bluuebunny/crossref_metadata_2025_split huggingface dataset:
Supporting the existence of two isolated evolutionary lineages ofGerres(Perciformes: Gerreidae) in America
Authors: García‐Rodríguez Francisco J. , Chollet‐Villalpando Jorge G. , Martínez‐Guevara Adriana , De La Cruz‐Agüero José 
Published: May 2019

AbstractFor many years in America, many authors have considered that theGerresgenus contained a single species, the yellowfin mojarraGerres cinereus(Walbaum, 1792); however, others have recognized two species in this genus in the Neotropics. In this study, specimens ofG. cinereus(sensulato) caught throughout its geographic range on both coasts of America were compared for the first time to analyse divergence among the sampled populations. A genetic analysis based on DNA sequences from three mitochondrial genes and one nuclear gene revealed a clear separation of two clades, one in the Pacific and one in the Atlantic. Geometric morphometric differences, based on body shape, sagittae otoliths and urohyal bone features, were significant between the two groups, including separation by an accurate classification a posteriori by a canonical variate analysis (CVA) > 82% in all data sets (overall mean >91%). Integration of the results of these approaches indicates that there is sufficient evidence to support species status forGerres simillimusRegan, 1907, and it should be considered a valid species in the neotropical Pacific.
PGC1α Inhibits Polyamine Synthesis to Suppress Prostate Cancer Aggressiveness
Authors: Kaminski Lisa , Torrino Stéphanie , Dufies Maeva , Djabari Zied , Haider Romain , Roustan François-René , Jaune Emilie , Laurent Kathiane , Nottet Nicolas , Michiels Jean-François , Gesson Maeva , Rocchi Stéphane , Mazure Nathalie M. , Durand Matthieu , Tanti Jean-François , Ambrosetti Damien , Clavel Stephan , Ben-Sahra Issam , Bost Frédéric 
Published: May 2019

Abstract

Although tumorigenesis is dependent on the reprogramming of cellular metabolism, the metabolic pathways engaged in the formation of metastases remain largely unknown. The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) plays a pleiotropic role in the control of cancer cell metabolism and has been associated with a good prognosis in prostate cancer. Here, we show that PGC1α represses the metastatic properties of prostate cancer cells via modulation of the polyamine biosynthesis pathway. Mechanistically, PGC1α inhibits the expression of c-MYC and ornithine decarboxylase 1 (ODC1), the rate-limiting enzyme for polyamine synthesis. Analysis of in vivo metastases and clinical data from patients with prostate cancer support the proposition that the PGC1α/c-MYC/ODC1 axis regulates polyamine biosynthesis and prostate cancer aggressiveness. In conclusion, downregulation of PGC1α renders prostate cancer cells dependent on polyamine to promote metastasis.

Significance:
These findings show that a major regulator of mitochondrial metabolism controls polyamine synthesis and prostate cancer aggressiveness, with potential applications in therapy and identification of new biomarkers.
Collagen Prolyl Hydroxylation–Dependent Metabolic Perturbation Governs Epigenetic Remodeling and Mesenchymal Transition in Pluripotent and Cancer Cells
Authors: D'Aniello Cristina , Cermola Federica , Palamidessi Andrea , Wanderlingh Luca G. , Gagliardi Miriam , Migliaccio Agnese , Varrone Francesca , Casalino Laura , Matarazzo Maria R. , De Cesare Dario , Scita Giorgio , Patriarca Eduardo J. , Minchiotti Gabriella 
Published: May 2019

Abstract

Collagen prolyl hydroxylation (CPH), which is catalyzed by prolyl 4-hydroxylase (P4H), is the most prevalent posttranslational modification in humans and requires vitamin C (VitC). Here, we demonstrate that CPH acts as an epigenetic modulator of cell plasticity. Increased CPH induced global DNA/histone methylation in pluripotent stem and tumor cells and promoted cell state transition (CST). Interfering with CPH by either genetic ablation of P4H subunit alpha-2 (P4HA2) or pharmacologic treatment reverted epigenetic changes and antagonized CST. Mechanistically, we suggest that CPH modifies the epigenetic landscape by reducing VitC for DNA and histone demethylases. Repurposed drugs targeting CPH-mediated metabolic perturbation, such as the antiasthmatic budesonide, blocked metastatic dissemination of breast cancer cells in vivo by preventing mesenchymal transition. Our study provides mechanistic insights into how metabolic cues and epigenetic factors integrate to control CST and paves the way for the development of novel antimetastatic strategies.

