bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial Functioning and the Relations among Health, Cognition, and Aging: Where Cell Biology Meets Cognitive Science
Authors: Geary David C.
Published: March 2021

Cognitive scientists have determined that there is a set of mechanisms common to all sensory, perceptual, and cognitive abilities and correlated with age- and disease-related declines in cognition. These mechanisms also contribute to the development and functional coherence of the large-scale brain networks that support complex forms of cognition. At the same time, these brain and cognitive patterns are correlated with myriad health outcomes, indicating that at least some of the underlying mechanisms are common to all biological systems. Mitochondrial functions, including cellular energy production and control of oxidative stress, among others, are well situated to explain the relations among the brain, cognition, and health. Here, I provide an overview of the relations among cognitive abilities, associated brain networks, and the importance of mitochondrial energy production for their functioning. These are then linked to the relations between cognition, health, and aging. The discussion closes with implications for better integrating research in cognitive science and cell biology in the context of developing more sensitive measures of age- and disease-related declines in cognition.
Growth and Viability of Cutaneous Squamous Cell Carcinoma Cell Lines Display Different Sensitivities to Isoform-Specific Phosphoinositide 3-Kinase Inhibitors
Authors: Mannella Viviana , Boehm Kira , Celik Suheyla , Ali Tasnim , Mirza Amnah N. , El Hasnaouy Mariam , Kaffa Andreas , Lyu Yanshuang , Kafaei Golahmadi Donya , Leigh Irene M. , Bergamaschi Daniele , Harwood Catherine A. , Maffucci Tania
Published: March 2021

Cutaneous squamous cell carcinomas (cSCCs) account for about 20% of keratinocyte carcinomas, the most common cancer in the UK. Therapeutic options for cSCC patients who develop metastasis are limited and a better understanding of the biochemical pathways involved in cSCC development/progression is crucial to identify novel therapeutic targets. Evidence indicates that the phosphoinositide 3-kinases (PI3Ks)/Akt pathway plays an important role, in particular in advanced cSCC. Questions remain of whether all four PI3K isoforms able to activate Akt are involved and whether selective inhibition of specific isoform(s) might represent a more targeted strategy. Here we determined the sensitivity of four patient-derived cSCC cell lines to isoform-specific PI3K inhibitors to start investigating their potential therapeutic value in cSCC. Parallel experiments were performed in immortalized keratinocyte cell lines. We observed that pan PI3Ks inhibition reduced the growth/viability of all tested cell lines, confirming the crucial role of this pathway. Selective inhibition of the PI3K isoform p110α reduced growth/viability of keratinocytes and of two cSCC cell lines while affecting the other two only slightly. Importantly, p110α inhibition reduced Akt phosphorylation in all cSCC cell lines. These data indicate that growth and viability of the investigated cSCC cells display differential sensitivity to isoform-specific PI3K inhibitors.
A Tale of Two Transcriptomic Responses in Agricultural Pests via Host Defenses and Viral Replication
Authors: Pantha Pramod , Chalivendra Subbaiah , Oh Dong-Ha , Elderd Bret D. , Dassanayake Maheshi
Published: March 2021

Autographa californica Multiple Nucleopolyhedrovirus (AcMNPV) is a baculovirus that causes systemic infections in many arthropod pests. The specific molecular processes underlying the biocidal activity of AcMNPV on its insect hosts are largely unknown. We describe the transcriptional responses in two major pests, Spodoptera frugiperda (fall armyworm) and Trichoplusia ni (cabbage looper), to determine the host–pathogen responses during systemic infection, concurrently with the viral response to the host. We assembled species-specific transcriptomes of the hemolymph to identify host transcriptional responses during systemic infection and assessed the viral transcript abundance in infected hemolymph from both species. We found transcriptional suppression of chitin metabolism and tracheal development in infected hosts. Synergistic transcriptional support was observed to suggest suppression of immune responses and induction of oxidative stress indicating disease progression in the host. The entire AcMNPV core genome was expressed in the infected host hemolymph with a proportional high abundance detected for viral transcripts associated with replication, structure, and movement. Interestingly, several of the host genes that were targeted by AcMNPV as revealed by our study are also targets of chemical insecticides currently used commercially to control arthropod pests. Our results reveal an extensive overlap between biological processes represented by transcriptional responses in both hosts, as well as convergence on highly abundant viral genes expressed in the two hosts, providing an overview of the host–pathogen transcriptomic landscape during systemic infection.
The Interaction of Diet and Mitochondrial Dysfunction in Aging and Cognition
Authors: Kaliszewska Aleksandra , Allison Joseph , Martini Matteo , Arias Natalia
Published: March 2021

Aging is inevitable and it is one of the major contributors to cognitive decline. However, the mechanisms underlying age-related cognitive decline are still the object of extensive research. At the biological level, it is unknown how the aging brain is subjected to progressive oxidative stress and neuroinflammation which determine, among others, mitochondrial dysfunction. The link between mitochondrial dysfunction and cognitive impairment is becoming ever more clear by the presence of significant neurological disturbances in human mitochondrial diseases. Possibly, the most important lifestyle factor determining mitochondrial functioning is nutrition. Therefore, with the present work, we review the latest findings disclosing a link between nutrition, mitochondrial functioning and cognition, and pave new ways to counteract cognitive decline in late adulthood through diet.
The Impact of Spaceflight and Microgravity on the Human Islet-1+ Cardiovascular Progenitor Cell Transcriptome
Authors: Camberos Victor , Baio Jonathan , Mandujano Ana , Martinez Aida F. , Bailey Leonard , Hasaniya Nahidh , Kearns-Jonker Mary
Published: March 2021

