bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone Marrow-Mesenchymal Stromal Cell Secretome as Conditioned Medium Relieves Experimental Skeletal Muscle Damage Induced by Ex Vivo Eccentric Contraction
Authors: Squecco Roberta , Tani Alessia , Chellini Flaminia , Garella Rachele , Idrizaj Eglantina , Rosa Irene , Zecchi-Orlandini Sandra , Manetti Mirko , Sassoli Chiara
Published: April 2021

Bone marrow-mesenchymal stem/stromal cells (MSCs) may offer promise for skeletal muscle repair/regeneration. Growing evidence suggests that the mechanisms underpinning the beneficial effects of such cells in muscle tissue reside in their ability to secrete bioactive molecules (secretome) with multiple actions. Hence, we examined the effects of MSC secretome as conditioned medium (MSC-CM) on ex vivo murine extensor digitorum longus muscle injured by forced eccentric contraction (EC). By combining morphological (light and confocal laser scanning microscopies) and electrophysiological analyses we demonstrated the capability of MSC-CM to attenuate EC-induced tissue structural damages and sarcolemnic functional properties’ modifications. MSC-CM was effective in protecting myofibers from apoptosis, as suggested by a reduced expression of pro-apoptotic markers, cytochrome c and activated caspase-3, along with an increase in the expression of pro-survival AKT factor. Notably, MSC-CM also reduced the EC-induced tissue redistribution and extension of telocytes/CD34+ stromal cells, distinctive cells proposed to play a “nursing” role for the muscle resident myogenic satellite cells (SCs), regarded as the main players of regeneration. Moreover, it affected SC functionality likely contributing to replenishment of the SC reservoir. This study provides the necessary groundwork for further investigation of the effects of MSC secretome in the setting of skeletal muscle injury and regenerative medicine.
Diet-Related Alterations of Gut Bile Salt Hydrolases Determined Using a Metagenomic Analysis of the Human Microbiome
Authors: Jia Baolei , Park Dongbin , Chun Byung Hee , Hahn Yoonsoo , Jeon Che Ok
Published: April 2021

The metabolism of bile acid by the gut microbiota is associated with host health. Bile salt hydrolases (BSHs) play a crucial role in controlling microbial bile acid metabolism. Herein, we conducted a comparative study to investigate the alterations in the abundance of BSHs using data from three human studies involving dietary interventions, which included a ketogenetic diet (KD) versus baseline diet (BD), overfeeding diet (OFD) versus underfeeding diet, and low-carbohydrate diet (LCD) versus BD. The KD increased BSH abundance compared to the BD, while the OFD and LCD did not change the total abundance of BSHs in the human gut. BSHs can be classified into seven clusters; Clusters 1 to 4 are relatively abundant in the gut. In the KD cohort, the levels of BSHs from Clusters 1, 3, and 4 increased significantly, whereas there was no notable change in the levels of BSHs from the clusters in the OFD and LCD cohorts. Taxonomic studies showed that members of the phyla Bacteroidetes, Firmicutes, and Actinobacteria predominantly produced BSHs. The KD altered the community structure of BSH-active bacteria, causing an increase in the abundance of Bacteroidetes and decrease in Actinobacteria. In contrast, the abundance of BSH-active Bacteroidetes decreased in the OFD cohort, and no significant change was observed in the LCD cohort. These results highlight that dietary patterns are associated with the abundance of BSHs and community structure of BSH-active bacteria and demonstrate the possibility of manipulating the composition of BSHs in the gut through dietary interventions to impact human health.
Role of Rho GTPase Interacting Proteins in Subcellular Compartments of Podocytes
Authors: Asano-Matsuda Kana , Ibrahim Sajida , Takano Tomoko , Matsuda Jun
Published: April 2021

The first step of urine formation is the selective filtration of the plasma into the urinary space at the kidney structure called the glomerulus. The filtration barrier of the glomerulus allows blood cells and large proteins such as albumin to be retained while eliminating the waste products of the body. The filtration barrier consists of three layers: fenestrated endothelial cells, glomerular basement membrane, and podocytes. Podocytes are specialized epithelial cells featured by numerous, actin-based projections called foot processes. Proteins on the foot process membrane are connected to the well-organized intracellular actin network. The Rho family of small GTPases (Rho GTPases) act as intracellular molecular switches. They tightly regulate actin dynamics and subsequent diverse cellular functions such as adhesion, migration, and spreading. Previous studies using podocyte-specific transgenic or knockout animal models have established that Rho GTPases are crucial for the podocyte health and barrier function. However, little attention has been paid regarding subcellular locations where distinct Rho GTPases contribute to specific functions. In the current review, we discuss cellular events involving the prototypical Rho GTPases (RhoA, Rac1, and Cdc42) in podocytes, with particular focus on the subcellular compartments where the signaling events occur. We also provide our synthesized views of the current understanding and propose future research directions.
PET and SPECT Imaging of the EGFR Family (RTK Class I) in Oncology
Authors: Rinne Sara S. , Orlova Anna , Tolmachev Vladimir
Published: April 2021

