bluuebunny/crossref_metadata_2025_split huggingface dataset:
RTL1/PEG11 imprinted in human and mouse brain mediates anxiety-like and social behaviors and regulates neuronal excitability in the locus coeruleus
Authors: Chou Ming-Yi , Hu Meng-Chuen , Chen Pin-Yu , Hsu Chi-Lin , Lin Ting-Yu , Tan Mao-Jia , Lee Chih-Yu , Kuo Meng-Fai , Huang Pei-Hsin , Wu Vin-Cent , Yang Shih-Hung , Fan Pi-Chuan , Huang Hsin-Yi , Akbarian Schahram , Loo Tsui-Han , Stewart Colin L , Huang Hsiang-Po , Gau Susan Shur-Fen , Huang Hsien-Sung 
Published: May 2022

Abstract
RTL1/PEG11, which has been associated with anxiety disorders, is a retrotransposon-derived imprinted gene in the placenta. However, imprinting patterns and functions of RTL1 in the brain have not been well-investigated. We found Rtl1 was paternally, but not maternally, expressed in brain stem, thalamus, and hypothalamus of mice, and imprinting status of RTL1 was maintained in human brain. Paternal Rtl1 knockout (Rtl1m+/p-) mice had higher neonatal death rates due to impaired suckling, and low body weights beginning on embryonic day 16.5. High paternal expression of Rtl1 was detected in the locus coeruleus (LC) and Rtl1m+/p- mice showed an increased delay in time of onset for action potentials and inward currents with decreased neuronal excitability of LC neurons. Importantly, Rtl1m+/p- mice exhibited behaviors associated with anxiety, depression, fear-related learning and memory, social dominance, and low locomotor activity. Taken together, our findings demonstrate RTL1 is imprinted in brain, mediates emotional and social behaviors, and regulates excitability in LC neurons.
Feminist constitutionalism: Mapping a discourse in contestation
Authors: Atrey Shreya 
Published: May 2022

Abstract
This article explores what we call feminist constitutionalism and what should be called feminist constitutionalism. It argues that feminist constitutionalism, properly understood, is a discourse in contestation and the competing substantive arguments that define such contestation. A study in feminist constitutionalism would revolve around unraveling this discourse rather than categorizing or labeling particular constitutional texts or judicial outcomes as feminist. The article thus interrogates the current impulse to brand a recent spate of good outcomes by the Supreme Court of India as conclusively feminist, against a long trajectory of gender jurisprudence which brings out a rich and complicated history which can neither be simply cast aside nor celebrated. The only way to make sense of the practice of feminist constitutionalism is thus to study the discourse itself. The article shows the kind of discourse analysis which may lend itself to feminist constitutionalism.
The gatekeepers: Executive lawyers and the executive power in comparative constitutional law
Authors: Casey Conor , Kenny David 
Published: May 2022

Abstract
The growth in the power of the executive branch of government has been accompanied by a related growth—heretofore unexplored in the literature on comparative constitutional law—of the role and importance of executive legal advisors. These influential but often secretive advisors can be the first—and sometimes the only—group to review the actions of the executive or legislative proposals before enactment, for compliance with the constitution. In this article, we compare this practice in four similar but somewhat distinct jurisdictions—the United Kingdom, Canada, the United States, and Ireland—to assess its impact on constitutionalism and the executive power. We conclude that the practice of constitutional review by executive lawyers is highly variable, changing between places and over time along four key axes that can either empower or constrain the executive to varying degrees. It can restrain executive action by holding it within constitutional boundaries; it can bolster the executive power by giving legalistic credibility to its actions while providing little restraint in practice; or it can create policy distortion by overly tightly binding executive and legislative action. Constitutional advice from executive legal advisors, then, does not operate as an exogenous constraint on executive power, but can be structured and manipulated by the executive to have various different effects. As such, we argue that this institution requires much more attention from both comparative constitutional lawyers and constitutional designers to map its effects on the constitutional order and to see what structures, processes, and cultural factors might shape it. Finally, we argue for increased transparency in the provision of executive constitutional advice, as without this, even understanding its effects is extremely difficult.
Total bodyweight and sex both drive pharmacokinetic variability of fluconazole in obese adults
Authors: Chen Lu , van Rhee Koen P , Wasmann Roeland E , Krekels Elke H J , Wiezer Marinus J , van Dongen Eric P A , Verweij Paul E , van der Linden Paul D , Brüggemann Roger J , Knibbe Catherijne A J 
Published: May 2022

Abstract

Background
Fluconazole is commonly used to treat or prevent fungal infections. It is typically used orally but in critical situations, IV administration is needed. Obesity may influence the pharmacokinetics and therapeutic efficacy of a drug. In this study, we aim to assess the impact of obesity on fluconazole pharmacokinetics given orally or IV to guide dose adjustments for the obese population.

