bluuebunny/crossref_metadata_2025_split huggingface dataset:
TusA influences Fe-S cluster assembly and iron homeostasis in
E. coli
by reducing the translation efficiency of Fur
Authors: Olivieri Paolo , Zupok Arkadiuz , Yildiz Tugba , Oltmanns Jonathan , Lehmann Angelika , Sokolowska Ewelina , Skirycz Aleksandra , Schünemann Volker , Leimkühler Silke 
Published: June 2024

ABSTRACT

All sulfur transfer pathways have generally a
l
-cysteine desulfurase as an initial sulfur-mobilizing enzyme in common, which serves as a sulfur donor for the biosynthesis of numerous sulfur-containing biomolecules in the cell. In
Escherichia coli
, the housekeeping
l
-cysteine desulfurase IscS has several interaction partners, which bind at different sites of the protein. So far, the interaction sites of IscU, Fdx, CyaY, and IscX involved in iron-sulfur (Fe-S) cluster assembly have been mapped, in addition to TusA, which is required for molybdenum cofactor biosynthesis and mnm
5
s
2
U34 tRNA modifications, and ThiI, which is involved in thiamine biosynthesis and s
4
U8 tRNA modifications. Previous studies predicted that the sulfur acceptor proteins bind to IscS one at a time.
E. coli
TusA has, however, been suggested to be involved in Fe-S cluster assembly, as fewer Fe-S clusters were detected in a

∆

tusA
mutant. The basis for this reduction in Fe-S cluster content is unknown. In this work, we investigated the role of TusA in iron-sulfur cluster assembly and iron homeostasis. We show that the absence of TusA reduces the translation of
fur
, thereby leading to pleiotropic cellular effects, which we dissect in detail in this study.

IMPORTANCE

Iron-sulfur clusters are evolutionarily ancient prosthetic groups. The ferric uptake regulator plays a major role in controlling the expression of iron homeostasis genes in bacteria. We show that a
∆tusA
mutant is impaired in the assembly of Fe-S clusters and accumulates iron. TusA, therefore, reduces
fur
mRNA translation leading to pleiotropic cellular effects.
Unraveling the role of toxin-antitoxin systems in
Burkholderia pseudomallei
: exploring bacterial pathogenesis and interactions within the HigBA families
Authors: Chapartegui-González Itziar , Stockton Jacob L. , Bowser Sarah , Badten Alexander J. , Torres Alfredo G. 
Published: June 2024

ABSTRACT

Burkholderia pseudomallei
(
Bpm
) is a Gram-negative intracellular pathogen that causes melioidosis in humans, a neglected, underreported, and lethal disease that can reach a fatal outcome in over 50% of the cases. It can produce both acute and chronic infections, the latter being particularly challenging to eliminate because of the intracellular life cycle of the bacteria and its ability to generate a “persister” dormant state. The molecular mechanism that allows the switch between growing and persister phenotypes is not well understood but it is hypothesized to be due at least in part to the participation of toxin-antitoxin (TA) systems. We have previously studied the link between one of those systems (defined as HigBA) with specific expression patterns associated with levofloxacin antibiotic exposure. Through
in silico
methods, we predicted the presence of another three pairs of genes encoding for additional putative HigBA systems. Therefore, our main goal was to establish which mechanisms are conserved as well as which pathways are specific among different
Bpm
TA systems from the same family. We hypothesize that the high prevalence, and sometimes even redundancy of these systems in the
Bpm
chromosomes indicates that they can interact with each other and not function as only individual systems, as it was traditionally thought, and might be playing an undefined role in
Bpm
lifecycle. Here, we show that both the toxin and the antitoxin of the different systems contribute to bacterial survival and that toxins from the same family can have a cumulative effect under environmental stressful conditions.

