bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic effects of the novel Leucyl-tRNA synthetase inhibitor BC-LI-0186 in non-small cell lung cancer
Authors: Kim Eun Young , Lee Jin Gu , Lee Jung Mo , Kim Arum , Yoo Hee Chan , Kim Kibum , Lee Minji , Lee Chulho , Han Gyoonhee , Han Jung Min , Chang Yoon Soo 
Published: May 2019

Objective: Leucyl-tRNA synthetase (LRS) is an aminoacyl-tRNA synthetase catalyzing ligation of leucine to its cognate tRNA and is involved in the activation of mTORC1 by sensing cytoplasmic leucine. In this study, the usefulness of LRS as a therapeutic target of non-small cell lung cancer (NSCLC) and the anticancer effect of the LRS inhibitor, BC-LI-0186, was evaluated. Methods: LRS expression and the antitumor effect of BC-LI-0186 were evaluated by immunohistochemical staining, immunoblotting, and live cell imaging. The in vivo antitumor effect of BC-LI-0186 was evaluated using Lox-Stop-Lox (LSL) K-ras G12D mice. Results: LRS was frequently overexpressed in NSCLC tissues, and its expression was positively correlated with mTORC1 activity. The guanosine-5’-triphosphate (GTP) binding status of RagB was related to the expression of LRS and the S6K phosphorylation. siRNA against LRS inhibited leucine-mediated mTORC1 activation and cell growth. BC-LI-0186 selectively inhibited phosphorylation of S6K without affecting phosphorylation of AKT and leucine-mediated co-localization of Raptor and LAMP2 in the lysosome. BC-LI-0186 induced cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3 and increase of p62 expression, showing that it has the autophagy-inducing property. BC-LI-0186 has the cytotoxic effect at nanomolar concentration and its GI50 value was negatively correlated with the degree of LRS expression. BC-LI-0186 showed the antitumor effect, which was comparable with that of cisplatin, and mTORC1 inhibitory effect in a lung cancer model. Conclusions: BC-LI-0186 inhibits the noncanonical mTORC1-activating function of LRS. These results provide a new therapeutic strategy for NSCLC and warrant future clinical development by targeting LRS.
Systematic evaluation of computed tomography angiography collateral scores for estimation of long-term outcome after mechanical thrombectomy in acute ischaemic stroke
Authors: Weiss Daniel , Kraus Bastian , Rubbert Christian , Kaschner Marius , Jander Sebastian , Gliem Michael , Lee John-Ih , Haensch Carl-Albrecht , Turowski Bernd , Caspers Julian 
Published: May 2019

Purpose This study compares computed tomography angiography-based collateral scoring systems in regard to their inter-rater reliability and potential to predict functional outcome after endovascular thrombectomy, and relates them to parenchymal perfusion as measured by computed tomography perfusion. Methods Eighty-four patients undergoing endovascular thrombectomy in anterior circulation ischaemic stroke were enrolled. Modified Tan Score, Miteff Score, Maas Score and Opercular Index Score ratio were assessed in pre-interventional computed tomography angiographies independently by two readers. Collateral scores were tested for inter-rater reliability by weighted-kappa, for correlations with three-months modified Rankin Scale, and their potential to differentiate between patients with favourable (modified Rankin Scale ≤2) and poor outcome (modified Rankin Scale ≥3). Correlations with relative cerebral blood volume and relative cerebral blood flow were tested in patients with available computed tomography perfusion. Results Very good inter-rater reliability was found for Modified Tan, Miteff and Opercular Index Score ratio, and substantial reliability for Maas. There were no significant correlations between collateral scores and three-months modified Rankin Scale, but significant group differences between patients with favourable and poor outcome for Maas, Miteff and Opercular Index Score ratio. Miteff and Maas were significant predictors of favourable outcome in binary logistic regression analysis. Miteff best differentiated between both outcome groups in receiver-operating characteristics, and Maas reached highest sensitivity for favourable outcome prediction of 96%. All collateral scores significantly correlated with mean relative cerebral blood volume and relative cerebral blood flow. Conclusions Computed tomography angiography scores are valuable in estimating functional outcome after mechanical thrombectomy and reliable across readers. The more complex scores, Maas and Miteff, show the best performances in predicting favourable outcome.
Molecular biology and targeted therapy in metastatic renal cell carcinoma
Authors: Whiting D , Sriprasad S 
Published: May 2019

