bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved paediatric antimicrobial prescribing with a smartphone application: a before and after interventional study
Authors: Primhak Sarah , Pool Natasha , Sam Michelle Shien Yee , Duffy Eamon , Ritchie Stephen R , Webb Rachel , Wilson Elizabeth , Voss Lesley , Best Emma J 
Published: July 2023

IntroductionChildren have a high consumption of antimicrobials that require complicated decision-making by prescribers. Despite this, antimicrobial stewardship (AMS) interventions are often not translated into paediatric medicine. Script is a smartphone application (app) launched in Auckland, New Zealand to support decision-making for antimicrobial prescribers. The aim was to improve adherence to existing local clinical guidelines for both adult and paediatric infections.MethodsInpatient and emergency department antimicrobial prescriptions were prospectively collected and evaluated for guideline adherence. Baseline prescribing data were collected and compared with prescribing at 4 months and 1 year after the app was launched. Prescriptions were graded as ‘appropriate’ or ‘inappropriate’ by investigators. Grading was done blinded to timing of the prescription relative to the intervention.ResultsFollowing the launch of the Script app, guideline adherence significantly increased from 241 of 348 (69%) antimicrobial prescriptions graded as appropriate during the baseline period to 301 of 359 (83%) after 4 months (p<0.0001). This improvement from baseline was sustained at 1 year with 263 of 323 (81%) adherence (p<0.001). At 1 year, this improvement could be demonstrated separately for medical, surgical and emergency department prescriptions.ConclusionThere was a significant and sustained improvement in adherence to paediatric antimicrobial guidelines following the introduction of a prescribing support app. The need to seek guidance for antimicrobial doses due to the age-based and weight-based calculations in paediatrics may mean that AMS interventions such as decision support and prescribing tools are particularly well suited to paediatric prescribing.
Study protocol for investigating the clinical performance of an automated blood test for glial fibrillary acidic protein and ubiquitin carboxy-terminal hydrolase L1 blood concentrations in elderly patients with mild traumatic BRAIN Injury and reference values (BRAINI-2 Elderly European study): a prospective multicentre observational study
Authors: Lagares Alfonso , Payen Jean-François , Biberthaler Peter , Poca M Antonia , Méjan Odile , Pavlov Vladislav , Viglino Damien , Sapin Vincent , Lassaletta Aurora , de la Cruz Javier 
Published: July 2023

IntroductionTwo blood brain-derived biomarkers, glial fibrillar acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), can rule out intracranial lesions in patients with mild traumatic brain injury (mTBI) when assessed within the first 12 hours. Most elderly patients were excluded from previous studies due to comorbidities. Biomarker use in elderly population could be affected by increased basal levels. This study will assess the performance of an automated test for measuring serum GFAP and UCH-L1 in elderly patients to predict the absence of intracranial lesions on head CT scans after mTBI, and determine both biomarkers reference values in a non-TBI elderly population.Methods and analysisThis is a prospective multicentre observational study on elderly patients (≥65 years) that will be performed in Spain, France and Germany. Two patient groups will be included in two independent substudies. (1) A cohort of 2370 elderly patients (1185<80 years and 1185≥80 years; BRAINI2-ELDERLY DIAGNOSTIC AND PROGNOSTIC STUDY) with mTBI and a brain CT scan that will undergo blood sampling within 12 hours after mTBI. The primary outcome measure is the diagnostic performance of GFAP and UCH-L1 measured using an automated assay for discriminating between patients with positive and negative findings on brain CT scans. Secondary outcome measures include the performance of both biomarkers in predicting early (1 week) and midterm (3 months) neurological status and quality of life after trauma. (2) A cohort of 480 elderly reference participants (BRAINI2-ELDERLY REFERENCE STUDY) in whom reference values for GFAP and UCHL1 will be determined.Ethics and disseminationEthical approval was obtained from the Institutional Review Boards of Hospital 12 de Octubre in Spain (Re#22/027) and Southeast VI (Clermont Ferrand Hospital) (Re# 22.01782.000095) in France. The study’s results will be presented at scientific meetings and published in peer-review publications.Trial registration numberNCT05425251.
Traditional and novel risk factors for incident aortic stenosis in community-dwelling older adults
Authors: Massera Daniele , Bartz Traci M , Biggs Mary L , Sotoodehnia Nona , Reiner Alexander P , Semba Richard D , Gottdiener John S , Psaty Bruce M , Owens David S , Kizer Jorge R 
Published: July 2023

