bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coregulation of extracellular vesicle production and fluconazole susceptibility in
Cryptococcus neoformans
Authors: Rizzo Juliana , Trottier Adèle , Moyrand Frédérique , Coppée Jean-Yves , Maufrais Corinne , Zimbres Ana Claudia G. , Dang Thi Tuong Vi , Alanio Alexandre , Desnos-Ollivier Marie , Mouyna Isabelle , Péhau-Arnaude Gérard , Commere Pierre-Henri , Novault Sophie , Ene Iuliana V. , Nimrichter Leonardo , Rodrigues Marcio L. , Janbon Guilhem 
Published: June 2023

ABSTRACT

Resistance to fluconazole (FLC), the most widely used antifungal drug, is typically achieved by altering the azole drug target and/or drug efflux pumps. Recent reports have suggested a link between vesicular trafficking and antifungal resistance. Here, we identified novel
Cryptococcus neoformans
regulators of extracellular vesicle (EV) biogenesis that impact FLC resistance. In particular, the transcription factor Hap2 does not affect the expression of the drug target or efflux pumps, yet it impacts the cellular sterol profile. Subinhibitory FLC concentrations also downregulate EV production. Moreover,
in vitro
spontaneous FLC-resistant colonies showed altered EV production, and the acquisition of FLC resistance was associated with decreased EV production in clinical isolates. Finally, the reversion of FLC resistance was associated with increased EV production. These data suggest a model in which fungal cells can regulate EV production in place of regulating the drug target gene expression as a first line of defense against antifungal assault in this fungal pathogen.

IMPORTANCE

Extracellular vesicles (EVs) are membrane-enveloped particles that are released by cells into the extracellular space. Fungal EVs can mediate community interactions and biofilm formation, but their functions remain poorly understood. Here, we report the identification of the first regulators of EV production in the major fungal pathogen
Cryptococcus neoformans
. Surprisingly, we uncover a novel role of EVs in modulating antifungal drug resistance. Disruption of EV production was associated with altered lipid composition and changes in fluconazole susceptibility. Spontaneous azole-resistant mutants were deficient in EV production, while loss of resistance restored initial EV production levels. These findings were recapitulated in
C. neoformans
clinical isolates, indicating that azole resistance and EV production are coregulated in diverse strains. Our study reveals a new mechanism of drug resistance in which cells adapt to azole stress by modulating EV production.
Analysis of peer reviewers’ response to invitations by gender and geographical region: cohort study of manuscripts reviewed at 21 biomedical journals before and during covid-19 pandemic
Authors: Ben Messaoud Khaoula , Schroter Sara , Richards Mark , Gayet-Ageron Angèle 
Published: June 2023

Abstract

Objectives
To describe gender and geographical inequalities in invitations to review and the response to these invitations and to assess whether inequalities increased during the covid-19 pandemic.

Design
Retrospective cohort study.

Setting
19 specialist medical journals and two large general medical journals from BMJ Publishing Group.

Population
Reviewers invited to review manuscripts submitted between 1 January 2018 and 31 May 2021. The cohort was followed up to 28 February 2022.

Main outcome measures
Reviewer’s agreement to review.

Results
A total of 180 092 reviewers were invited (39.0% (70 203/180 092) women), and 67 019 (37.2%) agreed to review. Invited reviewers were mainly (168 291; 93.5%) affiliated with high income countries: Europe (95 616; 53.1%), North America (51 923; 28.8%), Asia (14 240; 7.9%), Oceania (12 678; 7.0%), Africa (3224; 1.8%) and South America (2411; 1.3%). Independent factors associated with agreement to review were gender (odds ratio 0.92, 95% confidence interval 0.89 to 0.95, for women compared with men), geographical affiliation (3.66, 3.29 to 4.08, for Africa; 2.87, 2.72 to 3.04, for Asia; 3.36, 2.98 to 3.79 for South America; 1.05, 1.01 to 1.09, for North America; and 1.34, 1.27 to 1.43, for Oceania compared with Europe), and country income (3.34, 3.09 to 3.60, for upper middle income; 5.22, 4.76 to 5.73, for lower middle income; and 4.76, 3.86 to 5.87, for low income compared with high income country). Agreement was also independently associated with editor’s gender (0.96, 0.93 to 0.99, for women compared with men) and editor’s geographical affiliation (1.16, 1.03 to 1.30, for Oceania compared with Europe), last author’s geographical affiliation (0.82, 0.77 to 0.88, for Africa; 0.80, 0.77 to 0.83 for Asia; 0.95, 0.91 to 0.98, for North America; and 0.89, 0.84 to 0.94 for Oceania compared with Europe), impact factor (1.64, 1.15 to 2.42, for >10 compared with <5), and type of peer review process (0.44, 0.29 to 0.69, for open compared with anonymised). During the first and second phases of the pandemic, agreement was lower than in the pre-pandemic period (P<0.001). The interaction between time periods and covid-19 related topic and reviewer’s gender was non-significant. However, significant interaction was found between time periods and covid-19 related topic and reviewer’s geographical affiliation.

