bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional characterization of the
dbu
locus for D-branched-chain amino acid catabolism in
Pseudomonas putida
Authors: Fulton Ronnie L. , Downs Diana M. 
Published: January 2024

ABSTRACT

Pseudomonas putida
is a metabolically robust soil bacterium that employs a diverse set of pathways to utilize a wide range of nutrients. The versatility of this microorganism contributes to both its environmental ubiquity and its rising popularity as a bioengineering chassis. In
P. putida
, the newly named
dbu
locus encodes a transcriptional regulator (DbuR), D-amino acid oxidase (DbuA), Rid2 protein (DbuB), and a putative transporter (DbuC). Current annotation implicates this locus in the utilization of D-arginine. However, data obtained in this study showed that genes in the
dbu
locus are not required for D-arginine utilization, but, rather, this locus is involved in the catabolism of multiple D-branched-chain amino acids (D-BCAA). The oxidase DbuA was required for catabolism of each D-BCAA and D-phenylalanine, while the requirements for DbuC and DbuB were less stringent. The functional characterization of the
dbu
locus contributes to our understanding of the metabolic network of
P. putida
and proposes divergence in function between proteins annotated as D-arginine oxidases across the
Pseudomonas
genus.

IMPORTANCE

Pseudomonas putida
is a non-pathogenic bacterium that is broadly utilized as a host for bioengineering and bioremediation efforts. The popularity of
P. putida
as a chassis for such efforts is attributable to its physiological versatility and ability to metabolize a wide variety of compounds. Pathways for L-amino acid metabolism in this microbe have been rather well studied, primarily because of their relevance to efforts in foundational physiology research, as well as the commercial production of economically pertinent compounds. However, comparatively little is known about the metabolism of D-amino acids despite evidence showing the ability of
P. putida
to metabolize these enantiomers. In this work, we characterize the D-BCAA catabolic pathway of
P. putida
and its integration with the essential L-BCAA biosynthetic pathway. This work expands our understanding of the metabolic network of
Pseudomonas putida
, which has potential applications in efforts to model and engineer the metabolic network of this organism.
Deciphering the interaction of bacteria inoculants with the recipient endophytic community in grapevine micropropagated plants
Authors: Vergani Lorenzo , Patania Joa , Riva Valentina , Nerva Luca , Nuzzo Floriana , Gambino Giorgio , Borin Sara , Mapelli Francesca 
Published: January 2024

ABSTRACT

Engineering the plant microbiome with beneficial endophytic bacteria can improve the growth, health, and productivity of the holobiont. Here, we administered two beneficial bacterial strains,
Kosakonia
VR04 sp. and
Rhizobium
GR12 sp., to micropropagated grapevine cuttings obtained via somatic embryogenesis. While both strains colonized the plant endosphere, only
Rhizobium
GR12 sp. increased root biomass under nutritional-deficit conditions, as supported by the plant growth promotion traits detected in its genome. Phylogenetic and co-occurrence analyses revealed that the plant native bacterial community, originally dominated by Streptococcaceae and Micrococcaceae, dramatically changed depending on the inoculation treatments, as invading strains differently affected the relative abundance and the interactions of pre-existing taxa. After 30 days of plantlets’ growth,
Pantoea
became a predominant taxon, and considering untreated plantlets as references,
Rhizobium
sp. GR12 showed a minor impact on the endophytic bacterial community. On the other hand,
Kosakonia
sp. VR04 caused a major change in community composition, suggesting an opportunistic colonization pattern. Overall, the results corroborate the importance of preserving the native endophytic community structure and functions during plant microbiome engineering.

IMPORTANCE

A better comprehension of bacterial colonization processes and outcomes could benefit the use of plant probiotics in the field. In this study, we applied two different beneficial bacteria to grapevine micropropagated plantlets and described how the inoculation of these strains impacts endophytic microbiota assembly. We showed that under nutritional deficit conditions, the response of the receiving endophytic bacterial communities to the invasion of the beneficial strains related to the manifestation of plant growth promotion effects by the inoculated invading strains.
Rhizobium
sp. GR12 was able to preserve the native microbiome structure despite its effective colonization, highlighting the importance of the plant-endophyte associations for the holobiont performance. Moreover, our approach showed that the use of micropropagated plantlets could be a valuable strategy to study the interplay among the plant, its native microbiota, and the invader on a wider portfolio of species besides model plants, facilitating the application of new knowledge in agriculture.
Molecular determinants of multidrug-resistant tuberculosis in Sierra Leone
Authors: Blankson Harriet N. A. , Kamara Rashidatu Fouad , Barilar Ivan , Andres Sönke , Conteh Ousman S. , Dallenga Tobias , Foray Lynda , Maurer Florian , Kranzer Katharina , Utpatel Christian , Niemann Stefan 
Published: January 2024

