bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of α-(1→6)-linked mannan structures resembling yeast
N
-glycan outer chains in
Aspergillus fumigatus
mycelium
Authors: Kadooka Chihiro , Tanaka Yutaka , Kishida Rintaro , Hira Daisuke , Oka Takuji
Published: April 2024

The cellular surface of the pathogenic filamentous fungus
Aspergillus fumigatus
is enveloped in a mannose layer, featuring well-established fungal-type galactomannan and
O
-mannose-type galactomannan. This study reports the discovery of cell wall component in
A. fumigatus
mycelium, which resembles
N
-glycan outer chains found in yeast. The glycosyltransferases involved in its biosynthesis in
A. fumigatus
were identified, with a focus on two key α-(1→2)-mannosyltransferases, Mnn2 and Mnn5, and two α-(1→6)-mannosyltransferases, Mnn9 and Van1.
In vitro
examination revealed the roles of recombinant Mnn2 and Mnn5 in transferring α-(1→2)-mannosyl residues. Proton nuclear magnetic resonance (
1
H-NMR) analysis of cell wall extracts from the ∆
mnn2
∆
mnn5
strain indicated the existence of an α-(1→6)-linked mannan backbone in the
A. fumigatus
mycelium, with Mnn2 and Mnn5 adding α-(1→2)-mannosyl residues to this backbone. The α-(1→6)-linked mannan backbone was absent in strains where
mnn9
or
van1
was disrupted in the parental ∆
mnn2
∆
mnn5
strain in
A. fumigatus
. Mnn9 and Van1 functioned as α-(1→6)-linked mannan polymerases in heterodimers when co-expressed in
Escherichia coli
, indicating their crucial role in biosynthesizing the α-(1→6)-linked mannan backbone. Disruptions of these mannosyltransferases did not affect fungal-type galactomannan biosynthesis. This study provides insights into the complexity of fungal cell wall architecture and a better understanding of mannan biosynthesis in
A. fumigatus
.

IMPORTANCE

This study unravels the complexities of mannan biosynthesis in
A. fumigatus
, a key area for antifungal drug discovery. It reveals the presence of α-(1→6)-linked mannan structures resembling yeast N-glycan outer chains in
A. fumigatus
mycelium, offering fresh insights into the fungal cell wall’s design. Key enzymes, Mnn2, Mnn5, Mnn9, and Van1, are instrumental in this process, with Mnn2 and Mnn5 adding specific mannose residues and Mnn9 and Van1 assembling the α-(1→6)-linked mannan structures. Although fungal-type galactomannan’s presence in the cell wall is known, the existence of an α-(1→6)-linked mannan adds a new dimension to our understanding. This intricate web of mannan biosynthesis opens avenues for further exploration and enhances our understanding of fungal cell wall dynamics, paving the way for targeted drug development.
First report of the chromosomal integration of carbapenemase gene
bla
IMP-19
in
Acinetobacter baumannii
AB322: the legacy of integron in phage-plasmid?
Authors: Shih Yung-Luen , Bregente Carl Jay Ballena , Chen Pek Kee , Thuy Tran Thi Dieu , Chen Yu-Chen , Kuo Han-Yueh , Lu Hsu-Feng , Kao Cheng-Yen
Published: April 2024

Integration of carbapenemase gene
bla
IMP
into the chromosome of carbapenem-resistant
Acinetobacter baumannii
(CRAB) has not been reported. The aim of this study was to explore the genomic characteristics of CRAB AB322 isolated from a Taiwanese patient diagnosed with bacteremia in 2011, whose chromosome harbors
bla
IMP-19
. Disk diffusion and broth microdilution were employed to analyze the antimicrobial susceptibility of AB322 to 14 antimicrobials. Nanopore whole-genome sequencing platform was utilized for AB322 genome sequencing, and conjugation was further performed to investigate the transferability of
bla
IMP-19
to amikacin-resistant
A. baumannii
218 (AB218) and
Acinetobacter nosocomialis
254 (AN254). The results showed that AB322 was classified as multidrug-resistant
A. baumannii
but remained susceptible to ampicillin/sulbactam, colistin, and tigecycline. Whole-genome sequencing revealed the AB322 genome, consisting of a 4,098,985-bp chromosome, a 71,590-bp conjugative plasmid named pAB322-1, and an 8,726-bp plasmid named pAB322-2. Multilocus sequence typing analysis indicated that AB322 belonged to sequence type 1. AB322 chromosome harbored numerous acquired antimicrobial resistance genes, including
aph(3′)-Ia
,
aadA1b
,
aadA1
,
aac(6′)-Ib3
,
aac (3)-Ia
,
bla
ADC-25
,
bla
OXA-69
,
bla
IMP-19
,
catA1
,
sul1
, and
tet(A
), conferring resistance to β-lactams, aminoglycosides, chloramphenicol, sulfamethoxazole, and tetracyclines. Moreover,
bla
IMP-19
was identified to be situated within class 1 integron In240 and an incomplete PHAGE_Salmon_SJ46_NC_031129 on AB322 chromosome. However, conjugation experiments revealed that
bla
IMP-19
could not be transferred to AB218 and AN254 in our testing conditions. In conclusion, we first report the presence of chromosomal-integrated
bla
IMP-19
in CRAB, possibly mediated by integron. The future dissemination of
bla
IMP-19
among different species, leading to carbapenem resistance dissemination, requires close monitoring.

