bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intestinal TGR5 agonism improves hepatic steatosis and insulin sensitivity in Western diet-fed mice
Authors: Finn Patricia D. , Rodriguez David , Kohler Jill , Jiang Zhengfeng , Wan Sindy , Blanco Erick , King Andrew J. , Chen Tao , Bell Noah , Dragoli Dean , Jacobs Jeffrey W. , Jain Rakesh , Leadbetter Michael , Siegel Matthew , Carreras Christopher W. , Koo-McCoy Samantha , Shaw Karen , Le Cathy , Vanegas Sandra , Hsu I-Hsin , Kozuka Kenji , Okamoto Keiko , Caldwell Jeremy S. , Lewis Jason G. 
Published: January 2019

Takeda G protein-coupled receptor 5 (TGR5) agonists induce systemic release of glucagon-like peptides (GLPs) from intestinal L cells, a potentially therapeutic action against metabolic diseases such as nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), and Type 2 diabetes. Historically, TGR5 agonist use has been hindered by side effects, including inhibition of gallbladder emptying. Here, we characterize RDX8940, a novel, orally administered TGR5 agonist designed to have minimal systemic effects and investigate its activity in mice fed a Western diet, a model of NAFLD and mild insulin resistance. Agonist activity, binding selectivity, toxicity, solubility, and permeability of RDX8940 were characterized in standard in vitro models. RDX8940 pharmacokinetics and effects on GLP secretion, insulin sensitivity, and liver steatosis were assessed in C57BL/6 mice fed normal or Western diet chow and given single or repeated doses of RDX8940 or vehicle, with or without dipeptidyl peptidase-4 (DPP4) inhibitors. Gallbladder effects were assessed in CD-1 mice fed normal chow and given RDX8940 or a systemic TGR5 agonist or vehicle. Our results showed that RDX8940 is minimally systemic, potent, and selective, and induces incretin (GLP-1, GLP-2, and peptide YY) secretion. RDX8940-induced increases in plasma active GLP-1 (aGLP-1) levels were enhanced by repeated dosing and by coadministration of DPP4 inhibitors. RDX8940 increased hepatic exposure to aGLP-1 without requiring coadministration of a DPP4 inhibitor. In mice fed a Western diet, RDX8940 improved liver steatosis and insulin sensitivity. Unlike systemic TGR5 agonists, RDX8940 did not inhibit gallbladder emptying. These results indicate that RDX8940 may have therapeutic potential in patients with NAFLD/NASH.NEW & NOTEWORTHY Takeda G protein-coupled receptor 5 (TGR5) agonists have potential as a treatment for nonalcoholic steatohepatitis and nonalcoholic fatty liver disease (NAFLD) but have until now been associated with undesirable side effects associated with systemic TGR5 agonism, including blockade of gallbladder emptying. We demonstrate that RDX8940, a potent, selective, minimally systemic oral TGR5 agonist, improves liver steatosis and insulin sensitivity in a mouse model of NAFLD and does not inhibit gallbladder emptying in mice.
Ideas sobre la escrófula en Chile, antes de 1882
Authors: Duarte García de Cortázar Ignacio 
Published: January 2019

