bluuebunny/crossref_metadata_2025 huggingface dataset:
Tail-specific protease is an essential
Chlamydia
virulence factor that mediates the differentiation of elementary bodies into reticulate bodies
Authors: Banerjee Arkaprabha , Jacobs Kaylee R. , Wang Yihui , Doud Emma H. , Toh Evelyn , Stein Barry D. , Mosley Amber L. , Zhong Guangming , Morrison Richard P. , Morrison Sandra G. , Hu Shuai , Brothwell Julie A. , Nelson David E.
Published: November 2024

Tail-specific proteases (Tsp) are members of a widely distributed family of serine proteases that commonly target and process periplasmic proteins in Gram-negative bacteria. The obligately intracellular, Gram-negative
Chlamydia
encode a highly conserved Tsp homolog whose target and function are unclear. We identified a
Chlamydia muridarum
mutant with a nonsense mutation in
tsp
. Differentiation of the
tsp
mutant elementary bodies into vegetative reticulate bodies was delayed at 37°C and completely blocked at 40°C. Tsp localized to
C. muridarum
cells but was not detected outside the inclusion, suggesting that it targets chlamydial rather than host proteins. The abundance of key chlamydia outer membrane complex and virulence-related proteins differed in wild-type and
tsp
mutant elementary bodies, consistent with the possibility that Tsp regulates developmental cycle progression. The altered abundances of chlamydial structural and virulence factors could explain why the mutant, but not an isogenic recombinant with wild-type
tsp
, was highly attenuated in a mouse intravaginal infection model. Thus, chlamydial Tsp is required for timely differentiation of elementary bodies into reticulate bodies
in vitro
and is an essential virulence factor
in vivo
.
Gene expression profiling reveals host defense strategies for restricting
Candida albicans
invasion and gastritis to the limiting ridge of the murine stomach
Authors: Zeise Karen D. , Falkowski Nicole R. , Metcalf Joseph D. , Brown Christopher A. , Huffnagle Gary B.
Published: November 2024

Candida albicans
is a fungal constituent of the human gastrointestinal microbiota that can tolerate acidic environments like the stomach, where it can be associated with ulcers and chronic gastritis. In mice,
C. albicans
induces gastritis without concurrent intestinal inflammation, suggesting that the stomach is particularly prone to fungal infection. We previously showed that
C. albicans
invasion in the limiting ridge does not extend to or elicit an inflammatory response in the adjacent glandular region, indicating regionalized gastritis in the murine stomach. However, the molecular pathways involved in the host response to
C. albicans
specifically in the limiting ridge have not been investigated. Here, we found that gastric dysbiosis was associated with
C. albicans
limiting ridge colonization and gastritis. We isolated the limiting ridge and evaluated the expression of over 90 genes involved in mucosal responses.
C. albicans
infection triggered a type 3 immune response marked by elevated
Il17a
,
Il17f
,
Il1b
,
Tnf
, and
Il36g
, as well as an upregulation of
Il12a
,
Il4
,
Il10
, and
l13
. Chemokine gene induction (including
Ccl2
,
Ccl3
,
Ccl4
,
Ccl1l
,
Cxcl1
,
Cxcl2
,
Cxcl9
, and
Cxcl10
) coincided with an influx of neutrophils, monocytes/macrophages, and eosinophils. Hyphal invasion caused tissue damage, epithelial remodeling, and upregulation of genes linked to epithelium signaling and antimicrobial responses in the limiting ridge. Our findings support a need for continued exploration into the interactions between the immunological milieu, the host microbiota, and clinical interventions such as the use of antibiotics and immunotherapeutic agents and their collective impact on invasive candidiasis risk.
Applying Beer’s Law in the undergraduate cell biology laboratory: examining the mathematical relationship between optical density, cell concentration, and cell size using budding yeast
Authors: Brito Stacey O. , Rohan Wryn P. , Buffum-Robbins Isobel , Reyes Osorio Patricia Ruby , Tribble Andrea , Segarra Verónica A.
Published: November 2024

Undergraduate students majoring in the life sciences benefit from experience with data analyses that connect mathematical calculations to the biological systems they are studying. Monitoring the optical density and cell number of
Saccharomyces cerevisiae
liquid cultures allows students to gain quantitative experience generating standard curves and trendlines that capture the relationship between optical density and cell concentration for a given
S. cerevisiae
strain. Data comparisons across multiple strains can yield insights into the biophysical properties of cells that drive light absorbance and scattering. In this Tips and Tools article, we share a laboratory module that allows students to experience cell biology tools, laboratory measurements, and data analysis to determine the mathematical relationship between optical density and cell concentration in liquid microbial cultures. This module could be integrated into undergraduate classes ranging from general biology to upper-level cell biology or microbiology and can be a starting point for more complex investigations of microbial growth.
Novel virulence determinants in VP1 regulate the assembly of enterovirus-A71
Authors: Zhang Wenjing , Li Quanjie , Yi Dongrong , Zheng Ruifang , Liu Guihua , Liu Qian , Guo Saisai , Zhao Jianyuan , Wang Jing , Ma Ling , Ding Jiwei , Zhou Rui , Ren Yongcheng , Sun Tingting , Zhang Ao , Li Xiaoyu , Zhang Yongxin , Cen Shan
Published: November 2024

