bluuebunny/crossref_metadata_2025_split huggingface dataset:
ThePorphyromonas gingivalislipid A 1-phosphatase LpxE has unique features and requires a functional type IX secretion system for its activity
Authors: Wang Sunjun , Liu Yichao , Zhang Beichang , Aduse-Opoku Joseph , Buccafusca Roberto , Mastroianni Giulia , Machado Pedro , Roberts Mark A. J. , Curtis Michael A. , Garnett James A. 
Published: December 2024

ABSTRACTPorphyromonas gingivalisis a Gram-negative bacterium that plays a central role in the development of periodontal disease. It uses a type IX secretion system (T9SS) to export a range of virulence factors to the bacterial surface where they are attached to A-LPS, one of the two forms of lipopolysaccharide (LPS) produced inP. gingivalis, and then packaged into outer membrane vesicles (OMVs). We previously showed that 1-P dephosphorylation of the lipid A component of LPS is regulated by the T9SS outer membrane protein (OMP) PorV, and this is linked to membrane destabilisation and OMV blebbing/formation. In this study we aimed to extend this and investigate the role of other T9SS OMPs in OMV biogenesis. We examined gingipain activity, gingipain secretion, A-LPS production, OMV morphology, and lipid A structure inP. gingivalisW50 and T9SS OMP mutant strains, and our results support an essential role for these proteins in type IX secretion. In addition, we produced a lipid A 1-phosphatase (ΔlpxE) mutant and show that all T9SS OMPs are required for LpxE activity and correct vesicle formation. LpxE has a unique C-terminal extension, and we propose that a cargo protein exported by the T9SS can directly/indirectly interact with this and regulate LpxE activity. This study provides insight into a new mechanism that links type IX cargo sorting with OMV blebbing, which may also be present in other Bacteroidota that colonise the gut and oral cavity.
Yersinia pestisactively inhibits the production of extracellular vesicles by human neutrophils
Authors: Sheneman Katelyn R. , Cummins Timothy D. , Merchant Michael L. , Hood Joshua L. , Uriarte Silvia M. , Lawrenz Matthew B. 
Published: December 2024

AbstractYersinia pestisis the etiologic agent of the plague. A hallmark of plague is subversion of the host immune response by disrupting host signaling pathways required for inflammation. This non-inflammatory environment permits bacterial colonization and has been shown to be essential for disease manifestation. Previous work has shown thatY. pestisinhibits phagocytosis and degranulation by neutrophils. Manipulation of these key vesicular trafficking pathways suggests thatY. pestisinfluences EV secretion, cargo selection, trafficking, and/or maturation. Our goal was to define the EV population produced by neutrophils in response toY. pestisand determine how these vesicles might influence inflammation. Toward these goals, EVs were isolated from human neutrophils infected withY. pestisor a mutant lacking bacterial effector proteins known to manipulate host cell signaling. Mass spectrometry data revealed that cargoes packaged in EVs isolated from mutant infected cells were enriched with antimicrobials and cytotoxic proteins, contents which differed from uninfected andY. pestisinfected cells. Further, EVs produced in response toY. pestislacked inflammatory properties observed in those isolated from neutrophils responding to the mutant. Together, these data demonstrate thatY. pestisactively inhibits the production of antimicrobial EVs produced by neutrophils, likely contributing to immune evasion.
Killer Toxin K28 resistance in yeast relies on COG complex mediated trafficking of the defence factor Ktd1
Authors: Laidlaw Kamilla ME. , Nadir Hatwan H. , Milburn Amy , Xelhuantzi Martha S.C. , Stanislovas Justas , Droop Alastair P. , MacDonald Sandy , Andreev Ilya , Leech Andrew , Ungar Daniel , Sadhu Meru , MacDonald Chris 
Published: December 2024

