bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimum inhibitory concentrations of azithromycin in clinical isolates of
Mycobacterium avium
complex in Japan
Authors: Uwamino Yoshifumi , Aoki Wataru , Inose Rika , Kamoshita Yuka , Mikita Kei , Namkoong Ho , Nishimura Tomoyasu , Matsushita Hiromichi , Hasegawa Naoki 
Published: April 2024

ABSTRACT

The latest guidelines include azithromycin as a preferred regimen for treating
Mycobacterium avium
complex (MAC) pulmonary disease. However, serially collected susceptibility data on clinical MAC isolates are limited, and no breakpoints have been determined. We investigated the minimum inhibitory concentrations (MICs) of azithromycin and clarithromycin for all MAC strains isolated in 2021 from a single center in Japan, excluding duplicates. The MICs were determined using a panel based on the microbroth dilution method, according to the latest Clinical and Laboratory Standards Institute recommendations. The MICs were determined for 318 MAC strains. Although there was a significant positive correlation between the MICs of azithromycin and clarithromycin, the MICs of azithromycin tended to be higher than those of clarithromycin. Among the cases in which the strains were isolated, 18 patients initiated treatment, including azithromycin treatment, after sample collection. Some patients infected with stains with relatively high azithromycin MICs achieved a microbiological cure with azithromycin-containing regimens. This study revealed a higher MIC distribution for azithromycin than clarithromycin, raising questions about the current practice of estimating azithromycin susceptibility based on the clarithromycin susceptibility test result. However, this was a single-center study that included only a limited number of cases treated with azithromycin. Therefore, further multicenter studies that include a greater number of cases treated with azithromycin are warranted to verify the distribution of azithromycin MICs and examine the correlation between azithromycin MICs and treatment effectiveness.

IMPORTANCE

The macrolides serve as key drugs in the treatment of pulmonary
Mycobacterium avium
complex infection, and the administration of macrolide should be guided by susceptibility test results. Azithromycin is recommended as a preferred choice among macrolides, surpassing clarithromycin; however, drug susceptibility testing is often not conducted, and clarithromycin susceptibility is used as a surrogate. This study represents the first investigation into the minimum inhibitory concentration of azithromycin on a scale of several hundred clinical isolates, revealing an overall tendency for higher minimum inhibitory concentrations compared with clarithromycin. The results raise questions about the appropriateness of using clarithromycin susceptibility test outcomes for determining the administration of azithromycin. This study highlights the need for future discussions on the clinical breakpoints of azithromycin, based on large-scale clinical research correlating azithromycin susceptibility with treatment outcomes.
Mutation of the peptide-regulated transcription factor ComR for amidated peptide specificity and heterologous function in
Lactiplantibacillus plantarum
WCFS1
Authors: Brasino Michael , Wagnell Eli , Ozdemir E. Sila , Ranganathan Srivathsan , Merritt Justin 
Published: April 2024

ABSTRACT

There is a growing interest in the use of probiotic bacteria as biosensors for the detection of disease. However, there is a lack of bacterial receptors developed for specific disease biomarkers. Here, we have investigated the use of the peptide-regulated transcription factor ComR from S
treptococcus spp
. for specific peptide biomarker detection. ComR exhibits a number of attractive features that are potentially exploitable to create a biomolecular switch for engineered biosensor circuitry within the probiotic organism
Lactiplantibacillus plantarum
WCFS1. Through iterative design-build-test cycles, we developed a genomically integrated, ComR-based biosensor circuit that allowed WCFS1 to detect low nanomolar concentrations of ComR’s cognate peptide XIP. By screening a library of ComR proteins with mutant residues substituted at the K100 position
,
we identified mutations that increased the specificity of ComR toward an amidated version of its cognate peptide, demonstrating the potential for ComR to detect this important class of biomarker.

