bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole genome sequencing insight into carbapenem-resistant and multidrug-resistant
Acinetobacter baumannii
harboring chromosome-borne
bla
OXA-23
Authors: Wang Wei , Weng Jiahui , Wei Jie , Zhang Qinghuan , Zhou Yu , He Yanju , Zhang Limei , Li Wenting , Zhang Yi , Zhang Zhiren , Li Xiaobin
Published: August 2024

Carbapenem-resistant
Acinetobacter baumannii
(CRAB) poses a significant threat to hospitalized patients as effective therapeutic options are scarce. Based on the genomic characteristics of the CRAB strain AB2877 harboring chromosome-borne
bla
OXA-23
, which was isolated from the bronchoalveolar lavage fluid (BALF) of a patient in a respiratory intensive care unit (RICU), we systematically analyzed antibiotic resistance genes (ARGs) and the genetic context associated with ARGs carried by CRAB strains harboring chromosome-borne
bla
OXA-23
worldwide. Besides
bla
OXA-23
, other ARGs were detected on the chromosome of the CRAB strain AB2877 belonging to ST208/1806 (Oxford MLST scheme). Several key genetic contexts associated with the ARGs were identified on the chromosome of the CRAB strain AB2877, including (1) the MDR region associated with
bla
OXA-23
,
tet(B)-tetR(B
),
aph(3'')-Ib,
and
aph(6)-Id
(2); the resistance island AbGRI3 harboring
armA
and
mph(E)-msr(E
) (3); the Tn
3
-like composite transposon containing
bla
TEM-1D
and
aph(3')-Ia
; and (4) the structure “IS
Aba1-bla
ADC-25
.” The first two genetic contexts were most common in ST195/1816, followed by ST208/1806. The last two genetic contexts were found most frequently in ST208/1806, followed by ST195/1816.

IMPORTANCE

The
bla
OXA-23
gene can be carried by plasmid or chromosome, facilitating horizontal genetic transfer and increasing carbapenem resistance in healthcare settings. In this study, we focused on the genomic characteristics of CRAB strains harboring the chromosome-borne
bla
OXA-23
gene, and the important genetic contexts associated with
bla
OXA-23
and other ARGs were identified, and their prevalent clones worldwide were determined. Notably, although the predominant clonal CRAB lineages worldwide containing the MDR region associated with
bla
OXA-23
,
tet(B)-tetR(B
),
aph(3'')-Ib,
and
aph (6)-Id
was ST195/1816, followed by ST208/1806, the CRAB strain AB2877 in our study belonged to ST208/1806. Our findings contribute to the knowledge regarding the dissemination of CRAB strains and the control of nosocomial infection.
Isolation and characterization of
Septuagintavirus
; a novel clade of
Escherichia coli
phages within the subfamily
Vequintavirinae
Authors: Cortés-Martín Adrián , Buttimer Colin , Pozhydaieva Nadiia , Hille Frank , Shareefdeen Hiba , Bolocan Andrei S. , Draper Lorraine A. , Shkoporov Andrey N. , Franz Charles M. A. P. , Höfer Katharina , Ross R. Paul , Hill Colin
Published: August 2024

Escherichia coli
is a commensal inhabitant of the mammalian gut microbiota, frequently associated with various gastrointestinal diseases. There is increasing interest in comprehending the variety of bacteriophages (phages) that target this bacterium, as such insights could pave the way for their potential use in therapeutic applications. Here, we report the isolation and characterization of four newly identified
E. coli
infecting tailed phages (W70, A7-1, A5-4, and A73) that were found to constitute a novel genus,
Septuagintavirus
, within the subfamily
Vequintavirinae
. Genomes of these phages ranged from 137 kbp to 145 kbp, with a GC content of 41 mol%. They possess a maximum nucleotide similarity of 30% with phages of the closest phylogenetic genus,
Certrevirus
, while displaying limited homology to other genera of the
Vequintavirinae
family. Host range analysis showed that these phages have limited activity against a panel of
E. coli
strains, infecting 6 out of 16 tested isolates, regardless of their phylotype. Electrospray ionization-tandem mass spectrometry (ESI-MS/MS) was performed on the virion of phage W70, allowing the identification of 28 structural proteins, 19 of which were shared with phages of other genera of
Vequintavirinae
family. The greatest diversity was identified with proteins forming tail fiber structures, likely indicating the adaptation of virions of each phage genus of this subfamily for the recognition of their target receptor on host cells. The findings of this study provide greater insights into the phages of the subfamily
Vequintavirinae
, contributing to the pool of knowledge currently known about these phages.

