bluuebunny/crossref_metadata_2025 huggingface dataset:
Factor Analysis of Intoxicated Patients Disposition in Pediatric Emergency Department
Authors: Lee Hyun Jung , Cho Youngsoon , Jang Hye Young , Lim Hoon , Hwang Bo Young
Published: June 2023

Purpose: This study was conducted to analyze the factors associated with intoxicated patient's disposition in the pediatric emergency department. Methods: We retrospectively evaluated pediatric intoxicated patients visiting the pediatric emergency department of a hospital between January 1, 2011 and December 31, 2013. Specifically, we analyzed the association between hospitalization recommended rate and the following variables: patient age group, symptoms, intentional poisoning, decontamination and toxic level of substance. Results: We collected data from 345 patients. A high incidence was noted in the 1-4 years of age group and 10-15 years of age group. Unintentional poisoning occurred in 306 patients (88.7%). A total of 115 patients (33.3%) had symptoms when visiting. Forty three patients (12.5%) ingested cleaning substances, which was the most common agent. Potentially-toxic level was the most common level of the substance. The hospitalization recommended rate associated with visits in 2011 was 2.5 times greater than in 2012 and 2013, decontamination was 2.0 times greater than no decontamination, and poisoning with potentially-toxic substances was 2.6 times greater than poisoning with other toxic substances. Additionally, the hospitalization recommended rate associated with symptomatic patients was 2.4 times greater than that of asymptomatic patients and intentional poisoning was 2.4 times greater than unintentional poisoning. Conclusion: Patients with decontamination, ingestion of potentially-toxic substances, symptoms and intentional poisoning had increased hospitalization rates. In addition, the hospitalization rate for patients who visited in 2011 was greater than that of patients who visited in 2012 or 2013.
Unintentional Pharmaceutical Poisoning in the Emergency Department
Authors: Jo Hyo Rim , Lee Choung Ah , Park Ju Ok , Hwang Bo Na
Published: June 2023

Purpose: The social environment of easy access to medicines and arbitrary personal decisions leading to overdose aggravate unintentional medicine poisoning. This study aimed to investigate the characteristics of patients who visited emergency departments with unintentional medicine poisoning and reasons for poisoning based on age group. Methods: We retrospectively collected patients who experienced unintentional medicine poisoning based on data from the national injury surveillance system between 2013 and 2016. Subjects were classified into three groups based on age (0-14 years, 15-64 years, and ${geq}65;years$). We identified sex, insurance, time of poisoning, place, alcohol co-ingestion, hospitalization, death, and reason for poisoning in each age group. Results: A total of 27,472 patients visited an emergency department with poisoning during the study period; 1,958 patients who experienced unintentional poisoning were enrolled in this study. Respiratory medicine was the most frequent medicine in those younger than 15 years of age, and sedatives and antipsychotic drugs were the most common in patients older than 15 years of age. In total, 35.1% of patients older than 65 years were hospitalized. The most common reasons for poisoning were careless storage of medicine in those younger than 15 years of age and overdose due to arbitrary decisions in those older than 15 years of age. Conclusion: Unintentional medicine poisoning has distinct characteristics based on age group, and strategies to prevent poisoning should be approached differently based on age.
Antidotes Stocking and Delivery for Acute Poisoning Patients at 20 Emergency Departments in Korea 2015-2017
Authors: Lee Seungmin , Youn Han Deok , Chang Hanseok , Won Sinae , Kim Kyung Hwan , Oh Bum Jin
Published: June 2023

Purpose: The National Emergency Medical Center has been running a project for the storage and delivery of antidotes for acute poisoning patients of the Department of Health and Welfare, Korea. This study analyzed the results of this project over the past two years. Methods: The requests received by the National Emergency Medical Center and the data on the delivery process were analyzed. Results: This study analyzed a total of 121 patients with acute poisoning, who were requested to receive an antidote reserved at 20 key hospitals in 2015-2017, and whose age was $52.3{pm}23.5;years$; old; 54 were women. Intentional poisoning were 58.7%, and the home was the most common place of exposure (66.9%). The toxic substances were chemicals (32.2%), pesticides (27.3%), medicines (24.8%), and snake venom (4.1%). The patient's poison severity score was $2.4{pm}0.7$ (median 3) indicating moderate-to-severe toxicity. Antidote administration was the cases treated in key hospitals 67.8% (82/121), in which transferred patients accounted for 57.3% (47/82). After receiving an antidote request from a hospital other than the key hospitals, the median was 75.5 minutes (range 10 to 242 minutes) until the antidote reached the patient, and an average of 81.5 minutes was required. The results of emergency care were intensive care unit (70.3%), general wards (13.2%), death (10.7%), and discharge from emergency department (5.0%). Conclusion: This study showed that the characteristics of acute poisoning patients treated with an antidote were different from previous reports of poisoned patients in the emergency department, and basic data on the time required for delivery from key hospitals was different.
Usefulness of Predictors for Hepatotoxicity in Acetaminophen Poisoning Patient
Authors: Kim Eun Young , Chung Sung Phil , Ko Dong Ryul , Kong Tae Young , You Je Sung , Choa Min Hong , Kim Min Joung
Published: June 2023

