bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Bretons in French Politics: Regional Mobilization within and beyond the Central State
Authors: Cole Alistair , Pasquier Romain 
Published: October 2021

AbstractThis article revisits the French region of Brittany on the basis of sustained empirical research over a 25-year period. It identifies the twin use of influence and identity as forming a key part of an accepted and largely diffused territorial repertoire, based on affirming distinctiveness for reasons of vertical linkage, as well as horizontal capacity building. This article explores the different facets of this model of territorial influence. The two twin dimensions concern: first, a well-versed mechanism of lobbying central institutions and actors to defend the Breton interest; second, the use of territorial identity markers to forward the regional cause, relying on social movements and a broad capacity for regional mobilization. Within this overarching context, the Breton case demonstrates an intelligent instrumental use of identity and identity markers, but mainstream Breton forces recognize that this only makes sense in the light of the national level of regulation and structure of opportunities. The logic of this position is to integrate the Brittany region into a national model of territorial integration, while playing up identity markers to secure the maximum benefit for the region.
Field surveys can improve predictions of habitat suitability for reintroductions: a swift fox case study
Authors: Paraskevopoulou Zoe , Shamon Hila , Songer Melissa , Ruxton Graeme , McShea William J. 
Published: October 2021

AbstractReintroductions are challenging, and success rates are low despite extensive planning and considerable investment of resources. Improving predictive models for reintroduction planning is critical for achieving successful outcomes. The IUCN Guidelines for Reintroductions and Other Conservation Translocations recommend that habitat suitability assessments account for abiotic and biotic factors specific to the species to be reintroduced and, where needed, include habitat quality variables. However, habitat assessments are often based on remotely-sensed or existing geographical data that do not always reliably represent habitat quality variables. We tested the contribution of ground-based habitat quality metrics to habitat suitability models using a case study of the swift fox Vulpes velox, a mesocarnivore species for which a reintroduction is planned. Field surveys for habitat quality included collection of data on the main threat to the swift fox (the coyote Canis latrans), and for swift fox prey species. Our findings demonstrated that the inclusion of habitat quality variables derived from field surveys yielded better fitted models and a 16% increase in estimates of suitable habitat. Models including field survey data and models based only on interpolated geographical and remotely-sensed data had little overlap (38%), demonstrating the significant impact that different models can have in determining appropriate locations for a reintroduction. We advocate that ground-based habitat metrics be included in habitat suitability assessments for reintroductions of mesocarnivores.
The conscious state of the dying patient: An integrative review
Authors: O'Connor Tricia , Paterson Catherine , Gibson Jo , Strickland Karen 
Published: October 2021

Abstract

Objectives
The cognitive state of the dying in the last days of life may deteriorate, resulting in a reduced ability to communicate their care needs. Distressing symptoms, physical and existential, may go unrecognized and untreated. The objectives of this integrative review were to systematically interrogate the literature to determine the changing conscious state of dying adults and to identify changes in their care needs.

Methods
An integrative review protocol was registered with PROSPERO (CRD42020160475). The World Health Organization definition of palliative care informed the review. CINAHL, MEDLINE (OVID), Scopus, PsycINFO, Cochrane Library, and PubMed were searched from inception to October 2019 using search strategies for each database. Inclusion and exclusion criteria were applied. Methodological quality was appraised using the Joanna Briggs Institute Checklist for the Case Series appraisal tool. Extracted data were synthesized using a narrative approach.

Results
Of 5,136 papers identified, 11 quantitative case series studies were included. Six themes were identified: conscious state and change over time, awareness, pain, absence of holistic care, the voiceless patient, and signs and symptoms of dying.

Significance of results
In the last days of life, the physical and conscious state of the dying patient declines, resulting in an inability to express their care needs. Dignity in dying and freedom from pain and suffering are both an imperative and a human right; and unvoiced care needs can result in unnecessary suffering and distress. This review revealed that little is known about how healthcare professionals assess holistic care needs at this vulnerable time. Although much has been written about palliative and end-of-life care, the assessment of care needs when patients are no longer able to voice their own needs has largely been ignored, with little attention from clinical, educational, or research perspectives. This gap in evidence has important implications for the dying and their families.
Roles of circadian clocks in cancer pathogenesis and treatment
Authors: Lee Yool 
Published: October 2021