IMPORTANCE

The horizontal transfer of antimicrobial-resistant genes is crucial for the dissemination of resistance, especially as
Acinetobacter baumannii
has emerged as a clinically significant pathogen. However, in this study, we first report the integration of the
bla
IMP-19
gene into the chromosome of
A. baumannii
, and such horizontal transfer may be associated with integron-phage elements. Additionally, it is possible that these DNA fragments carrying antimicrobial-resistant genes could further spread to other pathogens by moving horizontally onto conjugative plasmids.
Microbial keratitis in Southern Malawi: a microbiological pilot study
Authors: Somerville Tobi F , Mdala Shaffi , Zungu Thokozani , Gandiwa Moira , Herbert Rose , Everett Dean , Corless Caroline E , Beare Nicholas A V , Neal Timothy , Horsburgh Malcolm J , Darby Alistair , Kaye Stephen B , Kayange Petros C
Published: April 2024

Objective

Microbial keratitis (MK) is a significant cause of blindness in sub-Saharan Africa. We investigated the feasibility of using a novel corneal impression membrane (CIM) for obtaining and processing samples by culture, PCR and whole-genome sequencing (WGS) in patients presenting with suspected MK in Malawi.

Methods and analysis

Samples were collected from patients presenting with suspected MK using a 12 mm diameter polytetrafluoroethylene CIM disc. Samples were processed using culture and PCR forAcanthamoeba, herpes simplex virus type 1 (HSV-1) and the bacterial 16S rRNA gene. Minimum inhibitory concentrations of isolates to eight antimicrobials were measured using susceptibility strips. WGS was used to characteriseStaphylococcus aureusisolates.

Results

71 eyes of 71 patients were included. The overall CIM isolation rate was 81.7% (58 positive samples from 71 participants). 69 (81.2%) of isolates were Gram-positive cocci. Coagulase-negativeStaphylococcus31.8% andStreptococcusspecies 14.1% were the most isolated bacteria. Seven (9.9%) participants were positive for HSV-1. Fungi andAcanthamoebawere not detected. Moxifloxacin and chloramphenicol offered the best coverage for both Gram-positive and Gram-negative isolates when susceptibility was determined using known antimicrobial first quartile concentrations and European Committee on Antimicrobial Susceptibility Testing breakpoints, respectively. WGS identified known virulence genes associated withS. aureuskeratitis.

Conclusions

In a resource-poor setting, a CIM can be used to safely sample the cornea in patients presenting with suspected MK, enabling identification of causative microorganisms by culture and PCR. Although the microbiological spectrum found was limited to the dry season, these preliminary results could be used to guide empirical treatment.
Recurrent Chagas’ disease meningomyelitis in an HIV-infected patient
Authors: de Almeida Igor Melo , da Rocha Aline Borges Moreira , Lindoso José Angelo Lauletta , de Freitas Vera Lúcia Teixeira , Oliveira Augusto CP , Vidal Jose E
Published: April 2024

Chagas’ disease reactivation leading to monophasic acute or subacute meningoencephalitis or space-occupying lesions is a well-described AIDS-defining condition in Latin America. We report a 59-year-old man native from the Northeast region of Brazil, with a second episode of subacute chagasic meningomyelitis. He had long-term multidrug-resistant HIV and had abandoned combined antiretroviral therapy (CD4+ lymphocyte count, 16 cells/mm³, and HIV viral load 169 403 copies/mL). He initially received benznidazole but switched to nifurtimox after developing myelotoxicity. He was discharged home having made a partial neurological improvement. Chagas’ disease should be included in the differential diagnosis of meningomyelitis in people living with HIV/AIDS who are from endemic areas of this parasitic disease.
‘Door-to-prophylaxis’ as a novel quality improvement metric in prevention of venous thromboembolism following traumatic injury
Authors: Van Gent Jan-Michael , Clements Thomas W , Lubkin David E , Kaminski Carter W , Bates Jonathan K , Sandoval Mariela , Puzio Thaddeus J , Cotton Bryan A
Published: April 2024

Objective

Venous thromboembolism (VTE) risk reduction strategies include early initiation of chemoprophylaxis, reducing missed doses, weight-based dosing and dose adjustment using anti-Xa levels. We hypothesized that time to initiation of chemoprophylaxis would be the strongest modifiable risk for VTE, even after adjusting for competing risk factors.

Methods

A prospectively maintained trauma registry was queried for patients admitted July 2017–October 2021 who were 18 years and older and received emergency release blood products. Patients with deep vein thrombosis or pulmonary embolism (VTE) were compared to those without (no VTE). Door-to-prophylaxis was defined as time from hospital arrival to first dose of VTE chemoprophylaxis (hours). Univariate and multivariate analyses were then performed between the two groups.

Results

2047 patients met inclusion (106 VTE, 1941 no VTE). There were no differences in baseline or demographic data. VTE patients had higher injury severity score (29 vs 24), more evidence of shock by arrival lactate (4.6 vs 3.9) and received more post-ED transfusions (8 vs 2 units); all p<0.05. While there was no difference in need for enoxaparin dose adjustment or missed doses, door-to-prophylaxis time was longer in the VTE group (35 vs 25 hours; p=0.009). On multivariate logistic regression analysis, every hour delay from time of arrival increased likelihood of VTE by 1.5% (OR 1.015, 95% CI 1.004 to 1.023, p=0.004).

