bluuebunny/crossref_metadata_2025 huggingface dataset:
Eyjafjallajökull Volcanic Ash 2010 Effects on GPS Positioning Performance in the Adriatic Sea Region
Authors: Mehmood Maria , Saleem Sajid , Filjar Renato
Published: December 2021

The Eyjafjallajökull volcanic ash crisis in 2010 temporarily suspended European air traffic operations, as the 39-day eruption caused widely dispersed ashes to enter the lower atmosphere. In this paper, we assessed the effects of this event on the ionosphere layer and, consequently, on GPS positioning. We collected and analysed the data from four IGS stations, nearest to the volcano, for the month of April 2010. We recorded Vertical Total Electron Content (VTEC) time series, analysed their dynamics, and compared them with the GPS positioning errors of a commercial-grade, un-aided, single-frequency GPS receiver (simulating the response of a mass-market GPS receiver). The geomagnetic indices during the time period show little geomagnetic disturbance, especially during the volcanic event. Our results show an enhancement in ionosphere error by up to 15% during the volcanic ash event and an enhanced variance in GPS position components errors. This study reveals the potential impact of the charged volcanic ash on single-frequency, unaided GPS positioning accuracy in the Adriatic Sea region and establishes a foundation for studying similar events in future.
Santa Ana Winds: Fractal-Based Analysis in a Semi-Arid Zone of Northern Mexico
Authors: Serpa-Usta Yeraldin , López-Lambraño Alvaro Alberto , Flores Dora-Luz , Gámez-Balmaceda Ena , Martínez-Acosta Luisa , Medrano-Barboza Juan Pablo , López John Freddy Remolina , López-Ramos Alvaro , López-Lambraño Mariangela
Published: December 2021

A fractal analysis based on the time series of precipitation, temperature, pressure, relative humidity, and wind speed was performed for 16 weather stations located in the hydrographic basin of the Guadalupe River in Baja California, Mexico. Days on which the phenomenon known as Santa Ana winds occurs were identified based on the corresponding criteria of wind speed (≥4.5 m/s) and wind direction (between 0° and 90°). Subsequently, the time series was formed with data representing the days on which this phenomenon occurs in each of the analyzed weather stations. A time series was additionally formed from the days in which the Santa Ana winds condition does not occur. Hurst exponents and fractal dimension were estimated applying the rescaled range method to characterize the established time series in terms of characteristics of persistence, anti-persistence, or randomness along with the calculation of the climate predictability Index. This enabled the behavior and correlation analysis of the meteorological variables associated with Santa Ana winds occurrence. Finally, this type of research study is instrumental in understanding the regional dynamics of the climate in the basin, and allows us to establish a basis for developing models that can forecast the days of occurrence of the Santa Ana winds, in such a way that actions or measures can be taken to mitigate the negative consequences generated when said phenomenon occurs, such as fires and droughts.
N2O Emissions from Two Austrian Agricultural Catchments Simulated with an N2O Submodule Developed for the SWAT Model
Authors: Wang Cong , Schürz Christoph , Zoboli Ottavia , Zessner Matthias , Schulz Karsten , Watzinger Andrea , Bodner Gernot , Mehdi-Schulz Bano
Published: December 2021

Nitrous oxide (N2O) is a potent greenhouse gas stemming mainly from nitrogen (N)-fertilizer application. It is challenging to quantify N2O emissions from agroecosystems because of the dearth of measured data and high spatial variability of the emissions. The eco-hydrological model SWAT (Soil and Water Assessment Tool) simulates hydrological processes and N fluxes in a catchment. However, the routine for simulating N2O emissions is still missing in the SWAT model. A submodule was developed based on the outputs of the SWAT model to partition N2O from the simulated nitrification by applying a coefficient (K2) and also to isolate N2O from the simulated denitrification (N2O + N2) with a modified semi-empirical equation. The submodule was applied to quantify N2O emissions and N2O emission factors from selected crops in two agricultural catchments by using NH4NO3 fertilizer and the combination of organic N and NO3− fertilizer as N input data. The setup with the combination of organic N and NO3− fertilizer simulated lower N2O emissions than the setup with NH4NO3 fertilizer. When the water balance was simulated well (absolute percentage error <11%), the impact of N fertilizer application on the simulated N2O emissions was captured. More research to test the submodule with measured data is needed.
Esophageal Cancer Stem-like Cells Resist Ferroptosis-Induced Cell Death by Active Hsp27-GPX4 Pathway
Authors: Liu Chen-Chi , Li Hsin-Hsien , Lin Jiun-Han , Chiang Ming-Chen , Hsu Tien-Wei , Li Anna Fen-Yau , Yen David Hung-Tsang , Hsu Han-Shui , Hung Shih-Chieh
Published: December 2021

Cancer stem cells (CSCs), a subpopulation of cancer cells responsible for tumor initiation and treatment failure, are more susceptible to ferroptosis-inducing agents than bulk cancer cells. However, regulatory pathways controlling ferroptosis, which can selectively induce CSC death, are not fully understood. Here, we demonstrate that the CSCs of esophageal squamous carcinoma cells enriched by spheroid culture have increased intracellular iron levels and lipid peroxidation, thereby increasing exposure to several products of lipid peroxidation, such as MDA and 4-HNE. However, CSCs do not reduce cell viability until glutathione is depleted by erastin treatment. Mechanistic studies revealed that damage from elevated lipid peroxidation is avoided through the activation of Hsp27, which upregulates GPX4 and thereby rescues CSCs from ferroptosis-induced cell death. Our results also revealed a correlation between phospho-Hsp27 and GPX4 expression levels and poor prognosis in patients with esophageal cancer. Together, these data indicate that targeting Hsp27 or GPX4 to block this intrinsic protective mechanism against ferroptosis is a potential treatment strategy for eradicating CSC in esophageal squamous cell carcinoma.
Investigation of Leoligin Derivatives as NF-κΒ Inhibitory Agents
Authors: Linder Thomas , Papaplioura Eleni , Ogurlu Diyana , Geyrhofer Sophie , Hummelbrunner Scarlet , Schachner Daniel , Atanasov Atanas G. , Mihovilovic Marko D. , Dirsch Verena M. , Schnürch Michael
Published: December 2021