ABSTRACT

Multidrug-resistant tuberculosis (MDR-TB) management has become a serious global health challenge. Understanding its epidemic determinants on the regional level is crucial for developing effective control measures. We used whole genome sequencing data of 238 of
Mycobacterium tuberculosis
complex (MTBC) strains to determine drug resistance profiles, phylogeny, and transmission dynamics of MDR/rifampicin-resistant (RR) MTBC strains from Sierra Leone. Forty-two strains were classified as RR, 196 as MDR, 5 were resistant to bedaquiline (BDQ) and clofazimine (CFZ), but none was found to be resistant to fluoroquinolones. Sixty-one (26%) strains were resistant to all first-line drugs, three of which had additional resistance to BDQ/CFZ. The strains were classified into six major MTBC lineages (L), with strains of L4 being the most prevalent, 62% (
n
= 147), followed by L6 (
Mycobacterium africanum
) strains, (21%,
n
= 50). The overall clustering rate (using ≤d12 single-nucleotide polymorphism threshold) was 44%, stratified into 31 clusters ranging from 2 to 16 strains. The largest cluster (
n
= 16) was formed by sublineage 2.2.1 Beijing Ancestral 3 strains, which developed MDR several times. Meanwhile, 10 of the L6 strains had a primary MDR transmission. We observed a high diversity of drug resistance mutations, including borderline resistance mutations to isoniazid and rifampicin, and mutations were not detected by commercial assays. In conclusion, one in five strains investigated was resistant to all first-line drugs, three of which had evidence of BDQ/CFZ resistance. Implementation of interventions such as rapid diagnostics that prevent further resistance development and stop MDR-TB transmission chains in the country is urgently needed.

IMPORTANCE
A substantial proportion of MDR-TB strains in Sierra Leone were resistant against all first line drugs; however this makes the all-oral-six-month BPaLM regimen or other 6-9 months all oral regimens still viable, mainly because there was no FQ resistance.Resistance to BDQ was detected, as well as RR, due to mutations outside of the hotspot region. While the prevalence of those resistances was low, it is still cause for concern and needs to be closely monitored.
Impact of AI-aided colonoscopy in clinical practice: a prospective randomised controlled trial
Authors: Schöler Johanna , Alavanja Marko , de Lange Thomas , Yamamoto Shunsuke , Hedenström Per , Varkey Jonas 
Published: January 2024

ObjectiveColorectal cancer (CRC) has a significant role in cancer-related mortality. Colonoscopy, combined with adenoma removal, has proven effective in reducing CRC incidence. However, suboptimal colonoscopy quality often leads to missed polyps. The impact of artificial intelligence (AI) on adenoma and polyp detection rate (ADR, PDR) is yet to be established.DesignWe conducted a randomised controlled trial at Sahlgrenska University Hospital in Sweden. Patients underwent colonoscopy with or without the assistance of AI (AI-C or conventional colonoscopy (CC)). Examinations were performed with two different AI systems, that is, Fujifilm CADEye and Medtronic GI Genius. The primary outcome was ADR.ResultsAmong 286 patients, 240 underwent analysis (average age: 66 years). The ADR was 42% for all patients, and no significant difference emerged between AI-C and CC groups (41% vs 43%). The overall PDR was 61%, with a trend towards higher PDR in the AI-C group. Subgroup analysis revealed higher detection rates for sessile serrated lesions (SSL) with AI assistance (AI-C 22%, CC 11%, p=0.004). No difference was noticed in the detection of polyps or adenomas per colonoscopy. Examinations were most often performed by experienced endoscopists, 78% (n=86 AI-C, 100 CC).ConclusionAmidst the ongoing AI integration, ADR did not improve with AI. Particularly noteworthy is the enhanced detection rates for SSL by AI assistance, especially since they pose a risk for postcolonoscopy CRC. The integration of AI into standard colonoscopy practice warrants further investigation and the development of improved software might be necessary before enforcing its mandatory implementation.Trial registration numberNCT05178095.
Personalising haemodialysis treatment with incremental dialysis for incident patients with end-stage kidney disease: an implementation study protocol
Authors: Armstrong Marni , Wityk Martin Tracy Lynn , Zimmermann Gabrielle L , Drall Kelsea , Pannu Neesh I 
Published: January 2024

