bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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 < 0.0001), and the number of B-lines (6.44, 95% CI 4.19–9.89, P < 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

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

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

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

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–<25) and (2) overweight range (BMI 25–<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

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

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

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

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

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 < .001), modest (scores 3–5, 1.30 [CI: 1.19–1.43], p < .001), and severe (scores ≥ 5, 1.38 [CI: 1.24–1.55], p < .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 <.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

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.
Attenuation of Colitis-Induced Visceral Hypersensitivity and Pain by Selective Silencing of TRPV1-Expressing Fibers in Rat Colon
Authors: Mazor Yoav , Engelmayer Nurit , Nashashibi Halla , Rottenfußer Lisa , Lev Shaya , Binshtok Alexander M
Published: March 2024

Background

Transient receptor potential vanilloid 1 (TRPV1) cation channels, expressed on nociceptors, are well established as key contributors to abdominal pain in inflammatory bowel disease (IBD). Previous attempts at blocking these channels have been riddled with side effects. Here, we propose a novel treatment strategy, utilizing the large pore of TRPV1 channels as a drug delivery system to selectively inhibit visceral nociceptors.

Methods

We induced colitis in rats using intrarectal dinitrobenzene sulfonic acid. Visceral hypersensitivity, spontaneous pain, and responsiveness of the hind paws to noxious heat stimuli were examined before and after the intrarectal application of membrane-impermeable sodium channel blocker (QX-314) alone or together with TRPV1 channel activators or blockers.

Results

Intrarectal co-application of QX-314 with TRPV1 channel activator capsaicin significantly inhibited colitis-induced gut hypersensitivity. Furthermore, in the model of colitis, but not in naïve rats, QX-314 alone was sufficient to reverse gut hypersensitivity. The blockade of TRPV1 channels prevented this effect of QX-314. Finally, applying QX-314 alone to the inflamed gut inhibited colitis-induced ongoing pain.

Conclusions

Selective silencing of gut nociceptors by a membrane-impermeable sodium channel blocker entering via exogenously or endogenously activated TRPV1 channels diminishes IBD-induced gut hypersensitivity. The lack of effect on naïve rats suggests a selective analgesic effect in the inflamed gut. Our results suggest that in the colitis model, TRPV1 channels are tonically active. Furthermore, our results emphasize the role of TRPV1-expressing nociceptive fibers in colitis-induced pain. These findings provide proof of concept for using charged activity blockers for the blockade of IBD-associated abdominal pain.
Awake sternal fixation; comparison of technical details and early results with sternal fixation methods performed via general anaesthesia
Authors: Gurz Selcuk , Dost Burhan , Pirzirenli Mehmet Gokhan , Buyukkarabacak Yasemin , Taslak Sengul Aysen , Kaya Cengiz , Temel Necmiye Gul , Ozdemir Emine , Basoglu Ahmet
Published: March 2024

OBJECTIVES

Isolated sternal fractures are rare pathologies that rarely require surgical fixation. Although different fixation techniques are used, it is routinely performed under general anaesthesia. In our study, we aimed to share the details of the awake sternal fixation technique performed in our clinic and to compare the early results with sternal fixation methods performed under general anaesthesia.

METHODS

Between January 2009 and January 2023, 129 patients who were diagnosed with sternal fracture and who underwent investigations and follow-up in our clinic were evaluated retrospectively. Thirteen patients who underwent surgical fixation for isolated sternal fracture were included in the study. Patients were categorized according to fixation and anaesthetic technique; group 1: fixation with steel wire under general anaesthesia (n = 4), group 2: fixation with titanium plate–screw under general anaesthesia (n = 4) and group 3: fixation with awake titanium plate–screw with parasternal intercostal plane block (n = 5). Demographics, surgical indication, radiological findings, surgical incision, surgical time and hospital stay were statistically compared.