ABSTRACTA/B toxins are a diverse family of protein toxins that enter host cells via endocytosis and induce cell death. In yeast, the A/B toxin K28 is internalised to endosomes of susceptible yeast, before following the retrograde trafficking pathway and ultimately triggering cell cycle arrest. The endolysosomal defence factor Ktd1 protects against K28, but its regulation remains unclear. Cog7, a subunit of the Golgi-associated tethering COG complex, has been implicated in K28 defence, though the mechanism is unknown. We developed a high throughput K28 sensitivity assay and bespoke analysis package to show that all lobe B COG subunits (Cog5 - 8) are required for K28 resistance. Although the COG complex modulates glycosylation of the surface molecules required to bind extracellular K28, our experiments reveal that the hypersensitivity ofcogmutants is primarily explained by defects in Ktd1 trafficking. Ktd1 mis-localisation incogmutants is reminiscent to disruptions in Snc1, a surface cargo that recycles multiple times via the Golgi. This work suggests not only that the COG complex is required for the precise trafficking Ktd1 required to mediate toxin defence, but that Ktd1 may survey endolysosomal compartments for internalised K28. This work underpins the importance of Ktd1 in defence against the A/B toxin K28, and implies various membrane trafficking regulators might influence toxin effects in other eukaryotic systems.
Towards a comprehensive framework for digital inclusion: a comparison of international measurements
Authors: Jia Shiwei , Du Jia Tina , Yan Hui 
Published: December 2024

PurposeMeasuring the extent of digital inclusion is a complex task. This study aims to monitor existing digital inclusion indices at the national level, compare their consistencies and differences and based on this, develop a more comprehensive measurement framework.Design/methodology/approachThe study selected the existing digital inclusion indices that met the screening criteria through a literature survey. Eight digital inclusion indices were included in the final selection and their measurement methodologies were collected. Thereafter, the study adopted a content analysis method to examine and compare the methodologies of the selected digital inclusion indices, with the coding framework grounded on the literature review.FindingsResults suggest that five dimensions of digital inclusion – Access, Skills, Usage, Acceptance and Impact – were measured. Access is the first priority dimension that all digital inclusion indices pay attention to. Skills and Usage are under-measured by methodological limitations in practical measurement tools. Acceptance and Impact are the least covered dimensions both in academic research and practical measurement. Based on this, we propose three suggestions for developing a more comprehensive global framework: designing from the national lens, using more objective and original data sources and improving the framework and indicators with theory.Originality/valueThe study provides scholars and policymakers in the field of digital inclusion with a reference point to create a more comprehensive measurement framework for digital inclusion.
Online controversial events: leveraging consumer engagement with users’ positive buzz
Authors: Li Xiaoling , Fan Tingting , Yu Hongyu , Yang Pianpian 
Published: December 2024

PurposeSocial media have escalated the frequency and intensity of brands’ online controversial events (OCEs), which differs conceptually from negative events. Despite this, there remains a scarcity of research exploring the nature of OCEs. This paper aims to investigate the impact of positive buzz on consumer engagement during OCEs.Design/methodology/approachUsing 47,468 posts from two popular Chinese social media (i.e. Weibo and Zhihu), we employ a zero-inflated negative binomial regression and content analysis to test our hypotheses.FindingsThe results indicate that positive buzz informativeness and sentiment positively affect consumer engagement in online brand communities, moderated by community type and time-related factors. Expert communities (vs social communities) weaken main effects, while date distance strengthens them.Originality/valueThis study is the first to propose the nature of brand’s OCEs and explores how positive buzz affects consumer engagement, highlighting the moderating roles of community type and date distance. This paper contributes to literature on user-generated content (UGC), OCEs and dual process theory, offering valuable insights for brands, consumers and community owners.
Modelling temperature distribution in three-side protected steel beams using evolutionary regression and gradient boosting to predict conductive heat flux
Authors: Li Yang , Guo Kangrui 
Published: December 2024

PurposeThe aim of the paper is to propose a simple and effective calculation method for a three-side protected steel beam temperature field.Design/methodology/approachThe calculation model is based on temperature increment equation of EN1993-1-2 and the Fourier's law to calculate the conductive heat flux. The ABAQUS heat transfer simulation is used to establish temperatures and heat flux database at the joints. The ratio of simulation and calculated heat flux is predicted by evolutionary regression and gradient boosting method.FindingsCombined evolutionary regression analysis (CERA) including both linear and polynomial regression reduce the residual of mean square error (MSE) by 7.1% compared to linear regression analysis (linear evolutionary regression analysis (LERA)). The evolutionary regression analysis (ERA) effectively reduces the temperature discrepancy with increase of evolution numbers. Gradient boosting predicts the k value and temperatures with the least residual of MSE. The average residual of MSE is 53.23 °C for the upper flange, 16.18 °C for the web and 19.44 °C for the lower flange.Originality/valueThis paper proposed an effective and fast temperature distribution model for the three-side protected steel beam combining machine learning methods to converge the conductive heat flux between specimens. A novel ERA able to fit output data with multiple inputs with explainable equations is proposed and validated by effectively converging the conductive heat flux to simulation results.
Easy‐Curing and pH‐Regulated CRISPR‐Cas9 Plasmids for Gene Editing and Plasmid Curing in Lactococcus cremoris
Authors: Garay‐Novillo Javier Nicolás , Ruiz‐Masó José Ángel , del Solar Gloria , Barra José Luis 
Published: December 2024

