bluuebunny/crossref_metadata_2025 huggingface dataset:
A Case of Subacute Combined Degeneration as a Manifestation of Pernicious Anaemia
Authors: Arriaga Rocha Marta , Trovão Bastos Martim , Mauríco Joana , Heitor Susana
Published: December 2021

Vitamin B12 deficiency affects multiple systems, including the central and peripheral nervous systems, producing a vast spectrum of neurological symptoms. It is particularly important due to its insidious presentation and because it can evolve to spastic paraplegia with permanent sequelae. The authors describe a case of a woman with asthenia, bilateral lower limb weakness, urinary retention, and faecal incontinence, with no structural cause on imaging studies. Blood tests showed anaemia (haemoglobin: 6.8 g/dL) and vitamin B12 deficiency (<100 pg/mL). After upper digestive endoscopy compatible with chronic atrophic gastritis and positive for anti-intrinsic factor antibodies was obtained, the diagnosis of subacute combined degeneration due to vitamin B12 deficiency in the context of pernicious anaemia was admitted. Although this entity is a rare cause of myelopathy, it is a frequent manifestation of vitamin B12 deficiency. Clinical suspicion is fundamental since the reversibility of the neurological lesion is dependent on early treatment.
Breast Lesion Characterisation with Diffusion Weighted Imaging Versus Dynamic Contrast Enhanced-MRI: A Prospective Observational Study in a Tertiary Care Hospital
Authors: Singh Amandeep , Purewal Jasmin , Gupta Kamlesh , Singh Gauravdeep
Published: December 2021

Purpose: Dynamic contrast-enhanced (DCE)-MRI has a promising role in breast cancer detection and lesion characterisation. Diffusion-weighted imaging (DWI) acts as an adjunct in the differentiation between benign and malignant lesions. The purpose of the study was to evaluate the efficacy of DCE-MRI and DWI in differentiating benign and malignant lesions.

Methods: In a prospective study conducted between March 2019 and February 2020, 60 patients with breast lesions underwent DWI combined with DCE-MRI of the breast. The time–intensity curves were plotted. Lesions were classified according to the latest American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS; 5th edition). The results were compared with the histopathological diagnosis. The sensitivity and specificity of DWI, DCE-MRI, and combined DWI and DCE-MRI were calculated for detection of benign and malignant breast lesions.

Results: Sixty patients underwent breast MRI in which 78 lesions were detected, out of which 28 were benign and 50 were malignant. Quantitative apparent diffusion coefficient measurement revealed 96% sensitivity and 82% specificity, with a positive predictive value of 92% and negative predictive value of 96%, for differentiating benign from malignant lesions. DCE-MRI findings showed 96% sensitivity and 78.5% specificity. The sensitivity of combined DWI and DCE-MRI was 98% and specificity was 86%, which was higher than DWI and DCE-MRI alone.

Conclusion: Multiparametric MRI of the breast has very high sensitivity for detecting and characterising breast lesions as benign or malignant lesions. DWI had higher specificity than DCE-MRI, and the combined use of DWI and DCE-MRI had greater efficacy than DWI and DCE-MRI alone.
John James Audubon’s prospectus forThe birds of America
Authors: Logan P. B. , Sidor M. A.
Published: December 2021

The prospectus for The birds of America, which was used by John James Audubon as a marketing tool while canvassing for potential subscribers, went through a series of editions between 1827 and 1838. From a single folded sheet describing the general scope of the work and its price, the prospectus grew to 16 pages that incorporated a separate title-page, the names of subscribers, favourable reviews, and a list of the individual prints that had been published. As the project came to a close, Audubon encapsulated the salient details in advertisements printed in publications in England and America. Six editions, based on 16 extant copies, were identified by W. H. Fries in 1973. Since that time, additional information has become available about the various editions, including ones of which Fries was not aware. A summary and reclassification of the editions is appropriate to assist in better understanding the history and rarity of this publication.
On Secondary Grammaticalization: The Case of hatta in Rural Jordanian Arabic
Authors: Jaradat Abdulazeez
Published: December 2021

Secondary grammaticalization is viewed as a continuation to a grammaticalization path (Traugott 2002) or an independent process that does not necessarily imply the occurrence of a precedent primary grammaticalization (Givón 1991). This paper provides a case from vernacular Arabic supporting the second view, namely, the secondary grammaticalization of the functional hatta (its evolution into a proclitic) in Rural Jordanian Arabic. Evidence supporting this view is the selectivity of secondary grammaticalization, which can be summarized as follows: if the source grammatical item has more than one type (i.e., function), some of these types may not undergo secondary grammaticalization. This implies that secondary grammaticalization may not be a late stage completing a grammaticalization path. It can be an independent process that has its own peculiarities and constraints. The constraint, which is the source of selectivity of secondary grammaticalization in this paper, is linked to prosodic prominence: if a grammatical item is typically prominent prosodically in daily conversations, it resists secondary grammaticalization. This finding should also contribute to the previously reported constraints on secondary grammaticalization. In addition to selectivity, it is reported in this paper that the lexical source of the grammatical hatta does not seem necessary to its secondary grammaticalization..
The Translation of Parallelism in Arabic Political Speeches between Loss and Compensation: A Comparative Study
Authors: Fadi Shamaileh Sana
Published: December 2021