The human epidermal growth factor receptor family (EGFR-family, other designations: HER family, RTK Class I) is strongly linked to oncogenic transformation. Its members are frequently overexpressed in cancer and have become attractive targets for cancer therapy. To ensure effective patient care, potential responders to HER-targeted therapy need to be identified. Radionuclide molecular imaging can be a key asset for the detection of overexpression of EGFR-family members. It meets the need for repeatable whole-body assessment of the molecular disease profile, solving problems of heterogeneity and expression alterations over time. Tracer development is a multifactorial process. The optimal tracer design depends on the application and the particular challenges of the molecular target (target expression in tumors, endogenous expression in healthy tissue, accessibility). We have herein summarized the recent preclinical and clinical data on agents for Positron Emission Tomography (PET) and Single Photon Emission Tomography (SPECT) imaging of EGFR-family receptors in oncology. Antibody-based tracers are still extensively investigated. However, their dominance starts to be challenged by a number of tracers based on different classes of targeting proteins. Among these, engineered scaffold proteins (ESP) and single domain antibodies (sdAb) show highly encouraging results in clinical studies marking a noticeable trend towards the use of smaller sized agents for HER imaging.
Magnetic Core–Shell Molecularly Imprinted Nano-Conjugates for Extraction of Antazoline and Hydroxyantazoline from Human Plasma—Material Characterization, Theoretical Analysis and Pharmacokinetics
Authors: Giebułtowicz Joanna , Korytowska Natalia , Sobiech Monika , Polak Sebastian , Wiśniowska Barbara , Piotrowski Roman , Kułakowski Piotr , Luliński Piotr
Published: April 2021

The aim of this study was to develop magnetic molecularly imprinted nano-conjugate sorbent for effective dispersive solid phase extraction of antazoline (ANT) and its metabolite, hydroxyantazoline (ANT-OH) in analytical method employing liquid chromatography coupled with mass spectrometry method. The core–shell material was characterized in terms of adsorption properties, morphology and structure. The heterogeneous population of adsorption sites towards ANT-OH was characterized by two Kd and two Bmax values: Kd (1) = 0.319 µg L−1 and Bmax (1) = 0.240 μg g−1, and Kd (2) = 34.6 µg L−1 and Bmax (2) = 5.82 μg g−1. The elemental composition of magnetic sorbent was as follows: 17.55, 37.33, 9.14, 34.94 wt% for Si, C, Fe and O, respectively. The extraction protocol was optimized, and the obtained results were explained using theoretical analysis. Finally, the analytical method was validated prior to application to pharmacokinetic study in which the ANT was administrated intravenously to three healthy volunteers. The results prove that the novel sorbent could be useful in extraction of ANT and ANT-OH from human plasma and that the analytical strategy could be a versatile tool to explain a potential and pharmacological activity of ANT and ANT-OH.
Exosomes from Plasma of Neuroblastoma Patients Contain Doublestranded DNA Reflecting the Mutational Status of Parental Tumor Cells
Authors: Degli Esposti Chiara , Iadarola Barbara , Maestri Simone , Beltrami Cristina , Lavezzari Denise , Morini Martina , De Marco Patrizia , Erminio Giovanni , Garaventa Alberto , Zara Federico , Delledonne Massimo , Ognibene Marzia , Pezzolo Annalisa
Published: April 2021

Neuroblastoma (NB) is an aggressive infancy tumor, leading cause of death among preschool age diseases. Here we focused on characterization of exosomal DNA (exo-DNA) isolated from plasma cell-derived exosomes of neuroblastoma patients, and its potential use for detection of somatic mutations present in the parental tumor cells. Exosomes are small extracellular membrane vesicles secreted by most cells, playing an important role in intercellular communications. Using an enzymatic method, we provided evidence for the presence of double-stranded DNA in the NB exosomes. Moreover, by whole exome sequencing, we demonstrated that NB exo-DNA represents the entire exome and that it carries tumor-specific genetic mutations, including those occurring on known oncogenes and tumor suppressor genes in neuroblastoma (ALK, CHD5, SHANK2, PHOX2B, TERT, FGFR1, and BRAF). NB exo-DNA can be useful to identify variants responsible for acquired resistance, such as mutations of ALK, TP53, and RAS/MAPK genes that appear in relapsed patients. The possibility to isolate and to enrich NB derived exosomes from plasma using surface markers, and the quick and easy extraction of exo-DNA, gives this methodology a translational potential in the clinic. Exo-DNA can be an attractive non-invasive biomarker for NB molecular diagnostic, especially when tissue biopsy cannot be easily available.
Functional Characterization of a Sugar Beet BvbHLH93 Transcription Factor in Salt Stress Tolerance
Authors: Wang Yuguang , Wang Shuang , Tian Ye , Wang Qiuhong , Chen Sixue , Li Hongli , Ma Chunquan , Li Haiying
Published: April 2021

The basic/helix–loop–helix (bHLH) transcription factor (TF) plays an important role for plant growth, development, and stress responses. Previously, proteomics of NaCl treated sugar beet leaves revealed that a bHLH TF, BvbHLH93, was significantly increased under salt stress. The BvbHLH93 protein localized in the nucleus and exhibited activation activity. The expression of BvbHLH93 was significantly up-regulated in roots and leaves by salt stress, and the highest expression level in roots and leaves was 24 and 48 h after salt stress, respectively. Furthermore, constitutive expression of BvbHLH93 conferred enhanced salt tolerance in Arabidopsis, as indicated by longer roots and higher content of chlorophyll than wild type. Additionally, the ectopic expression lines accumulated less Na+ and MDA, but more K+ than the WT. Overexpression of the BvBHLH93 enhanced the activities of antioxidant enzymes by positively regulating the expression of antioxidant genes SOD and POD. Compared to WT, the overexpression plants also had low expression levels of RbohD and RbohF, which are involved in reactive oxygen species (ROS) production. These results suggest that BvbHLH93 plays a key role in enhancing salt stress tolerance by enhancing antioxidant enzymes and decreasing ROS generation.
Biological Properties and Prospects for the Application of Eugenol—A Review
Authors: Ulanowska Magdalena , Olas Beata
Published: April 2021

