bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunogenicity and Safety of a Purified Vero Rabies Vaccine—Serum Free, Compared With 2 Licensed Vaccines, in a Simulated Rabies Post-Exposure Regimen in Healthy Adults in France: A Randomized, Controlled, Phase 3 Trial
Authors: Pineda-Peña Andrea-Clemencia , Jiang Qian , Petit Celine , Korejwo-Peyramond Joanna , Donazzolo Yves , Latreille Mathilde , Homery Marie-Claude , Babin Valerie , Benamor Sonia , Pichon Sylvie , Guinet-Morlot Françoise , Minutello Ada-Maria 
Published: March 2024

Abstract

Background
A next-generation Vero cell rabies vaccine (PVRV-NG2) was developed using the same Pitman–Moore strain as in the licensed purified Vero cell vaccine (PVRV; Verorab) and the human diploid cell vaccine (HDCV; Imovax Rabies®).

Methods
This dual-center, modified, double-blind, phase 3 study evaluated the immunogenic non-inferiority and safety of PVRV-NG2 with and without concomitant intramuscular human rabies immunoglobulin (HRIG) versus PVRV + HRIG and HDCV + HRIG in a simulated post-exposure prophylaxis (PEP) regimen. Healthy adults ≥18 years old (N = 640) were randomized 3:1:1:1 to PVRV-NG2 + HRIG, PVRV + HRIG, HDCV + HRIG, or PVRV-NG2 alone (administered as single vaccine injections on days [D] 0, D3, D7, D14, and 28, with HRIG on D0 in applicable groups). Rabies virus neutralizing antibodies (RVNA) titers were assessed pre- (D0) and post-vaccination (D14, D28, and D42) using the rapid fluorescent focus inhibition test. Non-inferiority, based on the proportion of participants achieving RVNA titers ≥0.5 IU/mL (primary objective), was demonstrated if the lower limit of the 95% CI of the difference in proportions between PVRV-NG2 + HRIG and PVRV + HRIG/HDCV + HRIG was &gt;−5% at D28. Safety was assessed up to 6 months after the last injection.

Results
Non-inferiority of PVRV-NG2 + HRIG compared with PVRV + HRIG and HDCV + HRIG was demonstrated. Nearly all participants (99.6%, PVRV-NG2 + HRIG; 100%, PVRV + HRIG; 98.7%, HDCV + HRIG; 100%, PVRV-NG2 alone) achieved RVNA titers ≥0.5 IU/mL at D28. Geometric mean titers were similar between groups with concomitant HRIG administration at all time points. Safety profiles were similar between PVRV-NG2 and comparator vaccines.

Conclusions
In a simulated PEP setting, PVRV-NG2 + HRIG showed comparable immunogenicity and safety to current standard-of-care vaccines.

Clinical Trials Registration
NCT03965962.
Simulation-based learning in nephrology
Authors: Maisons Valentin , Lanot Antoine , Luque Yosu , Sautenet Benedicte , Esteve Emmanuel , Guillouet Erwan , François Hélène , Bobot Mickaël 
Published: March 2024

ABSTRACT
Simulation is a technique to replace and amplify real experiences with guided ones that evoke or replicate substantial aspects of the real world in a fully interactive fashion. In nephrology (a particularly complex specialty), simulation can be used by patients, nurses, residents, and attending physicians alike. It allows one to learn techniques outside the stressful environment of care such as central venous catheter placement, arteriovenous fistula management, learning about peritoneal dialysis, or performing a kidney biopsy. Serious games and virtual reality are emerging methods that show promise. Simulation could also be important in relational aspects of working in a team or with the patient. The development of simulation as a teaching tool in nephrology allows for maintaining high-quality training for residents, tailored to their future practice, and minimizing risks for patients. Additionally, this education helps nephrologists maintain mastery of technical procedures, making the specialty attractive to younger generations. Unfortunately, the inclusion of simulation training programmes faces occasional logistical or funding limitations that universities must overcome with the assistance and innovation of teaching nephrologists. The impact of simulation-based teaching on clinical outcomes needs to be investigated in clinical studies.
Poor in-hospital congestion improvement in acute heart failure patients classified according to left ventricular ejection fraction: prognostic implications
Authors: Ruocco Gaetano , Girerd Nicolas , Rastogi Tripti , Lamiral Zohra , Palazzuoli Alberto 
Published: March 2024

Abstract

Aims
Residual congestion in acute heart failure (AHF) is associated with poor prognosis. However, there is a lack of data on the prognostic value of changes in a combined assessment of in-hospital congestion. The present study sought to assess the association between in-hospital congestion changes and subsequent prognosis according to left ventricular ejection fraction (LVEF) classification.

