bluuebunny/crossref_metadata_2025 huggingface dataset:
Letter: Shorter duration of intravenous terlipressin for variceal bleeding in patients with cirrhosis—A promising find
Authors: Nedumannil Leya , Mohamedrashed Mustafa , Sood Siddharth , Lewis Diana
Published: April 2024

LINKED CONTENT

This article is linked to Vaishnav et al papers. To view these articles, visit https://doi.org/10.1111/apt.17868 and https://doi.org/10.1111/apt.17982
Meta‐analysis: Persistence of advanced therapies in the treatment of inflammatory bowel disease
Authors: Yiu Tsz Hong , Ko Yanna , Pudipeddi Aviv , Natale Patrizia , Leong Rupert W.
Published: April 2024

Background

The expanding options in advanced therapies for ulcerative colitis (UC) and Crohn's disease (CD) present challenges in treatment selection. Persistence analysis assesses drug durability in real‐world settings, acting as a surrogate marker for medication efficacy and tolerance. Unlike traditional comparative studies, persistence analysis provides insights extending beyond the initial year of treatment.

Aim

To provide real‐world evidence on treatment effectiveness, tolerability and preferences of physicians and patients regarding various advanced therapies for IBD.

Methods

We conducted a systematic review of observational studies up to March 2023 assessing advanced therapies' persistence in UC and CD. Advanced therapies under examination included infliximab, adalimumab, vedolizumab, ustekinumab, golimumab, certolizumab and tofacitinib. We pooled the persistence of each agent and conducted a meta‐analysis to compare the persistence of newer agents with traditional TNF inhibitors (TNFi)—specifically infliximab and adalimumab.

Results

Among 63 observational studies, vedolizumab had the highest 1‐year persistence in UC (73.8%, 95% CI: 70.0%–77.6%) and ustekinumab in CD (77.5%, 95% CI: 72.9%–82.1%). Compared to TNFi, vedolizumab demonstrated increased persistence with a relative risk (RR) of 1.30 (95% CI: 1.19–1.41) for UC and 1.14 (95% CI: 1.09–1.20) for CD at 1 year, while ustekinumab demonstrated a RR of 1.15 (95% CI: 1.07–1.23) for CD at 1 year. Vedolizumab exhibited sustained increased persistence in UC over 2 years compared to TNFi (RR: 1.33, 95% CI 1.14–1.54).

Conclusion

This meta‐analysis highlights the superior persistence of ustekinumab and vedolizumab over TNFi, and offers valuable insights for clinicians navigating the challenging landscape of UC and CD therapeutic choices.
Adaptive use of error‐prone DNA polymerases provides flexibility in genome replication during tumorigenesis
Authors: Bainbridge Lewis J. , Daigaku Yasukazu
Published: April 2024

Human cells possess many different polymerase enzymes, which collaborate in conducting DNA replication and genome maintenance to ensure faithful duplication of genetic material. Each polymerase performs a specialized role, together providing a balance of accuracy and flexibility to the replication process. Perturbed replication increases the requirement for flexibility to ensure duplication of the entire genome. Flexibility is provided via the use of error‐prone polymerases, which maintain the progression of challenged DNA replication at the expense of mutagenesis, an enabling characteristic of cancer. This review describes our recent understanding of mechanisms that alter the usage of polymerases during tumorigenesis and examines the implications of this for cell survival and tumor progression. Although expression levels of polymerases are often misregulated in cancers, this does not necessarily alter polymerase usage since an additional regulatory step may govern the use of these enzymes. We therefore also examine how the regulatory mechanisms of DNA polymerases, such as Rad18‐mediated PCNA ubiquitylation, may impact the functionalization of error‐prone polymerases to tolerate oncogene‐induced replication stress. Crucially, it is becoming increasingly evident that cancer cells utilize error‐prone polymerases to sustain ongoing replication in response to oncogenic mutations which inactivate key DNA replication and repair pathways, such as BRCA deficiency. This accelerates mutagenesis and confers chemoresistance, but also presents a dependency that can potentially be exploited by therapeutics.
The wash zone and habitat use among three benthic fish species in stratified lakes
Authors: Ridgway Mark S. , Bell Allan H. , Middel Trevor A. , Wells Mathew G. , Taylor Courtney E. , Mitchell Krystal , Lacombe Nick A.
Published: April 2024

Mixing processes in lakes are important in determining sedimentation zones and in setting the so‐called “wash zone”, the area of lake bottom in contact with an oscillating thermocline during wind‐driven internal seiche events. The wash zone also aligns with a sharp change in sediment roughness and hardness. Taken together, these rapid changes in temperature and sediment indicate that the wash zone is a distinctive ecotone in stratified lakes. Depth stratified randomised netting was used to develop count‐based habitat use models for three common benthic fish species as a function of depth or temperature covariates. Using data from two lakes with quite different wash zone depths, we show the wash zone to describe fish habitat for two of three benthic fish species by utilising the top 50% of estimated fish abundance as an indicator of habitat use. White sucker (Catostomus commersoni) habitat use was within the boundaries of the wash zone. Lake whitefish (Coregonus clupeaformis) habitat was adjacent and within the wash zone. Longnose sucker (C. catostomus) habitat use was in the deep areas of lakes dominated by sediment focusing and did not overlap white sucker. Lake whitefish habitat use overlapped both catostomids, but peak abundance of both lake whitefish and white sucker overlapped pointing to potential interactions between these species. Smaller lakes have less vigorous mixing processes and a narrower wash zone, so with a decline in lake size the likely area of the wash zone as habitat for benthic feeding fish would become smaller.
Narcissus reflected: Grey and white matter features joint contribution to the default mode network in predicting narcissistic personality traits
Authors: Jornkokgoud Khanitin , Baggio Teresa , Bakiaj Richard , Wongupparaj Peera , Job Remo , Grecucci Alessandro
Published: April 2024

