bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of bile acids in carcinogenesis
Authors: Režen Tadeja , Rozman Damjana , Kovács Tünde , Kovács Patrik , Sipos Adrienn , Bai Péter , Mikó Edit 
Published: April 2022

AbstractBile acids are soluble derivatives of cholesterol produced in the liver that subsequently undergo bacterial transformation yielding a diverse array of metabolites. The bulk of bile acid synthesis takes place in the liver yielding primary bile acids; however, other tissues have also the capacity to generate bile acids (e.g. ovaries). Hepatic bile acids are then transported to bile and are subsequently released into the intestines. In the large intestine, a fraction of primary bile acids is converted to secondary bile acids by gut bacteria. The majority of the intestinal bile acids undergo reuptake and return to the liver. A small fraction of secondary and primary bile acids remains in the circulation and exert receptor-mediated and pure chemical effects (e.g. acidic bile in oesophageal cancer) on cancer cells. In this review, we assess how changes to bile acid biosynthesis, bile acid flux and local bile acid concentration modulate the behavior of different cancers. Here, we present in-depth the involvement of bile acids in oesophageal, gastric, hepatocellular, pancreatic, colorectal, breast, prostate, ovarian cancer. Previous studies often used bile acids in supraphysiological concentration, sometimes in concentrations 1000 times higher than the highest reported tissue or serum concentrations likely eliciting unspecific effects, a practice that we advocate against in this review. Furthermore, we show that, although bile acids were classically considered as pro-carcinogenic agents (e.g. oesophageal cancer), the dogma that switch, as lower concentrations of bile acids that correspond to their serum or tissue reference concentration possess anticancer activity in a subset of cancers. Differences in the response of cancers to bile acids lie in the differential expression of bile acid receptors between cancers (e.g. FXR vs. TGR5). UDCA, a bile acid that is sold as a generic medication against cholestasis or biliary surge, and its conjugates were identified with almost purely anticancer features suggesting a possibility for drug repurposing. Taken together, bile acids were considered as tumor inducers or tumor promoter molecules; nevertheless, in certain cancers, like breast cancer, bile acids in their reference concentrations may act as tumor suppressors suggesting a Janus-faced nature of bile acids in carcinogenesis.
A clinical decision aid for patients with suspected midfacial and mandibular fractures (the REDUCTION-I study): a prospective multicentre cohort study
Authors: Rozema Romke , Moumni Mostafa El , de Vries Gysbert T. , Spijkervet Frederik K. L. , Verbeek René , Kleinbergen Jurrijn Y. J. , Bens Bas W. J. , Doff Michiel H. J. , van Minnen Baucke ,   the REDUCTION study group
Published: April 2022

Abstract
Purpose
To assess physical examination findings related to maxillofacial trauma to identify patients at risk of midfacial and mandibular fractures and then to construct a clinical decision aid to rule out the presence of midfacial and mandibular fractures in emergency department patients.

Methods
We performed a prospective multicentre cohort study in four hospitals in the Netherlands, including consecutive patients with maxillofacial trauma. Each patient received a standardized physical examination consisting of 15 and 14 findings for midfacial and mandibular traumas, respectively. Consequently, clinical decision aids were constructed with the focus being on ruling out the presence of midfacial and mandibular fractures, and diagnostic accuracy was calculated.

Results
A total of 993 consecutive patients were identified of whom 766 and 280 patients were suspected of midfacial and mandibular fractures, respectively. Midfacial fractures were diagnosed in 339 patients (44.3%), whereas mandibular fractures were observed in 66 patients (23.6%). The decision aid for midfacial trauma consisting of peri-orbital hematoma, epistaxis, ocular movement limitation, infra-orbital nerve paresthesia, palpable step-off and tooth mobility or avulsion, produced a sensitivity of 89.7 (86.0–92.5), a specificity of 42.6 (38.0–47.4), and a negative predictive value of 83.9% (78.4–88.2). The decision aid for mandibular trauma consisting of the angular compression test, axial chin pressure test, objective malocclusion, tooth mobility or avulsion and the tongue blade bite test resulted in a sensitivity of 98.5 (91.9–99.7), a specificity of 34.6 (28.5–41.2), and a negative predictive value of 98.7% (92.8–99.8).