The transcription factor NF-κB is an essential mediator of inflammation; thus, the identification of compounds that interfere with the NF-κB signaling pathway is an important topic. The natural products leoligin and 5-methoxyleoligin have served as a starting point for the development of NF-κB inhibitors. Using our modular total synthesis method of leoligin, modifications at two positions were undertaken and the effects of these modifications on the biological activity were investigated. The first modification concerned the ester functionality, where it was found that variations in this position have a significant influence, with bulky esters lacking Michael-acceptor properties being favored. Additionally, the substituents on the aryl group in position 2 of the tetrahydrofuran scaffold can vary to some extent, where it was found that a 3,4-dimethoxy and a 4-fluoro substitution pattern show comparable inhibitory efficiency.
Effects of Physical Exercise and Virtual Training on Visual Attention Levels in Children with Autism Spectrum Disorders
Authors: Ji Chaoxin , Yang Jun
Published: December 2021

This study compared the effects of physical exercise (PE) and virtual training (VT) on the improvement of the visual attention mechanism in children with autism spectrum disorders (ASD). One hundred eighty-nine children with ASD were recruited from Orphan School in Liaoning Province, China. After screening, 100 children ultimately participated in the experiment. Children with ASD were randomly assigned to VT (VT, n = 34), PE (PE, n = 33) and control group (CG, n = 33). The VT group experiment was performed in a virtual environment through the game FIFA21 three times per week for 6 weeks. The PE group played physical football matches three times per week for 6 weeks. Children with ASD in the CG group did not receive VT or PE but only received psychological counseling. Visual attention of children with ASD is evaluated by using the multiple object tracking paradigm (MOT). After 6 weeks of observation, although none of the three groups saw improvements in the correct rate of ring tracking, the observations of the VT and PE groups were significant (p < 0.05) compared to the CG group in finding detection rate of probe stimulus. Through MOT tests, VT and PE improved the detection rate of probe stimulus in children with ASD. Therefore, this paper indicates that VT and PE can improve the visual attention ability of children with ASD.
In-Organization Ethics Power-Allocation Mechanisms and Members’ Decision-Making Behavior
Authors: Pang Yudan , Wang Xuefeng , Wu Hang , Zhang Fanfan
Published: December 2021

This study examines experimental evidence showing how ethics power allocation mechanisms affect an individual’s in-organization resource division and ethical behavior. We used two two-stage lab experiments to explore power seeking and usage; the experiments contained two stages of power contending and power usage. Stage one used two different power-seeking mechanisms in the honesty game. Stage two was based on the dictator game and the ultimatum game to measure an individual’s power usage. The results show that the decisions taken by power-holders could influence the optimization of collective resources, and power-holders who gain power with unethical methods could result in collective resource allocation inequities. With more balanced in-organization power, members tend to be more honest. Subjects also adjust their unethical behavior to adapt to the environment, which could cause the diffusion of unethical behavior. This paper re-designed the dictator game and the ultimatum game by adding an ethically vulnerable power acquisition mechanism. For organizations to prevent the disproportionate dispersion of resources and achieve more public benefits, it is meaningful for managers to create a proper in-organization ethical power allocation mechanism.
A Trimodality, Four-Step Treatment including Chemotherapy, Pleurectomy/Decortication and Radiotherapy in Early-Stage Malignant Pleural Mesothelioma: A Single-Institution Retrospective Case Series Study
Authors: Vicidomini Giovanni , Della Corte Carminia Maria , Noro Antonio , Di Liello Raimondo , Cappabianca Salvatore , Fiorelli Alfonso , Nardone Valerio , Messina Gaetana , Viscardi Giuseppe , Sangiovanni Angelo , Monti Riccardo , Accardo Marina , Morgillo Floriana , Ciardiello Fortunato , Franco Renato , Santini Mario
Published: December 2021

Background: Multimodality treatment is considered the best treatment strategy for malignant pleural mesothelioma (MPM). However, the ideal combination of them is still a matter of controversy. Here, we report a case series of MPM treated with a trimodality approach: induction chemotherapy (CT), pleurectomy/decortication (P/D), postoperative radiotherapy (RT) and post-operative CT. Methods: A retrospective case series of 17 MPM patients treated between 2013 and 2020 is presented. Patients had epithelial or mixed MPM diagnosed by video-assisted thoracoscopy and pathologic IMIG stage I or II disease. Treatment details and radiological data were collected. Induction therapy consisted of combination of cisplatin and pemetrexed, every 21 days for two cycles. P/D was performed 4–6 weeks after induction CT, post-operative RT 3–6 weeks after surgery, while post-operative CT was given 4–6 weeks after RT, with the same schedule of induction. Results: All patients showed objective response or stability of disease at the restaging following induction CT and underwent surgery by posterolateral thoracotomy. There were two cases of cardiac arrest as major intraoperative complication, both resolved by manual cardiac massage. Minor complications included one hemidiaphragm elevation, 1 anemia requiring blood transfusion, one wound infection, and two persistent air leaks. Median overall survival was 32.1 months, median progression free survival was 23.7 months. Conclusions: These results suggest the feasibility of these trimodality treatment scheme for early stage MPM patients. Larger series and long-term prospective studies are needed to confirm the validity of this strategy.
Analysis of the Single-Cell Heterogeneity of Adenocarcinoma Cell Lines and the Investigation of Intratumor Heterogeneity Reveals the Expression of Transmembrane Protein 45A (TMEM45A) in Lung Adenocarcinoma Cancer Patients
Authors: Neuperger Patrícia , Balog József Á. , Tiszlavicz László , Furák József , Gémes Nikolett , Kotogány Edit , Szalontai Klára , Puskás László G. , Szebeni Gábor J.
Published: December 2021