Despite the clinical significance of narcissistic personality, its neural bases have not been clarified yet, primarily because of methodological limitations of the previous studies, such as the low sample size, the use of univariate techniques and the focus on only one brain modality. In this study, we employed for the first time a combination of unsupervised and supervised machine learning methods, to identify the joint contributions of grey matter (GM) and white matter (WM) to narcissistic personality traits (NPT). After preprocessing, the brain scans of 135 participants were decomposed into eight independent networks of covarying GM and WM via parallel ICA. Subsequently, stepwise regression and Random Forest were used to predict NPT. We hypothesized that a fronto‐temporo parietal network, mainly related to the default mode network, may be involved in NPT and associated WM regions. Results demonstrated a distributed network that included GM alterations in fronto‐temporal regions, the insula and the cingulate cortex, along with WM alterations in cerebellar and thalamic regions. To assess the specificity of our findings, we also examined whether the brain network predicting narcissism could also predict other personality traits (i.e., histrionic, paranoid and avoidant personalities). Notably, this network did not predict such personality traits. Additionally, a supervised machine learning model (Random Forest) was used to extract a predictive model for generalization to new cases. Results confirmed that the same network could predict new cases. These findings hold promise for advancing our understanding of personality traits and potentially uncovering brain biomarkers associated with narcissism.
Change of voltage‐gated sodium channel repertoire in skeletal muscle of a MuSK myasthenia gravis mouse model
Authors: Butenko Olena , Jensen Stine Marie , Fillié‐Grijpma Yvonne E. , Verpalen Robyn , Verschuuren Jan J. , van der Maarel Silvère M. , Huijbers Maartje G. , Plomp Jaap J.
Published: April 2024

Muscle‐specific kinase myasthenia gravis (MuSK MG) is caused by autoantibodies against MuSK in the neuromuscular junction (NMJ). MuSK MG patients have fluctuating, fatigable skeletal muscle weakness, in particular of bulbar muscles. Severity differs greatly between patients, in spite of comparable autoantibody levels. One explanation for inter‐patient and inter‐muscle variability in sensitivity might be variations in compensatory muscle responses. Previously, we developed a passive transfer mouse model for MuSK MG. In preliminary ex vivo experiments, we observed that muscle contraction of some mice, in particular those with milder myasthenia, had become partially insensitive to inhibition by μ‐Conotoxin‐GIIIB, a blocker of skeletal muscle NaV1.4 voltage‐gated sodium channels. We hypothesised that changes in NaV channel expression profile, possibly co‐expression of (μ‐Conotoxin‐GIIIB insensitive) NaV1.5 type channels, might lower the muscle fibre's firing threshold and facilitate neuromuscular synaptic transmission. To test this hypothesis, we here performed passive transfer in immuno‐compromised mice, using ‘high’, ‘intermediate’ and ‘low’ dosing regimens of purified MuSK MG patient IgG4. We compared myasthenia levels, μ‐Conotoxin‐GIIIB resistance and muscle fibre action potential characteristics and firing thresholds. High‐ and intermediate‐dosed mice showed clear, progressive myasthenia, not seen in low‐dosed animals. However, diaphragm NMJ electrophysiology demonstrated almost equal myasthenic severities amongst all regimens. Nonetheless, low‐dosed mouse diaphragms showed a much higher degree of μ‐Conotoxin‐GIIIB resistance. This was not explained by upregulation of Scn5a (the NaV1.5 gene), lowered muscle fibre firing thresholds or histologically detectable upregulated NaV1.5 channels. It remains to be established which factors are responsible for the observed μ‐Conotoxin‐GIIIB insensitivity and whether the NaV repertoire change is compensatory beneficial or a bystander effect.
Institutional voids and new venture performance: The moderating role of founders' political ties
Authors: Tantawy Ahmed Adel , Amankwah‐Amoah Joseph , Puthusserry Pushyarag
Published: April 2024

Building on the institutional voids (IVs) and resource‐dependence perspectives, this study examines the moderating impact of new business founders' political ties on the relationship between IVs and new venture performance (NVP). We developed and tested a unique model using data obtained from 309 new ventures in the MENA region, specifically Egypt. The results demonstrate that founders' political ties enhance firms' complementary assets and mitigate the negative effects of IVs on NVP in developing markets. The theoretical and practical implications concerning NVP in a developing market environment are examined.
Metal ion activation and DNA recognition by the Deinococcus radiodurans manganese sensor DR2539
Authors: Mota Cristiano , Webster Myles , Saidi Melissa , Kapp Ulrike , Zubieta Chloe , Giachin Gabriele , Manso José Antonio , de Sanctis Daniele
Published: April 2024

