bluuebunny/crossref_metadata_2025 huggingface dataset:
Constructing Kurdishness in Turkey: Passive exposure as a boundary marker
Authors: Şengül Ceren
Published: May 2022

This article discusses the under-researched sonic aspect of belonging to Kurdishness in Turkey: listening to or hearing the language, so-called passive exposure, without necessarily speaking it. Drawing on ethnographic, in-depth interviews and participant observation across five different field sites in Turkey, this article illustrates that in Turkey, where the public space for Kurdish soundscape is limited, passive exposure to the Kurdish language within family environments acts as major means of transmission of belonging. This discussion contributes to the literature on boundary-making by illustrating that the absence of passive exposure hinders some of the means of boundary-making such as self-ascription.
Abstract in Kurmanji
Avakirina Kurdîniyê li Tirkiyeyê: Merûziya pasîf wekî nîşaneke sînorê
Ev gotar hêla dengî ya aîdiyeta Kurdîniyê li Tirkiyeyê, ya kêm-lêkolînkirî nîqaş dike: guhdarîkirin an bihîstina zimên, ango merûziya pasîf, bêyî şertê axaftina bi wî zimanî. Li gor hevdîtinên kûr ên etnografîk û çavdêrîkirina beşdarî ya li 5 qadên cuda yên li Tirkiyeyê, ev gotar nîşan dide ku dema qadên giştî ji bo derdora dengî ya kurdî bisînor bin, merûziya pasîf a zimanê kurdî di nav derdorên malbatî de dibe rêya sereke ya raguhastina aîdiyetê. Ev nîqaş tevkariya edebiyata li ser çêkirina-sînoran dike bi nîşandana wê yekê ku nebûna merûziya pasîf dibe asteng ji bo hin rêyên çêkirina-sînoran; bo nimûne, ji bo xwe-lêbarkirinê.
Abstract in Zazaki
Tirkîya de Awankerdişê Kurdbîyayîşî: Marûzîya Pasîfe Sey Nîşanê Sînoran
No nuşte cîhetê vengî yê Tirkîya de kurdbîyayîşî yo ke bes cigêrayîş nêdîyo, ey ser o vindeno: marûzîya pasîfe, yanî bê ke merdim yew ziwan qisey bikero, la ê ziwanî biheşno yan goşdarî bikero. Bi roportajanê xorînanê etnografîkan û panc waranê Tirkîya yê cîya-cîyayan de nîyadarîya beşdaran ra, na meqale musnena ke rayapêroyîya Tirkîya de ke tede manzaraya vengî ya kurdkî sînorkerdî ya, uca dorûverê keyeyan de ziwanê kurdkî rê bi hewayêko pasîf marûzbîyayîş beno wasitaya weşanê endamîya komelî ya bingeyêne. Na munaqeşeya ke kemerêk nana ro lîteraturê sînorronayîşî ser, nawnena ke eke marûzîya pasîfe çin bo, tayê îmkanê sînorronayîşî, sey xotedehesibnayîşî, asteng benê.
Abstract in Sorani
Available in print and PDF versions.
Establishing a journal, shaping a field: An interview with Dr Welat Zeydanlıoğlu
Authors: Schäfers Marlene
Published: May 2022

In this interview, founder and long-time managing editor of Kurdish Studies, Dr Welat Zeydanlıoğlu, tells the story of the journal’s establishment and recalls its development to becoming the leading English-speaking journal in the field of Kurdish studies today. He explains the relations between the journal and the Kurdish Studies Network, reflects on the difficulties that the journal has faced over the years, and outlines its major contributions to the field. The interview sheds light not only on the history of a journal but on the development of an entire scholarly field, while sketching the challenges lying ahead.
Abstract in Kurmanji
Avakirina kovarekê, şikildana qadekê: Hevpeyvîneke ligel Dr. Welat Zeydanlioglu
Di vê hevpeyvînê de, avaker û edîtorê rêvebirinê yê demdirêj ê Kurdish Studiesê, Dr. Welat Zeydanlioglu behsa çîroka avakirina kovarê dike û pêşketina wê ya ber bi bûyîna kovara sereke ya îngilîzî di qada Xebatên Kurdî de bi bîr tîne. Ew, têkiliyên di navbera kovarê û Kurdish Studies Networkê de rave dike, zehmetiyên ku kovar di nav salan de rûbirû maye nîşan dide û bi kurtasî behsa tevkariyên wê yên girîng ên bo qadê dike. Hevpeyvîn ne tenê dîroka kovarekê, lê herwiha pêşketina tevahiya qadeke zanistî ron dike ligel nexşkirina kêşeyên li pêş.
Abstract in Zazaki
Ronayîşê kovarêk, şekilnayîşê beşêk: Dr. Welat Zeydanliogluyî reyde roportaj
Nê roportajî de awanker û seredîtoro demgerg yê Kurdish Studiesî, Dr. Welat Zeydanlioglu, qalê hîkayeya ronayîşê kovare keno û ano vîr ke senî aver şîya ewro bîya kovara beşê kurdolojî ya sereke ke îngilizkî vejîyena. O têkilîya mabênê kovare û Torra Kurdolojî de îzah keno, zehmetîyê ke kovare serranê peyênan de dîyî, înan nawneno û beşdarîyanê nê warî yê tewr muhîman ser o vindeno. Roportaj tena tarîxê kovare rê roştî nêdano, la averşîyayîşê pêroyê beşê akademîkî kî ano çiman ver û eynî dem de zehmetîyê ke verê ma der ê, înan teswîr keno.
Abstract in Sorani
Available in PDF and print versions
Remittance and financial development in Africa: A multidimensional analysis
Authors: Ojeyinka Titus , Ajide Folorunsho
Published: May 2022