Enterovirus-A71 (EV-A71) is the second most common causative agent after coxsackievirus A16 of hand, foot, and mouth disease. The capsids of EV-A71 consist of 60 copies of each of the four viral structural proteins (VP1–VP4). VP1 is highly exposed and surface accessible, playing a central role in virus particle assembly, attachment, and entry. To gain insight into the role of highly conserved residues at positions 75, 78, and 88 in the capsid protein VP1 in these processes, an alanine-scanning analysis was performed using an infectious cDNA clone of EV-A71. Our study revealed that the substitutions of VP1-T75A, VP1-T78A, and VP1-G88A could affect the assembly of the virus capsid proteins, resulting in the production of abnormal virions with reduced infectivity. Specifically, the substitution of VP1-T75A affected the maturation cleavage of the VP0 precursor, leading to deficiencies in binding to receptor scavenger receptor class B2 (SCARB2), viral attachment, internalization, and even uncoating. For the mutants of T78A and G88A, a significant reduction in virion-associated genomic RNA was observed, suggesting that more noninfectious empty particles were produced during viral assembly. Interestingly, the VP1-T75A variant showed weak replication in cell cultures but demonstrated increased virulence in BALB/c neonatal mice, which might be due to the difference in viral receptors among mammalian species. Taken together, our data revealed the important role of the highly conserved residues T75, T78, and G88 in VP1 protein in the infectivity of EV-A71. Characterizing these novel determinants of EV-A71 virulence would contribute to rationally developing effective treatments and broadly protective vaccine candidates.

IMPORTANCE

EV-A71 causes hand, foot, and mouth disease in children. In this study, we discovered three highly conserved residues at positions 75, 78, and 88 of the capsid protein VP1 as the potential virulence determinants of EV-A71, which can influence viral replication by regulating the assembly of EV-A71. Mechanistic studies revealed that VP1-T75A could affect the maturation cleavage of the VP0 precursor, resulting in deficiencies in binding to the receptor SCARB2, viral attachment, internalization, and even uncoating. For the mutants of T78A and G88A, more noninfectious empty particles were produced during viral assembly. The discovery of these novel determinants of EV-A71 virulence will promote the study of the pathogenesis of enteroviruses.
Avian influenza A (H5N1) virus in dairy cattle: origin, evolution, and cross-species transmission
Authors: Mostafa Ahmed , Naguib Mahmoud M. , Nogales Aitor , Barre Ramya S. , Stewart James P. , García-Sastre Adolfo , Martinez-Sobrido Luis
Published: November 2024

Since the emergence of highly pathogenic avian influenza virus (HPAIV) H5N1 of clade 2.3.4.4b as a novel reassortant virus from subtype H5N8, the virus has led to a massive number of outbreaks worldwide in wild and domestic birds. Compared to the parental HPAIV H5N8 clade 2.3.4.4b, the novel reassortant HPAIV H5N1 displayed an increased ability to escape species barriers and infect multiple mammalian species, including humans. The virus host range has been recently expanded to include ruminants, particularly dairy cattle in the United States, where cattle-to-cattle transmission was reported. As with the avian 2.3.4.4.b H5N1 viruses, the cattle-infecting virus was found to transmit from cattle to other contact animals including cats, raccoons, rodents, opossums, and poultry. Although replication of the virus in cows appears to be mainly confined to the mammary tissue, with high levels of viral loads detected in milk, infected cats and poultry showed severe respiratory disease, neurologic signs, and eventually died. Furthermore, several human infections with HPAIV H5N1 have also been reported in dairy farm workers and were attributed to exposures to infected dairy cattle. This is believed to represent the first mammalian-to-human transmission report of the HPAIV H5N1. Fortunately, infection in humans and cows, as opposed to other animals, appears to be mild in most cases. Nevertheless, the H5N1 bovine outbreak represents the largest outbreak of the H5N1 in a domestic mammal close to humans, increasing the risk that this already mammalian adapted H5N1 further adapts to human-to-human transmission and starts a pandemic. Herein, we discuss the epidemiology, evolution, pathogenesis, and potential impact of the recently identified HPAIV H5N1 clade 2.3.4.4b in dairy cattle in the United States. Eventually, interdisciplinary cooperation under a One Health framework is required to be able to control this ongoing HPAIV H5N1 outbreak to stop it before further expansion of its host range and geographical distribution.
Type I interferon signaling in dendritic cells limits direct antigen presentation and CD8
+
T cell responses against an arthritogenic alphavirus
Authors: Bullock Christopher B. , Wang Leran , Ware Brian C. , Wagoner Ngan , Ohara Ray A. , Liu Tian-Tian , Desai Pritesh , Peters Bjoern , Murphy Kenneth M. , Handley Scott A. , Morrison Thomas E. , Diamond Michael S.
Published: November 2024

