bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melatonin does not reduce mortality in adult hospitalized patients with COVID-19: a multicenter retrospective observational study
Authors: Sánchez-Rico Marina , de la Muela Pedro , Herrera-Morueco Juan J , Geoffroy Pierre A , Limosin Frédéric , Hoertel Nicolas ,   AP-HP/Université de Paris/INSERM COVID-19 Research Collaboration/AP-HP COVID CDR Initiative/Entrepôt de Données de Santé AP-HP Consortium
Published: January 2022

In this multicenter retrospective observational study involving 58 562 adult patients hospitalized for COVID-19, melatonin use (N = 272) at a mean daily dose of 2.6 mg was not associated with reduced mortality.
Weather variables as important clinical predictors of bacterial diarrhoea among international travellers
Authors: Pender Melissa A , Smith Timothy , Brintz Ben J , Pandey Prativa , Shrestha Sanjaya K , Anuras Sinn , Demons Samandra , Sornsakrin Siriporn , Bodhidatta Ladaporn , Platts-Mills James A , Leung Daniel T 
Published: January 2022

Abstract

Background
Clinicians and travellers often have limited tools to differentiate bacterial from non-bacterial causes of travellers’ diarrhoea (TD). Development of a clinical prediction rule assessing the aetiology of TD may help identify episodes of bacterial diarrhoea and limit inappropriate antibiotic use. We aimed to identify predictors of bacterial diarrhoea among clinical, demographic and weather variables, as well as to develop and cross-validate a parsimonious predictive model.

Methods
We collected de-identified clinical data from 457 international travellers with acute diarrhoea presenting to two healthcare centres in Nepal and Thailand. We used conventional microbiologic and multiplex molecular methods to identify diarrheal aetiology from stool samples. We used random forest and logistic regression to determine predictors of bacterial diarrhoea.

Results
We identified 195 cases of bacterial aetiology, 63 viral, 125 mixed pathogens, 6 protozoal/parasite and 68 cases without a detected pathogen. Random forest regression indicated that the strongest predictors of bacterial over viral or non-detected aetiologies were average location-specific environmental temperature and red blood cell on stool microscopy. In 5-fold cross-validation, the parsimonious model with the highest discriminative performance had an area under the receiver operator curve of 0.73 using 3 variables with calibration intercept −0.01 (standard deviation, SD 0.31) and slope 0.95 (SD 0.36).

Conclusions
We identified environmental temperature, a location-specific parameter, as an important predictor of bacterial TD, among traditional patient-specific parameters predictive of aetiology. Future work includes further validation and the development of a clinical decision-support tool to inform appropriate use of antibiotics in TD.
Comparative evaluation of Sensititre YeastOne and VITEK 2 against the Clinical and Laboratory Standards Institute M27-E4 reference broth microdilution method for the antifungal susceptibility testing of Cryptococcus neoformans and Cryptococcus gattii
Authors: Zhang Min , Zhou Ziyi , Wang Dongjiang , Zhou Aiping , Song Guobin , Chen Xingchun , Guo Jian , Wu Wenjuan 
Published: January 2022

Abstract

The present study collected 280 isolates of Cryptococcus neoformans and 22 isolates of Cryptococcus gattii and evaluated the consistencies between Sensititre YeastOne (SYO), VITEK 2, and the reference broth microdilution (BMD) method for the antifungal susceptibility testing of fluconazole, voriconazole, and flucytosine. For amphotericin B, SYO was replaced with the BIO KONT amphotericin B microbroth dilution kit. The essential agreements (EAs) by SYO and VITEK 2 for C. neoformans var. grubii and C. neoformans var. neoformans were 98.15–99.63% and 88.89–100%, respectively, with fluconazole, voriconazole, and flucytosine. The EA for C. gattii VG Ⅰ against fluconazole was 29.41% by VITEK 2, while the other EAs for C. gattii strains were 100% by SYO and VITEK 2. The categorical agreements (CAs) by SYO and VITEK 2 for C. neoformans and C. gattii were 94.12–100%, while VITEK 2 failed to distinguish 5/6 fluconazole-resistant non-wild-type C. neoformans var. grubii isolates; this finding confirmed the limitation of testing fluconazole against C. neoformans as documented in the manufacturer's package insert. The EAs for amphotericin B were 97.42–100% for C. neoformans and C. gattii, but the CAs were 17.65–60% by BIO KONT and VITEK 2. Thus, SYO can be used for susceptibility testing of C. neoformans and C. gattii against fluconazole, voriconazole, and flucytosine, and VITEK 2 can be used for susceptibility testing of C. neoformans against voriconazole and flucytosine. Further studies using amphotericin B-resistant isolates are required to assess the agreement between VITEK 2, BIO KONT, and BMD.