Previous studies on the nexus between remittances and financial system development are less informative due to their failure to investigate how remittance inflows affect different aspects of the financial sector in Africa. In the study, we re-investigate the impact of the remittances on the African financial system in twenty-seven (27) countries for 1980-2017 using the Augmented Mean Group (AGM) estimating technique. The results show that remittance does not have any significant impact on different dimensions of financial development in Africa. This finding is robust to alternative estimating techniques. This implies that remittance inflow is not a major driver of financial development in African countries. The outcomes of this study show that it is important to go beyond the use of conventional measures of financial development and focus more on multidimensional aspects of the sector such as access and efficiency of both the financial institutions and financial markets. It is also worth noting that remittance inflows in African regions are under-documented due to the high level of the shadow economy. The study suggests that the African government should formulate policies encouraging African migrants to pass through formal channels when remitting for the benefits of the financial sector and the economy in general. The policy should also encourage remittance savings and their utilisation in the African productive sector.
An Analysis of the Macroeconomic Determinants of Peruvian Remittances
Authors: Zarate-Hoyos German
Published: May 2022

This paper evaluates the impact of several macroeconomic variables on the Peruvian remittances flow, as well as the existence of cointegration between them, during the period 1992 – 2017. To do so, the United States was chosen as the host country for the Peruvian migrants and the paper used quarterly data, American and Peruvian variables and a vector of error correction (VEC). Among the main results, evidence of co-integrated variables was confirmed, a structural break was found, and the impact of some macroeconomic determinants corroborate the predominance of the self-interest effect over the altruist one in the Peruvian migrants’ behavior.
Remittances and trade balance: A new transfer problem
Authors: Regmi Ram Hari
Published: May 2022

Remittances are an important inflow of funds in many developing economies. These remittances relate to the classic 'transfer problem' and hence likely affect the exchange rate. In this paper, I find that remittances have a significant negative impact on trade balances and that the driving force is the exchange rate. Additionally, I find that remittance has a positive impact on trade openness, and hence decrease in the trade balance is because the growth rate of imports is higher than the growth rate of exports.
Effects of systemic isotretinoin treatment on retinal nerve fiber layer thickness and corneal endothelial cell density
Authors: UZLU Dilek , BAYKAL SELÇUK Leyla , TURK Adem , OĞUZER Şeyda Ece , OZBAY Ahmet Duhan , YASAR Yasin
Published: May 2022

Objective To investigate the effects of systemic isotretinoin therapy on retinal nerve fiber layer (RNFL) thickness and corneal endothelial cell density (ECD)

Methods Thirty-three patients completed the study. All patients were given an ophthalmic examination at baseline and after six months of isotretinoin therapy. All patients underwent a detailed eye examination including best corrected visual acuity, intraocular pressure, refractive errors, biomicroscopic anterior segment and fundus examination. In addition, Schirmer test without topical anesthesia, tear break up time, retinal nerve fiber thickness measurements with optical coherence tomography (OCT) and specular microscopy measurements were performed on all patients.

Results There were 23 female (69.7 %) and 10 male (30.3 %) patients. Post treatment RNFL values were

significantly lower than pretreatment values on both right and left eyes (P=0.048 and P
Colorectal Cancer Burden, Screening and Awareness
Authors: Islam Md Tanvirul , Kamal Pasha AKM Mustafa
Published: May 2022

Abstract not available
JAFMC Bangladesh. Vol 17, No 2 (December) 2021: 1-2
(Far) Outside the box: Genomic approach to acute porphyria
Authors: Thunell S
Published: May 2022

If I were living in Caucasus I would be writing fairy tales there Chekov, 1888 The question of the reasons for the extreme variation in morbidity among the gene carriers of acute porphyria and the great diversity of the precipitating factors are approached by the aid of a model of interacting genomic circuits. It is based on the current paradigm of the acute porphyric attack as a result of a toxic proximal overload of the enzyme-deficient heme-biosynthetic patway. Porphyrogenic influx of precursors is seen as a consequence of uncontrolled induction of its gate-keeping enzyme, ubiquitous 5-aminolevulinate synthase (ALAS1), due to attenuated post-translational control of the enzyme combined with activated gene transcription. Focus is directed on the genomic control of the master-regulator of ALAS1-transcription, the nuclear receptor pair constitutively active receptor (CAR) and pregnane xenobiotic receptor (PXR). On activation by their ligands, i.e. lipophilic drugs, solvents, alcohols, hormonal steroids and biocides, these DNA-binding proteins transform xenobiotic or steroid stimuli to coordinated activations of gene transcription-programs for ALAS1 and apo-cytochromes P450 (apo-CYPs), thus effecting the formation of xenobiotic-metabolizing cytochrome P450 enzymes. The potency of the CAR/PXR-transduction axis is enhanced by co-activators generated in at least four other genomic circuits, each triggered by different external and internal stimuli clinically experienced to be porphyrogenic, and each controlled by co-activating and co-repressing modulators. The expressions of the genes for CAR and PXR are thus augmented by binding glucocorticoid receptor (GR) activated by a steroid hormone, e.g, cortisol generated in fasting, infection or different forms of stress. The promotor regions of ALAS1 and apoCYPs contain binding sites for at least three co-activating transcription factors enhancing CAR/PXR transduction: i.e. the ligand-independent growth hormone (GH)-pulse controlled hepatocyte nuclear factor 4 (HNF4), the insulin-responsive forkhead box class O-(FOXO) protein pathway activated in stress and infection, and the proliferator-activated receptor gamma co-activator 1 alpha (PGC-1alpha) circuit responding to glucagon liberated in fasting. Many interactions and cross-talk take place within the tangle of genomic circuits that control ALAS1-transcription, which may explain the extreme inter- and intra-individual variability in morbidity in acute porphyria. Reasons for gender-differences are found in sex-dependent control of HPA- and GH-activity as well as in direct, or GR-mediated effects on CAR/PCR activation. Constitutional differences in individual porphyric morbidity may be discussed along lines of mutations or duplications of genes for co-activating or co-repressing nuclear proteins active at different levels within the circuits.
Hemochromatosis gene sequence deviations in German patients with porphyria cutanea tarda
Authors: Frank J , Poblete-Gutiérrez P , Weiskirchen R , Gressner O , Merk HF , Lammert F
Published: May 2022