Conclusions
To reduce bias and improve diversity, editors need to identify and implement effective strategies and continually evaluate progress against these to ensure that more women and researchers from upper middle income and low income countries are involved in review.
Cardiorenal protective effects of canagliflozin in CREDENCE according to glucose lowering
Authors: Charytan David M , Mahaffey Kenneth W , Jardine Meg J , Cannon Christopher P , Neal Bruce , Lambers Heerspink Hiddo J , Agarwal Rajiv , Bakris George L , de Zeeuw Dick , Levin Adeera , Pollock Carol , Zhang Hong , Zinman Bernard , Rosenthal Norman , Perkovic Vlado , Di Tanna Gian Luca , Yu Jie , Rogers Kris , Arnott Clare , Wheeler David C 
Published: June 2023

IntroductionRelationships between glycemic-lowering effects of sodium glucose co-transporter 2 inhibitors and impact on kidney and cardiovascular outcomes are uncertain.Research design and methodsWe analyzed 4395 individuals with prebaseline and postbaseline hemoglobin A1c (HbA1c) randomized to canagliflozin (n=2193) or placebo (n=2202) in The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial. Effects on HbA1c were assessed using mixed models. Mediation of treatment effects by achieved glycemic control was analyzed using proportional hazards regression with and without adjustment for achieved HbA1c. End points included combined kidney or cardiovascular death, end-stage kidney disease or doubling of serum creatinine (primary trial outcome), and individual end point components.ResultsHbA1c lowering was modified by baseline estimated glomerular filtration rate (eGFR). For baseline eGFR 60–90, 45–59, and 30–44 mL/min/1.73 m2, overall HbA1c (canagliflozin vs placebo) decreased by −0.24%, −0.14%, and −0.08% respectively and likelihood of >0.5% decrease in HbA1c decreased with ORs of 1.47 (95% CI 1.27 to 1.67), 1.12 (0.94 to 1.33) and 0.99 (0.83 to 1.18), respectively. Adjustment for postbaseline HbA1c marginally attenuated canagliflozin effects on primary and kidney composite outcomes: unadjusted HR 0.67 (95% CI 0.57 to 0.80) and 0.66 (95% CI 0.53 to 0.81); adjusted for week 13 HbA1c, HR 0.71 (95% CI 0.060 to 0.84) and 0.68 (95% CI 0.55 to 0.83). Results adjusted for time-varying HbA1c or HbA1c as a cubic spline were similar and consistent with preserved clinical benefits across a range of excellent and poor glycemic control.ConclusionsThe glycemic effects of canagliflozin are attenuated at lower eGFR but effects on kidney and cardiac end points are preserved. Non-glycemic effects may be primarily responsible for the kidney and cardioprotective benefits of canagliflozin.22
Interventions to improve migrants’ access to sexual and reproductive health services: a scoping review
Authors: Bouaddi Oumnia , Zbiri Saad , Belrhiti Zakaria 
Published: June 2023