Understanding the transcriptomic impact of microgravity and the spaceflight environment is relevant for future missions in space and microgravity-based applications designed to benefit life on Earth. Here, we investigated the transcriptome of adult and neonatal cardiovascular progenitors following culture aboard the International Space Station for 30 days and compared it to the transcriptome of clonally identical cells cultured on Earth. Cardiovascular progenitors acquire a gene expression profile representative of an early-stage, dedifferentiated, stem-like state, regardless of age. Signaling pathways that support cell proliferation and survival were induced by spaceflight along with transcripts related to cell cycle re-entry, cardiovascular development, and oxidative stress. These findings contribute new insight into the multifaceted influence of reduced gravitational environments.
Distinct Pharmacological Properties of Gaseous CO and CO-Releasing Molecule in Human Platelets
Authors: Kaczara Patrycja , Przyborowski Kamil , Mohaissen Tasnim , Chlopicki Stefan
Published: March 2021

Carbon monoxide (CO)—gaseous or released by CO-RMs—both possess antiplatelet properties; however, it remains uncertain whether the mechanisms involved are the same. Here, we characterise the involvement of soluble guanylate cyclase (sGC) in the effects of CO—delivered by gaseous CO–saturated buffer (COG) and generated by CORM-A1—on platelet aggregation and energy metabolism, as well as on vasodilatation in aorta, using light transmission aggregometry, Seahorse XFe technique, and wire myography, respectively. ODQ completely prevented the inhibitory effect of COG on platelet aggregation, but did not modify antiplatelet effect of CORM-A1. In turn, COG did not affect, whereas CORM-A1 substantially inhibited energy metabolism in platelets. Even though activation of sGC by BAY 41-2272 or BAY 58-2667 inhibited significantly platelet aggregation, their effects on energy metabolism in platelets were absent or weak and could not contribute to antiplatelet effects of sGC activation. In contrast, vasodilatation of murine aortic rings, induced either by COG or CORM-A1, was dependent on sGC. We conclude that the source (COG vs. CORM-A1) and kinetics (rapid vs. slow) of CO delivery represent key determinants of the mechanism of antiplatelet action of CO, involving either impairment of energy metabolism or activation of sGG.
Gene Expression Analysis of Induced Plum pox virus (Sharka) Resistance in Peach (Prunus persica) by Almond (P. dulcis) Grafting
Authors: Rubio Manuel , Martínez-García Pedro J. , Nikbakht-Dehkordi Azam , Prudencio Ángela S. , Gómez Eva M. , Rodamilans Bernardo , Dicenta Federico , García Juan A. , Martínez-Gómez Pedro
Published: March 2021

No natural sources of resistance to Plum pox virus (PPV, sharka disease) have been identified in peach. However, previous studies have demonstrated that grafting a “Garrigues” almond scion onto “GF305” peach rootstock seedlings heavily infected with PPV can progressively reduce disease symptoms and virus accumulation. Furthermore, grafting a “Garrigues” scion onto the “GF305” rootstock has been shown to completely prevent virus infection. This study aims to analyse the rewiring of gene expression associated with this resistance to PPV transmitted by grafting through the phloem using RNA-Seq and RT-qPCR analysis. A total of 18 candidate genes were differentially expressed after grafting “Garrigues” almond onto healthy “GF305” peach. Among the up-regulated genes, a HEN1 homolog stands out, which, together with the differential expression of RDR- and DCL2-homologs, suggests that the RNA silencing machinery is activated by PPV infection and can contribute to the resistance induced by “Garrigues” almond. Glucan endo-1,3-beta D-glucosidase could be also relevant for the “Garrigues”-induced response, since its expression is much higher in “Garrigues” than in “GF305”. We also discuss the potential relevance of the following in PPV infection and “Garrigues”-induced resistance: several pathogenesis-related proteins; no apical meristem proteins; the transcription initiation factor, TFIIB; the speckle-type POZ protein; in addition to a number of proteins involved in phytohormone signalling.
GmNF-YC4-2 Increases Protein, Exhibits Broad Disease Resistance and Expedites Maturity in Soybean
Authors: O’Conner Seth , Zheng Wenguang , Qi Mingsheng , Kandel Yuba , Fuller Robert , Whitham Steven A. , Li Ling
Published: March 2021

The NF-Y gene family is a highly conserved set of transcription factors. The functional transcription factor complex is made up of a trimer between NF-YA, NF-YB, and NF-YC proteins. While mammals typically have one gene for each subunit, plants often have multigene families for each subunit which contributes to a wide variety of combinations and functions. Soybean plants with an overexpression of a particular NF-YC isoform GmNF-YC4-2 (Glyma.04g196200) in soybean cultivar Williams 82, had a lower amount of starch in its leaves, a higher amount of protein in its seeds, and increased broad disease resistance for bacterial, viral, and fungal infections in the field, similar to the effects of overexpression of its isoform GmNF-YC4-1 (Glyma.06g169600). Interestingly, GmNF-YC4-2-OE (overexpression) plants also filled pods and senesced earlier, a novel trait not found in GmNF-YC4-1-OE plants. No yield difference was observed in GmNF-YC4-2-OE compared with the wild-type control. Sequence alignment of GmNF-YC4-2, GmNF-YC4-1 and AtNF-YC1 indicated that faster maturation may be a result of minor sequence differences in the terminal ends of the protein compared to the closely related isoforms.
Immunological Prognostic Factors in Multiple Myeloma
Authors: Bębnowska Dominika , Hrynkiewicz Rafał , Grywalska Ewelina , Pasiarski Marcin , Sosnowska-Pasiarska Barbara , Smarz-Widelska Iwona , Góźdź Stanisław , Roliński Jacek , Niedźwiedzka-Rystwej Paulina
Published: March 2021

