bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural, microstructural and dielectric properties of Ba1−xLaxTi(1−x∕4)O3 prepared by sol gel method
Authors: El Ghandouri Abdelhak , Sayouri Salaheddine , Lamcharfi Tajeddine , Elbasset Abdelhalim 
Published: June 2019

Detailed structural and dielectric properties of Lanthanum-doped barium titanate [Formula: see text]Lax[Formula: see text]O3 ceramic powders BLTx (where [Formula: see text]; 0.10; 0.20; 0.30 and 0.40)/BT, BLT10, BLT20, BLT30 and BLT40, synthesized by the sol gel process, calcined at 900∘C for 3[Formula: see text]h and sintered at 1250∘C for 6[Formula: see text]h, have been investigated. The phase formation and crystal structure of the samples were checked by X-ray diffraction (XRD) and Raman spectroscopy. The samples crystallize in the pure perovskite structure that transforms from tetragonal to pseudocubic under doping with La; results that have been confirmed by Rietveld Refinement technique. The estimated average crystallite size of the samples was about 23[Formula: see text]nm. Dielectric parameters (dielectric permittivity and losses) were determined in the temperature range room temperature (RT) — 280∘C and in the frequency range 500[Formula: see text]Hz–2[Formula: see text]MHz. La doping gives rise to a strong decrease of the ferro-to-paraelectric transition temperature, and the frequency dependence of the permittivity shows that the samples with [Formula: see text] and [Formula: see text] reach their resonance frequency. The frequency dependence of impedance and electric modulus properties were studied over a wide frequency range from 1[Formula: see text]kHz to 2[Formula: see text]MHz at various temperatures to confirm the contributions from grains and grain-boundaries. The complex impedance analysis data have been presented in the Nyquist plot which is used to identify the corresponding equivalent circuit and fundamental circuit parameters; it was found that the grain boundaries resistance is dominant at room temperature. The frequency dependence of the parameters permittivity, losses and AC conductivity reveals that the relaxation process is of the Maxwell–Wagner type of interfacial polarization.
Design and Outcomes of a Community Trial to Increase Pap Testing in Pacific Islander Women
Authors: Tanjasiri Sora Park , Mouttapa Michele , Sablan-Santos Lola , Weiss Jie W. , Chavarria Alisa , Lacsamana Jasmine DeGuzman , May Vanessa Tuiòne , Quitugua Lourdes , Tupua Marina , Schmidt-Vaivao Dorothy 
Published: June 2019

Abstract

Background:
Pap tests remain an essential cervical cancer detection method in the United States, yet they are underutilized among Pacific Islanders (PI) who experience elevated cervical cancer incidence and mortality. This study describes the design, methods, participants, and outcomes of a multiyear (2010–2016), community-based randomized intervention trial in southern California. Based upon strong collectivistic norms, the trial tested the efficacy of a unique social support intervention targeting Chamorro, Samoan, and Tongan women and their male husbands/partners.

Methods:
A single-session educational intervention was designed and tailored for ethnic- and gender-specific groups to increase men's social support for their female wives/partners to receive a Pap test, and for women to receive a Pap test. The comparison group received preexisting brochures on Pap testing (for women) or general men's health (for men). Pretest and 6-month follow-up data were analyzed.

Results:
Intervention and comparison groups were mostly equivalent on pretest demographics and outcome variables. Intervention women who were not compliant with Pap screening recommendations at pretest were significantly more likely to have scheduled and received a Pap test at 6-month follow-up. However, 6-month follow-up results indicated no intervention effect on changes in women's Pap testing knowledge, fatalistic attitudes, or perceived social support from their male partner.

Conclusions:
Ethnic- and gender-tailored community interventions can successfully increase Pap test behaviors for PI women, although more research is needed on the specific pathways leading to behavior change.

Impact:
Collaborative community-based interventions lead to increases in women's cancer prevention and early detection for Pacific Islander and other collectivistic communities.
A Phase I Trial of the VEGF Receptor Tyrosine Kinase Inhibitor Pazopanib in Combination with the MEK Inhibitor Trametinib in Advanced Solid Tumors and Differentiated Thyroid Cancers
Authors: Kurzrock Razelle , Ball Douglas W. , Zahurak Marianna L. , Nelkin Barry D. , Subbiah Vivek , Ahmed Shabina , O'Connor Ashley , Karunsena Enusha , Parkinson Rose M. , Bishop Justin A. , Ha Yoonji , Sharma Rajni , Gocke Christopher D. , Zinner Ralph , Rudek Michelle A. , Sherman Steven I. , Azad Nilofer S. 
Published: June 2019

Abstract

Purpose:
Differentiated thyroid cancer (DTC) responds to VEGF receptor inhibitors. VEGF signals through RAS/RAF/MEK signaling. We evaluated the safety and efficacy of the VEGF receptor inhibitor pazopanib and MEK inhibitor trametinib in advanced solid tumors and DTC.

