bluuebunny/crossref_metadata_2025 huggingface dataset:
Leaf-Scale Study of Biogenic Volatile Organic Compound Emissions from Willow (Salix spp.) Short Rotation Coppices Covering Two Growing Seasons
Authors: Karlsson Tomas , Klemedtsson Leif , Rinnan Riikka , Holst Thomas
Published: November 2021

In Europe, willow (Salix spp.) trees have been used commercially since the 1980s at a large scale to produce renewable energy. While reducing fossil fuel needs, growing short rotation coppices (SRCs), such as poplar or willow, may have a high impact on local air quality as these species are known to produce high amounts of isoprene, which can lead to the production of tropospheric ozone (O3). Here, we present a long-term leaf-scale study of biogenic volatile organic compound (BVOC) emissions from a Swedish managed willow site with the aim of providing information on the seasonal variability in BVOC emissions during two growing seasons, 2015–2016. Total BVOC emissions during these two seasons were dominated by isoprene (>96% by mass) and the monoterpene (MT) ocimene. The average standardized (STD, temperature of 30 °C and photosynthetically active radiation of 1000 µmol m−2 s−1) emission rate for isoprene was 45.2 (±42.9, standard deviation (SD)) μg gdw−1 h−1. Isoprene varied through the season, mainly depending on the prevailing temperature and light, where the measured emissions peaked in July 2015 and August 2016. The average STD emission for MTs was 0.301 (±0.201) μg gdw−1 h−1 and the MT emissions decreased from spring to autumn. The average STD emission for sesquiterpenes (SQTs) was 0.103 (±0.249) μg gdw−1 h−1, where caryophyllene was the most abundant SQT. The measured emissions of SQTs peaked in August both in 2015 and 2016. Non-terpenoid compounds were grouped as other VOCs (0.751 ± 0.159 μg gdw−1 h−1), containing alkanes, aldehydes, ketones, and other compounds. Emissions from all the BVOC groups decreased towards the end of the growing season. The more sun-adapted leaves in the upper part of the plantation canopy emitted higher rates of isoprene, MTs, and SQTs compared with more shade-adapted leaves in the lower canopy. On the other hand, emissions of other VOCs were lower from the upper part of the canopy compared with the lower part. Light response curves showed that ocimene and α-farnesene increased with light but only for the sun-adapted leaves, since the shade-adapted leaves did not emit ocimene and α-farnesene. An infestation with Melampsora spp. likely induced high emissions of, e.g., hexanal and nonanal in August 2015. The results from this study imply that upscaling BVOC emissions with model approaches should account for seasonality and also include the canopy position of leaves as a parameter to allow for better estimates for the regional and global budgets of ecosystem emissions.
Investigation of Atmospheric Conditions Associated with a Storm Surge in the South-West of Iran
Authors: Abbasi Esmaeil , Etemadi Hana , Smoak Joseph M. , Rousta Iman , Olafsson Haraldur , Baranowski Piotr , Krzyszczak Jaromir
Published: November 2021

Severe thunderstorms are often accompanied by strong vertical air currents, temporary wind gusts, and heavy rainfall. The development of this atmospheric phenomenon over tropical shallow water zones, such as bays, can lead to intensification of atmospheric disturbances and produce a small-scale storm surge. Here, the storm surge that occurred on 19 March 2017 in the Persian Gulf coastal area has been investigated. Air temperature, precipitation, mean sea level pressure, wave height, wind direction, wind speed, geopotential height, zonal components, meridional winds, vertical velocity, relative humidity, and specific humidity obtained from the European Centre for Medium-Range Weather Forecasts (ECMWF) and Global Forecast System (FNL) were used to implement the Weather Research and Forecasting (WRF) model. The results showed that the main cause of the storm surge was the occurrence of a supercell thunderstorm over the Persian Gulf. The formation of this destructive phenomenon resulted from a downburst under Cumulonimbus cloud and high-velocity air subsidence, after collision with the sea surface coinciding with the high tide. This caused a severe, yet temporary, gust, which in turn caused the creation of the four waves of 3.1 m height along the coast of Bandar Dayyer.
Projected Changes in the Atmospheric Dynamics of Climate Extremes in France
Authors: Yiou Pascal , Faranda Davide , Thao Soulivanh , Vrac Mathieu
Published: November 2021

Extremes of temperature, precipitation and wind have caused damages in France, in the agriculture, transportation and health sectors. Those types of events are largely driven by the atmospheric circulation. The dependence on the global climate change is not always clear, and it is the subject of extreme event attribution (EEA). This study reports an analysis of the atmospheric circulation over France for seven events that struck France in the 21st century, in various seasons. We focus on the atmospheric dynamics that leads to those extremes and examine how the probability of atmospheric patterns and their predictability responds to climate change. We analyse how the features of those events evolve in simulations following an SSP585 scenario for future climate. We identify how thermodynamical and dynamical changes of the atmosphere affect the predictability of the atmospheric circulation. Those using a range of CMIP6 simulations helps determining uncertainties linked to climate models.
El Niño–Global Atmospheric Oscillation as the Main Mode of Interannual Climate Variability
Authors: Serykh Ilya V. , Sonechkin Dmitry M.
Published: November 2021

