bluuebunny/crossref_metadata_2025 huggingface dataset:
Principi di immunobiologia del trapianto ed attivazione della risposta immune
Authors: Tsalouchos Aris , Salvadori Maurizio
Published: July 2021

To achieve an effective immune response it is important that T cells can recognize a wide variety of non-self antigens; this allows for restrained immune activation and subsequent antigen-specific killing. This task is accomplished through the generation of a repertoire of T cells in a single individual with specificity for an enormous number of potential foreign antigens presented as peptides on the surface of major histocompatibility complex (MHC) molecules. Variations in MHC structure among individuals increase the variety of peptides that can be presented to T cells; this mechanism protects the species as a whole by ensuring adequate T-cell responses to a given foreign organism. Although slightly different, these MHC polymorphisms expressed in the donor kidney are recognized after kidney transplantation between non genetically-identical humans, and induce alloresponses that in the absence of immunosuppression result in rejection of the allograft. In this chapter, we review basic immunological principles important to the field of kidney transplantation.
Densitometria ossea: una breve guida per il nefrologo
Authors: Iannuzzella Francesco , Pioli Giulio , Maiorana Mariarosa , Gregorini Mariacristina
Published: July 2021

Studies in patients with chronic kidney disease have definitively shown that “dual-energy X-ray absorptiometry” (DXA) may be helpful in assessing fracture risk. Moreover, it is essential to diagnose osteoporosis and evaluate response to treatment. In order to obtain the best utility from DXA, nephrologists need to know the fundamentals of this technique, its indications in clinical practice, and the potential pitfalls in the interpretation of its results. This review will provide an overview of the fundamentals, methodology, and current clinical applications of DXA with special focus on the nephrologist’s perspective.
…oltre la malattia: Medicina narrativa per una terapia dell’anima
Authors: Ciaccia Luigi
Published: July 2021

Purpose: A patient diagnosed with chronic kidney disease (CKD) is forced to reorganise his/her entire lifestyle according to the rhythm of dialysis, a life-saving therapy that becomes a life-long sentence. Slowly, the clinic becomes a prison of pain and frustration, worsening the symptoms and affecting the medical staff as well. Thus, I decided to work on the doctor-patient relationship in order to guide those under therapy in finding a new perception of themselves “beyond the disease”. Methods: In pursuing this goal, I adopted the methodology of narrative medicine, structured through three interviews: the first one on the disease; the second one on the past (i.e. emotions, fond memories, etc.); the third one on future projects. I also launched other weekly activities, such as sharing good news from the newspaper, watching movies, and organising outdoor activities. Results Throughout the project, I observed a significant improvement in the well-being of the patients, through a decrease in their stress levels and an increased response to therapy. Furthermore, I was able to establish a group dynamic among the patients as well as between them and the staff. Conclusions; At the end of the first year, the project was renewed, and its scope widened. We collected some photos and thoughts of the patients during our outdoor activities and published them in a book, which was given to the patients for Christmas, as the symbol of both the end of the first year and the start of another… beyond the disease. (narrative nephrology)
La terapia immunosoppressiva nel trapianto di rene
Authors: Tsalouchos Aris , Salvadori Maurizio
Published: July 2021

Immunosuppressive therapy in renal transplantation can be distinguished in induction therapy and maintenance therapy. Induction therapy is an intense immunosuppressive therapy administered at the time of kidney transplantation to reduce the risk of acute allograft rejection. In general, the induction immunosuppressive strategies used at kidney transplant centers fall into one of these two categories. One strategy relies upon high doses of conventional immunosuppressive agents, while the other utilizes antibodies directed against T-cell antigens in combination with lower doses of conventional agents. Maintenance immunosuppressive therapy is administered to almost all kidney transplant recipients to help prevent acute rejection and loss of the renal allograft. Although an adequate level of immunosuppression is required to dampen the immune response to the allograft, the level of chronic immunosuppression is decreased over time (as the risk of acute rejection decreases) to help lower the overall risk of infection and malignancy; these risks directly correlate with the degree of overall immunosuppression. The optimal maintenance immunosuppressive therapy in kidney transplantation is not established. The major immunosuppressive agents that are available in various combination regimens are glucocorticoids (primarily oral prednisone), azathioprine, mycophenolate mofetil (MMF), enteric-coated mycophenolate sodium (EC-MPS), cyclosporine (in non-modified or modified [microemulsion] form), Tacrolimus, everolimus, rapamycin (sirolimus), and Belatacept.
La voce del paziente: Accesso alla lista d’attesa e post trapianto: raccontaci la tua testimonianza. . .
Authors: Sternfeld Pavia Luisa
Published: July 2021

Abstract non richiesto.
Valutazione Del Benessere Psico-Fisico Nell’aderenza Terapeutica Nelle Donne Con Malattia Renale Policistica Autosomica Dominante: Uno Studio Osservazionale
Authors: Brioni Elena , Magnaghi Cristiano , Delli Zotti Giulia Bruna , Sangiovanni Eleonora , Sciarrone Alibrandi Maria Teresa , Apuzzo Luigi , Manunta Paolo , Logias Francesco , Burrai Francesco
Published: July 2021