IMPORTANCE

Toxin-antitoxin (TA) systems play a significant role in bacterial persistence, a phenomenon where bacterial cells enter a dormant or slow-growing state to survive adverse conditions such as nutrient deprivation, antibiotic exposure, or host immune responses. By studying TA systems in
Burkholderia pseudomallei
, we can gain insights into how this pathogen survives and persists in the host environment, contributing to its virulence and ability to cause melioidosis chronic infections.
Vibrio cholerae
O1 experiences mild bottlenecks through the gastrointestinal tract in some but not all cholera patients
Authors: Lypaczewski Patrick , Chac Denise , Dunmire Chelsea N. , Tandoc Kristine M. , Chowdhury Fahima , Khan Ashraful I. , Bhuiyan Taufiqur R. , Harris Jason B. , LaRocque Regina C. , Calderwood Stephen B. , Ryan Edward T. , Qadri Firdausi , Shapiro B. Jesse , Weil Ana A. 
Published: June 2024

ABSTRACT

Vibrio cholerae
O1 causes the diarrheal disease cholera, and the small intestine is the site of active infection. During cholera, cholera toxin is secreted from
V. cholerae
and induces a massive fluid influx into the small intestine, which causes vomiting and diarrhea. Typically,
V. cholerae
genomes are sequenced from bacteria passed in stool, but rarely from vomit, a fluid that may more closely represents the site of active infection. We hypothesized that
V. cholerae
O1 population bottlenecks along the gastrointestinal tract would result in reduced genetic variation in stool compared to vomit. To test this, we sequenced
V. cholerae
genomes from 10 cholera patients with paired vomit and stool samples. Genetic diversity was low in both vomit and stool, consistent with a single infecting population rather than coinfection with divergent
V. cholerae
O1 lineages. The amount of single-nucleotide variation decreased from vomit to stool in four patients, increased in two, and remained unchanged in four. The variation in gene presence/absence decreased between vomit and stool in eight patients and increased in two. Pangenome analysis of assembled short-read sequencing demonstrated that the toxin-coregulated pilus operon more frequently contained deletions in genomes from vomit compared to stool. However, these deletions were not detected by PCR or long-read sequencing, indicating that interpreting gene presence or absence patterns from short-read data alone may be incomplete. Overall, we found that
V. cholerae
O1 isolated from stool is genetically similar to
V. cholerae
recovered from the upper intestinal tract.

IMPORTANCE

Vibrio cholerae
O1, the bacterium that causes cholera, is ingested in contaminated food or water and then colonizes the upper small intestine and is excreted in stool. Shed
V. cholerae
genomes from stool are usually studied, but
V. cholerae
isolated from vomit may be more representative of where
V. cholerae
colonizes in the upper intestinal epithelium.
V. cholerae
may experience bottlenecks, or large reductions in bacterial population sizes and genetic diversity, as it passes through the gut. Passage through the gut may select for distinct
V. cholerae
mutants that are adapted for survival and gut colonization. We did not find strong evidence for such adaptive mutations, and instead observed that passage through the gut results in modest reductions in
V. cholerae
genetic diversity, and only in some patients. These results fill a gap in our understanding of the
V. cholerae
life cycle, transmission, and evolution.
Lactobacilli decrease the susceptibility of
Salmonella
Typhimurium to azithromycin
Authors: Blais Lya , Couture Laurence , Laforest-Lapointe Isabelle , Côté Jean-Philippe 
Published: June 2024

ABSTRACT

Bacteria are involved in numerous interactions during infection and among host-associated microbial populations.
Salmonella enterica
serovar Typhimurium is a foodborne pathogen of great importance as well as a model organism to study interactions within a microbial community. In this study, we found that
S
. Typhimurium becomes tolerant to azithromycin when co-cultured with lactobacilli strains. Similarly, acidified media, from cell-free supernatant of lactobacilli cultures for instance, also induced the tolerance of
S
. Typhimurium to azithromycin. The addition of membrane disruptors restored the normal sensitivity to azithromycin in acidified media, but not when lactobacilli were present. These results suggested that the acidification of the media led to modification in envelope homeostasis, but that a different mechanism promoted the tolerance to azithromycin in the presence of lactobacilli strains. To further understand how lactobacilli strains modify the sensitivity of
S
. Typhimurium to azithromycin, a high-throughput assay was performed using the single-gene deletion collection of the
S
. Typhimurium (1) in co-culture with
Lacticaseibacillus rhamnosus
and (2) in sterile acidic conditions (pH 5.5 media only). As expected, both screens identified genes involved in envelope homeostasis and membrane permeability. Our results also suggest that changes in the metabolism of
S
. Typhimurium induce the tolerance observed in the presence of
L. rhamnosus
. Our results thus highlight two different mechanisms by which lactobacilli induce the tolerance of
S
. Typhimurium to azithromycin.

