bluuebunny/crossref_metadata_2025_split huggingface dataset:
bb0689
contributes to the virulence of
Borrelia burgdorferi
in a murine model of Lyme disease
Authors: Waldron Connor , George Sierra , Thompson Christina , Liao Yu Hsien , Ouyang Zhiming 
Published: December 2024

ABSTRACT

Borrelia burgdorferi
, the Lyme disease pathogen, continuously changes its gene expression profile in order to adapt to ticks and mammalian hosts. The alternative sigma factor RpoS plays a central role in borrelial host adaptation. Global transcriptome analyses suggested that more than 100 genes might be regulated by RpoS, but the main part of the regulon remains unexplored. Here, we showed that the expression of
bb0689
, a gene encoding an outer surface lipoprotein with unknown function, was activated by RpoS. By analyzing gene expression using luciferase reporter assays and quantitative reverse transcription PCR, we found that expression of
bb0689
was induced by an elevated temperature, a reduced pH, and increased cell density during
in vitro
cultivation. The transcriptional start site and a functional promoter for gene expression were identified in the 5′ regulatory region of
bb0689
. The promoter was responsive to environmental stimuli and influenced by RpoS. We also showed that
bb0689
expression was expressed in
B. burgdorferi
during animal infection, suggesting the importance of this gene for infection. We further generated a
bb0689
mutant and found that the infectivity of the mutant was severely attenuated in a murine infection model. Although
bb0689
-deficient spirochetes exhibited no defect during
in vitro
growth, they were defective in resistance to osmotic stress.
Cis
-complementation of the mutant with a wild-type copy of
bb0689
fully rescued all phenotypes. Collectively, these results demonstrate that the RpoS-regulated gene
bb0689
is a key contributor to the optimal infection of
B. burgdorferi
in animals.
Rickettsia
disrupts and reduces endothelial tight junction protein zonula occludens-1 in association with inflammasome activation
Authors: Velatooru Loka Reddy , Arroyave Esteban , Rippee-Brooks Meagan D. , Burch Megan , Yang Ethan , Zhu Bing , Walker David H. , Zhang Yang , Fang Rong 
Published: December 2024

ABSTRACT

Rickettsia
spp. cause life-threatening diseases in humans. The fundamental pathophysiological changes in fatal rickettsial diseases are disrupted endothelial barrier and increased microvascular permeability. However, it remains largely unclear how rickettsiae induce microvascular endothelial injury. In the present study, we demonstrated that
Rickettsia conorii
infection disrupts the continuous immunofluorescence expression of the interendothelial tight junction protein, zonula occludens-1 (ZO-1), in infected monolayers of microvascular endothelial cells (MVECs), accompanied by significantly diminished total expression levels of ZO-1. Interestingly,
R. conorii
activated inflammasome in MVECs, as evidenced by cleaved caspase-1 and IL-1β in the cell lysates in association with significantly elevated expression levels of nucleotide binding and oligomerization domain, leucine-rich repeat, and pyrin containing protein 3 (NLRP3). Furthermore, selective inhibition of NLRP3 by MCC950 significantly suppressed the activation and cleavage of caspase-1 induced by
R. conorii
in endothelial cells, which further prevented the disruption of interendothelial junctions and reduction of ZO-1 expression. Of note, pharmaceutical inhibition of NLRP3 mitigated the disrupted endothelial integrity caused by
R. conorii
, measured by fluorescein isothiocyanate-dextran passage in a Transwell assay, independent of bacterial growth and cellular cytotoxicity. Taken together, our results suggest that
R. conorii
affected microvascular endothelial junction integrity likely via diminishing and interrupting the junctional protein ZO-1 in association with activating NLRP3 inflammasome. These data not only highlight the potential of ZO-1 as a biomarker for
Rickettsia
-induced microvascular injury but also provide insight into targeting NLRP3 inflammasome/ZO-1 signaling as a potentially adjunctive therapeutic approach for severe rickettsioses.
Excellent capability for molecular detection of
Aedes
-borne dengue, Zika, and chikungunya viruses but with a need for increased capacity for yellow fever and Japanese encephalitis viruses: an external quality assessment in 36 European laboratories
Authors: Presser Lance D. , Baronti Cécile , Moegling Ramona , Pezzi Laura , Lustig Yaniv , Gossner Céline M. , Reusken Chantal B. E. M. , Charrel Rémi N. ,   on behalf of EVD-LabNet
Published: December 2024