RESULTS

The mean age of the patients included in the study was 55.15 ± 15.01 years and 84.6% (n = 11) were male. The most common reason for fixation was displaced fracture (53.8%). Fixation surgery was performed due to pain in 30.8% (n = 4) and non-union in 15.4% (n = 2) of the fractures. The mean duration of surgery were 98.75 ± 16.52, 77.5 ± 35 and 41 ± 14.74 min, respectively. Duration of surgery was significantly lower in group 3 compared to the other groups (P = 0.012). The hospital stay duration for group 1 was 6 days, group 2 was 4 days and group 3 was 1 day. A notable difference was observed among all groups (P = 0.019).

CONCLUSIONS

Awake sternal fixation technique with titanium plate–screw system under superficial parasternal intercostal plane block is an easy and effective method for surgical treatment of isolated sternal fractures. This technique showed a direct positive effect on the duration of surgery and hospital stay.
Risk of infective endocarditis after hybrid melody mitral valve replacement in infants: the French experience
Authors: Padovani Paul , Jalal Zakaria , Fouilloux Virginie , Benbrik Nadir , Grunenwald Céline , Thambo Jean-Benoit , Aldebert Philippe , Tagorti Maha , Roubertie François , Baron Olivier , Ovaert Caroline , Ly Mohamedou , Baruteau Alban-Elouen
Published: March 2024

OBJECTIVES

Surgical management of mitral valve disease is challenging in infants <1 year old. We aimed at reviewing the French experience with Melody mitral valve replacement in critically ill infants.

METHODS

A retrospective cohort study reporting the French experience with Melody mitral valve replacement.

RESULTS

Seven symptomatic infants [complete atrioventricular septal defect (n = 4, Down syndrome: n = 3), hammock valve (n = 3)] underwent Melody mitral valve replacement [age: 3 months (28 days to 8 months), weight: 4.3 kg (3.2–6.4 kg)] because of severe mitral valve regurgitation (6) or mixed valve disease (1) and 14 mm (11–16 mm) mitral valve annulus. In 2 patients whose valve was felt irreparable, Melody mitral valve replacement was performed straightaway. The others underwent 2 (1–3) previous attempts of valve repair; 3 were on extracorporeal membrane oxygenation. Melody mitral valve replacement led to competent valve and low gradient [3 mmHg, (1–4 mmHg)]. One patient died 3 days post-implant from extracorporeal membrane oxygenation-related stroke. Of the 6 discharged home patients, 3 (50%) were readmitted for a definite diagnosis (1) or high suspicion (2) of infective endocarditis, of which 2 died. Over the follow-up, 1 underwent balloon expansions of the valve at 9- and 16-months post-implant, and mechanical mitral valve replacement at 2 years; another is currently planned for transcatheter Melody valve dilation.

CONCLUSIONS

Melody mitral valve replacement may be considered in selected infants with small mitral valve annulus as an alternative to mechanical mitral valve replacement. Our experience highlights a high-risk of late infective endocarditis that deserves further consideration.
Protective Role of NS1-Specific Antibodies in the Immune Response to Dengue Virus Through Antibody-Dependent Cellular Cytotoxicity
Authors: Sanchez-Vargas Luis A , Mathew Anuja , Salje Henrik , Sousa David , Casale Nicole A , Farmer Aaron , Buddhari Darunee , Anderson Kathryn , Iamsirithaworn Sopon , Kaewhiran Surachai , Friberg Heather , Currier Jeffrey R , Rothman Alan L
Published: March 2024

Background

Dengue virus (DENV) nonstructural protein 1 (NS1) has multiple functions within infected cells, on the cell surface, and in secreted form, and is highly immunogenic. Immunity from previous DENV infections is known to exert both positive and negative effects on subsequent DENV infections, but the contribution of NS1-specific antibodies to these effects is incompletely understood.

Methods

We investigated the functions of NS1-specific antibodies and their significance in DENV infection. We analyzed plasma samples collected in a prospective cohort study prior to symptomatic or subclinical secondary DENV infection. We measured binding to purified recombinant NS1 protein and to NS1-expressing CEM cells, antibody-mediated natural killer (NK) cell activation by plate-bound NS1 protein, and antibody-dependent cellular cytotoxicity (ADCC) of NS1-expressing target cells.

