bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliability of Tibialis Anterior Muscle Voluntary Activation Using the Interpolated Twitch Technique and the Central Activation Ratio in People with Stroke
Authors: Olsen Sharon , Signal Nada , Niazi Imran Khan , Alder Gemma , Rashid Usman , Nedergaard Rasmus Bach , Taylor Denise
Published: February 2021

Voluntary activation (VA) is measured by applying supramaximal electrical stimulation to a muscle during a maximal voluntary contraction (MVC). The amplitude of the evoked muscle twitch is used to determine any VA deficit, and indicates incomplete central neural drive to the motor units. People with stroke experience VA deficits and greater levels of central fatigue, which is the decrease in VA that occurs following exercise. This study investigated the between-session reliability of VA and central fatigue of the tibialis anterior muscle (TA) in people with chronic stroke (n = 12), using the interpolated twitch technique (ITT), adjusted-ITT, and central activation ratio (CAR) methods. On two separate sessions, supramaximal electrical stimulation was applied to the TA when it was at rest and maximally activated, at the start and end of a 30-s isometric dorsiflexor MVC. The most reliable measures of VA were obtained using the CAR calculation on transformed data, which produced an ICC of 0.92, and a lower bound confidence interval in the good range (95% CI 0.77 to 0.98). Reliability was lower for the CAR calculation on non-transformed data (ICC 0.82, 95% CI 0.63 to 0.91) and the ITT and adjusted-ITT calculations on transformed data (ICCs 0.82, 95% CIs 0.51 to 0.94), which had lower bound confidence intervals in the moderate range. The two ITT calculations on non-transformed data demonstrated the poorest reliability (ICCs 0.62, 95% CI 0.25 to 0.74). Central fatigue measures demonstrated very poor reliability. Thus, the reliability for VA in people with chronic stroke ranged from good to poor, depending on the calculation method and statistical analysis method, whereas the reliability for central fatigue was very poor.
A New Proposal for Phoneme Acquisition: Computing Speaker-Specific Distribution
Authors: Choi Mihye , Shukla Mohinish
Published: February 2021

Speech is an acoustically variable signal, and one of the sources of this variation is the presence of multiple speakers. Empirical evidence has suggested that adult listeners possess remarkably sensitive (and systematic) abilities to process speech signals, despite speaker variability. It includes not only a sensitivity to speaker-specific variation, but also an ability to utilize speaker variation with other sources of information for further processing. Recently, many studies also showed that young children seem to possess a similar capacity. This suggests continuity in the processing of speaker-dependent speech variability, and suggests that this ability could also be important for infants learning their native language. In the present paper, we review evidence for speaker variability and speech processing in adults, and speaker variability and speech processing in young children, with an emphasis on how they make use of speaker-specific information in word learning situations. Finally, we will build on these findings to make a novel proposal for the use of speaker-specific information processing in phoneme learning in infancy.
Shaken Baby Syndrome: Magnetic Resonance Imaging Features in Abusive Head Trauma
Authors: Cartocci Gaia , Fineschi Vittorio , Padovano Martina , Scopetti Matteo , Rossi-Espagnet Maria Camilla , Giannì Costanza
Published: February 2021

In the context of child abuse spectrum, abusive head trauma (AHT) represents the leading cause of fatal head injuries in children less than 2 years of age. Immature brain is characterized by high water content, partially myelinated neurons, and prominent subarachnoid space, thus being susceptible of devastating damage as consequence of acceleration–deceleration and rotational forces developed by violent shaking mechanism. Diagnosis of AHT is not straightforward and represents a medical, forensic, and social challenge, based on a multidisciplinary approach. Beside a detailed anamnesis, neuroimaging is essential to identify signs suggestive of AHT, often in absence of external detectable lesions. Magnetic resonance imaging (MRI) represents the radiation-free modality of choice to investigate the most typical findings in AHT, such as subdural hematoma, retinal hemorrhage, and hypoxic-ischemic damage and it also allows to detect more subtle signs as parenchymal lacerations, cranio-cervical junction, and spinal injuries. This paper is intended to review the main MRI findings of AHT in the central nervous system of infants, with a specific focus on both hemorrhagic and non-hemorrhagic injuries caused by the pathological mechanisms of shaking. Furthermore, this review provides a brief overview about the most appropriate and feasible MRI protocol to help neuroradiologists identifying AHT in clinical practice.
Bispecific Antibodies in Prostate Cancer Therapy: Current Status and Perspectives
Authors: Heitmann Jonas S. , Pfluegler Martin , Jung Gundram , Salih Helmut R.
Published: February 2021

Prostate carcinoma (PC) is the second most common cancer in men. When the disease becomes unresponsive to androgen deprivation therapy, the remaining treatment options are of limited benefit. Despite intense efforts, none of the T cell-based immunotherapeutic strategies that meanwhile have become a cornerstone for treatment of other malignancies is established in PC. This refers to immune checkpoint inhibition (CI), which generally reinforces T cell immunity as well as chimeric antigen receptor T (CAR-T) cells and bispecific antibodies (bsAbs) that stimulate the T cell receptor/CD3-complex and mobilize T cells in a targeted manner. In general, compared to CAR-T cells, bsAb would have the advantage of being an “off the shelf” reagent associated with less preparative effort, but at present, despite enormous efforts, neither CAR-T cells nor bsAbs are successful in solid tumors. Here, we focus on the various bispecific constructs that are presently in development for treatment of PC, and discuss underlying concepts and the state of clinical evaluation as well as future perspectives.
Immune Therapy Resistance and Immune Escape of Tumors
Authors: Seliger Barbara , Massa Chiara
Published: February 2021

