bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Data Augmentation and Time-Scale Modification to Improve ASR of Children’s Speech in Noisy Environments
Authors: Kathania Hemant Kumar , Kadiri Sudarsana Reddy , Alku Paavo , Kurimo Mikko
Published: September 2021

Current ASR systems show poor performance in recognition of children’s speech in noisy environments because recognizers are typically trained with clean adults’ speech and therefore there are two mismatches between training and testing phases (i.e., clean speech in training vs. noisy speech in testing and adult speech in training vs. child speech in testing). This article studies methods to tackle the effects of these two mismatches in recognition of noisy children’s speech by investigating two techniques: data augmentation and time-scale modification. In the former, clean training data of adult speakers are corrupted with additive noise in order to obtain training data that better correspond to the noisy testing conditions. In the latter, the fundamental frequency (F0) and speaking rate of children’s speech are modified in the testing phase in order to reduce differences in the prosodic characteristics between the testing data of child speakers and the training data of adult speakers. A standard ASR system based on DNN–HMM was built and the effects of data augmentation, F0 modification, and speaking rate modification on word error rate (WER) were evaluated first separately and then by combining all three techniques. The experiments were conducted using children’s speech corrupted with additive noise of four different noise types in four different signal-to-noise (SNR) categories. The results show that the combination of all three techniques yielded the best ASR performance. As an example, the WER value averaged over all four noise types in the SNR category of 5 dB dropped from 32.30% to 12.09% when the baseline system, in which no data augmentation or time-scale modification were used, was replaced with a recognizer that was built using a combination of all three techniques. In summary, in recognizing noisy children’s speech with ASR systems trained with clean adult speech, considerable improvements in the recognition performance can be achieved by combining data augmentation based on noise addition in the system training phase and time-scale modification based on modifying F0 and speaking rate of children’s speech in the testing phase.
An Initial Machine Learning-Based Victim’s Scream Detection Analysis for Burning Sites
Authors: Saeed Fairuz Samiha , Bashit Abdullah Al , Viswanathan Vishu , Valles Damian
Published: September 2021

Fire incidents are responsible for severe damage and thousands of deaths every year all over the world. Extreme temperatures, low visibility, toxic gases, and unknown locations of victims create difficulties and delays in rescue operations, escalating the risk of injury or death. It is time-critical to detect the victims trapped inside the burning sites for facilitating the rescue operations. This research work presents an audio-based automated system for victim detection in fire emergencies, investigating two machine learning (ML) methods: support vector machines (SVM) and long short-term memory (LSTM). The performance of these two ML techniques has been evaluated based on a variety of performance metrics. Our analyses show that both ML methods provide superior scream detection performance, with SVM slightly overperforming LSTM. Because of its lower complexity, SVM is a better candidate for real-time implementation in our autonomous embedded system vehicle (AESV).
Recent Advances and Insights into Bromelain Processing, Pharmacokinetics and Therapeutic Uses
Authors: Colletti Alessandro , Li Shuyi , Marengo Mauro , Adinolfi Salvatore , Cravotto Giancarlo
Published: September 2021

Bromelain is a mixture of proteolytic enzymes that is extracted primarily from pineapples. It is present in almost all the aerial parts of the plant—the peels, leaves, stems and fruit—although only the fruit and stems contain significant amounts. The market-demand for bromelain is quickly increasing, especially in the health sector as it can be used as a drug and/or nutraceutical. Although the complete molecular mechanism has not been fully identified, bromelain possesses several properties, including anti-inflammatory, anti-oedema, antithrombotic and fibrinolytic, mucolytic, anticancer and cicatrizing effects that have been evaluated in several clinical trials. However, one of the main limitations for the clinical use of this supplement is the varying composition of extracts, which leads to heterogeneity in results and, therefore, difficulty in making evidence-based prescriptions. In fact, different geographic locations, land and modes of cultivation, as well as extraction methods, can all give extracts with different activities, depending on the plant part used. Additionally, although novel extraction techniques have been developed to improve bromelain purification and extraction and give higher yields without loss in enzymatic activity, these methods are still expensive and challenging. This review will describe the state of the art in the main conventional and unconventional extraction and purification methods of bromelain and discuss the advantages and limitations of these strategies. Pharmacokinetic and pharmacodynamic profiles and the clinical applications that have arisen from randomized controlled clinical trials are also discussed. Finally, future perspectives for bromelain extracts will be presented.
Flattening of the Density Spectrum in Compressible Hall-MHD Simulations
Authors: Montagud-Camps Victor , Němec František , Šafránková Jana , Němeček Zdeněk , Verdini Andrea , Grappin Roland , Papini Emanuele , Franci Luca
Published: September 2021

Observations of proton density fluctuations of the solar wind at 1 au have shown the presence of a decade-long transition region of the density spectrum above sub-ion scales, characterized by a flattening of the spectral slope. We use the proton density fluctuations data collected by the BMSW instrument on-board the Spektr-R satellite in order to delimit the plasma parameters under which the transition region can be observed. Under similar plasma conditions to those in observations, we carry out 3D compressible magnetohydrodynamics (MHD) and Hall-MHD numerical simulations and find that Hall physics is necessary to generate the transition region. The analysis of the kω power spectrum in the Hall-MHD simulation indicates that the flattening of the density spectrum is associated with fluctuations having frequencies smaller than the ion cyclotron frequency.
Diagnostic Relations between Pressure and Entropy Perturbations for Acoustic and Entropy Modes
Authors: Leble Sergey , Smirnova Ekaterina
Published: September 2021

