bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Slow-Release Urea Administration on Production Performance, Health Status, Diet Digestibility, and Environmental Sustainability in Lactating Dairy Cows
Authors: Grossi Silvia , Compiani Riccardo , Rossi Luciana , Dell’Anno Matteo , Castillo Israel , Sgoifo Rossi Carlo Angelo
Published: August 2021

The effects of partially replacing soybean meal (SBM) with a slow-release urea source (SRU) on production performance, feed efficiency, digestibility, and environmental sustainability of dairy cows were evaluated. A total of 140 lactating Holstein Frisian cows were allocated into two study groups: (i) control (diet entirely based on SBM), and (ii) treatment (diet of 0.22% on dry matter basis (d.m.)) of SRU. Milk yield, dry matter intake (DMI), feed conversion rate (FCR), body condition score (BCS), reproductive parameters, and milk quality were evaluated. The chemical composition of the feeds and feces were analyzed to calculate the in vivo digestibility of the two diets. The carbon footprint (CFP) and predicted methane (CH4) emissions were evaluated. The inclusion of SRU significantly increases milk yield, DMI, and FCR (p < 0.0001), whereas milk quality, BCS, and reproductive indicators were not affected (p > 0.05). In the treatment group, the digestibility of crude protein (CP) (p = 0.012), NDF (p = 0.039), and cellulose (p = 0.033) was significantly higher, while the other nutritional parameters weren’t affected. All the environmental parameters were significantly improved in the treatment group (p < 0.0001). Replacing SBM with SRU can be a strategy to enhance dairy cows’ sustainability due to improved production efficiency, reduced feed CFP, and predicted CH4 production.
Purple Corn Anthocyanin Affects Lipid Mechanism, Flavor Compound Profiles, and Related Gene Expression of Longissimus Thoracis et Lumborum Muscle in Goats
Authors: Tian Xingzhou , Lu Qi , Zhao Shengguo , Li Jiaxuan , Luo Qingyuan , Wang Xu , Zhang Yangdong , Zheng Nan
Published: August 2021

The current study aimed to investigate the effect of anthocyanins on muscle flavor compound profiles in goats. Goats in three groups were fed a basic diet or a diet supplemented with 0.5 g/d or 1 g/d anthocyanin-rich purple corn pigment (PCP). Compared to the control group, plasma total cholesterol was significantly decreased (p < 0.05) in the anthocyanin groups. The feeding of anthocyanin increased (p < 0.05) flavor compound types and total alcohol level, whereas it decreased (p < 0.05) total hydrocarbons, aromatics, esters, and miscellaneous compounds in the longissimusthoracis et lumborum muscle (LTL). Adding PCP to the diet enriched (p < 0.05) vegetal, herbaceous, grease, and fruity flavors compared to the control group. The 0.5 g/d PCP group had increased (p < 0.05) abundance of peroxisome proliferator-activated receptor gamma, but there was a decreased (p < 0.05) level of lipoprotein lipase in LTL. Collectively, this study indicated that anthocyanin can improve mutton flavor by decreasing plasma lipid parameters and by modulating the abundance of several flavor-related genes of goats.
Vibration Actuator System with Small-Scale Size Capable of Visual Inspection of Large Complex Iron Structures
Authors: Yaguchi Hiroyuki , Itoh Yusuke
Published: August 2021

Deterioration of social infrastructure equipment has become a major problem in countries around the world. In the present study, a novel vibration actuator system capable of movement on an iron structure having complicated surfaces, such as steps, is proposed. A vibration actuator capable of reciprocating movement with a small-scale size was prototyped and tested. In consideration of mobility, the size of the vibration actuator is designed to be smaller than 50 mm and the total mass is lighter than 20 g. The experimental result demonstrates that the maximum efficiency of the vibration actuator was 28.1%, and the maximum pulling power was 1.8 N. Furthermore, a vibration actuator system in which two vibration actuators and a wheel having a magnetic force connected by a flexible silicone rubber material was prototyped. This actuator system can move over a step of 48 mm in the horizontal plane and 25 mm in the vertical plane without control. Finally, a machine test was conducted on the frame surface moving, which is difficult even for robots. This actuator system can move at an average speed of 12.1 mm/s within the frame.
High Resolution STEM Images of the Human Tooth Enamel Crystals
Authors: Reyes-Gasga José , Brès Etienne F.
Published: August 2021

High-resolution scanning transmission electron microscopy (STEM) images of human tooth enamel crystals, mainly in the high-angle annular dark-field (STEM-HAADF) mode, are presented in this work along the [1000], [10-11]. and [1-210] directions. These images allow knowing some structural details at the nanometric level of the human tooth enamel crystals and of the central dark line (CDL) observed at their centers. The transmission electron microscopy (TEM) and high-resolution TEM (HRTEM) images of the CDL showed the Fresnel contrast. In the STEM bright-field (STEM-BF) and annular-dark-field (STEM-ADF) images, the CDL was observed as an unstrain hydroxyapatite (HAP)-like zone but surrounded by a strained zone. In the STEM-HAADF images, the CDL appeared with a weak contrast, and its contrasts’ thickness was registered between 3 and 8 Å. The arrangement obtained in the STEM-HAADF images by identifying the bright points with the Ca atoms produced the superposition of the HAP atomic sites, mainly along the [0001] direction. The findings provide further information on the structure details at the center of enamel crystals, which favors the anisotropic carious dissolution at the CDL.
Q-Switched 1064/532 nm Laser with Picosecond Pulse to Treat Benign Hyperpigmentations: A Single-Center Retrospective Study
Authors: Silvestri Martina , Bennardo Luigi , Zappia Elena , Tamburi Federica , Cameli Norma , Cannarozzo Giovanni , Nisticò Steven Paul
Published: August 2021

