bluuebunny/crossref_metadata_2025 huggingface dataset:
Of Metals and Men: Kofman, Conversion and The Merchant of Venice
Authors: Large Duncan
Published: February 2021

Mindful that philosophy is for Kofman always sublated ( relevé) by literature and psychoanalysis, this essay examines Kofman's rarely discussed text ‘Conversions: The Merchant of Venice under the Sign of Saturn’ (1987) in the light of themes from elsewhere in her work. Typical of her method, Conversions is a richly philosophical reading of a psychoanalytic interpretation of a literary text. It is also Kofman's most sustained engagement with Shakespeare. In the study she builds on her earlier interest in the trope of metaphor and, drawing on Freud's reading of Shakespeare's play, derives a generalized theory of convertibility or ambivalence. Where the play seeks to establish symbolic equivalences between men and metals — between the triads Antonio/Bassano/Shylock and the lead/gold/silver of the three caskets — Kofman's analysis focuses instead on their respective Janus faces and alchemical transmutations. Beneath the explicit thematizations she follows Freud in discerning the interconvertibility of love and death, but she also goes beyond Freud in arguing that its condition of possibility is the structural ambivalence of time itself.
Reading Derrida Reading Kofman
Authors: Michaud Ginette
Published: February 2021

This article examines the relationship that Jacques Derrida and Sarah Kofman developed throughout their lifetimes, both as close friends and as philosophers who shared many common research interests. In his tribute to Sarah Kofman, published in Les Cahiers du Grif in 1997, Derrida stated that ‘These interests and exercises go far beyond the limits of a short narrative, indeed of a terminable analysis’, thus challenging the reader to delve into these ‘elliptical greetings’. The numerous interactions present in Kofman's and Derrida's respective bodies of work are not without conflicts nor dissymmetry, and their often oblique modes of acknowledgement are far from any ‘balance’ on either side. Revisiting some of the différends among two great thinkers of différance, this article highlights the Derridean logic of gift and debt at work between them. Focusing on the posthumous tribute Derrida pays to his friend (left untitled, which is itself a revealing gesture), one can sense that there is much at stake in that piece that touches on the major question of forgiveness and the affirmation of survie or living on, thus setting a scene of reading where Derrida's debt towards Kofman turns out to be more telling than one may have expected.
Sarah Kofman and the Allure of Music
Authors: Toma Cosmin
Published: February 2021

This article delves into the discreet yet persistent presence of music in Sarah Kofman's work. Three strands or movements of unequal length are explored here, each of which touches upon a specific volume of Kofman's: Nietzsche and Metaphor, L'Imposture de la beauté and, lastly, Rue Ordener, Rue Labat. More specifically, the article shows how her interpretations of Nietzsche's writings on music are almost paradigmatically neutral in their readerly fidelity to the originals, whereas Rue Ordener, Rue Labat suggests a more emotionally charged rapport with music. In closing, the article considers the possibility that these two, ostensibly divergent modes of reading and writing are very much in tune with each other in that they blur the line between interprétation as philosophical commentary and interprétation as musical performance.
The Margins of a Nightmare
Authors: Johnson Joseph R.
Published: February 2021

A pivotal fusion of philosophy and life-writing, Sarah Kofman's Comment s'en sortir ? (1983) concludes with a highly experimental essay that uses medieval language as a means of recalling traumatic childhood events. Between the medieval and the personal past (which Kofman terms her own ‘middle ages’), the text of a nightmare stands as a sort of bridge. In this article, I closely consider the meaning and symbolism of the nightmare, with a particular eye to how its central figures condense information that can be gleaned by consulting various sources that Kofman is known to have read. I argue that Kofman's essay, as well as her nightmare, function as a referential space in which medieval material at once conceals and discloses the points of greatest suffering.
Prevalencia, características clínicas y socioeconómicas de teniasis y cisticercosis en una población de Lurín - 2004
Authors: Castillo-Contreras Ofelia , De Coll-Vela Juan , Lermo-Sandoval Jorge , López-Peña Gregory , Vega-Peláez Julián
Published: February 2021

Objetivo: Determinar la prevalencia de teniasis intestinal y seroprevalencia de cisticercosis de los vendedores de chicharrones de Lurín en Lima-Perú, y conocer sus características epidemiológicas, socioeconómicas y síntomas asociados con la parasitosis. Material y métodos: Se realizó un estudio transversal en vendedores de chicharrones del asentamiento humano “Julio C. Tello” de Lurín. Previo consentimiento informado de los participantes. Se utilizó una encuesta socioepidemiológica y se recolectó muestras de sangre para detectar anticuerpos específicos a Cisticerco (EITB) y de heces para la detección de coproantigenos de Taenia sp. (ELISA). Las muestras se procesaron en el Laboratorio de Cisticercosis del Instituto Nacional  de Ciencias Neurológicas. El protocolo fue aprobado por el Comité de Ética de la Facultad de Medicina de San Fernando. Resultados: De 49 encuestados, el 89,8% participaba en la preparación de chicharrones y atención al público. El 81,6% refirió lavarse las manos siempre después de defecar, 65,3% refirió hacerlo antes de consumir alimentos. Hubo 41 muestras de sangre que resultaron negativas para cisticercosis. La detección de coproantigenos de Taenia sp. fueron negativos en todos los casos. No se encontró huevos de Taenia sp. en el examen de microsedimentación. Los locales contaban con servicios de agua y desagüe. Discusión: Las condiciones sanitarias y hábitos higiénicos adecuados reducirían el riesgo de infección. El consumo de carne de cerdo en forma de chicharrón podría no estar asociado a la trasmisión de este parásito. Conclusión: Los datos obtenidos indican que no existe teniasis ni cisticercosis en dicha población estudiada.
El sistema de coagulación y COVID-19
Authors: Rios Pérez Jorge A.
Published: February 2021