Ross River virus (RRV) and other alphaviruses cause chronic musculoskeletal syndromes that are associated with viral persistence, which suggests deficits in immune clearance mechanisms, including CD8
+
T-cell responses. Here, we used a recombinant RRV-gp33 that expresses the immunodominant CD8
+
T-cell epitope of lymphocytic choriomeningitis virus (LCMV) to directly compare responses with a virus, LCMV, that strongly induces antiviral CD8
+
T cells. After footpad injection, we detected fewer gp33-specific CD8
+
T cells in the draining lymph node (DLN) after RRV-gp33 than LCMV infection, despite similar viral RNA levels in the foot. However, less RRV RNA was detected in the DLN compared to LCMV, with RRV localizing principally to the subcapsular region and LCMV to the paracortical T-cell zones. Single-cell RNA-sequencing analysis of adoptively transferred gp33-specific transgenic CD8
+
T cells showed rapid differentiation into effector cells after LCMV but not RRV infection. This defect in RRV-specific CD8
+
T effector cell maturation was corrected by local blockade of type I interferon (IFN) signaling, which also resulted in increased RRV infection in the DLN. Studies in
Wdfy4
−/−
, CD11c-Cre
B2m
fl/fl
, or Xcr1-Cre
Ifnar1
fl/fl
mice that respectively lack cross-presenting capacity, MHC-I antigen presentation by dendritic cells (DCs), or type I IFN signaling in the DC1 subset show that RRV-specific CD8
+
T-cell responses can be improved by enhanced direct antigen presentation by DCs. Overall, our experiments suggest that antiviral type I IFN signaling in DCs limits direct alphavirus infection and antigen presentation, which likely delays CD8
+
T-cell responses.

IMPORTANCE

Chronic arthritis and musculoskeletal disease are common outcomes of infections caused by arthritogenic alphaviruses, including Ross River virus (RRV), due to incomplete virus clearance. Unlike other viral infections that are efficiently cleared by cytotoxic CD8
+
T cells, RRV infection is surprisingly unaffected by CD8
+
T cells as mice lacking or having these cells show similar viral persistence in joint and lymphoid tissues. To elucidate the basis for this deficient response, we measured the RRV-specific CD8
+
T-cell population size and activation state relative to another virus known to elicit a strong T-cell response. Our findings reveal that RRV induces fewer CD8
+
T cells due to limited infection of immune cells in the draining lymph node. By increasing RRV susceptibility in antigen-presenting cells, we elicited a robust CD8
+
T-cell response. These results highlight antigen availability and virus tropism as possible targets for intervention against RRV immune evasion and persistence.
Comparative genomics of obligate predatory bacteria belonging to phylum
Bdellovibrionota
highlights distribution and predicted functions of lineage-specific protein families
Authors: Davis Sidney C. , Cerra Joseph , Williams Laura E.
Published: November 2024

Comparative genomics of predatory bacteria is important to understand their ecology and evolution and explore their potential to treat drug-resistant infections. We compared chromosomes of 18 obligate predators from phylum
Bdellovibrionota
(16 intraperiplasmic, two epibiotic) and 15 non-predatory bacteria. Phylogenetics of conserved single-copy genes and analysis of genome-wide average amino acid identity provide evidence for at least five
Bdellovibrio
species and support recent reclassifications of predatory taxa. To define shared and differential genome content, we grouped predicted protein sequences into gene clusters based on sequence similarity. Few gene clusters are shared by all 33 bacteria or all 18 predatory bacteria; however, we identified gene clusters conserved within lineages, such as intraperiplasmic
Bdellovibrio
, and not found in other bacteria. Many of these are predicted to function in cell envelope biogenesis, signal transduction, and other roles important for predatory lifestyles. Among intraperiplasmic
Bdellovibrio
, we detected high abundance of gene clusters predicted to encode transglycosylases, endopeptidases, and lysozymes, and we identified six gene clusters (amidase, L,D-transpeptidase, four transglycosylases) with evidence of recent gene duplication and gene family expansion. Focusing on peptidoglycan metabolism, we defined a suite of gene clusters that include peptidoglycan-degrading and -modifying enzymes and occur only in predatory bacteria, suggesting these proteins may have evolved activities specific to predation. Our analyses highlight key genome content differences between obligate predatory bacteria and non-predatory relatives and identify gene clusters that may encode enzymes adapted to predatory lifestyles. These lineage-specific proteins are strong candidates for functional characterization to clarify their role in predation.

IMPORTANCE

Evolution of predation as a bacterial lifestyle involves selective pressure on and adaptation of enzymes that contribute to killing and digestion of prey bacteria, in some cases from within the prey itself. Such enzymes are a hallmark of obligate predatory bacteria belonging to phylum
Bdellovibrionota
, which includes the well-studied predator
Bdellovibrio
. By comparing protein sequences of obligate predatory bacteria and their non-predatory relatives, we define key genome content differences that distinguish bacterial predators and identify lineage-specific enzymes that may have evolved unique activities due to selective pressures related to a predatory lifestyle. In addition to providing insights into the ecology and evolution of predatory bacteria, comparative genomics studies, like this, can inform efforts to develop predatory bacteria and/or their enzymes as potential biocontrol agents to combat drug-resistant bacterial infections.
Influence of flow discharge and minibasin shape on the flow behavior and depositional mechanics of ponded turbidity currents
Authors: Reece J. Kevin , Dorrell Robert M. , Straub Kyle M.
Published: November 2024