The interannual variability of the global mean monthly anomalies of near-surface air temperature, sea-level pressure, wind speed near the surface, amount of precipitation and total cloudiness was investigated. The amplitudes of the anomalies of these hydrometeorological characteristics between opposite phases of the Global Atmospheric Oscillation (GAO) were calculated. The regional element of the GAO in the tropics of the Indian and Pacific Oceans is the Southern Oscillation. The results show that the oscillations of these characteristics are associated with the GAO not only in the tropical belt of the Earth but also in the middle and high latitudes, especially in the Arctic and northern Eurasia. The physical mechanism by which the transition of the GAO from the negative to the positive phase influences the weakening of the Pacific trade winds, and, as a consequence, the onset of El Niño is described.
On the Discrete Weibull Marshall–Olkin Family of Distributions: Properties, Characterizations, and Applications
Authors: Gillariose Jiju , Balogun Oluwafemi Samson , Almetwally Ehab M. , Sherwani Rehan Ahmad Khan , Jamal Farrukh , Joseph Joshin
Published: November 2021

In this article, we introduce a new flexible discrete family of distributions, which accommodates wide collection of monotone failure rates. A sub-model of geometric distribution or a discrete generalization of the exponential model is proposed as a special case of the derived family. Besides, we point out a comprehensive record of some of its mathematical properties. Two distinct estimation methods for parameters estimation and two different methods for constructing confidence intervals are explored for the proposed distribution. In addition, three extensive Monte Carlo simulations studies are conducted to assess the advantages between estimation methods. Finally, the utility of the new model is embellished by dint of two real datasets.
Borreliae Part 2: Borrelia Relapsing Fever Group and Unclassified Borrelia
Authors: Trevisan Giusto , Cinco Marina , Trevisini Sara , di Meo Nicola , Ruscio Maurizio , Forgione Patrizia , Bonin Serena
Published: November 2021

Borreliae of the relapsing fever group (RFG) are heterogenous and can be divided mainly into three groups according to vectors, namely the soft-tick-borne relapsing fever (STBRF) Borreliae, the hard-tick-borne relapsing fever (HTBRF) Borreliae, the louse-borne relapsing fever (LBRF) Borreliae, and the avian relapsing fever ones. With respect to the geographical distribution, the STBRF Borreliae are further subdivided into Old World and New World strains. Except for the Avian relapsing fever group Borreliae, which cause avian spirochetosis, all the others share infectivity in humans. They are indeed the etiological agent of both endemic and epidemic forms of relapsing fever, causing high spirochaetemia and fever. Vectors are primarily soft ticks of Ornithodoros spp. in the STBRF group; hard ticks, notably Ixodes sp., Amblyomma sp., Dermacentor sp., and Rhipicephalus sp., in the HTBRF group; and the louse pediculus humanus humanus in the TBRF one. A recent hypothesis was supported for a common ancestor of RFG Borreliae, transmitted at the beginning by hard-body ticks. Accordingly, STBRF Borreliae switched to use soft-bodied ticks as a vector, which was followed by the use of lice by Borrelia recurrentis. There are also new candidate species of Borreliae, at present unclassified, which are also described in this review.
The Receptor-like Kinase TaCRK-7A Inhibits Fusarium pseudograminearum Growth and Mediates Resistance to Fusarium Crown Rot in Wheat
Authors: Wu Tianci , Guo Feilong , Xu Gangbiao , Yu Jinfeng , Zhang Li , Wei Xuening , Zhu Xiuliang , Zhang Zengyan
Published: November 2021

The fungus F. pseudograminearum can cause the destructive disease Fusarium crown rot (FCR) of wheat, an important staple crop. Functional roles of FCR resistance genes in wheat are largely unknown. In the current research, we characterized the antifungal activity and positive-regulatory function of the cysteine-rich repeat receptor-like kinase TaCRK-7A in the defense against F. pseudograminearum in wheat. Antifungal assays showed that the purified TaCRK-7A protein inhibited the growth of F. pseudograminearum. TaCRK-7A transcript abundance was elevated after F. pseudograminearum attack and was positively related to FCR-resistance levels of wheat cultivars. Intriguingly, knocking down of TaCRK-7A transcript increased susceptibility of wheat to FCR and decreased transcript levels of defense-marker genes in wheat. Furthermore, the transcript abundances of TaCRK-7A and its modulated-defense genes were responsive to exogenous jasmonate treatment. Taken together, these results suggest that TaCRK-7A can directly inhibit F. pseudograminearum growth and mediates FCR-resistance by promoting the expression of wheat defense genes in the jasmonate pathway. Thus, TaCRK-7A is a potential gene resource in FCR-resistant wheat breeding program.
Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis
Authors: Fernandes Carlos , Videira Afonso J. C. , Veloso Caroline D. , Benfeito Sofia , Soares Pedro , Martins João D. , Gonçalves Beatriz , Duarte José F. S. , Santos António M. S. , Oliveira Paulo J. , Borges Fernanda , Teixeira José , Silva Filomena S. G.
Published: November 2021

