Class IA PI3Ks regulate subcellular and functional dynamics of IDO1.

Knowledge of a protein's spatial dynamics at the subcellular level is key to understanding its function(s), interactions, and associated intracellular events. Indoleamine 2,3-dioxygenase 1 (IDO1) is a cytosolic enzyme that controls immune responses via tryptophan metabolism, mainly through its enzymic activity. When phosphorylated, however, IDO1 acts as a signaling molecule in plasmacytoid dendritic cells (pDCs), thus activating genomic effects, ultimately leading to long-lasting immunosuppression. Whether the two activities-namely, the catalytic and signaling functions-are spatially segregated has been unclear. We found that, under conditions favoring signaling rather than catabolic events, IDO1 shifts from the cytosol to early endosomes. The event requires interaction with class IA phosphoinositide 3-kinases (PI3Ks), which become activated, resulting in full expression of the immunoregulatory phenotype in vivo in pDCs as resulting from IDO1-dependent signaling events. Thus, IDO1's spatial dynamics meet the needs for short-acting as well as durable mechanisms of immune suppression, both under acute and chronic inflammatory conditions. These data expand the theoretical basis for an IDO1-centered therapy in inflammation and autoimmunity.

Novel Anti-Hexokinase 1 Antibodies Are Associated With Poor Prognosis in Patients With Primary Biliary Cholangitis.

INTRODUCTION: Antibodies to hexokinase 1 (HK1) and kelch-like 12 (KLHL12) have been identified as potential biomarkers in primary biliary cholangitis (PBC), and this study assesses changes of these antibodies over time and if they are associated with clinical outcomes. METHODS: Two hundred fifty-four PBC patients (93.3% female, 51 ± 12.3 years old) were tested for anti-HK1 and anti-KLHL12, antimitochondrial (AMA), anti-gp210, and anti-sp100 antibodies. One hundred sixty-nine patients were tested twice and 49 three times within 4.2 (0.8-10.0) years. Biochemistry and clinical features at diagnosis, response to therapy, events of decompensation, and liver-related death or transplantation were evaluated. RESULTS: Anti-HK1 and anti-KLHL2 were detected in 46.1% and 22.8% patients, respectively. AMA were positive in 93.7%, anti-sp100 in 26.4%, and anti-gp210 in 21.3% of patients. Anti-HK1 and anti-KLHL12 positivity changed over time in 13.3% and 5.5% of patients, respectively. Anti-HK1 or anti-KLHL12 were present in 37.5% of AMA-negative patients, and in 40% of AMA, anti-gp210, and anti-sp100 negative. No significant differences were observed between those with or without HK1 and KLHL12 antibodies, but transplant-free survival and time to liver decompensation were significantly lower in patients anti-HK1 positive (P = 0.039; P = 0.04) and in those anti-sp100 positive (P = 0.01; P = 0.007). No changes in survival and events of liver decompensation were observed according to the positivity of AMA, anti-KLHL12, or anti-gp210 antibodies. DISCUSSION: HK1 and KLHL12 antibodies are present in 40% of PBC patients who are seronegative by the conventional PBC-specific antibodies. The novel antibodies remain rather steady during the course of the disease, and HK1 antibodies are associated with unfavourable outcomes.

Accuracy of frozen section in intraoperative margin assessment for breast-conserving surgery: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: It is well established that tumor-free margin is an important factor for reducing local recurrence and reoperation rates. This systematic review with meta-analysis of frozen section intraoperative margin assessment aims to evaluate the accuracy, and reoperation and survival rates, and to establish its importance in breast-conserving surgery. METHODS: A thorough review was conducted in all online publication-databases for the related literature up to March 2020. MeSH terms used: "Breast Cancer", "Segmental Mastectomy" and "Frozen Section". We included the studies that evaluated accuracy of frozen section, reoperation and survival rates. To ensure quality of the included articles, the QUADAS-2 tool (adapted) was employed. The assessment of publication bias by graphical and statistical methods was performed using the funnel plot and the Egger's test. The review protocol was registered in PROSPERO (CRD42019125682). RESULTS: Nineteen studies were deemed suitable, with a total of 6,769 cases. The reoperation rate on average was 5.9%. Sensitivity was 0.81, with a Confidence Interval of 0.79-0.83, p = 0.0000, I2 = 95.1%, and specificity was 0.97, with a Confidence Interval of 0.97-0.98, p = 0.0000, I-2 = 90.8%, for 17 studies and 5,615 cases. Accuracy was 0.98. Twelve studies described local recurrence and the highest cumulative recurrence rate in 3 years was 7.5%. The quality of the included studies based on the QUADAS-2 tool showed a low risk of bias. There is no publication bias (p = 0.32) and the funnel plot showed symmetry. CONCLUSION: Frozen section is a reliable procedure with high accuracy, sensitivity and specificity in intraoperative margin assessment of breast-conserving surgery. Therefore, this modality of margin assessment could be useful in reducing reoperation rates.

