bluuebunny/crossref_metadata_2025 huggingface dataset:
Hormonal Regulation of Oligodendrogenesis I: Effects across the Lifespan
Authors: Long Kimberly L. P. , Breton Jocelyn M. , Barraza Matthew K. , Perloff Olga S. , Kaufer Daniela
Published: February 2021

The brain’s capacity to respond to changing environments via hormonal signaling is critical to fine-tuned function. An emerging body of literature highlights a role for myelin plasticity as a prominent type of experience-dependent plasticity in the adult brain. Myelin plasticity is driven by oligodendrocytes (OLs) and their precursor cells (OPCs). OPC differentiation regulates the trajectory of myelin production throughout development, and importantly, OPCs maintain the ability to proliferate and generate new OLs throughout adulthood. The process of oligodendrogenesis, the creation of new OLs, can be dramatically influenced during early development and in adulthood by internal and environmental conditions such as hormones. Here, we review the current literature describing hormonal regulation of oligodendrogenesis within physiological conditions, focusing on several classes of hormones: steroid, peptide, and thyroid hormones. We discuss hormonal regulation at each stage of oligodendrogenesis and describe mechanisms of action, where known. Overall, the majority of hormones enhance oligodendrogenesis, increasing OPC differentiation and inducing maturation and myelin production in OLs. The mechanisms underlying these processes vary for each hormone but may ultimately converge upon common signaling pathways, mediated by specific receptors expressed across the OL lineage. However, not all of the mechanisms have been fully elucidated, and here, we note the remaining gaps in the literature, including the complex interactions between hormonal systems and with the immune system. In the companion manuscript in this issue, we discuss the implications of hormonal regulation of oligodendrogenesis for neurological and psychiatric disorders characterized by white matter loss. Ultimately, a better understanding of the fundamental mechanisms of hormonal regulation of oligodendrogenesis across the entire lifespan, especially in vivo, will progress both basic and translational research.
Implications of Breast Cancer Chemotherapy-Induced Inflammation on the Gut, Liver, and Central Nervous System
Authors: Brown Taurean , Sykes DeLawrence , Allen Antiño R.
Published: February 2021

Breast Cancer is still one of the most common cancers today; however, with advancements in diagnostic and treatment methods, the mortality and survivorship of patients continues to decrease and increase, respectively. Commonly used treatments today consist of drug combinations, such as doxorubicin and cyclophosphamide; docetaxel, doxorubicin, and cyclophosphamide; or doxorubicin, cyclophosphamide, and paclitaxel. Although these combinations are effective at destroying cancer cells, there is still much to be understood about the effects that chemotherapy can have on normal organ systems such as the nervous system, gastrointestinal tract, and the liver. Patients can experience symptoms of cognitive impairments or “chemobrain”, such as difficulty in concentrating, memory recollection, and processing speed. They may also experience gastrointestinal (GI) distress symptoms such as diarrhea and vomiting, as well as hepatotoxicity and long term liver damage. Chemotherapy treatment has also been shown to induce peripheral neuropathy resulting in numbing, pain, and tingling sensations in the extremities of patients. Interestingly, researchers have discovered that this array of symptoms that cancer patients experience are interconnected and mediated by the inflammatory response.
A Cellulose Paper-Based Fluorescent Lateral Flow Immunoassay for the Quantitative Detection of Cardiac Troponin I
Authors: Natarajan Satheesh , Jayaraj Joseph , Prazeres Duarte Miguel F.
Published: February 2021

This paper presents a lateral flow assay (LFA) for the quantitative, fluorescence-based detection of the cardiac biomarker troponin I (cTnI) that features an analytical strip made of cellulose filter paper. The results show that the wicking and test time are comparable to those obtained with conventional nitrocellulose (NC)-based LFAs. Further, the cellulose paper provides an excellent background with no auto-fluorescence that is very adequate in detecting fluorescent lines. While fluorescence that was generated with cellulose strips was lower when compared to that generated in NC strips, signals could be improved by layering carbon nanofibers (CNF) on the cellulose. A nonlinear behavior of the concentration–response relationship was observed for the LFA architectures with NC, cellulose, and cellulose-CNF in the 0 to 200 ng/mL cTnI concentration range. The measurements were consistent and characterized by coefficients of variation lower than 2.5%. Detection and quantitation limits that were in the range 1.28–1.40 ng/mL and 2.10–2.75 ng/mL were obtained for LFA with cellulose and cellulose CNF strips that are equivalent to the limits obtained with the standard NC LFA. Overall, we showed that commercially available filter paper can be used in the analytical strip of LFA.
Long-Lasting Cognitive Abnormalities after COVID-19
Authors: Ferrucci Roberta , Dini Michelangelo , Groppo Elisabetta , Rosci Chiara , Reitano Maria Rita , Bai Francesca , Poletti Barbara , Brugnera Agostino , Silani Vincenzo , D’Arminio Monforte Antonella , Priori Alberto
Published: February 2021