Mitochondriotropic antioxidants (MC3, MC6.2, MC4 and MC7.2) based on dietary antioxidants and analogs (caffeic, hydrocaffeic, trihydroxyphenylpropanoic and trihydroxycinnamic acids) were developed. In this study, we evaluate and compare the cytotoxicity profile of novel mitochondria-targeted molecules (generally known as MitoCINs) on human HepG2 and differentiated SH-SY5Y cells with the quinone-based mitochondria-targeted antioxidants MitoQ and SkQ1 and with two non-targeted antioxidants, resveratrol and coenzyme Q10 (CoQ10). We further evaluate their effects on mitochondrial membrane potential, cellular oxygen consumption and extracellular acidification rates. Overall, MitoCINs derivatives reduced cell viability at concentrations about six times higher than those observed with MitoQ and SkQ1. A toxicity ranking for both cell lines was produced: MC4 < MC7.2 < MC3 < MC6.2. These results suggest that C-6 carbon linker and the presence of a pyrogallol group result in lower cytotoxicity. MC3 and MC6.2 affected the mitochondrial function more significantly relative to MitoQ, SkQ1, resveratrol and CoQ10, while MC4 and MC7.2 displayed around 100–1000 times less cytotoxicity than SkQ1 and MitoQ. Based on the mitochondrial and cytotoxicity cellular data, MC4 and MC7.2 are proposed as leads that can be optimized to develop safe drug candidates with therapeutic application in mitochondrial oxidative stress-related diseases.
Under Conditions of Amyloid Formation Bovine Carbonic Anhydrase B Undergoes Fragmentation by Acid Hydrolysis
Authors: Marchenkov Victor , Ryabova Natalya , Balobanov Vitaly , Glukhov Anatoly , Ilyina Nelly , Katina Natalya
Published: November 2021

The development of many severe human diseases is associated with the formation of amyloid fibrils. Most of the available information on the process of amyloid formation has been obtained from studies of small proteins and peptides, wherein the features of complex proteins’ aggregation remain insufficiently investigated. Our work aimed to research the amyloid aggregation of a large model protein, bovine carbonic anhydrase B (BCAB). It has previously been demonstrated that, when exposed to an acidic pH and elevated temperature, this protein forms amyloid fibrils. Here, we show that, under these conditions and before amyloid formation, BCAB undergoes fragmentation by acid hydrolysis to give free individual peptides and associated peptides. Fragments in associates contain a pronounced secondary structure and act as the main precursor of amyloid fibrils, wherein free peptides adopt mostly unstructured conformation and form predominantly irregular globular aggregates. Reduced acidity decreases the extent of acid hydrolysis, causing BCAB to form amorphous aggregates lacking the thioflavin T binding β-structure. The presented results provide new information on BCAB amyloid formation and show the importance of protein integrity control when working even in mildly acidic conditions.
Circulating Omentin-1 as a Biomarker at the Intersection of Postmenopausal Breast Cancer Occurrence and Cardiometabolic Risk: An Observational Cross-Sectional Study
Authors: Christodoulatos Gerasimos Socrates , Antonakos Georgios , Karampela Irene , Psallida Sotiria , Stratigou Theodora , Vallianou Natalia , Lekka Antigoni , Marinou Ioanna , Vogiatzakis Evaggelos , Kokoris Styliani , Papavassiliou Athanasios G. , Dalamaga Maria
Published: November 2021

Aberrant circulating omentin-1, which is an anti-inflammatory and pro-apoptotic adipokine, has been reported in various solid tumors. Therefore, we investigated whether or not circulating omentin-1 could be associated with postmenopausal BC (PBC) and could be used as a potential diagnostic and clinical tool taking into consideration clinicopathologic features, tumor markers, as well as anthropometric, metabolic, and inflammatory parameters. Serum omentin-1, tumor markers (CA15-3 and CEA); metabolic (insulin, glucose, HOMA index, and serum lipids), anthropometric (BMI, waist circumference, and fat mass), and inflammatory (TNF-α, IL-6, hsCRP) parameters; classic adipokines (leptin and adiponectin); the Mediterranean diet (MedDiet) score; and cardiovascular (CVD) risk were determined in 103 postmenopausal women with pathologically confirmed incident invasive BC, 103 controls matched on age, 51 patients with benign breast lesions (BBL), and 50 obese postmenopausal women of similar age. The mean serum omentin-1 was significantly lower in cases than in controls and patients with BBL (p < 0.001). In the patients, omentin-1 was inversely associated with tumor, metabolic and inflammatory biomarkers, cancer stage, and the number of infiltrated lymph nodes (p < 0.05). In all study participants, omentin-1 was negatively correlated with CVD risk and positively correlated with MedDiet score. Lower circulating omentin-1 was independently associated with PBC occurrence above and beyond known risk factors. According to the ROC curve analysis, the overall diagnostic performance of omentin-1 (0.84, 95% CI 0.79–0.89) is similar to CA15-3. Circulating omentin-1 may be a biomarker at the intersection of PBC and cardiometabolic risk in postmenopausal women, and could be modulated by the adoption of a MedDiet. Further mechanistic and large multicentric prospective and longitudinal studies are required to elucidate the ontological role of omentin-1 in BC and CVD risks, as well as its diagnostic and prognostic ability and its therapeutic potential.
Antioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated from Ziziphus jujuba Mill. against Cisplatin-Induced Kidney Epithelial Cell Death
Authors: Lee Dahae , Kang Kyo Bin , Hwang Gwi Seo , Choi You-Kyoung , Kim Tae Kon , Kang Ki Sung
Published: November 2021