IMPORTANCE

Using bacteria to detect disease is an exciting possibility under active study. Detecting extracellular peptides with specific amino acid sequences would be particularly useful as these are important markers of health and disease (biomarkers). In this work, we show that a probiotic bacteria (
Lactiplantibacillus plantarum
) can be genetically engineered to detect specific extracellular peptides using the protein ComR from Streptococcus bacteria. In its natural form, ComR allowed the probiotic bacteria to detect a specific peptide, XIP. We then modified XIP to be more like the peptide biomarkers found in humans and engineered ComR so that it activated with this modified XIP and not the original XIP. This newly engineered ComR also worked in the probiotic bacteria, as expected. This suggests that with additional engineering, ComR might be able to activate with human peptide biomarkers and be used by genetically engineered probiotic bacteria to better detect disease.
Early-life gut microbiota associates with allergic rhinitis during 13-year follow-up in a Finnish probiotic intervention cohort
Authors: Kallio Sampo , Jian Ching , Korpela Katri , Kukkonen Anna Kaarina , Salonen Anne , Savilahti Erkki , Kuitunen Mikael , M. de Vos Willem 
Published: April 2024

ABSTRACT

Perinatal and early-life factors reported to affect risk of allergic diseases may be mediated by changes in the gut microbiota. Here, we explored the associations between the infant gut microbiota and allergic morbidity in childhood until 13 years of age in a subgroup of the FLORA probiotic intervention cohort. A mixture of four probiotic strains with galacto-oligosaccharides was administrated to the mothers from the 36th week of the pregnancy and later to their infants until 6 months of age. The infants were monitored for the manifestations of atopic eczema, food allergy, allergic rhinitis, and asthma by a pediatrician at 2 and 5 years of age; the allergic status was subsequently verified by a questionnaire at 10 and 13 years of age. The fecal microbiota at 3 months was profiled by 16S rRNA amplicon sequencing targeting the V3-V4 region, with and without adjusting for potentially important early-life factors. Overall, the positive diagnosis for allergic rhinitis between 2 and 13 years was associated with microbiota composition both in non-adjusted and adjusted models. This association was more pronounced in children born to one parent with confirmed atopic diseases compared to those who had two atopic parents and was characterized by a lower relative abundance of
Bifidobacterium
and
Escherichia/Shigella spp
. and a higher proportion of
Bacteroides
. While the probiotic and galacto-oligosaccharides intervention in the entire cohort was previously shown to reduce the prevalence of eczema to a certain extent, no associations were found between the 3-month gut microbiota and childhood eczema in the studied sub-cohort.

IMPORTANCE
Allergic diseases have increased in prevalence during the past decades globally. Although probiotics have been considered a promising strategy for preventing certain allergy related symptoms, studies connecting the infant gut microbiota and later life allergic morbidity in various populations remain limited. The present study supports an association between the infant microbiota and allergic morbidity after first years of life, which has been rarely examined.

CLINICAL TRIALS

Registered at ClinicalTrials.gov
(NCT00298337)
.
Genome sequence-based species classification of
Enterobacter cloacae
complex: a study among clinical isolates
Authors: Qiu Xuemei , Ye Kun , Ma Yanning , Zhao Qiang , Wang Lifeng , Yang Jiyong 
Published: April 2024

ABSTRACT

Accurate species-level identification of
Enterobacter cloacae
complex (ECC) is crucial for related research. The classification of ECC is based on strain-to-strain phylogenetic congruence, as well as genomic features including average nucleotide identity (ANI) and digitalized DNA-DNA hybridization (dDDH). ANI and dDDH derived from whole-genome sequencing have emerged as a reliable metric for assessing genetic relatedness between genomes and are increasingly recognized as a standard for species delimitation. Up to now, there are two different classification methods for ECC. The first one categorizes
E. hormaechei
, a species within ECC, into five subspecies (
E. hormaechei
subsp.
steigerwaltii,
subsp.
oharae,
subsp.
xiangfangensis,
subsp.
hoffmannii,
and subsp.
hormaechei
). The second classifies
E. hormaechei
as three species:
E. hormaechei, “E. xiangfangensis,” “E. hoffmanii.”
While the former is well-accepted in the academic area, the latter may have a greater ability to distinguish different species of ECC. To assess the suitability of these identification criteria for clinical ECC isolates, we conducted a comprehensive analysis involving phylogenetic analysis, ANI and dDDH value alignment, virulence gene identification, and capsule typing on 256 clinical ECC strains isolated from the bloodstream. Our findings indicated that the method of categorizing
E. hormaechei
into five subspecies has better correlation and consistency with the molecular characteristics of clinical ECC isolates, as evidenced by phylogenetic analysis, virulence genes, and capsule typing. Therefore, the subspecies-based classification method appears more suitable for taxonomic assignments of clinical ECC isolates.