BACKGROUND: Autosomal dominant polycystic kidney disease is the most common inherited renal disease and affects less than 1 every 400-1,000 people. There are many effective treatments, including blood pressure management, physical activity, low sodium diet and hydration. Therapeutic education is part of a patient’s care and treatment. This approach is an essential strategy in order to face the current healthcare scenario, in which the number of people affected by chronic diseases is progressively increasing. OBJECTIVES: This article aims to analyze the effect of therapeutic education in patients with ADPKD, the level of adherence to pharmacological therapy and their compliance to dietetic and lifestyle recommendations as part of a nursing-led education. METHODS: This is a prospective, longitudinal, observational pilot study. The following measurements were used: Kidney Disease Quality of life - Short Form, Hospital Anxiety and Depression Scale, Body Uneasiness Test. At the T0 visit, a nurse selected patients and carried out a personalized educational intervention with the aims of adhering to drug therapies, monitoring blood pressure and dietary behavior (physical activity and water intake). At the T1 visit, patients performed psychological tests. At the T2 visit, the following evaluations were performed: a psychological interview together with the delivery and evaluation of the tests performed, an interview with the nurse to evaluate the adherence to the prescriptions, and a control of parameters such as physical activity, diet, water intake, drug therapy, and blood pressure. RESULTS: Therapeutic education can have a positive impact on patients’ health by improving adherence to the pharmacological therapy, diet and lifestyle. CONCLUSIONS: Therapeutic education improve the patient’s knowledge, treatments and correct behaviors as well as promotes an independent management of the disease. Through an educational intervention, the patient acquires the ability and the awareness to modify the wrong behaviors and to guarantee a balance between his needs and the pathology, thus improving the quality of life.
ON INTERACTION OF MATERIAL AND PROCEDURAL LAW IN THE CONTEXT OF REFORMING THE NOMENCLATURE OF SCIENTIFIC SPECIALTIES IN JURISPRUDENCE
Authors: Suslova S.I.
Published: July 2021

Introduction: the influence of the material branches of law on the content and development of procedural branches has long been substantiated in the legal literature. At the same time, civil law scholars, limited by the scope of the nomenclature of scientific specialties in legal sciences, do not have the opportunity to conduct dissertation research aimed at identifying the influence of procedural branches on the norms of substantive law. With regard to scientific research, the study of such an impact is currently permissible only within the specialty 12.00.15. Reforming the nomenclature of scientific specialties towards its enlargement creates the basis for the development of the scientific theory of intersectoral relations, developed by M.Iu. Chelyshev. An in-depth study of the intersectoral interaction of civil law and civil procedure will contribute not only to the development of scientific knowledge, but also will allow solving practical problems at a different methodological level. Purpose: to analyze the stages of the formation of scientific specialties in the context of the relationship between civil law and procedure, to identify the advantages and disadvantages of uniting and dividing civil law and procedure in scientific research, to analyze dissertations in different periods of development of the science of civil law and the science of civil procedure, to formulate ways to improve directions of research to bridge the gap between the science of civil law and procedure. Methods: empirical methods of description, interpretation; theoretical methods of formal and dialectical logic. The legal-dogmatic private scientific method was used. Results: identified the main views on the ratio of material and procedural branches in legal science; it is illustrated that the intersectoral approach is currently admissible only for dissertations in the specialty 12.00.15, which led to an almost complete absence of scientific research on this topic in civil science; substantiated the need to establish the bilateral nature of the relationship and interaction of material and procedural block. Conclusions: reforming the nomenclature of scientific specialties by right in the direction of their enlargement should have a positive effect on bridging the gap that has developed between works on civil law and civil law procedure in the last years of their separate existence. This is especially true of civil science, which developed its own scientific theories in isolation from the possibilities of their implementation within the framework of procedural law. The methodological basis for solving these problems has already been formed – this is an intersectoral method, the application of which is justified and demonstrated in the works of M.Iu. Chelyshev.
The Correlation Between Adiponectin Levels With C-Reactive Protein in Adult Obese Non-Diabetic Among Staffs of DR. M. Djamil Hospital Padang
Authors: Putri Dian Eka , Yaswir Rismawati , Desywar Desywar , Efrida Efrida
Published: July 2021

The adiponectin and C-reactive protein (CRP) are markers of chronic low-grade inflammation related to obesity. This study aims to determine a correlation between adiponectin level and CRP level in adult obese individuals. This study was analyzed with a cross-sectional design of 55 subjects at Dr. M Jamil Central Hospital Padang from January to September 2019. The subjects included were type 1 obese (25≤BMI≤29.9 kg/m2) and type 2 obese (BMI 30.0 kg/m2). Enzyme-linked immunoassay (ELISA) was used to measure adiponectin and High Sensitivity C-Reactive Protein (Hs-CRP) levels. Univariate statistical analysis is processed and presented in distribution, frequency, mean (standard deviation), median (minimum-maximum value). Bivariate data were analyzed using the Pearson correlation test, significant if p<0.05. The study consists of 16 males and 39 females. The mean age was 35 years old (the range 23 to 57 years old), the mean BMI was 30.8 (4.5) kg/m2. This study consists of 28 subjects, type 1 obese and 27 types II obese. The mean adiponectin level in type 2 obese is lower than in type 2 obese groups. The mean CRP levels are high in all populations. Pearson ln-adiponectin and CRP correlation test in the entire population: r =-0.105 (p=0.444).
A Survival Analysis with Cox Regression Interaction Model of Type II Diabetes Mellitus in Indonesian
Authors: Lomo Simeftiany Indrilemta , Sugiyarto Sugiyarto , Darmawan Endang
Published: July 2021