Patients and Methods:
Patients with advanced solid tumors were enrolled in a phase I, multicenter trial with a DTC expansion cohort. Patients received pazopanib 400–800 mg and trametinib 1–2 mg daily. Efficacy in the expansion cohort was assessed with objective response (OR) at 6 months of treatment.

Results:
Twenty-six patients were enrolled in five dose levels. MTD was not reached; the recommended phase II dose was pazopanib 800 mg orally and trametinib 2 mg orally every day. There was one dose-limiting toxicity on dose level 1 with grade 3 fatigue and muscle weakness. Common grade 3 adverse events were elevated transaminases (19%), diarrhea (15%), hypertension (12%), and fatigue (8%). Thirteen patients were enrolled in the DTC cohort; OR was 33% (95% confidence interval, 9.9, 65.1%) and median progression-free survival was 10.7 months. The cohort was terminated after planned interim analysis suggested insufficiently increased activity against the historical control of pazopanib alone. Reduction in tumor diameter negatively correlated with p-ERK change in tumor (Spearman ρ = −0.71; P = 0.05). NRAS mutation was associated with response (Fisher exact P = 0.008).

Conclusions:
Pazopanib + trametinib was tolerable at full single-agent doses with clinical activity in DTC but did not achieve the prespecified response rate target.
Dissecting the Stromal Signaling and Regulation of Myeloid Cells and Memory Effector T Cells in Pancreatic Cancer
Authors: Blair Alex B. , Kim Victoria M. , Muth Stephen T. , Saung May Tun , Lokker Nathalie , Blouw Barbara , Armstrong Todd D. , Jaffee Elizabeth M. , Tsujikawa Takahiro , Coussens Lisa M. , He Jin , Burkhart Richard A. , Wolfgang Christopher L. , Zheng Lei 
Published: June 2019

Abstract

Purpose:
Myeloid cells are a prominent immunosuppressive component within the stroma of pancreatic ductal adenocarcinoma (PDAC). Previously, targeting myeloid cells has had limited success. Here, we sought to target the myeloid cells through modifying a specific stromal component.

Experimental Design:
A murine model of metastatic PDAC treated with an irradiated whole-cell PDAC vaccine and PDAC specimens from patients treated with the same type of vaccine were used to assess the immune-modulating effect of stromal hyaluronan (HA) degradation by PEGPH20.

Results:
Targeting stroma by degrading HA with PEGPH20 in combination with vaccine decreases CXCL12/CXCR4/CCR7 immunosuppressive signaling axis expression in cancer-associated fibroblasts, myeloid, and CD8+ T cells, respectively. This corresponds with increased CCR7− effector memory T-cell infiltration, an increase in tumor-specific IFNγ, and improved survival. In the stroma of human PDACs treated with the same vaccine, decreased stromal CXCR4 expression significantly correlated with decreased HA and increased cytotoxic activities, suggesting CXCR4 is an important therapeutic target.

Conclusions:
This study represents the first to dissect signaling cascades following PDAC stroma remodeling via HA depletion, suggesting this not only overcomes a physical barrier for immune cell trafficking, but alters myeloid function leading to downstream selective increases in effector memory T-cell infiltration and antitumor activity.
Identification of Targetable Recurrent MAP3K8 Rearrangements in Melanomas Lacking Known Driver Mutations
Authors: Lehmann Brian D. , Shaver Timothy M. , Johnson Douglas B. , Li Zhu , Gonzalez-Ericsson Paula I. , Sánchez Violeta , Shyr Yu , Sanders Melinda E. , Pietenpol Jennifer A. 
Published: June 2019

