bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pupil-associated states modulate excitability but not stimulus selectivity in primary auditory cortex
Authors: Schwartz Zachary P. , Buran Brad N. , David Stephen V. 
Published: November 2019

Recent research in mice indicates that luminance-independent fluctuations in pupil size predict variability in spontaneous and evoked activity of single neurons in auditory and visual cortex. These findings suggest that pupil is an indicator of large-scale changes in arousal state that affect sensory processing. However, it is not known whether pupil-related state also influences the selectivity of auditory neurons. We recorded pupil size and single-unit spiking activity in the primary auditory cortex (A1) of nonanesthetized male and female ferrets during presentation of natural vocalizations and tone stimuli that allow measurement of frequency and level tuning. Neurons showed a systematic increase in both spontaneous and sound-evoked activity when pupil was large, as well as desynchronization and a decrease in trial-to-trial variability. Relationships between pupil size and firing rate were nonmonotonic in some cells. In most neurons, several measurements of tuning, including acoustic threshold, spectral bandwidth, and best frequency, remained stable across large changes in pupil size. Across the population, however, there was a small but significant decrease in acoustic threshold when pupil was dilated. In some recordings, we observed rapid, saccade-like eye movements during sustained pupil constriction, which may indicate sleep. Including the presence of this state as a separate variable in a regression model of neural variability accounted for some, but not all, of the variability and nonmonotonicity associated with changes in pupil size.NEW & NOTEWORTHY Cortical neurons vary in their response to repeated stimuli, and some portion of the variability is due to fluctuations in network state. By simultaneously recording pupil and single-neuron activity in auditory cortex of ferrets, we provide new evidence that network state affects the excitability of auditory neurons, but not sensory selectivity. In addition, we report the occurrence of possible sleep states, adding to evidence that pupil provides an index of both sleep and physiological arousal.
Bidirectional Regulation between NDRG1 and GSK3β Controls Tumor Growth and Is Targeted by Differentiation Inducing Factor-1 in Glioblastoma
Authors: Ito Hiroshi , Watari Kosuke , Shibata Tomohiro , Miyamoto Tomofumi , Murakami Yuichi , Nakahara Yukiko , Izumi Hiroto , Wakimoto Hiroaki , Kuwano Michihiko , Abe Tatsuya , Ono Mayumi 
Published: November 2019

Abstract

The development of potent and selective therapeutic approaches to glioblastoma (GBM), one of the most aggressive primary brain tumors, requires identification of molecular pathways that critically regulate the survival and proliferation of GBM. Previous studies have reported that deregulated expression of N-myc downstream regulated gene 1 (NDRG1) affects tumor growth and clinical outcomes of patients with various types of cancer including glioma. Here, we show that high level expression of NDRG1 in tumors significantly correlated with better prognosis of patients with GBM. Loss of NDRG1 in GBM cells upregulated GSK3β levels and promoted cell proliferation, which was reversed by selective inhibitors of GSK3β. In contrast, NDRG1 overexpression suppressed growth of GBM cells by decreasing GSK3β levels via proteasomal degradation and by suppressing AKT and S6 cell growth signaling, as well as cell-cycle signaling pathways. Conversely, GSK3β phosphorylated serine and threonine sites in the C-terminal domain of NDRG1 and limited the protein stability of NDRG1. Furthermore, treatment with differentiation inducing factor-1, a small molecule derived from Dictyostelium discoideum, enhanced NDRG1 expression, decreased GSK3β expression, and exerted marked NDRG1-dependent antitumor effects in vitro and in vivo. Taken together, this study revealed a novel molecular mechanism by which NDRG1 inhibits GBM proliferation and progression. Our study thus identifies the NDRG1/GSK3β signaling pathway as a key growth regulatory program in GBM, and suggests enhancing NDRG1 expression in GBM as a potent strategy toward the development of anti-GBM therapeutics.