Eugenol is a phenolic aromatic compound obtained mainly from clove oil. Due to its known antibacterial, antiviral, antifungal, anticancer, anti-inflammatory and antioxidant properties, it has long been used in various areas, such as cosmetology, medicine, and pharmacology. However, high concentrations can be toxic. A dose of 2.5 mg/kg body weight is regarded as safe. This paper reviews the current state of knowledge regarding the activities and application of eugenol and its derivatives and recent research of these compounds. This review is based on information concerning eugenol characteristics and recent research from articles in PubMed. Eugenol remains of great interest to researchers, since its multidirectional action allows it to be a potential component of drugs and other products with therapeutic potential against a range of diseases.
Anticancer Potential of Betulonic Acid Derivatives
Authors: Lombrea Adelina , Scurtu Alexandra Denisa , Avram Stefana , Pavel Ioana Zinuca , Turks Māris , Lugiņina Jevgeņija , Peipiņš Uldis , Dehelean Cristina Adriana , Soica Codruta , Danciu Corina
Published: April 2021

Clinical trials have evidenced that several natural compounds, belonging to the phytochemical classes of alkaloids, terpenes, phenols and flavonoids, are effective for the management of various types of cancer. Latest research has proven that natural products and their semisynthetic variants may serve as a starting point for new drug candidates with a diversity of biological and pharmacological activities, designed to improve bioavailability, overcome cellular resistance, and enhance therapeutic efficacy. This review was designed to bring an update regarding the anticancer potential of betulonic acid and its semisynthetic derivatives. Chemical derivative structures of betulonic acid including amide, thiol, and piperidine groups, exert an amplification of the in vitro anticancer potential of betulonic acid. With the need for more mechanistic and in vivo data, some derivatives of betulonic acids may represent promising anticancer agents.
Bis(trifluoromethylsulfonyl)imide Ionic Liquids Applied for Fine-Tuning the Cure Characteristics and Performance of Natural Rubber Composites
Authors: Sowińska Anna , Maciejewska Magdalena , Grajewska Anna
Published: April 2021

The goal of this work was to apply ionic liquids (ILs) with bis(trifluoromethylsulfonyl)imide anion (TFSI) for fine-tuning the cure characteristics and physico-chemical properties of elastomer composites based on a biodegradable natural rubber (NR) matrix. ILs with TFSI anion and different cations, such as alkylpyrrolidinium, alkylammonium, and alkylsulfonium cations, were applied to increase the efficiency of sulfur vulcanization and to improve the performance of NR composites. Thus, the influence of ILs on the vulcanization of NR compounds, as well as crosslink density and physical properties of NR vulcanizates, including tensile properties, thermal stability, and resistance to thermo-oxidative aging was explored. The activity of ILs seems to be strongly dependent on their cation. Pyrrolidinium and ammonium ILs effectively supported the vulcanization, reducing the optimal vulcanization time and temperature of NR compounds and increasing the crosslink density of the vulcanizates. Consequently, vulcanizates with these ILs exhibited higher tensile strength than the benchmark without IL. On the other hand, sulfonium ILs reduced the torque increment owing to the lower crosslinking degree of elastomer but significantly improved the resistance of NR composites to thermo-oxidation. Thus, TFSI ILs can be used to align the curing behavior and performance of NR composites for particular applications.
Molecular Mechanism of Cannabinoids in Cancer Progression
Authors: Pagano Cristina , Navarra Giovanna , Coppola Laura , Bifulco Maurizio , Laezza Chiara
Published: April 2021

Cannabinoids are a family of heterogeneous compounds that mostly interact with receptors eliciting several physiological effects both in the central and peripheral nervous systems and in peripheral organs. They exert anticancer action by modulating signaling pathways involved in cancer progression; furthermore, the effects induced by their use depend on both the type of tumor and their action on the components of the endocannabinoid system. This review will explore the mechanism of action of the cannabinoids in signaling pathways involved in cancer proliferation, neovascularisation, migration, invasion, metastasis, and tumor angiogenesis.
Inhibition Effect of Chloroquine and Integrin-Linked Kinase Knockdown on Translation in Melanoma Cells
Authors: Gil Dorota , Laidler Piotr , Zarzycka Marta , Dulińska-Litewka Joanna
Published: April 2021