The interplay between seafloor sediment-laden density-driven flows, turbidity currents, and topography helps to shape continental margins. However, these interactions are poorly understood, especially those within enclosed depressions termed minibasins. In this study, novel experiments quantify the three-dimensional (3-D) dynamics of turbidity currents interacting with a range of minibasin geometries that, for the first time, scale within the parameter space of natural systems. Controls on flow dynamics are quantified by measuring the evolving velocity and sediment transport fields, in addition to maps of bathymetry. This study focuses on three aspects of turbidity current interactions with minibasins. First, the results suggest that sediment transport and deposition in minibasins is likely dominated by evolving flow conditions. Contrary to earlier studies in two-dimensional (2-D) flumes, this study supports a time-to-flow equilibrium in minibasins that scales with the time to replace ambient fluid with turbid influx, and this replacement time likely takes days to achieve in many field-scale minibasins. Second, in all experiments, horizontal flow circulation is observed, which is critical for distributing sediment throughout minibasins. However, the strength of the horizontal circulation reduces as the ratio of minibasin length to width increases, which leads to stagnant or even upstream-directed flow near the bed, elevated height of the velocity maximum in flows, the lowering of near-bed shear stresses, and more homogeneous deposits through a reduction in bed reworking. Finally, the results indicate that fluid detrainment from minibasins significantly reduces sediment fall velocities, severely lowering the sediment-trapping efficiency for small or light particles. This reduction in effective fall velocities of sediments suggests a mechanism that fractionates fine particulates (e.g., clays), nutrients (e.g., organic carbon), and pollutants (e.g., microplastics) along transport paths down topographically complex margins.
Iron isotope fractionation during transcrustal magmatic differentiation: Implications for continental crustal formation in subduction zones
Authors: Xu Jian , Xia Xiao-Ping , Wang Qiang , Zhang Le , Cui Ze-Xian , Yang Qing , Zhang Wan-Feng
Published: November 2024

Earth’s continental crust is hypothesized to originate from mantle melting in subduction zones. However, mantle melts are typically Fe-rich, with light Fe isotopes (δ56Fe = 0.05‰), unlike the Fe-depleted and heavy Fe isotope (δ56Fe can be up to 0.2‰) compositions of continental crust. The mechanisms responsible for this paradox remain elusive. Here, we report Fe isotope data from a suite of co-magmatic Middle Triassic continental arc rocks in the Ailaoshan tectonic zone (Yunnan, SW China). Gabbroic diorites have light Fe isotopes (δ56Fe = 0.04‰–0.09‰), while granodiorites and normal-arc granites have slightly heavier values (δ56Fe = 0.07‰–0.14‰). Adakitic granites, with high Sr/Y (61–183) and La/Yb (47–90) ratios, exhibit the heaviest δ56Fe (0.16‰–0.19‰). Rayleigh fractionation modeling results suggest that fractionation of isotopically light Fe minerals (e.g., olivine, pyroxene, and amphibole) can reproduce the Fe isotopic variations in most samples, but fails to explain the high Sr/Y, La/Yb, and δ56Fe values of adakitic granites, which would require Fe-rich garnet fractionation. Notably, the different Fe isotopes of the adakitic granites and non-adakitic rocks reveal two distinct transcrustal magmatic differentiation pathways: lower crustal, high-pressure, garnet-dominated fractionation; and middle–upper crustal, amphibole-dominated fractionation. The heavy Fe isotopic and Fe-depleted characteristics of the Ailaoshan magmatic arc suites are more comparable to the calc-alkaline arc magmas from normal to thick crust arcs (e.g., the Andean arc), but remarkably different from the tholeiitic arc magmas from thin crust arcs (e.g., the Mariana arc). This study highlights the role of amphibole and garnet fractionation in magmatic calc-alkaline differentiation. We propose that a thickened crust would permit a longer magmatic differentiation column, thus facilitating felsic and Fe-depleted continental crustal formation. The fractionated Fe-rich, garnet-bearing arc cumulates with light Fe isotopes are density-unstable and may be recycled into the mantle by lower crustal foundering.
Long-read sequencing for detection and subtyping of Prader-Willi and Angelman syndromes
Authors: Akbari Vahid , Dada Sarah , Shen Yaoqing , Dixon Katherine , Hejla Duha , Galbraith Andrew , Choufani Sanaa , Weksberg Rosanna , Boerkoel Cornelius F , Stewart Laura , Gibson William T , Jones Steven J M
Published: November 2024

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are imprinting disorders caused by genetic or epigenetic aberrations of 15q11.2-q13. Their clinical testing is often multitiered; diagnostic testing begins with methylation-specific multiplex ligation-dependent probe amplification or methylation-sensitive PCR and then proceeds to molecular subtyping to determine the mechanism and recurrence risk. Currently, correct classification of a proband’s PWS/AS subtype often requires parental samples, a costly process for families and health systems. The use of nanopore sequencing for molecular diagnosis of PWS and AS has been explored by Yamadaet al; however, to confirm heterodisomy parental data were still required. Here, we investigate genome-wide nanopore sequencing in a larger cohort of PWS (18) and AS (6) as a singular test to detect the molecular subtype, without parental data. We accurately subtyped these cases including uniparental heterodisomy, mixed iso-/heterodisomy, type 1 and 2 deletions, microdeletion andUBE3Aindels. One PWS case with a previously unresolved diagnosis subtyped as maternal isodisomy. This work highlights the application of long-read sequencing and other imprinted regions outside of the PWS/AS critical region to resolve the molecular diagnosis and subtyping of PWS and AS without parental data. The work also outlines an approach to generically detect heterodisomy through the interrogation of distant imprinted regions.
Long-term clinical follow-up of irritant-induced occupational asthma
Authors: Lantto Jussi , Suojalehto Hille , Jantunen Hanna , Lindström Irmeli
Published: November 2024

Background

Occupational exposure to irritants is associated with poor asthma control, but the long-term clinical characteristics of irritant-induced occupational asthma (IIA) are poorly known.