Significance:
A phenotype-based high-throughput screening reveals unforeseen metabolic control of cell plasticity and identifies budesonide as a drug candidate for metastatic cancer.
DNA Damage Response Inhibitor Combinations Exert Synergistic Antitumor Activity in Aggressive B-Cell Lymphomas
Authors: Restelli Valentina , Lupi Monica , Chilà Rosaria , Vagni Micaela , Tarantelli Chiara , Spriano Filippo , Gaudio Eugenio , Bertoni Francesco , Damia Giovanna , Carrassa Laura 
Published: May 2019

Abstract
The DNA damage response (DDR) kinases ATR, Chk1, and Wee1 play vital roles in the response to replication stress and in maintaining cancer genomic stability. Inhibitors of these kinases are currently under clinical investigation. Mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) are aggressive lymphomas whose clinical outcome is still largely unsatisfactory. These cell lymphoma subtypes are highly dependent on both Chk1 and Wee1 for survival. We investigated the activity of the ATR inhibitor AZD6738 as single agent and in combination with either Chk1 (AZD6738) or Wee1 (AZD1775) inhibitors in several preclinical models of MCL and DLBCL. This study included preclinical in vitro activity screening on a large panel of cell lines, both as single agent and in combination, and validation experiments on in vivo models. Cellular and molecular mechanisms of the observed synergistic effect as well as pharmacodynamic analysis of in vivo samples were studied. AZD6738 exerted a strong synergistic cytotoxic effect in combination with both AZD7762 and AZD1775 in the 2 lymphoma subtypes regardless of their TP53, MYC, and ATM mutational status. These DDR inhibitor combinations, similarly to the Chk1/Wee1 inhibitor combination, caused a marked S-phase delay, with an increase in cyclin-dependent kinases (CDK) activity, increased DNA damage, and decreases in Wee1, MYC, and RRM2 protein levels. The synergistic in vitro activity translated to striking in vivo antitumor activity. DDR–DDR inhibitor combinations could potentially offer promising novel therapeutic strategies for patients with B-cell lymphoma.
RORγ Agonists Enhance the Sustained Antitumor Activity through Intrinsic Tc17 Cytotoxicity and Tc1 Recruitment
Authors: Liu Xikui , Zawidzka Elizabeth M. , Li Hongxiu , Lesch Charles A. , Dunbar Jenna , Bousley Dick , Zou Weiping , Hu Xiao , Carter Laura L. 
Published: May 2019

Abstract
Activation of RORγ with synthetic small-molecule agonists has been shown to enhance type 17 effector (CD4+ Th17 and CD8+ Tc17 cells) cell functions and decrease immunosuppressive mechanisms, leading to improved antitumor efficacy in adoptive cell transfer and syngeneic murine tumor models. However, whether Tc17 cells possess intrinsic cytotoxicity and the mechanism they use to lyse target cells is controversial. We report here that Tc17 cells were lytic effectors dependent on perforin and granzyme A. In contrast to Tc1 cells, Tc17 cells resisted activation-induced cell death and maintained granzyme A levels, which conferred the ability to lyse target cells in serial encounters. Thus, although the acute lytic capacity of Tc17 cells could be inferior to Tc1 cells, comparable lysis was achieved over time. In addition to direct lytic activity, Tc17 cells infiltrated early into the tumor mass, recruited other CD8+ T cells to the tumor, and enhanced the survival and lytic capability of these cells during repeated target encounters. Synthetic RORγ agonists further augmented Tc17 survival and lytic activity in vitro and in vivo, controlling tumor growth not only through direct cytotoxicity, but also through recruitment and improved function of other effector cells in the tumor microenvironment, which suggests complementary and cooperate activities for effective immunotherapy.
Association of Arsenic Exposure With Cardiac Geometry and Left Ventricular Function in Young Adults
Authors: Pichler Gernot , Grau-Perez Maria , Tellez-Plaza Maria , Umans Jason , Best Lyle , Cole Shelley , Goessler Walter , Francesconi Kevin , Newman Jonathan , Redon Josep , Devereux Richard , Navas-Acien Ana 
Published: May 2019

Background:
Arsenic exposure has been related to numerous adverse cardiovascular outcomes. The aim of this study was to investigate the cross-sectional and prospective association between arsenic exposure with echocardiographic measures of left ventricular (LV) geometry and functioning.