Results

We found that antibody responses to NS1 were highly serotype cross-reactive and that subjects who experienced subclinical DENV infection had significantly higher antibody responses to NS1 in preinfection plasma than subjects who experienced symptomatic infection. We observed strong positive correlations between antibody binding and NK activation.

Conclusions

These findings demonstrate the involvement of NS1-specific antibodies in ADCC and provide evidence for a protective effect of NS1-specific antibodies in secondary DENV infection.
Application of a user experience design approach for an EHR-based clinical decision support system
Authors: Gao Emily , Radpavar Ilana , Clark Emma J , Ryan Gery W , Ross Mindy K
Published: March 2024

Objective

We applied a user experience (UX) design approach to clinical decision support (CDS) tool development for the specific use case of pediatric asthma. Our objective was to understand physicians’ workflows, decision-making processes, barriers (ie, pain points), and facilitators to increase usability of the tool.

Materials and methods

We used a mixed-methods approach with semi-structured interviews and surveys. The coded interviews were synthesized into physician-user journey maps (ie, visualization of a process to accomplish goals) and personas (ie, user types). Interviews were conducted via video. We developed physician journey maps and user personas informed by their goals, systems interactions, and experiences with pediatric asthma management.

Results

The physician end-user personas identified were: efficiency, relationship, and learning. Features of a potential asthma CDS tool sought varied by physician practice type and persona. It was important to the physician end-user that the asthma CDS tool demonstrate value by lowering workflow friction (ie, difficulty or obstacles), improving the environment surrounding physicians and patients, and using it as a teaching tool. Customizability versus standardization were important considerations for uptake.

Discussion

Different values and motivations of physicians influence their use and interaction with the EHR and CDS tools. These different perspectives can be captured by applying a UX design approach to the development process. For example, with the importance of customizability, one approach may be to build a core module with variations depending on end-user preference.

Conclusion

A UX approach can drive design to help understand physician-users and meet their needs; ultimately with the goal of increased uptake.
Parental betaine supplementation promotes gosling growth with epigenetic modulation of IGF gene family in the liver
Authors: Ma Shuai , Wang Yan , Chen Liang , Wang Wenzheng , Zhuang Xinjuan , Liu Yuelong , Zhao Ruqian
Published: March 2024

Betaine is widely used as a feed additive in the chicken industry to promote laying performance and growth performance, yet it is unknown whether betaine can be used in geese to improve the laying performance of goose breeders and the growth traits of offspring goslings. In this study, laying goose breeders at 39 wk of age were fed basal (Control, CON) or betaine-supplemented diets at low (2.5 g/kg, LBT) or high (5 g/kg, HBT) levels for 7 wk, and the breeder eggs laid in the last week were collected for incubation. Offspring goslings were examined at 35 and 63 d of age. The laying rate tended to be increased (P = 0.065), and the feed efficiency of the breeders was improved by betaine supplementation, while the average daily gain of the offspring goslings was significantly increased (P < 0.05). Concentrations of insulin-like growth factor 2 (IGF-2) in serum and liver were significantly increased in the HBT group (P < 0.05), with age-dependent alterations of serum T3 levels. Concurrently, hepatic mRNA expression of the IGF gene family was significantly increased in goslings derived from betaine-treated breeders (P < 0.05). A higher ratio of proliferating cell nuclear antigen (PCNA)-immunopositive nuclei was found in the liver sections of the HBT group, which was confirmed by significantly upregulated hepatic expression of PCNA mRNA and protein (P < 0.05). Moreover, hepatic expression of thyroxine deiodinase type 1 (Dio1) and thyroid hormone receptor β (TRβ) was also significantly upregulated in goslings of the HBT group (P < 0.05). These changes were associated with significantly higher levels of global DNA 5-mC methylation, together with increased expression of methyl transfer genes (P < 0.05), including betaine-homocysteine methyltransferase (BHMT), glycine N-methyltransferase (GNMT), and DNA (cytosine-5-)-methyltransferase 1 (DNMT1). The promoter regions of IGF-2 genes, as well as the predicted TRβ binding site on the IGF-2 gene, were significantly hypomethylated (P < 0.05). These results indicate that gosling growth can be improved by dietary betaine supplementation in goose breeders via epigenetic modulation of the IGF gene family, especially IGF-2, in the liver.
Management of Outpatient Pediatric Burns at a Pediatric Burn Center
Authors: Bostancı Süleyman Arif , Demir Sabri , Ertürk Ahmet , Demirtaş Gökhan , Öztorun Can İhsan , Güney Doğuş , Demirkaya Şükrüye , Erten Elif Emel , Azılı Müjdem Nur , Şenel Emrah
Published: March 2024

