Chung-Der
Published: August 2020

The zebrafish has a tetrachromatic vision that is able to distinguish ultraviolet (UV) and visible wavelengths. Recently, zebrafish color preferences have gained much attention because of the easy setup of the instrument and its usefulness to screen behavior-linked stimuli. However, several published papers dealing with zebrafish color preferences have contradicting results that underscore the importance of method standardization in this field. Different laboratories may report different results because of variations in light source, color intensity, and other parameters such as age, gender, container size, and strain of fish. In this study, we aim to standardize the color preference test in zebrafish by measuring light source position, light intensity, gender, age, animal size to space ratio, and animal strain. Our results showed that color preferences for zebrafish are affected by light position, age, strain, and social interaction of the fish, but not affected by fish gender. We validated that ethanol can significantly induce color preference alteration in zebrafish which may be related to anxiety and depression. We also explored the potential use of the optimized method to examine color preference ranking and index differences in various zebrafish strains and species, such as the tiger barb and glass catfish. In conclusion, zebrafish color preference screening is a powerful tool for high-throughput neuropharmacological applications and the standardized protocol established in this study provides a useful reference for the zebrafish research community.
Effects of Depressive Symptoms, Feelings, and Interoception on Reward-Based Decision-Making: Investigation Using Reinforcement Learning Model
Authors: Ogishima Hiroyoshi , Maeda Shunta , Tanaka Yuki , Shimada Hironori
Published: August 2020

Background: In this study, we examined the relationships between reward-based decision-making in terms of learning rate, memory rate, exploration rate, and depression-related subjective emotional experience, in terms of interoception and feelings, to understand how reward-based decision-making is impaired in depression. Methods: In all, 52 university students were randomly assigned to an experimental group and a control group. To manipulate interoception, the participants in the experimental group were instructed to tune their internal somatic sense to the skin-conductance-response waveform presented on a display. The participants in the control group were only instructed to stay relaxed. Before and after the manipulation, the participants completed a probabilistic reversal-learning task to assess reward-based decision-making using reinforcement learning modeling. Similarly, participants completed a probe-detection task, a heartbeat-detection task, and self-rated scales. Results: The experimental manipulation of interoception was not successful. In the baseline testing, reinforcement learning modeling indicated a marginally-significant correlation between the exploration rate and depressive symptoms. However, the exploration rate was significantly associated with lower interoceptive attention and higher depressive feeling. Conclusions: The findings suggest that situational characteristics may be closely involved in reward exploration and highlight the clinically-meaningful possibility that intervention for affective processes may impact reward-based decision-making in those with depression.
Affective and Sexual Needs of Residents in Psychiatric Facilities: A Qualitative Approach
Authors: Landi Giulia , Marchi Mattia , Ettalibi Mohamed Yassir , Mattei Giorgio , Pingani Luca , Sacchi Valentina , Galeazzi Gian Maria
Published: August 2020

Background: The affective and sexual needs of psychiatric patients are often under-considered, although they contribute significantly to their general well-being. Such topics are critical for Residential Psychiatric Facilities Users (RPFUs), whose daily life is paced by therapeutic settings. The aim of this paper is to better understand how sexuality and affectivity are expressed by the RPFUs at the Mental Health Department of Modena, within psychiatric residential settings. Methods: Adult RPFUs took part into two audio recorded focus groups. Digital transcripts were analyzed using MAXQDA software in order to perform qualitative narrative analysis, so as to develop a hierarchical code system a posteriori (derived from the data). Results: Eleven participants (eight RPFUs and three investigators) attended the first focus group, and eight participants (5 RPFUs and 3 investigators) attended the second focus group. 175 interventions were analyzed and coded under seven thematic areas: (a) contraception and sexually transmitted disease prevention (N = 17); (b) affective needs (N = 11); (c) personal experiences (N = 61); (d) regulation of sexual relations (N = 18); (e) Mental Health Professionals’ (MHPs) openness towards the topic (N = 17); (f) MHPs’ responses to RPFUs’ sexual behaviors (N = 33); and (g) RPFUs proposals (N = 18). The highlighted topics suggest that affective and sexual relations commonly occur within residential psychiatric facilities, even if mental health services often fail to recognize and address RPFUs’ affective and sexual needs as well as to provide effective solutions to manage them. Conclusions: RPFUs expressed a request for support to fulfill their affective and sexual needs and dedicated spaces for sexual activities to relieve their discomfort, while MHPs highlighted a need for awareness, training, and shared problem-solving strategies.
The Clinicopathological and Prognostic Significance of Nrf2 and Keap1 Expression in Hepatocellular Carcinoma
Authors: Lee Kiryang , Kim Seunghye , Lee Yangkyu , Lee Hyejung , Lee Youngeun , Park Hyunjin , Nahm Ji Hae , Ahn Soomin , Yu Su Jong , Lee Kyoungbun , Kim Haeryoung
Published: August 2020