Las anormalidades de la coagulación y el desarrollo de complicaciones trombóticas por COVID-19 parecen estar desencadenadas por una inflamación descontrolada, y ser clínicamente diferentes de otras entidades como la coagulación intravascular diseminada. Los mecanismos subyacentes incluyen la disfunción endotelial e interacciones entre el sistema inmunológico y el de coagulación. Los eventos trombóticos parecen ser más frecuentes en pacientes críticos con COVID-19. Por ende, una estrategia distinta para el manejo de la trombosis asociada a COVID-19 podría ser necesaria. Sin embargo, son necesarios ensayos clínicos para determinar las estrategias más adecuadas en el manejo de los eventos trombóticos asociados a COVID-19.
Apendicitis Aguda
Authors: Flores-Mena Miguel David
Published: February 2021

La Apendicitis Aguda es un proceso inflamatorio infeccioso localizado que es la causa más frecuente de abdomen agudo que requiere Cirugía de Emergencia. Su mayor incidencia es entre los 15 y 30 años. Aproximadamente 1 de cada 15 a 20 personas desarrolla apendicitis aguda durante su vida.
Hijos de la Peste. Una historia de las epidemias en el Perú
Authors: Morales-Soto Nelson Raúl
Published: February 2021

El autor, Marcel Velázquez Castro, ensayista y crítico literario, Doctor en Literatura Latinoamericana, anota en la Introducción: “Este libro ofrece un conjunto de exploraciones e inquisiciones críticas sobre la historia, el miedo, la violencia y el humor en tiempos de plagas. Un archivo de procesos sociales, ideologías y paisajes humanos de diferentes épocas: textos e imágenes que dialogan entre sí y nos ayudan a comprender la experiencia contemporánea. Escrito desde, sobre y contra Lima, posee inevitablemente una perspectiva singular; sin embargo, las respuestas culturales ante la experiencia global de la COVID-19 constituyen un repertorio de variaciones de otros tiempos y otras subjetividades que nos siguen habitando a todos”.
Hipótesis de terremoto destructor en el litoral central: Impacto sanitario y social
Authors: Morales-Soto Nelson Raúl
Published: February 2021

El Editor menciona que “Históricamente el territorio peruano ha sido escenario de grandes desastres originados en la naturaleza -inundaciones y huaycos los más frecuentes, terremotos y aluviones los más mortíferos- o causados por la mano del hombre -guerras externas e internas- ocasionando grandes daños a la vida o la propiedad afectando el desarrollo nacional.
Deshumanización de la medicina o deshumanización de la sociedad
Authors: Morales-Soto Nelson Raúl
Published: February 2021

En la Presentación del libro el AN Dr. Patricio Wagner Grau, Presidente de la Academia Nacional de Medicina, 2013-2015, anota: “La deshumanización es hoy un fenómeno universal. Deshumanizar significa perder o ignorar las características y atributos propios de la esencia de lo humano. El ser humano es persona y, por tanto, resuena, resplandece en el ámbito del universo.
¿Reduce la metformina el riesgo de muerte en el COVID-19?
Authors: Calderón-Velasco Rolando
Published: February 2021

La acumulacion de datos sugiere que el uso de metformina en la diabetes tipo 2 puede reducir el riesgo de muerte por COVID-19.
Fecundity and Seed Dormancy Variation Within and Among Echinochloa Species
Authors: Tahir Hussain , Roma-Burgos Nilda
Published: February 2021

The Echinochloa genus contains two of the world's top five worst weeds. The persistence and weediness of Echinochloa spp. are partly due to its seed longevity and variable seed dormancy. In the USA, specifically in Arkansas, multiple species infest the same field in many cases. Persistence could vary across species and dormancy affects infestation level. Studies were conducted to evaluate the seed production potential and dormancy of Echinochloa species in the State. Ninety-four accessions were characterized in a common garden in Fayetteville, Arkansas, USA. The species were Echinochloa colona (L.) Link, E. crus-galli (L.) P. Beauv, E. muricata P. Beauv and E. walteri (Pursh). Only one accession was identified as E. walteri and was excluded from data analysis. Seeds were after-ripened for 6 months at room temperature and germinated at 32°C day/23°C night with 12-h daylength. Germination was monitored for 14 d. The Echinochloa species in Arkansas were predominantly E. colona (78%). E. colona had the highest seed production and the lowest seed dormancy among species. Dormancy within each species varied greatly, especially for E. colona, with a germination capacity (GC) of 41–99%. Only 2.7% of 73 E. colona accessions were dormant. E. crus-galli had 56–79% GC; 33% of the accessions were dormant. E. muricata had 2–39% germination, with all accessions considered dormant. E. colona had the highest fecundity, with 72,973 seeds per plant. This was 2.3- and 2.6x higher than that of E. crus-galli and E. muricata, respectively. High seed production and high germination capacity must have contributed to the dominance of E. colona among other Echinochloa species. E. muricata is expected to persist longer in the soil seedbank compared to E. colona and E. crus-galli. Seed production, dormancy and longevity will affect interspecies population dynamics in response to management tactics.
miR-103a-3p and miR-22-5p Are Reliable Reference Genes in Extracellular Vesicles From Cartilage, Adipose Tissue, and Bone Marrow Cells
Authors: Ragni Enrico , Colombini Alessandra , De Luca Paola , Libonati Francesca , Viganò Marco , Perucca Orfei Carlotta , Zagra Luigi , de Girolamo Laura
Published: February 2021