The treatment of metastatic renal cell carcinoma is challenging as it has proven to be relatively resistant to conventional oncological treatments. An improved understanding of the molecular biology of renal cell carcinoma has led to the development of a number of targeted therapies in metastatic renal cell carcinoma. This includes vascular endothelial growth factor inhibitors, tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors and most recently immune checkpoint inhibitors. This article will review the mechanisms of development and progression of renal cell carcinoma as well as the mechanisms of current approved treatments in metastatic disease. Level of evidence: Not applicable for this multicentre audit.
Differences in outcome after cruciate retaining and posterior stabilized total knee arthroplasty
Authors: Singleton Neal , Nicholas Bryden , Gormack Nick , Stokes Andrew 
Published: May 2019

Background: Both cruciate retaining (CR) and posterior stabilized (PS) implants are commonly used for primary total knee arthroplasty. There is evidence to support improved range of motion in PS knee replacements, but there is no evidence showing functional superiority. The aim of this study was to compare functional outcomes between CR and PS knee replacements. Patient and methods: Prospectively collected regional joint registry data were used to compare preoperative and postoperative one, 5- and 10-year Oxford and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores in 1287 primary total knee replacements. Differences in functional scores between CR and PS knees were calculated. Results: The PS group had better functional scores than the CR group at baseline (mean Oxford score 15.59 vs. 14.52 ( p = 0.026) and mean WOMAC score 59.51 vs. 62.35 ( p = 0.012)), at 1 year postoperatively (mean Oxford score 37.94 vs. 36.63 ( p = 0.015) and mean WOMAC score 16.20 vs. 19.73 ( p = 0.001)) with a similar trend at 5 years postoperatively (mean Oxford score 39.66 vs. 38.50 ( p = 0.054) and mean WOMAC score 16.89 vs. 18.83 ( p = 0.131)). There was no difference in the overall functional improvement between the PS and CR groups at 1, 5, or 10 years. WOMAC subcomponent scores showed greater improvement in stiffness; 3.76 versus 3.36 ( p = 0.012) in PS knees at 1 year postoperatively. No significant differences were observed at 5 or 10 years. Conclusions: PS knee replacements showed greater improvement in stiffness at 1 year postoperatively. There was no difference observed at 5 or 10 years postoperatively. PS knees had better functional outcomes at 1 year with a similar trend at 5 years postoperatively. Level of evidence: III.
Correlation of radiological parameters to functional outcome in complex proximal humerus fracture fixation: A study of 127 cases
Authors: Dheenadhayalan J , Prasad V Durga , Devendra A , Rajasekaran S 
Published: May 2019

Objective: The purpose of this study is to analyze the radiological and functional outcome of complex proximal humerus fractures treated by open reduction and plate fixation, and how radiological parameters correlate with functional outcome. Design: Retrospective study. Setting: Level-1 trauma center. Patients/methods: One hundred twenty-seven patients were analyzed, with a mean follow-up of 5 (3–7) years. Outcome measurements: Radiological parameters studied were neck-shaft angle (NSA), greater tuberosity (GT) to articular surface (AS) distance, medial hinge reduction, and presence (or absence) of calcar screw. Functional outcome evaluated by DASH and Constant–Murley (C-M) score. Results: The mean age is 53.8 years. All patients had a union in 14 (12–18) weeks. The mean NSA is 135° (112–155°). One hundred and thirteen patients with an NSA of >120° had a good functional outcome. Fourteen patients with NSA ≤120° had shoulder abduction <90°. The mean GT to AS distance is 7.2 mm (−2 to 16). The superior displacement of GT above AS is associated with abduction of <90° (16 patients). The mean medial gap is 3 mm (0–17). In 14 patients with a medial gap of >4 mm and without calcar screw, varus collapse is observed. All patients had a good outcome on DASH score and 122 patients had good to excellent outcome on C-M score. Five patients with poor outcome on C-M score had NSA <120° and displacement of GT above AS. Conclusion: Radiographic indicators for poor outcome are varus angulation with NSA <120°, superior displacement of GT above AS, the presence of medial gap >4 mm, and absence of calcar specific screw. This “terrible triad” of proximal humerus fracture should be avoided during operative fixation.
Association Between Parental Understanding of Pitch Smart Guidelines and Youth Baseball Player Injuries
Authors: Zabawa Luke , Alland Jeremy A. 
Published: May 2019