Nuclear factor E2-related factor2 (Nrf2) activation is associated with both cytoprotective effects and malignant behavior of cancer cells. This study aimed to evaluate the clinicopathological implications of the expression of Nrf2, pNrf2, and its regulator Keap1 in human hepatocellular carcinomas (HCCs). Tissue microarrays consisting of 285 surgically resected HCCs were immunohistochemically stained with pNrf2, Nrf2, Keap1, stemness-related markers (keratin 19 (K19), epithelial cell adhesion molecule (EpCAM)), carbonic anhydrase IX (CAIX), epithelial–mesenchymal transition (EMT)-related markers (ezrin, uPAR, E-cadherin), and p53, and the results were correlated with the clinicopathological features. pNrf2 expression was significantly associated with increased proliferative activity, as well as EpCAM, ezrin, p53, and CAIX expression and E-cadherin loss (p < 0.05, all). Strong cytoplasmic Nrf2 expression was associated with CAIX and ezrin expression (p < 0.05, both). Keap1 was associated with increased proliferative activity, portal vein invasion, EMT-related markers, and p53 expression in CAIX-negative HCCs (p < 0.05, all). Both pNrf2 and cytoplasmic Nrf2 expression were associated with decreased overall survival (p < 0.05, both), and cytoplasmic Nrf2 expression was an independent predictor of decreased overall survival on multivariate analysis (hazard ratio 4.15, p < 0.001). Both pNrf2 and cytoplasmic Nrf2 expression were associated with poor survival and aggressive behavior of HCC. In addition, Keap1 expression was also associated with aggressive HCC behavior in CAIX-negative HCCs, suggesting that Keap1 expression should be interpreted in the context of hypoxia status.
Recent Advances in Desmoid Tumor Therapy
Authors: Napolitano Andrea , Mazzocca Alessandro , Spalato Ceruso Mariella , Minelli Alessandro , Baldo Francesca , Badalamenti Giuseppe , Silletta Marianna , Santini Daniele , Tonini Giuseppe , Incorvaia Lorena , Vincenzi Bruno
Published: August 2020

The desmoid tumor is a locally aggressive proliferative disease within the family of soft-tissue sarcomas. Despite its relatively good prognosis, the clinical management of desmoid tumors requires constant multidisciplinary evaluation due to its highly variable clinical behavior. Recently, active surveillance has being regarded as the appropriate strategy at diagnosis, as indolent persistence or spontaneous regressions are not uncommon. Here, we review the most recent advances in desmoid tumor therapy, including low-dose chemotherapy and treatment with tyrosine kinase inhibitors. We also explore the recent improvements in our knowledge of the molecular biology of this disease, which are leading to clinical trials with targeted agents.
Cisplatin Decreases ENaC Activity Contributing to Renal Salt Wasting Syndrome
Authors: Soares Antonio G. , Mironova Elena , Archer Crystal R. , Contreras Jorge , Stockand James D. , Abd El-Aziz Tarek Mohamed
Published: August 2020

Cisplatin (CDDP) is an important anticancer drug. A common side effect of CDDP is renal salt and water-wasting syndrome (RSWS). The origin of RSWS is obscure. Emerging evidence, though, suggests that broad inhibition of sodium transport proteins by CDDP may result in decreases in tubular reabsorption, causing increases in sodium and water excretion. In this sense, CDDP would be acting like a diuretic. The effect of CDDP on the epithelial Na+ channel (ENaC), which is the final arbiter fine-tuning renal Na+ excretion, is unknown. We test here whether CDDP affects ENaC to promote renal salt and water excretion. The effects of CDDP and benzamil (BZM), a blocker of ENaC, on excretion of a sodium load were quantified. Similar to BZM, CDDP facilitated renal Na+ excretion. To directly quantify the effects on ENaC, principal cells in split-open tubules were patch clamped. CDDP, at doses comparable to those used for chemotherapy (1.5 µM), significantly decreased ENaC activity in native tubules. To further elaborate on this mechanism, the dose-dependent effects of CDDP on mouse ENaC (mENaC) heterologously expressed in Chinese Hamster Ovary (CHO) cells were tested using patch clamping. As in native tubules, CDDP significantly decreased the activity of mENaC expressed in CHO cells. Dose–response curves and competition with amiloride identified CDDP as a weak inhibitor of ENaC (apparent IC50 = 1 µM) that competes with amiloride for inhibition of the channel, weakening the inhibitory actions of the latter. Such observations are consistent with CDDP being a partial modulator of ENaC, which possibly has a binding site that overlaps with that of amiloride. These findings are consistent with inhibition of ENaC by CDDP contributing to the RSWS caused by this important chemotherapy drug.
Activation of Epidermal Growth Factor Receptor Sensitizes Glioblastoma Cells to Hypoxia-Induced Cell Death
Authors: Luger Anna-Luisa , Lorenz Nadja I. , Urban Hans , Divé Iris , Engel Anna L. , Strassheimer Florian , Dettmer Katja , Zeiner Pia S. , Shaid Shabnam , Struve Nina , Kriegs Malte , Hofmann Ute , Oefner Peter J. , Harter Patrick N. , Steinbach Joachim P. , Ronellenfitsch Michael W.
Published: August 2020

