bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Open and Forest Habitats on Distribution and Diversity of Bumblebees (Bombus) in the Małopolska Upland (Southern Poland): Case Study
Authors: Bąk-Badowska Jolanta , Wojciechowska Anna , Czerwik-Marcinkowska Joanna
Published: December 2021

Bumblebees are an important insect group occurring in different land ecosystems, but the number of these species has declined dramatically across Poland as well as in Europe in recent years. The fragmentation of bumblebee habitats influences the abundance and richness in community composition and trophic and competitive interactions. During the years 2003–2006 and 2017–2020, we studied the diversity and distribution of bumblebee species in two natural (boron-mixed Vaccinio-Piceetea and riparian forest Querco-Fagetea) and two semi-natural (segetal-ruderal Stellarietea mediae ruderal Artemisietea vulgaris) habitats in southern Poland. For that, we evaluated how habitats as well as local flowering communities influenced bumblebees’ abundance, richness, and community composition in 16 sites (which are located in four parks). Bumblebee communities responded to environmental factors in different ways according to the type of habitat. Vegetation factors were the most important drivers of bumblebee community structures. Forests showed the lowest bumblebee abundance, richness, and diversity, and the highest dominance levels of these parameters were found in the open ruderal-segetal habitats. The meadows from the Molinio arrhenatheretea class were characterized by bumblebee communities with a more complex structure. Species diversity was positively correlated with open ruderal-segetal habitats, and negatively with mixed forest cover, while abundance was positively correlated with forest cover. Studies like this are necessary to anticipate the impact of habitat fragmentation on bumblebee decline.
Breast Cancer Cell Subtypes Display Different Metabolic Phenotypes That Correlate with Their Clinical Classification
Authors: Ripoll Consuelo , Roldan Mar , Ruedas-Rama Maria J. , Orte Angel , Martin Miguel
Published: December 2021

Metabolic reprogramming of cancer cells represents an orchestrated network of evolving molecular and functional adaptations during oncogenic progression. In particular, how metabolic reprogramming is orchestrated in breast cancer and its decisive role in the oncogenic process and tumor evolving adaptations are well consolidated at the molecular level. Nevertheless, potential correlations between functional metabolic features and breast cancer clinical classification still represent issues that have not been fully studied to date. Accordingly, we aimed to investigate whether breast cancer cell models representative of each clinical subtype might display different metabolic phenotypes that correlate with current clinical classifications. In the present work, functional metabolic profiling was performed for breast cancer cell models representative of each clinical subtype based on the combination of enzyme inhibitors for key metabolic pathways, and isotope-labeled tracing dynamic analysis. The results indicated the main metabolic phenotypes, so-called ‘metabophenotypes’, in terms of their dependency on glycolytic metabolism or their reliance on mitochondrial oxidative metabolism. The results showed that breast cancer cell subtypes display different metabophenotypes. Importantly, these metabophenotypes are clearly correlated with the current clinical classifications.
Forensic Facial Comparison: Current Status, Limitations, and Future Directions
Authors: Bacci Nicholas , Davimes Joshua G. , Steyn Maryna , Briers Nanette
Published: December 2021

Global escalation of crime has necessitated the use of digital imagery to aid the identification of perpetrators. Forensic facial comparison (FFC) is increasingly employed, often relying on poor-quality images. In the absence of standardized criteria, especially in terms of video recordings, verification of the methodology is needed. This paper addresses aspects of FFC, discussing relevant terminology, investigating the validity and reliability of the FISWG morphological feature list using a new South African database, and advising on standards for CCTV equipment. Suboptimal conditions, including poor resolution, unfavorable angle of incidence, color, and lighting, affected the accuracy of FFC. Morphological analysis of photographs, standard CCTV, and eye-level CCTV showed improved performance in a strict iteration analysis, but not when using analogue CCTV images. Therefore, both strict and lenient iterations should be conducted, but FFC must be abandoned when a strict iteration performs worse than a lenient one. This threshold ought to be applied to the specific CCTV equipment to determine its utility. Chance-corrected accuracy was the most representative measure of accuracy, as opposed to the commonly used hit rate. While the use of automated systems is increasing, trained human observer-based morphological analysis, using the FISWG feature list and an Analysis, Comparison, Evaluation, and Verification (ACE-V) approach, should be the primary method of facial comparison.
Biological Efficacy of Cochlioquinone-9, a Natural Plant Defense Compound for White-Backed Planthopper Control in Rice
Authors: Jang Yoon-Hee , Yun Sopheap , Park Jae-Ryoung , Kim Eun-Gyeong , Yun Byoung-Ju , Kim Kyung-Min
Published: December 2021

Rice is exposed to various biotic stresses in the natural environment. The white-backed planthopper (Sogatella furcifera, WBPH) is a pest that causes loss of rice yield and threatens the global food supply. In most cases, pesticides are used to control WBPH. However, excessive use of pesticides increases pesticide resistance to pests and causes environmental pollution. Therefore, it is necessary to develop natural product-based pesticides to control WBPH. Plants produce a variety of secondary metabolites for protection. Secondary metabolites act as a defense against pathogens and pests and are valuable as pesticides and breeding materials. Cochlioquinone is a secondary metabolite that exhibits various biological activities, has a negative effect on the growth and development of insects, and contributes to plant defense. Here, we compared plant growth after treatment with cochlioquinone-9 (cq-9), a quinone family member. cq-9 improved the ability of plants to resist WBPH and had an effect on plant growth. Gene expression analysis revealed that cq-9 interacts with various defense-related genes to confer resistance to WBPH, suggesting that it is related to flavonoid compounds. Overall, this study provides insight into the mechanisms of WBPH resistance and suggests that cq-9 represents an environmentally friendly agent for WBPH control.
Ubiquitin Ligase Redundancy and Nuclear-Cytoplasmic Localization in Yeast Protein Quality Control
Authors: Breckel Carolyn Allain , Hochstrasser Mark
Published: December 2021

