bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural mechanisms of social homeostasis
Authors: Matthews Gillian A. , Tye Kay M. 
Published: March 2019

AbstractSocial connections are vital to survival throughout the animal kingdom and are dynamic across the life span. There are debilitating consequences of social isolation and loneliness, and social support is increasingly a primary consideration in health care, disease prevention, and recovery. Considering social connection as an “innate need,” it is hypothesized that evolutionarily conserved neural systems underlie the maintenance of social connections: alerting the individual to their absence and coordinating effector mechanisms to restore social contact. This is reminiscent of a homeostatic system designed to maintain social connection. Here, we explore the identity of neural systems regulating “social homeostasis.” We review findings from rodent studies evaluating the rapid response to social deficit (in the form of acute social isolation) and propose that parallel, overlapping circuits are engaged to adapt to the vulnerabilities of isolation and restore social connection. By considering the neural systems regulating other homeostatic needs, such as energy and fluid balance, we discuss the potential attributes of social homeostatic circuitry. We reason that uncovering the identity of these circuits/mechanisms will facilitate our understanding of how loneliness perpetuates long‐term disease states, which we speculate may result from sustained recruitment of social homeostatic circuits.
Optimal cutoff value of bipolar low‐voltage in electroanatomic voltage mapping during atrial fibrillation rhythm
Authors: Kawaji Tetsuma , Hojo Shun , Kushiyama Akihiro , Nakatsuma Kenji , Kaneda Kazuhisa , Kato Masashi , Yokomatsu Takafumi , Miki Shinji 
Published: March 2019

AbstractBackgroundElectroanatomic voltage mapping (EAVM) of the left atrium (LA) with multielectrodes is usually acquired during sinus rhythm (SR), and the feasibility of EAVM during atrial fibrillation (AF) rhythm is unclear.MethodsWe performed EAVM of LA during both SR and AF rhythm in 44 patients undergoing catheter ablation for AF and validated the optimal cutoff value of low‐voltage area (LVA) during AF rhythm for detecting LVA defined as bipolar voltages ≤0.5 mV during SR.ResultsIn each session, mean 829 and 552 points were acquired by multielectrodes during SR and AF rhythm, respectively. Mean proportion of LVA was 4.9% among LA surface area of 276.2 cm2. Differences of LVA proportions between SR and AF rhythm were 5.8% (P < 0.001), 4.2% (P < 0.001), 2.7% (P < 0.001), 1.2% (P = 0.01), and –0.5% (P = 0.17) at the cutoff value of 0.4, 0.35, 0.3, 0.25, and 0.2 mV during AF rhythm, respectively. There was a good correlation between LVA proportions during SR and AF rhythm with cutoff value of 0.2 mV (R = 0.88, P < 0.001) and 37 patients (84.1%) had the discrepancy of LVA proportions within 3%. Furthermore, there was no significant difference between LVA proportions at each segment of LA. The discrepancy was relatively large in patients with large LA dimension and LVA during SR.ConclusionEAVM during AF rhythm was feasible and the optimal cutoff value of LVA was 0.2 mV for detecting LVA ≤ 0.5 mV during SR. However, the evidence is restricted to patients with relatively small LVA.
Classification of postoperative behavior disturbances in preschool children: A qualitative study
Authors: Lopez Ursula , Martin Jennifer , van Assche Mitsouko , Fleury Schubert Aline , Fournet Maryll , Quartier Vincent , Habre Walid , Van der Linden Martial 
Published: March 2019

AbstractBackground/AimNegative postoperative changes in children are frequent and have been described for decades. However, there is currently no theoretical framework, nor any consensual operational criteria for identifying them. This study aims at characterizing the many dimensions involved in postoperative behavioral disturbances in early childhood, using a qualitative analysis applied for the first time to these symptoms.MethodFifty‐seven parents of preschool children (1‐5 years old; 38 boys), who underwent general anesthesia, were interviewed 10 days after surgery. Semi‐structured interviews investigated behavioral disturbances classically described in preschool children. Qualitative analysis of the transcripts allied both deductive and inductive reasoning, and inductive coding was carried out using constant comparison method with dedicated qualitative software.ResultsParents reported both positive and negative postoperative changes. Negative changes were classified in four main categories: (a) Externalizing and (b) Internalizing problems behaviors, (c) Feeding sleeping disruption and (d) Somatic problems, each comprising different sub‐categories. Importantly within these categories, the symptoms distribution changed in 5 years old children, compared to younger children. Finally, our method allowed defining whether these (negative or positive) changes were significant or not, that is, the importance of postoperative behavioral changes.ConclusionThe results of this study highlight the heterogeneity of postoperative disturbances in preschool children. These results are of primary importance for the definition and measurement of postoperative behavioral disturbances.
Long-term medical and psychosocial outcomes in congenital diaphragmatic hernia survivors
Authors: Tan Jason K , Banton Georgia , Minutillo Corrado , Hall Graham L , Wilson Andrew , Murray Conor , Nathan Elizabeth A , Verheggen Maureen , Ramsay James , Samnakay Naeem , Dickinson Jan 
Published: March 2019