Conclusion
The constructed clinical decision aids for maxillofacial trauma may aid in stratifying patients suspected for midfacial and mandibular fractures to reduce unnecessary diagnostic imaging.

Clinical Trial Registration
The study was registered at ClinicalTrials.gov with the identifier NCT03314480.
The importance of transparency in naming conventions, designs, and operations of safety features: from modern ADAS to fully autonomous driving functions
Authors: Murtaza Mohsin , Cheng Chi-Tsun , Fard Mohammad , Zeleznikow John 
Published: April 2022

AbstractThis paper investigates the importance of standardising and maintaining the transparency of advanced driver-assistance systems (ADAS) functions nomenclature, designs, and operations in all categories up until fully autonomous vehicles. The aim of this paper is to reveal the discrepancies in ADAS functions across automakers and discuss the underlying issues and potential solutions. In this pilot study, user manuals of various brands are reviewed systematically and critical analyses of common ADAS functions are conducted. The result shows that terminologies used to describe ADAS functions vary widely across manufacturers and sometimes do not reflect their fundamental functions intuitively. Operational conditions and control procedures also vary across the selected models under this study. Due to this lack of consensus across the industry, drivers are not aware or well informed about ADAS functions in their vehicles, leading to a very low utilization rate and may lead to misuse of those functions. This paper provides insightful suggestions for the transport industry, Artificial Intelligence (AI) experts, and regulators to design frameworks and guidelines in governing the naming convention, operating conditions, control procedures, and information disclosure of ADAS. Such guidelines can be the foundations for regulating future AI-based self-driving functions.
Treating Agricultural Runoff with a Mobile Carbon Filtration Unit
Authors: Phillips Bryn M. , Fuller Laura B. McCalla , Siegler Katie , Deng Xin , Tjeerdema Ron S. 
Published: April 2022

AbstractSeveral classes of pesticides have been shown to impair water quality in California, including organophosphates, pyrethroids and neonicotinoids. Vegetative treatment systems (VTS) can reduce pesticide loads and associated toxicity in agricultural runoff, but many water-soluble pesticides such as neonicotinoids are not effectively treated by VTS, and VTS installation is not always an option for growers required to remove non-crop vegetation for food safety concerns. Recent studies have shown that biochar filtration can be used to remove soluble contaminants, especially when coupled with other VTS components. We evaluated a mobile carbon filter system consisting of a trailer-mounted tank containing approximately 600L (~ 180 kg) of biochar. Input water from a 437-hectare agricultural drainage was pre-filtered and treated with biochar during two multi-week study periods. Laboratory toxicity tests and chemical and nutrient analyses were conducted on input and output water. Pesticide concentrations were initially reduced by greater than 99%. Treatment efficacy declined linearly and was expected to remain at least 50% effective for up to 34 weeks. Toxicity was assessed with Ceriodaphnia dubia, Hyalella azteca and Chironomus dilutus. Significant input toxicity was reduced to non-toxic levels in 6 of 16 samples. Some input concentrations of the neonicotinoid imidacloprid and the pyrethroid cypermethrin exceeded organism-specific toxicity thresholds and benchmarks, but the overall causes of toxicity were complex mixtures of agricultural chemicals. Nutrients were not reduced by the biochar. Results demonstrate the utility of biochar in treating agricultural runoff and provide measures of the longevity of biochar under field conditions.
The Value of the Biomarkers Neuron-Specific Enolase and S100 Calcium-Binding Protein for Prediction of Mortality in Children Resuscitated After Cardiac Arrest
Authors: Bangshøj Johanne , Liebetrau Benedikte , Wiberg Sebastian , Gjedsted Jakob , Kjærgaard Jesper , Hassager Christian , Wanscher Michael 
Published: April 2022