ABSTRACTIn this work, we developed a plasmid‐based CRISPR‐Cas9 strategy for editing Lactococcus cremoris, which allows easy generation of plasmid‐free strains with the desired modification. We constructed versatile shuttle vectors based on the theta‐type pAMβ1 promiscuous replicon and p15A ori, expressing both the Cas9 nuclease gene (under pH‐regulated promoters derived from P170) and a single‐guide RNA for specific targeting (under a strong constitutive promoter). The vectors designed for plasmid targeting were very effective for low‐ and high‐copy‐number plasmid curing in L. cremoris, and their targeting efficiency was shown to be tunable by regulating cas9 expression. For chromosome editing, we implemented a host‐independent method that enhances double‐homologous recombination events using plasmids expressing the genes encoding λRed‐phage Redβ recombinase and Escherichia coli single‐stranded DNA binding protein (EcSSB). By coupling either the endogenous recombination machinery or the Redβ‐EcSSB‐assisted recombination system with our novel chromosome‐targeting CRISPR‐Cas9 plasmids, we efficiently generated and selected thousands of gene‐edited cells. Examination of the impact of the constructed CRISPR‐Cas9 vectors on host fitness revealed no Cas9‐associated toxicity, and, remarkably, these vectors exhibited a very high loss rate when growing the bacterial host cells in the absence of selective pressure.
Risk Stratification and Adjuvant Chemotherapy for High‐Risk Stage IA Lung Adenocarcinoma: The Unmet Needs
Authors: Shen Chen , Liu Haoran , Li Bofei , Wang Jiaming , Wang Yiyang , Bao Feichao , Gu Zhitao , Fang Wentao 
Published: December 2024

ABSTRACTIntroductionTo identify high‐risk patients for recurrence in resected stage IA lung adenocarcinoma and evaluate the impact of adjuvant chemotherapy (ACT) on their prognosis, as well as explore potential novel adjuvant therapies.MethodsConsecutive stage IA patients with ≥ 5% solid or micropapillary subtypes were analyzed. A nomogram was developed using Cox proportional hazards regression to predict recurrence‐free survival (RFS). In the high‐risk group after stratification, RFS was compared between patients receiving ACT and those under observation, as well as between patients with and without driver gene alterations.ResultsThis real‐world study included 1328 patients, with a 5‐year RFS of 79.0%. T stage and predominant subtype were independent risk factors for RFS. Patients with T1c or solid/micropapillary‐predominant tumors were stratified into a high‐risk group (n = 483) using the nomogram. A significant difference in 5‐year RFS was observed between the high‐ and low‐risk groups (73.6% vs. 84.3%, p < 0.001). Among high‐risk patients, sixty‐seven (13.8%) received ACT; however, there was no improvement in 5‐year RFS compared to observation alone (69.1% vs. 75.0%, p = 0.655). Testing rates for EGFR mutation and ALK fusion among high‐risk patients were only 52.4% and 43.9%, respectively, while mutation rates reached up to 55.7% and 9.4%, respectively. These molecular alterations exhibited numerically worse 5‐year RFS compared to wild‐type (EGFR mutation, 70.6% vs. 87.8%, p = 0.108; ALK fusion, 66.3% vs. 73.6%, p = 0.404), though not significant.ConclusionsACT failed to meet the needs of stage IA patients with histological high‐risk features. Further exploration of effective adjuvant target therapies is warranted for this patient subgroup.
Association of intravitreal and topical anti‐inflammatory therapies on short‐term anatomical and functional outcomes following epiretinal membrane surgery
Authors: Sutinen Pinja , Hecht Idan , Karesvuo Minna , Jeon Sohee , Karesvuo Petteri , Tuuminen Raimo 
Published: December 2024