The accumulation of manganese ions is crucial for scavenging reactive oxygen species and protecting the proteome of Deinococcus radiodurans (Dr). However, metal homeostasis still needs to be tightly regulated to avoid toxicity. DR2539, a dimeric transcription regulator, plays a key role in Dr manganese homeostasis. Despite comprising three well‐conserved domains – a DNA‐binding domain, a dimerisation domain, and an ancillary domain – the mechanisms underlying both, metal ion activation and DNA recognition remain elusive. In this study, we present biophysical analyses and the structure of the dimerisation and DNA‐binding domains of DR2539 in its holo‐form and in complex with the 21 base pair pseudo‐palindromic repeat of the dr1709 promoter region, shedding light on these activation and recognition mechanisms. The dimer presents eight manganese binding sites that induce structural conformations essential for DNA binding. The analysis of the protein‐DNA interfaces elucidates the significance of Tyr59 and helix α3 sequence in the interaction with the DNA. Finally, the structure in solution as determined by small‐angle X‐ray scattering experiments and supported by AlphaFold modeling provides a model illustrating the conformational changes induced upon metal binding.
A MODEL OF GROSS CAPITAL FLOWS: RISK SHARING AND FINANCIAL FRICTIONS
Authors: Lee Hyunju
Published: April 2024

This article builds a two‐country model of gross capital flows where agents share tradable output risk using two bonds, subject to stochastic collateral constraints. Equilibrium portfolios are short in domestic bonds and long in foreign bonds because the endogenous movements of the real exchange rate provide a hedge against domestic output shocks. Under negative domestic shocks, these external positions transfer wealth from home to abroad. During the Great Recession, the model shows that such wealth transfer from the United States mitigated the consumption drop abroad. Quantitatively, financial frictions account for about half of the collapse in U.S. gross flows in 2008.
Factors associated with prevalence and severity of erosive tooth wear in patients with reflux oesophagitis
Authors: Kitasako Yuichi , Momma Eri , Tanabe Tomohide , Koeda Mai , Hoshikawa Yoshimasa , Hoshino Shintaro , Kawami Noriyuki , Ikeda Masaomi , Iwakiri Katsuhiko
Published: April 2024

Background

Extrinsic factors for erosive tooth wear (ETW) have been widely reported, but the intrinsic factors for wear remain unclear.

Objectives

The aim of this study was to evaluate the factors associated with the prevalence of ETW in patients with reflux oesophagitis (RO). To prevent severe ETW with RO, factors associated with severity of ETW were also evaluated.

Methods

A total of 270 patients with RO were recruited. A modified tooth wear index was used to evaluate the prevalence and severity of ETW. Salivary secretion and buffering capacity were assessed prior to endoscopy. Subjects were asked to complete a medical condition and oral self‐care questionnaire. Univariate and multivariate analyses were employed to identify factors collectively associated with the prevalence and severity of ETW.

Results

A total of 212 cases were categorized as patients with ETW (148 with mild ETW and 64 with severe ETW). Multivariate analyses indicated that saliva secretion, severity of RO and proton pump inhibitor (PPI) resistance were associated with the prevalence of ETW, whereas age, BMI and severity of RO were associated with the severity of ETW. The odds ratio of saliva secretion and BMI were less than 1, meaning that higher saliva secretion resulted in a lower prevalence of ETW and lower BMI was associated with severe ETW.

Conclusion

Saliva secretion, severity of RO and PPI resistance were associated with the prevalence of ETW, whereas age, BMI and severity of RO were associated with the severity of ETW. Lower saliva secretion and BMI were significant factors for ETW.
Improvement of oral function and its impact on oral food intake in subacute stroke patients: A prospective study with dental intervention
Authors: Sekimoto Yu , Matsuo Koichiro , Sakai Ayu , Shibata Seiko , Minakuchi Shunsuke
Published: April 2024

Background

The association between oral food intake and oral function during the subacute stage of stroke is not well known.

Objective

To investigate (1) oral function changes in subacute stroke patients and (2) association between oral function and oral intake status at several time points.

Methods

In a prospective study involving 324 stroke patients at a convalescent rehabilitation unit, four oral function parameters (maximum tongue pressure, MTP; lip‐tongue motor function, LTMF; maximum occlusal force, MOF and oral health assessment tool, OHAT) were quantitatively measured upon admission (T0), at 1 month (T1) and 2 months (T2). Oral feeding status was assessed using the Functional Oral Intake Scale (FOIS) and divided based on the FOIS score into the dysphagic and regular diet groups. The changes in oral functions at the three time points were tested using generalized estimating equation analysis. The association between FOIS groups and oral functions at T1 and T2 was analysed by means of logistic regression analysis.

Results

All oral function parameters improved significantly over time during the hospital stay (mean differences: 4.9 for MTP, 0.6 for LTMF, 1.1 for MOF and −1.8 for OHAT). The FOIS groups were significantly associated with MTP (p < .05) and OHAT (p < .05) at both T1 and T2.

Conclusion

Our findings suggest that oral function significantly improves in patients during subacute stroke rehabilitation and better oral health can be associated with better oral intake. Improved oral function through dental intervention and oral rehabilitation may contribute to gains in oral food intake.
Epidemiology, clinical characteristics, outcome and biofilm forming properties in candidaemia: A single‐centre retrospective 4‐year analysis from Hungary
Authors: Kovács Fruzsina , Balla Noémi , Bozó Aliz , Harmath Andrea , Jakab Ágnes , Tóth Zoltán , Nagy Fruzsina , Majoros László , Kovács Renátó
Published: April 2024

Background

Candidaemia is a life‐threatening disease that is associated with high mortality, especially in intensive care units (ICUs). The number of comprehensive studies dealing with the epidemiologic characteristics of biofilm‐related properties is limited.