Intratumoral heterogeneity (ITH) is responsible for the majority of difficulties encountered in the treatment of lung-cancer patients. Therefore, the heterogeneity of NSCLC cell lines and primary lung adenocarcinoma was investigated by single-cell mass cytometry (CyTOF). First, we studied the single-cell heterogeneity of frequent NSCLC adenocarcinoma models, such as A549, H1975, and H1650. The intra- and inter-cell-line single-cell heterogeneity is represented in the expression patterns of 13 markers—namely GLUT1, MCT4, CA9, TMEM45A, CD66, CD274 (PD-L1), CD24, CD326 (EpCAM), pan-keratin, TRA-1-60, galectin-3, galectin-1, and EGFR. The qRT-PCR and CyTOF analyses revealed that a hypoxic microenvironment and altered metabolism may influence cell-line heterogeneity. Additionally, human primary lung adenocarcinoma and non-involved healthy lung tissue biopsies were homogenized to prepare a single-cell suspension for CyTOF analysis. The CyTOF showed the ITH of human primary lung adenocarcinoma for 14 markers; particularly, the higher expressions of GLUT1, MCT4, CA9, TMEM45A, and CD66 were associated with the lung-tumor tissue. Our single-cell results are the first to demonstrate TMEM45A expression in human lung adenocarcinoma, which was verified by immunohistochemistry.
Influence of Gender on Radiosensitivity during Radiochemotherapy of Advanced Rectal Cancer
Authors: Schuster Barbara , Hecht Markus , Schmidt Manfred , Haderlein Marlen , Jost Tina , Büttner-Herold Maike , Weber Klaus , Denz Axel , Grützmann Robert , Hartmann Arndt , Geinitz Hans , Fietkau Rainer , Distel Luitpold V.
Published: December 2021

Gender is increasingly recognized as an important factor in medicine, although it has long been neglected in medical research in many areas. We have studied the influence of gender in advanced rectal cancer with a special focus on radiosensitivity. For this purpose, we studied a cohort of 495 men (84.1% ≥ T3, 63.6% N1, 17.6%, M1) and 215 women (84.2% ≥ T3, 56.7% N1, 22.8%, M1) who all suffered from advanced rectal cancer and were treated with radiochemotherapy. The energy deposited, DNA double-strand break (dsb) repair, occurrence of chromosomal aberrations, duration of therapy, tumor regression and tumor-infiltrating lymphocytes, laboratory parameters, quality of life and survival were assessed. The residual DNA dsb damage 24 h after irradiation in lymphocytes was identical in both sexes. Furthermore, chromosomal aberrations accurately reflecting radiosensitivity, were similar in both sexes. There were no gender-dependent differences in tumor regression, tumor-infiltrating lymphocytes and outcome indicating no differences in the radiosensitivity of cancer cells. The irradiated tumor volume in women was slightly lower than in men, related to body weight, no difference was observed. However, when the total energy deposited was calculated and related to the body weight, women were exposed to higher amounts of ionizing radiation. During radiochemotherapy, decreases in blood lymphocyte counts and albumin and several quality-of-life parameters such as nausea and vomiting, loss of appetite, and diarrhea were significantly worse in women. There is no difference in radiation sensitivity between men and women in both normal tissue and tumors. During radiochemotherapy, the quality of life deteriorates more in women than in men. However, women also recover quickly and there are no long-term differences in quality of life.
Sociodemographic and Medical Determinants of Quality of Life in Long-Term Childhood Acute Lymphoblastic Leukemia Survivors Enrolled in EORTC CLG Studies
Authors: Sleurs Charlotte , Musoro Jammbe , Rowsell Ali , Kicinski Michal , Suciu Stefan , Chantziara Sofia , Coens Corneel , Pe Madeline , Missotten Pierre , Vandecruys Els , Uyttebroeck Anne , Dresse Marie-Françoise , Pluchart Claire , Ferster Alina , Freycon Claire , van der Werff ten Bosch Jutte , Rohrlich Pierre-Simon , Benoit Yves , Darlington Anne-Sophie , Piette Caroline
Published: December 2021