Methods:
A total of 1337 young adult participants free of diabetes mellitus and cardiovascular disease were recruited from the SHFS (Strong Heart Family Study). The sum of inorganic and methylated arsenic concentrations in urine (ΣAs) at baseline was used as a biomarker of arsenic exposure. LV geometry and functioning were assessed using transthoracic echocardiography at baseline and follow-up.

Results:
Mean follow-up was 5.6 years, and median (interquartile range) of ΣAs was 4.2 (2.8–6.9) µg/g creatinine. Increased arsenic exposure was associated with prevalent LV hypertrophy, with an odds ratio (95% CI) per a 2-fold increase in ΣAs of 1.47 (1.05–2.08) in all participants and of 1.58 (1.04–2.41) among prehypertensive or hypertensive individuals. Measures of LV geometry, including LV mass index, left atrial systolic diameter, interventricular septum, and LV posterior wall thickness, were positively and significantly related to arsenic exposure. Among measures of LV functioning, stroke volume, and ejection fraction were associated with arsenic exposure.

Conclusions:
Arsenic exposure was related to an increase in LV wall thickness and LV hypertrophy in young American Indians with a low burden of cardiovascular risk factors. The relationship was stronger in participants with prehypertension or hypertension, suggesting that potential cardiotoxic effects of arsenic might be more pronounced in individuals already undergoing cardiovascular adaptive mechanisms following elevated systemic blood pressure.
ENSO Normals: A New U.S. Climate Normals Product Conditioned by ENSO Phase and Intensity and Accounting for Secular Trends
Authors: Arguez Anthony , Inamdar Anand , Palecki Michael A. , Schreck Carl J. , Young Alisa H. 
Published: May 2019

AbstractClimate normals are traditionally calculated every decade as the average values over a period of time, often 30 years. Such an approach assumes a stationary climate, with several alternatives recently introduced to account for monotonic climate change. However, these methods fail to account for interannual climate variability [e.g., El Niño–Southern Oscillation (ENSO)] that systematically alters the background state of the climate similar to climate change. These effects and their uncertainties are well established, but they are not reflected in any readily available climate normals datasets. A new high-resolution set of normals is derived for the contiguous United States that accounts for ENSO and uses the optimal climate normal (OCN)—a 10-yr (15 yr) running average for temperature (precipitation)—to account for climate change. Anomalies are calculated by subtracting the running means and then compositing into 5 ENSO phase and intensity categories: Strong La Niña, Weak La Niña, Neutral, Weak El Niño, and Strong El Niño. Seasonal composites are produced for each of the five phases. The ENSO normals are the sum of these composites with the OCN for a given month. The result is five sets of normals, one for each phase, which users may consult with respect to anticipated ENSO outcomes. While well-established ENSO patterns are found in most cases, a distinct east–west temperature anomaly pattern emerges for Weak El Niño events. This new product can assist stakeholders in planning for a broad array of possible ENSO impacts in a changing climate.
The Influence of Cochlear Implantation on Tinnitus in Patients with Single‐Sided Deafness: A Systematic Review
Authors: Peter Nicole , Liyanage Nuwan , Pfiffner Flurin , Huber Alexander , Kleinjung Tobias 
Published: May 2019