IntroductionIncremental dialysis is a personalised dialysis prescription based on residual kidney function that allows for the initial use of shorter duration, less frequent and less intense dialysis. It has been associated with enhanced quality of life and decreased healthcare costs when compared with conventional dialysis. While nephrologists report prescribing incremental dialysis, few dialysis programmes offer a systematic approach in offering and evaluating its use. To move evidence into practice, and in order to improve the safety and quality of providing incremental dialysis care, we have designed an implementation study. This study aims to evaluate the systematic assessment of patients starting facility-based haemodialysis for eligibility for incremental dialysis, and the prescription and monitoring of incremental dialysis treatment.Methods and analysisA hybrid effectiveness and implementation study design is being used to evaluate the implementation of the programme at dialysis sites in Alberta, Canada. The Reach, Effectiveness, Adoption, Implementation and Maintenance framework will be used to capture individual-level and organisational-level impact of the project. Clinical outcomes related to kidney function will be monitored on an ongoing basis, and patient-reported outcomes and experience measures will be collected at baseline and then quarterly throughout the first year of dialysis.Ethics and disseminationThe study was approved by the Health Research Ethics Board of the University of Alberta. The study is funded by the Strategic Clinical Networks of Alberta Health Services. The study will help answer important questions on the effectiveness of incremental dialysis, and inform the acceptability, adoption, feasibility, reach and sustainability of incremental dialysis within provision of haemodialysis care.
Utilisation of community healthcare services among older adults with disabilities in Luohu district, Shenzhen: a community-based survey
Authors: Shi Lu , Pang Tiantian , Zheng Qingming , Liu Gang , Zhang Wei , Leung Willie 
Published: January 2024

ObjectiveChina faces the challenge of an ageing population with disabilities. Community healthcare centres (CHCs) serve as frontline community healthcare providers for older adults with and without disabilities. Despite their significance, there is a lack of literature examining the utilisation of CHC services among older adults. This study aims to examine and compare the utilisation and satisfaction of CHC healthcare services among older adults with and without disabilities.SettingData from the 2019 Community Health Diagnosis Questionnaire, which interviewed 259 older adults residing in the Luohu district of Shenzhen, were used in the current study.Primary outcome measuresParticipants self-reported outcomes including use of CHCs, use of home health services from CHCs and satisfaction with CHCs. Five different disability types and an integrated disability variable were assessed as independent variables. Linear probability models were used to determine the relationship between disability types and outcome variables.ResultsAmong 259 older adults aged 60 years and older, 70.66% self-identified as having a disability. No statistically significant associations were found between the use of CHCs, the use of home health services from CHCs and satisfaction with CHCs, and disability status. However, older adults with mobility and cognitive disabilities were more likely to receive home health services from CHCs.ConclusionCommunity health promotion policies should be implemented to improve access to health services for older adults with and without disabilities. In addition, CHCs should implement effective health management plans to ensure the health needs of older adults with disabilities.
Investigating the characteristics of health-related data collection tools used in randomised controlled trials in low-income and middle-income countries: protocol for a systematic review
Authors: Karthikeyan Rithvik , Al-Shamaa Noor , Kelly Eve Jacqueline , Henn Patrick , Shiely Frances , Divala Titus , Fadahunsi Kayode Philip , O'Donoghue John 
Published: January 2024