Patients with porphyria cutanea tarda (PCT) reveal a susceptibility to reversible inactivation of hepatic uroporphyrinogen decarboxylase, which might be triggered by alcohol, hepatitis C virus infection, and iron overload. Inherited factors that may predispose to clinically overt PCT also include sequence deviations in the HFE gene that is mutated in classical hemochromatosis. Here, we studied the prevalence of both common and rare hemochromatosis gene variations in 51 PCT patients and 54 healthy controls of German origin. The frequency of the common HFE gene mutation C282Y was 15.7 % in PCT patients and 2.8 % in healthy control individuals (P < 0.001). By contrast, the frequencies of the common H63D mutation did not differ, and the allele frequencies of the less frequently observed sequence deviations as substitution S65C in the HFE gene and mutation Y250X in the TFR2 gene underlying hemochromatosis type 3 (HFE3) were < 0.02 both in PCT patients and controls. Our results comprise the first molecular studies of both common and rare hemochromatosis gene variants in German PCT patients, indicating a significant role of the C282Y mutation in the pathogenesis of PCT.
Impact of Rehabilitation Interventions on Walking Endurance in Children with Cerebral Palsy. A Systematic Literature Review
Authors: Kavaliauskaitė Ieva , Petrulytė Jovita , Budrienė Lina , Raistenskis Juozas
Published: May 2022

Background. Decreased walking endurance in children with CP results in impaired gait function and adversely affects participation. Appropriate rehabilitation interventions can significantly increase walking endurance and associated functional efficiency.

The aim. To evaluate the effectiveness of different rehabilitation interventions for walking endurance of children with CP by analyzing scientific research.

Methods. The selection of articles was performed in the “PubMed” database, according to the keywords and criteria identifying the study topic. The selection scheme was performed according to the PRISMA guidelines.

Results. 15 articles were included in the systematic review. Statistically significantly (p<0,05) higher walking endurance was found after: “Gait Trainer GT1” workout; muscle strength-power training; strength-endurance training + usual interventions (INT) and passive movement intervention, all compared to INT. Also, after: treadmill + INT (vs. walking + INT); treadmill with the “3DCaLT” robotic system (vs. treadmill); virtual reality with treadmill + INT (vs. treadmill + INT); whole-body vibration (vs. placebo).

Conclusions. In children with cerebral palsy, certain gait training, muscle strength training, and passive movement interventions increase walking endurance more effectively compared to non-combined usual interventions. When choosing from several gait training interventions, the effectiveness of walking endurance training depends on the specifics of the intervention. Also, walking endurance is effectively enhanced by whole-body vibration (compared to placebo) and a virtual reality component combined with gait training (compared to the same intervention without a virtual reality component).

Keywords: children, cerebral palsy, walking endurance, rehabilitation, systematic review.
Pendidikan Karakter dalam Membangun Kecerdasan Moral bagi Anak Usia Dini Perspektif Thomas Lickona
Authors: Susanti Salamah Eka
Published: May 2022

Padadasarnya pendidikan  berfungsi membentuk karakter yang baik, karena karakter yang baik merupakan modal awal bagi manusia untuk menjadi yang mampu mewujudkan kehidupan yang sejahtera. Menurut Thomas Lickona seorang pakar pendidikan karakter mengemukakan, bahwa konsep mengenai pendidikan karakter yang sering dipakai sebagai rujukannya yaitu diawali dengan knowing, filling, dan action. Nilai- nilai karakter yang digagas oleh Thomas Lickona diantaranya yaitu : Pertama, dengan kejujuran. Kedua, dengan adil. Ketiga, dengan tanggung jawab. Keempat, dengan berani. Kelima, dengan mau bekerja. Keenam, dengan disiplin. Selain itu Thomas Lickona juga mengemukakan, ada lima pendekatan dalam pendidikan karakter, yaitu sebagai berikut : (1). Pendekatan penanaman nilai (inculcation approach) , (2). Pendekatan perkembangan moral kognitif (cognitive moral development approach, (3). Pendekatan analisis nilai (values analysis approach), (4) pendekatan klarifikasi nilai (values clarification approach), (5). Pendekatan pembelajaran berbuat (action learning approach).
GOVERNMENTAL SUPPORT FOR SMALL AND MEDIUM-SIZED ENTERPRISES-NON-RAW EXPORTERS THROUGH THE ORGANIZATION OF A «SINGLE WINDOW FOR EXPORTERS»
Authors:   Plekhanov Russian University of Economics, Moscow, Russian Federation, POPENKOVA DARIA
Published: May 2022