The diverse functions of proteins depend on their proper three-dimensional folding and assembly. Misfolded cellular proteins can potentially harm cells by forming aggregates in their resident compartments that can interfere with vital cellular processes or sequester important factors. Protein quality control (PQC) pathways are responsible for the repair or destruction of these abnormal proteins. Most commonly, the ubiquitin-proteasome system (UPS) is employed to recognize and degrade those proteins that cannot be refolded by molecular chaperones. Misfolded substrates are ubiquitylated by a subset of ubiquitin ligases (also called E3s) that operate in different cellular compartments. Recent research in Saccharomyces cerevisiae has shown that the most prominent ligases mediating cytoplasmic and nuclear PQC have overlapping yet distinct substrate specificities. Many substrates have been characterized that can be targeted by more than one ubiquitin ligase depending on their localization, and cytoplasmic PQC substrates can be directed to the nucleus for ubiquitylation and degradation. Here, we review some of the major yeast PQC ubiquitin ligases operating in the nucleus and cytoplasm, as well as current evidence indicating how these ligases can often function redundantly toward substrates in these compartments.
Hyperbaric Oxygen Treatment: Effects on Mitochondrial Function and Oxidative Stress
Authors: Schottlender Nofar , Gottfried Irit , Ashery Uri
Published: December 2021

Hyperbaric oxygen treatment (HBOT)—the administration of 100% oxygen at atmospheric pressure (ATA) greater than 1 ATA—increases the proportion of dissolved oxygen in the blood five- to twenty-fold. This increase in accessible oxygen places the mitochondrion—the organelle that consumes most of the oxygen that we breathe—at the epicenter of HBOT’s effects. As the mitochondrion is also a major site for the production of reactive oxygen species (ROS), it is possible that HBOT will increase also oxidative stress. Depending on the conditions of the HBO treatment (duration, pressure, umber of treatments), short-term treatments have been shown to have deleterious effects on both mitochondrial activity and production of ROS. Long-term treatment, on the other hand, improves mitochondrial activity and leads to a decrease in ROS levels, partially due to the effects of HBOT, which increases antioxidant defense mechanisms. Many diseases and conditions are characterized by mitochondrial dysfunction and imbalance between ROS and antioxidant scavengers, suggesting potential therapeutic intervention for HBOT. In the present review, we will present current views on the effects of HBOT on mitochondrial function and oxidative stress, the interplay between them and the implications for several diseases.
Diet Impact on Obesity beyond Calories and Trefoil Factor Family 2 (TFF2) as an Illustration: Metabolic Implications and Potential Applications
Authors: Ghanemi Abdelaziz , Yoshioka Mayumi , St-Amand Jonny
Published: December 2021

Obesity is a health problem with increasing impacts on public health, economy and even social life. In order to reestablish the energy balance, obesity management focuses mainly on two pillars; exercise and diet. Beyond the contribution to the caloric intake, the diet nutrients and composition govern a variety of properties. This includes the energy balance-independent properties and the indirect metabolic effects. Whereas the energy balance-independent properties are close to “pharmacological” effects and include effects such as antioxidant and anti-inflammatory, the indirect metabolic effects represent the contribution a diet can have on energy metabolism beyond the caloric contribution itself, which include the food intake control and metabolic changes. As an illustration, we also described the metabolic implication and hypothetical pathways of the high-fat diet-induced gene Trefoil Factor Family 2. The properties the diet has can have a variety of applications mainly in pharmacology and nutrition and further explore the “pharmacologically” active food towards potential therapeutic applications.
Effects of Metformin in Heart Failure: From Pathophysiological Rationale to Clinical Evidence
Authors: Salvatore Teresa , Galiero Raffaele , Caturano Alfredo , Vetrano Erica , Rinaldi Luca , Coviello Francesca , Di Martino Anna , Albanese Gaetana , Marfella Raffaele , Sardu Celestino , Sasso Ferdinando Carlo
Published: December 2021

Type 2 diabetes mellitus (T2DM) is a worldwide major health burden and heart failure (HF) is the most common cardiovascular (CV) complication in affected patients. Therefore, identifying the best pharmacological approach for glycemic control, which is also useful to prevent and ameliorate the prognosis of HF, represents a crucial issue. Currently, the choice is between the new drugs sodium/glucose co-transporter 2 inhibitors that have consistently shown in large CV outcome trials (CVOTs) to reduce the risk of HF-related outcomes in T2DM, and metformin, an old medicament that might end up relegated to the background while exerting interesting protective effects on multiple organs among which include heart failure. When compared with other antihyperglycemic medications, metformin has been demonstrated to be safe and to lower morbidity and mortality for HF, even if these results are difficult to interpret as they emerged mainly from observational studies. Meta-analyses of randomized controlled clinical trials have not produced positive results on the risk or clinical course of HF and sadly, large CV outcome trials are lacking. The point of force of metformin with respect to new diabetic drugs is the amount of data from experimental investigations that, for more than twenty years, still continues to provide mechanistic explanations of the several favorable actions in heart failure such as, the improvement of the myocardial energy metabolic status by modulation of glucose and lipid metabolism, the attenuation of oxidative stress and inflammation, and the inhibition of myocardial cell apoptosis, leading to reduced cardiac remodeling and preserved left ventricular function. In the hope that specific large-scale trials will be carried out to definitively establish the metformin benefit in terms of HF failure outcomes, we reviewed the literature in this field, summarizing the available evidence from experimental and clinical studies reporting on effects in heart metabolism, function, and structure, and the prominent pathophysiological mechanisms involved.
Targeting Inflammasome Activation in COVID-19: Delivery of RNA Interference-Based Therapeutic Molecules
Authors: Gedefaw Lealem , Ullah Sami , Lee Thomas M. H. , Yip Shea Ping , Huang Chien-Ling
Published: December 2021