IMPORTANCE

Escherichia coli
is a well-known bacterium that inhabits diverse ecological niches, including the mammalian gut microbiota. Certain strains are associated with gastrointestinal diseases, and there is a growing interest in using bacteriophages, viruses that infect bacteria, to combat bacterial infections. Here, we describe the isolation and characterization of four novel
E. coli
bacteriophages that constitute a new genus,
Septuagintavirus
, within the subfamily
Vequintavirinae
. We conducted mass spectrometry on virions of a representative phage of this novel clade and compared it to other phages within the subfamily. Our analysis shows that virion structure is highly conserved among all phages, except for proteins related to tail fiber structures implicated in the host range. These findings provide greater insights into the phages of the subfamily
Vequintavirinae
, contributing to the existing pool of knowledge about these phages.
Outer membrane vesicles of
Acinetobacter baumannii
DS002 carry circular DNA similar to bovine meat and milk factors (BMMFs) and SPHINX 2.36 and probably play a role in interdomain lateral gene transfer
Authors: Dhurve Ganeshwari , Behera Sandhya Rani , Kodetham Gopinath , Siddavattam Dayananda
Published: August 2024

The discovery of Replication Competent Circular DNA molecules in mammalian cells and tissues is being linked to debilitating diseases, such as multiple sclerosis (MS), bovine spongiform encephalopathy (BSE), and colorectal cancer (CRC). These circular DNA molecules, otherwise known as bovine meat and milk factors (BMMFs) and Slow Progressive Hidden INfections of variable (X) latency (SPHINX), bear significant (80%) sequence similarity with the plasmids of
Acinetobacter baumannii
strains. Nanostructures, such as bacterial outer membrane vesicles (OMVs) serve as vehicles for transporting biomolecular cargo and have the potential to facilitate interkingdom lateral mobility of DNA. Strengthening the proposed hypothesis, this study demonstrates that OMVs derived from
A. baumannii
DS002 carrying four plasmids and genome (pTS236) of phage, AbDs1, successfully reached different parts of the body, including the central nervous system, following the injection of fluorescein isothiocyanate (FITC)-labeled OMVs into experimental mice. Out of the four OMV-associated plasmids, three (pTS4586, pTS9900, and pTS134338) were identified within the lumen, and the fourth one (pTS11291) was found on the surface of OMVs. In addition to the indigenous plasmids, the phage-encoded protein, Orf96, anchored on the surface of the OMVs by establishing a strong interaction with the OMV-associated porin, OmpA. Intriguingly, a subset of labeled OMVs, when incubated with Neuro2A cells, translocated across the membrane and reached to the cytoplasmic space of the cells. Collectively, the experimental evidence presented herein underscores the promising potential of OMVs as vehicles for delivering molecular cargo containing plasmids and phage genomes to diverse mammalian tissues and cells.

IMPORTANCE

Several independent studies have demonstrated the existence of replication competent circular DNA molecules of bacterial and viral origin in mammalian cells and tissues. However, studies about their origin and lateral mobility to mammalian cells are scarce. Our work describes the existence of circular DNA, similar to that of DNA molecules identified in mammalian cells, OMVs derived from soil isolate of
A. baumannii
DS002. Furthermore, the work also provides visual evidence that demonstrates the passage of labeled OMVs to different organs of experimental mice within hours after intravenously administering OMVs into experimental mice. Some of the labeled OMVs have even crossed the membrane of Neuro2A, suggesting the existence of interkingdom horizontal mobility between bacteria and mammals.
Near-extremal Kerr-like ECO in the Kerr/CFT correspondence in higher spin perturbations
Authors: Djogama M. Zhahir , Sakti Muhammad F. A. R. , Zen Freddy P. , Satriawan Mirza
Published: August 2024

The Kerr/CFT correspondence has been established to explore the quantum theory of gravity in the near-horizon geometry of an extreme Kerr black holes. The quantum gravitational corrections on the near-horizon region may manifest in form of a partially reflective membrane that replace the horizon. In such modification, the black holes now can be seen as a horizonless exotic compact object (ECO). In this paper, we consider the properties of Kerr-like ECOs in near-extremal condition using Kerr/CFT correspondence. We study the quasinormal modes and absorption cross-section in that background and compare these by using CFT dual computation. The corresponding dual CFT one needs to incorporate finite size/finite N effects in the dual CFT terminology. We also extend the dual CFT analysis for higher spin perturbations such as photon and graviton. We find consistency between properties of the ECOs from gravity sides and from CFT sides. The quasinormal mode spectrum is in line with non-extreme case, where the differences are in the length of the circle, on which the dual CFT lives, and phase shift of the incoming perturbation. The absorption cross-section has oscillatory feature that start to disappear near extremal limit. The particle spin determines the phase shift and conformal weight. We also obtain that the echo time-delay depends on the position of the membrane and extremality of the ECOs.
Effects of hydrostatic pressure, temperature, and position-dependent mass on the nonlinear optical properties of triple delta-doped GaAs quantum well
Authors: Tuzemen A. Turker , Al E. B. , Sayrac H. , Dakhlaoui H. , Mora-Ramos M. E. , Ungan F.
Published: August 2024

In this study, we thoroughly investigate the impacts of hydrostatic pressure, temperature, and position-dependent mass (PDM) on the nonlinear optical properties of asymmetric triple δ-doped GaAs quantum wells. Our analysis covers total optical absorption coefficients, relative refractive index changes, nonlinear optical rectification, second harmonic generation, and third harmonic generation. Initially, we employ PDM to solve the time-independent Schrödinger equation using the diagonalization method under effective mass and parabolic band approaches, considering pressure and temperature dependencies. Utilizing the first four energy eigenvalues and eigenfunctions, we apply the compact density matrix method to compute the system’s nonlinear optical properties numerically. The results indicate a shift in optical property peak positions toward lower (higher) energy spectra with increasing hydrostatic pressure (temperature). Furthermore, the influence of PDM shifts the system’s optical properties toward the higher energy spectrum, resembling the effect of temperature. From an experimental and theoretical perspective, one of the topics that researchers work on most is GaAs-based δ-doped systems (δ-doped heterojunction bipolar transistors, δ-doped field effect transistors, δ-multiple independent gate field effect transistors, etc.). We believe these findings will provide valuable insights for the researchers involved in GaAs-based δ-doped optoelectronic device design.
A Security Model for Web-Based Communication
Authors: Tehrani Pouyan Fotouhi , Osterweil Eric , Schmidt Thomas C. , Wählisch Matthias
Published: August 2024

Web access involves various protocols to resolve domain names to IP addresses, establish data exchange channels with Web servers, and to authenticate communication partners. Each protocol has its own set of requirements and security measures. In addition to technical features, operating the Web also introduces organizational and political aspects which are important to consider when deploying a secure basis for Web-based communication.