Objective

To evaluate whether any distinguishable features contribute to IIA patients’ poor outcomes and whether clinical characteristics change over time.

Methods

We re-evaluated 28 IIA patients with a median of 6.8 years (IQR 4.6–11.1) after their diagnosis at the Finnish Institute of Occupational Health in 2004–2018. We measured their lung function, non-specific bronchial hyper-responsiveness, inflammation profile and exercise capacity using an ergometric bicycle test. The participants also underwent an Asthma Control Test (ACT) and responded to questionnaires assessing their laryngeal hypersensitivity (LHQ) and dysfunctional breathing (Nijmegen Questionnaires, NQ).

Results

At follow-up, 22 (79%) participants used inhaled corticosteroids, 4 (14%) had asthma exacerbation within 1 year, 11 (39%) had ACT<20 (ie, poor asthma symptom control), 7 (26%) had abnormal spirometry and 8 (36%) had a positive methacholine challenge test result. 17 (61%) participants showed at least one elevated eosinophilic inflammation marker. Six (23%) had an abnormal LHQ score and 7 (26%) had an abnormal NQ score. 15 (58%) participants showed reduced physical capacity that was related to extensive asthma medication, poor asthma symptom control and acute IIA phenotype. A higher ACT score was the only significant change between diagnosis and follow-up (p=0.014).

Conclusion

Most of the IIA patients had normal lung function at follow-up, which had only changed a little over time. Reduced physical capacity was a common finding and appears to be related to poor asthma symptom control.
Routine radiographs of hands and feet do not have diagnostic or prognostic value in patients with clinically suspect arthralgia: a large longitudinal study
Authors: Dumoulin Quirine A , van der Helm - van Mil Annette H M , van Steenbergen Hanna W
Published: November 2024

Background

Conventional radiographs of hands and feet are used to depict structural damage in rheumatoid arthritis (RA). This is also commonly done in clinical practice in symptomatic patients at risk for RA (clinically suspect arthralgia (CSA)), but its rationale is unclear. We aimed to investigate the prevalence of radiographic erosive disease in patients with CSA and its progression over time.

Methods

Patients with symptomatic arthralgia of the Leiden CSA cohort were studied during 2-year follow-up or until development of inflammatory arthritis (IA). Erosive disease was defined according to the radiologist, or according to the RA-specific erosive definition in light of the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) 2010 RA criteria. Serial radiographs were evaluated according to the Sharp van der Heijde Scoring method (SHS) and radiographic erosive progression was determined. Additionally, it was evaluated if baseline erosive disease associated with IA development. Analyses were stratified for anticitrullinated protein antibody status.

Results

1497 radiographs of hands and feet of 749 patients with CSA were studied. Median SHS-erosion score at baseline was 0 (IQR 0–1). RA-specific erosive disease was present in 1.7% according to the radiologist, and 2.5% according to the ACR/EULAR criteria. No patients with CSA progressed ≥5 SHS-erosion points during follow-up. Erosive disease at CSA onset was not associated with IA development (HR 0.98 (95% CI 0.40 to 2.44)).

Conclusions

At CSA onset, radiographic erosive disease is rare. In addition, it is rarely progressive within the CSA phase and not predictive for IA development. Therefore, for clinical practice, routinely made radiographs of hands and feet (such as regularly done at RA diagnosis) can be omitted in the at-risk stage of arthralgia.
Tenecteplase thrombolytic therapy for acute ischaemic stroke in China: a real-world, multicentre, retrospective, controlled study
Authors: Liu Ye , Lu Guozhi , Li Dan , Wu Guang , Zhou Xiaoyu , Qu Rongbo , Fang Yongren , He ZhiJiao , Zhang Anqi , Hong Lan , Fang Kun , Cheng Xin , Dong Qiang
Published: November 2024

Background and aims

Tenecteplase (TNK) offers logistical advantages in stroke thrombolytic therapy with its single bolus administration compared with alteplase. We aim to investigate the real-world evidence regarding its safety and effectiveness in China.

Methods

We conducted a retrospective study on patients receiving alteplase or TNK for acute ischaemic stroke (AIS) within 4.5 hours of onset between 1 March 2019 and 1 October 2023, from 18 stroke centres in China. Using propensity score matching (PSM), TNK-treated patients were matched 1:1 with alteplase-treated patients. The primary outcome was the rate of symptomatic intracranial haemorrhage (sICH) within 72 hours post-thrombolysis. Secondary outcomes comprised the rate of parenchymal haemorrhage type 2, any intracranial haemorrhage, any systematic bleeding and mortality at 90 days, as well as 24-hour National Institutes of Health Stroke Scale (NIHSS), early neurological improvement at 24 hours, modified Rankin Scale (mRS) shift, percentage of mRS 0–1 and mRS 0–2 at 90 days.