Diagnostics and decomposition of atmospheric disturbances in a planar flow are considered and applied to numerical modelling with the direct possibility to use in atmosphere monitoring especially in such strong events which follow magnetic storms and other large scale atmospheric phenomena. The study examines a situation in which the stationary equilibrium temperature of a gas may depend on a vertical coordinate, which essentially complicates the diagnostics. The relations connecting perturbations for acoustic and entropy (stationary) modes are analytically established and led to the solvable diagnostic equations. These equations specify acoustic and entropy modes in an arbitrary stratified gas under the condition of stability. The diagnostic relations are independent of time and specify the acoustic and the entropy modes. They provide the ability to decompose the total vector of perturbations into acoustic and non-acoustic (entropy) parts uniquely at any instant within the total accessible heights range. As a prospective model, we consider the diagnostics at the height interval 120–180 km, where the equilibrium temperature of a gas depends linearly on the vertical coordinate. For such a heights range it is possible to proceed with analytical expressions for pressure and entropy perturbations of gas variables. Individual profiles of acoustic and entropy parts for some data are illustrated by the plots for the pure numerical data against those obtained by the model. The total energy of a flow is determined for both approaches and its vertical profiles are compared.
Qualitative and Quantitative Resistance against Early Blight Introgressed in Potato
Authors: Wolters Pieter J. , Wouters Doret , Kromhout Emil J. , Huigen Dirk Jan , Visser Richard G. F. , Vleeshouwers Vivianne G. A. A.
Published: September 2021

Early blight is a disease of potato that is caused by Alternaria species, notably A. solani. The disease is usually controlled with fungicides. However, A. solani is developing resistance against fungicides, and potato cultivars with genetic resistance to early blight are currently not available. Here, we identify two wild potato species, which are both crossable with cultivated potato (Solanum tuberosum), that show promising resistance against early blight disease. The cross between resistant S. berthaultii and a susceptible diploid S. tuberosum gave rise to a population in which resistance was inherited quantitatively. S. commersonii subsp. malmeanum was also crossed with diploid S. tuberosum, despite a differing endosperm balance number. This cross resulted in triploid progeny in which resistance was inherited dominantly. This is somewhat surprising, as resistance against necrotrophic plant pathogens is usually a quantitative trait or inherited recessively according to the inverse-gene-for-gene model. Hybrids with high levels of resistance to early blight are present among progeny from S. berthaultii as well as S. commersonii subsp. malmeanum, which is an important step towards the development of a cultivar with natural resistance to early blight.
The Activity of Chosen Antioxidant Enzymes in Ostrich Meat in Relation to the Type of Packaging and Storage Time in Refrigeration
Authors: Horbańczuk Olaf , Jóźwik Artur , Wyrwisz Jarosław , Marchewka Joanna , Atanasov Atanas , Wierzbicka Agnieszka
Published: September 2021

The aim of the study was to investigate the changes in the activity of antioxidant enzymes, i.e., superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity in ostrich meat, as influenced by various packaging systems and storage time under refrigeration. Three packaging methods were used: vacuum packaging (VP) and modified atmosphere packaging (MAP) in two combinations of gases, MAP1 (40% O2/40% CO2/20% N2) and MAP2 (60% O2/30% CO2/10% N2). Meat samples were taken from the M. ilifibularis (IF) muscles of eight ostriches in each treatment group. The meat samples were stored in a refrigerator in 2 °C and analyzed at days 0, 4, 8, 12 and 16. The lowest level of SOD activity during storage was observed in ostrich muscles packed in vacuum, as compared to MAP1 and MAP2. In turn, the highest increase in GPx activity was recorded in VP, especially up to day 8 of storage, when this parameter reached maximum value (54.37). GR increased up to the eighth day of storage in MAP1 and VP. Between the 12th and 16th days of storage, stabilization of the GR activity level was observed only in VP, while under MAP1, it further decreased. DPPH remained relatively stable until the eighth day of storage and after this period, a decrease in this parameter was recorded, reaching the lowest value on day 12 for all types of packaging systems.
Re-Evaluation of Combinational Efficacy and Synergy of the Italian Protocol In Vitro: Are We Truly Optimizing Benefit or Permitting Unwanted Toxicity?
Authors: Subramanian Chitra , McCallister Reid , Kuszynski Dawn , Cohen Mark S.
Published: September 2021