Type II diabetes mellitus is a metabolic syndrome characterized by hyperglycemia. Diabetes is still one of the world's health threats where the number of people with disabilities and mortality rates continue to increase over time. This study aims to analyze the survival of patients with type II diabetes mellitus as well as factors that affect it using survival analysis.  This study used medical record data of type II diabetes mellitus patients undergoing treatment for the period 2015-2019 at PKU Muhammadiyah Gamping Hospital and PKU Muhammadiyah Hospital Yogyakarta.
Detección del riesgo de corrosión al lado de las reparaciones por parcheo
Authors: Andrade Perdrix María del Carmen , Castro-Borges P. , Pazini Enio
Published: July 2021

En general, la corrosión genera fisuras paralelas a las armaduras que aparecen aleatoriamente produciendo un saltado del recubrimiento irregular. Durante la inspección para definir el plan de reparación por parcheo las áreas más fisuradas se consideran como las más corroídas. A su vez, se toma como unidad de área a reparar la extensión de las áreas fisuradas. Sin embargo, como la extensión corroída es mayor que la fisurada, el daño reaparece en años posteriores. La cantidad de área a reparar es pues un aspecto que tiene implicaciones económicas y de seguridad. En el presente trabajo se discute la posibilidad de crear pares galvánicos entre las zonas reparadas y las adyacentes. El articulo también aborda el efecto del uso de imprimaciones de la armadura y el uso de “puentes de unión” entre el hormigón original y el material de reparación. También se describen las tres técnicas que se pueden utilizar para determinar cuánto hormigón contaminado debe retirarse: dos tipos de análisis químico (medida del pH o del contenido de cloruros) y medida de los parámetros de corrosión (velocidad de corrosion) en las áreas fisuradas o adyacentes a la zona reparada.
Minority Viewpoint: Capturing Ethnic Minority Voices in Renfrewshire
Authors: Ishaq Mohammed , Hussain Asifa Maaria , Ilyas Muhammad
Published: July 2021

The research reported in this paper is an abridged version of a study exploring the views of ethnic minority communities in Renfrewshire. The study provided a voice to these communities in relation to their awareness of Renfrewshire Council's services and initiatives targeting ethnic minority groups. The study also surveyed the extent to which ethnic minorities engage with ethnic minority organisations designed to support their needs, the challenges they face and how they feel they are viewed by the indigenous ‘white’ community. Based on a series of focus groups, the findings reveal a lack of awareness among participants of Council services and initiatives aimed at ethnic minority communities. There is a varied level of engagement with ethnic minority voluntary and third sector organisations, a range of challenges including language barriers, perceived and actual racism, and some apprehension as to how ethnic minority groups are perceived by the indigenous white community. There are implications for key stakeholders such as the Council and others who should review their policies and practices to ensure that the needs and concerns of ethnically diverse communities in Renfrewshire are being addressed.
Estado nutricional y caries de infancia temprana en niños de 0 a 3 años: Revisión de la literatura
Authors: Arévalo Illescas Paola Lisseth , Cuenca León Katherine , Vélez León Eleonor , Villavicencio Coral Bryan
Published: July 2021

Objective: To compile information relating nutritional status and early childhood caries in children aged 0 to 3 years. Materials and methods: Search was made of scientific articles from November 2020 to January 2021 in both Spanish and English in databases such as: Google Scholar, Scielo, Pubmed, Dialnet, Science Direct, with the use of the keywords: dental caries, eating behavior, breastfeeding, demineralization, sucrose. Including original articles and literature review articles. Excluding articles that did not pertain to the subject of nutrition and caries. Results: Early childhood caries begins shortly after tooth eruption and is most frequently transmitted vertically (from mother to child), with Streptococcus mutans, being the most cariogenic microorganism. It has been demonstrated in several studies that malnutrition is not related to early childhood caries, but excessive consumption of sugars, breastfeeding and frequent nighttime bottle-feeding are. For this reason, fluoride toothpastes (1000-1100 ppm of fluoride) should be used in infants between 0 and 3 years of age in order to eliminate bacterial plaque and the formation of dental caries. Conclusions: There is a close relationship between nutrition and dental caries in children 0-3 years of age, but the most important factor is the intervention of parents in the application of oral care in infants; it is important to know the sugar content of foods in order to prevent the development of early childhood caries.
INTERAÇÕES NA SALA DE AULA:
Authors: Lima Eliane Soares de
Published: July 2021

Em face do discurso de mudança fortalecido pela publicação dos últimos referenciais curriculares nacionais, propompos discutir a transformação imposta à prática dos professores do ensino básico. O objetivo é o de apresentar uma racionalização da atividade docente concebida em sua dimensão narrativa, ou seja, como ação que constrói no seu desenrolar a significação de uma situação regida por códigos de conduta, normas e procedimentos (pré-)estabelecidos. Para isso, examinaremos as mudanças ocorridas na dinâmica de funcionamento narrativo da prática didático-pedagógica tradicional a esta que se tem chamado de renovada. Espera-se, assim, poder colaborar de alguma maneira com a necessidade de esclarecimento e divulgação, entre os professores, sobre essa problemática.
A CONSTITUIÇÃO DA DIALOGIA EM BAKHTIN E FREIRE: CONVERGÊNCIAS DISCURSIVAS EM PRODUÇÕES TEXTUAIS DO GÊNERO AUTOBIOGRÁFICO COM ALUNOS DA EJA
Authors: Cardoso Elma Karine Costa , Gusmão Maria Aparecida Pacheco
Published: July 2021