Background: The epidermal growth factor receptor (EGFR) signaling pathway is genetically activated in approximately 50% of glioblastomas (GBs). Its inhibition has been explored clinically but produced disappointing results, potentially due to metabolic effects that protect GB cells against nutrient deprivation and hypoxia. Here, we hypothesized that EGFR activation could disable metabolic adaptation and define a GB cell population sensitive to starvation. Methods: Using genetically engineered GB cells to model different types of EGFR activation, we analyzed changes in metabolism and cell survival under conditions of the tumor microenvironment. Results: We found that expression of mutant EGFRvIII as well as EGF stimulation of EGFR-overexpressing cells impaired physiological adaptation to starvation and rendered cells sensitive to hypoxia-induced cell death. This was preceded by adenosine triphosphate (ATP) depletion and an increase in glycolysis. Furthermore, EGFRvIII mutant cells had higher levels of mitochondrial superoxides potentially due to decreased metabolic flux into the serine synthesis pathway which was associated with a decrease in the NADPH/NADP+ ratio. Conclusions: The finding that EGFR activation renders GB cells susceptible to starvation could help to identify a subgroup of patients more likely to benefit from starvation-inducing therapies.
MR1-Restricted T Cells in Cancer Immunotherapy
Authors: Flores-Villanueva Pedro , Sobhani Navid , Wang Xu , Li Yong
Published: August 2020

Major histocompatibility complex class I-related (MR1) was first identified as a cell membrane protein involved in the development and expansion of a unique set of T cells expressing an invariant T-cell receptor (TCR) α-chain. These cells were initially discovered in mucosal tissues, such as the intestinal mucosa, so they are called mucosal-associated invariant T (MAIT) cells. MR1 senses the presence of intermediate metabolites of riboflavin and folic acid synthesis that have been chemically modified by the side-products of glycolysis, glyoxal or methylglyoxal. These modified metabolites form complexes with MR1 and translocate from the endoplasmic reticulum to the plasma membrane where MAIT cells’ TCRs recognize them. Recent publications report that atypical MR1-restricted cytotoxic T cells, differing from MAIT cells in TCR usage, antigen, and transcription factor profile, recognize an as yet unknown cancer-specific metabolite presented by MR1 in cancer cells. This metabolite may represent another class of neoantigens, beyond the neo-peptides arising from altered tumor proteins. In an MR1-dependent manner, these MR1-restricted T cells, while sparing noncancerous cells, kill many cancer cell lines and attenuate cell-line-derived and patient-derived xenograft tumors. As MR1 is monomorphic and expressed in a wide range of cancer tissues, these findings raise the possibility of universal pan-cancer immunotherapies that are dependent on cancer metabolites.
Impact of Grip Strength in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib
Authors: Endo Kei , Kuroda Hidekatsu , Kanazawa Jo , Sato Takuro , Fujiwara Yudai , Abe Tamami , Sato Hiroki , Kooka Youhei , Oikawa Takayoshi , Sawara Kei , Takikawa Yasuhiro
Published: August 2020

Although sarcopenia is characterized by a loss of muscle strength and skeletal muscle mass, few studies have evaluated the effect of muscle strength on hepatocellular carcinoma (HCC) patients. We evaluated the impact of sarcopenia-related factors (grip strength (GS) and the skeletal muscle index (SMI)) on the survival among lenvatinib-treated unresectable HCC (u-HCC) patients. This single-center cohort study was conducted at a university hospital. The study population included 63 lenvatinib-treated u-HCC patients managed between April 2018 and April 2020. A decreased GS and decreased SMI were found in 21 (33.3%) and 22 (34.9%) patients, respectively. The overall survival (OS) of the normal GS group was significantly higher than that of the decreased GS group, while that of the normal and decreased SMI groups did not differ markedly. There were no significant differences in the progression-free survival between the normal GS and decreased GS groups or the normal SMI and decreased SMI groups. A multivariate Cox proportional hazards model showed that modified albumin-bilirubin-grade (mALBI) 2b (hazard ratio (HR) 4.39) and a decreased GS (HR 3.55) were independently associated with an increased risk of poor prognosis. In addition to the hepatic functional reserve, a decreased GS was a poor prognostic factor in lenvatinib-treated u-HCC patients.