Introduction: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy, with very poor prognosis as a majority of the patients have advanced disease at the time of diagnosis. Currently, adjuvant therapy for most patients consists of either mitotane (M) alone or in combination with multi-drug chemotherapeutics such as etoposide (E), doxorubicin (D), and cisplatin (P), known as the Italian protocol (IP; EDPM). This multi-drug treatment regimen, however, carries significant toxicity potential for patients. One way to improve toxicity profiles with these drugs in combination is to understand where their synergy occurs and over what dosing range so that lower dose regimens could be applied in combination with equal or improved efficacy. We hypothesize that a better understanding of the synergistic effects as well as the regulation of steroidogenic enzymes during combination therapy may provide more optimized combinational options with good potency and lower toxicity profiles. Methods: Two human ACC cell lines, NCI-H295R (hormonally active) and SW13 (hormonally inactive), were grown in 2D culture in appropriate growth medium. The viability of the cells after treatment with varying concentrations of the drugs (E, D, and P) either alone or in combinations with M was determined using the CellTiter Glow assay after 72 h, and the combination index for each was calculated using Compusyn by the Chou–Talalay method. The expression levels of enzymes associated with steroidogenesis were evaluated by RT-PCR in NCI-H295R. Results: When both cell lines were treated with M (ranging 25–50 μM), +E (ranging 18.75–75 μM), and +D (ranging 0.625–2.5 μM) we observed a synergistic effect (CI < 1) with potency equivalent to the full Italian protocol (IP), whereas combining M + P + D had an antagonistic effect (CI > 1) indicating the negative effect of adding cisplatin in the combination. Comparing the hormonally active and inactive cell lines, M + P + E was antagonistic in NCI-H295R and synergistic in SW13. Treatment of NCI-H295R cells with antagonistic combinations (M + P + D, M + P + E) resulted in a significant decrease in the levels of steroidogenic enzymes STAR, CYP11A1, and CYP21A2 compared to IP (p < 0.05) while M + E + D resulted in increased expression or no significant effect compared to IP across all genes tested. Conclusions: The synergistic effect for M + E + D was significant and equivalent in potency to the full IP in both cell lines and resulted in a steroidogenic gene expression profile similar to or better than that of full IP, warranting further evaluation. Future in vivo evaluation of the combination of M + E + D (with removal of P from the IP regimen) may lower toxicity while maintaining anticancer efficacy in ACC.
A Role of Stress Sensor Nrf2 in Stimulating Thermogenesis and Energy Expenditure
Authors: Chang Seo-Hyuk , Lee Jeong-Soo , Yun Ui Jeong , Park Kye Won
Published: September 2021

During chronic cold stress, thermogenic adipocytes generate heat through uncoupling of mitochondrial respiration from ATP synthesis. Recent discovery of various dietary phytochemicals, endogenous metabolites, synthetic compounds, and their molecular targets for stimulating thermogenesis has provided promising strategies to treat or prevent obesity and its associated metabolic diseases. Nuclear factor E2 p45-related factor 2 (Nrf2) is a stress response protein that plays an important role in obesity and metabolisms. However, both Nrf2 activation and Nrf2 inhibition can suppress obesity and metabolic diseases. Here, we summarized and discussed conflicting findings of Nrf2 activities accounting for part of the variance in thermogenesis and energy metabolism. We also discussed the utility of Nrf2-activating mechanisms for their potential applications in stimulating energy expenditure to prevent obesity and improve metabolic deficits.
Outcome of Community-Based Early Intervention and Rehabilitation for Children with Cerebral Palsy in Rural Bangladesh: A Quasi-Experimental Study
Authors: Karim Tasneem , Muhit Mohammad , Jahan Israt , Galea Claire , Morgan Catherine , Smithers-Sheedy Hayley , Badawi Nadia , Khandaker Gulam
Published: September 2021

We evaluated the outcome of a community-based early intervention and habilitation for children with cerebral palsy (CP) in Bangladesh. Children registered on the Bangladesh CP Register (BCPR) were recruited in two groups for this study: Group A received a comprehensive six-month long community-based caregiver-led intervention program at the “Shishu Shorgo” (Bengali title, which translates to ‘Children’s Heaven’) Early Intervention and Rehabilitation Centres developed to support participants from the BCPR. Group B received standard care. A quasi-experimental study was conducted. Data were obtained at baseline, at the end of the program (i.e., 6 months), and at a 12-month follow-up. Outcome measures for children included gross motor functional measure (GMFM-66), Communication Function Classification System (CFCS), and Viking Speech Scale (VSS) and, for adult caregivers, the depression, anxiety, and stress scale (DASS 21). Between October 2016 and March 2017, 156 children with CP were recruited (77 in Group A and 79 in Group B). The total score of GMFM-66, CFCS level, and VSS level significantly improved statistically in Group A (p < 0.05 for all) and deteriorated in Group B (p < 0.001, p = 0.095, p = 0.232). The intervention showed promising outcomes particularly for children with CP under five years of age. There is a need for caregiver-led community-based programs for children with CP in LMICs.
Bihemispheric Navigated Transcranial Magnetic Stimulation Mapping for Action Naming Compared to Object Naming in Sentence Context
Authors: Ohlerth Ann-Katrin , Bastiaanse Roelien , Negwer Chiara , Sollmann Nico , Schramm Severin , Schröder Axel , Krieg Sandro M.
Published: September 2021

