bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antitoxin MqsA decreases antibiotic susceptibility through the global regulator AgtR in
Pseudomonas fluorescens
Authors: Zhang Si-Ping , Ye Yi-Ping , Hou Jun , Ye Zi-Rui , Wang Zhi-Song , Yu Xiao-Quan , Guo Ding-Ding , Wang Yong , He Yong-Xing 
Published: October 2023

ABSTRACT

Type II toxin-antitoxin systems are highly prevalent in bacterial genomes and play crucial roles in the general stress response. Previously, we demonstrated that the type II antitoxin PfMqsA regulates biofilm formation through the global regulator AgtR in
Pseudomonas fluorescens
. Here, we found that both the C-terminal DNA-binding domain of PfMqsA and AgtR are involved in bacterial antibiotic susceptibility. Electrophoretic mobility shift assay (EMSA) analyses revealed that AgtR, rather than PfMqsA, binds to the intergenic region of
emhABC-emhR
, in which
emhABC
encodes an resistance-nodulation-cell division efflux pump and
emhR
encodes a repressor. Through quantitative real-time reverse-transcription PCR and EMSA analysis, we showed that AgtR directly activates the expression of the
emhR
by binding to the DNA motif [5´-
CTAAGAAATATACTTAC
-3´], leading to repression of the
emhABC
. Furthermore, we demonstrated that PfMqsA modulates the expression of EmhABC and EmhR. These findings enhance our understanding of the mechanism by which antitoxin PfMqsA contributes to antibiotic susceptibility.
Autogenous reproduction by
Ornithodoros turicata
(Ixodida: Argasidae) females and vertical transmission of the tick-borne pathogen
Borrelia turicatae
(Spirochaetales:
Borreliaceae
)
Authors: Filatov Serhii , Krishnavajhala Aparna , Lopez Job E. 
Published: October 2023

ABSTRACT

Ornithodoros turicata
is a vector of relapsing fever spirochetes in North America and transmits
Borrelia turicatae
to a variety of vertebrate hosts. The remarkably long lifespan of
O. turicata
and its ability to maintain spirochetes horizontally (between life stages) and vertically (to progeny) promote the perpetuation of
B. turicatae
in nature. Nevertheless, the reproductive biology of
O. turicata
is poorly understood. In this report, we collected ticks from a park within a neighborhood of Austin, TX. They were reared to adulthood, and male ticks were individually housed with females. We observed autogenous reproduction, which is the ability to produce eggs without the need for a blood meal, and further investigated vertical transmission of
B. turicatae
by quantifying filial infection rates in a cohort of progeny ticks. These results indicate that
O. turicata
transovarially transmits
B. turicatae
during autogenous reproduction and further signify the tick as a natural reservoir of the spirochetes.

IMPORTANCE

Previous research has implicated
Ornithodoros
ticks, including
Ornithodoros turicata
, as long-term reservoirs of relapsing fever (RF) spirochetes. Considering the tick’s long lifespan and their efficiency in maintaining and transferring spirochetes within the population, the infection could persist in a given enzootic focus for decades. However, little is known about the relative importance of horizontal and vertical transmission routes in the persistence and evolution of RF
Borrelia
. Our observations on the reproductive biology of
O. turicata
in the absence of vertebrate hosts indicate an additional mechanism by which
Borrelia turicatae
can be maintained in the environment. This work establishes the foundation for studying
O. turicata
reproduction and spirochete-vector interactions, which will aid in devising control measures for
Ornithodoros
ticks and RF spirochetes.
Reduction is sufficient for the disassembly of ricin and Shiga toxin 1 but not
Escherichia coli
heat-labile enterotoxin
Authors: Guyette Jessica L. , Serrano Albert , Huhn III G. Robb , Taylor Michael , Malkòm Pat , Curtis David , Teter Ken 
Published: October 2023