Methods and results
Patients (N = 244, 80.3 ± 7.6 years, 50.8% male) admitted for acute HF in two European tertiary care centres underwent clinical assessment (congestion score included dyspnoea at rest, rales, third heart sound, jugular venous distention, peripheral oedema, and hepatomegaly; simplified congestion score included rales and peripheral oedema), echocardiography, lung ultrasound, and natriuretic peptides (NP) measurement at admission and discharge. The primary outcome was a composite of all-cause mortality and/or HF re-hospitalization. In the 244 considered patients (95 HF with reduced EF, 57 HF with mildly reduced EF, and 92 HF with preserved EF), patients with limited improvement in clinical congestion score (hazard ratio 2.33, 95% CI 1.51–3.61, P = 0.0001), NP levels (2.29, 95% CI 1.55–3.38, P &lt; 0.0001), and the number of B-lines (6.44, 95% CI 4.19–9.89, P &lt; 0.001) had a significantly higher risk of outcome compared with patients experiencing more sizeable decongestion. The same pattern of association was observed when adjusting for confounding factors. A limited improvement in clinical congestion score and in the number of B-lines was related to poor prognosis for all LVEF categories.

Conclusion
In AHF, the degree of congestion reduction assessed over the in-hospital stay period can stratify the subsequent event risk. Limited reduction in both clinical congestion and B-lines number are related to poor prognosis, irrespective of HF subtype.
Cost-effectiveness of low-dose colchicine in patients with chronic coronary disease in The Netherlands
Authors: Fiolet Aernoud T L , Keusters Willem , Blokzijl Johan , Nidorf S Mark , Eikelboom John W , Budgeon Charley A , Tijssen Jan G P , Römer Tjeerd , Westendorp Iris , Cornel Jan Hein , Thompson Peter L , Frederix Geert W J , Mosterd Arend , de Wit G Ardine 
Published: March 2024

Abstract

Aims
Recent trials have shown that low-dose colchicine (0.5 mg once daily) reduces major cardiovascular events in patients with acute and chronic coronary syndromes. We aimed to estimate the cost-effectiveness of low-dose colchicine therapy in patients with chronic coronary disease when added to standard background therapy.

Methods and results
This Markov cohort cost-effectiveness model used estimates of therapy effectiveness, transition probabilities, costs, and quality of life obtained from the Low-Dose Colchicine 2 trial, as well as meta-analyses and public sources. In this trial, low-dose colchicine was added to standard of care and compared with placebo. The main outcomes were cardiovascular events, including myocardial infarction, stroke, and coronary revascularization, quality-adjusted life year (QALY), the cost per QALY gained (incremental cost-effectiveness ratio), and net monetary benefit. In the model, low-dose colchicine therapy yielded 0.04 additional QALYs compared with standard of care at an incremental cost of €455 from a societal perspective and €729 from a healthcare perspective, resulting in a cost per QALY gained of €12 176/QALY from a societal perspective and €19 499/QALY from a healthcare perspective. Net monetary benefit was €1414 from a societal perspective and €1140 from a healthcare perspective. Low-dose colchicine has a 96 and 94% chance of being cost-effective, from a societal and a healthcare perspective, respectively, when using a willingness to pay of €50 000/QALY. Net monetary benefit would decrease below zero when annual low-dose colchicine costs would exceed an annual cost of €221 per patient.