Este texto tem por objetivo apresentar os resultados de um estudo sobre a produção textual de textos autobiográficos dos alunos da Educação de Jovens e Adultos.  A pesquisa foi realizada em uma escola pública estadual da cidade de Vitória da Conquista, Bahia. As narrativas autobiográficas dos alunos foram produzidas com atividades interventivas com vistas a trabalhar categorias previamente estabelecidas. Neste artigo, abordamos três dessas categorias. A análise dos dados das produções iniciais e finais de textos autobiográficos apontou para um crescimento em três categorias, pois os educandos representaram os elementos estruturais do gênero, apontaram as várias vozes discursivas constituídas na interação social e também evidenciaram a importância da escola como meio de libertação e empoderamento social.
DISCUSSÃO DE GRUPO ALIADA A TECNOLOGIA DIGITAL DE INFORMAÇÃO E COMUNICAÇÃO NO PROCESSO DE DESENVOLVIMENTO DA ESCRITA
Authors: Gitahy Raquel Rosan Christino , FERNANDEZ ARTEMISA PIAI SILVA DE , Terçariol Adriana Aparecida de Lima
Published: July 2021

O presente artigo objetiva investigar como a discussão de grupo, aliada a tecnologia digital da informação e comunicação, influi no desenvolvimento da produção de textos dissertativos. Foram participantes da pesquisa um grupo de 06 (seis) estudantes de um curso particular de redação, com idades entre 18 (dezoito) e 25 (vinte e cinco) anos. Os dados foram coletados combinando-se a observação da discussão em grupo e análise documental de textos dissertativos produzidos. Conclui-se que o grupo de discussão auxiliou na aprendizagem colaborativa e no desenvolvimento do pensamento crítico, possibilitando com que o aluno mostrasse conhecimento em seu texto escrito sobre o que estava dizendo; a quem estava dizendo; as estratégias de dizer e se colocasse como autor do texto.
SERS-Based Evaluation of the DNA Methylation Pattern Associated With Progression in Clonal Leukemogenesis of Down Syndrome
Authors: Moisoiu Vlad , Sas Valentina , Stefancu Andrei , Iancu Stefania D. , Jurj Ancuta , Pasca Sergiu , Iluta Sabina , Zimta Alina-Andreea , Tigu Adrian B. , Teodorescu Patric , Turcas Cristina , Blag Cristina , Dima Delia , Popa Gheorghe , Arghirescu Smaranda , Man Sorin , Colita Anca , Leopold Nicolae , Tomuleasa Ciprian
Published: July 2021

Here we show that surface-enhanced Raman scattering (SERS) analysis captures the relative hypomethylation of DNA from patients with acute leukemia associated with Down syndrome (AL-DS) compared with patients diagnosed with transient leukemia associated with Down syndrome (TL-DS), an information inferred from the area under the SERS band at 1005 cm–1 attributed to 5-methycytosine. The receiver operating characteristic (ROC) analysis of the area under the SERS band at 1005 cm–1 yielded an area under the curve (AUC) of 0.77 in differentiating between the AL-DS and TL-DS groups. In addition, we showed that DNA from patients with non-DS myeloproliferative neoplasm (non-DS-MPN) is hypomethylated compared to non-DS-AL, the area under the SERS band at 1005 cm–1 yielding an AUC of 0.78 in separating between non-DS-MPN and non-DS-AL. Overall, in this study, the area of the 1005 cm–1 DNA SERS marker band shows a stepwise decrease in DNA global methylation as cells progress from a pre-leukemia to a full-blown acute leukemia, highlighting thus the potential of SERS as an emerging method of analyzing the methylation landscape of DNA in the context of leukemia genesis and progression.
Ribose-Binding Protein Mutants With Improved Interaction Towards the Non-natural Ligand 1,3-Cyclohexanediol
Authors: Tavares Diogo , van der Meer Jan Roelof
Published: July 2021

Bioreporters consist of genetically modified living organisms that respond to the presence of target chemical compounds by production of an easily measurable signal. The central element in a bioreporter is a sensory protein or aptamer, which, upon ligand binding, modifies expression of the reporter signal protein. A variety of naturally occurring or modified versions of sensory elements has been exploited, but it has proven to be challenging to generate elements that recognize non-natural ligands. Bacterial periplasmic binding proteins have been proposed as a general scaffold to design receptor proteins for non-natural ligands, but despite various efforts, with only limited success. Here, we show how combinations of randomized mutagenesis and reporter screening improved the performance of a set of mutants in the ribose binding protein (RbsB) of Escherichia coli, which had been designed based on computational simulations to bind the non-natural ligand 1,3-cyclohexanediol (13CHD). Randomized mutant libraries were constructed that used the initially designed mutants as scaffolds, which were cloned in an appropriate E. coli bioreporter system and screened for improved induction of the GFPmut2 reporter fluorescence in presence of 1,3-cyclohexanediol. Multiple rounds of library screening, sorting, renewed mutagenesis and screening resulted in 4.5-fold improvement of the response to 1,3-cyclohexanediol and a lower detection limit of 0.25 mM. All observed mutations except one were located outside the direct ligand-binding pocket, suggesting they were compensatory and helping protein folding or functional behavior other than interaction with the ligand. Our results thus demonstrate that combinations of ligand-binding-pocket redesign and randomized mutagenesis can indeed lead to the selection and recovery of periplasmic-binding protein mutants with non-natural compound recognition. However, current lack of understanding of the intermolecular movement and ligand-binding in periplasmic binding proteins such as RbsB are limiting the rational production of further and better sensory mutants.
Innate Immune Cells in Pressure Overload-Induced Cardiac Hypertrophy and Remodeling
Authors: Liu Xin , Shi Guo-Ping , Guo Junli
Published: July 2021