ABSTRACT

Many AB toxins contain an enzymatic A moiety that is anchored to a cell-binding B moiety by a disulfide bridge. After receptor-mediated endocytosis, some AB toxins undergo retrograde transport to the endoplasmic reticulum (ER) where reduction of the disulfide bond occurs. The reduced A subunit then dissociates from the holotoxin and enters the cytosol to alter its cellular target. Intoxication requires A chain separation from the holotoxin, but, for many toxins, it is unclear if reduction alone is sufficient for toxin disassembly. Here, we examined the link between reduction and disassembly for several ER-translocating toxins. We found disassembly of the reduced
Escherichia coli
heat-labile enterotoxin (Ltx) required an interaction with one specific ER-localized oxidoreductase: protein disulfide isomerase (PDI). In contrast, the reduction and disassembly of ricin toxin (Rtx) and Shiga toxin 1 (Stx1) were coupled events that did not require PDI and could be triggered by reductant alone. PDI-deficient cells accordingly exhibited high resistance to Ltx with continued sensitivity to Rtx and Stx1. The distinct structural organization of each AB toxin thus appears to determine whether holotoxin disassembly occurs spontaneously upon disulfide reduction or requires the additional input of PDI.
Epitope-dependent effect of long-term cART on maintenance and recovery of HIV-1-specific CD8
+
T cells
Authors: Kuse Nozomi , Gatanaga Hiroyuki , Zhang Yu , Chikata Takayuki , Oka Shinichi , Takiguchi Masafumi 
Published: October 2023

ABSTRACT

The frequency of HIV-1-specific T cells is reduced and their functional ability remains impaired in people living with HIV-1 (PLWH) under combined antiretroviral therapy (cART). However, no studies have yet reported on T-cell responses to large numbers of well-characterized HIV-1 epitopes before and under cART within the same individuals. Therefore, how cART affects the maintenance of HIV-1-specific CD8
+
T cells and which HIV-1-specific CD8
+
T cells would be useful for curative treatment remain unclear. We investigated T-cell responses to 63 HIV-1 epitopes at pre-cART and under cART in 90 PLWH who received long-term cART. The frequency of T-cell responses to HIV-1 epitopes under long-term cART varied from 0% to 100%, indicating an epitope-dependent effect of long-term cART on HIV-1-specific CD8
+
T cells. The magnitude of the responses under cART was 26.2% of that at pre-cART. The frequency of T-cell responses to protective epitopes under cART was higher than that to non-protective ones. T-cell responses to HIV-1 epitopes were detected at pre-cART in most non-AIDS HIV patients, whereas they were not detectable at pre-cART in half of the AIDS patients. Long-term cART enhanced the ability of HIV-1-specific T cells to proliferate
in vitro
in non-AIDS HIV patients, while it restored this ability of the T cells in AIDS patients. This study demonstrated that CD8
+
T cells specific for large numbers of HIV-1 epitopes were maintained in an epitope-dependent fashion under long-term cART and implied that some HIV-1-specific T cells are still candidates as effector cells for curative treatment.

IMPORTANCE

HIV-1-specific CD8
+
T cells are anticipated to become effector cells for curative treatment using the “shock and kill” approach in people living with HIV-1 (PLWH) under combined antiretroviral therapy (cART). Previous studies demonstrated that the frequency of HIV-1-specific CD8
+
T cells is reduced under cART and their functional ability remains impaired. These studies analyzed T-cell responses to a small number of HIV-1 epitopes or overlapping HIV-1 peptides. Therefore, the features of CD8
+
T cells specific for HIV-1 epitopes under cART remain only partially clarified. Here, we analyzed CD8
+
T cells specific for 63 well-characterized epitopes in 90 PLWH. We demonstrated that CD8
+
T cells specific for large numbers of HIV-1 epitopes were maintained in an epitope-dependent fashion under long-term cART and that long-term cART enhanced or restored the ability of HIV-1-specific T cells to proliferate
in vitro
. This study implies that some HIV-1-specific T cells would be useful as effector cells for curative treatment.
Global distribution, receptor binding, and cross-species transmission of H6 influenza viruses: risks and implications for humans
Authors: Yan Zhanfei , Li You , Huang Shujian , Wen Feng 
Published: October 2023

ABSTRACT
The H6 subtype of avian influenza virus (AIV) is a pervasive subtype that is ubiquitously found in both wild bird and poultry populations across the globe. Recent investigations have unveiled its capacity to infect mammals, thereby expanding its host range beyond that of other subtypes and potentially facilitating its global transmission. This heightened breadth also endows H6 AIVs with the potential to serve as a genetic reservoir for the emergence of highly pathogenic avian influenza strains through genetic reassortment and adaptive mutations. Furthermore, alterations in key amino acid loci within the H6 AIV genome foster the evolution of viral infection mechanisms, which may enable the virus to surmount interspecies barriers and infect mammals, including humans, thus posing a potential threat to human well-being. In this review, we summarize the origins, dissemination patterns, geographical distribution, cross-species transmission dynamics, and genetic attributes of H6 influenza viruses. This study holds implications for the timely detection and surveillance of H6 AIVs.
High prevalence of lipopolysaccharide mutants and R2-pyocin susceptible variants in
Pseudomonas aeruginosa
populations sourced from cystic fibrosis lung infections
Authors: Mei Madeline , Pheng Preston , Kurzeja-Edwards Detriana , Diggle Stephen P. 
Published: October 2023