ObjectiveSurvival rates for congenital diaphragmatic hernia (CDH) are increasing. The long-term outcomes of CDH survivors were compared with a healthy control group to assess the morbidity for guidance of antenatal counselling and long-term follow-up programmes.Participants and designParticipants born with CDH in Western Australia 1993–2008 were eligible with matched controls from the general population. Participants had comprehensive lung function tests, echocardiogram, low-dose chest CT scan and completed a Strengths and Difficulties Questionnaire (SDQ) and quality of life (QOL) questionnaire.Results34 matched case–control pairs were recruited. Demographic data between groups were similar. Cases were smaller at follow-up (weight Z-score of −0.2vs0.3; p=0.03; height Z-score of −0.3vs0.6; p=0.01). Cases had lower mean Z-scores for forced expiratory volume in 1 s (FEV1) (−1.49 vs −0.01; p=0.004), FEV1/forced vital capacity (−1.92 vs −1.2; p=0.009) and forced expiratory flow at 25-75% (FEF25-75) (−1.18vs0.23; p=0.007). Cases had significantly worse respiratory mechanics using forced oscillation technique. Subpleural triangles architectural distortion, linear opacities and scoliosis on chest CT were significantly higher in cases. Prosthetic patch requirement was associated with worse lung mechanics and peak cough flow. Cases had significantly higher rates of gastro-oesophageal reflux disease (GORD) and GORD medication usage. Developmental delay was significantly higher in cases. More cases had a total difficulties score in the high to very high range (25% vs 0%, p=0.03) on the SDQ and reported lower objective QOL scores (70.2 vs 79.8, p=0.02).ConclusionSurvivors of CDH may have significant adverse long-term medical and psychosocial issues that would be better recognised and managed in a multidisciplinary clinic.
Lonicera japonica Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in Mice: Molecular Mechanisms of Action
Authors: Miao Hui , Zhang Yi , Huang Zhenlin , Lu Bin , Ji Lili 
Published: March 2019

Liver fibrosis is a worldwide clinical issue that generally causes hepatic cirrhosis. Lonicerae Japonicae Flos (dried flower buds of Lonicera japonica Thunb) is a traditional heat-clearing and detoxifying herbal medicine in China. This study aims to observe the protection of the water extract of Lonicerae Japonicae Flos (FL) from carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Liver fibrosis was induced in mice by intraperitoneal injection of 2[Formula: see text]ml/kg CCl4 twice a week for 4 weeks. FL’s attenuation of CCl4-induced liver fibrosis in mice was evidenced by the results of Masson’s trichrome and Sirius red staining, liver hydroxyproline content and serum amount of collagen IV. FL reduced hepatic stellate cells (HSCs) activation and reversed the epithelial-mesenchymal transition (EMT) process in mice treated with CCl4. FL also alleviated liver oxidative stress injury and enhanced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) anti-oxidant signaling pathway in mice treated with CCl4. Additionally, the main phenolic acids in FL including chlorogenic acid (CGA) and caffeic acid (CA) both reduced HSCs activation in vitro. In summary, FL attenuates CCl4-induced liver fibrosis in mice by inhibiting HSCs activation, reversing EMT and reducing liver oxidative stress injury via inducing Nrf2 activation. CGA may be the main active compound contributing to the antifibrotic activity of FL.
THE EFFECT OF REVENUE SHARES ON LOCAL GOVERNMENT SPENDING: EVIDENCE FROM PHILIPPINE PROVINCES
Authors: CANARE TRISTAN 
Published: March 2019