The article considers a measure of governmental support for small and medium-sized enterprises-non-raw exporters, operating on marketplaces, and conducting active online trading through the Single Window for Export. The considered experience of foreign countries, where support has been provided for several decades, is taken as a benchmark for application in Russia. In Russia, discussions about supporting small and medium-sized enterprises-non-raw exporters have been going on for a long time, and certain actions have begun towards creating a Single Window, and training programs for sellers of marketplaces. However, against the background of Asian countries, where the share of e-commerce is historically higher than in Russia, and enterprises have much more experience in trading on marketplaces, Russia is still at the initial stage, trying to take the first steps in this direction. Considering the experience of countries with a developed e-commerce system will allow drawing lessons and conclusions, taking some measures as a basis, and shift them to Russian realities. This article is part of a series of articles devoted to small and medium-sized enterprises operating on marketplaces and considers the issue of governmental support. At that, the very marketplaces play a great role in assisting small businesses. Only in the case of public-private partnership is it possible to achieve the best effect in providing governmental support.
Note on the Odd Perfect Numbers
Authors: Vega Frank
Published: May 2022

The Riemann Hypothesis is a conjecture that the Riemann zeta function has its zeros only at the negative even integers and complex numbers with real part $\frac{1}{2}$. In 2011, Sol{\'e} and and Planat stated that the Riemann Hypothesis is true if and only if $\frac{\pi^2}{6} \times \prod_{q\leq q_{n}}\left(1+\frac{1}{q} \right) >e^{\gamma}\times \log\theta(q_{n})$ is satisfied for all primes $q_{n}> 3$, where $\theta(x)$ is the Chebyshev function, $\gamma\approx 0.57721$ is the Euler-Mascheroni constant and $\log$ is the natural logarithm. We state the conjecture that $\frac{\pi^2}{6.4} \times \prod_{q \leq q_{n}} \left(1 + \frac{1}{q} \right) > e^{\gamma} \times \log\theta(q_{n})$ is satisfied for infinitely many prime numbers $q_{n}> 10^{8}$. Under the assumption of this conjecture and the Riemann Hypothesis, we prove that there is not any odd perfect number at all.
Determinantes das exportações brasileiras de petróleo: uma análise por modelos ARDL no período de 2000 a 2019
Authors: Sousa Rafael Moraes de , Veríssimo Michele Polline
Published: May 2022

É possível notar um aumento expressivo da participação dos produtos primários na pauta exportadora brasileira ao longo dos anos 2000, com destaque para o petróleo bruto, que se torna o segundo produto mais exportado em 2019. Neste contexto, este artigo investiga os principais determinantes das exportações brasileiras de petróleo bruto, utilizando modelos ARDL com dados de 2000 a 2019, a fim de inferir a contribuição do setor para a sustentação da hipótese de reprimarização da economia no longo prazo. Os resultados obtidos apontam que, no caso brasileiro, o setor beneficia-se, sobretudo, de elevações da renda (demanda) e dos preços externos no curto prazo. No longo prazo, o efeito positivo da renda externa permanece, somado à melhoria do quadro institucional e ao aumento da capacidade produtiva dada pela descoberta das reservas do Pré-sal.
Os Impactos da financeirização sobre o circuito finance-investimento-poupança-funding
Authors: Santos Diogo , Da Cunha Resende Marco Flávio
Published: May 2022

O objetivo deste trabalho é avaliar os efeitos da financeirização do capitalismo contemporâneo sobre o circuito pós-Keynesiano finance-investimento­-poupança­-funding (FISF) a partir de uma sistematização das principais evidências trazidas pela literatura sobre financeirização. Para isso, é realizada uma apresentação do circuito FISF e em seguida se investiga os impactos da financeirização sobre cada um de seus componentes. Conclui-se que a despeito de alguns efeitos positivos, todos os elementos do circuito são impactados negativamente. Porém, é no componente funding que se concentram os maiores efeitos da financeirização sobre o circuito. Esses impactos possuem consequências sobre a estabilidade financeira da economia, o crescimento econômico e o papel do Estado.
PENGUKURAN KINERJA SUPPLY CHAIN MANAGEMENT DENGAN MENGGUNAKAN METODE SUPPLY CHAIN OPERATION REFERANCE (SCOR 12.0) BERBASIS ANALYTICAL HIERARCHY PROCESS (AHP) DAN OBJECTIVE MATRIX (OMAX)
Authors: Hidayat Ahmad Nurul , Dahda Said Salim
Published: May 2022

Supply chain management is a matter that is very meaningful in supporting the sustainability of a company. The company's strategy must be carried out well, this is very dependent on the company's ability, especially on the supply chain capability. Small and medium enterprises should be able to implement and improve their business supply chains well to have sustainability. Small and medium enterprises have a very limited structure where the level of application of the supply chain form is simple but complex. Measurement of supply chain capabilities is very helpful in carrying out its business processes. The purpose of this research is to ensure the value of the ability and achievement of each company's indicators. In measuring performance, assisted by the Supply Chain Operation Process (SCOR) type 12.0, Analytical Hierarchy Process (AHP) is used to develop the performance appraisal process in decision analysis and the Objective Matrix (OMAX) method for the assessment system. With KPI (Key Performance Indicator) that has been verified, there are 31 matrix indicators. Based on the results of the study, it was proven that the supply chain performance value in the small and medium industries got a value of 7.44 as the productivity index value, which was included in the yellow category. By carrying out improvements to indicators that have a small value, it is expected to help improve supply chain performance in the company
Progress of Nanomaterials in Photodynamic Therapy Against Tumor
Authors: Chen Lei , Huang Jiahui , Li Xiaotong , Huang Miaoting , Zeng Shaoting , Zheng Jiayi , Peng Shuyi , Li Shiying
Published: May 2022