Immune therapy approaches such as checkpoint inhibitors or adoptive cell therapy represent promising therapeutic options for cancer patients, but their efficacy is still limited, since patients frequently develop innate or acquired resistances to these therapies. Thus, one major goal is to increase the efficiency of immunotherapies by overcoming tumor-induced immune suppression, which then allows for immune-mediated tumor clearance. Innate resistance to immunotherapies could be caused by a low immunogenicity of the tumor itself as well as an immune suppressive microenvironment composed of cellular, physical, or soluble factors leading to escape from immune surveillance and disease progression. So far, a number of strategies causing resistance to immunotherapy have been described in various clinical trials, which broadly overlap with the immunoediting processes of cancers. This review summarizes the novel insights in the development of resistances to immune therapy as well as different approaches that could be employed to overcome them.
Identifying the Need to Discuss Infertility Concerns Affecting Testicular Cancer Patients: An Evaluation (INDICATE Study)
Authors: Krouwel Esmée M. , Jansen Thijs G. , Nicolai Melianthe P. J. , Dieben Sandra W. M. , Luelmo Saskia A. C. , Putter Hein , Pelger Rob C. M. , Elzevier Henk W.
Published: February 2021

Men with testicular cancer (TC) risk impaired fertility. Fertility is a major concern for TC patients due to diagnosis in almost always reproductive ages and high overall survival. This study assessed counselling in regards to the risk of impaired fertility and sperm cryopreservation. A cross-sectional survey was performed on 566 TC patients diagnosed between 1995–2015. Of the 566 survivors, 201 questionnaires were completed (35.5%). Eighty-eight percent was informed about possible impaired fertility, 9.5% was not informed. The majority (47.3%) preferred the urologist to provide information. Collecting sperm was troublesome but successful for 25.6%, 4.8% did not succeed in collecting sperm. The reasons were high pressure due to disease, pain after surgery and uncomfortable setting. Due to impaired fertility, 19% of the respondents reported grief and 9.3% stated as being less satisfied in life. Sperm cryopreservation was performed by 41.3% (n = 83). One third (n = 63, 31.3%) had children after treatment, of which 11.1% made use of preserved sperm (n = 7). The results of this survey indicate the importance of timely discussion of fertility issues with TC patients. While being discussed with most men, dissatisfaction and grief may occur as a result of impaired fertility and a lack of counselling. Overall, 6.5% made use of cryopreserved sperm (n = 13). Men prefer their urologist providing counselling on fertility.
Targeting Oncoimmune Drivers of Cancer Metastasis
Authors: Kudo-Saito Chie , Ozaki Yukinori , Imazeki Hiroshi , Hayashi Hideyuki , Masuda Jun , Ozawa Hiroki , Ogiwara Yamato
Published: February 2021

Residual metastasis is a major cause of cancer-associated death. Recent advances in understanding the molecular basis of the epithelial–mesenchymal transition (EMT) and the related cancer stem cells (CSCs) have revealed the landscapes of cancer metastasis and are promising contributions to clinical treatments. However, this rarely leads to practical advances in the management of cancer in clinical settings, and thus cancer metastasis is still a threat to patients. The reason for this may be the heterogeneity and complexity caused by the evolutional transformation of tumor cells through interactions with the host environment, which is composed of numerous components, including stromal cells, vascular cells, and immune cells. The reciprocal evolution further raises the possibility of successful tumor escape, resulting in a fatal prognosis for patients. To disrupt the vicious spiral of tumor–immunity aggravation, it is important to understand the entire metastatic process and the practical implementations. Here, we provide an overview of the molecular and cellular links between tumors’ biological properties and host immunity, mainly focusing on EMT and CSCs, and we also highlight therapeutic agents targeting the oncoimmune determinants driving cancer metastasis toward better practical use in the treatment of cancer patients.
PD-L1 Is an Independent Prognostic Marker in Middle Eastern PTC and Its Expression Is Upregulated by BRAFV600E Mutation
Authors: Siraj Abdul K. , Parvathareddy Sandeep Kumar , Pratheeshkumar Poyil , Divya Sasidharan Padmaja , Al-Sobhi Saif S. , Al-Dayel Fouad , Al-Kuraya Khawla S.
Published: February 2021