Political discourse is characterized by stylistic and rhetorical features that distinguish it from other text genres. When a rhetorical feature such as parallelism is used frequently in Arabic political speeches, it becomes significant to highlight the fact that this recurrence of structure is deliberate. According to Islam and Cahyani (2020: 273):
(T)he deliberate use of a word or phrase more than once in a sentence or a text to create a sense of pattern or form or to emphasize certain elements in the mind of the reader or listener (…) can be utilized (as) a major rhetorical strategy for producing emphasis, clarity, amplification, or emotional effect.
The objective of this study is to highlight the loss and the compensation of parallelism when translated from Arabic into English in political speeches at bottom-up level: word, sentence and chunk levels. This study shows that parallelism is used very frequently in Arabic political speeches and it is very popular among Arab political speakers as a rhetorical device to achieve persuasion, assertion and emotional effect on its audience.
.
Stress Misassignment in the Pronunciation of English by Arabic-speaking Learners: Erratic Practice or Crosslinguistic Influence?
Authors: A. Sa'di Rami
Published: December 2021

The role of L1 interference in English stress assignment produced by Arabic-speaking EFL learners has received little research attention. This study aims to investigate whether faulty stress assignment by Arab learners is arbitrary or systematic. It also attempts to discover a linkage, if any, between Arabic phonotactic rules of stress placement and stress misplacement in English by Saudi learners. 120 learners from Prince Sattam bin Abdulaziz University were randomly chosen from 3 different levels of English proficiency (lower-intermediate, upper-intermediate, advanced); they were asked to pronounce 72 stimulus words that covered all morpho-syllabic word structures that the learners often mispronounced. The recordings were analysed using WASP spectrogram software and also by two independent raters. Results strongly indicated that crosslinguistic influence may have caused the learners to consistently a) place the stress on a specific syllable in a word even when this word has multiple stress assignments with a difference in meaning, b) stress the second item in a compound noun instead of the first, c) place the stress on the penultimate syllable of most polysyllabic words, d) place the stress on the second syllable of contracted negative auxiliary verbs , and e) misplace stress irrespective of their level of English proficiency..
Rupert Brooke’s “The Soldier” Revisited: A New Perspective
Authors: T. Yousef Nisreen
Published: December 2021

Though Rupert Brooke’s “The Soldier” has often been interpreted, categorized or dismissed as a poem on idealized patriotism, its underlying nationalistic and colonialist/imperialist dimensions have not been duly treated alongside its patriotic dimension. Since the 1980s, there has been a resurgence of interest in such interrelated themes as patriotism, nationalism, and postcolonialism due to the engagement of some political, philosophical, and literary theorists with a wide range of conceptual and moral debates. The purpose of this paper is to re-examine Brooke’s poem in greater detail and, consequently, to update the previous research on this poem in the light of these debates. The main thesis of the paper is that Brook’s “The Soldier” is a multifaceted poem which has a variety of different features which can be interpreted on various levels, namely patriotism, nationalism, and colonialism/imperialism..
ТРАДИЦИИ СТРАННИЧЕСТВА И ХРАМОПОПЕЧЕНИЕ: НА МАТЕРИАЛАХ ВОЛОГОДСКОЙ ГУБЕРНИИ ВТОРОЙ ПОЛОВИНЫ XIX – НАЧАЛА XX ВЕКА
Authors: Шушвал Наталья Александровна
Published: December 2021

В статье на архивных и этнографических материалах Вологодской губ. рассказывается о месте и роли странничества в деле храмопопечения. Само храмопопечение в крестьянском сообществе представляло собой заботу об устройстве храма – его внешнем и внутреннем благолепии, а также отношение к нему, бытующее в крестьянской среде во второй половине XIX – начале XX в., и все виды и формы коммуникаций, вызванные этим отношением. Сбор доброхотных подаяний для нужд храма являлся частью индивидуальных форм храмопопечения и органичной частью странничества. В статье прослеживается, как происходила организация сборов на храм внутри приходского сообщества, какую роль в ней исполняли священнослужители, какими качествами обладали сами сборщики и что являлось мотивами для участия в данной практике храмопопечения. Сборщики на храм иногда собирали средства без разрешения епархиального начальства, выпадали из церковной нормативности, но при этом полностью соответствовали пониманию крестьянами истинного благочестия. Несмотря на стремление церкви регулировать данный вид попечения, оно было ярким проявлением крестьянской религиозности. В статье можно увидеть, что странничество в крестьянской среде было бы невозможно без таких явлений крестьянской жизни, как странноприимство, идеи милосердия и представления о храме как о сакральном центре крестьянской общины.
The article on the archival and ethnographic materials of the Vologda province tells about the place and the role of wandering in the matter of church care. The care of the church itself in the peasant community was a concern for the structure of the church – its external and internal splendor, as well as the attitude towards it that existed in the peasant environment in the second half of the 19th – early 20th centuries and all types and forms of communication caused by this attitude. Collecting voluntary alms for the needs of the temple was part of individual forms of church care and an organic part of wandering. The article notes how the church fund-raising had organized within the parish community, what role the clergy played in it, what qualities the collectors themselves possessed, and what were the motives for participating in this practice of temple care. Canvassers sometimes raised funds for the church without the permission of the diocesan authorities, which fell out of church standards, but at the same time fully corresponded to the peasants’ understanding of true piety. Despite the desire of the church to regulate this type of care, it was a vivid manifestation of peasant religiosity. It can be seen in the article that wandering among the peasant environment would have been impossible without such a phenomenon of peasant life as hospitality, the idea of mercy, and the idea of the temple as the sacred center of the peasant community.
Effect of pH on the Electrochemical Behavior of Hydrogen Peroxide in the Presence of Pseudomonas aeruginosa
Authors: Espinoza-Vergara Javier , Molina Paulo , Walter Mariana , Gulppi Miguel , Vejar Nelson , Melo Francisco , Urzua Marcela , Muñoz Hugo , Zagal José H. , Zhou Xiaorong , Azocar Manuel I. , Paez Maritza A.
Published: December 2021