Conclusion

The current retrospective study of severely injured patients with trauma who required emergency release blood products found that increased door-to-prophylaxis time was significantly associated with an increased likelihood for VTE. Chemoprophylaxis initiation is one of the few modifiable risk factors available to combat VTE, therefore early initiation is paramount. Similar to door-to-balloon time in treating myocardial infarction and door-to-tPA time in stroke, “door-to-prophylaxis time” should be considered as a hospital metric for prevention of VTE in trauma.

Level of evidence

Level III, retrospective study with up to two negative criteria.
The Kerr–Bumblebee exact massive and massless scalar quasibound states and Hawking radiation
Authors: Senjaya David
Published: April 2024

In this letter, we will focus on the Klein–Gordon equation with rotating axially symmetric black hole solution of the Einstein–Bumblebee theory, so called the Kerr–Bumblebee black hole, as its 3 + 1 background space-time. We start with constructing the covariant Klein–Gordon equation component by component and with the help of the ansatz of separation of variables, we successfully separate the polar part and found the exact solution in terms of Spheroidal Harmonics while the radial exact solution is discovered in terms of the Confluent Heun function. The quantization of the quasibound state is done by applying the polynomial condition of the Confluent Heun function that is resulted in a complex-valued energy levels expression for a massive scalar field, where the real part is the scalar particle’s energy while the imaginary part represents the quasibound stats’s decay. And for a massless scalar, a pure imaginary energy levels is obtained. The quasibound states, thus, describe the decaying nature of the relativistic scalar field bound in the curved Kerr–Bumblebee space-time. We also investigate the Hawking radiation of the Kerr–Bumblebee black hole’s apparent horizon via the Damour–Ruffini method by making use the obtained exact scalar’s wave functions. The radiation distribution function and the Hawking temperature are successfully obtained.
$$f\left( R,\square R\right) $$-gravity and equivalency with the modified GUP Scalar field models
Authors: Paliathanasis Andronikos
Published: April 2024

Inspired by the generalization of scalar field gravitational models with a minimum length we study the equivalent theory in modified theories of gravity. The quadratic generalized uncertainty principle (GUP) gives rise to a deformed Heisenberg algebra in the application, resulting in the emergence of additional degrees of freedom described by higher-order derivatives. The new degrees of freedom can be attributed to the introduction of a new scalar field, transforming the resulting theory into a two-scalar field theory. Thus, in order to describe all the degrees of freedom we investigate special forms of the sixth-order modify $$f\left( R,\square R\right) -$$

f

R
,
□
R

-

theory of gravity, where the gravitational Lagrangian has similar properties to that of the GUP scalar field theory. Finally, the cosmological applications are discussed, and we show that the de Sitter universe can be recovered without introducing a cosmological constant.
Multifaceted online coordinated behavior in the 2020 US presidential election
Authors: Tardelli Serena , Nizzoli Leonardo , Avvenuti Marco , Cresci Stefano , Tesconi Maurizio
Published: April 2024

Organized attempts to manipulate public opinion during election run-ups have dominated online debates in the last few years. Such attempts require numerous accounts to act in coordination to exert influence. Yet, the ways in which coordinated behavior surfaces during major online political debates is still largely unclear. This study sheds light on coordinated behaviors that took place on Twitter (now X) during the 2020 US Presidential Election. Utilizing state-of-the-art network science methods, we detect and characterize the coordinated communities that participated in the debate. Our approach goes beyond previous analyses by proposing a multifaceted characterization of the coordinated communities that allows obtaining nuanced results. In particular, we uncover three main categories of coordinated users: (i) moderate groups genuinely interested in the electoral debate, (ii) conspiratorial groups that spread false information and divisive narratives, and (iii) foreign influence networks that either sought to tamper with the debate or that exploited it to publicize their own agendas. We also reveal a large use of automation by far-right foreign influence and conspiratorial communities. Conversely, left-leaning supporters were overall less coordinated and engaged primarily in harmless, factual communication. Our results also showed that Twitter was effective at thwarting the activity of some coordinated groups, while it failed on some other equally suspicious ones. Overall, this study advances the understanding of online human interactions and contributes new knowledge to mitigate cyber social threats.
Efficient excitation-transfer across fully connected networks via local-energy optimization
Authors: Sgroi S. , Zicari G. , Imparato A. , Paternostro M.
Published: April 2024

We study the excitation transfer across a fully connected quantum network whose sites energies can be artificially designed. Starting from a simplified model of a broadly-studied physical system, we systematically optimize its local energies to achieve high excitation transfer for various environmental conditions, using an adaptive Gradient Descent technique and Automatic Differentiation. We show that almost perfect transfer can be achieved with and without local dephasing, provided that the dephasing rates are not too large. We investigate our solutions in terms of resilience against variations in either the network connection strengths, or size, as well as coherence losses. We highlight the different features of a dephasing-free and dephasing-driven transfer. Our work gives further insight into the interplay between coherence and dephasing effects in excitation-transfer phenomena across fully connected quantum networks. In turn, this will help designing optimal transfer in artificial open networks through the simple manipulation of local energies.
Enhancing fuel distribution of downward steps in supersonic combustion chambers using shock generators
Authors: Kamyarpour Naser , Hosseinnejad Farhad , Seyyedi Seyyed Masoud , Hashemi-Tilehnoee M.
Published: April 2024