Multiple myeloma (MM) is a plasma cell neoplasm characterized by an abnormal proliferation of clonal, terminally differentiated B lymphocytes. Current approaches for the treatment of MM focus on developing new diagnostic techniques; however, the search for prognostic markers is also crucial. This enables the classification of patients into risk groups and, thus, the selection of the most optimal treatment method. Particular attention should be paid to the possible use of immune factors, as the immune system plays a key role in the formation and course of MM. In this review, we focus on characterizing the components of the immune system that are of prognostic value in MM patients, in order to facilitate the development of new diagnostic and therapeutic directions.
iEnhancer-GAN: A Deep Learning Framework in Combination with Word Embedding and Sequence Generative Adversarial Net to Identify Enhancers and Their Strength
Authors: Yang Runtao , Wu Feng , Zhang Chengjin , Zhang Lina
Published: March 2021

As critical components of DNA, enhancers can efficiently and specifically manipulate the spatial and temporal regulation of gene transcription. Malfunction or dysregulation of enhancers is implicated in a slew of human pathology. Therefore, identifying enhancers and their strength may provide insights into the molecular mechanisms of gene transcription and facilitate the discovery of candidate drug targets. In this paper, a new enhancer and its strength predictor, iEnhancer-GAN, is proposed based on a deep learning framework in combination with the word embedding and sequence generative adversarial net (Seq-GAN). Considering the relatively small training dataset, the Seq-GAN is designed to generate artificial sequences. Given that each functional element in DNA sequences is analogous to a “word” in linguistics, the word segmentation methods are proposed to divide DNA sequences into “words”, and the skip-gram model is employed to transform the “words” into digital vectors. In view of the powerful ability to extract high-level abstraction features, a convolutional neural network (CNN) architecture is constructed to perform the identification tasks, and the word vectors of DNA sequences are vertically concatenated to form the embedding matrices as the input of the CNN. Experimental results demonstrate the effectiveness of the Seq-GAN to expand the training dataset, the possibility of applying word segmentation methods to extract “words” from DNA sequences, the feasibility of implementing the skip-gram model to encode DNA sequences, and the powerful prediction ability of the CNN. Compared with other state-of-the-art methods on the training dataset and independent test dataset, the proposed method achieves a significantly improved overall performance. It is anticipated that the proposed method has a certain promotion effect on enhancer related fields.
Molecular Docking and Molecular Dynamics Simulation Studies of Triterpenes from Vernonia patula with the Cannabinoid Type 1 Receptor
Authors: Siraj Md Afjalus , Rahman Md. , Tan Ghee , Seidel Veronique
Published: March 2021

A molecular docking approach was employed to evaluate the binding affinity of six triterpenes, namely epifriedelanol, friedelin, α-amyrin, α-amyrin acetate, β-amyrin acetate, and bauerenyl acetate, towards the cannabinoid type 1 receptor (CB1). Molecular docking studies showed that friedelin, α-amyrin, and epifriedelanol had the strongest binding affinity towards CB1. Molecular dynamics simulation studies revealed that friedelin and α-amyrin engaged in stable non-bonding interactions by binding to a pocket close to the active site on the surface of the CB1 target protein. The studied triterpenes showed a good capacity to penetrate the blood–brain barrier. These results help to provide some evidence to justify, at least in part, the previously reported antinociceptive and sedative properties of Vernonia patula.
Celastrol Prevents Oxidative Stress Effects on FSHR, PAPP, and CYP19A1 Gene Expression in Cultured Human Granulosa-Lutein Cells
Authors: Martín-Ramírez Rita , González-Fernández Rebeca , Rotoli Deborah , Hernández Jairo , Martín-Vasallo Pablo , Palumbo Angela , Ávila Julio
Published: March 2021

Regulation of oxidative stress (OS) is important to prevent damage to female reproductive physiology. While normal OS levels may have a regulatory role, high OS levels may negatively affect vital processes such as folliculogenesis or embryogenesis. The aim of this work was to study OS induced by glucose, a reactive oxygen species generator, or peroxynitrite, a reactive nitrogen species generator, in cultured human granulosa-lutein (hGL) cells from oocyte donors, analyzing expression of genes involved in oocyte maturation (FSHR, PAPP, and CYP19A1) and OS damage response (ALDH3A2). We also evaluated the effect of celastrol as an antioxidant. Our results showed that although both glucose and peroxynitrite produce OS increments in hGL cells, only peroxynitrite treatment increases ALDH3A2 and PAPP gene expression levels and decreases FSHR gene expression levels. Celastrol pre-treatment prevents this effect of peroxynitrite. Interestingly, when celastrol alone was added, we observed a reduction of the expression of all genes studied, which was independent of both OS inductors. In conclusion, regulation of OS imbalance by antioxidant substances such as celastrol may prevent negative effects of OS in female fertility. In addition to the antioxidant activity, celastrol may well have an independent role on regulation of gene expression in hGL cells.
BODIPY Conjugate of Epibrassinolide as a Novel Biologically Active Probe for In Vivo Imaging
Authors: Starodubtseva Anastasiia , Kalachova Tetiana , Iakovenko Oksana , Stoudková Vera , Zhabinskii Vladimir , Khripach Vladimir , Ruelland Eric , Martinec Jan , Burketová Lenka , Kravets Volodymyr
Published: March 2021