The twofold role of autophagy in cancer is often the therapeutic target. Numerous regulatory pathways are shared between autophagy and other molecular processes needed in tumorigenesis, such as translation or survival signaling. Thus, we have assumed that ILK knockdown should promote autophagy, and used together with chloroquine, an autophagy inhibitor, it could generate a better anticancer effect by dysregulation of common signaling pathways. Expression at the protein level was analyzed using Western Blot; siRNA transfection was done for ILK. Analysis of cell signaling pathways was monitored with phospho-specific antibodies. Melanoma cell proliferation was assessed with the crystal violet test, and migration was evaluated by scratch wound healing assays. Autophagy was monitored by the accumulation of its marker, LC3-II. Our data show that ILK knockdown by siRNA suppresses melanoma cell growth by inducing autophagy through AMPK activation, and simultaneously initiates apoptosis. We demonstrated that combinatorial treatment of melanoma cells with CQ and siILK has a stronger antitumor effect than monotherapy with either of these. It generates the synergistic antitumor effects by the decrease of translation of both global and oncogenic proteins synthesis. In our work, we point to the crosstalk between translation and autophagy regulation.
CD34+ Stromal Cells/Telocytes as a Source of Cancer-Associated Fibroblasts (CAFs) in Invasive Lobular Carcinoma of the Breast
Authors: Díaz-Flores Lucio , Gutiérrez Ricardo , González-Gómez Miriam , García Maria Pino , Díaz-Flores Lucio , Carrasco José Luís , Martín-Vasallo Pablo
Published: April 2021

Several origins have been proposed for cancer-associated fibroblasts (CAFs), including resident CD34+ stromal cells/telocytes (CD34+SCs/TCs). The characteristics and arrangement of mammary CD34+SCs/TCs are well known and invasive lobular carcinoma of the breast (ILC) is one of the few malignant epithelial tumours with stromal cells that can express CD34 or αSMA, which could facilitate tracking these cells. Our objective is to assess whether tissue-resident CD34+SCs/TCs participate in the origin of CAFs in ILCs. For this purpose, using conventional and immunohistochemical procedures, we studied stromal cells in ILCs (n:42) and in normal breasts (n:6, also using electron microscopy). The results showed (a) the presence of anti-CD34+ or anti-αSMA+ stromal cells in varying proportion (from very rare in one of the markers to balanced) around nests/strands of neoplastic cells, (b) a similar arrangement and location of stromal cells in ILC to CD34+SCs/TCs in the normal breast, (c) both types of stromal cells coinciding around the same nest of neoplastic cells and (d) the coexpression of CD34 and αSMA in stromal cells in ILC. In conclusion, our findings support the hypothesis that resident CD34+SCs/TCs participate as an important source of CAFs in ILC. Further studies are required in this regard in other tumours.
X-ray Fluorescence Uptake Measurement of Functionalized Gold Nanoparticles in Tumor Cell Microsamples
Authors: Schmutzler Oliver , Graf Sebastian , Behm Nils , Mansour Wael Y. , Blumendorf Florian , Staufer Theresa , Körnig Christian , Salah Dina , Kang Yanan , Peters Jan N. , Liu Yang , Feliu Neus , Parak Wolfgang J. , Burkhardt Anja , Gargioni Elisabetta , Gennis Sabrina , Chandralingam Sharah , Höeg Finn , Maison Wolfgang , Rothkamm Kai , Schulz Florian , Grüner Florian
Published: April 2021

Quantitative cellular in vitro nanoparticle uptake measurements are possible with a large number of different techniques, however, all have their respective restrictions. Here, we demonstrate the application of synchrotron-based X-ray fluorescence imaging (XFI) on prostate tumor cells, which have internalized differently functionalized gold nanoparticles. Total nanoparticle uptake on the order of a few hundred picograms could be conveniently observed with microsamples consisting of only a few hundreds of cells. A comparison with mass spectroscopy quantification is provided, experimental results are both supported and sensitivity limits of this XFI approach extrapolated by Monte-Carlo simulations, yielding a minimum detectable nanoparticle mass of just 5 pg. This study demonstrates the high sensitivity level of XFI, allowing non-destructive uptake measurements with very small microsamples within just seconds of irradiation time.
MRI-Based Assessment of Masticatory Muscle Changes in TMD Patients after Whiplash Injury
Authors: Lee Yeon-Hee , Lee Kyung Mi , Auh Q-Schick
Published: April 2021

Objective: to investigate the change in volume and signal in the masticatory muscles and temporomandibular joint (TMJ) of patients with temporomandibular disorder (TMD) after whiplash injury, based on magnetic resonance imaging (MRI), and to correlate them with other clinical parameters. Methods: ninety patients (64 women, 26 men; mean age: 39.36 ± 15.40 years), including 45 patients with symptoms of TMD after whiplash injury (wTMD), and 45 age- and sex-matched controls with TMD due to idiopathic causes (iTMD) were included. TMD was diagnosed using the study diagnostic criteria for TMD Axis I, and MRI findings of the TMJ and masticatory muscles were investigated. To evaluate the severity of TMD pain and muscle tenderness, we used a visual analog scale (VAS), palpation index (PI), and neck PI. Results: TMD indexes, including VAS, PI, and neck PI were significantly higher in the wTMD group. In the wTMD group, muscle tenderness was highest in the masseter muscle (71.1%), and muscle tenderness in the temporalis (60.0%), lateral pterygoid muscle (LPM) (22.2%), and medial pterygoid muscle (15.6%) was significantly more frequent than that in the iTMD group (all p < 0.05). The most noticeable structural changes in the masticatory muscles occurred in the LPM with whiplash injury. Volume (57.8% vs. 17.8%) and signal changes (42.2% vs. 15.6%) of LPM were significantly more frequent in the wTMD group than in the iTMD group. The presence of signal changes in the LPM was positively correlated with the increased VAS scores only in the wTMD group (r = 0.346, p = 0.020). The prevalence of anterior disc displacement without reduction (ADDWoR) (53.3% vs. 28.9%) and disc deformity (57.8% vs. 40.0%) were significantly higher in the wTMD group (p < 0.05). The presence of headache, sleep problems, and psychological distress was significantly higher in the wTMD group than in the iTMD group. Conclusion: abnormal MRI findings and their correlations with clinical characteristics of the wTMD group were different from those of the iTMD group. The underlying pathophysiology may differ depending on the cause of TMD, raising the need for a treatment strategy accordingly.
Adjunctive Use of Statins for COVID-19
Authors: Sathekge Mike , Byttebier Geert , De Spiegeleer Bart , Saxberg Bo , Ueckermann Veronica , Belmans Luc , Alexander Myriam , Fedson David
Published: April 2021