Multicultural classroom discourse dataset on teachers' and students' dialogic empathy.

This dataset belongs to a large-scale educational intervention project introducing cultural literacy learning in schools. The dataset includes transcribed dialogic interactions from 111 lessons conducted in classrooms of five countries: England, Portugal, Germany, Spain, and Cyprus. The lessons were part of the same Cultural Literacy Learning Programme made available to teachers from three age groups (pre-primary, primary, secondary) to implement with their ordinary classes during ten sessions. The data are from the third and eighth sessions and followed the same structure, content, and objectives. As the main goal of the project to which the dataset belongs was on cultural literacy learning, understood as dialogic dispositions and values, the data were coded according to a Dialogic Empathy coding scheme presented in detail in Macagno et al. (2020). This rich multicultural, and multilinguistic, dataset is offered for further analysis by different types of researchers, such as linguists interested in intercultural pragmatics or educational psychologists interested in cross-sectional studies of dialogue and reasoning skills.

Systematic radiological approach to utero-ovarian pathologies.

Ultrasound is the first-line imaging modality for the evaluation of suspected adnexal masses, endometriosis and uterine tumors, whereas MRI is used as a secondary diagnostic tool to better characterize these lesions. The aim of this review is to summarize the latest advances in the imaging of these utero-ovarian pathologies.

Pregnancy outcomes after chemotherapy for trophoblastic neoplasia.

INTRODUCTION: The successful development of chemotherapy enabled a fertilitysparing treatment for patients with trophoblastic neoplasia. After disease remission, the outcome of a subsequent pregnancy becomes a great concern for these women. OBJECTIVE: To analyze existing studies in the literature that describe the reproductive outcomes of patients with trophoblastic neoplasia treated with chemotherapy. METHOD: Systematic review was performed searching for articles on Medline/ Pubmed, Lilacs and Cochrane Library databases, using the terms "gestational trophoblastic disease" and "pregnancy outcome". RESULTS: A total of 18 articles were included. No evidence of decreased fertility after chemotherapy for trophoblastic neoplasia was observed. The abortion rates in patients who conceived within 6 months after chemotherapy was higher compared to those who waited longer. Some studies showed increased rates of stillbirth and repeat hydatidiform moles. Only one work showed increased congenital abnormalities. CONCLUSION: The pregnancies conceived after chemotherapy for trophoblastic neoplasia should be followed with clinical surveillance due to higher rates of some pregnancy complications. However, studies in the literature provide reassuring data about reproductive outcomes of these patients.

Arguing collaboratively: Argumentative discourse types and their potential for knowledge building.

BACKGROUND: There is growing interest in using argumentative discourse in educational settings. However, in a previous study, we found that discourse goals (persuasion vs. consensus) while arguing can affect student outcomes in both content learning and reasoning. AIMS: In this study, we look at argumentative discourse data from a previous study to ask how differences in discourse might account for the differences we observed in learning and reasoning outcomes. SAMPLE: One hundred and five dialogues (57 disputative, 48 consensus) between 7th grade science students attending a public high school near Tarragona, Spain. METHODS: Participants were randomly assigned to conditions and paired with peers who disagreed with them on three topics related to renewable energy sources. After instruction on each topic, they were asked to either 'argue to convince' (persuasion condition) or 'argue to reach consensus' (consensus condition) on that topic. Conversations were audio-recorded and transcribed for analysis. RESULTS: Students in the persuasion condition engaged in shorter conversational exchanges around argumentative claims and were more likely to use moves that foreclosed discussion, whereas students in the consensus condition were more likely to use moves that elicited, elaborated on, and integrated their partners' ideas. CONCLUSIONS: When arguing to reach - rather than defend - a conclusion, students are more likely to coconstruct knowledge by exchanging and integrating arguments. These findings are consistent with predictions about the potential of argumentation for knowledge building and suggest that teachers must attend to discourse goals when using argumentation to support learning and reasoning.