Results

We identified 1113 patients with AIS who received TNK and 2360 patients who received alteplase. Following PSM, 1113 TNK-treated patients with AIS were matched to 1113 patients treated with alteplase. No significant differences were observed in rates of sICH (1.8% vs 1.98%, p=0.864) or other safety outcomes. Moreover, TNK-treated patients demonstrated a lower rate of any intracranial haemorrhage (OR: 0.51, 95% CI: 0.31 to 0.86, p=0.012). A higher proportion of patients achieving early neurological improvement at 24 hours (OR: 1.76, 95% CI: 1.48 to 2.09, p=0.000), better 90-day mRS (OR: 0.67, 95% CI: 0.57 to 0.79, p=0.000) as well as higher percentages of 90-day mRS 0–1 (OR: 1.27, 95% CI: 1.05 to 1.54, p=0.012) and mRS 0–2 (OR: 1.41, 95% CI: 1.14 to 1.75, p=0.001) compared with alteplase.

Conclusions

Thrombolysis with TNK is not associated with an increased risk of sICH, and may result in better early neurological improvement and 90-day functional outcomes compared with alteplase in patients with AIS.
Hydrocortisone improves post-resuscitation myocardial dysfunction by inhibiting the NF-κB pathway
Authors: Fang Yaqin , Song Fenglin , Gao Chunyan , Wang Zhiming
Published: November 2024

Myocardial dysfunction is a major cause of early mortality after successful cardiopulmonary resuscitation (CPR) following cardiac arrest (CA). Following the return of spontaneous circulation, myocardial ischemia–reperfusion injury can activate the NF-κB pathway, leading to the transcription of inflammatory genes that impair myocardial function. While clinical studies show hydrocortisone (HC) improves outcomes in CA patients during CPR, its specific role in modulating the NF-κB pathway is unclear. In this study, we established an in vitro model by inducing hypoxia/reoxygenation (H/R) injury in H9C2 cardiomyocytes using Na2S2O4, followed by HC treatment. The results showed that HC treatment of H/R-injured cardiomyocytes promoted proliferation, inhibited apoptosis, and suppressed the NF-κB pathway, thereby reducing interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α) levels. Moreover, inhibition of the NF-κB pathway enhanced the proliferative capacity of H/R cardiomyocytes, decreased apoptosis rates, and reduced IL-6, IL-8, and TNF-α expression levels, with these effects being further amplified by HC treatment. These findings were further supported by in vivo experiments. In conclusion, our study suggests that HC may promote H/R cardiomyocyte proliferation, inhibit apoptosis, and alleviate inflammatory responses by suppressing the NF-κB pathway, providing new evidence to support its potential clinical application in CA management.
Exploring the factors influencing car drivers’ perception and crash probability with food delivery riders
Authors: SayedMohammed Shabna , Kharbeche Mohamed , Muley Deepti , Alhajyaseen Wael , AlQaradawi Mohammed
Published: November 2024

Motorcycle food delivery riders (MFDRs) face significant crash risk with some of these crashes attributed to other vehicle drivers. This research assesses drivers’ perceptions and observed riding behaviors of MFDRs through a survey and analyzes driver factors that increase MFDR crash risk. Drivers indicated that MFDRs exhibited reckless riding (tailgating, filtering, and weaving), and drivers’ demographics, driving characteristics, and personality trait anger affected these observations. Personality trait anger influenced fault identified in a crash and motorcycle riding perception, while driver demographics had a minor effect on the perceptions. Drivers’ motorcycle riding experience affected understanding of MFDR riding behaviors and MFDR riding perception. Driver’s age, employment, motorcycle riding experience, violations, emotional state while driving (hurry), observed MFDR violations factor score, and motorcycle riding perception affected crash probability. The results could be used to develop strategies to promote traffic safety in mixed environments by providing motorcycle riding behavior awareness and improving driver training.
An interdisciplinary research field transformed into an intermedial science exploration programme: how to explore neurotronics research and development in a school student laboratory programme
Authors: Sacristán Daniel , Stamer Insa , Kohlstedt Hermann , Beyer Isabella , Parchmann Ilka
Published: November 2024

This work presents the development and implementation of an interdisciplinary and intermedial science outreach programme designed for school students. The programme integrates biological systems and technological advancements to provide students with hands-on laboratory experiences and immersive media, including virtual reality videos and augmented reality posters. Through a co-creation process involving scientists and educators, the programme aims to enhance students understanding of bio-inspired information pathways and neurogenesis. Preliminary evaluations indicate high engagement and educational value, suggesting that such interdisciplinary approaches can significantly enrich science education.

Graphical abstract
Triphasic Bone Scintigraphy Is Not Useful in Diagnosis and May Delay Surgical Treatment of CRPS of the Hand
Authors: PIÑAL Francisco del , LIM Jin Xi , WILLIAMS Daniel C. , RÚAS Jaime S. , STUDER Alexis T.
Published: November 2024

Background: Triphasic bone scintigraphy (TPBS) is often used to diagnose complex regional pain syndrome (CRPS). The primary aim of this study is to determine if the diagnosis of CRPS in patients with a positive TPBS (TPBS +ve) is accurate. A secondary aim is to determine if there was delay in treatment of patients who underwent TPBS compared to those who did not have a TPBS.