ObjectivesCalcific aortic stenosis (AS) is the most common valvular disease in older adults, yet its risk factors remain insufficiently studied in this population. Such studies are necessary to enhance understanding of mechanisms, disease management and therapeutics.MethodsThe Cardiovascular Health Study is a population-based investigation of older adults that completed adjudication of incident AS over long-term follow-up. We evaluated traditional cardiovascular risk factors or disease, as well as novel risk factors from lipid, inflammatory and mineral metabolism pathways, in relation to incident moderate or severe AS (including AS procedures) and clinically significant AS (severe AS, including procedures).ResultsOf 5390 participants (age 72.9±5.6 years, 57.6% female, 12.5% black), 287 developed moderate or severe AS, and 175 clinically significant AS, during median follow-up of 13.1 years. After full adjustment, age (HR=1.66 per SD (95% CI=1.45, 1.91)), male sex (HR=1.41 (1.06, 1.87)), diabetes (HR=1.53 (1.10, 2.13)), coronary heart disease (CHD, HR=1.36 (1.01, 1.84)), lipoprotein-associated phospholipase-A2(LpPLA2) activity (HR=1.21 per SD (1.07, 1.37)) and sCD14 (HR=1.16 per SD (1.01, 1.34)) were associated with incident moderate/severe AS, while black race demonstrated an inverse association (HR=0.40 (0.24, 0.65)), and creatinine-based estimated glomerular filtration rate (eGFRcr) showed a U-shaped relationship. Findings were similar for clinically significant AS, although CHD and sCD14 fell short of significance, but interleukin-(IL) 6 showed a positive association.ConclusionThis comprehensive evaluation of risk factors for long-term incidence of AS identified associations for diabetes and prevalent CHD, LpPLA2activity, sCD14 and IL-6, and eGFRcr. These factors may hold clues to biology, preventive efforts and potential therapeutics for those at highest risk.
Artificial intelligence-assisted interpretation of systolic function by echocardiogram
Authors: Yamaguchi Natsumi , Kosaka Yoshitaka , Haga Akihiko , Sata Masataka , Kusunose Kenya 
Published: July 2023

ObjectivePrecise and reliable echocardiographic assessment of left ventricular ejection fraction (LVEF) is needed for clinical decision-making. Recently, artificial intelligence (AI) models have been developed to estimate LVEF accurately. The aim of this study was to evaluate whether an AI model could estimate an expert read of LVEF and reduce the interinstitutional variability of level 1 readers with the AI-LVEF displayed on the echocardiographic screen.MethodsThis prospective, multicentre echocardiographic study was conducted by five cardiologists of level 1 echocardiographic skill (minimum level of competency to interpret images) from different hospitals. Protocol 1: Visual LVEFs for the 48 cases were measured without input from the AI-LVEF. Protocol 2: the 48 cases were again shown to all readers with inclusion of AI-LVEF data. To assess the concordance and accuracy with or without AI-LVEF, each visual LVEF measurement was compared with an average of the estimates by five expert readers as a reference.ResultsA good correlation was found between AI-LVEF and reference LVEF (r=0.90, p<0.001) from the expert readers. For the classification LVEF, the area under the curve was 0.95 on heart failure with preserved EF and 0.96 on heart failure reduced EF. For the precision, the SD was reduced from 6.1±2.3 to 2.5±0.9 (p<0.001) with AI-LVEF. For the accuracy, the root-mean squared error was improved from 7.5±3.1 to 5.6±3.2 (p=0.004) with AI-LVEF.ConclusionsAI can assist with the interpretation of systolic function on an echocardiogram for level 1 readers from different institutions.
Predictors of worse outcome after postponing non-emergency cardiac interventions during the COVID-19 pandemic
Authors: Andreß Stefanie , Felbel Dominik , Mack Alex , Rattka Manuel , d’Almeida Sascha , Buckert Dominik , Rottbauer Wolfgang , Imhof Armin , Stephan Tilman 
Published: July 2023