This study investigates the impact of a shock generator on the fuel distribution of downward step fuel injection in a scramjet engine’s combustor. Computational simulations of CFD are employed to analyze the three-dimensional structure of multi-jets released in a downward-step configuration. The inlet is subjected to a free stream supersonic flow with [Formula: see text], while hydrogen gas is injected at [Formula: see text] through injectors situated on the vertical planes of the downward step. A shock generator with a [Formula: see text] angle is positioned at the top of the domain to induce a bow shock, which significantly affects fuel distribution. The research assesses the influence of free stream and jet pressure on the fuel distribution behind the jets. The results indicate that increasing the free stream flow strengthens the induced bow shock, leading to enhanced fuel jet interactions and improved fuel mixing behind the jets.
Continuous Krishna–Parthasarathy entropic uncertainty principle
Authors: Krishna K. Mahesh
Published: April 2024

In 2002, Krishna and Parthasarathy7 derived discrete quantum version of Maassen–Uffink8 entropic uncertainty principle. In this paper, using the notion of continuous operator-valued frames, we derive an entropic uncertainty principle for arbitrary family of operators indexed by measure spaces having finite measure. We give an application to the special case of compact groups.
EVALUATE NODE IMPORTANCE BY DECOMPOSING NETWORK WITH A RECURSIVE PERCOLATION PROCESS
Authors: WANG HUI , YANG ZHENYU , LIU RUN-RAN , HU DONGHUI , LI MING
Published: April 2024

Due to structural heterogeneity, the main function and structure of networked systems are significantly influenced by some important nodes rather than each member. In practical, the properties of important nodes could be different from network to network, and thus a variety of algorithms have been specially designed to identify important nodes of different networks and of different dynamics. In this paper we propose a widely applicable algorithm by employing the percolation model in statistical physics, which describes the behavior of connected clusters when nodes are connected randomly. This algorithm appropriately combines the local and global properties of a network, thus it stresses the significance of nodes that neither have a visibly local importance, such as degree and clustering, nor have a visibly global importance, such as betweenness. The effectiveness of our algorithm has been illustrated in a series of networks, including model networks with different degree distributions and different degree correlations, and empirical networks. As a shell decomposition process, the framework of our algorithm has extensive application prospects in analyzing network structure, such as community, core–periphery structure, and shell structures.
Modules and rings satisfying strong accr
Authors: Ahmed Elmakki , Ridha Chatbouri
Published: April 2024

Let [Formula: see text] be a commutative ring with identity and [Formula: see text] an [Formula: see text]-module. We say that [Formula: see text] satisfies strong accr[Formula: see text] if for every submodule [Formula: see text] of [Formula: see text] and for every sequence [Formula: see text] of elements of [Formula: see text] the ascending sequence of submodules of the form, [Formula: see text] is stationary. We say that a ring [Formula: see text] satisfies strong accr[Formula: see text] if [Formula: see text] regarded as a module over [Formula: see text] satisfies strong accr[Formula: see text] In this paper, we give a necessary and sufficient condition for the pulback (respectively, the Nagata’s idealization [Formula: see text]) to be strong accr[Formula: see text] ring. We also prove a new characterization for a valuation ring to be strong accr[Formula: see text]
Recurrent Appearance Flow for Occlusion-Free Virtual Try-On
Authors: Gu Xiaoling , Zhu Junkai , Wong Yongkang , Wu Zizhao , Yu Jun , Fan Jianping , Kankanhalli Mohan
Published: April 2024

Image-based virtual try-on aims at transferring a target in-shop garment onto a reference person, and has garnered significant attention from the research communities recently. However, previous methods have faced severe challenges in handling occlusion problems. To address this limitation, we classify occlusion problems into three types based on the reference person’s arm postures:
single-arm occlusion
,
two-arm non-crossed occlusion
, and
two-arm crossed occlusion
. Specifically, we propose a novel Occlusion-Free Virtual Try-On Network (OF-VTON) that effectively overcomes these occlusion challenges. The OF-VTON framework consists of two core components: (i) a new
Recurrent Appearance Flow based Deformation
(RAFD) model that robustly aligns the in-shop garment to the reference person by adopting a
multi-task learning strategy
. This model jointly produces the dense appearance flow to warp the garment and predicts a human segmentation map to provide semantic guidance for the subsequent image synthesis model. (ii) a powerful
Multi-mask Image SynthesiS
(MISS) model that generates photo-realistic try-on results by introducing a new
mask generation and selection mechanism
. Experimental results demonstrate that our proposed OF-VTON significantly outperforms existing state-of-the-art methods by mitigating the impact of occlusion problems. Our code is available at
https://github.com/gxl-groups/OF-VTON
.
Teacher-Student Framework for Polyphonic Semi-supervised Sound Event Detection: Survey and Empirical Analysis
Authors: Diffallah Zhor , Ykhlef Hadjer , Bouarfa Hafida
Published: April 2024

Polyphonic sound event detection refers to the task of automatically identifying sound events occurring simultaneously in an auditory scene. Due to the inherent complexity and variability of real-world auditory scenes, building robust detectors for polyphonic sound event detection poses a significant challenge. The task becomes furthermore challenging without sufficient annotated data to develop sound event detection systems under a supervised learning regime. In this article, we explore the recent developments in polyphonic sound event detection, with a particular emphasis on the application of Teacher-Student techniques within the semi-supervised learning paradigm. Unlike previous works, we have consolidated and organized the fragmented literature on Teacher-Student techniques for polyphonic sound event detection. By examining the latest research, categorizing Teacher-Student approaches, and conducting an empirical study to assess the performance of each approach, this survey offers valuable insights and practical guidance for researchers and practitioners in the field. Our findings highlight the potential benefits of utilizing multiple learners, ensuring consistent predictions, and making thoughtful choices regarding perturbation strategies.
Governing Smart City IoT Interventions: A Complex Adaptive Systems Perspective
Authors: Venumuddala Vinay Reddy , Prakash Amit , Chaudhuri Bidisha
Published: April 2024