Mortality and morbidity associated with COVID-19 continue to be significantly high worldwide, owing to the absence of effective treatment strategies. The emergence of different variants of SARS-CoV-2 is also a considerable source of concern and has led to challenges in the development of better prevention and treatment strategies, including vaccines. Immune dysregulation due to pro-inflammatory mediators has worsened the situation in COVID-19 patients. Inflammasomes play a critical role in modulating pro-inflammatory cytokines in the pathogenesis of COVID-19 and their activation is associated with poor clinical outcomes. Numerous preclinical and clinical trials for COVID-19 treatment using different approaches are currently underway. Targeting different inflammasomes to reduce the cytokine storm, and its associated complications, in COVID-19 patients is a new area of research. Non-coding RNAs, targeting inflammasome activation, may serve as an effective treatment strategy. However, the efficacy of these therapeutic agents is highly dependent on the delivery system. MicroRNAs and long non-coding RNAs, in conjunction with an efficient delivery vehicle, present a potential strategy for regulating NLRP3 activity through various RNA interference (RNAi) mechanisms. In this regard, the use of nanomaterials and other vehicle types for the delivery of RNAi-based therapeutic molecules for COVID-19 may serve as a novel approach for enhancing drug efficacy. The present review briefly summarizes immune dysregulation and its consequences, the roles of different non-coding RNAs in regulating the NLRP3 inflammasome, distinct types of vectors for their delivery, and potential therapeutic targets of microRNA for treatment of COVID-19.
Comparison of Oxidative and Hypoxic Stress Responsive Genes from Meta-Analysis of Public Transcriptomes
Authors: Suzuki Takayuki , Ono Yoko , Bono Hidemasa
Published: December 2021

Analysis of RNA-sequencing (RNA-seq) data is an effective means to analyze the gene expression levels under specific conditions and discover new biological knowledge. More than 74,000 experimental series with RNA-seq have been stored in public databases as of 20 October 2021. Since this huge amount of expression data accumulated from past studies is a promising source of new biological insights, we focused on a meta-analysis of 1783 runs of RNA-seq data under the conditions of two types of stressors: oxidative stress (OS) and hypoxia. The collected RNA-seq data of OS were organized as the OS dataset to retrieve and analyze differentially expressed genes (DEGs). The OS-induced DEGs were compared with the hypoxia-induced DEGs retrieved from a previous study. The results from the meta-analysis of OS transcriptomes revealed two genes, CRIP1 and CRIP3, which were particularly downregulated, suggesting a relationship between OS and zinc homeostasis. The comparison between meta-analysis of OS and hypoxia showed that several genes were differentially expressed under both stress conditions, and it was inferred that the downregulation of cell cycle-related genes is a mutual biological process in both OS and hypoxia.
Drug Delivery Challenges in Brain Disorders across the Blood–Brain Barrier: Novel Methods and Future Considerations for Improved Therapy
Authors: Achar Aneesha , Myers Rosemary , Ghosh Chaitali
Published: December 2021

Due to the physiological and structural properties of the blood–brain barrier (BBB), the delivery of drugs to the brain poses a unique challenge in patients with central nervous system (CNS) disorders. Several strategies have been investigated to circumvent the barrier for CNS therapeutics such as in epilepsy, stroke, brain cancer and traumatic brain injury. In this review, we summarize current and novel routes of drug interventions, discuss pharmacokinetics and pharmacodynamics at the neurovascular interface, and propose additional factors that may influence drug delivery. At present, both technological and mechanistic tools are devised to assist in overcoming the BBB for more efficient and improved drug bioavailability in the treatment of clinically devastating brain disorders.
Heart–Brain Relationship in Stroke
Authors: Kelley Roger E. , Kelley Brian P.
Published: December 2021