ABSTRACT

Chronic, highly antibiotic-resistant infections in cystic fibrosis (CF) lungs contribute to increasing morbidity and mortality.
Pseudomonas aeruginosa
, a common CF pathogen, exhibits resistance to multiple antibiotics, contributing to antimicrobial resistance (AMR). These bacterial populations display genetic and phenotypic diversity, but it is unclear how this diversity affects susceptibility to bacteriocins. R-pyocins, i.e., bacteriocins produced by
P. aeruginosa
, are phage-tail-like antimicrobials. R-pyocins have potential as antimicrobials, however, recent research suggests the diversity of
P. aeruginosa
variants within CF lung infections leads to varying susceptibility to R-pyocins. This variation may be linked to changes in lipopolysaccharide (LPS), acting as the R-pyocin receptor. Currently, it is unknown how frequently R-pyocin-susceptible strains are in chronic CF lung infection, particularly when considering the heterogeneity within these strains. In this study, we tested the R2-pyocin susceptibility of 139
P
.
aeruginosa
variants from 17 sputum samples of 7 CF patients and analyzed LPS phenotypes. We found that 83% of sputum samples did not have R2-pyocin-resistant variants, while nearly all samples contained susceptible variants. There was no correlation between LPS phenotype and R2-pyocin susceptibility, though we estimate that about 76% of sputum-derived variants lack an O-specific antigen, 40% lack a common antigen, and 24% have altered LPS cores. The absence of a correlation between LPS phenotype and R-pyocin susceptibility suggests that LPS packing density may play a significant role in R-pyocin susceptibility among CF variants. Our research supports the potential of R-pyocins as therapeutic agents, as many infectious CF variants are susceptible to R2-pyocins, even within diverse bacterial populations.

IMPORTANCE

Cystic fibrosis (CF) patients often experience chronic, debilitating lung infections caused by antibiotic-resistant
Pseudomonas aeruginosa
, contributing to antimicrobial resistance (AMR). The genetic and phenotypic diversity of
P. aeruginosa
populations in CF lungs raises questions about their susceptibility to non-traditional antimicrobials, like bacteriocins. In this study, we focused on R-pyocins, a type of bacteriocin with high potency and a narrow killing spectrum. Our findings indicate that a large number of infectious CF variants are susceptible to R2-pyocins, even within diverse bacterial populations, supporting their potential use as therapeutic agents. The absence of a clear correlation between lipopolysaccharide (LPS) phenotypes and R-pyocin susceptibility suggests that LPS packing density may play a significant role in R-pyocin susceptibility among CF variants. Understanding the relationship between LPS phenotypes and R-pyocin susceptibility is crucial for developing effective treatments for these chronic infections.
Theoretical and Methodological Approaches to the Analysis of the Spatial Distribution of Endemic Diseases of Geochemical Nature
Authors: Korobova E. M. , Baranchukov V. S. , Kolmykova L. I. 
Published: October 2023