IntroductionMigrants’ access to sexual and reproductive health (SRH) services is constrained by several individual, organisational and structural barriers. To address these barriers, many interventions have been developed and implemented worldwide to facilitate the access and utilisation of SRH services for migrant populations. The aim of this scoping review was to identify the characteristics and scope of interventions, their underlying theory of change, reported outcomes and key enablers and challenges to improve access to SRH services for migrants.MethodsA scoping review was conducted according to the Arksey and O’Malley (2005) guidelines. We searched three electronic databases (MEDLINE, Scopus and Google Scholar) and carried out additional searches using manual searching and citations tracking of empirical studies addressing interventions aimed at improving access and utilisation of SRH services for migrant populations published in Arabic, French or English between 4 September 1997 and 31 December 2022.ResultsWe screened a total of 4267 papers, and 47 papers met our inclusion criteria. We identified different forms of interventions: comprehensive (multiple individual, organisational and structural components) and focused interventions addressing specific individual attributes (knowledge, attitude, perceptions and behaviours). Comprehensive interventions also address structural and organisational barriers (ie, the ability to pay). The results suggest that coconstruction of interventions enables the building of contextual sensitive educational contents and improved communication and self-empowerment as well as self-efficacy of migrant populations, and thus improved access to SRH.ConclusionMore attention needs to be placed on participative approaches in developing interventions for migrants to improve access to SRH services.
Impact of primary care usual provider type and provider interdependence on outcomes for patients with diabetes: a cohort study
Authors: Everett Christine , Christy Jacob , Batchelder Heather , Morgan Perri A , Docherty Sharron , Smith Valerie A , Anderson John B , Viera Anthony , Jackson George L 
Published: June 2023

BackgroundInterprofessional primary care (PC) teams are key to the provision of high-quality care. PC providers often ‘share’ patients (eg, a patient may see multiple providers in the same clinic), resulting in between-visit interdependence between providers. However, concern remains that PC provider interdependence will reduce quality of care, causing some organisations to hesitate in creating multiple provider teams. If PC provider teams are formalised, the PC usual provider of care (UPC) type (physician, nurse practitioner (NP) or physician assistant/associate (PA)) should be determined for patients with varying levels of medical complexity.ObjectiveTo evaluate the impact of PC provider interdependence, UPC type and patient complexity on diabetes-specific outcomes for adult patients with diabetes.DesignCohort study using electronic health record data from 26 PC practices in central North Carolina, USA.ParticipantsAdult patients with diabetes (N=10 498) who received PC in 2016 and 2017.OutcomeTesting for diabetes control, testing for lipid levels, mean glycated haemoglobin (HbA1c) values and mean low-density lipoprotein (LDL) values in 2017.ResultsReceipt of guideline recommended testing was high (72% for HbA1c and 66% for LDL testing), HbA1c values were 7.5% and LDL values were 88.5 mg/dL. When controlling for a range of patient and panel level variables, increases in PC provider interdependence were not significantly associated with diabetes-specific outcomes. Similarly, there were no significant differences in the diabetes outcomes for patients with NP/PA UPCs when compared with physicians. The number and type of a patient’s chronic conditions did impact the receipt of testing, but not average values for HbA1c and LDL.ConclusionsA range of UPC types on PC multiple provider teams can deliver guideline-recommended diabetes care. However, the number and type of a patient’s chronic conditions alone impacted the receipt of testing, but not average values for HbA1c and LDL.
End-of-life experiences in the dying process: scoping and mixed-methods systematic review
Authors: Silva Taís Oliveira , Ribeiro Henrique Gonçalves , Moreira-Almeida Alexander 
Published: June 2023

ObjectivesTo identify the current state of understanding about end-of-life experiences (ELEs) and examine evidence concerning prevalence, the impact on the process of dying and the perceptions/explanations of patients, relatives and healthcare professionals (HCPs) with regard to ELEs.MethodsScoping review and mixed-methods systematic review (ScR and MMSR). Nine academic databases were searched for a screening of the available scientific literature (ScR). Articles reporting qualitative, quantitative or mixed-methods studies were selected (MMSR), the quality of which was assessed using the Joanna Briggs Institute (JBI) standardised critical appraisal tools. The quantitative data were synthesised in narrative form while a meta-aggregation approach was adopted for the qualitative results.ResultsThe ScR identified 115 reports, with 70.4% published after 2010, 55.6% from the USA and the most common terminology for ELE was deathbed visions (29%). The MMSR included 36 papers, describing 35 studies in various settings. The combination of quantitative and qualitative evidence indicated a greater prevalence of ELEs in samples of patients and HCPs compared with relatives. The most common ELEs were visions and dreams of the presence of deceased relatives/friends with references to making ready for a journey. The impact of ELEs was mainly positive, and there was a tendency to interpret them as spiritual experiences inherent to the process of dying.ConclusionsELEs are often reported by patients, relatives and HCPs and have a significant, generally positive impact on the process of dying. Guidelines for the furtherance of studies and clinical applications are discussed.
Atherosclerosis-related biomarker PABPC1 predicts pan-cancer events
Authors: Lin Miao , Hu Liubing , Shen Si , Liu Jiyue , Liu Yanyan , Xu Yixian , Chen Honglin , Sugimoto Kazuo , Li Jianshuang , Kamitsukasa Ikuo , Hiwasa Takaki , Wang Hao , Xu Anding 
Published: June 2023