Considering the mechanisms capable of causing brain alterations in COVID-19, we aimed to study the occurrence of cognitive abnormalities in the months following hospital discharge. We recruited 38 (aged 22–74 years; 27 males) patients hospitalized for complications of SARS-CoV-2 infection in nonintensive COVID units. Participants underwent neuropsychological testing about 5 months after hospital discharge. Of all patients, 42.1% had processing speed deficits, while 26.3% showed delayed verbal recall deficits. Twenty-one percent presented with deficits in both processing speed and verbal memory. Bivariate analysis revealed a positive correlation between the lowest arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2) (P/F) ratio during hospitalization and verbal memory consolidation performance (SRT-LTS score, r = 0.404, p = 0.027), as well as a positive correlation between SpO2 levels upon hospital arrival and delayed verbal recall performance (SRT-D score, rs = 0.373, p = 0.042). Acute respiratory distress syndrome (ARDS) during hospitalization was associated with worse verbal memory performance (ARDS vs. no ARDS: SRT-LTS mean score = 30.63 ± 13.33 vs. 44.50 ± 13.16, p = 0.007; SRT-D mean score = 5.95 ± 2.56 vs. 8.10 ± 2.62, p = 0.029). Cognitive abnormalities can frequently be found in COVID-19 patients 5 months after hospital discharge. Increased fatigability, deficits of concentration and memory, and overall decreased cognitive speed months after hospital discharge can interfere with work and daily activities.
Telehealth in Neurodegenerative Diseases: Opportunities and Challenges for Patients and Physicians
Authors: De Marchi Fabiola , Contaldi Elena , Magistrelli Luca , Cantello Roberto , Comi Cristoforo , Mazzini Letizia
Published: February 2021

Telehealth, by definition, is distributing health-related services while using electronic technologies. This narrative Review describes the technological health services (telemedicine and telemonitoring) for delivering care in neurodegenerative diseases, Alzheimer’s disease, Parkinson’s Disease, and amyotrophic lateral Sclerosis, among others. This paper aims to illustrate this approach’s primary experience and application, highlighting the strengths and weaknesses, with the goal of understanding which could be the most useful application for each one, in order to facilitate telehealth improvement and use in standard clinical practice. We also described the potential role of the COVID-19 pandemic to speed up this service’s use, avoiding a sudden interruption of medical care.
Diagnostic, Surgical, and Technical Considerations for Lumbar Interbody Fusion in Patients with Osteopenia and Osteoporosis: A Systematic Review
Authors: Soldozy Sauson , Montgomery Samuel R. , Sarathy Danyas , Young Steven , Skaff Anthony , Desai Bhargav , Sokolowski Jennifer D. , Sandhu Faheem A. , Voyadzis Jean-Marc , Yağmurlu Kaan , Buchholz Avery L. , Shaffrey Mark E. , Syed Hasan R.
Published: February 2021

Objective: Osteoporosis is increasing in incidence as the ageing population continues to grow. Decreased bone mineral density poses a challenge for the spine surgeon. In patients requiring lumbar interbody fusion, differences in diagnostics and surgical approaches may be warranted. In this systematic review, the authors examine studies performing lumbar interbody fusion in patients with osteopenia or osteoporosis and suggest avenues for future study. Methods: A systematic literature review of the PubMed and MEDLINE databases was performed for studies published between 1986 and 2020. Studies evaluating diagnostics, surgical approaches, and other technical considerations were included. Results: A total of 13 articles were ultimately selected for qualitative analysis. This includes studies demonstrating the utility of Hounsfield units in diagnosis, a survey of surgical approaches, as well as exploring the use of vertebral augmentation and cortical bone screw trajectory. Conclusions: This systematic review provides a summary of preliminary findings with respect to the use of Hounsfield units as a diagnostic tool, the benefit or lack thereof with respect to minimally invasive approaches, and the question of whether or not cement augmentation or cortical bone trajectory confers benefit in osteoporotic patients undergoing lumbar interbody fusion. While the findings of these studies are promising, the current state of the literature is limited in scope and, for this reason, definitive conclusions cannot be drawn from these data. The authors highlight gaps in the literature and the need for further exploration and study of lumbar interbody fusion in the osteoporotic spine.
Numerical Analysis of Bearing Capacity of a Ring Footing on Geogrid Reinforced Sand
Authors: Hosamo Haidar , Sliteen Iyad , Ding Songxiong
Published: February 2021

A ring footing is found to be of practical importance in supporting symmetrical constructions for example silos, oil storage container etc. In the present paper, numerical analysis was carried out with explicit code FLAC3D 7.0 to investigate bearing capacity of a ring footing on geogrid reinforced sand. Effects of the ratio n of its inner/outer diameter (Di/D) of a ring footing, an optimum depth to lay the geogrid layer were examined. It was found that an intersection zone was developed in soil under inner-side (aisle) of ring footing, contributing to its bearing capacity. Substantial increase of bearing capacities could be realized if ratio n of a ring footing was around 0.6. Numerical results also showed that, bearing capacity of a ring footing could increase significantly if a single-layer geogrid was laid at a proper depth under the footing. Similar contribution was found if a double-layer geogrid was implemented. However, such increases appeared to be rather limited if a triple-layer geogrid or a four-layer geogrid was used. A double-layer geogrid was recommended to increase the bearing capacity of a ring footing; the depth to lay this double-layer geogrid was also discussed.
Anisotropic Magnetism in Gradient Porous Carbon Composite Aerogels
Authors: Bahner Jochen , Hug Nicolas , Polarz Sebastian
Published: February 2021