(1) Benign melanoses are a frequent issue in aesthetic dermatology. Solar lentigo, ephelides, café au lait spots, and other melanoses represent a cosmetic issue for a growing number of subjects. The Q-switched 1064/532-nanometer (nm) laser may be considered the gold standard for management of these aesthetic issues. A new generation of Q-switched lasers, capable of concentrating the energy pulse in the spectrum of hundreds of picoseconds, is emerging, promising better results than previous ones. In this paper, we report the use of a Q-switched laser with a picosecond pulse to manage hypermelanoses. (2) Methods: 36 patients seeking melanosis removal were retrospectively enrolled at Magna Graecia University of Catanzaro. Treatment parameters, although variable, were the following: 1064 nm with a pulse duration of 450 picoseconds (ps) for dermic lesions and 532 nm with 370 ps for epidermal lesions. Up to four treatments, with a minimum interval between laser treatments of 30 days, were performed. After the last session, patients’ satisfaction was assessed at a three-month follow up with a Visual Analogue Scale (VAS). Two blinded dermatologists measured the aesthetic outcome using a five-point scale comparing pictures before laser sessions and during follow-up. (3) Results: 36 patients were enrolled; 23 were females (63.9%) and 13 males (36.1%). The mean reported age was 49.2 ± 18.9 years. All participants were assessed with a complete/almost complete melanosis removal at the dermatological evaluation, with a mean VAS score of 9.39 ± 0.90. (4) Conclusions: The Q-switched 1064/532 nm laser may be considered the main weapon in treating benign hypermelanosis. The picosecond pulse seems to guarantee better results than other devices. However, a clinical trial comparing Q-switched nanosecond pulse with picosecond pulse is necessary to confirm this study’s findings.
2 × 2 Matrices: Manifolds, Realizations, Applications
Authors: Uriostegui Kenan , Wolf Kurt Bernardo
Published: August 2021

Both geometric and wave optical models, as well as classical and quantum mechanics, realize linear transformations with matrices; for plane optics, these are 2×2 and of unit determinant. Students and some researchers could assume that the structure of this matrix group is fairly evident and hardly interesting. However, the properties and applications even of this lowest 2×2 case are already unexpectedly rich. While in mechanics they cover classical angular momentum, quantum spin, and represent ‘2+1’ relativity, in optical models they lead from the geometrical description of light propagation in the paraxial regime to wave optics via linear canonical transforms requiring a more penetrating view of their manifold structure and multiple covers. The purpose of this review article is to highlight the topological space of 2×2 matrices as it applies to classical versus quantum and wave models, to underline how the latter requires the double cover of the former, thus using 2×2 matrices as an alternative viewpoint of the quantization process, beside the traditional characterization by commutation and non-commutations of position and momentum.
Copyright Protection of 3D Digitized Artistic Sculptures by Adding Unique Local Inconspicuous Errors by Sculptors
Authors: Vasiljević Ivana , Obradović Ratko , Đurić Isidora , Popkonstantinović Branislav , Budak Igor , Kulić Luka , Milojević Zoran
Published: August 2021

In recent years, digitization of cultural heritage objects, for the purpose of creating virtual museums, is becoming increasingly popular. Moreover, cultural institutions use modern digitization methods to create three-dimensional (3D) models of objects of historical significance to form digital libraries and archives. This research aims to suggest a method for protecting these 3D models from abuse while making them available on the Internet. The proposed method was applied to a sculpture, an object of cultural heritage. It is based on the digitization of the sculpture altered by adding local clay details proposed by the sculptor and on sharing on the Internet a 3D model obtained by digitizing the sculpture with a built-in error. The clay details embedded in the sculpture are asymmetrical and discreet to be unnoticeable to an average observer. The original sculpture was also digitized and its 3D model created. The obtained 3D models were compared and the geometry deviation was measured to determine that the embedded error was invisible to an average observer and that the watermark can be extracted. The proposed method simultaneously protects the digitized image of the artwork while preserving its visual experience. Other methods cannot guarantee this.
A Semi-Empirical Fluid Dynamic Model of a Vacuum Microgripper Based on CFD Analysis
Authors: Urbano Dario Giuseppe , Noventa Gianmaria , Ghidoni Antonio , Lezzi Adriano M.
Published: August 2021

Vacuum microgrippers are devices used to handle and manipulate small objects. Despite their simple working principle and low cost, they show low efficiency in detaching performance, especially when the object to be grasped is very small. In this work, a particular design for vacuum microgrippers with an incorporated automatic release tool is considered. The final goal of this study was to present a numerical model that can supply reliable estimates of the aerodynamic force acting on the release tool and of the air flow rate inside the gripper as a function of geometric parameters and the outlet pressure value. A complete CFD analysis of a simplified model of the device is presented. Grid independence analysis was also performed to define a suitable grid and guarantee a good trade-off between accuracy and computing time. According to Design of Experiments (DOE) techniques, 81 simulations were performed, changing the values of the outlet pressure (p2), the body inner diameter (D), the lateral holes’ diameter (d) and the releasing mass length (L). Every design variable could assume three different values. Linear regression, based on the least square method, was employed to determine mass flow rate and lifting force empirical correlations.
Interactive Machine Learning-Based Multi-Label Segmentation of Solid Tumors and Organs
Authors: Bounias Dimitrios , Singh Ashish , Bakas Spyridon , Pati Sarthak , Rathore Saima , Akbari Hamed , Bilello Michel , Greenberger Benjamin A. , Lombardo Joseph , Chitalia Rhea D. , Jahani Nariman , Gastounioti Aimilia , Hershman Michelle , Roshkovan Leonid , Katz Sharyn I. , Yousefi Bardia , Lou Carolyn , Simpson Amber L. , Do Richard K. G. , Shinohara Russell T. , Kontos Despina , Nikita Konstantina , Davatzikos Christos
Published: August 2021