Photodynamic therapy (PDT) is an advanced therapeutic strategy with light-triggered, minimally invasive, high spatiotemporal selective and low systemic toxicity properties, which has been widely used in the clinical treatment of many solid tumors in recent years. Any strategies that improve the three elements of PDT (light, oxygen, and photosensitizers) can improve the efficacy of PDT. However, traditional PDT is confronted some challenges of poor solubility of photosensitizers and tumor suppressive microenvironment. To overcome the related obstacles of PDT, various strategies have been investigated in terms of improving photosensitizers (PSs) delivery, penetration of excitation light sources, and hypoxic tumor microenvironment. In addition, compared with a single treatment mode, the synergistic treatment of multiple treatment modalities such as photothermal therapy, chemotherapy, and radiation therapy can improve the efficacy of PDT. This review summarizes recent advances in nanomaterials, including metal nanoparticles, liposomes, hydrogels and polymers, to enhance the efficiency of PDT against malignant tumor.
Pyroptosis-Related Signature and Tumor Microenvironment Infiltration Characterization in Head and Neck Squamous Cell Carcinoma
Authors: Wu Zeng-Hong , Wu Bian , Li Cheng , Zhang You-Jing , Zhou Tao
Published: May 2022

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most widespread and deadly cancer. Until now, very few studies have systematically evaluated the role of pyroptosis-related genes (PRGs) and lncRNAs in HNSCC patients.

Methods: We integrated the genomic data to comprehensively assess the role of pyroptosis with the tumor microenvironment cell-infiltrating characteristics in HNSCC. In addition, we also constructed a set of the scoring system to calculate the pyroptosis dysfunction in each patient.

Results: The analysis of the CNV alteration frequency displayed that CNV changes were common in 33 PRGs, and the frequency of copy number gain and loss was similar. CASP8 demonstrated the highest mutation frequency. Considering the individual heterogeneity, a scoring system to quantify the pyroptosis pattern in each patient was constructed based on these phenotypic-related genes, which we named as the PyroptosisScore. The results indicated that the low PyroptosisScore group experienced increased extensive TMB than the high group, with the most significant mutated genes being TP53 and TTN. Finally, we tried to find some useful pyroptosis-related lncRNAs, and 14 differentially expressed lncRNAs were selected as independent prognosis factors of HNSCC patients based on the multivariate Cox analysis.

Conclusion: This work suggests the pyroptosis features and the potential mechanisms of the tumor microenvironment. The exploration may assist in identifying novel biomarkers and help patients predict prognosis, clinical diagnosis, and management.
#socialiseresponsibly. Analyzing the Rhetorical Structure of Heineken TV Commercials During the Pandemic
Authors: Wildfeuer Janina , Coffie Joseph Adika
Published: May 2022

This work analyzes the efforts by the company Heineken to address in their marketing campaigns the social responsibility and wellbeing of their customers during the pandemic. By particularly looking at the audio-visual design strategies used in 15 TV commercials produced and published during the years 2020–2022, a multimodal analysis of the filmic montage structures examines how the company establishes a coherent process of core marketing and convinces recipients to socialize responsibly under pandemic conditions. The analysis follows the current trend in empirical multimodality research to pursue analyses of digital corpora with the theories and methods developed in the field. Particularly, it uses an ELAN annotation scheme for the description of specific camera techniques (such as camera distance and perspective) as well as the discourse relations holding between the shots and segments identified in the commercials. The findings show that the company mainly uses one specific type of rhetorical structure, the narrative commentary, that puts the social actors shown in many different scenes into the foreground and therefore strongly focuses on the company's strategy of positive social behavior.
The Scientific Rationale for the Introduction of Renalase in the Concept of Cardiac Fibrosis
Authors: Stojanovic Dijana , Mitic Valentina , Stojanovic Miodrag , Milenkovic Jelena , Ignjatovic Aleksandra , Milojkovic Maja
Published: May 2022

Cardiac fibrosis represents a redundant accumulation of extracellular matrix proteins, resulting from a cascade of pathophysiological events involved in an ineffective healing response, that eventually leads to heart failure. The pathophysiology of cardiac fibrosis involves various cellular effectors (neutrophils, macrophages, cardiomyocytes, fibroblasts), up-regulation of profibrotic mediators (cytokines, chemokines, and growth factors), and processes where epithelial and endothelial cells undergo mesenchymal transition. Activated fibroblasts and myofibroblasts are the central cellular effectors in cardiac fibrosis, serving as the main source of matrix proteins. The most effective anti-fibrotic strategy will have to incorporate the specific targeting of the diverse cells, pathways, and their cross-talk in the pathogenesis of cardiac fibroproliferation. Additionally, renalase, a novel protein secreted by the kidneys, is identified. Evidence demonstrates its cytoprotective properties, establishing it as a survival element in various organ injuries (heart, kidney, liver, intestines), and as a significant anti-fibrotic factor, owing to its, in vitro and in vivo demonstrated pleiotropy to alleviate inflammation, oxidative stress, apoptosis, necrosis, and fibrotic responses. Effective anti-fibrotic therapy may seek to exploit renalase’s compound effects such as: lessening of the inflammatory cell infiltrate (neutrophils and macrophages), and macrophage polarization (M1 to M2), a decrease in the proinflammatory cytokines/chemokines/reactive species/growth factor release (TNF-α, IL-6, MCP-1, MIP-2, ROS, TGF-β1), an increase in anti-apoptotic factors (Bcl2), and prevention of caspase activation, inflammasome silencing, sirtuins (1 and 3) activation, and mitochondrial protection, suppression of epithelial to mesenchymal transition, a decrease in the pro-fibrotic markers expression (’α-SMA, collagen I, and III, TIMP-1, and fibronectin), and interference with MAPKs signaling network, most likely as a coordinator of pro-fibrotic signals. This review provides the scientific rationale for renalase’s scrutiny regarding cardiac fibrosis, and there is great anticipation that these newly identified pathways are set to progress one step further. Although substantial progress has been made, indicating renalase’s therapeutic promise, more profound experimental work is required to resolve the accurate underlying mechanisms of renalase, concerning cardiac fibrosis, before any potential translation to clinical investigation.
Inter-ankle Systolic Blood Pressure Difference Is a Marker of Increased Fasting Blood-Glucose in Asian Pregnant Women
Authors: Zhang Ruo , Viswambharan Hema , Cheng Chew Weng , Garstka Malgorzata Anna , Kain Kirti
Published: May 2022