Resumen Desde la antigüedad la escrófula o lamparón era descrita como tumefacción crónica de ganglios linfáticos cervicales, que afectaba principalmente a niños, adolescentes y jóvenes. Se pensaba que algunas veces también podía comprometer otras partes del cuerpo y cursar con caquexia letal. En el presente artículo se intentó indagar las ideas reinantes en Chile sobre las características y tratamiento de la escrófula, antes del descubrimiento del bacilo tuberculoso. Se revisaron estadísticas principalmente hospitalarias, textos extranjeros disponibles y opiniones de médicos que trabajaron en Chile. Se consignaba el diagnóstico de escrófula en aproximadamente 2,2% de los pacientes, y tisis en 3,8%. Sin embargo, ambas condiciones pueden haber sido inadecuadamente identificadas, especialmente debido a sub-diagnóstico de tisis pulmonar en casos clasificados como neumonía o pleuresía. En el tiempo descrito se opinaba que la escrófula era causada principalmente por transmisión hereditaria, alimentación inadecuada o sífilis en individuos predispuestos por un temperamento linfático. No se encontraron textos chilenos en que se normaran criterios para el diagnóstico de escrófula. Para el tratamiento se mencionaban plantas medicinales y algunos compuestos químicos administrados en infusiones o emplastos. Quedan dudas para interpretar lo que se pensaba sobre el significado y límites de las condiciones denominadas escrófula, escrofuloso y tisis. Este problema se aprecia también en la literatura clínica internacional y se atribuye principalmente al insuficiente desarrollo científico y metodológico de la medicina de la época.
Bacterial Translocation and Risk of Liver Cancer in a Finnish Cohort
Authors: Yang Baiyu , Petrick Jessica L. , Thistle Jake E. , Pinto Ligia A. , Kemp Troy J. , Tran Hao Quang , Gewirtz Andrew T. , Waterboer Tim , Fedirko Veronika , Jenab Mazda , Graubard Barry I. , Weinstein Stephanie J. , Albanes Demetrius , McGlynn Katherine A. 
Published: January 2019

Abstract

Background:
Elevated systemic exposure to gut-derived bacterial products has been associated with hepatic inflammation and chronic liver diseases, potentially increasing the risk of liver cancer. However, only one prior study prospectively examined exposure to bacterial products in the circulation and risk of liver cancer, with a relatively limited coverage of biomarkers.

Methods:
We conducted a nested case–control study (224 liver cancer cases and 224 matched controls) in a large cohort of Finnish male smokers followed from baseline (1985–1988) to 2014. The associations between a panel of biomarkers for bacterial translocation and the risk of liver cancer were assessed using multivariable-adjusted conditional logistic regression. The biomarkers included immunoglobulin (Ig) A, IgG, and IgM against lipopolysaccharide (LPS) and flagellin, soluble CD14 (an LPS coreceptor), and the LPS-binding protein.

Results:
Anti-flagellin IgA [odds ratios (OR), 2.79; 95% confidence intervals (CI), 1.34–5.78; Ptrend = 0.01] and anti-LPS IgA (2.44; 95% CI, 1.33–4.48; Ptrend &lt; 0.01) were significantly associated with risk of liver cancer. When restricting the analysis to histologically classified hepatocellular carcinoma, the ORs were 4.18 (95% CI, 1.60–10.92; Ptrend &lt; 0.01) and 2.48 (95% CI, 1.16–5.29; Ptrend &lt; 0.01), respectively. The results were not substantially changed after excluding cases diagnosed within the first 5 years of follow-up and those with hepatitis C virus infection.

Conclusions:
Antibodies to flagellin and LPS were associated with increased risk of liver cancer.

Impact:
Gut-derived bacterial translocation into the circulation may play a role in the development of primary liver cancer. Our findings could contribute to the understanding of primary liver cancer etiology and further prevention efforts.
Impact of the Ageing Population on the Burden of Stroke: The Dijon Stroke Registry
Authors: Béjot Yannick , Bailly Henri , Graber Mathilde , Garnier Lucie , Laville Annabel , Dubourget Lucile , Mielle Nathalie , Chevalier Corinne , Durier Jérôme , Giroud Maurice 
Published: January 2019