In this paper, we propose an algorithmic security model based on the widely deployed technologies DNS(SEC) and Web PKI to cover the three dimensions
identification
,
resolution
, and
transaction
. Our model enables quantification and qualification of the security assurance provided by an online service provider. To verify the applicability of our model, we investigate the online presence of
Alerting Authorities
in the U.S., selected
German Emergency Service
providers, and
UN member states
. We observe partially enhanced security relative to global Internet trends, yet find cause for concern as only about 6% of unique hosts cater to secure resolution. About 46% of investigated organizations use shared certificates with 1% of all organizations having no or invalid certificates. Two thirds of organizations are not uniquely identifiable and as such lack the basic requirement of trustworthy communication.
Mixture-of-Languages Routing for Multilingual Dialogues
Authors: Pei Jiahuan , Yan Guojun , De Rijke Maarten , Ren Pengjie
Published: August 2024

We consider multilingual dialogue systems and ask how the performance of a dialogue system can be improved by using information that is available in other languages than the language in which a conversation is being conducted. We adopt a collaborative chair-experts framework, where each expert agent can be either monolingual or cross-lingual, and a chair agent follows a mixture-of-experts procedure for globally optimizing multilingual task-oriented dialogue systems. We propose a mixture-of-languages routing framework that includes four functional components, i.e., input embeddings of multilingual dialogues, language model, pairwise alignment between the representation of every two languages, and mixture-of-languages. We quantify language characteristics of unity and diversity using a number of similarity metrics, i.e., genetic similarity and word and sentence similarity based on embeddings. Our main finding is that the performance of multilingual task-oriented dialogue systems can be greatly impacted by three key aspects, i.e., data sufficiency, language characteristics, and model design in a mixture-of-languages routing framework.
Unmaking-with AI: Tactics for Decentering through Design
Authors: Nicenboim Iohanna , Søndergaard Marie Louise Juul , Lindley Joseph , Reddy Anuradha , Strengers Yolande , Redström Johan , Giaccardi Elisa
Published: August 2024

This article explores the intersections and resonances between unmaking and more-than-human design. We begin by aligning unmaking with decentering, a fundamental practice in more-than-human design, through their shared movement and materiality. Using Lindström and Ståhl’s notion of the double movement in un/making, we analyze a series of workshops focused on designing with AI, annotating what was un/made and de/centered during the workshops’ activities. Through this analysis, we introduce two key contributions that highlight some opportunities in the diffractive alignment between unmaking and more-than-human design: firstly, the notion of “unmaking-with” as an emergent concept to describe a posthumanist unmaking practice, and secondly, three decentering tactics—situating, materializing, and enacting—that instantiate this practice through design. Finally, we discuss how unmaking can enrich more-than-human design and, conversely, how more-than-human design can help define the epistemological scope of unmaking.
Federated Learning Using Multi-Modal Sensors with Heterogeneous Privacy Sensitivity Levels
Authors: Hsu Chih-Fan , Li Yi-Chen , Tsai Chung-Chi , Wang Jian-Kai , Hsu Cheng-Hsin
Published: August 2024

Data from multi-modal sensors, such as Red-Green-Blue (RGB) cameras, thermal cameras, microphones, and mmWave radars, have gradually been adopted in various classification problems for better accuracy. Some sensors, like RGB cameras and microphones, however, capture privacy-invasive data, which are less likely to be used in centralized learning. Although the Federated Learning (FL) paradigm frees clients from sharing their sensor data, doing so results in reduced classification accuracy and increased training time. In this article, we introduce a novel Heterogeneous Privacy Federated Learning (HPFL) paradigm to better capitalize on the less privacy-invasive sensor data, such as thermal images and mmWave point clouds, by uploading them to the server for closing the performance gap between FL and centralized learning. HPFL not only allows clients to keep the more privacy-invasive sensor data private, such as RGB images and human voices, but also gives each client total freedom to define the levels of their privacy concern on individual sensor modalities. For example, more sensitive users may prefer to keep their thermal images private, while others do not mind sharing these images. We carry out extensive experiments to evaluate the HPFL paradigm using two representative classification problems: semantic segmentation and emotion recognition. Several key findings demonstrate the merits of HPFL: (i) compared to FedAvg, it improves foreground accuracy by 18.20% in semantic segmentation and boosts the F1-score by 4.20% in emotion recognition, (ii) with heterogeneous privacy concern levels, it achieves an even larger F1-score improvement of 6.17–16.05% in emotion recognition, and (iii) it also outperforms the state-of-the-art FL approaches by 12.04–17.70% in foreground accuracy and 2.54–4.10% in F1-score.
Modulating endothelial cell dynamics in fat grafting: the impact of DLL4 siRNA via adipose stem cell extracellular vesicles
Authors: Deng Sen-Lin , Fu Qiang , Liu Qing , Huang Fu-Jun , Zhang Miao , Zhou Xun
Published: August 2024