Abstract—
Throughout millions of years of geological history (in the Phanerozoic), the coevolution of all living organisms took place in a fierce competition for resources and opportunities for the maximum reproduction. Due to the geochemical heterogeneity of the primary (pre-Quaternary) biosphere, this resulted in a self-regulating system of ecological niches, within which all local biocenoses and their animal and plant species were maximally adapted to the parameters of the habitat. However, with the emergence of reason, the situation changed fundamentally. Human beings became the dominant species and began the conscious development of new territories, including geochemically unfavorable ones, which led to the formation of zones of stable endemic diseases. Based on this premise, for all existing species, there should be areas with physiologically optimal habitat conditions, i.e., those under which the species has evolved to its present state. It follows that, by being able to record the geochemical parameters of the undisturbed biosphere, it is possible to obtain characteristics that are ecologically ideal for local animal and plant species. In theoretical terms, this allowed us to put forward the hypothesis that by fixing the difference between observed and ideal geochemical conditions, it is possible to build maps of risk of diseases of geochemical nature, including in areas subjected to anthropogenic pollution. The paper outlines the methodology and gives examples of construction of such maps. The obtained results can have an important practical value in organizing the system of sanitary–epidemiological service, in solving the problems of liquidation of the consequences of anthropogenic pollution, and in carrying out preventive measures to minimize the risk of diseases of geochemical nature.
Diagnosis and management of congenital diaphragmatic hernia: a 2023 update from the Canadian Congenital Diaphragmatic Hernia Collaborative
Authors: Puligandla Pramod , Skarsgard Erik , Baird Robert , Guadagno Elena , Dimmer Alexandra , Ganescu Olivia , Abbasi Nimrah , Altit Gabriel , Brindle Mary , Fernandes Sairvan , Dakshinamurti Shyamala , Flageole Helene , Hebert Audrey , Keijzer Richard , Offringa Martin , Patel Dylan , Ryan Greg , Traynor Michael , Zani Augusto , Chiu Priscilla 
Published: October 2023

ObjectiveThe Canadian Congenital Diaphragmatic Hernia (CDH) Collaborative sought to make its existing clinical practice guideline, published in 2018, into a ‘living document’.Design and main outcome measuresCritical appraisal of CDH literature adhering to Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Evidence accumulated between 1 January 2017 and 30 August 2022 was analysed to inform changes to existing or the development of new CDH care recommendations. Strength of consensus was also determined using a modified Delphi process among national experts in the field.ResultsOf the 3868 articles retrieved in our search that covered the 15 areas of CDH care, 459 underwent full-text review. Ultimately, 103 articles were used to inform 20 changes to existing recommendations, which included aspects related to prenatal diagnosis, echocardiographic evaluation, pulmonary hypertension management, surgical readiness criteria, the type of surgical repair and long-term health surveillance. Fifteen new CDH care recommendations were also created using this evidence, with most related to the management of pain and the provision of analgesia and neuromuscular blockade for patients with CDH.ConclusionsThe 2023 Canadian CDH Collaborative’s clinical practice guideline update provides a management framework for infants and children with CDH based on the best available evidence and expert consensus.
Two-year recall for people with no diabetic retinopathy: a multi-ethnic population-based retrospective cohort study using real-world data to quantify the effect
Authors: Olvera-Barrios Abraham , Rudnicka Alicja R , Anderson John , Bolter Louis , Chambers Ryan , Warwick Alasdair N , Welikala Roshan , Fajtl Jiri , Barman Sarah , Remagnino Paolo , Wu Yue , Lee Aaron Y , Chew Emily Y , Ferris Frederick L , Hingorani Aroon , Sofat Reecha , A. Egan Catherine , Tufail Adnan , Owen Christopher G 
Published: October 2023

Background/aims
The English Diabetic Eye Screening Programme (DESP) offers people living with diabetes (PLD) annual screening. Less frequent screening has been advocated among PLD without diabetic retinopathy (DR), but evidence for each ethnic group is limited. We examined the potential effect of biennial versus annual screening on the detection of sight-threatening diabetic retinopathy (STDR) and proliferative diabetic retinopathy (PDR) among PLD without DR from a large urban multi-ethnic English DESP.

Methods
PLD in North-East London DESP (January 2012 to December 2021) with no DR on two prior consecutive screening visits with up to 8 years of follow-up were examined. Annual STDR and PDR incidence rates, overall and by ethnicity, were quantified. Delays in identification of STDR and PDR events had 2-year screening intervals been used were determined.

Findings
Among 82 782 PLD (37% white, 36% South Asian, and 16% black people), there were 1788 incident STDR cases over mean (SD) 4.3 (2.4) years (STDR rate 0.51, 95% CI 0.47 to 0.55 per 100-person-years). STDR incidence rates per 100-person-years by ethnicity were 0.55 (95% CI 0.48 to 0.62) for South Asian, 0.34 (95% CI 0.29 to 0.40) for white, and 0.77 (95% CI 0.65 to 0.90) for black people. Biennial screening would have delayed diagnosis by 1 year for 56.3% (1007/1788) with STDR and 43.6% (45/103) with PDR. Standardised cumulative rates of delayed STDR per 100 000 persons for each ethnic group were 1904 (95% CI 1683 to 2154) for black people, 1276 (95% CI 1153 to 1412) for South Asian people, and 844 (95% CI 745 to 955) for white people.