Urban infrastructure systems (UIS) encompass physical infrastructure and human stakeholders, delivering essential services through distributed flow networks. These systems exhibit properties of Complex Adaptive Systems (CAS), such as self-organization and adaptivity, which makes them resilient to perturbations from the outside. Smart city strategies advocate for external technology interventions to improve the efficiency and sustainability of UIS. Internet of Things (IoT) is a key enabler for such strategies that helps to gather data from various infrastructure components and optimize flow networks in UIS. Although beneficial, such interventions often give rise to ethical concerns, underscoring the need for appropriate governance measures. In this study, we adopt a CAS perspective to analyse the ethical concerns of a proposed smart city IoT platform in the cities of Karnataka, India. Based on our analysis, we present a framework to aid city authorities in formulating appropriate strategies to govern Smart City IoT interventions in general.
High Efficiency Deep-learning Based Video Compression
Authors: Tang Lv , Zhang Xinfeng
Published: April 2024

Although deep learning technique has achieved significant improvement on image compression, but its advantages are not fully explored in video compression, which leads to the performance of deep-learning-based video compression (DLVC) is obviously inferior to that of hybrid video coding framework. In this article, we proposed a novel network to improve the performance of DLVC from its most important modules, including
Motion Process
(MP),
Residual Compression
(RC), and
Frame Reconstruction
(FR). In MP, we design a split second-order attention and multi-scale feature extraction module to fully remove the warping artifacts from multi-scale feature space and pixel space, which can help reduce the distortion in the following process. In RC, we propose a channel selection mechanism to gradually drop redundant information while preserving informative channels for a better rate-distortion performance. Finally, in FR, we introduce a residual multi-scale recurrent network to improve the quality of the current reconstructed frame by progressively exploiting temporal context information between it and its several previous reconstructed frames. Extensive experiments are conducted on the three widely used video compression datasets (HEVC, UVG, and MCL-JVC), and the performance demonstrates the superiority of our proposed approach over the state-of-the-art methods.
Dust Growth and Evolution in Protoplanetary Disks
Authors: Birnstiel Tilman
Published: April 2024

Over the past decade, advancement of observational capabilities, specifically the Atacama Large Millimeter/submillimeter Array (ALMA) and Spectro-Polarimetric High-contrast Exoplanet REsearch (SPHERE) instruments, alongside theoretical innovations like pebble accretion, have reshaped our understanding of planet formation and the physics of protoplanetary disks. Despite this progress, mysteries persist along the winded path of micrometer-sized dust, from the interstellar medium, through transport and growth in the protoplanetary disk, to becoming gravitationally bound bodies. This review outlines our current knowledge of dust evolution in circumstellar disks, yielding the following insights:

▪
Theoretical and laboratory studies have accurately predicted the growth of dust particles to sizes that are susceptible to accumulation through transport processes like radial drift and settling.

▪
Critical uncertainties in that process remain the level of turbulence, the threshold collision velocities at which dust growth stalls, and the evolution of dust porosity.

▪
Symmetric and asymmetric substructures are widespread. Dust traps appear to be solving several long-standing issues in planet formation models, and they are observationally consistent with being sites of active planetesimal formation.

▪
In some instances, planets have been identified as the causes behind substructures. This underlines the need to study earlier stages of disks to understand how planets can form so rapidly.

In the future, better probes of the physical conditions in optically thick regions, including densities, turbulence strength, kinematics, and particle properties, will be essential for unraveling the physical processes at play.
Energy and Greenhouse Gas Emission Savings Associated with Implementation of an Abbreviated Cardiac MRI Protocol
Authors: Ibrahim Fadi , Cadour Farah , Campbell-Washburn Adrienne E. , Allen Bradley D. , Vosshenrich Jan , Brown Maura J. , Thavendiranathan Paaladinesh , Hanneman Kate
Published: April 2024

Implementation of an abbreviated cardiac MRI protocol with a change in timing of cine steady-state free precession acquisitions after contrast material administration optimizes scanner efficiency, resulting in energy and greenhouse gas savings.
La-based Transition Metal Oxide Perovskites as Electrocatalysts for Electrochemical Carbon Dioxide Reduction
Authors: Barman Madhurima , Kobi Sushobhan , Sarkar Arindam
Published: April 2024

We report here the feasibility of using LaTMO3-based perovskites (TM = Co, Cr, Fe, Mn, Ni, i.e., non-Cu 3d transition metals) as electrocatalysts for electrochemical CO2 reduction reaction (eCO2RR). Phase pure LaTMO3 perovskites, having TM-ions in multiple oxidation states for all and O-defects for LaFeO3 and LaNiO3, have been synthesized and tested as electrocatalysts for eCO2RR in flow cell type set-up. The above characteristics of the La-TM-oxides have been found to influence the current densities during eCO2RR at the various applied potentials, with favorable effects of the presence of O-defects (as for LaFeO3 and LaNiO3). Upon eCO2RR, both C1 and C2 liquid products have been obtained, including ethanol, with a partial current density of −2.66 mA cm−2 at −1.2 V vs RHE (for LaFeO3). The types of products and the faradic efficiencies have been found to depend on the TM-ion present (in the LaTMO3); in particular, the oxidation state(s), associated O-defect(s) and electronic conductivity. Furthermore, the electrocatalysts have been found to be stable during eCO2RR. Overall, the present work highlights the potential of La-TM-oxide perovskites for usage as stable electrocatalysts for eCO2RR, and also provides insights into the proper selection of “TM” and reaction conditions for obtaining the desired product(s).
Progesterone amplifies allergic inflammation and airway pathology in association with higher lung ILC2 responses
Authors: Trivedi Shubhanshi , Deering-Rice Cassandra E. , Aamodt Samuel E. , Huecksteadt Thomas P. , Myers Elizabeth J. , Sanders Karl A. , Paine Robert , Warren Kristi J.
Published: April 2024