Abstract

Melanomas are characterized by driver and loss-of-function mutations that promote mitogen-activated protein kinase (MAPK) signaling. MEK inhibitors are approved for use in BRAF-mutated melanoma; however, early-phase clinical trials show occasional responses in driver-negative melanoma, suggesting other alterations conferring MAPK/ERK dependency. To identify additional structural alterations in melanoma, we evaluated RNA-Seq from a set of known MAPK/ERK regulators using a novel population-based algorithm in The Cancer Genome Atlas (TCGA). We identified recurrent MAP3K8 rearrangements in 1.7% of melanomas in TCGA, occurring in more than 15% of tumors without known driver mutations (BRAF, NRAS, KIT, GNAQ, GNA11, and NF1). Using an independent tumor set, we validated a similar rearrangement frequency by FISH. MAP3K8-rearranged melanomas exhibit a low mutational burden and absence of typical UV-mutational patterns. We identified two melanoma cell lines that harbor endogenous truncating MAP3K8 rearrangements that demonstrate exquisite dependency. Rearrangement and amplification of the MAP3K8 locus in melanoma cells result in increased levels of a truncated, active MAP3K8 protein; oncogenic dependency on the aberrant MAP3K8; and a concomitant resistance to BRAF inhibition and sensitivity to MEK or ERK1/2 inhibition. Our findings reveal and biochemically characterize targetable oncogenic MAP3K8 truncating rearrangements in driver mutation–negative melanoma, and provide insight to therapeutic approaches for patients with these tumors. These data provide rationale for using MEK or ERK inhibitors in a subset of driver-negative, MAPK/ERK–dependent melanomas harboring truncating MAP3K8 rearrangements.

Implications:
This is the first mechanistic study and therapeutic implications of truncating MAP3K8 rearrangements in driver-negative melanoma.
β-Catenin Activation Promotes Immune Escape and Resistance to Anti–PD-1 Therapy in Hepatocellular Carcinoma
Authors: Ruiz de Galarreta Marina , Bresnahan Erin , Molina-Sánchez Pedro , Lindblad Katherine E. , Maier Barbara , Sia Daniela , Puigvehi Marc , Miguela Verónica , Casanova-Acebes María , Dhainaut Maxime , Villacorta-Martin Carlos , Singhi Aatur D. , Moghe Akshata , von Felden Johann , Tal Grinspan Lauren , Wang Shuang , Kamphorst Alice O. , Monga Satdarshan P. , Brown Brian D. , Villanueva Augusto , Llovet Josep M. , Merad Miriam , Lujambio Amaia 
Published: June 2019

Abstract

PD-1 immune checkpoint inhibitors have produced encouraging results in patients with hepatocellular carcinoma (HCC). However, what determines resistance to anti–PD-1 therapies is unclear. We created a novel genetically engineered mouse model of HCC that enables interrogation of how different genetic alterations affect immune surveillance and response to immunotherapies. Expression of exogenous antigens in MYC;Trp53−/− HCCs led to T cell–mediated immune surveillance, which was accompanied by decreased tumor formation and increased survival. Some antigen-expressing MYC;Trp53−/− HCCs escaped the immune system by upregulating the β-catenin (CTNNB1) pathway. Accordingly, expression of exogenous antigens in MYC;CTNNB1 HCCs had no effect, demonstrating that β-catenin promoted immune escape, which involved defective recruitment of dendritic cells and consequently impaired T-cell activity. Expression of chemokine CCL5 in antigen-expressing MYC;CTNNB1 HCCs restored immune surveillance. Finally, β-catenin–driven tumors were resistant to anti–PD-1. In summary, β-catenin activation promotes immune escape and resistance to anti–PD-1 and could represent a novel biomarker for HCC patient exclusion.

Significance:
Determinants of response to anti–PD-1 immunotherapies in HCC are poorly understood. Using a novel mouse model of HCC, we show that β-catenin activation promotes immune evasion and resistance to anti–PD-1 therapy and could potentially represent a novel biomarker for HCC patient exclusion.
See related commentary by Berraondo et al., p. 1003.
This article is highlighted in the In This Issue feature, p. 983
Cluster Randomized Trial Examining the Impact of Automated Best Practice Alert on Rates of Implantable Defibrillator Therapy
Authors: Lee Jae , Szeto Libby , Pasupula Deepak Kumar , Hussain Aliza , Waheed Anam , Adhikari Shubash , Sharbaugh Michael , Thoma Floyd , Althouse Andrew D. , Fischer Gary , Lee Joon Sup , Saba Samir ,   the ALERT-ICD Investigators
Published: June 2019

Background:
Implantable cardioverter-defibrillators (ICDs) are indicated in patients with left ventricular ejection fraction ≤35%, but many eligible patients do not receive this therapy. In this cluster randomized trial, we investigated the impact of a best practice alert (BPA) through the electronic health records on the rates of electrophysiology referrals, ICD implantations, and all-cause mortality in severe cardiomyopathy patients.