This study introduces a groundbreaking method for enhancing autologous fat graft survival using adipose-derived stem cell extracellular vesicles (ADSC EVs) to deliver DLL4 siRNA. By targeting the delta-like ligand 4 (DLL4) gene, crucial in endothelial cell dynamics, this innovative approach significantly improves endothelial cell functions and angiogenesis, marking a substantial advancement in tissue engineering and regenerative medicine.
Extracellular vesicle miR-206 improves chronic binge alcohol-mediated decreased myoblast differentiation in SIV-infected female macaques
Authors: Bourgeois Brianna L. , Gallegos Eden M. , Levitt Danielle E. , Bergeaux Peter J. , Molina Patricia E. , Simon Liz
Published: August 2024

Alcohol decreases skeletal muscle myoblast differentiation into myotubes, which is associated with decreased expression of microRNA-206. We show that delivering exogenous miR-206 in plasma-derived extracellular vesicles (EVs) to myoblasts derived from alcohol-administered animals increases myotube differentiation. These results support the potential therapeutic utility of EVs in delivering muscle-enriched microRNAs to improve skeletal muscle stem cell differentiation.
Purinergic agonists increase [Ca2+]i in rat conjunctival goblet cells through ryanodine receptor type 3
Authors: Fjaervoll Haakon K. , Fjaervoll Ketil A. , Yang Menglu , Reiten Ole K. , Bair Jeffrey , Lee Changrim , Utheim Tor P. , Dartt Darlene
Published: August 2024

ATP and benzoylbenzoyl-ATP (BzATP) induce mucin secretion through an increase in free cytosolic calcium concentration ([Ca2+]i) in conjunctival goblet cells (CGCs). The mechanisms through which ATP and BzATP increase [Ca2+]i in CGCs are unclear. Ryanodine receptors (RyRs) are fundamental in [Ca2+]i regulation in excitable cells. Herein, we find that ATP and BzATP increase [Ca2+]i through the activation of protein kinase A, voltage-gated calcium channels, and RyRs, and that RyRs are crucial for nonexcitable CGCs’ Ca2+i homeostasis.
Factors influencing airway smooth muscle tone: a comprehensive review with a special emphasis on pulmonary surfactant
Authors: Hanusrichterova Juliana , Mokry Juraj , Al-Saiedy Mustafa R. , Koetzler Rommy , Amrein Matthias W. , Green Francis H. Y. , Calkovska Andrea
Published: August 2024

A thin film of pulmonary surfactant lines the surface of the airways and alveoli, where it lowers the surface tension in the peripheral lungs, preventing collapse of the bronchioles and alveoli and reducing the work of breathing. It also possesses a barrier function for maintaining the blood-gas interface of the lungs and plays an important role in innate immunity. The surfactant film covers the epithelium lining both large and small airways, forming the first line of defense between toxic airborne particles/pathogens and the lungs. Furthermore, surfactant has been shown to relax airway smooth muscle (ASM) after exposure to ASM agonists, suggesting a more subtle function. Whether surfactant masks irritant sensory receptors or interacts with one of them is not known. The relaxant effect of surfactant on ASM is absent in bronchial tissues denuded of an epithelial layer. Blocking of prostanoid synthesis inhibits the relaxant function of surfactant, indicating that prostanoids might be involved. Another possibility for surfactant to be active, namely through ATP-dependent potassium channels and the cAMP-regulated epithelial chloride channels [cystic fibrosis transmembrane conductance regulators (CFTRs)], was tested but could not be confirmed. Hence, this review discusses the mechanisms of known and potential relaxant effects of pulmonary surfactant on ASM. This review summarizes what is known about the role of surfactant in smooth muscle physiology and explores the scientific questions and studies needed to fully understand how surfactant helps maintain the delicate balance between relaxant and constrictor needs.
A positively charged residue at the Kv1.1 T1 interface is critical for voltage-dependent activation and gating kinetics
Authors: Hasan Sonia Majed , Aswad Nawal , Al-Sabah Suleiman
Published: August 2024

This is the first Kv1.1 study to characterize the electrophysiological and structural phenotype of a tetramerization (T1) domain mutation. Surprisingly, the mutated α-subunits were able to tetramerize, albeit with different gating kinetics and voltage dependence. This novel finding points to a clear role of T1 in the channel’s voltage dependence and gating. Mimicking the heterozygous condition resulted in milder alterations in channel function when compared with previously reported mutations. This is in agreement with the child’s milder symptoms.
Activation of skeletal muscle mechanoreceptors and nociceptors reduces the exercise performance of the contralateral homologous muscles
Authors: Zambolin Fabio , Laginestra Fabio Giuseppe , Favaretto Thomas , Giuriato Gaia , Ottaviani Matteo Maria , Schena Federico , Duro-Ocana Pablo , McPhee Jamie Stewart , Venturelli Massimo
Published: August 2024

We found that activation of mechanosensitive and nociceptive nerve afferents of a rested muscle group experiencing delayed onset muscle soreness was associated with reduced exercise performance of the homologous exercising muscles of the contralateral limb. This occurred with lower muscle voluntary activation of the exercising muscle at the point of task failure.
Time to reach equilibrium deep body temperatures in young and older adults resting in the heat: a descriptive secondary analysis
Authors: Meade Robert D. , Notley Sean R. , Kenny Glen P.
Published: August 2024