ObjectiveDeferral of non-emergency cardiac procedures is associated with increased early emergency cardiovascular hospitalisation. This study aimed to identify predictors of worse clinical outcome after deferral of non-emergency cardiovascular interventions.MethodsThis observational case-control study included consecutive patients whose non-emergency cardiac intervention has been postponed during COVID-19-related lockdown between 19 March and 30 April 2020 (n=193). Cox regression was performed to identify predictors of the combined 1-year end point emergency cardiovascular hospitalisation and death. All patients undergoing non-emergency interventions in the corresponding time period 2019 served as control group (n=216).ResultsThe combined end point of death and emergency cardiovascular hospitalisation occurred in 70 (36.3%) of 193 patients with a postponed cardiovascular intervention. The planned intervention was deferred by a median of 23 (19–36) days. Arterial hypertension (HR 2.27; 95% CI 1.00 to 5.12; p=0.049), chronic kidney disease (HR 1.89; 95% CI 1.03 to 3.49; p=0.041) as well as severe valvular heart disease (HR 3.08; 95% CI 1.68 to 5.64; p<0.001) were independent predictors of death or emergency hospitalisation. Kaplan-Maier estimators of the combined end point were 31% in patients with arterial hypertension, 56% in patients with severe valvular heart disease and 77% with both risk factors (HR 12.4, 95% CI 3.8 to 40.7; p<0.001) and only 9% in patients without these risk factors (log rank p<0.001). N-terminal pro-B-type natriuretic peptide (NT-proBNP) cut-point of ≥1109 pg/mL best predicts the occurrence of primary end point event in deferred patients (area under the curve 0.71; p<0.001; sensitivity 63.8%, specificity 69.4%).ConclusionOur results suggest that patients with either arterial hypertension, chronic kidney or severe valvular heart disease are at very high risk for emergency hospitalisation and increased mortality in case of postponed cardiac interventions even in supposed stable clinical status. Risk seems to be even higher in patients suffering from a combination of these conditions. If the ongoing or future pandemics force hospitals again to postpone cardiac interventions, the biomarker NT-proBNP is an applicable parameter for outpatient monitoring to identify those at risk for adverse cardiovascular events.
Delivery of essential pediatric congenital surgical care within Brazil’s universal health coverage system: a national survey of pediatric surgeons
Authors: Truche Paul R , Naus Abbie E , Botelho Fabio , Ferreira Julia , Bowder Alexis , Caddell Luke , Zimmerman Kathrin , de Freitas Faria Isabella Maria , Lopes Bellisa Caldas , Costa Eduardo Corrêa , Dantas Fernanda Lage Lima , Cavalcante Augusto J S A , Carvalho Carlos A L B , Abib Simone , Mooney David P , Alonso Nivaldo 
Published: July 2023

ObjectiveIn this study, we assess the delivery of congenital pediatric surgical care under Brazil’s system of universal health coverage and evaluate differences in delivery between public and private sectors.MethodsA cross-sectional national survey of pediatric surgeons in Brazil was conducted. Participants were asked which of 23 interventions identified through theDisease Control Priorities 3 (Surgical Interventions for Congenital Anomalies)they perform and to report barriers faced while providing surgical care. Responses were weighted by state and stratified by sector (public vs private).ResultsA sample of 352 responses was obtained and weighted to represent 1378 practicing pediatric surgeons registered in Brazil during the survey time. 73% spend the majority of their time working in the public sector (‘Sistema Único de Saúde’ and Foundation hospitals), and most of them also work in the private sector. Generally, Brazilian pediatric surgeons have the expertise to provide thoracic, abdominal, and urologic procedures. Surgeons working mostly in the public sector were more likely to report a lack of access to essential medications (25% vs 9%, p<0.01) and a lack of access to hospital beds for surgical patients (52% vs 32%, p<0.01).ConclusionsBrazilian pediatric surgeons routinely perform thoracic, abdominal, and urologic surgery. Those working in government-financed hospitals face barriers related to infrastructure, which may impact Brazilians who rely on Brazil’s universal health coverage system. Policies that support pediatric surgeons working in the public sector may promote the workforce available to provide congenital pediatric surgical care.
LncRNA AGPG Confers Endocrine Resistance in Breast Cancer by Promoting E2F1 Activity
Authors: Yu Shiyi , Wang Ying , Gong Xue , Fan Zhehao , Wang Zheng , Liang Zhengyan , Wu Rui , Cao Binjie , Wang Ning , Bi Caili , Lv Dan , Sun Haibo 
Published: July 2023