Background: Injuries continue to rise among youth baseball players despite extensive research into prevention and the availability of throwing guidelines such as Pitch Smart. More research is needed to understand whether adherence to the current guidelines decreases injuries. Purpose: To understand the degree to which parents are aware of the Pitch Smart guidelines, whether parents adhere to the guidelines, and whether adherence results in decreased injuries in youth baseball players. Study Design: Cross-sectional study. Methods: An anonymous, internet-based survey consisting of 44 items was distributed to parents of adolescent baseball players affiliated with various youth baseball organizations across the midwestern United States; 15 items on the survey served as assessment questions of the Pitch Smart guidelines. Absolute and percentage correct scores were calculated and compared by use of a Student t test. A chi-square analysis was used to compare discrete data. A binary logistic regression analysis was conducted to determine whether showcase participation predicted player injury. Results: A total of 853 parents completed the survey. The mean ± SD age of the players on whom parents reported was 11.37 ± 3.5 years (range, 6-20 years). Among the cohort, 422 players regularly pitched. Regarding Pitch Smart guidelines, the percentage of correct answers by parents was 55.44% ± 0.3% for a player with a reported injury history and 62.14% ± 0.2% for a player without an injury history ( P = .012). The number of correct answers was 8.03 ± 4.0 for the group with an injury history and 9.17 ± 3.2 for the group with no history of injury ( P = .004). Binary logistic regression analysis, which controlled for age, indicated that showcase participation ( P = .001, β = 1.043 ± 0.026, R2 = 0.178) was a significant predictor of player injury. Conclusion: Pitchers are at an increased risk of injury compared with nonpitchers. Parents who are knowledgeable about the Pitch Smart throwing guidelines and actively follow them are significantly less likely to have a child with an injury. Excessive showcase participation is predictive of player injury when the analysis controls for age.
Fixing What’s Most Broken in the US Immigration System: A Profile of the Family Members of US Citizens and Lawful Permanent Residents Mired in Multiyear Backlogs
Authors: Kerwin Donald , Warren Robert 
Published: May 2019

Executive Summary The US Department of State (DOS) reports that as of November 2018, nearly 3.7 million persons had been found by US Citizenship and Immigration Services (USCIS) to have a close family relationship to a US citizen or lawful permanent resident (LPR) that qualified them for a visa, but were on “the waiting list in the various numerically-limited immigrant categories” ( DOS 2018 ). These backlogs in family-based “preference” (numerically capped) categories represent one of the most egregious examples of the dysfunction of the US immigration system. They consign family members of US citizens and LPRs that potentially qualify for a visa and that avail themselves of US legal procedures to years of insecurity, frustration, and (often) separation from their families. Often criticized in the public sphere for jumping the visa queue, it would be more accurate to say that this population, in large part, comprises the queue. While they wait for their visa priority date to become current, those without immigration status are subject to removal. In addition, most cannot adjust to LPR status in the United States, but must leave the country for consular processing and, when they do, face three- or 10-year bars on readmission, depending on the duration of their unlawful presence in the United States. This population will also be negatively affected by the Department of Homeland Security’s (DHS) proposed rule to expand the public charge ground of inadmissibility ( Kerwin, Warren, and Nicholson 2018 ). In addition, persons languishing in backlogs enjoy few prospects in the short term for executive or legislative relief, given political gridlock over immigration reform and the Trump administration’s support for reduced family-based immigration.
Competitive interaction with keystone taxa induced negative priming under biochar amendments
Authors: Chen Lijun , Jiang Yuji , Liang Chao , Luo Yu , Xu Qinsong , Han Cheng , Zhao Qiguo , Sun Bo 
Published: May 2019