AbstractCircadian clocks are ubiquitous timing mechanisms that generate approximately 24-h rhythms in cellular and bodily functions across nearly all living species. These internal clock systems enable living organisms to anticipate and respond to daily changes in their environment in a timely manner, optimizing temporal physiology and behaviors. Dysregulation of circadian rhythms by genetic and environmental risk factors increases susceptibility to multiple diseases, particularly cancers. A growing number of studies have revealed dynamic crosstalk between circadian clocks and cancer pathways, providing mechanistic insights into the therapeutic utility of circadian rhythms in cancer treatment. This review will discuss the roles of circadian rhythms in cancer pathogenesis, highlighting the recent advances in chronotherapeutic approaches for improved cancer treatment.
HUGO Gene Nomenclature Committee (HGNC) recommendations for the designation of gene fusions
Authors: Bruford Elspeth A. , Antonescu Cristina R. , Carroll Andrew J. , Chinnaiyan Arul , Cree Ian A. , Cross Nicholas C. P. , Dalgleish Raymond , Gale Robert Peter , Harrison Christine J. , Hastings Rosalind J. , Huret Jean-Loup , Johansson Bertil , Le Beau Michelle , Mecucci Cristina , Mertens Fredrik , Verhaak Roel , Mitelman Felix 
Published: October 2021

AbstractGene fusions have been discussed in the scientific literature since they were first detected in cancer cells in the early 1980s. There is currently no standardized way to denote the genes involved in fusions, but in the majority of publications the gene symbols in question are listed either separated by a hyphen (-) or by a forward slash (/). Both types of designation suffer from important shortcomings. HGNC has worked with the scientific community to determine a new, instantly recognizable and unique separator—a double colon (::)—to be used in the description of fusion genes, and advocates its usage in all databases and articles describing gene fusions.
Association between polygenic risk for Alzheimer’s disease, brain structure and cognitive abilities in UK Biobank
Authors: Tank Rachana , Ward Joey , Flegal Kristin E. , Smith Daniel J. , Bailey Mark E. S. , Cavanagh Jonathan , Lyall Donald M. 
Published: October 2021

AbstractPrevious studies testing associations between polygenic risk for late-onset Alzheimer’s disease (LOAD-PGR) and brain magnetic resonance imaging (MRI) measures have been limited by small samples and inconsistent consideration of potential confounders. This study investigates whether higher LOAD-PGR is associated with differences in structural brain imaging and cognitive values in a relatively large sample of non-demented, generally healthy adults (UK Biobank). Summary statistics were used to create PGR scores for n = 32,790 participants using LDpred. Outcomes included 12 structural MRI volumes and 6 concurrent cognitive measures. Models were adjusted for age, sex, body mass index, genotyping chip, 8 genetic principal components, lifetime smoking, apolipoprotein (APOE) e4 genotype and socioeconomic deprivation. We tested for statistical interactions between APOE e4 allele dose and LOAD-PGR vs. all outcomes. In fully adjusted models, LOAD-PGR was associated with worse fluid intelligence (standardised beta [β] = −0.080 per LOAD-PGR standard deviation, p = 0.002), matrix completion (β = −0.102, p = 0.003), smaller left hippocampal total (β = −0.118, p = 0.002) and body (β = −0.069, p = 0.002) volumes, but not other hippocampal subdivisions. There were no significant APOE x LOAD-PGR score interactions for any outcomes in fully adjusted models. This is the largest study to date investigating LOAD-PGR and non-demented structural brain MRI and cognition phenotypes. LOAD-PGR was associated with smaller hippocampal volumes and aspects of cognitive ability in healthy adults and could supplement APOE status in risk stratification of cognitive impairment/LOAD.
CRISPR screens identify cholesterol biosynthesis as a therapeutic target on stemness and drug resistance of colon cancer
Authors: Gao Shanshan , Soares Fraser , Wang Shiyan , Wong Chi Chun , Chen Huarong , Yang Zhenjie , Liu Weixin , Go Minnie Y. Y. , Ahmed Musaddeque , Zeng Yong , O’Brien Catherine Adell , Sung Joseph J. Y. , He Housheng Hansen , Yu Jun 
Published: October 2021

