bluuebunny/crossref_metadata_2025 huggingface dataset:
Pengaruh Konsumsi Bonggol Nanas (Ananas comosus) Terhadap Penurunan Kadar Volatile Sulfur Compound (VSC) Pada Penderita Hipertensi Sekunder Di Puskesmas Padongko
Authors: Eva Andy Fairuz Zuraida , Novawaty Eva , Selviani Yusrini , Masriadi Masriadi , Irawati Erna , Febriyanti Feby
Published: April 2021

Latar belakang: Mulut kering atau Xerostomia merupakan produksi saliva yang berkurang mengakibatkan sebagian besar fungsi saliva tidak dapat berperan dengan baik sehingga dapat menimbulkan meningkatnya Halitosis. Halitosis adalah kata lain yang berasal dari halitus (udara yang dihembuskan) dan osis (perubahan patologis) Foetor oris, Oral malodor, Mouth odor, Bad breath, and Bad mouth odor adalah nama lain untuk menggambarkan halitosis. Penelitian ini ingin mengetahui pengaruh konsumsi bonggol nanas (Ananas comosus) terhadap penurunan kadar Halitosis pada penderita Hipertensi yang mengkomsumsi obat-obatan anti hipertensi. Tujuan: Mengetahui pengaruh konsumsi bonggol nanas (Ananas comosus) terhadap penurunan kadar Volatile sulfur compound (VSC) pada penderita hipertensi sekunder di puskesmas padongko. Bahan dan Metode: Metode True Exsperimental dengan menggunakan desain penelitian Pretest-Posttest. Objek penelitian yaitu penderita Hipertensi sekunder yang mengkonsumsi obat-obatan anti Hipertensi dengan jumlah 16 orang. Pengolahan data menggunakan SPSS versi 25 dengan menggunkan uji normalitas Shapiro-Wilk dan Selanjutnya di lakukan Uji Wilcoxon. Hasil: uji Wilcoxon dengan tingkat signifikansi P = 0,000 (< 0,05), Sehingga dapat disimpulkan bahwa ada perbedaan skor kadar Volatile sulfur compound (VSC) pada penderita hipertensi sekunder dengan pemberian perlakuan konsumsi bonggol nanas (Ananas comosus). Kesimpulan: Ada pengaruh komsumsi Bonggol nanas (Ananas comosus) terhdap penurunan kadar Volatile sulfur compound (VSC) pada penderita Hipertensi sekunder.
Frederica Montseny. Més enllà del mite
Authors: Vergés Gifra Joan , Pérez Muñoz Max , Aisa-Pàmpols Ferran , Vilanou Torrano Conrad , Alcoberro Pericay Ramon , Tavera i Garcia Susanna , Costa i Gramunt Teresa , Vega Masana Eulàlia , Bernat Mateu Carme , Marín Silvestre Dolors , Balcells Gonzàlez Albert , Padrós González Alba , Arañó Vega Laia , Garcia i Raffi Josep Vicent , Pessarrodona Artigues Marta , Pons Mir Agustí
Published: April 2021

La vida de Frederica Montseny (1905-1994) resumeix bé una part considerable de la història de l’anarcosindicalisme català, espanyol i europeu. Tanmateix, la seva escriptura, el seu pensament, la seva obra, no són tan coneguts. En el volum que el lector té a les mans, un conjunt d'historiadors, crítics culturals, crítics literaris i filòsofs repassen la trajectòria de qui fou la primera ministra de la història política espanyola, consideren les idees que traspuen els escrits que va publicar, analitzen les novel·les, els assajos i els llibres de testimoniatge que va escriure, destaquen la importància de Montseny en la història del feminisme, etcètera. El propòsit del llibre no és en absolut doctrinal, ni amaga cap intenció hagiogràfica. Però sí que persegueix fer una certa justícia a l’obra d’una dona excepcional en molts sentits.
PROBLEMS OF NATION-BUILDING PROCESSES IN UKRAINE AT THE PRESENT STAGE
Authors: KRASIVSKYI Orest , PIDBEREZHNYK Nadiia
Published: April 2021

The article deals with the problematic aspects of nation-building processes in Ukraine at the present stage. A methodological basis is a comprehensive approach to problem analysis. The categories «nation», «Ukrainian nation», «Ukrainian people» are characterized. The main markers of national identity are identified among which: national consciousness, national interest, national territory, national idea, culture, language, history, common origin, religion. The nation was found to contain both ethnic, cultural and political components. From the dominance of one of these characteristics is formed in essence, an ethnic or political nation. The basic internal and external factors that negatively effecting nation-building processes in Ukraine are investigated. The internal ones include: lack of clear legislative criteria for inclusion in the ethnic community and real indicators of the ethnic composition of the Ukrainian people; loss of title ethnic identity based on linguistic marker; political speculation about the ethno-cultural features of the regions of Ukraine, linguistic and mental differences of the citizens of Ukraine; lack of an effective system of national-patriotic education and formation of national consciousness. External factors include: hybrid war of the Russian Federation against Ukraine, aimed at loss of territorial integrity and state sovereignty of Ukraine, aggravation of interethnic relations; intensive globalization processes that require new approaches to public policy on preserving and developing national identity; negative impact of information flows of foreign countries on the formation of information and cultural space of Ukraine; political and cultural expansion of neighboring countries (Hungary, Poland, Romania, Russia) into Ukraine, which goes beyond the support of their national minorities and poses a direct threat to Ukraine's national security.