Intergovernmental fiscal transfer (IFT) is one of the several sources of funds of sub-national governments. There are two general types of IFT — conditional and unconditional. In many developing economies including the Philippines, the usual existing IFT is a form of unconditional fiscal transfer called revenue shares. In the Philippines, this revenue-sharing scheme is called the internal revenue allotment (IRA). Empirical literature says that unconditional IFTs are the type of fiscal transfers with the least effect on local government spending. The literature posits that the reason for this is that local governments use these transfers to substitute for own-sourced revenues such as local taxes. This explanation was formalized through a framework presented in this paper. Using panel data from Philippine provinces for the years 2001 to 2015, this paper attempted to determine the effect of revenue shares, in the form of IRA, on local government expenditures. Using different econometric methodologies, this paper arrived at several conclusions. First, IRA has a strong positive effect on total local government spending with a marginal effect slightly greater than one — much higher than what comparable studies found using data from other countries. Secondly, the effect of IRA on local government expenditures is even stronger for provinces with relatively greater ability to generate its own funds. Next, IRA and other externally sourced revenues have much stronger marginal effects on local government spending than do own-sourced revenues. Finally, IRA has widely varying effects on different components of local government expenditures.
SOD
Authors: Brocanelli Marco , Wang Xiaorui 
Published: March 2019

A major concern for today’s smartphones is their much faster battery drain than traditional feature phones, despite their greater battery capacities. The difference is mainly contributed by those more powerful but also much more power-consuming smartphone components, such as the multi-core application processor and the high-definition (HD) display. While the application processor must be active when any smart apps are being used, it is also unnecessarily waken up, even during idle periods, to perform operations related to basic phone functions (i.e., incoming calls and text messages). In addition, the power-hungry HD display is also used unnecessarily for such basic functions.
In this article, we investigate how to increase the battery life of smartphones by minimizing the use of application processor and HD display for operations related to basic functions. We find that the application processor is often waken up by a process running on it, called the Radio Interface Layer Daemon (RILD), which interfaces the user and apps to the GSM/LTE cellular network. In particular, we demonstrate that a great amount of energy could be saved if RILD is stopped, such that the application processor can sleep more often. Based on this key finding, we design a Smart On Demand (SOD) configuration that reduces the smartphone energy consumption by running RILD operations on a secondary low-power microcontroller and by using a secondary low-power display to interface the user with basic functions. As a result, basic phone functions can be handled at much lower energy costs and the power-consuming components, i.e., application processor and HD display, are waken up only when one needs to use any smart apps, in an on-demand manner. We have built a hardware prototype of SOD and evaluated it with real user traces. Our results show that SOD can increase its battery life by up to 2.5 more days.
Hemodynamic characterization of a transgenic rat strain stably expressing the calcium sensor protein GCaMP2
Authors: Oláh Attila , Ruppert Mihály , Orbán Tamás István , Apáti Ágota , Sarkadi Balázs , Merkely Béla , Radovits Tamás 
Published: March 2019

A novel transgenic rat strain has recently been generated that stably expresses the genetically engineered calcium sensor protein GCaMP2 in different cell types, including cardiomyocytes, to investigate calcium homeostasis. To investigate whether the expression of the GCaMP2 protein itself affects cardiac function, in the present work we aimed at characterizing in vivo hemodynamics in the GCaMP2 transgenic rat strain. GCaMP2 transgenic rats and age-matched Sprague-Dawley control animals were investigated. In vivo hemodynamic characterization was performed by left ventricular (LV) pressure-volume analysis. Postmortem heart weight data showed cardiac hypertrophy in the GCaMP2 group (heart-weight-to-tibial-length ratio: 0.26 ± 0.01 GCaMP2 vs. 0.23 ± 0.01 g/cm Co, P < 0.05). We detected elevated mean arterial pressure and increased total peripheral resistance in transgenic rats. GCaMP2 transgenesis was associated with prolonged contraction and relaxation. LV systolic function was not altered in transgenic rats, as indicated by conventional parameters and load-independent, sensitive indices. We found a marked deterioration of LV active relaxation in GCaMP2 animals (τ: 16.8 ± 0.7 GCaMP2 vs. 12.2 ± 0.3 ms Co, P < 0.001). Our data indicated myocardial hypertrophy, arterial hypertension, and impaired LV active relaxation along with unchanged systolic performance in the heart of transgenic rats expressing the GCaMP2 fluorescent calcium sensor protein. Special caution should be taken when using transgenic models in cardiovascular studies. NEW & NOTEWORTHY Genetically encoded Ca2+-sensors, like GCaMP2, are important tools to reveal molecular mechanisms for Ca2+-sensing. We provided left ventricular hemodynamic characterization of GCaMP2 transgenic rats and found increased afterload, cardiac hypertrophy, and prolonged left ventricular relaxation, along with unaltered systolic function and contractility. Special caution should be taken when using this rodent model in cardiovascular pharmacological and toxicological studies.
Regulation of miRNA Biogenesis and Histone Modification by K63-Polyubiquitinated DDX17 Controls Cancer Stem-like Features
Authors: Kao Shih-Han , Cheng Wei-Chung , Wang Yi-Ting , Wu Han-Tsang , Yeh Han-Yu , Chen Yu-Ju , Tsai Ming-Hsui , Wu Kou-Juey 
Published: March 2019

