bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional Silencing of ALDH2 Confers a Dependency on Fanconi Anemia Proteins in Acute Myeloid Leukemia
Authors: Yang Zhaolin , Wu Xiaoli S. , Wei Yiliang , Polyanskaya Sofya A. , Iyer Shruti V. , Jung Moonjung , Lach Francis P. , Adelman Emmalee R. , Klingbeil Olaf , Milazzo Joseph P. , Kramer Melissa , Demerdash Osama E. , Chang Kenneth , Goodwin Sara , Hodges Emily , McCombie W. Richard , Figueroa Maria E. , Smogorzewska Agata , Vakoc Christopher R. 
Published: April 2021

Abstract

Hundreds of genes become aberrantly silenced in acute myeloid leukemia (AML), with most of these epigenetic changes being of unknown functional consequence. Here, we demonstrate how gene silencing can lead to an acquired dependency on the DNA repair machinery in AML. We make this observation by profiling the essentiality of the ubiquitination machinery in cancer cell lines using domain-focused CRISPR screening, which revealed Fanconi anemia (FA) proteins UBE2T and FANCL as unique dependencies in AML. We demonstrate that these dependencies are due to a synthetic lethal interaction between FA proteins and aldehyde dehydrogenase 2 (ALDH2), which function in parallel pathways to counteract the genotoxicity of endogenous aldehydes. We show DNA hypermethylation and silencing of ALDH2 occur in a recurrent manner in human AML, which is sufficient to confer FA pathway dependency. Our study suggests that targeting of the ubiquitination reaction catalyzed by FA proteins can eliminate ALDH2-deficient AML.

Significance:
Aberrant gene silencing is an epigenetic hallmark of human cancer, but the functional consequences of this process are largely unknown. In this study, we show how an epigenetic alteration leads to an actionable dependency on a DNA repair pathway through the disabling of genetic redundancy.
This article is highlighted in the In This Issue feature, p. 2113
NKX3.1 Localization to Mitochondria Suppresses Prostate Cancer Initiation
Authors: Papachristodoulou Alexandros , Rodriguez-Calero Antonio , Panja Sukanya , Margolskee Elizabeth , Virk Renu K. , Milner Teresa A. , Martina Luis Pina , Kim Jaime Y. , Di Bernardo Matteo , Williams Alanna B. , Maliza Elvis A. , Caputo Joseph M. , Haas Christopher , Wang Vinson , De Castro Guarionex Joel , Wenske Sven , Hibshoosh Hanina , McKiernan James M. , Shen Michael M. , Rubin Mark A. , Mitrofanova Antonina , Dutta Aditya , Abate-Shen Cory 
Published: April 2021

Abstract

Mitochondria provide the first line of defense against the tumor-promoting effects of oxidative stress. Here we show that the prostate-specific homeoprotein NKX3.1 suppresses prostate cancer initiation by protecting mitochondria from oxidative stress. Integrating analyses of genetically engineered mouse models, human prostate cancer cells, and human prostate cancer organotypic cultures, we find that, in response to oxidative stress, NKX3.1 is imported to mitochondria via the chaperone protein HSPA9, where it regulates transcription of mitochondrial-encoded electron transport chain (ETC) genes, thereby restoring oxidative phosphorylation and preventing cancer initiation. Germline polymorphisms of NKX3.1 associated with increased cancer risk fail to protect from oxidative stress or suppress tumorigenicity. Low expression levels of NKX3.1 combined with low expression of mitochondrial ETC genes are associated with adverse clinical outcome, whereas high levels of mitochondrial NKX3.1 protein are associated with favorable outcome. This work reveals an extranuclear role for NKX3.1 in suppression of prostate cancer by protecting mitochondrial function.