Purpose: The purpose of this study was to determine whether hepatotoxicity could be predicted early using biochemical markers in patients with acetaminophen (AAP) poisoning and to assess the usefulness of predictive factors for acute liver injury or hepatotoxicity. Methods: This study was a retrospective observational study involving a medical records review. The participants were patients who were admitted to the emergency department (ED) with AAP overdose at two hospitals over a 10-year period. Demographic data, age, time from ingestion to visit, initial AAP level, initial hepatic aminotransferases, and initial prothrombin time were recorded. Acute liver injury was defined as a peak serum ALT >50 U/L or double the admission value, and hepatotoxicity was defined as a peak ALT >1,000 U/L. Receiver operating characteristic curve analyses were performed to compare the prognostic performance among variables. Results: A total of 97 patients were admitted to the ED with AAP overdose, of whom 26 had acute liver injury and 6 had hepatotoxicity. Acute liver injury was associated with the time interval after taking the drug, and hepatotoxicity was associated with the initial PT and the ALT level. The scoring system proposed by the authors has a significant ability to predict both acute liver injury and hepatotoxicity. Conclusion: To predict the prognosis of AAP poisoning patients, the time interval after taking AAP was important, and initial prothrombin time and ALT level were useful tests. Also a scoring system combining variables may be useful.
Evaluation of Cut-off Values in Acute Acetaminophen Intoxication Following the Revised Guideline of the United Kingdom
Authors: Park Sung Jin , Cha Kyungman , So Byung Hak , Kim Hyung Min , Jeoung Won Jung
Published: June 2023

Purpose: In 2012, a revised guideline for acute acetaminophen overdose was proposed in the UK, recommending that the treatment threshold should be lowered to 100 mcg/ml at 4 hours after ingestion without risk stratification of hepatotoxicity. However, the poison centers in some developing countries do not have laboratory resources to provide serum drug levels in time. The primary aim of the study is to evaluate the cut-off value of reported dose per kilogram to determine when N-acetylcysteine treatment is warranted under the revised guideline. Methods: Data were collected retrospectively from the toxicology registry of an urban emergency medical center between 1st January 2010 and 30th June 2017. Inclusion criteria were single acute overdose of more than 75 mg/kg in 15 hours from ingestion and over 14 years of age. Subgroups were created by 25 mg/kg increments of reported dose, then sensitivity, specificity, positive predictive value and negative predictive value were calculated for the cut-off values of 100 mg/kg, 125 mg/kg, 150 mg/kg and 175 mg/kg for toxic serum level over '100-treatment line'. Results: A total of 99 patients were enrolled in the study; 24 patients showed toxic serum levels (24.2%). Zero of 17 patients with an ingestion dose under 100 mg/kg showed toxic level (0%), and 0 of 15 under 125 mg/kg (0%), 2 of 14 under 150 mg/kg (14.3%), and 4 of 12 under 175 mg/kg (33.3%) had toxic levels. The higher the ingested dose per kilogram of weight, the higher the frequency of the toxic serum concentration on the first test (${chi}^2$ test for trend, ${chi}^2=22.66$, p-value<0.001) and the sensitivity of each value was 100%, 100%, 92% and 76%. Conclusion: In acute single acetaminophen intoxication, the ingestion dose of 100 mg/kg of weight will be useful in determining the need for the N-acetylcysteine antidote in the indigent laboratory environment.
A Case of Zaltoprofen Induced Kounis Syndrome
Authors: Lee Seong You , Sung Won Young , Lee Jang Young , Seo Sang Won , Lee Won Suk
Published: June 2023

Kounis syndrome is defined as the occurrence of acute coronary syndrome associated with vasoactive mediators, such as histamines in the setting of hypersensitivity and allergic reactions or anaphylactic insults. The condition can be caused by various drugs, foods, or environmental factors that cause allergic reactions. A 35-year-old male visited the emergency room with anaphylaxis accompanied by chest pain approximately 20 minutes after taking zaltoprofen, a nonsteroidal anti-inflammatory drug. After acute treatment for the anaphylaxis, the patient was stabilized and all symptoms disappeared, but the ischemic changes in the electrocardiogram and elevation of the cardiac enzymes were observed. The emergency cardiac angiography and echocardiography were all normal. The allergic reaction of this patient to zaltoprofen was believed to cause a temporary coronary arterial vasospasm, inducing Type 1 Kounis syndrome. Thus far, there have been case reports of Kounis syndrome caused by a range of nonsteroidal anti-inflammatory drugs, but there are no reports of the condition being caused by zaltoprofen. According to the pathophysiology, both cardiac and allergic symptoms must be solved simultaneously, so rapid treatment and diagnosis are needed. Doctors treating acute allergic reactions and anaphylaxis patients must check the cardiovascular symptoms thoroughly and consider the possibility of Kounis syndrome.
Does D-amino acids metabolism mirror evolutionary origins of plant cells and their adaptation to the environment?
Authors: Tcherkez Guillaume , Porras-Dominguez Jaime , Lothier Jeremy , Limami Anis
Published: June 2023

D-amino acids are the D stereoisomers of common L-amino acids found in
proteins. In the past two decades, the occurrence of D-amino acids in
plants has been reported and circumstantial evidence for a role in
several processes has been provided, including the interaction with soil
microorganisms or an interference with cellular signalling. However,
examples are relatively scarce and D-amino acids can also be
detrimental, some of them inhibiting growth and development. Thus, the
persistence of a D-amino acid metabolism in plants is rather surprising
and evolutive origins of D-amino acid metabolism is presently unclear.
Systemic analysis of sequences associated with enzymes of D-amino acid
metabolism shows that they are not simply inherited from cyanobacterial
metabolism. In effect, the history of enzymes of plant D-amino acid
metabolism likely involves several steps, cellular compartments, gene
transfers and losses. Regardless of evolutive steps, enzymes of D-amino
acid metabolism like D-amino acid transferases or racemases have been
kept by higher plants and not simply eliminated, hence it is likely that
they fulfil important metabolic roles, which can be illustrated with
serine, tryptophan, and folate metabolism. We suggest that D-amino acid
metabolism was perhaps crucial to support metabolic functions required
during land plants evolution.
Accumulation and light-harvesting function of IsiA in cyanobacterial cells with monomeric and trimeric Photosystem I
Authors: Lambrev Petar , Akhtar Parveen , Balog-Vig Fanny , Kuntam Soujanya , Tóth Szilvia Z.
Published: June 2023