AbstractCancer stem cells (CSCs) are responsible for tumor progression, recurrence, and drug resistance. To identify genetic vulnerabilities of colon cancer, we performed targeted CRISPR dropout screens comprising 657 Drugbank targets and 317 epigenetic regulators on two patient-derived colon CSC-enriched spheroids. Next-generation sequencing of pooled genomic DNAs isolated from surviving cells yielded therapeutic candidates. We unraveled 44 essential genes for colon CSC-enriched spheroids propagation, including key cholesterol biosynthetic genes (HMGCR, FDPS, and GGPS1). Cholesterol biosynthesis was induced in colon cancer tissues, especially CSC-enriched spheroids. The genetic and pharmacological inhibition of HMGCR/FDPS impaired self-renewal capacity and tumorigenic potential of the spheroid models in vitro and in vivo. Mechanistically, HMGCR or FDPS depletion impaired cancer stemness characteristics by activating TGF-β signaling, which in turn downregulated expression of inhibitors of differentiation (ID) proteins, key regulators of cancer stemness. Cholesterol and geranylgeranyl diphosphate (GGPP) rescued the growth inhibitory and signaling effect of HMGCR/FDPS blockade, implying a direct role of these metabolites in modulating stemness. Finally, cholesterol biosynthesis inhibitors and 5-FU demonstrated antitumor synergy in colon CSC-enriched spheroids, tumor organoids, and xenografts. Taken together, our study unravels novel genetic vulnerabilities of colon CSC-enriched spheroids and suggests cholesterol biosynthesis as a potential target in conjunction with traditional chemotherapy for colon cancer treatment.
Enzalutamide versus bicalutamide in patients with nonmetastatic castration-resistant prostate cancer: a prespecified subgroup analysis of the STRIVE trial
Authors: Penson David F. , Armstrong Andrew J. , Concepcion Raoul S. , Agarwal Neeraj , Olsson Carl A. , Karsh Lawrence I. , Dunshee Curtis J. , Duggan William , Shen Qi , Sugg Jennifer , Haas Gabriel P. , Higano Celestia S. 
Published: October 2021

Abstract
Background
In the phase 2, randomized, double-blind STRIVE trial, enzalutamide significantly reduced the risk of prostate cancer progression or death versus bicalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) and nonmetastatic CRPC (nmCRPC). The objective of this protocol-specified subgroup analysis of STRIVE was to investigate the benefit of enzalutamide versus bicalutamide specifically in patients with nmCRPC.

Methods
Patients (N = 139) were stratified by disease stage and randomized to enzalutamide 160 mg/day plus androgen deprivation therapy (ADT; n = 70) or bicalutamide 50 mg/day plus ADT (n = 69).

Results
Baseline characteristics of patients with nmCRPC were comparable between groups. At a median of 17 months follow-up, enzalutamide reduced the risk of progression or death by 76% versus bicalutamide in patients with nmCRPC (hazard ratio [HR], 0.24; 95% CI 0.14–0.42). Enzalutamide reduced risk of prostate-specific antigen progression by 82% versus bicalutamide in patients with nmCRPC (HR, 0.18; 95% CI 0.10–0.34). The most frequently reported adverse events by patients receiving enzalutamide were fatigue (36.2%), hot flush (20.3%), decreased appetite (17.4%), dizziness (17.4%), and nausea (17.4%).

Conclusions
This STRIVE subgroup analysis of patients with nmCRPC illustrates the benefit of enzalutamide in reducing the risk of progression or death versus bicalutamide in patients with nmCRPC.

Trial registration
ClinicalTrials.gov identifier NCT01664923.
Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer
Authors: Li Kai , Shi Houhui , Zhang Benxia , Ou Xuejin , Ma Qizhi , Chen Yue , Shu Pei , Li Dan , Wang Yongsheng 
Published: October 2021

AbstractMyeloid-derived suppressor cells (MDSCs) are a heterogenic population of immature myeloid cells with immunosuppressive effects, which undergo massive expansion during tumor progression. These cells not only support immune escape directly but also promote tumor invasion via various non-immunological activities. Besides, this group of cells are proved to impair the efficiency of current antitumor strategies such as chemotherapy, radiotherapy, and immunotherapy. Therefore, MDSCs are considered as potential therapeutic targets for cancer therapy. Treatment strategies targeting MDSCs have shown promising outcomes in both preclinical studies and clinical trials when administrated alone, or in combination with other anticancer therapies. In this review, we shed new light on recent advances in the biological characteristics and immunosuppressive functions of MDSCs. We also hope to propose an overview of current MDSCs-targeting therapies so as to provide new ideas for cancer treatment.
Coordination of root auxin with the fungus Piriformospora indica and bacterium Bacillus cereus enhances rice rhizosheath formation under soil drying
Authors: Xu Feiyun , Liao Hanpeng , Zhang Yingjiao , Yao Minjie , Liu Jianping , Sun Leyun , Zhang Xue , Yang Jinyong , Wang Ke , Wang Xiaoyun , Ding Yexin , Liu Chen , Rensing Christopher , Zhang Jianhua , Yeh Kaiwun , Xu Weifeng 
Published: October 2021

