bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of life and cost‐effectiveness of convalescent plasma compared to standard care for hospitalized COVID‐19 patients in the CONCOR‐1 trial
Authors: Tse Preston , Yan Jiajun , Liu Yang , Jamula Erin , Heddle Nancy , Bazin Renée , Robitaille Nancy , Cook Richard , Turgeon Alexis , Fergusson Dean , Glesby Marshall , Loftsgard Kent Cadogan , Cushing Melissa , Chassé Michaël , Daneman Nick , Finzi Andrés , Sachais Bruce , Bégin Philippe , Callum Jeannie , Arnold Donald M. , Xie Feng 
Published: March 2024

AbstractBackgroundThe CONvalescent Plasma for Hospitalized Adults With COVID‐19 Respiratory Illness (CONCOR‐1) trial was a multicenter randomized controlled trial assessing convalescent plasma in hospitalized COVID‐19 patients. This study evaluates the cost‐effectiveness of convalescent plasma and its impact on quality‐of‐life to provide insight into its potential as an alternative treatment in resource‐constrained settings.MethodsIndividual patient data on health outcomes and resource utilization from the CONCOR‐1 trial were used to conduct the analysis from the Canadian public payer's perspective with a time horizon of 30 days post‐randomization. Baseline and 30‐day EQ‐5D‐5L were measured to calculate quality‐adjusted survival. All costs are presented in 2021 Canadian dollars. The base case assessed the EQ‐5D‐5L scores of hospitalized inpatients reporting at both timepoints, and a utility score of 0 was assigned for patients who died within 30 days. Costs for all patients enrolled were used. The sensitivity analysis utilizes EQ‐5D‐5L scores from the same population but only uses costs from this population.Results940 patients were randomized: 627 received CCP and 313 received standard care. The total costs were $28,716 (standard deviation, $25,380) and $24,258 ($22,939) for the convalescent plasma and standard care arms respectively. EQ‐5D‐5L scores were 0.61 in both arms (p = .85) at baseline. At 30 days, EQ‐5D‐5L scores were 0.63 and 0.64 for patients in the convalescent plasma and standard care arms, respectively (p = .46). The incremental cost was $4458 and the incremental quality‐adjusted life day was −0.078.DiscussionConvalescent plasma was less effective and more costly than standard care in treating hospitalized COVID‐19.
Positive correlation between echocardiographic tricuspid E peak velocity and central venous pressure in dogs: A preliminary study
Authors: Jafari‐Giv Zahra , Vajhi Alireza , Farzad‐Mohajeri Saeed , Hassankhani Mahdi , Alian Samakkhah Shohreh , Hemmati Amin , Mohammadzade‐Akbari Alireza , Noroozzadegan Mohammadhossein 
Published: March 2024

AbstractIn the absence of vascular obstruction, central venous pressure (CVP) is a hydrostatic pressure in the cranial and caudal vena cava, providing valuable information about cardiac function and intravascular volume status. It is also a component in evaluating volume resuscitation in patients with septic shock and monitoring patients with right heart disease, pericardial disease, or volume depletion. Central venous pressure is calculated in dogs by invasive central venous catheterization, which is considered high‐risk and impractical in critically ill patients. This study aimed to investigate the feasibility of using echocardiographic tricuspid E/E' as a noninvasive method to estimate CVP in anesthetized healthy dogs under controlled hypovolemic conditions. Ten male mixed‐breed dogs were included in the study after a thorough health assessment. For hypovolemia induction, blood withdrawal was performed, and echocardiographic factors of the tricuspid valve, including peak E and E' velocities, were measured during CVP reduction. Repeated measures analysis of variance and Bonferroni post hoc tests were employed to compare the average difference between measured echocardiographic indices and CVP values derived from catheterization and intermittent measurement methods. Spearman's ρ correlation coefficient was used to evaluate the correlation between echocardiographic indices and CVP. E peak velocity had a significant negative correlation with venous blood pressure phases (r = −0.44, P = .001), indicating a decrease in peak E velocity with progressive CVP reduction. However, tricuspid valve E' peak velocity and E/E' did not correlate with CVP, suggesting that these parameters are not reliable for CVP estimation in dogs.
The vascular geometry of the choriocapillaris is associated with spatially heterogeneous molecular exchange with the outer retina
Authors: Faust Caitlin D. , Klettner Christian A. , Toso Marc , Hageman Gregory S. , Eames Ian , Luthert Philip J. , Zouache Moussa A. 
Published: March 2024