Cartilage cells (CCs), adipose tissue (ASC)- and bone marrow (BMSC)-derived mesenchymal stromal cells (MSCs) have been shown as promising candidates for the treatment of osteoarthritis (OA). Despite their adaptive ability, exposure to chronic catabolic and inflammatory processes can limit their survival and healing potential. An attractive cell-free alternative or complementary strategy is represented by their secreted extracellular vesicles (EVs), having homeostatic properties on OA chondrocytes and synovial cells. In view of clinical translation, a thorough characterization of the shuttled therapeutic molecules, like miRNAs, is greatly needed to fingerprint and develop the most effective EV formulation for OA treatment. To date, a crucial pitfall is given by the lack of EV-miRNA-associated reference genes (RGs) for the reliable quantification and comparison among different therapeutic EV-based therapeutic products. In this study, the stability of 12 putative miRNA RGs (let-7a-5p, miR-16-5p, miR-22-5p, miR-23a-3p, miR-26a-5p, miR-29a-5p, miR-101-3p, miR-103a-3p, miR-221-3p, miR-423-5p, miR-425-5p and miR-660-5p), already proposed by literature in EV products from alternative sources, was assessed in EVs isolated from three donor-matched ASCs, BMSCs, and CCs through geNorm, NormFinder, BestKeeper, and ΔCt algorithms and the geometric mean of rankings. ASC-EVs and BMSC-EVs shared more similar molecular signatures than cartilage-derived EVs, although overall miR-103a-3p consistently ranked as the first and miR-22-5p as the second most stable EV-miRNA RG, whereas miR-221-3p behaved poorly. Further, to emphasize the impact of incorrect RG choice, the abundance of four OA-therapeutic miRNAs (miR-93-5p, miR-125b-5p, miR-455-3p, and miR-27b-3p) was compared. The use of miR-221-3p led to less accurate EV fingerprinting and, when applied to sift therapeutic potency prediction, to misleading indication of the most appropriate clinical product. In conclusion, miR-103a-3p and miR-22-5p will represent reliable RGs for the quantification of miRNAs embedded in MSC- and CC-EVs, a mandatory step for the molecular definition and comparison of the clinical potency of these innovative cell-free-based therapeutic products for OA in particular, as well as for a wider array of regenerative-medicine-based approaches.
Hypoxia-Responsive Oxygen Nanobubbles for Tissues-Targeted Delivery in Developing Tooth Germs
Authors: Kim Eun-Jung , Lee Ji-Eun , Yoon Semi , Lee Dong-Joon , Mai Han Ngoc , Ida-Yonemochi Hiroko , Choi Jonghoon , Jung Han-Sung
Published: February 2021

Hypoxia is a state of inadequate supply of oxygen. Increasing evidence indicates that a hypoxic environment is strongly associated with abnormal organ development. Oxygen nanobubbles (ONBs) are newly developed nanomaterials that can deliver oxygen to developing tissues, including hypoxic cells. However, the mechanisms through which nanobubbles recover hypoxic tissues, such as developing tooth germs remain to be identified. In this study, tooth germs were cultured in various conditions: CO2chamber, hypoxic chamber, and with 20% ONBs for 3 h. The target stages were at the cap stage (all soft tissue) and bell stage (hard tissue starts to form). Hypoxic tooth germs were recovered with 20% ONBs in the media, similar to the tooth germs incubated in a CO2chamber (normoxic condition). The tooth germs under hypoxic conditions underwent apoptosis both at the cap and bell stages, and ONBs rescued the damaged tooth germs in both the cap and bell stages. Using kidney transplantation for hard tissue formationin vivo, amelogenesis and dentinogenesis imperfecta in hypoxic conditions at the bell stage were rescued with ONBs. Furthermore, glucose uptake by tooth germs was highly upregulated under hypoxic conditions, and was restored with ONBs to normoxia levels. Our findings indicate that the strategies to make use of ONBs for efficient oxygen targeted delivery can restore cellular processes, such as cell proliferation and apoptosis, glucose uptake, and hypomineralization in hypoxic environments.
Cardiac Imaging for Risk Assessment of Malignant Ventricular Arrhythmias in Patients With Mitral Valve Prolapse
Authors: Tayal Bhupendar , Delling Francesca N. , Malahfji Maan , Shah Dipan J.
Published: February 2021

Recent studies have described the occurrence of complex ventricular arrhythmias and sudden cardiac death among patients with mitral valve prolapse (MVP). The reported incidence rate of sudden cardiac death or ventricular tachycardia is about 1–1.5% among patients with MVP. Various imaging markers have been associated with this increased risk, including mitral annular disjunction, replacement fibrosis by late gadolinium enhancement, and mechanical dispersion. In this review, we briefly discuss how multimodality cardiac imaging can be applied to identify MVP patients with high risk of sudden cardiac death and complex ventricular arrhythmias.
Linking Aortic Mechanical Properties, Gene Expression and Microstructure: A New Perspective on Regional Weakening in Abdominal Aortic Aneurysms
Authors: Forneris Arianna , Kennard Jacob , Ismaguilova Alina , Shepherd Robert D. , Studer Deborah , Bromley Amy , Moore Randy D. , Rinker Kristina D. , Di Martino Elena S.
Published: February 2021

Background: Current clinical practice for the assessment of abdominal aortic aneurysms (AAA) is based on vessel diameter and does not account for the multifactorial, heterogeneous remodeling that results in the regional weakening of the aortic wall leading to aortic growth and rupture. The present study was conducted to determine correlations between a novel non-invasive surrogate measure of regional aortic weakening and the results from invasive analyses performed on corresponding ex vivo aortic samples. Tissue samples were evaluated to classify local wall weakening and the likelihood of further degeneration based on non-invasive indices.