Brassinosteroids (BRs) are plant hormones of steroid nature, regulating various developmental and adaptive processes. The perception, transport, and signaling of BRs are actively studied nowadays via a wide range of biochemical and genetic tools. However, most of the knowledge about BRs intracellular localization and turnover relies on the visualization of the receptors or cellular compartments using dyes or fluorescent protein fusions. We have previously synthesized a conjugate of epibrassinolide with green fluorescent dye BODIPY (eBL-BODIPY). Here we present a detailed assessment of the compound bioactivity and its suitability as probe for in vivo visualization of BRs. We show that eBL-BODIPY rapidly penetrates epidermal cells of Arabidopsis thaliana roots and after long exposure causes physiological and transcriptomic responses similar to the natural hormone.
Acceptance of Google Meet during the Spread of Coronavirus by Arab University Students
Authors: Al-Maroof Rana Saeed , Alshurideh Muhammad Turki , Salloum Said A. , AlHamad Ahmad Qasim Mohammad , Gaber Tarek
Published: March 2021

The COVID-19 pandemic not only affected our health and medical systems but also has created large disruption of education systems at school and universities levels. According to the United Nation’s report, COVID-19 has influenced more than 1.6 billion learners from all over the world (190 countries or more). To tackle this problem, universities and colleges have implemented various technologically based platforms to replace the physical classrooms during the spread of Coronavirus. The effectiveness of these technologies and their educational impact on the educational sector has been the concern of researchers during the spread of the pandemic. Consequently, the current study is an attempt to explore the effect of Google Meet acceptance among Arab students during the pandemic in Oman, UAE, and Jordan. The perceived fear factor is integrated into a hybrid model that combines crucial factors in TAM (Technology acceptance Model) and VAM (Value-based Adoption Model). The integration embraces perceived fear factor with other important factors in TAM perceived ease of use (PEOU) and perceived usefulness (PU) on the one hand and technically influential factor of VAM, which are perceived technicality (PTE) and perceived enjoyment (PE) on the other hand. The data, collected from 475 participants (49% males and 51% females students), were analyzed using the partial least squares-structural equation modelling (PLS-SEM). The results have shown that TAM hypotheses of usefulness and easy to use have been supported. Similarly, the results have supported the hypotheses related to VAM factors of being technically useful and enjoying, which helps in reducing the atmosphere of fear that is created due to the spread of Coronavirus.
New Species of Soldier Fly—Sargus bipunctatus (Scopoli, 1763) (Diptera: Stratiomyidae), Recorded from a Human Corpse in Europe—A Case Report
Authors: Michalski Marek , Gadawski Piotr , Klemm Joanna , Szpila Krzysztof
Published: March 2021

The only European Stratiomyidae species known for feeding on human corpses was the black soldier fly Hermetia illucens (Linnaeus, 1758). Analysis of fauna found on a human corpse, discovered in central Poland, revealed the presence of feeding larvae of another species from this family: the twin-spot centurion fly Sargus bipunctatus (Scopoli, 1763). The investigated corpse was in a stage of advanced decomposition. The larvae were mainly observed in the adipocere formed on the back and lower limbs of the corpse, and in the mixture of litter and lumps of adipocere located under the corpse. Adult specimens and larvae were identified based on morphological characters, and final identification was confirmed using DNA barcoding. Implementing a combination of morphological and molecular methods provided a reliable way for distinguishing the larvae of S. bipunctatus and H. illucens. The potential of S. bipunctatus for practical applications in forensic entomology is currently difficult to assess. Wide and reliable use of S. bipunctatus in the practice of forensic entomology requires further studies of the bionomy of this fly.
Characterizing and Quantifying Arbovirus Transmission by Aedes aegypti Using Forced Salivation and Analysis of Bloodmeals
Authors: Miller Megan R. , Sorensen Madeleine R. , Markle Erin D. , Clarkson Taylor C. , Knight Ashley L. , Savran Michelle J. , Foy Brian D.
Published: March 2021