AbstractVision relies on the continuous exchange of material between the photoreceptors, retinal pigment epithelium and choriocapillaris, a dense microvascular bed located underneath the outer retina. The anatomy and physiology of the choriocapillaris and their association with retinal homeostasis have proven difficult to characterize, mainly because of the unusual geometry of this vascular bed. By analysing tissue dissected from 81 human eyes, we show that the thickness of the choriocapillaris does not vary significantly over large portions of the macula or with age. Assessments of spatial variations in the anatomy of the choriocapillaris in three additional human eyes indicate that the location of arteriolar and venular vessels connected to the plane of the choriocapillaris is non‐random, and that venular insertions cluster around arteriolar ones. Mathematical models built upon these anatomical analyses reveal that the choriocapillaris contains regions where the transport of passive elements is dominated by diffusion, and that these diffusion‐limited regions represent areas of reduced exchange with the outer retina. The width of diffusion‐limited regions is determined by arterial flow rate and the relative arrangement of arteriolar and venular insertions. These analyses demonstrate that the apparent complexity of the choriocapillaris conceals a fine balance between several anatomical and functional parameters to effectively support homeostasis of the outer retina.
imageKey points
The choriocapillaris is the capillary bed supporting the metabolism of photoreceptors and retinal pigment epithelium, two critical components of the visual system located in the outer part of the retina.
The choriocapillaris has evolved a planar multipolar vascular geometry that differs markedly from the branched topology of most vasculatures in the human body.
Here, we report that this planar multipolar vascular geometry is associated with spatially heterogenous molecular exchange between choriocapillaris and outer retina.
Our data and analyses highlight a necessary balance between choriocapillaris anatomical and functional parameters to effectively support homeostasis of the outer retina.
Motor unit modes in the calf muscles during a submaximal isometric contraction are changed by brief stretches
Authors: Weinman Logan E. , Del Vecchio Alessandro , Mazzo Melissa R. , Enoka Roger M. 
Published: March 2024

AbstractThe purpose of our study was to investigate the influence of a stretch intervention on the common modulation of discharge rate among motor units in the calf muscles during a submaximal isometric contraction. The current report comprises a computational analysis of a motor unit dataset that we published previously (Mazzo et al., 2021). Motor unit activity was recorded from the three main plantar flexor muscles while participants performed an isometric contraction at 10% of the maximal voluntary contraction force before and after each of two interventions. The interventions were a control task (standing balance) and static stretching of the plantar flexor muscles. A factorization analysis on the smoothed discharge rates of the motor units from all three muscles yielded three modes that were independent of the individual muscles. The composition of the modes was not changed by the standing‐balance task, whereas the stretching exercise reduced the average correlation in the second mode and increased it in the third mode. A centroid analysis on the correlation values showed that most motor units were associated with two or three modes, which were presumed to indicate shared synaptic inputs. The percentage of motor units adjacent to the seven centroids changed after both interventions: Control intervention, mode 1 decreased and the shared mode 1 + 2 increased; stretch intervention, shared modes either decreased (1 + 2) or increased (1 + 3). These findings indicate that the neuromuscular adjustments during both interventions were sufficient to change the motor unit modes when the same task was performed after each intervention.
imageKey points
Based on covariation of the discharge rates of motor units in the calf muscles during a submaximal isometric contraction, factor analysis was used to assign the correlated discharge trains to three motor unit modes.
The motor unit modes were determined from the combined set of all identified motor units across the three muscles before and after each participant performed a control and a stretch intervention.
The composition of the motor unit modes changed after the stretching exercise, but not after the control task (standing balance).
A centroid analysis on the distribution of correlation values found that most motor units were associated with a shared centroid and this distribution, presumably reflecting shared synaptic input, changed after both interventions.
Our results demonstrate how the distribution of multiple common synaptic inputs to the motor neurons innervating the plantar flexor muscles changes after a brief series of stretches.
Monocarboxylate transporter 4 deficiency enhances high‐intensity interval training‐induced metabolic adaptations in skeletal muscle
Authors: Tamura Yuki , Jee Eunbin , Kouzaki Karina , Kotani Takaya , Nakazato Koichi 
Published: March 2024