Deep body (rectal) temperature took 3–5 h on average and up to 6–8 h at the individual level to reach thermal equilibrium in young and older adults resting in the heat. Furthermore, stable rectal temperatures were delayed by up to 2 h relative to the achievement of heat balance (0 kJ/min rate of heat storage). We provide the first quantification of the temporal profiles of thermal strain during extended rest in conditions simulating hot weather.
Glutamatergic and purinergic transmitters and astrocyte modulation in the synaptic transmission in the NTS of rats exposed to short-term sustained hypoxia
Authors: Bazilio Darlan S. , Moraes Davi J. A. , Machado Benedito H.
Published: August 2024

Our findings indicate that the neurotransmission of autonomic and respiratory components of the peripheral chemoreflex in the nucleus tractus solitarius (NTS) is mediated by glutamatergic and purinergic mechanisms and reveal a selective involvement of NTS astrocytes in controlling the chemoreflex parasympathetic response in rats exposed to sustained hypoxia (SH) and the baseline duration of expiration mainly in control rats, indicating a selective role for astrocytes modulation in the NTS of control and SH rats.
Podocyte cell-specific Npr1 is required for blood pressure and renal homeostasis in male and female mice: role of sex-specific differences
Authors: Ramasamy Chandramohan , Neelamegam Kandasamy , Ramachandran Samivel , Xia Huijing , Kapusta Daniel R. , Danesh Farhad R. , Pandey Kailash N.
Published: August 2024

Our results demonstrate that the podocyte-specific deletion of Npr1 showed increased blood pressure (BP) and altered biomarkers of renal functions, with greater magnitudes in animals fed a high-salt diet in a sex-dependent manner. The results suggest a direct and sex-dependent effect of Npr1 ablation in podocytes on the regulation of BP and renal function and reveal that podocytes may be considered an important target for the ANP-BNP/NPRA/cGMP signaling cascade.
Virtual Commissioning with TIA Step7 and Simulink without S‐Functions
Authors: Horvath Dusan , Klauco Martin , Stremy Maximilian
Published: August 2024

This paper presents the development and validation of a custom MATLAB library, designed to facilitate seamless and efficient real‐time communication between the Siemens S7‐PLCSIM Advanced simulator and MATLAB/Simulink. The library uses Siemens.Simulation.Runtime.API to enable this integration and its architecture is structured into three classes—PLCSimAdv, PLCSR, and PLCSW. To demonstrate the library’s capabilities, we have chosen the validation parameters and conducted functional experiments including real‐time communication at the millisecond level, integration and control of a simulated industrial process, and simultaneous operation with multiple virtual controllers. One of the library’s preliminary conditions was to avoid the requests for regenerating of any version of control program or Simulink model as it is presently by S‐functions in TIA portal. The results suggest that the proposed library provides a robust tool for various applications in industrial automation, from the digital twin modelling or simulation of advanced technologies to the operation of traditional control systems. This work has the potential to significantly streamline the simulation, control, and validation of automated processes and opens new ways for research and development in automation and control systems.
Predictive Analysis of Maritime Congestion Using Dynamic Big Data and Multiscale Feature Analysis
Authors: Wu Yalin
Published: August 2024

The maritime industry is one of the most crucial sectors in the global economy, facilitating the transportation of goods and commodities across vast distances. However, maritime network congestion has become an increasingly critical challenge that significantly affects shipping efficiency and the overall operational performance of the industry. This study proposes an innovative congestion prediction approach using dynamic big data analysis of vessel trajectories and multiscale feature analysis. First, the dynamic analysis of vessel trajectories aims to extract valuable information from ships’ data as they navigate the oceans, enabling proactive traffic management and optimized routing. Second, the multiscale feature analysis provides a comprehensive understanding of maritime network congestion by examining it from different perspectives and scales, leading to more accurate predictions and effective congestion management strategies. Furthermore, this study introduces an enhanced Faster R‐CNN vessel detection model for real‐time tracking, integrating convolutional and SKNet networks. To improve short‐term traffic flow prediction accuracy, this study employs multiscale feature analysis through wavelet transformation. The foundational traffic data undergo wavelet decomposition for a detailed representation across frequencies. Gated recurrent unit (GRU) neural network and autoregressive moving average (ARMA) models are utilized to predict trend and noise components, respectively. Fusion of predictions demonstrates superior accuracy and is validated against real data. Empirical results showcase minimal errors and heightened prediction accuracy compared to actual data.
Side Effects following School Deworming among School‐Age Children in Oti Region, Ghana
Authors: Ouédraogo Jean Claude Romaric Pingdwindé , Addo-Lartey Adolphina Addoley
Published: August 2024