Keywords: ethnicity,nation, national identity, nationalization, Ukraine, Ukrainian nation, hybrid war.
SOCIAL POLICY IN THE DISCOURSE OF POLITICAL PARTIES IN THE SNAP ELECTION TO THE VERKHOVNA RADA IN 2014
Authors: MATIIV Yuliia
Published: April 2021

The article describes the political parties' approach to implementing the state's social policy during the snap election to the Verkhovna Rada of Ukraine in 2014. A discursive dimension of political parties' activities in the area of social policy was studied. Specific examples have shown political parties as a subject of social policy formation. It was found out that the events of the Revolution of Dignity and the beginning of Russia's military aggression against Ukraine forced Ukrainian politicians to reconsider existing approaches to the formation of party programs. The author analyzed the reflection of social policy in the election programs of the parties that had formed parliamentary groups: «Blok Petra Poroshenka «Solidarnist», «Narodnyi front», Radykalnoi partii Oleha Liashka, «Opozytsiinyi blok», «Obiednannia «Samopomich», «Vseukrainskoho obiednannia «Batkivshchyna». Domestic political events were reflected in the party's discourse on social policy, shifting the priorities in the election programs of political forces in the direction of security policy, improving defense capabilities, and fighting corruption. The main tendencies related to the change of political parties' approaches to forming state social policy are revealed. Dominating the liberal approach to social policy issues in parliamentary parties' programs was aimed at reducing the state's role. At the same time, the speeches of political forces on social policy were mostly full of populist slogans and, in most cases, did not contain any specifics, including ways to solve social problems in society. Trying to get as much electoral support as possible, politicians did not bother to develop real program steps in the social sphere. Instead, the social sphere problems, which had a systemic character, were not solved based on a clear "road map" of actions. The discourse of the political parties participating in the election race, which eventually formed the parliament, did not present a comprehensive program for forming and implementing social policy in the new political environment.

Keywords: political parties, social policy, social state, Verkhovna Rada of Ukraine, political discourse.
FROM COOPERATION TO ENMITY: CONFRONTATION BETWEEN THE CARPATHIAN SICH AND THE CZECHOSLOVAK SECURITY AGENCIES (1938 – 1939)
Authors: PAHIRIA Oleksandr
Published: April 2021

The article studies the evolution of relationships between the Carpathian Sich paramilitary organization and the Czechoslovak security agencies on the territory of Podkarpatska Rus' (Capratho-Ukraine) at the turn of 1938 – 1939 as they escalated towards mutual hostility. Drawing on the vast archival sources the article traces three conflict lines between the sides: 1) interference by Sich members into the area of public order and security; 2) anti-Czech demonstrations sparked by the controversial decision of Prague to nominate the Czech army general Lev Prchala to the post of the third minister in the Carpatho-Ukraine autonomous government; 3) attempts by Sich members to steal weapons and ammunition from the depots of the Czechoslovak gendarmerie. Though frictions between the sides were visible even before, it was the mid-January 1939 decision of the Prague government to appoint general Prchala that stirred up Carpatho-Ukrainian society, led to the escalation of Czech-Ukrainian relations, and increased inter-ethnic tensions in Carpatho-Ukraine. It fostered the radicalization of the Carpathian Sich and boosted its aggression against the Czech presence in the region. These events put high on the Carpathian Sich agenda the necessity to replace the Czechoslovak security corps on the territory of Carpatho-Ukraine. They resulted in several armed clashes with the Czechs and attempts by Sich members to seize weapons from the gendarmerie deposits. As a rule, the autonomous government took the Sich side in these conflicts while pursuing its plans to increase the influence on the law enforcement agencies in the region. Amid heightened tensions, the armed conflict, which broke out between the Carpathian-Sich and Czechoslovak troops in Khust and its vicinities before the dissolution of the Czecho-Slovak Republic, was not a coincidence, but the logical outcome of the exponential escalation of their relations in the previous months. The studied antagonism reflected certain tendencies in the whole Second Czecho-Slovak republic, where the autonomous region of Slovakia and Podkarpatska Rus' had been striving for more powers in security and sought to get rid of excessive Prague patronage. In this regard, Carpathian Sich's actions against the Czechoslovak gendarmerie had many similarities with the Hlinka Guard's anti-Czech campaign in Slovakia.

Keywords
Czech-Slovakia, Capratho-Ukraine, Carpathian Sich, Lev Prchala, gendarmerie
Markov Regime-Switching Autoregressive Model of Stock Market Returns in Nigeria
Authors: A. Adejumo Oluwasegun , Albert Seno , J. Asemota Omorogbe
Published: April 2021

This study is designed to model and forecast Nigeria’s stock market using the All-Share Index (ASI) as a proxy. By employing the Markov regime-switching autoregressive (MS-AR) model with data from April 2005 to September 2019, the study analyzes the stock market volatility in three distinct regimes (accumulation or distribution – regime 1; big-move – regime 2; and excess or panic phases – regime 3) of the bull and bear periods. Six MS-AR candidate models are estimated and based on the minimum AIC value, MS(3)-AR(2) is returned as the optimal model among the six candidate models. The MS(3)-AR(2) analysis provides evidence of regime-switching behaviour in the stock market. The study also shows that only extreme events can switch the ASI returns from regime 1 to regime 2 and to regime 3, or vice versa. It further specifies an average duration period of 9, 3 and 4 weeks for the accumulation/distribution, big-move and excess/panic regimes respectively which is an evidence of favorable market for investors to trade. Based on Root Mean Square Error and Mean Absolute Error, the fitted MS-AR model is adjudged the most appropriate ASI returns forecasting model. The study recommends investments in stock across the regimes that are switching between accumulation/distribution and big-move phases for promising returns.
Determinants of Money Supply in Nigeria
Authors: R. Adediyan Aderopo
Published: April 2021