There is a strong association between female biological sex and severe asthma. We investigated the allergic immune response, lung pathology, and airway mechanics in the well-described chicken egg ovalbumin (OVA) model with steady levels of progesterone delivered throughout the treatment period. We found that progesterone enhances the activation of mouse group 2 innate lymphoid cells (ILC2). Human ILC2 are also hyper-responsive to progesterone and interleukin 33 (IL-33), and likely contribute to airway exacerbations following allergen exposures in women with asthma.
Nurse Manager Practice Environment and Its Influencing Factors: A Multicenter Cross-Sectional Study
Authors: Chen Yushuang , He Xifei , Liu Qinghua
Published: April 2024

Objective. This study aimed to evaluate the current status and related factors of practice environments of nurse managers in China. Background. Insufficient nurse staffing and poor working environment directly increase the burnout and turnover of nurse leaders. Nurse managers play a pivotal role in healthcare organizations, and their performance has been inextricably linked to achieving optimal patient, staff, and healthcare organizational outcomes. However, there are few studies exploring the influencing factors of nurse manager practice environment. Methods. A cross-sectional study was undertaken to examine a sample of 405 nursing managers who were selected from 10 hospitals located across three provinces in China. The general characteristics questionnaire, the Nurse Manager Practice Environment Scale, the Perceived Stress Scale, and the Career Growth Scale were used. Data were analyzed by descriptive statistics, univariate analysis, and multiple stepwise linear regression. Results. The total scores of the nurse manager practice environments were 236.71 ± 27.635 (with 270 being the highest possible score), which was at a generally high level. The three lowest scores were adequate budgeted resources, fair and manageable workload, and nurse manager-physician relationships. Nurse manager practice environment was predicted by hospital geographic location, having (or not) training experience in higher ranked hospitals, levels of perceived stress, and career growth scores. Conclusion. Chinese nursing managers reported a relatively favorable nursing practice environment. Policymakers should pay more attention to the practice environment of nursing managers in small city hospitals, and they could regularly evaluate, monitor, and promote practice environment determinants that are sensitive to disparities between different hospitals. In addition, hospital managers can take action by implementing diversity training programs, developing stress-reduction initiatives, and creating robust career development programs for nurse managers to support nurse managers better. Implications for nursing management: a better understanding of the current practice environment of nursing managers is beneficial for improving nursing managers’ work environment, which in turn will promote the quality of care delivered and nursing management work. For nurse managers, the characteristics of the management and work environment of the small city hospitals should be benchmarked and learned against the district capital hospitals. Also, hospital administrators were required to adopt strategies to foster psychological support of nurse managers and create pathways and opportunities for professional growth to create a supportive working environment.
The Parameter Identification of Structure with TMD considering Seismic Soil‐Structure Interaction
Authors: Liu Shutong , Li Haochen , Tang Song , Xie Jinlun , Yang Shutong , Li Peizhen
Published: April 2024

Parameter identification is of great significance for the postearthquake performance evaluation of structure equipped with tuned mass damper (TMD). However, the soil‐structure interaction (SSI) effects have not been considered in the parameter identification of structure with TMD yet, which influence the dynamic characteristics and seismic responses of structures. This paper aims at proposing a framework for identifying the physical parameters of soil‐structure‐TMD system. Firstly, the accelerated particle swarm optimization (APSO) algorithm is combined with the search space reduction (SSR) method. Then, the frequency response function and transmissibility function are adopted for output‐input and input‐only cases, respectively, and a simplified mechanical model for soil‐structure‐TMD system is employed. Next, the measured responses are used to identify the physical parameters of structure with TMD considering SSI effects. Finally, the effectiveness of the proposed identification method is investigated, and the influences of frequency band and noise pollution on the identification performance are discussed. The results show that the proposed strategy can identify the system physical parameters accurately and quickly. It is worth noting that high frequency bands and noise pollution may lead to estimation error, especially for output‐only case.
Uncovering Risks Associated with Smoking Types and Intensities in Esophageal Cancer within High-Prevalence Regions in Africa: A Comprehensive Meta-analysis
Authors: Kamsu Gabriel T. , Ndebia Eugene J.
Published: April 2024