Significance:
Our findings uncover a nonnuclear function for NKX3.1 that is a key mechanism for suppression of prostate cancer. Analyses of the expression levels and subcellular localization of NKX3.1 in patients at risk of cancer progression may improve risk assessment in a precision prevention paradigm, particularly for men undergoing active surveillance.
See related commentary by Finch and Baena, p. 2132.
This article is highlighted in the In This Issue feature, p. 2113
Integrated Genomic Analysis Identifies Driver Genes and Cisplatin-Resistant Progenitor Phenotype in Pediatric Liver Cancer
Authors: Hirsch Theo Z. , Pilet Jill , Morcrette Guillaume , Roehrig Amélie , Monteiro Benedict J.E. , Molina Laura , Bayard Quentin , Trépo Eric , Meunier Léa , Caruso Stefano , Renault Victor , Deleuze Jean-François , Fresneau Brice , Chardot Christophe , Gonzales Emmanuel , Jacquemin Emmanuel , Guerin Florent , Fabre Monique , Aerts Isabelle , Taque Sophie , Laithier Véronique , Branchereau Sophie , Guettier Catherine , Brugières Laurence , Rebouissou Sandra , Letouzé Eric , Zucman-Rossi Jessica 
Published: April 2021

AbstractPediatric liver cancers (PLC) comprise diverse diseases affecting infants, children, and adolescents. Despite overall good prognosis, PLCs display heterogeneous response to chemotherapy. Integrated genomic analysis of 126 pediatric liver tumors showed a continuum of driver mechanisms associated with patient age, including new targetable oncogenes. In 10% of patients with hepatoblastoma, all before three years old, we identified a mosaic premalignant clonal expansion of cells altered at the 11p15.5 locus. Analysis of spatial and longitudinal heterogeneity revealed an important plasticity between “hepatocytic,” “liver progenitor,” and “mesenchymal” molecular subgroups of hepatoblastoma. We showed that during chemotherapy, “liver progenitor” cells accumulated massive loads of cisplatin-induced mutations with a specific mutational signature, leading to the development of heavily mutated relapses and metastases. Drug screening in PLC cell lines identified promising targets for cisplatin-resistant progenitor cells, validated in mouse xenograft experiments. These data provide new insights into cisplatin resistance mechanisms in PLC and suggest alternative therapies.Significance:PLCs are deadly when they resist chemotherapy, with limited alternative treatment options. Using a multiomics approach, we identified PLC driver genes and the cellular phenotype at the origin of cisplatin resistance. We validated new treatments targeting these molecular features in cell lines and xenografts.This article is highlighted in the In This Issue feature, p. 2355
Loss of Soluble (Pro)renin Receptor Attenuates Angiotensin-II Induced Hypertension and Renal Injury
Authors: Ramkumar Nirupama , Stuart Deborah , Peterson Caitlin S. , Hu Chunyan , Wheatley William , Min Cho Jae , Symons J David , Kohan Donald E. 
Published: April 2021

Rationale:
Cleavage of the extracellular domain of the PRR ([pro]renin receptor) yields a soluble fragment (sPRR). Although changes in plasma sPRR levels have been reported in hypertension, the causal role of sPRR in blood pressure regulation is unknown.

Objective:
Determine the role of sPRR in blood pressure regulation at baseline and following Ang II (angiotensin II)–induced hypertension.

Methods and Results:

CRISPR-Cas9 was used to mutate the cleavage site of the PRR such that sPRR is not generated. Because the gene encoding PRR is on the X-chromosome and male mutant sPRR mice are infertile, only male mice were studied. Mutant sPRR mice had virtually undetectable plasma sPRR levels compared with littermate controls. Mutant sPRR mice had normal survival and development and no apparent histological abnormalities in the kidney, heart, or aorta despite lower body weight. During normal Na
+
intake, no differences in food or water intake, urinary water or Na
+
excretion, or acid-base status were observed between control and mutant sPRR mice. Compared with controls, mutant sPRR mice had lower blood pressure at baseline and an attenuated hypertensive response to 2 weeks of Ang II infusion (400 ng/kg per minute) which was partially reversed by infusion of mouse recombinant sPRR. Mutant sPRR mice also had lower albuminuria, renal tubular injury, and oxidative stress relative to control mice post-Ang II infusion. Furthermore, mesenteric arteries from mutant sPRR mice displayed reduced Ang II–induced vasocontraction and greater acetylcholine, but not sodium nitroprusside, evoked vasorelaxation under baseline conditions.