Studies on money supply determinants focus on the Classicists or Monetarists, Keynesians and post-Keynesians variables like income and money multiplier. This research extends the literature on money supply determinants to include the influence of financial liberalization on money supply with a reference to Nigeria between 1980 and 2019, using the Autoregressive Distributed Lag (ARDL) approach. Data used for the study were collected from the 2019 CBN Annual Statistical Bulletin. The study found that financial liberalization is an important factor in determining money supply in Nigeria, in addition to currency ratio, required reserve ratio and high-powered money. As a result, the extent of the liberalization of the financial sector matters in decisions on the regulation of money supply in the economy.
A Successful Treatment of Chronic Migraine With Hyperbaric Oxygen Therapy
Authors: Shafee Rahmah , Hamzah Mohd Amirullah , Muniandy Rajesh Kumar
Published: April 2021

The World Health Organization (WHO) ranks migraine as the most prevalent and disabling neurological condition. Management of migraines can be broadly divided into lifestyle and trigger management, acute treatments, and preventive treatments. Despite pharmacological advances, this medical problem has remained undertreated.

A 40-year-old male presented to the authors’ hospital and complained of severe, constant, and throbbing pain over the right side of his head. There was occasional photophobia but no visual disturbances. Oral analgesics were not helpful. After careful evaluation, he was advised to receive hyperbaric oxygen therapy sessions. He underwent one session per day, 5 days per week for 4 weeks. At the end of the 20 sessions, the patient reported an improvement in his symptoms, and did not require any oral medication. The authors concluded that hyperbaric oxygen therapy should be explored further as a treatment for pharmacologically resistant migraine.
Semio-Pragmatics as Politics: On Guattari and Deleuze's Theory of Language
Authors: Caló Susana
Published: April 2021

Focusing on Guattari and Deleuze's collaborative critique of structural linguistics, this article claims that rather than offering an ‘escape from language’, Guattari and Deleuze recast language as a social and political practice. Through a reading of Guattari and Deleuze's analysis of Saussure, their reinterpretation of Hjelmslev, and a discussion of the concepts of order-words and minor use of language, the article shows how, to do this, the authors develop a social and semiotic critique whereby the very concept of language changes from representation to intervention in a material and social field.
Rationale for the Use of Pirfenidone in Heart Failure With Preserved Ejection Fraction
Authors: Graziani Francesca , Lillo Rosa , Crea Filippo
Published: April 2021

Heart failure with preserved ejection fraction (HFpEF) is a major public health problem with growing prevalence and poor outcomes, mainly due to the lack of an effective treatment. HFpEF pathophysiology is heterogeneous and complex. Recently a “new paradigm” has been proposed, suggesting that cardiovascular and non-cardiovascular coexisting comorbidities lead to a systemic inflammatory state, perturbing the physiology of the endothelium and the perivascular environment and engaging molecular pathways that ultimately converge to myocardial fibrosis. If inflammation and fibrosis are the “fil rouge” in the heterogeneous spectrum of HFpEF, anti-fibrotic and anti-inflammatory drugs may have a role in its treatment. Pirfenidone is an orally bioavailable drug with antifibrotic and anti-inflammatory properties already approved for the treatment of idiopathic pulmonary fibrosis. Pirfenidone has been recently tested in animal models of myocardial fibrosis with promising results. Here we will review the rationale underlying the potential therapeutic effect of Pirfenidone in HFpEF.
Mixed-Convective Processes Within Seafloor Sediments Arising From Fresh Groundwater Discharge
Authors: Solórzano-Rivas S. C. , Werner Adrian D. , Irvine Dylan J.
Published: April 2021

The dependence of near-shore ecosystems on the freshwater component of submarine groundwater discharge (SFGD) is well recognized. Previous studies of SFGD have typically assumed that SFGD occurs through aquitards that are in direct contact with seawater. These studies provide no guidance on the distribution of freshwater discharge to the seafloor where SFGD occurs through sandy sediments, even though in most situations, seabed sediments are permeable. We find that SFGD may occur in unconfined, seafloor sediments as density-driven flow in the form of fingers, or otherwise, diffusive freshwater discharge is also possible. Unstable, buoyancy-driven flow within seabed sediments follows similar patterns (except inverted) to the downward free convection of unstable (dense over less-dense groundwater) situations. Consequently, the same theoretical controlling factors as those developed for downward mixed-convective flow are expected to apply. Although, there are important differences, in particular the boundary conditions, between subsea freshwater-seawater interactions and previous mixed-convective problems. Simplified numerical experiments in SEAWAT indicate that the behavior of fresh buoyant plumes depends on the aquifer lower boundary, which in turn controls the rate and pattern of SFGD to the seafloor. This article provides an important initial step in the understanding of SFGD behavior in regions of sandy seafloor sediments and analyses for the first time the mixed-convective processes that occur when freshwater rises into an otherwise saline groundwater body.
Diversity and Evolution of Mineralized Skeletal Tissues in Chondrichthyans
Authors: Berio Fidji , Broyon Morgane , Enault Sébastien , Pirot Nelly , López-Romero Faviel A. , Debiais-Thibaud Mélanie
Published: April 2021