The patient presenting with stroke often has cardiac-related risk factors which may be involved in the mechanism of the stroke. The diagnostic assessment is predicated on recognition of this potential relationship. Naturally, an accurate history is of utmost importance in discerning a possible cause and effect relationship. The EKG is obviously an important clue as well as it allows immediate assessment for possible cardiac arrhythmia, such as atrial fibrillation, for possible acute ischemic changes reflective of myocardial ischemia, or there may be indirect factors such as the presence of left ventricular hypertrophy, typically seen with longstanding hypertension, which could be indicative of a hypertensive mechanism for a patient presenting with intracerebral hemorrhage. For all presentations in the emergency room, the vital signs are important. An elevated body temperature in a patient presenting with acute stroke raises concern about possible infective endocarditis. An irregular–irregular pulse is an indicator of atrial fibrillation. A markedly elevated blood pressure is not uncommon in both the acute ischemic and acute hemorrhagic stroke setting. One tends to focus on possible cardioembolic stroke if there is the sudden onset of maximum neurological deficit versus the stepwise progression more characteristic of thrombotic stroke. Because of the more sudden loss of vascular supply with embolic occlusion, seizure or syncope at onset tends to be supportive of this mechanism. Different vascular territory involvement on neuroimaging is also a potential indicator of cardioembolic stroke. Identification of a cardiogenic source of embolus in such a setting certainly elevates this mechanism in the differential. There have been major advances in management of acute cerebrovascular disease in recent decades, such as thrombolytic therapy and endovascular thrombectomy, which have somewhat paralleled the advances made in cardiovascular disease. Unfortunately, the successful limitation of myocardial damage in acute coronary syndrome, with intervention, does not necessarily mirror a similar salutary effect on functional outcome with cerebral infarction. The heart can also affect the brain from a cerebral perfusion standpoint. Transient arrhythmias can result in syncope, while cardiac arrest can result in hypoxic–ischemic encephalopathy. Cardiogenic dementia has been identified as a mechanism of cognitive impairment associated with severe cardiac failure. Structural cardiac abnormalities can also play a role in brain insult, and this can include tumors, such as atrial myxoma, patent foramen ovale, with the potential for paradoxical cerebral embolism, and cardiomyopathies, such as Takotsubo, can be associated with precipitous cardioembolic events.
IL-20 Cytokines Are Involved in Epithelial Lesions Associated with Virus-Induced COPD Exacerbation in Mice
Authors: Le Roux Mélina , Ollivier Anaïs , Kervoaze Gwenola , Beke Timothé , Gillet Laurent , Pichavant Muriel , Gosset Philippe
Published: December 2021

(1) Background: viral infections are a frequent cause of chronic obstructive pulmonary disease (COPD) exacerbations, which are responsible for disease progression and mortality. Previous reports showed that IL-20 cytokines facilitate bacterial lung infection, but their production and their role in COPD and viral infection has not yet been investigated. (2) Methods: C57BL/6 WT and IL-20 Rb KO mice were chronically exposed to air or cigarette smoke (CS) to mimic COPD. Cytokine production, antiviral response, inflammation and tissue damages were analyzed after PVM infection. (3) Results: CS exposure was associated with an increase in viral burden and antiviral response. PVM infection in CS mice enhanced IFN-γ, inflammation and tissue damage compared to Air mice. PVM infection and CS exposure induced, in an additive manner, IL-20 cytokines expression and the deletion of IL-20 Rb subunit decreased the expression of interferon-stimulated genes and the production of IFN-λ2/3, without an impact on PVM replication. Epithelial cell damages and inflammation were also reduced in IL-20 Rb-/- mice, and this was associated with reduced lung permeability and the maintenance of intercellular junctions. (4) Conclusions: PVM infection and CS exposure additively upregulates the IL-20 pathway, leading to the promotion of epithelial damages. Our data in our model of viral exacerbation of COPD identify IL-20 cytokine as a potential therapeutic target.
The Differential Effects of HDL Subpopulations on Lipoprotein Lipase (LPL)-Mediated VLDL Catabolism
Authors: Wieczorek Ewa , Ćwiklińska Agnieszka , Kuchta Agnieszka , Kortas-Stempak Barbara , Gliwińska Anna , Jankowski Maciej
Published: December 2021

High-density lipoprotein (HDL) subpopulations functional assessment is more relevant for HDL anti-atherogenic activity than cholesterol level. The aim of the study was to assess the impact of HDL-2 and HDL-3 on lipoprotein lipase (LPL)-mediated very-low-density lipoprotein (VLDL) catabolism related to hypertriglyceridemia development. VLDL and HDLs were isolated from serum by ultracentrifugation. VLDL was incubated with LPL in the absence and presence of total HDL or HDL subpopulations. Next, VLDL remnants were separated, and their composition and electrophoretic mobility was assessed. Both HDL subpopulations increased the efficiency of triglyceride lipolysis and apolipoprotein CII and CIII removal from VLDL up to ~90%. HDL-3 exerted significantly greater impact than HDL-2 on apolipoprotein E (43% vs. 18%, p < 0.001), free cholesterol (26% vs. 18%, p < 0.05) and phospholipids (53% vs. 43%, p < 0.05) removal from VLDL and VLDL remnant electrophoretic mobility (0.18 vs. 0.20, p < 0.01). A greater release of these components was also observed in the presence of total HDL with a low HDL-2/HDL-3 cholesterol ratio. Both HDL subpopulations affect VLDL composition during lipolysis, but HDL-3 exhibited a greater effect on this process. Altered composition of HDL related to significant changes in the distribution between HDL-2 and HDL-3 can influence the VLDL remnant features, affecting atherosclerosis progression.
Signal Enhancement in Oriented Immunosorbent Assays: A Balance between Accessibility of Antigen Binding Sites and Avidity
Authors: Susini Vanessa , Fierabracci Vanna , Barria Gaia , Dodoli Lisa , Caponi Laura , Paolicchi Aldo , Franzini Maria
Published: December 2021