Background. Preventive chemotherapy with anthelminthic drugs is meant to control soil‐transmitted helminthiases, but some children may experience adverse reactions. Objective. This study investigated why some school‐age children did not receive the medication as well as the side effects experienced by those who did during the 2019 preventive chemotherapy in Krachi East Municipal, Oti Region, Ghana. Methods. Using a two‐stage stratified sampling, a community‐based cross‐sectional study was conducted among 352 school‐age children and their caregivers living in three urban and five rural communities. Results. Most children (93.8%) were in primary school, aged 11 to 12 years (28.1%), male (53.1%), and resided in an urban area (83.8%). Due to concerns about side effects (28.1%), absenteeism (25.0%), and sickness (9.4%), 32 (9.09%) children did not receive the anthelminthic medication. Of the 320 children who received and ingested the anthelmintic drug, 50.3% experienced at least one side effect. Common side effects included dizziness (58.4%), feeling weak (27.3%), and stomach issues such as vomiting (17.4%), abdominal pain (11.8%), and nausea (6.2%). In adjusted analyses, children aged 11‐12 years had higher odds of side effects (aOR: 2.40, 95% CI: 1.22–4.76) than children aged 7‐8 years. Male children were also less likely than female children to experience adverse effects (aOR: 0.43, 95% CI: 0.27–0.68). Discussion. Ghana’s national goal of 100% therapeutic coverage was unmet. Medication consumption during prophylactic chemotherapy may be hampered due to the high prevalence of side effects among school‐age children. It is necessary to educate caregivers on how to handle these negative effects.
Mathematical Modeling of Tumor Growth in Preclinical Mouse Models with Applications in Biomarker Discovery and Drug Mechanism Studies
Authors: Zhou Huajun , Mao Binchen , Guo Sheng
Published: August 2024

Oncology drug efficacy is evaluated in mouse models by continuously monitoring tumor volumes, which can be mathematically described by growth kinetic models. Although past studies have investigated various growth models, their reliance on small datasets raises concerns about whether their findings are truly representative of tumor growth in diverse mouse models under different vehicle or drug treatments. In this study, we systematically evaluated six parametric models (exponential, exponential quadratic, monomolecular, logistic, Gompertz, and von Bertalanffy) and the semiparametric generalized additive model (GAM) on fitting tumor volume data from more than 30,000 mice in 930 experiments conducted in patient-derived xenografts, cell line–derived xenografts, and syngeneic models. We found that the exponential quadratic model is the best parametric model and can adequately model 87% studies, higher than other models including von Bertalanffy (82%) and Gompertz (80%) models; the latter is often considered the standard growth model. At the mouse group level, 7.5% of growth data could not be fit by any parametric model and were fitted by GAM. We show that endpoint gain integrated in time, a GAM-derived efficacy metric, is equivalent to exponential growth rate, a metric we previously proposed and conveniently calculated by simple algebra. Using five studies on paclitaxel, anti-PD1 antibody, cetuximab, irinotecan, and sorafenib, we showed that exponential and exponential quadratic models achieve similar performance in uncovering drug mechanism and biomarkers. We also compared exponential growth rate–based association analysis and exponential modeling approach in biomarker discovery and found that they complement each other. Modeling methods herein are implemented in an open-source R package freely available at https://github.com/hjzhou988/TuGroMix.

Significance:

We present a general strategy for mathematically modeling tumor growth in mouse models using data from 30,000 mice and show that modeling and nonmodeling approaches are complementary in biomarker discovery and drug mechanism studies.
Preparation and Rationale for a Patient-Centered Clinical Outcome Assessment Set of Fluid Overload for Drug Development in Nephrotic Syndrome
Authors: Salmon Eloise , Carlozzi Noelle E. , Lai Jin-Shei , Spino Catherine , Wang Yujie , Capellari Emily , Scherr Rebecca , Sifre Kayla , Sullivan Shawn , Hurt Courtney , Creguer Tina , Helm Kelly , Lafayette Richard A. , Nachman Patrick H. , Selewski David T. , Peipert John Devin
Published: August 2024

Introduction: Fluid overload is a source of substantial morbidity for adults and children with nephrotic syndrome (NS). Preparation and Rationale for a Fluid Overload in Nephrotic Syndrome Clinical Outcomes Assessment Set for Drug Development (Prepare-NS, 5UG3FD007308) was funded by the US Food and Drug Administration to develop a core set of patient-reported and observer-reported (for young children) outcome measures of fluid overload for use in pharmaceutical trials across the lifespan. Methods: The Prepare-NS study team developed the proposed context of use with input from stakeholders. We conducted a scoping review to assess the available literature on relevant patient- and observer-reported measures and performed secondary analyses of existing qualitative and quantitative data. Results: The outcome set will aim to serve individuals 2 years of age and older with primary NS conditions (specifically focal segmental glomerulosclerosis, minimal change disease, IgM nephropathy, membranous nephropathy, and childhood-onset NS not biopsied). The existing literature describing patient-reported outcomes in NS largely relies on nonspecific measures of health-related quality of life; fluid overload has been associated with lower scores on these measures. Conclusion: To address the gap in measure availability and fluid overload content, the Prepare-NS team has launched a set of qualitative studies for concept elicitation from the population of interest to inform development of new measures. The resulting measures subsequently will undergo psychometric evaluation and validation in a survey study.
Intermediate vs. High Oxygen Saturation Targets in Preterm Infants: A National Cohort Study
Authors: Taylor Richard S. , Singh Balpreet , Mukerji Amit , Dorling Jon , Alvaro Ruben , Lodha Abhay , El-Naggar Walid , Yoon Eugene W. , Shah Prakesh S. ,   on behalf of the Canadian Neonatal Network Investigators
Published: August 2024