Abstract
Moderate soil drying (MSD) is a promising agricultural technique that can reduce water consumption and enhance rhizosheath formation promoting drought resistance in plants. The endophytic fungus Piriformospora indica (P. indica) with high auxin production may be beneficial for rhizosheath formation. However, the integrated role of P. indica with native soil microbiome in rhizosheath formation is unclear. Here, we investigated the roles of P. indica and native bacteria on rice rhizosheath formation under MSD using high-throughput sequencing and rice mutants. Under MSD, rice rhizosheath formation was significantly increased by around 30% with P. indica inoculation. Auxins in rice roots and P. indica were responsible for the rhizosheath formation under MSD. Next, the abundance of the genus Bacillus, known as plant growth-promoting rhizobacteria, was enriched in the rice rhizosheath and root endosphere with P. indica inoculation under MSD. Moreover, the abundance of Bacillus cereus (B. cereus) with high auxin production was further increased by P. indica inoculation. After inoculation with both P. indica and B. cereus, rhizosheath formation in wild-type or auxin efflux carrier OsPIN2 complemented line rice was higher than that of the ospin2 mutant. Together, our results suggest that the interaction of the endophytic fungus P. indica with the native soil bacterium B. cereus favors rice rhizosheath formation by auxins modulation in rice and microbes under MSD. This finding reveals a cooperative contribution of P. indica and native microbiota in rice rhizosheath formation under moderate soil drying, which is important for improving water use in agriculture.
Barriers to clinical adoption of pharmacogenomic testing in psychiatry: a critical analysis
Authors: Virelli Catherine R. , Mohiuddin Ayeshah G. , Kennedy James L. 
Published: October 2021

AbstractPharmacogenomics (PGx) is the study of genetic influences on an individual’s response to medications. Improvements in the quality and quantity of PGx research over the past two decades have enabled the establishment of commercial markets for PGx tests. Nevertheless, PGx testing has yet to be adopted as a routine practice in clinical care. Accordingly, policy regulating the commercialization and reimbursement of PGx testing is in its infancy. Several papers have been published on the topic of challenges, or ‘barriers’ to clinical adoption of this healthcare innovation. However, many do not include recent evidence from randomized controlled trials, economic utility studies, and qualitative assessments of stakeholder opinions. The present paper revisits the most cited barriers to adoption of PGx testing: evidence for clinical utility, evidence for economic effectiveness, and stakeholder awareness. We consider these barriers in the context of reviewing PGx literature published over the past two decades and emphasize data from commercial PGx testing companies, since they have published the largest datasets. We conclude with a discussion of existing limitations to PGx testing and recommendations for progress.
Efficacy and safety of cabozantinib for patients with advanced hepatocellular carcinoma based on albumin-bilirubin grade
Authors: Kelley Robin Kate , Miksad Rebecca , Cicin Irfan , Chen YenHsun , Klümpen Heinz-Josef , Kim Stefano , Lin Zhong-Zhe , Youkstetter Jillian , Hazra Saswati , Sen Suvajit , Cheng Ann-Lii , El-Khoueiry Anthony B. , Meyer Tim , Abou-Alfa Ghassan K. 
Published: October 2021

Abstract
Background
Albumin-bilirubin (ALBI) grade is an objective measure of liver function for patients with hepatocellular carcinoma (HCC). The tyrosine kinase inhibitor cabozantinib is approved for patients with advanced HCC who have received prior sorafenib based on the phase 3 CELESTIAL trial (NCT01908426). Cabozantinib improved overall survival (OS) and progression-free survival (PFS) versus placebo in patients with previously treated HCC.

Methods
Patients were randomised 2:1 to receive cabozantinib 60 mg or placebo orally every day. Clinical outcomes in patients with ALBI grade 1 or 2 at baseline were evaluated in CELESTIAL. ALBI scores were retrospectively calculated based on baseline serum albumin and total bilirubin, with an ALBI grade of 1 defined as  ≤ −2.60 score and a grade of 2 as a score of > −2.60 to  ≤ −1.39.