Background: due to increasing survival rates in childhood acute lymphoblastic leukemia (ALL), the number of survivors has been expanding. A significant proportion of these survivors can experience long-term emotional and psychosocial problems. However, the exact risk factors remain inconclusive. We investigated potential risk factors for decreased daily life quality and life challenges in long-term childhood ALL survivors enrolled between 1971 and 1998 in EORTC studies. Methods: self-report questionnaires were collected from 186 survivors (109 females; mean age at diagnosis 5.62 years, range 0.2–14.7; median time since diagnosis of 20.5 years (12.9–41.6)), including the Short-Form Health Survey (SF-12) and Impact of Cancer-Childhood Survivors (IOC-CS). Multivariable linear regression models were used to assess the impact of gender, age at diagnosis, relapse/second neoplasm, National Cancer Institute (NCI) risk group and cranial radiotherapy on 2 subscales of the SF-12 (physical and mental health) and five subscales of the IOC-CS (life challenges, body and health, personal growth, thinking and memory problems and socializing). Results: mental component scores of SF-12 were not significantly associated with any risk factor. Physical component scores were lower in relapsed, irradiated and NCI high-risk patients. Regarding IOC-CS negative impact subscales, life challenges was more negatively impacted by cancer in female, younger (i.e., <6 years) and relapsed patients. Regarding the positive impact scales, personal growth was more positively impacted in relapsed patients, whereas body and health, and socializing, were less positively impacted in these patients, compared to non-relapsed patients. Socializing was more positively impacted in older patients (>6 years). Conclusions: this study demonstrates that long-term outcomes can be both adverse and positive, depending on the patient’s demographic and clinical characteristics. Younger, female, and relapsed patients might encounter more life challenges years after their disease, while physical challenges could occur more often in relapsed and high-risk patients. Finally, the positive effect on socializing in the older patients sheds new light on the importance of peer interactions for this subgroup. Specific individual challenges thus need specialized support for specific subgroups.
Building a Foundation for Precision Onco-Nutrition: Docosahexaenoic Acid and Breast Cancer
Authors: Thompson Henry J. , Neil Elizabeth S. , McGinley John N. , Fitzgerald Vanessa K. , El Bayoumy Karam , Manni Andrea
Published: December 2021

In vivo evidence of heterogeneous effects of n-3 fatty acids (N3FA) on cell signaling pathways associated with the reduced growth of breast cancer has been reported and is consistent with the expectation that N3FA will not exert uniform effects on all molecular subtypes of the disease. Similarly, available evidence indicates that many metabolites of N3FA are synthesized by mammalian cells and that they exert metabolite-specific biological activities. To begin to unravel the complex relationships among molecular subtypes and effects exerted by specific N3FA metabolites on those pathways, proof-of-concept experiments were conducted using cell lines representative of common molecular subtypes of human breast cancer. N3FA differed in anticancer activity with docosahexaenoic acid (DHA) having greater anticancer activity than eicosapentaenoic acid. 4-oxo-docosahexaenoic (4-oxo-DHA), a penultimate metabolite of 5-lipoxygenase mediated DHA metabolism, induced dose-dependent inhibition of cell number accumulation with apoptosis as a primary effector mechanism. Interrogation of protein expression data using the Ingenuity Pathway Analysis (IPA) bioinformatics platform indicated that 4-oxo-DHA differentially impacted six canonical pathways and the cellular functions they regulate across common molecular subtypes of breast cancer. This included the endocannabinoid pathway for cancer inhibition that has not been previously reported. These findings provide a rationale for juxtaposing molecular subtype targeted treatment strategies with the adjuvant use of specific N3FA metabolites as an example of precision onco-nutrition (PON) for the management and control of breast cancer.
Understanding the Role and Clinical Applications of Exosomes in Gynecologic Malignancies: A Review of the Current Literature
Authors: Roy Molly , Yang Yu-Ping , Bosquet Olivia , Deo Sapna K. , Daunert Sylvia
Published: December 2021

Background: Gynecologic malignancies are those which arise in the female reproductive organs of the ovaries, cervix, and uterus. They carry a great deal of morbidity and mortality for patients, largely due to challenges in diagnosis and treatment of these cancers. Although advances in technology and understanding of these diseases have greatly improved diagnosis, treatment, and ultimately survival for patients with gynecologic malignancies over the last few decades, there is still room for improvements in diagnosis and treatment, for which exosomes may be the key. This paper reviews the current knowledge regarding gynecologic tumor derived-exosomal genetic material and proteins, their role in cancer progression, and their potential for advancing the clinical care of patients with gynecologic cancers through novel diagnostics and therapeutics. Literature Review: Ovarian tumor derived exosome specific proteins are reviewed in detail, discussing their role in ovarian cancer metastasis. The key microRNAs in cervical cancer and their implications in future clinical use are discussed. Additionally, uterine cancer-associated fibroblast (CAF)-derived exosomes which may promote endometrial cancer cell migration and invasion through a specific miR-148b are reviewed. The various laboratory techniques and commercial kits for the isolation of exosomes to allow for their clinical utilization are described as well. Conclusion: Exosomes may be the key to solving many unanswered questions, and closing the gaps so as to improve the outcomes of patients with gynecologic cancers around the world. The potential utilization of the current knowledge of exosomes, as they relate to gynecologic cancers, to advance the field and bridge the gaps in diagnostics and therapeutics highlight the promising future of exosomes in gynecologic malignancies.
PAK4 and NAMPT as Novel Therapeutic Targets in Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, and Mantle Cell Lymphoma
Authors: Khan Husain Yar , Uddin Md. Hafiz , Balasubramanian Suresh Kumar , Sulaiman Noor , Iqbal Marium , Chaker Mahmoud , Aboukameel Amro , Li Yiwei , Senapedis William , Baloglu Erkan , Mohammad Ramzi M. , Zonder Jeffrey , Azmi Asfar S.
Published: December 2021