Burn injuries are a serious emergency. Most burn injuries in children can be treated as outpatients. The aim of this study was to present the clinical and epidemiologic characteristics of pediatric burn injuries treated in our outpatient burn clinic. This study included pediatric patients treated in an outpatient burn clinic over an 8-year period. The demographic and clinical characteristics of the patients were retrospectively analyzed. The patients were divided into 4 groups according to their age groups, and the differences between the groups were investigated. Statistical analysis was performed using IBM SPSS Statistics, Version 25.0. P < .05 was accepted as statistically significant. Of the total 5167 patients, 2811 (54.4%) were male. Scald burns were the most common cause of burns (81.4%). Contact burns accounted for 12.2% of all burns. There were no differences between sexes for any variable. The highest incidence was seen in children in the 2- to 5-year-old age group (28.3%). There were differences between age groups in terms of sex, burn area, burn visit, burn type, burn location, need for wound dressing under anesthesia, and need for grafting. Among the patients, 4.9% were hospitalized due to the need for wound dressing under anesthesia. However, most of the patients (95.1%) were treated as outpatients. In conclusion, the majority of pediatric burn patients can be treated as outpatients. This allows pediatric patients to complete treatment in a psychologically comfortable environment and has low complication rates. Outpatient treatment should become the standard for children who are suitable for outpatient follow-up and who have home support.
Data-driven multivariate regression-based anomaly detection and recovery of unmanned aerial vehicle flight data
Authors: Yang Lei , Li Shaobo , Li Chuanjiang , Zhu Caichao
Published: March 2024

Flight data anomaly detection is crucial for ensuring the safe operation of unmanned aerial vehicles (UAVs) and has been extensively studied. However, the accurate modeling and analysis of flight data is challenging due to the influence of random noise. Meanwhile, existing methods are often inadequate in parameter selection and feature extraction when dealing with large-scale and high-dimensional flight data. This paper proposes a data-driven multivariate regression-based framework considering spatio-temporal correlation for UAV flight data anomaly detection and recovery, which integrates the techniques of correlation analysis (CA), one-dimensional convolutional neural network and long short-term memory (1D CNN-LSTM), and error filtering (EF), named CA-1DCL-EF. Specifically, CA is first performed on original UAV flight data to select parameters with correlation to reduce the model input and avoid the negative impact of irrelevant parameters on the model. Next, a regression model based on 1D CNN-LSTM is designed to fully extract the spatio-temporal features of UAV flight data and realize parameter mapping. Then, to overcome the effect of random noise, a filtering technique is introduced to smooth the errors to improve the anomaly detection performance. Finally, two common anomaly types are injected into real UAV flight datasets to verify the effectiveness of the proposed method.
Sensitivity analysis for the generalization of experimental results
Authors: Huang Melody Y
Published: March 2024