Conclusions:
Loss of sPRR reduces blood pressure at baseline and decreases Ang II–induced hypertension and renal injury. These effects of sPRR loss are associated with greater endothelium-dependent but not independent vasorelaxation of resistance-sized arteries.
Jesuit Missionaries and Enslavement at the Turn of the Eighteenth Century: An Assessment from the Loyola Plantation in French Guiana
Authors: Auger Réginald , Guay Jean-François , Houle-Wierzbicki Zocha , Lussier-Piette Raphaelle , Rousselle Antoine Loyer , Le Roux Yannick 
Published: April 2021

Abstract
We present an overview of the archaeological research carried out on a sugar plantation operated by the Jesuits in French Guiana. The Jesuits’ production was exported to Europe to provide funds to develop their missions among Native people living in French Guiana and Amazonia. We present a brief history of the plantation and discuss the place the missionaries occupied in the colonial venture and their role in the economy of the colony. Loyola was a large and successful plantation compared with other plantations in French Guiana, and its success rested on the exploitation of enslaved labor. Recent research on the area covered by the plantation storehouse, its chapel, and the forecourt in front has allowed us to reassess our initial interpretation of the chronology and development of the plantation. In doing so, we realized that the Jesuits rigorously conformed to the architectural principles of the Enlightenment to symbolize their prestige in the colony.
<p><strong>A new name for extant <em>Potamogeton × mirabilis</em> (Potamogetonaceae)</strong></p>
Authors: KOTTAIMUTHU RAMALINGAM , KUMAR JOHN KENNEDY JOHN PRAVEEN , DINESHKUMAR PANJAVARNAM , LOGESHWARI MARUTHAN 
Published: April 2021

The genus Potamogeton Linnaeus (1753: 126) is commonly called as pond weeds and they are the largest genera in the family Potamogetonaceae with about 88 species (POWO 2021). Furthermore the genus is noted for its high phenotypic plasticity and frequent hybridization that prompts impressive challenges in the delimitation and identification of species (Kaplan et al. 2009, 2013). A few instances of the homonymy among living and fossil monocots have been as of late settled by various workers (Turner 2014, Doweld 2016, 2018, Govaerts 2018, Kottaimuthu & Basu 2020). Recently we found that the extant hybrid Potamogeton × mirabilis Kaplan et al. (2009: 630) is an illegitimate later homonym according to Art.53.1. of ICN (Turland et al. 2018) because the name was already used by Kutuzkina (1957) to a fossil-species from Kyrgyzstan (formerly USSR). Hence a new replacement name is proposed for this nothospecies.
A simple method for surface radiation estimating using FY-4A data
Authors: Wang Lijuan , Zuo Hongchao , Wang Wei 
Published: April 2021

AbstractFY-4A is a geostationary meteorological satellite with four advanced payloads, which can be used to quantitatively detect the earth's atmospheric system with multi spectral and high spatial-temporal resolution. However, the applicable model limits the application of the FY-4A satellite data. In this paper, the empirical statistical model developed for the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor is extended for FY-4A Advanced Geosynchronous Radiation Imager (AGRI), and it is applied to observed data to evaluate the applicability of the model for AGRI measurements. To improve the accuracy of radiation estimation, the artificial intelligent particle swarm optimization (PSO) algorithm was used for model optimizing. Results show that the estimated radiation has diurnal variation, which accords with the characteristics of radiation variation. The estimated net surface shortwave radiation (Sn) and observed values show good correlation. However, large deviations from observations are found in the estimated values when the empirical model based on MODIS is directly used to process AGRI data. Thus, the empirical statistical model based on MODIS can be applied to AGRI data, but the empirical parameters need to be revised. Optimization of the empirical statistical model by the PSO algorithm can effectively improve the accuracy of radiation estimate. The Mean absolute percentage error (MAPE) of Sn estimated by optimized models is reduced to 15%. The MAPE of the net surface long-wave radiation (Ln) estimated by optimized models is reduced to 31%, and the MAPE of the net radiation (Rn) estimated by optimized models is reduced to 27%. However, for the uncertainty caused by error accumulation effect, the influence of PSO optimization on Rn is not as obvious as that of Ln. However, from the analysis of error distribution, it shows that PSO optimization does improve the estimation results of Rn. Based on AGRI data, the surface radiation can be estimated simply, and the regional or larger scale surface radiation retrieval can quickly realize by this method which has large application potential and popularization value.
An Empirical Investigation of the Disaggregated Import Demand Function: Non-linear ARDL Framework
Authors: Kathuria Khyati , Kumar Nand 
Published: April 2021