IMPORTANCE

This study provides valuable insights into the intricate interactions between bacteria during infections and within host-associated microbial communities. Specifically, it sheds light on the significant role of lactobacilli in inducing antibiotic tolerance in
Salmonella enterica
serovar Typhimurium, a critical foodborne pathogen and model organism for microbial community studies. The findings not only uncover the mechanisms underlying this antibiotic tolerance but also reveal two distinct pathways through which strains of lactobacilli might influence
Salmonella
’s response to antibiotics. Understanding these mechanisms has the potential to enhance our knowledge of bacterial infections and may have implications for the development of strategies to combat antibiotic resistance in pathogens, such as
Salmonella
. Furthermore, our results underscore the necessity to explore beyond the direct antimicrobial effects of antibiotics, emphasizing the broader microbial community context.
Unveiling hidden sources of dynamic functional connectome through a novel regularized blind source separation approach
Authors: Ran Jialu , Wang Yikai , Guo Ying 
Published: June 2024

Abstract
The investigation of the brain’s functional connectome and its dynamic changes can provide valuable insights into brain organization and its reconfiguration. However, the analysis of dynamic functional connectivity (dFC) using functional magnetic resonance imaging (fMRI) faces major challenges, including the high dimensionality of brain networks, unknown latent sources underlying observed dFC, and the large number of brain connections that increase the risk of spurious findings. In this paper, we propose a new regularized blind source separation (BSS) method called dyna-LOCUS to address these challenges. dyna-LOCUS decomposes observed dFC measures to reveal latent source connectivity traits and their dynamic temporal expression profiles. By utilizing low-rank factorization and novel regularizations, dyna-LOCUS achieves efficient and reliable mapping of connectivity traits underlying the dynamic brain functional connectome, characterizes temporal changes of the connectivity traits that contribute to the reconfiguration in the observed dFC, and generates parsimonious and interpretable results in identifying whole-brain dFC states. We introduce a highly efficient iterative Node-Rotation algorithm that solves the nonconvex optimization problem for learning dyna-LOCUS. Simulation studies demonstrate the advantages of our proposed method. Application of dyna-LOCUS to the Philadelphia Neurodevelopmental Cohort (PNC) study unveils latent connectivity traits and key brain connections and regions driving each of these neural circuits, reveals temporal expression levels and interactions of these connectivity traits, and generates new findings regarding gender differences in the neurodevelopment of an executive function-related connectivity trait.
Perspectives from the frontline: Nurses’ experiences of adolescent engagement in sexual and reproductive health services
Authors: Kelly Jane , Low Maya , Glinski Charné Dee , Laurenzi Christina , Gittings Lesley , Myende Philani , Joska Rachel , Gqaleni-Ntozonke Babalo , Taleni Babalwa , Marikeni Zoliswa , Sidloyi Lulama , Saliwe Bongiwe , Toska Elona 
Published: June 2024

Background: Nurses have a critical role to play in the delivery of sexual and reproductive health (SRH) services to adolescents and young people. Nurses’ interactions with adolescents and young people can shape sexual and reproductive behaviours and outcomes, including willingness to access and engage with healthcare services. However, little research from low- and middle-income contexts has explored nurses’ firsthand perspectives regarding their relationships with adolescents and young people in the context of SRH service provision, especially since the COVID-19 pandemic. Aim: This study explored nurses’ perceptions of working with adolescents and young people as well as how these impressions manifest in one-on-one exchanges between nurses and young patients. Method: Semi-structured interviews were conducted with 20 nurses providing SRH services to adolescents and young people and based at public health facilities in urban, peri-urban and rural areas within a health sub-district of the Eastern Cape province of South Africa. Data were analysed using an inductive thematic approach. Results: While many nurses described the challenges facing adolescents and young people in an empathic way and expressed a desire and willingness to engage with and educate them, some found it ‘difficult to break through’. Nurses linked this difficulty to the shame adolescents and young people feel when discussing SRH concerns, but also to them having ‘attitude’ and ‘not listening’. Findings highlight how while nurses may genuinely care about providing services to their young patients, internal and social biases may impact their motivation and willingness to effectively support adolescents and young people within the context of SRH service provision. To improve patient–provider relations, we suggest a focus on practical and participatory interventions to improve interpersonal dynamics.
Factors influencing deprescribing in primary care for those towards the end of life: A qualitative interview study with patients and healthcare practitioners
Authors: van der Waal Maike S , Teunissen Saskia CCM , Uyttewaal Allegonda G , Verboeket-Crul Cathelijne , Smits-Pelser Hanneke , Geijteman Eric CT , Grant Matthew P 
Published: June 2024