AbstractThe aim of the present study was to assess the ability of the biomarkers neuron-specific enolase (NSE) and S100 calcium-binding protein b (S100b) to predict 30 day mortality in children resuscitated from cardiac arrest (CA). It was a prospective observational study at a single tertiary heart centre. Consecutive children were admitted after resuscitated in-hospital and out-of-hospital CA. Levels of NSE and S100b were analyzed from 12 to 24 hours, from 24 to 48 hours, and from 48 to 72 hours after admission. The primary endpoint was 30-day mortality. Differences in biomarker levels between survivors and non-survivors were analyzed with the Mann-Whitney U test. Receiver operating characteristics (ROC) curves were applied to assess the predictive ability of the biomarkers and the areas under the ROC curves (AUC) were presented. A total of 32 resuscitated CA patients were included, and 12 (38%) patients died within 30 days after resuscitation. We observed significantly higher levels of NSE and S100b in non-survivors compared to survivors at all timepoints from 12 to 72 hours after CA. NSE achieved AUCs from 0.91–0.98 for prediction of 30 day mortality, whereas S100b achieved AUCs from 0.93–0.94. An NSE cut-off of 61 μg/L sampled between 12–24 hours from admission achieved a sensitivity of 80% and a specificity of 100% for prediction of 30 day mortality. In children resuscitated from CA, the biomarkers NSE and S100b appear to be solid predictors of mortality after 30 days.
Development of Diaphragmatic Hernia in Patients with Penetrating Left Thoracoabdominal Stab Wounds
Authors: Yucel Metin , Kulali Fatma , Yildiz Abdullah 
Published: April 2022

AbstractBackgroundThis study aimed to investigate the consequences of repairing versus not repairing diaphragmatic injury caused by penetrating left thoracoabdominal stab wounds.MethodsDiagnostic laparoscopy was performed to evaluate the left diaphragm in patients with penetrating left thoracoabdominal stab wounds who did not have an indication for emergency laparotomy. Patients who did not consent to laparoscopy were discharged without undergoing surgery. Post‐discharge radiological images of patients who underwent diaphragmatic repair and radiological images of patients who could not undergo laparoscopy, both during hospitalization and after discharge, were evaluated and compared.ResultsDiagnostic laparoscopy was performed on 109 patients. Diaphragmatic injuries were detected and repaired in 32 (29.36%) of these patients. Seventeen patients were lost to follow‐up. After a mean follow‐up of 57.67 months, none of the remaining 15 patients developed a diaphragmatic hernia. On the other hand, 43 patients refused to undergo diagnostic laparoscopy. Twenty of them were lost from follow‐up. The diaphragmatic injury was detected in seven of the remaining 23 patients (30.44%) during initial computed tomography (CT) examinations. In this group, the mean follow‐up time was 42.57 months, and delayed diaphragmatic hernia developed in one patient (14.30%). Patients who underwent diaphragmatic repair were compared to patients who did not undergo diagnostic laparoscopy but had diaphragmatic injuries detected on their CT. No statistical differences were detected.ConclusionsDiaphragmatic injuries caused by penetrating stab wounds can sometimes heal spontaneously. However, diagnostic laparoscopy is still relevant for revealing and repairing possible diaphragmatic injuries.
Methotrexate significantly reduces the humoral vaccination response against SARS-CoV-2 in older but not younger patients with rheumatoid arthritis
Authors: Feuchtenberger Martin , Kovacs Magdolna Szilvia , Eder Anna , Nigg Axel , Schäfer Arne 
Published: April 2022

AbstractTo assess the humoral response to vaccination against SARS-CoV-2 in patients with rheumatoid arthritis treated with methotrexate (MTX). In total, 142 fully vaccinated individuals were included at 6 ± 1 weeks after their second vaccination [BioNTech/Pfizer (70.4%), AstraZeneca (20.4%), and Moderna (9.2%)]. The primary goal was to assess the humoral immune response as measured by titres of neutralising antibodies against the S1 antigen of SARS-CoV-2. In a cross-sectional, single-centre study, titres were compared between patient subgroups with (n = 80) and without (n = 62) methotrexate exposure. MTX patients showed a significantly reduced humoral response to vaccination in the oldest patient subgroup (> 70 years: P = 0.038), whereas titres of neutralising antibodies were not significantly different between MTX and non-MTX patients in patients less than 70 years of age (< 56 years: P = 0.234; 56–70 years: P = 0.446). In patients > 70 years, non-MTX patients showed a maximum immune response in 76.5% of cases, whereas this percentage was reduced to 53.7% in study participants on MTX medication (effect size d = 0.21). Older age in patients with rheumatoid arthritis in combination with methotrexate results in a significantly reduced humoral response after vaccination against SARS-CoV-2. Our data underline the importance of age regarding the humoral response and may support the temporary cessation of methotrexate, particularly in elderly patients in the context of vaccination against SARS-CoV-2.
Simulation framework for crystallization in melt flows of semi-crystalline polymers based on phenomenological models
Authors: Descher Stefan , Wünsch Olaf 
Published: April 2022