Conclusion
Adding low-dose colchicine to standard of care in patients with chronic coronary disease is cost-effective according to commonly accepted thresholds in Europe and Australia and compares favourably in cost-effectiveness to other drugs used in chronic coronary disease.
The ‘People’s War’ in Concrete and Stone: Death and the Negotiation of Collective Identity in Second World War Britain
Authors: Noakes Lucy 
Published: March 2024

Abstract
This article explores ideas and feelings about the burial of the war’s dead, and their memorialisation. It investigates the relationship between a drive to remember the conflict’s dead as members of the collective wartime nation, and a desire by many of the bereaved to emphasise familial ties and the individual lives of the dead. While this was not a new concern—and had already been seen, for example, in debates about where to bury, and how to commemorate, the dead of the First World War in Britain—it gained an additional politics in the Second World War. In this conflict, ideas about the nation, about the state’s duty to its citizens and about citizens’ reciprocal duties towards the wartime state were interwoven with ideas about domestic reconstruction in the war’s aftermath. This article traces the articulation of these ideas through contemporary discussions of, and feelings about, burial and memorialisation, using these as a means of thinking about the meaning of the ‘people’s war’ both during and after the conflict.
Comparing climate pledges and eco-taxation in a networked agricultural supply chain organisation
Authors: Dragicevic Arnaud Z , Pereau Jean-Christophe 
Published: March 2024

Abstract
This paper examines the effectiveness of climate pledges and eco-taxation as strategies for mitigating climate change within a networked agricultural supply chain organisation. We utilise variational inequality techniques within a multicriteria decision-making framework and validate our theoretical findings through numerical simulations using a machine learning augmented algorithm. By employing this approach, we position the Agricultural Sector Roadmap, aimed at capping global warming at 1.5°C, within the wider agricultural sector’s climate action framework. Our results demonstrate that environmental taxation emerges as the most effective approach for addressing climate change. Eco-taxation leads to a 57.87 per cent reduction in global emissions, whereas climate pledges only account for a 20.59 per cent reduction at the same level of production. Furthermore, eco-taxation results in a 45.68 per cent greater reduction in emission intensity compared to climate pledges. In contrast to climate commitments, an eco-fiscal policy is capable of achieving the objectives established by the European Union.
Identifying risk factors for developing obesity: a record linkage longitudinal study in metropolitan Sydney using the 45 and Up Study
Authors: Vuong Kylie , Kabir Alamgir , Conway Damian P , Williamson Margaret , Harris Mark F , Barr Margo L 
Published: March 2024

Abstract

Background
Primary care clinicians have key responsibilities in obesity prevention and weight management.

Aims
We aimed to identify risk factors for developing obesity among people aged ≥45 years.

Methods
We conducted a record linkage longitudinal study of residents of metropolitan Sydney, Australia using data from the: (1) 45 and Up Study at baseline (2005–2009) and first follow-up (2012–2015); (2) Medicare claims; (3) Pharmaceutical Benefits Scheme; and (4) deaths registry. We examined risk factors for developing obesity (body mass index [BMI]: 30–40) at follow-up, separately for people within the: (1) healthy weight range (BMI 18.5–&lt;25) and (2) overweight range (BMI 25–&lt;30) at baseline. Covariates included demographics, modifiable behaviours, health status, allied health use, and medication use. Crude and adjusted relative risks were estimated using Poisson regression modelling.

Results
At follow-up, 1.1% (180/16,205) of those in the healthy weight range group, and 12.7% (1,939/15,266) of those in the overweight range group developed obesity. In both groups, the following were associated with developing obesity: current smoking at baseline, physical functioning limitations, and allied health service use through team care planning, while any alcohol consumption and adequate physical activity were found to be associated with a lower risk of developing obesity. In the healthy weight group, high psychological distress and the use of antiepileptics were associated with developing obesity. In the overweight group, female sex and full-time work were associated with developing obesity, while older age was found to be associated with a lower risk of developing obesity.

Conclusions
These findings may inform the targeting of preventive interventions for obesity in clinical practice and broader public health programs.
The Role of Foreign Aid in Procuring Civil War Party Consent to Peacekeeping
Authors: Karreth Johannes , Passmore Timothy J A , Tir Jaroslav 
Published: March 2024