Methods: Of 225 consecutive patients presenting to the first author’s practice with a diagnosis of CRPS, 65 had TPBS performed before referral with 62 having TPBS +ve. The remaining 160 were clinically diagnosed and a TPBS was not done (TPBS-ND). Patients were classified into five categories – wrong diagnosis, dystonic-psychogenic hand, causalgia, flare reaction and irritative carpal tunnel syndrome (ICTS). Patients with flare reaction and ICTS were considered as having true CRPS and the rest were considered as misdiagnosis. The patients’ demographics, duration of symptoms, pre- and postoperative pain, functional score and patient satisfaction were compared.

Results: Of the 62 TPBS +ve, there were 38 (61%) misdiagnosis. The proportion of misdiagnoses was fewer in the TPBS-ND group (45%; p = 0.036). Thirty-two of the 62 TPBS group (52%) and 92/160 (56%) of the TPBS-ND group had surgical treatment. At a mean follow-up of 19 months, pain dropped 6.5 ± 2.5 points in the TPBS +ve group. Disabilities of the arm, shoulder and hand (DASH) score fell by 56 ± 27. The mean single assessment numeric evaluation (SANE) score was 8.6 ± 2.3. These results did not differ substantially from those of the TPBS-ND group.

Conclusions: A significant number of patients in this study who had TPBS +ve were misdiagnosed in this study. Outcomes after treatment of CRPS were consistently good despite the results of the TPBS. Patients with TPBS +ve had a significant delay to diagnosis. We conclude that TPBS is not useful in the management of CRPS.

Level of Evidence: Level III (Therapeutic)
Efficient Federated Recommender System with Adaptive Model Pruning and Momentum-based Batch Adjustment
Authors: Shi Hongjian , Di Yicheng , Ruan Xinyu , Liao Mingrui , Zhang Qian , Ma Ruhui , Guan Haibing
Published: November 2024

With the development of 5G communication and smart devices, the prosperity of online content has boosted the research of Recommender System (RS). Due to the data scarcity problem, researchers employ knowledge transfer techniques to improve the accuracy of RS. Data sharing or data augmentation are promising methods for such a problem, but the data suffers from privacy leakage during sharing. Thus, Federated Learning (FL) has been adopted to collaboratively train recommender models while preserving data privacy. Federated Recommender System (FRS) combines FL and RS to provide distributed recommendation services to the users. However, the existing FRS suffers from massive communication and system heterogeneity, where the necessity of model transmission and the diversity of the clients bring significant communication overhead to the system. In this paper, we propose Efficient Federated Recommender System with Adaptive Model Pruning and Momentum-based Batch Adjustment (
eFRSA
2
) to reduce the communication overhead of FRS.
eFRSA
2
contains two modules. Adaptive Model Pruning utilizes magnitude pruning to reduce the communication volume and adaptively modifies the compression ratios of different clients to maintain the model accuracy. Momentum-based Batch Adjustment adjusts the local training batch number by a similar method of gradient descent with momentum to align the local computation time of the clients and reduce the communication overhead. The experimental results demonstrate that
eFRSA
2
can reduce up to 90% communication volume and mitigate the system heterogeneity by over 75%, demonstrating the priority of
eFRSA
2
in training efficiency. Source code can be found at https://github.com/shhjwu5/eFRSA2.
Transverse Quantum Superfluids
Authors: Kuklov Anatoly , Pollet Lode , Prokof’ev Nikolay , Svistunov Boris
Published: November 2024

Even when ideal solids are insulating, their states with crystallographic defects may have superfluid properties. It became clear recently that edge dislocations in 4He featuring a combination of microscopic quantum roughness and superfluidity of their cores may represent a new paradigmatic class of quasi-one-dimensional superfluids. The new state of matter, termed transverse quantum fluid (TQF), is found in a variety of physical setups. The key ingredient defining the class of TQF systems is infinite compressibility, which is responsible for all other unusual properties such as the quadratic spectrum of normal modes (or even the absence of sharp quasiparticles), irrelevance of the Landau criterion, off-diagonal long-range order at T = 0, and the exponential dependence of the phase slip probability on the inverse flow velocity. From a conceptual point of view, the TQF state is a striking demonstration of the conditional character of many dogmas associated with superfluidity, including the necessity of elementary excitations, in general, and the ones obeying Landau criterion in particular.
From Processed Foods to Ultraprocessed Foods: Evolution of an Industry Model and Impact on Dietary Quality, Health, and Society
Authors: Ubbink Job , Levine Allen S.
Published: November 2024

The impact of food technology and product development on the nutritional quality of foods is discussed in the context of food classification schemes, clinical research, and sociocultural studies. Food processing operations are analyzed in terms of their beneficial and detrimental consequences for the nutritional value of foods and ingredients. Several classification schemes are discussed, including dietary guidelines, nutrition information panels, and nutritional scores. The health impact of processed and ultraprocessed foods is discussed in connection with the processing–formulation scheme previously developed by the authors. The importance of product development as a driver for the food industry is highlighted, and formulation-based approaches to improve the healthfulness of industrially produced foods are discussed. Finally, the public perception of processed foods and its impact on the industry are discussed, and the need for a broad engagement among stakeholders to ensure the sustainability of our food system and healthy diets for individuals is emphasized.
Review—In Situ X-ray and Infrared Spectroscopic Studies of Electrochemical Systems
Authors: Marinkovic Nebojsa S. , Sasaki Kotaro , Adzic Radoslav R.
Published: November 2024