Iron deficiency is a common challenge faced by cyanobacteria in oceanic
environments and the acclimation to iron deficiency is crucial for their
survival. In response to iron deficiency, many cyanobacterial species
induce the production of a pigment-protein complex called IsiA. IsiA
proteins associate with photosystem I (PSI) and can function as
light-harvesting antennas or dissipate excess energy. They may also
serve as Chl storage during iron limitation and aid in the recovery of
the photosynthetic apparatus. In this study we examined the functional
role of IsiA in cells of Synechocystis sp. PCC 6803 grown under
iron-limitation conditions by measuring the cellular IsiA content and
its capability to transfer energy to PSI. We specifically test the
effect of the oligomeric state of PSI by comparing wild-type (WT)
Synechocystis sp. PCC 6803 to mutants lacking specific subunits
of PSI, namely PsaL/PsaI (Δ psaL mutant) and PsaF/PsaJ (ΔFIJL
mutant). Time-resolved fluorescence spectroscopy revealed that IsiA
formed functional PSI -IsiA
supercomplexes, wherein IsiA effectively transfers energy to PSI on a
timescale of 10 ps at room temperature, confirming the primary role of
IsiA as an accessory light-harvesting antenna to PSI. However, a
significant fraction (40%) remained unconnected to PSI in the form of
IsiA aggregates, supporting the notion of a dual functional role of
IsiA. The absence of PsaL and PsaF subunits led to reduced accumulation
of IsiA under iron deficiency with PSI monomers only binding 3-4 IsiA
complexes on average. Taken together, the results show that IsiA is
capable of transferring energy to trimeric and to monomeric PSI but to
varying degrees and that the acclimatory production of IsiA under iron
stress is controlled by its ability to perform its light-harvesting
function.
Improved 2-Point Hybrid Block Model for Direct Integration of Third and Fourth-Order Initial Value Problems
Authors: Adeyefa Emmanuel Oluseye , Olanegan Olayemi Ola
Published: June 2023

This research presents a novel numerical method for estimating solutions
to higher-order differential equations with initial value problems
(IVPs). By directly integrating a system of third and fourth-order
differential equations using a 2-point implicit algorithm built with
collocation and interpolation, significant improvements in efficiency
are achieved. The proposed hybrid method, incorporating the first and
second derivatives of the discrete algorithm, enhances accuracy and
convergence rates. Convergence analysis confirms the zero-stability and
consistency of the method, and numerical experiments demonstrate its
superiority over existing methods for solving third and fourth-order
equation systems. This work contributes a valuable numerical approach
for efficient and accurate estimation of higher-order differential
equations with IVPs.
Potential effects of the marine carbon cycle on the multiple equilibria window of the Atlantic Meridional Overturning Circulation
Authors: Boot Amber , Heydt Anna S. von der , Dijkstra Henk A.
Published: June 2023

The Atlantic Meridional Overturning Circulation (AMOC) is considered to
be a tipping element in the Earth System with multiple stable states.
Here, we investigate the multiple equilibria window of the AMOC within a
coupled ocean circulation-carbon cycle box model. We show that adding
couplings between the ocean circulation and the carbon cycle model
affects the multiple equilibria window of the AMOC. Increasing the total
carbon content of the system will widen the multiple equilibria window
of the AMOC, since higher atmospheric pCO2 values are accompanied by
stronger freshwater forcing over the Atlantic ocean which acts to
increase the window. Our results suggest that future changes in the
marine carbon cycle can influence AMOC stability in future climates.
Winter intrusions of Atlantic Water in Kongsfjorden: oceanic preconditioning and atmospheric triggering
Authors: Rovere Francesco De , Zanchettin Davide , Rubino Angelo , Langone Leonardo , Calogiuri Francesco , Ruggieri Paolo , Lupi Angelo , Chiggiato Jacopo
Published: June 2023

Kongsfjorden is an Arctic fjord in Svalbard, which is largely influenced
by the West Spitsbergen Current (WSC), transporting warm and salty
Atlantic Water (AW) into the Arctic. The geostrophic control typically
prevents AW from entering the fjord in winter, whereas energetic wind
events develop the Spitsbergen Trough Current (STC), ultimately flooding
fjords facing the West Spitsbergen Shelf with AW. However, an exhaustive
understanding of the interplay between these two opposite mechanisms and
a clear knowledge of conditions leading to AW winter intrusions are
still lacking. In this study, observational and reanalysis data show
that wind reversal events trigger AW intrusions, while the ocean density
is a key preconditioning factor limiting the occurrence of AW intrusions
to specific winters only. Wind reversals are strong southerly wind
events linked to the setup of a high pressure anomaly over the Barents
Sea, followed by a circulation reversal with northerly winds. Winters
with AW intrusions feature fresher and less dense fjord waters compared
to AW, resulting in the breakdown of the geostrophic control mechanism
at the fjord mouth, which opens the fjord to waters advected from the
WSC by wind reversals. The low salinity signal is consistent with a
large freshwater production through summer Arctic sea-ice melting in the
Barents Sea. Another mechanism is observed only in winter 2014: southern
winds blew continuously for two months and transported surface AW from
the WSC to the fjord, eventually forcing AW to intrude near the surface,
on top of denser local waters.
Physics informed neural networks for solving flow problems modeled by the Shallow Water Equations
Authors: Qi Xin , Almeida Gustavo Adolfo Mazza de , Maldonado Sergio
Published: June 2023