Objective

This study evaluated the clinical characteristics of candidaemia, to assess the biofilm‐forming properties of isolates, and to identify the risk factors of mortality.

Patients and Methods

A total of 149 candidaemia episodes from the University of Debrecen, Clinical Centre, between January 2020 and December 2023 were investigated retrospectively. The susceptibility of Candida isolates to fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin was evaluated and compared to the susceptibility of 1‐day‐old biofilms. Multivariate logistic regression analysis was applied to identify the independent predictors of 30‐day mortality rate.

Results

The most common Candida species was Candida albicans (41%), followed by C. parapsilosis (20%), C. glabrata (14%), C. tropicalis (13%), rare Candida species (7%), and C. krusei (5%). Sixty‐six percent of Candida isolates were biofilm formers and 44% had high metabolic activity. The 30‐day mortality rate was 52%, which was higher in ICUs (65%). The logistic regression analysis revealed several factors significantly influencing mortality including ICU admission (odds ratio [OR] 2.99, 95% confidence interval [CI] 1.17–8.04, p = 0.025), fluconazole treatment (OR 4.12, 95% CI 1.62–11.42, p = .004), and pneumonia (OR 0.261, 95% CI 0.1–0.67, p = .006).

Conclusions

This comprehensive analysis supports the better characterisation of candidaemia in healthcare settings, which ultimately may reduce mortality among patients.
Benchmark dose profiles for bivariate exposures
Authors: Akkaya Hocagil Tugba , Ryan Louise M. , Cook Richard J. , Dang Khue‐Dung , Carter R. Colin , Richardson Gale A. , Day Nancy L. , Coles Claire D. , Carmichael Olson Heather , Jacobson Sandra W. , Jacobson Joseph L.
Published: April 2024

While benchmark dose (BMD) methodology is well‐established for settings with a single exposure, these methods cannot easily handle multidimensional exposures with nonlinear effects. We propose a framework for BMD analysis to characterize the joint effect of a two‐dimensional exposure on a continuous outcome using a generalized additive model while adjusting for potential confounders via propensity scores. This leads to a dose–response surface which can be summarized in two dimensions by a contour plot in which combinations of exposures leading to the same expected effect are identified. In our motivating study of prenatal alcohol exposure, cognitive deficits in children are found to be associated with both the frequency of drinking as well as the amount of alcohol consumed on each drinking day during pregnancy. The general methodological framework is useful for a broad range of settings, including combinations of environmental stressors, such as chemical mixtures, and in explorations of the impact of dose rate rather than simply cumulative exposure on adverse outcomes.
Binary Vapor Cycle for Waste Heat Recovery from Marine Engine Exhaust
Authors: Machado Kamille V. , Ordonez Juan C. , Souza Jeferson A. , Marques Crístofer H.
Published: April 2024

The considerable energy waste in maritime transport and the need to obtain alternatives to reduce emissions of polluting gases are factors that have motivated the study of waste heat recovery systems for marine engines. The system studied herein relies on a binary vapor cycle that uses water for the topping cycle while three organic fluids were investigated for the bottoming cycle: R601a, R134a, and R22. Each of these belongs to a different category of fluid, namely, dry fluid, isentropic fluid, and wet fluid, respectively. Two engines of different ratings and two different pressures of the heat recovery steam generator have been considered for each engine. Various outlet pressures for the topping turbine, which is the most liable to erosion and corrosion due to wet steam, have been investigated. The maximum efficiency achieved for the waste heat recovery system peaked at 21% while the maximum electric power accounted for 4.2% of engine brake power. Therefore, the employment of a waste heat recovery system based on a binary cycle seems a promising alternative to harnessing heat from the exhaust gases of marine engines.
Material Classification Map Using Dual-Energy Method at Low-Energy X-Ray Spectrum: An Experimental and Monte Carlo Simulation Study
Authors: Ghafarzadeh Mahdi , Kabir Mostafa , Kejani Mohammad Tavakoli
Published: April 2024

The objective of this article is to develop an effective method for material discrimination, distinguishing specifically between light metallic materials and heavy ones at low X-ray energies. In this research, Monte Carlo simulations are employed to investigate the influential factors affecting material discrimination. Initially, for result validation, the experimental setup is fully simulated based on the Monte Carlo method. The X-ray spectrum of 160 keV is simulated, and then it is registered after interacting with step wedges made of iron, aluminum, graphite, and ABS at specific thicknesses, capturing the radiation flux at each step. The results are compared with the experimental findings obtained from a dual-layer detector, demonstrating excellent agreement. In practice, the dual-layer detector comprises a low-energy GOS detector, a copper filter, and a high-energy CsI(Tl) detector. The energy spectra of the registered X-rays on each layer of detectors are obtained using the Monte Carlo method. Materials with low, medium, and high atomic numbers are chosen for analysis. These materials are categorized into three groups: organic materials (comprising both light and heavy organic and biological substances), light metals, and heavy metals. Discrimination between materials is achieved independently of their thickness by utilizing a material classification map (MCM) derived from a graph depicting the transmission ratio of low-energy X-ray photons versus the linear attenuation coefficient ratio for various materials with different atomic numbers. The results have been successfully validated through testing with various materials and thicknesses using both the experimental setup and Monte Carlo simulations.
Peri-Ultrasound Modeling to Investigate the Performance of Different Nonlinear Ultrasonic Techniques for Damage Monitoring in Plate Structures
Authors: Zhang Guangdong , Li Xiongbing , Kundu Tribikram
Published: April 2024

