bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL6 Signaling in Cancer: Not Always Bad News
Authors: Huynh Jennifer , Ernst Matthias 
Published: September 2021

Abstract
Understanding the molecular mechanisms that underpin the pleiotropic effects of IL6 in disease are critical to better inform when this cytokine should be therapeutically targeted to provide the most benefit to patients. This is particularly important for cancer and other pathologic conditions strongly linked to chronic inflammation. Shriki and colleagues provide mechanistic evidence that IL6 protects against chronic liver injury and its ensuing tumor development, thereby challenging the prevailing paradigm that IL6 always acts as a tumor-promoting cytokine. These observations contribute to an emerging view of dichotomous and complex activities of IL6 in solid malignancies and will help understand which patients under which circumstances receive the most benefit from therapies that interfere with IL6 signaling.
See related article by Shriki et al., p. 4766
Genetic Polymorphisms Involved in Mitochondrial Metabolism and Pancreatic Cancer Risk
Authors: Peduzzi Giulia , Gentiluomo Manuel , Tavano Francesca , Arcidiacono Paolo Giorgio , Ermini Stefano , Vodicka Pavel , Boggi Ugo , Cavestro Giulia Martina , Capurso Gabriele , Morelli Luca , Milanetto Anna Caterina , Pezzilli Raffaele , Lawlor Rita T. , Carrara Silvia , Lovecek Martin , Souček Pavel , Guo Feng , Hackert Thilo , Uzunoğlu Faik G. , Gazouli Maria , Párniczky Andrea , Kupcinskas Juozas , Bijlsma Maarten F. , Bueno-de-Mesquita Bas , Vermeulen Roel , van Eijck Casper H.J. , Jamroziak Krzysztof , Talar-Wojnarowska Renata , Greenhalf William , Gioffreda Domenica , Petrone Maria C. , Landi Stefano , Archibugi Livia , Puzzono Marta , Funel Niccola , Sperti Cosimo , Piredda Maria L. , Mohelnikova-Duchonova Beatrice , Lu Ye , Hlaváč Viktor , Gao Xin , Schneider Martin , Izbicki Jakob R. , Theodoropoulos George , Bunduc Stefania , Kreivenaite Edita , Busch Olivier R. , Małecka-Panas Ewa , Costello Eithne , Perri Francesco , Testoni Sabrina Gloria Giulia , Vanella Giuseppe , Pasquali Claudio , Oliverius Martin , Brenner Hermann , Loos Martin , Götz Mara , Georgiou Konstantinos , Erőss Bálint , Maiello Evaristo , Szentesi Andrea , Bazzocchi Francesca , Basso Daniela , Neoptolemos John P. , Hegyi Péter , Kiudelis Vytautas , Canzian Federico , Campa Daniele 
Published: September 2021

Abstract

Background:
The mitochondrial metabolism has been associated with pancreatic ductal adenocarcinoma (PDAC) risk. Recent evidence also suggests the involvement of the genetic variability of the mitochondrial function in several traits involved in PDAC etiology. However, a systematic investigation of the genetic variability of mitochondrial genome (mtSNP) and of all the nuclear genes involved in its functioning (n-mtSNPs) has never been reported.

Methods:
We conducted a two-phase association study of mtSNPs and n-mtSNPs to assess their effect on PDAC risk. We analyzed 35,297 n-mtSNPs and 101 mtSNPs in up to 55,870 individuals (12,884 PDAC cases and 42,986 controls). In addition, we also conducted a gene-based analysis on 1,588 genes involved in mitochondrial metabolism using Multi-marker Analysis of GenoMic Annotation (MAGMA) software.

Results:
In the discovery phase, we identified 49 n-mtSNPs and no mtSNPs associated with PDAC risk (P &lt; 0.05). In the second phase, none of the findings were replicated. In the gene-level analysis, we observed that three genes (TERT, SUGCT, and SURF1) involved in the mitochondrial metabolism showed an association below the Bonferroni-corrected threshold of statistical significance (P = 0.05/1588 = 3.1 × 10−5).

Conclusions:
Even though the mitochondrial metabolism might be involved in PDAC etiology, our results, obtained in a study with one of the largest sample sizes to date, show that neither n-mtSNPs nor mtSNPs are associated with PDAC risk.