Pressure overload and heart failure are among the leading causes of cardiovascular morbidity and mortality. Accumulating evidence suggests that inflammatory cell activation and release of inflammatory mediators are of vital importance during the pathogenesis of these cardiac diseases. Yet, the roles of innate immune cells and subsequent inflammatory events in these processes remain poorly understood. Here, we outline the possible underlying mechanisms of innate immune cell participation, including mast cells, macrophages, monocytes, neutrophils, dendritic cells, eosinophils, and natural killer T cells in these pathological processes. Although these cells accumulate in the atrium or ventricles at different time points after pressure overload, their cardioprotective or cardiodestructive activities differ from each other. Among them, mast cells, neutrophils, and dendritic cells exert detrimental function in experimental models, whereas eosinophils and natural killer T cells display cardioprotective activities. Depending on their subsets, macrophages and monocytes may exacerbate cardiodysfunction or negatively regulate cardiac hypertrophy and remodeling. Pressure overload stimulates the secretion of cytokines, chemokines, and growth factors from innate immune cells and even resident cardiomyocytes that together assist innate immune cell infiltration into injured heart. These infiltrates are involved in pro-hypertrophic events and cardiac fibroblast activation. Immune regulation of cardiac innate immune cells becomes a promising therapeutic approach in experimental cardiac disease treatment, highlighting the significance of their clinical evaluation in humans.
NAP1L1 Functions as a Tumor Promoter via Recruiting Hepatoma-Derived Growth Factor/c-Jun Signal in Hepatocellular Carcinoma
Authors: Zhang Ye-wei , Chen Qian , Li Bo , Li Hai-Yang , Zhao Xue-Ke , Xiao Yan-yi , Liu Shu , Zuo Shi
Published: July 2021

NAP1L1 has been reported to be significantly involved in the carcinogenesis of hepatocellular carcinoma (HCC). Yet, its detailed molecular basis is still to be determined. Based on the analysis of The Cancer Genome Atlas (TCGA) database, NAP1L1 mRNA was found to be upregulated and predicted the poor prognosis initially. Subsequently, consistent with the prediction, the upregulated expression of NAP1L1 mRNA and protein levels was confirmed by quantitative polymerase chain reaction (qPCR), Western blot, and immunohistochemistry assays. Upregulated NAP1L1 protein positively promoted the disease progression and poor prognosis of HCC. In addition, NAP1L1 protein expression was considered as an independent prognostic factor in HCC. Inhibition of NAP1L1 expression by siRNA or shRNA pathway significantly reduced the cell proliferation and cell cycle transformation in vitro and in vivo. Mechanism analysis first showed that the function of NAP1L1 was to recruit hepatoma-derived growth factor (HDGF), an oncogene candidate widely documented in tumors. Furthermore, the latter interacted with c-Jun, a key oncogenic transcription factor that can induce the expression of cell cycle factors and thus stimulate the cell growth in HCC. Finally, transfecting HDGF or c-Jun could reverse the suppressive effects on HCC growth in NAP1L1-suppressed HCC cells. Our data indicate that NAP1L1 is a potential oncogene and acts via recruiting HDGF/c-Jun in HCC.
Identification of a Novel Immune Landscape Signature for Predicting Prognosis and Response of Endometrial Carcinoma to Immunotherapy and Chemotherapy
Authors: Liu Jinhui , Wang Yichun , Mei Jie , Nie Sipei , Zhang Yan
Published: July 2021

Uterine Corpus Endometrial Carcinoma (UCEC) is the most common gynecological cancer. Here, we have investigated the significance of immune-related genes in predicting the prognosis and response of UCEC patients to immunotherapy and chemotherapy. Based on the Cancer Genome Atlas (TCGA) database, the single-sample gene-set enrichment analysis (ssGSEA) scores was utilized to obtain enrichment of 29 immune signatures. Univariate, multivariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to generate an immune-related prognostic signature (IRPS). The biological functions of IRPS-associated genes were evaluated using GSEA, Tumor Immune Estimation Resource (TIMER) Database analysis, Mutation analysis, Immunophenoscore (IPS) analysis, Gene Expression Profiling Interactive Analysis (GEPIA), Genomics of Drug Sensitivity in Cancer (GDSC) and Immune Cell Abundance Identifier (ImmuCellAI). Potential small molecule drugs for UCEC were predicted using the connectivity map (Cmap). The mRNA and protein expression levels of IRPS-associated genes were tested via quantitative real-time PCR (qPCR) and immunohistology. Two immune-related genes (CCL13 and KLRC1) were identified to construct the IRPS. Both genes were related to the prognosis of UCEC patients (P < 0.05). The IRPS could distinguish patients with different prognosis and was closely associated with the infiltration of several types of immune cells. Our findings showed that patients with low IRPS benefited more from immunotherapy and developed stronger response to several chemotherapies, which was also confirmed by the results of ImmuCellAI. Finally, we identified three small molecular drugs that might improve the prognosis of patients with high IRPS. IRPS can be utilized to predict the prognosis of UCEC patients and provide valuable information about their therapeutic response to immunotherapy and chemotherapy.
Extracellular Vesicle-Based Detection of Pancreatic Cancer
Authors: Verel-Yilmaz Yesim , Fernández Juan Pablo , Schäfer Agnes , Nevermann Sheila , Cook Lena , Gercke Norman , Helmprobst Frederik , Jaworek Christian , Pogge von Strandmann Elke , Pagenstecher Axel , Bartsch Detlef K. , Bartsch Jörg W. , Slater Emily P.
Published: July 2021