AbstractBackgroundBiochar amendments have been widely proposed as a conventional and efficient strategy to promote soil organic carbon (SOC) sequestration via negative priming. Unfortunately, the extent and biological mechanisms responsible for biochar-induced negative priming are still not fully understood. Despite traditional explanations focused on the environmental filtering mechanisms of biochar amendments on microbial biomass and community composition underlying the priming effect on SOC dynamics, whether and how a biochar-induced competitive interaction with keystone taxa determines SOC mineralization in natural ecosystems has been minimally explored.ResultsHere, we paid particular attention to the relationships between the diversity and network structure of soil bacterial and fungal communities and SOC mineralization. A 3-year field experiment was conducted comprising five treatments: no fertilization, conventional fertilization, and conventional fertilization with three rates of biochar amendments. Biochar amendments considerably increased soil moisture capacity and pH and subsequently shaped the composition and co-occurrence networks of soil bacterial and fungal communities. Importantly, network analysis revealed that the biochar amendments triggered the competitive interaction with putative keystone taxa in the bacterial and fungal networks. Structural equation modeling suggested that the competitive interaction with keystone taxa promoted bacterial and fungal diversity and consequently reduced carbohydrate catabolism and soil metabolic quotient. Stable isotope probing incubations further provided consistent evidence of competition by keystone taxa with the increases in bacterial and fungal diversity under the biochar amendments.ConclusionsWe found that biochar-induced competition with keystone taxa stimulated the bacterial and fungal diversity and consequently decreased SOC mineralization. The comprehensive understanding of the unexplored biological mechanisms underlying the biochar-induced negative priming may provide crucial implications for enabling SOC sequestration.
Cancer Drug Use in the Last Month of Life in Men With Castration-Resistant Prostate Cancer
Authors: Hu Jason , Aprikian Armen G. , Vanhuyse Marie , Dragomir Alice 
Published: May 2019

PURPOSE: Several new drug therapies have been approved in CRPC in the past decade. However, little is known about their potential overuse at the end of life. Cancer therapy use at the end of life has been considered an indicator of overtreatment. The study objective was to describe CRPC drug use in the last month of life of CRPC patients in Quebec. PATIENTS AND METHODS: Using administrative databases from the province of Quebec in Canada, we identified patients who received medical or surgical castration treatment, received one or more CRPC drugs (chemotherapy, abiraterone, or bone-targeted therapy), and died between 2001 and 2013. CRPC drug use in the last month of life was the primary outcome. RESULTS: The cohort consisted of 1,148 patients with CRPC. A total of 316 men (27.5%) received a CRPC drug in the last month of life. For those who received chemotherapy, abiraterone, and bone-targeted therapy, 10.2%, 27.8%, and 31.8% received them in the last month of life, respectively. In multivariable analyses, age older than 75 years (odds ratio [OR], 0.75; 95% CI, 0.57 to 0.99), and prostate cancer diagnosis received less than 24 months earlier (OR, 0.43; 95% CI, 0.26 to 0.72) were associated with less CRPC drug use. Relative to dying between 2005 and 2011, dying between 2012 and 2013 (OR 1.60; 95% CI, 1.18 to 2.18) was associated with greater CRPC drug use. CONCLUSION: More than one quarter of patients received CRPC drug therapies in the last month of life. Persistent chemotherapy, abiraterone, bone-targeted therapies, and medical castration drugs in the last month of life may be an indicator of inappropriate and expensive end-of-life care.
Insulin Resistance and Atherosclerosis: Implications for Insulin-Sensitizing Agents
Authors: Di Pino Antonino , DeFronzo Ralph A 
Published: May 2019

AbstractPatients with type 2 diabetes mellitus (T2DM) are at high risk for macrovascular complications, which represent the major cause of mortality. Despite effective treatment of established cardiovascular (CV) risk factors (dyslipidemia, hypertension, procoagulant state), there remains a significant amount of unexplained CV risk. Insulin resistance is associated with a cluster of cardiometabolic risk factors known collectively as the insulin resistance (metabolic) syndrome (IRS). Considerable evidence, reviewed herein, suggests that insulin resistance and the IRS contribute to this unexplained CV risk in patients with T2DM. Accordingly, CV outcome trials with pioglitazone have demonstrated that this insulin-sensitizing thiazolidinedione reduces CV events in high-risk patients with T2DM. In this review the roles of insulin resistance and the IRS in the development of atherosclerotic CV disease and the impact of the insulin-sensitizing agents and of other antihyperglycemic medications on CV outcomes are discussed.
CLARITY-BPA Program in Rats: Is It Translatable to Humans?
Authors: Hagobian Todd 
Published: May 2019