Impact:
This large case–control study does not support a role of the genetic variability of the mitochondrial function in PDAC risk.
Avaliação de Programas Educacionais no Contexto da Educação Remota e COVID 19
Authors: Reis Francisco José Candido dos , Navarro Anderson Marliere 
Published: September 2021

No início de 2020 o mundo foi surpreendido pelo surgimento e rápido avanço da Covid-19. O impacto sobre os programas educacionais foi enorme. Sendo o distanciamento social uma das poucas formas de mitigar o avanço da pandemia, o ensino remoto emergencial (ERE) passou a ser uma imposição. Neste contexto ganha grande relevância avaliar estas iniciativas a fim de promover rapidamente as mudanças necessárias para que se consiga, minimamente, cumprir os objetivos dos programas educacionais.
Neste artigo discutiremos os fundamentos para a avaliação de programas educacionais no contexto da ERE e da Covid-19. Apresentaremos os princípios básicos de uma avaliação de programas educacionais que são aplicáveis desde a uma aula isoladamente, até ao curso como um todo. Discutiremos a aplicação dos modelos experimentais, Kirkpatrick, modelo lógico e CIPP (Contexto, Insumo, Processo e Produto).
A avaliação das atividades educacionais que utilizaram o ERE, implementado durante a pandemia em 2020, é uma oportunidade para rever práticas e induzir mudanças substanciais no processo de formação das próximas gerações de profissionais da saúde e dos docentes.
Desenvolvimento Docente para Educação Remota Emergencial em 2020: a experiência da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP-USP)
Authors: Carmona Fábio , Bollela Valdes Roberto 
Published: September 2021

Após a suspensão das aulas presenciais em 2020, devido à pandemia da Covid-19, foi necessário viabilizar educação remota emergencial para milhares de estudantes de todos os níveis do ensino no Brasil. Quase ninguém estava preparado para enfrentar um desafio desta grandeza. Por conta da falta de familiaridade com as estratégias de educação mediada por tecnologia, única modalidade de ensino disponível naquele momento, essa situação logo trouxe à tona sinais de fadiga e estresse entre professores e estudantes. Era perceptível também a necessidade, por parte dos professores, de treinamento para apropriarem-se dos recursos existentes na universidade para a educação remota. A energia dispendida para preparação das aulas, atividades e avaliações no contexto da educação remota era enorme e seria necessário adquirir competências básicas para manter os processos de ensino-aprendizagem e avaliação dos estudantes acontecendo e com boa qualidade. Estes sinais e pedidos de ajuda, por parte dos professores e estudantes, começam a ficar evidentes no final de maio de 2020 na Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP-USP). Estudantes reclamavam de sobrecarga de conteúdo, sobreposição e desorganização das atividades propostas para o ambiente virtual e estavam muito ansiosos com a avaliação que teriam ao final do semestre. Por outro lado, víamos professores inseguros para oferecerem atividades online, ou em dúvida sobre como cuidar de vários aspectos, tais como registro de frequência, participação ativa nas aulas, e, principalmente, avaliação do estudante. Enfim, como utilizar recursos de educação remota, partindo de pouca ou quase nenhuma experiência prévia? Neste contexto, o Centro de Desenvolvimento Docente para o Ensino (CDDE) da FMRP-USP identifica as necessidades dos docentes e propõe um treinamento voltado para a plataforma e-Disciplinas da USP, assegurando os princípios básicos de boa educação e avaliação dos estudantes. Daí nasce o módulo básico de educação remota para profissões da saúde, que busca atender docentes com diferentes necessidades na FMRP-USP. Para aqueles professores com maior expertise em educação a distância, realizamos dois cursos completos empregando o ensino híbrido a partir da estratégia da sala de aula invertida, mas de maneira remota (remote flipped classroom). Para um público mais iniciante ou que não teria condições de se dedicar ao curso completo, disponibilizamos ajuda personalizada. Esta é a experiência que apresentamos neste artigo e que servirá de base para adequações necessárias para o enfrentamento do desafio da educação durante e após a fase mais aguda da pandemia da Covid-19.
O futuro da Educação na Universidade: avanços possíveis e necessários
Authors: Carmona Fabio , Cesaretti Mário Luís Ribeiro , Oliveira Anamaria Siriani de , Bollela Valdes Roberto 
Published: September 2021