Significance:
This study identifies NDRG1 as a potent and endogenous suppressor of glioblastoma cell growth, suggesting the clinical benefits of NDRG1-targeted therapeutics against glioblastoma.
CD44 Promotes PD-L1 Expression and Its Tumor-Intrinsic Function in Breast and Lung Cancers
Authors: Kong Tim , Ahn Ryuhjin , Yang Kangning , Zhu Xianbing , Fu Zheng , Morin Geneviève , Bramley Rachel , Cliffe Nikki C. , Xue Yibo , Kuasne Hellen , Li Qinghao , Jung Sungmi , Gonzalez Anne V. , Camilleri-Broet Sophie , Guiot Marie-Christine , Park Morag , Ursini-Siegel Josie , Huang Sidong 
Published: November 2019

Abstract

The PD-L1 (CD274) immune-checkpoint ligand is often upregulated in cancers to inhibit T cells and elicit immunosuppression. Independent of this activity, PD-L1 has recently been shown to also exert a cancer cell–intrinsic function promoting tumorigenesis. Here, we establish this tumor-intrinsic role of PD-L1 in triple-negative breast cancer (TNBC) and non–small cell lung cancer (NSCLC). Using FACS-assisted shRNA screens, we identified the cell-surface adhesion receptor CD44 as a key positive regulator of PD-L1 expression in these cancers. Mechanistically, CD44 activated PD-L1 transcription in part through its cleaved intracytoplasmic domain (ICD), which bound to a regulatory region of the PD-L1 locus containing a consensus CD44-ICD binding site. Supporting this genetic interaction, CD44 positively correlated with PD-L1 expression at the mRNA and protein levels in primary tumor samples of TNBC and NSCLC patients. These data provide a novel basis for CD44 as a critical therapeutic target to suppress PD-L1 tumor–intrinsic function.

Significance:
CD44 is a potential target to suppress PD-L1 function in TNBC. This finding has the potential to open a new area of therapy for TNBC.
A PSCA/PGRN–NF-κB–Integrin–α4 Axis Promotes Prostate Cancer Cell Adhesion to Bone Marrow Endothelium and Enhances Metastatic Potential
Authors: Zhao Zhigang , Li Ermao , Luo Lianmin , Zhao Shankun , Liu Luhao , Wang Jiamin , Kang Ran , Luo Jintai 
Published: November 2019

Abstract

Distant metastasis, predominantly to bone, is the leading cause of morbidity and mortality in prostate cancer. However, the mechanisms underlying prostate cancer metastases remain unknown. Prostate cancer cells exhibited discrete adhesion to bone marrow endothelial cells (BMEC), resulting in osteotropic metastasis. Prior data showed an increased metastatic propensity of prostate stem cell antigen (PSCA)–positive prostate cancer cells. The current study sought to characterize the roles of PSCA in the adhesion of prostate cancer cells to BMECs. Cell adhesion was assessed using the adhesion assay and transendothelial migration. The expression and regulation of integrins were evaluated by qRT-PCR, Western blot, promoter-luciferase activity, and chromatin immunoprecipitation (ChIP). Functionally, the potential interacting partners of PSCA in prostate cancer cells were identified by coimmunoprecipitation and mass spectrometry (MS) analysis. The association of PSCA expression with bone metastasis was further analyzed in an in vivo model and prostate cancer patients. We found that overexpression of PSCA enhanced the adhesion capability of prostate cancer cells to BMECs through upregulating integrin-α4 expression, concurrent with transcriptionally activated NF-κB. Growth factor progranulin (PGRN) was identified as a potential interacting partner of PSCA in prostate cancer cells. Functional studies showed that downregulation of PGRN and PSCA with siRNAs in prostate cancer cells significantly suppressed the integrin-α4 expression and the adhesion to BMECs in vitro, respectively, which were restorable by exogenous PGRN. Importantly, PSCA depletion significantly reduced tumors' presence in the bone of a mouse model. Furthermore, PSCA expression is elevated in prostate cancer tissue, and significantly associated with increased Gleason score, advanced stage, bone metastasis, and poor prognosis in prostate cancer patients. We conclude that PSCA/PGRN promoted the adhesion of prostate cancer cells to BMECs through NF-κB/integrin-α4 pathways, to facilitate metastases.

Implications:
The findings presented here suggest PSCA/PGRN as a potential therapeutic target for prostate cancer metastases, especially for bone metastasis.
Uso e abuso de drogas entre universitários e a sua interface com as políticas públicas
Authors: Camargo Elisa Carneiro Pereira , Gonçalves Jamila Souza , Felipe Adriana Olimpia Barbosa , Fava Silvana Maria Coelho Leite , Zago Márcia Maria Fontão , Dázio Eliza Maria Rezende 
Published: November 2019