ABSTRACT

Mosquito-borne viruses represent a large global health burden. With geographic expansion of competent vectors for chikungunya virus (CHIKV), dengue virus (DENV), and Zika virus (ZIKV) in Europe, it is anticipated that the number of autochthonous cases of these tropical viruses in Europe will increase. Therefore, regular assessment of diagnostic capabilities in Europe is important. Our aim was to evaluate the mosquito-borne virus molecular detection capability of expert European laboratories by conducting an external quality assessment in October 2023. Molecular panels included 12 plasma samples: one alphavirus (CHIKV), four orthoflaviviruses (ZIKV, yellow fever virus [YFV], DENV, and Japanese encephalitis virus [JEV]), and two negative control samples. Mosquito-borne virus detection was assessed among 36 laboratories in 24 European countries. Adequate capabilities were lacking for YFV and JEV. Many laboratories relied on a mix of laboratory-developed tests (some of which were pan-orthoflavivirus or pan-alphavirus in combination with sequencing) and commercial assays. 47.2% of laboratories characterized all external quality assessment (EQA) samples correctly. Correct result rates were 100% for CHIKV and ZIKV and >99% for DENV, but laboratories lacked capacity, specificity, and sensitivity for JEV and YFV. Three of the viruses in this panel emerged and transiently circulated in Europe: CHIKV, ZIKV, and DENV. Molecular detection was excellent for those viruses, but <50% is accurate for the remainder of the panel. With the possibility or continuation of imported cases and a growing global concern about climate change and vector expansion, progress toward rapid, accurate mosquito-borne virus diagnostics in Europe is recommended, as well as regular EQAs to monitor it.

IMPORTANCE

The external quality assessment (EQA) focused on
Aedes
-borne viruses: chikungunya virus (CHIKV), dengue virus (DENV), Zika virus (ZIKV), and yellow fever virus (YFV). Japanese encephalitis virus, an orthoflavivirus that is spread by mosquito species belonging to the genus
Culex
, was included in the quality assessment as well. CHIKV, DENV, and ZIKV have proven potential for transient and limited circulation in Europe upon introduction of viremic travelers returning to
Aedes albopictus
-endemic regions. Results of this EQA were excellent for those viruses, but <50% is accurate for the remainder of the panel (YFV and Japanese encephalitis virus). Considering imported cases and the threat of climate change and competent vector expansion, progress toward rapid, accurate mosquito-borne virus diagnostics in Europe is recommended.
Inhibition and evasion of neutrophil microbicidal responses by
Legionella longbeachae
Authors: Hanford Hannah E. , Price Christopher T. D. , Uriarte Silvia , Abu Kwaik Yousef 
Published: December 2024

ABSTRACT

Legionella
species evade degradation and proliferate within alveolar macrophages as an essential step for the manifestation of disease. However, most intracellular bacterial pathogens are restricted in neutrophils, which are the first line of innate immune defense against invading pathogens. Bacterial degradation within neutrophils is mediated by the fusion of microbicidal granules to pathogen-containing phagosomes and the generation of reactive oxygen species (ROS) by the phagocyte NADPH oxidase complex. Here, we show that human neutrophils fail to trigger microbicidal processes and, consequently, fail to restrict
L. longbeachae
. In addition, neutrophils infected with
L. longbeachae
fail to undergo a robust pro-inflammatory response, such as degranulation and IL-8 production. Here, we identify three strategies employed by
L. longbeachae
for evading restriction by neutrophils and inhibiting the neutrophil microbicidal response to other bacteria co-inhabiting in the same cell. First,
L. longbeachae
excludes the cytosolic and membrane-bound subunits of the phagocyte NADPH oxidase complex from its phagosomal membrane independent of the type 4 secretion system (T4SS). Consequently, infected neutrophils fail to generate robust ROS in response to
L. longbeachae
. Second,
L. longbeachae
impedes the fusion of azurophilic granules to its phagosome and the phagosomes of bacteria co-inhabiting the same cell through T4SS-independent mechanisms. Third,
L. longbeachae
protects phagosomes of co-inhabiting bacteria from degradation by ROS through a
trans
-acting T4SS-dependent mechanism. Collectively, we conclude that
L. longbeachae
evades restriction by human neutrophils
via
T4SS-independent mechanisms and utilizes
trans
-acting T4SS-dependent mechanisms for inhibition of neutrophil ROS generation throughout the cell cytosol.