The interaction between obesity, cardiometabolic disorders and COVID-19 represents a syndemic that requires both social intervention and a multipharmacological approach [...]
Posterior Shoulder Dislocation with Engaging Reverse Hill–Sachs Lesion: A Retrospective Study of Ten Patients Treated with Arthroscopy or Open Reduction and Stabilization
Authors: Ippolito Giorgio , Zitiello Michele , De Marinis Giancarlo , D’Angelo Fabio , Surace Michele F. , Ronga Mario , Sepe Vincenzo , Garro Luca , Faoro Luca , Ferraro Sergio
Published: April 2021

This study compares two surgical techniques used to treat patients with posterior shoulder dislocation with an engaging reverse Hill–Sachs lesion. We assessed ten patients who were treated at the Surgical Orthopedic and Traumatological Institute (ICOT) of Latina and the Clinic of Orthopedic and Traumatological Surgery of the ASST Sette Laghi of Varese between 2016 and 2019. The patients were divided into two groups: the first comprising six patients who underwent the open surgery McLaughlin procedure as modified by Neer, the second including four patients who underwent the arthroscopic McLaughlin procedure. All patients received postoperative rehabilitation to achieve the best possible functional recovery of the affected shoulder. We then assessed the shoulder range of motion, the pain level, and the impact on quality of life with four tests: the Constant Scale, the Simple Shoulder Test (SST), the OXFORD Scale, and The University of California—Los Angeles (UCLA) Shoulder Scale. The mean scores of the first group were: 81.3 ± 9.8 SD (Constant Scale), 10.8 ± 1.06 SD (SST), 42.5 ± 5.4 SD (Oxford Scale), 30.8 ± 3.02 SD (UCLA Shoulder Scale); we calculated the following mean scores in the second group: 80.25 ± 4.1 SD (Constant Scale), 11.5 ± 0.8 SD (SST), 42 ± 4.06 SD (Oxford Scale), 32 ± 2.9 SD (UCLA Shoulder Scale). We found no significant differences between the two groups.
MRI-Based Radiomics and Radiogenomics in the Management of Low-Grade Gliomas: Evaluating the Evidence for a Paradigm Shift
Authors: Habib Ahmed , Jovanovich Nicolina , Hoppe Meagan , Ak Murat , Mamindla Priyadarshini , R. Colen Rivka , Zinn Pascal O.
Published: April 2021

Low-grade gliomas (LGGs) are tumors that affect mostly adults. These neoplasms are comprised mainly of oligodendrogliomas and diffuse astrocytomas. LGGs remain vexing to current management and therapeutic modalities although they exhibit more favorable survival rates compared with high-grade gliomas (HGGs). The specific genetic subtypes that these tumors exhibit result in variable clinical courses and the need to involve multidisciplinary teams of neurologists, epileptologists, neurooncologists and neurosurgeons. Currently, the diagnosis of an LGG pivots mainly around the preliminary radiological findings and the subsequent definitive surgical diagnosis (via surgical sampling). The introduction of radiomics as a high throughput quantitative imaging technique that allows for improved diagnostic, prognostic and predictive indices has created more interest for such techniques in cancer research and especially in neurooncology (MRI-based classification of LGGs, predicting Isocitrate dehydrogenase (IDH) and Telomerase reverse transcriptase (TERT) promoter mutations and predicting LGG associated seizures). Radiogenomics refers to the linkage of imaging findings with the tumor/tissue genomics. Numerous applications of radiomics and radiogenomics have been described in the clinical context and management of LGGs. In this review, we describe the recently published studies discussing the potential application of radiomics and radiogenomics in LGGs. We also highlight the potential pitfalls of the above-mentioned high throughput computerized techniques and, most excitingly, explore the use of machine learning artificial intelligence technologies as standalone and adjunct imaging tools en route to enhance a personalized MRI-based tumor diagnosis and management plan design.
How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based Approaches
Authors: Ghidini Michele , Petrillo Angelica , Botticelli Andrea , Trapani Dario , Parisi Alessandro , La Salvia Anna , Sajjadi Elham , Piciotti Roberto , Fusco Nicola , Khakoo Shelize
Published: April 2021