Lay Summary
Sensititre YeastOne showed a good agreement with the CLSI broth microdilution method for C. neoformans and C. gattii against voriconazole and flucytosine. The limitation regarding fluconazole testing against C. neoformans documented in VITEK 2 manufacturer's package insert was confirmed.
Base excision repair system targeting DNA adducts of trioxacarcin/LL-D49194 antibiotics for self-resistance
Authors: Chen Xiaorong , Bradley Noah P , Lu Wei , Wahl Katherine L , Zhang Mei , Yuan Hua , Hou Xian-Feng , Eichman Brandt F , Tang Gong-Li 
Published: January 2022

AbstractTwo families of DNA glycosylases (YtkR2/AlkD, AlkZ/YcaQ) have been found to remove bulky and crosslinking DNA adducts produced by bacterial natural products. Whether DNA glycosylases eliminate other types of damage formed by structurally diverse antibiotics is unknown. Here, we identify four DNA glycosylases—TxnU2, TxnU4, LldU1 and LldU5—important for biosynthesis of the aromatic polyketide antibiotics trioxacarcin A (TXNA) and LL-D49194 (LLD), and show that the enzymes provide self-resistance to the producing strains by excising the intercalated guanine adducts of TXNA and LLD. These enzymes are highly specific for TXNA/LLD-DNA lesions and have no activity toward other, less stable alkylguanines as previously described for YtkR2/AlkD and AlkZ/YcaQ. Similarly, TXNA-DNA adducts are not excised by other alkylpurine DNA glycosylases. TxnU4 and LldU1 possess unique active site motifs that provide an explanation for their tight substrate specificity. Moreover, we show that abasic (AP) sites generated from TxnU4 excision of intercalated TXNA-DNA adducts are incised by AP endonuclease less efficiently than those formed by 7mG excision. This work characterizes a distinct class of DNA glycosylase acting on intercalated DNA adducts and furthers our understanding of specific DNA repair self-resistance activities within antibiotic producers of structurally diverse, highly functionalized DNA damaging agents.
The DNA dioxygenase Tet1 regulates H3K27 modification and embryonic stem cell biology independent of its catalytic activity
Authors: Chrysanthou Stephanie , Tang Qin , Lee Joun , Taylor Samuel J , Zhao Yilin , Steidl Ulrich , Zheng Deyou , Dawlaty Meelad M 
Published: January 2022

Abstract
Tet enzymes (Tet1/2/3) oxidize 5-methylcytosine to promote DNA demethylation and partner with chromatin modifiers to regulate gene expression. Tet1 is highly expressed in embryonic stem cells (ESCs), but its enzymatic and non-enzymatic roles in gene regulation are not dissected. We have generated Tet1 catalytically inactive (Tet1m/m) and knockout (Tet1−/−) ESCs and mice to study these functions. Loss of Tet1, but not loss of its catalytic activity, caused aberrant upregulation of bivalent (H3K4me3+; H3K27me3+) developmental genes, leading to defects in differentiation. Wild-type and catalytic-mutant Tet1 occupied similar genomic loci which overlapped with H3K27 tri-methyltransferase PRC2 and the deacetylase complex Sin3a at promoters of bivalent genes and with the helicase Chd4 at active genes. Loss of Tet1, but not loss of its catalytic activity, impaired enrichment of PRC2 and Sin3a at bivalent promoters leading to reduced H3K27 trimethylation and deacetylation, respectively, in absence of any changes in DNA methylation. Tet1−/−, but not Tet1m/m, embryos expressed higher levels of Gata6 and were developmentally delayed. Thus, the critical functions of Tet1 in ESCs and early development are mediated through its non-catalytic roles in regulating H3K27 modifications to silence developmental genes, and are more important than its catalytic functions in DNA demethylation.
Rational design of small-molecules to recognize G-quadruplexes of c-MYC promoter and telomere and the evaluation of their in vivo antitumor activity against breast cancer
Authors: Long Wei , Zheng Bo-Xin , Li Ying , Huang Xuan-He , Lin Dan-Min , Chen Cui-Cui , Hou Jin-Qiang , Ou Tian-Miao , Wong Wing-Leung , Zhang Kun , Lu Yu-Jing 
Published: January 2022