IMPORTANCE

Standardizing taxonomy of the
Enterobacter cloacae
complex (ECC) is necessary for data integration across diverse studies. The study utilized whole-genome data to accurately identify 256 clinical ECC isolated from bloodstream infections using average nucleotide identity (ANI), digitalized DNA-DNA hybridization (dDDH), and phylogenetic analysis. Through comprehensive assessments including phylogenetic analysis, ANI and dDDH comparisons, virulence gene, and capsule typing of the 256 clinical isolates, it was concluded that the classification method based on subspecies exhibited better correlation and consistency with the molecular characteristics of clinical ECC isolates. In summary, this research contributes to the precise identification of clinical ECC at the species level and expands our understanding of ECC.
Risk of cancer in patients with bile acid diarrhoea: a Danish nationwide matched cohort study
Authors: Nyboe Andersen Nynne , Wildt Signe , Iversen Aske Thorn , Poulsen Gry , Jess Tine , Munck Lars Kristian , Borup Christian 
Published: April 2024

ObjectiveBile acid diarrhoea is a common cause of chronic diarrhoea. Increased levels of potentially carcinogenic bile acids in faeces, theoretically, may increase the risk of colorectal cancer in particular, but the long-term disease course is unknown. We aimed to investigate the overall and site-specific cancer risk in bile acid diarrhoea.DesignAdult patients with bile acid diarrhoea were identified using nationwide Danish registries from 2003 to 2020 by a diagnostic gold-standard 75-selenium tauroselcholic acid procedure followed within 6 months by sequestrant prescription. The risk of overall and site-specific cancers in cases with bile acid diarrhoea was compared with sex, age and comorbidity-adjusted matched controls. A competing risk model estimated cumulative incidence functions and cause-specific HRs.ResultsWe identified 2260 patients with bile acid diarrhoea with a mean follow-up of 5.5 years (SD 4.2). The overall cancer risk was increased by an HR of 1.32 (95% CI 1.12 to 1.54). The risk of site-specific cancer was increased in 3 of 10 cancer groups: haematological, HR 2.41 (1.36 to 4.02); skin, HR 1.33 (1.01 to 1.71); and male genital cancers, HR 1.85 (1.11 to 2.92). No increased risk of colorectal cancer was detected in patients with bile acid diarrhoea, HR 0.73 (0.34 to 1.63).ConclusionsBile acid diarrhoea was associated with an increased overall risk of cancer, especially haematological cancers, but the risk of colorectal cancer was not increased. The lack of a diagnostic code for bile acid diarrhoea and potential residual confounding are limitations, and the findings should be replicated in other cohorts.
Real-world efficacy, roll-out and uptake of intramuscular tixagevimab/cilgavimab as COVID-19 pre-exposure prophylaxis in people with multiple sclerosis and neuroimmunological conditions during the COVID-19 pandemic
Authors: Rath Louise , Yeh Wei Zhen , Roldan Angie , Wesselingh Robb , Zhong Michael , Tan Tracie , Seery Nabil , Bridge Francesca , Foong YiChao , Skibina Olga , Nesbitt Cassie , Butzkueven Helmut , Monif Mastura , van der Walt Anneke 
Published: April 2024