Despite extensive research efforts, advanced gastric cancer still has a dismal prognosis with conventional treatment options. Immune checkpoint inhibitors have revolutionized the treatment landscape for many solid tumors. Amongst gastric cancer subtypes, tumors with microsatellite instability and Epstein Barr Virus positive tumors provide the strongest rationale for responding to immunotherapy. Various predictive biomarkers such as mismatch repair status, programmed death ligand 1 expression, tumor mutational burden, assessment of tumor infiltrating lymphocytes and circulating biomarkers have been evaluated. However, results have been inconsistent due to different methodologies and thresholds used. Clinical implementation therefore remains a challenge. The role of immune checkpoint inhibitors in gastric cancer is emerging with data from monotherapy in the heavily pre-treated population already available and studies in earlier disease settings with different combinatorial approaches in progress. Immune checkpoint inhibitor combinations with chemotherapy (CT), anti-angiogenics, tyrosine kinase inhibitors, anti-Her2 directed therapy, poly (ADP-ribose) polymerase inhibitors or dual checkpoint inhibitor strategies are being explored. Moreover, novel strategies including vaccines and CAR T cell therapy are also being trialed. Here we provide an update on predictive biomarkers for response to immunotherapy with an overview of their strengths and limitations. We discuss clinical trials that have been reported and trials in progress whilst providing an account of future steps needed to improve outcome in this lethal disease.
Working towards an ERAS Protocol for Pancreatic Transplantation: A Narrative Review
Authors: Elango Madhivanan , Papalois Vassilios
Published: April 2021

Enhanced recovery after surgery (ERAS) initially started in the early 2000s as a series of protocols to improve the perioperative care of surgical patients. They aimed to increase patient satisfaction while reducing postoperative complications and postoperative length of stay. Despite these protocols being widely adopted in many fields of surgery, they are yet to be adopted in pancreatic transplantation: a high-risk surgery with often prolonged length of postoperative stay and high rate of complications. We have analysed the literature in pancreatic and transplantation surgery to identify the necessary preoperative, intra-operative and postoperative components of an ERAS pathway in pancreas transplantation.
Evaluation of Late Postural Complications in Breast Cancer Patients Undergoing Breast-Conserving Therapy in Relation to the Type of Axillary Intervention-Cross-Sectional Study
Authors: Głowacka-Mrotek Iwona , Tarkowska Magdalena , Leksowski Lukasz , Nowikiewicz Tomasz , Zegarski Wojciech
Published: April 2021

Purpose: The aim of the study was to evaluate posture in patients undergoing breast-conserving therapy (BCT) in relation to the type of surgical intervention to the axilla. Methods: The study was conducted on patients who had undergone breast-conserving surgical treatment for breast cancer 5–6 years earlier. In 54 patients, BCT+ALND (axillary lymph node dissection) was performed, while 63 patients were subjected to BCT+SLND (sentinel lymph node dissection). The control group consisted of 54 females. The study was conducted using digital postural assessment. Results: No statistically significant differences were observed with respect to the parameters between the BCT+SLNB and BCT+ALND groups (p > 0.05). However, the differences were highly significant between the CG (control group) and the studied groups (BCT+ALND, BCT+SLNB) for the following parameters: BETA angle of thoracolumbar spine inclination (p = 0.002), GAMMA angle of thoracic spine inclination (p = 0.0044), TKA (thoracic kyphosis angle) (p < 0.0001) and shoulder level inclination (p = 0.0004). The BCT+ALND patients were characterized by higher dependency of raised shoulder (p = 0.0028) and inferior angle of the scapula (p = 0.00018) on the operated side compared to BCT+SLNB patients. Conclusions: Postural imbalance occurs independent of the type of axillary intervention. Disturbances within the upper torso (abnormal position of shoulders and inferior angles of scapulae) are more pronounced in patients after ALND.
Sex-Related Differences in Drugs with Anti-Inflammatory Properties
Authors: Farkouh André , Baumgärtel Christoph , Gottardi Roman , Hemetsberger Margit , Czejka Martin , Kautzky-Willer Alexandra
Published: April 2021

There is increasing evidence of sex differences in the action of anti-inflammatory drugs, with women being at significantly higher risk of adverse effects. Nevertheless, clinicians’ awareness of the implications of these sex differences on dosing and adverse event monitoring in routine practice is still in need of improvement. We reviewed the literature evaluating sex differences in terms of pharmacokinetics and pharmacodynamics of anti-inflammatory drugs. The anti-thrombotic activity of selective and non-selective COX-inhibitors tends to be stronger in men than women. Side effect profiles differ with regards to gastro-intestinal, renal and hepatic complications. Glucocorticosteroids were found to be more effective in men; women were more sensitive to corticosteroids when their oestradiol levels were high, a finding important for women taking hormonal contraception. TNF-alpha inhibitors have a longer half-life in men, leading to stronger immunosuppression and this a higher incidence of infections as side effects. Although research on sex differences in the effectiveness and safety of drugs is increasing, findings are often anecdotal and controversial. There is no systematic sex-differentiated reporting from clinical trials, and women are often under-represented. As personalized medicine is gaining in importance, sex, and gender aspects need to become integral parts of future research and policy making.
A Comparative Analysis for 2D Object Recognition: A Case Study with Tactode Puzzle-Like Tiles
Authors: Silva Daniel , Sousa Armando , Costa Valter
Published: April 2021