Porosity is of high importance for functional materials, as it allows for high surface areas and the accessibility of materials. While the fundamental interplay between different pore sizes and functionalities is quite well understood, few studies on gradually changing properties in a material exist. To date, only a few examples of such materials have been synthesized successfully. Herein, we present a facile method for synthesizing macroscopic carbon aerogels with locally changing pore sizes and functionalities. We used ultracentrifugation to fractionate differently functionalized and sized polystyrene nanoparticles. The assembly into gradient templates was conducted in a resorcinol–formaldehyde (RF) sol, which acted as a liquid phase and carbon precursor. We show that the modification of nanoparticles and a sol–gel precursor is a powerful tool for introducing dopants (sulfur and phosphorous) and metal nanoparticles (e.g., Ni) into gradient porous carbons formed during the carbonization of the RF sol. Understanding the underlying interactions between particles and precursors will lead to a plethora of possibilities in the material design of complex functionally graded materials. We showed this by exchanging parts of the template with magnetite–polystyrene composites as templating nanoparticles. This led to the incorporation of magnetite nanoparticles in the formed gradient porous carbon aerogels. Finally, gradually increasing concentrations of magnetite were obtained, ultimately leading to macroscopic carbon aerogels with locally changing magnetic properties, while the graded porosity was maintained.
Pancreatic Tumorigenesis: Oncogenic KRAS and the Vulnerability of the Pancreas to Obesity
Authors: Luo Yongde , Li Xiaokun , Ma Jianjia , Abbruzzese James L. , Lu Weiqin
Published: February 2021

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies and KRAS (Kirsten rat sarcoma 2 viral oncogene homolog) mutations have been considered a critical driver of PDAC initiation and progression. However, the effects of mutant KRAS alone do not recapitulate the full spectrum of pancreatic pathologies associated with PDAC development in adults. Historically, mutant KRAS was regarded as constitutively active; however, recent studies have shown that endogenous levels of mutant KRAS are not constitutively fully active and its activity is still subject to up-regulation by upstream stimuli. Obesity is a metabolic disease that induces a chronic, low-grade inflammation called meta-inflammation and has long been recognized clinically as a major modifiable risk factor for pancreatic cancer. It has been shown in different animal models that obesogenic high-fat diet (HFD) and pancreatic inflammation promote the rapid development of mutant KRAS-mediated PDAC with high penetrance. However, it is not clear why the pancreas with endogenous levels of mutant KRAS is vulnerable to chronic HFD and inflammatory challenges. Recently, the discovery of fibroblast growth factor 21 (FGF21) as a novel anti-obesity and anti-inflammatory factor and as a downstream target of mutant KRAS has shed new light on this problem. This review is intended to provide an update on our knowledge of the vulnerability of the pancreas to KRAS-mediated invasive PDAC in the context of challenges engendered by obesity and associated inflammation.
Preclinical and Clinical Status of PSMA-Targeted Alpha Therapy for Metastatic Castration-Resistant Prostate Cancer
Authors: Juzeniene Asta , Stenberg Vilde Yuli , Bruland Øyvind Sverre , Larsen Roy Hartvig
Published: February 2021

Bone, lymph node, and visceral metastases are frequent in castrate-resistant prostate cancer patients. Since such patients have only a few months’ survival benefit from standard therapies, there is an urgent need for new personalized therapies. The prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer and is a molecular target for imaging diagnostics and targeted radionuclide therapy (theragnostics). PSMA-targeted α therapies (PSMA-TAT) may deliver potent and local radiation more selectively to cancer cells than PSMA-targeted β− therapies. In this review, we summarize both the recent preclinical and clinical advances made in the development of PSMA-TAT, as well as the availability of therapeutic α-emitting radionuclides, the development of small molecules and antibodies targeting PSMA. Lastly, we discuss the potentials, limitations, and future perspectives of PSMA-TAT.
Prognostic Significance of Gene Expression and DNA Methylation Markers in Circulating Tumor Cells and Paired Plasma Derived Exosomes in Metastatic Castration Resistant Prostate Cancer
Authors: Zavridou Martha , Strati Areti , Bournakis Evangelos , Smilkou Stavroula , Tserpeli Victoria , Lianidou Evi
Published: February 2021

Liquid biopsy, based on the analysis of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), provides non-invasive real-time monitoring of tumor evolution and therapeutic efficacy. We performed for the first time a direct comparison study on gene expression and DNA methylation markers in CTCs and paired plasma-derived exosomes and evaluated their prognostic significance in metastatic castration resistant prostate cancer. This prospective liquid biopsy (LB) study was based on a group of 62 metastatic castration resistant prostate cancer (mCRPC) patients and 10 healthy donors (HD) as controls. Identical blood draws were used to: (a) enumerate CTC and tumor-derived extracellular vesicles (tdEVs) using CellSearch (CS) and (b) analyze CTCs and paired plasma-derived exosomes at the gene expression and DNA methylation level. CTCs were enumerated using CellSearch in 57/62 patients, with values ranging from 5 to 854 cells/7.5 mL PB. Our results revealed for the first time a significantly higher positivity of gene expression markers (CK-8, CK-18, TWIST1, PSMA, AR-FL, AR-V7, AR-567 and PD-L1 mRNA) in EpCAM-positive CTCs compared to plasma-derived exosomes. GSTP1, RASSF1A and SCHLAFEN were methylated both in CTC and exosomes. In CTCs, Kaplan–Meier analysis revealed that CK-19 (p = 0.009), PSMA (p = 0.001), TWIST1 (p = 0.001) expression and GSTP1 (p = 0.001) methylation were correlated with OS, while in exosomes GSTP1 (p = 0.007) and RASSF1A (p = 0.001) methylation was correlated with OS. Our direct comparison study of CTCs and exosomes at gene expression and DNA methylation level, revealed for the first time a significantly higher positivity in EpCAM-positive CTCs compared to plasma-derived exosomes. Future perspective of this study should be the evaluation of clinical utility of molecular biomarkers in CTCs and exosomes on independent multicentric cohorts with mCRPC patients.
TAp73β Can Promote Hepatocellular Carcinoma Dedifferentiation
Authors: Iscan Evin , Ekin Umut , Yildiz Gokhan , Oz Ozden , Keles Umur , Suner Aslı , Cakan-Akdogan Gulcin , Ozhan Gunes , Nekulova Marta , Vojtesek Borivoj , Uzuner Hamdiye , Karakülah Gökhan , Alotaibi Hani , Ozturk Mehmet
Published: February 2021