Abstract
Successful peacekeeping depends heavily on the conflict parties providing unrestricted consent to the intervention. Consent is, however, often withheld or limited by one or more parties who calculate a higher cost to peace than to continued fighting. We highlight the role of international economic incentives in the form of foreign development aid in overcoming hurdles to obtaining consent. We argue that past aid sends a credible signal of future, post-conflict material benefits if the belligerents work toward peace. This conditionality of future benefits thereby incentivizes the belligerents to work toward peace and stability, including providing unrestricted consent to peacekeeping missions. Analyses of 119 post-Cold War civil wars and a brief narrative of East Timor demonstrate that foreign aid significantly and substantially increases the likelihood of unrestricted consent. The findings have implications for the literature on international influences on domestic political contestation and for research on the effectiveness of peacekeeping operations.
Mapping of DDX11 genetic interactions defines sister chromatid cohesion as the major dependency
Authors: Amitzi Leanne , Cozma Ecaterina , Tong Amy Hin Yan , Chan Katherine , Ross Catherine , O’Neil Nigel , Moffat Jason , Stirling Peter , Hieter Philip 
Published: March 2024

Abstract
DDX11/Chl1R is a conserved DNA helicase with roles in genome maintenance, DNA replication, and chromatid cohesion. Loss of DDX11 in humans leads to the rare cohesinopathy Warsaw breakage syndrome. DDX11 has also been implicated in human cancer where it has been proposed to have an oncogenic role and possibly to constitute a therapeutic target. Given the multiple roles of DDX11 in genome stability and its potential as an anticancer target, we set out to define a complete genetic interaction profile of DDX11 loss in human cell lines. Screening the human genome with clustered regularly interspaced short palindromic repeats (CRISPR) guide RNA drop out screens in DDX11-wildtype (WT) or DDX11-deficient cells revealed a strong enrichment of genes with functions related to sister chromatid cohesion. We confirm synthetic lethal relationships between DDX11 and the tumor suppressor cohesin subunit STAG2, which is frequently mutated in several cancer types and the kinase HASPIN. This screen highlights the importance of cohesion in cells lacking DDX11 and suggests DDX11 may be a therapeutic target for tumors with mutations in STAG2.
The MAB-5/Hox family transcription factor is important for Caenorhabditis elegans innate immune response to Staphylococcus epidermidis infection
Authors: Kywe Christopher , Lundquist Erik A , Ackley Brian D , Lansdon Patrick 
Published: March 2024

Abstract
Innate immunity functions as a rapid defense against broad classes of pathogenic agents. While the mechanisms of innate immunity in response to antigen exposure are well-studied, how pathogen exposure activates the innate immune responses and the role of genetic variation in immune activity is currently being investigated. Previously, we showed significant survival differences between the N2 and the CB4856 Caenorhabditis elegans isolates in response to Staphylococcus epidermidis infection. One of those differences was expression of the mab-5 Hox family transcription factor, which was induced in N2, but not CB4856, after infection. In this study, we use survival assays and RNA-sequencing to better understand the role of mab-5 in response to S. epidermidis. We found that mab-5 loss-of-function (LOF) mutants were more susceptible to S. epidermidis infection than N2 or mab-5 gain-of-function (GOF) mutants, but not as susceptible as CB4856 animals. We then conducted transcriptome analysis of infected worms and found considerable differences in gene expression profiles when comparing animals with mab-5 LOF to either N2 or mab-5 GOF. N2 and mab-5 GOF animals showed a significant enrichment in expression of immune genes and C-type lectins, whereas mab-5 LOF mutants did not. Overall, gene expression profiling in mab-5 mutants provided insight into MAB-5 regulation of the transcriptomic response of C. elegans to pathogenic bacteria and helps us to understand mechanisms of innate immune activation and the role that transcriptional regulation plays in organismal health.
Where Are the Formerly Y-linked Genes in the Ryukyu Spiny Rat that has Lost its Y Chromosome?
Authors: Li Jiachen , Song Siliang , Zhang Jianzhi 
Published: March 2024