The influence of pH on the electrochemical behavior of hydrogen peroxide in the presence ofPseudomonas aeruginosawas investigated using electrochemical techniques. Cyclic and square wave voltammetry were used to monitor the enzymatic activity. A modified cobalt phthalocyanine (CoPc) carbon electrode (OPG), a known catalyst for reducing O2to H2O2, was used to detect species resulting from the enzyme activity. The electrolyte was a sterilized aqueous medium containing Mueller-Hinton (MH) broth. The open-circuit potential (OCP) of thePseudomonas aeruginosaculture in MH decreased rapidly with time, reaching a stable state after 4 h. Peculiarities in the E / I response were observed in voltammograms conducted in less than 4 h of exposure to the culture medium. Such particular E/I responses are due to the catalase’s enzymatic action related to the conversion of hydrogen peroxide to oxygen, confirming the authors’ previous findings related to the behavior of other catalase-positive microorganisms. The enzymatic activity exhibits maximum activity at pH 7.5, assessed by the potential at which oxygen is reduced to hydrogen peroxide. At higher or lower pHs, the oxygen reduction reaction (ORR) occurs at higher overpotentials, i.e., at more negative potentials. In addition, and to assess the influence of bacterial adhesion on the electrochemical behavior, measurements of the bacterial-substrate metal interaction were performed at different pH using atomic force microscopy.
Recent Developments in the Immobilization of Laccase on Carbonaceous Supports for Environmental Applications - A Critical Review
Authors: Adamian Younes , Lonappan Linson , Alokpa Komla , Agathos Spiros N. , Cabana Hubert
Published: December 2021

Τhe ligninolytic enzyme laccase has proved its potential for environmental applications. However, there is no documented industrial application of free laccase due to low stability, poor reusability, and high costs. Immobilization has been considered as a powerful technique to enhance laccase’s industrial potential. In this technology, appropriate support selection for laccase immobilization is a crucial step since the support could broadly affect the properties of the resulting catalyst system. Through the last decades, a large variety of inorganic, organic, and composite materials have been used in laccase immobilization. Among them, carbon-based materials have been explored as a support candidate for immobilization, due to their properties such as high porosity, high surface area, the existence of functional groups, and their highly aromatic structure. Carbon-based materials have also been used in culture media as supports, sources of nutrients, and inducers, for laccase production. This study aims to review the recent trends in laccase production, immobilization techniques, and essential support properties for enzyme immobilization. More specifically, this review analyzes and presents the significant benefits of carbon-based materials for their key role in laccase production and immobilization.
Functional Hydrogel Dressings for Treatment of Burn Wounds
Authors: Shu Wentao , Wang Yinan , Zhang Xi , Li Chaoyang , Le Hanxiang , Chang Fei
Published: December 2021

The therapy of burns is a challenging clinical issue. Burns are long-term injuries, and numerous patients suffer from chronic pain. Burn treatment includes management, infection control, wound debridement and escharotomy, dressing coverage, skin transplantation, and the use of skin substitutes. The future of advanced care of burn wounds lies in the development of “active dressings”. Hydrogel dressings have been employed universally to accelerate wound healing based on their unique properties to overcome the limitations of existing treatment methods. This review briefly introduces the advantages of hydrogel dressings and discusses the development of new hydrogel dressings for wound healing along with skin regeneration. Further, the treatment strategies for burns, ranging from external to clinical, are reviewed, and the functional classifications of hydrogel dressings along with their clinical value for burns are discussed.
RETRACTED: Disposable Polymeric Nanostructured Plasmonic Biosensors for Cell Culture Adhesion Monitoring
Authors: Vila Judith Camaló , Castro-Aguirre Nerea , López-Muñoz Gerardo A. , Ferret-Miñana Ainhoa , De Chiara Francesco , Ramón-Azcón Javier
Published: December 2021