Hepatocyte dedifferentiation is a major source of hepatocellular carcinoma (HCC), but its mechanisms are unknown. We explored the p73 expression in HCC tumors and studied the effects of transcriptionally active p73β (TAp73β) in HCC cells. Expression profiles of p73 and patient clinical data were collected from the Genomic Data Commons (GDC) data portal and the TSVdb database, respectively. Global gene expression profiles were determined by pan-genomic 54K microarrays. The Gene Set Enrichment Analysis method was used to identify TAp73β-regulated gene sets. The effects of TAp73 isoforms were analyzed in monolayer cell culture, 3D-cell culture and xenograft models in zebrafish using western blot, flow cytometry, fluorescence imaging, real-time polymerase chain reaction (RT-PCR), immunohistochemistry and morphological examination. TAp73 isoforms were significantly upregulated in HCC, and high p73 expression correlated with poor patient survival. The induced expression of TAp73β caused landscape expression changes in genes involved in growth signaling, cell cycle, stress response, immunity, metabolism and development. Hep3B cells overexpressing TAp73β had lost hepatocyte lineage biomarkers including ALB, CYP3A4, AFP, HNF4α. In contrast, TAp73β upregulated genes promoting cholangiocyte lineage such as YAP, JAG1 and ZO-1, accompanied with an increase in metastatic ability. Our findings suggest that TAp73β may promote malignant dedifferentiation of HCC cells.
Deep Learning Based HPV Status Prediction for Oropharyngeal Cancer Patients
Authors: Lang Daniel M. , Peeken Jan C. , Combs Stephanie E. , Wilkens Jan J. , Bartzsch Stefan
Published: February 2021

Infection with the human papillomavirus (HPV) has been identified as a major risk factor for oropharyngeal cancer (OPC). HPV-related OPCs have been shown to be more radiosensitive and to have a reduced risk for cancer related death. Hence, the histological determination of HPV status of cancer patients depicts an essential diagnostic factor. We investigated the ability of deep learning models for imaging based HPV status detection. To overcome the problem of small medical datasets, we used a transfer learning approach. A 3D convolutional network pre-trained on sports video clips was fine-tuned, such that full 3D information in the CT images could be exploited. The video pre-trained model was able to differentiate HPV-positive from HPV-negative cases, with an area under the receiver operating characteristic curve (AUC) of 0.81 for an external test set. In comparison to a 3D convolutional neural network (CNN) trained from scratch and a 2D architecture pre-trained on ImageNet, the video pre-trained model performed best. Deep learning models are capable of CT image-based HPV status determination. Video based pre-training has the ability to improve training for 3D medical data, but further studies are needed for verification.
Argonaute Proteins Take Center Stage in Cancers
Authors: Nowak Iwona , Sarshad Aishe A.
Published: February 2021

Argonaute proteins (AGOs) play crucial roles in RNA-induced silencing complex (RISC) formation and activity. AGOs loaded with small RNA molecules (miRNA or siRNA) either catalyze endoribonucleolytic cleavage of target RNAs or recruit factors responsible for translational silencing and target destabilization. miRNAs are well characterized and broadly studied in tumorigenesis; nevertheless, the functions of the AGOs in cancers have lagged behind. Here, we discuss the current state of knowledge on the role of AGOs in tumorigenesis, highlighting canonical and non-canonical functions of AGOs in cancer cells, as well as the biomarker potential of AGO expression in different of tumor types. Furthermore, we point to the possible application of the AGOs in development of novel therapeutic approaches.
Second Relapse of Pediatric Patients with Acute Myeloid Leukemia: A Report on Current Treatment Strategies and Outcome of the AML-BFM Study Group
Authors: Rasche Mareike , Steidel Emma , Zimmermann Martin , Bourquin Jean-Pierre , Boztug Heidrun , Janotova Iveta , Kolb E. Anders , Lehrnbecher Thomas , von Neuhoff Nils , Niktoreh Naghmeh , Mühlegger Nora , Sramkova Lucie , Stary Jan , Walter Christiane , Creutzig Ursula , Dworzak Michael , Reinhardt Dirk
Published: February 2021

Successful management of relapse is critical to improve outcomes of children with acute myeloid leukemia (AML). We evaluated response, survival and prognostic factors after a second relapse of AML. Among 1222 pediatric patients of the population-based AML-Berlin–Frankfurt–Munster (BFM) study group (2004 until 2017), 73 patients met the quality parameters for inclusion in this study. Central review of source documentation warranted the accuracy of reported data. Treatment approaches included palliation in 17 patients (23%), intensive therapy with curative intent (n = 46, 63%) and other regimens (n = 10). Twenty-five patients (35%) received hematopoietic stem cell transplantation (HSCT), 21 of whom (88%) had a prior HSCT. Survival was poor, with a five-year probability of overall survival (pOS) of 15 ± 4% and 31 ± 9% following HSCT (n = 25). Early second relapse (within one year after first relapse) was associated with dismal outcome (pOS 2 ± 2%, n = 44 vs. 33 ± 9%, n = 29; p < 0.0001). A third complete remission (CR) is required for survival: 31% (n = 14) of patients with intensive treatment achieved a third CR with a pOS of 36 ± 13%, while 28 patients (62%) were non-responders (pOS 7 ± 5%). In conclusion, survival is poor but possible, particularly after a late second relapse and an intensive chemotherapy followed by HSCT. This analysis provides a baseline for future treatment planning.
Multimodal Therapy of Upper Gastrointestinal Malignancies
Authors: Ronellenfitsch Ulrich , Klose Johannes , Kleeff Jörg
Published: February 2021

n/a
Clinical Candidates Targeting the ATR–CHK1–WEE1 Axis in Cancer
Authors: Gorecki Lukas , Andrs Martin , Korabecny Jan
Published: February 2021