Background: For people with limited lifetime expectancy, the benefit of many medications may be outweighed by their potential harms. Despite the relevance of reducing unnecessary medication use, deprescribing is poorly enacted in primary care practice. Aim: This study aims to describe factors, as identified by primary care professionals and patients, that influence deprescribing in the last phase of life. Design: Semi-structured interviews were conducted and analysed using a thematic approach. Setting/participants: This study was performed in primary care settings, including general practices, hospices and community care teams in The Netherlands. Purposefully identified primary care professionals (general practitioners, pharmacists, nurses) and patients with limited lifetime expectancy due to advanced chronic illness or cancer and their caretakers were interviewed. Results: Three themes emerged detailing factors influencing deprescribing in the last phase of life in primary care: (1) non-maleficence, the wish to avoid additional psychological or physical distress; (2) reactive care, the lack of priority and awareness of eligible patients; and (3) discontinuity of care within primary care and between primary care and specialty care. Conclusions: Deprescribing is an incremental process, complicated by the unpredictability of life expectancy and attitudes of patients and health care professionals that associate continued medication use with clinical stability. Opportunities to facilitate the deprescribing process and its acceptance include the routinely systematic identification of patients with limited life expectancy and potentially inappropriate medications, and normalisation of deprescribing as component of regular primary care, occurring for all patients and continuing into end-of-life care.
Intravascular Ultrasound May Not Impact Graft Sizing in Endovascular Repair of Blunt Thoracic Aortic Injury
Authors: Falkenhain Alec , Schaper Nicholas , Arismendi Tyler , Smeds Matthew R , Bose Saideep 
Published: June 2024

Objectives Thoracic endovascular aortic repair (TEVAR) is the preferred treatment for severe blunt thoracic aortic injuries (BTAI). Successful outcomes rely on accurate endograft sizing, but initial imaging may underestimate aortic diameters. This study examines the impact of intravascular ultrasound (IVUS) on endograft sizing and clinical outcomes in BTAI patients. Methods A prospectively collected multi-institutional dataset from the Aortic Trauma Foundation was analyzed. Patients with BTAI undergoing TEVAR with IVUS were compared to patients who underwent TEVAR alone. Demographics and operative variables were compared, focusing on IVUS effects on endograft sizing by examining maximal proximal and distal aortic diameter on initial CT imaging compared to the graft diameters used during TEVAR. Results 293 patients underwent TEVAR for BTAI with IVUS utilized in 124 cases (42.3%). The average graft size in the IVUS and non-IVUS groups were similar proximally (26.91 ± 4.3 mm IVUS vs 27.77 ± 4.7 mm non-IVUS, P = 0.116) and distally (25.96 ± 4.7 mm IVUS vs 26.51 ± 4.7 mm non-IVUS). IVUS did not impact the difference between graft size and initial CT measurements proximally (4.32 ± 4.8 mm IVUS vs 4.23 ± 3.9 mm non-IVUS, P = 0.859) or distally (4.17 ± 5.9 mm IVUS vs 4.50 ± 4.3 mm non-IVUS, P = 0.606). Although delayed hemorrhagic and ischemic stroke occurred less frequently in IVUS patients (0.8% IVUS vs 7.1% non- IVUS, P = 0.024), in-hospital mortality was similar between groups (5.6% IVUS vs 7.7% non-IVUS, P = 0.581). Conclusions IVUS is not associated with significant changes in endograft sizing compared to sizing based on CT scan alone in BTAI patients. IVUS was not associated with differences in mortality but was associated with a decrease in delayed hemorrhagic and ischemic stroke. Routine IVUS in BTAI patients may not be necessary for accurate sizing, but there may be a relationship between IVUS and stroke.
Ultrasound imaging for sternoclavicular joint involvement in enthesitis-related arthritis: A closer look at capsular enthesitis
Authors: Zunica Fiammetta , Loiodice Martina , Riccaboni Francesca , Carlucci Patrizia , Zuccotti Gian Vincenzo , Ricci Vincenzo 
Published: June 2024