Over the last years, optical biosensors based on plasmonic nanomaterials have gained great scientific interest due to their unquestionable advantages compared to other biosensing technologies. They can achieve sensitive, direct, and label-free analysis with exceptional potential for multiplexing and miniaturization. Recently, it has been demonstrated the potential of using optical discs as high throughput nanotemplates for the development of plasmonic biosensors in a cost-effective way. This work is a pilot study focused on the development of an integrated plasmonic biosensor for the monitoring of cell adhesion and growth of human retinal pigmented cell line (ARPE-19) under different media conditions (0 and 2% of FBS). We observed an increase of the plasmonic band displacement under 2% FBS compared to 0% conditions over time (1, 3, and 5 h). These preliminary results show that the proposed plasmonic biosensing approach is a direct, non-destructive, and real-time tool that could be employed in the study of living cells behavior and culture conditions. Furthermore, this setup could assess the viability of the cells and their growth over time with low variability between the technical replicates improving the experimental replicability.
Transcriptome-wide N6-Methyladenosine Methylome Profiling Reveals m6A Regulation of Skeletal Myoblast Differentiation in Cattle (Bos taurus)
Authors: Yang Xinran , Wang Jianfang , Ma Xinhao , Du Jiawei , Mei Chugang , Zan Linsen
Published: December 2021

N6-methyladenosine (m6A) is the most prevalent methylation modification of eukaryotic mRNA, and it plays an important role in regulating gene expression. Previous studies have found that m6A methylation plays a role in mammalian skeletal muscle development. However, the effect of m6A on bovine skeletal myogenesis are still unclear. Here, we selected proliferating myoblasts (GM) and differentiated myotubes (on the 4th day of differentiation, DM) for m6A-seq and RNA-seq to explore the m6A methylation modification pattern during bovine skeletal myogenesis. m6A-seq analysis revealed that m6A methylation was an abundant modification of the mRNA in bovine myoblasts and myotubes. We scanned 5,691–8,094 m6A-modified transcripts, including 1,437 differentially methylated genes (DMGs). GO and KEGG analyses revealed that DMGs were primarily involved in transcriptional regulation and RNA metabolism, as well as insulin resistance and metabolic pathways related to muscle development. The combined analysis further identified 268 genes that had significant changes at both m6A and mRNA levels, suggesting that m6A modification may regulate myoblast differentiation by mediating the expression of these genes. Furthermore, we experimentally confirmed four genes related to myogenesis, including MYOZ2, TWIST1, KLF5 and MYOD1, with differential changes in both m6A and mRNA levels during bovine myoblast differentiation, indicating that they can be potential candidate targets for m6A regulation of skeletal myogenesis. Our results may provide new insight into molecular genetics and breeding of beef cattle, and provide a reference for investigating the mechanism of m6A regulating skeletal muscle development.
An Inhibitor of Grp94 Inhibits OxLDL-Induced Autophagy and Apoptosis in VECs and Stabilized Atherosclerotic Plaques
Authors: Wei Qun , Ren Hui , Zhang Jun , Yao Wen , Zhao Baoxiang , Miao Junying
Published: December 2021

Background: Oxidized low-density lipoprotein (oxLDL) induces vascular endothelial cell (VEC) injury and atherosclerosis through activating endoplasmic reticulum stress. Expression of glucose-regulated protein 94 (Grp94) is induced by endoplasmic reticulum stress and Grp94 is involved in cardiovascular diseases. This study aimed to determine the role of Grp94 in oxLDL-induced vascular endothelial cell injury and atherosclerosis.

Methods and Results: An inhibitor of Grp94, HCP1, was used to investigate the role of Grp94 in oxLDL-induced VEC injury in human umbilical vein endothelial cells and atherosclerosis in apolipoprotein E−/− mice. Results showed that HCP1 inhibited autophagy and apoptosis induced by oxLDL in VECs. And we found that Grp94 might interact with adenosine monophosphate-activated protein kinase (AMPK) and activate its activity. HCP1 inhibited AMPK activity and overexpression of Grp94 blocked the effect of HCP1. Besides, HCP1 activated the activity of mechanistic target of rapamycin complex 1 (mTORC1), co-treatment with AMPK activator acadesine eliminated the effect of HCP1 on mTORC1 activity as well as autophagy. In apolipoprotein E−/− mice, HCP1 suppressed autophagy and apoptosis of atherosclerotic plaque endothelium. In addition, HCP1 increased the content of collagen, smooth muscle cells, and anti-inflammatory macrophages while reducing the activity of MMP-2/9 and pro-inflammatory macrophages in the atherosclerotic lesion.

Conclusion: HCP1 inhibited oxLDL-induced VEC injury and promoted the stabilization of atherosclerotic plaque in apoE−/− mice. Grp94 might be a potential therapeutic target in the clinical treatment of atherosclerosis.
Mapping International Geopolitical Agenda. Continuing National Conceptions of the Emerging European Crisis
Authors: Grasland Claude , Toureille Etienne , Leconte Romain , Severo Marta
Published: December 2021

This study proposes a geopolitical analysis of opinion dynamics based on a statistical exploration of a press dataset covering 2014–2019. This exploration questions three case studies of geopolitical and international interest: international migration, political borders, and pandemics. Through the framework of geopolitical agenda, the aim of this study is to question the “crisis” status of changes in the media coverage of the three topics in a cross-analysis and multilingual analysis of 20 western European newspapers. It concludes that there is a prevalence of national agendas.
Tracking Saudi EFL Students’ Reflections of Online Learning During Coronavirus: Different Rounds
Authors: Al Shlowiy Ahmed
Published: December 2021