Methods
We performed a prospective pharmacokinetic study with intensive sampling in obese subjects undergoing bariatric surgery (n = 17, BMI ≥ 35 kg/m2) and non-obese healthy controls (n = 8, 18.5 ≤ BMI &lt; 30.0 kg/m2). Participants received a semi-simultaneous oral dose of 400 mg fluconazole capsules, followed after 2 h by 400 mg IV. Population pharmacokinetic modelling and simulation were performed using NONMEM 7.3.

Results
A total of 421 fluconazole concentrations in 25 participants (total bodyweight 61.0–174 kg) until 48 h after dosing were obtained. An estimated bioavailability of 87.5% was found for both obese and non-obese subjects, with a 95% distribution interval of 43.9%–98.4%. With increasing total bodyweight, both higher CL and Vd were found. Sex also significantly impacted Vd, being 27% larger in male compared with female participants.

Conclusions
In our population of obese but otherwise healthy individuals, obesity clearly alters the pharmacokinetics of fluconazole, which puts severely obese adults, particularly if male, at risk of suboptimal exposure, for which adjusted doses are proposed.
Comparative genomic analysis of ESBL-producing Escherichia coli from faecal carriage and febrile urinary tract infection in children: a prospective multicentre study
Authors: Bidet Philippe , Birgy André , Ouldali Naim , Béchet Stéphane , Levy Corinne , Madhi Fouad , Sobral Elsa , Cohen Robert , Bonacorsi Stéphane 
Published: May 2022

Abstract

Background
The reliability of ESBL-producing Escherichia coli (ESBL-Ec) faecal carriage monitoring to guide probabilistic treatment of febrile urinary tract infection (FUTI) in children remains unclear.

Objectives
To compare the genomic characteristics of ESBL-Ec isolates from faecal carriage and FUTI to assess their correlation and identify a FUTI-associated virulence profile.

Methods
We conducted a prospective multicentre hospital and ambulatory-based study. We analysed the genotypes and virulence factors of both faecal and FUTI ESBL-Ec by whole genome sequencing. Correlations were assessed by non-parametric Spearman coefficient and virulence factors were assessed by chi-squared tests with Bonferroni correction.

Results
We included 218 ESBL-Ec causing FUTI and 154 ESBL-Ec faecal carriage isolates. The most frequent ST was ST131 (44%) in both collections. We found high correlation between carriage and ESBL-Ec FUTI regarding genes/alleles (rho = 0.88, P &lt; 0.0001) and combinations of virulence genes, MLST and serotypes (rho = 0.90, P &lt; 0.0001, rho = 0.99, P = 0.0003, rho = 0.97, P = 0.005 respectively). Beside this strong correlation, we found five genes that were significantly associated with FUTI (papC, papGII, hlyC, hek and traJ). The strongest association with FUTI was found with adhesin gene allele papGII (54% in FUTI versus 16% in carriage) and for papGII and gene traJ alone or in combination (63% versus 24%).

Conclusions
The genomic profile of ESBL-Ec causing FUTI in children strongly correlates with faecal carriage isolates except for a few genes. The presence of papGII and/or traJ in a previously identified carriage strain could be used as a marker of uropathogenicity and may guide the empirical antimicrobial choice in subsequent FUTI.
In vitro activity of mecillinam, temocillin and nitroxoline against MDR Enterobacterales
Authors: Plambeck Lars , Fuchs Frieder , Sattler Janko , Hamprecht Axel 
Published: May 2022

Abstract

Background
With increasing resistance to common antibiotics the treatment of urinary tract infections has become challenging and alternative therapeutic options are needed. In the present study, we evaluate the activity of three older and less frequently used antibiotics against MDR Enterobacterales.