Despite of intense research and a wealth of data, the phenomena occurring during electrocatalysis are still a major obstacle in many chemical processes. Molecular analysis of the electrode/electrolyte interface is needed to correctly describe the reaction through identifying the species involved, their interaction with the environment and kinetics in situ, i.e. while the reaction is taking place. That can be done by coupling the electrochemical system with complementary non-electrochemical techniques. Particularly revealing are in situ X-ray spectroscopic techniques to analyze the electrode itself, providing the information on the changes in the catalyst during the reaction. The synergy of the traditional electrochemical techniques with the complementary spectroscopic methodologies offer understanding of the electrode/electrolyte interface above and beyond traditional experimental mainframe. Here we demonstrate how in situ X-ray absorption spectroscopy (XAS), in situ infrared reflection/absorption spectroscopy (IRRAS), and traditional voltammetric studies can increase our understanding of electrochemical processes during oxidation of ethanol. The results show the pronounced role of electrode surface in determining reaction kineticks and revealed the selectivity of the catalyst to complete oxidation pathway. They further provide understanding of the parameters that enhance its oxidation for future designing catalysts for alcohol oxidation fuel cells.
Manufacturing and Characterization of Three Modified Vegetable Oil–Added Polylactic Acid Composites
Authors: Şen İbrahim , Atagür Metehan , Tuna Sibel , Eroğlu Murat , Kurtlu Meral Akkoyun , Sever Kutlay
Published: November 2024

Polylactic acid (PLA) was modified with three types of modified vegetable oils (MVOs), which are the epoxidized soybean oil (ESBO), maleinized sunflower oil (MSO), and maleinized olive oil (MOO), at different weight fractions. A corotating twin screw extruder was used to produce composite materials by the melt‐mixing process. The effect of MVO content, from 2.5% to 10%, on the morphology, mechanical properties, density, and water absorption was investigated in detail. The addition of ESBO and maleinized vegetable oils leads to a slight decrease in the density of PLA from 1.252 to 1.231 g/cm3. As the concentration of MVO in PLA increases, the amount of water absorption also increases, and the highest water absorption value was observed in P10MSO. The FTIR spectra of all concentrations of the MOO and MSO have two peaks at 1781 and 1861 cm−1, attributed to the C=O stretching which is related to maleic acid copolymerization. In general, the elastic modulus (EM) was slightly changed by the addition of MVOs to PLA, while the tensile strength (TS) decreased. Due to the plasticizing effect of MVOs, an increase in the Izod impact strength was obtained.
Metataxonomic Analysis of Microbial Communities in Aquaponic Systems at Two Facilities in the Midwest United States
Authors: Rogge Matthew L. , Impullitti Ann E. , Phelps Nicholas B. D.
Published: November 2024

Aquaponic production relies on microbial activity to convert fish wastes into nutrients for plants. An aquaponic system contains multiple compartments that each have varying environmental pressures that can impact the types of microbes living in the compartment. Furthermore, differences in fish and plant species, system startup and management, and water source can impact microbial communities that colonize an aquaponic system. In this study, we sampled two aquaponic facilities that each operated six replicate aquaponic systems. Metataxonomic analyses were performed on the samples to compare the microbial communities of aquaponic facilities in Minnesota (MN) and Wisconsin (WI), assess the consistency of the microbial communities across multiple systems within a single facility, and evaluate the abundance and types of microbes present within each compartment of a system. Proteobacteria, Bacteroidetes, and Actinobacteria were common in both facilities, but nitrifying organisms were in greater abundance at the WI facility. Microbial communities were largely consistent among systems within a facility, but microbial communities among different compartments of the systems varied. Nitrifying organisms were primarily associated with the biofilter compartment of the MN systems but were found throughout the WI systems, which do not have a dedicated biofiltration compartment. While nitrifying organisms have an important role in an aquaponic system, they comprise less than 10% of the total microbial community of the aquaponic systems we sampled. Other taxa are likely to have equally important roles in the productivity of an aquaponic system, but those taxa and their functions have not been well characterized, and it is unclear how system startup, management, and other factors impact colonization and maintenance of these taxa.
Automatic Identification and Segmentation of Long‐Span Rail‐and‐Road Cable‐Stayed Bridges Using UAV LiDAR Point Cloud
Authors: Shen Yueqian , Deng Zili , Wang Jinguo , Fu Shihan , Chen Dong
Published: November 2024

Bridge information models are essential for bridge inspection, assessment, and management. LiDAR technology, particularly UAV LiDAR, offers a cost‐effective means to capture dense and accurate 3D coordinates of a bridge’s surface. However, the structure of large‐scale bridges is complex, and existing commercial software still demands substantial manual effort to segment the components when constructing bridge information models for large‐scale bridges. This study introduces a novel approach to automatically segment the components of a long‐span rail‐and‐road cable‐stayed bridge from the entire point cloud obtained through UAV LiDAR. In this proposed approach, the geometric and topological constraints of various bridge components are thoroughly examined, and a combination of the coarse‐to‐fine concept and top‐down strategy is employed. The key structural elements, including piers, cable towers, wind fairing plate, stay‐cable, main truss, railway surfaces, and deck surfaces, are identified and segmented. The proposed methodology achieves an average accuracy of over 96% at the point level validated using datasets acquired by UAV LiDAR.