This paper investigates the application of physics-informed neural
networks (PINNs) to solve free-surface flow problems governed by the
two-dimensional shallow water equations (SWEs). Two types of PINNs are
developed and analysed: a physics-informed fully connected neural
network (PIFCN) and a physics-informed convolutional neural network
(PICN). The PINNs eliminate the need for labelled data for training by
employing the SWEs, initial and boundary conditions as components of the
loss function to be minimized. Solutions obtained by both PINNs are
compared against those delivered by a finite volume (FV) solver for two
idealized problems admitting analytical solutions, and one real-world
flood event. The results of these tests show that the prediction
accuracy and computation time (i.e., training time) of both PINNs may be
less affected by the resolution of the domain discretization than the FV
model. Overall, the PICN shows a better trade-off between computational
speed and accuracy than the PIFCN. Also, our results for the two
idealized problems indicated that PICN and PIFCN can provide more
accurate predictions than the FV model, while the FV simulation with
coarse resolution (e.g., 5 m and 10 m) outperformed PICN and PIFCN in
terms of the speed-accuracy trade-off. Results from the real-world test
showed the finely resolved (10 m resolution) FV simulation generally
provided the most accurate approximations at flooding peaks. However,
both PINNs showed better speed-accuracy trade-off than the FV model in
terms of predicting the temporal distribution of water depth, while FV
models outperformed the PINNs in their predictions of discharge.
Filling the gap of wind observations inside tropical cyclones
Authors: Tridon Frederic , Battaglia Alessandro , Rizik Ali , Illingworth Anthony J.
Published: June 2023

The WIVERN (WInd VElocity Radar Nephoscope) mission, currently under the
Phase-0 of the ESA Earth Explorer program, promises to provide new
insight in the coupling between winds and microphysics by globally
observing, for the first time, vertical profiles of horizontal winds in
cloudy areas. The objective of this work is to explore the potential of
the WIVERN conically scanning Doppler 94GHz radar for filling the wind
observation gap inside tropical cyclones. To this aim, realistic WIVERN
notional observations of TCs are produced by combining the CloudSat
94GHz radar reflectivity observations from 2007 to 2009 with ECMWF
co-located winds. Despite the short wavelength of the radar (3mm), which
causes strong attenuation in presence of large amount of liquid
hydrometeors, the system can profile most of the tropical cyclones,
particularly the cloudy areas above the freezing level and the
precipitating stratiform regions. The statistical analysis of the
results shows that, (i) because of its lower sensitivity, a nadir
pointing WIVERN would detect 80% of the clouds (60% of winds with 3m/s
accuracy) observed by CloudSat, (ii) but thanks to its scanning
capability, WIVERN would actually provide 52 times more observations of
clouds (40~times more observations of horizontal winds)
than CloudSat in TCs, (iii) this corresponds to more than 400 (300)
million observations of clouds (accurate winds) every year. Such
observations could be used in data assimilation models in order to
improve numerical weather prediction and by modellers in order to shed
light on the physical processes underpinning the evolution of tropical
cyclones.
Learning Atmospheric Boundary Layer Turbulence
Authors: Shamekh Sara , Gentine Pierre
Published: June 2023

Accurately representing vertical turbulent fluxes in the planetary
boundary layer is vital for moisture and energy transport. Nonetheless,
the parameterization of the boundary layer remains a major source of
inaccuracy in climate models. Recently, machine learning techniques have
gained popularity for representing oceanic and atmospheric processes,
yet their high dimensionality limits interpretability. This study
introduces a new neural network architecture employing non-linear
dimensionality reduction to predict vertical turbulent fluxes in a dry
convective boundary layer. Our method utilizes turbulent kinetic energy
and scalar profiles as input to extract a physically constrained
two-dimensional latent space, providing the necessary yet minimal
information for accurate flux prediction.We obtained data by coarse-graining Large Eddy Simulations covering a
broad spectrum of boundary layer conditions, from weakly to strongly
unstable. These regimes are employed to constrain the latent space
disentanglement, enhancing interpretability. By applying this
constraint, we decompose the vertical turbulent flux of various scalars
into two main modes of variability: wind shear and convective
transport.Our data-driven parameterization accurately predicts vertical turbulent
fluxes (heat and passive scalars) across turbulent regimes, surpassing
state-of-the-art schemes like the eddy-diffusivity mass flux scheme. By
projecting each variability mode onto its associated scalar gradient, we
estimate the diffusive flux and learn the eddy diffusivity. The
diffusive flux is found to be significant only in the surface layer for
both modes and becomes negligible in the mixed layer. The retrieved eddy
diffusivity is considerably smaller than previous estimates used in
conventional parameterizations, highlighting the predominant
non-diffusive nature of transport.
Introducing Flashiness-Intensity-Duration-Frequency (F-IDF): A New Metric to Quantify Flash Flood Intensity
Authors: Li Zhi , Gao Shang , Chen Mengye , Zhang Jiaqi , Gourley Jonathan J. , Wen Yixin , Yang Tiantian , Hong Yang
Published: June 2023

Flash flooding is one of the most damaging weather types, yet it remains
challenging to quantify its severity. We propose a novel development –
the Flashiness-Intensity-Duration-Frequency (F-IDF) curve – to quantify
and spatially analyze flash flood intensity based on the frequency and
duration of the event. As a proof-of-concept, we mapped Contiguous US
(CONUS)-wide F-IDF values at 3,722 stream gage locations and explored
their relations with 59 basin attributes. It is found that (1)
Climatological precipitation amounts exhibit the most positive
correlation with flashiness while a basin’s drainage area is the most
negatively correlated; (2) Correlation of flashiness with basin
attributes decreases with increasing F-IDF return periods and shorter
event durations. Both aspects are attributable to the rainfall signal
overwhelming the underlying basin attributes as the intensities become
more extreme. This new term can have implications for hydrology,
especially for hydrologic modelers, decision-makers, and emergency
responders.
A Stereo Camera Simulator for Large-Eddy Simulations of Continental Shallow Cumulus clouds based on three-dimensional Path-Tracing
Authors: Burchart Yannick Rainer , Beekmans Christoph , Neggers Roel
Published: June 2023