IMPORTANCE

Legionella longbeachae
is commonly found in soil environments where it interacts with a wide variety of protist hosts and microbial competitors. Upon transmission to humans
, L. longbeachae
invades and replicates within alveolar macrophages, leading to the manifestation of pneumonia. In addition to alveolar macrophages, neutrophils are abundant immune cells acting as the first line of defense against invading pathogens. While most intracellular bacterial species are killed and degraded by neutrophils, we show that
L. longbeachae
evades degradation. The pathogen impairs the major neutrophils’ microbicidal processes, including the fusion of microbicidal granules to the pathogen-containing vacuole. By inhibiting of assembly of the phagocyte NADPH oxidase complex, the pathogen blocks neutrophils from generating microbicide reactive oxygen species. Overall,
L. longbeachae
employs unique virulence strategies to evade the major microbicidal processes of neutrophils.
Draft genome sequences of three xerophilic
Aspergillus
section
Restricti
species isolated from house dust in Japan
Authors: Hagiuda Ryo , Hirose Dai 
Published: December 2024

ABSTRACT

We present the nuclear and complete mitochondrial genome sequences of
Aspergillus clavatophorus
NBRC 116038,
Aspergillus magnivesiculatus
NBRC 116037, and
Aspergillus verrucosus
NBRC 115547
T
, all isolated from house dust in Japan. These sequence data are crucial for elucidating the evolutionary characteristics of section
Restricti
, a unique taxon comprising exclusively xerophilic species.
Clade-specific long-read sequencing increases the accuracy and specificity of the
gyrB
phylogenetic marker gene
Authors: Nichols Robert G. , Davenport Emily R. 
Published: December 2024

ABSTRACT

Phylogenetic marker gene sequencing is often used as a quick and cost-effective way of evaluating microbial composition within a community. While 16S rRNA gene sequencing (16S) is commonly used for bacteria and archaea, other marker genes are preferable in certain situations, such as when 16S sequences cannot distinguish between taxa within a group. Another situation is when researchers want to study cospeciation of host taxa that diverged much more recently than the slowly evolving 16S rRNA gene. For example, the bacterial gyrase subunit B (
gyrB
) gene has been used to investigate cospeciation between the microbiome and various hominid species. However, to date, only primers that generate short-read Illumina MiSeq-length amplicons exist to investigate
gyrB
of the Bacteroidaceae, Bifidobacteriaceae, and Lachnospiraceae families. Here, we update this methodology by creating
gyrB
primers for the Bacteroidaceae, Bifidobacteriaceae, and Lachnospiraceae families for long-read PacBio sequencing and characterize them against established short-read
gyrB
primer sets. We demonstrate both bioinformatically and analytically that these longer amplicons offer more sequence space for greater taxonomic resolution, lower off-target amplification rates, and lower error rates with PacBio CCS sequencing versus established short-read sequencing. The availability of these long-read
gyrB
primers will prove to be integral to the continued analysis of cospeciation between bacterial members of the gut microbiome and recently diverging host species.

IMPORTANCE

Previous studies have shown that the marker gene gyrase subunit B (
gyrB
) can be used to study codiversification between the gut microbiome and hominids. However, only primers for short-read sequencing have been developed which have limited resolution for subspecies assignment. In the present study, we create new
gyrB
primer sets for long-read sequencing approaches and compare them to the existing short-read
gyrB
primers. We show that using longer reads leads to better taxonomic resolution, lower off-target amplification, and lower error rates, which are vital for accurate estimates of codiversification.
Impact of rapid antibiotic susceptibility testing for Gram-negative bacteremia varies by pathogen type and resistance: a secondary analysis of the RAPIDS GN trial
Authors: Banerjee Ritu , Giri Abhigya , Komarow Lauren , Souli Maria , Doernberg Sarah B. , Patel Robin ,   on behalf of the Antibacterial Resistance Leadership Group
Published: December 2024

ABSTRACT

In this secondary analysis of 386 subjects with Gram-negative bacteremia enrolled in the RAPIDS GN trial, rapid antibiotic susceptibility testing had a greater benefit on the management of bacteremia caused by antibiotic-resistant compared to antibiotic-susceptible isolates, especially for
Escherichia coli, Klebsiella
species
,
and
Proteus
species.