Due to a grim prognosis, there is an urgent need to detect pancreatic ductal adenocarcinoma (PDAC) prior to metastasis. However, reliable diagnostic imaging methods or biomarkers for PDAC or its precursor lesions are still scarce. ADAM8, a metalloprotease-disintegrin, is highly expressed in PDAC tissue and negatively correlates with patient survival. The aim of our study was to determine the ability of ADAM8-positive extracellular vesicles (EVs) and cargo microRNAs (miRNAs) to discriminate precursor lesions or PDAC from healthy controls. In order to investigate enrichment of ADAM8 on EVs, these were isolated from serum of patients with PDAC (n = 52), precursor lesions (n = 7) and healthy individuals (n = 20). Nanoparticle Tracking Analysis and electron microscopy indicated successful preparation of EVs that were analyzed for ADAM8 by FACS. Additionally, EV cargo analyses of miRNAs from the same serum samples revealed the presence of miR-720 and miR-451 by qPCR and was validated in 20 additional PDAC samples. Statistical analyses included Wilcoxon rank test and ROC curves. FACS analysis detected significant enrichment of ADAM8 in EVs from patients with PDAC or precursor lesions compared to healthy individuals (p = 0.0005). ADAM8-dependent co-variates, miR-451 and miR-720 were also diagnostic, as patients with PDAC had significantly higher serum levels of miR-451 and lower serum levels of miR-720 than healthy controls and reached high sensitivity and specificity (AUC = 0.93 and 1.00, respectively) to discriminate PDAC from healthy control. Thus, detection of ADAM8-positive EVs and related cargo miR-720 and miR-451 may constitute a specific biomarker set for screening individuals at risk for PDAC.
Distinct Signaling Pathways Distinguish in vivo From in vitro Growth in Murine Ovarian Follicle Activation and Maturation
Authors: Amoushahi Mahboobeh , Lykke-Hartmann Karin
Published: July 2021

Women with cancer and low ovarian reserves face serious challenges in infertility treatment. Ovarian tissue cryopreservation is currently used for such patients to preserve fertility. One major challenge is the activation of dormant ovarian follicles, which is hampered by our limited biological understanding of molecular determinants that activate dormant follicles and help maintain healthy follicles during growth. Here, we investigated the transcriptomes of oocytes isolated from dormant (primordial) and activated (primary) follicles under in vivo and in vitro conditions. We compared the biological relevance of the initial molecular markers of mature metaphase II (MII) oocytes developed in vivo or in vitro. The expression levels of genes involved in the cell cycle, signal transduction, and Wnt signaling were highly enriched in oocytes from primary follicles and MII oocytes. Interestingly, we detected strong downregulation of the expression of genes involved in mitochondrial and reactive oxygen species (ROS) production in oocytes from primordial follicles, in contrast to oocytes from primary follicles and MII oocytes. Our results showed a dynamic pattern in mitochondrial and ROS production-related genes, emphasizing their important role(s) in primordial follicle activation and oocyte maturation. The transcriptome of MII oocytes showed a major divergence from that of oocytes of primordial and primary follicles.
p73 as a Tissue Architect
Authors: Maeso-Alonso Laura , López-Ferreras Lorena , Marques Margarita M. , Marin Maria C.
Published: July 2021

The TP73 gene belongs to the p53 family comprised by p53, p63, and p73. In response to physiological and pathological signals these transcription factors regulate multiple molecular pathways which merge in an ensemble of interconnected networks, in which the control of cell proliferation and cell death occupies a prominent position. However, the complex phenotype of the Trp73 deficient mice has revealed that the biological relevance of this gene does not exclusively rely on its growth suppression effects, but it is also intertwined with other fundamental roles governing different aspects of tissue physiology. p73 function is essential for the organization and homeostasis of different complex microenvironments, like the neurogenic niche, which supports the neural progenitor cells and the ependyma, the male and female reproductive organs, the respiratory epithelium or the vascular network. We propose that all these, apparently unrelated, developmental roles, have a common denominator: p73 function as a tissue architect. Tissue architecture is defined by the nature and the integrity of its cellular and extracellular compartments, and it is based on proper adhesive cell-cell and cell-extracellular matrix interactions as well as the establishment of cellular polarity. In this work, we will review the current understanding of p73 role as a neurogenic niche architect through the regulation of cell adhesion, cytoskeleton dynamics and Planar Cell Polarity, and give a general overview of TAp73 as a hub modulator of these functions, whose alteration could impinge in many of the Trp73–/– phenotypes.
Recent Advances in Mass Spectrometry-Based Glycomic and Glycoproteomic Studies of Pancreatic Diseases
Authors: Tabang Dylan Nicholas , Ford Megan , Li Lingjun
Published: July 2021