BackgroundAtherosclerosis (AS) and tumours are the leading causes of death worldwide and share common risk factors, detection methods and molecular markers. Therefore, searching for serum markers shared by AS and tumours is beneficial to the early diagnosis of patients.MethodsThe sera of 23 patients with AS-related transient ischaemic attack were screened by serological identification of antigens through recombinant cDNA expression cloning (SEREX), and cDNA clones were identified. Pathway function enrichment analysis was performed on cDNA clones to identify their biological pathways and determine whether they were related to AS or tumours. Subsequently, gene–gene and protein–protein interactions were performed and AS-associated markers would be discovered. The expression of AS biomarkers in human normal organs and pan-cancer tumour tissues were explored. Then, immune infiltration level and tumour mutation burden of various immune cells were evaluated. Survival curves analysis could show the expression of AS markers in pan-cancer.ResultsAS-related sera were screened by SEREX, and 83 cDNA clones with high homology were obtained. Through functional enrichment analysis, it was found that their functions were closely related to AS and tumour functions. After multiple biological information interaction screening and the external cohort validating, poly(A) binding protein cytoplasmic 1 (PABPC1) was found to be a potential AS biomarker. To assess whether PABPC1 was related to pan-cancer, its expression in different tumour pathological stages and ages was screened. Since AS-associated proteins were closely related to cancer immune infiltration, we investigated and found that PABPC1 had the same role in pan-cancer. Finally, analysis of Kaplan-Meier survival curves revealed that high PABPC1 expression in pan-cancer was associated with high risk of death.ConclusionsThrough the findings of SEREX and bioinformatics pan-cancer analysis, we concluded that PABPC1 might serve as a potential biomarker for the prediction and diagnosis of AS and pan-cancer.
Acute effect of a beverage containing Brazil and cashew nuts on oxidative stress, lipemia, and blood pressure of women with cardiometabolic risk (Brazilian Nuts Study): a randomized clinical trial
Authors: Bonifácio Dandara Baia , Caldas Ana Paula Silva , Costa Mirian Aparecida de Campos , Rocha Daniela Mayumi Usuda Prado , Hermsdorff Helen Hermana Miranda , Bressan Josefina 
Published: June 2023

Nuts are important sources of antioxidants that combat oxidative stress and improve lipid profile as well as vascular function. However, the intake of typical Brazilian nuts and its acute effect on cardiovascular health needs to be better understood. Thus, the present study aimed to evaluate the acute effect of a beverage containing cashew ( Anacardium occidentale L.) and Brazil nuts ( Bertholletia excelsa H.B.K.) on postprandial oxidative stress, lipemia, and blood pressure of adult women aged 20 to 55 years with cardiometabolic risk. This was an acute, randomized, parallel arm, controlled clinical trial. The participants received either a beverage containing nuts (30 g Brazil nuts + 15 g cashew nuts) or a beverage without nuts with similar macronutrient composition. Oxidative stress markers and lipid profiles were evaluated at fasting and 4 h after beverage consumption. Blood pressure was measured during fasting and after beverage intake (1, 2, 3, and 4 h). In the postprandial state, there was a greater reduction in malondialdehyde levels in the intervention group compared to the control group (−12.3 ± 0.59 vs. −10.7 ± 0.43 µmol/mL; p < 0.05), which was positively correlated with the concentrations of TG ( r = 0.399; p < 0.05), VLDL ( r = 0.399; p < 0.05), TG/HDL ( r = 0.380; p < 0.05), and blood pressure (iAUC SBP r = 0.391; p < 0.05, iAUC DBP r = 0.409; p < 0.05). The remaining oxidative stress markers showed similar postprandial changes between groups. In women with cardiometabolic risk, a beverage containing Brazilian nuts promoted a significant acute reduction on postprandial malondialdehyde levels. The study was registered in the Brazilian Clinical Trials Registry—ReBEC (protocol: RBR-3ntxrm).
MillenniumDB: An Open-Source Graph Database System
Authors: Vrgoč Domagoj , Rojas Carlos , Angles Renzo , Arenas Marcelo , Arroyuelo Diego , Buil-Aranda Carlos , Hogan Aidan , Navarro Gonzalo , Riveros Cristian , Romero Juan 
Published: June 2023