ObjectivesThis systematic review provides an overview of the available studies (published by January 29, 2018) with descriptive data analysis about the influence of cochlear implantation on tinnitus in patients with single‐sided deafness (SSD).Data SourcesPubMed, EMBASE, Web of Science, Cochrane Library, and Google Scholar.Review MethodsOriginal studies about the influence of cochlear implantation on tinnitus, measured with different tinnitus questionnaires or visual analog scale, in patients with SSD were included. The pre‐ and postimplantation tinnitus scores of the included studies were extracted for the further systematic review.ResultsThe systematic search yielded 1028 studies. After evaluating titles, abstracts, and full texts, 1011 of these were dismissed. From the remaining 17 studies, 4 showed a low directness of evidence or high risk of bias and were therefore excluded. Due to the nature of cochlear implantation in SSD, only cohort studies and no randomized trials exist, which limits the evaluation in a systematic review. Generally, the mean tinnitus questionnaire scores decreased after cochlear implantation in these 13 studies with a total of 153 patients. The most widely used tinnitus questionnaire was the Tinnitus Handicap Inventory. In these studies, 34.2% of patients demonstrated complete suppression, 53.7% an improvement, 7.3% a stable value, and 4.9% an increase of tinnitus, and none of the patients reported an induction of tinnitus.ConclusionThis review shows a clear improvement of tinnitus complaints after cochlear implantation in patients with SSD. Therefore, tinnitus might be considered as an additional indication for cochlear implantation in SSD.
Can the current hypodontia care pathway promote shared decision-making?
Authors: Barber Sophy , Pavitt Sue , Meads David , Khambay Balvinder , Bekker Hilary 
Published: May 2019

Objective: To determine the extent to which the current care pathway in hypodontia promotes shared decision-making (SDM). Design: Exploratory cross-sectional study using qualitative methods. Setting: Orthodontic department of two NHS teaching hospitals in Yorkshire. Participants: Young people aged 12–16 years with hypodontia of any severity and at any stage of treatment, and their parents and guardians. Methods: (1) Observation and audio-recording of interdisciplinary consultation in hypodontia clinics (n = 5) without any researcher interference; (2) short, structured interviews with young people with hypodontia (n = 8) and their parent (n = 8) using a topic guide to explore themes around decision-making. Audio-recordings were transcribed and analysed using a thematic framework. Results: Consultations were used as an opportunity for interdisciplinary discussion, information provision and treatment planning. Evidence of good communication was observed but patient engagement was low. The decision to be made was usually stated and treatment options discussed, but time constraints limited the scope for adequate information exchange and assessment of understanding. No methods were used to establish patient and family preferences or values. Interviews suggested parents expect the dental team to make decisions and young people rely on parental advocacy. Despite little evidence of SDM, participants reported satisfaction with their treatment. Conclusions: The current care pathway for hypodontia does not support clinicians in the steps of SDM. Recommendations for improving SDM processes include support to identify preference-based decisions, greater access to comprehensive and accessible patient information to enable preparation for consultation, alternative methods for effective communication of complex information and use of preference elicitation tools to aid value-driven decision-making.
Per-operative glue embolization with surgical decompression: A multimodality treatment for aggressive vertebral haemangioma
Authors: Prabhuraj AR , Mishra Ajit , Mishra Rakesh Kumar , Pruthi Nupur , Saini Jitender , Arvinda HR 
Published: May 2019

Objective The aim of this study is to share our experience in per-operative embolization of aggressive vertebral haemangioma and to compare the surgical outcome with existing modalities of management. Background Vertebral haemangioma accounts for 12% of benign lesions of the vertebral column detected incidentally. Rarely they may enlarge, cause pain and neurological deficit because of spinal cord compression, vertebral body or arch expansion, or pathological fracture. Treatment options for symptomatic vertebral haemangioma include pre-operative transarterial embolization, surgical excision, radiotherapy, and percutaneous injection of alcohol or methyl methacrylate. We present our experience of per-operative glue embolization for aggressive (Enneking stage 3) vertebral haemangiomas. Materials and methods We describe five patients with symptomatic vertebral haemangioma at the dorsal level who underwent per-operative glue embolization. After initial laminectomy, a tumorogram was obtained under fluoroscopic guidance through direct contrast injection via spinal needle inserted through the pedicles of vertebra at the involved level. Varied concentration of glue was injected via the same spinal needle. All patients underwent surgical decompression of the intraspinal epidural component in the same sitting along with posterior spinal stabilization of the adjacent levels in two patients. Results In all five patients, complete embolization of the tumour was possible per-operatively through the transpedicular approach along with adjunctive surgical decompression, and the blood loss was significantly less. Clinical follow-up of these patients at 12–48 months showed reduction in size of the epidural component, relief of cord compression, and significant improvement in their neurological deficits with no recurrence. Conclusion We conclude that per-operative embolization is a safe and efficacious adjunctive procedure with surgical decompression with or without spinal stabilization for the treatment of symptomatic vertebral haemangiomas.
Goals, Recommendations, and the How-To Strategies for Developing and Facilitating Patient Safety and System Integration Simulations
Authors: Dubé Mirette , Shultz Jonas , Barnes Sue , Pascal Bobbi , Kaba Alyshah 
Published: May 2019