Abstract
It has been predicted that the highly degenerate mammalian Y chromosome will be lost eventually. Indeed, Y was lost in the Ryukyu spiny rat Tokudaia osimensis, but the fate of the formerly Y-linked genes is not completely known. We looked for all 12 ancestrally Y-linked genes in a draft T. osimensis genome sequence. Zfy1, Zfy2, Kdm5d, Eif2s3y, Usp9y, Uty, and Ddx3y are putatively functional and are now located on the X chromosome, whereas Rbmy, Uba1y, Ssty1, Ssty2, and Sry are missing or pseudogenized. Tissue expressions of the mouse orthologs of the retained genes are significantly broader/higher than those of the lost genes, suggesting that the destinies of the formerly Y-linked genes are related to their original expressions. Interestingly, patterns of gene retention/loss are significantly more similar than by chance across four rodent lineages where Y has been independently lost, indicating a level of certainty in the fate of Y-linked genes even when the chromosome is gone.
Associations Between Depression Symptom Burden and Delirium Risk: A Prospective Cohort Study
Authors: Gaba Arlen , Li Peng , Zheng Xi , Gao Chenlu , Cai Ruixue , Hu Kun , Gao Lei 
Published: March 2024

Abstract

Background and Objectives
Delirium and depression are prevalent in aging. There is considerable clinical overlap, including shared symptoms and comorbid conditions, including Alzheimer’s disease, functional decline, and mortality. Despite this, the long-term relationship between depression and delirium remains unclear. This study assessed the associations of depression symptom burden and its trajectory with delirium risk in a 12-year prospective study of older hospitalized individuals.

Research Design and Methods
A total of 319 141 UK Biobank participants between 2006 and 2010 (mean age 58 years [range 37–74, SD = 8], 54% women) reported frequency (0–3) of 4 depressive symptoms (mood, disinterest, tenseness, or lethargy) in the preceding 2 weeks prior to initial assessment visit and aggregated into a depressive symptom burden score (0–12). New-onset delirium was obtained from hospitalization records during 12 years of median follow-up. 40 451 (mean age 57 ± 8; range 40–74 years) had repeat assessment on average 8 years after their first visit. Cox proportional hazard models examined whether depression symptom burden and trajectory predicted incident delirium.

Results
A total of 5 753 (15 per 1 000) newly developed delirium during follow-up. Increased risk for delirium was seen for mild (aggregated scores 1–2, hazards ratio, HR = 1.16, [95% confidence interval (CI): 1.08–1.25], p &lt; .001), modest (scores 3–5, 1.30 [CI: 1.19–1.43], p &lt; .001), and severe (scores ≥ 5, 1.38 [CI: 1.24–1.55], p &lt; .001) depressive symptoms, versus none in the fully adjusted model. These findings were independent of the number of hospitalizations and consistent across settings (eg, surgical, medical, or critical care) and specialty (eg, neuropsychiatric, cardiorespiratory, or other). Worsening depression symptoms (≥1 point increase), compared to no change/improved score, were associated with an additional 39% increased risk (1.39 [1.03–1.88], p = .03) independent of baseline depression burden. The association was strongest in those over 65 years at baseline (p for interaction &lt;.001).

Discussion and Implications
Depression symptom burden and worsening trajectory predicted delirium risk during hospitalization. Increased awareness of subclinical depression symptoms may aid delirium prevention.
Examining the Role of Self-Harm in the Relationship between Emergency Department Service Utilization and Trauma-Induced Homelessness among Homeless Individuals in Texas
Authors: Choudhury Sumaita , Choi Sharon Lee , Lee Yehyang , Manser Stacey Stevens 
Published: March 2024

Abstract
Homelessness is a complex public health problem in the United States. Current or ongoing history of trauma among individuals adds to the complexity and challenges of homelessness. Our study assessed the moderating role of self-harm in the association between emergency department (ED) service utilization and trauma-induced homelessness (TIH) among adults in Texas. Homeless adults (N = 282) who completed their baseline Vulnerability Index Service Prioritization Decision Assistance Prescreen Tool survey between February 2021 and February 2022 at a Local Mental Health Authority in Texas were selected. The outcome variable, TIH, was assessed by current period of homelessness due to experiencing trauma or abuse. The main independent variable was ED utilization, while self-harm in the past year was assessed as the moderating variable. A multivariate logistic regression with a moderation analysis was conducted while adjusting for the covariates. Individuals who utilized ED services and engaged in self-harm and risky behaviors had greater odds of experiencing current period of TIH. Male respondents were less likely to experience TIH. Finally, engaging in self-harm significantly moderated the association between ED service use and TIH. This study may help inform efforts to develop tailored interventions and promote resilience-based approaches to improve health outcomes among individuals experiencing homelessness due to TIH.