Interpretation
Biennial screening would have delayed detection of some STDR and PDR by 1 year, especially among those of black ethnic origin, leading to healthcare inequalities.
Two-year MRI-defined structural damage and patient-reported outcomes following surgery or exercise for meniscal tears in young adults
Authors: Clausen Stine Haugaard , Skou Søren T , Boesen Mikael Ploug , Radev Dimitar Ivanon , Kurt Engin Yeter , Damsted Camma , Hölmich Per , Lind Martin , Tørring Sofus , Isaksen Christin , Varnum Claus , Englund Martin , Thorlund Jonas Bloch 
Published: October 2023

ObjectiveTo investigate potential differences in structural knee joint damage assessed by MRI and patient-reported outcomes (PROMs) at 2-year follow-up between young adults randomised to early surgery or exercise and education with optional delayed surgery for a meniscal tear.MethodsA secondary analysis of a multicentre randomised controlled trial including 121 patients (18–40 years) with an MRI-verified meniscal tear. For this study, only patients with 2-year follow-up were included. The main outcomes were the difference in worsening of structural knee damage, assessed by MRI using the Anterior Cruciate Ligament OsteoArthrits Score, and the difference in change in the mean score of four Knee Injury and Osteoarthritis Outcome Score (KOOS4) subscales covering pain, symptoms, function in sport and recreation, and quality of life, from baseline to 2 years.ResultsIn total, 82/121 (68%) patients completed the 2-year follow-up (39 from the surgical group and 43 from the exercise group). MRI-defined cartilage damage had developed or progressed in seven (9.1%) patients and osteophytes developed in two (2.6%) patients. The worsening of structural damage from baseline to 2-year follow-up was similar between groups. The mean (95% CI) adjusted differences in change in KOOS4between intervention groups from baseline to 2 years was −1.4 (−9.1, 6.2) points. The mean improvement in KOOS4was 16.4 (10.4, 22.4) in the surgical group and 21.5 (15.0, 28.0) in the exercise group. No between group differences in improvement were found in the KOOS subscales.ConclusionsThe 2-year worsening of MRI-defined structural damage was limited and similar in young adult patients with a meniscal tear treated with surgery or exercise with optional delayed surgery. Both groups had similar clinically relevant improvements in KOOS4, suggesting the choice of treatment strategy does not impact 2-year structural knee damage or PROMs.Trial registration numberNCT02995551.
Does the format of result presentation and type of conclusion in Cochrane plain language summaries matter? A randomised controlled trial
Authors: Prakash V , Gore Kirti , Shukla Gunjan , Tapiawala Priyanshi , Thakkar Smit 
Published: October 2023

ObjectivesThis study aimed to investigate whether the format and type of conclusion in Cochrane plain language summaries (PLSs) influence readers’ perception of treatment benefit and decision-making.DesignAn online parallel group, three-arm randomised controlled trial was conducted.SettingThe study was conducted online.ParticipantsThe participants were physiotherapy students.InterventionsThe participants read two Cochrane PLSs, one with a positive conclusion (strong evidence of benefit) and another with a negative conclusion (strong evidence of non-benefit). Each participant read the results of both reviews presented in one of three formats: (1) numerical, (2) textual or (3) numerical and textual.Main outcome measuresThe primary outcome measure was the participants’ perception of treatment benefit.ResultsAll three groups of participants perceived the treatment to have positive effects when the Cochrane PLS had a positive conclusion, regardless of the format of presentation (mean perception of treatment benefit score: textual 7.7 (SD 2.3), numerical 7.9 (SD 1.8), numerical and textual 7.7 (SD 1.7), p=0.362). However, when the Cochrane PLS had a negative conclusion, all three groups of participants failed to perceive a negative effect (mean perception of treatment benefit score: textual 5.5 (SD 3.3), numerical 5.6 (SD 2.7), numerical and textual 5.9 (SD 2.8), p=0.019).ConclusionsThe format of Cochrane PLSs does not appear to significantly impact physiotherapy students’ perception of treatment benefit, understanding of evidence, persuasiveness or confidence in their decision. However, participants’ perception of treatment benefit does not align with the conclusion when the Cochrane PLS indicates strong evidence of non-benefit from the intervention.Trial registration numberCTRI/2022/10/046476.