IntroductionHealth-related data collection tools, including digital ones, have become more prevalent across clinical studies in the last number of years. However, using digital data collection tools in low-income and middle-income countries presents unique challenges. In this review, we aim to provide an overview of the data collection tools currently being used in randomised controlled trials (RCTs) conducted in low-resource settings and evaluate the tools based on the characteristics outlined in the modified Mobile Survey Tool framework. These include functionality, reliability, usability, efficiency, maintainability, portability, effectiveness, cost–benefit, satisfaction, freedom from risk and context coverage. This evidence may provide a guide to selecting a suitable data collection tool for researchers planning to conduct research in low-income and middle-income countries for future studies.Methods and analysisSearches will be conducted in four electronic databases: PubMed, CINAHL, Web of Science and EMBASE. For inclusion, studies must be a RCT, mention a health-related data collection tool and conducted in a low- and middle-income country. Only studies with available full-text and written in English will be included. The search was restricted to studies published between January 2005 and June 2023. This systematic review will use the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) tool. Two review authors will screen the titles and abstracts of search results independently for inclusion. In the initial screening process, the full-text articles will be retrieved if the abstract contains limited information about the study. Disagreements will be resolved through discussion. If the disagreement cannot be resolved, a third author (JO’D) will adjudicate. The study selection process will be outlined in a PRISMA flow-diagram. Data will be analysed using a narrative synthesis approach. The included studies and their outcomes will be presented in a table.Ethics and disseminationFormal ethical approval is not required as primary data will not be collected in this study. The findings from this systematic review will be published in a peer-reviewed journal.PROSPERO registration numberCRD42023405738.
Neuroimaging of neuropsychological disturbances following ischaemic stroke (CONNECT): a prospective cohort study protocol
Authors: Chao Xian , Wang Jinjing , Dong Yiran , Fang Yirong , Yin Dawei , Wen Jie , Wang Peng , Sun Wen 
Published: January 2024

IntroductionNeuropsychiatric distubance is a common clinical manifestation in acute ischemic stroke. However, it is frequently overlooked by clinicians. This study aimed to explore the possible aetiology and pathogenesis of neuropsychiatric disturbances following ischaemic stroke (NDIS) from an anatomical and functional perspective with the help of neuroimaging methods.Method and analysisCONNECT is a prospective cohort study of neuroimaging and its functional outcome in NDIS. We aim to enrol a minimum of 300 individuals with first-ever stroke. The neuropsychological disturbances involved in this study include depression, anxiety disorder, headache, apathy, insomnia, fatigue and cognitive impairment. Using scales that have been shown to be effective in assessing the above symptoms, the NDIS evaluation battery requires at least 2 hours at baseline. Moreover, all patients will be required to complete 2 years of follow-up, during which the NDIS will be re-evaluated at 3 months, 12 months and 24 months by telephone and 6 months by outpatient interview after the index stroke. The primary outcome of our study is the incidence of NDIS at the 6-month mark. Secondary outcomes are related to the severity of NDIS as well as functional rehabilitation of patients. Functional imaging evaluation will be performed at baseline and 6-month follow-up using specific sequences including resting-state functional MRI, diffusion tensor imaging, T1-weighted imaging, T2-weighted imaging, diffusion-weighted imaging, arterial spin labelling, quantitative susceptibility mapping and fluid-attenuated inversion recovery imaging. In addition, we collect haematological information from patients to explore potential biological and genetic markers of NDIS through histological analysis.Ethics and disseminationThe CONNECT Study was approved by the Ethics Review Committee of the First Hospital of the University of Science and Technology of China (2021-ky012) and written informed consent will be obtained from all participants. Results will be disseminated via a peer-reviewed journal.Trial registration numberChiCTR2100043886.
Diagnostic utility of diagnostic investigations to identify neuropathic pain in low back-related leg pain: protocol for a systematic review
Authors: Mistry Jai , Walton David M , Noblet Tim , Bowling Benjamin , Heneghan Nicola R , Rushton Alison B 
Published: January 2024