Preoperative language mapping with navigated transcranial magnetic stimulation (nTMS) is currently based on the disruption of performance during object naming. The resulting cortical language maps, however, lack accuracy when compared to intraoperative mapping. The question arises whether nTMS results can be improved, when another language task is considered, involving verb retrieval in sentence context. Twenty healthy German speakers were tested with object naming and a novel action naming task during nTMS language mapping. Error rates and categories in both hemispheres were compared. Action naming showed a significantly higher error rate than object naming in both hemispheres. Error category comparison revealed that this discrepancy stems from more lexico-semantic errors during action naming, indicating lexico-semantic retrieval of the verb being more affected than noun retrieval. In an area-wise comparison, higher error rates surfaced in multiple right-hemisphere areas, but only trends in the left ventral postcentral gyrus and middle superior temporal gyrus. Hesitation errors contributed significantly to the error count, but did not dull the mapping results. Inclusion of action naming coupled with a detailed error analysis may be favorable for nTMS mapping and ultimately improve accuracy in preoperative planning. Moreover, the results stress the recruitment of both left- and right-hemispheric areas during naming.
Intervention Strategies for the Seismic Improvement of Masonry Buildings Based on FME Validation: The Case of a Terraced Building Struck by the 2016 Central Italy Earthquake
Authors: Valluzzi Maria , Sbrogiò Luca , Saretta Ylenia
Published: September 2021

Residential masonry buildings represent a large stock among highly vulnerable structures in medium–high seismic hazard areas, often built without any anti-seismic provisions. Their rehabilitation and/or strengthening according to optimised intervention strategies is topical and may contribute to revaluating zones characterized by depopulation phenomena. In this paper, a terraced building struck by the 2016 Central Italy earthquake is analysed through a frame by macro element (FME) model. The building is composed of six two-storey units made of stone and clay block masonry walls and semi-rigid diaphragms. The numerical model was calibrated based on the damage pattern caused by the earthquake and then used to carry out parametric analyses on the strengthened conditions by simulating both one unit and the entire terrace. The effects of interventions applied to either vertical or horizontal components, both singularly and in combination, were analysed in terms of nonlinear static analyses, and quantified by a performance factor, according to the upgraded seismic code in Italy. Kinematic analyses also completed the assessment of the building. Results compared the capacity of interventions in attaining the targets defined for improvement at both local and overall levels.
NSCLC Biomarkers to Predict Response to Immunotherapy with Checkpoint Inhibitors (ICI): From the Cells to In Vivo Images
Authors: Liberini Virginia , Mariniello Annapaola , Righi Luisella , Capozza Martina , Delcuratolo Marco Donatello , Terreno Enzo , Farsad Mohsen , Volante Marco , Novello Silvia , Deandreis Désirée
Published: September 2021

Lung cancer remains the leading cause of cancer-related death, and it is usually diagnosed in advanced stages (stage III or IV). Recently, the availability of targeted strategies and of immunotherapy with checkpoint inhibitors (ICI) has favorably changed patient prognosis. Treatment outcome is closely related to tumor biology and interaction with the tumor immune microenvironment (TME). While the response in molecular targeted therapies relies on the presence of specific genetic alterations in tumor cells, accurate ICI biomarkers of response are lacking, and clinical outcome likely depends on multiple factors that are both host and tumor-related. This paper is an overview of the ongoing research on predictive factors both from in vitro/ex vivo analysis (ranging from conventional pathology to molecular biology) and in vivo analysis, where molecular imaging is showing an exponential growth and use due to technological advancements and to the new bioinformatics approaches applied to image analyses that allow the recovery of specific features in specific tumor subclones.
Harnessing the Immune System to Fight Multiple Myeloma
Authors: Krejcik Jakub , Barnkob Mike Bogetofte , Nyvold Charlotte Guldborg , Larsen Thomas Stauffer , Barington Torben , Abildgaard Niels
Published: September 2021

Multiple myeloma (MM) is a heterogeneous plasma cell malignancy differing substantially in clinical behavior, prognosis, and response to treatment. With the advent of novel therapies, many patients achieve long-lasting remissions, but some experience aggressive and treatment refractory relapses. So far, MM is considered incurable. Myeloma pathogenesis can broadly be explained by two interacting mechanisms, intraclonal evolution of cancer cells and development of an immunosuppressive tumor microenvironment. Failures in isotype class switching and somatic hypermutations result in the neoplastic transformation typical of MM and other B cell malignancies. Interestingly, although genetic alterations occur and evolve over time, they are also present in premalignant stages, which never progress to MM, suggesting that genetic mutations are necessary but not sufficient for myeloma transformation. Changes in composition and function of the immune cells are associated with loss of effective immune surveillance, which might represent another mechanism driving malignant transformation. During the last decade, the traditional view on myeloma treatment has changed dramatically. It is increasingly evident that treatment strategies solely based on targeting intrinsic properties of myeloma cells are insufficient. Lately, approaches that redirect the cells of the otherwise suppressed immune system to take control over myeloma have emerged. Evidence of utility of this principle was initially established by the observation of the graft-versus-myeloma effect in allogeneic stem cell-transplanted patients. A variety of new strategies to harness both innate and antigen-specific immunity against MM have recently been developed and intensively tested in clinical trials. This review aims to give readers a basic understanding of how the immune system can be engaged to treat MM, to summarize the main immunotherapeutic modalities, their current role in clinical care, and future prospects.
Current Immunotherapeutic Strategies for the Treatment of Glioblastoma
Authors: Dapash Mark , Castro Brandyn , Hou David , Lee-Chang Catalina
Published: September 2021