The sensitivity of immunoassays was reported to be increased by the orientation of antibodies. We investigated how the size and valence of antigens and orientation and valence of antibodies contribute to the analytical sensitivity of ELISA. Antigens differing in size and number of epitopes were compared using oriented and non-oriented ELISAs: the orientation of antibodies was obtained coating half-fragment antibodies on maleimide microplates, while, in non-oriented ELISA, whole antibodies were randomly physisorbed. The oriented assay performed better than the non-oriented one at each concentration (0.4–3.3 ng/mL) of a small monomeric antigen (cardiac Troponin I, 24 kDa, Rh 3 nm). No significant differences were observed with a large monovalent antigen (prostate-specific antigen-alpha(1) antichymotrypsin, 90 kDa, Rh > 3 nm), since its steric hindrance overcame the increased availability of antigen binding sites given by orientation. Large multivalent antigens (ferritin, 280 kDa, Rh 6 nm; α-fetoprotein, >70 kDa, Rh > 3.3 nm) performed better in non-oriented assays. In this case, the repeated epitopes on the surface of the antigens favored the engagement of both antigen binding sites of the whole IgG, thus suggesting that avidity represented the leading force in this experimental setting. In conclusion, the design of high-sensitivity ELISAs should consider the dimension and valency of antigens in addition to the affinity and avidity of antibodies.
Assessment of the Kinematic Adaptations in Parkinson’s Disease Using the Gait Profile Score: Influences of Trunk Posture, a Pilot Study
Authors: Callais Franco do Nascimento Tauana , Martins Gervásio Flavia , Pignolo Antonia , Augusto Santos Bueno Guilherme , Araújo do Carmo Aline , Martins Ribeiro Darlan , D’Amelio Marco , Augusto dos Santos Mendes Felipe
Published: December 2021

Introduction: Postural abnormalities are common in patients with Parkinson’s disease (PD) and lead to gait abnormalities. Relationships between changes in the trunk posture of PD patients and gait profile score (GPS) and gait spatiotemporal parameters are poorly investigated. The aim of the current study was to investigate the relationships between trunk posture, GPS, and gait spatiotemporal parameters, in patients with PD. Materials and Methods: Twenty-three people with PD and nineteen age-matched healthy people participated in this study. A 3D gait kinematical analysis was applied to all participants using the Plug-In Gait Full BodyTM tool. Trunk and limb kinematics patterns and gait spatio-temporal parameters of patients with PD and the control group were compared. Additionally, correlations between trunk kinematics patterns, gait spatio-temporal parameters, and GPS of the PD group were tested. Results: Cadence, opposite foot off, step time, single support, double support, foot off, gait speed, trunk kinematics, and GPS showed significant differences between the two groups (p ≤ 0.05). Posture of the trunk during gait was not related to the spatio-temporal parameters and gait profile score in the PD group. The trunk flexor pattern influenced GPS domains, mainly of the ankle and the knee. Discussion and Conclusions: Flexed posture of the trunk in patients with PD seems to influence both ankle and knee movement patterns during the gait. The GPS analysis provided direct and simplified kinematic information for the PD group. These results may have implications for understanding the importance of considering the positioning of the trunk during gait.
High Intellectual Potential and High Functioning Autism: Clinical and Neurophysiological Features in a Pediatric Sample
Authors: Riccioni Assia , Pro Stefano , Di Criscio Lorena , Terribili Monica , Siracusano Martina , Moavero Romina , Valeriani Massimiliano , Mazzone Luigi
Published: December 2021

High Intellectual Potential (HIP) and High Functioning Autism (HFA) are two different conditions sharing some clinical and neurobiological features. The aim of the present study was to characterize a sample of HIP children (n: 16; M/F: 14/2; median age: 10 years) in comparison to those with HFA (n: 17; M/F: 16/1; median age: 13 years) and to neurotypically developed (NTD) children (n: 10; M/F: 4/6; median age: 11 years) from a clinical and neurophysiological perspective. Specifically, a standardized clinical assessment of cognitive and adaptive skills, autistic symptoms, executive functions and behavioral features was performed. Moreover, event-related potentials (ERPs) were recorded, referring specifically to the mismatch negativity (MMN) and P300 paradigm. Our data highlighted the presence of similarities between the intellectually gifted individuals and the ones with autism (i.e., a nonhomogeneous intellective profile, an adaptive skills impairment, subthreshold autistic symptoms and increased perfectionism). Interestingly, a distinct neurophysiological characterization between groups came out, with evidence of a reduced MMN amplitude only in the HFA group. Furthermore, no differences within groups in the P300 component emerged. Therefore, our results start to provide a more informative characterization of the HIP phenotype in comparison to those of HFA and NTD, highlighting the potential role of the MMN amplitude index in helping clinicians and researchers to distinguish between HIP and HFA. Nevertheless, further research on the topic is strongly needed.
Quantification of the Absorption and Scattering Effects of Diffusers in a Room with Absorbent Ceiling
Authors: Arvidsson Emma , Nilsson Erling , Bard Hagberg Delphine , Karlsson Ola J. I.
Published: December 2021

In ordinary public rooms, such as classrooms and offices, an absorbent ceiling is the typical first acoustic action. This treatment provides a good acoustic baseline. However, an improvement of specific room acoustic parameters, operating for specific frequencies, can be needed. It has been seen that diffusing elements can be effective additional treatment. In order to choose the right design, placement, and quantity of diffusers, a model to estimate the effect on the acoustics is necessary. This study evaluated whether an SEA model could be used for that purpose, particularly for the cases where diffusers are used in combination with an absorbent ceiling. It was investigated whether the model could handle different quantities of diffusing elements, varied diffusion characteristics, and varied installation patterns. It was found that the model was sensitive to these changes, given that the output from the model in terms of acoustic properties will be reflected by the change of diffuser configuration design. It was also seen that the absorption and scattering of the diffusers could be quantified in a laboratory environment: a reverberation chamber. Through the SEA model, these quantities could be transformed to a full-scale room for estimation of the room acoustic parameters.
Impact of Environmental Exposure on the Service Life of Façade Claddings—A Statistical Analysis
Authors: Barrelas Joana , Dias Ilídio , Silva Ana , de Brito Jorge , Flores-Colen Inês , Tadeu António
Published: December 2021

