bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a Real-Time Single-Leg Hop Movement Quality Assessment to Identify Lower-Extremity Biomechanical Risk Factors
Authors: Herron Annabelle , Yom Jae , Grooms Dustin R. , Simon Janet E. 
Published: December 2024

Context: The single-leg hop is based solely on performance with no measure of movement quality. The purpose of this study was to (1) develop a real-time screening tool to capture single-leg functional performance and movement quality and (2) to provide preliminary validation (criterion validity) of a trained clinician’s real-time movement quality assessment with 3D kinematics. Study Design: Cross-sectional. Methods: Fifty-nine adolescent athletes volunteered (15.2 [1.1] y, 165.8 [9.2] cm, and 61.5 [13.9] kg, 51 females and 8 males). Each participant performed 3 trials of the single-leg hop on their dominant leg. A 3-dimensional inertial measurement system was used to capture knee joint kinematics. A movement quality checklist for use during a single-leg hop (movement quality single-leg hop) was developed to score biomechanical errors based on lower-extremity injury risk factors. Four criteria were developed for the checklist: (1) knee valgus, (2) foot rotation, (3) lateral trunk flexion, and (4) erect posture. An independent t test was conducted for each dependent variable (knee flexion displacement and knee abduction displacement) by each independent variable (movement category presence of (1) lateral trunk flexion, (2) knee valgus, (3) foot rotation, and (4) erect posture/sound during landing [yes or no]). The alpha level was set at α < .05 for all analyses. Results: Knee flexion displacement was significantly decreased (P < .001, mean difference 9.40 [1.88]) and knee abduction displacement was significantly increased (P < .001, mean difference 9.41 [0.47]) for those who had knee valgus documented by the clinician. In additional, for those with visually documented erect posture/sound of landing, there was a significant decrease in knee flexion displacement (P < .001, mean difference 10.13 [2.34]). Conclusion: The movement quality single-leg hop checklist has shown promising preliminary validation (criterion validity) for clinicians to assess movement quality. Increased knee abduction and decreased knee flexion are common risk factors associated with knee injuries and this clinician friendly real-time checklist may highlight individuals who are at risk of sustaining a knee injury.
TolCV1 inhibition by NPPB renders
Vibrio vulnificus
less virulent and more susceptible to antibiotics
Authors: Gong Yue , Jiang Rui , Guo Rui Hong , Jo Se Jin , Jeong Hyeongju , Moon Kyuho , Rhee Joon Haeng , Kim Young Ran 
Published: December 2024

ABSTRACT

Bacterial efflux pumps play important roles in the antibiotic resistance and excretion of virulence factors. We previously characterized that TolCV1, a component of efflux pumps, plays critical roles in resistance to antibiotics and bile and also RtxA1 toxin secretion of
Vibrio vulnificus
. In this context, we speculated that TolCV1 blockers would have a dual effect of enhancing susceptibility to antibiotics and suppressing virulence of
V. vulnificus
. Here, we show that the chloride channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) increases susceptibility to antibiotics and suppresses cytotoxicity of
V. vulnificus
through inhibition of TolCV1. NPPB significantly decreased TolCV1 in
V. vulnificus
cells by liberating the protein from the cell body. Checkerboard assay showed that NPPB enhanced the antimicrobial activities of antibiotics such as kanamycin, tetracycline, erythromycin, and ampicillin against
V. vulnificus
. Moreover, NPPB inhibited the secretion of RtxA1 toxin and protected host cells from
V. vulnificus
-induced cytotoxicity. In addition, NPPB markedly suppressed
V. vulnificus
growth in the presence of bile salts and enhanced the therapeutic effect of tetracycline in
V. vulnificus
-infected mice. The safety and efficacy of NPPB were confirmed at the cellular and animal levels. Collectively, TolCV1 inhibition by NPPB renders
V. vulnificus
less virulent and more susceptible to antibiotics.
Evaluation of a potent LpxC inhibitor for post-exposure prophylaxis treatment of antibiotic-resistant
Burkholderia pseudomallei
in a murine infection model
Authors: Heine Henry S. , Purcell Bret K. , Duncan Clayton , Miller Lynda , Craig John E. , Chase Amanda , Honour Lynne , Vicchiarelli Michael , Drusano George L. , Zhou Pei 
Published: December 2024

ABSTRACT

LPC-233 (a.k.a. VB-233) is a potent antibiotic targeting the essential enzyme LpxC in Gram-negative bacteria. We present herein the pharmacokinetics and pharmacodynamics data of LPC-233 for treating murine infections caused by
Burkholderia pseudomallei
, a potential biodefense pathogen. A range of doses was evaluated in a post-aerosol exposure model of
B. pseudomallei
-infected mice. After the aerosol challenge with the
B. pseudomallei
strain K96243, treatment was initiated with 10, 30, or 90 mg/kg of LPC-233 orally every 12 h (q12h) or 90 mg/kg intraperitoneally q12h for 14 days. A vehicle-control arm and a positive-control arm consisting of one of the recommended standards of care, ceftazidime (150 mg/kg, q6h) injected subcutaneously, were included. LPC-233 significantly and dose-dependently rescued mice from
B. pseudomallei
infection in comparison with the vehicle (
P
< 0.0001). At dose levels of 30 mg/kg or higher, the survival rate with LPC-233 was significantly higher than that from the ceftazidime arm (
P
range: 0.001–0.05). LPC-233 reversed the murine body weight loss caused by the
B. pseudomallei
infection more rapidly than ceftazidime did, suggesting that it is a faster-acting antibiotic in this dosing regimen. Despite the outstanding survival advantage of LPC-233 over ceftazidime, no significant differences in tissue burdens (liver, lung, spleen, and blood) were observed among any of the treatment groups surviving to the termination of the experiment, suggesting that similar to commercial antibiotics, LPC-233 treatment for lethal
B. pseudomallei
infection may likely require both an acute phase of intensive treatment and an eradication phase of prolonged treatment.
In vitro
test of the novel antibiotic lefamulin alone and in combination with doxycycline against
Mycoplasma genitalium
Authors: Salado-Rasmussen Kirsten , Nørgaard Christina , Pedersen Thomas Roland , Paukner Susanne , Jensen Jørgen Skov 
Published: December 2024