Glioblastoma (GBM) is a lethal primary brain tumor. Despite extensive effort in basic, translational, and clinical research, the treatment outcomes for patients with GBM are virtually unchanged over the past 15 years. GBM is one of the most immunologically “cold” tumors, in which cytotoxic T-cell infiltration is minimal, and myeloid infiltration predominates. This is due to the profound immunosuppressive nature of GBM, a tumor microenvironment that is metabolically challenging for immune cells, and the low mutational burden of GBMs. Together, these GBM characteristics contribute to the poor results obtained from immunotherapy. However, as indicated by an ongoing and expanding number of clinical trials, and despite the mostly disappointing results to date, immunotherapy remains a conceptually attractive approach for treating GBM. Checkpoint inhibitors, various vaccination strategies, and CAR T-cell therapy serve as some of the most investigated immunotherapeutic strategies. This review article aims to provide a general overview of the current state of glioblastoma immunotherapy. Information was compiled through a literature search conducted on PubMed and clinical trials between 1961 to 2021.
Hepatic Cancer Stem Cells: Molecular Mechanisms, Therapeutic Implications, and Circulating Biomarkers
Authors: Gramantieri Laura , Giovannini Catia , Suzzi Fabrizia , Leoni Ilaria , Fornari Francesca
Published: September 2021

Hepatocellular carcinoma (HCC) is one of the deadliest cancers. HCC is associated with multiple risk factors and is characterized by a marked tumor heterogeneity that makes its molecular classification difficult to apply in the clinics. The lack of circulating biomarkers for the diagnosis, prognosis, and prediction of response to treatments further undermines the possibility of developing personalized therapies. Accumulating evidence affirms the involvement of cancer stem cells (CSCs) in tumor heterogeneity, recurrence, and drug resistance. Owing to the contribution of CSCs to treatment failure, there is an urgent need to develop novel therapeutic strategies targeting, not only the tumor bulk, but also the CSC subpopulation. Clarification of the molecular mechanisms influencing CSC properties, and the identification of their functional roles in tumor progression, may facilitate the discovery of novel CSC-based therapeutic targets to be used alone, or in combination with current anticancer agents, for the treatment of HCC. Here, we review the driving forces behind the regulation of liver CSCs and their therapeutic implications. Additionally, we provide data on their possible exploitation as prognostic and predictive biomarkers in patients with HCC.
Genomic Characterization and Therapeutic Targeting of HPV Undetected Cervical Carcinomas
Authors: Ruiz Fiona J. , Sundaresan Aishwarya , Zhang Jin , Pedamallu Chandra S. , Halle Mari K. , Srinivasasainagendra Vinodh , Zhang Jianqing , Muhammad Naoshad , Stanley Jennifer , Markovina Stephanie , Tiwari Hemant K. , Grigsby Perry W. , Krakstad Camilla , Schwarz Julie K. , Ojesina Akinyemi I.
Published: September 2021

Cervical cancer tumors with undetectable HPV (HPVU) have been underappreciated in clinical decision making. In this study, two independent CC datasets were used to characterize the largest cohort of HPVU tumors to date (HPVU = 35, HPV+ = 430). Genomic and transcriptome tumor profiles and patient survival outcomes were compared between HPV+ and HPVU tumors. In vitro analyses were done to determine efficacy of the selective CDK4/6 inhibitor palbociclib on HPVU cancer cell lines. Patients with HPVU CC tumors had worse progression-free and overall survival outcomes compared to HPV+ patients. TP53, ARID1A, PTEN, ARID5B, CTNNB1, CTCF, and CCND1 were identified as significantly mutated genes (SMGs) enriched in HPVU tumors, with converging functional roles in cell cycle progression. In vitro HPVU, but not HPV+, cancer cell lines with wild type RB1 were sensitive to palbociclib monotherapy. These results indicate that HPVU status can be translated into the clinic as a predictive biomarker of poor patient response to standard of care treatments. We suggest primary cervix tumors be routinely tested for HPV prior to treatment to identify patients who will benefit from more aggressive precision-driven therapy. Our results identify palbociclib as a lead candidate as an alternative treatment strategy for HPVU CC patients.
Integrating Cancer Vaccines in the Standard-of-Care of Ovarian Cancer: Translating Preclinical Models to Human
Authors: Chiang Cheryl Lai-Lai , Rovelli Raphaël , Sarivalasis Apostolos , Kandalaft Lana E.
Published: September 2021

As the majority of ovarian cancer (OC) patients are diagnosed with metastatic disease, less than 40% will survive past 5 years after diagnosis. OC is characterized by a succession of remissions and recurrences. The most promising time point for immunotherapeutic interventions in OC is following debulking surgery. Accumulating evidence shows that T cells are important in OC; thus, cancer vaccines capable of eliciting antitumor T cells will be effective in OC treatment. In this review, we discuss different cancer vaccines and propose strategies for their incorporation into the OC standard-of-care regimens. Using the murine ID8 ovarian tumor model, we provide evidence that a cancer vaccine can be effectively combined with OC standard-of-care to achieve greater overall efficacy. We demonstrate several important similarities between the ID8 model and OC patients, in terms of response to immunotherapies, and the ID8 model can be an important tool for evaluating combinatorial regimens and clinical trial designs in OC. Other emerging models, including patient-derived xenograft and genetically engineered mouse models, are continuing to improve and can be useful for evaluating cancer vaccination therapies in the near future. Here, we provide a comprehensive review of the completed and current clinical trials evaluating cancer vaccines in OC.
Mutations in MYBPC3 and MYH7 in Association with Brugada Type 1 ECG Pattern: Overlap between Brugada Syndrome and Hypertrophic Cardiomyopathy?
Authors: Farnè Marianna , Balla Cristina , Margutti Alice , Selvatici Rita , De Raffele Martina , Di Domenico Assunta , Imbrici Paola , De Maria Elia , Biffi Mauro , Bertini Matteo , Rapezzi Claudio , Ferlini Alessandra , Gualandi Francesca
Published: September 2021