Selective killing of cancer cells while sparing healthy ones is the principle of the perfect cancer treatment and the primary aim of many oncologists, molecular biologists, and medicinal chemists. To achieve this goal, it is crucial to understand the molecular mechanisms that distinguish cancer cells from healthy ones. Accordingly, several clinical candidates that use particular mutations in cell-cycle progressions have been developed to kill cancer cells. As the majority of cancer cells have defects in G1 control, targeting the subsequent intra‑S or G2/M checkpoints has also been extensively pursued. This review focuses on clinical candidates that target the kinases involved in intra‑S and G2/M checkpoints, namely, ATR, CHK1, and WEE1 inhibitors. It provides insight into their current status and future perspectives for anticancer treatment. Overall, even though CHK1 inhibitors are still far from clinical establishment, promising accomplishments with ATR and WEE1 inhibitors in phase II trials present a positive outlook for patient survival.
Surgical Management of Tracheal Invasion by Well-Differentiated Thyroid Cancer
Authors: Matsumoto Fumihiko , Ikeda Katsuhisa
Published: February 2021

Well-differentiated thyroid carcinoma (WDTC) is a slow-growing cancer with a good prognosis, but may show extraglandular progression involving the invasion of tumor-adjacent tissues, such as the trachea, esophagus, and recurrent laryngeal nerve. Tracheal invasion by WDTC is infrequent. Since this condition is rare, relevant high-level evidence about it is lacking. Tracheal invasion by a WDTC has a negative impact on survival, with intraluminal tumor development constituting a worse prognostic factor than superficial tracheal invasion. In WDTC, curative resection is often feasible with a small safety margin, and complete resection can ensure a good prognosis. Despite its resectability, accurate knowledge of the tracheal and peritracheal anatomy and proper selection of surgical techniques are essential for complete resection. However, there is no standard guideline on surgical indications and the recommended procedure in trachea-invading WDTC. This review discusses the indications for radical resection and the three currently available major resection methods: shaving, window resection, and sleeve resection with end-to-end anastomosis. The review shows that the decision for radical resection should be based on the patient’s general condition, tumor status, expected survival duration, and the treating facility’s strengths and weaknesses.
Definition, Epidemiology, Pathophysiology, and Essential Criteria for Diagnosis of Pediatric Chronic Myeloid Leukemia
Authors: Suttorp Meinolf , Millot Frédéric , Sembill Stephanie , Deutsch Hélène , Metzler Markus
Published: February 2021

Depending on the analytical tool applied, the hallmarks of chronic myeloid leukemia (CML) are the Philadelphia Chromosome and the resulting mRNA fusion transcript BCR-ABL1. With an incidence of 1 per 1 million of children this malignancy is very rare in the first 20 years of life. This article aims to; (i) define the disease based on the WHO nomenclature, the appropriate ICD 11 code and to unify the terminology, (ii) delineate features of epidemiology, etiology, and pathophysiology that are shared, but also differing between adult and pediatric patients with CML, (iii) give a short summary on the diseases to be considered as a differential diagnosis of pediatric CML, (iv) to describe the morphological, histopathological and immunophenotypical findings of CML in pediatric patients, (v) illustrate rare but classical complications resulting from rheological problems observed at diagnosis, (vi) list essential and desirable diagnostic criteria, which hopefully in the future will help to unify the attempts when approaching this rare pediatric malignancy.
Influence of Alumina Precursor Properties on Cu-Fe Alumina Supported Catalysts for Total Toluene Oxidation as a Model Volatile Organic Air Pollutant
Authors: Žumbar Tadej , Ristić Alenka , Dražić Goran , Lazarova Hristina , Volavšek Janez , Pintar Albin , Zabukovec Logar Nataša , Tušar Nataša Novak
Published: February 2021

The structure–property relationship of catalytic supports for the deposition of redox-active transition metals is of great importance for improving the catalytic efficiency and reusability of the catalysts. In this work, the role of alumina support precursors of Cu-Fe/Al2O3 catalysts used for the total oxidation of toluene as a model volatile organic air pollutant is elucidated. Surface characterization of the catalysts revealed that the surface area, pore volume and acid site concentration of the alumina supports are important but not the determining factors for the catalytic activity of the studied catalysts for this type of reaction. The determining factors are the structural order of the support precursor, the homogeneous distribution of the catalytic sites and reducibility, which were elucidated by XRD, NMR, TEM and temperature programed reduction (TPR). Cu–Fe/Al2O3 prepared from bayerite and pseudoboehmite as highly ordered precursors showed better catalytic performance compared to Cu-Fe/Al2O3 derived from the amorphous alumina precursor and dawsonite. Homogeneous distribution of FexOy and CuOx with defined Cu/Fe molar ratio on the Al2O3 support is required for the efficient catalytic performance of the material. The study showed a beneficial effect of low iron concentration introduced into the alumina precursor during the alumina support synthesis procedure, which resulted in a homogeneous metal oxide distribution on the support.
Characterization and Biomarker Analyses of Post-COVID-19 Complications and Neurological Manifestations
Authors: Sun Bing , Tang Norina , Peluso Michael J. , Iyer Nikita S. , Torres Leonel , Donatelli Joanna L. , Munter Sadie E. , Nixon Christopher C. , Rutishauser Rachel L. , Rodriguez-Barraquer Isabel , Greenhouse Bryan , Kelly John D. , Martin Jeffrey N. , Deeks Steven G. , Henrich Timothy J. , Pulliam Lynn
Published: February 2021