PD-L1 inhibition is a promising therapeutic target whose efficacy has been demonstrated in several cancers. Immunohistochemistry was performed to assess PD-L1 protein expression in PTC. We further conducted in vitro analysis to investigate the role of PD-L1 in regulating BRAFV600E in PTC cell lines. PD-L1 over-expression was noted in 32.4% (473/1458) of cases and significantly associated with aggressive clinico-pathological parameters. Importantly, PD-L1 was found to be an independent poorer prognostic marker. We also found PD-L1 to be significantly associated with BRAF mutation and patients with co-existing PD-L1 over-expression and BRAF mutation had a poor disease-free survival compared to patients with BRAF mutation alone. In vitro analysis showed high expression of PD-L1 in BRAF-mutated PTC cell lines compared to a BRAF wild-type cell line. Inhibition of BRAF using vemurafenib induced PD-L1 expression in BRAF-mutated cell lines without affecting cell growth. Knockdown of PD-L1 in BRAF-mutated cell lines significantly decreased the cell growth and induced apoptosis. Our data suggest that PD-L1 might represent a useful prognostic marker in Middle Eastern PTC and PD-L1 inhibition could be a potential therapeutic option for aggressive PTC cancers, such as the tall cell variant, BRAF mutation-positive patients that are unresponsive to standard treatment.
Candidate Biomarkers for Specific Intraoperative Near-Infrared Imaging of Soft Tissue Sarcomas: A Systematic Review
Authors: Rijs Zeger , Shifai A. Naweed , Bosma Sarah E. , Kuppen Peter J. K. , Vahrmeijer Alexander L. , Keereweer Stijn , Bovée Judith V. M. G. , van de Sande Michiel A. J. , Sier Cornelis F. M. , van Driel Pieter B. A. A.
Published: February 2021

Surgery is the mainstay of treatment for localized soft tissue sarcomas (STS). The curative treatment highly depends on complete tumor resection, as positive margins are associated with local recurrence (LR) and prognosis. However, determining the tumor margin during surgery is challenging. Real-time tumor-specific imaging can facilitate complete resection by visualizing tumor tissue during surgery. Unfortunately, STS specific tracers are presently not clinically available. In this review, STS-associated cell surface-expressed biomarkers, which are currently already clinically targeted with monoclonal antibodies for therapeutic purposes, are evaluated for their use in near-infrared fluorescence (NIRF) imaging of STS. Clinically targeted biomarkers in STS were extracted from clinical trial registers and a PubMed search was performed. Data on biomarker characteristics, sample size, percentage of biomarker-positive STS samples, pattern of biomarker expression, biomarker internalization features, and previous applications of the biomarker in imaging were extracted. The biomarkers were ranked utilizing a previously described scoring system. Eleven cell surface-expressed biomarkers were identified from which 7 were selected as potential biomarkers for NIRF imaging: TEM1, VEGFR-1, EGFR, VEGFR-2, IGF-1R, PDGFRα, and CD40. Promising biomarkers in common and aggressive STS subtypes are TEM1 for myxofibrosarcoma, TEM1, and PDGFRα for undifferentiated soft tissue sarcoma and EGFR for synovial sarcoma.
Cardiac Amyloidosis Therapy: A Systematic Review
Authors: Iodice Franco , Di Mauro Marco , Migliaccio Marco , Iannuzzi Angela , Pacileo Roberta , Caiazza Martina , Esposito Augusto
Published: February 2021

Heart involvement in Cardiac Amyloidosis (CA) results in a worsening of the prognosis in almost all patients with both light-chain (AL) and transthyretin amyloidosis (ATTR). The mainstream CA is a restrictive cardiomyopathy with hypertrophic phenotype at cardiac imaging that clinically leads to heart failure with preserved ejection fraction (HFpEF). An early diagnosis is essential to reduce cardiac damage and to improve the prognosis. Many therapies are available, but most of them have late benefits to cardiac function; for this reason, novel therapies are going to come soon.
CD8 and CD4 T Cell Populations in Human Kidneys
Authors: van der Putten Carlos , Remmerswaal Ester B.M. , Terpstra Matty L. , van der Bom Nelly D. , Kers Jesper , ten Berge Ineke J.M. , Geerlings Suzanne E. , van Lier René A.W. , Bemelman Frederike J. , van Aalderen Michiel C.
Published: February 2021

Background: At border sites, and in internal organs, tissue resident memory T cells (TRM) contribute to the immune barrier against pathogens like viruses, bacteria, fungi, and cancer. However, information on the presence and function of these cells in the human kidney is scant. In order to better understand the T cell-mediated immunological defense in this organ, we aimed to determine phenotypic and functional aspects of CD8 and CD4 T cells present in healthy and allograft kidney tissue. Methods: Using multichannel flow cytometry, we assessed the phenotype and function of T cells in healthy renal tissue samples (n = 5) and kidney allograft tissue (n = 7) and compared these aspects to T cells in peripheral blood from healthy controls (n = 13). Results: Kidney tissue samples contained substantial amounts of CD8 and CD4 T cells. In contrast to the circulating cells, kidney T cells frequently expressed CD69 and CD103, and were more often actively cycling. Furthermore, nearly all kidney T cells expressed CXCR3, and often expressed CXCR6 compared to T cells in the circulation. Markedly, kidney T cells produced greater quantities of IFNγ than circulating cells and were frequently polyfunctional. Conclusion: Functional T cells with the characteristic traits of TRM reside in human kidney tissues. These cells are more often actively cycling and frequently express CXCR3 and CXCR6.
The Chloroplast Trans-Splicing RNA–Protein Supercomplex from the Green Alga Chlamydomonas reinhardtii
Authors: Kück Ulrich , Schmitt Olga
Published: February 2021