The sudden shift into online learning due to COVID-19 has produced many challenges and new educational approaches across all educational systems. Language learning systems were enforced to utilize fully remote education solutions. Responding to COVID-19 is a crucial investigation to find out the challenges, barriers, suggestions, concerns, and deficiencies of teaching English in Saudi Arabia. It also assists in developing the Saudi English as a Foreign Language (EFL) context in the future and support its students, teachers, and policymakers. This study tracks the influence of this shift on the EFL students in a Saudi high school. Data collection depends on reflective questions sent to the students through the survey and WhatsApp Group three times during the pandemic: April 2020, October 2020, and April 2021. The results show that students faced several threats, ambiguities, and deficiencies that are classified into: (a) students’ emotions, (b) learning environment, (c) student characteristics, and (d) deficiencies and needs. The students gradually acquired experience to deal with those issues and cope with their frustration. Then, they performed in either positive or negative ways depending on their acceptance of the online learning context. The study ends with some implications to efficiently use different virtual tools in the EFL context.
Role of G Protein-Coupled Receptors in Hepatic Stellate Cells and Approaches to Anti-Fibrotic Treatment of Non-Alcoholic Fatty Liver Disease
Authors: Kimura Takefumi , Singh Simran , Tanaka Naoki , Umemura Takeji
Published: December 2021

The prevalence of non-alcoholic fatty liver disease (NAFLD) is globally increasing. Gaining control over disease-related events in non-alcoholic steatohepatitis (NASH), an advanced form of NAFLD, is currently an unmet medical need. Hepatic fibrosis is a critical prognostic factor in NAFLD/NASH. Therefore, a better understanding of the pathophysiology of hepatic fibrosis and the development of related therapies are of great importance. G protein-coupled receptors (GPCRs) are cell surface receptors that mediate the function of a great variety of extracellular ligands. GPCRs represent major drug targets, as indicated by the fact that about 40% of all drugs currently used in clinical practice mediate their therapeutic effects by acting on GPCRs. Like many other organs, various GPCRs play a role in regulating liver function. It is predicted that more than 50 GPCRs are expressed in the liver. However, our knowledge of how GPCRs regulate liver metabolism and fibrosis in the different cell types of the liver is very limited. In particular, a better understanding of the role of GPCRs in hepatic stellate cells (HSCs), the primary cells that regulate liver fibrosis, may lead to the development of drugs that can improve hepatic fibrosis in NAFLD/NASH. In this review, we describe the functions of multiple GPCRs expressed in HSCs, their roles in liver fibrogenesis, and finally speculate on the development of novel treatments for NAFLD/NASH.
Identification and Characterization of Circular RNAs in Association With the Deposition of Intramuscular Fat in Aohan Fine-Wool Sheep
Authors: Zhao Le , Zhou Lisheng , Hao Xiaojing , Wang Lei , Han Fuhui , Liu Lirong , Duan Xinming , Guo Feng , He Jianning , Liu Nan
Published: December 2021

Aohan fine-wool sheep (AFWS) is a high-quality fine-wool sheep breed that supplies wool and meat. Research is needed on the molecular mechanism behind intramuscular fat (IMF) deposition that greatly improves mutton quality. The widely expressed non-coding RNA is physiologically used in roles such as competitive endogenous RNA (ceRNA) that includes circular RNAs (circRNAs). Although circRNAs were studied in many fields, little research was devoted to IMF in sheep. We used the longissimus dorsi muscle of 2 and 12-month-old AWFS as research material to identify circRNAs related to IMF deposition in these sheep by RNA-seq screening for differentially expressed circRNAs in the two age groups. A total of 11,565 candidate circRNAs were identified, of which the 104 differentially expressed circRNAs in the two age groups were analyzed. Enrichment analysis was performed using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. The enriched pathways included lipid transport (GO:0006869), negative regulation of canonical Wnt signaling pathway (GO:0090090), fat digestion and absorption (ko04975), and sphingolipid metabolism (ko00600). The differentially expressed circRNAs included ciRNA455, circRNA9086, circRNA7445, circRNA4557, and others. The source genes involved in these pathways might regulate IMF deposition. We used the TargetScan and miRanda software for interaction analysis, and a network diagram of circRNA-miRNA interactions was created. CircRNA455-miR-127, circRNA455-miR-29a, circRNA455-miR-103, circRNA4557-mir149-5p, and circRNA2440-mir-23a might be involved in the IMF deposition process. The targeting relationship of circRNA4557-miR-149-5p was verified by a dual-luciferase reporter assay. The RT-qPCR results of seven randomly selected circRNAs were consistent with the sequencing results. This study provides additional information on circRNA regulation of IMF deposition in AFWS and is a useful resource for future research on this sheep breed.
Evaluation of the Effects of 1,25VitD3 on Inflammatory Responses and IL-25 Expression
Authors: Li Nana , Saghafi Nafiseh , Ghaneifar Zahra , Rezaee Seyed Abdorahim , Rafatpanah Houshang , Abdollahi Elham
Published: December 2021

VitD3 may contribute to a successful pregnancy through modulation of immune responses, so VitD3 deficiency may have a role in the immunopathogenesis of unexplained recurrent spontaneous abortion (URSA). However, the mechanisms of immunomodulatory actions of VitD3 in decreasing the risk of recurrent spontaneous abortion have not been understood well.