Randomized controlled trials (RCT’s) allow researchers to estimate causal effects in an experimental sample with minimal identifying assumptions. However, to generalize or transport a causal effect from an RCT to a target population, researchers must adjust for a set of treatment effect moderators. In practice, it is impossible to know whether the set of moderators has been properly accounted for. I propose a two parameter sensitivity analysis for generalizing or transporting experimental results using weighted estimators. The contributions in the article are threefold. First, I show that the sensitivity parameters are scale-invariant and standardized, and introduce an estimation approach for researchers to account for both bias in their estimates from omitting a moderator, as well as potential changes to their inference. Second, I propose several tools researchers can use to perform sensitivity analysis: (1) numerical measures to summarize the uncertainty in an estimated effect to omitted moderators; (2) graphical summary tools to visualize the sensitivity in estimated effects; and (3) a formal benchmarking approach for researchers to estimate potential sensitivity parameter values using existing data. Finally, I demonstrate that the proposed framework can be easily extended to the class of doubly robust, augmented weighted estimators.
Nodulating another way: what can we learn from lateral root base nodulation in legumes?
Authors: Horta Araújo Natasha , Nouwen Nico , Arrighi Jean-François
Published: March 2024

To improve our understanding of how legumes interact with nitrogen-fixing rhizobia, we highlight the importance of studying an original lateral root base nodulation process present in certain legumes.
Seeing and turbulence profile simulations over complex terrain at the Thai National Observatory using a chemistry-coupled regional forecasting model
Authors: Macatangay Ronald , Rattanasoon Somsawatt , Butterley Timothy , Bran Sherin Hassan , Sonkaew Thiranan , Sukaum Boonchoo , Sookjai Donrudee , Panya Mana , Supasri Titaporn
Published: March 2024

This study utilized advanced numerical simulations with the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) to predict anticipated astronomical seeing conditions at the Thai National Observatory (TNO). The study evaluated the effects of both gas-phase and aerosol-phase chemical processes in the Earth’s atmosphere, along with the impact of spatial and temporal resolution on model performance. These simulations were validated against measurements from the Differential Image Motion Monitor (DIMM) and the Slope Detection and Ranging (SLODAR) technique. Due to the inherent temporal variability of the DIMM observations, a 24-h moving average window was applied to both DIMM data and WRF-Chem model outputs. This reduced the percentage root-mean-square error in the comparison between the two data sets from 23 per cent to 11 per cent and increased the correlation coefficient from 0.21 to 0.59. Chemistry played a minor role during the study period, contributing 3.49 per cent to astronomical seeing. However, it did affect the model’s accuracy. Additionally, the study revealed that higher spatial and temporal resolution simulations did not necessarily improve the model’s accuracy. When compared to SLODAR observations of the refractive index structure constant (Cn2dh), the simulations captured altitude variations within ±25 per cent above 5 km and 25–50 per cent below 5 km. Dome seeing also played a role, contributing to around 90 per cent or more in the lowest altitude layer. The results emphasized the significance of seeing predictions in providing valuable insights into complex atmospheric phenomena and how to mitigate the effects of atmospheric turbulence on telescopes.
A dependable distance estimator to black hole low-mass X-ray binaries
Authors: Abdulghani Y , Lohfink A M , Chauhan J
Published: March 2024

Black hole low-mass X-ray binaries (BH-LMXBs) are excellent observational laboratories for studying many open questions in accretion physics. However, determining the physical properties of BH-LMXBs necessitates knowing their distances. With the increased discovery rate of BH-LMXBs, many canonical methods cannot produce accurate distance estimates at the desired pace. In this study, we develop a versatile statistical framework to obtain robust distance estimates soon after discovery. Our framework builds on previous methods where the soft spectral state and the soft-to-hard spectral state transitions, typically present in an outbursting BH-LMXB, are used to place constraints on mass and distance. We further develop the traditional framework by incorporating general relativistic corrections, accounting for spectral/physical parameter uncertainties, and employing assumptions grounded in current theoretical and observational knowledge. We tested our framework by analysing a sample of 50 BH-LMXB sources using X-ray spectral data from the Swift/XRT, MAXI/GSC, and RXTE/PCA missions. By modelling their spectra, we applied our framework to 26 sources from the 50. Comparison of our estimated distances to previous distance estimates indicates that our findings are dependable and in agreement with the accurate estimates obtained through parallax and H i absorption methods. Investigating the accuracy of our constraints, we have found that estimates obtained using both the soft and transition spectral information have a median uncertainty (1σ) of 20 per cent, while estimates obtained using only the soft spectral state spectrum have a median uncertainty (1σ) of around 50 per cent. Furthermore, we have found no instrument-specific biases.
Defining the contribution of microRNA-specific Argonautes with slicer capability in animals
Authors: Pal Anisha , Vasudevan Vaishnav , Houle François , Lantin Michael , Maniates Katherine A , Huberdeau Miguel Quévillon , Abbott Allison L , Simard Martin J
Published: March 2024