In eukaryotes, RNA trans-splicing is a significant RNA modification process for the end-to-end ligation of exons from separately transcribed primary transcripts to generate mature mRNA. So far, three different categories of RNA trans-splicing have been found in organisms within a diverse range. Here, we review trans-splicing of discontinuous group II introns, which occurs in chloroplasts and mitochondria of lower eukaryotes and plants. We discuss the origin of intronic sequences and the evolutionary relationship between chloroplast ribonucleoprotein complexes and the nuclear spliceosome. Finally, we focus on the ribonucleoprotein supercomplex involved in trans-splicing of chloroplast group II introns from the green alga Chlamydomonas reinhardtii. This complex has been well characterized genetically and biochemically, resulting in a detailed picture of the chloroplast ribonucleoprotein supercomplex. This information contributes substantially to our understanding of the function of RNA-processing machineries and might provide a blueprint for other splicing complexes involved in trans- as well as cis-splicing of organellar intron RNAs.
Targeting Aberrant FGFR Signaling to Overcome CDK4/6 Inhibitor Resistance in Breast Cancer
Authors: Sobhani Navid , Fassl Anne , Mondani Giuseppina , Generali Daniele , Otto Tobias
Published: February 2021

Breast cancer (BC) is the most common cause of cancer-related death in women worldwide. Therapies targeting molecular pathways altered in BC had significantly enhanced treatment options for BC over the last decades, which ultimately improved the lives of millions of women worldwide. Among various molecular pathways accruing substantial interest for the development of targeted therapies are cyclin-dependent kinases (CDKs)—in particular, the two closely related members CDK4 and CDK6. CDK4/6 inhibitors indirectly trigger the dephosphorylation of retinoblastoma tumor suppressor protein by blocking CDK4/6, thereby blocking the cell cycle transition from the G1 to S phase. Although the CDK4/6 inhibitors abemaciclib, palbociclib, and ribociclib gained FDA approval for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative BC as they significantly improved progression-free survival (PFS) in randomized clinical trials, regrettably, some patients showed resistance to these therapies. Though multiple molecular pathways could be mechanistically responsible for CDK4/6 inhibitor therapy resistance, one of the most predominant ones seems to be the fibroblast growth factor receptor (FGFR) pathway. FGFRs are involved in many aspects of cancer formation, such as cell proliferation, differentiation, and growth. Importantly, FGFRs are frequently mutated in BC, and their overexpression and/or hyperactivation correlates with CDK4/6 inhibitor resistance and shortened PFS in BC. Intriguingly, the inhibition of aberrant FGFR activity is capable of reversing the resistance to CDK4/6 inhibitors. This review summarizes the molecular background of FGFR signaling and discusses the role of aberrant FGFR signaling during cancer development in general and during the development of CDK4/6 inhibitor resistance in BC in particular, together with other possible mechanisms for resistance to CDK4/6 inhibitors. Subsequently, future directions on novel therapeutic strategies targeting FGFR signaling to overcome such resistance during BC treatment will be further debated.
Mesenchymal Stem Cells for Mitigating Radiotherapy Side Effects
Authors: Wang Kai-Xuan , Cui Wen-Wen , Yang Xu , Tao Ai-Bin , Lan Ting , Li Tao-Sheng , Luo Lan
Published: February 2021

Radiation therapy for cancers also damages healthy cells and causes side effects. Depending on the dosage and exposure region, radiotherapy may induce severe and irreversible injuries to various tissues or organs, especially the skin, intestine, brain, lung, liver, and heart. Therefore, promising treatment strategies to mitigate radiation injury is in pressing need. Recently, stem cell-based therapy generates great attention in clinical care. Among these, mesenchymal stem cells are extensively applied because it is easy to access and capable of mesodermal differentiation, immunomodulation, and paracrine secretion. Here, we summarize the current attempts and discuss the future perspectives about mesenchymal stem cells (MSCs) for mitigating radiotherapy side effects.
Mechanical Stress Induce PG-E2 in Murine Synovial Fibroblasts Originating from the Temporomandibular Joint
Authors: Nazet Ute , Feulner Laura , Muschter Dominique , Neubert Patrick , Schatz Valentin , Grässel Susanne , Jantsch Jonathan , Proff Peter , Schröder Agnes , Kirschneck Christian
Published: February 2021

Genetic predisposition, traumatic events, or excessive mechanical exposure provoke arthritic changes in the temporomandibular joint (TMJ). We analysed the impact of mechanical stress that might be involved in the development and progression of TMJ osteoarthritis (OA) on murine synovial fibroblasts (SFs) of temporomandibular origin. SFs were subjected to different protocols of mechanical stress, either to a high-frequency tensile strain for 4 h or to a tensile strain of varying magnitude for 48 h. The TMJ OA induction was evaluated based on the gene and protein secretion of inflammatory factors (Icam-1, Cxcl-1, Cxcl-2, Il-1ß, Il-1ra, Il-6, Ptgs-2, PG-E2), subchondral bone remodelling (Rankl, Opg), and extracellular matrix components (Col1a2, Has-1, collagen and hyaluronic acid deposition) using RT-qPCR, ELISA, and HPLC. A short high-frequency tensile strain had only minor effects on inflammatory factors and no effects on the subchondral bone remodelling induction or matrix constituent production. A prolonged tensile strain of moderate and advanced magnitude increased the expression of inflammatory factors. An advanced tensile strain enhanced the Ptgs-2 and PG-E2 expression, while the expression of further inflammatory factors were decreased. The tensile strain protocols had no effects on the RANKL/OPG expression, while the advanced tensile strain significantly reduced the deposition of matrix constituent contents of collagen and hyaluronic acid. The data indicates that the application of prolonged advanced mechanical stress on SFs promote PG-E2 protein secretion, while the deposition of extracellular matrix components is decreased.
Quantitative Fiber-Enhanced Raman Sensing of Inorganic Nitrogen Species in Water
Authors: Kerdoncuff Hugo , Deleebeeck Lisa C. , Lassen Mikael
Published: February 2021