Este artigo traz uma reflexão sobre transformações possíveis e necessárias, a partir das experiências vividas por docentes, estudantes e instituições de ensino ao longo do ano de 2020, na medida em que sobreviviam, aprendiam e se adaptavam à pandemia da COVID-19. Não resta dúvidas de que a maneira de ensinar deverá estar alicerçada em conhecimentos pedagógicos, práticas colaborativas, na tecnologia educacional, infraestrutura de informática e práticas avaliativas que favoreçam a aprendizagem, através do feedback e da interação mais próxima entre aprendiz e professor. O futuro aponta para o ensino híbrido que deve auxiliar os estudantes a alcançarem a competência para a prática profissional. O desenvolvimento de habilidades interpessoais será fundamental, em especial na formação de profissionais da área da saúde. A oferta de oportunidades para o desenvolvimento docente e a estruturação de comunidades de prática para a aprendizagem colaborativa também serão essenciais.
A maior flexibilização dos currículos e a mediação tecnológica do processo de ensino e aprendizagem devem favorecer intercâmbios e a internacionalização das instituições de ensino. Deste modo, tanto o ensino de graduação, pós-graduação lato e stricto-sensu tende a ampliar seu escopo e deixará de ficar circunscrito aos seus nichos de origem, expandindo-se para a realização de convênios nacionais e internacionais.
Os espaços universitários e os momentos presenciais deverão estar adaptados a nova realidade, que permita ao estudante a aquisição de competências clínicas e relacionais essenciais e que requerem atividades presenciais em cenários da prática profissional. Na área da saúde garantir estes momentos de formação seguirá como um requisito fundamental, assim, as salas de aula, os laboratórios e os campos de estágios devem ser seguros, permitindo uma orientação e supervisão direta por parte dos docentes e preceptores. Além disso, será necessário reafirmar que não existe dilema entre a formação de profissionais da saúde e a segurança do paciente, como houve a partir da suspensão das atividades práticas da maioria dos estudantes dos cursos da saúde no Brasil. Formar profissionais da saúde, num contexto de emergência sanitária, tem importância equivalente a cuidar de pessoas em qualquer cenário. Isso vale também para o acesso a equipamentos de proteção individual e a vacinas. Os desafios estão lançados e as possibilidades de avanço emergem e precisam ser aproveitadas a partir de um trabalho coeso entre gestores universitários, corpo docente, técnico administrativo e discentes.
Blame and Complicity in International Relations: Making Non-intervention Morally Bearable
Authors: Balzacq Thierry , Rousseau Elise 
Published: September 2021

Abstract
On various occasions, states have condemned other nations or groups for mass atrocities they commit; but this rarely leads to any step to redress the untoward situation. This article therefore asks: What functions does blame serve when the blamers lack – or are reluctant to use – the power or authority to punish transgressors? Unlike approaches that focus on the effects of blaming on the wrongdoer, we argue that openly attributing responsibility for wrongdoings to another state or non-state actor has become a normative strategy to shape the way a government is perceived domestically and abroad. Specifically, international blame serves two main objectives: an immediate, communicative function, that is, to express moral protest, and a future-oriented purpose, that is, to dispel future indictment of complicity. We suggest that a corollary of this normative strategy is to make non-intervention morally acceptable. Thus, while in principle the blamer might stand up for the violated norm and value the victims, the strategic use of blame tends to legitimate inaction, by diverting attention away from blaming’s deontic commitments. The article therefore warns against the instrumental use of blame as an act of supererogation (that is, an act that is not compulsory but whose performance is praiseworthy), and as a form of moral clearance (whereby the blamer acknowledges the issue but leaves responsibility for finding solution to the international society). Rather, while blaming ascribes responsibility for the act to an agent, we argue, it also puts the blamer in a specific moral situation: the necessity to take measures that interrupt the unfolding action. Our analysis leads us to put forward a plausible norm that broadens the scope of complicity in international politics: states become complicit in the wrongdoing of other actors (states or non-states) whenever they violate moral obligations that blaming demands. In other words, to blame is to commit oneself to act, though the exact nature of this action varies.
White Cannibalism in the Illegal Slave Trade
Authors: Barcia Manuel 
Published: September 2021

Abstract
The Portuguese schooner Arrogante was captured in late November 1837 by HMS Snake, off the coast of Cuba. At the time, the Arrogante had more than 330 Africans on board, who had been shipped from the Upper Guinea coast. Once the vessel arrived in Montego Bay, Jamaica, the British authorities apprenticed those who had survived. Shortly after landing, however, the Arrogante’s sailors were accused of slaughtering an African man, cooking his flesh, and forcing the rest of those enslaved on board to eat it. Furthermore, they were also accused of cooking and eating themselves the heart and liver of the same man. This article focuses not so much on the actual event, as on the transatlantic process that followed, during which knowledge was produced and contested, and relative meanings and predetermined cultural notions associated with Europeans and Africans were probed and queried.
Essential but Ill-Prepared: How the COVID-19 Pandemic Affects the Mental Health of the Grocery Store Workforce
Authors: Mayer Brian , Arora Mona , Helm Sabrina , Barnett Melissa 
Published: September 2021