BackgroundIn Australia, tixagevimab/cilgavimab 150 mg/150 mg was a government-funded pre-exposure prophylaxis for COVID-19 people with multiple sclerosis (pwMS) and other neuroimmunological conditions (pwNIc) treated with anti-CD20 antibodies or sphingosine-1-phosphate receptor modulators were eligible.ObjectiveTo analyse the roll-out, uptake and real-world efficacy of tixagevimab/cilgavimab in the prevention and severity of COVID-19. To assess compliance with uptake depending on the location of delivery.MethodsWe undertook a single-centre study. 440 pwMS and pwNIc were eligible. Logistic regression was used to assess predictors of COVID-19 during follow-up and to assess predictors of uptake among those who consented.ResultsOf the eligible pwMS and pwNIc in our service, 52.7% (233/440) requested a consultation and were included in this study. Consultation resulted in 71.7% of people (167/233) receiving the treatment. Of these, 94.0% (157/167) had received three or more COVID-19 vaccines. Among those who received a single dose of tixagevimab/cilgavimab, 19.16% (32/167) tested positive for COVID-19 during the observational window. The majority of these were on ocrelizumab (68.8% (22/32)). None of those with COVID-19 required hospitalisation or supplemental oxygen. There was no difference in odds of COVID-19 during the observation period between those who received and did not receive tixagevimab/cilgavimab (adjusted OR, aOR 2.16 (95% CI 0.82 to 6.85), p=0.43). Uptake of tixagevimab/cilgavimab was highest when offered at the hospital infusion centre (aOR 3.09 (95% CI 1.08 to 9.94) relative to referral to the local pharmacy, p=0.04).ConclusionTixagevimab/cilgavimab administration did not protect against subsequent COVID-19 in our cohort. Compliance with uptake was influenced by administration location.
Repurposing of dextromethorphan as an adjunct therapy in patients with major depressive disorder: a randomised, group sequential adaptive design, controlled clinical trial protocol
Authors: Maji Shampa , Mohapatra Debadatta , Jena Monalisa , Srinivasan Anand , Maiti Rituparna 
Published: April 2024

BackgroundTherapeutic latency, lack of efficacy and adverse drug reactions are the major concerns in current antidepressant therapies. To overcome these treatment hurdles, add-on therapy to conventional antidepressant medications may lead to better therapeutic outcomes. The present randomised controlled trial has been planned to evaluate the efficacy and safety of add-on dextromethorphan to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder (MDD).Methods and analysisA randomised, double-blind, add-on, placebo-controlled, group sequential design clinical trial will be conducted on patients with MDD who will be randomly assigned to the control and the test group in a 1:1 ratio. Patients in the test group will get dextromethorphan 30 mg once daily, whereas patients in the control group will receive a placebo once daily as an add-on to ongoing SSRI treatment for 8 weeks. All patients will be evaluated for the primary outcome (change in the Montgomery-Åsberg Depression Rating Scale score) and secondary outcomes (treatment response rate, remission rate, Clinical Global Impression, serum brain-derived neurotrophic factor, serum dextromethorphan and treatment-emergent adverse events) over the period of 8 weeks. Intention-to-treat analysis will be done for all parameters using suitable statistical tools.Ethics and disseminationThis study was approved by the Institutional Ethics Committee of All India Institute of Medical Sciences, Bhubaneswar, India, and the study conformed to the provisions of the Declaration of Helsinki and ICMR’s ethical guidelines for biomedical research on human subjects (2017). Written informed consent will be obtained from the participants before recruitment. The results of this study will be published in peer-reviewed publications.Trial registration numberNCT05181527.
Social inequality in prevalence of NCD risk factors: a cross-sectional analysis from the population-based Tromsø Study 2015–2016
Authors: Hetland Rebecca A , Wilsgaard Tom , Hopstock Laila Arnesdatter , Ariansen Inger , Johansson Jonas , Jacobsen Bjarne K , Grimsgaard Sameline 
Published: April 2024

ObjectiveWe aimed to examine associations between educational level, serving as an indicator of socioeconomic position, and prevalence of WHO-established leading behavioural and biological risk factors for non-communicable diseases (NCDs), in middle-aged to older women and men.DesignPopulation-based cross-sectional study.SettingAll inhabitants of the municipality of Tromsø, Norway, aged ≥40 years, were invited to the seventh survey (2015–2016) of the Tromsø Study; an ongoing population-based cohort study.ParticipantsOf the 32 591 invited; 65% attended, and a total of 21 069 women (53%) and men aged 40–99 years were included in our study.Outcome measuresWe assessed associations between educational level and NCD behavioural and biological risk factors: daily smoking, physical inactivity (sedentary in leisure time), insufficient fruit/vegetable intake (<5 units/day), harmful alcohol use (>10 g/day in women, >20 g/day in men), hypertension, obesity, intermediate hyperglycaemia and hypercholesterolaemia. These were expressed as odds ratios (OR) per unit decrease in educational level, with 95% CIs, in women and men.ResultsIn women (results were not significantly different in men), we observed statistically significant associations between lower educational levels and higher odds of daily smoking (OR 1.69; 95% CI 1.60 to 1.78), physical inactivity (OR 1.38; 95% CI 1.31 to 1.46), insufficient fruit/vegetable intake (OR 1.54, 95% CI 1.43 to 1.66), hypertension (OR 1.25; 95% CI 1.20 to 1.30), obesity (OR 1.23; 95% CI 1.18 to 1.29), intermediate hyperglycaemia (OR 1.12; 95% CI 1.06 to 1.19), and hypercholesterolaemia (OR 1.07; 95% CI 1.03 to 1.12), and lower odds of harmful alcohol use (OR 0.75; 95% CI 0.72 to 0.78).ConclusionWe found statistically significant educational gradients in women and men for all WHO-established leading NCD risk factors within a Nordic middle-aged to older general population. The prevalence of all risk factors increased at lower educational levels, except for harmful alcohol use, which increased at higher educational levels.
Walking for transport and all-cause mortality: a prospective cohort study of Australian community-dwelling older adults
Authors: Shah Shivangi , Chen Yang , Owen Alice , Woods Robyn L , Ryan Joanne , Owen Neville , Wolfe Rory , Dunstan David W , Beck Ben , Britt Carlene , Gasevic Danijela 
Published: April 2024