Fast and efficient water quality monitoring is essential in the pursuit of reducing the impact of human activities on the environment. We address this issue by presenting a sensing system and method based on Raman spectroscopy in liquid-filled capillaries, that enables quantitative measurement of polyatomic anions in solution. We demonstrate quantitative measurement of nitrate concentrations in water via multivariate analysis with partial least squares regression. We achieve a limit of detection of 0.13 millimolar for a measurement time of 30 s. Our Raman method is compared with gravimetrically measured concentration with good agreement and reproducibility. The Raman monitoring method can be performed in a continuous manner, thus suitable for fast continuous monitoring of water and wastewater quality.
Recent Advances in Perylene Diimide-Based Active Materials in Electrical Mode Gas Sensing
Authors: Ali Salman , Gupta Akhil , Shafiei Mahnaz , Langford Steven J.
Published: February 2021

This review provides an update on advances in the area of electrical mode sensors using organic small molecule n-type semiconductors based on perylene. Among small organic molecules, perylene diimides (PDIs) are an important class of materials due to their outstanding thermal, chemical, electronic, and optical properties, all of which make them promising candidates for a wide range of organic electronic devices including sensors, organic solar cells, organic field-effect transistors, and organic light-emitting diodes. This is mainly due to their electron-withdrawing nature and significant charge transfer properties. Perylene-based sensors of this type show high sensing performance towards various analytes, particularly reducing gases like ammonia and hydrazine, but there are several issues that need to be addressed including the selectivity towards a specific gas, the effect of relative humidity, and operating temperature. In this review, we focus on the strategies and design principles applied to the gas-sensing performance of PDI-based devices, including resistive sensors, amperometric sensors, and operating at room temperature. The device properties and sensing mechanisms for different analytes, focusing on hydrazine and ammonia, are studied in detail, and some future research perspectives are discussed for this promising field. We hope the discussed results and examples inspire new forms of molecular engineering and begin to open opportunities for other rylene diimide classes to be applied as active materials.
Review of Methods for Assessing the Impact of WWTPs on the Natural Environment
Authors: Bąk Joanna , Barbusiński Krzysztof , Thomas Maciej
Published: February 2021

Environmental management in facilities such as wastewater treatment plants (WWTPs) allows for the implementation of the Deming cycle, and thus the constant improvement of the mitigation of the environmental impact. The correct diagnosis of the current state of functioning of the WWTPs, the identification of aspects that may have a measurable impact on the environment, and their assessment are of key importance. The article discusses the possible causes of the impact of WWTPs on the natural environment. Among other problems, such issues as energy consumption, noise and the formation of bioaerosols and odor nuisances were taken into account. Different ways of assessing the impact of wastewater treatment plants on the environment were collated, taking into account the need to assess not only the technological process itself but also the buildings during their use. The results of methods for assessing the environmental impact of wastewater treatment plants in selected countries were also compared.
Prediction of Multi-Scalar Standardized Precipitation Index by Using Artificial Intelligence and Regression Models
Authors: Malik Anurag , Kumar Anil , Rai Priya , Kuriqi Alban
Published: February 2021

Accurate monitoring and forecasting of drought are crucial. They play a vital role in the optimal functioning of irrigation systems, risk management, drought readiness, and alleviation. In this work, Artificial Intelligence (AI) models, comprising Multi-layer Perceptron Neural Network (MLPNN) and Co-Active Neuro-Fuzzy Inference System (CANFIS), and regression, model including Multiple Linear Regression (MLR), were investigated for multi-scalar Standardized Precipitation Index (SPI) prediction in the Garhwal region of Uttarakhand State, India. The SPI was computed on six different scales, i.e., 1-, 3-, 6-, 9-, 12-, and 24-month, by deploying monthly rainfall information of available years. The significant lags as inputs for the MLPNN, CANFIS, and MLR models were obtained by utilizing Partial Autocorrelation Function (PACF) with a significant level equal to 5% for SPI-1, SPI-3, SPI-6, SPI-9, SPI-12, and SPI-24. The predicted multi-scalar SPI values utilizing the MLPNN, CANFIS, and MLR models were compared with calculated SPI of multi-time scales through different performance evaluation indicators and visual interpretation. The appraisals of results indicated that CANFIS performance was more reliable for drought prediction at Dehradun (3-, 6-, 9-, and 12-month scales), Chamoli and Tehri Garhwal (1-, 3-, 6-, 9-, and 12-month scales), Haridwar and Pauri Garhwal (1-, 3-, 6-, and 9-month scales), Rudraprayag (1-, 3-, and 6-month scales), and Uttarkashi (3-month scale) stations. The MLPNN model was best at Dehradun (1- and 24- month scales), Tehri Garhwal and Chamoli (24-month scale), Haridwar (12- and 24-month scales), Pauri Garhwal (12-month scale), Rudraprayag (9-, 12-, and 24-month), and Uttarkashi (1- and 6-month scales) stations, while the MLR model was found to be optimal at Pauri Garhwal (24-month scale) and Uttarkashi (9-, 12-, and 24-month scales) stations. Furthermore, the modeling approach can foster a straightforward and trustworthy expert intelligent mechanism for projecting multi-scalar SPI and decision making for remedial arrangements to tackle meteorological drought at the stations under study.
Dielectric Permittivity Model for Polymer–Filler Composite Materials by the Example of Ni- and Graphite-Filled Composites for High-Frequency Absorbing Coatings
Authors: Prokopchuk Artem , Zozulia Ivan , Didenko Yurii , Tatarchuk Dmytro , Heuer Henning , Poplavko Yuriy
Published: February 2021