Objective: The purpose of this research was to investigate the influence of 1,25VitD3 on IL-25 and related cytokines of Th17 cells including IL-17A, IL-6, and IL-23 in peripheral blood mononuclear cells of healthy women as a control group and women with unexplained recurrent spontaneous abortion.

Method: Isolation of peripheral blood mononuclear cells (PBMCs) was performed from peripheral blood of the subjects of the studied groups (20 women with URSA as a case group, and 20 control women). The effects of 1,25VitD3 (50 nM, for 24 h) on the studied parameters were evaluated and were compared to the positive and negative controls in vitro. Flow cytometry analysis was used to determine the percentages of regulatory T cells and Th17 cells. For gene expression measurement and cytokines assay, real-time PCR and ELISA were carried out.

Results: The proportion of Th17 cells in women with URSA was considerably higher than in the control group. IL-25 mRNA and protein levels in cultured PBMCs from women with URSA were lower than the controls. 1,25VitD3 increased IL-25 expressions at both the protein and mRNA levels in PBMCs from women with URSA relative to the control group. Additionally, 1,25VitD3 treatment not only significantly decreased the percentage of Th17 cells frequency but also reduced expressions of IL-6, IL-17A, and IL-23 in PBMCs from women with URSA.

Conclusion: 1,25VitD3 may diminish inflammatory responses cells via downregulation of IL-25 expression. It could be an interesting subject for future researches in the field of the immunopathology of URSA to identify molecular pathways in URSA treatment.
Skin Immunity and Tolerance: Focus on Epidermal Keratinocytes Expressing HLA-G
Authors: Mestrallet Guillaume , Rouas-Freiss Nathalie , LeMaoult Joel , Fortunel Nicolas O. , Martin Michele T.
Published: December 2021

Although the role of epidermal cells in skin regeneration has been extensively documented, their functions in immunity and tolerance mechanisms are largely underestimated. The aim of the present review was to outline the state of knowledge on resident immune cells of hematopoietic origin hosted in the epidermis, and then to focus on the involvement of keratinocytes in the complex skin immune networks acting in homeostasis and regeneration conditions. Based on this knowledge, the mechanisms of immune tolerance are reviewed. In particular, strategies based on immunosuppression mediated by HLA-G are highlighted, as recent advances in this field open up perspectives in epidermis-substitute bioengineering for temporary and permanent skin replacement strategies.
First Report of Gametogenesis and Spawning for the Invasive Alga Caulerpa cylindracea in the Tyrrhenian Sea: The Key Role of Water Motion and Temperature
Authors: Caronni Sarah , Delaria Maria Anna , Gentili Rodolfo , Montagnani Chiara , Navone Augusto , Panzalis Pieraugusto , Citterio Sandra
Published: December 2021

In this study, gamete release by Caulerpa cylindracea was investigated for the first time in the Tyrrhenian Sea (Sardinia, Western Mediterranean), focusing on the main environmental factors triggering gametogenesis and spawning of the species. For this purpose, a combination of field and laboratory experiments was conducted. First, a 2-year mensurative experiment was performed in the field during summer to individuate and quantify the occurrence of C. cylindracea gametogenesis and spawning events, linking them to environmental conditions. Then, based on the results of the field work, a laboratory experiment was performed to directly test, under controlled conditions, the effect on the above-mentioned processes of two abiotic factors that appeared to play a key role in species gamete release processes in the area: sea water temperature and water movement. During the 2 years of field research, several gametogenesis events were recorded in the study area and two spawning events also occurred. Significant differences were observed between the ratio of fertile and total thalli and between releasing thalli (RT) and fertile thalli (FT), among sites with different hydrodynamic conditions and sampling periods with different sea water temperatures. Overall, these results suggest that C. cylindracea sexual reproduction also occurs in the Tyrrhenian Sea, and that, therefore, new genotypes that favor the invasive profile of the species could be produced in the basin, where both its gametogenesis and spawning seem to be mainly regulated by water movement and sea water temperature.
Constructing Prediction Models for Freezing of Gait by Nomogram and Machine Learning: A Longitudinal Study
Authors: Xu Kun , Zhou Xiao-xia , He Run-cheng , Zhou Zhou , Liu Zhen-hua , Xu Qian , Sun Qi-ying , Yan Xin-xiang , Wu Xin-yin , Guo Ji-feng , Tang Bei-sha
Published: December 2021

Objectives: Although risk factors for freezing of gait (FOG) have been reported, there are still few prediction models based on cohorts that predict FOG. This 1-year longitudinal study was aimed to identify the clinical measurements closely linked with FOG in Chinese patients with Parkinson's disease (PD) and construct prediction models based on those clinical measurements using Cox regression and machine learning.

Methods: The study enrolled 967 PD patients without FOG in the Hoehn and Yahr (H&Y) stage 1–3 at baseline. The development of FOG during follow-up was the end-point. Neurologists trained in movement disorders collected information from the patients on a PD medication regimen and their clinical characteristics. The cohort was assessed on the same clinical scales, and the baseline characteristics were recorded and compared. After the patients were divided into the training set and test set by the stratified random sampling method, prediction models were constructed using Cox regression and random forests (RF).