AbstractPolymer components are shaped mostly out of the molten state. As in the case of semi-crystalline polymers, crystallization can be suppressed by shock cooling, thermal process design allows to influence the solid bodies properties. A simulation approach that enables to predict these properties based on a forecast of crystallinity is presented in this paper. The main effects to consider and possibilities of modeling and simulation are discussed. A detailed description of how to create an experimental foundation using dynamic scanning calorimetry (DSC) and a rheometer is provided. Suppression of crystallization is modeled by a novel phenomenological approach, based on data over a large band of cooling rates. Special focus is put on parameter identification and extension of insufficient DSC data. The mechanical behavior is modeled using a weighted approach based on a nonlinear-thermoviscoelastic model for the molten state and a highly viscous Newtonian model for the solid state. Parameterization of both models is highlighted. An implementation in OpenFOAM is documented, emphasizing specific methods that were applied. Results of simulations for a simplified profile extrusion and injection molding case are presented. Basic relationships are forecasted correctly by the method, and important findings are presented for both processes.
Validating the knowledge bank approach for personalized prediction of survival in acute myeloid leukemia: a reproducibility study
Authors: Xu Yujun , Mansmann Ulrich 
Published: April 2022

AbstractReproducibility is not only essential for the integrity of scientific research but is also a prerequisite for model validation and refinement for the future application of predictive algorithms. However, reproducible research is becoming increasingly challenging, particularly in high-dimensional genomic data analyses with complex statistical or algorithmic techniques. Given that there are no mandatory requirements in most biomedical and statistical journals to provide the original data, analytical source code, or other relevant materials for publication, accessibility to these supplements naturally suggests a greater credibility of the published work. In this study, we performed a reproducibility assessment of the notable paper by Gerstung et al. (Nat Genet 49:332–340, 2017) by rerunning the analysis using their original code and data, which are publicly accessible. Despite an open science setting, it was challenging to reproduce the entire research project; reasons included: incomplete data and documentation, suboptimal code readability, coding errors, limited portability of intensive computing performed on a specific platform, and an R computing environment that could no longer be re-established. We learn that the availability of code and data does not guarantee transparency and reproducibility of a study; paradoxically, the source code is still liable to error and obsolescence, essentially due to methodological and computational complexity, a lack of reproducibility checking at submission, and updates for software and operating environment. The complex code may also hide problematic methodological aspects of the proposed research. Building on the experience gained, we discuss the best programming and software engineering practices that could have been employed to improve reproducibility, and propose practical criteria for the conduct and reporting of reproducibility studies for future researchers.
A New Therapeutic Approach for Dystussia and Atussia in Neurogenic Dysphagia: Effect of Aerosolized Capsaicin on Peak Cough Flow
Authors: Lüthi-Müller Eliane , Kool Jan , Mylius Veit , Diesener Paul 
Published: April 2022