Abstract
DNA G4-structures from human c-MYC promoter and telomere are considered as important drug targets; however, the developing of small-molecule-based fluorescent binding ligands that are highly selective in targeting these G4-structures over other types of nucleic acids is challenging. We herein report a new approach of designing small molecules based on a non-selective thiazole orange scaffold to provide two-directional and multi-site interactions with flanking residues and loops of the G4-motif for better selectivity. The ligands are designed to establish multi-site interactions in the G4-binding pocket. This structural feature may render the molecules higher selectivity toward c-MYC G4s than other structures. The ligand–G4 interaction studied with 1H NMR may suggest a stacking interaction with the terminal G-tetrad. Moreover, the intracellular co-localization study with BG4 and cellular competition experiments with BRACO-19 may suggest that the binding targets of the ligands in cells are most probably G4-structures. Furthermore, the ligands that either preferentially bind to c-MYC promoter or telomeric G4s are able to downregulate markedly the c-MYC and hTERT gene expression in MCF-7 cells, and induce senescence and DNA damage to cancer cells. The in vivo antitumor activity of the ligands in MCF-7 tumor-bearing mice is also demonstrated.
Association of diuretic use with increased risk for long-term post-transplantation diabetes mellitus in kidney transplant recipients
Authors: Sokooti Sara , Klont Frank , Tye Sok Cin , Kremer Daan , Douwes Rianne M , Hopfgartner Gérard , Dullaart Robin P F , Heerspink Hiddo J L , Bakker Stephan J L 
Published: January 2022

ABSTRACT

Background
Post-transplantation diabetes mellitus (PTDM) is a major clinical problem in kidney transplant recipients (KTRs). Diuretic-induced hyperglycaemia and diabetes have been described in the general population. We aimed to investigate whether diuretics also increase PTDM risk in KTRs.

Methods
We included 486 stable outpatient KTRs (with a functioning graft ≥1 year) without diabetes from a prospective cohort study. Participants were classified as diuretic users and non-users based on their medication use verified by medical records.

Results
At the baseline study, 168 (35%) KTRs used a diuretic (thiazide, n = 74; loop diuretic, n = 76; others, n = 18) and 318 KTRs did not use a diuretic. After 5.2 years [interquartile range (IQR) 4.0‒5.9] of follow up, 54 (11%) KTRs developed PTDM. In Cox regression analyses, diuretic use was associated with incident PTDM, independent of age, sex, fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) {hazard ratio [HR] 3.28 [95% confidence interval (CI) 1.84–5.83]; P &lt;0.001}. Further adjustment for potential confounders, including lifestyle, family history of cardiovascular disease, use of other medication, kidney function, transplantation-specific parameters, BMI, lipids and blood pressure did not materially change the association. Moreover, in Cox regression analyses, both thiazide and loop diuretics associated with the development of PTDM, independent of age, sex, FPG and HbA1c [HR 2.70 (95% CI 1.24–5.29); P = 0.012 and HR 5.08 (95% CI 2.49–10.34); P &lt;0.001), respectively].

Conclusions
This study demonstrates that diuretics overall are associated with an increased risk of developing PTDM in KTRs, independent of established risk factors for PTDM development. The association was present for both thiazide and loop diuretics.
CONVINCE in the context of existing evidence on haemodiafiltration
Authors: Vernooij Robin W M , Bots Michiel L , Strippoli Giovanni F M , Canaud Bernard , Cromm Krister , Woodward Mark , Blankestijn Peter J ,   CONVINCE scientific committee, Davenport Andrew , Canaud Bernard , Barth Claudia , Strippoli Giovanni , Hegbrant Jörgen , Fischer Kathrin , Cromm Krister , Török Mariëtta , Woodward Mark , Rose Matthias , Bots Michiel 
Published: January 2022

ABSTRACT
Haemodiafiltration (HDF) provides a greater removal of larger solutes and protein-bound compounds than conventional high-flux haemodialysis (HD). There are indications that the patients receiving the highest convection volumes of HDF result in improved survival compared with HD. However, the comparative efficacy of HDF versus HD remains unproven. Here we provide a comparative account of the methodology and aims of ‘the comparison of high-dose HDF with high-flux HD’ (CONVINCE) study in the context of the totality of evidence and how this study will contribute to reaching a higher level of certainty regarding the comparative efficacy of HDF versus HD in people with end-stage kidney disease.
Kidney injury rates after unilateral nephrectomy in childhood—a systematic review and meta-analysis
Authors: Groen in ‘t Woud Sander , Gobino Alessandro , Roeleveld Nel , van den Heuvel Lambert P W J , Feitz Wout F J , van der Zanden Loes F M , Schreuder Michiel F 
Published: January 2022

ABSTRACT

Background
Unilateral nephrectomy is a relatively common procedure in children which results in a solitary functioning kidney (SFK). Living with an SFK predisposes to kidney injury, but it remains unknown which children are most at risk. We aimed to investigate kidney injury rates in patients who underwent unilateral nephrectomy in childhood and to investigate differences among nephrectomies performed for a congenital anomaly, malignancy or other condition.