Cisplatin is a platinum-based chemotherapeutic agent for treating solid tumors; however, it presents a risk factor for nephropathy. In the present study, we investigated the antioxidant and anti-inflammatory effects of 3-dehydroxyceanothetric acid 2-methyl ester (3DC2ME) isolated from Ziziphus jujuba Mill. in LLC-PK1 cells following cisplatin-induced cytotoxicity. These cells were exposed to 3DC2ME for 2 h, followed by treatment with cisplatin for 24 h. The treated cells were subjected to cell viability analysis using the Ez-Cytox assay. Reactive oxygen species (ROS) were detected via 2′, 7′- dichlorodihydrofluorescein diacetate (DCFH-DA) staining. In addition, western blotting and fluorescent immunostaining were performed to evaluate protein expressions related to oxidative stress and inflammation pathways. Pretreatment with 3DC2ME protected LLC-PK1 cells from cisplatin-induced cytotoxicity and oxidative stress. In addition, pretreatment with 3DC2ME upregulated heme oxygenase 1 (HO-1) via the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in the cisplatin-treated LLC-PK1 cells. Furthermore, the increase in the expressions of IκB kinase α/β (IKKα/β), inhibitor of kappa B alpha (IκBα), nuclear factor kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in these cells was inhibited. These results provide basic scientific evidence for understanding the antioxidant and anti-inflammatory effects of 3DC2ME isolated from Z. jujuba against cisplatin-induced kidney epithelial cell death.
Harmony but Not Uniformity: Role of Strigolactone in Plants
Authors: Rehman Naveed Ur , Li Xi , Zeng Peichun , Guo Shaoying , Jan Saad , Liu Yunfeng , Huang Yifeng , Xie Qingjun
Published: November 2021

Strigolactones (SLs) represent an important new plant hormone class marked by their multifunctional roles in plants and rhizosphere interactions, which stimulate hyphal branching in arbuscular mycorrhizal fungi (AMF) and seed germination of root parasitic plants. SLs have been broadly implicated in regulating root growth, shoot architecture, leaf senescence, nodulation, and legume–symbionts interaction, as well as a response to various external stimuli, such as abiotic and biotic stresses. These functional properties of SLs enable the genetic engineering of crop plants to improve crop yield and productivity. In this review, the conservation and divergence of SL pathways and its biological processes in multiple plant species have been extensively discussed with a particular emphasis on its interactions with other different phytohormones. These interactions may shed further light on the regulatory networks underlying plant growth, development, and stress responses, ultimately providing certain strategies for promoting crop yield and productivity with the challenges of global climate and environmental changes.
Enhancement of the Immunostimulatory Effect of Phosphodiester CpG Oligodeoxynucleotides by an Antiparallel Guanine-Quadruplex Structural Scaffold
Authors: Safitri Fika Ayu , Tu Anh Thi Tram , Hoshi Kazuaki , Shobo Miwako , Zhao Dandan , Witarto Arief Budi , Sumarsono Sony Heru , Giri-Rachman Ernawati Arifin , Tsukakoshi Kaori , Ikebukuro Kazunori , Yamazaki Tomohiko
Published: November 2021

Guanine-quadruplex-based CpG oligodeoxynucleotides (G4 CpG ODNs) have been developed as potent immunostimulatory agents with reduced sensitivity to nucleases. We designed new monomeric G4 ODNs with an antiparallel topology using antiparallel type duplex/G4 ODNs as robust scaffolds, and we characterized their topology and effects on cytokine secretion. Based on circular dichroism analysis and quantification of mRNA levels of immunostimulatory cytokines, it was found that monomeric antiparallel G4 CpG ODNs containing two CpG motifs in the first functional loop, named G2.0.0, could maintain antiparallel topology and generate a high level of immunostimulatory cytokines in RAW264 mouse macrophage-like cell lines. We also found that the flanking sequence in the CpG motif altered the immunostimulatory effects. Gc2c.0.0 and Ga2c.0.0 are monomeric antiparallel G4 CpG ODNs with one cytosine in the 3′ terminal and one cytosine/adenine in the 5′ terminal of CpG motifs that maintained the same resistance to degradation in serum as G2.0.0 and improved interleukin-6 production in RAW264 and bone marrow-derived macrophages. The immunostimulatory activity of antiparallel G4 CpG ODNs is superior to that of linear natural CpG ODNs. These results provide insights for the rational design of highly potent CpG ODNs using antiparallel G4 as a robust scaffold.
Short Vestibular and Cognitive Training Improves Oral Reading Fluency in Children with Dyslexia
Authors: Caldani Simona , Moiroud Lionel , Miquel Carole , Peiffer Vanessa , Florian Alessandro , Bucci Maria Pia
Published: November 2021

(1) Background: This study explored the effect of short vestibular and cognitive training on the reading speed in dyslexic children. (2) Methods: The reading speed was evaluated by using a reading test (Évaluation de la Lecture en FluencE, ELFE) in a crossover design before (baseline) and after vestibular training (post VT) and no vestibular training (post no VT). Nineteen dyslexic children (9.48 ± 0.15 years) participated in the study. The vestibular and cognitive training (software developed by BeonSolution S.r.l.) consisted in four exercises presented on a Wacom tablet 10″ done for 16 min per session two times per week for four weeks; each exercise was composed of eight levels with increased difficulty. (3) Results: Following vestibular and cognitive training, dyslexic children increased their reading speed; interestingly, such an increase persisted at least one month after training. (4) Conclusions: Vestibular and cognitive training could improve the vestibular network, which is well known for being involved in several cognition functions leading to reading improvement in dyslexic children. Adaptive mechanisms could be responsible for maintaining such improvement for at least one month.
The Directionality of Fronto-Posterior Brain Connectivity Is Associated with the Degree of Individual Autistic Traits
Authors: Tarasi Luca , Magosso Elisa , Ricci Giulia , Ursino Mauro , Romei Vincenzo
Published: November 2021