Methods: A combined, image-based fluid dynamic and in-vivo strain analysis approach was used to estimate the Regional Aortic Weakness (RAW) index and assess individual aortas of AAA patients prior to elective surgery. Nine patients were treated with complete aortic resection allowing the systematic collection of tissue samples that were used to determine regional aortic mechanics, microstructure and gene expression by means of mechanical testing, microscopy and transcriptomic analyses.

Results: The RAW index was significantly higher for samples exhibiting lower mechanical strength (p = 0.035) and samples classified as low elastin content (p = 0.020). Samples with higher RAW index had the greatest number of genes differentially expressed compared to any constitutive metric. High RAW samples showed a decrease in gene expression for elastin and a down-regulation of pathways responsible for cell movement, reorganization of cytoskeleton, and angiogenesis.

Conclusions: This work describes the first AAA index free of assumptions for material properties and accounting for patient-specific mechanical behavior in relation to aneurysm strength. Use of the RAW index captured biomechanical changes linked to the weakening of the aorta and revealed changes in microstructure and gene expression. This approach has the potential to provide an improved tool to aid clinical decision-making in the management of aortic pathology.
Association of Mid- to Late-Life Blood Pressure Patterns With Risk of Subsequent Coronary Heart Disease and Death
Authors: Liu Menghui , Zhang Shaozhao , Chen Xiaohong , Zhong Xiangbin , Xiong Zhenyu , Yang Daya , Lin Yifen , Huang Yiquan , Li Yuqi , Wang Lichun , Zhuang Xiaodong , Liao Xinxue
Published: February 2021

Background: The elevated blood pressure (BP) at midlife or late-life is associated with cardiovascular disease and death. However, there is limited research on the association between the BP patterns from middle to old age and incident coronary heart disease (CHD) and death.

Methods: A cohort of the Atherosclerosis Risk in Communities (ARIC) Study enrolled 9,829 participants who attended five in-person visits from 1987 to 2013. We determined the association of mid- to late-life BP patterns with incident CHD and all-cause mortality using multivariable-adjusted Cox proportional hazards models.

Results: During a median of 16.7 years of follow-up, 3,134 deaths and 1,060 CHD events occurred. Compared with participants with midlife normotension, the adjusted hazard ratio for all-cause mortality and CHD was 1.14 (95% CI, 1.04–1.25) and 1.28 (95% CI, 1.10–1.50) in those with midlife hypertension, respectively. In further analyses, compared with a pattern of sustained normotension from mid- to late-life, there was no significant difference for the risk of incident death (HR, 1.15; 95% CI, 0.96–1.37) and CHD (HR, 1.33; 95% CI, 0.99–1.80) in participants with a pattern of midlife normotension and late-life hypertension with effective BP control. A higher risks of death and CHD were found in those with pattern of mid- to late-life hypertension with effective BP control (all-cause mortality: HR, 1.24; 95% CI, 1.08–1.43; CHD: HR, 1.65; 95% CI 1.30–2.09), pattern of midlife normotension and late-life hypertension with poor BP control (all-cause mortality: HR, 1.27; 95% CI, 1.12–1.44; CHD: HR, 1.53; 95% CI, 1.23–1.92), and pattern of mid- to late-life hypertension with poor BP control (all-cause mortality: HR, 1.49; 95% CI, 1.30–1.71; CHD: HR, 1.87; 95% CI, 1.48–2.37).

Conclusions: The current findings underscore that the management of elderly hypertensive patients should not merely focus on the current BP status, but the middle-aged BP status. To achieve optimal reductions in the risk of CHD and death, it may be necessary to prevent, diagnose, and manage of hypertension throughout middle age.
An Analysis of Japanese EFL Learners’ Lexical Network Changes
Authors: Aotani Noriko , Takahashi Shin’ya
Published: February 2021

In order to compare Japanese EFL learners’ lexical knowledge before and after undertaking extensive reading tasks, this study picked up eight words from the reading material and investigated how learners’ perceived relationship between these words changed during the task. Data were collected from 58 Japanese EFL learners who were divided into three groups, each of which was given the same reading material but with different tasks (translation task, multiple-choice question task, and no task (control)). Participants judged the degree of relationship between target words twice, before and after the assigned task. The results revealed that participants in the translation task group tended to find the relationships between the words more easily than the participants in other groups, and they were also more aware of changes in their own ability to recognize word association. In addition, the authors also analyzed the data by using AMISESCAL (Asymmetric von Mises Scaling), a statistical model that visualizes asymmetric relations among elements on a two-dimensional map. Visualization of learners’ lexical network threw some light on the restructuring process of how words were interconnected in their lexical representation.
Origins and History of the Minimal Model of Glucose Regulation
Authors: Bergman Richard N.
Published: February 2021