Object recognition represents the ability of a system to identify objects, humans or animals in images. Within this domain, this work presents a comparative analysis among different classification methods aiming at Tactode tile recognition. The covered methods include: (i) machine learning with HOG and SVM; (ii) deep learning with CNNs such as VGG16, VGG19, ResNet152, MobileNetV2, SSD and YOLOv4; (iii) matching of handcrafted features with SIFT, SURF, BRISK and ORB; and (iv) template matching. A dataset was created to train learning-based methods (i and ii), and with respect to the other methods (iii and iv), a template dataset was used. To evaluate the performance of the recognition methods, two test datasets were built: tactode_small and tactode_big, which consisted of 288 and 12,000 images, holding 2784 and 96,000 regions of interest for classification, respectively. SSD and YOLOv4 were the worst methods for their domain, whereas ResNet152 and MobileNetV2 showed that they were strong recognition methods. SURF, ORB and BRISK demonstrated great recognition performance, while SIFT was the worst of this type of method. The methods based on template matching attained reasonable recognition results, falling behind most other methods. The top three methods of this study were: VGG16 with an accuracy of 99.96% and 99.95% for tactode_small and tactode_big, respectively; VGG19 with an accuracy of 99.96% and 99.68% for the same datasets; and HOG and SVM, which reached an accuracy of 99.93% for tactode_small and 99.86% for tactode_big, while at the same time presenting average execution times of 0.323 s and 0.232 s on the respective datasets, being the fastest method overall. This work demonstrated that VGG16 was the best choice for this case study, since it minimised the misclassifications for both test datasets.
Transfer Learning in Magnetic Resonance Brain Imaging: A Systematic Review
Authors: Valverde Juan Miguel , Imani Vandad , Abdollahzadeh Ali , De Feo Riccardo , Prakash Mithilesh , Ciszek Robert , Tohka Jussi
Published: April 2021

(1) Background: Transfer learning refers to machine learning techniques that focus on acquiring knowledge from related tasks to improve generalization in the tasks of interest. In magnetic resonance imaging (MRI), transfer learning is important for developing strategies that address the variation in MR images from different imaging protocols or scanners. Additionally, transfer learning is beneficial for reutilizing machine learning models that were trained to solve different (but related) tasks to the task of interest. The aim of this review is to identify research directions, gaps in knowledge, applications, and widely used strategies among the transfer learning approaches applied in MR brain imaging; (2) Methods: We performed a systematic literature search for articles that applied transfer learning to MR brain imaging tasks. We screened 433 studies for their relevance, and we categorized and extracted relevant information, including task type, application, availability of labels, and machine learning methods. Furthermore, we closely examined brain MRI-specific transfer learning approaches and other methods that tackled issues relevant to medical imaging, including privacy, unseen target domains, and unlabeled data; (3) Results: We found 129 articles that applied transfer learning to MR brain imaging tasks. The most frequent applications were dementia-related classification tasks and brain tumor segmentation. The majority of articles utilized transfer learning techniques based on convolutional neural networks (CNNs). Only a few approaches utilized clearly brain MRI-specific methodology, and considered privacy issues, unseen target domains, or unlabeled data. We proposed a new categorization to group specific, widely-used approaches such as pretraining and fine-tuning CNNs; (4) Discussion: There is increasing interest in transfer learning for brain MRI. Well-known public datasets have clearly contributed to the popularity of Alzheimer’s diagnostics/prognostics and tumor segmentation as applications. Likewise, the availability of pretrained CNNs has promoted their utilization. Finally, the majority of the surveyed studies did not examine in detail the interpretation of their strategies after applying transfer learning, and did not compare their approach with other transfer learning approaches.
Destabilisation and Accelerated Roll-Back of a Mixed Sediment Barrier in Response to a Managed Breach
Authors: Dornbusch Uwe
Published: April 2021

Sea level rise increases the pressure on many coastlines to retreat landwards which will lead to coastlines previously held in position through management, being allowed to retreat where this is no longer affordable or sustainable. Barrier beaches have historically rolled back in response to different hydrodynamic events and sea level rise, but very little is known as to how quickly and how far roll-back is going to occur once management has ceased. Data from more than 40 topographical surveys collected over 7 years along the 1.5 km long, almost swash-aligned shingle barrier at Medmerry (southern England) are used together with hydrodynamic data in a wide-ranging assessment of barrier roll-back. This study shows that roll-back is progressing through time along the barrier in downdrift direction in response to a gradual reduction in cross-sectional area through longshore transport. The Barrier Inertia concept provides a practical means to assess stability/instability for events experienced, but also a tool to assess the short- to medium term risk to the coast downdrift of the immediate study area where flood risk still needs to be managed. Roll-back is influenced particularly by the creation of an artificial tidal breach and removal of its sediment, the elevation of the underlying marsh and clay sediments, the number and severity of storms experienced and the presence of legacy groynes; roll-back has exceeded modelled predictions and expert judgement by an order of magnitude.
Risk Factors and Outcomes of Non-albicans Candida Bloodstream Infection in Patients with Candidemia at Siriraj Hospital—Thailand’s Largest National Tertiary Referral Hospital
Authors: Ngamchokwathana Chaiyapong , Chongtrakool Piriyaporn , Waesamaae Amiroh , Chayakulkeeree Methee
Published: April 2021