The diversity of skeletal tissues in extant vertebrates includes mineralized and unmineralized structures made of bone, cartilage, or tissues of intermediate nature. This variability, together with the diverse nature of skeletal tissues in fossil species question the origin of skeletonization in early vertebrates. In particular, the study of skeletal tissues in cartilaginous fishes is currently mostly restrained to tessellated cartilage, a derived form of mineralized cartilage that evolved at the origin of this group. In this work, we describe the architectural and histological diversity of neural arch mineralization in cartilaginous fishes. The observed variations in the architecture include tessellated cartilage, with or without more massive sites of mineralization, and continuously mineralized neural arches devoid of tesserae. The histology of these various architectures always includes globular mineralization that takes place in the cartilaginous matrix. In many instances, the mineralized structures also include a fibrous component that seems to emerge from the perichondrium and they may display intermediate features, ranging from partly cartilaginous to mostly fibrous matrix, similar to fibrocartilage. Among these perichondrial mineralized tissues is also found, in few species, a lamellar arrangement of the mineralized extracellular matrix. The evolution of the mineralized tissues in cartilaginous fishes is discussed in light of current knowledge of their phylogenetic relationships.
Clinical Relevance of CD4 Cytotoxic T Cells in High-Risk Neuroblastoma
Authors: Tang Xao X. , Shimada Hiroyuki , Ikegaki Naohiko
Published: April 2021

Neuroblastoma is the most common extracranial childhood solid tumor. The majority of high-risk neuroblastoma is resistant/refractory to the current high intensity therapy, and the survival of these patients remains poor for the last three decades. To effectively treat these extremely unfavorable neuroblastomas, innovative immunotherapy approaches would be the most promising. In this article, we discuss the identity of tumor-infiltrating effector cells and immunosuppressive cells in high-risk neuroblastoma. Neuroblastoma is unique in that it expresses little or no classical HLA Class I and II. In contrast, high-risk neuroblastomas express the stress-responsive non-classical Class I, HLA-E molecule. HLA-E is the ligand of activating receptors NKG2C/E that are expressed on memory NK cells, CD8+T cells and CD4 CTLs. By examining a comprehensive RNA-seq gene expression dataset, we detected relatively high levels ofCD4expression in high-risk neuroblastoma tissues. The majority of CD4+ cells were CD3+, and thus they were likely tumor-associated CD4+T cells. In addition, high-level of both CD4 and NKG2C/E expression was associated with prolonged survival of the high-risk neuroblastoma patients, but CD8 levels were not, further suggesting that the CD4+ NKG2C/E+ T cells or CD4 CTL conferred cytotoxicity against the neuroblastoma cells. However, this T cell mediated- “protective effect” declined over time, in part due to the progressive formation of immunosuppressive tumor microenvironment. These observations suggest that to improve survival of high-risk neuroblastoma patients, it is essential to gain insights into how to enhance CD4 CTL cytotoxicity and control the immunosuppressive tumor microenvironment during the course of the disease.
Novel Insights Into Rheumatoid Arthritis Through Characterization of Concordant Changes in DNA Methylation and Gene Expression in Synovial Biopsies of Patients With Differing Numbers of Swollen Joints
Authors: Li Yim Andrew Y. F. , Ferrero Enrico , Maratou Klio , Lewis Huw D. , Royal George , Tough David F. , Larminie Chris , Mannens Marcel M. A. M. , Henneman Peter , de Jonge Wouter J. , van de Sande Marleen G. H. , Gerlag Danielle M. , Prinjha Rab K. , Tak Paul P.
Published: April 2021

In this study, we sought to characterize synovial tissue obtained from individuals with arthralgia and disease-specific auto-antibodies and patients with established rheumatoid arthritis (RA), by applying an integrative multi-omics approach where we investigated differences at the level of DNA methylation and gene expression in relation to disease pathogenesis. We performed concurrent whole-genome bisulphite sequencing and RNA-Sequencing on synovial tissue obtained from the knee and ankle from 4 auto-antibody positive arthralgia patients and thirteen RA patients. Through multi-omics factor analysis we observed that the latent factor explaining the variance in gene expression and DNA methylation was associated with Swollen Joint Count 66 (SJC66), with patients with SJC66 of 9 or more displaying separation from the rest. Interrogating these observed differences revealed activation of the immune response as well as dysregulation of cell adhesion pathways at the level of both DNA methylation and gene expression. We observed differences for 59 genes in particular at the level of both transcript expression and DNA methylation. Our results highlight the utility of genome-wide multi-omics profiling of synovial samples for improved understanding of changes associated with disease spread in arthralgia and RA patients, and point to novel candidate targets for the treatment of the disease.
Impact of Early Versus Late Antiretroviral Treatment Initiation on Naive T Lymphocytes in HIV-1-Infected Children and Adolescents – The-ANRS-EP59-CLEAC Study
Authors: Frange Pierre , Montange Thomas , Le Chenadec Jérôme , Batalie Damien , Fert Ingrid , Dollfus Catherine , Faye Albert , Blanche Stéphane , Chacé Anne , Fourcade Corine , Hau Isabelle , Levine Martine , Mahlaoui Nizar , Marcou Valérie , Tabone Marie-Dominique , Veber Florence , Hoctin Alexandre , Wack Thierry , Avettand-Fenoël Véronique , Warszawski Josiane , Buseyne Florence
Published: April 2021

Background

The early initiation of antiretroviral therapy (ART) in HIV-1-infected infants reduces mortality and prevents early CD4 T-cell loss. However, the impact of early ART on the immune system has not been thoroughly investigated in children over five years of age or adolescents. Here, we describe the levels of naive CD4 and CD8 T lymphocytes (CD4/CD8TN), reflecting the quality of immune reconstitution, as a function of the timing of ART initiation (early (<6 months) versus late (≥24 months of age)).