It has long been hoped that our understanding of the pathogenesis of diabetes would be helped by the use of mathematical modeling. In 1979 Richard Bergman and Claudio Cobelli worked together to find a “minimal model” based upon experimental data from Bergman’s laboratory. Model was chosen as the simplest representation based upon physiology known at the time. The model itself is two quasi-linear differential equations; one representing insulin kinetics in plasma, and a second representing the effects of insulin and glucose itself on restoration of the glucose after perturbation by intravenous injection. Model would only be sufficient if it included a delay in insulin action; that is, insulin had to enter a remote compartment, which was interstitial fluid (ISF). Insulin suppressed endogenous glucose output (by liver) slowly. Delay proved to be due to initial suppression of lipolysis; resultant lowering of free fatty acids reduced liver glucose output. Modeling also demanded that normalization of glucose after injection included an effect of glucose itself on glucose disposal and endogenous glucose production – these effects were termed “glucose effectiveness.” Insulin sensitivity was calculated from fitting the model to intravenous glucose tolerance test data; the resulting insulin sensitivity index, SI, was validated with the glucose clamp method in human subjects. Model allowed us to examine the relationship between insulin sensitivity and insulin secretion. Relationship was described by a rectangular hyperbola, such that Insulin Secretion x Insulin Sensitivity = Disposition Index (DI). Latter term represents ability of the pancreatic beta-cells to compensate for insulin resistance due to factors such as obesity, pregnancy, or puberty. DI has a genetic basis, and predicts the onset of Type 2 diabetes. An additional factor was clearance of insulin by the liver. Clearance varies significantly among animal or human populations; using the model, clearance was shown to be lower in African Americans than Whites (adults and children), and may be a factor accounting for greater diabetes prevalence in African Americans. The research outlined in the manuscript emphasizes the powerful approach by which hypothesis testing, experimental studies, and mathematical modeling can work together to explain the pathogenesis of metabolic disease.
Fructo-Oligosaccharides Modify Human DC Maturation and Peanut-Induced Autologous T-Cell Response of Allergic Patients In Vitro
Authors: Hayen Simone M. , Knulst André C. , Garssen Johan , Otten Henny G. , Willemsen Linette E. M.
Published: February 2021

Background

Dendritic cells (DCs) play an important role in antigen presentation, and are an interesting target for immune-modulation in allergies. Short- and long-chain fructo-oligosaccharides (scFOS/lcFOS, FF) have immunomodulatory capacities, and may influence the outcome of DC antigen presentation.

Objective

This study investigated the effect of FF during DC maturation and allergen presentation using cells of peanut-allergic patients in an autologous DC-T cell assay.

Methods

CD14+and CD4+T cells were isolated from peanut-allergic patients. CD14+monocytes were differentiated into immature DCs (imDCs), and matured (matDCs) in the presence or absence of crude peanut-extract (CPE) and/or FF, and co-cultured in an autologous DC-T cell assay. T cell polarization, proliferation and cytokine production were measured.

Results

Expression of maturation surface molecule markers on matDCs was not affected by CPE and/or FF. By contrast, the IL-10 secretion by matDCs increased compared to imDCs, upon exposure to CPE and FF compared to CPE alone. Also the IP-10 secretion increased in CPE/FF-matDCs compared to imDC. CPE-matDCs enhanced IL-13 release in the DC-T-cell assay and Treg polarization in presence or absence of FF. CPE/FF-DCs tended to increase the Treg/Th1 and Treg/Th2 ratios compared to matDCs. The proliferation of both Treg and Th2 cells tended to increase when T cells were co-cultured with CPE-matDCs compared to matDCs, which became significant when CPE-matDCs were also exposed to FF and a same tendency was shown for Th1 proliferation.

Conclusion

Only in the presence of FF, CPE-matDCs produced increased regulatory and Th1-related mediators. CPE-matDCs modified T cell polarization and proliferation, and additional exposure to FF tended to enhance Treg/Th2 and Treg/Th1 ratios instructed by CPE/FF-matDCs. However this effect was not strong enough to suppress CPE-matDCs induced IL-13 release by Th-cells. This indicates the ability of FF to modify DC maturation in the presence of an allergen supporting a more Treg/Th1 prone direction of the successive allergen specific Th2 cell response.
The Changes of Leukocytes in Brain and Blood After Intracerebral Hemorrhage
Authors: Mei Shuhao , Shao Yijie , Fang Yuanjian , Lu Jia'nan , Zheng Jingwei , Xu Shenbin , Wu Haijian , Sun Zeyu , Yu Jun , Chen Sheng , Wang Zhen , Zhang Jianmin
Published: February 2021

Preclinical and clinical research has demonstrated that inflammation is a critical factor regulating intracerebral hemorrhage (ICH)-induced brain injury. Growing evidence suggests that myeloid cells and lymphocytes have an effect on the pathophysiological processes associated with ICH, such as inflammation, immune responses, perihematomal edema formation, blood–brain barrier (BBB) integrity, and cell death. However, the underlying mechanisms remain largely unknown. We aimed to explore the role immune cells played at different stages of the ICH. To achieve this, novel bioinformatics algorithms were employed to analyze the gene expression profiles and three different analytical tools were utilized to predict the abundances of cell types. In this study, we found that natural killer (NK) cells infiltrated into the brain parenchyma after ICH. Infiltrating NK cells may mediate brain injury through degranulation and recruitment of other cells. Besides, in the acute phase of ICH, monocytes in peripheral blood carried out phagocytosis and secretion of cytokines. On the other hand, in the subacute stage, non-classical monocytes were activated and showed a stronger ability to carry out heme metabolism, wound healing, and antigen processing and presentation. In conclusion, our findings emphasize the significance of intracerebral infiltrating immunocytes in ICH and demonstrate that ICH is a systemic disease affected by peripheral blood. The hub genes identified might be promising therapeutic targets. We also provide a reference on how to use bioinformatics approaches to explore non-neoplastic immune-related diseases.
Novel Secreted Protein of Mycoplasma bovis MbovP280 Induces Macrophage Apoptosis Through CRYAB
Authors: Zhao Gang , Zhu Xifang , Zhang Hui , Chen Yingyu , Schieck Elise , Hu Changmin , Chen Huanchun , Guo Aizhen
Published: February 2021