microRNAs regulate gene expression through interaction with an Argonaute protein. While some members of this protein family retain an enzymatic activity capable of cleaving RNA molecules complementary to Argonaute-bound small RNAs, the role of the slicer residues in the canonical microRNA pathway is still unclear in animals. To address this, we created Caenorhabditis elegans strains with mutated slicer residues in the endogenous ALG-1 and ALG-2, the only two slicing Argonautes essential for the miRNA pathway in this animal model. We observe that the mutation in ALG-1 and ALG-2 catalytic residues affects overall animal fitness and causes phenotypes reminiscent of miRNA defects only when grown and maintained at restrictive temperature. Furthermore, the analysis of global miRNA expression shows that the slicer residues of ALG-1 and ALG-2 contribute differentially to regulate the level of specific subsets of miRNAs in young adults. We also demonstrate that altering the catalytic tetrad of those miRNA-specific Argonautes does not result in any defect in the production of canonical miRNAs. Together, these data support that the slicer residues of miRNA-specific Argonautes contribute to maintaining levels of a set of miRNAs for optimal viability and fitness in animals particularly exposed to specific growing conditions.
An autocatalytic CRISPR-Cas amplification effect propelled by the LNA-modified split activators for DNA sensing
Authors: Sun Ke , Pu Lei , Chen Chuan , Chen Mutian , Li Kaiju , Li Xinqiong , Li Huanqing , Geng Jia
Published: March 2024

CRISPR-Cas systems with dual functions offer precise sequence-based recognition and efficient catalytic cleavage of nucleic acids, making them highly promising in biosensing and diagnostic technologies. However, current methods encounter challenges of complexity, low turnover efficiency, and the necessity for sophisticated probe design. To better integrate the dual functions of Cas proteins, we proposed a novel approach called CRISPR-Cas Autocatalysis Amplification driven by LNA-modified Split Activators (CALSA) for the highly efficient detection of single-stranded DNA (ssDNA) and genomic DNA. By introducing split ssDNA activators and the site-directed trans-cleavage mediated by LNA modifications, an autocatalysis-driven positive feedback loop of nucleic acids based on the LbCas12a system was constructed. Consequently, CALSA enabled one-pot and real-time detection of genomic DNA and cell-free DNA (cfDNA) from different tumor cell lines. Notably, CALSA achieved high sensitivity, single-base specificity, and remarkably short reaction times. Due to the high programmability of nucleic acid circuits, these results highlighted the immense potential of CALSA as a powerful tool for cascade signal amplification. Moreover, the sensitivity and specificity further emphasized the value of CALSA in biosensing and diagnostics, opening avenues for future clinical applications.
Vorinostat, temozolomide or bevacizumab with irradiation and maintenance BEV/TMZ in pediatric high-grade glioma: A Children’s Oncology Group Study
Authors: Lulla Rishi R , Buxton Allen , Krailo Mark D , Lazow Margot A , Boue Daniel R , Leach James L , Lin Tong , Geller James I , Kumar Shiva Senthil , Nikiforova Marina N , Chandran Uma , Jogal Sachin S , Nelson Marvin D , Onar-Thomas Arzu , Haas-Kogan Daphne A , Cohen Kenneth J , Kieran Mark W , Gajjar Amar , Drissi Rachid , Pollack Ian F , Fouladi Maryam
Published: March 2024

Background

Outcomes for children with high-grade gliomas (HGG) remain poor. This multicenter phase II trial evaluated whether concurrent use of vorinostat or bevacizumab with focal radiotherapy (RT) improved 1-year event-free survival (EFS) compared to temozolomide in children with newly diagnosed HGG who received maintenance temozolomide and bevacizumab.