Tobacco is usually cited among the well-known risk factors of esophageal cancer; nevertheless, the extent of the contribution of the type of smoking and its intensity to the disease has not been comprehensively elucidated in Africa. We searched MEDLINE/PubMed, Excerpta Medica Database, Web of Science, Scopus, Cochrane Library, and African Journals Online studies published before September 2023. The quality of the studies was assessed using the Newcastle–Ottawa scale, and the funnel plot was used for assessing potential publication bias. Meta-analyses were conducted to estimate summary effects using random-effects models. This study included 22,319 participants from 27 studies. The results strongly indicate a significant association between tobacco use and a higher risk of esophageal cancer. The risk of esophageal cancer is notably higher among pipe smokers [OR = 4.68; 95% confidence interval (CI), 3.38–6.48], followed by hand-rolled cigarette smokers (OR = 3.79; 95% CI, 2.68–5.35), in comparison with those who smoked commercially manufactured cigarettes (OR = 2.46; 95% CI, 1.69–3.60). Our findings also showed that the risk of esophageal cancer is highest in people smoking >183 packs per year (OR = 5.47; 95% CI, 3.93–7.62), followed by those smoking 93 to 183 packs per year (OR = 3.90; 95% CI, 3.13–4.86), in comparison with those smoking ≤92 packs per year (OR = 2.90; 95% CI, 2.19–3.84). Our findings strongly show that among the different types of tobacco use in Africa, pipe and hand-roller smokers face a higher risk of esophageal cancer.
Assessing Management of Abnormal Cervical Cancer Screening Results and Concordance with Guideline Recommendations in Three US Healthcare Settings
Authors: Cheng David , Rieu-Werden Meghan L. , Lykken Jacquelyn M. , Werner Claudia L. , Feldman Sarah , Silver Michelle I. , Atlas Steven J. , Tiro Jasmin A. , Haas Jennifer S. , Kamineni Aruna
Published: April 2024

Background:

Follow-up of abnormal results is essential to cervical cancer screening, but data on adherence to follow-up are limited. We describe patterns of follow-up after screening abnormalities and identify predictors of guideline-concordant follow-up.

Methods:

We identified the index screening abnormality (positive human papillomavirus test or atypical squamous cells of undetermined significance or more severe cytology) among women of ages 25 to 65 years at three US healthcare systems during 2010 to 2019. We estimated the cumulative incidence of surveillance testing, colposcopy, or treatment after the index abnormality and initial colposcopy. Logistic regressions were fit to identify predictors of guideline-concordant follow-up according to contemporaneous guidelines.

Results:

Among 43,007 patients with an index abnormality, the cumulative incidence of any follow-up was 49.6% by 4 years for those with atypical squamous cells of undetermined significance/human papillomavirus–negative and higher for abnormalities warranting immediate colposcopy. The 1-year cumulative incidence of any follow-up after colposcopy was 70% for patients with normal results or cervical intraepithelial neoplasia I and 90% for patients with cervical intraepithelial neoplasia II+. Rates of concordant follow-up after screening and colposcopy were 52% and 47%, respectively. Discordant follow-up was associated with factors including age, race/ethnicity, overweight/obese body mass index, and specific types of public payor coverage or being uninsured.

Conclusions:

Adherence to the recommended follow-up of cytologic and histopathologic abnormalities is inconsistent in clinical practice. Concordance was poor for mild abnormalities and improved, although suboptimal, for more severe abnormalities.

Impact:

There remain gaps in the cervical cancer screening process in clinical practice. Further study is needed to understand the barriers to the appropriate management of cervical abnormalities.
Exercise and QUality Diet after Leukemia: A Randomized Weight Loss Trial among Adult Survivors of Childhood Leukemia in the Childhood Cancer Survivor Study
Authors: Friedman Danielle N. , Chou Joanne F. , Clark Jeanne M. , Moskowitz Chaya S. , Ford Jennifer S. , Armstrong Gregory T. , Mubdi Nidha Z. , McDonald Aaron , Nathan Paul C. , Sklar Charles A. , Ramanathan Lakshmi V. , Robison Leslie L. , Oeffinger Kevin C. , Tonorezos Emily S.
Published: April 2024

Background:

Obesity is prevalent in childhood cancer survivors and interacts with cancer treatments to potentiate risk for cardiovascular (CV) death. We tested a remote weight-loss intervention trial that was effective among adults with CV risk factors in a cohort of adult survivors of childhood acute lymphoblastic leukemia (ALL) with overweight/obesity.

Methods:

In this phase III efficacy trial, survivors of ALL enrolled in the Childhood Cancer Survivor Study with a body mass index ≥25 kg/m2 were randomized to a remotely delivered weight-loss intervention versus self-directed weight loss, stratified by history of cranial radiotherapy. The primary endpoint was the difference in weight loss at 24 months in an intent-to-treat analysis. Analyses were performed using linear mixed-effects models.

Results:

Among 358 survivors (59% female; median attained age: 37 years; IQR: 33–43 years), the baseline mean (SD) weight was 98.6 kg (24.0) for the intervention group (n = 181) and 94.9 kg (20.3) for controls (n = 177). Adherence to the intervention was poor; 15% of individuals in the intervention group completed 24/30 planned coaching calls. Weight at 24 months was available for 274 (77%) participants. After controlling for cranial radiotherapy, sex, race/ethnicity, and age, the mean (SE) change in weight from baseline to 24 months was −0.4 kg (0.8) for the intervention group and 0.2 kg (0.6) for control participants (P = 0.59).

Conclusions:

A remote weight-loss intervention that was successful among adults with CV conditions did not result in significant weight loss among adult survivors of childhood ALL.

Impact:

Future interventions in this population must be tailored to the unique needs of survivors to encourage engagement and adherence.

See related In the Spotlight, p. 1147
A First-in-Human Phase 1 Study of a Tumor-Directed RNA-Interference Drug against HIF2α in Patients with Advanced Clear Cell Renal Cell Carcinoma
Authors: Brugarolas James , Obara Gregory , Beckermann Kathryn E. , Rini Brian , Lam Elaine T. , Hamilton James , Schluep Thomas , Yi Min , Wong So , Mao Zhongping Lily , Gamelin Erick , Tannir Nizar M.
Published: April 2024

Purpose:

ARO-HIF2 is an siRNA drug designed to selectively target hypoxia-inducible factor-2α (HIF2α) interrupting downstream pro-oncogenic signaling in clear cell renal cell carcinoma (ccRCC). The aims of this Phase 1 study (AROHIF21001) were to evaluate safety, tolerability, pharmacokinetics, and establish a recommended Phase 2 dose.