Methods and Results:

Providers in the Heart and Vascular Institute (n=106) and in General Internal Medicine (n=89) were randomized to receive or not receive a BPA recommending consideration for ICD implantation. Patients belonging to the BPA and no BPA groups of providers were followed to the end points of electrophysiology referrals, ICD implantations, and all-cause mortality. Between 2013 and 2015, patients with reduced left ventricular ejection fraction were managed by 93 providers in the BPA (n=997 patients) and 102 providers in the no BPA (n=909 patients) groups. Patients in the 2 groups had comparable baseline characteristics. After a median follow-up of 36 months, 638 (33%) patients were referred to electrophysiology, 536 (27%) received an ICD, and 445 (23%) died. Patients in the BPA group were more likely to be referred to electrophysiology (hazard ratio=1.23;
P
=0.026), to receive ICD therapy (hazard ratio=1.35;
P
=0.006), and exhibited a trend towards slightly lower mortality (hazard ratio=0.85;
P
=0.091).

Conclusions:
Delivering a BPA through the electronic health record recommending to providers consideration of ICD implantation when the left ventricular ejection fraction is ≤35% improves the rates of electrophysiology referrals and ICD therapy in patients with severe left ventricular dysfunction.
Emergency Department Door-to-Puncture Time Since 2014
Authors: Czap Alexandra L. , Grotta James C , Parker Stephanie A. , Yamal Jose-Miguel , Bowry Ritvij , Sheth Sunil A. , Rajan Suja S. , Hwang Hyunsoo , Singh Noopur , Bratina Patti , Bryndziar Tomas , Alexandrov Andrei V. , Alexandrov Anne W. , Dusenbury Wendy , Swatzell Victoria , Jones William , Ackerson Kimberly , Schimpf Brandi , Wright Patrick , Jagolino-Cole Amanda L. 
Published: June 2019

Background and Purpose—
The impact of a mobile stroke unit (MSU) on access to intraarterial thrombectomy (IAT) is a prespecified BEST-MSU substudy (Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services). On the MSU, IAT decision-making steps, such as computed tomography, neurological exam, and tPA (tissue-type plasminogen activator) treatment are completed before emergency department arrival. We hypothesized that such pre-ED assessment of potential IAT patients on an MSU improves the time from ED arrival to skin puncture time (door-to-puncture-time, DTPT).

Methods—
BEST-MSU is a prospective comparative effectiveness study of MSU versus standard management by emergency medical services (EMS). We compared ED DTPT among the following groups of MSU and EMS patients: all IAT patients, IAT patients post-tPA, and IAT patients post-tPA meeting thrombolytic adjudication criteria over the first 4 years of the study.

Results—

From August 2014 to July 2018, a total of 161 patients underwent IAT. Ninety-four patients presented to the ED via the MSU and 67 by EMS. One hundred forty patients received tPA before IAT, 85 in the MSU arm, and 55 in the EMS arm. One hundred twenty-six patients received tPA within thrombolytic adjudication criteria: 76 MSU and 50 EMS. DTPT in minutes was shorter for MSU patients (all IAT MSU versus EMS 89 versus 99,
P
=0.01; IAT post-tPA MSU versus EMS 93 versus 100,
P
=0.03; and IAT post-tPA within adjudicated criteria MSU versus EMS 93 versus 99.5,
P
=0.03). From 2014 to 2018, DTPT decreased at a faster rate for EMS compared with MSU-managed patients, improving by about an hour.

Conclusions—
Pre-ED IAT evaluation on an MSU results in faster DTPT compared with arrival by EMS. Since 2014, dramatic improvement in ED IAT metrics has attenuated this difference. However, DTPT in all groups indicates substantial room for improvement.
Microcope gen. nov.—a new deep-sea genus of Munnopsidae (Crustacea, Isopoda,Asellota), with description of two new species from the Southern Hemisphere
Authors: MALYUTINA MARINA V. 
Published: June 2019

A new genus of Munnopsidae Lilljeborg, Microcope gen. nov., is described including Eurycope ovata Birstein, 1970 from the northwestern Pacific, and two new species, collected in the Cape Basin, and Atlantic Sector of the Southern Ocean. The new genus combines characters common for some genera of Eurycopinae Hansen and Betamorphinae Kussakin, but cannot be related to any known genus of the existing subfamilies and, thus, still remains incertae sedis. Microcope gen. nov. is characterized by minute eurycopine-like broad oval body with fused pereonites 5–7 on the one hand, and betamorpha-like face, pereopods 2–4 and uropods, with extended distomedial projection of the protopod on the other hand. The following combination of characters distinguishes the new genus: short head hidden under the anterior flange of pereonite 1, absence of rostrum, slender male pleopods 2, flattened female pleopod 2, and distinct shape and armament of pereopods 5–7 and pleopod 3. The descriptions of Microcope gen. nov., as well as the two new species, M. denticulate sp. nov., and M. levissima sp. nov., are presented.
Properties of Convectively Induced Turbulence over Developing Oceanic Convection
Authors: Barber Katelyn A. , Deierling Wiebke , Mullendore Gretchen , Kessinger Cathy , Sharman Robert , Muñoz-Esparza Domingo 
Published: June 2019