We seek the development and evaluation of a fast, accurate, and consistent method for general-purpose segmentation, based on interactive machine learning (IML). To validate our method, we identified retrospective cohorts of 20 brain, 50 breast, and 50 lung cancer patients, as well as 20 spleen scans, with corresponding ground truth annotations. Utilizing very brief user training annotations and the adaptive geodesic distance transform, an ensemble of SVMs is trained, providing a patient-specific model applied to the whole image. Two experts segmented each cohort twice with our method and twice manually. The IML method was faster than manual annotation by 53.1% on average. We found significant (p < 0.001) overlap difference for spleen (DiceIML/DiceManual = 0.91/0.87), breast tumors (DiceIML/DiceManual = 0.84/0.82), and lung nodules (DiceIML/DiceManual = 0.78/0.83). For intra-rater consistency, a significant (p = 0.003) difference was found for spleen (DiceIML/DiceManual = 0.91/0.89). For inter-rater consistency, significant (p < 0.045) differences were found for spleen (DiceIML/DiceManual = 0.91/0.87), breast (DiceIML/DiceManual = 0.86/0.81), lung (DiceIML/DiceManual = 0.85/0.89), the non-enhancing (DiceIML/DiceManual = 0.79/0.67) and the enhancing (DiceIML/DiceManual = 0.79/0.84) brain tumor sub-regions, which, in aggregation, favored our method. Quantitative evaluation for speed, spatial overlap, and consistency, reveals the benefits of our proposed method when compared with manual annotation, for several clinically relevant problems. We publicly release our implementation through CaPTk (Cancer Imaging Phenomics Toolkit) and as an MITK plugin.
Advances in Biomaterials for Breast Reconstruction
Authors: Park Jun-Ho , Park Ji-Ung , Chang Hak
Published: August 2021

Breast cancer is one of the most commonly diagnosed malignancies in women. Along with increasing demands for breast reconstruction, the attention given to the psychological and aesthetic benefits of breast reconstruction has also increased. As breast reconstruction and augmentation demands increase, biomaterials for breast reconstruction are being developed, and the related industry is growing quickly worldwide. Among the various biomaterials used for breast enlargement, breast implants have undergone a remarkable evolution since the 1960s. Despite unsatisfactory results and unexpected complications, research dedicated to achieving an ideal breast implant has progressed. In accordance with attention to tissue engineering, a three-dimensional (3D) bioprinting technique for breast tissue regeneration has emerged to overcome the current limitations of breast biomaterials. Along with solid implants, injectable liquid-type fillers are also part of ongoing studies.
Ambient Air Pollution Exposure and Risk of Developmental Delay in Children and Teenagers in Taiwan
Authors: Chen Hung-Lin , Zhang Ruihong , Tsai Stella Chin-Shaw , Chou Ruey-Hwang , Hsu Yi-Chao , Fan Hueng-Chuen , Muo Chih-Hsin , Hsu Chung Y. , Chang Kuang-Hsi
Published: August 2021

(1) Background: Studies on the association between air pollution and developmental delay in children are limited. Therefore, we evaluated the risk of developmental delay in Taiwanese children exposed to air pollution. (2) Methods: We merged the two nationwide databases, and the annual average pollutant concentrations were grouped into tertiles to evaluate the risk of developmental delay (ICD-9 code 315.9). We identified the patients’ active residential locations based on the location of the clinic or hospital in which they sought treatment for acute upper respiratory infections (ICD 9 code 460). The two nationwide databases were linked for analysis based on the active residential locations of each participant and the locations of the 74 ambient air quality monitoring stations. (3) Results: We observed an increased risk of developmental delay in children and teenagers exposed to SO2, CO, and NO2. The adjusted odds ratios (ORs) of developmental delay for comparison among the tertiles with respect to SO2, CO, and NO2 exposures were 1.12 (95% confidence interval [CI], 1.01–1.24), 1.21 (95% CI, 1.09–1.34), and 1.40 (95% CI, 1.261.55), respectively. (4) Conclusions: The present findings suggest that air pollution exposure increases the risk of developmental delay in children and teenagers in Taiwan.
Cell Adhesion Molecules in Normal Skin and Melanoma
Authors: D’Arcy Cian , Kiel Christina
Published: August 2021

Cell adhesion molecules (CAMs) of the cadherin, integrin, immunoglobulin, and selectin protein families are indispensable for the formation and maintenance of multicellular tissues, especially epithelia. In the epidermis, they are involved in cell–cell contacts and in cellular interactions with the extracellular matrix (ECM), thereby contributing to the structural integrity and barrier formation of the skin. Bulk and single cell RNA sequencing data show that >170 CAMs are expressed in the healthy human skin, with high expression levels in melanocytes, keratinocytes, endothelial, and smooth muscle cells. Alterations in expression levels of CAMs are involved in melanoma propagation, interaction with the microenvironment, and metastasis. Recent mechanistic analyses together with protein and gene expression data provide a better picture of the role of CAMs in the context of skin physiology and melanoma. Here, we review progress in the field and discuss molecular mechanisms in light of gene expression profiles, including recent single cell RNA expression information. We highlight key adhesion molecules in melanoma, which can guide the identification of pathways and strategies for novel anti-melanoma therapies.
Effects of Treadmill Exercise on Neural Mitochondrial Functions in Parkinson’s Disease: A Systematic Review of Animal Studies
Authors: Nhu Nguyen Thanh , Cheng Yu-Jung , Lee Shin-Da
Published: August 2021