Patients and Methods:

Subjects with ccRCC and progressive disease after at least 2 prior therapies that included VEGF and immune checkpoint inhibitors were progressively enrolled into dose-escalation cohorts of ARO-HIF2 administered intravenously at 225, 525, or 1,050 mg weekly.

Results:

Twenty-six subjects received ARO-HIF2. The most common treatment emergent adverse events (AE) irrespective of causality were fatigue (50.0%), dizziness (26.9%), dyspnea (23.1%), and nausea (23.1%). Four subjects (15.4%) had treatment-related serious AEs. AEs of special interest included neuropathy, hypoxia, and dyspnea. ARO-HIF2 was almost completely cleared from plasma circulation within 48 hours with minimal renal clearance. Reductions in HIF2α were observed between pre- and post-dosing tumor biopsies, but the magnitude was quite variable. The objective response rate was 7.7% and the disease control rate was 38.5%. Responses were accompanied by ARO-HIF2 uptake in tumor cells, HIF2α downregulation, as well as rapid suppression of tumor produced erythropoietin (EPO) in a patient with paraneoplastic polycythemia.

Conclusions:

ARO-HIF2 downregulated HIF2α in advanced ccRCC—inhibiting tumor growth in a subset of subjects. Further development was hampered by off-target neurotoxicity and low response rate. This study provides proof of concept that siRNA can target tumors in a specific manner.
Immunologic Profiling of Immune-Related Cutaneous Adverse Events with Checkpoint Inhibitors Reveals Polarized Actionable Pathways
Authors: Lacouture Mario E. , Goleva Elena , Shah Neil , Rotemberg Veronica , Kraehenbuehl Lukas , Ketosugbo Kwami F. , Merghoub Taha , Maier Tara , Bang Alexander , Gu Stephanie , Salvador Trina , Moy Andrea P. , Lyubchenko Taras , Xiao Olivia , Hall Clifton F. , Berdyshev Evgeny , Crooks James , Weight Ryan , Kern Jeffrey A. , Leung Donald Y.M.
Published: April 2024

Purpose:

Immune-related cutaneous adverse events (ircAE) occur in ≥50% of patients treated with checkpoint inhibitors, but the underlying mechanisms for ircAEs are poorly understood.

Experimental Design:

Phenotyping/biomarker analyses were conducted in 200 patients on checkpoint inhibitors [139 with ircAEs and 61 without (control group)] to characterize their clinical presentation and immunologic endotypes. Cytokines were evaluated in skin biopsies, skin tape strip extracts, and plasma using real-time PCR and Meso Scale Discovery multiplex cytokine assays.

Results:

Eight ircAE phenotypes were identified: pruritus (26%), maculopapular rash (MPR; 21%), eczema (19%), lichenoid (11%), urticaria (8%), psoriasiform (6%), vitiligo (5%), and bullous dermatitis (4%). All phenotypes showed skin lymphocyte and eosinophil infiltrates. Skin biopsy PCR revealed the highest increase in IFNγ mRNA in patients with lichenoid (P < 0.0001) and psoriasiform dermatitis (P < 0.01) as compared with patients without ircAEs, whereas the highest IL13 mRNA levels were detected in patients with eczema (P < 0.0001, compared with control). IL17A mRNA was selectively increased in psoriasiform (P < 0.001), lichenoid (P < 0.0001), bullous dermatitis (P < 0.05), and MPR (P < 0.001) compared with control. Distinct cytokine profiles were confirmed in skin tape strip and plasma. Analysis determined increased skin/plasma IL4 cytokine in pruritus, skin IL13 in eczema, plasma IL5 and IL31 in eczema and urticaria, and mixed-cytokine pathways in MPR. Broad inhibition via corticosteroids or type 2 cytokine–targeted inhibition resulted in clinical benefit in these ircAEs. In contrast, significant skin upregulation of type 1/type 17 pathways was found in psoriasiform, lichenoid, bullous dermatitis, and type 1 activation in vitiligo.

Conclusions:

Distinct immunologic ircAE endotypes suggest actionable targets for precision medicine-based interventions.
Classifying Glioma via Liquid Biopsy: Progress toward an Unmet Clinical Need
Authors: Abdullah Kalil G.
Published: April 2024

The diagnosis and classification of glioma by liquid biopsy represent a critical unmet need in neuro-oncology. A recent study demonstrates targeted next-generation sequencing of cell-free DNA from cerebrospinal fluid as an evolving option for liquid biopsy in patients with glioma.

See related article by Iser et al., p. 2974
FLT3 Agonists and Secondary Hematopoietic Malignancies: A Potential Class Effect
Authors: Raeder Henry W. , Drazer Michael W.
Published: April 2024

Expansion of conventional dendritic cells via FMS-like tyrosine kinase 3 agonism has promising therapeutic potential in the treatment of advanced solid tumors. In this study, we discuss the results of a clinical trial using GS-3583, an FMS-like tyrosine kinase 3 agonist, that was stopped after a patient in the study developed acute myeloid leukemia.

See related article by Tolcher et al., p. 2954