IntroductionNeuropathic pain in low back-related leg pain has gained increasing interest in contemporary research. Identification of neuropathic pain in low back-related leg pain is essential to inform precision management. Diagnostic investigations are commonly used to identify neuropathic pain in low back-related leg pain; yet the diagnostic utility of these investigations is unknown. This systematic review aims to investigate the diagnostic utility of diagnostic investigations to identify neuropathic pain in low back-related leg pain.Methods and analysisThis protocol has been designed and reported in accordance with the Cochrane Handbook for Diagnostic Test Accuracy studies, Centre for Reviews and Dissemination and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols checklist, respectively. The search strategy will involve two independent reviewers searching electronic databases (CINAHL, EMBASE, MEDLINE, Web of Science, Cochrane Library, AMED, Pedro), key journals (Spine, The Clinical Journal of Pain, PAIN, European Journal of Pain, The Journal of Pain, Musculoskeletal Science and Practice) and grey literature (British National Bibliography for report literature, OpenGrey, EThOS) from inception to 31 July 2023 to identify studies. Studies evaluating the diagnostic accuracy of diagnostic investigation to identify neuropathic pain in patients with low back-related leg pain will be eligible, studies not written in English will be excluded. The reviewers will extract the data from included studies, assess risk of bias (Quality Assessment of Diagnostic Accuracy Studies 2) and determine confidence in findings (Grading of Recommendations, Assessment, Development and Evaluation guidelines). Methodological heterogeneity will be assessed to determine if a meta-analysis is possible. If pooling of data is not possible then a narrative synthesis will be done.Ethics and disseminationEthical approval is not required. Findings will be published in a peer-reviewed journal, presented at relevant conferences and shared with the Patient Partner Advisor Group at Western University, Canada.PROSPERO registration numberCRD42023438222.
Combination of oligo-fractionated irradiation with nivolumab can induce immune modulation in gastric cancer
Authors: Mimura Kosaku , Ogata Takashi , Nguyen Phuong H D , Roy Souvick , Kared Hassen , Yuan Yate-Ching , Fehlings Michael , Yoshimoto Yuya , Yoshida Daisaku , Nakajima Shotaro , Sato Hisashi , Machida Nozomu , Yamada Takanobu , Watanabe Yohei , Tamaki Tomoaki , Fujikawa Hirohito , Inokuchi Yasuhiro , Hayase Suguru , Hanayama Hiroyuki , Saze Zenichiro , Katoh Hiroyuki , Takahashi Fumiaki , Oshima Takashi , Goel Ajay , Nardin Alessandra , Suzuki Yoshiyuki , Kono Koji 
Published: January 2024

BackgroundTumor-associated antigen (TAA)-specific CD8(+) T cells are essential for nivolumab therapy, and irradiation has been reported to have the potential to generate and activate TAA-specific CD8(+) T cells. However, mechanistic insights of T-cell response during combinatorial immunotherapy using radiotherapy and nivolumab are still largely unknown.MethodsTwenty patients included in this study were registered in the CIRCUIT trial (ClinicalTrials.gov,NCT03453164). All patients had multiple distant metastases and were intolerance or had progressed after primary and secondary chemotherapy without any immune checkpoint inhibitor. In the CIRCUIT trial, eligible patients were treated with a total of 22.5 Gy/5 fractions/5 days of radiotherapy to the largest or symptomatic lesion prior to receiving nivolumab every 2 weeks. In these 20 patients, T-cell responses during the combinatorial immunotherapy were monitored longitudinally by high-dimensional flow cytometry-based, multiplexed major histocompatibility complex multimer analysis using a total of 46 TAAs and 10 virus epitopes, repertoire analysis of T-cell receptor β-chain (TCRβ), together with circulating tumor DNA analysis to evaluate tumor mutational burden (TMB).ResultsAlthough most TAA-specific CD8(+) T cells could be tracked longitudinally, several TAA-specific CD8(+) T cells were detected de novo after irradiation, but viral-specific CD8(+) T cells did not show obvious changes during treatment, indicating potential irradiation-driven antigen spreading. Irradiation was associated with phenotypical changes of TAA-specific CD8(+) T cells towards higher expression of killer cell lectin-like receptor subfamily G, member 1, human leukocyte antigen D-related antigen, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain, CD160, and CD45RO together with lower expression of CD27 and CD127. Of importance, TAA-specific CD8(+) T cells in non-progressors frequently showed a phenotype of CD45RO(+)CD27(+)CD127(+) central memory T cells compared with those in progressors. TCRβ clonality (inverted Pielou’s evenness) increased and TCRβ diversity (Pielou’s evenness and Diversity Evenness score) decreased during treatment in progressors (p=0.029, p=0.029, p=0.012, respectively). TMB score was significantly lower in non-progressors after irradiation (p=0.023).ConclusionOligo-fractionated irradiation induces an immune-modulating effect with potential antigen spreading and the combination of radiotherapy and nivolumab may be effective in a subset of patients with gastric cancer.