BackgroundWalking for transport may prolong survival in younger and middle-aged adults; however, evidence for older adults is scarce. We examined a prospective relationship between transport-related walking and all-cause mortality among adults aged 70 years and over.MethodsCommunity-dwelling, apparently healthy older adults (n=11 539; mean age 75.1 years, 53.1% females), participants of the ASPirin in Reducing Events in the Elderly Longitudinal Study of Older Persons, reported their frequency of transport-related walking (never, rarely/once a week, more than once a week or every day). All-cause mortality was verified by two independent sources. Cox proportional-hazards models (HR and 95% CI) assessed the association between transport-related walking and all-cause mortality.ResultsOf participants, 44.1% reported walking every day, 31.5% more than once a week, 21.7% rarely or once a week and 2.7% never engaged in transport-related walking. During the median follow-up of 8.6 years (IQR: 7.4–10.1), 1599 participants (13.9%) died. Compared with those who reported never walking for transport, the risk of all-cause mortality was lower for those walking rarely or once a week (HR 0.73, 95% CI 0.56 to 0.96); more than once a week (HR 0.76, 95% CI 0.59 to 0.99) and every day (HR 0.74, 95% CI 0.57 to 0.96). Analyses were adjusted for age, sex, education, smoking, alcohol consumption, living status, rurality, household income, socioeconomic status, chronic conditions, body mass index and overall physical activity levels.ConclusionsEngaging in any weekly transport-related walking helps older adults prolong survival. Public health campaigns and urban planning should promote and support transport-related walking to boost physical activity levels of older adults and support healthier ageing.
Shared decision-making with athletes: a survey study of healthcare professionals’ perspectives
Authors: Nelis Sofie , Dijkstra Hendrik Paul , Damman Olga Catherina , Farooq Abdulaziz , Verhagen Evert 
Published: April 2024

ObjectivesShared decision-making (SDM) is a trending topic in athlete health care; however, little is known about its use in a sports context. This study aimed to measure knowledge and self-perceived practice of SDM among healthcare professionals working with athletes. This study evaluates SDM attitudes and preferences and explores how healthcare professionals perceive the factors influencing SDM.MethodsA web-based cross-sectional survey with open-ended and closed-ended questions.ResultsOur survey was completed by 131 healthcare professionals. The majority (63.6%) reported to prefer SDM and to be confident in their SDM skills (81.1%). Despite this inclination and confidence, only one in four clinicians reported consistent practice of SDM when feasible. Additionally, most clinicians lacked SDM knowledge. The barriers perceived by healthcare professionals included time constraints (17.6%), limited patient knowledge (17.6%), limited patient motivation (13.5%) and language barriers (16.2%). Importantly, two-thirds of the participants believed that SDM in athlete health care differs from SDM in non-athletes due to the high-pressure environment, the tension between performance and health, and the involvement of multiple stakeholders with potentially conflicting interests.ConclusionsAlthough healthcare professionals preferred SDM, they did not fully understand nor routinely practice it. Most healthcare professionals perceive SDM in athlete health care to differ from SDM in the general population. Therefore, to inform the implementation of SDM in athlete health care, future research is crucial to understand better what makes practising SDM unique in this setting.