Methods

The ANRS-EP59-CLEAC study enrolled 27 children (5-12 years of age) and nine adolescents (13-17 years of age) in the early-treatment group, and 19 children (L-Ch) and 21 adolescents (L-Ado) in the late-treatment group. T lymphocytes were analyzed by flow cytometry and plasma markers were analyzed by ELISA. Linear regression analysis was performed with univariate and multivariate models.

Results

At the time of evaluation, all patients were on ART and had a good immunovirological status: 83% had HIV RNA loads below 50 copies/mL and the median CD4 T-cell count was 856 cells/µL (interquartile range: 685-1236 cells/µL). In children, early ART was associated with higher CD8TN percentages (medians: 48.7% vs. 31.0%, P = 0.001), and a marginally higher CD4TN (61.2% vs. 53.1%, P = 0.33). In adolescents, early ART was associated with low CD4TN percentages and less differentiated memory CD8 T cells. CD4TN and CD8TN levels were inversely related to cellular activation and gut permeability.

Conclusion

In children and adolescents, the benefits of early ART for CD8TN were clear after long-term ART. The impact of early ART on CD4TN appears to be modest, because pediatric patients treated late respond to HIV-driven CD4 T-lymphocyte loss by the de novo production of TN cells in the thymus. Our data also suggest that current immune activation and/or gut permeability has a negative impact on TN levels.

Clinical Trial Registration

ClinicalTrials.gov, identifier NCT02674867.
BTLA Expression and Function Are Impaired on SLE B Cells
Authors: Wiedemann Annika , Lettau Marie , Weißenberg Sarah Y. , Stefanski Ana-Luisa , Schrezenmeier Eva-Vanessa , Rincon-Arevalo Hector , Reiter Karin , Alexander Tobias , Hiepe Falk , Lino Andreia C. , Dörner Thomas
Published: April 2021

B- and T-lymphocyte attenuator (BTLA/CD272) is an inhibitory checkpoint molecule expressed on T and B cells. Prior studies reported defective function of BTLA by T cells in patients with systemic lupus erythematosus (SLE), whereas nothing is known about its role on B cells in SLE, a disease with various B cell abnormalities. Peripheral blood mononuclear cells (PBMCs) from 23 healthy donors (HD) and 34 SLE patients were stained for BTLA and its expression on B cells was assessed. PBMCs or CD27-IgD+ naive B cells were stimulated together with an activating anti-BTLA antibody or an inhibitor of spleen tyrosine kinase (SYK) and differentiation as well as the expression of activation markers CD71, PD-1 and CD86 were analyzed. Our phenotypic and functional studies revealed reduced BTLA expression on CD27-IgD+ naïve B cells from SLE patients (p=0.0017) related to anti-dsDNA antibody titers (p=0.0394) and SIGLEC-1/CD169 expression on monocytes (p=0.0196), a type I interferon marker related to disease activity. BTLA engagement was found to control CpG/TLR9 activation limiting plasmablast (p=0.0156) and B cell memory induction (p=0.0078) in normal B cells in contrast to other B cell activation pathways (CD40, BCR). These BTLA functions were impaired in SLE B cells. Inhibition of SYK was found to mimic the effects of BTLA activity in vitro. Thus, is it possible that reduced BTLA expression and function of CD27-IgD+ antigen- and T cell-inexperienced SLE B cells could be overcome by SYK inhibition which should be tested in future studies as potential therapeutic principle.
Impacts of Multiple Stressors on a Benthic Foraminiferal Community: A Long-Term Experiment Assessing Response to Ocean Acidification, Hypoxia and Warming
Authors: Bernhard Joan M. , Wit Johannes C. , Starczak Victoria R. , Beaudoin David J. , Phalen William G. , McCorkle Daniel C.
Published: April 2021

Ocean chemistry is changing as a result of human activities. Atmospheric carbon dioxide (CO2) concentrations are increasing, causing an increase in oceanic pCO2 that drives a decrease in oceanic pH, a process called ocean acidification (OA). Higher CO2 concentrations are also linked to rising global temperatures that can result in more stratified surface waters, reducing the exchange between surface and deep waters; this stronger stratification, along with nutrient pollution, contributes to an expansion of oxygen-depleted zones (so called hypoxia or deoxygenation). Determining the response of marine organisms to environmental changes is important for assessments of future ecosystem functioning. While many studies have assessed the impact of individual or paired stressors, fewer studies have assessed the combined impact of pCO2, O2, and temperature. A long-term experiment (∼10 months) with different treatments of these three stressors was conducted to determine their sole or combined impact on the abundance and survival of a benthic foraminiferal community collected from a continental-shelf site. Foraminifera are well suited to such study because of their small size, relatively rapid growth, varied mineralogies and physiologies. Inoculation materials were collected from a ∼77-m deep site south of Woods Hole, MA. Very fine sediments (<53 μm) were used as inoculum, to allow the entire community to respond. Thirty-eight morphologically identified taxa grew during the experiment. Multivariate statistical analysis indicates that hypoxia was the major driving factor distinguishing the yields, while warming was secondary. Species responses were not consistent, with different species being most abundant in different treatments. Some taxa grew in all of the triple-stressor samples. Results from the experiment suggest that foraminiferal species’ responses will vary considerably, with some being negatively impacted by predicted environmental changes, while other taxa will tolerate, and perhaps even benefit, from deoxygenation, warming and OA.
Effects of Ocean Acidification on Carbon and Nitrogen Fixation in the Hermatypic Coral Galaxea fascicularis
Authors: Zheng Xinqing , Wang Chenying , Sheng Huaxia , Niu Gaofeng , Dong Xu , Yuan Lingling , Shi Tuo
Published: April 2021