Diffuse large B-cell lymphoma (DLBCL), grade 3b follicular lymphoma (FL), and mantle cell lymphoma (MCL) are aggressive non-Hodgkin’s lymphomas (NHL). Cure rates are suboptimal and novel treatment strategies are needed to improve outcomes. Here, we show that p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyl transferase (NAMPT) is critical for lymphoma subsistence. Dual targeting of PAK4-NAMPT by the Phase I small molecule KPT-9274 suppressed cell proliferation in DLBCL, FL, and MCL. Growth inhibition was concurrent with apoptosis induction alongside activation of pro-apoptotic proteins and reduced pro-survival markers. We observed NAD suppression, ATP reduction, and consequent cellular metabolic collapse in lymphoma cells due to KPT-9274 treatment. KPT-9274 in combination with standard-of-care chemotherapeutics led to superior inhibition of cell proliferation. In vivo, KPT-9274 could markedly suppress the growth of WSU-DLCL2 (DLBCL), Z-138, and JeKo-1 (MCL) sub-cutaneous xenografts, and a remarkable increase in host life span was shown, with a 50% cure of a systemic WSU-FSCCL (FL) model. Residual tumor analysis confirmed a reduction in total and phosphorylated PAK4 and activation of the pro-apoptotic cascade. This study, using various preclinical experimental models, demonstrates the therapeutic potential of targeting PAK4-NAMPT in DLBCL, FL, and MCL. The orally bioavailable, safe, and efficacious PAK4-NAMPT dual inhibitor KPT-9274 warrants further clinical investigation.
Genetic and Biochemical Characterizations of aLhr1 Helicase in the Thermophilic Crenarchaeon Sulfolobus acidocaldarius
Authors: Suzuki Shoji , Kurosawa Norio , Yamagami Takeshi , Matsumoto Shunsuke , Numata Tomoyuki , Ishino Sonoko , Ishino Yoshizumi
Published: December 2021

Homologous recombination (HR) refers to the process of information exchange between homologous DNA duplexes and is composed of four main steps: end resection, strand invasion and formation of a Holliday junction (HJ), branch migration, and resolution of the HJ. Within each step of HR in Archaea, the helicase-promoting branch migration is not fully understood. Previous biochemical studies identified three candidates for archaeal helicase promoting branch migration in vitro: Hjm/Hel308, PINA, and archaeal long helicase related (aLhr) 2. However, there is no direct evidence of their involvement in HR in vivo. Here, we identified a novel helicase encoded by Saci_0814, isolated from the thermophilic crenarchaeon Sulfolobus acidocaldarius; the helicase dissociated a synthetic HJ. Notably, HR frequency in the Saci_0814-deleted strain was lower than that of the parent strain (5-fold decrease), indicating that Saci_0814 may be involved in HR in vivo. Saci_0814 is classified as an aLhr1 under superfamily 2 helicases; its homologs are conserved among Archaea. Purified protein produced in Escherichia coli showed branch migration activity in vitro. Based on both genetic and biochemical evidence, we suggest that aLhr1 is involved in HR and may function as a branch migration helicase in S. acidocaldarius.
In Vitro Monitoring of Human T Cell Responses to Skin Sensitizing Chemicals—A Systematic Review
Authors: Aparicio-Soto Marina , Curato Caterina , Riedel Franziska , Thierse Hermann-Josef , Luch Andreas , Siewert Katherina
Published: December 2021

Background: Chemical allergies are T cell-mediated diseases that often manifest in the skin as allergic contact dermatitis (ACD). To prevent ACD on a public health scale and avoid elicitation reactions at the individual patient level, predictive and diagnostic tests, respectively, are indispensable. Currently, there is no validated in vitro T cell assay available. The main bottlenecks concern the inefficient generation of T cell epitopes and the detection of rare antigen-specific T cells. Methods: Here, we systematically review original experimental research papers describing T cell activation to chemical skin sensitizers. We focus our search on studies published in the PubMed and Scopus databases on non-metallic allergens in the last 20 years. Results: We identified 37 papers, among them 32 (86%) describing antigen-specific human T cell activation to 31 different chemical allergens. The remaining studies measured the general effects of chemical allergens on T cell function (five studies, 14%). Most antigen-specific studies used peripheral blood mononuclear cells (PBMC) as antigen-presenting cells (APC, 75%) and interrogated the blood T cell pool (91%). Depending on the individual chemical properties, T cell epitopes were generated either by direct administration into the culture medium (72%), separate modification of autologous APC (29%) or by use of hapten-modified model proteins (13%). Read-outs were mainly based on proliferation (91%), often combined with cytokine secretion (53%). The analysis of T cell clones offers additional opportunities to elucidate the mechanisms of epitope formation and cross-reactivity (13%). The best researched allergen was p-phenylenediamine (PPD, 12 studies, 38%). For this and some other allergens, stronger immune responses were observed in some allergic patients (15/31 chemicals, 48%), illustrating the in vivo relevance of the identified T cells while detection limits remain challenging in many cases. Interpretation: Our results illustrate current hardships and possible solutions to monitoring T cell responses to individual chemical skin sensitizers. The provided data can guide the further development of T cell assays to unfold their full predictive and diagnostic potential, including cross-reactivity assessments.
Triticale Green Plant Regeneration Is Due to DNA Methylation and Sequence Changes Affecting Distinct Sequence Contexts in the Presence of Copper Ions in Induction Medium
Authors: Orłowska Renata , Pachota Katarzyna Anna , Androsiuk Piotr , Bednarek Piotr Tomasz
Published: December 2021