The complex spatial and temporal structure of cumulus clouds complicates
their representation in weather and climate models. Classic
meteorological instrumentation struggles to fully capture these
features. Networks of multiple high-resolution hemispheric cameras are
increasingly used to fill this data gap, and provide information on this
missing multi-dimensional spatial information. In this study, a
path-tracing algorithm is used to generate virtual camera images of
resolved clouds in Large-Eddy Simulations (LES). These images are then
used as a camera network simulator, allowing reconstructions of
three-dimensional cloud edges from the model output. Because the actual
LES cloud field is fully-known, the combined path-tracing and
reconstruction method can be statistically analyzed. The method is
applied to LES realizations of summertime shallow cumulus at the Jülich
Observatory for Cloud Evolution (JOYCE), Germany, which also routinely
operates a camera network. We find that the Blender path-tracing method
allows accurate reconstruction of up to 70% of the visible cloud edges,
depending on camera distance and accuracy thresholds. Additionally, we
conducted sensitivity tests and find that our method remains consistent
and independent of changes in its hyperparameters. The sensitivity of
the stereo reconstruction algorithm to cloud optical thickness is
investigated, finding a cloud boundary placement error of approximately
182 m. This error can be considered typical for cloud boundary
reconstruction using stereo camera imagery in general. The results
provide proof of principle for future use of the method for evaluating
LES clouds against real camera imagery, and for further optimizing the
configuration of such camera networks.
Importance of transport analysis in large urban projects
Authors: Stefanovic Nebojsa , Danilovic-Hristic Natasa
Published: June 2023

In a series of urban analyses used in the development of urban plans, there is also a traffic analysis. It is aimed at assessing the impact of the capacity of planned contents on the transport network of the narrower and wider area. In this paper, a large city project for the Belgrade waterfront area was selected as a case study and the analysis done as a transport study for the planning process for this location. Traffic analysis deals with the assessment of how much load planned purposes (housing, business, commercial, public facilities, etc.) will generate and how this will affect the existing and planned road network, standing out approach with six basic phases used in the research and description of the differences between three conceptualized network designs. For these purposes, the appropriate software is used, which for the set network load parameters at different times of the day creates scenarios of the number of vehicles and dominant directions of movement and indicates the shortcomings of the network that needs to be adapted to the requirements of users (0 -with modest attractiveness based on previous plans for the area, 1-3 for different network designs in the peak hours). This type of analysis with its results provides an input or planning the spatial organization of content and connections within the area and with a wider environment.
Accounting Personnel Quality, Audit Risk, and Auditor Responses
Authors: Gul Ferdinand A. , Lin Bin , Yang Zhifeng , Zhang Min , Zhu Haoran
Published: June 2023

This study draws on human capital theory to measure the quality of accounting personnel based on their education level and investigate whether the education level of the client firm’s accounting personnel affects auditors’ assessment of audit risk by examining audit outcomes. It shows that auditors charge higher fees and are more likely to make audit adjustments for companies whose accounting personnel have a lower level of education. The relationship between the education level of accounting personnel and audit fees (audit adjustments) is robust to an instrumental variable model, an entropy balancing approach, and a difference-in-differences analysis. Audit firms strategically assign more experienced partners to audit companies whose accounting personnel’s average education levels are relatively low. Taken together, these findings suggest that the education level of clients’ accounting personnel affects auditors’ assessment of audit risk and audit outcomes.

JEL Classifications: M40; M42; J01; J24.
The Dark Side of Robotic Process Automation (RPA): Understanding Risks and Challenges with RPA
Authors: Eulerich Marc , Waddoups Nathan , Wagener Martin , Wood David A.
Published: June 2023

SYNOPSIS

Auditors and corporate accountants are rapidly adopting robotic process automation (RPA) to assist with accounting tasks. The purpose of this paper is to increase understanding of the risks and challenges associated with RPA. This is particularly important given most existing reports focus on the benefits of using RPA. We interview multiple professionals to ascertain challenges, drawbacks, or pitfalls of using RPA. We identify five key challenges related to RPA usage: (1) RPA is often used as a quick-fix band-aid instead of fixing core system issues, (2) RPA can cause serious control and security issues, (3) the true cost of RPA is often misunderstood and understated, (4) RPA governance is complicated and challenging, and (5) RPA usage can lead to a loss of process knowledge. Raising these issues should allow practitioners to make more informed decisions regarding RPA implementations and help inform them regarding the problematic areas that require better governance.
The Development of the Process Mining Event Log Generator (PMELG) Tool
Authors: Hawkins Steven R. , Pickerd Jeffrey , Summers Scott L. , Wood David A.
Published: June 2023

SYNOPSIS

Process mining is an emerging technology that allows users to visualize all potential variations of business processes within an organization. It holds significant potential for impacting the field of accounting. However, training professionals and students in its use is challenging due to a lack of event data applicable to accounting and auditing scenarios. To address this issue, we developed an easy-to-use tool called the Process Mining Event Log Generator (PMELG) for generating process mining data files for the order-to-cash process. With the PMELG tool, users can create realistic datasets that incorporate key accounting and auditing concepts, such as segregation of duties issues, internal control violations, operational inefficiencies, and fraudulent behavior. We validate this tool with professionals and academics. Both groups believe the tool will be beneficial for both practitioners and academic audiences.
The Exosome-Transmitted lncRNA LOC100132249 Induces Endothelial Dysfunction in Diabetic Retinopathy
Authors: Hu Zizhong , Wang Jingfan , Pan Ting , Li Xinsheng , Tao Chao , Wu Yan , Wang Xingxing , Zhang Zhengyu , Liu Yu , Zhang Weiwei , Xu Changlin , Wu Xinjing , Gu Qinyuan , Fan Yuanyuan , Qian Huiming , Mugisha Aime , Yuan Songtao , Liu Qinghuai , Xie Ping
Published: June 2023