IMPORTANCE
Rapid blood culture diagnostics are costly, and their use has not demonstrated clear clinical benefit for patients with Gram-negative sepsis, possibly because prior trials did not enroll sufficient numbers of patients with antibiotic-resistant infections. This analysis of patients with sepsis previously enrolled in a randomized controlled clinical trial demonstrates that rapid susceptibility testing of bacteria from blood cultures had the greatest impact for patients with antibiotic-resistant infections. Specifically, after rapid testing results were reported, patients infected with resistant bacteria received appropriate antibiotic therapy more quickly than patients with susceptible bacteria. These findings highlight the need to evaluate blood culture diagnostics in areas with high antibiotic resistance where these diagnostics are likely to have the greatest impact.
Males have higher psychological readiness to return to sports than females after anterior cruciate ligament reconstruction: a systematic review and meta-analysis
Authors: Obradovic Anja , Manojlovic Marko , Rajcic Aleksandra , Jankovic Stefan , Andric Nikola , Ralic Vuk , Zlicic Tamara , Aleksic Branko , Ninkovic Srdjan , Veraksa Aleksander , Drid Patrik 
Published: December 2024

ObjectivesTo examine sex differences in psychological readiness to return to sport following anterior cruciate ligament (ACL) reconstruction as well as to determine whether males and females separately fulfilled cut-off values (≥65) of psychological readiness necessary to return to sport.Information sourcesWeb of Science, Scopus and PubMed were comprehensively searched from inception to January 2024 to identify relevant studies.Eligibility criteriaObservational investigations that compared males and females with a history of ACL reconstruction concerning psychological readiness to return to sport.Risk of biasStudies were rated using the Methodological Index for Non-Randomised Studies.Included studiesOnly 11 reports fulfilled the eligibility criteria and were included in the quantitative analysis. A total of 2618 participants were subjected to the primary ACL reconstruction, out of 1631 males and 987 females. Psychological readiness to return to sport was evaluated approximately 9±2.9 months following surgery.Synthesis of resultsThe main findings demonstrated that males had slightly higher psychological readiness to return to the sport than females (standardised mean difference 0.33; 95% CI 0.14 to 0.52; p=0.0007; I2=77%) after ACL surgery. In addition, the mean psychological readiness to return to the sport of males was 70.1±8.8 points and of females 65.1±8.8 points, indicating that both sexes exceeded recommendations necessary to return to sport.ConclusionMales had slightly higher psychological readiness to return to sport than females approximately 9±2.9 months after ACL reconstruction and both sexes exceeded the highlighted recommendations necessary to return to sport.PROSPERO registration numberCRD42024497769: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024497769.
Association between NT-proBNP levels and risk of atrial fibrillation: a systematic review and meta-analysis of cohort studies
Authors: Wang Wanyue , Zhou Tao , Li Jinyue , Yuan Chenxi , Li Chenyang , Chen Shufeng , Shen Chong , Gu Dongfeng , Lu Xiangfeng , Liu Fangchao 
Published: December 2024

Background and aims
N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a well-established biomarker in clinical practice, particularly for heart failure, but its role in predicting atrial fibrillation (AF) risk is not fully understood. This meta-analysis aimed to evaluate the association between NT-proBNP levels and AF incidence, and to explore the potential of NT-proBNP in enhancing AF risk prediction models.

Methods
We systematically searched databases (PubMed, Embase, Cochrane Library, Web of Science and Scopus) up to August 2024 for prospective studies that reported associations between baseline NT-proBNP levels and incident AF. HRs or relative risks (RRs) with 95% CIs were pooled using random-effects models.

Results

This analysis included 136 089 participants from 16 cohorts, with 8017 incident AF cases. Elevated NT-proBNP levels were associated with a higher risk of developing AF (top vs bottom quartile, RR=3.84, 95% CI 3.03 to 4.87; per SD increment, RR=1.70, 95% CI 1.54 to 1.88). A significant non-linear dose-response relationship was observed (P
non-linearity
<0.05), and stronger associations were noted in older populations and when serum samples were used. Adding NT-proBNP to traditional AF risk models improved predictive accuracy, suggesting its value in AF risk stratification.

Conclusions
NT-proBNP levels are strongly associated with an increased risk of AF, particularly in older adults. Incorporating NT-proBNP into risk prediction models may enhance early identification of individuals at risk of AF, with potential implications for population-based screening.