The supply of metabolites from symbionts to scleractinian corals is crucial to coral health. Members of the Symbiodiniaceae can enhance coral calcification by providing photosynthetically fixed carbon (PFC) and energy, whereas dinitrogen (N2)-fixing bacteria can provide additional nutrients such as diazotrophically-derived nitrogen (DDN) that sustain coral productivity especially when alternative external nitrogen sources are scarce. How these mutualistic associations benefit corals in the future acidifying ocean is not well understood. In this study, we investigated the possible effects of ocean acidification (OA; pHs 7.7 and 7.4 vs. 8.1) on calcification in the hermatypic coralGalaxea fasciculariswith respect to PFC and DDN assimilation. Our measurements based on isotopic tracing showed no significant differences in the assimilation of PFC among different pH treatments, but the assimilation of DDN decreased significantly after 28 days of stress at pH 7.4. The decreased DDN assimilation suggests a nitrogenous nutrient deficiency in the coral holotiont, potentially leading to reduced coral calcification and resilience to bleaching and other stressful events. This contrasting impact of OA on carbon and N flux demonstrates the flexibility ofG. fascicularisin coping with OA, apparently by sustaining a largely undamaged photosystem at the expense of N2fixation machinery, which competes with coral calcification for energy from photosynthesis. These findings shed new light on the critically important but more vulnerable N cyclingin hospite, and on the trade-off between coral hosts and symbionts in response to future climate change.
Modeling Transit Flow Through Port Gates and Connecting Channel in Baltic Sea—Liepaja Port—Liepaja Lake System
Authors: Frishfelds Vilnis , Sennikovs Juris , Bethers Uldis , Murawski Jens , Timuhins Andrejs
Published: April 2021

This study investigates a water transport features by extending Copernicus Marine Environment Service (CMEMS) to the Liepaja coast-port-channel-lake system with a two-way nested model. The Liepaja lake and Liepaja port are connected by Trade channel. The Liepaja port has three gates—the openings in wave breakers connecting the port aquatory with the Baltic sea. Each of gates has a corresponding dredged channel for securing the navigation. A hydrodynamic model is set up to study the flow and water level in this system. The area of the port gates, port and Trade channel are resolved by 33 m grid. The model results are verified against currents and sea level observations inside/outside port, Trade channel and Liepaja lake. Results and observations show that strong currents occur in the Trade channel in case of rapid sea level change in Baltic sea despite the Trade channel is rather shallow at the connection with Liepaja lake. The northern part of the Liepaja lake gets filled with brackish water during storm surge events. The channel has notable alternating current also during a relatively calm weather due to the port seiches. Long and narrow shape of the channel implies the Helmholtz type oscillations between the lake and the port with a period in approximately semidiurnal range. Hydrodynamic simulations describe well these oscillations but the phase of hourly scale oscillations in the port may differ in case of weak external forcing. Water exchange is significantly increased by the transit (gate to gate) sea currents. This transit flow usually occurs between South or Central gate and the North gate carrying sea water into the port. Northward flow of the surface layer is more characteristic in the port aquatory due the prevailing south-western winds. There are intense morphological processes at the coastline and underwater slope near the Liepaja port due to a sandy western coastline of Latvia, long fetch of the waves and strong currents at the port gates. Liepaja port is one of the Latvian ports in HywasPort operational service of hydrodynamics, waves and siltation.
Long Non-coding RNA LINC00847 Induced by E2F1 Accelerates Non-small Cell Lung Cancer Progression Through Targeting miR-147a/IFITM1 Axis
Authors: Li Huan , Chen Yao-kai , Wan Qiu , Shi An-qi , Wang Min , He Ping , Tang Li-xin
Published: April 2021

Background: Long non-coding RNAs (lncRNAs) can remarkably regulate human malignancies in terms of the development and the progression. Previously, lncRNA LINC00847 (LINC00847) has been reported to present dysregulation in several tumors. However, the expression and function of LINC00847 in non-small cell lung cancer (NSCLC) have not been investigated.

Methods: RT-qPCR was performed to determine the expressions of LINC00847 in collected tissue samples and cell lines. The clinical significance of LINC00847 was statistically analyzed. CCK-8 test, cell scratch test and trans-well test were used to evaluate the proliferation, invasion and migration abilities of NSCLC cells, respectively. The xenograft tumor model was constructed to confirm the effects of LINC00847 knockdown on NSCLC in vivo. Further, luciferase reporter assays and Western blot were performed to explore molecular mechanisms underlying the functions of LINC00847.