Pregnancy outcomes after chemotherapy for trophoblastic neoplasia / Futuro reprodutivo após tratamento quimioterápico da neoplasia trofoblástica

SUMMARY Introduction The successful development of chemotherapy enabled a fertilitysparing treatment for patients with trophoblastic neoplasia. After disease remission, the outcome of a subsequent pregnancy becomes a great concern for these women. Objective To analyze existing studies in the literature that describe the reproductive outcomes of patients with trophoblastic neoplasia treated with chemotherapy. Method Systematic review was performed searching for articles on Medline/ Pubmed, Lilacs and Cochrane Library databases, using the terms “gestational trophoblastic disease” and “pregnancy outcome”. Results A total of 18 articles were included. No evidence of decreased fertility after chemotherapy for trophoblastic neoplasia was observed. The abortion rates in patients who conceived within 6 months after chemotherapy was higher compared to those who waited longer. Some studies showed increased rates of stillbirth and repeat hydatidiform moles. Only one work showed increased congenital abnormalities. Conclusion The pregnancies conceived after chemotherapy for trophoblastic neoplasia should be followed with clinical surveillance due to higher rates of some pregnancy complications. However, studies in the literature provide reassuring data about reproductive outcomes of these patients.

RESUMO Introdução o sucesso do desenvolvimento da quimioterapia no tratamento da neoplasia trofoblástica proporcionou a possibilidade de conservação da fertilidade das pacientes, tornando o futuro reprodutivo uma nova preocupação após a remissão da doença Objetivo analisar os estudos existentes na literatura que descrevem o futuro reprodutivo de pacientes com neoplasia trofoblástica tratadas com quimioterapia. Método revisão sistemática que buscou artigos nas bases de dados Medline/Pubmed, Lilacs e Biblioteca Cochrane, utilizando as palavras-chave “gestational trophoblastic disease” e “pregnancy outcome”. Resultados foram selecionados 18 artigos de acordo com critérios de inclusão e exclusão. Não foi observada diminuição da fertilidade após a quimioterapia para neoplasia trofoblástica. Pacientes que engravidaram até 6 meses do término da quimioterapia apresentaram maiores taxas de abortamento quando comparadas às que esperaram mais de 6 meses. Alguns artigos encontraram maiores taxas de natimorto e nova mola hidatiforme. Apenas um estudo mostrou aumento da taxa de malformação. Conclusão as gestações subsequentes à neoplasia trofoblástica devem ser acompanhadas com vigilância clínica em decorrência da maior taxa de complicações na gestação, principalmente nas mulheres que engravidam até 6 meses após o término da quimioterapia. No entanto, os dados encontrados nos estudos tranquilizam quanto ao futuro reprodutivo dessas pacientes.

Occupation, tobacco use, coffee, and bladder cancer in the county of Mataro (Spain).

This report presents the results of an epidemiologic case-control study. The study includes 58 cases and 116 controls from both sexes, selected from the Admission Register of the Hospital and from the Death Registry Office of the local city authorities. Controls have been matched to cases by age, sex, place of residence and source of selection. The results demonstrated no increased risk associated with coffee consumption. Habitual smokers present a 2.3 times higher risk than nonsmokers. The estimated relative risk for occupation standardized by age and smoking habit, is 5.5. A multiplicative effect of the simultaneous action of smoking and occupational exposure has been observed to be an estimated relative risk of 11.7. The attributable risk of the population has been estimated to be 39% for smokers and 12% for occupational exposure. A strong association was found between bladder cancer and occupational exposure to carcinogenic substances, especially in the dye and print textile industries.