Peri-ultrasound modeling which is based on nonlocal peridynamics is found and proven to be effective for modeling nonlinear waves propagating and interacting with damages in structures. This work presents the peri-ultrasound modeling to investigate the performance of three commonly used nonlinear ultrasonic (NLU) techniques—wave mixing, higher harmonic generation (HHG), and sideband peak count-index (or SPC-I) for monitoring damages (or cracks) in three-dimensional (3D) plate structures. Cracks can be defined as “thin cracks” and “thick cracks” according to the horizon size mentioned in peridynamics. Peri-ultrasound modeling results reveal that the SPC-I results are consistent with other reported numerical modeling and experimental results available in the literature. However, the modulation indicator (MI) from the wave mixing model only shows consistent trends for thin cracks but not for thick cracks and its reliability is affected by the initial excitation bandwidth. The relative acoustic nonlinearity factor β from the HHG technique shows consistent trends for thick cracks but not for thin cracks. It can be concluded from the obtained parametric analysis results that the SPC-I technique is more robust and reliable for monitoring damages in engineering structures.
Tribological Properties and Wear Mechanisms of Laser Cladded Cu–Mo Coatings at 25–500 °C
Authors: Ma Jiqiang , Cui Hongxun , Tan Hui , Zhu Shengyu , Cheng Jun , Li Qinglin , Yang Jun
Published: April 2024

Surface modification is the major means to improving the wear resistance of copper alloys. In this study, Cu–Mo coatings were prepared on Cu–Cr–Zr alloy by laser cladding, and the high-temperature tribological properties against 7075 aluminum alloy were explored. The results show that the coatings are a two-phase structure of Mo encapsulated in Cu-mesh. The hardness and resistivity of the coatings are 61–73 Hb and (3.2–6.3) × 10−8 Ωm, respectively. The wear resistance of the coatings is determined by the hardness, which is related to the Mo content at lower temperatures, and it is controlled by the tribo-oxides layer composed of copper and molybdenum oxides at higher temperatures. As the temperature increases, the main wear mechanism of the coatings changes from abrasive wear to adhesive wear.
Effect of Neurofeedback Training Along With Swimming Exercise on the Stress, Anxiety, Depression, Severity of Dependence, and Craving in Methamphetamine-Dependent Patients
Authors: Fadaei Atefeh , Najafi Mahmoud , Miladi-Gorji Hossein , Tajik-Mansoury Mohammad Ali , Afkar Mohammad
Published: April 2024

This study investigated whether neurofeedback (NFB) training and swimming exercise (Swim) would reduce the stress, anxiety, depression, severity of dependence, and cravings in patients addicted to methamphetamines. Participants were allocated randomly to four groups: control group, NFB, Swim, and NFB/Swim. All groups completed the study questionnaire before and after treatment. The NFB, Swim, and NFB/Swim groups reported significantly less stress, cravings, and severity of dependence than the control group. The Swim and NFB/Swim groups had significantly lower depression scores than the control group. Also, the NFB/Swim group experienced less anxiety than the control group. However, the NFB/Swim group had lower levels of stress than the Swim group, and lower levels of anxiety and severity of dependence than the NFB group. These findings suggest that NFB training along with swimming exercise was effective in managing methamphetamine-related behavioral disturbances, which may help patients to manage their cravings.
Metagenome-assembled genomes from enrichment cultures grown on xenobiotic solvents
Authors: Jia Chongjian , Wu Cuiyu , Li Yingshi , Wang Shuhuan , Liu Jinhuan , Liu Jiying , Su Haimei , Tian Xin , Li Junhui
Published: April 2024

Microbes play a significant role in the cleanup of xenobiotic contaminants. Based on metagenomes derived from long-term enrichment cultures grown on xenobiotic solvents, we report 166 metagenome-assembled genomes, of which 137 are predicted to be more than 90% complete. These genomes broaden the representation of xenobiotic degraders.
ColiSeq: a multiplex amplicon assay that provides strain level resolution of
Escherichia coli
directly from clinical specimens
Authors: Williamson Charles H. D. , Vazquez Adam J. , Nunnally Amalee E. , Kyger Kristen , Fofanov Viacheslav Y. , Furstenau Tara N. , Hornstra Heidie M. , Terriquez Joel , Keim Paul , Sahl Jason W.
Published: April 2024