Objetivo: analisar o significado do uso e do abuso de álcool e/ou de outras drogas entre os universitários em consonância com as políticas públicas brasileiras sobre drogas. Método: participaram 49 universitários de uma Instituição Pública de Ensino Superior da região Sudeste do Brasil. Resultados: pela Análise de Conteúdo de Bardin elaborou-se a categoria analítica: “Dissonância entre as políticas públicas e o significado do uso de drogas entre universitários”. O uso e o abuso de drogas inicia-se na adolescência; estimulado pelos familiares e amigos, e remete à felicidade e à fuga dos problemas. Conclusão: é fundamental conhecer o significado do uso e do abuso de drogas, sob a ótica do universitário para a elaboração e a implementação de políticas públicas.
Alterações mentais em trabalhadores de unidades de terapia intensiva
Authors: Silva Andressa Fernanda , Robazzi Maria Lúcia do Carmo Cruz 
Published: November 2019

Objetivo: investigar as evidências científicas sobre alterações mentais em trabalhadores de Unidades de Terapia Intensiva (UTI). Método: revisão integrativa cuja busca aconteceu nas bases de dados EMBASE, MEDLINE e SCOPUS e nas bibliotecas virtuais/coleções BVS e SCIENCE DIRECT. De 141 artigos primários identificados, 33 (23,4%) atenderam aos critérios de inclusão e foram publicados em 29 periódicos de várias áreas de conhecimento. Resultados: as alterações mentais identificadas foram: estresse, sofrimento e tensão no trabalho, depressão, astenia, fadiga, sobrecarga mental e Burnout. No trabalho, também acontecemconflitos, violência e maus tratos e os trabalhadores das UTI apresentaram predisposição ao uso de psicotrópicos. Conclusão: o tema é relevante pois há um rol de alterações mentais dos trabalhadores de UTI que podem levá-los aos absenteísmos.
O uso de bebida alcoólica entre gestantes adolescentes
Authors: Cândido Tarcila Cristina Rodrigues , Ferreira Gabriela Coutinho , Moreira Denis Da Silva , Sousa Bárbara De Oliveira Prado , Cordeiro Samara Macedo , Alfredo Evellin Ribeiro , Felipe Adriana Olimpia Barbosa 
Published: November 2019

Objetivo: identificar o consumo de bebida alcoólica entre as adolescentes gestantes. Método: estudo de abordagem quantitativa, descritiva e de corte transversal. Os participantes foram 27 adolescentes gestantes adscritas nas Estratégia de Saúde da Família. Resultados: constatou-se que 54% referiram fazer uso de bebida alcoólica nos últimos 12 meses e 7,4% apresentavam chance de ter diagnóstico de dependência alcoólica. Das 5 participantes que relataram ser a segunda gestação, 80% afirmaram ter utilizado álcool na gravidez anterior. Identificou-se que em relação de risco sobre o padrão de consumo de álcool 81,4% se enquadram na zona I, 14,8% na zona II e 7,4% na zona IV. Conclusão: reafirma-se a necessidade de ações de prevenção do uso de álcool na gestação e a relevância do papel do enfermeiro no acompanhamento integral durante o pré-natal.
Sex‐Specific Differences in Survival and Heart Failure Hospitalization After Cardiac Resynchronization Therapy With or Without Defibrillation
Authors: Leyva Francisco , Qiu Tian , Zegard Abbasin , McNulty David , Evison Felicity , Ray Daniel , Gasparini Maurizio 
Published: November 2019

Background

Women are underrepresented in cardiac resynchronization therapy (
CRT
) trials. Some studies suggest that women fare better than men after
CRT
. We sought to explore clinical outcomes in women and men undergoing
CRT
‐defibrillation or CRT‐pacing in real‐world clinical practice.

Methods and Results

A national database (Hospital Episode Statistics for England) was used to quantify clinical outcomes in 43 730 patients (women: 10 890 [24.9%]; men: 32 840 [75.1%]) undergoing
CRT
over 7.6 years, (median follow‐up 2.2 years, interquartile range, 1–4 years). In analysis of the total population, the primary end point of total mortality (adjusted hazard ratio [
aHR
], 0.73; 95% CI, 0.69–0.76) and the secondary end point of total mortality or heart failure hospitalization (
aHR
, 0.79, 95% CI 0.75–0.82) were lower in women, independent of known confounders. Total mortality (
aHR
, 0.73; 95% CI, 0.70–0.76) and total mortality or heart failure hospitalization (
aHR
, 0.79; 95% CI, 0.75–0.82) were lower for
CRT
‐defibrillation than for
CRT
‐pacing. In analyses of patients with (
aHR
, 0.89; 95% CI, 0.80–0.98) or without (
aHR
, 0.70; 95% CI, 0.66–0.73) a myocardial infarction, women had a lower total mortality. In sex‐specific analyses, total mortality was lower after
CRT
‐defibrillation in women (
aHR
, 0.83;
P
=0.013) and men (
aHR
, 0.69;
P
<0.001).