<b><i>Background:</i></b> We aimed to evaluate the impact of the ageing population on temporal trends in burden of stroke and to provide projections for the coming years. <b><i>Methods:</i></b> Stroke cases (ischemic strokes, spontaneous intracerebral hemorrhages, or undetermined strokes) were prospectively identified between 1987 and 2015 in Dijon, France, using a population-based registry. Age-standardized incidence rates of first-ever and recurrent stroke were calculated, and their temporal trends were assessed using age- and sex-adjusted annual incidence rate ratios (RR). <b><i>Results:</i></b> The population of Dijon increased by 3.8% over time, with an increase by 28% in the number of residents aged ≥75 years. We recorded 5,899 strokes including 5,101 patients with a first-ever event. Incidence of first-ever stroke was stable both in people &#x3c; 75 and ≥75 years old, but an increase in standardized incidence rates of total strokes was noted due to a rise in the incidence of recurrent stroke (from 4.7/100,000/year in 1987–1994 to 12.3/100,000/year in 2009–2015 in people &#x3c; 75 years old, RR 1.036; <i>p</i> &#x3c; 0.001; from 74/100,000/year in 1987–1994 to 200/100,000/year in 2009–2015 in people ≥75 years, RR 1.040; <i>p</i> &#x3c; 0.001). The absolute number of first-ever strokes increased by 43%, and that of total stroke events rose by 58% over time, with a more pronounced increase in people ≥75 years old (+47 and +65% respectively). The annual number of patients who survived &#x3e; 90 days after a first-ever stroke increased by 90%. According to demographic projections, the total number of strokes will increase by 55% (+65% patients ≥75 years, and +25% patients &#x3c; 75 years) by 2,030 in Dijon. <b><i>Conclusions:</i></b> Ageing and growth of the population led to a rise in the absolute number of strokes, especially in the elderly, that is expected to increase dramatically in the coming years. Improved stroke care was accompanied with an increase in stroke survivors that contributed to a rise in recurrent events. Urgent action is needed to meet this epidemiological challenge.
Implicações da identificação de subfácies e alterações deutéricas para a gênese e a evolução do albita granito rico em F no depósito de Sn-Nb-Ta-ETR Madeira (Mina Pitinga, Amazonas, Brasil)
Authors: Rodrigues Juliano Nunes , Ronchi Luiz Henrique , Bastos Neto Artur Cezar , Pereira Vitor Paulo 
Published: January 2019

O albita granito de Pitinga, localizado no estado do Amazonas, em geral porfirítico e de composição modal monzogranítica a granodiorítica, possui uma complexa variação mineralógica e petrográfica, resultante tanto de processos da transição magmático-hidrotermal como de alterações deutéricas. O mapeamento da frente de lavra norte no contato das subfácies de borda (albita granito de borda) e de núcleo (albita granito de núcleo), a petrografia e a geoquímica de amostras representativas revelam duas paragêneses parcialmente superpostas de alteração no albita granito de borda, uma marrom avermelhada com relictos de mica verde rica em ferro e outra vermelha, onde a mica verde foi substituída por clorita e fluorita e/ou argila amarela. Adicionalmente, o albita granito de núcleo cinza porfirítico é transformado gradualmente em porfirítico branco, mais rico em albita; amarelo, quando argilizado por ilita e caulinita; com manchas localizadas de óxidos de ferro vermelhas, silicificado e criolitizado. Tanto o quartzo tardio (silicificação) como a criolita possuem inclusões fluidas aquosas primárias com temperaturas de homogeneização entre 100 e 250ºC e salinidade até 26% peso eq. NaCl. Ambas as subfácies, albita granito de borda e de núcleo, são cortadas por corpos irregulares brancos afaníticos compostos essencialmente por quartzo e albita. O padrão de elementos terras raras dos corpos afaníticos brancos é similar ao padrão do albita granito de borda e do albita granito de núcleo, porém com a soma total de elementos terras raras menor, sugerindo cogeneticidade. A subfácies albita granito de borda resulta do resfriamento concêntrico da câmara magmática inicial produzindo uma borda que sofreu alteração autometassomática por fluidos deutéricos, criando os óxidos de ferro que lhe conferem a cor marrom-avermelhada.
Caracterização litoquímica e geocronológica de granitos do Batólito Águas Belas-Canindé, no Domínio Pernambuco-Alagoas, na Província Borborema
Authors: Neves Charles Henrique Fernandes Sales das , Ferreira Valderez Pinto , Neves Sergio Pacheco 
Published: January 2019