Brugada syndrome (BrS) is an inherited disorder with high allelic and genetic heterogeneity clinically characterized by typical coved-type ST segment elevation at the electrocardiogram (ECG), which may occur either spontaneously or after provocative drug testing. BrS is classically described as an arrhythmic condition occurring in a structurally normal heart and is associated with the risk of ventricular fibrillation and sudden cardiac death (SCD). We studied five patients with spontaneous or drug-induced type 1 ECG pattern, variably associated with symptoms and a positive family history through a Next Generation Sequencing panels approach, which includes genes of both channelopathies and cardiomyopathies. We identified variants in MYBPC3 and in MYH7, hypertrophic cardiomyopathy (HCM) genes (MYBPC3: p.Lys1065Glnfs*12 and c.1458-1G > A, MYH7: p.Arg783His, p.Val1213Met, p.Lys744Thr). Our data propose that Brugada type 1 ECG may be an early electrocardiographic marker of a concealed structural heart disease, possibly enlarging the genotypic overlap between Brugada syndrome and cardiomyopathies.
Cep192, a Novel Missing Link between the Centrosomal Core and Corona in Dictyostelium Amoebae
Authors: Pitzen Valentin , Sander Sophia , Baumann Otto , Gräf Ralph , Meyer Irene
Published: September 2021

The Dictyostelium centrosome is a nucleus-associated body with a diameter of approx. 500 nm. It contains no centrioles but consists of a cylindrical layered core structure surrounded by a microtubule-nucleating corona. At the onset of mitosis, the corona disassembles and the core structure duplicates through growth, splitting, and reorganization of the outer core layers. During the last decades our research group has characterized the majority of the 42 known centrosomal proteins. In this work we focus on the conserved, previously uncharacterized Cep192 protein. We use superresolution expansion microscopy (ExM) to show that Cep192 is a component of the outer core layers. Furthermore, ExM with centrosomal marker proteins nicely mirrored all ultrastructurally known centrosomal substructures. Furthermore, we improved the proximity-dependent biotin identification assay (BioID) by adapting the biotinylase BioID2 for expression in Dictyostelium and applying a knock-in strategy for the expression of BioID2-tagged centrosomal fusion proteins. Thus, we were able to identify various centrosomal Cep192 interaction partners, including CDK5RAP2, which was previously allocated to the inner corona structure, and several core components. Studies employing overexpression of GFP-Cep192 as well as depletion of endogenous Cep192 revealed that Cep192 is a key protein for the recruitment of corona components during centrosome biogenesis and is required to maintain a stable corona structure.
Recent Advances in Silicon FET Devices for Gas and Volatile Organic Compound Sensing
Authors: Mukherjee Anwesha , Rosenwaks Yossi
Published: September 2021

Highly sensitive and selective gas and volatile organic compound (VOC) sensor platforms with fast response and recovery kinetics are in high demand for environmental health monitoring, industry, and medical diagnostics. Among the various categories of gas sensors studied to date, field effect transistors (FETs) have proved to be an extremely efficient platform due to their miniaturized form factor, high sensitivity, and ultra-low power consumption. Despite the advent of various kinds of new materials, silicon (Si) still enjoys the advantages of excellent and reproducible electronic properties and compatibility with complementary metal–oxide–semiconductor (CMOS) technologies for integrated multiplexing and signal processing. This review gives an overview of the recent developments in Si FETs for gas and VOC sensing. We categorised the Si FETs into Si nanowire (NW) FETs; planar Si FETs, in which the Si channel is either a part of the silicon on insulator (SOI) or the bulk Si, as in conventional FETs; and electrostatically formed nanowire (EFN) FETs. The review begins with a brief introduction, followed by a description of the Si NW FET gas and VOC sensors. A brief description of the various fabrication strategies of Si NWs and the several functionalisation methods to improve the sensing performances of Si NWs are also provided. Although Si NW FETs have excellent sensing properties, they are far from practical realisation due to the extensive fabrication procedures involved, along with other issues that are critically assessed briefly. Then, we describe planar Si FET sensors, which are much closer to real-world implementation. Their simpler device architecture combined with excellent sensing properties enable them as an efficient platform for gas sensing. The third category, the EFN FET sensors, proved to be another potential platform for gas sensing due to their intriguing properties, which are elaborated in detail. Finally, the challenges and future opportunities for gas sensing are addressed.
Odor Recognition of Thermal Decomposition Products of Electric Cables Using Odor Sensing Arrays
Authors: Liu Yuanchang , Furuno Shintaro , Akagawa Sosuke , Yatabe Rui , Onodera Takeshi , Fujiwara Nobuyuki , Takeda Hidekazu , Uchida Seiichi , Toko Kiyoshi
Published: September 2021