Objective

This cross-sectional study aimed to determine the relationship between clinical blood pressures and blood pressures measured using Doppler with blood glucose in pregnancy by ethnicity.

Methods

We recruited 179 (52% White European, 48% Asian) pregnant women at 24-28 weeks of gestation who underwent a glucose tolerance test in an antenatal clinic in Bradford Royal Infirmary, the UK, from 2012 to 2013. Systolic blood pressures in the arm (left and right brachial) and ankle [left and right posterior tibial (PT) and dorsalis pedalis (DP)] blood pressures were measured using a Doppler probe. The inter-arm (brachial) and inter-ankle (PT and DP) systolic blood pressure differences were obtained. A multivariate linear regression model adjusted for age, body mass index, and diabetes risk was used to assess the relationship between blood pressures and blood glucose.

Results

Asian pregnant women had higher blood glucose but lower ankle blood pressures than White Europeans. In White Europeans, brachial blood pressures and clinical blood pressures were positively associated with fasting blood glucose (FBG), but brachial blood pressures did not perform better as an indicator of FBG than clinical blood pressures. In Asians, increased inter-ankle blood pressure difference was associated with increased FBG. For each 10 mmHg increase in the inter-ankle blood pressure difference, FBG increased by 0.12 mmol/L (Beta=0.12, 95%CI: 0.01-0.23).

Conclusion

The relationship between blood pressures with blood glucose differed by ethnicity. In Asians, inter-ankle systolic blood pressure difference was positively associated with blood glucose. This is first ever report on ankle blood pressures with blood glucose in pregnancy which suggests future potential as a non-invasive gestational diabetes risk screening tool.
Vitamin D Supplementation Improves Mitochondrial Function and Reduces Inflammation in Placentae of Obese Women
Authors: Phillips Elysse A. , Hendricks Nora , Bucher Matthew , Maloyan Alina
Published: May 2022

Background

About 30% of women entering pregnancy in the US are obese. We have previously reported mitochondrial dysregulation and increased inflammation in the placentae of obese women. Vitamin D (VitD) is a major player in calcium uptake and was shown to modulate mitochondrial respiration and the immune/inflammation system. Studies show decreased VitD levels in obese individuals; however, the effect of maternal obesity on VitD metabolism and its association with placental function remains understudied.

Methods

Maternal and cord blood plasma and placental samples were collected upon C-section from normal-weight (NW, body mass index [BMI]<25) and obese (OB, BMI>30) women with uncomplicated pregnancies at term. We measured 25(OH)D3 (calcidiol) levels in maternal and cord blood plasma using ELISA. We assessed the expression of CYP27B1, an activator of calcidiol, and Vitamin D receptor (VDR) in placentae from NW and OB, and women with gestational diabetes and preeclampsia. In addition, we examined the effects of VitD supplementation on mitochondrial function and inflammation in trophoblasts from NW and OB, using the Seahorse Bioanalyzer and Western blot, respectively.

Results

Vitamin D levels in blood from OB but not NW women and in cord blood from babies born to NW and OB women showed a significant inverse correlation with maternal pre-pregnancy BMI (r=-0.50, p<0.1 and r=-0.55, p=0.004 respectively). Cord plasma VitD levels showed a positive correlation with placental efficiency, i.e., the ratio between fetal and placental weight, as well as with maternal blood VitD levels (r=0.69 and 0.83 respectively, p<0.00). While we found no changes in CYP27B1 in OB vs. NW women, VDR expression were decreased by 50% (p<0.03) independent of fetal sex. No changes in VDR expression relative to BMI-matched controls were observed in the placentae of women with gestational diabetes or preeclampsia. Cytotrophoblasts isolated from placentae of OB women showed a dose-dependent increase in VDR expression after 24-hour treatment with calcitriol (10 nM and 100 nM), an active form of VitD. Trophoblasts isolated from OB women and treated with calcitriol improved mitochondrial respiration (p<0.05). We also found a two-fold increase in expression of the NLRP3 inflammasome and the pro-inflammatory cytokine IL-18 in trophoblasts isolated from placentae of OB women (p<0.05), with IL-18 expression being reversed by calcitriol treatment (100 nM).