Introduction: Enthesitis-related arthritis is a specific subtype of juvenile idiopathic arthritis characterised by the co-presence of arthritis and enthesitis or the evidence of one of them coupled with at least two among sacroiliac joint tenderness, inflammatory back pain, presence of human leukocyte antigen-B27, acute symptomatic anterior uveitis, onset in a male child aged 6 years or older or history of spondyloarthropathy in a first-degree relative. Small joints like the sternoclavicular joint are rarely affected, and the prevalence of their involvement in enthesitis-related arthritis has been poorly assessed in the pertinent literature. Case report: The authors report an atypical case of left sternoclavicular joint arthritis/enthesitis in a 12-year-old male child with juvenile idiopathic arthritis. The B-mode sonographic findings of articular effusion, synovial hypertrophy and capsular bulging, coupled with the microvascular mapping with colour Doppler of the sternoclavicular joint, have been crucial to optimising the pharmacological approach in clinical practice. In this sense, the sonographic examination presented as a natural extension of the physical examination to accurately define the poor control of disease activity using first-line pharmacological agents. Discussion: The present case report can be considered the first to accurately report the B-mode and the colour Doppler findings of a pathological sternoclavicular joint in a patient enthesitis-related arthritis. Ultrasound imaging demonstrated intra-articular effusion, capsular bulging and synovial hypertrophy clearly defining sternoclavicular joint arthritis. Interestingly, the hypervascularisation involved both the synovial tissue and the capsule–bone interface – that is, the enthesis of the joint capsule – suggesting a potential co-existence of arthritis and enthesitis of the sternoclavicular joint in enthesitis-related arthritis patients. Conclusion: The high-resolution point-of-care ultrasound seems to be a potential ‘game changer’ in paediatrics to promptly optimise the pharmacological management in enthesitis-related arthritis patients. Indeed, unlike other imaging modalities such as magnetic resonance imaging, modern high-frequency ultrasound transducers guarantee a superior spatial resolution of superficial joints and allow an accurate mapping of small-size and low-flow vascular elements of synovial and capsular tissues optimising the grading of disease activity and avoiding the use of contrast agent.
Wrist and ankle acupuncture relief moderate to severe postoperative pain after functional endoscopic sinus surgery: A randomized controlled study
Authors: Guo Suying , Wang Yaqin , Ai Jianwei , Zhao Jingyi , Huang Shaoting , Wang Junge 
Published: June 2024

Introduction The study aimed to validate the effectiveness of Wrist and Ankle Acupuncture (WAA) in attenuating moderate to severe postoperative pain following Functional Endoscopic Sinus Surgery (FESS). Methods Participants were randomly allocated into a treatment group ( n = 57) and a control group ( n = 58). The treatment group underwent WAA treatment, while the control group received sham acupuncture treatment. The Numeric Rating Scale (NRS) was employed to assess postoperative pain. The sleep efficiency, the amount of rescue medication, and the adverse events were also evaluated for both groups. Results A significant immediate reduction in NRS scores was observed in the treatment group ( p < .01). At 2, 4, 8, 22, and 24 h after first treatment, pain intensity decreased in the WAA group compared with the control group ( p < .01). Moreover, the WAA group demonstrated superior sleep efficiency relative to the control group on the night after surgery ( p < .01). And the mean number of rescue tablets used on the WAA group was obviously lower than the control group ( p < .01). There were no serious adverse events in both groups, and all adverse events completely disappeared within 3 days. Conclusion WAA effectively alleviated postoperative discomfort associated with nasal packing subsequent to FESS and enhanced sleep quality during the postoperative night. The anatomical superficiality of the acupuncture points employed reduces the risk of adverse events while yielding effective analgesic results, thus validating its suitability for clinical application.