Purpose: The aim of this article is to outline overall goals, recommendations, and provide practical How-To strategies for developing and facilitating patient safety and system integration (PSSI) simulations for healthcare team members and organizations. Background: Simulation is increasingly being used as a quality improvement tool to better understand the tasks, environments, and processes that support the delivery of healthcare services. These PSSI simulations paired with system-focused debriefing can occur prior to implementing a new process or workflow to proactively identify system issues. They occur as part of a continuous cycle of quality improvement and have unique considerations for planning, implementation, and delivery of healthcare. Method: The Delphi technique was used to develop the recommendations and How-To strategies to guide those interested in conducting a PSSI simulations. The Delphi technique is a structured communication technique and systematic process of gathering information from a group of identified experts through a series of questionnaires to gain consensus regarding judgments on complex processes, where precise information is not available in the literature. The Delphi technique permitted an iterative and multistaged approach to transform expert opinions into group consensus. Results: The goals, recommendations, and How-To strategies include a focus on project management, stakeholder engagement, sponsorship, scenario design, prebriefing and debriefing, and evaluation metrics. The intent is to proactively identify system issues and disseminate actionable findings. Conclusions: This article highlights salient features to consider when using simulation as a strategy and tool for patient safety and quality improvement.
Midterm Clinical and Radiological Outcome After Autologous Matrix-induced Chondrogenesis (AMIC) for Osteochondral Lesions of the Talus
Authors: Weigelt Lizzy , Pfirrmann Christian , Wirth Stephan 
Published: May 2019

Category: Ankle Introduction/Purpose: Autologous matrix-induced chondrogenesis (AMIC) has recently become an interesting treatment option for osteochondral lesions of the talus since it combines safety and efficacy with overcoming several drawbacks of other surgical techniques. With AMIC, donor side morbidity of osteochondral autografts is eliminated, two-step procedures like matrix-induced autologous chondrocyte implantation are minimized to a more cost-effective single step and restrictions due to limited availability of osteochondral allografts are resolved. The purpose of this study was to evaluate the therapeutic efficacy of AMIC by analyzing AMIC-repaired osteochondral talar lesions in consecutively treated patients after a minimum follow-up of 2 years. Methods: All patients with an osteochondral lesion of the talus treated with the AMIC technique completing a minimum follow-up of 2 years were enrolled in the study for clinical and radiological follow-up. Patients with additional procedures such as lateral ligament reconstruction or corrective calcaneal osteotomy were excluded. 31 of the 47 eligible patients (28 males, 13 females; mean age at surgery 35.7 (range, 13-75) years); body mass index 27.1+-4.7 kg/m2) could be retrospectively evaluated after a mean follow-up of 4.6 (range, 2.3-7.9) years. The preoperative defect size was 0.9+-0.5 (range 0.4-2.3) cm2. Only two osteochondral lesions were localized laterally. Data analysis included general demographics, the visual analogue scale (VAS) for pain, the American Orthopaedic Foot and Ankle Society (AOFAS) score for ankle function, the Tegner Score for sports activity, and the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scoring system for radiological evaluation. Results: The VAS improved significantly from 6.5+-2.0 preoperatively to 1.5+-2.2 at follow-up (p<0.001). The mean AOFAS score was 93.0+-8.2 (range, 74-100) points. The sports activity level improved significantly from 3.5+-1.8 points preoperatively to 4.9+-1.8 points at follow-up (p<0.001), but 29% did not reach their pre-injury level of activity. The MOCART score averaged 61.5+-21.2 (range, 0-95) points. Complete filling of the defect was seen in 41%, hypertrophy of the cartilage layer in 53%. Normal or nearly normal signal intensity was detected in 67%. All patients showed subchondral bone edema or cysts. The MRI findings did not correlate with the clinical outcome. 91% were satisfied with the outcome and would undergo the same procedure again. Conclusion: AMIC is a reliable procedure to treat osteochondral lesions of the talus. Significant pain reduction and high ankle function were observed after a mean midterm follow-up of 4.5 years. MRI findings did not reflect the good clinical results and therefore should only be performed to rule out other pathologies that might cause persistent symptoms.