Introduction: Optimal oxygen saturation targets remain unknown for extremely preterm infants. Methods: Cohort analysis of eligible preterm infants born <29 weeks’ gestation admitted between 2011 and 2018 to centers submitting data to the Canadian Neonatal Network (CNN) database. Site questionnaires to determine saturation targets, alarm settings, and date of change, allowed assignation of centers to intermediate (88–93%) or high (90–95%) saturation targets. A 6-month washout period was applied to sites which switched targets during the study period. Our primary outcome was survival free of major morbidity. Secondary outcomes were death, necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity, and evidence of brain injury during admission. Generalized estimating equations were applied to compensate for demographic differences and site practices. Results: There were 2,739 infants in the high (mean gestational age [GA] 26 ± 1.6 weeks) and 6,813 infants in the intermediate (mean GA 26.2 ± 1.6 weeks) saturation target group. Survival without morbidity was higher in the intermediate target group (adjusted odds ratio [aOR] 1.59; 95% CI: 1.04, 2.45). There was no difference in mortality between groups (aOR 0.81; 95% CI: 0.59, 1.11), in NEC, treated retinopathy, or brain injury. On subgroup analysis, restricting data to sites which switched targets during the study, intermediate saturation targets were associated with lower rates of BPD (aOR 0.45; 95% CI: 0.28, 0.72). Conclusion: For neonates <29 weeks’ gestation, intermediate saturation target was associated with higher odds of survival without major morbidity compared to higher oxygen saturation target.
Interplay of Large Neutral Amino Acids, Metabolic Syndrome, and Apolipoprotein E ε4 on Brain Integrity at Midlife
Authors: Youn Cherry , Caillaud Marie L. , Li Yanrong , Gallagher Isabelle , Strasser Barbara , Tanaka Hirofumi , Haley Andreana P.
Published: August 2024

Introduction: Large neutral amino acids (LNAAs) tryptophan and phenylalanine have been implicated in the pathogenesis of neurodegenerative diseases. Given limited research on the effects of LNAA on brain health across different life stages, vascular risk, and genetic backgrounds, our study aimed to explore the interaction of LNAA levels, metabolic syndrome (MetS), and the presence of the apolipoprotein E ε4 (ApoE ε4) allele brain integrity at midlife. Methods: Sixty-eight adults aged 40–61 underwent a health assessment to calculate the number of MetS components, quantify LNAA, measure white matter hyperintensity (WMH) volume, and genotype ApoE ε4. Multivariate linear regression analyses were performed to test the joint effect of LNAA, MetS, and ApoE ε4 on WMH while adjusting for sex, age, and education. Results: Significant 3-way interactions were observed between serum tryptophan (β = 0.042, SE = 0.018, p < 0.05) and phenylalanine (β = 0.044, SE = 0.013, p < 0.01) levels, number of MetS components, and ApoE ε4 alleles status on WMH volume. Neither individual LNAA levels nor MetS components alone predicted WMH volume. Conclusions: The study highlights significant 3-way interactions between LNAA, MetS, and genetic risk factors in the pathology of WMH, particularly in individuals genetically predisposed to Alzheimer’s disease. These interactions suggest differential impacts of LNAA on WMH volume dependent on both genetic and metabolic factors. Results emphasize the need for personalized metabolic and genetic profile assessments in neurodegenerative disease management.
Sociodemographic and Clinical Characteristics Associated with Genetic Testing among Cancer Survivors: Evidence from Three Cancer Registries
Authors: Hong Young-Rock , Wang Ruixuan , Chen Guanming , Khan Mishal , Vadaparampil Susan , Bian Jiang , George Thomas J. , Braithwaite Dejana
Published: August 2024

Introduction: Genetic tests, including germline and tumor (somatic) testing, can optimize the clinical care and outcomes for cancer patients and their family members. However, evidence on cancer patients’ use of genetic testing and discussions about it with healthcare providers is limited. Methods: Study participants included cancer survivors aged 18 or older, drawn from the 2021 Health Information and National Trends Survey (HINTS)-Surveillance, Epidemiology, and End Results (SEER) linked database, which comprises three US cancer registries: Iowa, New Mexico, and the Greater Bay Area. Sociodemographic factors (e.g., age, sex, income, education) at the time of the survey and clinical characteristics (e.g., cancer site, stage) at the time of diagnosis were compared based on self-reported genetic testing status and provider discussions, using survey design-adjusted analysis. Results: The weighted study sample comprised 415,978 cancer survivors with a mean age of 70.5 years at the time of the survey. Overall, 17.0% reported having germline testing, 8.5% having tumor testing, and 8.6% discussing tumor testing with their healthcare providers. Higher proportions of germline genetic testing were observed among survivors under age 65 at the time of the survey, females, holding college degrees, and with private insurance coverage compared to their respective counterparts – males, aged 65 or above when surveyed, with lower educational attainment, and with public insurance or uninsured. The proportion of those who reported tumor testing was greater for those diagnosed in recent years (2015–2017 vs. before 2002). Regarding clinical characteristics, survivors with ovarian and breast cancers had a 7.0–36.4% higher prevalence of both testing compared to those with other cancer types lacking germline indication. More cancer survivors diagnosed at distant stages (vs. regional) or between 2015 and 2017 (vs. 2003–2010) reported having provider discussions about tumor testing. Conclusion: Findings showed that the highest reports of germline testing were among young female cancer survivors and those with higher education and private insurance. Survivors diagnosed in recent years or with advanced-stage disease were more likely to report discussing tumor testing with providers. Further research is warranted to better understand the barriers and educational needs of cancer patients, caregivers, and providers to optimize genetic testing strategies.
N3 Disease in Esophageal Cancer: Results from a Nationwide Registry
Authors: van der Zijden Charlène J. , Olthof Pim B. , van der Sluis Pieter C. , Wijnhoven Bas P.L. , Erodotou Maria , Hartgrink Henk H. , van Etten Boudewijn , van Esser Stijn , Lagarde Sjoerd M. , Dekker Jan Willem T.
Published: August 2024