Arbovirus transmission studies are dependent on the ability to estimate the titer of virus transmitted from infectious mosquitoes to a host. There are several methods for estimating virus titer in mosquito saliva, including (1) using forced salivation (FS) whereby the infectious mosquito’s proboscis is forced into a capillary tube containing media to collect and test their saliva for virus, and (2) by quantifying virus expectorated into host tissues or into the blood contained in an artificial feeder immediately after blood feeding. We studied FS and bloodmeals to estimate and compare titers of Zika virus and chikungunya virus transmitted by the mosquito vector Aedes aegypti. Infectious virus and viral genomes of both viruses were detected more often from individual mosquitoes using immersion oil for the FS media compared to fetal bovine serum (FBS) plus glycerol, but the FS media had no influence on virus quantification from positive samples. FS virus titers were equivalent when comparing individuals or groups of mosquitoes that never received a blood meal compared to those that were blood fed immediately prior, showing that blood feeding does not influence FS. This suggested that performing FS on mosquitoes after blood feeding might be an efficient way to estimate virus transmitted during blood feeding. However, detecting virus from the blood remaining in an artificial feeder post-blood feeding was mostly unsuccessful relative to quantifying virus from FS of the post-blood fed mosquitoes. In contrast, immunocompromised mice always became infected after being fed on by Zika-infected mosquitoes, even when no infectious virus was detected in their saliva by FS post-blood feed. Due to this discrepancy, we tested the ingested bloodmeals of individual mosquitoes that fed on artificial blood feeders for virus, and compared these to virus in their saliva harvested from FS and to virus in their bodies. These experiments revealed ~50–100 times higher virus titers in the dissected bloodmeals compared to those detected in the same mosquitoes’ saliva, demonstrating how mosquitoes re-ingest much of their saliva during artificial blood feeding, and highlighting a large increase in virus transmission during Aedes aegypti blood feeding. Both FS and the dissected bloodmeals of artificially blood-fed mosquitoes showed that the quantity of viral RNA expectorated by mosquitoes was 2–5 logs more than the quantity of infectious virus. The results from this study add critical information to understanding and quantifying the transmission of Aedes aegypti arboviruses.
Predation on Drosophila suzukii within Hedges in the Agricultural Landscape
Authors: Siffert Alexandra , Cahenzli Fabian , Kehrli Patrik , Daniel Claudia , Dekumbis Virginie , Egger Barbara , Furtwengler Jana , Minguely Camille , Stäheli Nicola , Widmer Franco , Mazzi Dominique , Collatz Jana
Published: March 2021

The invasive Drosophila suzukii feeds and reproduces on various cultivated and wild fruits and moves between agricultural and semi-natural habitats. Hedges in agricultural landscapes play a vital role in the population development of D. suzukii, but also harbor a diverse community of natural enemies. We investigated predation by repeatedly exposing cohorts of D. suzukii pupae between June and October in dry and humid hedges at five different locations in Switzerland. We sampled predator communities and analyzed their gut content for the presence of D. suzukii DNA based on the COI marker. On average, 44% of the exposed pupae were predated. Predation was higher in dry than humid hedges, but did not differ significantly between pupae exposed on the ground or on branches and among sampling periods. Earwigs, spiders, and ants were the dominant predators. Predator communities did not vary significantly between hedge types or sampling periods. DNA of D. suzukii was detected in 3.4% of the earwigs, 1.8% of the spiders, and in one predatory bug (1.6%). While the molecular gut content analysis detected only a small proportion of predators that had fed on D. suzukii, overall predation seemed sufficient to reduce D. suzukii populations, in particular in hedges that provide few host fruit resources.
Gender Differences in Risk Factor Profile and Clinical Characteristics in 89 Consecutive Cases of Cerebral Venous Thrombosis
Authors: Bajko Zoltan , Motataianu Anca , Stoian Adina , Barcutean Laura , Andone Sebastian , Maier Smaranda , Drăghici Iulia-Adela , Cioban Andrada , Balasa Rodica
Published: March 2021

Gender has been shown to be an important variable in cerebral venous thrombosis (CVT) risk and significantly influences its clinical manifestations and outcome. The aim of our study was to investigate the gender-specific risk factor profile and clinical picture of this rare cerebrovascular disorder. Materials and methods: We retrospectively reviewed the medical records of 89 consecutive cases of CVT at a tertiary neurology clinic in Târgu Mures, Romania, between June 2009 and January 2021 to analyze the gender-related differences in etiology, clinical presentation, and outcome. Results: Women comprised 62.5% of the cohort. Females were significantly younger than males (37.3 years versus 48.8 years, respectively, p = 0.001), and the main risk factors were hormone related in 37.9% of the cases, followed by primary thrombophilia (34.4%), smoking (25.8%), obesity (17.2%), infections (17.2%), mechanical factors (17.2%), cancer (8.6%), systemic autoimmune disorders (8.6%), and hematological disorders (8.6%). In male patients, the main risk factors were smoking (41.9%), primary thrombophilia (29%), infections (22.6%), heavy alcohol consumption (16.1%), and venous thromboembolism in the medical history (12.9%). Frequency of headache was higher in females than in males (75.9% versus 67.7%), whereas frequency of coma (6.5% in males versus 1.7% in females) and dizziness (19.4% in males versus 10.3% in females) was higher in males. CVT onset was acute in 41.4% of females and 38.7% of males. The Rankin score at discharge was significantly lower in females compared with males (0.6 versus 1.6), reflecting a more favorable short-term outcome. Mortality was 6.4% in males and 1.7% in females. Conclusions: CVT is a multifactorial disorder that has a broad spectrum of risk factors with important gender-related differences in clinical manifestation and prognosis. Female patients, especially those with hormone-related risk factors, have a more favorable outcome than male patients.
Effects of Different Dialysis Strategies on Inflammatory Cytokine Profile in Maintenance Hemodialysis Patients with COVID-19: A Randomized Trial
Authors: Esposito Pasquale , Cipriani Leda , Verzola Daniela , Grignano Maria Antonietta , De Amici Mara , Testa Giorgia , Grosjean Fabrizio , Russo Elisa , Garibotto Giacomo , Rampino Teresa , Viazzi Francesca
Published: March 2021