Conclusions

We show that VitD deficiency is at least partially responsible for mitochondrial dysfunction and increased inflammation in the placentae of obese women. Vitamin D supplementation could be beneficial in improving placental dysfunction seen in obese women.
AMH Regulation by Steroids in the Mammalian Testis: Underlying Mechanisms and Clinical Implications
Authors: Edelsztein Nadia Y. , Valeri Clara , Lovaisa María M. , Schteingart Helena F. , Rey Rodolfo A.
Published: May 2022

Anti-Müllerian hormone (AMH) is a distinctive biomarker of the immature Sertoli cell. AMH expression, triggered by specific transcription factors upon fetal Sertoli cells differentiation independently of gonadotropins or sex steroids, drives Müllerian duct regression in the male, preventing the development of the uterus and Fallopian tubes. AMH continues to be highly expressed by Sertoli until the onset of puberty, when it is downregulated to low adult levels. FSH increases testicular AMH output by promoting immature Sertoli cell proliferation and individual cell expression. AMH secretion also showcases a differential regulation exerted by intratesticular levels of androgens and estrogens. In the fetus and the newborn, Sertoli cells do not express the androgen receptor, and the high androgen concentrations do not affect AMH expression. Conversely, estrogens can stimulate AMH production because estrogen receptors are present in Sertoli cells and aromatase is stimulated by FSH. During childhood, sex steroids levels are very low and do not play a physiological role on AMH production. However, hyperestrogenic states upregulate AMH expression. During puberty, testosterone inhibition of AMH expression overrides stimulation by estrogens and FSH. The direct effects of sex steroids on AMH transcription are mediated by androgen receptor and estrogen receptor α action on AMH promoter sequences. A modest estrogen action is also mediated by the membrane G-coupled estrogen receptor GPER. The understanding of these complex regulatory mechanisms helps in the interpretation of serum AMH levels found in physiological or pathological conditions, which underscores the importance of serum AMH as a biomarker of intratesticular steroid concentrations.
Case Report: Phenotype-Driven Diagnosis of Atypical Dravet-Like Syndrome Caused by a Novel Splicing Variant in the SCN2A Gene
Authors: Sharkov Artem , Sparber Peter , Stepanova Anna , Pyankov Denis , Korostelev Sergei , Skoblov Mikhail
Published: May 2022

Febrile-associated epileptic encephalopathy is a large genetically heterogeneous group that is associated with pathogenic variants in SCN1A, PCDH19, SCN2A, SCN8A, and other genes. The disease onset ranges from neonatal or early-onset epileptic encephalopathy to late-onset epilepsy after 18 months. Some etiology-specific epileptic encephalopathies have target therapy which can serve as a clue for the correct genetic diagnosis. We present genetic, clinical, electroencephalographic, and behavioral features of a 4-year-old girl with epileptic encephalopathy related to a de novo intronic variant in the SCN2A gene. Initial NGS analysis revealed a frameshift variant in the KDM6A gene and a previously reported missense variant in SCN1A. Due to lack of typical clinical signs of Kabuki syndrome, we performed X-chromosome inactivation that revealed nearly complete skewed inactivation. Segregation analysis showed that the SCN1A variant was inherited from a healthy father. The proband had resistance to multiple antiseizure medications but responded well to sodium channel inhibitor Carbamazepine. Reanalysis of NGS data by a neurogeneticist revealed a previously uncharacterized heterozygous variant c.1035–7A>G in the SCN2A gene. Minigene assay showed that the c.1035–7A>G variant activates a cryptic intronic acceptor site which leads to 6-nucleotide extension of exon 9 (NP_066287.2:p.(Gly345_Gln346insTyrSer). SCN2A encephalopathy is a recognizable severe phenotype. Its electro-clinical and treatment response features can serve as a hallmark. In such a patient, reanalysis of genetic data is strongly recommended in case of negative or conflicting results of DNA analysis.
A Ubiquitin-Proteasome Gene Signature for Predicting Prognosis in Patients With Lung Adenocarcinoma
Authors: Tang Yunliang , Guo Yinhong
Published: May 2022

Background: Dysregulation of the ubiquitin-proteasome system (UPS) can lead to instability in the cell cycle and may act as a crucial factor in both tumorigenesis and tumor progression. However, there is no established prognostic signature based on UPS genes (UPSGs) for lung adenocarcinoma (LUAD) despite their value in other cancers.

Methods: We retrospectively evaluated a total of 703 LUAD patients through multivariate Cox and Lasso regression analyses from two datasets, the Cancer Genome Atlas (n = 477) and GSE31210 (n = 226). An independent dataset (GSE50081) containing 128 LUAD samples were used for validation.

Results: An eight-UPSG signature, including ARIH2, FBXO9, KRT8, MYLIP, PSMD2, RNF180, TRIM28, and UBE2V2, was established. Kaplan-Meier survival analysis and time-receiver operating characteristic curves for the training and validation datasets revealed that this risk signature presented with good performance in predicting overall and relapsed-free survival. Based on the signature and its associated clinical features, a nomogram and corresponding web-based calculator for predicting survival were established. Calibration plot and decision curve analyses showed that this model was clinically useful for both the training and validation datasets. Finally, a web-based calculator (https://ostool.shinyapps.io/lungcancer) was built to facilitate convenient clinical application of the signature.