An odor sensing system with chemosensitive resistors was used to identify the gases generated from overheated cables to prevent fire. Three different electric cables for a distribution cabinet were used. The cables had an insulation layer made of polyvinyl chloride (PVC) or cross-linked polyethylene (XLPE). The heat resistance of the cables was tested by differential thermal and thermogravimetric analyses. The thermal decomposition products of the cables were investigated by gas chromatography-mass spectrometry (GC-MS). For the odor sensing system, two types of 16-channel array were used to detect the generated gases. One contains high-polarity GC stationary phase materials and the other contains GC stationary phase materials of high to low polarity. The system could distinguish among three cable samples at 270 °C with an accuracy of about 75% through both arrays trained with machine learning. Furthermore, the system could achieve a recall rate of 90% and a precision rate of 70% when the abnormal temperature was set above the cables’ allowable conductor temperature at 130 °C. The odor sensing system could effectively detect the abnormal heating of the cables before the occurrence of fire. Therefore, it is helpful for fire prediction and detection systems in factories and substations.
Do I Look Gawky? The Association between Pubertal Asynchrony and Peer Victimization
Authors: Natsuaki Misaki N. , Stepanyan Sofia T. , Neiderhiser Jenae M. , Shaw Daniel S. , Ganiban Jody M. , Reiss David , Leve Leslie D.
Published: September 2021

Pubertal synchrony is defined as the degree of coherence to which puberty-related body changes (e.g., breast development, growth spurt, voice change, underarm hair growth) are coordinated. During the pubertal transition, youth’s body parts grow asynchronously, making each youth’s physical appearance unique. Physical appearance is a known correlate of youth’s psychosocial functioning during adolescence, but we know little about how pubertal asynchrony plays a role in their peer relationships. Using data from an adoption study (the Early Growth and Development Study; n = 413; 237 boys, 176 girls), this study examined the effect of pubertal asynchrony on peer victimization. Results revealed sex-specific effects of pubertal asynchrony; pubertal asynchrony was associated with a higher risk of peer victimization for girls but a lower risk for boys. Findings highlight the intersection of physical development and social context in understanding youth’s experiences of puberty.
Optically Tunable Terahertz Metasurfaces Using Liquid Crystal Cells Coated with Photoalignment Layers
Authors: Shih Yi-Hong , Lin Xin-Yu , Silalahi Harry Miyosi , Lee Chia-Rong , Huang Chia-Yi
Published: September 2021

An optically tunable terahertz filter was fabricated using a metasurface-imbedded liquid crystal (LC) cell with photoalignment layers in this work. The LC director in the cell is aligned by a pump beam and makes angles θ of 0, 30, 60 and 90° with respect to the gaps of the split-ring resonators (SRRs) of the metasurface under various polarized directions of the pump beam. Experimental results display that the resonance frequency of the metasurface in the cell increases with an increase in θ, and the cell has a frequency tuning region of 15 GHz. Simulated results reveal that the increase in the resonance frequency arises from the birefringence of the LC, and the LC has a birefringence of 0.13 in the terahertz region. The resonance frequency of the metasurface is shifted using the pump beam, so the metasurface-imbedded LC cell with the photoalignment layers is an optically tunable terahertz filter. The optically tunable terahertz filter is promising for applications in terahertz telecommunication, biosensing and terahertz imaging.
Thermal Deformations of Crystal Structures in the L-Aspartic Acid/L-Glutamic Acid System and DL-Aspartic Acid
Authors: Sadovnichii Roman , Kotelnikova Elena , Lorenz Heike
Published: September 2021

The method of temperature-resolved powder X-ray diffraction (TRPXRD) was used to determine the elevated temperature behavior of L-aspartic acid (L-asp), DL-aspartic acid (DL-asp), L-glutamic acid (L-glu), and an L-asp0.25,L-glu0.75 solid solution. These amino acids were not found to undergo any solid-phase (polymorph) transformations. When heated, they all experienced only thermal deformations. The corresponding parameters of the monoclinic cells of L-asp and DL-asp, and the orthorhombic cells of L-glu and L-asp0.25,L-glu0.75, were calculated for the entire range of studied temperatures (up to 220 °C). The data obtained were used to calculate the parameters of the thermal deformation tensors, and to plot the figures of their thermal expansion coefficients. A correlation between the maximum and minimum values of thermal expansion coefficients and the length, type, direction, and number of hydrogen bonds in the crystal structures of the investigated amino acids was established. The observed negative thermal expansion (contraction) of crystal structures of L-asp and DL-asp along the ac plane can be explained as a result of shear deformations occurring in monoclinic crystals with a non-fixed angle β. The studies were related to the presence of amino acids in various natural and technological processes occurring at different temperatures.
Cluster Headache Pathophysiology—A Disorder of Network Excitability?
Authors: Pohl Heiko , Sandor Peter S. , Michels Lars , Gantenbein Andreas R.
Published: September 2021