Diabetic retinopathy (DR), one of the most common microangiopathic complications in diabetes, causes severe visual damage among working-age populations. Retinal vascular endothelial cells, the key cell type in DR pathogenesis, are responsible for abnormal retinal angiogenesis in advanced stages of DR. The roles of exosomes in DR have been largely unknown. In this study, we report the first evidence that exosomes derived from the vitreous humor of patients with proliferative DR (PDR-exo) promote proliferation, migration, and tube formation of human retinal vascular endothelial cells (HRVECs). We identified long noncoding RNA (lncRNA) LOC100132249 enrichment in PDR-exo via high-throughput sequencing. This lncRNA, also mainly derived from HRVECs, promoted angiogenesis both in vitro and in vivo. Mechanistically, LOC100132249 acted as a competing endogenous sponge of miRNA-199a-5p (miR-199a-5p), thus regulating the endothelial-mesenchymal transition promoter SNAI1 via activation of the Wnt/β-catenin pathway and ultimately resulting in endothelial dysfunction. In conclusion, our findings underscored the pathogenic role of endothelial-derived exosomes via the LOC100132249/miR-199a-5p/SNAI1 axis in DR angiogenesis and may shed light on new therapeutic strategies for future treatment of DR.

Article Highlights

This study provides the first evidence that exosomes derived from vitreous humor from patients with proliferative diabetic retinopathy participate in angiogenesis. The findings demonstrate an unreported long noncoding RNA (lncRNA), LOC100132249, by exosomal sequencing of vitreous humor. The newly found lncRNA LOC100132249, mainly derived from endothelial cells, promotes angiogenesis via an miRNA-199a-5p/SNAI1/Wnt/β-catenin axis in a pro–endothelial-mesenchymal transition manner.
Fasting Ketone Bodies and Incident Type 2 Diabetes in the General Population
Authors: Szili-Torok Tamas , de Borst Martin H. , Garcia Erwin , Gansevoort Ron T. , Dullaart Robin P.F. , Connelly Margery A. , Bakker Stephan J.L. , Tietge Uwe J.F.
Published: June 2023

With rising incidence and prevalence of type 2 diabetes, prevention including identification of prospective biomarkers becomes increasingly relevant. Although ketone bodies recently received a renewed interest as potential biomarkers, data linking these metabolites to diabetes risk are scarce. Therefore, the present prospective study investigated a potential association between fasting ketone bodies and incident type 2 diabetes in the general population. This study from the PREVEND cohort included 3,307 participants from the general population initially free of diabetes or impaired fasting glucose. Baseline fasting ketone body concentrations were measured by nuclear magnetic resonance spectroscopy. One hundred twenty-six participants (3.8%) developed type 2 diabetes during a median (interquartile range) follow-up of 7.3 (6.3–7.6) years. In Kaplan-Meier analysis, sex-stratified ketone body levels strongly positively associated with incident type 2 diabetes, which was confirmed in Cox regression analyses adjusted for several potential confounders. There was no significant interaction by sex. Both 3-β-hydroxybutyrate and acetoacetate+acetone individually associated with incident type 2 diabetes. In conclusion, fasting plasma ketone body levels are strongly positively associated with incident type 2 diabetes in the general population independent of several other recognized risk factors. These results may have important implications for diabetes prevention including dietary strategies.

Article Highlights

The identification of biomarkers that predict type 2 diabetes is increasingly relevant for personalized medicine strategies. Data regarding ketone bodies and incident type 2 diabetes are scarce. This study shows that ketone bodies, either combined or as individual subspecies, are strongly associated with incident type 2 diabetes in the general population, independent of potential confounders. These results may have important implications for diabetes prevention including dietary strategies.
118-LB: Feasibility of a Prototype Dual Function Glucose Sensing Insulin Delivery Cannula in People with Type 1 Diabetes
Authors: LU JEAN , YI YUAN CHENG , KONG YEE W. , NETZER EMMA , WU HUANPING , SEIDL THOMAS , O'NEAL DAVID N.
Published: June 2023

Background: SynerGTM (Pacific Diabetes Technology, Portland, OR), a prototype subcutaneous cannula combining glucose sensing and insulin infusion could reduce the burden on people with diabetes (PWD) using insulin pump therapy (IPT) and glucose sensors.

Aim: To assess and refine SynerGTM sensor accuracy, evaluate insulin infusion site function, and user tolerability.

Method: Adults with type 1 diabetes established on IPT participated. Following a 48-hour run-in using a commercially available infusion set with a study pump (Medtronic 780G), a SynerGTM set was inserted subcutaneously in the anterior abdomen and attached to the pump. Participants were blinded to the investigational device readings. A standardised meal was eaten 60 minutes post-insertion. Glucose was measured on arterialised blood by YSI and finger-stick test strips (Roche Accu-Chek Guide) every 10 minutes for 60 minutes before and every 15 minutes for 4 hours after the meal. An insulin bolus was delivered immediately prior to the study meal using SynerGTM. Insulin continued to be delivered using SynerGTM at home and fingerstick readings continued. A second meal test as described above was performed on day 4 before study conclusion. A commercially available (Dexcom G6) continuous glucose monitor (CGM) was inserted prior to the 48 hour run-in preceding day 1 and worn throughout the study.