Metal ions in the induction medium are essential ingredients allowing green plant regeneration. For instance, Cu(II) and Ag(I) ions may affect the mitochondrial electron transport chain, influencing the Yang cycle and synthesis of S-adenosyl-L-methionine, the prominent donor of the methylation group for all cellular compounds, including cytosines. If the ion concentrations are not balanced, they can interfere with the proper flow of electrons in the respiratory chain and ATP production. Under oxidative stress, methylated cytosines might be subjected to mutations impacting green plant regeneration efficiency. Varying Cu(II) and Ag(I) concentrations in the induction medium and time of anther culture, nine trials of anther culture-derived regenerants of triticale were derived. The methylation-sensitive AFLP approach quantitative characteristics of tissue culture-induced variation, including sequence variation, DNA demethylation, and DNA de novo methylation for all symmetric-CG, CHG, and asymmetric-CHH sequence contexts, were evaluated for all trials. In addition, the implementation of mediation analysis allowed evaluating relationships between factors influencing green plant regeneration efficiency. It was demonstrated that Cu(II) ions mediated relationships between: (1) de novo methylation in the CHH context and sequence variation in the CHH, (2) sequence variation in CHH and green plant regeneration efficiency, (3) de novo methylation in CHH sequences and green plant regeneration, (4) between sequence variation in the CHG context, and green plant regeneration efficiency. Cu(II) ions were not a mediator between de novo methylation in the CG context and green plant regeneration. The latter relationship was mediated by sequence variation in the CG context. On the other hand, we failed to identify any mediating action of Ag(I) ions or the moderating role of time. Furthermore, demethylation in any sequence context seems not to participate in any relationships leading to green plant regeneration, sequence variation, and the involvement of Cu(II) or Ag(I) as mediators.
Osthole Inhibits Expression of Genes Associated with Toll-like Receptor 2 Signaling Pathway in an Organotypic 3D Skin Model of Human Epidermis with Atopic Dermatitis
Authors: Kordulewska Natalia Karolina , Topa Justyna , Stryiński Robert , Jarmołowska Beata
Published: December 2021

The Toll-like receptor (TLR) family signature has been linked to the etiopathology of atopic dermatitis (AD), a chronic inflammatory skin disease associated with skin barrier dysfunction and immune system imbalance. We aimed to investigate whether osthole (a plant-derived compound) can inhibit the genetic profile of key genes associated with TLR2 signaling (TIRAP, MyD88, IRAK1, TRAF6, IκBα, NFκB) after stimulation with LPS or histamine in a 3D in vitro model of AD. Overexpression of the aforementioned genes may directly increase the secretion of proinflammatory cytokines (CKs) and chemokines (ChKs), which may exacerbate the symptoms of AD. Relative gene expressions were quantified by qPCR and secretion of CKs and ChKs was evaluated by ELISA assay. LPS and histamine increased the relative expression of genes related to the TLR2 pathway, and osthole successfully reduced it. In summary, our results show that osthole inhibits the expression of genes associated with the TLR signaling pathway in a skin model of AD. Moreover, the secretion of CKs and ChKs after treatment of AD with osthole in a 3D skin model in vitro suggests the potential of osthole as a novel compound for the treatment of AD.
Association between Exosomal miRNAs and Coronary Artery Disease by Next-Generation Sequencing
Authors: Chang Sheng-Nan , Chen Jien-Jiun , Wu Jo-Hsuan , Chung Yao-Te , Chen Jin-Wun , Chiu Chu-Hsuan , Liu Chia-Ju , Liu Meng-Tsun , Chang Yi-Cheng , Li Chin , Lin Jou-Wei , Hwang Juey-Jen , Lien Wen-Pin
Published: December 2021

Background: Among various bio-informative molecules transferred by exosomes between cells, micro RNAs (miRNAs), which remain remarkably stable even after freeze-and-thaw cycles, are excellent candidates for potential biomarkers for coronary artery disease (CAD). Methods: Blood samples were collected from the coronary arteries of 214 patients diagnosed with three-vessel CAD and 140 without CAD. After precipitation extraction, the amounts of exosomes were found to decrease with increased age and three-vessel CAD. Next-generation sequencing was performed to further explore the possible relationship between exosomal miRNAs and CAD. Results: Eight exosomal miRNAs showed altered expression associated with CAD. The up-regulated miRNAs in CAD were miRNA-382-3p, miRNA-432-5p, miRNA-200a-3p, and miRNA-3613-3p. The down-regulated miRNAs were miRNA-125a-5p, miRNA-185-5p, miRNA-151a-3p, and miRNA-328-3p. Conclusion: We successfully demonstrated particular exosomal miRNAs that may serve as future biomarkers for CAD.
Sexual Risk Behaviors of Adolescents with Type 1 Diabetes in Comparison with Their Peers
Authors: Kandyla Betina , Tsitsika Artemis , Soldatou Alexandra , Tzavara Chara , Karanasios Spyridon , Karavanaki Kyriaki
Published: December 2021