Results: At the end of the study, 26.4% (255/967) of the patients suffered from FOG. Patients with FOG had significantly longer disease duration, greater age at baseline and H&Y stage, lower proportion in Tremor Dominant (TD) subtype, a higher proportion in wearing-off, levodopa equivalent daily dosage (LEDD), usage of L-Dopa and catechol-O-methyltransferase (COMT) inhibitors, a higher score in scales of Unified Parkinson's Disease Rate Scale (UPDRS), 39-item Parkinson's Disease Questionnaire (PDQ-39), Non-Motor Symptoms Scale (NMSS), Hamilton Depression Rating Scale (HDRS)-17, Parkinson's Fatigue Scale (PFS), rapid eye movement sleep behavior disorder questionnaire-Hong Kong (RBDQ-HK), Epworth Sleepiness Scale (ESS), and a lower score in scales of Parkinson's Disease Sleep Scale (PDSS) (P < 0.05). The risk factors associated with FOG included PD onset not being under the age of 50 years, a lower degree of tremor symptom, impaired activities of daily living (ADL), UPDRS item 30 posture instability, unexplained weight loss, and a higher degree of fatigue. The concordance index (C-index) was 0.68 for the training set (for internal validation) and 0.71 for the test set (for external validation) of the nomogram prediction model, which showed a good predictive ability for patients in different survival times. The RF model also performed well, the C-index was 0.74 for the test set, and the AUC was 0.74.

Conclusions: The study found some new risk factors associated with the FOG including a lower degree of tremor symptom, unexplained weight loss, and a higher degree of fatigue through a longitudinal study, and constructed relatively acceptable prediction models.
Case Report: Niraparib as Maintenance Therapy in A Patient With Ovarian Carcinosarcoma
Authors: Zhang Jie Qing , Zhao Bing Bing , Wang Mao Mao , Li Li
Published: December 2021

Ovarian carcinosarcoma (OCS) is a rare, highly aggressive and rapidly progressing malignant tumor with an extremely poor prognosis. So far, due to the low incidence of OCS, there are no large-scale prospective studies exploring the standard care of OCS patients. There is no uniform and effective treatment for OCS. Within the development of precision medicine, targeted therapies (such as PARP inhibitors) have been widely used in epithelial ovarian cancer and various other solid tumors. Here, we report a BRCAwt patient with advanced OCS who experienced a second and a third cytoreductive surgery in June 2017 and October 2019 and has been on niraparib maintenance therapy for more than 20 months after receiving second-line and third-line chemotherapy.
Cost-Effectiveness Analysis of Fourth- or Further-Line Ripretinib in Advanced Gastrointestinal Stromal Tumors
Authors: Liao Weiting , Xu Huiqiong , Hutton David , Wu Qiuji , Zhou Kexun , Luo Hui , Lei Wanting , Feng Mingyang , Yang Yang , Wen Feng , Li Qiu
Published: December 2021

Background

The INVICTUS trial assessed the efficacy and safety of ripretinib compared with placebo in the management of advanced gastrointestinal stromal tumors.

Method

We used a Markov model with three health states: progression-free disease, progression disease and death. We parameterized the model from time-to-event data (progression-free survival, overall survival) of ripretinib and placebo arms in the INVICTUS trial and extrapolated to a patient’s lifetime horizon. Estimates of health state utilities and costs were based on clinical trial data and the published literature. The outcomes of this model were measured in quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Uncertainty was tested via univariate and probabilistic sensitivity analyses.

Results

The base-case model projected improved outcomes (by 0.29 QALYs) and additional costs (by $70,251) and yielded an ICER of $244,010/QALY gained for ripretinib versus placebo. The results were most sensitive to progression rates, the price of ripretinib, and health state utilities. The ICER was most sensitive to overall survival. When overall survival in the placebo group was lower, the ICER dropped to $127,399/QALY. The ICER dropped to $150,000/QALY when the monthly cost of ripretinib decreased to $14,057. Probabilistic sensitivity analyses revealed that ripretinib was the cost-effective therapy in 41.1% of simulations at the willingness-to-pay (WTP) threshold of $150,000.

Conclusion

As the fourth- or further-line therapy in advanced gastrointestinal stromal tumors, ripretinib is not cost-effective in the US. Ripretinib would achieve its cost-effectiveness with a price discount of 56% given the present effectiveness.
MAPK Activated Protein Kinase 3 Is a Prognostic-Related Biomarker and Associated With Immune Infiltrates in Glioma
Authors: Ren Jing , Sun Jinmin , Li Mengwei , Zhang Zifan , Yang Dejun , Cao Haowei
Published: December 2021

Glioma is the most common primary brain tumor that causes significant morbidity and mortality. MAPK activated protein kinase 3 (MAPKAPK3/MK3) is a serine/threonine protein kinase regulating various cellular responses and gene expression. However, the role of MK3 in tumor progress, prognosis, and immunity for glioma remains unclear. Here, we determined the expression and prognostic values of MK3. We further analyzed the correlation of MK3 expression with immune infiltrations by using the biochemical methods and bioinformatic approaches with available databases. We find that MK3 is aberrantly upregulated in glioma. In addition, the higher MK3 expression is closely linked to the poor clinicopathologic features of glioma patients. Importantly, MK3 expression is negatively correlated with the prognosis of patients with glioma. Mechanistically, we demonstrated that the correlated genes of MK3 were mainly enriched in pathways that regulate tumor immune responses. The MK3 level was significantly associated with tumor-infiltrating immune cells and positively correlated with the majority of tumor immunoinhibitors, chemokines, and chemokine receptors in glioma. Thus, these findings suggest the novel prognostic roles of MK3 and define MK3 as a promising target for glioma immunotherapy.
Hyperactivity and Inattention in Young Patients Born With an Atrial Septal or Ventricular Septal Defect
Authors: Lau-Jensen Sara Hirani , Asschenfeldt Benjamin , Evald Lars , Hjortdal Vibeke E.
Published: December 2021