Os Plútons Serra da Caiçara (616 ± 3 milhões de anos — Ma), composto de hornblenda quartzo sienito a hornblenda quartzo álcali feldspato sienito grossos, Santana do Ipanema (621 ± 5 Ma), constituído por monzogranitos a sienogranitos equigranulares, e Maravilha (627 ± 5 Ma), formado por monzogranitos porfiríticos com forte foliação magmática, são algumas das intrusões que compõem o Batólito Águas Belas-Canindé, Domínio Pernambuco-Alagoas, Província Borborema, no nordeste do Brasil. As idades U-Pb em zircão (Sensitive High Resolution Ion Micro Probe — SHRIMP) dos plútons indicam intrusão associada ao período de formação da foliação de baixo ângulo regional, gerada durante a convergência da Orogênese Brasiliana. Os granitos e sienitos são cálcio-alcalinos de alto potássio a shoshoníticos, metaluminosos a levemente peraluminosos, da série magnetita granitos e magnesianos. Os padrões normalizados de elementos terras raras (ETR) para essas rochas indicam fracionamento moderado a alto, apresentando (La/Lu)N entre 14 e 82 e leves anomalias negativas de Eu. Diagramas de elementos incompatíveis normalizados em relação ao condrito mostram anomalias marcantes em Nb- Ta e Ti, típicas de magmas relacionados a zonas de subducção. Anfibólios e biotitas, analisados nos três plútons, têm composições típicas de granitos da série cálcio-alcalina e possuem valores de Fe# semelhantes aos da rocha total. O conjunto de dados geoquímicos sugere que o magma foi gerado em ambiente de arco, derivado da fusão de rochas basálticas de alto K, em condições oxidantes, e evolui por cristalização fracionada.
Estratigrafia da transição entre os grupos Bambuí e Paranoá no Distrito Federal
Authors: Carvalho Maria Gabriela De , Alvarenga Carlos José Souza de 
Published: January 2019

O norte do Distrito Federal (DF) inclui uma expressiva sucessão de rochas carbonáticas de posicionamento estratigráfico divergente, tendo sido incluídos tanto no Grupo Bambuí como no Grupo Paranoá. Neste trabalho, os carbonatos do Grupo Paranoá foram individualizados e separados daqueles da Formação Sete Lagoas do Grupo Bambuí. O primeiro é composto de uma unidade siliciclástica formada predominantemente por intercalações rítmicas de siltitos e arenitos sobreposta por rochas pelito-carbonáticas, com lentes de calcários dolomíticos, onde é possível observar o estromatólito Conophyton metulum Kirichenko. A Formação Sete Lagoas do Grupo Bambuí recobre de forma discordante as rochas do Grupo Paranoá e foi subdividida em duas sucessões estratigráficas distintas. A Sucessão 1 da Formação Sete Lagoas inclui três unidades litoestratigráficas distintas: (i) a unidade basal começa por um dolarenito cinza, sobreposto por uma sucessão rítmica de calcilutitos/calcarenitos arroxeados com argilas não carbonáticas, (ii) na unidade intermediária, predominam calcarenitos puros sucedidos pela (iii) unidade de dolomitos. Uma superfície erosiva marcada por níveis de brecha limita a Sucessão 2, que começa com 1–2 metros de siltitos seguidos por calcarenitos com camadas de argilosas crescentes em direção ao topo. O norte do DF está na zona externa da Faixa Brasília, onde foram identificadas duas fases de deformações, perpendiculares entre si, orientadas com direções grosseiramente NS e EW.
Controle litoestrutural e caracterização geofísica do Complexo Alcalino Planalto da Serra, Mato Grosso
Authors: Zaffari Gabriel Luiz , Ruiz Amarildo Salina , Vidotti Roberta Mary , Campos Francisco Abel Pompeu de 
Published: January 2019