Background: Adolescents with type 1 diabetes mellitus (T1D) may differ from peers regarding sexual risk behaviors. Objectives: To explore sexual risk behaviors of adolescents with T1D in comparison with peers. Materials and methods: The subjects were 174 adolescents, 58 adolescents with T1D (mean ± SD age 16.3 ± 2.0 yrs, disease duration 6.7 ± 3.5 yrs and HbA1c:8.0 ± 1.3%) and 116 without (matched 1:2). Anonymous, self-reported questionnaires were used to evaluate sexual education and behaviors. Results: Fewer adolescents with T1D than those without had a sexual experience (74.1% vs. 87.4%, p = 0.033), with similar age of sexual debut. Among adolescents with T1D, ≥2 risky behaviors were observed less frequently than adolescents without T1D (8.62% vs. 23.27%, p = NS respectively) and in fewer girls than boys in both adolescents with T1D (0% vs. 18.5%, p = NS) and adolescents without T1D (11% vs. 44%, p = 0.022). Adolescents with T1D with ≥2 risky behaviors were older (p = 0.031), younger at first sexual intercourse (p = 0.031), with higher maternal education (p = 0.039). Early sexual debut was associated with higher maternal education (p = 0.014) and HbA1c (p = 0.049). Most adolescents without T1D with ≥2 risky behaviors were boys and older than peers. Conclusions: Adolescents with T1D and females were more cautious than adolescents without T1D regarding sex. The associations of increased risky behaviors with male gender, older age, younger age at sexual debut and higher maternal education in adolescents with T1D merit further investigation.
Effects of After-School Volleyball Program on Body Composition in Overweight Adolescent Girls
Authors: Trajković Nebojša , Lazić Anja , Trkulja-Petković Drena , Barišić Valentin , Milić Vladan , Nikolić Siniša , Sporiš Goran
Published: December 2021

The current study aimed to investigate the effects of an after-school volleyball program on body composition in overweight adolescent girls. Forty-two girls were randomly divided into a volleyball group (VG) (n = 22 age: 15.6 ± 0.5 years) and control group (CG) (n = 20; age: 15.5 ± 0.7 years). Both groups continued with their usual physical education activities, while VG was included as small-sided games, two times a week, after school, on modified volleyball courts. Body mass, body mass index (BMI), body fat in kg, body fat percentage, and muscle mass were analyzed by a bioelectrical impedance method. There was a significant interaction of group (VG vs. CG) × time (pre-vs. post) for weight [F1, 40 = 7.933; p = 0.004] and BMI [F1, 40 = 5.764; p = 0.015]. Additionally, a significant main effect of time was found for body fat (kg) [F1, 40 = 17.650; p < 0.001] and body fat (%) [F1, 40 = 18.721; p < 0.001]. The results of the current study show that a twelve-week after-school volleyball program, including two sessions a week, can improve body composition in overweight adolescent girls.
Aripiprazole-Induced Oculogyric Crisis: A Pediatric Case Series and A Brief Narrative Review
Authors: Bernardo Pia , Rubino Alfonso , Santoro Claudia , Bravaccio Carmela , Pozzi Marco , Pisano Simone
Published: December 2021

Oculogyric crisis (OGC) represent an unusual type of dystonic movement disorder, usually reported as an adverse event of antipsychotic drugs, with acute or tardive onset, likely due to a functional disruption of dopaminergic neurotransmission. It is seldom reported in children with aripiprazole, an atypical antipsychotic commonly used in youths. In this manuscript, we report on a case series of three pediatric patients and provide a brief narrative review of the literature, in order to increase the awareness of clinicians and to foster future research in this area.
Application of a Combined Peptidomics and In Silico Approach for the Identification of Novel Dipeptidyl Peptidase-IV-Inhibitory Peptides in In Vitro Digested Pinto Bean Protein Extract
Authors: Martini Serena , Cattivelli Alice , Conte Angela , Tagliazucchi Davide
Published: December 2021

The conventional approach in bioactive peptides discovery, which includes extensive bioassay-guided fractionation and purification processes, is tedious, time-consuming and not always successful. The recently developed bioinformatics-driven in silico approach is rapid and cost-effective; however, it lacks an actual physiological significance. In this study a new integrated peptidomics and in silico method, which combines the advantages of the conventional and in silico approaches by using the pool of peptides identified in a food hydrolysate as the starting point for subsequent application of selected bioinformatics tools, has been developed. Pinto bean protein extract was in vitro digested and peptides were identified by peptidomics. The pool of obtained peptides was screened by in silico analysis and structure–activity relationship modelling. Three peptides (SIPR, SAPI and FVPH) were selected as potential inhibitors of the dipeptidyl-peptidase-IV (DPP-IV) enzyme by this integrated approach. In vitro bioactivity assay showed that all three peptides were able to inhibit DPP-IV with the tetra-peptide SAPI showing the highest activity (IC50 = 57.7 μmol/L). Indeed, a new possible characteristic of peptides (i.e., the presence of an S residue at the N-terminus) able to inhibit DPP-IV was proposed.
Colorimetric Measurement of Deltamethrin Pesticide Using a Paper Sensor Based on Aggregation of Gold Nanoparticles
Authors: Zhu Jingyang , Yin Lifeng , Zhang Weiyi , Chen Meilian , Feng Dongsheng , Zhao Yong , Zhu Yongheng
Published: December 2021

Deltamethrin (DEL) is one of the most commonly used pyrethroid pesticides that can cause serious harms to the ecological environment and human health. Herein, we have developed a paper-based colorimetric sensor impregnated with gold nanoparticles (AuNPs) for on-site determination of DEL pesticide. AuNPs show obvious color change on paper device with the presence of DEL. Measuring the gray intensity of the AuNPs on the reaction zone of the paper sensor allows accurate quantitative analysis. The detection mechanism of DEL on paper sensor was confirmed by UV-Vis spectrophotometry (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscope (TEM). Under optimal conditions, the colorimetric sensor exhibited high sensitivity, rapid detection, and low detection limit within the values stipulated by Chinese detection standards (LOD = 0.584 mg/L). Besides, detecting DEL in vegetable and fruit samples also gave satisfying results, which were much consistent with those obtained by spectrophotometry. Overall, this work provided a user-friendly, cost-effective and visualized detection platform, which could be applied to rapidly detect DEL pesticides in the food safety field.
Genetic Diversity of the Surubim-Do-Iguaçu, a Giant Catfish Species Threatened with Extinction: Recommendations for Species Conservation
Authors: Souza-Shibatta Lenice , Ferreira Dhiego G. , Assumpção Lucileine de , Shibatta Oscar A. , Sofia Silvia H. , Pini Suelen F. R. , Silva Patricia S. da , Makrakis Sergio , Makrakis Maristela C.
Published: December 2021