Façade claddings, as the outer protection layer of the building’s envelope, are directly exposed to environmental degradation agents. The façades’ orientation and their distance from the sea, among other location and protection-related factors, influence their vulnerability to climate loads, in particular wind and air humidity. These loads, as well as exposure to air pollution, affect the degradation process of claddings and the durability of façades. Therefore, studying the impact of the environmental exposure conditions on the service life of different external claddings provides useful information on their performance over time, which can support (i) decision-makers in the selection of the best façade cladding solutions and (ii) further research on the impact of climate change on building components. This study covers six types of cladding: rendered façades (R), natural stone cladding (NSC), ceramic tiling system (CTS), painted surfaces (PS), external thermal insulation composite systems (ETICS), and architectural concrete façades (ACF). Three hundred façades located in Portugal are analysed according to three main groups of variables, which characterize (i) the façades, (ii) their degradation condition, and (iii) the environmental deterioration loads and context. The statistical analysis results reveal that the environmental variables affect the cladding degradation process. South-oriented façades present lower degradation conditions than façades facing north. The distance from the sea and high exposure to pollutants add to the degradation conditions, reducing the expected service life of façades. The results reveal that claddings can be organized according to two main groups: the most durable (CTS, NSC, and ACF) and the least durable (R, PS, and ETICS) systems. This study enables a comprehensive analysis of the data, useful to draw conclusions about the influence of environmental exposure conditions on the degradation and service life of façade claddings.
Rituximab and Bendamustine (BR) Compared with Rituximab, Bendamustine, and Cytarabine (R-BAC) in Previously Untreated Elderly Patients with Mantle Cell Lymphoma
Authors: Bega Giulia , Olivieri Jacopo , Riva Marcello , Scapinello Greta , Paolini Rossella , Finotto Silvia , Sartori Roberto , Lucchini Elisa , Guandalini Gianmarco , Facchinelli Davide , Tisi Maria Chiara , Basso Marco , Ballotta Laura , Piazza Francesco , Ferrarini Isacco , Visco Carlo
Published: December 2021

Background: Rituximab plus bendamustine (BR), and rituximab, bendamustine, and cytarabine (R-BAC) are well-known induction therapies in elderly patients with mantle cell lymphoma (MCL), according to clinical guidelines. However, a direct comparison between the two regimens has never been performed. Methods: In this multicentre retrospective study, we compared the outcome of patients with newly diagnosed MCL, treated with BR or R-BAC. Primary endpoint was 2-year progression-free survival (PFS). Inclusion bias was assessed using a propensity score stratified by gender, age, MCL morphology, and MIPI score. Results: After adjusting by propensity score, we identified 156 patients (53 BR, 103 R-BAC) with median age of 72 (53–90). Median follow-up was 46 months (range 12–133). R-BAC was administered in a 2-day schedule or with attenuated dose in 51% of patients. Patients treated with R-BAC achieved CR in 91% of cases, as compared with 60% for BR (p < 0.0001). The 2-year PFS was 87 ± 3% and 64 ± 7% for R-BAC and BR, respectively (p = 0.001). In terms of toxicity, R-BAC was associated with significantly more pronounced grade 3–4 thrombocytopenia than BR (50% vs. 17%). Conclusions: This study indicates that R-BAC, even when administered with judiciously attenuated doses, is associated with significantly prolonged 2-year PFS than BR in elderly patients with previously untreated MCL.
Current Roles of PET/CT in Thymic Epithelial Tumours: Which Evidences and Which Prospects? A Pictorial Review
Authors: Lococo Filippo , Chiappetta Marco , Triumbari Elizabeth Katherine Anna , Evangelista Jessica , Congedo Maria Teresa , Pizzuto Daniele Antonio , Brascia Debora , Marulli Giuseppe , Annunziata Salvatore , Margaritora Stefano
Published: December 2021

Background: The use of 18F FDG PET/CT scan in thymic epithelial tumours (TET) has been reported in the last two decades, but its application in different clinical settings has not been clearly defined. Methods: We performed a pictorial review of pertinent literature to describe different roles and applications of this imaging tool to manage TET patients. Finally, we summarized future prospects and potential innovative applications of PET in these neoplasms. Results: 18FFDG PET/CT scan may be of help to distinguish thymic hyperplasia from thymic epithelial tumours but evidences are almost weak. On the contrary, this imaging tool seems to be very performant to predict the grade of malignancy, to a lesser extent pathological response after induction therapy, Masaoka Koga stage of disease and long-term prognosis. Several other radiotracers have some application in TETs but results are limited and almost controversial. Finally, the future of PET/CT and theranostics in TETs is still to be defined but more detailed analysis of metabolic data (such as texture analysis applied on thymic neoplasms), along with promising preclinical and clinical results from new “stromal PET tracers”, leave us an increasingly optimistic outlook. Conclusions: PET plays different roles in the management of thymic epithelial tumours, and its applications may be of help for physicians in different clinical settings.
Tumor Mutation Burden, Expressed Neoantigens and the Immune Microenvironment in Diffuse Gliomas
Authors: Yu Guangyang , Pang Ying , Merchant Mythili , Kesserwan Chimene , Gangalapudi Vineela , Abdelmaksoud Abdalla , Ranjan Alice , Kim Olga , Wei Jun S. , Chou Hsien-Chao , Wen Xinyu , Sindiri Sivasish , Song Young K. , Xi Liqiang , Kaplan Rosandra N. , Armstrong Terri S. , Gilbert Mark R. , Aldape Kenneth , Khan Javed , Wu Jing
Published: December 2021