Escherichia coli
is a diverse pathogen, causing a range of disease in humans, from self-limiting diarrhea to urinary tract infections (UTIs). Uropathogenic
E. coli
(UPEC) is the most frequently observed uropathogen in UTIs, a common disease in high-income countries, incurring billions of dollars yearly in treatment costs. Although
E. coli
is easily grown and identified in the clinical laboratory, genotyping the pathogen is more complicated, yet critical for reducing the incidence of disease. These goals can be achieved through whole-genome sequencing of
E. coli
isolates, but this approach is relatively slow and typically requires culturing the pathogen in the laboratory. To genotype
E. coli
rapidly and inexpensively directly from clinical samples, including but not limited to urine, we developed and validated a multiplex amplicon sequencing assay, called ColiSeq. The assay consists of targets designed for
E. coli
species confirmation, high resolution genotyping, and mixture deconvolution. To demonstrate its utility, we screened the ColiSeq assay against 230 clinical urine samples collected from a hospital system in Flagstaff, Arizona, USA. A limit of detection analysis demonstrated the ability of ColiSeq to identify
E. coli
at a concentration of ~2 genomic equivalent (GEs)/mL and to generate high-resolution genotyping at a concentration of 1 × 10
5
GEs/mL. The results of this study suggest that ColiSeq could be a valuable method to understand the source of UPEC strains and guide infection mitigation efforts. As sequence-based diagnostics become accepted in the clinical laboratory, workflows such as ColiSeq will provide actionable information to improve patient outcomes.

IMPORTANCE

Urinary tract infections (UTIs), caused primarily by
Escherichia coli
, create an enormous health care burden in the United States and other high-income countries. The early detection of
E. coli
from clinical samples, including urine, is important to target therapy and prevent further patient complications. Additionally, understanding the source of
E. coli
exposure will help with future mitigation efforts. In this study, we developed, tested, and validated an amplicon sequencing assay focused on direct detection of
E. coli
from urine. The resulting sequence data were demonstrated to provide strain level resolution of the pathogen, not only confirming the presence of
E. coli
, which can focus treatment efforts, but also providing data needed for source attribution and contact tracing. This assay will generate inexpensive, rapid, and reproducible data that can be deployed by public health agencies to track, diagnose, and potentially mitigate future UTIs caused by
E. coli
.
Remote neuropsychological assessment of patients with neurological disorders and injuries—a study protocol for a cross-sectional case-control validation study
Authors: Berginström Nils , Andersson Linus
Published: April 2024

Introduction

There are great potential benefits of being able to conduct neuropsychological assessments remotely, especially for hard-to-reach or less mobile patient groups. Such tools need to be equivalent to standard tests done in the clinic and also easy to use in a variety of clinical populations.

Methods and analysis

This study protocol describes a cross-sectional study aimed at validating the newly developed digitalized neuropsychological test battery Mindmore Remote in patients with neurological disorders and injuries. Diagnoses comprise traumatic brain injury, stroke, Parkinson’s disease, multiple sclerosis, brain tumour and epilepsy. 50 patients in each patient group will be included. In addition, 50 healthy controls will be recruited. All participants will undergo both testing with Mindmore Remote at home and traditional neuropsychological assessment face-to-face in a randomised order. The primary outcome is the association between tests from the Mindmore Remote battery and their equivalent traditional neuropsychological tests. Further, bias between methods and differences between groups will also be investigated.

Ethics and dissemination

The study protocol has been approved by the Swedish Ethical Review Authority (2022-06230-01) and adheres to the declaration of Helsinki. All participants will be given oral and written information about the study and sign informed consent forms before entering the study. All participants are informed that they can terminate their participation in the study at any given time, without giving any explanation, and participating in the study or not will not affect their care at the clinic. Neither authors nor personnel involved in the research project are affiliated with Mindmore AB. The results from the study will be published in peer-reviewed scientific journals and presented at national and international conferences on the topic.

Trial registration number

NCT05819008.
Building the Road Ahead
Authors: LEUTERT Wendy
Published: April 2024

Chinese state-owned enterprises (SOEs) are the primary implementers of China’s Belt and Road Initiative (BRI). This article identifies three trends in Chinese SOEs’ development of overseas infrastructure through the BRI. Specifically, they are diversifying project models, pursuing more small and medium-sized projects, and partnering with new international actors. It also considers the implications of these shifts for Chinese SOEs and host countries.
China–Pakistan Economic Corridor
Authors: LIN Minwang
Published: April 2024

China and Pakistan celebrated the 10th anniversary of the launch of the China–Pakistan Economic Corridor (CPEC) in 2023. Over the past decade, the CPEC has been developed amid controversies and challenges, and has achieved notable successes, especially in large-scale infrastructure construction, which has laid the foundation for Pakistan’s economic development in the long term. However, the ever-changing domestic and international environment has not alleviated the challenges and risks facing the future development of the CPEC. Domestic instability in Pakistan, as well as intensifying strategic competition between the United States and China, could affect the future of the CPEC.
What is Proactive Human-Robot Interaction? - A Review of a Progressive Field and Its Definitions
Authors: van Den broek Marike Koch , Moeslund Thomas B.
Published: April 2024

During the past 15 years, an increasing amount of works have investigated proactive robotic behavior in relation to Human–Robot Interaction (HRI). The works engage with a variety of research topics and technical challenges. In this article, a review of the related literature identified through a structured block search is performed. Variations in the corpus are investigated, and a definition of Proactive HRI is provided. Furthermore, a taxonomy is proposed based on the corpus and exemplified through specific works. Finally, a selection of noteworthy observations is discussed.
Time‐Dependent Fuzzy Reliability Analysis of Concrete Slab during the Initial Water Storage Period of CFRD: A Case Study
Authors: Sun Gang , Hu Kongzhong , Liu Lifang , Li Junru
Published: April 2024