The article estimates the disaggregated import demand function for India using annual time series data for the period 1995–2017. The empirical results reveal strong evidence of long-run stable relationship among the variables considered in the study. The disaggregated import demand function is estimated for India using linear and non-linear ARDL model. The estimated linear ARDL model shows that gross capital formation, exports and relative prices affect import demand positively and significantly, both in the short and long run. While the impact of final consumption expenditure was found to be insignificant in the short run, it affects import demand significantly and positively in the long run. On the other hand, the result of the non-linear ARDL model shows the evidence of asymmetry in the impact of relative prices (positive and negative changes) on import demand, both in the short and long run. JEL Codes: F41, B17, B41, C51
COVID-19 and student well-being: Catholic school staff perspectives and experiences
Authors: Testa Doris 
Published: April 2021

Background: COVID-19 has dramatically changed how school communities operate. Many schools have had to navigate enforced closures and modify their usual teaching and learning practices. Furthermore, they have had to rethink how they address student well-being issues. In Australian Catholic schools, there is little data on the concerns of Catholic school staff during enforced school closures. Aims: This article describes findings from a study of the experiences and concerns of school staff in two Catholic primary school communities to understand how staff in these settings experienced and re-imagined or reinforced student well-being practices and processes. Methods: Data were collected by means of a survey assessing staff experiences and concerns, with a particular focus on student well-being. Results: Results indicated that enforced school closures were perceived as negatively affecting student well-being programmes with staff members being particularly concerned about students who were socially, educationally, culturally and economically disadvantaged. However, negative impacts were mitigated by a school culture underpinned by a pastoral and health-promoting perspective. Strong leadership in the face of systemic lethargy prompted schools to utilise their engagement and partnership arrangements for additional support. Conclusion: During forced school closures, an inclusive school ethos, environment and culture ensured an effective response to the diverse needs of staff, students and other school community members.
A Case for Raising the Camera: A Driving Simulator Test of Camera-Monitor Systems
Authors: Bernhard Christoph , Reinhard René , Kleer Michael , Hecht Heiko 
Published: April 2021

Objective This experiment provides a first-of-its-kind driving-simulator study to investigate the feasibility of camera-monitor systems (CMS) with displaced side-mounted cameras in sedans. Background Among the increasing number of studies investigating the replacement of side-mounted rearview mirrors with CMS, the placement of side-mounted cameras has been largely neglected. Moreover, user preferences with respect to camera placement have not been validated in a driving simulator. Past research merely has shown that the vertical camera position can affect distance perception. Method In a driving simulator experiment, we investigated the effects of rearward camera placement on driver acceptance and performance. Thirty-six participants performed multiple lane changes in a last safe-gap paradigm. The camera position, ego-velocity, and velocity of the approaching vehicle varied across the experiment. Results The results suggest a clear preference for a high rearward perspective, whereas participants disliked the lower viewpoint. However, these stark differences were only marginally mirrored in lane change performance. Average safety margins tended to decrease and their variation tended to increase for the low camera position. Conclusion Even if the impact of the camera position on driving behavior seems to be small in sedans, driver expectations show clear-cut preferences. When designing CMS, this should be taken into account, as these preferences could promote the use of CMS and thus their positive impact on safety. Application Designers should place side-mounted cameras as high as possible to increase acceptance of CMS. Low camera positions are not recommended, as they might decrease safety margins and are not appreciated by drivers.
Country, sector and method effects in studying remunicipalization: a meta-analysis
Authors: Voorn Bart 
Published: April 2021

A growing literature demonstrates increasing remunicipalization of local public services. Yet, while this literature is becoming extensive, many debates still exist about remunicipalization’s causes. This article reports the findings of a meta-analysis of the remunicipalization literature, focusing on the question: how do country, sector and method effects affect the findings of remunicipalization studies? I include articles on remunicipalization under different terms (‘remunicipalization’, ‘reverse privatization’, ‘insourcing’ and ‘contracting in’), using a large range of methods (case studies, surveys and document analysis) and covering a large period (1995–2019). I find 30 causes of remunicipalization that are considered and found in the literature. Political and pragmatic factors appear to be most frequently considered and found as causes of remunicipalization in the literature; environmental factors are less often considered but seem highly relevant. Moreover, I uncover large differences between the qualitative and quantitative literatures. I offer a research agenda to allow greater future synthesis in the remunicipalization literature. Points for practitioners The literature on remunicipalization is highly fragmented and remunicipalization can have many different causes. Remunicipalization appears to be both a political and a pragmatic trend, but the literature is still too fragmented to know for sure. Be aware of the potential biases and limitations in current research on (causes of) remunicipalization.
Increasing adolescent girls’ social competence through cognitive counseling by social workers
Authors: Cheung Chau-kiu 
Published: April 2021