AbstractSwallowing and cough are crucial components of airway protection. In patients with neurogenic dysphagia (ND), there is a high prevalence of dystussia (impaired cough) and atussia (absence of cough). As a result, the ability to detect and remove aspirated material from the airway decreases, exacerbating the sequelae associated with ND, including aspiration pneumonia, a leading cause of mortality in ND. This controlled intervention study aimed to quantify the cough response to aerosolized capsaicin (AC) in patients with ND and assess the potential of AC as a therapeutic tool in treating ND-related dystussia and atussia. Furthermore, we propose a novel application method that enables AC treatment to be performed at home. Spirometry was used to measure peak cough flow (PCF) of voluntary cough (cough on command) and reflexive cough (cough secondary to pharyngeal exposure to AC) in 30 subjects with and 30 without ND. The capsaicin aerosol was generated by adding 1–10 drops of liquid cayenne extract (1.5–2% capsaicin) to 100 mL carbonated water (0.00075–0.001% to 0.0075–0.01% capsaicin). Voluntary PCF in the ND group was significantly lower than in the control group (p < 0.001), while there was no significant difference in reflexive PCF (p = 0.225). Within the ND group, reflexive PCF was significantly higher than voluntary PCF (p = 0.001), while in healthy controls, reflexive PCF was significantly lower (p < 0.001). The data show that AC increased the tracheobronchial clearance efficacy in ND patients with dystussia and atussia, as it enabled subjects to access their individual cough potential, which is present, but inaccessible, due to neurological disorder.
Solving three major biases of the ETAS model to improve forecasts of the 2019 Ridgecrest sequence
Authors: Grimm Christian , Hainzl Sebastian , Käser Martin , Küchenhoff Helmut 
Published: April 2022

AbstractStrong earthquakes cause aftershock sequences that are clustered in time according to a power decay law, and in space along their extended rupture, shaping a typically elongate pattern of aftershock locations. A widely used approach to model earthquake clustering, theEpidemic Type Aftershock Sequence(ETAS) model, shows three major biases. First, the conventional ETAS approach assumes isotropic spatial triggering, which stands in conflict with observations and geophysical arguments for strong earthquakes. Second, the spatial kernel has unlimited extent, allowing smaller events to exert disproportionate trigger potential over an unrealistically large area. Third, the ETAS model assumes complete event records and neglects inevitable short-term aftershock incompleteness as a consequence of overlapping coda waves. These three aspects can substantially bias the parameter estimation and lead to underestimated cluster sizes. In this article, we combine the approach of Grimm et al. (Bulletin of the Seismological Society of America, 2021), who introduced a generalized anisotropic and locally restricted spatial kernel, with theETAS-Incomplete(ETASI) time model of Hainzl (Bulletin of the Seismological Society of America, 2021), to define an ETASI space-time model with flexible spatial kernel that solves the abovementioned shortcomings. We apply different model versions to a triad of forecasting experiments of the 2019 Ridgecrest sequence, and evaluate the prediction quality with respect to cluster size, largest aftershock magnitude and spatial distribution. The new model provides the potential of more realistic simulations of on-going aftershock activity, e.g. allowing better predictions of the probability and location of a strong, damaging aftershock, which might be beneficial for short term risk assessment and disaster response.
Myocardial function in COVID-19 patients after hospital discharge: a descriptive study comparing the first and second ‘wave’ patients
Authors: Elffers T. W. , de Graaf M. A. , Regeer M. V. , Omara S. , Schalij M. J. , Groeneveld G. H. , Roukens A. H. E. , Geelhoed J. J. M. , Antoni M. L. 
Published: April 2022

AbstractIn hospitalized COVID-19 patients, myocardial injury and echocardiographic abnormalities have been described. The present study investigates cardiac function in COVID-19 patients 6 weeks post-discharge and evaluates its relation to New York Heart Association (NYHA) class. Furthermore cardiac function post-discharge between the first and second wave COVID-19 patients was compared. We evaluated 146 patients at the outpatient clinic of the Leiden University Medical Centre. NYHA class of II or higher was reported by 53% of patients. Transthoracic echocardiography was used to assess cardiac function. Overall, in 27% of patients reduced left ventricular (LV) ejection fraction was observed and in 29% of patients LV global longitudinal strain was impaired (> − 16%). However no differences were observed in these parameters reflecting LV function between the first and second wave patients. Right ventricular (RV) dysfunction as assessed by tricuspid annular systolic planar excursion (< 17 mm) was present in 14% of patients, this was also not different between the first and second wave patients (15% vs. 12%; p = 0.63); similar results were found for RV fraction area change and RV strain. Reduced LV and RV function were not associated with NYHA class. In COVID-19 patients at 6 weeks post-discharge, mild abnormalities in cardiac function were found. However these were not related to NYHA class and there was no difference in cardiac function between the first and second wave patients. Long term symptoms post-COVID might therefore not be explained by mildly abnormal cardiac function.