This study aimed to investigate the risk factors for and the outcomes of patients with candidemia caused by non-albicans Candida. Candidemia patients treated at Siriraj Hospital (Bangkok, Thailand) during January 2016 to December 2017 were enrolled. A total of 156 patients (mean age: 65 years, 56.4% male) were included. The most prevalent underlying conditions were diabetes (32.1%), chronic cardiac disease (28.2%), chronic kidney disease (26.9%), and hematologic malignancies (21.2%). Candida species isolated from patient blood were C. tropicalis (49.4%), C. albicans (28.8%), C. glabrata (16.7%), and C. parapsilosis (5.1%). Fluconazole resistance was significantly increased in C. tropicalis (37.8%). No independent risk factors were associated with patients with non-albicans Candida candidemia compared to those with C. albicans candidemia. There was no significant difference in mortality between patients with non-albicans Candida candidemia and patients with C. albicans candidemia (OR: 1.35, 95% CI: 0.64–2.85). When compared with C. albicans candidemia, multivariate analysis revealed chronic liver disease (OR: 11.39, 95% CI: 1.38–94.02), neutropenia (OR: 4.31, 95% CI: 1.34–13.87), and male gender (OR: 2.34, 95% CI: 1.04–5.29) to be independent risk factors for C. tropicalis candidemia. The observed high resistance of C. tropicalis to fluconazole indicates that fluconazole should not be used for empirical antifungal treatment in these patients.
Response Predictivity to Neoadjuvant Therapies in Breast Cancer: A Qualitative Analysis of Background Parenchymal Enhancement in DCE-MRI
Authors: La Forgia Daniele , Vestito Angela , Lasciarrea Maurilia , Comes Maria Colomba , Diotaiuti Sergio , Giotta Francesco , Latorre Agnese , Lorusso Vito , Massafra Raffaella , Palmiotti Gennaro , Rinaldi Lucia , Signorile Rahel , Gatta Gianluca , Fanizzi Annarita
Published: April 2021

Background: For assessing the predictability of oncology neoadjuvant therapy results, the background parenchymal enhancement (BPE) parameter in breast magnetic resonance imaging (MRI) has acquired increased interest. This work aims to qualitatively evaluate the BPE parameter as a potential predictive marker for neoadjuvant therapy. Method: Three radiologists examined, in triple-blind modality, the MRIs of 80 patients performed before the start of chemotherapy, after three months from the start of treatment, and after surgery. They identified the portion of fibroglandular tissue (FGT) and BPE of the contralateral breast to the tumor in the basal control pre-treatment (baseline). Results: We observed a reduction of BPE classes in serial MRI checks performed during neoadjuvant therapy, as compared to baseline pre-treatment conditions, in 61.3% of patients in the intermediate step, and in 86.7% of patients in the final step. BPE reduction was significantly associated with sequential anthracyclines/taxane administration in the first cycle of neoadjuvant therapy compared to anti-HER2 containing therapies. The therapy response was also significantly related to tumor size. There were no associations with menopausal status, fibroglandular tissue (FGT) amount, age, BPE baseline, BPE in intermediate, and in the final MRI step. Conclusions: The measured variability of this parameter during therapy could predict therapy effectiveness in early stages, improving decision-making in the perspective of personalized medicine. Our preliminary results suggest that BPE may represent a predictive factor in response to neoadjuvant therapy in breast cancer, warranting future investigations in conjunction with radiomics.
State-of-the-Art Analysis of Intrapreneurship: A Review of the Theoretical Construct and Its Bibliometrics
Authors: Galván-Vela Esthela , Arango Herrera Eduardo , Sorzano Rodríguez Deisy Milena , Ravina-Ripoll Rafael
Published: April 2021

Business complexity demands that companies look for alternative ways to ensure their survival. Thus, one means to generate a competitive position, growth and development is intrapreneurship, which refers to entrepreneurship that arises within established organizations. However, current studies of the phenomenon are sometimes limited to contributions that lack substantive theory. Given this problem, the objective of this study was to determine the current state of the art of intrapreneurship based on a documentary analysis. Similarly, a bibliometric analysis was carried out that evaluated the existing publications. A total of 133 documents related to the term were found. After analyzing these documents, we concluded that new studies on the matter need to be developed. Therefore, a future agenda is proposed and the implications of this phenomenon on the performance of current companies are discussed.
Comparing CEO Compensation Effects of Public and Private Acquisitions
Authors: Brander James A. , Egan Edward J. , Endl Sophie
Published: April 2021

We estimate the effect of acquisition performance and acquisition activity on CEO compensation for the full set of CEOs of large public U.S. corporations in the Execucomp database over the period 1992–2016. Most previous work has focused on publicly traded acquisition targets. We focus on the comparison between public and private targets, showing significant differences between the two. One primary finding, based on panel data regressions (using both fixed and random effects) is that the performance of private acquisitions, as measured by abnormal announcement returns, has a statistically significant positive effect of plausible economic magnitude on CEO compensation. Public acquisitions exhibit a smaller positive effect that is statistically insignificant. For both, acquisition activity (number of acquisitions) has a statistically significant positive effect on compensation. Our main results suggest that agency considerations are important for both public and private acquisitions but are more important for public acquisitions.
Persistent Food Shortages in Venetian Crete: A First Hypothesis
Authors: Sotiropoulou Irene
Published: April 2021

This paper examines the persistent food shortages in the island of Crete under Venetian rule (1204–1669) through the prism of the monetary system of Venetian territories and in combination with the other economic policies of the Venetian empire. From the available sources and analysis, it seems that the policies of Venice which prioritised the food security of the metropolis, the financial support to the elites, and the elite-favouring monetary and taxation system were contradictory and self-defeating. In particular, the monetary structure of the colonial economy and the taxation system seem to have been forcing both Cretans and Venetian settlers to produce wine for export instead of grain despite the repeated food shortages. The parallel circulation of various high-value (white money) and low-value (black money) currencies in the same economy and the insistence of the Venetian administration to receive taxes in white money seems to have been consistently undermining the food security policy adopted by the same authorities. The paper contributes to the discussion of how parallel currencies can stabilise an economy or can create structural destabilisation propensities, depending on coeval economic structures that usually go unexamined when we examine monetary instruments.