Methods
MEDLINE and EMBASE were searched for studies reporting kidney injury rates [i.e. proteinuria, hypertension and/or a decreased glomerular filtration rate (GFR)] of patients who underwent unilateral nephrectomy during childhood. Studies including five or more patients with at least 12 months of follow-up were eligible. Analyses were performed using random effects models and stratified by indication for nephrectomy. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines were used for reporting.

Results
Over 5000 unique articles were screened, of which 53 studies reporting on &gt;4000 patients were included in the analyses. Proteinuria, hypertension and a decreased GFR were present in 15.3, 14.5 and 11.9% of patients, respectively. Heterogeneity among the studies was large in several subgroups, impairing quantitative meta-analyses. However, none of our analyses indicated differences in injury rates between a congenital anomaly or malignancy as an indication for nephrectomy.

Conclusions
Unilateral nephrectomy during childhood results in signs of kidney injury in &gt;10% of patients, with no clear difference between the indications for nephrectomy. Therefore, structured follow-up is necessary in all children who underwent nephrectomy, regardless of the indication.
Effects of Prenatal Nicotine, THC, or Co-Exposure on Cognitive Behaviors in Adolescent Male and Female Rats
Authors: Lallai Valeria , Manca Letizia , Sherafat Yasmine , Fowler Christie D 
Published: January 2022

Abstract

Introduction
Although there has been a decrease in the prevalence of tobacco smoking, exposure to nicotine during pregnancy remains a substantial problem worldwide. Further, given the recent escalation in e-cigarette use and legalization of cannabis, it has become essential to understand the effects of nicotine and cannabinoid co-exposure during early developmental stages.

Aims and Methods
We systematically examined the effects of nicotine and/or THC prenatal exposure on cognitive behaviors in male and female offspring. Dams were exposed to nicotine vape or vehicle, and oral edible THC or vehicle, throughout pregnancy. Adolescent offspring were then tested in the prepulse inhibition test, novel object recognition task, and novelty suppressed feeding task.

Results
At birth, pups from mothers exposed to nicotine vape or oral THC exhibited reduced body weight, compared to control pups. Prenatal nicotine vape exposure resulted in a decreased baseline startle reactivity in adolescent male and female rats, and in females, enhanced sensorimotor gating in the prepulse inhibition test. Prenatal nicotine and THC co-exposure resulted in significant deficits in the prepulse inhibition test in males. Deficits in short-term memory were also found in males prenatally exposed to THC, either alone or with nicotine co-exposure, and in females exposed to THC alone. Finally, in males, a modest increase in anxiety-associated behaviors was found with THC or nicotine exposure in the latency to approach a novel palatable food.

Conclusions
These studies demonstrate differential effects of prenatal exposure to e-cigarette nicotine vape and/or edible THC on cognitive function, with differing effects within male and female groups.

Implications
These studies demonstrate an impact of nicotine, THC, or co-exposure during early developmental stages in utero on behavioral outcomes in adolescence. These findings have important translational implications given the continued use of nicotine and THC containing products by pregnant women worldwide, which can be applied to support healthcare and policy efforts restricting nicotine and THC use during pregnancy.
The unexpected influencer: Pope Francis and European perceptions of the recent refugee crisis
Authors: Deiana Claudio , Mazzarella Gianluca , Meroni Elena Claudia , Tiozzo Pezzoli Luca 
Published: January 2022