The suppression of unnecessary radio-electronic noise and the protection of electronic devices from electromagnetic interference by the use of pliable highly microwave radiation absorbing composite materials based on polymers or rubbers filled with conductive and magnetic fillers have been proposed. Since the working frequency bands of electronic devices and systems are rapidly expanding up to the millimeter wave range, the capabilities of absorbing and shielding composites should be evaluated for increasing operating frequency. The point is that the absorption capacity of conductive and magnetic fillers essentially decreases as the frequency increases. Therefore, this paper is devoted to the absorbing capabilities of composites filled with high-loss dielectric fillers, in which absorption significantly increases as frequency rises, and it is possible to achieve the maximum frequency selective of absorption due to electromagnetic and electromechanical resonances.
The Effect of a Phase Change on the Temperature Evolution during the Deposition Stage in Fused Filament Fabrication
Authors: Costa Sidonie F. , Duarte Fernando M. , Covas José A.
Published: February 2021

Additive Manufacturing Techniques such as Fused Filament Fabrication (FFF) produce 3D parts with complex geometries directly from a computer model without the need of using molds and tools, by gradually depositing material(s), usually in layers. Due to the rapid growth of these techniques, researchers have been increasingly interested in the availability of strategies, models or data that may assist process optimization. In fact, 3D printed parts often exhibit limited mechanical performance, which is usually the result of poor bonding between adjacent filaments. In turn, the latter is influenced by the temperature field history during deposition. This study aims at evaluating the influence of the phase change from the melt to the solid state undergone by semi-crystalline polymers such as Polylactic Acid (PLA), on the heat transfer during the deposition stage. The energy equation considering solidification is solved analytically and then inserted into a MatLab® code to model cooling in FFF. The deposition and cooling of simple geometries is studied first, in order to assess the differences in cooling of amorphous and semi-crystalline polymers. Acrylonitrile Butadiene Styrene (ABS) was taken as representing an amorphous material. Then, the deposition and cooling of a realistic 3D part is investigated, and the influence of the build orientation is discussed.
CSF Rhinorrhea: A Rare Clinical Presentation of Choroid Plexus Papilloma
Authors: Mula-Hussain Layth , Malone Julia , dos Santos Marlise P. , Sinclair John , Malone Shawn
Published: February 2021

Choroid plexus papilloma (CPP) is a rare brain tumour occurring mostly in infants and children. Most CPPs are intraventricular and present with symptoms and signs of increased intracranial pressure (ICP). This case report describes a middle-aged female who presented with spontaneous cerebrospinal fluid (CSF) rhinorrhea from a tumour located in the cerebellopontine angle (CPA). She underwent craniotomy with subtotal tumour resection and remained progression and rhinorrhea-free for several years. Upon clinical progression, the patient was treated with Cyberknife stereotactic radiosurgery. The patient clinically improved and demonstrated a favourable radiologic response to radiosurgery.
Immune Checkpoint Inhibition as Primary Adjuvant Therapy for an IDH1-Mutant Anaplastic Astrocytoma in a Patient with CMMRD: A Case Report—Usage of Immune Checkpoint Inhibition in CMMRD
Authors: Rittberg Rebekah , Harlos Craig , Rothenmund Heidi , Das Anirban , Tabori Uri , Sinha Namita , Singh Harminder , Chodirker Bernie , Kim Christina A.
Published: February 2021

Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessive hereditary cancer syndrome due to biallelic germline mutation involving one of the four DNA mismatch repair genes. Here we present a case of a young female with CMMRD, homozygous for the c.2002A>G mutation in the PMS2 gene. She developed an early stage adenocarcinoma of the colon at the age of 14. Surveillance MRI of the brain at age 18 resulted in the detection of an asymptomatic brain cancer. On resection, this was diagnosed as an anaplastic astrocytoma. Due to emerging literature suggesting benefit of immunotherapy in this patient population, she was treated with adjuvant dual immune checkpoint inhibition, avoiding radiation. The patient remains stable with no evidence of progression 20 months after resection. The patient’s clinical course, as well as the rational for considering adjuvant immunotherapy in patients with CMMRD are discussed in this report.
Spatial Niche Expansion at Multiple Habitat Scales of a Tropical Freshwater Turtle in the Absence of a Potential Competitor
Authors: Petrozzi Fabio , Ajong Stephanie N. , Pacini Nic , Dendi Daniele , Bi Sery Gonedele , Fa Julia E. , Luiselli Luca
Published: February 2021

