bluuebunny/crossref_metadata_2025_split huggingface dataset:
Personalized Clinical Decision Making Through Implementation of a Molecular Tumor Board: A German Single-Center Experience
Authors: Hoefflin Rouven , Geißler Anna-Lena , Fritsch Ralph , Claus Rainer , Wehrle Julius , Metzger Patrick , Reiser Meike , Mehmed Leman , Fauth Lisa , Heiland Dieter Henrik , Erbes Thalia , Stock Friedrich , Csanadi Agnes , Miething Cornelius , Weddeling Britta , Meiss Frank , von Bubnoff Dagmar , Dierks Christine , Ge Isabell , Brass Volker , Heeg Steffen , Schäfer Henning , Boeker Martin , Rawluk Justyna , Botzenhart Elke Maria , Kayser Gian , Hettmer Simone , Busch Hauke , Peters Christoph , Werner Martin , Duyster Justus , Brummer Tilman , Boerries Melanie , Lassmann Silke , von Bubnoff Nikolas 
Published: August 2018

Purpose Dramatic advances in our understanding of the molecular pathophysiology of cancer, along with a rapidly expanding portfolio of molecular targeted drugs, have led to a paradigm shift toward personalized, biomarker-driven cancer treatment. Here, we report the 2-year experience of the Comprehensive Cancer Center Freiburg Molecular Tumor Board (MTB), one of the first interdisciplinary molecular tumor conferences established in Europe. The role of the MTB is to recommend personalized therapy for patients with cancer beyond standard-of-care treatment. Methods This retrospective case series includes 198 patients discussed from March 2015 through February 2017. The MTB guided individual molecular diagnostics, assessed evidence of actionability of molecular alterations, and provided therapy recommendations, including approved and off-label treatments as well as available matched clinical trials. Results The majority of patients had metastatic solid tumors (73.7%), mostly progressive (77.3%) after a mean of 2.0 lines of standard treatment. Diagnostic recommendations resulted in 867 molecular diagnostic tests for 172 patients (five per case), including exome analysis in 36 cases (18.2%). With a median turnaround time of 28 days, treatment recommendations were given to 104 patients (52.5%). These included single-agent targeted therapies (42.3%), checkpoint inhibitors (37.5%), and combination therapies (18.3%). Treatment recommendations were implemented in 33 of 104 patients (31.7%), of whom 19 (57.6%) showed stable disease or partial response, including 14 patients (7.1% of the entire population) receiving off-label treatments. Conclusion Personalized extended molecular-guided patient care is effective for a small but clinically meaningful proportion of patients in challenging clinical situations. Limited access to targeted drugs, lack of trials, and submission at late disease stage prevents broader applicability, whereas genome-wide analyses are not a strict requirement for predictive molecular testing.
FOS, a Critical Downstream Mediator of PGR and EGF Signaling Necessary for Ovulatory Prostaglandins in the Human Ovary
Authors: Choi Yohan , Rosewell Katherine L , Brännström Mats , Akin James W , Curry Thomas E , Jo Misung 
Published: August 2018

Abstract

Context
Fos null mice failed to ovulate and form a corpus luteum (CL) even when given exogenous gonadotropins, suggesting that ovarian Fos expression is critical for successful ovulation and CL formation. However, little is known about FOS in the human ovary.

Objectives
To determine the expression, regulation, and function of FOS in human periovulatory follicles.

Design/Participants
Timed periovulatory follicles were obtained from normally cycling women. Granulosa/lutein cells were collected from in vitro fertilization patients.

Main Outcome Measures
The in vivo expression after human chorionic gonadotropin (hCG) administration and in vitro regulation of FOS, JUN, JUNB, and JUND was evaluated at the mRNA and protein level. Binding of progesterone receptor (PGR) and FOS to their target genes was assessed by chromatin immunoprecipitation analyses. Prostaglandin E2 (PGE2) and progesterone were measured.

Results
The expression of FOS, JUNB, and JUND drastically increased in ovulatory follicles after hCG administration. In human granulosa/lutein cell cultures, hCG increased the expression of FOS and JUN proteins. Inhibitors of PGR and epidermal growth factor (EGF) receptors reduced hCG-induced increases in the expression and phosphorylation of FOS. PGR bound to the FOS gene. A selective FOS inhibitor blocked hCG-induced increases in PGE2 and the expression of prostaglandin (PG) synthases and transporters (PTGES, SLCO2A1, and ABCC1). FOS bound to the promoter regions of these genes.