Modification of proteins by glycans plays a crucial role in mediating biological functions in both healthy and diseased states. Mass spectrometry (MS) has emerged as the most powerful tool for glycomic and glycoproteomic analyses advancing knowledge of many diseases. Such diseases include those of the pancreas which affect millions of people each year. In this review, recent advances in pancreatic disease research facilitated by MS-based glycomic and glycoproteomic studies will be examined with a focus on diabetes and pancreatic cancer. The last decade, and especially the last five years, has witnessed developments in both discovering new glycan or glycoprotein biomarkers and analyzing the links between glycans and disease pathology through MS-based studies. The strength of MS lies in the specificity and sensitivity of liquid chromatography-electrospray ionization MS for measuring a wide range of biomolecules from limited sample amounts from many sample types, greatly enhancing and accelerating the biomarker discovery process. Furthermore, imaging MS of glycans enabled by matrix-assisted laser desorption/ionization has proven useful in complementing histology and immunohistochemistry to monitor pancreatic disease progression. Advances in biological understanding and analytical techniques, as well as challenges and future directions for the field, will be discussed.
Rule Talk: Instructing Proper Play With Impersonal Deontic Statements
Authors: Zinken Jörg , Kaiser Julia , Weidner Matylda , Mondada Lorenza , Rossi Giovanni , Sorjonen Marja-Leena
Published: July 2021

The present paper explores how rules are enforced and talked about in everyday life. Drawing on a corpus of board game recordings across European languages, we identify a sequential and praxeological context for rule talk. After a game rule is breached, a participant enforces proper play and then formulates a rule with an impersonal deontic statement (e.g. “It’s not allowed to do this”). Impersonal deontic statements express what may or may not be done without tying the obligation to a particular individual. Our analysis shows that such statements are used as part of multi-unit and multi-modal turns where rule talk is accomplished through both grammatical and embodied means. Impersonal deontic statements serve multiple interactional goals: they account for having changed another’s behavior in the moment and at the same time impart knowledge for the future. We refer to this complex action as an “instruction.” The results of this study advance our understanding of rules and rule-following in everyday life, and of how resources of language and the body are combined to enforce and formulate rules.
Metformin Suppresses the Progress of Diabetes-Accelerated Atherosclerosis by Inhibition of Vascular Smooth Muscle Cell Migration Through AMPK–Pdlim5 Pathway
Authors: Yan Yi , Li Ting , Li Zhonghao , He Mingyuan , Wang Dejiang , Xu Yingyi , Yang Xuewen , Bai Yuanyuan , Lao Yi , Zhang Zhiyong , Wu Wei
Published: July 2021

Backgrounds: Our previous work revealed that AMP-activated protein kinase (AMPK) activation inhibits vascular smooth muscle cell migration in vitro by phosphorylating PDZ and LIM domain 5 (Pdlim5). As metformin is an AMPK activator, we used a mouse vascular smooth muscle cell (VSMC) line and a Myh11-cre-EGFP mice to investigate whether metformin could inhibit the migration of VSMCs in vitro and in a wire-injury model in vivo. It is recognized that VSMCs contribute to the major composition of atherosclerotic plaques. In order to investigate whether the AMPK–Pdlim5 pathway is involved in the protective function of metformin against atherosclerosis, we utilized ApoE−/− male mice to investigate whether metformin could suppress diabetes-accelerated atherosclerosis by inhibition of VSMC migration via the AMPK–Pdlim5 pathway.

Methods: The mouse VSMC cell line was exogenously transfected wild type, phosphomimetic, or unphosphorylatable Pdlim5 mutant before metformin exposure. Myh11-cre-EGFP mice were treated with saline solution or metformin after these were subjected to wire injury in the carotid artery to study whether metformin could inhibit the migration of medial VSMCs into the neo-intima. In order to investigate whether the AMPK–Pdlim5 pathway is involved in the protective function of metformin against atherosclerosis, ApoE−/− male mice were divided randomly into control, streptozocin (STZ), and high-fat diet (HFD)-induced diabetes mellitus; STZ+HFD together with metformin or Pdlim5 mutant carried the adenovirus treatment groups.

Results: It was found that metformin could induce the phosphorylation of Pdlim5 and inhibit cell migration as a result. The exogenous expression of phosphomimetic S177D-Pdlim5 inhibits lamellipodia formation and migration in VSMCs. It was also demonstrated that VSMCs contribute to the major composition of injury-induced neointimal lesions, while metformin could alleviate the occlusion of the carotid artery. The data of ApoE−/− mice showed that increased plasma lipids and aggravated vascular smooth muscle cell infiltration into the atherosclerotic lesion in diabetic mice were observed Metformin alleviated diabetes-induced metabolic disorders and atherosclerosis and also reduced VSMC infiltration in atherosclerotic plaques, while the Pdlim5 phospho-abolished mutant that carried adenovirus S177A-Pdlim5 undermines the protective function of metformin.

Conclusions: The activation of the AMPK–Pdlim5 pathway by metformin could interrupt the migratory machine of VSMCs and inhibit cell migration in vitro and in vivo. The maintenance of AMPK activity by metformin is beneficial for suppressing diabetes-accelerated atherosclerosis.
Research('s) Sweet Hearts: Experimental Biomedical Models of Diabetic Cardiomyopathy
Authors: Richter Claudia , Hinkel Rabea
Published: July 2021