Background: A consistent correlation between tumor mutation burden (TMB) and tumor immune microenvironment has not been observed in gliomas as in other cancers. Methods: Driver germline and somatic mutations, TMB, neoantigen, and immune cell signatures were analyzed using whole exome sequencing (WES) and transcriptome sequencing of tumor and WES of matched germline DNA in a cohort of 66 glioma samples (44 IDH-mutant and 22 IDH-wildtype). Results: Fourteen samples revealed a hypermutator phenotype (HMP). Eight pathogenic (P) or likely pathogenic (LP) germline variants were detected in 9 (19%) patients. Six of these 8 genes were DNA damage repair genes. P/LP germline variants were found in 22% of IDH-mutant gliomas and 12.5% of IDH-wildtype gliomas (p = 0.7). TMB was correlated with expressed neoantigen but showed an inverse correlation with immune score (R = −0.46, p = 0.03) in IDH-wildtype tumors and no correlation in IDH-mutant tumors. The Antigen Processing and Presentation (APP) score correlated with immune score and was surprisingly higher in NHMP versus HMP samples in IDH-wildtype gliomas, but higher in HMP versus NHMP in IDH-mutant gliomas. Conclusion: TMB was inversely correlated with immune score in IDH-wildtype gliomas and showed no correlation in IDH-mutant tumors. APP was correlated with immune score and may be further investigated as a biomarker for response to immunotherapy in gliomas. Studies of germline variants in a larger glioma cohort are warranted.
Differential Transcriptional Reprogramming by Wild Type and Lymphoma-Associated Mutant MYC Proteins as B-Cells Convert to a Lymphoma Phenotype
Authors: Mahani Amir , Arvidsson Gustav , Sadeghi Laia , Grandien Alf , Wright Anthony P. H.
Published: December 2021

The MYC transcription factor regulates a vast number of genes and is implicated in many human malignancies. In some hematological malignancies, MYC is frequently subject to missense mutations that enhance its transformation activity. Here, we use a novel murine cell system to (i) characterize the transcriptional effects of progressively increasing MYC levels as normal primary B-cells transform to lymphoma cells and (ii) determine how this gene regulation program is modified by lymphoma-associated MYC mutations (T58A and T58I) that enhance its transformation activity. Unlike many previous studies, the cell system exploits primary B-cells that are transduced to allow regulated MYC expression under circumstances where apoptosis and senescence pathways are abrogated by the over-expression of the Bcl-xL and BMI1 proteins. In such cells, transition from a normal to a lymphoma phenotype is directly dependent on the MYC expression level, without a requirement for secondary events that are normally required during MYC-driven oncogenic transformation. A generalized linear model approach allowed an integrated analysis of RNA sequencing data to identify regulated genes in relation to both progressively increasing MYC level and wild type or mutant status. Using this design, a total of 7569 regulated genes were identified, of which the majority (n = 7263) were regulated in response to progressively increased levels of wild type MYC, while a smaller number of genes (n = 917) were differentially regulated, compared to wild type MYC, in T58A MYC- and/or T58I MYC-expressing cells. Unlike most genes that are similarly regulated by both wild type and mutant MYC genes, the set of 917 genes did not significantly overlap with known lipopolysaccharide regulated genes, which represent genes regulated by MYC in normal B cells. The genes that were differently regulated in cells expressing mutant MYC proteins were significantly enriched in DNA replication and G2 phase to mitosis transition genes. Thus, mutants affecting MYC proteins may augment quantitative oncogenic effects on the expression of normal MYC-target genes with qualitative oncogenic effects, by which sets of cell cycle genes are abnormally targeted by MYC as B cells transition into lymphoma cells. The T58A and T58I mutations augment MYC-driven transformation by distinct mechanisms.
First-Line Pembrolizumab Mono- or Combination Therapy of Non-Small Cell Lung Cancer: Baseline Metabolic Biomarkers Predict Outcomes
Authors: Lang David , Ritzberger Linda , Rambousek Vanessa , Horner Andreas , Wass Romana , Akbari Kaveh , Kaiser Bernhard , Kronbichler Jürgen , Lamprecht Bernd , Gabriel Michael
Published: December 2021