This systematic review sought to determine the effects of treadmill exercise on the neural mitochondrial respiratory deficiency and neural mitochondrial quality-control dysregulation in Parkinson’s disease. PubMed, Web of Science, and EMBASE databases were searched through March 2020. The English-published animal studies that mentioned the effects of treadmill exercise on neural mitochondria in Parkinson’s disease were included. The CAMARADES checklist was used to assess the methodological quality of the studies. Ten controlled trials were included (median CAMARADES score = 5.7/10) with various treadmill exercise durations (1–18 weeks). Seven studies analyzed the neural mitochondrial respiration, showing that treadmill training attenuated complex I deficits, cytochrome c release, ATP depletion, and complexes II–V abnormalities in Parkinson’s disease. Nine studies analyzed the neural mitochondrial quality-control, reporting that treadmill exercise improved mitochondrial biogenesis, mitochondrial fusion, and mitophagy in Parkinson’s disease. The review findings supported the hypothesis that treadmill training could attenuate both neural mitochondrial respiratory deficiency and neural mitochondrial quality-control dysregulation in Parkinson’s disease, suggesting that treadmill training might slow down the progression of Parkinson’s disease.
Extra- and Intra-Cellular Mechanisms of Hepatic Stellate Cell Activation
Authors: Yan Yufei , Zeng Jiefei , Xing Linhao , Li Changyong
Published: August 2021

Hepatic fibrosis is characterized by the pathological accumulation of extracellular matrix (ECM) in the liver resulting from the persistent liver injury and wound-healing reaction induced by various insults. Although hepatic fibrosis is considered reversible after eliminating the cause of injury, chronic injury left unchecked can progress to cirrhosis and liver cancer. A better understanding of the cellular and molecular mechanisms controlling the fibrotic response is needed to develop novel clinical strategies. It is well documented that activated hepatic stellate cells (HSCs) is the most principal cellular players promoting synthesis and deposition of ECM components. In the current review, we discuss pathways of HSC activation, emphasizing emerging extra- and intra-cellular signals that drive this important cellular response to hepatic fibrosis. A number of cell types and external stimuli converge upon HSCs to promote their activation, including hepatocytes, liver sinusoidal endothelial cells, macrophages, cytokines, altered ECM, hepatitis viral infection, enteric dysbiosis, lipid metabolism disorder, exosomes, microRNAs, alcohol, drugs and parasites. We also discuss the emerging signaling pathways and intracellular events that individually or synergistically drive HSC activation, including TGFβ/Smad, Notch, Wnt/β-catenin, Hedgehog and Hippo signaling pathways. These findings will provide novel potential therapeutic targets to arrest or reverse fibrosis and cirrhosis.
Vivo-Morpholino-Based Antiviral for SARS-CoV-2: Implications for Novel Therapies in the Treatment of Acute COVID-19 Disease
Authors: Hildreth James E. K. , Moulton Jon D. , Alcendor Donald J.
Published: August 2021

Therapeutic modalities designed specifically to inhibit COVID-19 infection and replication would limit progressive COVID-19-associated pulmonary disease in infected patients and prevent or limit systemic disease. If effective, antivirals could reduce viral transmission rates by reducing viral burden and allow time for immune clearance. For individuals infected with acute-stage disease, antivirals in support of the existing vaccines could reduce COVID-19 hospitalizations and deaths. Here, we evaluate MRCV-19, a phosphorodiamidate morpholino oligo with delivery dendrimer (Vivo-Morpholino), to prevent coronavirus infection in a cell culture model. This is a novel antiviral that effectively inhibits SARS-CoV-2 replication in vitro. By design, MRCV-19 targets the SARS-CoV-2 5’UTR and overlaps the pp1a start site of translation in order to block access of the translation initiation complex to the start. MRCV-19 testing is conducted in a high-throughput, 384-well plate format with a 10-point dose-response curve (common ratio of 2) assayed in duplicate with parallel cytotoxicity evaluations. MRCV-19 was shown to be more effective than hydroxychloroquine and remdesivir in our CPE reduction assay with low toxicity. The clinical translational impact of this study is providing the basis for evaluating MRCV-19 on a large scale in an appropriate infection model for toxicity and systemic high-level inhibition of SARS-CoV-2, which could lead in time to phase I testing in humans.
Sustained Axonal Degeneration in Prolonged Disorders of Consciousness
Authors: Bagnato Sergio , D’Ippolito Maria Enza , Boccagni Cristina , De Tanti Antonio , Lucca Lucia Francesca , Nardone Antonio , Salucci Pamela , Fiorilla Teresa , Pingue Valeria , Gennaro Serena , Ursino Maria , Colombo Valentina , Barone Teresa , Rubino Francesca , Andriolo Maria
Published: August 2021

(1) Background: Sustained axonal degeneration may play a critical role in prolonged disorder of consciousness (DOCs) pathophysiology. We evaluated levels of neurofilament light chain (NFL), an axonal injury marker, in patients with unresponsive wakefulness syndrome (UWS) and in the minimally conscious state (MCS) after traumatic brain injury (TBI) and hypoxic-ischemic brain injury (HIBI). (2) Methods: This prospective multicenter blinded study involved 70 patients with prolonged DOC and 70 sex-/age-matched healthy controls. Serum NFL levels were evaluated at 1–3 and 6 months post-injury and compared with those of controls. NFL levels were compared by DOC severity (UWS vs. MCS) and etiology (TBI vs. HIBI). (3) Results: Patients’ serum NFL levels were significantly higher than those of controls at 1–3 and 6 months post-injury (medians, 1729 and 426 vs. 90 pg/mL; both p < 0.0001). NFL levels were higher in patients with UWS than in those in MCS at 1–3 months post-injury (p = 0.008) and in patients with HIBI than in those with TBI at 6 months post-injury (p = 0.037). (4) Conclusions: Patients with prolonged DOC present sustained axonal degeneration that is affected differently over time by brain injury severity and etiology.
Low-Cost Fiber Rope Reinforced Polymer (FRRP) Confinement of Square Columns with Different Corner Radii
Authors: Hussain Qudeer , Ruangrassamee Anat , Tangtermsirikul Somnuk , Joyklad Panuwat , Wijeyewickrema Anil
Published: August 2021