Altered patterns of brain connectivity have been found in autism spectrum disorder (ASD) and associated with specific symptoms and behavioral features. Growing evidence suggests that the autistic peculiarities are not confined to the clinical population but extend along a continuum between healthy and maladaptive conditions. The aim of this study was to investigate whether a differentiated connectivity pattern could also be tracked along the continuum of autistic traits in a non-clinical population. A Granger causality analysis conducted on a resting-state EEG recording showed that connectivity along the posterior-frontal gradient is sensitive to the magnitude of individual autistic traits and mostly conveyed through fast oscillatory activity. Specifically, participants with higher autistic traits were characterized by a prevalence of ascending connections starting from posterior regions ramping the cortical hierarchy. These findings point to the presence of a tendency within the neural mapping of individuals with higher autistic features in conveying proportionally more bottom-up information. This pattern of findings mimics those found in clinical forms of autism, supporting the idea of a neurobiological continuum between autistic traits and ASD.
Challenges in Treating Charcot-Marie-Tooth Disease and Related Neuropathies: Current Management and Future Perspectives
Authors: Pisciotta Chiara , Saveri Paola , Pareyson Davide
Published: November 2021

There is still no effective drug treatment available for Charcot-Marie-Tooth neuropathies (CMT). Current management relies on rehabilitation therapy, surgery for skeletal deformities, and symptomatic treatment of pain; fatigue and cramps are frequent complaints that are difficult to treat. The challenge is to find disease-modifying therapies. Several approaches, including gene silencing, to counteract the PMP22 gene overexpression in the most frequent CMT1A type are under investigation. PXT3003 is the compound in the most advanced phase for CMT1A, as a second-phase III trial is ongoing. Gene therapy to substitute defective genes or insert novel ones and compounds acting on pathways important for different CMT types are being developed and tested in animal models. Modulation of the Neuregulin pathway determining myelin thickness is promising for both hypo-demyelinating and hypermyelinating neuropathies; intervention on Unfolded Protein Response seems effective for rescuing misfolded myelin proteins such as P0 in CMT1B. HDAC6 inhibitors improved axonal transport and ameliorated phenotypes in different CMT models. Other potential therapeutic strategies include targeting macrophages, lipid metabolism, and Nav1.8 sodium channel in demyelinating CMT and the P2X7 receptor, which regulates calcium influx into Schwann cells, in CMT1A. Further approaches are aimed at correcting metabolic abnormalities, including the accumulation of sorbitol caused by biallelic mutations in the sorbitol dehydrogenase (SORD) gene and of neurotoxic glycosphingolipids in HSN1.
Measuring the Effects of Social Isolation and Dissatisfaction on Depressive Symptoms during the COVID-19 Pandemic: The Moderating Role of Sleep and Physical Activity
Authors: Vargas Ivan , Howie Erin Kaye , Muench Alexandria , Perlis Michael L.
Published: November 2021

Social distancing was universally implemented to reduce the spread of the COVID-19 virus. Long-term social distancing can lead to increased feelings of social isolation or dissatisfaction with one’s daily interpersonal interactions, which can subsequently result in reduced psychological health (e.g., greater depression). The present study quantified this association, and the extent to which it was moderated by measures of sleep and physical activity, by surveying 3658 adults (mean age = 46.0 years) from across the United States. Participants answered questions related to their social experiences, sleep, physical activity, and depressive symptoms during the early stages of the pandemic (March–June 2020). Results showed that social isolation and social dissatisfaction were associated with greater depressive symptoms. As predicted, self-reported sleep quality and physical activity moderated these associations, such that lower sleep quality and physical activity exacerbated their effect on depressive symptoms.
Spontaneous and Perturbational Complexity in Cortical Cultures
Authors: Colombi Ilaria , Nieus Thierry , Massimini Marcello , Chiappalone Michela
Published: November 2021

Dissociated cortical neurons in vitro display spontaneously synchronized, low-frequency firing patterns, which can resemble the slow wave oscillations characterizing sleep in vivo. Experiments in humans, rodents, and cortical slices have shown that awakening or the administration of activating neuromodulators decrease slow waves, while increasing the spatio-temporal complexity of responses to perturbations. In this study, we attempted to replicate those findings using in vitro cortical cultures coupled with micro-electrode arrays and chemically treated with carbachol (CCh), to modulate sleep-like activity and suppress slow oscillations. We adapted metrics such as neural complexity (NC) and the perturbational complexity index (PCI), typically employed in animal and human brain studies, to quantify complexity in simplified, unstructured networks, both during resting state and in response to electrical stimulation. After CCh administration, we found a decrease in the amplitude of the initial response and a marked enhancement of the complexity during spontaneous activity. Crucially, unlike in cortical slices and intact brains, PCI in cortical cultures displayed only a moderate increase. This dissociation suggests that PCI, a measure of the complexity of causal interactions, requires more than activating neuromodulation and that additional factors, such as an appropriate circuit architecture, may be necessary. Exploring more structured in vitro networks, characterized by the presence of strong lateral connections, recurrent excitation, and feedback loops, may thus help to identify the features that are more relevant to support causal complexity.
The Integration of Stressful Life Experiences Scale and the Inventory of Complicated Spiritual Grief: The Italian Validation of Two Instruments for Meaning-Focused Assessments of Bereavement
Authors: Neimeyer Robert A. , Testoni Ines , Ronconi Lucia , Biancalani Gianmarco , Antonellini Marco , Dal Corso Laura
Published: November 2021