O Complexo Alcalino Planalto da Serra está alojado nas rochas metassedimentares do Grupo Cuiabá, na Zona Interna da Faixa Paraguai, sendo composto de rochas ultramáficas alcalinas, como peridotitos, piroxenitos, carbonatitos, apatititos e bebedouritos. Os trabalhos iniciais indicavam formação desse complexo durante o Cretáceo, correlacionada ao magmatismo alcalino associado ao Lineamento Azimute 125º. Novos dados geocronológicos, obtidos pelos métodos de Rb/Sr, Ar-Ar e Sm/Nd, indicaram, no entanto, a idade de formação do complexo alcalino próximo a 600 Ma, remontando assim a um modelo de intrusão de diques e stocks diferente do já descrito. Com o intuito de compreender a relação entre as rochas alcalinas e o Grupo Cuiabá, tanto na relação temporal quanto ao modelo de intrusão, foram utilizados dois métodos de trabalho: o emprego de dados aerogeofísicos, gamaespectometria e magnetometria, e o mapeamento litoestrutural nos sítios de ocorrência das intrusões alcalinas (Chibata e Lau-Massao). O alto contraste entre características magnéticas dos metassedimentos do Grupo Cuiabá e as rochas alcalinas permitiu a identificação e a delimitação de sete anomalias magnéticas relacionadas às intrusões alcalinas do Complexo Planalto da Serra. Baixos teores de potássio nos dados de gamaespectometria permitiram delimitação dos corpos alcalinos. Feições como deformação penetrativa e reorientação mineral, presentes nas bordas de diques alcalinos, corroboram com modelo de intrusão sin a tardi-tectônica. A relação entre as idades, características deformacionais e metamórficas indica que os registros tectônicos verificados nas rochas alcalinas são correlatos aos observados nas rochas metamórficas do Grupo Cuiabá, Faixa Paraguai.
Entre Imagem e Palavra
Authors: Barros Luzia 
Published: January 2019

Analisamos neste artigo os contos "Galo cantou na baía”, de Manuel Lopes (1936), e “Um ladrão” (1939), de Graciliano Ramos. Considerando que naquele momento histórico a literatura era um ambiente privilegiado para promover debates urgentes em prol de populações que viviam em situação de extrema vulnerabilidade, abordamos, desde a perspectiva do foco narrativo, as estratégias discursivas empregadas pelos autores então política e claramente orientados e engajados.
Reversal of Aortic Enlargement Induced by Increased Biomechanical Forces Requires AT1R Inhibition in Conjunction With AT2R Activation
Authors: Zhou Zhen , Peters Andrew M. , Wang Shanzhi , Janda Alexandra , Chen Jiyuan , Zhou Ping , Arthur Erin , Kwartler Callie S. , Milewicz Dianna M. 
Published: January 2019

Objective—
Pharmacological inhibition of the AT1R (angiotensin II type 1 receptor) with losartan can attenuate ascending aortic remodeling induced by transverse aortic constriction (TAC). In this study, we investigated the role of the AT2R (angiotensin II type 2 receptor) and MasR (Mas receptor) in TAC-induced ascending aortic dilation and remodeling.

Approach and Results—

Wild-type C57BL/6J mice were subjected to sham or TAC surgeries in the presence and absence of various drugs. Aortic diameters were assessed by echocardiography, central blood pressure was measured in the ascending aorta 2 weeks post-operation, and histology and gene expression analyses completed. An angiotensin-converting enzyme inhibitor, captopril, decreased systolic blood pressure to the same level as losartan but did not attenuate aortic dilation, adventitial inflammation, medial collagen deposition, elastin breakage, or
Mmp9
(matrix metalloproteinase-9) expression when compared with TAC mice. In contrast, co-administration of captopril with an AT2R agonist, compound 21, attenuated aortic dilation, medial collagen content, elastin breaks, and
Mmp9
expression, whereas co-administration of captopril with a MasR agonist (AVE0991) did not reverse aortic dilation and led to aberrant aortic remodeling. An AT2R antagonist, PD123319, reversed the protective effects of losartan in TAC mice. Treatment with compound 21 alone showed no effect on TAC-induced aortic enlargement, blood pressure, elastin breakage, or
Mmp9
expression.