This research investigates the behavior of square concrete columns externally wrapped by low-cost and easily available fiber rope reinforced polymer (FRRP) composites. This study mainly aims to explore the axial stress-strain relationships of FRRP-confined square columns. Another objective is to assess suitable predictive models for the ultimate strength and strain of FRRP-confined square columns. A total of 60 square concrete columns were cast, strengthened, and tested under compression. The parameters were the corner radii of square columns (0, 13, and 26 mm) and different materials of FRRP composites (polyester, hemp, and cotton FRRP composites). The strength and deformability of FRRP-confined specimens were observed to be higher than the unconfined specimens. It was observed that strength gains of FRRP-confined concrete columns and corner radii were directly proportional. The accuracy of ultimate strength and strain models developed for synthetic FRRP-confined square columns was assessed using the test results of this study, showing the need for the development of improved predictive models for FRRP-confined square columns. Newly developed unified models were found to be accurate in predicting the ultimate strength and strain of FRRP-confined columns.
Asymmetric Fiber Supercapacitors Based on a FeC2O4/FeOOH-CNT Hybrid Material
Authors: Adusei Paa Kwasi , Johnson Kevin , Kanakaraj Sathya N. , Zhang Guangqi , Fang Yanbo , Hsieh Yu-Yun , Khosravifar Mahnoosh , Gbordzoe Seyram , Nichols Matthew , Shanov Vesselin
Published: August 2021

The development of new flexible and lightweight electronics has increased the demand for compatible energy storage devices to power them. Carbon nanotube (CNT) fibers have long been known for their ability to be assembled into yarns, offering their integration into electronic devices. They are hindered, however, by their low intrinsic energy storage properties. Herein, we report a novel composite yarn, synthesized through solvothermal processes, that attained energy densities in the range between 0.17 µWh/cm2 and 3.06 µWh/cm2, and power densities between 0.26 mW/cm2 and 0.97 mW/cm2, when assembled in a supercapacitor with a PVDF-EMIMBF4 electrolyte. The created unique composition of iron oxalate + iron hydroxide + CNT as an anode worked well in synergy with the much-studied PANI + CNT cathode, resulting in a highly stable yarn energy storage device that maintained 96.76% of its energy density after 4000 cycles. This device showed no observable change in performance under stress/bend tests which makes it a viable candidate for powering wearable electronics.
The Function of the Mutant p53-R175H in Cancer
Authors: Chiang Yen-Ting , Chien Yi-Chung , Lin Yu-Heng , Wu Hui-Hsuan , Lee Dung-Fang , Yu Yung-Luen
Published: August 2021

Wild-type p53 is known as “the guardian of the genome” because of its function of inducing DNA repair, cell-cycle arrest, and apoptosis, preventing the accumulation of gene mutations. TP53 is highly mutated in cancer cells and most TP53 hotspot mutations are missense mutations. Mutant p53 proteins, encoded by these hotspot mutations, lose canonical wild-type p53 functions and gain functions that promote cancer development, including promoting cancer cell proliferation, migration, invasion, initiation, metabolic reprogramming, angiogenesis, and conferring drug resistance to cancer cells. Among these hotspot mutations, p53-R175H has the highest occurrence. Although losing the transactivating function of the wild-type p53 and prone to aggregation, p53-R175H gains oncogenic functions by interacting with many proteins. In this review, we summarize the gain of functions of p53-R175H in different cancer types, the interacting proteins of p53-R175H, and the downstream signaling pathways affected by p53-R175H to depict a comprehensive role of p53-R175H in cancer development. We also summarize treatments that target p53-R175H, including reactivating p53-R175H with small molecules that can bind to p53-R175H and alter it into a wild-type-like structure, promoting the degradation of p53-R175H by targeting heat-shock proteins that maintain the stability of p53-R175H, and developing immunotherapies that target the p53-R175H–HLA complex presented by tumor cells.
The RNA-Binding Protein ESRP1 Modulates the Expression of RAC1b in Colorectal Cancer Cells
Authors: Manco Marta , Ala Ugo , Cantarella Daniela , Tolosano Emanuela , Medico Enzo , Altruda Fiorella , Fagoonee Sharmila
Published: August 2021

RNA binding proteins are well recognized as critical regulators of tumorigenic processes through their capacity to modulate RNA biogenesis, including alternative splicing, RNA stability and mRNA translation. The RNA binding protein Epithelial Splicing Regulatory Protein 1 (ESRP1) can act as a tumor suppressor or promoter in a cell type- and disease context-dependent manner. We have previously shown that elevated expression of ESRP1 in colorectal cancer cells can drive tumor progression. To gain further insights into the pro-tumorigenic mechanism of action of ESRP1, we performed cDNA microarray analysis on two colorectal cells lines modulated for ESRP1 expression. Intriguingly, RAC1b was highly expressed, both at mRNA and protein levels, in ESRP1-overexpressing cells, while the opposite trend was observed in ESRP1-silenced CRC cells. Moreover, RAC1 and RAC1b mRNA co-immunoprecipitate with ESRP1 protein. Silencing of RAC1b expression significantly reduced the number of soft agar colonies formed by ESRP1-overexpressing cells, suggesting that ESRP1 acted, at least partially, through RAC1b in its tumor-promoting activities in CRC cells. Thus, our data provide molecular cues on targetable candidates in CRC cases with high ESRP1 expression.
Mother-to-Child Transmission of Human T-Cell Leukemia Virus Type 1: Mechanisms and Nutritional Strategies for Prevention
Authors: Itabashi Kazuo , Miyazawa Tokuo
Published: August 2021