Summary Despite the common basis of cognitive theory for cognitive counseling and social competence development, no research has charted the effectiveness of the counseling in raising social competence in young female residents of the residential service. To examine the effectiveness, this study analyzed data gleaned from monthly surveys of young female residents and their social workers regarding the latter’s daily life cognitive counseling. The data consisted of 391 cases pairing the female residents and social workers in Hong Kong over 33 months. Findings The cases afforded a cross-lagged analysis showing the raising of the girl’s social competence by the worker’s cognitive counseling earlier in the previous month. In substantiating this raising, the analysis also indicated that earlier social competence did not affect the counseling. Applications The findings imply the worth of promoting the social worker’s daily life cognitive counseling to advance girl residents’ social competence. Such counseling is particularly helpful to girls with lower education, who are lower in social competence.
pCONUS 2 and pCONUS 2-HPC for the treatment of wide-necked intracranial aneurysms: Periprocedural, 6-month, and early 2-year follow-up outcomes
Authors: Yeomans J , Sastry A 
Published: April 2021

Background/Purpose pCONUS 2 and pCONUS 2-HPC are novel neck-bridging devices designed to support endovascular coil occlusion of wide-necked intracranial bifurcation aneurysms. This study summarises periprocedural outcomes, 6-month, and early 2-year follow-up results following its introduction in an interventional neuroradiology centre. Materials/Methods This prospective, single-arm study assessed 20 aneurysms treated over a 40 month time period from time of procedure to 2 years post-procedure. Data collected included patient demographics, aneurysm features, and intraprocedural, 6-month, and 2-year post-procedural complications and angiographic features. Results The mean age of the cohort was 59+-SD 7.7 years. 16 unruptured aneurysms were treated (pCONUS 2 13/16, pCONUS 2-HPC 3/16) and 4 ruptured aneurysms were treated with pCONUS 2-HPC. Unruptured cases received dual antiplatelet therapy pre- and post-procedure while ruptured cases received single antiplatelet therapy. 9/20 aneurysms were located at the MCA bifurcation and 7/20 at the basilar tip. The remaining 4 aneurysms were at various bifurcations in the anterior circulation. 11/20 were small (<10mm) and 9/20 were large (10–25mm). There was one periprocedural complication: a retroperitoneal bleed. There were no post-procedural intracranial complications or at 6-months follow-up. At 6 months, satisfactory occlusion was achieved in 94% of cases (15/16). There was one delayed death at 2-year follow-up from an unrelated cause. Conclusion pCONUS 2 and pCONUS 2-HPC have excellent short and medium-term safety profiles and clinical outcomes with no procedure-related mortality or morbidity and good occlusion rates at 6-month follow-up. The use of pCONUS 2-HPC with single antiplatelet therapy is feasible and did not cause any complications.
Giant cell tumour of hand bones: outcomes of treatment
Authors: Puri Ajay , Rajalbandi Rohit , Gulia Ashish 
Published: April 2021

The purpose of this study was to report the incidence of giant cell tumour of the hand bones in an Asian population, document treatment options and report outcomes of treatment. Of 698 giant cell tumours of bone that underwent surgery between January 2011 and December 2020 at our institute, only 22 (3%) were in the hand. Fourteen occurred in the metacarpals, eight in the phalanges. Fifteen were primary tumours and seven had recurrent disease. Twenty lesions had an associated soft tissue component. Two patients treated for primary disease and one who had been treated for recurrence had local recurrence. Recurrence occurred in two of nine patients treated with curettage, one of three with resection and none of five with ray or digit amputation. Both curettage and resection/amputation are acceptable treatment options for the rare condition of giant cell tumour of bone in the hand, with a need to individualize treatment decisions based on the site and extent of disease to minimize treatment morbidity while maximizing disease control. Level of evidence: IV