Result: In 15 participants 99% of 679 data pairs of SynerGTM vs. YSI and 1305 data pairs vs. capillary glucose measurement were in zones A and B of the consensus error grid. MARD was 13.5% and 13.5% respectively. No artifact sensor spikes were observed with bolused insulin. SynerGTM was well tolerated and there were no significant differences in CGM time in range or TDD of insulin compared with run-in.

Conclusion: This study proves the feasibility of SynerGTM as the first single through-the-skin device providing co-located insulin infusion and glucose sensing for PWD who take insulin.

Disclosure

J. Lu: None. C. Yuan: None. Y. W. Kong: None. E. Netzer: None. H. Wu: None. T. Seidl: None. D. N. O'neal: None.

Funding

JDRF (IND-2016-261)
1784-PUB: Empagliflozin (EMPA) Enhances Vascular Insulin Sensitivity and Lowers Plasma ICAM in Subjects with Type 2 Diabetes (T2D)
Authors: NGUYEN THI , JAHN LINDA , HARTLINE LEE , AYLOR KEVIN W. , BARRETT EUGENE
Published: June 2023

Background: The mechanism(s) by which sodium-glucose cotransporter 2 inhibitor (SGLT2i) use improves cardiovascular and renal outcomes in T2D are not well-defined. We hypothesized that EMPA would increase vascular insulin sensitivity and decrease endothelial cell (EC) stress markers in T2D. Study Design: Ten 18-60 years-old persons with T2D, 6.5 < a1c 3 months, were studied. we measured vascular stiffness (pulse wave separation analysis), ec function (flow-mediated dilation (fmd)), and stress biomarkers (elisa) before after a 2-hour, 1 mu min kg euglycemic clamp at 0 12 weeks treatment with 10 mg empa daily. results: not wk 0, but wks, insulin decreased forward backward arterial pressures from 28±3 to 20±2 24±3 13±1 mmhg, respectively, (p<0.02, each) improved the fmd response (p="0.02)," indicating function. peripheral systolic diastolic unchanged by week declined (p<0.03, treatment. lowered baseline post-insulin plasma icam-1 (p<0.002, increased vcam-1 (p<0.0005). infusion pecam-1 (p<0.03) vasoconstrictor endothelin-1 (p<0.01) comparably or without e-selectin s100a8 9 did change significantly either empa. decrease suggests that inflammation. insulin’s action lower appeared independent of empa, may contribute empa’s beneficial actions. Interpretation: EMPA for 12 weeks enhanced insulin’s action to: 1) diminish arterial stiffness, 2) enhance EC function including biomarker release, and 3) lower blood pressure. Improved vascular insulin sensitivity may contribute to the improved CVD outcomes seen with SGLTi treatment.

Disclosure

T.Nguyen: None. L.Jahn: None. L.Hartline: None. K.W.Aylor: None. E.Barrett: None.

Funding

National Institutes of Health (R01HL142250)
1803-PUB: Effectiveness and Safety of the Insulin Degludec U100 vs. Glargine U300 in People with Type 1 diabetes—The IneoxPlus Real-World Study
Authors: RUIZ DE ADANA MARIA S. , DOMÍNGUEZ-LÓPEZ MARTA E. , DEL ROSARIO VALLEJO MORA MARÍA , COLOMO NATALIA , LINARES FRANCISCA , MORILLAS VIRGINIA , JOSÉ VALLEJO HERRERA MARÍA , PATRICIA ALONSO GALLARDO SILVIA , TERESA PADILLA FUENTES MARÍA , NAVAS VELA LUIS I. , MALDONADO-ARAQUE CRISTINA , OLVEIRA GABRIEL , ROJO MARTÍNEZ GEMMA
Published: June 2023

Objective: The INEOX-Plus study aims to compare the efficacy and safety of Deg-U100 and Gla-U300 in people with T1d incorporated to the Flash Glucose Monitoring (FGM) technology for over 6 months.

Materials and Methods: Cross-sectional study in 161 of the 260 T1D participants of the INEOX randomized study (NCT 03328845) who were initially randomized between 2017 and 2019 to receive Gla-U300 or Deg-U100 insulin and incorporated to FGM technology after. Participants were re-evaluated in the INEOX_Plus visit, at an average 2.8 years after the final INEOX visit. Sociodemographic variables, insulin dose, plasma HbA1c and episodes of severe hypoglycemia and ketosis in the previous year were collected together with data on Freestyle libre 2® system downloaded from the last 90 days: sensor use, number of daily scans, GMI, mean glucose, CV, TIR 70-180, TBR 69-54, TBR <54, TAR 181-250, TAR >250 and hypoglycemia events- number/90 days and rate/year-.

Results: 90 men (56%) and 71 women (44%), mean age 44±11 years, with diabetes evolution of 23.5±10 years belonging to the INEOX study accepted to participate; 75 subjects (46%) used Gla-U300 and 86 (54%) Deg-U100. A significant reduction in HbA1c was observed between the final INEOX and INEOX-Plus visit (7.65±1.04% vs 7.43±0.84%, p= 0.002) regardless of the type and dose of second-generation long-acting insulin analogue used. There were no episodes of severe hypoglycemia or ketoacidosis reported. We did not find significant differences in insulin doses, HbA1c and FGM metrics except in the Hypoglycemia events incidence rate -213.65 vs 260.05 events/person/year; p=0.001 - for Gla-U300 vs Deg-U100 respectively.

Conclusions: For people with T1D in routine clinical follow-up with FGM, Gla-U300 and Deg-U100 insulin have a similar effect on the efficacy and safety variables except for significantly lower incidence rate of yearly hypoglycemia events for Gla-U300 users.