Approximately 95% of mother-to-child transmission (MTCT) of human T-cell leukemia virus type-1 (HTLV-1) is derived from prolonged breastfeeding, which is a major cause of adult T-cell leukemia (ATL). Exclusive formula feeding (ExFF) is therefore generally used to prevent MTCT. A recent cohort study revealed that 55% of pregnant carriers chose short-term breastfeeding for ≤3 months in Japan. Our meta-analysis showed that there was no significant increase in the risk of MTCT when breastfeeding was carried out for ≤3 months compared with ExFF (pooled relative risk (RR), 0.72; 95% confidence interval (CI), 0.30–1.77), but there was an almost threefold increase in risk when breastfeeding was carried out for up to 6 months (pooled RR, 2.91; 95% CI, 1.69–5.03). Thus, short-term breastfeeding for ≤3 months may be useful in preventing MTCT. Breastmilk is the best nutritional source for infants, and any approach to minimizing MTCT by avoiding or limiting breastfeeding must be balanced against the impact on the child’s health and mother–child bonding. To minimize the need for nutritional interventions, it is necessary to identify factors that predispose children born to carrier mothers to MTCT and thereby predict MTCT development with a high degree of accuracy.
Clinicopathological Features and Survival Outcomes of Primary Pulmonary Invasive Mucinous Adenocarcinoma
Authors: Gow Chien-Hung , Hsieh Min-Shu , Liu Yi-Nan , Lee Yi-Hsuan , Shih Jin-Yuan
Published: August 2021

Pulmonary invasive mucinous adenocarcinoma (IMA) has unique histological patterns. This study aimed to comprehensively evaluate the clinicopathological features, prognosis, and survival outcomes of IMAs. We retrospectively identified 77 patients with pulmonary IMA and reviewed their clinical and pathological features. Another 520 patients with non-IMA-type ADC were retrieved for comparison with patients with IMA. A new two-tier grading system (high-grade and low-grade IMAs) modified from the pancreatic intraepithelial neoplasia classification system was used for survival analyses. Compared to patients with non-IMA-type ADC, patients with IMA tended to have never smoked (p = 0.01) and had early-stage IMA at initial diagnosis (p < 0.001). For stage I–II diseases, the five-year overall survival (OS) rates were 76% in IMAs and 50% in non-IMA-type ADCs, and a longer OS was observed in patients with IMA (p = 0.002). KRAS mutations were the most commonly detected driver mutations, which occurred in 12 of the 28 (43%) patients. High-grade IMAs were associated with a shorter recurrence-free survival (RFS) for stage I–IIIA diseases (p = 0.010) than low-grade IMAs but not for OS. In conclusion, patients with stage I and II IMA had better OS than those with non-IMA-type ADC. A new two-tier grading system might be useful for predicting RFS in stage I–IIIA IMAs.
The Association of Annexin A1 and Chemosensitivity to Osimertinib in Lung Cancer Cells
Authors: Chuang Min-Chun , Lung Jr-Hau , Chen Yi-Chuan , Lin Yu-Ching , Li Ya-Chin , Hung Ming-Szu
Published: August 2021

Annexin A1 (ANXA1) has been reported to promote tumor growth and resistance to chemotherapy drugs in lung cancer cells. In this study, we focused on the association of ANXA1 and chemosensitivity with a third generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), Osimertinib, in lung cancer cells with EGFR mutations. The overexpression of ANXA1 was observed in the lung cancer cells studied. The downregulation of ANXA1 with small interference RNA (siRNA) decreased the growth of lung cancer cells. In lung cancer cells with EGFR mutations, the knockdown of ANXA1 increased the chemosensitivity to Osimertinib, and decreased the tumorigenesis, invasion and migration of lung cancer cells. Further study showed that the knockdown of ANXA1 inhibited the phosphorylation of EGFR and down-stream Akt pathways and promoted apoptosis in lung cancer cells treated with Osimertinib. A mice xenograft lung cancer model was established in our study and showed that ANXA1 siRNA enhanced the effects of Osimertinib in vivo. Our study results showed that ANXA1 plays critical roles in chemosensitivity to EGFR-TKI in lung cancer cells with the EGFR mutation. Our efforts may be used in the development of lung cancer treatment strategies in the future.
EVI2B Is a New Prognostic Biomarker in Metastatic Melanoma with IFNgamma Associated Immune Infiltration
Authors: Yonekura Satoru , Ueda Kosuke
Published: August 2021

Background: To assess the prognostic role and the antitumor immunological relevance of ecotropic viral integration site 2B (EVI2B) in metastatic melanoma. Methods: In this study, we integrated clinical data, mRNA expression data, and the distribution and fraction of tumor infiltrating lymphocytes (TILs) using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets (GSE65904 and GSE19234). Results: The univariate and multivariate analyses showed that higher gene expression of EVI2B was significantly associated with longer prognoses. The EVI2B-high melanoma tissue had favorable histological parameters such as a brisk global distribution pattern and clustering structure of TILs (i.e., Banfield and Raftery index) with enriched CD8+ T cells over regulatory T cells and increased cytotoxicity scores. In addition, EVI2B expression positively correlated with IFN-γ signature genes (CXCL10, CXCL9, HLA-DRA, IDO1, IFNG, and STAT1) and other various immunomodulatory genes. Conclusion: EVI2B is a novel prognostic biomarker with IFN-γ associated immune infiltration in metastatic melanoma.
Neoadjuvant Modified Short-Course Radiotherapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer
Authors: Doi Hiroshi , Yokoyama Hiroyuki , Beppu Naohito , Fujiwara Masayuki , Harui Shogo , Kakuno Ayako , Yanagi Hidenori , Hishikawa Yoshio , Yamanaka Naoki , Kamikonya Norihiko
Published: August 2021