Mycoplasma bovis causes important diseases and great losses on feedlots and dairy farms. However, there are only a few measures to control M. bovis-related diseases. As in other mycoplasma species, this is predominantly because the virulence related factors of this pathogen are largely unknown. Therefore, in this study, we aimed to identify novel virulence-related factors among the secreted proteins of M. bovis. Using bioinformatic tools to analyze its secreted proteins, we preliminarily predicted 39 secreted lipoproteins, and then selected 11 of them for confirmation based on SignalP scores >0.6 or SceP scores >0.8 and conserved domains. These 11 genes were cloned after gene modification based on the codon bias of Escherichia coli and expressed. Mouse antiserum to each recombinant protein was developed. A western blotting assay with these antisera confirmed that MbovP280 and MbovP475 are strongly expressed and secreted proteins, but only MbovP280 significantly reduced the viability of bovine macrophages (BoMac). In further experiments, MbovP280 induced the apoptosis of BoMac treated with both live M. bovis and MbovP280 protein. The conserved coiled-coil domain of MbovP280 at amino acids 210–269 is essential for its induction of apoptosis. Further, immunoprecipitation, mass spectrometry, and coimmunoprecipitation assays identified the anti-apoptosis regulator αB-crystallin (CRYAB) as an MbovP280-binding ligand. An αβ-crystallin knockout cell line BoMac-cryab−, Mbov0280-knockout M. bovis strain T9.297, and its complemented M. bovis strain CT9.297 were constructed and the apoptosis of BoMac-cryab− induced by these strains was compared. The results confirmed that CRYAB is critical for MbovP280 function as an apoptosis inducer in BoMac. In conclusion, in this study, we identified MbovP280 as a novel secreted protein of M. bovis that induces the apoptosis of BoMac via its coiled-coil domain and cellular ligand CRYAB. These findings extend our understanding of the virulence mechanism of mycoplasmal species.
Case Report: Anti-MOG Antibody Seroconversion Accompanied by Dimethyl Fumarate Treatment
Authors: Takahashi Keita , Takeuchi Hideyuki , Fukai Ryoko , Nakamura Haruko , Morihara Keisuke , Higashiyama Yuichi , Takahashi Toshiyuki , Doi Hiroshi , Tanaka Fumiaki
Published: February 2021

Here we report three cases of anti-myelin oligodendrocyte glycoprotein (MOG) antibody–associated disease (MOGAD) mimicking multiple sclerosis in which seropositivity for anti-MOG antibodies occurred during disease-modifying drug dimethyl fumarate (DMF) treatment. These patients developed relapses with anti-MOG antibody seroconversion after switching from fingolimod or steroid pulse therapy to DMF, which was associated with peripheral lymphocyte recovery. MOGAD is considered a humoral immune disease, and DMF reportedly enhances Th2-skewed humoral immune activity. Therefore, we suggest that DMF, but not fingolimod, may exacerbate humoral immune imbalance and enhance autoantibody production, leading to aggravation of MOGAD.
Bystander Memory T Cells and IMiD/Checkpoint Therapy in Multiple Myeloma: A Dangerous Tango?
Authors: Sponaas Anne Marit , Waage Anders , Vandsemb Esten N. , Misund Kristine , Børset Magne , Sundan Anders , Slørdahl Tobias Schmidt , Standal Therese
Published: February 2021

In this review article we discuss the role of the memory T cells in multiple myeloma (MM) and how they may influence immune responses in patients that received immunomodulating drugs and check point therapy.
Ecological Specialization Within a Carnivorous Fish Family Is Supported by a Herbivorous Microbiome Shaped by a Combination of Gut Traits and Specific Diet
Authors: Escalas Arthur , Auguet Jean-Christophe , Avouac Amandine , Seguin Raphaël , Gradel Antoine , Borrossi Lucie , Villéger Sébastien
Published: February 2021

Animals have been developing key associations with micro-organisms through evolutionary processes and ecological diversification. Hence, in some host clades, phylogenetic distance between hosts is correlated to dissimilarity in microbiomes, a pattern called phylosymbiosis. Teleost fishes, despite being the most diverse and ancient group of vertebrates, have received little attention from the microbiome perspective and our understanding of its determinants is currently limited. In this study, we assessed the gut microbiome of 12 co-occurring species of teleost representing a large breadth of ecological diversity and originating from a single family (i.e., the Sparidae). We tested how host evolutionary history, diet composition and morphological traits are related to fish gut microbiome. Despite fish species having different microbiomes, there is no phylosymbiosis signal in this fish family, but gut length and diet had a strong influence on the microbiome. We revealed that the only species with a specialized herbivorous diet, Sarpa salpa had a 3.3 times longer gut than carnivorous species and such a long gut favor the presence of anaerobic bacteria typical of herbivorous gut microbiomes. Hence, dietary uniqueness is paired with both unique gut anatomy and unique microbiome.
Fatal Adverse Events Associated With Immune Checkpoint Inhibitors in Non–small Cell Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Yu Xiaolin , Zhang Xiaomei , Yao Ting , Zhang Ye , Zhang Yanxia
Published: February 2021

Background: Immune checkpoint inhibitors (ICIs) have previously been reported to have a promising potential in terms of the improvement of outcomes in non–small cell lung cancer (NSCLC). Fatal adverse events (FAEs) of ICIs are relatively uncommon, and the incidence and risk in NSCLC remain unclear. In the present study, we conducted a systematic review and meta-analysis to evaluate the risk of FAEs in NSCLC patients administered with ICIs.