AbstractHigh‐intensity exercise stimulates glycolysis, subsequently leading to elevated lactate production within skeletal muscle. While lactate produced within the muscle is predominantly released into the circulation via the monocarboxylate transporter 4 (MCT4), recent research underscores lactate's function as an intercellular and intertissue signalling molecule. However, its specific intracellular roles within muscle cells remains less defined. In this study, our objective was to elucidate the effects of increased intramuscular lactate accumulation on skeletal muscle adaptation to training. To achieve this, we developed MCT4 knockout mice and confirmed that a lack of MCT4 indeed results in pronounced lactate accumulation in skeletal muscle during high‐intensity exercise. A key finding was the significant enhancement in endurance exercise capacity at high intensities when MCT4 deficiency was paired with high‐intensity interval training (HIIT). Furthermore, metabolic adaptations supportive of this enhanced exercise capacity were evident with the combination of MCT4 deficiency and HIIT. Specifically, we observed a substantial uptick in the activity of glycolytic enzymes, notably hexokinase, glycogen phosphorylase and pyruvate kinase. The mitochondria also exhibited heightened pyruvate oxidation capabilities, as evidenced by an increase in oxygen consumption when pyruvate served as the substrate. This mitochondrial adaptation was further substantiated by elevated pyruvate dehydrogenase activity, increased activity of isocitrate dehydrogenase – the rate‐limiting enzyme in the TCA cycle – and enhanced function of cytochrome c oxidase, pivotal to the electron transport chain. Our findings provide new insights into the physiological consequences of lactate accumulation in skeletal muscle during high‐intensity exercises, deepening our grasp of the molecular intricacies underpinning exercise adaptation.
imageKey points
We pioneered a unique line of monocarboxylate transporter 4 (MCT4) knockout mice specifically tailored to the ICR strain, an optimal background for high‐intensity exercise studies.
A deficiency in MCT4 exacerbates the accumulation of lactate in skeletal muscle during high‐intensity exercise.
Pairing MCT4 deficiency with high‐intensity interval training (HIIT) results in a synergistic boost in high‐intensity exercise capacity, observable both at the organismal level (via a treadmill running test) and at the muscle tissue level (through an ex vivo muscle contractile function test).
Coordinating MCT4 deficiency with HIIT enhances both the glycolytic enzyme activities and mitochondrial capacity to oxidize pyruvate.
Magnetic Flux Leakage Defect Identification Method for Small-Diameter Pipeline Elbow Based on the Improved YOLOv5
Authors: Qin Haodong , Zhang Ying , Zhao Pengcheng , Zhao Yongtao , Sun Jipei , Pan Chuanyu 
Published: March 2024

Abstract
The elbow is an important constituent of oil and gas pipeline systems and plays a key role in changing the direction of pipelines. Corrosion defects pose a significant risk to the safe operation of elbows. Magnetic flux leakage (MFL) detection has been developed as a suitable technique for identifying defects in pipelines. To address the distortion of elbow defect signals in the images arising from variations in the liftoff value of the leakage detector, this paper proposed an image identification method based on an improved YOLOv5 network. The differences in defect images are simulated by analyzing the liftoff value of the magnetization unit. A defect image enhancement method of multiscale retinex with color restoration fusion homomorphic filtering (MSRCR-HF) is employed to enhance the features of defective MFL signal images. To further improve the accuracy of the model, the YOLOv5 network is optimized by integrating the convolutional block attention module (CBAM) and the space-to-depth-nonstrided convolution (SPD-Conv) module. The results show that the proposed image enhancement method effectively accentuates the features of defect images. Moreover, the suggested image identification method exhibits superior accuracy in identification. The mean average precision (mAP) values for the original image set and the enhanced image set are 85.0% and 91.4%, respectively. Consequently, the proposed method is shown to be highly viable for the automatic identification of MFL defects in small-diameter pipe elbows.
Development of Risk Informed Aging Management Program in Decommissioning
Authors: Uesaka Masao , Murakami Kenta 
Published: March 2024