As the SARS-CoV-2 pandemic continues, reports have demonstrated neurologic sequelae following COVID-19 recovery. Mechanisms to explain long-term neurological sequelae are unknown and need to be identified. Plasma from 24 individuals recovering from COVID-19 at 1 to 3 months after initial infection were collected for cytokine and antibody levels and neuronal-enriched extracellular vesicle (nEV) protein cargo analyses. Plasma cytokine IL-4 was increased in all COVID-19 participants. Volunteers with self-reported neurological problems (nCoV, n = 8) had a positive correlation of IL6 with age or severity of the sequalae, at least one co-morbidity and increased SARS-CoV-2 antibody compared to those COVID-19 individuals without neurological issues (CoV, n = 16). Protein markers of neuronal dysfunction including amyloid beta, neurofilament light, neurogranin, total tau, and p-T181-tau were all significantly increased in the nEVs of all participants recovering from COVID-19 compared to historic controls. This study suggests ongoing peripheral and neuroinflammation after COVID-19 infection that may influence neurological sequelae by altering nEV proteins. Individuals recovering from COVID-19 may have occult neural damage while those with demonstrative neurological symptoms additionally had more severe infection. Longitudinal studies to monitor plasma biomarkers and nEV cargo are warranted to assess persistent neurodegeneration and systemic effects.
Long-Term Effects of Very Low Dose Particle Radiation on Gene Expression in the Heart: Degenerative Disease Risks
Authors: Garikipati Venkata Naga Srikanth , Arakelyan Arsen , Blakely Eleanor A. , Chang Polly Y. , Truongcao May M. , Cimini Maria , Malaredy Vandana , Bajpai Anamika , Addya Sankar , Bisserier Malik , Brojakowska Agnieszka , Eskandari Abrisham , Khlgatian Mary K. , Hadri Lahouaria , Fish Kenneth M. , Kishore Raj , Goukassian David. A.
Published: February 2021

Compared to low doses of gamma irradiation (γ-IR), high-charge-and-energy (HZE) particle IR may have different biological response thresholds in cardiac tissue at lower doses, and these effects may be IR type and dose dependent. Three- to four-month-old female CB6F1/Hsd mice were exposed once to one of four different doses of the following types of radiation: γ-IR 137Cs (40-160 cGy, 0.662 MeV), 14Si-IR (4-32 cGy, 260 MeV/n), or 22Ti-IR (3-26 cGy, 1 GeV/n). At 16 months post-exposure, animals were sacrificed and hearts were harvested and archived as part of the NASA Space Radiation Tissue Sharing Forum. These heart tissue samples were used in our study for RNA isolation and microarray hybridization. Functional annotation of twofold up/down differentially expressed genes (DEGs) and bioinformatics analyses revealed the following: (i) there were no clear lower IR thresholds for HZE- or γ-IR; (ii) there were 12 common DEGs across all 3 IR types; (iii) these 12 overlapping genes predicted various degrees of cardiovascular, pulmonary, and metabolic diseases, cancer, and aging; and (iv) these 12 genes revealed an exclusive non-linear DEG pattern in 14Si- and 22Ti-IR-exposed hearts, whereas two-thirds of γ-IR-exposed hearts revealed a linear pattern of DEGs. Thus, our study may provide experimental evidence of excess relative risk (ERR) quantification of low/very low doses of full-body space-type IR-associated degenerative disease development.
Differences on Motor Competence in 4-Year-Old Boys and Girls Regarding the Quarter of Birth: Is There a Relative Age Effect?
Authors: Navarro-Patón Rubén , Arufe-Giráldez Víctor , Sanmiguel-Rodríguez Alberto , Mecías-Calvo Marcos
Published: February 2021

The aim of this study was to evaluate the differences on motor competence between boys and girls aged 4 years old and investigate the existence of Relative Age Effect on their motor competence. In total, 132 preschool children were evaluated, of whom 60 (45.50%) were girls and 72 (54.5%) were boys. The distribution of the participants was from quarter 1 [n = 28 (21.2%)], quarter 2 [n = 52 (39.4%)], quarter 3 [n = 24 (18.2%)], and quarter 4 [(n = 28 (21.2%)], respectively. The Movement Assessment Battery for Children-2 (MABC-2) was used to collect the data. The data show the main effects on quarter of birth factor in manual dexterity (MD; p < 0.001), in aiming and catching (A&C; p < 0.001), in balance (Bal; p < 0.001) and in total test score (TTS; p < 0.001). There are also statistical differences on gender factor in MD (p < 0.001) and in TTS (p = 0.031). A significant effect was also found in the interaction between two factors (gender and quarter of birth) in MD (p < 0.001), A&C (p < 0.001), and Bal (p < 0.001). There are differences in all the variables studied according to the quarter of birth and only in manual dexterity and in the total score if compared according to gender (the scores are higher in girls).
Comparison of the Technical Performance of Leather, Artificial Leather, and Trendy Alternatives
Authors: Meyer Michael , Dietrich Sascha , Schulz Haiko , Mondschein Anke
Published: February 2021