Patients’ accounts of cluster headache attacks, ictal restlessness, and electrophysiological studies suggest that the pathophysiology involves Aδ-fibre nociceptors and the network processing their input. Continuous activity of the trigeminal autonomic reflex throughout the in-bout period results in central sensitization of these networks in many patients. It is likely that several factors force circadian rhythmicity upon the disease. In addition to sensitization, circadian changes in pain perception and autonomic innervation might influence the excitability of the trigeminal cervical complex. Summation of several factors influencing pain perception might render neurons vulnerable to spontaneous depolarization, particularly at the beginning of rapid drops of the pain threshold (“summation headache”). In light of studies suggesting an impairment of short-term synaptic plasticity in CH patients, we suggest that the physiologic basis of CH attacks might be network overactivity—similarly to epileptic seizures. Case reports documenting cluster-like attacks support the idea of distinct factors being transiently able to induce attacks and being relevant in the pathophysiology of the disorder. A sustained and recurring proneness to attacks likely requires changes in the activity of other structures among which the hypothalamus is the most probable candidate.
Visualization of the Inferior Alveolar Nerve and Lingual Nerve Using MRI in Oral and Maxillofacial Surgery: A Systematic Review
Authors: Al-Haj Husain Adib , Solomons Mark , Stadlinger Bernd , Pejicic Rada , Winklhofer Sebastian , Piccirelli Marco , Valdec Silvio
Published: September 2021

We evaluate the preoperative visualization of the inferior alveolar nerve (IAN) and lingual nerve (LN) as reported using radiation-free magnetic resonance imaging (MRI). An accurate visualization shall minimize the postoperative risk for nerve injuries in oral and maxillofacial surgery. PubMed MEDLINE, EMBASE, Biosis, and Cochrane databases were selected for the PICOS search strategy by two reviewers using medical subject headings (MeSH) terms. Thirty studies were included in the systematic review. Based on these studies’ findings, the use of black bone MRI sequences, especially 3D short-tau inversion recovery (STIR), provides superior soft-tissue resolution and high sensitivity in detecting pathological changes. Due to the implementation variability regarding scan parameters and the use of different magnetic field strengths, studies with well-designed protocols and a low risk of bias should be conducted to obtain stronger evidence. With improved cost and time efficiency and considering the benefit–risk ratio, MRI is a promising imaging modality that could become part of routine clinical practice in the future.
Effects of Strategy Training and Elaboration vs. Retrieval Settings on Learning of Cell Biology Using Concept Mapping
Authors: Becker Lukas Bernhard , Welter Virginia Deborah Elaine , Großschedl Jörg
Published: September 2021

Concept mapping (CM) can be an effective strategy to facilitate understanding-based learning of complex and abstract scientific content. In our study, we tried to answer two questions that have not yet been clarified: (1) How effective is CM if the learners do not have the textual learning material available when constructing their concept maps (retrieval setting) in contrast to when the material is available (elaboration setting)? (2) Do potential effects of the two settings depend on the intensity of a previous CM strategy training? To this end, we established a quasi-experimental four-group plan and collected data of N = 93 undergraduate students. The participants received either a detailed CM strategy training or just a short introduction and were then asked to apply CM in a retrieval or elaboration setting. The quality of constructed concept maps and content-related learning success were assessed to determine potential group differences. Overall, our results show a significantly positive but setting-independent effect of the CM strategy training on methodical CM skills. However, the different setting conditions differed neither regarding concept map quality nor content-related learning success, implying that CM in retrieval settings could be as effective as in elaboration settings.
Fashion Design Education and Sustainability: Towards an Equilibrium between Craftsmanship and Artistic and Business Skills?
Authors: Murzyn-Kupisz Monika , Hołuj Dominika
Published: September 2021

Fashion designers can have a key role to play in making fashion more sustainable, as they are able to influence and contribute to all dimensions of fashion impact (economic, environmental, social, and cultural), both positive and negative. Fashion design education should be seen as a chance to make aspiring designers aware of the challenges and potential of design for sustainability and equip them with the knowledge and skills necessary to implement sustainable fashion approaches. Starting from this premise, the approach to various sustainability themes was examined in the particular national context of post-secondary schools offering fashion majors in Poland, one which so far has not been researched in any depth. The authors conducted interviews and analysed the publications, documents, web pages, and Facebook profiles of such schools. Their activities were examined and classified in respect of the main dimensions of comprehensive fashion education: art, craftsmanship, and business. The analysis provides a picture of the current situation and a review of the specific features of sustainable fashion education in both the global and Polish contexts. Contemporary fashion education requires multidimensional adjustments to curricula, reflecting the complex nature of sustainability problems. This is a global challenge, which in the Polish case is additionally exacerbated by insufficient and uncoordinated public support, problems related to the institutional context of private and public schools, and the low level of sustainability awareness among consumers.
Digital and Media Literacies in the Polish Education System—Pre- and Post-COVID-19 Perspective
Authors: Cicha Karina , Rutecka Paulina , Rizun Mariia , Strzelecki Artur
Published: September 2021

Digital and media literacies refer to a specific set of skills and abilities. The range of these skills as they concern the educational process has been broadly discussed. In this paper, we analyzed the Polish educational system to determine the scope of the sorts of digital skills young people and students should achieve in order to be considered digitally and media literate. We compared sets of recommendations from the last ten years issued by different national governmental and nonprofit organizations for the Polish education system. We identified a set of skills that should be expected to be possessed by young people and students during their education. Additionally, we discussed results regarding the situation caused by the COVID-19 pandemic and the shift from regular education to distance learning.