Methods
Susceptibility of mecillinam, temocillin and nitroxoline was assessed in Enterobacterales isolated from urinary specimens with elevated MICs of third-generation cephalosporins. Susceptibility was determined by the recommended reference MIC methods and additionally by disc diffusion. All isolates were characterized for common β-lactamases by phenotypic and molecular assays.

Results
In total 394 Enterobacterales were included. The most common resistance mechanisms were ESBLs (n = 273), AmpC (n = 132), carbapenemases [n = 12, including OXA-48-like (n = 8), VIM (n = 2), KPC (n = 1) and NDM (n = 1)] or others (n = 2). Resistance was observed in 59% of isolates to ceftazidime, in 41% to piperacillin/tazobactam and in 54% to ciprofloxacin. In comparison, resistance was less frequent against mecillinam (15%), temocillin (13%) or nitroxoline (2%). Mecillinam showed higher activity in Enterobacter spp., Escherichia coli and in OXA-48-like-producing isolates compared with temocillin, which was more active in Proteus mirabilis and in ESBL-producing isolates. Activity of nitroxoline was high against all isolates, including carbapenemase-producing isolates. Correlation between disc diffusion and MIC methods was good for mecillinam and moderate for temocillin and nitroxoline.

Conclusions
Mecillinam, temocillin and nitroxoline show good to excellent in vitro activity in MDR Enterobacterales. The activity of mecillinam and temocillin was higher in certain species and restricted depending on β-lactamase production while nitroxoline showed universally high activity irrespective of species or β-lactamase present.
Investigation of Fentanyl Usage in the Seattle Area
Authors: Reinhart Alexandria A , Simpson Celia , Yarid Nicole , Haruff Richard , Baird Geoffrey S 
Published: May 2022

Abstract

Background
Fentanyl was developed in the 1960s as an alternative to morphine, but quickly became a drug of abuse due to its potency, inexpensiveness, and ease of synthesis. One source of exposure is mixing fentanyl into other drugs of abuse (e.g., heroin), but users also actively seek out this potent opioid. While monitoring for pain medication compliance and office-based opioid treatment, we noticed increasing fentanyl use. We sought to investigate this increase in the local population, and see if this reflected the regional health, morbidity, and mortality statistics.

Methods
This data review was determined not to involve “human subjects” as defined by federal regulations by the University of Washington (UW) Human Subjects Division (STUDY00014988). Local data were extracted from the laboratory information system and analyzed. Data from the King County Medical Examiner’s Office derives from cases sent to the Washington State Toxicology Laboratory. The Addictions, Drug, and Alcohol Institute (ADAI) at the UW compiled data from the Washington State Department of Health, the Forensic Laboratory Services Bureau, Washington State Patrol, and the state Office of Financial Management.

Results
We found a significant increase in fentanyl positivity in clinical LC-MS/MS assays, an increase in deaths due to fentanyl, and an increase in the fentanyl usage documented by the public health laboratory.

Conclusions
Clinical data from community toxicology testing performed at academic medical centers can reflect trends in society at large, and as such, there may be a compelling reason to publish and use these data to inform public health approaches.
Realisations, Arrangements, and Ecstasies—Narratives of Religious Experience in the Hare Kṛṣṇa Movement
Authors: Čargonja Hrvoje 
Published: May 2022

AbstractIn Gauḍīya Vaiṣṇava emotional-aesthetic theology and practice, religious experience is understood as realisation or actualisation of the personal relationship with Kṛṣṇa, the original and the supreme form of God. Within such devotional framework, there are two distinct but not exclusive types of accounts of this realisation: ecstasies and arrangements. These two types of stories reflect one of the temporal ambiguities involved in the notion of experience: immediacy/reflection exemplified by the two words for experience in German Erlebnis and Erfahrung. Except for the differences in their temporality, these two types of stories differ in their intersubjectivity. Arrangements are more readily imparted in the public discourse, whereas ecstasy narratives are shared predominantly in private and confidential settings. The difference reflects Gauḍīya orthodoxy’s caution towards deviant ritual behaviour. Although ecstasies with their immediate and extraordinary affectivity are hoped for and cherished, Hare Kṛṣṇa devotees generally stress historical, reflected dimension of experience. Developing a devotional and moral character is valued over transient eudaimonian episodes. In this way, the article shows how temporal ambiguity of experience is culturally elaborated through distinct concepts and narrative types, enabling the intersubjective management of religious affections and articulations of personal religious identities.
Delphinidin induces autophagic flux blockage and apoptosis by inhibiting both multidrug resistance gene 1 and DEAD-box helicase 17 expressions in liver cancer cells
Authors: Sun Shenghui , Xu Kun , Yan Mingjing , Cui Ju , Zhu Kaiyi , Yang Yao , Zhang Xiaoyi , Tang Weiqing , Huang Xiuqing , Dou Lin , Chen Beidong , Lin Yajun , Zhang Xiyue , Man Yong , Li Jian , Shen Tao 
Published: May 2022