Conclusions

Compared with men, women lived longer and were less likely to be hospitalized for heart failure after
CRT
. In both sexes,
CRT
‐defibrillation was superior to
CRT
‐pacing with respect to survival and heart failure hospitalization. The longest survival after
CRT
was observed in women without a history of myocardial infarction.
Outcomes of Multi‐Organ Transplant in Adult Patients With Congenital Heart Disease
Authors: Wong Kristen , Tecson Kristen , Cedars Ari 
Published: November 2019

Background

The prevalence of adult congenital heart disease (
ACHD
) is increasing in the United States because of improved survival into adulthood. The unique physiology of ACHD commonly leads to multiorgan dysfunction, prompting interest in outcomes after multiorgan (heart+X) transplantation.

Methods and Results

We queried the SRTR (Scientific Registry of Transplant Recipients) database to examine 5‐year outcomes in
ACHD
patients (aged ≥18 years) who underwent dual organ (heart+kidney/liver/lung) transplantation between 2000 and 2016. Cox proportional hazards models were constructed to look at survival of dual organ transplant recipients versus heart‐only recipients in the
ACHD
population and heart+lung recipients versus heart‐only recipients in the
ACHD
populations and versus non‐
ACHD
recipients of heart+lung transplant. We then constructed a multivariable model to investigate independent risk factors for 5‐year mortality after multiorgan transplant. Overall, 5‐year mortality was greater for multiorgan (heart+kidney/liver/lung) transplant compared with heart‐only transplant. On further analysis, only heart+lung transplant was associated with increased mortality. Outcomes after heart+lung transplant were no different between the
ACHD
and non‐
ACHD
population. Risk factors for increased risk of 5‐year mortality in
ACHD
patients after multiorgan transplant included heart+lung transplant, previous cardiac surgery, and severe functional limitation.

Conclusions

The mortality risk associated with multiorgan heart transplant in
ACHD
patients is attributable primarily to heart+lung transplants. Multiorgan transplant in
ACHD
does not convey increased risk compared with the non‐
ACHD
population. Need for multiorgan transplant should not be an impediment to listing
ACHD
patients needing a heart transplant.
Thrombectomy and Thrombolysis of Isolated Posterior Cerebral Artery Occlusion
Authors: Strambo Davide , Bartolini Bruno , Beaud Valérie , Marto João Pedro , Sirimarco Gaia , Dunet Vincent , Saliou Guillaume , Nannoni Stefania , Michel Patrik 
Published: November 2019

Background and Purpose—
We investigated efficacy and safety of acute revascularization with intravenous thrombolysis (IVT) and endovascular treatment (EVT) in ischemic stroke from isolated posterior cerebral artery occlusion, by assessing recanalization, disability, visual, cognitive outcomes, and hemorrhagic complications.

Methods—
For this retrospective single-center cohort study, we selected all consecutive patients with stroke with isolated posterior cerebral artery occlusion from the Acute Stroke Registry and Analysis of Lausanne registry between January 2003 and July 2018, and compared (1) IVT with conservative treatment (CTr) and (2) EVT to best medical therapy (BMT, ie, CTr or IVT) in terms of 3-month disability and visual field defect, and cognitive domains impaired after stroke. Unadjusted analysis, multivariable logistic regression, and propensity score matched analyses were performed.

Results—

Among 106 patients with isolated posterior cerebral artery occlusion, 21 received EVT (13 bridging), 34 IVT alone, and 51 CTr. Median age was 76 years, 47% were female and median National Institutes of Health Stroke Scale score was 7. Complete 24-hour recanalization was more frequent with IVT than CTr (51% versus 9%; OR [95% CI]=10.62 [2.13–52.92]) and with EVT compared with BMT (68% versus 34%; OR [95% CI]=4.11 [1.35–12.53]). Higher proportions of good disability, visual and cognitive outcomes were observed in IVT versus CTr,
adj
ORs (95% CI)=1.65 (0.60−4.52), 2.01 (0.58−7.01), 2.94 (0.35−24.4), respectively, and in EVT versus BMT,
adj
ORs (95% CI)=1.44 (0.51−4.10), 4.28 (1.00−18.29), 4.37 (0.72−26.53), respectively. Hemorrhagic complications and mortality did not increase with IVT or EVT.