Results: Increased expressions of LINC00847 were observed in NSCLC samples as well as cell lines. Additionally, E2F1 could be capable of directly binding to the LINC00847 promoter region, followed by promoting its expression. Clinically, LINC00847 high-expression could lead to poor prognosis of NSCLC patients. Functionally, LINC00847 knockdown noticeably repressed NSCLC cell growth and metastasis. Mechanically, miR-147a/IFITM1 axis was a downstream target of LINC00847, and silencing of miR-147a could rescue the anti-cancer effects of LINC00847 knockdown on NSCLC cell behaviors.

Conclusion: Overall, up regulation of LINC00847 induced by E2F1 promoted the progression of NSCLC by modulating miR-147a/IFITM1 axis, representing a novel regulatory mechanism for NSCLC progression.
Bacterial Manipulation of the Integrated Stress Response: A New Perspective on Infection
Authors: Knowles Alex , Campbell Susan , Cross Neil , Stafford Prachi
Published: April 2021

Host immune activation forms a vital line of defence against bacterial pathogenicity. However, just as hosts have evolved immune responses, bacteria have developed means to escape, hijack and subvert these responses to promote survival. In recent years, a highly conserved group of signalling cascades within the host, collectively termed the integrated stress response (ISR), have become increasingly implicated in immune activation during bacterial infection. Activation of the ISR leads to a complex web of cellular reprogramming, which ultimately results in the paradoxical outcomes of either cellular homeostasis or cell death. Therefore, any pathogen with means to manipulate this pathway could induce a range of cellular outcomes and benefit from favourable conditions for long-term survival and replication. This review aims to outline what is currently known about bacterial manipulation of the ISR and present key hypotheses highlighting areas for future research.
CRBA: A Competitive Rate-Based Algorithm Based on Competitive Spiking Neural Networks
Authors: Cachi Paolo G. , Ventura Sebastián , Cios Krzysztof J.
Published: April 2021

In this paper we present a Competitive Rate-Based Algorithm (CRBA) that approximates operation of a Competitive Spiking Neural Network (CSNN). CRBA is based on modeling of the competition between neurons during a sample presentation, which can be reduced to ranking of the neurons based on a dot product operation and the use of a discrete Expectation Maximization algorithm; the latter is equivalent to the spike time-dependent plasticity rule. CRBA's performance is compared with that of CSNN on the MNIST and Fashion-MNIST datasets. The results show that CRBA performs on par with CSNN, while using three orders of magnitude less computational time. Importantly, we show that the weights and firing thresholds learned by CRBA can be used to initialize CSNN's parameters that results in its much more efficient operation.
Wrist Position Sense in Two Dimensions: Between-Hand Symmetry and Anisotropic Accuracy Across the Space
Authors: Albanese Giulia A. , Holmes Michael W. R. , Marini Francesca , Morasso Pietro , Zenzeri Jacopo
Published: April 2021

A deep investigation of proprioceptive processes is necessary to understand the relationship between sensory afferent inputs and motor outcomes. In this work, we investigate whether and how perception of wrist position is influenced by the direction along which the movement occurs. Most previous studies have tested Joint Position Sense (JPS) through 1 degree of freedom (DoF) wrist movements, such as flexion/extension (FE) or radial/ulnar deviation (RUD). However, the wrist joint has 3-DoF and many activities of daily living produce combined movements, requiring at least 2-DoF wrist coordination. For this reason, in this study, target positions involved movement directions that combined wrist flexion or extension with radial or ulnar deviation. The chosen task was a robot-aided Joint Position Matching (JPM), in which blindfolded participants actively reproduced a previously passively assumed target joint configuration. The JPM performance of 20 healthy participants was quantified through measures of accuracy and precision, in terms of both perceived target direction and distance along each direction of movement. Twelve different directions of movement were selected and both hands tested. The left and right hand led to comparable results, both target extents and directions were differently perceived according to the target direction on the FE/RUD space. Moreover, during 2-DoF combined movements, subjects’ perception of directions was impaired when compared to 1-DoF target movements. In summary, our results showed that human perception of wrist position on the FE/RUD space is symmetric between hands but not isotropic among movement directions.
Strategies to Refine Gastric Stimulation and Pacing Protocols: Experimental and Modeling Approaches
Authors: Cheng Leo K. , Nagahawatte Nipuni D. , Avci Recep , Du Peng , Liu Zhongming , Paskaranandavadivel Niranchan
Published: April 2021

Gastric pacing and stimulation strategies were first proposed in the 1960s to treat motility disorders. However, there has been relatively limited clinical translation of these techniques. Experimental investigations have been critical in advancing our understanding of the control mechanisms that innervate gut function. In this review, we will discuss the use of pacing to modulate the rhythmic slow wave conduction patterns generated by interstitial cells of Cajal in the gastric musculature. In addition, the use of gastric high-frequency stimulation methods that target nerves in the stomach to either inhibit or enhance stomach function will be discussed. Pacing and stimulation protocols to modulate gastric activity, effective parameters and limitations in the existing studies are summarized. Mathematical models are useful to understand complex and dynamic systems. A review of existing mathematical models and techniques that aim to help refine pacing and stimulation protocols are provided. Finally, some future directions and challenges that should be investigated are discussed.
Peritumoral Brain Edema in Meningiomas May Be Related to Glymphatic Dysfunction
Authors: Toh Cheng Hong , Siow Tiing Yee , Castillo Mauricio
Published: April 2021