Abstract
In this systems paper, we present MillenniumDB: a novel graph database engine that is modular, persistent, and open source. MillenniumDB is based on a graph data model, which we call domain graphs, that provides a simple abstraction upon which a variety of popular graph models can be supported, thus providing a flexible data management engine for diverse types of knowledge graph. The engine itself is founded on a combination of tried and tested techniques from relational data management, state-of-the-art algorithms for worst-case-optimal joins, as well as graph-specific algorithms for evaluating path queries. In this paper, we present the main design principles underlying MillenniumDB, describing the abstract graph model and query semantics supported, the concrete data model and query syntax implemented, as well as the storage, indexing, query planning and query evaluation techniques used. We evaluate MillenniumDB over real-world data and queries from the Wikidata knowledge graph, where we find that it outperforms other popular persistent graph database engines (including both enterprise and open source alternatives) that support similar query features.
Approaching the Traveling Tournament Problem with Randomized Beam Search
Authors: Frohner Nikolaus , Neumann Bernhard , Pace Giulio , Raidl Günther R. 
Published: June 2023

Abstract
The traveling tournament problem is a well-known sports league scheduling problem famous for its practical hardness. Given an even number of teams with symmetric distances between their venues, a double round-robin tournament has to be scheduled minimizing the total travel distances over all teams. We consider the most common constrained variant without repeaters and a streak limit of three, for which we study a beam search approach based on a state-space formulation guided by heuristics derived from different lower bound variants. We solve the arising capacitated vehicle routing subproblems either exactly for small- to medium-sized instances up to 18 teams or heuristically also for larger instances up to 24 teams. In a randomized variant of the search, we employ random team ordering and add small amounts of Gaussian noise to the nodes' guidance for diversification when multiple runs are performed. This allows for a simple yet effective parallelization of the beam search. A final comparison is done on the NL, CIRC, NFL, and GALAXY benchmark instances with 12 to 24 teams, for which we report a mean gap difference to the best known feasible solutions of 1.2% and five new best feasible solutions.
The Quagmire of Arrested Development in Tropical Cyclones
Authors: Slocum Christopher J. , Knaff John A. 
Published: June 2023

Abstract
The 48-h intensity forecasts for Hurricane Pamela (2021) from numerical weather prediction models, statistical–dynamical aids, and forecasters were a major forecast bust with Pamela making landfall as a minor rather than major hurricane. From the satellite presentation, Pamela exhibited a symmetric pattern referred to as central cold cover (CCC) in the subjective Dvorak intensity technique. Per the technique, the CCC pattern is accompanied by arrested development in intensity despite the seemingly favorable convective signature. To understand forecast uncertainty during occurrences, central cold cover frequency from 2011 to 2021 is documented. From these cases, composites of longwave infrared brightness temperatures from geostationary satellites for CCC cases are presented, and the surrounding tropical cyclone large-scale environment is quantified and compared with other tropical cyclones at similar latitudes and intensities. These composites show that central cold cover has a consistent presentation, but varies in the preceding hours for storms that eventually intensify or weaken. And, the synoptic-scale environment surrounding the tropical cyclone thermodynamically supports the vigorous deep convection associated with CCC. Finally, intensity forecast errors from numerical weather prediction models and statistical–dynamical aids are examined in comparison to similar tropical cyclones. This work shows that guidance struggles during CCC cases with intensity errors from these models being in the lowest percentiles of performance, particularly for 24- and 36-h forecasts.

Significance Statement
The appearance of symmetric cold clouds near the center of developing tropical cyclones is most often associated with future intensification. This simple relationship is widely used by statistical tropical cyclone intensity forecast models. Here, we reexamine and confirm that one subjectively determined nighttime cold cyclone cloud pattern termed the “central cold cover” pattern in Vern Dvorak’s seminal technique for estimating tropical cyclone intensity from infrared satellite images is indeed related to slow or arrested development, and represents a failure mode for these simple forecast models.