Background: Patients with extensive lymph node metastases have a poor prognosis. Clinical staging of lymph node metastases poses significant challenges given the limited sensitivity and specificity of imaging techniques. The aim of this study was to investigate the overall survival (OS) of patients with N3 disease in a real-world Dutch population and the added value of surgery in these patients. Methods: Patients with cN3M0 esophageal or gastroesophageal cancer were identified from the Netherlands Cancer Registry (2012–2019). Treatment consisted of neoadjuvant chemo(radio)therapy followed by resection or chemo(radio)therapy, radiotherapy, or esophagectomy alone. OS was calculated using the Kaplan-Meier method. Results: Some 21,566 patients were diagnosed with esophageal cancer of whom 359 (1.7%) had cN3M0 disease. Median OS of these patients was 12.5 months (95% CI: 10.7–14.3). Median OS following chemoradiotherapy alone and neoadjuvant therapy plus surgery was 13.3 months (95% CI: 10.7–15.9) and 23.7 months (95% CI: 18.3–29.2), respectively. Of all patients who underwent esophagectomy, 391 (2.8%) had (y)pN3 disease, and median OS was 16.1 months (95% CI: 14.8–17.4). Twenty-one patients (5.4%) were correctly classified as cN3, and 3-year OS was 21%. Conclusion(s): Clinical staging appears to be difficult, apparently in patients with N3 esophageal cancer. Surgery seems to be of benefit to these patients. More research is required to address the ongoing challenges in clinical staging and the best neoadjuvant therapy.
Gender Disparity of Automatic Implantable Cardioverter-Defibrillator Placement for Primary Prevention: National Inpatient Sample Analysis
Authors: Srivastava Shreya , Nahass Meghan , Hiltner Emily , Sethi Ankur , Kassotis John
Published: August 2024

Introduction: Automatic implantable cardioverter-defibrillators (AICDs) for the primary prevention of sudden cardiac death have become standard care for patients with systolic heart failure (sHF) and ejection fraction ≤35%. While the prevalence of sHF and rates of hospitalization are higher in men, one would expect equivalent rates of implantation in women. Methods: We used the Healthcare Cost and Utilization Project’s National Inpatient Sample (NIS) from 2009 to 2018 to identify patient visits with sHF and AICD implantation. The comorbidities and outcomes were compared based on gender. Results: There were 15,247,854 inpatient admissions for sHF, of which 60.3% were males (95% CI: 60.1%–60.4%) and 39.8% females (95% CI: 39.7%–39.9%). Approximately 2% of patients (294,726) underwent the insertion of an AICD for primary prevention: 72.3% males (95% CI: 71.9%–72.7%) and 27.72% females (95% CI: 27.3%–28.1%). There was no significant difference in age (p = 0.29), length of stay (p = 0.09), and inpatient mortality (p = 0.18). Conclusion: In this study, women accounted for approximately 40% of patients admitted with the diagnosis of sHF; however, they accounted for less than 30% of patients who underwent the insertion of an AICD. Further research is needed to better understand this gender disparity and identify reasons for the lower rates of AICD placement in women.
Comparison between the International Outcome Inventory for Hearing Aids Questionnaire and Real-Ear Measurement
Authors: Nam Gi-Sung , Lee Young Jae , Song Hansoo , Oh Jeonghyun , Cho Sung Il
Published: August 2024

Introduction: The international outcome inventory for hearing aids (IOI-HA) is a questionnaire widely used to assess the subjective benefits of hearing aids. This study aimed to evaluate the relationship between IOI-HA outcomes and target mismatch in real-ear measurement (REM). Methods: Thirty-four ears of 25 patients who had worn hearing aids were evaluated using the Korean version of the IOI-HA and REM after fitting for 2 months. Real-ear insertion gain (REIG) was measured at three different levels of input intensity – 50, 65, and 80 dB sound pressure level (SPL) – and a frequency range of 0.25–6 kHz. Factors 1 and 2 and total IOI-HA scores were compared with the mismatches of REIGs and target gains of REM. Results: Factor 1, factor 2, and total IOI-HA scores were 14.6 ± 3.5, 11.4 ± 2.2, and 25.9 ± 5.1, respectively. The averages of the difference of REIGs and target gains in REM at 50, 65, and 80 dB SPL input levels were −3.1 ± 6.7, −2.3 ± 7.2, and −3.0 ± 8.2, respectively. Factors 1 and 2 scores of the IOI-HA showed significant correlations with target mismatch in REM at 1 kHz and 0.75 kHz frequencies, respectively. Total IOI-HA scores had significant correlations with target mismatches in REM at 0.75 and 1 kHz frequencies. Conclusion: IOI-HA scores correlated with target mismatch in REM at mid frequencies. The IOI-HA can be a useful screening measure for evaluating the necessity of further adjustments in hearing aids through REM at mid frequencies.