The pathogenesis of peritumoral brain edema (PTBE) in meningiomas remains unclear. The glymphatic system is recently recognized as a pathway for waste clearance and maintaining fluid balance in the brain parenchymal interstitium. We aimed to investigate if the PTBE volume of meningiomas correlates with their glymphatic function. A total of 80 meningioma patients (mean age, 58.8 years; 37 men) and 44 normal subjects (mean age 53.3 years; 23 men) who had preoperative diffusion-tensor imaging for calculation of the analysis along the perivascular space (ALPS) index were retrospectively included. Information collected from each patient included sex, age, tumor grade, Ki-67 index, tumor location, tumor volume, PTBE volume and ALPS index. Comparisons of ALPS index among meningiomas without PTBE, meningiomas with PTBE, and normal subjects were performed using analysis of covariance with Bonferroni correction and adjustments for age and sex. Pearson correlation coefficient and multivariable linear regression analyses were performed to identify factors associated with PTBE volume. Group comparisons revealed that the ALPS index was significantly higher (P < 0.05) in meningiomas without PTBE vs. meningiomas with PTBE and normal subjects. On the other hand, ALPS index was not different between meningiomas with PTBE and normal subjects. On Pearson correlation and multivariable linear regression analyses, the ALPS index was the only factor significantly (P < 0.05) associated with PTBE volume. In conclusion, PTBE volume inversely correlated with ALPS index in meningiomas. PTBE formation in meningiomas may be related to glymphatic dysfunction.
Feasibility of Methylated CLIP4 in Stool for Early Detection of Colorectal Cancer: A Training Study in Chinese Population
Authors: Cao Yang , Zhao Guodong , Cao Yaping , Chen Zhiliang , Liu Xiaoyu , Yuan Mufa , Yang Jun , Wang Xiaomei , Ma Yong , Liu Zhaocheng , Xiong Shangmin , Zheng Minxue , Fei Sujuan
Published: April 2021

Background

Early detection of colorectal cancer (CRC) and precancerous lesion is vitally important for mitigating CRC morbidity and mortality. Aberrant DNA methylations in certain promoter regions have been identified to be closely associated with CRC development and progression, suggesting their potential as diagnostic biomarkers for early detection. In this study, we evaluated the performance of methylated CLIP4 in stool specimens as a potential biomarker for CRC detection.

Methods

A total of 321 subjects out of 365 enrolled participants were included in the final analysis, including 154 CRC patients, 23 advanced adenoma (AA) patients, 49 small polyp (SP) patients, and 95 healthy controls. CLIP4 methylation level was examined by qPCR with bisulfite converted DNA purified from approximately 5 g stool specimen.

Results

Methylated CLIP4 test showed high sensitivities of 78.3% (95% CI: 55.8%–91.7%) and 90.3% (95% CI: 84.2%–94.3%) for detecting AA and CRC, respectively, with a specificity of 88.4% (95% CI: 79.8%–93.8%). CLIP4 methylation level discriminated AA and CRC patients from control subjects with area under the curve values of 0.892 (95% CI: 0.795–0.988) and 0.961 (95% CI: 0.938–0.983). Further analysis indicated no significant difference in sensitivities among different ages, genders, stages, locations, sides, tumor sizes and differentiation statuses.

Conclusions

Methylated CLIP4 showed a strong potential as a noninvasive biomarker for early CRC detection.
A Novel Role for Brain and Acute Leukemia Cytoplasmic (BAALC) in Human Breast Cancer Metastasis
Authors: Birgersson Madeleine , Chi Mengna , Miller Chrissy , Brzozowski Joshua S. , Brown Jeffrey , Schofield Lachlan , Taylor Olivia G. , Pearsall Elizabeth A. , Hewitt Jasmine , Gedye Craig , Lincz Lisa F. , Skelding Kathryn A.
Published: April 2021

Brain and Acute Leukemia, Cytoplasmic (BAALC) is a protein that controls leukemia cell proliferation, differentiation, and survival and is overexpressed in several cancer types. The gene is located in the chromosomal region 8q22.3, an area commonly amplified in breast cancer and associated with poor prognosis. However, the expression and potential role of BAALC in breast cancer has not widely been examined. This study investigates BAALC expression in human breast cancers with the aim of determining if it plays a role in the pathogenesis of the disease. BAALC protein expression was examined by immunohistochemistry in breast cancer, and matched lymph node and normal breast tissue samples. The effect of gene expression on overall survival (OS), disease-free and distant metastasis free survival (DMFS) was assessed in silico using the Kaplan-Meier Plotter (n=3,935), the TCGA invasive breast carcinoma (n=960) and GOBO (n=821) data sets. Functional effects of BAALC expression on breast cancer proliferation, migration and invasion were determined in vitro. We demonstrate herein that BAALC expression is progressively increased in primary and breast cancer metastases when compared to normal breast tissue. Increased BAALC mRNA is associated with a reduction in DMFS and disease-free survival, but not OS, in breast cancer patients, even when corrected for tumor grade. We show that overexpression of BAALC in MCF-7 breast cancer cells increases the proliferation, anchorage-independent growth, invasion, and migration capacity of these cells. Conversely, siRNA knockdown of BAALC expression in Hs578T breast cancer cells decreases proliferation, invasion and migration. We identify that this BAALC associated migration and invasion is mediated by focal adhesion kinase (FAK)-dependent signaling and is accompanied by an increase in matrix metalloproteinase (MMP)-9 but not MMP-2 activity in vitro. Our data demonstrate a novel function for BAALC in the control of breast cancer metastasis, offering a potential target for the generation of anti-cancer drugs to prevent breast cancer metastasis.