Abstract
The Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA) program was the most comprehensive study to date examining a full range of health effects of varying bisphenol A (BPA) exposure in rats. The major concern of the CLARITY-BPA program that has not previously been discussed is whether exposing rats to varying doses to BPA is translatable to humans, even at the “typical” exposure ranges for humans. This perspective will provide evidence that the vast majority of pharmaceutical drug development and other trials in animals have not been replicated in human randomized studies. Similarly, to truly understand whether BPA exposure affects human health, clinical trials are needed to examine BPA administration in humans in controlled settings.
Providing dental care in prisons
Authors: Howard Paul 
Published: May 2019

This paper will summarize some of the clinical and organizational challenges for dentists and dental care professionals who are interested in working in custodial environments. This briefly covers some of the difficulties and pressures that the dental team face in providing dental care within these very specific environments. There are some features unique to this population group that can negatively affect their dental health experiences, related to socio-economic, lifestyle and other factors. In general, prisoners enjoy poorer dental health and mental health than the general population and present a greater degree of learning difficulties than the population at large. This requires additional skills and training for the dental teams treating this group and presents a number of challenges not always found in the provision of routine primary care dentistry. CPD/Clinical Relevance: Although the article describes the provision of care for the prison environment in England, this is mirrored in other parts of the United Kingdom and the same general considerations will apply and be recognized in prisons in other national systems of dental care. Many of the areas covered are relevant independent of the systems in which care is delivered.
HOMENAGEM A THIERRY SALMON
Authors: Molinari Renata M. , De Paula Eduardo , De Castro Maurício Paroni 
Published: May 2019

Título: Homenagem a Thierry Salmon
Resumo: “Homenagem à Thierry Salmon” é um dossiê publicado na revista Prove di Drammaturgia (nº.2, 2002), sob a curadoria de Renata M. Molinari – dramaturga por dezesseis anos junto a Salmon. Resultado de um simpósio realizado pela Università di Bologna, no qual atores e atrizes, iluminador, sonoplasta, preparadores corporal e vocal, se reuniram para relembrar, refletir e compartilhar as questões centrais relativas ao “Projeto Amazonas”. Entre outros elementos presentes no rol das atenções de Thierry Salmon, os temas compartilhados eram relativos às tensões referentes aos universos feminino e masculino, ao espaço-memória, a permeabilidade e o imprevisto como elementos instaladores de oportunidades para se colocar em jogo com o real.
Palavras-chave: Thierry Salmon, Teatro, Encenação, Atuação, Real.

Titolo: Omaggio a Thierry Salmon
Riassunto: “Omaggio a Thierry Salmon” è un dossier pubblicato nella rivista Prove di Drammaturgia (nº.2, 2002), a cura di Renata M. Molinari – drammaturg per più di sedici anni accanto a Salmon. Risultato di un colloquio tenuto all`Università di Bologna, in cui attori e attrici, light and sound designer, coreografa, preparatori fisici e vocali, si raccolsero per ricordare e riflettere sul lavoro con Thierry Salmon, condividendo le questioni centrali riguardanti il Progetto Amazzone. Tra gli altri elementi messi in risalto nell’elenco delle priorità di Thierry Salmon in questo progetto e oltre, emergono i temi della relazione tra universo femminile e maschile, lo spazio della memoria, la permeabilità e l’imprevisto come fondamenti dell’opportunità di mettersi in gioco con il reale.
Parole chiave: Thierry Salmon, Teatro, Regia, Recitazione/Rappresentazione, Reale.

Title: Tribute to Thierry Salmon
Abstract: Tribute to Thierry Salmon is a dossier published in the magazine Prove di Drammaturgia (n°.2, 2002), under the curatorship of Renata M. Molinari – dramaturge for sixteen years alongside Salmon. It is the result of a symposium held at the University of Bologna, in which actors and actresses, light and sound designers, movement and vocal instructors, gathered together to remember, reflect and share the important questions related to the Amazon Project. Among other things that concerned Thierry Salmon, the topics shared were related to the tension between the female and male universes, between space and memory, between permeability and unexpected, as elements that open opportunities to bring the real in the theatrical game.
Keywords: Thierry Salmon, Theatre, Staging, Acting, Real.