Abstract
This paper proposes to solve the issues related to aging management program (AMP) during the decommissioning phase by using risk information. The AMP for the decommissioning plants has not been established while the number of permanently shut down and decommissioned nuclear power plants are increasing in the world. The first issue is the change of the functional importance of the safety systems at the beginning of decommissioning. We propose to evaluate the importance using the probabilistic risk assessment (PRA) model with the change of specification in the decommissioning plant and to determine new importance grade. The second issue is to make the maintenance based on the appropriate risk information. This risk information should be based on the progress of decommissioning, reflected and evaluated in the PRA model, as well as information obtained from maintenance inspections, including the ROP process, and failure experience during routine operation. To address these issues, the maintenance program in decommissioning that uses the evaluation of risk information according to the decommissioning phase is proposed in this paper.
A novel hybridization capture method for direct whole genome sequencing of clinical specimens to inform Legionnaires’ disease investigations
Authors: Weeber Phillip , Singh Navjot , Lapierre Pascal , Mingle Lisa , Wroblewski Danielle , Nazarian Elizabeth J. , Haas Wolfgang , Weiss Don , Musser Kimberlee A. 
Published: March 2024

ABSTRACT

The unprecedented precision and resolution of whole genome sequencing (WGS) can provide definitive identification of infectious agents for epidemiological outbreak tracking. WGS approaches, however, are frequently impeded by low pathogen DNA recovery from available primary specimens or unculturable samples. A cost-effective hybrid capture assay for
Legionella pneumophila
WGS analysis directly on primary specimens was developed. DNA from a diverse range of sputum and autopsy specimens PCR-positive for
L. pneumophila
serogroup 1 (LPSG1) was enriched with this method, and WGS was performed. All tested specimens were determined to be enriched for
Legionella
reads (up to 209,000-fold), significantly improving the discriminatory power to compare relatedness when no clinical isolate was available. We found the WGS data from some enriched specimens to differ by less than five single-nucleotide polymorphisms (SNPs) when compared to the WGS data of a matched culture isolate. This testing and analysis retrospectively provided previously unconfirmed links to environmental sources for clinical specimens of sputum and autopsy lung tissue. The latter provided the additional information needed to identify the source of these culture-negative cases associated with the South Bronx 2015 Legionnaires’ disease (LD) investigation in New York City. This new method provides a proof of concept for future direct clinical specimen hybrid capture enrichment combined with WGS and bioinformatic analysis during outbreak investigations.

IMPORTANCE

Legionnaires’ disease (LD) is a severe and potentially fatal type of pneumonia primarily caused by inhalation of
Legionella
-contaminated aerosols from man-made water or cooling systems. LD remains extremely underdiagnosed as it is an uncommon form of pneumonia and relies on clinicians including it in the differential and requesting specialized testing. Additionally, it is challenging to obtain clinical lower respiratory specimens from cases with LD, and when available, culture requires specialized media and growth conditions, which are not available in all microbiology laboratories. In the current study, a method for
Legionella pneumophila
using hybrid capture by RNA baiting was developed, which allowed us to generate sufficient genome resolution from
L. pneumophila
serogroup 1 PCR-positive clinical specimens. This new approach offers an additional tool for surveillance of future LD outbreaks where isolation of
Legionella
is not possible and may help solve previously unanswered questions from past LD investigations.
Proteins à la carte: riboproteogenomic exploration of bacterial N-terminal proteoform expression
Authors: Fijalkowski Igor , Snauwaert Valdes , Van Damme Petra 
Published: March 2024