Diabetes and the often accompanying cardiovascular diseases including cardiomyopathy represent a complex disease, that is reluctant to reveal the molecular mechanisms and underlying cellular responses. Current research projects on diabetic cardiomyopathy are predominantly based on animal models, in which there are not only obvious advantages, such as genetics that can be traced over generations and the directly measurable influence of dietary types, but also not despisable disadvantages. Thus, many studies are built up on transgenic rodent models, which are partly comparable to symptoms in humans due to their genetic alterations, but on the other hand are also under discussion regarding their clinical relevance in the translation of biomedical therapeutic approaches. Furthermore, a focus on transgenic rodent models ignores spontaneously occurring diabetes in larger mammals (such as dogs or pigs), which represent with their anatomical similarity to humans regarding their cardiovascular situation appealing models for testing translational approaches. With this in mind, we aim to shed light on the currently most popular animal models for diabetic cardiomyopathy and, by weighing the advantages and disadvantages, provide decision support for future animal experimental work in the field, hence advancing the biomedical translation of promising approaches into clinical application.
The Link Between Ferroptosis and Cardiovascular Diseases: A Novel Target for Treatment
Authors: Hu Huilin , Chen Yunqing , Jing Lele , Zhai Changlin , Shen Liang
Published: July 2021

Ferroptosis is an iron-dependent cell death, which is characterized by iron overload and lipid peroxidation. Ferroptosis is distinct from apoptosis, necroptosis, autophagy, and other types of cell death in morphology and function. Ferroptosis is regulated by a variety of factors and controlled by several mechanisms, including mitochondrial activity and metabolism of iron, lipid, and amino acids. Accumulating evidence shows that ferroptosis is closely related to a majority of cardiovascular diseases (CVDs), including cardiomyopathy, myocardial infarction, ischemia/reperfusion injury, heart failure, and atherosclerosis. This review summarizes the current status of ferroptosis and discusses ferroptosis as a potential therapeutic target for CVDs.
The Influence of Weathering, Water Sources, and Hydrological Cycles on Lithium Isotopic Compositions in River Water and Groundwater of the Ganges–Brahmaputra–Meghna River System in Bangladesh
Authors: Yoshimura Toshihiro , Araoka Daisuke , Kawahata Hodaka , Hossain H. M. Zakir , Ohkouchi Naohiko
Published: July 2021

The silicate weathering of continental rocks plays a vital role in determining ocean chemistry and global climate. Spatiotemporal variations in the Li isotope ratio (δ7Li) of terrestrial waters can be used to identify regimes of current and past weathering processes. Here we examine: 1) monthly dissolved δ7Li variation in the Ganges River’s lower reaches; and 2) the spatiotemporal variation of river water of the Brahmaputra, Meghna rivers, and groundwater in Bangladesh. From the beginning to maximum flood discharges of the rainy season (i.e., from June to September), Li concentrations and δ7Li in the Ganges River show remarkable changes, with a large influence from Himalayan sources. However, most Li discharge across the rainy season is at steady-state and strongly influenced by the secondary mineral formation in the low-altitude floodplain. Secondary mineral formation strongly influences the Meghna River’s Li isotopic composition along with fractionation lines similar to the Ganges River. A geothermal input is an additional Li source for the Brahmaputra River. For groundwater samples shallower than ∼60 m depth, both δ7Li and Li/Na are highly scattered regardless of the sampling region, suggesting the variable extent of fractionation. For deep groundwater (70–310 m) with a longer residence time (3,000 to 20,000 years), the lower δ7Li values indicate more congruent weathering. These results suggest that Li isotope fractionation in rivers and groundwater depends on the timescale of water-mineral interaction, which plays an essential role in determining the isotopic signature of terrestrial Li inputs to the ocean.
Iron Redistribution Upon Thermokarst Processes in the Yedoma Domain
Authors: Monhonval Arthur , Strauss Jens , Mauclet Elisabeth , Hirst Catherine , Bemelmans Nathan , Grosse Guido , Schirrmeister Lutz , Fuchs Matthias , Opfergelt Sophie
Published: July 2021

Ice-rich permafrost has been subject to abrupt thaw and thermokarst formation in the past and is vulnerable to current global warming. The ice-rich permafrost domain includes Yedoma sediments that have never thawed since deposition during the late Pleistocene and Alas sediments that were formed by previous thermokarst processes during the Lateglacial and Holocene warming. Permafrost thaw unlocks organic carbon (OC) and minerals from these deposits and exposes OC to mineralization. A portion of the OC can be associated with iron (Fe), a redox-sensitive element acting as a trap for OC. Post-depositional thaw processes may have induced changes in redox conditions in these deposits and thereby affected Fe distribution and interactions between OC and Fe, with knock-on effects on the role that Fe plays in mediating present day OC mineralization. To test this hypothesis, we measured Fe concentrations and proportion of Fe oxides and Fe complexed with OC in unthawed Yedoma and previously thawed Alas deposits. Total Fe concentrations were determined on 1,292 sediment samples from the Yedoma domain using portable X-ray fluorescence; these concentrations were corrected for trueness using a calibration based on a subset of 144 samples measured by inductively coupled plasma optical emission spectrometry after alkaline fusion (R2 = 0.95). The total Fe concentration is stable with depth in Yedoma deposits, but we observe a depletion or accumulation of total Fe in Alas deposits, which experienced previous thaw and/or flooding events. Selective Fe extractions targeting reactive forms of Fe on unthawed and previously thawed deposits highlight that about 25% of the total Fe is present as reactive species, either as crystalline or amorphous oxides, or complexed with OC, with no significant difference in proportions of reactive Fe between Yedoma and Alas deposits. These results suggest that redox driven processes during past thermokarst formation impact the present-day distribution of total Fe, and thereby the total amount of reactive Fe in Alas versus Yedoma deposits. This study highlights that ongoing thermokarst lake formation and drainage dynamics in the Arctic influences reactive Fe distribution and thereby interactions between Fe and OC, OC mineralization rates, and greenhouse gas emissions.