The market for biogenic and synthetic alternatives to leather is increasing aiming to replace animal-based materials with vegan alternatives. In parallel, bio-based raw materials should be used instead of fossil-based synthetic raw materials. In this study, a shoe upper leather and an artificial leather, and nine alternative materials (Desserto®, Kombucha, Pinatex®, Noani®, Appleskin®, Vegea®, SnapPap®, Teak Leaf®, and Muskin®) were investigated. We aimed to compare the structure and technical performance of the materials, which allows an estimation of possible application areas. Structure and composition were characterized by microscopy and FTIR spectroscopy, the surface properties, mechanical performance, water vapor permeability, and water absorption by standardized physical tests. None of the leather alternatives showed the universal performance of leather. Nevertheless, some materials achieved high values in selected properties. It is speculated that the grown multilayer structure of leather with a very tight surface and a gradient of the structural density over the cross-section causes this universal performance. To date, this structure could neither be achieved with synthetic nor with bio-based materials.
Novel Active Food Packaging Films Based on Whey Protein Incorporated with Seaweed Extract: Development, Characterization, and Application in Fresh Poultry Meat
Authors: Andrade Mariana A. , Barbosa Cássia H. , Souza Victor G. L. , Coelhoso Isabel M. , Reboleira João , Bernardino Susana , Ganhão Rui , Mendes Susana , Fernando Ana Luísa , Vilarinho Fernanda , Sanches Silva Ana , Ramos Fernando
Published: February 2021

Algae and seaweeds are used in cookery since the beginnings of human civilization, particularly in several Asian cultures. Phenolic compounds are secondary metabolites produced by aquatic and terrestrial plants for their natural defense against external stimuli, which possess powerful antimicrobial and antioxidant properties that can be very important for the food industry. The main objective of this study was to develop a whey protein concentrate active coating, incorporated with a Fucus vesiculosus extract in order to delay the lipid oxidation of chicken breasts. Ten hydroethanolic extracts from F. vesiculosus were obtained and their antioxidant capacity was evaluated through two antioxidant activity assays: the DPPH radical scavenging activity and β-carotene bleaching assay. The total content in phenolics compounds was also determined by Folin-Ciocalteu method. The chosen extract was the one obtained from the freeze-dried F. vesiculosus using 75% (v/v) ethanol as extraction solvent. The extract was successfully incorporated into a whey protein film and successfully strengthened the thickness, tensile strength, and elastic modulus. The active film also was able to inhibit the chicken breasts lipid oxidation for 25 days of storage.
Twinning Behavior in Cold-Rolling Ultra-Thin Grain-Oriented Silicon Steel
Authors: Zhang Bo , Meng Li , Ma Guang , Zhang Ning , Li Guobao , Liu Kun , Zhong Sheng
Published: February 2021

Twinning behaviors in grains during cold rolling have been systematically studied in preparing ultra-thin grain-oriented silicon steel (UTGO) using a commercial glassless grain-oriented silicon steel as raw material. It is found that the twinning system with the maximum Schmid factor and shear mechanical work would be activated. The area fraction of twins increased with the cold rolling reduction. The orientations of twins mainly appeared to be α-fiber (<110>//RD), most of which were {001}<110> orientation. Analysis via combining deformation orientation simulation and twinning orientation calculation suggested that {001}<110> oriented twinning occurred at 40–50% rolling reduction. The simulation also confirmed more {100} <011> oriented twins would be produced in the cold rolling process and their orientation also showed less deviation from ideal {001}<110> orientation when a raw material with a higher content of exact Goss oriented grains was used.
Reproducibility and Concurrent Validity of Manual Palpation with Rehabilitative Ultrasound Imaging for Assessing Deep Abdominal Muscle Activity: Analysis with Preferential Ratios
Authors: Valentín-Mazarracin Irene , Nogaledo-Martín Miriam , López-de-Uralde-Villanueva Ibai , Fernández-de-las-Peñas César , Stokes María , Arias-Buría José L. , Díaz-Arribas María J. , Plaza-Manzano Gustavo
Published: February 2021