The concrete‐faced rockfill dam (CFRD) has been widely constructed worldwide, and the reliability of the concrete panels, the most important containment structure, is critical to the safety of the CFRDs and downstream communities. Several practical projects show that concrete slab cracking usually occurs during the water storage period, which can be attributed to the rapid increase of hydrostatic pressure and uneven settlement of the dam body. In this paper, a time‐dependent reliability analysis method considering the fuzziness of the failure criterion is presented to assess the slab cracking risk of the Houziyan CFRD during the water storage period. Based on the observed deformation, the material parameters are calibrated to ensure the fidelity of the numerical simulation. Based on the Drucker–Prager yield criterion and tensile strength criterion, the response surface method is utilized to construct the performance functions at different moments, and then the time‐dependent reliability analysis considering the fuzzy failure criteria is implemented for the concrete slab. The case study of the Houziyan CFRD shows that, during the initial period of water storage, the reliability index of the concrete slab decreases with the rise of the water level. With a stable water level, the probability of cracking of the concrete slab slowly decreases as the deformation of the dam body and slab tend to be coordinated. Especially, considering the fuzziness of the failure criteria, the reliability index decreased by about 2%, indicating that the proposed evaluation method is biased toward safety. The method proposed in this paper can reflect the evolution law of concrete slab reliability with the operating environment and provides a new approach to evaluate the performance of the concrete slab during the water storage period.
The Emerging Role of AI in Patient Education: A Comparative Analysis of the Accuracy of Large Language Models for Pelvic Organ Prolapse
Authors: Rahimli Ocakoglu Sakine , Coskun Burhan
Published: April 2024

Introduction: This study aimed to evaluate the accuracy, completeness, precision, and readability of outputs generated by three large language models (LLMs); these are GPT by OpenAI, BARD by Google, and Bing by Microsoft, in comparison to patient education material on pelvic organ prolapse (POP) provided by the Royal College of Obstetricians and Gynecologists (RCOG). Methods: A total of 15 questions were retrieved from the RCOG website and input into the three LLMs. Two independent reviewers evaluated the outputs for accuracy, completeness, and precision. Readability was assessed using the Simplified Measure of Gobbledygook (SMOG) score and the Flesch-Kincaid Grade Level (FKGL) score. Results: Significant differences were observed in completeness and precision metrics. ChatGPT ranked highest in completeness (66.7%), while Bing led in precision (100%). No significant differences were observed in accuracy across all models. In terms of readability, ChatGPT exhibited higher difficulty than BARD, Bing, and the original RCOG answers. Conclusion: While all models displayed a variable degree of correctness, ChatGPT excelled in completeness, significantly surpassing BARD and Bing. However, Bing led in precision, providing the most relevant and concise answers. Regarding readability, ChatGPT exhibited higher difficulty. We observed that while all LLMs showed varying degrees of correctness in answering RCOG questions on patient information for POP, ChatGPT was the most comprehensive, but its answers were harder to read. Bing, on the other hand, was the most precise. The findings highlight the potential of LLMs in health information dissemination and the need for careful interpretation of their outputs.
Considerações sobre Taeniomyia Stein, 1918 e descrição de Anthojuba, Gen. N. (Diptera, Anthomyidae)
Authors: Albuquerque Dalcy de Oliveira , Couri Márcia Souto
Published: April 2024

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Biologia de Eulaema Nigrita. 2. Atividades nidais
Authors: Pereira-Martins Silma Regina
Published: April 2024

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Novos Táxons de Anacolini (Coleoptera, Cerambycidae, Prioninae)
Authors: Galileo Maria Helena M. , Martins Ubirajara R.
Published: April 2024

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The silvestrii species group of amphisbaena, with the description of two new brasilian species (Reptilia: Amphisbaenia)
Authors: Vanzolini P. E.
Published: April 2024

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Abstract 188: Abnormal Heart Rate Responses to Exercise and Susceptibility to Ventricular Fibrillation: Effect of Endurance Exercise Training
Authors: Billman George E , Kukielka Monica
Published: April 2024

BACKGROUND
: Both a large heart rate (HR) increase at exercise onset and a slow heart rate recovery following the termination of exercise have been linked to an increased susceptibility to ventricular fibrillation (VF). Endurance exercise training can enhance cardiac vagal and reduce cardiac sympathetic regulation and could, thereby, improve the exercise HR response and decrease the risk for VF.

METHODS
: To test this hypothesis, a 2-min coronary occlusion was made during the last min of an 18-min exercise test in dogs with healed myocardial infarctions: 20 had VF (S, susceptible) and 13 did not (R, resistant). On a previous day, HR and heart rate variability (HRV, 0.24 to 1.04 Hz frequency component; an index of cardiac vagal activity) responses to submaximal exercise were measured before and 30, 60 & 120s after exercise onset and 30, 60 & 120s following the termination of exercise.