Uncontrolled inflammation plays a relevant role in the pathogenesis of coronavirus disease-19 (COVID-19). Here, we studied the time trend of inflammatory markers in a population of hemodialysis (HD) patients affected by COVID-19, undergoing two different dialysis approaches. In a prospective study, thirty-one maintenance HD patients with COVID-19 were randomized to expanded HD (HDx), performed using a medium cut-off membrane, or standard treatment using a protein-leaking dialyzer (PLD). Circulating levels of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), soluble TLR4 (sTLR4), and interferon-gamma (IFN-γ), were collected at diagnosis, and one and two weeks after. Compared with 14 non-infected HD patients, COVID-19 patients showed lymphopenia and higher ferritin and lactate dehydrogenase levels. Moreover, COVID-19 patients had higher levels of IL-10 (15.2 (12.5) vs. 1.2 (1.4) pg/mL, p = 0.02). Twenty-nine patients were randomized to HDx (n = 15) or PLD (n = 14). After a single treatment, IL-8 showed a significant reduction in both groups, whereas IL-10 decreased only in HDx. All over the study, there were no significant modifications in circulating cytokine levels between the two groups, except for a parallel increase of IL-8 and IL-10 at one week control in the HDx group. No correlations were found between cytokine levels and clinical outcomes. In maintenance HD patients, COVID-19 is not related to a sustained inflammatory response. Therefore, modulation of inflammation seems not to be a suitable therapeutic target in this specific population.
Preoperative Cognitive Impairment as a Predictor of Postoperative Outcomes in Elderly Patients Undergoing Spinal Surgery for Degenerative Spinal Disease
Authors: Kim Hyung Cheol , An Seong Bae , Jeon Hyeongseok , Kim Tae Woo , Oh Jae Keun , Shin Dong Ah , Yi Seong , Kim Keung Nyun , Lee Phil Hyu , Kang Suk Yun , Ha Yoon
Published: March 2021

Cognitive status has been reported to affect the peri-operative and post-operative outcomes of certain surgical procedures. This prospective study investigated the effect of preoperative cognitive impairment on the postoperative course of elderly patients (n = 122, >65 years), following spine surgery for degenerative spinal disease. Data on demographic characteristics, medical history, and blood analysis results were collected. Preoperative cognition was assessed using the mini-mental state examination, and patients were divided into three groups: normal cognition, mild cognitive impairment, and moderate-to-severe cognitive impairment. Discharge destinations (p = 0.014) and postoperative cardiopulmonary complications (p = 0.037) significantly differed based on the cognitive status. Operation time (p = 0.049), white blood cell count (p = 0.022), platelet count (p = 0.013), the mini-mental state examination score (p = 0.033), and the Beck Depression Inventory score (p = 0.041) were significantly associated with the length of hospital stay. Our investigation demonstrated that improved understanding of preoperative cognitive status may be helpful in surgical decision-making and postoperative care of elderly patients with degenerative spinal disease.
What Is the Quality of Life in Patients Treated with Levothyroxine for Hypothyroidism and How Are We Measuring It? A Critical, Narrative Review
Authors: Borson-Chazot Françoise , Terra Jean-Louis , Goichot Bernard , Caron Philippe
Published: March 2021

Thyroid hormone replacement therapy (THRT, generally using oral levothyroxine (LT4)) is a safe, effective means of treating hypothyroidism. However, a proportion of LT4-treated patients with biochemically normal thyroid function tests complain of persistent symptoms that impact their health-related quality of life (QoL). The objectives of this critical, narrative review of the literature were to identify studies of QoL in LT4-treated patients with hypothyroidism, examine the instruments used to measure QoL, determine whether normal QoL is restored by THRT, and identify factors associated with QoL. The PubMed database was searched from 1 January 2000 to 31 December 2020. A total of 809 publications were screened, 129 full-text articles were retrieved, and 58 were analyzed. The studies of overt hypothyroidism evidenced an improvement in psychological and emotional well-being after three to six months of THRT with LT4, although contrasting results were found for patients with subclinical hypothyroidism. Combination treatment with LT4 and liothyronine was not generally associated with better QoL. In hypothyroidism, QoL appears to be influenced by a number of physiological, behavioral, cognitive and/or lifestyle factors that are not strictly related to thyroid hormone levels.
Efficacy of Targeted Temperature Management after Pediatric Cardiac Arrest: A Meta-Analysis of 2002 Patients
Authors: Wieczorek Wojciech , Meyer-Szary Jarosław , Jaguszewski Milosz J. , Filipiak Krzysztof J. , Cyran Maciej , Smereka Jacek , Gasecka Aleksandra , Ruetzler Kurt , Szarpak Lukasz
Published: March 2021

Cardiac arrest (CA) is associated with high mortality and poor life quality. Targeted temperature management (TTM) or therapeutic hypothermia is a therapy increasing the survival of adult patients after CA. The study aim was to assess the feasibility of therapeutic hypothermia after pediatric CA. We performed a systematic review and meta-analysis of randomized controlled trials and observational studies evaluating the use of TTM after pediatric CA. The primary outcome was survival to hospital discharge or 30-day survival. Secondary outcomes included a one-year survival rate, survival with a Vineland adaptive behavior scale (VABS-II) score ≥ 70, and occurrence of adverse events. Ten articles (n = 2002 patients) were included, comparing TTM patients (n = 638) with controls (n = 1364). In a fixed-effects meta-analysis, survival to hospital discharge in the TTM group was 49.7%, which was higher than in the non-TTM group (43.5%; odds ratio, OR = 1.22; 95% confidence interval, CI: 1.00, 1.50; p = 0.06). There were no differences in the one-year survival rate or the occurrence of adverse events between the TTM and non-TTM groups. Altogether, the use of TTM was associated with a higher survival to hospital discharge; however, it did not significantly increase the annual survival. Additional high-quality prospective studies are necessary to confer additional TTM benefits.
Multi-Objective Optimization of Functionally Graded Beams Using a Genetic Algorithm with Non-Dominated Sorting
Authors: Wu Chih-Ping , Li Kuan-Wei
Published: March 2021