Background: Bereavement is an inevitable event that can cause pain, discomfort, and negative consequences in daily life. Spirituality and religiosity can help people cope with loss and bereavement. Sometimes, however, the death of a loved one can challenge core religious beliefs and faith, which has been found to be a risk factor for prolonged mourning. Objectives: (1) Determine whether the Italian versions of the Integration of Stressful Life Experiences Scale (ISLES) and Inventory of Complicated Spiritual Grief (ICSG) are valid in translation; (2) Evaluate the impact of socio-demographic variables on ISLES and ICSG dimensions; (3) Test whether Complicated Spiritual Grief mediates the relation between meaning reconstruction after loss and integration of the loss experience; (4) Test whether the representation of death as a form of passage or annihilation further moderated the relation between Complicated Spiritual Grief and integration of the loss. Methods: The sample is composed of 348 participants who had lost a loved person in the prior two years. Results: The ISLES and ICSG were validated in Italian and are more appropriately interpreted as having a unifactorial structure. A greater spiritual crisis was manifested in participants with less education, who did not actively participate in religious life, and who had lost a friend rather than a close relative. As hypothesised, spiritual struggle in grief mediated the role of continuing bonds, Emptiness and Meaninglessness, and Sense of Peace in predicting integration of the loss. Furthermore, death representation moderated the impact of spiritual grief on loss, such that those participants who viewed death as a form of annihilation rather than passage reported greater integration of the loss. Conclusion: The role of meaning making in integrating significant loss is partly accounted for by spiritual struggle in a way that can be analysed in Italian contexts through the use of these newly validated instruments.
CyberGenomics: Application of Behavioral Genetics in Cybersecurity
Authors: Domarkienė Ingrida , Ambrozaitytė Laima , Bukauskas Linas , Rančelis Tautvydas , Sütterlin Stefan , Knox Benjamin James , Maennel Kaie , Maennel Olaf , Parish Karen , Lugo Ricardo Gregorio , Brilingaitė Agnė
Published: November 2021

Cybersecurity (CS) is a contemporary field for research and applied study of a range of aspects from across multiple disciplines. A cybersecurity expert has an in-depth knowledge of technology but is often also recognized for the ability to view technology in a non-standard way. This paper explores how CS specialists are both a combination of professional computing-based skills and genetically encoded traits. Almost every human behavioral trait is a result of many genome variants in action altogether with environmental factors. The review focuses on contextualizing the behavior genetics aspects in the application of cybersecurity. It reconsiders methods that help to identify aspects of human behavior from the genetic information. And stress is an illustrative factor to start the discussion within the community on what methodology should be used in an ethical way to approach those questions. CS positions are considered stressful due to the complexity of the domain and the social impact it can have in cases of failure. An individual risk profile could be created combining known genome variants linked to a trait of particular behavior using a special biostatistical approach such as a polygenic score. These revised advancements bring challenging possibilities in the applications of human behavior genetics and CS.
Performance of 16S Metagenomic Profiling in Formalin-Fixed Paraffin-Embedded versus Fresh-Frozen Colorectal Cancer Tissues
Authors: Borgognone Alessandra , Serna Garazi , Noguera-Julian Marc , Alonso Lidia , Parera Mariona , Català-Moll Francesc , Sanchez Lidia , Fasani Roberta , Paredes Roger , Nuciforo Paolo
Published: November 2021

Formalin-fixed, paraffin-embedded (FFPE) tissues represent the most widely available clinical material to study colorectal cancer (CRC). However, the accuracy and clinical validity of FFPE microbiome profiling in CRC is uncertain. Here, we compared the microbial composition of 10 paired fresh-frozen (FF) and FFPE CRC tissues using 16S rRNA sequencing and RNA-ISH. Both sample types showed different microbial diversity and composition. FF samples were enriched in archaea and representative CRC-associated bacteria, such as Firmicutes, Bacteroidetes and Fusobacteria. Conversely, FFPE samples were mainly enriched in typical contaminants, such as Sphingomonadales and Rhodobacterales. RNA-ISH in FFPE tissues confirmed the presence of CRC-associated bacteria, such as Fusobacterium and Bacteroides, as well as Propionibacterium allowing discrimination between tumor-associated and contaminant taxa. An internal quality index showed that the degree of similarity within sample pairs inversely correlated with the dominance of contaminant taxa. Given the importance of FFPE specimens for larger studies in human cancer genomics, our findings may provide useful indications on potential confounding factors to consider for accurate and reproducible metagenomics analyses.
N-of-1 Trials in Pediatric Oncology: From a Population-Based Approach to Personalized Medicine—A Review
Authors: Kyr Michal , Svobodnik Adam , Stepanova Radka , Hejnova Renata
Published: November 2021

Pediatric oncology is a critical area where the more efficient development of new treatments is urgently needed. The speed of approval of new drugs is still limited by regulatory requirements and a lack of innovative designs appropriate for trials in children. Childhood cancers meet the criteria of rare diseases. Personalized medicine brings it even closer to the horizon of individual cases. Thus, not all the traditional research tools, such as large-scale RCTs, are always suitable or even applicable, mainly due to limited sample sizes. Small samples and traditional versus subject-specific evidence are both distinctive issues in personalized pediatric oncology. Modern analytical approaches and adaptations of the paradigms of evidence are warranted. We have reviewed innovative trial designs and analytical methods developed for small populations, together with individualized approaches, given their applicability to pediatric oncology. We discuss traditional population-based and individualized perspectives of inferences and evidence, and explain the possibilities of using various methods in pediatric personalized oncology. We find that specific derivatives of the original N-of-1 trial design adapted for pediatric personalized oncology may represent an optimal analytical tool for this area of medicine. We conclude that no particular N-of-1 strategy can provide a solution. Rather, a whole range of approaches is needed to satisfy the new inferential and analytical paradigms of modern medicine. We reveal a new view of cancer as continuum model and discuss the “evidence puzzle”.
Locoregional Therapies for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis
Authors: Zane Kylie E. , Makary Mina S.
Published: November 2021