RESULTS
: Larger HR increases and a slower HR recovery (ANOVA, both P<0.01) were noted in the susceptible dogs (HR: 30s after exercise onset, S 179 ± 8.4 vs. R 156.8 ± 3.4 beats/min; 30s post exercise, S 186 ± 7.8 vs. R 164.2 ± 5.7 beats/min). These HR differences were accompanied by corresponding differences in cardiac vagal activity (HRV: 30s after exercise onset, S 4.0 ± 0.4 vs. R 4.8 ± 04 ln ms
2
; 30s post exercise, S 2.4 ± 0.3 vs. R 3.8 3 0.4 ln ms
2
). The dogs then received either a 10-wk exercise program (treadmill running; S n = 9; R n = 8) or an equivalent sedentary period (S n = 11; R n = 5). After 10-weeks, the response to exercise was not altered in the sedentary animals. In contrast, exercise training increased cardiac vagal activity such that HR at exercise onset was reduced while HR recovery increased. As a result, differences were no longer noted between the groups (30s after exercise onset: HR, S 151.4 ± 6.6 vs. R 149.5 ± 7.3 beats/min; HRV, S 5.8 ± 0.4 vs. R 5.6 ± 0.4 ln ms
2
; 30s post exercise: HR, S 159.4 ± 7.7 vs. R 153.5 ± 5.3 beats/min; HRV, S 4.0 ± 0.6 vs. R 4.9 ± 0.5 ln ms
2
). After training, the exercise plus ischemia tested provoked VF in sedentary but not trained susceptible dogs.

CONCLUSION
: Endurance exercise training can alter cardiac autonomic balance (increased cardiac vagal activity) to restore a more normal heart rate regulation and could, thereby, prevent ventricular fibrillation in high-risk individuals.
Abstract 563: Fibroblast Infiltration Reduces Conduction Velocity and Leads to Reentry Multiplication in Cardiomyocyte Monolayers
Authors: Muñoz Viviana , Berenfeld Omer , Jalife José
Published: April 2024

Background

: Cardiac fibrosis acts as an electrical obstacle and is thought to cause discontinuous propagation and arrhythmias. Fibrosis results from proliferation of fibroblasts which can form gap junctions with myocytes.

Methods and Results:

We conducted optical mapping experiments in 35 x 35 mm hetero-cellular neonatal rat monolayers of cardiac origin to test the hypothesis that fibroblast infiltration modifies the dynamics of reentry. When one half of the monolayer had a randomly distributed myocyte/fibroblast mixture (~50/50%), and the other half had >95% myocytes, slow (2.75 Hz) sustained reentry stabilized in the region with more fibroblasts. The wavefronts propagated 2:1 to the 95% myocyte region at twice the conduction velocity (CV) (27.75 vs 12.86 cm/s). In separate experiments, as the percentage of fibroblasts in the monolayers was increased, the number of wavebreaks and reentry circuits increased and the excitation pattern became progressively more complex. In 4-s movies, when the preparations contained 5% fibroblasts, phase maps revealed only 1–2 singularity points corresponding to organizing cores of sustained reentrant activity. At 30% fibroblasts, the number of wavebreaks increased to 5±2 and the activity was much more irregular and disorganized. Finally, at 70% fibroblasts, the monolayers underwent extremely complex self-sustained activity with 42±5 repeated wavebreaks forming small wavelets that remained confined to small areas and rotated around their own singularity points. All wavelets rotated at the same frequency and the more stable ones clustered at or near the center of the preparations.

Conclusions:

Co-culturing fibroblasts with myocytes significantly reduces CV while creating a substrate for increased stability and multiplication of reentry. These results predict that increased fibrosis in cardiac muscle would increase the complexity of wave propagation and reduce the frequency of reentry.
Abstract 4161: Cholesterol Levels in Different LDL Subclasses and CHD Incidence in Apparently Healthy Men and Women: The EPIC-Norfolk Prospective Population Study
Authors: Arsenault Benoit J , Lemieux Isabelle , Després Jean-Pierre , Boekholdt Matthijs S , Wareham Nicholas J , Bingham Sheila A , Khaw Kay-Tee
Published: April 2024

Background:

Measurement of cholesterol levels in small LDL particles represents a novel metabolic marker that might add to the coronary risk prediction attributed to LDL cholesterol and LDL particle size taken separately. We examined, in a nested case-control study performed in the prospective EPIC-Norfolk cohort, the association of LDL cholesterol in small LDL particles to future CHD in apparently healthy men and women aged 45 to 79 years who developed fatal or nonfatal CHD over 10-year follow-up.

Methods and results:

Cases (n=1035) were matched to 1920 controls who remained free of CHD, by age, gender and enrollment time. Electrophoretic characteristics of LDL particles were measured using 2–16% nondenaturing polyacrylamide gradient gel electrophoresis. Cholesterol levels in small LDL particles (<255 Å) were higher in cases than in controls (1.26 ± 0.87 vs. 1.07 ± 0.78 mmol/l, P<0.001) Participants in the top tertile of cholesterol concentrations in small LDL particles were characterized by the highest waist circumference, by the highest triglyceride, C-reactive protein and apolipoprotein B levels and by the lowest HDL cholesterol concentrations. These participants had an unadjusted odds ratio (OR) for future CHD of 1.72 (95% CI, 1.42 to 2.09; P<0.001) which remained significant after adjustment for classical risk factors such as age, smoking, diabetes, body mass index, systolic blood pressure and LDL cholesterol concentrations (OR, 1.43; 95% CI, 1.16 to 1.76; P=0.001). However, after further adjustments for triglyceride and HDL cholesterol levels, the association between cholesterol in small LDL particles and CHD was no longer significant (OR, 1.18; 95% CI, 0.95 to 1.48; NS).

Conclusions:

Cholesterol concentrations in different LDL subclasses show different relationships with CHD incidence in a European cohort representative of a contemporary Western population.