Objectives: Frontline essential workers face elevated risks of exposure to COVID-19 because of the interactive nature of their jobs, which require high levels of interaction with the general public and coworkers. The impact of these elevated risks on the mental health of essential workers, especially outside the health care sector, is not well studied. To address this knowledge gap, we examined correlations between perceptions of workplace risks and mental health distress among grocery store workers in Arizona. Methods: We collected the first statewide sample of essential workers outside the health care sector focused on mental health and well-being. A total of 3344 grocery store workers in Arizona completed an online survey in July 2020. We used multiple regression models to identify demographic and work-based correlates of mental health distress. Results: Levels of mental health distress among respondents were high: 557 of 3169 (17.6%) reported severe levels and 482 of 3168 (15.2%) reported moderate levels. Perceptions of workplace safety were strongly correlated with significantly reduced levels of mental health distress (ß = −1.44; SE = 0.20) and reduced perceived stress (ß = −0.97; SE = 0.16). Financially disadvantaged workers and employees aged <55 reported high levels of mental health distress. Perceptions of safety and protection in the workplace were significantly correlated with availability of safety trainings, social distancing, and policies governing customer behaviors. Conclusions Lacking sufficient workplace protections, grocery store employees in Arizona experienced high levels of mental health distress during the COVID-19 pandemic. Providing clear federal and state policies to employers to guide implementation of workplace protections may help reduce sources of mental health distress.
The association of left ventricular histologically verified myocardial fibrosis with pulmonary hypertension in severe aortic stenosis
Authors: Gumauskiene Birute , Drebickaite Egle , Pangonyte Dalia , Vaskelyte Jolanta Justina , Padervinskiene Lina , Jakuska Povilas , Budrikis Algimantas , Ereminas Rokas , Ereminiene Egle 
Published: September 2021

Objectives: To evaluate the association between histologically verified left ventricular (LV) myocardial fibrosis (MF) and its bio- and functional markers with pulmonary hypertension (PH) in severe aortic stenosis (AS). Methods: About 34 patients with isolated severe AS underwent 2D echocardiography, cardiac magnetic resonance (CMR) imaging, and plasma NT-proBNP evaluation before aortic valve replacement (AVR). LV measurements were analyzed by CMR and LV strain using feature tracking software (Medis Suite QStrain 2.0). Myocardial biopsy sampled at the time of AVR was assessed by a histomorphometric analysis. PH was defined as pulmonary artery systolic pressure (PASP) ⩾ 45 mm Hg. Results: Patients with severe AS and PH (mean PASP 53 ± 3.7 mm Hg) had higher extent of diffuse MF versus patients without PH (12 (10.4–12.7)% vs 6.6 (4.6–8.2)% (p = 0.00)). The extent of diffuse MF correlated with LV dilatation ( r = 0.7, p = 0.02), indices of LV dysfunction (lower ejection fraction ( r = −0.6, p < 0.001), global longitudinal ( r = −0.5, p = 0.02) and circumferential strain ( r = −0.5, p = 0.05), elevated NT-proBNP ( r = 0.5, p = 0.005) and elevated PASP ( r = 0.6, p < 0.001)). Histological MF > 10% (AUC 94.9%), LV global longitudinal strain > −15.5% (AUC 86.3%), and NT-proBNP > 2090 ng/l (AUC 85.1%) were independent predictors of PH in severe AS. Conclusions: The extent of diffuse myocardial fibrosis in combination with reduced longitudinal left ventricular strain and increased plasma levels of NT-proBNP relates to pulmonary hypertension in severe aortic stenosis.
Association between long non-coding RNA (lncRNA) GAS5 polymorphism rs145204276 and cancer risk
Authors: Zhao Shushan , Liu Ping , Ruan Zhe , Li Jianhuang , Zeng Shan , Zhong Meizuo , Tang Lanhua 
Published: September 2021