AbstractPurposeHere we examine the association of anti‐inflammatory therapy with anatomical and functional outcomes of epiretinal membrane surgery.MethodsThe study included consecutive patients having gone through epiretinal membrane surgery at Helsinki University Hospital, Finland, between 2017 and 2021. The association of perioperative intravitreal and postoperative topical anti‐inflammatory therapies with surgical outcomes was assessed.ResultsIn total, 214 eyes of 214 patients with a mean age of 71.2 ± 8.2 years were studied. At 1‐month, perioperative intravitreal use of triamcinolone acetonide (n = 27) was associated with a significant proportional and absolute improvement in foveal thickness (−15.9 ± 18.4% vs. −4.2 ± 25.6%, p = 0.003 and −86.2 ± 109.6 μm vs. −33.7 ± 94.3 μm, p = 0.004), and central subfield macular thickness (−14.7 ± 16.5% vs. −6.3 ± 16.9%, p = 0.009 and −80.6 ± 102.8 μm vs. −36.1 ± 75.9 μm, p = 0.004) when compared to those without triamcinolone acetonide. Furthermore, best‐corrected visual acuity (BCVA) gain showed a non‐significant yet corresponding trend favouring intraoperative intravitreal use of triamcinolone acetonide (0.21 ± 0.27 vs. 0.09 ± 0.28 LogMAR units, p = 0.062). Postoperative use of topical non‐steroidal anti‐inflammatory drugs (NSAIDs) (n = 36) as adjunct therapy showed no significant advantage in anatomical outcomes or BCVA gain when compared to those without NSAIDs (all p > 0.05). Triamcinolone acetonide remained significant for proportional and absolute improvement in foveal thickness (p = 0.019 and p = 0.006) and in central subfield macular thickness (p = 0.013 and p = 0.006) when controlled for confounding factors patient age and gender and topical NSAID use.ConclusionsIntraoperative intravitreal use of triamcinolone acetonide improved short‐term anatomical outcomes in patients who underwent epiretinal membrane surgery.
Lycorine Suppresses Non‐Small‐Cell Lung Cancer Progression Through Activating STING Pathway and Stimulating an Antitumor Immune Response
Authors: Jiang Ze‐Bo , Xu Cong , Xu Pan , Huang Dong‐Hui , Kang Li‐Ping 
Published: December 2024

ABSTRACTNon‐small‐cell lung cancer (NSCLC) stands as a primary contributor to cancer‐related deaths worldwide. It has been demonstrated that Lycorine (LYD), a naturally occurring active sesquiterpene present in Chinese medicinal plants, exhibits anti‐cancer properties across various cancer cell lines. However, the underlying mechanisms of LYD‐induced anti‐tumor in NSCLC are not fully known. This study demonstrated that LYD significantly reduced the proliferation of NSCLC and induced apoptosis by increasing intracellular ROS levels. The inhibition of ROS using N‐acetylcysteine (NAC) eliminated the apoptosis effects of LYD, resulting in increased cell viability. Additionally, LYD treatment significantly activated the STING pathway in NSCLC and induced the expression of CXCL10, CXCL9 and CCL5 in NSCLC cells. Mechanistically, LYD was found to significantly reduce the protein levels of P70S6K and S6K, which are key proteins involved in cell growth and survival. Notably, in vivo experiments demonstrated that LYD significantly inhibited the growth of H358 xenograft and LLC1 tumor, exhibiting anti‐tumor activity by elevating CD8+ T cells in the NSCLC mouse model. Our findings suggest that LYD possesses potent anti‐cancer properties in NSCLC by inducing apoptosis through ROS generation and modulating the STING pathway and key chemokines. Furthermore, LYD also exerts its antitumor effects by inhibiting crucial proteins involved in cell growth. Overall, LYD shows promise as a potential therapeutic agent for NSCLC treatment.
Family Experience of Detention for Migratory Reasons: Findings From a Qualitative Systematic Review
Authors: Gervais Christine , Souza Sophie Lampron‐de , Pariseau‐Legault Pierre , Chammas Grace , Côté Isabel , Cliche Karolane 
Published: December 2024