Conclusions
The increase of FOS/activator protein 1 in human periovulatory follicles after hCG administration is mediated by collaborative actions of PGR and EGF signaling and critical for the upregulated expression of key ovulatory genes required for the rise in ovulatory PG in human granulosa cells.
Comparison of Intermittent Intravenous Boluses of Phenylephrine and Norepinephrine to Prevent and Treat Spinal-Induced Hypotension in Cesarean Deliveries: Randomized Controlled Trial
Authors: Sharkey Aidan M. , Siddiqui Naveed , Downey Kristi , Ye Xiang Y. , Guevara Jennifer , Carvalho Jose C. A. 
Published: August 2018

BACKGROUND:
Phenylephrine (PE) is currently the vasopressor of choice to prevent and treat spinal-induced hypotension at cesarean delivery (CD). However, its use is often associated with reflex bradycardia. Norepinephrine (NE) has been put forward as an alternative vasopressor during CD due to its ability to treat hypotension while maintaining heart rate (HR). Recent studies have focused on the role of NE used as an infusion with favorable results compared to PE. No studies have compared equipotent bolus doses of PE and NE at CD. We hypothesized that when used in equipotent doses as an intermittent bolus regimen to prevent and treat spinal-induced hypotension, NE would result in a reduction in the incidence of bradycardia compared to PE.

METHODS:
This was a double-blind, randomized clinical trial of women undergoing elective CD under spinal anesthesia. Women were randomized to receive either PE 100 µg or NE 6 µg when the systolic blood pressure (SBP) was below baseline. In addition to the randomized treatment, ephedrine was given intravenously to both groups if the SBP was below baseline and the HR <60 bpm or if the SBP was <80% of baseline for 2 consecutive readings. The primary outcome was bradycardia (HR <50 bpm) in the predelivery period. Secondary outcomes included hypotension (SBP <80% of baseline), hypertension (SBP >120% of baseline), tachycardia (HR >120% of baseline), ≥2 episodes of bradycardia, nausea, vomiting, umbilical artery and vein blood gases, and Apgar scores.

RESULTS:
One hundred twelve patients were randomized. The incidence of bradycardia was lower in the NE group compared to the PE group (10.7% vs 37.5%; P < .001; difference [95% confidence interval {CI}], −26.8% [−41.8% to −11.7%]), implying an estimated 71% relative reduction (95% CI, 35%–88%). The distribution of the number of bradycardia episodes was also different between the 2 groups (P = .007). Further testing showed that the patients in the PE group had a higher risk of multiple bradycardia episodes (≥2 episodes) compared to the NE group (19.6% for PE versus 3.6% for NE; P = .008). The proportion of patients requiring rescue boluses of ephedrine was lower in the NE group compared to the PE group (7.2% for NE versus 21.4% for PE; P < .03; difference [95% CI], −14.3% [−27.0% to −1.6%]). No differences were observed between the 2 groups in the incidence of other secondary outcomes.

CONCLUSIONS:
When used as an intermittent bolus regimen to prevent and treat spinal-induced hypotension during CD, NE resulted in a significant reduction in the incidence of bradycardia as compared to an equipotent bolus regimen of PE. We conclude that the hemodynamic profile offered by NE during CD is superior to that of PE due to less fluctuations in HR and possibly cardiac output.
Comparative Regimens of Lipid Rescue From Bupivacaine-Induced Asystole in a Rat Model
Authors: Liu Le , Jin Zhousheng , Cai Xixi , Xia Yun , Zhang Meiling , Papadimos Thomas J. , Xu Xuzhong , Shi Kejian 
Published: August 2018

BACKGROUND:
It is currently unknown whether bupivacaine-induced asystole is better resuscitated with lipid emulsion (LE) administered peripherally or centrally, and whether different LE regimens administered peripherally demonstrated similar effects. In this study, we compared the effects of various regimens of lipid administration in a rat model of bupivacaine-induced asystole.

METHODS:
Forty-five adult male Sprague-Dawley rats were subjected to bupivacaine-induced asystole and randomly divided into 3 lipid regimens groups: (1) 20% LE was administered continuously via the internal jugular vein (CV-infusion group); (2) 20% LE was administered continuously via the tail vein (PV-infusion group); and (3) 20% LE was administered as divided boluses via the tail vein (PV-bolus group). The maximum dose of LE did not exceed 10 mL·kg−1. External chest compressions were administered until the return of spontaneous circulation (ROSC) or the end of a 40-minute resuscitation period.