Abstract

Resistance to endocrine therapy represents a major concern for patients with estrogen receptor α–positive (ERα+) breast cancer. Endocrine therapy resistance is commonly mediated by activated E2F signaling. A better understanding of the mechanisms governing E2F1 activity in resistant cells could reveal strategies for overcoming resistance. Here, we identified the long noncoding RNA (lncRNA) actin gamma 1 pseudogene 25 (AGPG) as a regulator of E2F1 activity in endocrine-resistant breast cancer. Expression of AGPG was increased in endocrine-resistant breast cancer cells, which was driven by epigenomic activation of an enhancer. AGPG was also abnormally upregulated in patient breast tumors, especially in the luminal B subtype, and high AGPG expression was associated with poor survival of patients with ERα+ breast cancer receiving endocrine therapy. The upregulation of AGPG mediated resistance to endocrine therapy and cyclin-dependent kinase 4/6 inhibition in breast cancer cells. Mechanistically, AGPG physically interacted with PURα, thus releasing E2F1 from PURα and leading to E2F1 signaling activation in ERα+ breast cancer cells. In patients with breast cancer, E2F1 target genes were positively and negatively correlated with expression of AGPG and PURα, respectively. Coadministration of chemically modified AGPG siRNA and tamoxifen strongly suppressed tumor growth in endocrine-resistant cell line–derived xenografts. Together, these results demonstrate that AGPG can drive endocrine therapy resistance and indicate that it is a promising biomarker and potential therapeutic target in breast cancer.

Significance:
Blockade of formation of the PURα/E2F1 complex by lncRNA AGPG activates E2F1 and promotes endocrine resistance, providing potential strategies for combatting endocrine-resistant breast cancer.
Learning Individual Survival Models from PanCancer Whole Transcriptome Data
Authors: Kumar Neeraj , Skubleny Daniel , Parkes Michael , Verma Ruchika , Davis Sacha , Kumar Luke , Aissiou Amira , Greiner Russell 
Published: July 2023

Abstract

Purpose:
Personalized medicine attempts to predict survival time for each patient, based on their individual tumor molecular profile. We investigate whether our survival learner in combination with a dimension reduction method can produce useful survival estimates for a variety of patients with cancer.

Experimental Design:
This article provides a method that learns a model for predicting the survival time for individual patients with cancer from the PanCancer Atlas: given the (16,335 dimensional) gene expression profiles from 10,173 patients, each having one of 33 cancers, this method uses unsupervised nonnegative matrix factorization (NMF) to reexpress the gene expression data for each patient in terms of 100 learned NMF factors. It then feeds these 100 factors into the Multi-Task Logistic Regression (MTLR) learner to produce cancer-specific models for each of 20 cancers (with &gt;50 uncensored instances); this produces “individual survival distributions” (ISD), which provide survival probabilities at each future time for each individual patient, which provides a patient's risk score and estimated survival time.

Results:
Our NMF-MTLR concordance indices outperformed the VAECox benchmark by 14.9% overall. We achieved optimal survival prediction using pan-cancer NMF in combination with cancer-specific MTLR models. We provide biological interpretation of the NMF model and clinical implications of ISDs for prognosis and therapeutic response prediction.

Conclusions:
NMF-MTLR provides many benefits over other models: superior model discrimination, superior calibration, meaningful survival time estimates, and accurate probabilistic estimates of survival over time for each individual patient. We advocate for the adoption of these cancer survival models in clinical and research settings.
Cancer Prediction With Machine Learning of Thrombi From Thrombectomy in Stroke: Multicenter Development and Validation
Authors: Heo JoonNyung , Lee Hyungwoo , Seog Young , Kim Sungeun , Baek Jang-Hyun , Park Hyungjong , Seo Kwon-Duk , Kim Gyu Sik , Cho Han-Jin , Baik Minyoul , Yoo Joonsang , Kim Jinkwon , Lee Jun , Chang Yoonkyung , Song Tae-Jin , Seo Jung Hwa , Ahn Seong Hwan , Lee Heow Won , Kwon Il , Park Eunjeong , Kim Byung Moon , Kim Dong Joon , Kim Young Dae , Nam Hyo Suk 
Published: July 2023

BACKGROUND:
We aimed to develop and validate machine learning models to diagnose patients with ischemic stroke with cancer through the analysis of histopathologic images of thrombi obtained during endovascular thrombectomy.