This study aimed to assess the clinical outcomes and predictive factors of neoadjuvant modified short-course radiotherapy (mSC-RT) for locally advanced rectal cancer (LARC). Data from 97 patients undergoing mSC-RT followed by radical surgery for LARC were retrospectively analyzed. A 2.5 Gy dose twice daily up to a total dose of 25 Gy in 10 fractions was administered through mSC-RT, and this was delivered with oral chemotherapy in 95 (97.9%) patients. Radical surgery was performed 6 (range, 3–13) weeks after mSC-RT. The median follow-up among surviving patients was 43 (8–86) months. All patients completed neoadjuvant radiotherapy with no acute toxicity grade ≥ 3. Three- and five-year local control rates were 96.3% and 96.3%, respectively. Three- and five-year overall survival (OS) rates were 92.7% and 79.8%, respectively. Univariate analyses revealed that poor OS was associated with no concurrent administration of capecitabine, C-reactive-protein-to-albumin ratio ≥ 0.053, carcinoembryonic antigen ≥ 3.4 ng/mL, and neutrophil-to-lymphocyte ratio (NLR) ≥ 1.83 (P = 0.045, 0.001, 0.041, and 0.001, respectively). Multivariate analyses indicated that NLR ≥ 1.83 was independently associated with poor OS (p = 0.018). mSC-RT followed by delayed surgery for LARC was deemed feasible and resulted in good clinical outcomes, whereas poor OS was associated with high NLR.
A Clinical Phase 1B Study of the CD3xCD123 Bispecific Antibody APVO436 in Patients with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
Authors: Uckun Fatih M. , Lin Tara L. , Mims Alice S. , Patel Prapti , Lee Cynthia , Shahidzadeh Anoush , Shami Paul J. , Cull Elizabeth , Cogle Christopher R. , Watts Justin
Published: August 2021

APVO436 is a recombinant T cell-engaging humanized bispecific antibody designed to redirect host T cell cytotoxicity in an MHC-independent manner to CD123-expressing blast cells from patients with hematologic malignancies and has exhibited single-agent anti-leukemia activity in murine xenograft models of acute myeloid leukemia (AML). In this first-in-human (FIH) multicenter phase 1B study, we sought to determine the safety and tolerability of APVO436 in R/R AML/myelodysplastic syndrome (MDS) patients and identify a clinically active recommended phase 2 dose (RP2D) level for its further clinical development. A total of 46 R/R AML/MDS patients who had failed 1–8 prior lines of therapy received APVO436 as weekly intravenous (IV) infusions at 10 different dose levels, ranging from a Minimum Anticipated Biological Effect Level (MABEL) of 0.3 mcg to 60 mcg. APVO436 exhibited a favorable safety profile with acceptable tolerability and manageable drug-related adverse events (AEs), and its maximum tolerated dose (MTD) was not reached at a weekly dose of 60 mcg. The most common APVO436-related AEs were infusion-related reactions (IRR) occurring in 13 (28.3%) patients and cytokine release syndrome (CRS) occurring in 10 (21.7%). The single dose RP2D level was identified as 0.2 mcg/kg. Preliminary efficacy signals were observed in both AML and MDS patients: Prolonged stable disease (SD), partial remissions (PR), and complete remissions (CR) were observed in R/R AML patients as best overall responses to APVO436 at the RP2D level. Three of six evaluable MDS patients had marrow CRs. The safety and preliminary evidence of efficacy of APVO436 in R/R AML and MDS patients warrant further investigation of its clinical impact potential.
Ewing Sarcoma-Derived Extracellular Vesicles Impair Dendritic Cell Maturation and Function
Authors: Gassmann Hendrik , Schneider Kira , Evdokimova Valentina , Ruzanov Peter , Schober Sebastian J. , Xue Busheng , von Heyking Kristina , Thiede Melanie , Richter Guenther H. S. , Pfaffl Michael W. , Noessner Elfriede , Stein Lincoln D. , Sorensen Poul H. , Burdach Stefan E. G. , Thiel Uwe
Published: August 2021

Ewing sarcoma (EwS) is an aggressive pediatric cancer of bone and soft tissues characterized by scant T cell infiltration and predominance of immunosuppressive myeloid cells. Given the important roles of extracellular vesicles (EVs) in cancer-host crosstalk, we hypothesized that EVs secreted by EwS tumors target myeloid cells and promote immunosuppressive phenotypes. Here, EVs were purified from EwS and fibroblast cell lines and exhibited characteristics of small EVs, including size (100–170 nm) and exosome markers CD63, CD81, and TSG101. Treatment of healthy donor-derived CD33+ and CD14+ myeloid cells with EwS EVs but not with fibroblast EVs induced pro-inflammatory cytokine release, including IL-6, IL-8, and TNF. Furthermore, EwS EVs impaired differentiation of these cells towards monocytic-derived dendritic cells (moDCs), as evidenced by reduced expression of co-stimulatory molecules CD80, CD86 and HLA-DR. Whole transcriptome analysis revealed activation of gene expression programs associated with immunosuppressive phenotypes and pro-inflammatory responses. Functionally, moDCs differentiated in the presence of EwS EVs inhibited CD4+ and CD8+ T cell proliferation as well as IFNγ release, while inducing secretion of IL-10 and IL-6. Therefore, EwS EVs may promote a local and systemic pro-inflammatory environment and weaken adaptive immunity by impairing the differentiation and function of antigen-presenting cells.
Electroconvulsive Shock, but Not Transcranial Magnetic Stimulation, Transiently Elevates Cell Proliferation in the Adult Mouse Hippocampus
Authors: Zhang Tian Rui , Guilherme Evelyn , Kesici Aydan , Ash Alyssa M. , Vila-Rodriguez Fidel , Snyder Jason S.
Published: August 2021