RESULTS:
The survival rate, rate of ROSC, systolic blood pressure, heart rate, heart rate–blood pressure product, and coronary perfusion pressure during 2–40 minutes in the CV-infusion and PV-bolus groups were significantly higher than those in the PV-infusion group (P < .01), and the plasma total bupivacaine concentration and myocardial bupivacaine content were significantly lower (P < .05). Time to heartbeat return and time to ROSC in the CV-infusion and PV-bolus groups were significantly shorter than those in the PV-infusion group (P < .05).

CONCLUSIONS:
In the rat model of bupivacaine-induced asystole, a divided LE bolus regimen administered peripherally provided a better resuscitation outcome than that of a continuous LE infusion regimen peripherally, and performed in a similar fashion as the continuous LE infusion regimen administered centrally.
Geometrical confinement controls the asymmetric patterning of brachyury in cultures of pluripotent cells
Authors: Blin Guillaume , Wisniewski Darren , Picart Catherine , Thery Manuel , Puceat Michel , Lowell Sally 
Published: August 2018

ABSTRACT
Diffusible signals are known to orchestrate patterning during embryogenesis, yet diffusion is sensitive to noise. The fact that embryogenesis is remarkably robust suggests that additional layers of regulation reinforce patterning. Here, we demonstrate that geometrical confinement orchestrates the spatial organisation of initially randomly positioned subpopulations of spontaneously differentiating mouse embryonic stem cells. We use micropatterning in combination with pharmacological manipulations and quantitative imaging to dissociate the multiple effects of geometry. We show that the positioning of a pre-streak-like population marked by brachyury (T) is decoupled from the size of its population, and that breaking radial symmetry of patterns imposes polarised patterning. We provide evidence for a model in which the overall level of diffusible signals together with the history of the cell culture define the number of T+ cells, whereas geometrical constraints guide patterning in a multi-step process involving a differential response of the cells to multicellular spatial organisation. Our work provides a framework for investigating robustness of patterning and provides insights into how to guide symmetry-breaking events in aggregates of pluripotent cells.
Pgc-1α repression and high-fat diet induce age-related macular degeneration-like phenotypes in mice
Authors: Zhang Meng , Chu Yi , Mowery Joseph , Konkel Brandon , Galli Susana , Theos Alexander C. , Golestaneh Nady 
Published: August 2018

ABSTRACT
Age-related macular degeneration (AMD) is the major cause of blindness in the elderly in developed countries and its prevalence is increasing with the aging population. AMD initially affects the retinal pigment epithelium (RPE) and gradually leads to secondary photoreceptor degeneration. Recent studies have associated mitochondrial damage with AMD, and we have observed mitochondrial and autophagic dysfunction and repressed peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α; also known as Ppargc1a) in native RPE from AMD donor eyes and their respective induced pluripotent stem cell-derived RPE. To further investigate the effect of PGC-1α repression, we have established a mouse model by feeding Pgc-1α+/− mice with a high-fat diet (HFD) and investigated RPE and retinal health. We show that when mice expressing lower levels of Pgc-1α are exposed to HFD, they present AMD-like abnormalities in RPE and retinal morphology and function. These abnormalities include basal laminar deposits, thickening of Bruch's membrane with drusen marker-containing deposits, RPE and photoreceptor degeneration, decreased mitochondrial activity, increased levels of reactive oxygen species, decreased autophagy dynamics/flux, and increased inflammatory response in the RPE and retina. Our study shows that Pgc-1α is important in outer retina biology and that Pgc-1α+/− mice fed with HFD provide a promising model to study AMD, opening doors for novel treatment strategies.
Correction of cognitive deficits in mouse models of Down syndrome by a pharmacological inhibitor of DYRK1A
Authors: Nguyen Thu Lan , Duchon Arnaud , Manousopoulou Antigoni , Loaëc Nadège , Villiers Benoît , Pani Guillaume , Karatas Meltem , Mechling Anna E. , Harsan Laura-Adela , Limanton Emmanuelle , Bazureau Jean-Pierre , Carreaux François , Garbis Spiros D. , Meijer Laurent , Herault Yann 
Published: August 2018