Objective The long non-coding RNA (lncRNA) growth arrest‑specific transcript 5 (GAS5) plays an important role in various tumors, and an increasing number of studies have explored the association of the GAS5 rs145204276 polymorphism with cancer risk with inconclusive results. Methods PubMed, Medline, EMBASE, Cochrane databases, and Web of Science were searched, and nine studies involving 6107 cases and 7909 controls were deemed eligible. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to evaluate the relationship between rs145204276 and cancer risk in six genetic models. Results The pooled results suggest that the variant allele del was not associated with overall cancer risk. However, the subgroup analysis showed that allele del was significantly associated with a 22% decreased risk of gastrointestinal cancer (OR = 0.78, 95% CI: 0.72–0.85). Both sensitivity analyses and trial sequential analyses (TSA) demonstrated that the subgroup results were reliable and robust. Moreover, False-Positive Report Probability (FPRP) analysis indicated that the results had true significant correlations. Conclusion These findings provide evidence that the GAS5 rs145204276 polymorphism is associated with the susceptibility to gastrointestinal cancer. Further studies with different ethnicities and larger sample sizes are warranted to confirm these results.
Renin–angiotensin system inhibitors and clinical outcomes in patients with atrial fibrillation and heart failure: a propensity score-matched study from the Chinese Atrial Fibrillation Registry
Authors: Lin Jing , He Liu , Qiao Qing , Du Xin , Ma Chang-Sheng , Dong Jian-Zeng 
Published: September 2021

Objective The effect of renin–angiotensin system inhibitors (RASIs) in patients with heart failure (HF) and atrial fibrillation (AF) remains unclear. This study aimed to investigate associations between RASI use and all-cause mortality and cardiovascular outcomes in patients with AF and HF. Methods Using data from the China Atrial Fibrillation Registry study, we included 938 patients with AF and HF with a left ventricular ejection fraction <50%. Cox regression models for RASIs vs. non-RASIs with all-cause mortality as the primary outcome were fitted in a 1:1 propensity score-matched cohort. A sensitivity analysis was performed by using a multivariable time-dependent Cox regression model. As an internal control, we assessed the relation between β-blocker use and all-cause mortality. Results During a mean follow-up of 35 months, the risk of all-cause mortality was similar in RASI users compared with non-users (hazard ratio: 0.92; 95% confidence interval: 0.67–1.26). Similar results were obtained in the sensitivity analysis. In contrast, β-blocker use was associated with significantly lower all-cause mortality in the same population. Conclusions RASI use was not associated with better outcomes in patients with AF and HF in this prospective cohort, which raises questions about their value in this specific subset. Trail Registration: ChiCTR-OCH-13003729.
Radial Head Lag: A Possible Biomechanical Mechanism for Osteochondritis Dissecans of the Capitellum in Baseball Pitchers
Authors: Rotman Dani , Kwak Jae-Man , Rojas Lievano Jorge , Hooke Alexander , Camp Christopher L. , Fitzsimmons James S. , O’Driscoll Shawn W. 
Published: September 2021

Background: Osteochondritis dissecans (OCD) of the capitellum is common in throwing athletes and is believed to result from repetitive overloading on the radiocapitellar (RC) joint, although the cause and mechanism remain unclear. The torsional forces (moments) generated by the triceps during elbow extension pull only on the ulna; therefore, the radial head moves passively across the capitellum and is effectively “dragged along” by the ulna. Any laxity in the proximal radioulnar joint could lead to asynchronous motion between the radius and ulna, resulting in the radial head lagging behind the coronoid and possibly malarticulating with the capitellum during such motion. Hypothesis: Radial head motion on the capitellum lags behind ulnohumeral joint motion during simulated throwing. Study Design: Controlled laboratory study. Methods: A total of 8 cadaveric elbows were tested under simulated throwing, including active extension of the elbow generated by pulling of the triceps under valgus stress, as well as during passive extension under valgus stress to serve as a reference. Ulnohumeral motion was tracked using a video camera. Radial head motion was tracked using an intra-articular, thin-film pressure sensor mounted on the capitellum, and the longitudinal movement of the center of force (COF) of the radial head was measured. Radial head motion was compared between passive and active motion for each 10° of elbow extension from 90° to 20°. Results: Elbow motion during simulated active extension reached an angular velocity of 366 deg/s. Radial head motion during simulated active extension significantly lagged compared with its motion during passive extension at every elbow extension angle examined between 70° and 20° ( P < .001). The maximal lag reached a mean of 4 mm (range, 2-7 mm). In other words, RC and ulnohumeral motion were asynchronous during simulated throwing. Conclusion: This study describes a novel phenomenon: motion of the radial head across the capitellum during rapid extension, such as in baseball pitching, lags behind that seen during passive elbow motion. According to a new proposed theory of OCD lesion development, this lag should result in RC incongruency and elevated shear forces on the capitellum due to edge loading. Clinical Relevance: We propose a new biomechanical explanation for OCD of the capitellum in baseball pitchers: radial head lag. Understanding this process is the first step in efforts to prevent this common injury.