A mixed layer-wise (LW) higher-order shear deformation theory (HSDT) is developed for the thermal buckling analysis of simply-supported, functionally graded (FG) beams subjected to a uniform temperature change. The material properties of the FG beam are assumed to be dependent on the thickness and temperature variables, and the effective material properties are estimated using either the rule of mixtures or the Mori–Tanaka scheme. The results shown in the numerical examples indicate the mixed LW HSDT solutions for critical temperature change parameters are in excellent agreement with the accurate solutions available in the literature. A multi-objective optimization of FG beams is presented to maximize the critical temperature change parameters and to minimize their total mass using a non-dominated sorting-based genetic algorithm. Some specific forms for the volume fractions of the constituents of the FG beam are assumed in advance, such as the one- and three-parameter power-law functions. The former is used in the thermal buckling analysis of the FG beams for comparison purposes, and the latter is used in their optimal design.
Review and Prospects for Autonomous Observing Systems in Vessels of Opportunity
Authors: Rosa Teresa L. , Piecho-Santos A. Miguel , Vettor Roberto , Guedes Soares C.
Published: March 2021

This paper focuses on the state of the art on Autonomous Observing Systems (AOS) used in Vessels of Opportunity (VOO) for collecting in situ atmospheric, oceanic and biogeochemical data. The designation Vessels of Opportunity includes all kinds of ships, even if not having scientific goals, which may carry proper devices that autonomously measure environmental variables. These vessels can be merchant, military, research, cruise liners, fishing, ferries, or even private yachts or sailing boats. The use of AOS can provide the opportunity for highly refined oceanographic data and improved derived data estimation, for local, regional or global scales studies. However, making the collected information accessible, both for scientific and technical purposes, provides a challenge in data management and analysis, which must, above all, ensure trusted useful data to the stakeholders. An overall review of the systems implemented is presented. This includes the definition of objectives, the recruitment of vessels and a review on the installation of proper acquisition devices; the selection and collection of Essential Oceanic Variables (EOV); the mechanisms for transmitting the information, and the quality control analysis and dissemination of data. The present and future capabilities of VOO for measuring EOV, within the Portuguese context are referred.
A Reference Spectrum Model for Estimating Source Levels of Marine Shipping Based on Automated Identification System Data
Authors: MacGillivray Alexander , de Jong Christ
Published: March 2021

Underwater sound mapping is increasingly being used as a tool for monitoring and managing noise pollution from shipping in the marine environment. Sound maps typically rely on tracking data from the Automated Information System (AIS), but information available from AIS is limited and not easily related to vessel noise emissions. Thus, robust sound mapping tools not only require accurate models for estimating source levels for large numbers of marine vessels, but also an objective assessment of their uncertainties. As part of the Joint Monitoring Programme for Ambient Noise in the North Sea (JOMOPANS) project, a widely used reference spectrum model (RANDI 3.1) was validated against statistics of monopole ship source level measurements from the Vancouver Fraser Port Authority-led Enhancing Cetacean Habitat and Observation (ECHO) Program. These validation comparisons resulted in a new reference spectrum model (the JOMOPANS-ECHO source level model) that retains the power-law dependence on speed and length but incorporates class-specific reference speeds and new spectrum coefficients. The new reference spectrum model calculates the ship source level spectrum, in decidecade bands, as a function of frequency, speed, length, and AIS ship type. The statistical uncertainty (standard deviation of the deviation between model and measurement) in the predicted source level spectra of the new model is estimated to be 6 dB.
Real Life Use of Bendamustine in Elderly Patients with Lymphoid Neoplasia
Authors: Dogliotti Irene , Ragaini Simone , Vassallo Francesco , Boccellato Elia , De Luca Gabriele , Perutelli Francesca , Boccomini Carola , Clerico Michele , Botto Barbara , Grimaldi Daniele , Orsucci Lorella , Ferrero Simone , Vitale Candida , Ferrero Dario , Coscia Marta , Cavallo Federica
Published: March 2021

Background. Bendamustine is a cytotoxic alkylating drug with a broad range of indications as a single agent or in combination therapy in lymphoid neoplasia patients. However, its tolerability in elderly patients is still debated. Methods: An observational, retrospective study was carried out; patients with chronic lymphocytic leukemia (CLL) or lymphoma, aged ≥ 65 years old, treated with bendamustine-based regimens in first or subsequent lines between 2010 and 2020 were considered eligible. Results: Overall, 179 patients aged ≥ 65 years were enrolled, 53% between 71 and 79 years old. Cumulative Illness Rating Scale (CIRS) comorbidity score was ≥6 in 54% patients. Overall survival (OS) at 12 months was 95% (95% confidence interval [CI]: 90–97%); after a median follow up of 50 months, median OS was 84 months. The overall response rate was 87%, with 56% complete responses; the median time to progression (TTP) was 61 months. The baseline factors affecting OS by multivariable analysis were sex, histological diagnosis, renal function, and planned bendamustine dose, while only type of lymphoma and bendamustine dose impacted on TTP. Main adverse events were neutropenia (grade ≥ 3: 43%) and infections (any grade: 36%), with 17% of patients requiring hospital admission. Conclusions: The responses to bendamustine, as well as survival, are relevant even in advanced age patients, with a manageable incidence of acute toxicity.
Drug-Drug Interactions Leading to Adverse Drug Reactions with Rivaroxaban: A Systematic Review of the Literature and Analysis of VigiBase
Authors: Fernandez Silvia , Lenoir Camille , Samer Caroline Flora , Rollason Victoria
Published: March 2021