Steindachneridion melanodermatum is the largest catfish of the Lower Iguaçu River and is endangered due to the habitat fragmentation caused by dams. Currently, the wild population’s last refuge is restricted to an area of 190 km. This study presents the first analysis of its genetic diversity and population structure, using microsatellite loci and mtDNA. The population has an adequate level of genetic diversity, but signs of a recent bottleneck were observed. The Baixo Iguaçu Hydroelectric Power Plant has recently fragmented the population and threatened it with extinction in a reduced area of nearly 30 km. Based on our results, we strongly advise against the stocking of breeding specimens below the Salto Caxias HPP to not compromise the integrity of the native gene pools at the receptor sites. In addition, we recommend manual fish transposition, trap-and-haul, to maintain the genetic connectivity of individuals upstream and downstream of the dam as a conservation strategy. Furthermore, studies on behavior and swimming capacities, and suitable fishways for this species must be developed. We strongly recommend that the Lower Iguaçu River and its tributaries be protected and preserved as free from additional barriers to prevent future habitat disruption for the benefit of S. melanodermatum and several other endemic and endangered species.
Positive Interactions Drive Bat Distribution in a Remote Oceanic Archipelago (Azores, Portugal)
Authors: Rainho Ana
Published: December 2021

One of the fundamental interests in ecology is understanding which factors drive species’ distribution. We aimed to understand the drivers of bat distribution and co-occurrence patterns in a remote, insular system. The two bat species known to occur in the Azores archipelago were used as a model. Echolocation calls were recorded at 414 point-locations haphazardly distributed across the archipelago. Calls were analysed and assigned to each species. Binominal generalised linear models were adjusted using different descriptors at two scales: archipelago and island. The presence of the co-occurring species was included at both scales. The results show that island isolation, habitat and climate play an essential role on the archipelago and island scales, respectively. However, the positive interaction between bat species was the most critical driver of species’ distribution at the island scale. This high co-occurrence pattern at the island scale may result from both species’ maximising foraging profit in a region where prey abundance may be highly variable. However, further research is necessary to clarify the mechanisms behind this positive interaction. Both species are threatened and lack specific management and protection measures. Maintaining this positive interaction between the two species may prove to be fundamental for their conservation.
Structure and Functionality of the Mesozooplankton Community in a Coastal Marine Environment: Portofino Marine Protected Area (Liguria)
Authors: Vassallo Paolo , Bellardini Daniele , Castellano Michela , Dapueto Giulia , Povero Paolo
Published: December 2021

This research is part of the LTER (Long-Term Ecological Research) project, a network of terrestrial, freshwater, transitional water and marine sites, on which ecological research is conducted on a multi-decade scale. LTER studies ecosystems, their dynamics and evolution, the relationships between biodiversity and ecological functionality, water quality, productivity, the role of resource availability, the effects of pollution and climate change. The research focuses on the study of the variability of zooplankton groups in the Portofino marine protected area, in Punta Faro. The samplings were carried out in the years 2018–2019, and the results were compared with the values of the years 2003–2005, interesting from a meteorological climatic and biological point of view. The plankton community of the Punta Faro system was analyzed by means of a modeling approach to obtain information on the functionality and health status of the system and to verify whether this has undergone any alterations in the last decade. The analyses carried out show a clear difference between the three-year period 2003–2005 and the two-year period 2018–2019, highlighting how environmental changes, such as the increase in temperature, have led to higher costs of system functioning in the last two years. The mesozooplankton community has changed both in terms of abundance of organisms and in terms of organization and functionality.
Deep Learning Supplants Visual Analysis by Experienced Operators for the Diagnosis of Cardiac Amyloidosis by Cine-CMR
Authors: Germain Philippe , Vardazaryan Armine , Padoy Nicolas , Labani Aissam , Roy Catherine , Schindler Thomas Hellmut , El Ghannudi Soraya
Published: December 2021

Background: Diagnosing cardiac amyloidosis (CA) from cine-CMR (cardiac magnetic resonance) alone is not reliable. In this study, we tested if a convolutional neural network (CNN) could outperform the visual diagnosis of experienced operators. Method: 119 patients with cardiac amyloidosis and 122 patients with left ventricular hypertrophy (LVH) of other origins were retrospectively selected. Diastolic and systolic cine-CMR images were preprocessed and labeled. A dual-input visual geometry group (VGG ) model was used for binary image classification. All images belonging to the same patient were distributed in the same set. Accuracy and area under the curve (AUC) were calculated per frame and per patient from a 40% held-out test set. Results were compared to a visual analysis assessed by three experienced operators. Results: frame-based comparisons between humans and a CNN provided an accuracy of 0.605 vs. 0.746 (p < 0.0008) and an AUC of 0.630 vs. 0.824 (p < 0.0001). Patient-based comparisons provided an accuracy of 0.660 vs. 0.825 (p < 0.008) and an AUC of 0.727 vs. 0.895 (p < 0.002). Conclusion: based on cine-CMR images alone, a CNN is able to discriminate cardiac amyloidosis from LVH of other origins better than experienced human operators (15 to 20 points more in absolute value for accuracy and AUC), demonstrating a unique capability to identify what the eyes cannot see through classical radiological analysis.