ABSTRACTGrowing evidence supports the implication of DYRK1A in the development of cognitive deficits seen in Down syndrome (DS) and Alzheimer's disease (AD). We here demonstrate that pharmacological inhibition of brain DYRK1A is able to correct recognition memory deficits in three DS mouse models with increasing genetic complexity [Tg(Dyrk1a), Ts65Dn, Dp1Yey], all expressing an extra copy of Dyrk1a. Overexpressed DYRK1A accumulates in the cytoplasm and at the synapse. Treatment of the three DS models with the pharmacological DYRK1A inhibitor leucettine L41 leads to normalization of DYRK1A activity and corrects the novel object cognitive impairment observed in these models. Brain functional magnetic resonance imaging reveals that this cognitive improvement is paralleled by functional connectivity remodelling of core brain areas involved in learning/memory processes. The impact of Dyrk1a trisomy and L41 treatment on brain phosphoproteins was investigated by a quantitative phosphoproteomics method, revealing the implication of synaptic (synapsin 1) and cytoskeletal components involved in synaptic response and axonal organization. These results encourage the development of DYRK1A inhibitors as drug candidates to treat cognitive deficits associated with DS and AD.
The kinetochore–microtubule interface at a glance
Authors: Monda Julie K. , Cheeseman Iain M. 
Published: August 2018

ABSTRACT
Accurate chromosome segregation critically depends on the formation of attachments between microtubule polymers and each sister chromatid. The kinetochore is the macromolecular complex that assembles at the centromere of each chromosome during mitosis and serves as the link between the DNA and the microtubules. In this Cell Science at a Glance article and accompanying poster, we discuss the activities and molecular players that are involved in generating kinetochore–microtubule attachments, including the initial stages of lateral kinetochore–microtubule interactions and maturation to stabilized end-on attachments. We additionally explore the features that contribute to the ability of the kinetochore to track with dynamic microtubules. Finally, we examine the contributions of microtubule-associated proteins to the organization and stabilization of the mitotic spindle and the control of microtubule dynamics.
Range of Extension Correlates with Posterior Capsule Length after Knee Remobilization
Authors: ZHOU HAODONG , TRUDEL GUY , UHTHOFF HANS K. , LANEUVILLE ODETTE 
Published: August 2018

ABSTRACT

Introduction
Knee injuries are common in sports, and postinjury immobilization is often required to protect healing tissues and alleviate pain, but both the injury and the immobilization can lead to a knee contracture. Knee flexion contractures limit performance. Previous research has identified posterior knee capsule fibrosis as a contributor to immobility-induced knee flexion contractures. This study aims to measure posterior knee capsule length at various durations of remobilization after knee immobilization and to correlate with the recovery of knee range of motion.

Methods
Two hundred fifty-nine male Sprague-Dawley rats had one knee extra-articularly immobilized in flexion with a Delrin® plate at a 45° angle for one of six durations: 1, 2, 4, 8, 16, or 32 wk, followed by spontaneous remobilization after plate removal, which lasted zero, one, two, and four times the duration of immobilization. The contralateral knees served as controls. The posterior knee capsule length was measured by histomorphometry. These measures were correlated with previously published range of motion data from the same cohort of specimens.

Results
Knees immobilized for 1 and 2 wk partially recovered posterior capsule length (P > 0.05). Knees immobilized beyond 2 wk failed to recover posterior capsule length, irrespective of the duration of remobilization (P < 0.05). The residual posterior capsule shortening correlated with the lack of knee extension (P < 0.003).

Conclusions
For knee injuries requiring more than 2 wk of immobilization, unassisted remobilization will not restore posterior knee capsule shortening and the reduction in knee extension. These results support the role of the posterior capsule in knee joint contracture and the need to minimize the duration of immobility and to assist the recovery of the range of knee extension after a sport injury.
Augmented Anabolic Responses after 8-wk Cycling with Blood Flow Restriction
Authors: CONCEIÇÃO MIGUEL S. , JUNIOR EDSON M. M. , TELLES GUILHERME D. , LIBARDI CLEITON A. , CASTRO ALEX , ANDRADE ANDRÉ L. L. , BRUM PATRÍCIA C. , URIAS ÚRSULA , KURAUTI MIRIAN AYUMI , JÚNIOR JOSÉ MARIA COSTA , BOSCHERO ANTONIO CARLOS , CAVAGLIERI CLÁUDIA R. , CAMERA DONNY M. , CHACON-MIKAHIL MARA P. T. 
Published: August 2018

ABSTRACT

Introduction
Low-intensity endurance training (ET) performed with blood flow restriction (BFR) can improve muscle strength, cross-sectional area (CSA) and cardiorespiratory capacity. Whether muscle strength and CSA as well as cardiorespiratory capacity (i.e., V˙O2max) and underlying molecular processes regulating such respective muscle adaptations are comparable to resistance and ET is unknown.