Hepatocellular carcinoma is the fourth leading cause of cancer worldwide, and the fastest increasing cause of cancer mortality in the United States. Its propensity for vascular invasion leads to the presence of portal vein tumor thrombus in up to half of patients. PVTT results in a classification of advanced disease, given the risk recurrence secondary to intravascular spread, and formal guidelines recommend systemic therapy in these patients. However, recent advances in locoregional therapies including TACE, TARE, and ablation have demonstrated the potential to drastically improve overall survival in patients with HCC complicated by PVTT.
Mismatch Repair Status in Patient-Derived Colorectal Cancer Organoids Does Not Affect Intrinsic Tumor Cell Sensitivity to Systemic Therapy
Authors: Küçükköse Emre , Wensink G. Emerens , Roelse Celine M. , van Schelven Susanne J. , Raats Daniëlle A. E. , Boj Sylvia F. , Koopman Miriam , Laoukili Jamila , Roodhart Jeanine M. L. , Kranenburg Onno
Published: November 2021

DNA mismatch repair deficiency (dMMR) in metastatic colorectal cancer (mCRC) is associated with poor survival and a poor response to systemic treatment. However, it is unclear whether dMMR results in a tumor cell-intrinsic state of treatment resistance, or whether alternative mechanisms play a role. To address this, we generated a cohort of MMR-proficient and -deficient Patient-Derived Organoids (PDOs) and tested their response to commonly used drugs in the treatment of mCRC, including 5-fluorouracil (5-FU), oxaliplatin, SN-38, binimetinib, encorafenib, and cetuximab. MMR status did not correlate with the response of PDOs to any of the drugs tested. In contrast, the presence of activating mutations in the KRAS and BRAF oncogenes was significantly associated with resistance to chemotherapy and sensitivity to drugs targeting oncogene-activated pathways. We conclude that mutant KRAS and BRAF impact the intrinsic sensitivity of tumor cells to chemotherapy and targeted therapy. By contrast, tumor cell-extrinsic mechanisms—for instance signals derived from the microenvironment—must underlie the association of MMR status with therapy response. Future drug screens on rationally chosen cohorts of PDOs have great potential in developing tailored therapies for specific CRC subtypes including, but not restricted to, those defined by BRAF/KRAS and MMR status.
Clinical Value of NGS Genomic Studies for Clinical Management of Pediatric and Young Adult Bone Sarcomas
Authors: Gutiérrez-Jimeno Miriam , Alba-Pavón Piedad , Astigarraga Itziar , Imízcoz Teresa , Panizo-Morgado Elena , García-Obregón Susana , Catalán-Lambán Ana , San-Julián Mikel , Lamo-Espinosa José M. , Echebarria-Barona Aizpea , Zalacain Marta , Alonso Marta M. , Patiño-García Ana
Published: November 2021

Genomic techniques enable diagnosis and management of children and young adults with sarcomas by identifying high-risk patients and those who may benefit from targeted therapy or participation in clinical trials. Objective: to analyze the performance of an NGS gene panel for the clinical management of pediatric sarcoma patients. We studied 53 pediatric and young adult patients diagnosed with sarcoma, from two Spanish centers. Genomic data were obtained using the Oncomine Childhood Cancer Research Assay, and categorized according to their diagnostic, predictive, or prognostic value. In 44 (83%) of the 53 patients, at least one genetic alteration was identified. In 80% of these patients, the diagnosis was obtained (n = 11) or changed (n = 9), and thus genomic data affected therapy. The most frequent initial misdiagnosis was Ewing’s sarcoma, instead of myxoid liposarcoma (FUS-DDDIT3), rhabdoid soft tissue tumor (SMARCB1), or angiomatoid fibrous histiocytoma (EWSR1-CREB1). In our series, two patients had a genetic alteration with an FDA-approved targeted therapy, and 30% had at least one potentially actionable alteration. NGS-based genomic studies are useful and feasible in diagnosis and clinical management of pediatric sarcomas. Genomic characterization of these rare and heterogeneous tumors also helps in the search for prognostic biomarkers and therapeutic opportunities.
Voltage-Gated Sodium Channels as Potential Biomarkers and Therapeutic Targets for Epithelial Ovarian Cancer
Authors: Brummelhuis Iris S. , Fiascone Stephen J. , Hasselblatt Kathleen T. , Frendl Gyorgy , Elias Kevin M.
Published: November 2021

Abnormal ion channel expression distinguishes several types of carcinoma. Here, we explore the relationship between voltage-gated sodium channels (VGSC) and epithelial ovarian cancer (EOC). We find that EOC cell lines express most VGSC, but at lower levels than fallopian tube secretory epithelial cells (the cells of origin for most EOC) or control fibroblasts. Among patient tumor samples, lower SCN8A expression was associated with improved overall survival (OS) (median 111 vs. 52 months; HR 2.04 95% CI: 1.21–3.44; p = 0.007), while lower SCN1B expression was associated with poorer OS (median 45 vs. 56 months; HR 0.69 95% CI 0.54–0.87; p = 0.002). VGSC blockade using either anti-epileptic drugs or local anesthetics (LA) decreased the proliferation of cancer cells. LA increased cell line sensitivity to platinum and taxane chemotherapies. While lidocaine had similar additive effects with chemotherapy among EOC cells and fibroblasts, bupivacaine showed a more pronounced impact on EOC than fibroblasts when combined with either carboplatin (ΔAUC −37% vs. −16%, p = 0.003) or paclitaxel (ΔAUC −37% vs. −22%, p = 0.02). Together, these data suggest VGSC are prognostic biomarkers in EOC and may inform new targets for therapy.
The Associations between Perioperative Blood Transfusion and Long-Term Outcomes after Stomach Cancer Surgery
Authors: Hsu Fu-Kai , Chang Wen-Kuei , Lin Kuan-Ju , Liu Chun-Yu , Fang Wen-Liang , Chang Kuang-Yi
Published: November 2021