Hippocampal plasticity is hypothesized to play a role in the etiopathogenesis of depression and the antidepressant effect of medications. One form of plasticity that is unique to the hippocampus and is involved in depression-related behaviors in animal models is adult neurogenesis. While chronic electroconvulsive shock (ECS) strongly promotes neurogenesis, less is known about its acute effects and little is known about the neurogenic effects of other forms of stimulation therapy, such as repetitive transcranial magnetic stimulation (rTMS). Here, we investigated the time course of acute ECS and rTMS effects on markers of cell proliferation and neurogenesis in the adult hippocampus. Mice were subjected to a single session of ECS, 10 Hz rTMS (10–rTMS), or intermittent theta burst stimulation (iTBS). Mice in both TMS groups were injected with BrdU 2 days before stimulation to label immature cells. One, 3, or 7 days later, hippocampi were collected and immunostained for BrdU + cells, actively proliferating PCNA + cells, and immature DCX + neurons. Following ECS, mice displayed a transient increase in cell proliferation at 3 days post-stimulation. At 7 days post–stimulation there was an elevation in the number of proliferating neuronal precursor cells (PCNA + DCX +), specifically in the ventral hippocampus. iTBS and rTMS did not alter the number of BrdU + cells, proliferating cells, or immature neurons at any of the post-stimulation time points. Our results suggest that neurostimulation treatments exert different effects on hippocampal neurogenesis, where ECS may have greater neurogenic potential than iTBS and 10–rTMS.
Hidradenitis Suppurativa: Where We Are and Where We Are Going
Authors: Scala Emanuele , Cacciapuoti Sara , Garzorz-Stark Natalie , Megna Matteo , Marasca Claudio , Seiringer Peter , Volz Thomas , Eyerich Kilian , Fabbrocini Gabriella
Published: August 2021

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease primarily affecting apocrine gland-rich areas of the body. It is a multifactorial disease in which genetic and environmental factors play a key role. The primary defect in HS pathophysiology involves follicular occlusion of the folliculopilosebaceous unit, followed by follicular rupture and immune responses. Innate pro-inflammatory cytokines (e.g., IL-1β, and TNF-α); mediators of activated T helper (Th)1 and Th17 cells (e.g., IFN-γ, and IL-17); and effector mechanisms of neutrophilic granulocytes, macrophages, and plasma cells are involved. On the other hand, HS lesions contain anti-inflammatory mediators (e.g., IL-10) and show limited activity of Th22 cells. The inflammatory vicious circle finally results in pain, purulence, tissue destruction, and scarring. HS pathogenesis is still enigmatic, and a valid animal model for HS is currently not available. All these aspects represent a challenge for the development of therapeutic approaches, which are urgently needed for this debilitating disease. Available treatments are limited, mostly off-label, and surgical interventions are often required to achieve remission. In this paper, we provide an overview of the current knowledge surrounding HS, including the diagnosis, pathogenesis, treatments, and existing translational studies.
Role of Glycoproteins during Fruit Ripening and Seed Development
Authors: Mendez-Yañez Angela , Ramos Patricio , Morales-Quintana Luis
Published: August 2021

Approximately thirty percent of the proteins synthesized in animal or plant cells travel through the secretory pathway. Seventy to eighty percent of those proteins are glycosylated. Thus, glycosylation is an important protein modification that is related to many cellular processes, such as differentiation, recognition, development, signal transduction, and immune response. Additionally, glycosylation affects protein folding, solubility, stability, biogenesis, and activity. Specifically, in plants, glycosylation has recently been related to the fruit ripening process. This review aims to provide valuable information and discuss the available literature focused on three principal topics: (I) glycosylations as a key posttranslational modification in development in plants, (II) experimental and bioinformatics tools to analyze glycosylations, and (III) a literature review related to glycosylations in fruit ripening. Based on these three topics, we propose that it is necessary to increase the number of studies related to posttranslational modifications, specifically protein glycosylation because the specific role of glycosylation in the posttranslational process and how this process affects normal fruit development and ripening remain unclear to date.
Psychological Distress Symptoms and Resilience Assets in Adolescents in Residential Care
Authors: Lemos Ida , Brás Marta , Lemos Mariana , Nunes Cristina
Published: August 2021

Most studies with institutionalised children and adolescents focus on evaluating the impact of negative life events on emotional development. However, few have investigated the relationship between resilience assets and the teenagers’ psychopathological problems. The purpose of the present study was to investigate differences in psychological distress symptoms and in resilience assets in institutionalised and non-institutionalised adolescents. A total of 266 adolescents aged between 12 and 19 years old took part in the study (60.5% female): 125 lived in residential care and 144 resided with their families. Results found a significant and inverse relation between psychopathology and the perception of individual resilience assets, specifically with self-efficacy and self-awareness in the community sample, and with empathy in the institutionalised sample. Overall, and regardless of the age group, adolescents in residential care tend to perceive themselves as significantly less resilient in perceived self-efficacy and empathy, and they report fewer goals and aspirations for the future. The importance of promoting mental health and resilience assets in adolescents, particularly in those in residential care, is discussed. This can be achieved through early interventions that may prevent emotional suffering and deviant life paths, with transgenerational repercussions.