Conclusion: An UPSG based model was developed and validated in this study, which may be useful as a novel prognostic predictor for LUAD.
Case Report: Rare Homozygous RNASEH1 Mutations Associated With Adult-Onset Mitochondrial Encephalomyopathy and Multiple Mitochondrial DNA Deletions
Authors: Manini Arianna , Caporali Leonardo , Meneri Megi , Zanotti Simona , Piga Daniela , Arena Ignazio Giuseppe , Corti Stefania , Toscano Antonio , Comi Giacomo Pietro , Musumeci Olimpia , Carelli Valerio , Ronchi Dario
Published: May 2022

Mitochondrial DNA (mtDNA) maintenance disorders embrace a broad range of clinical syndromes distinguished by the evidence of mtDNA depletion and/or deletions in affected tissues. Among the nuclear genes associated with mtDNA maintenance disorders, RNASEH1 mutations produce a homogeneous phenotype, with progressive external ophthalmoplegia (PEO), ptosis, limb weakness, cerebellar ataxia, and dysphagia. The encoded enzyme, ribonuclease H1, is involved in mtDNA replication, whose impairment leads to an increase in replication intermediates resulting from mtDNA replication slowdown. Here, we describe two unrelated Italian probands (Patient 1 and Patient 2) affected by chronic PEO, ptosis, and muscle weakness. Cerebellar features and severe dysphagia requiring enteral feeding were observed in one patient. In both cases, muscle biopsy revealed diffuse mitochondrial abnormalities and multiple mtDNA deletions. A targeted next-generation sequencing analysis revealed the homozygous RNASEH1 mutations c.129-3C>G and c.424G>A in patients 1 and 2, respectively. The c.129-3C>G substitution has never been described as disease-related and resulted in the loss of exon 2 in Patient 1 muscle RNASEH1 transcript. Overall, we recommend implementing the use of high-throughput sequencing approaches in the clinical setting to reach genetic diagnosis in case of suspected presentations with impaired mtDNA homeostasis.
MicroRNA-182-5p Attenuates Asthmatic Airway Inflammation by Targeting NOX4
Authors: Wang Zhiguang , Song Yilan , Jiang Jingzhi , Piao Yihua , Li Li , Bai Qiaoyun , Xu Chang , Liu Hanye , Li Liangchang , Piao Hongmei , Yan Guanghai
Published: May 2022

Bronchial asthma is characterized by chronic airway inflammation, airway hyperresponsiveness, and airway remodeling. MicroRNA (miRNA) has recently been implicated in the pathogenesis of asthma. However, the mechanisms of different miRNAs in asthma are complicated, and the mechanism of miRNA-182-5p in asthma is still unclear. Here, we aim to explore the mechanism of miRNA182-5p in asthma-related airway inflammation. Ovalbumin (OVA)-induced asthma model was established. MiRNA Microarray Analysis was performed to analyze the differentially expressed miRNAs in the asthma model. We found that the expression of miRNA-182-5p was significantly decreased in OVA-induced asthma. In vitro, IL-13 stimulation of BEAS-2B cells resulted in a significant up-regulation of NOX4 (nicotinamide adenine dinucleotide phosphate oxidase 4), accompanied by mitochondrial damage-induced apoptosis, NLRP3 (NOD-like receptor family pyrin domain-containing 3)/IL-1β activation, and reduced miRNA-182-5p. In contrast, overexpression of miRNA-182-5p significantly inhibited epithelial cell apoptosis and NLRP3/IL-1β activation. In addition, we found that miRNA-182-5p could bind to the 3’ untranscripted region of NOX4 mRNA and inhibit epithelial cell inflammation by reducing oxidative stress and mitochondrial damage. In vivo, miRNA-182-5p agomir treatment significantly reduced the percentage of eosinophils in bronchoalveolar lavage fluid, and down-regulated Th2 inflammatory factors, including IL-4, IL-5, and OVA induced IL-13. Meanwhile, miRNA-182-5p agomir reduced the peribronchial inflammatory cell infiltration, goblet cell proliferation and collagen deposition. In summary, targeting miRNA-182-5p may provide a new strategy for the treatment of asthma.
The Beneficial Role of Probiotic Lactobacillus in Respiratory Diseases
Authors: Du Tingfeng , Lei Aihua , Zhang Naiyu , Zhu Cuiming
Published: May 2022

Respiratory diseases cause a high incidence and mortality worldwide. As a natural immunobiotic, Lactobacillus has excellent immunomodulatory ability. Administration of some Lactobacillus species can alleviate the symptoms of respiratory diseases such as respiratory tract infections, asthma, lung cancer and cystic fibrosis in animal studies and clinical trials. The beneficial effect of Lactobacillus on the respiratory tract is strain dependent. Moreover, the efficacy of Lactobacillus may be affected by many factors, such as bacteria dose, timing and host background. Here, we summarized the beneficial effect of administered Lactobacillus on common respiratory diseases with a focus on the mechanism and safety of Lactobacillus in regulating respiratory immunity.
Case Report: Peripheral Ulcerative Keratitis in Systemic Solid Tumour Malignancies
Authors: Foo Valencia Hui Xian , Mehta Jodhbir , Chan Anita Sook Yee , Ong Hon Shing
Published: May 2022

Purpose

To describe a case series of peripheral ulcerative keratitis (PUK) as a paraneoplastic condition in three patients with known underlying systemic solid tumor malignancies.

Observations

Three patients with different systemic malignancies (1 recurrent breast cancer, 1 metastatic thyroid cancer, and 1 metastatic gastric adenocarcinoma) were identified to have PUK with significant corneal stromal melt. Autoimmune and infective work up for other etiologies were all negative. They all responded well to topical steroids and intravenous methylprednisolone. One patient had recurrences of her PUK and required repeated amniotic grafts and tectonic keratoplasties before her corneal condition stabilized.

Conclusions and Importance

PUK can be a rare manifestation of systemic solid tumor malignancies. Although PUK may not be an indicator of progression of the underlying malignancy, it can be sight-threatening. This case series highlights the necessity for clinicians to refer patients with systemic malignancies presenting with inflamed eyes for an early ophthalmological review. This facilitates the detection of this blinding disease, allowing for early therapeutic interventions and potentially better visual outcomes for these patients.