Resource partitioning, the division of limited resources by species to help avoid competition, has been observed in freshwater turtle assemblages in several natural systems but has rarely been studied in tropical African ecosystems. Here, we investigate habitat preferences of two congeneric species in the family Pelomedusidae, Pelusios castaneus and P. cupulatta, in riverine/wetland habitats in the southern Ivory Coast (West Africa). Pelusios castaneus is a widespread species across West-central African savannahs and open forests, whereas P. cupulatta is endemic to the Upper Guinean forest region in West Africa. The two species have a similar diet composition (mainly carnivorous) but diverge considerably in body size, P. cupulatta being much larger. We use hand-fishing-nets and fishing funnel traps to record turtles in 18 distinct sites and analyze habitat preferences by species at two spatial scales. At a macro-habitat scale, P. castaneus is captured mainly in marshlands, whereas P. cupulatta is found in both rivers and wetlands. The two species differ significantly in their use of: (i) banks (P. castaneus being found primarily in spots with grassy banks, whereas P. cupulatta is found in spots with forested banks), and (ii) aquatic vegetation (P. cupulatta prefers spots with more abundant aquatic vegetation than P. castaneus), but both species select sites with no or moderate current. Additionally, in sites where P. cupulatta is not found, P. castaneus expands its spatial niche at multiple habitat scales, notably invading waterbodies with forested banks. Our results suggest that these two Pelomedusid turtle species potentially compete in the freshwater habitats in the southern Ivory Coast.
Primary Dermal Melanoma: A Rare Clinicopathological Variant Mimicking Metastatic Melanoma
Authors: Simonetti Oriana , Molinelli Elisa , Brisigotti Valerio , Brancorsini Donatella , Talevi Davide , Offidani Annamaria
Published: February 2021

Primary dermal melanoma (PDM) is a rare distinct variant of cutaneous melanoma, predominantly occurring on the extremities of young or middle-aged adults. In comparison to conventional melanoma, PDM is characterized by unexpectedly prolonged survival and long-term survival. Thus, correct identification of this variant is crucial to avoid potential misdiagnosis and establish correct treatment and follow-up. In addition, no consensus and specific guidelines exist on the management of this peculiar subtype of cutaneous melanoma.
Targeting NSP16 Methyltransferase for the Broad-Spectrum Clinical Management of Coronaviruses: Managing the Next Pandemic
Authors: Alshiraihi Ilham M. , Klein Gerald L. , Brown Mark A.
Published: February 2021

With the approval and distribution of demonstrably safe COVID-19 vaccines bearing exceptionally high efficacy profiles, it may be tempting to envision a return to “normal” in the coming months. However, if there is one lesson to be learned from the ongoing pandemic, it is that, in a world of evolving zoonotic viruses, we must be better prepared for the next deadly outbreak. While the acute nature of the COVID-19 pandemic demanded a highly specific approach, it is advisable to consider the breadth of seemingly endless possibilities in our approach to managing the next inevitable occurrence of an outbreak. Though there is little chance of discovering a “magic pill” to combat all future pathogens, the highly conserved nature of non-surface viral proteins exposes an “Achilles’ heel” in the structural genome of viral pathogens. Herein, we consider the potential of targeting such proteins to develop broad-spectrum therapeutics for the future. To illustrate this point, we outline the therapeutic potential of targeting the nonstructural protein 16 methyltransferase, which is conserved across most coronaviruses.
Testosterone/Epitestosterone Ratios—Further Hints to Explain Hyperandrogenemia in Children with Autism
Authors: Gasser Benedikt , Kurz Johann , Mohaupt Markus
Published: February 2021

Background: Epitestosterone [E] has for a long time been considered as a biologically inactive androgen. However, recently a distinct antiandrogenic activity of this naturally occurring endogenous epimer of Testosterone has been demonstrated. Especially the ratios of testosterone/epitestosterone (T/E) seem to be key as inhibition of epitestosterone on androgen activity was postulated. As in autism, a higher androgen activity was implied. We, therefore, suggested higher levels of T/E ratios of children with autism versus children with typical development. Methods: Urine probes of 22 girls with autism (BMI 18.7 ± 4.3; average age 12.3 ± 3.8 years) and a sample of 51 controls (BMI 17.0 ± 2.6; average age 11.9 ± 4 years), as well as 61 boys with autism (BMI 17.04 ± 2. average age 11.9 ± 2.5 years) and 61 control boys (BMI 17.0 ± 2.6; average age 11.1 ± 3.0 years), were analyzed with gas chromatography mass spectrometry. RESULTS: The average T/E ratio of all boys with autism was 2.5 ± 1.8 versus 2.4 ± 1.3 in boys with typical development, respectively. No significant difference between boys with autism versus boys with typical development could be detected (p = 0.977). In girls with autism, the average T/E ratio was 1.4 ± 0.9 versus 2.0 ± 1.4 in girls with typical development, whereby a significant difference could be detected (p = 0.0285). Further, polynomial analysis of the third degree were conducted, showing a dependence from age with reasonable coefficients of determination (0.075 < R2 < 0.22, all samples). Discussion: As encompassing steroid hormone analysis are expensive and work-intensive, we hoped to find an easily applicable biomarker to support diagnostics in autism. However, as a relatively small sample of only 22 girls with autism were analyzed and menstrual cycle and pubertal status were only partly controllable through the matching of BMI and age, the question arises if it was an incidental finding. Nevertheless, one suggestion might be that epitestosterone has the effect of a competitive inhibition on the androgen receptor, which would probably help to explain the higher prevalence of autism in boys as compared to girls. Presumably, as no significant difference was detected in boys, this effect might not be as relevant from a steroid hormone perspective, and other effects such as altered 17/20-hydroxylase activity as previously shown in boys and girls with autism seem to have more relevance. Analysis of larger samples, including plenty of metabolites and enzymatic cascades, as well as the role of backdoor pathway activity of androgen synthesis of girls with autism, are demanded in order to validate current findings of altered steroid hormones in autism.
A Longitudinal Study on the Relationship of Oral Health at 4 Years of Age with That in Adulthood
Authors: Yamada Sho , Sakashita Reiko , Ogura Mikinori , Nakanishi Eiko , Sato Takuichi
Published: February 2021