Results
Cabozantinib improved OS and PFS versus placebo in both ALBI grade 1 (hazard ratio [HR] [95% CI]: 0.63 [0.46–0.86] and 0.42 [0.32–0.56]) and ALBI grade 2 (HR [95% CI]: 0.84 [0.66–1.06] and 0.46 [0.37–0.58]) subgroups. Adverse events were consistent with those in the overall population. Rates of grade 3/4 adverse events associated with hepatic decompensation were generally low and were more common among patients in the ALBI grade 2 subgroup.

Discussion
These results provide initial support of cabozantinib in patients with advanced HCC irrespective of ALBI grade 1 or 2.

Trial registration number
ClinicalTrials.gov number, NCT01908426.
Graded heterogeneity of metabotropic signaling underlies a continuum of cell-intrinsic temporal responses in unipolar brush cells
Authors: Guo Chong , Huson Vincent , Macosko Evan Z. , Regehr Wade G. 
Published: October 2021

AbstractMany neuron types consist of populations with continuously varying molecular properties. Here, we show a continuum of postsynaptic molecular properties in three types of neurons and assess the functional correlates in cerebellar unipolar brush cells (UBCs). While UBCs are generally thought to form discrete functional subtypes, with mossy fiber (MF) activation increasing firing in ON-UBCs and suppressing firing in OFF-UBCs, recent work also points to a heterogeneity of response profiles. Indeed, we find a continuum of response profiles that reflect the graded and inversely correlated expression of excitatory mGluR1 and inhibitory mGluR2/3 pathways. MFs coactivate mGluR2/3 and mGluR1 in many UBCs, leading to sequential inhibition-excitation because mGluR2/3-currents are faster. Additionally, we show that DAG-kinase controls mGluR1 response duration, and that graded DAG kinase levels correlate with systematic variation of response duration over two orders of magnitude. These results demonstrate that continuous variations in metabotropic signaling can generate a stable cell-autonomous basis for temporal integration and learning over multiple time scales.
Efficient and precise single-cell reference atlas mapping with Symphony
Authors: Kang Joyce B. , Nathan Aparna , Weinand Kathryn , Zhang Fan , Millard Nghia , Rumker Laurie , Moody D. Branch , Korsunsky Ilya , Raychaudhuri Soumya 
Published: October 2021

AbstractRecent advances in single-cell technologies and integration algorithms make it possible to construct comprehensive reference atlases encompassing many donors, studies, disease states, and sequencing platforms. Much like mapping sequencing reads to a reference genome, it is essential to be able to map query cells onto complex, multimillion-cell reference atlases to rapidly identify relevant cell states and phenotypes. We present Symphony (https://github.com/immunogenomics/symphony), an algorithm for building large-scale, integrated reference atlases in a convenient, portable format that enables efficient query mapping within seconds. Symphony localizes query cells within a stable low-dimensional reference embedding, facilitating reproducible downstream transfer of reference-defined annotations to the query. We demonstrate the power of Symphony in multiple real-world datasets, including (1) mapping a multi-donor, multi-species query to predict pancreatic cell types, (2) localizing query cells along a developmental trajectory of fetal liver hematopoiesis, and (3) inferring surface protein expression with a multimodal CITE-seq atlas of memory T cells.
High-resolution positron emission microscopy of patient-derived tumor organoids
Authors: Khan Syamantak , Shin June Ho , Ferri Valentina , Cheng Ning , Noel Julia E. , Kuo Calvin , Sunwoo John B. , Pratx Guillem 
Published: October 2021

AbstractTumor organoids offer new opportunities for translational cancer research, but unlike animal models, their broader use is hindered by the lack of clinically relevant imaging endpoints. Here, we present a positron-emission microscopy method for imaging clinical radiotracers in patient-derived tumor organoids with spatial resolution 100-fold better than clinical positron emission tomography (PET). Using this method, we quantify 18F-fluorodeoxyglucose influx to show that patient-derived tumor organoids recapitulate the glycolytic activity of the tumor of origin, and thus, could be used to predict therapeutic response in vitro. Similarly, we measure sodium-iodine symporter activity using 99mTc- pertechnetate and find that the iodine uptake pathway is functionally conserved in organoids derived from thyroid carcinomas. In conclusion, organoids can be imaged using clinical radiotracers, which opens new possibilities for identifying promising drug candidates and radiotracers, personalizing treatment regimens, and incorporating clinical imaging biomarkers in organoid-based co-clinical trials.