METHODS:
This was a retrospective study using a prospective multicenter registry which enrolled consecutive patients with acute ischemic stroke from South Korea who underwent endovascular thrombectomy. This study included patients admitted between July 1, 2017 and December 31, 2021 from 6 academic university hospitals. Whole-slide scanning was performed for immunohistochemically stained thrombi. Machine learning models were developed using transfer learning with image slices as input to classify patients into 2 groups: cancer group or other determined cause group. The models were developed and internally validated using thrombi from patients of the primary center, and external validation was conducted in 5 centers. The model was also applied to patients with hidden cancer who were diagnosed with cancer within 1 month of their index stroke.

RESULTS:
The study included 70 561 images from 182 patients in both internal and external datasets (119 patients in internal and 63 in external). Machine learning models were developed for each immunohistochemical staining using antibodies against platelets, fibrin, and erythrocytes. The platelet model demonstrated consistently high accuracy in classifying patients with cancer, with area under the receiver operating characteristic curve of 0.986 (95% CI, 0.983–0.989) during training, 0.954 (95% CI, 0.937–0.972) during internal validation, and 0.949 (95% CI, 0.891–1.000) during external validation. When applied to patients with occult cancer, the model accurately predicted the presence of cancer with high probabilities ranging from 88.5% to 99.2%.

CONCLUSIONS:
Machine learning models may be used for prediction of cancer as the underlying cause or detection of occult cancer, using platelet-stained immunohistochemical slide images of thrombi obtained during endovascular thrombectomy.
Why Children Believe They Are Owned
Authors: Starmans Christina , Friedman Ori 
Published: July 2023

AbstractOwners decide what happens to their property, and so adults typically view autonomous beings as non-owned. If children likewise consider autonomy when judging what is owned, this may have implications for how they view themselves. If children believe that parents have power over them, that they themselves lack autonomy, and that only the autonomous cannot be owned, this may lead them to believe that they are owned by their parents. Across three experiments, we found that 4- to 7-year-old children (N = 206) consistently affirm that children are owned by their parents. In Experiment 1, children judged that children and domesticated animals are owned, but denied this for adults and wild animals. In Experiment 2, children were more likely to see children as owned by their parents than by their teachers, and also denied that children own either kind of adult. Finally, in Experiment 3, children were less likely to view a child who makes decisions against parental authority as owned. These judgments are unlikely to mirror what children have been told. Instead, they likely result from children spontaneously using autonomy principles, and possibly other principles of ownership, in reasoning about the ownership of living entities.
A New Definition of Ethical Mentophobia
Authors: Chauvet David 
Published: July 2023

Abstract
It has become difficult to deny animal consciousness. However, we have nonepistemic reasons for denying it that are related to our interests. In particular, research has shown that we reject animal consciousness to morally preserve our meat consumption. It is therefore possible that mentophobia is expressed in ways other than the denial of the nonhuman animal mind. We revisit the concept of mentophobia to show that it includes at least one other way of belittling other animals by attacking their mental abilities or traits, namely, through denigration. We thus distinguish denial-mentophobia and denigration-mentophobia, paving the way for empirical research that may be useful in debates on the moral or political status of nonhuman animals. This distinction also has important consequences for the concept of mentophobia regarding the concept of dementalization in that it increases their nonredundancy.
Prospects for State and Individual Responsibility in Cases of Aggression in the Context of Russia’s Armed Aggression Against Ukraine
Authors: Shatilo Volodymyr A. , Kharytonov Sergiy O. , Kovbasa Volodymyr M. , Svintsytskyi Andrii V. , Lyseiuk Andrii M. 
Published: July 2023

Abstract
Notwithstanding the war that raged through the former Yugoslavia in the 1990s, Russia’s aggression against Ukraine is admittedly the first armed conflict of such a scale to take place almost in the heart of Europe. The Russian–Ukrainian war poses a threat to the international order, and risks escalating into a Third World War, especially if Belarus sides with Russia to participate in the armed conflict. While it could seem that in the 21st century all issues and conflicts arising between states should be resolved at the diplomatic level, in accordance with the requirements and norms of relevant international pacts and treaties, humanity still turns to such a destructive and cruel way of resolving them as war. This article explores the issue of accountability prospects for crimes perpetrated in the context of Russia’s invasion of Ukraine, both from the viewpoint of State responsibility and from that of individual criminal responsibility.