Background: Whether perioperative packed red blood cell (pRBC) transfusion is associated with inferior long-term outcomes after stomach cancer surgery remains controversial. Methods: This research used a retrospective cohort study. Patients with stage I~III stomach cancer undergoing tumor resection were collected at a tertiary medical center. Patient characteristics, surgical features and pathologic findings were gathered from an electronic medical chart review. The associations of perioperative pRBC transfusion with postoperative disease-free and overall survivals were evaluated using Cox regression analysis with an inverse probability of treatment weighting (IPTW). Restricted cubic spline functions were employed to characterize dose-response relationships between the amount of transfusion and cancer outcomes after surgery. Results: Among the 569 patients, 160 (28.1%) received perioperative pRBC transfusion. Perioperative transfusion was associated with worse disease-free survival (IPTW adjusted HR: 1.42, 95% CI: 1.18–1.71, p < 0.001) and overall survival (IPTW adjusted HR: 1.27, 95% CI: 1.05–1.55, p = 0.014). A non-linear dose-response relationship was noted between the amount of transfusions and worse disease-free or overall survival. Conclusions: Perioperative pRBC transfusion was associated with worse disease-free and overall survival after stomach cancer surgery, and strategies aiming to minimize perioperative transfusion exposure should be further considered to reduce the potential risk.
Dynamics of Serum Thymidine Kinase 1 at the First Cycle of Neoadjuvant Chemotherapy Predicts Outcome of Disease in Estrogen-Receptor-Positive Breast Cancer
Authors: Tribukait Bernhard
Published: November 2021

Pathologic complete response (pCR) predicts the long-term outcome of neoadjuvantly treated (NAC) breast cancer (BC) but is reached in <10% of hormone-receptor-positive patients. Biomarkers enabling adjustment or interruption of an ineffective therapy are desired. Here, we evaluated whether changes in the serum concentration of thymidine kinase 1 (sTK1) during NAC could be utilized as a biomarker. In the PROMIX trial, women with localized HER2- BC received neoadjuvant epirubicin/docetaxel in six cycles. sTK1 was measured with an ELISA in 54 patients at cycles 1–4 and in an additional 77 patients before and 48 h after treatment 1. Treatment resulted in a 2-fold increase of sTK1 before and a 3-fold increase 48 h after the cycles, except for the first cycle, where half of the patients reacted with a significant decrease and the other half with an increase of sTK1. In Kaplan–Meier estimates of ER+ patients divided by the median of the post/pre-treatment sTK1 ratio at the first treatment cycle, OS was 97.7% and 78% (p = 0.005), and DFS was 90.7% and 68% (p = 0.006), respectively. Thus, the response of sTK1 at the first cycle of chemotherapy could be used both as an early biomarker for the guidance of chemotherapy and for the study of inherent tumor chemo-sensitivity, which could predict long-term outcome prior to therapy.
B3 Lesions at Vacuum-Assisted Breast Biopsy under Ultrasound or Mammography Guidance: A Single-Center Experience on 3634 Consecutive Biopsies
Authors: Girardi Veronica , Guaragni Monica , Ruzzenenti Nella , Palmieri Fabrizio , Fogazzi Gianluca , Cozzi Andrea , Lucchini Diana , Buffoli Alberto , Schiaffino Simone , Sardanelli Francesco
Published: November 2021

The rate of upgrade to cancer for breast lesions with uncertain malignant potential (B3 lesions) diagnosed at needle biopsy is highly influenced by several factors, but large series are seldom available. We retrospectively assessed the upgrade rates of a consecutive series of B3 lesions diagnosed at ultrasound- or mammography-guided vacuum-assisted biopsy (VAB) at an EUSOMA-certified Breast Unit over a 7-year timeframe. The upgrade rate was defined as the number of ductal carcinoma in situ (DCIS) or invasive cancer at pathology after excision or during follow-up divided by the total number of B3 lesions. All lesions were reviewed by one of four pathologists with a second opinion for discordant assessments of borderline cases. Excision or surveillance were defined by the multidisciplinary tumor board, with 6- and 12-month follow-up. Out of 3634 VABs (63% ultrasound-guided), 604 (17%) yielded a B3 lesion. After excision, 17/604 B3 lesions were finally upgraded to malignancy (2.8%, 95% confidence interval [CI] 1.8–4.5%), 10/17 (59%) being upgraded to DCIS and 7/17 (41%) to invasive carcinoma. No cases were upgraded during follow-up. B3a lesions showed a significantly lower upgrade rate (0.4%, 95% CI 0.1–2.1%) than B3b lesions (4.7%, 95% CI 2.9–7.5%, p = 0.001), that had a 22.0 adjusted odds ratio for upgrade (95% CI 2.1–232.3). No significant difference was found in upgrade rates according to imaging guidance or needle caliper. Surveillance-oriented management can be considered for B3a lesions, while surgical excision should be pursued for B3b lesions.