Methods: Potentially relevant studies were identified in PubMed, EMBASE, and Cochrane library database from inception to September 16, 2020. The systematic review and meta-analysis included randomized controlled trials that reported treatment-related FAEs in NSCLC. The pooled incidence and risk ratios (RRs) were calculated to evaluate prospective risk.

Results: Twenty clinical trials that included a total of 13,483 patients were selected for the meta-analysis. The overall incidence of FAEs was 0.65% [95% confidence interval (CI) = 0.31–1.07, I2 = 50.2%] in ICI monotherapy, 1.17% (95% CI = 0.74–1.69, I2 = 56.3%) in chemotherapy, and 2.01% (95% CI = 1.42–2.69, I2 = 5.9%) in the combination therapy (ICI and chemotherapy). ICI monotherapy was associated with lower incidence of FAEs caused by blood system disorders (RR = 0.23, 95% CI = 0.07–0.73, P = 0.013, I2 = 0%) and infectious diseases (RR = 0.29, 95% CI = 0.13–0.63, P = 0.002, I2 = 0%). The incidence of pneumonitis significantly increased in immunotherapy (RR = 5.72, 95% CI = 1.14–28.80, P = 0.03, I2 = 0%).

Conclusions: The results of the present study demonstrate that ICI monotherapy decreases the risk of FAEs, whereas the combined regimens with chemotherapy have the opposite tendency as compared to conventional chemotherapy. While the patients who received chemotherapy suffered the risks of death mainly from myelosuppression and infection, those who received immunotherapy were mainly threatened by immune-related pneumonitis.
Formalin Itch Test: Low-Dose Formalin Induces Histamine-Independent, TRPA1-Mediated Itch in Mice
Authors: Liu Xu , Zhang Jiang-Tao , Hu Yue , Shan Wen-Qi , Wang Zhi-Hong , Fu Qing-Yue , Fu Dan-Ni , Ji Jiang , Liu Tong
Published: February 2021

Chronic itch is a common distressing symptom of many diseases, which reduced patient's quality of life. The mechanistic study on itch and screening for new anti-itch drugs require the development of new pre-clinical itch animal models. Herein, we established an acute itch model by intradermal (i.d.) injection of low-dose formalin into the neck or cheek in mice. In mice, i.d. injection of formalin (0.1–5%) in the nape of the neck evoked robust scratching behavior in a dose-dependent manner and the dose–response curves showed an inverted “U” shape. I.d. injection of formalin (0.3–0.6%) into the cheek evoked scratching in mice but wiping in rats, while formalin (1.25–5%) induced mixed wiping and scratching behavior in both mice and rats. Further, we found that 0.3% formalin-induced scratching was histamine-independent and significantly attenuated by transient receptor potential ion channel A1 (TRPA1) inhibitor (HC030031) or in TRPA1 knockout (KO) mice, but not affected by transient receptor potential ion channel V1 (TRPV1) inhibitor (capsazepine) or in TRPV1 KO mice. Additionally, 0.3% formalin-induced up-regulation of phosphorylation of extracellular regulated protein kinases (p-ERK) in the dorsal root ganglion (DRG) and scratching were suppressed by intrathecal injection of MEK inhibitor U0126 in mice. Incubation of 0.03% formalin induced the accumulation of intracellular reactive oxygen species (ROS) in the cultured DRG-derived cell line ND7-23, and formalin-induced itch was suppressed by antioxidants in mice. Finally, perfusion of 0.03% formalin induced elevation of intracellular calcium in a subset of primary cultured DRG neurons of mice. Thus, these results indicate that low-dose formalin induced non-histaminergic itch by activation of TRPA1 in mice, which may be employed as a useful acute itch model for screening potential anti-itch drugs.
In vitro Models of the Blood–Brain Barrier: Tools in Translational Medicine
Authors: Williams-Medina Alberto , Deblock Michael , Janigro Damir
Published: February 2021

Medical progress has historically depended on scientific discoveries. Until recently, science was driven by technological advancements that, once translated to the clinic, fostered new treatments and interventions. More recently, technology-driven medical progress has often outpaced laboratory research. For example, intravascular devices, pacemakers for the heart and brain, spinal cord stimulators, and surgical robots are used routinely to treat a variety of diseases. The rapid expansion of science into ever more advanced molecular and genetic mechanisms of disease has often distanced laboratory-based research from day-to-day clinical realities that remain based on evidence and outcomes. A recognized reason for this hiatus is the lack of laboratory tools that recapitulate the clinical reality faced by physicians and surgeons. To overcome this, the NIH and FDA have in the recent past joined forces to support the development of a “human-on-a-chip” that will allow research scientists to perform experiments on a realistic replica when testing the effectiveness of novel experimental therapies. The development of a “human-on-a-chip” rests on the capacity to growin vitrovarious organs-on-a-chip, connected with appropriate vascular supplies and nerves, and our ability to measure and perform experiments on these virtually invisible organs. One of the tissue structures to be scaled down on a chip is the human blood–brain barrier. This review gives a historical perspective onin vitromodels of the BBB and summarizes the most recent 3D models that attempt to fill the gap between research modeling and patient care. We also present a summary of how thesein vitromodels of the BBB can be applied to study human brain diseases and their treatments. We have chosen NeuroAIDS, COVID-19, multiple sclerosis, and Alzheimer's disease as examples ofin vitromodel application to neurological disorders. Major insight pertaining to these illnesses as a consequence of more profound understanding of the BBB can reveal new avenues for the development of diagnostics, more efficient therapies, and definitive clarity of disease etiology and pathological progression.
The Rcs System in Enterobacteriaceae: Envelope Stress Responses and Virulence Regulation
Authors: Meng Jiao , Young Glenn , Chen Jingyu
Published: February 2021