Quantitative biomarkers derived from positron-emission tomography/computed tomography (PET/CT) have been suggested as prognostic variables in immune-checkpoint inhibitor (ICI) treated non-small cell lung cancer (NSCLC). As such, data for first-line ICI therapy and especially for chemotherapy–ICI combinations are still scarce, we retrospectively evaluated baseline 18F-FDG-PET/CT of 85 consecutive patients receiving first-line pembrolizumab with chemotherapy (n = 70) or as monotherapy (n = 15). Maximum and mean standardized uptake value, total metabolic tumor volume (MTV), total lesion glycolysis, bone marrow-/and spleen to liver ratio (BLR/SLR) were calculated. Kaplan–Meier analyses and Cox regression models were used to assess progression-free/overall survival (PFS/OS) and their determinant variables. Median follow-up was 12 months (M; 95% confidence interval 10–14). Multivariate selection for PFS/OS revealed MTV as most relevant PET/CT biomarker (p < 0.001). Median PFS/OS were significantly longer in patients with MTV ≤ 70 mL vs. >70 mL (PFS: 10 M (4–16) vs. 4 M (3–5), p = 0.001; OS: not reached vs. 10 M (5–15), p = 0.004). Disease control rate was 81% vs. 53% for MTV ≤/> 70 mL (p = 0.007). BLR ≤ 1.06 vs. >1.06 was associated with better outcomes (PFS: 8 M (4–13) vs. 4 M (3–6), p = 0.034; OS: 19 M (12-/) vs. 6 M (4–12), p = 0.005). In patients with MTV > 70 mL, concomitant BLR ≤ 1.06 indicated a better prognosis. Higher MTV is associated with inferior PFS/OS in first-line ICI-treated NSCLC, with BLR allowing additional risk stratification.
A Functional Network Model of the Metastasis Suppressor PEBP1/RKIP and Its Regulators in Breast Cancer Cells
Authors: Ahmed Mahmoud , Lai Trang Huyen , Kim Wanil , Kim Deok Ryong
Published: December 2021

Drug screening strategies focus on quantifying the phenotypic effects of different compounds on biological systems. High-throughput technologies have the potential to understand further the mechanisms by which these drugs produce the desired outcome. Reverse causal reasoning integrates existing biological knowledge and measurements of gene and protein abundances to infer their function. This approach can be employed to appraise the existing biological knowledge and data to prioritize targets for cancer therapies. We applied text mining and a manual literature search to extract known interactions between several metastasis suppressors and their regulators. We then identified the relevant interactions in the breast cancer cell line MCF7 using a knockdown dataset. We finally adopted a reverse causal reasoning approach to evaluate and prioritize pathways that are most consistent and responsive to drugs that inhibit cell growth. We evaluated this model in terms of agreement with the observations under treatment of several drugs that produced growth inhibition of cancer cell lines. In particular, we suggested that the metastasis suppressor PEBP1/RKIP is on the receiving end of two significant regulatory mechanisms. One involves RELA (transcription factor p65) and SNAI1, which were previously reported to inhibit PEBP1. The other involves the estrogen receptor (ESR1), which induces PEBP1 through the kinase NME1. Our model was derived in the specific context of breast cancer, but the observed responses to drug treatments were consistent in other cell lines. We further validated some of the predicted regulatory links in the breast cancer cell line MCF7 experimentally and highlighted the points of uncertainty in our model. To summarize, our model was consistent with the observed changes in activity with drug perturbations. In particular, two pathways, including PEBP1, were highly responsive and would be likely targets for intervention.
Childhood Malignant Brain Tumors: Balancing the Bench and Bedside
Authors: Thorbinson Colin , Kilday John-Paul
Published: December 2021

Brain tumors are the leading cause of childhood cancer deaths in developed countries. They also represent the most common solid tumor in this age group, accounting for approximately one-quarter of all pediatric cancers. Developments in neuro-imaging, neurosurgical techniques, adjuvant therapy and supportive care have improved survival rates for certain tumors, allowing a future focus on optimizing cure, whilst minimizing long-term adverse effects. Recent times have witnessed a rapid evolution in the molecular characterization of several of the common pediatric brain tumors, allowing unique clinical and biological patient subgroups to be identified. However, a resulting paradigm shift in both translational therapy and subsequent survival for many of these tumors remains elusive, while recurrence remains a great clinical challenge. This review will provide an insight into the key molecular developments and global co-operative trial results for the most common malignant pediatric brain tumors (medulloblastoma, high-grade gliomas and ependymoma), highlighting potential future directions for management, including novel therapeutic options, and critical challenges that remain unsolved.
Cell-of-Origin and Genetic, Epigenetic, and Microenvironmental Factors Contribute to the Intra-Tumoral Heterogeneity of Pediatric Intracranial Ependymoma
Authors: Servidei Tiziana , Lucchetti Donatella , Navarra Pierluigi , Sgambato Alessandro , Riccardi Riccardo , Ruggiero Antonio
Published: December 2021

Intra-tumoral heterogeneity (ITH) is a complex multifaceted phenomenon that posits major challenges for the clinical management of cancer patients. Genetic, epigenetic, and microenvironmental factors are concurrent drivers of diversity among the distinct populations of cancer cells. ITH may also be installed by cancer stem cells (CSCs), that foster unidirectional hierarchy of cellular phenotypes or, alternatively, shift dynamically between distinct cellular states. Ependymoma (EPN), a molecularly heterogeneous group of tumors, shows a specific spatiotemporal distribution that suggests a link between ependymomagenesis and alterations of the biological processes involved in embryonic brain development. In children, EPN most often arises intra-cranially and is associated with an adverse outcome. Emerging evidence shows that EPN displays large intra-patient heterogeneity. In this review, after touching on EPN inter-tumoral heterogeneity, we focus on the sources of ITH in pediatric intra-cranial EPN in the framework of the CSC paradigm. We also examine how single-cell technology has shed new light on the complexity and developmental origins of EPN and the potential impact that this understanding may have on the therapeutic strategies against this deadly pediatric malignancy.