Background: Patients with congenital heart defects have a well-established risk of neuropsychiatric comorbidities. Inattention and hyperactivity are three to four times more frequent in children with complex congenital heart defects. We have previously shown a higher burden of overall attention deficit/hyperactivity disorder (ADHD) symptoms in adults with simple congenital heart defects as well. However, it is unknown whether the higher burden of ADHD symptoms is mainly driven by hyperactivity, inattention, or both.

Methods: The participants [simple congenital heart defect = 80 (26.6 years old), controls = 36 (25.3 years old)] and a close relative for each (n = 107) responded to the long version of the Conners' Adults ADHD Rating Scales questionnaire. Our primary and secondary outcomes are mean T-scores in the ADHD scores and symptom sub-scores.

Results: Patients with simple congenital heart defects reported a higher mean T-score at all three DSM-IV ADHD scores (ADHD—combined: 52.8 vs. 44.9, p = 0.007, ADHD—inattention: 55.5 vs. 46.4, p = 0.002, and ADHD—hyperactivity: 49.4 vs. 44.0, p = 0.03) and in all four ADHD symptom sub-scores (inattention/memory problems: 50.3 vs. 44.2, p = 0.001, hyperactivity/restlessness: 49.7 vs. 45.9, p = 0.03, impulsivity/emotional lability: 50.0 vs. 41.3, p = 0.001, and self-esteem problems: 53.8 vs. 46.3, p = 0.003). The results were maintained after the removal of outliers (incongruent responses), albeit the hyperactivity/restlessness ADHD symptom sub-score lost significance. Self- and informant ratings differed significantly on the ADHD—inattention score for the congenital heart defect group, where informants rated the ADHD—inattention scores better than the congenital heart defect patients rated themselves.

Conclusions: Patients with a simple congenital heart defect have a higher symptom burden across all ADHD scores and all symptom sub-scores. The higher burden of ADHD is driven by both inattention and hyperactivity symptoms, though the inattention symptoms seem more prominent. Close relatives were less aware of the inattention symptoms than the congenital heart defect patients themselves. Routine screening for ADHD symptoms may be warranted to facilitate adequate help and guidance as these symptoms are easily overlooked.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03871881.
Coumarin Derivative N6 as a Novel anti-hantavirus Infection Agent Targeting AKT
Authors: Li Zhoupeng , Wang Fang , Liu Yongsheng , Zhai Dongshen , Zhang Xiaoxiao , Ying Qikang , Jia Min , Xue Xiaoyan , Meng Jingru , Li Jing , Wu Xingan , Li Mingkai
Published: December 2021

Hantaviruses are globally emerging zoonotic viruses that can cause hemorrhagic fever with renal syndrome (HFRS) in Asia and Europe, which is primarily caused by Hantaan virus (HTNV) infection, results in profound morbidity and mortality. However, no specific treatment is available for this disease. Coumarin derivatives have been reported as antiviral molecules, while studies about the bioactivity of coumarin derivatives against HTNV infection are limited. To study the potential antiviral activity of coumarin derivatives, 126 coumarin derivatives are synthesized, and their inhibitory activity against HTNV is analyzed in vitro. Among these compounds, N6 inhibits HTNV with relatively high selectivity index at 10.9, and the viral titer of HTNV is reduced significantly after 5, 10, and 20 μM N6 treatments. Furthermore, the administration of N6 at the early stage of HTNV infection can inhibit the replication and production of infectious HTNV in host cell, this therapeutic efficacy is confirmed in HTNV-infected newborn mice at the early stage of infection. The molecular docking results show that N6 forms interactions with the key amino acid residues at its active site, and reveals several molecular interactions responsible for the observed affinity, and the treatment of N6 can inhibit the expression of p (Ser473)Akt and HTNV nucleocapsid protein significantly. As such, these observations demonstrate that coumarin derivative N6 might be used as a potential agent against HTNV infection.
Photogyrotactic Concentration of a Population of Swimming Microalgae Across a Porous Layer
Authors: Prakash Praneet , Croze Ottavio A.
Published: December 2021

The light environment controls the swimming of microalgae through a light-seeking and avoiding behaviour, which is known as phototaxis. In this work, we exploit phototaxis to control the migration and concentration of populations of the soil microalga Chlamydomonas reinhardtii. By imaging a suspension of these microalgae in a cuvette illuminated from above by blue light, we study how phototaxis changes the stability of the suspension and demonstrate how a thin, porous layer at the top of the cuvette prevents phototaxing microalgae from sinking, leading to the up-concentration of the microalgae in the region above the porous layer. We discuss the potential implications of our findings for microalgae in biotechnological applications and the natural environment.