The bacterial cell envelope is a protective barrier at the frontline of bacterial interaction with the environment, and its integrity is regulated by various stress response systems. The Rcs (regulator of capsule synthesis) system, a non-orthodox two-component regulatory system (TCS) found in many members of the Enterobacteriaceae family, is one of the envelope stress response pathways. The Rcs system can sense envelope damage or defects and regulate the transcriptome to counteract stress, which is particularly important for the survival and virulence of pathogenic bacteria. In this review, we summarize the roles of the Rcs system in envelope stress responses (ESRs) and virulence regulation. We discuss the environmental and intrinsic sources of envelope stress that cause activation of the Rcs system with an emphasis on the role of RcsF in detection of envelope stress and signal transduction. Finally, the different regulation mechanisms governing the Rcs system’s control of virulence in several common pathogens are introduced. This review highlights the important role of the Rcs system in the environmental adaptation of bacteria and provides a theoretical basis for the development of new strategies for control, prevention, and treatment of bacterial infections.
Metabolic Potential, Ecology and Presence of Associated Bacteria Is Reflected in Genomic Diversity of Mucoromycotina
Authors: Muszewska Anna , Okrasińska Alicja , Steczkiewicz Kamil , Drgas Olga , Orłowska Małgorzata , Perlińska-Lenart Urszula , Aleksandrzak-Piekarczyk Tamara , Szatraj Katarzyna , Zielenkiewicz Urszula , Piłsyk Sebastian , Malc Ewa , Mieczkowski Piotr , Kruszewska Joanna S. , Bernat Przemysław , Pawłowska Julia
Published: February 2021

Mucoromycotina are often considered mainly in pathogenic context but their biology remains understudied. We describe the genomes of six Mucoromycotina fungi representing distant saprotrophic lineages within the subphylum (i.e., Umbelopsidales and Mucorales). We selected two Umbelopsis isolates from soil (i.e., U. isabellina, U. vinacea), two soil-derived Mucor isolates (i.e., M. circinatus, M. plumbeus), and two Mucorales representatives with extended proteolytic activity (i.e., Thamnidium elegans and Mucor saturninus). We complement computational genome annotation with experimental characteristics of their digestive capabilities, cell wall carbohydrate composition, and extensive total lipid profiles. These traits inferred from genome composition, e.g., in terms of identified encoded enzymes, are in accordance with experimental results. Finally, we link the presence of associated bacteria with observed characteristics. Thamnidium elegans genome harbors an additional, complete genome of an associated bacterium classified to Paenibacillus sp. This fungus displays multiple altered traits compared to the remaining isolates, regardless of their evolutionary distance. For instance, it has expanded carbon assimilation capabilities, e.g., efficiently degrades carboxylic acids, and has a higher diacylglycerol:triacylglycerol ratio and skewed phospholipid composition which suggests a more rigid cellular membrane. The bacterium can complement the host enzymatic capabilities, alter the fungal metabolism, cell membrane composition but does not change the composition of the cell wall of the fungus. Comparison of early-diverging Umbelopsidales with evolutionary younger Mucorales points at several subtle differences particularly in their carbon source preferences and encoded carbohydrate repertoire. Nevertheless, all tested Mucoromycotina share features including the ability to produce 18:3 gamma-linoleic acid, use TAG as the storage lipid and have fucose as a cell wall component.
Molecular Mechanisms Behind Anti SARS-CoV-2 Action of Lactoferrin
Authors: Miotto Mattia , Di Rienzo Lorenzo , Bò Leonardo , Boffi Alberto , Ruocco Giancarlo , Milanetti Edoardo
Published: February 2021

Despite the huge effort to contain the infection, the novel SARS-CoV-2 coronavirus has rapidly become pandemic, mainly due to its extremely high human-to-human transmission capability, and a surprisingly high viral charge of symptom-less people. While the seek for a vaccine is still ongoing, promising results have been obtained with antiviral compounds. In particular, lactoferrin is regarded to have beneficial effects both in preventing and soothing the infection. Here, we explore the possible molecular mechanisms with which lactoferrin interferes with SARS-CoV-2 cell invasion, preventing attachment and/or entry of the virus. To this aim, we search for possible interactions lactoferrin may have with virus structural proteins and host receptors. Representing the molecular iso-electron surface of proteins in terms of 2D-Zernike descriptors, we 1) identified putative regions on the lactoferrin surface able to bind sialic acid present on the host cell membrane, sheltering the cell from the virus attachment; 2) showed that no significant shape complementarity is present between lactoferrin and the ACE2 receptor, while 3) two high complementarity regions are found on the N- and C-terminal domains of the SARS-CoV-2 spike protein, hinting at a possible competition between lactoferrin and ACE2 for the binding to the spike protein.