ABSTRACTIn response to growing international migration, several states have adopted controversial measures, including detaining migrants, which have detrimental impacts on migrants' physical, mental and social health. Although family is often at the heart of migratory decisions, few studies have used a family lens to examine this phenomenon. This paper reports on the findings of a qualitative systematic review that aims to describe the experience of migrant families dealing with detention. Articles were searched in relevant databases, and the quality of studies was assessed independently by two reviewers using the JBI Critical Appraisal Checklists. Twenty‐two out of 897 articles met the inclusion criteria and were subsequently included. Three themes emerged from the thematic synthesis that capture the experience of migrant families affected by detention: (1) alterations of the family structure, (2) disruptions in instrumental and emotional functioning and (3) weakening of the family identity. Results robustly evidenced the detrimental effects of detention on families and the urge to stop this practice. Limitations included the difficulty of distinguishing between the experience of detention and deportation in some studies, as well as limited information about the long‐term effect of detention on family health and integration in the host society.
Comparative effectiveness of Roux‐en‐Y gastric bypass and sleeve gastrectomy in achieving diabetes remission in patients with diabetes‐related vascular diseases: A multicentred study
Authors: Ghusn Wissam , Ma Pearl , Ikemiya Kayla , Salame Marita , Hage Karl , Mosleh Kamal Abi , Storm Andrew C. , Kendrick Michael , Abu Dayyeh Barham K. , Higa Kelvin , Ghanem Omar M. 
Published: December 2024

SummaryMetabolic and bariatric surgeries (MBS), including Roux‐en‐Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG), have proven effective in promoting long‐term diabetes remission among patients with type‐2 diabetes (T2D). In this multicentre retrospective cohort study, we investigated the effectiveness of RYGB and SG in achieving diabetes remission, specifically among patients with T2D and vascular complications, while accounting for similar baseline diabetes severity. Although various scores predict diabetes remission after bariatric surgery, they do not consider diabetes‐related vascular complications, which can influence outcomes even in patients with similar baseline T2D severity. We collected preoperative data on microvascular (retinopathy, nephropathy, neuropathy) and macrovascular comorbidities (coronary artery disease, cerebrovascular accidents, peripheral artery disease) to compare the efficacy of RYGB and SG. Among 961 patients analysed, those with vascular complications showed higher remission rates with RYGB (OR: 1.97) compared to SG, despite similar baseline diabetes severity. Notably, RYGB patients with microvascular complications had a significant advantage in achieving T2D remission (OR: 2.95). However, no significant differences in remission were observed in patients with macrovascular complications. These findings suggest that RYGB may be more effective than SG in specific patient populations, particularly those with microvascular complications, emphasizing the need for personalized treatment strategies.
Contact heat evoked potentials reveal distinct patterns of spinal cord impairment in degenerative cervical myelopathy beyond MRI lesions
Authors: Scheuren Paulina Simonne , Hupp Markus , Pfender Nikolai , Seif Maryam , Zipser Carl Moritz , Wanivenhaus Florian , Spirig José Miguel , Betz Michael , Freund Patrick , Schubert Martin , Farshad Mazda , Curt Armin , Hubli Michèle , Rosner Jan 
Published: December 2024

AbstractBackgroundMagnetic resonance imaging may suggest spinal cord compression and structural lesions in degenerative cervical myelopathy (DCM) but cannot reveal functional impairments in spinal pathways. We aimed to assess the value of contact heat evoked potentials (CHEPs) in addition to MRI and hypothesized that abnormal CHEPs may be evident in DCM independent of MR‐lesions and are related to dynamic mechanical cord stress.MethodsIndividuals with DCM underwent neurologic examination including segmental sensory (pinprick, light touch) and motor testing. The presence or absence of hyperintense signal on T2‐weighted MRI (T2‐positive/negative) was assessed. Phase‐contrast MRI was used to assess spinal cord motion as an indicator of dynamic mechanical stress. Dermatomal somatosensory evoked potentials and CHEPs were recorded after stimulation of dermatomes C6, C8, and T4 (CHEPs only) to assess spinal cord integrity.ResultsOf 138 individuals included in this study (age 56 ± 13 years), 35% (N = 48) presented with T2‐positive and 65% (N = 90) presented with T2‐negative DCM. Abnormal CHEPs were present in T2‐positive DCM (C6:41%; C8:32%; T4:24%) and T2‐negative DCM (C6:35%; C8:54%; T4:26%). Multisegmental CHEP abnormalities at C6 and C8 were related to increased spinal cord motion (p = 0.030; ϵ2 = 0.072), and reduced upper extremity pinprick (p = 0.046; ϵ2 = 0.063) and motor scores (p = 0.005; ϵ2 = 0.108).ConclusionsCHEPs revealed distinct patterns of spinal cord impairment independent of structural T2‐positive lesions, which were associated with measures of cord motion. CHEPs thus provide valuable complementary diagnostic insights into spinal cord integrity beyond MRI. This is especially important in incipient myelopathy to inform early diagnosis and timely interventions before the development of definite cord lesions.