This longitudinal study aimed to clarify the relationship of oral health in infancy with that in adulthood among participants who were the subjects of the oral health promotion project (OHPP) conducted in Miyako Island, Okinawa Prefecture, Japan, since 1984. Twenty-seven subjects, around 35 years of age, were examined for dental caries, periodontal diseases (community periodontal index), dental plaque, occlusion, and bite-force and compared with those at 4 and 13–15 years of age. The dental caries status and maximum bite force in adulthood was significantly reflected for those at 4 and 13–15 years of age (p < 0.05). CPI in adulthood was related to the dental caries status at 4 and 13–15 years of age but not to the gingival score at 4 years of age, and it was weakly related to the gingival score at 13–15 years (r = 0.264, p > 0.05). Most of the normal occlusion at 4 years of age became normal permanent occlusion in adulthood (88.9%). Most of the cases involving the discrepancy factor retained the same condition in both the deciduous and permanent dentitions (83.3%) (p < 0.001). Those who participated in the OHPP soon after birth showed significantly fewer DMFT (p < 0.05) compared with those who did not. This study revealed that oral health at 4 years of age was related to that in adulthood, suggesting that fostering good oral health soon after birth is of great importance.
Minimum Divergence Estimators, Maximum Likelihood and the Generalized Bootstrap
Authors: Broniatowski Michel
Published: February 2021

This paper states that most commonly used minimum divergence estimators are MLEs for suited generalized bootstrapped sampling schemes. Optimality in the sense of Bahadur for associated tests of fit under such sampling is considered.
Searching for a Theory That Fits the Data: A Personal Research Odyssey
Authors: Juselius Katarina
Published: February 2021

This survey paper discusses the Cointegrated Vector AutoRegressive (CVAR) methodology and how it has evolved over the past 30 years. It describes major steps in the econometric development, discusses problems to be solved when confronting theory with the data, and, as a solution, proposes a so-called theory-consistent CVAR scenario. A number of early CVAR applications are motivated by the urge to find out why the empirical results did not support Milton Friedman’s concept of monetary inflation. The paper also proposes a method for combining partial CVAR analyses into a large-scale macroeconomic model. It argues that an empirically-based approach to macroeconomics preferably should be based on Keynesian disequilibrium economics, where imperfect knowledge expectations replace so called rational expectations and where the financial sector plays a key role for understanding the long persistent movements in the data. Finally, the paper argues that the CVAR is potentially a candidate for Haavelmo’s “design of experiment for passive observations” and provides several illustrations.
Moderate Innovator Trap—Does the Convergence of Innovation Performance Occur in the World Economy?
Authors: Kowalski Arkadiusz Michał , Rybacki Jakub
Published: February 2021

Based on β and σ convergence analysis, we find a high persistence of innovation gaps for international innovation indices reported by the European Commission. Our research confirms the diverging scientific potential across the analyzed economies. Estimation provides evidence of convergence in the case of R&D expenses and the relative position on the global technological frontier. We propose a simple fixed effect panel regression measuring relative innovativeness potential. Our model suggests that current ranking leaders, i.e., Nordic countries (Sweden, Denmark, and Finland) and Germany, are likely to further outpace the United States. Central and Eastern European countries are achieving the greatest relative gains but are unlikely to exceed 70% of US potential. Peripheral European countries, South Africa, Turkey, and Russia are projected to further lose their innovativeness position despite their weaker initial position.
An Investigation of EAP Teachers’ Views and Experiences of E-Learning Technology
Authors: Dhillon Sundeep , Murray Neil
Published: February 2021

The near universal use of electronic learning (e-learning) in higher education (HE) today requires that students and teachers are equipped with the requisite digital literacy skills. The small-scale pilot study we report on here explored the views and experiences of EAP (English for Academic Purposes) teachers regarding their development of digital literacy skills, their application of e-learning technology in their teaching, and their perceptions of its value as a learning tool—areas on which there has been little research to date. A convergent parallel mixed methods approach was adopted, in which a survey was administered to the research participants and a follow-up focus group conducted. The data were analysed, with findings revealing that the EAP practitioners surveyed utilised a range of online tools such as video, plagiarism software and corpus linguistics tools. A number of benefits and limitations associated with e-learning were cited by participants, including increased student engagement and motivation, the development of learner autonomy, and the cultural capital it represented in respect of students’ future careers. Meanwhile, the limitations identified included a lack of time for teachers to develop digital literacy and insufficient pre- and in-service training opportunities focused on the effective use of digital technologies and managing technical issues. We conclude with a series of recommendations to facilitate EAP teachers’ development and use of e-learning in their practice.