Disclosure

M.S.Ruiz de adana: None. L.I.Navas vela: None. C.Maldonado-araque: None. G.Olveira: Other Relationship; Abbott Diabetes, Novo Nordisk, Speaker's Bureau; Lilly. G.Rojo martínez: None. M.E.Domínguez-lópez: None. M.Vallejo mora: None. N.Colomo: None. F.Linares: None. V.Morillas: Other Relationship; Boehringer Ingelheim and Eli Lilly Alliance. M.Vallejo herrera: None. S.Alonso gallardo: None. M.Padilla fuentes: None.

Funding

Instituto de Salud Carlos III (PI 17/00861)
1805-PUB: Results of a Two-Part Feasibility Study Assessing Inhaled Insulin for Meals with MDI or Automated Insulin Delivery (AID) Compared with Standard AID Therapy
Authors: KAISERMAN KEVIN , ULLOA JOHANNA , PLEITEZ JENNIFER , SYLVAN JOSEPH , CODORNIZ KEVIN , LEE SCOTT , JACOBSON CHRISTOPHER , BLEVINS THOMAS
Published: June 2023

Background: Technosphere Insulin (TI) is an ultra-rapid acting inhaled insulin and when used with basal insulin may be a safe and effective alternative to AID systems in type 1 diabetes.

Methods: During study part 1, subjects using an AID were given an in-clinic standardized meal with either all meal insulin as TI (n=21) at meal start or rapid-acting insulin given via an AID (n=5) 15 minutes prior. Capillary glucose was measured at intervals for 2 hours. During study part 2, HbA1c was compared for 3 groups at baseline and 90 days: AID control (n=5), TI+AID (TI for meals only; n=9), or TI+insulin degludec (TI for meals and corrections, degludec for daily basal; n=10).

Results: The figure shows in study part 1, TI led to significantly lower post-prandial glucose than AID control for the standardized meal. In study part 2, comparable HbA1c reduction from baseline was observed in all 3 groups. No events of severe hypoglycemia and one episode of diabetic ketoacidosis not related to TI per investigator were reported.

Conclusion: This initial evaluation indicates that 1) TI had a more favorable glycemic response for 2 hours after the meal compared to AID control, and 2) HbA1c baseline to 90 days was comparable for the AID and the TI arms without serious safety issues. Adding TI for meals or switching to TI and basal insulin may provide comparable safety and efficacy to AID alone.

Disclosure

K.Kaiserman: Employee; MannKind Corporation, Research Support; Medtronic, Stock/Shareholder; MannKind Corporation. J.Ulloa: Employee; MannKind Corporation. J.Pleitez: Employee; MannKind Corporation. J.Sylvan: Employee; MannKind Corporation. K.Codorniz: Research Support; Medtronic, MannKind Corporation. S.Lee: Consultant; MannKind Corporation. C.Jacobson: Advisory Panel; MannKind Corporation, Medtronic. T.Blevins: Other Relationship; Medtronic, Research Support; Lilly Diabetes, Novo Nordisk, Dexcom, Inc., Abbott Diabetes, Tandem Diabetes Care, Inc., Medtronic, Speaker's Bureau; Lilly Diabetes, Novo Nordisk A/S.
1807-PUB: Monocarbonyl Curcumin Analogs C66 and B2BrBC Improve Redox Status in Streptozotocin-Induced Diabetic Rats
Authors: STOJCHEVSKI RADOSLAV , ANGELOVSKI MARIJA , VELICHKOVIKJ SARA , HADZI-PETRUSHEV NIKOLA , BOGDANOV JANE B. , MLADENOV MITKO , PORETSKY LEONID , AVTANSKI DIMITER
Published: June 2023

Curcumin is a natural polyphenolic compound with recognized antioxidant and anti-inflammatory effects. However, low water solubility, poor bioavailability, and rapid metabolism in vivo make its use challenging. To overcome these drawbacks, numerous curcumin analogs have been developed. The aim of the present study was to investigate the effect of two experimental curcumin monocarbonyl analogs [(2E,6E)-2,6-bis[(2-trifluoromethyl)benzylidene]cyclohexanone (C66)] and (2E,6E)-2,6-bis(2-bromobenzylidene)cyclohexanone) (B2BrBC)] on oxidative stress markers and antioxidant enzymes in streptozotocin (STZ)-induced diabetes rat model. The study involved a total of 53 male Wistar rats divided into two experiments in order to assess their therapeutic and preventive effects: STZ injection (60 mg/kg) followed by C66 or B2BrBC treatment (both 50 µmol/kg) daily for 30 days before the sacrifice (Experiment 1), and a single dose of C66 or B2BrBC treatment (both 125 µmol/kg) 6 hours before STZ injection, and sacrifice after 72 hours (Experiment 2). Plasma, liver, and kidney samples were obtained and used to measure the oxidative stress biomarkers [malondialdehyde (MDA) and advanced oxidation protein products (AOPP)] and the activity of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)]. The results demonstrated that both curcumin analogs displayed protective and restorative effects and counteracted the effect of STZ on the tested redox biomarkers and antioxidant enzymes, most prominently after 30 days post-treatment (Experiment 1). We conclude that the beneficial effects of C66 and B2BrBC in the STZ diabetes model provide a basis for further studies involving C66 and B2BrBC and other curcumin analogs in diabetes.

Disclosure

R.Stojchevski: None. M.Angelovski: None. S.Velichkovikj: None. N.Hadzi-petrushev: None. J.B.Bogdanov: None. M.Mladenov: None. L.Poretsky: None. D.Avtanski: None.

Funding

Gerald and Dorothy Friedman New York Foundation for Medical Research