Purpose
To determine the respective chronic (i.e., 8 wk) functional, morphological, and molecular responses of ET-BFR training compared with conventional, unrestricted resistance training (RT) and ET.

Methods
Thirty healthy young men were randomly assigned to one of three experimental groups: ET-BFR (n = 10, 4 d·wk−1, 30-min cycling at 40% of V˙O2max), RT (n = 10, 4 d·wk−1, 4 sets of 10 repetitions leg press at 70% of one repetition maximum with 60 s rest) or ET (n = 10, 4 d·wk−1, 30-min cycling at 70% of V˙O2max) for 8 wk. Measures of quadriceps CSA, leg press one repetition maximum, and V˙O2max as well as muscle biopsies were obtained before and after intervention.

Results
Both RT and ET-BFR increased muscle strength and hypertrophy responses. ET-BFR also increased V˙O2max, total cytochrome c oxidase subunit 4 isoform 1 abundance and vascular endothelial growth factor mRNA abundance despite the lower work load compared to ET.

Conclusions
Eight weeks of ET-BFR can increase muscle strength and induce similar muscle hypertrophy responses to RT while V˙O2max responses also increased postintervention even with a significantly lower work load compared with ET. Our findings provide new insight to some of the molecular mechanisms mediating adaptation responses with ET-BFR and the potential for this training protocol to improve muscle and cardiorespiratory capacity.
Atingindo o consumidor de entretenimento on demand: Product Placement em House of Cards
Authors: Celia Elisa Rocha 
Published: August 2018

Este trabalho analisa a publicidade na relação dialógica e interativa que se estabelece entre os produtores de séries sob demanda e consumidores alcançados pela estratégia de Product Placement. As teorias são: identidade, posicionamento e imagem de marca, com base em Khauaja e Mattar, Pinho, Tavares, Depexe e Petermann, dentre outros. Como caso, será observada a produção estadunidense “House of Cards”, criada para o serviço de streaming Netflix, que se utiliza da técnica para arrecadar fundos.
Globalização do Mercado de Vinhos Finos e o Protagonismo Promocional das Redes Sociais
Authors: Aguiar Miriam 
Published: August 2018

Fruto de um estudo comparativo entre Brasil e França, este artigo analisa as mudanças em curso no mercado de vinhos finos, resultantes do processo de globalização e ajustes às novas realidades sociais e contextos diferenciados nos quais o produto se insere. A comunicação sobre o vinho, atualmente ampliada e diversificada pelas tecnologias digitais, multiplica consumidores e contribui para a formação de uma opinião especializada de contornos particulares. Aspectos como o perfil singular do mercado, a sensualidade e notoriedade associadas ao consumo do vinho, a perspectiva personalista das interações pelas redes sociais, além da demanda por renovação constante das mensagens veiculadas caracterizam e influenciam o teor dessa comunicação, crescentemente utilizada como ferramenta promocional da indústria vitivinícola. Palavras-chave: comunicação, consumo, mercados de qualidade.
La photographie et l’histoire. Lecture conjointe des Konvolut N et Y des Passages de Walter Benjamin
Authors: Rafele Antonio 
Published: August 2018

Cet article met en lumière les liens qui unissent, dans le Livres des passages de Walter Benjamin, les réflexions sur la photographie et les fragments consacrés à la philosophie de l’histoire. On y montre plus particulièrement – dans un renvoi constant à la pensée postmoderne et à la théorie des médias – les implications esthétiques (les objets et la forme de consommation), gnoséologiques (l’observateur et les images) et sociologiques (les circonstances, le temps et la persona). This article aims to investigate to investigate the textual relations that link, in the thought of Walter Benjamin (Das Passagen-Werk), the reflections on photography and the fragments dedicated to the philosophy of history. Particularly, we focus on their aesthetics (the objects and the forms of consumption), gnoseological (the observer and the images) and sociological (the circumstances, the time and the persona) implications.