PROSPERO registration number
CRD42024538714.
Rationale and design of the randomised, controlled Percutaneous coronary intervention using Assisted Robotic TechnologY (PARTY) trial
Authors: Leung James , Xu James , French John K , Kachwalla Hashim , Kaddapu Krishna , Badie Tamer , Mussap Christian , Rajaratnam Rohan , Leung Dominic Y , Lo Sidney T , Juergens Craig 
Published: December 2024

IntroductionPercutaneous coronary intervention (PCI) is performed by interventional cardiologists who, over their career, are exposed to substantial X-ray radiation and also face potential musculoskeletal injuries from the prolonged wearing of heavy protective equipment. Patients are also at risk from radiation exposure. Robotic-assisted PCI (R-PCI) allows millimetre control of the coronary guide-catheter, guidewires and intracoronary devices via three joysticks and touchscreens located within in a shielded ‘cockpit’, away from radiation. Initial studies have demonstrated efficacy and safety of R-PCI with significant radiation reductions. However, these studies are non-randomised, registry based or observational data with short clinical follow-up. We aim to perform the first randomised controlled trial investigating R-PCI compared with manual PCI (M-PCI) with longer clinical follow-up.Methods and analysisThe Percutaneous coronary intervention using Assisted Robotic TechnologY (PARTY) trial is a single-centre, prospective, randomised, open-label clinical trial comparing R-PCI to M-PCI. Eligible patients between 18 and 85 years undergoing coronary angiography, and are subsequently deemed to require PCI, will be screened. A key exclusion criterion is if the operator determines that the participant or coronary anatomy is unsuitable for R-PCI. Patients will be randomised to R-PCI or M-PCI in a 1:1 fashion. The primary outcome is radiation exposure to the patient, as measured by personal radiation dosimeters. Other procedural, safety and efficacy outcomes will be compared. Patients will be followed up until hospital discharge (or 72 hours, whichever occurs first), and then by telephone at 30 and 365 days.Trial registration numberACTRN12623000480684.
Effect of displaced abomasum on milk production, reproductive performance, and culling of Holstein dairy cattle in Iran
Authors: Asgari Zeinab , Sadeghi-Sefidmazgi Ali , Pakdel Abbas , Shahinfar Saleh 
Published: December 2024

Displaced abomasum (DA) is an important digestive condition that adversely affects the economic performance and the productive lifespan of a dairy cow. Due to increasing DA incidence in recent years, the present research was performed to estimate the potential effects of DA on the performance of Iranian Holstein. Production data were analyzed using a linear mixed model. Cox proportional hazard regression was used to assess the associations of DA occurrence with the time from calving to first service, pregnancy (in 120 and 220 DIM, respectively) and culling. The least-square means showed that DA was significantly ( P < 0.0001) associated with reduced milk, fat, and protein yields, especially during peak milk production. Results of survival analyzes showed that DA could be associated with reduced probability pregnancy in the first service at 120 DIM (hazard ratio = 0.57; 95% CI = 0.51–0.64), and at 220 DIM (hazard ratio = 0.81; 95% CI = 0.76–0.86) and with an increased hazard of culling in the same lactation (hazard ratio = 3.85; 95% CI = 3.13–4.74). Considering negative effects of DA in dairy cows, it can be concluded, quantitative knowledge of the consequences of DA may convince dairy farmers to apply preventive strategies to reduce the incidence of DA in the herd.
Cytokine Release Syndrome After CAR T‐Cell Therapy in a 35‐Year‐Old Patient With Pneumocystis jiroveci Pneumonia and Cytomegalovirus Viremia
Authors: Helms Kristina A. 
Published: December 2024

Background: The risk of cytokine release syndrome (CRS) in patients with infections prior to chimeric antigen receptor T‐cell (CAR T‐cell) therapy represents an important and underreported event. Patients with active infections needing prompt CAR T‐cell therapy to treat aggressive hematologic malignancies remain a clinical challenge.Case Report: This case describes the clinical course of a 35‐year‐old male patient with relapsed/refractory T‐cell/histiocyte‐rich large B‐cell lymphoma who received axicabtagene ciloleucel. The patient developed ASTCT Grade II CRS on day +5, necessitating hospital admission and intravenous antibiotics, dexamethasone and tocilizumab. The patient was found to have a Pneumocystis jirovecii pneumonia (PJP) infection 3 days prior to CAR T‐cell infusion and cytomegalovirus (CMV) viremia 3 days after CAR T‐cell infusion. He received TMP‐SMX for 21 days to treat PJP and valganciclovir to treat CMV viremia. PET/CT on day +26 demonstrated near resolution of pulmonary nodules and significant partial response of disease according to Deauville criteria.Conclusion: This case highlights the risk of CRS in immunocompromised patients with infections, and presents a unique case of CRS associated with PJP and CMV infections. Although the patient’s clinical course was fraught with complications, he achieved a significant partial response to CAR T‐cell therapy with the help of a multidisciplinary medical team.