Rivaroxaban has become an alternative to vitamin K antagonists, which are considered to be at higher risk of drug-drug interactions (DDI) and more difficult to use. However, DDI do occur. We systematically reviewed studies that evaluated them and analysed DDI and subsequent adverse drug reactions (ADR) reported in spontaneous reports and VigiBase. We systematically searched articles that explored DDI with rivaroxaban up to 20 August 2018 via Medline, Embase and Google Scholar. Data from VigiBase came from spontaneous reports recovered up to 2 January 2018, where Omega was used to detect signals and identify potential interactions in terms of triplets with two drugs and one ADR. We identified 31 studies and 28 case reports. Studies showed significant variation in the pharmacokinetic for rivaroxaban, and an increased risk of haemorrhage or thromboembolic events due to DDI was highlighted in case reports. From VigiBase, a total of 21,261 triplets were analysed and the most reported was rivaroxaban–aspirin–gastrointestinal haemorrhage. In VigiBase, only 34.8% of the DDI reported were described or understood, and most were pharmacodynamic DDI. These data suggest that rivaroxaban should be considered to have significant potential for DDI, especially with CYP3A/P-gp modulators or with drugs that impair haemostasis.
Brain Structure, Cardiorespiratory Fitness, and Executive Control Changes after a 9-Week Exercise Intervention in Young Adults: A Randomized Controlled Trial
Authors: Zhu Lina , Yu Qian , Herold Fabian , Cheval Boris , Dong Xiaoxiao , Cui Lei , Xiong Xuan , Chen Aiguo , Yin Hengchan , Kong Zhaowei , Mueller Notger , Kramer Arthur F. , Zou Liye
Published: March 2021

Cardiorespiratory fitness (CRF) is assumed to exert beneficial effects on brain structure and executive control (EC) performance. However, empirical evidence of exercise-induced cognitive enhancement is not conclusive, and the role of CRF in younger adults is not fully understood. Here, we conducted a study in which healthy young adults took part in a moderate aerobic exercise intervention program for 9 weeks (exercise group; n = 48), or control condition of non-aerobic exercise intervention (waitlist control group; n = 72). Before and after the intervention period maximal oxygen uptake (VO2max) as an indicator of CRF, the Flanker task as a measure of EC performance and grey matter volume (GMV), as well as cortical thickness via structural magnetic resonance imaging (MRI), were assessed. Compared to the control group, the CRF (heart rate, p < 0.001; VO2max, p < 0.001) and EC performance (congruent and incongruent reaction time, p = 0.011, p < 0.001) of the exercise group were significantly improved after the 9-week aerobic exercise intervention. Furthermore, GMV changes in the left medial frontal gyrus increased in the exercise group, whereas they were significantly reduced in the control group. Likewise, analysis of cortical morphology revealed that the left lateral occipital cortex (LOC.L) and the left precuneus (PCUN.L) thickness were considerably increased in the exercise group, which was not observed in the control group. The exploration analysis confirmed that CRF improvements are linked to EC improvement and frontal grey matter changes. In summary, our results support the idea that regular endurance exercises are an important determinant for brain health and cognitive performance even in a cohort of younger adults.
Ensemble of Multiple Classifiers for Multilabel Classification of Plant Protein Subcellular Localization
Authors: Wattanapornprom Warin , Thammarongtham Chinae , Hongsthong Apiradee , Lertampaiporn Supatcha
Published: March 2021

The accurate prediction of protein localization is a critical step in any functional genome annotation process. This paper proposes an improved strategy for protein subcellular localization prediction in plants based on multiple classifiers, to improve prediction results in terms of both accuracy and reliability. The prediction of plant protein subcellular localization is challenging because the underlying problem is not only a multiclass, but also a multilabel problem. Generally, plant proteins can be found in 10–14 locations/compartments. The number of proteins in some compartments (nucleus, cytoplasm, and mitochondria) is generally much greater than that in other compartments (vacuole, peroxisome, Golgi, and cell wall). Therefore, the problem of imbalanced data usually arises. Therefore, we propose an ensemble machine learning method based on average voting among heterogeneous classifiers. We first extracted various types of features suitable for each type of protein localization to form a total of 479 feature spaces. Then, feature selection methods were used to reduce the dimensions of the features into smaller informative feature subsets. This reduced feature subset was then used to train/build three different individual models. In the process of combining the three distinct classifier models, we used an average voting approach to combine the results of these three different classifiers that we constructed to return the final probability prediction. The method could predict subcellular localizations in both single- and multilabel locations, based on the voting probability. Experimental results indicated that the proposed ensemble method could achieve correct classification with an overall accuracy of 84.58% for 11 compartments, on the basis of the testing dataset.