Abstract

Objectives
To investigate the function and regulatory mechanisms of delphinidin in the treatment of hepatocellular carcinoma.

Methods
HepG2 and HuH-7 cells were treated with different concentrations of delphinidin. Cell viability was analysed by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The cell autophagy and autophagic flux were analysed by LC3b-green fluorescent protein (GFP)-Adv and LC3b-GFP-monomeric red fluorescent protein-Adv transfected HepG2 and HuH-7 cells, respectively. Cell apoptosis was analysed by Hoechst33342 staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining and DNA laddering. Cell autophagy, apoptosis and survival related protein expressions were detected by Western blotting.

Key findings
After treatment with different concentrations of delphinidin, the cell survival rate was significantly decreased. Delphinidin could block the autophagic flux, resulting in a significant increase in autophagosomes, and led to an increase in cell apoptosis. The combined application of delphinidin and cisplatin could promote the antitumour effect and reduce the dose of cisplatin in tumour cells. Further mechanism studies reveal that delphinidin could inhibit the multidrug resistance gene 1 (MDR1) and the tumour-promoting transcription cofactor DEAD-box helicase 17 (DDX17) expression in tumour cells. Overexpression of DDX17 could reverse delphinidin’s antitumor function in tumour cells.

Conclusions
Delphinidin has a strong anti-tumour effect by inducing tumour cell autophagic flux blockage and apoptosis by inhibiting of both MDR1 and DDX17 expression.
Clonidine ameliorates cisplatin-induced nephrotoxicity: impact on OCT2 and p38 MAPK pathway
Authors: Fawzy Mariam H , Khodeer Dina M , Elsayed Norhan M , Ahmed Yasser M , Saeed Noha M 
Published: May 2022

Abstract

Objectives
To explore clonidine (Clon) nephroprotective effects as an inhibitor of organic cationic transporter 2 (OCT2) and p38 mitogen-activated protein kinase (p38 MAPK) against cisplatin (CP)-induced nephrotoxicity. OCT2 is mainly responsible for renal accumulation of CP. Clon has been recently recognized as an OCT2 inhibitor and exerts beneficial effects on renal function and p38 MAPK. This study further investigates its underlying anti-inflammatory, antioxidative and antiapoptotic effects.

Methods
Rats were randomly assigned into five groups: (I) CON, (II) CP, (III) CP + Clon 0.125, (IV) CP + Clon 0.25, (V) CP + Clon 0.5, and (VI) Clon 0.5 alone. Clon was administered orally at 0.125, 0.25 and 0.5 mg/kg/day dosages for 10 days. On day 7, rats in groups from (II) to (V) received a single intraperitoneal injection of CP (10 mg/kg).

Key findings
Clon 0.25 mg/kg displayed the best nephroprotective outcomes, justified by the significant amelioration of parameters like renal function, oxidative stress, and inflammatory status, as well as modulated the OCT2 expression, phosphorylation of p38 and p53, compared with Clon 0.125 and 0.5 mg/kg.

Conclusion
This study suggests the promising nephroprotective impact of Clon as an OCT2 inhibitor against CP nephrotoxicity and its proficient role in attenuating oxidative stress, inflammatory status and apoptotic status.
Serial (1–3)-beta-D-Glucan (BDG) monitoring shows high variability among premature neonates
Authors: Ferreras-Antolin Laura , Aziz Nasreen , Warris Adilia 
Published: May 2022