Conclusion
s—We show increased odds of recanalization following IVT and even higher after EVT. We observed a trend for a positive effect on disability, visual, and cognitive outcomes with IVT over CTr and with EVT over BMT.
The Role of International Agreements in Organising Tax Imposed on Intellectual Property Rights in Egypt, Palestine, and Jordan
Authors: Falah Hasan , Hassan Amjad 
Published: November 2019

Abstract
Recognising the potential abundance of revenue and penetration of intellectual property as protected in various forms (copyrights, trademarks, patents, industrial designs, technical expertise, and trade secrets), into every aspect of society, states have endeavoured to regulate and protect these rights through national legislation and international agreements that emphasise the need to organise and protect these tax rights to support cooperation and integration among countries, as well as resolving international disputes on double taxation and combating tax evasion. This Article examines existing intellectual property legislation in Palestine, Jordan, and Egypt. Legislations in these three countries have agreed to subject to tax intellectual property revenues and activities, recognising them as one of the most important sources of state income. However, Palestinian legislation has not been clear in setting laws to deal with intellectual property revenues, contrary to counterparties in Egypt and Jordan.
Real World and Tropical Cyclone World. Part I: High-Resolution Climate Model Verification
Authors: Sharmila S. , Walsh K. J. E. , Thatcher M. , Wales S. , Utembe S. 
Published: November 2019

AbstractRecent global climate models with sufficient resolution and physics offer a promising approach for simulating real-world tropical cyclone (TC) statistics and their changing relationship with climate. In the first part of this study, we examine the performance of a high-resolution (~40-km horizontal grid) global climate model, the atmospheric component of the Australian Community Climate and Earth System Simulator (ACCESS) based on the Met Office Unified Model (UM8.5) Global Atmosphere (GA6.0). The atmospheric model is forced with observed sea surface temperature, and 20 years of integrations (1990–2009) are analyzed for evaluating the simulated TC statistics compared with observations. The model reproduces the observed climatology, geographical distribution, and interhemispheric asymmetry of global TC formation rates reasonably well. The annual cycle of regional TC formation rates over most basins is also well captured. However, there are some regional biases in the geographical distribution of TC formation rates. To identify the sources of these biases, a suite of model-simulated large-scale climate conditions that critically modulate TC formation rates are further evaluated, including the assessment of a multivariate genesis potential index. Results indicate that the model TC genesis biases correspond well to the inherent biases in the simulated large-scale climatic states, although the relative effects on TC genesis of some variables differs between basins. This highlights the model’s mean-state dependency in simulating accurate TC formation rates.
Does ENSO Regularity Increase in a Warming Climate?
Authors: Berner Judith , Christensen Hannah M. , Sardeshmukh Prashant D. 
Published: November 2019

AbstractThe impact of a warming climate on El Niño–Southern Oscillation (ENSO) is investigated in large-ensemble simulations of the Community Earth System Model (CESM1). These simulations are forced by historical emissions for the past and the RCP8.5-scenario emissions for future projections. The simulated variance of the Niño-3.4 ENSO index increases from 1.4°C2 in 1921–80 to 1.9°C2 in 1981–2040 and 2.2°C2 in 2041–2100. The autocorrelation time scale of the index also increases, consistent with a narrowing of its spectral peak in the 3–7-yr ENSO band, raising the possibility of greater seasonal to interannual predictability in the future. Low-order linear inverse models (LIMs) fitted separately to the three 60-yr periods capture the CESM1 increase in ENSO variance and regularity. Remarkably, most of the increase can be attributed to the increase in the 23-month damping time scale of a single damped oscillatory ENSO eigenmode of these LIMs by 5 months in 1981–2040 and 6 months in 2041–2100. These apparently robust projected increases may, however, be compromised by CESM1 biases in ENSO amplitude and damping time scale. An LIM fitted to the 1921–80 observations has an ENSO eigenmode with a much shorter 8-month damping time scale, similar to that of several other eigenmodes. When the mode’s damping time scale is increased by 5 and 6 months in this observational LIM, a much smaller increase of ENSO variance is obtained than in the CESM1 projections. This may be because ENSO is not as dominated by a single ENSO eigenmode in reality as it is in the CESM1.
Changing the guard: The dissolution of the nationalist–Marxist orthodoxy in the agrarian and agricultural history of India
Authors: Dewey Clive 
Published: November 2019

Shubhra Chakrabarti and Utsa Patnaik, eds, Agrarian and Other Histories: Essays for Binay Bhushan Chaudhuri, New Delhi: Tulika Books, 2017, 326 pp. Deepak Kumar and Bipasha Raha, eds, Tilling the Land: Agricultural Knowledge and Practices in Colonial India, Delhi: Primus Books, 2016, 323 pp.