Conclusions—
Our data indicate that when AT1R signaling is blocked, AT2R activation is a key modulator to prevent aortic dilation that occurs with TAC. These data suggest that angiotensin-converting enzyme inhibitor may not be as effective as losartan for slowing aneurysm growth because losartan requires intact AT2R signaling to prevent aortic enlargement.
Rok 1919: pamięć Wilna – pamięć w Wilnie
Authors: Krupowies Walentyna 
Published: January 2019

1919: Memory of Vilnius – memory in VilniusThis article applies the framework of three types of memory – individual, communicative and cultural – as an effective tool for describing the phenomenon of “circulation” of the content of memory in communities of memory. I approach the Polish community in Vilnius, especially the intelligentsia, as a community of memory, and show how the three forms of memory were activated at a particular historical time. I argue that the year 1919 and the time of reviving Vilnius University was crucial for the transfer of the content of communicative memory in general, and family memory in particular, to cultural memory. The effort to revive the university was directly related to the restoration of cultural memory in the urban landscape of Vilnius. The person who played the main role in this process was Ferdynand Ruszczyc, the artistic supervisor of revitalisation of university buildings, the author of toponyms and the key figure of cultural life of the city at the time. Rok 1919: pamięć Wilna – pamięć w WilnieW swoim artykule przywołuję wyodrębnione przez współczesnych badaczy trzy formy pamięci: indywidualną, komunikacyjną, kulturową – i traktuję je jako poręczne narzędzie do opisywania zjawiska „cyrkulacji” treści pamięci we wspólnotach pamiętających. Za taką pamiętającą wspólnotę uznaję polską społeczność Wilna, zwłaszcza inteligencję, i ukazuję, w jaki sposób aktywizowały się te trzy formy pamięci w konkretnym czasie historycznym. Stawiam tezę, iż rok 1919 i czas pracy nad wskrzeszeniem uniwersytetu był kluczowy dla przeniesienia treści pamięci komunikacyjnej, zwłaszcza jej postaci rodzinnej, do pamięci kulturowej. Prace nad wskrzeszeniem uniwersytetu łączyły się bezpośrednio z przywracaniem pamięci kulturowej w przestrzeni miasta. Zasadniczą rolę w tym procesie odegrał Ferdynand Ruszczyc jako artystyczny opiekun prac rewitalizacyjnych gmachów uniwersyteckich, autor toponimów i kluczowa postać ówczesnej kultury wileńskiej.
Na pograniczu pamięci współczesnych – (nie)pamięć o przeszłości słowackich Węgrów w słowackiej literaturze XXI wieku
Authors: Słowikowska Agnieszka 
Published: January 2019

At the peripheries of memory: (Non-)memory about the past of Slovak Hungarians in twenty-first-century Slovak literatureThe aim of this article is to analyse the portrayal of Hungarians in the context of the Second World War in twenty-first-century Slovak literature on the example of the novels Stalo sa prveho septembra (alebo inokedy) (It happened on the first of September (or whenever)) by Pavol Rankov (2008) and Nedeľne šachy s Tisom (Sunday chess with Tiso) by Silvester Lavrík (2016). The article argues that the two novels demonstrate two types of forgetting described by Paul Connerton: “repressive erasure” and “forgetting that is constitutive in the formation of a new identity”. I analyse how these types of forgetting functioned in Slovak society, and conclude that the question of the Hungarian minority is becoming less of a taboo in contemporary Slovak literature, even if it still remains at the peripheries of Slovak memory about the Second World War. Na pograniczu pamięci współczesnych – (nie)pamięć o przeszłości słowackich Węgrów w słowackiej literaturze XXI wiekuCelem niniejszego artykułu jest udzielenie odpowiedzi na pytanie, jakie miejsce zajmuje pamięć o Węgrach w kontekście II wojny światowej w słowackiej literaturze XXI wieku na przykładzie powieści Stalo sa prveho septembra (alebo inokedy) Pavla Rankova (2008) oraz Nedeľne šachy s Tisom Silvestra Lavríka (2016). W wybranych przeze mnie powieściach można zaobserwować dwa typy zapomnienia wyróżnione przez Paula Connertona: „represyjne wymazywanie z pamięci” oraz „zapomnienie konstruktywne dla tworzenia nowej tożsamości”. Tym samym w tekstach widoczne są dwa główne sposoby zapomnienia o wydarzeniach II wojny światowej, które istniały w słowackim społeczeństwie. Wynikiem analizy jest stwierdzenie, że kwestia mniejszości węgierskiej we współczesnej literaturze słowackiej przestaje być kwestią tabu, chociaż nadal znajduje się na pograniczach słowackiej pamięci dotyczącej II wojny światowej.