Abstract
Convectively induced turbulence (CIT) is an aviation hazard that continues to be a forecasting challenge as operational forecast models are too coarse to resolve turbulence affecting aircraft. In particular, little is known about tropical maritime CIT. In this study, a numerical simulation of a tropical oceanic CIT case where severe turbulence was encountered by a commercial aircraft is performed. The Richardson number (Ri), subgrid-scale eddy dissipation rate (EDR), and second-order structure functions (SF) are used as diagnostics to determine which may be used for CIT related to developing and mature convection. Model-derived subgrid-scale EDR in past studies of midlatitude continental CIT was shown to be a good diagnostic of turbulence but underpredicted turbulence intensity and areal coverage in this tropical simulation. SF diagnosed turbulence with moderate to severe intensity near convection and agreed most with observations. Further, SF were used to diagnose turbulence for developing convection. Results show that the areal coverage of turbulence associated with developing convection is less than mature convection. However, the intensity of turbulence in the vicinity of developing convection is greater than the turbulence intensity in the vicinity of mature convection highlighting developing convection as an additional concern to aviation.
Narratives about Political Violence and Reconciliation in Peru
Authors: Ríos Jerónimo 
Published: June 2019

The narratives of members of the armed forces, former members of the Shining Path, and victims of Peru’s armed conflict between 1980 and 2000 include very different views of the responsibility for the violence, the notion of terrorism, the concepts of truth, justice, reparation, and nonrepetition, and the meaning of reconciliation itself. Analysis of in-depth interviews reveals a society that, decades after the violence, in 2018, the Year of National Dialogue and Reconciliation, is still fractured and far from any type of recovery of its social fabric and symbolic resolution of its internal armed conflict. Las narrativas de miembros de las Fuerzas Militares, exmiembros de Sendero Luminoso y diferentes víctima del conflicto armado interno acontecido en Perú entre 1980 y 2000 incluyen perspectivas muy diferentes sobre la responsabilidad de la violencia, la noción de terrorismo, los aspectos relativos a verdad, justicia, reparación y no repetición, o el significado mismo de la reconciliación. El análisis de entrevistas en profundidad muestra una sociedad que décadas después de la violencia, en el año 2018, denominado como “Año del Diálogo y la Reconciliación Nacional”, se mantiene fracturada y alejada de cualquier atisbo de recomposición de su tejido social y superación simbólica de su conflicto armado interno.
Balloon Sinuplasty Utilization in the Pediatric Population: A National Database Perspective
Authors: Thong Gerard , Dombrowski Natasha D. , Kawai Kosuke , Cunningham Michael J. , Adil Eelam A. 
Published: June 2019

ObjectiveBalloon sinuplasty (BS) is a surgical management option in the treatment of chronic rhinosinusitis. The purpose of this study was to examine BS utilization among children with a national database.Study DesignRetrospective review.SettingNational pediatric database.Subjects and MethodsAll cases of children aged ≤18 years who underwent BS or traditional endoscopic sinus surgery (ESS) 5 years before and after the introduction of BS billing codes were studied with the Pediatric Health Information System database. We evaluated overall trends, demographics, performing physicians, readmissions, and cost data.ResultsA total of 14,079 patients met inclusion criteria: 13,555 underwent traditional ESS and 524 had a BS procedure. There was no significant increase in BS rates between 2011 and 2016. BS was more commonly performed among younger children than ESS (median age [interquartile range], 6 years [4‐10] vs 9 years [6‐13]; P <. 001). There were 23 (4.4%) readmissions within 30 days in the balloon cohort versus 474 (3.5%) in the ESS cohort. The median cost of balloon maxillary antrostomy (US $6560 [$5420‐$8250]) was higher than that of traditional maxillary antrostomy (US $5630 [$4130‐$7700], P <. 001). Physicians who performed BS had a larger volume of ESS procedures when compared with those who did not perform BS.ConclusionRates of BS performance in the pediatric population have not increased over time. Results showed no difference in readmission rates between BS and ESS. BS was associated with higher costs as compared with ESS. The role of BS in the pediatric chronic rhinosinusitis population remains unclear.