Abstract

This study aimed to characterize the baseline values and dynamics of serum (1,3)-Beta-D-Glucan (BDG) in neonates at high risk of neonatal invasive candidiasis (NIC); as well as to determine the effect of various clinical variables on these levels. Single center prospective cohort study was performed including 20 high-risk neonates (gestational age &lt; 29 weeks and/or birth weight ≤ 1000 gr). Samples for BDG (Fungitell® assay) were obtained twice weekly during 6 weeks. Nineteen neonates were enrolled with a median gestational age of 25 weeks (IQR 24–27), median birth weight of 730 gr (IQR 650–810). None of the neonates was diagnosed with NIC. 190 serum samples were included. The median BDG value was 59 pg/ml (IQR 30–148), mean was 119 pg/ml (SD ± 154). A total of 42.1% (80/190) samples showed values ≥80 pg/ml, with all the neonates presenting at least one test above this cut-off. Neonatal age did not show an association with BDG levels. Exposure to steroids and the use of a heel prick as sampling method were associated with statistically significant higher BDG levels. The BDG levels showed high variability and in a significant proportion of samples values were above the threshold for positivity (e.g., ≥80 pg/ml) in the absence of NIC. The exposure to postnatal steroids and the heel prick as the method of blood sampling were associated with higher BDG levels.

Lay Summary
Neonatal invasive candidiasis (NIC) presents high morbi-mortality. The diagnosis of NIC is often challenging. Blood cultures have limitations and better diagnostic tools are needed. Beta-D-glucan is a diagnostic marker which could be potentially used, although still more clinical data are required.
Galaxy correlation function and local density from photometric redshifts using the stochastic order redshift technique (SORT)
Authors: Kakos James , Primack Joel R , Rodríguez-Puebla Aldo , Tejos Nicolas , Yung L Y Aaron , Somerville Rachel S 
Published: May 2022

ABSTRACT
The stochastic order redshift technique (sort) is a simple, efficient, and robust method to improve cosmological redshift measurements. The method relies upon having a small (∼10 per cent) reference sample of high-quality redshifts. Within pencil-beam-like sub-volumes surrounding each galaxy, we use the precise dN/dz distribution of the reference sample to recover new redshifts and assign them one-to-one to galaxies such that the original rank order of redshifts is preserved. Preserving the rank order is motivated by the fact that random variables drawn from Gaussian probability density functions with different means but equal standard deviations satisfy stochastic ordering. This process is repeated for sub-volumes surrounding each galaxy in the survey. This results in every galaxy being assigned multiple ‘recovered’ redshifts from which a new redshift estimate is determined. An earlier paper applied sort to a mock Sloan Digital Sky Survey at z ≲ 0.2 and accurately recovered the two-point correlation function (2PCF) on scales ≳ 4 h−1Mpc. In this paper, we test the performance of sort in surveys spanning the redshift range 0.75 &lt; z &lt; 2.25. We used two mock surveys extracted from the Small MultiDark–Planck and Bolshoi–Planck N-body simulations with dark matter haloes that were populated by the Santa Cruz semi-analytic model. We find that sort overall improves redshift estimates, accurately recovers the redshift-space 2PCF ξ(s) on scales ≳ 2.5 h−1Mpc, and provides improved local density estimates in regions of average or higher density, which may allow for improved understanding of how galaxy properties relate to their environments.
Annotation Query (AnnoQ): an integrated and interactive platform for large-scale genetic variant annotation
Authors: Liu Zhu , Mushayahama Tremayne , Queme Bryan , Ebert Dustin , Muruganujan Anushya , Mills Caitlin , Thomas Paul D , Mi Huaiyu 
Published: May 2022

Abstract
The Annotation Query (AnnoQ) (http://annoq.org/) is designed to provide comprehensive and up-to-date functional annotations for human genetic variants. The system is supported by an annotation database with ∼39 million human variants from the Haplotype Reference Consortium (HRC) pre-annotated with sequence feature annotations by WGSA and functional annotations to Gene Ontology (GO) and pathways in PANTHER. The database operates on an optimized Elasticsearch framework to support real-time complex searches. This implementation enables users to annotate data with the most up-to-date functional annotations via simple queries instead of setting up individual tools. A web interface allows users to interactively browse the annotations, annotate variants and search variant data. Its easy-to-use interface and search capabilities are well-suited for scientists with fewer bioinformatics skills such as bench scientists and statisticians. AnnoQ also has an API for users to access and annotate the data programmatically. Packages for programming languages, such as the R package, are available for users to embed the annotation queries in their scripts. AnnoQ serves researchers with a wide range of backgrounds and research interests as an integrated annotation platform.