The abdominal drawing-in maneuver (ADIM) is a clinical tool used for identifying preferential activity of deep abdominal muscles. However, concurrent validity and reproducibility of palpation during the ADIM has not been formally investigated. The aims of this study were (1) to assess intra- and interrater reliability of manual palpation during the ADIM, and (2) to determine the concurrent validity of manual palpation during the ADIM by calculating preferential activation ratio cut-off as assessed with ultrasound imaging (RUSI). Thirty-two subjects (n = 16 patients with nonspecific low back pain and 16 comparable healthy individuals) performed the ADIM in a supine hook-lying position. Two experienced assessors evaluated the presence or absence of preferential contraction of the deep abdominal muscles by palpation during the ADIM on 2 different days. Intrarater (test-retest) and interrater reliability of palpation were calculated using Cohen’s kappa coefficients. Muscle thickness of the transverse abdominis (TrA), internal oblique (IO), and external oblique (EO) muscles at rest and during the ADIM were also measured. TrA-Contraction Ratio (TrA-CR), TrA-Preferential Activation Ratio (TrA-PAR), and Modified-TrA-PR (M-TrA-PAR) were calculated. The concurrent validity of manual palpation was determined using the correlation between manual palpation and imaging and by calculating ROC curve (operating characteristics curve), Youden index, and sensitivity and specificity. Intra- and interrater reliability of manual palpation during the ADIM was excellent (k: 0.82–1.00) and good to excellent (k: 0.71–1.00), respectively. Interrater reliability for muscle thickness ranged from good to excellent (ICC3,1 0.79–0.91). Manual palpation and TrA ratio showed low to moderate correlations (r: 0.36–0.60). When evaluating the diagnostic accuracy of manual palpation, the best predictive model (ROC value: 0.89; p < 0.001) for correct a preferential contraction of TrA was obtained when the M-TrA-PAR was ≥0.08 (sensitivity: 0.95–1.00; specificity: 0.62). Good to excellent intra- and interrater reliability of manual palpation was found during the ADIM in both patients and healthy groups. Manual palpation showed concurrent validity for identifying the preferential activity of the TrA muscle supporting its use in clinical practice.
Automatic Pharyngeal Phase Recognition in Untrimmed Videofluoroscopic Swallowing Study Using Transfer Learning with Deep Convolutional Neural Networks
Authors: Lee Ki-Sun , Lee Eunyoung , Choi Bareun , Pyun Sung-Bom
Published: February 2021

Background: Video fluoroscopic swallowing study (VFSS) is considered as the gold standard diagnostic tool for evaluating dysphagia. However, it is time consuming and labor intensive for the clinician to manually search the recorded long video image frame by frame to identify the instantaneous swallowing abnormality in VFSS images. Therefore, this study aims to present a deep leaning-based approach using transfer learning with a convolutional neural network (CNN) that automatically annotates pharyngeal phase frames in untrimmed VFSS videos such that frames need not be searched manually. Methods: To determine whether the image frame in the VFSS video is in the pharyngeal phase, a single-frame baseline architecture based the deep CNN framework is used and a transfer learning technique with fine-tuning is applied. Results: Compared with all experimental CNN models, that fine-tuned with two blocks of the VGG-16 (VGG16-FT5) model achieved the highest performance in terms of recognizing the frame of pharyngeal phase, that is, the accuracy of 93.20 (±1.25)%, sensitivity of 84.57 (±5.19)%, specificity of 94.36 (±1.21)%, AUC of 0.8947 (±0.0269) and Kappa of 0.7093 (±0.0488). Conclusions: Using appropriate and fine-tuning techniques and explainable deep learning techniques such as grad CAM, this study shows that the proposed single-frame-baseline-architecture-based deep CNN framework can yield high performances in the full automation of VFSS video analysis.
Role of the Appendicular Skeletal Muscle Index for Predicting the Recurrence-Free Survival of Head and Neck Cancer
Authors: Yeh Kun-Yun , Ling Hang Huong , Ng Shu-Hang , Wang Cheng-Hsu , Chang Pei-Hung , Chou Wen-Chi , Chen Fang-Ping , Lin Yu-Ching
Published: February 2021

Background: This study investigates whether the appendicular skeletal muscle index (ASMI) was an independent prognostic predictor for patients with locally advanced head and neck cancer (LAHNC) receiving concurrent chemoradiotherapy (CCRT) and whether there were any differences in lean mass loss in different body regions during CCRT. Methods: In this prospective study, we analyzed the clinicopathological variables and the total body composition data before and after treatment. The factors associated with the 2-year recurrence-free survival rate (RFSR) were analyzed via logistic regression analysis. Results: A total of 98 patients were eligible for analysis. The body weight, body mass index, and all parameters of body composition significantly decreased after CCRT. The pretreatment ASMI was the only independent prognostic factor for predicting the 2-year RFSR (hazard ratio, 0.235; 95% confidence interval, 0.062–0.885; p = 0.030). There was at least 5% reduction in total lean and fat mass (p < 0.001); however, the highest lean mass loss was observed in the arms (9.5%), followed by the legs (7.2%), hips (7.1%), waist (4.7%), and trunk (3.6%). Conclusions: The pretreatment ASMI was the only independent prognostic predictor for the 2-year RFSR of LAHNC patients undergoing CCRT. Asynchronous loss of lean mass may be observed in different body parts after CCRT.
Using Peer Review for Student Performance Enhancement: Experiences in a Multidisciplinary Higher Education Setting
Authors: Serrano-Aguilera Juan Jose , Tocino Alicia , Fortes Sergio , Martín Cristian , Mercadé-Melé Pere , Moreno-Sáez Rafael , Muñoz Antonio , Palomo-Hierro Sara , Torres Antoni
Published: February 2021

Nowadays one of the main focuses of the Spanish University system is achieving the active learning paradigm in the context of its integration into the European Higher Education Area. This goal is being addressed by means of the application of novel teaching mechanisms. Among a wide variety of learning approaches, the present work focuses on peer review, understood as a collaborative learning technique where students assess other student’s work and provide their own feedback. In this way, peer review has the overarching goal of improving the student learning during this process. Peer review has been successfully applied and analyzed in the literature. Indeed, many authors also recommend improving the design and implementation of self and peer review, which has been our main goal. This paper presents an empirical study based on the application of peer review assessment in different higher education BSc and MSc courses. In this way, six courses from different studies at the University of Malaga in Spain are subject to the application of peer review strategies to promote student learning and develop cross-wise skills such as critical thinking, autonomy and responsibility. Based on these experiences, a deep analysis of the results is performed, showing that a proper application of the peer review methodology provides reliable reviews (with close scores to the ones from the teacher) as well as an improvement in the students’ performance.