Abstract
This article analyses the impact of non-informative communication on Europeans’ perceptions of European Union (EU) action on the issue of migration. We exploit the fact that Pope Francis’s visit to Lesbos Island in 16 April 2016, overlaps with the days of the interviews for a Special Eurobarometer survey, such that some respondents were unintentionally exposed to the Pope’s speech while others were not. Comparing Catholics and non-Catholics before and after the Pope’s visit in a difference-in-differences setting, we show that the papal message persuaded exposed Catholic individuals that EU action on the issue of migration is insufficient. The effect is temporary and varies according to the demographic characteristics of the respondents and by the country’s share of asylum applicants in 2015. Moreover, media exposure of the Pope’s visit, measured by the Global Database of Events, Language, and Tone, was greater in Catholic countries, and this might explain the effect found.
Feminist Institutional Change: The Case of the UK Women and Equalities Committee
Authors: Childs Sarah 
Published: January 2022

Abstract
The UK Government’s decision to establish the Women and Equalities Committee in 2015 redressed an institutional deficit at Westminster—the lack of a Departmental Select Committee holding the Women’s Minister and Government Equalities Office to account. This ‘effective’ reform was by no means a foregone conclusion, however. A feminist institutionalist (FI) approach demonstrates the limitations of traditional accounts of institutional change in accounting for this reform. With greater analytical space given to women’s agency and introducing the concept of gendered parliamentarianism, FI captures the gendered constraints and conducive conditions that marked this moment of parliamentary re-gendering: identifying the critical role of women MPs; the new relations between them and women parliamentary Clerks and officials and the wider—crucially gendered—(extra) parliamentary actors and dynamics in play.
The Xanthomonas type-III effector XopS stabilizes CaWRKY40a to regulate defense responses and stomatal immunity in pepper (Capsicum annuum)
Authors: Raffeiner Margot , Üstün Suayib , Guerra Tiziana , Spinti Daniela , Fitzner Maria , Sonnewald Sophia , Baldermann Susanne , Börnke Frederik 
Published: January 2022

Abstract
As a critical part of plant immunity, cells that are attacked by pathogens undergo rapid transcriptional reprogramming to minimize virulence. Many bacterial phytopathogens use type III effector (T3E) proteins to interfere with plant defense responses, including this transcriptional reprogramming. Here, we show that Xanthomonas outer protein S (XopS), a T3E of Xanthomonas campestris pv. vesicatoria (Xcv), interacts with and inhibits proteasomal degradation of WRKY40, a transcriptional regulator of defense gene expression. Virus-induced gene silencing of WRKY40 in pepper (Capsicum annuum) enhanced plant tolerance to Xcv infection, indicating that WRKY40 represses immunity. Stabilization of WRKY40 by XopS reduces the expression of its targets, which include salicylic acid-responsive genes and the jasmonic acid signaling repressor JAZ8. Xcv bacteria lacking XopS display significantly reduced virulence when surface inoculated onto susceptible pepper leaves. XopS delivery by Xcv, as well as ectopic expression of XopS in Arabidopsis thaliana or Nicotiana benthamiana, prevented stomatal closure in response to bacteria and biotic elicitors. Silencing WRKY40 in pepper or N. benthamiana abolished XopS’s ability to prevent stomatal closure. This suggests that XopS interferes with both preinvasion and apoplastic defense by manipulating WRKY40 stability and downstream gene expression, eventually altering phytohormone crosstalk to promote pathogen proliferation.
Correlation of vacuole morphology with stomatal lineage development by whole-cell electron tomography
Authors: Cao Wenhan , Li Zhenping , Huang Shuxian , Shi Yuwei , Zhu Ying , Lai Man Nga , Lok Pui Lok , Wang Xiangfeng , Cui Yong , Jiang Liwen 
Published: January 2022

AbstractStomatal movement is essential for plants to optimize transpiration and therefore photosynthesis. Rapid changes in the stomatal aperture are accompanied by adjustment of vacuole volume and morphology in guard cells (GCs). In Arabidopsis (Arabidopsis thaliana) leaf epidermis, stomatal development undergoes a cell-fate transition including four stomatal lineage cells: meristemoid, guard mother cell, young GC, and GC. Little is known about the mechanism underlying vacuole dynamics and vacuole formation during stomatal development. Here, we utilized whole-cell electron tomography (ET) analysis to elucidate vacuole morphology, formation, and development in different stages of stomatal lineage cells at nanometer resolution. The whole-cell ET models demonstrated that large vacuoles were generated from small vacuole stepwise fusion/maturation along stomatal development stages. Further ET analyses verified the existence of swollen intraluminal vesicles inside distinct vacuoles at certain developmental stages of stomatal lineage cells, implying a role of multivesicular body fusion in stomatal vacuole formation. Collectively, our findings demonstrate a mechanism mediating vacuole formation in Arabidopsis stomatal development and may shed light on the role of vacuoles in stomatal movement.