Abstract

Markers of cancer stemness predispose patients to tumor aggressiveness, drug and immunotherapy resistance, relapse, and metastasis. DDX17 is a cofactor of the Drosha–DGCR8 complex in miRNA biogenesis and transcriptional coactivator and has been associated with cancer stem-like properties. However, the precise mechanism by which DDX17 controls cancer stem-like features remains elusive. Here, we show that the E3 ligase HectH9 mediated K63-polyubiquitination of DDX17 under hypoxia to control stem-like properties and tumor-initiating capabilities. Polyubiquitinated DDX17 disassociated from the Drosha–DGCR8 complex, leading to decreased biogenesis of anti-stemness miRNAs. Increased association of polyubiquitinated DDX17 with p300-YAP resulted in histone 3 lysine 56 (H3K56) acetylation proximal to stemness-related genes and their subsequent transcriptional activation. High expression of HectH9 and six stemness-related genes (BMI1, SOX2, OCT4, NANOG, NOTCH1, and NOTCH2) predicted poor survival in patients with head and neck squamous cell carcinoma and lung adenocarcinoma. Our findings demonstrate that concerted regulation of miRNA biogenesis and histone modifications through posttranslational modification of DDX17 underlies many cancer stem-like features. Inhibition of DDX17 ubiquitination may serve as a new therapeutic venue for cancer treatment.

Significance:
Hypoxia-induced polyubiquitination of DDX17 controls its dissociation from the pri-miRNA–Drosha–DCGR8 complex to reduce anti-stemness miRNA biogenesis and association with YAP and p300 to enhance transcription of stemness-related genes.
Pan-TAM Tyrosine Kinase Inhibitor BMS-777607 Enhances Anti–PD-1 mAb Efficacy in a Murine Model of Triple-Negative Breast Cancer
Authors: Kasikara Canan , Davra Viralkumar , Calianese David , Geng Ke , Spires Thomas E. , Quigley Michael , Wichroski Michael , Sriram Ganapathy , Suarez-Lopez Lucia , Yaffe Michael B. , Kotenko Sergei V. , De Lorenzo Mariana S. , Birge Raymond B. 
Published: March 2019

AbstractTyro3, Axl, and Mertk (TAM) represent a family of homologous tyrosine kinase receptors known for their functional role in phosphatidylserine (PS)-dependent clearance of apoptotic cells and also for their immune modulatory functions in the resolution of inflammation. Previous studies in our laboratory have shown that Gas6/PS-mediated activation of TAM receptors on tumor cells leads to subsequent upregulation of PD-L1, defining a putative PS→TAM receptor→PD-L1 inhibitory signaling axis in the cancer microenvironment that may promote tolerance. In this study, we tested combinations of TAM inhibitors and PD-1 mAbs in a syngeneic orthotopic E0771 murine triple-negative breast cancer model, whereby tumor-bearing mice were treated with pan-TAM kinase inhibitor (BMS-777607) or anti–PD-1 alone or in combination. Tyro3, Axl, and Mertk were differentially expressed on multiple cell subtypes in the tumor microenvironment. Although monotherapeutic administration of either pan-TAM kinase inhibitor (BMS-777607) or anti–PD-1 mAb therapy showed partial antitumor activity, combined treatment of BMS-777607 with anti–PD-1 significantly decreased tumor growth and incidence of lung metastasis. Moreover, combined treatment with BMS-777607 and anti–PD-1 showed increased infiltration of immune stimulatory T cells versus either monotherapy treatment alone. RNA NanoString profiling showed enhanced infiltration of antitumor effector T cells and a skewed immunogenic immune profile. Proinflammatory cytokines increased with combinational treatment. Together, these studies indicate that pan-TAM inhibitor BMS-777607 cooperates with anti–PD-1 in a syngeneic mouse model for triple-negative breast cancer and highlights the clinical potential for this combined therapy.Significance:These findings show that pan-inhibition of TAM receptors in combination with anti–PD-1 may have clinical value as cancer therapeutics to promote an inflammatory tumor microenvironment and improve host antitumor immunity.
MRI Imaging of the Hemodynamic Vasculature of Neuroblastoma Predicts Response to Antiangiogenic Treatment
Authors: Zormpas-Petridis Konstantinos , Jerome Neil P. , Blackledge Matthew D. , Carceller Fernando , Poon Evon , Clarke Matthew , McErlean Ciara M. , Barone Giuseppe , Koers Alexander , Vaidya Sucheta J. , Marshall Lynley V. , Pearson Andrew D.J. , Moreno Lucas , Anderson John , Sebire Neil , McHugh Kieran , Koh Dow-Mu , Yuan Yinyin , Chesler Louis , Robinson Simon P. , Jamin Yann 
Published: March 2019