ABSTRACT

In recent years, it has become evident that the true complexity of bacterial proteomes remains underestimated. Gene annotation tools are known to propagate biases and overlook certain classes of truly expressed proteins, particularly proteoforms—protein isoforms arising from a single gene. Recent (re-)annotation efforts heavily rely on ribosome profiling by providing a direct readout of translation to fully describe bacterial proteomes. In this study, we employ a robust riboproteogenomic pipeline to conduct a systematic census of expressed N-terminal proteoform pairs, representing two isoforms encoded by a single gene raised by annotated and alternative translation initiation, in
Salmonella
. Intriguingly, conditional-dependent changes in relative utilization of annotated and alternative translation initiation sites (TIS) were observed in several cases. This suggests that TIS selection is subject to regulatory control, adding yet another layer of complexity to our understanding of bacterial proteomes.

IMPORTANCE

With the emerging theme of genes within genes comprising the existence of alternative open reading frames (ORFs) generated by translation initiation at in-frame start codons, mechanisms that control the relative utilization of annotated and alternative TIS need to be unraveled and our molecular understanding of resulting proteoforms broadened. Utilizing complementary ribosome profiling strategies to map ORF boundaries, we uncovered dual-encoding ORFs generated by in-frame TIS usage in
Salmonella
. Besides demonstrating that alternative TIS usage may generate proteoforms with different characteristics, such as differential localization and specialized function, quantitative aspects of conditional retapamulin-assisted ribosome profiling (Ribo-RET) translation initiation maps offer unprecedented insights into the relative utilization of annotated and alternative TIS, enabling the exploration of gene regulatory mechanisms that control TIS usage and, consequently, the translation of N-terminal proteoform pairs.
Host-derived protease promotes aggregation of
Staphylococcus aureus
by cleaving the surface protein SasG
Authors: Crosby Heidi A. , Keim Klara , Kwiecinski Jakub M. , Langouët-Astrié Christophe J. , Oshima Kaori , LaRivière Wells B. , Schmidt Eric P. , Horswill Alexander R. 
Published: March 2024

ABSTRACT

Staphylococcus aureus
is one of the leading causes of hospital-acquired infections, many of which begin following attachment and accumulation on indwelling medical devices or diseased tissue. These infections are often linked to the establishment of biofilms, but another often overlooked key characteristic allowing
S. aureus
to establish persistent infection is the formation of planktonic aggregates. Such aggregates are physiologically similar to biofilms and protect pathogens from innate immune clearance and increase antibiotic tolerance. The cell-wall-associated protein SasG has been implicated in biofilm formation via mechanisms of intercellular aggregation but the mechanism in the context of disease is largely unknown. We have previously shown that the expression of cell-wall-anchored proteins involved in biofilm formation is controlled by the ArlRS-MgrA regulatory cascade. In this work, we demonstrate that the ArlRS two-component system controls aggregation, by repressing the expression of
sasG
by activation of the global regulator MgrA. We also demonstrate that SasG must be proteolytically processed by a non-staphylococcal protease to induce aggregation and that strains expressing functional full-length
sasG
aggregate significantly upon proteolysis by a mucosal-derived host protease found in human saliva. We used fractionation and N-terminal sequencing to demonstrate that human trypsin within saliva cleaves within the A domain of SasG to expose the B domain and induce aggregation. Finally, we demonstrated that SasG is involved in virulence during mouse lung infection. Together, our data point to SasG, its processing by host proteases, and SasG-driven aggregation as important elements of
S. aureus
adaptation to the host environment.

IMPORTANCE

Here, we demonstrate that the
Staphylococcus aureus
surface protein SasG is important for cell-cell aggregation in the presence of host proteases. We show that the ArlRS two-component regulatory system controls SasG levels through the cytoplasmic regulator MgrA. We identified human trypsin as the dominant protease triggering SasG-dependent aggregation and demonstrated that SasG is important for
S. aureus
lung infection. The discovery that host proteases can induce
S. aureus
aggregation contributes to our understanding of how this pathogen establishes persistent infections. The observations in this study demonstrate the need to strengthen our knowledge of
S. aureus
surface adhesin function and processing, regulation of adhesin expression, and the mechanisms that promote biofilm formation to develop strategies for preventing chronic infections.