Methods

Patients ≥ 3 and < 22 years with localized, non-brainstem HGG were randomized to receive RT (dose 54–59.4Gy) with vorinostat, temozolomide, or bevacizumab followed by 12 cycles of bevacizumab and temozolomide maintenance therapy.

Results

Among 90 patients randomized, the 1-year EFS for concurrent bevacizumab, vorinostat, or temozolomide with RT was 43.8% (±8.8%), 41.4% (±9.2%), and 59.3% (±9.5%), respectively, with no significant difference among treatment arms. Three- and five-year EFS for the entire cohort was 14.8% and 13.4%, respectively, with no significant EFS difference among the chemoradiotherapy arms. IDH mutations were associated with more favorable EFS (P = .03), whereas H3.3 K27M mutations (P = .0045) and alterations in PIK3CA or PTEN (P = .025) were associated with worse outcomes. Patients with telomerase- and alternative lengthening of telomeres (ALT)-negative tumors (n = 4) had an EFS of 100%, significantly greater than those with ALT or telomerase, or both (P = .002). While there was no difference in outcomes based on TERT expression, high TERC expression was associated with inferior survival independent of the telomere maintenance mechanism (P = .0012).

Conclusions

Chemoradiotherapy with vorinostat or bevacizumab is not superior to temozolomide in children with newly diagnosed HGG. Patients with telomerase- and ALT-negative tumors had higher EFS suggesting that, if reproduced, mechanism of telomere maintenance should be considered in molecular-risk stratification in future studies.
Evaluation of Three Cytomegalovirus IgG Lateral Flow Assays for Rapid Determination of CMV Serostatus
Authors: Joncas-Schronce Laurel , Ali Fatima , Pepper Gregory , Stapleton Renee D , Rubenfeld Gordon D , Boeckh Michael , Limaye Ajit P
Published: March 2024

Background

Cytomegalovirus (CMV) serostatus is a major determinant of CMV infection, disease risk, and transplant outcomes. Current clinical serology assays are limited by relatively slow turnaround time, design for batched testing, need for trained personnel, and/or specialized equipment. Rapid diagnostic assays in development have a role in emerging settings, such as critically ill patients, but have not been systematically evaluated.

Methods

We assessed the performance of 3 rapid lateral flow assays (LFAs) for the detection of CMV immunoglobulin (Ig)G antibodies compared with a reference commercially available CMV IgG enzyme-linked immunosorbent assay in residual serum samples from 200 consecutive adults who underwent clinical CMV serology testing. Samples with discrepant results between the LFA and reference assay were tested by a second reference assay. A subset of serum samples was assessed for interoperator variability. Operating characteristics of the QooLabs LFA were separately assessed in plasma samples.

Results

The sensitivity and specificity of the individual LFA assays using serum varied significantly: 86%/83%, 99/93%, and 57/97%, for Healgen, QNow automated reader, and nanoComposix, respectively, compared with the reference assay. Results for the QNow assay were comparable between automated and manual reads. Among a subset of 10 serum samples assessed by 5 individual operators, 44 of 50 (88%) results were concordant. Among 50 plasma samples assessed by the QooLabs LFA, the sensitivity and specificity were 72% and 96%.

Conclusions

The ease of performance, rapid turnaround time, and good operating characteristics provide the rationale for further evaluation of the Qoolabs QNow LFA in specialized settings where rapid assessment of CMV serostatus would be advantageous.