Abstract

Childhood neuroblastoma is a hypervascular tumor of neural origin, for which antiangiogenic drugs are currently being evaluated; however, predictive biomarkers of treatment response, crucial for successful delivery of precision therapeutics, are lacking. We describe an MRI-pathologic cross-correlative approach using intrinsic susceptibility (IS) and susceptibility contrast (SC) MRI to noninvasively map the vascular phenotype in neuroblastoma Th-MYCN transgenic mice treated with the vascular endothelial growth factor receptor inhibitor cediranib. We showed that the transverse MRI relaxation rate R2* (second−1) and fractional blood volume (fBV, %) were sensitive imaging biomarkers of hemorrhage and vascular density, respectively, and were also predictive biomarkers of response to cediranib. Comparison with MRI and pathology from patients with MYCN-amplified neuroblastoma confirmed the high degree to which the Th-MYCN model vascular phenotype recapitulated that of the clinical phenotype, thereby supporting further evaluation of IS- and SC-MRI in the clinic. This study reinforces the potential role of functional MRI in delivering precision medicine to children with neuroblastoma.

Significance:
This study shows that functional MRI predicts response to vascular-targeted therapy in a genetically engineered murine model of neuroblastoma.
Drak, Drak, Goose: A New Signaling Axis in Glioblastoma
Authors: Lathia Justin D. 
Published: March 2019

Abstract
While many molecular alterations in glioblastoma (GBM), the most common primary malignant brain tumor, have been defined, the intricate signaling networks associated with these alterations that represent actionable therapeutic targets are less well established. Chen and colleagues leverage a Drosophila GBM model to identify a conserved signaling axis downstream of the EGFR and PI3K that involves the death-associated protein kinase (Drak), a cytoplasmic serine/threonine kinase orthologous to the human kinase STK17A. Functional studies revealed that targeting this signaling axis attenuated mitosis and cytokinesis, providing a new pathway for therapeutic development in GBM.
See related article by Chen et al., p. 1085
Circulating Inflammation Markers and Risk of Gastric and Esophageal Cancers: A Case–Cohort Study Within the Japan Public Health Center–Based Prospective Study
Authors: Camargo M. Constanza , Song Minkyo , Shimazu Taichi , Charvat Hadrien , Yamaji Taiki , Sawada Norie , Kemp Troy J. , Pfeiffer Ruth M. , Hildesheim Allan , Pinto Ligia A. , Tsugane Shoichiro , Rabkin Charles S. 
Published: March 2019

Abstract

Background:
Circulating inflammation proteins may be important mediators or markers of carcinogenic mechanisms. There have been few studies with limited numbers of analytes in patients with upper gastrointestinal (GI) tract tumors. We therefore evaluated risk associations of gastric and esophageal cancers with prediagnostic levels of a wide range of these molecules.

Methods:
We performed a case–cohort analysis within the Japan Public Health Center–Based Prospective Study Cohort II, including incident cases of gastric (n = 446) and esophageal (n = 68) cancers and a random subcohort (n = 774). A total of 64 biomarkers were measured in baseline plasma using Luminex bead-based assays. The median time between blood collection and diagnosis was 8.1 years for gastric cancer and 9.4 years for esophageal cancer. HRs for association with each marker were adjusted for potential confounders using Cox regression.

Results:
In separate models, sEGFR and TSLP were nominally associated with gastric cancer risk, and CRP, CXCL11/ITAC, and CCL15/MIP1D were associated with esophageal cancer. However, no association satisfied statistical significance after FDR correction. Associations did not differ by time from blood collection to cancer (&lt;5 vs. ≥5 years).

Conclusions:
Our study failed to identify associations of circulating inflammation markers with risk of upper GI tract tumors.

Impact:
To date, this is the largest assessment of inflammation-related proteins with gastric and esophageal cancer risks. However, the evaluated molecules may not fully represent the complex inflammation processes preceding malignant transformation. Further investigation of other markers in prospective studies is warranted, as demonstration of associations may have important implications for prevention and treatment of these cancers.