ABSTRACT

Mycoplasma genitalium
, a sexually transmitted bacterium, is a significant cause of urethritis in men and various reproductive tract infections in women, including cervicitis, pelvic inflammatory disease, endometritis, and potentially infertility. Treatment has become increasingly challenging due to the emergence of resistance to both first-line (azithromycin) and second-line (moxifloxacin) antibiotics. The need for new treatment options is critical. This study evaluates the
in vitro
efficacy of the novel antibiotic lefamulin against 54
M
.
genitalium
isolates, including highly resistant variants. Additionally, the potential synergistic effects of combining lefamulin with doxycycline were assessed in eight selected isolates. Lefamulin exhibited strong antibacterial activity across all tested isolates, with minimal inhibitory concentrations (MICs) ranging from 0.0005 to 0.064 µg/mL. Minimal bactericidal concentrations ranged from 0.001 to 0.128 µg/mL and were equal to the MIC in 40 of 54 isolates and within two- and fourfold MIC in the rest of the isolates. Notably, lefamulin’s MIC values were significantly lower than those of azithromycin, doxycycline, and moxifloxacin, underscoring its potent efficacy. Checkerboard assays revealed no antagonistic interaction between lefamulin and doxycycline, with some additive effects observed in certain isolates. These findings highlight lefamulin’s potential as a highly effective treatment for
M. genitalium
infections, particularly those involving multi-drug-resistant strains. Given the increasing rates of resistance and the limitations of current therapies, lefamulin may represent a promising new option for managing this challenging pathogen. Further clinical studies are warranted to confirm these
in vitro
results and explore the therapeutic potential of lefamulin in combination with doxycycline.
RhlR-mediated cooperation in cystic fibrosis-adapted isolates of
Pseudomonas aeruginosa
Authors: Cruz Renae L. , Freeman Tiia S. , Asfahl Kyle L. , Smalley Nicole E. , Dandekar Ajai A. 
Published: December 2024

ABSTRACT

Pseudomonas aeruginosa
uses quorum sensing (QS) to regulate the expression of dozens of genes, many of which encode shared products, called “public goods.”
P. aeruginosa
possesses two complete acyl-homoserine lactone (AHL) QS circuits: the LasR-I and RhlR-I systems. Canonically, these systems are hierarchically organized: RhlR-I activity depends on LasR-I activation. However, in contrast to laboratory strains, isolates from people with cystic fibrosis can engage in AHL QS using only the transcription factor RhlR. In these isolates, RhlR regulates AHL QS and the production of secreted public goods, such as the exoprotease elastase, which are accessible to both producing and non-producing cells. When
P. aeruginosa
strains that use LasR to regulate elastase production are grown on casein as the sole carbon and energy source, LasR-null mutant “cheaters” commonly arise in populations due to a selective growth advantage. We asked if these social dynamics might differ in “RhlR cooperators”: populations that use RhlR, not LasR, to regulate public goods. We passaged RhlR cooperators from several genetic backgrounds in casein broth. We found that cheaters emerged among most RhlR cooperators. However, in one isolate background, E90, RhlR-null mutants were dramatically outcompeted by RhlR cooperators. In this background, the mechanism by which RhlR mutants are outcompeted by RhlR cooperators is AHL-dependent and occurs in stationary phase but is not the same as previously described “policing” mechanisms. Our data suggest that cheating, or the lack thereof, does not explain the lack of RhlR mutants observed in most infection environments.

IMPORTANCE

Quorum sensing (QS) mutants arise in a variety of populations of bacteria, but mutants of the gene encoding the transcription factor RhlR in
Pseudomonas aeruginosa
appear to be infrequent. Our work provides insight on the mechanisms through which RhlR-mediated cooperation is maintained in a LasR-null population of
P. aeruginosa
. Characterizing the selective pressure(s) that disfavor mutations from occurring in RhlR may enhance our understanding of
P. aeruginosa
evolution in chronic infections and potentially guide the development of therapeutics targeting the RhlR-I QS circuit.
SbcB facilitates natural transformation in
Vibrio cholerae
in an exonuclease-independent manner
Authors: Dalia Triana N. , Dalia Ankur B. 
Published: December 2024

ABSTRACT

Natural transformation (NT) is a conserved mechanism of horizontal gene transfer in bacterial species. During this process, DNA is taken up into the cytoplasm where it can be integrated into the host genome by homologous recombination. We have previously shown that some cytoplasmic exonucleases inhibit NT by degrading ingested DNA prior to its successful recombination. However, one exonuclease, SbcB, counterintuitively promotes NT in
Vibrio cholerae
. Here, through a systematic analysis of the distinct steps of NT, we show that SbcB acts downstream of DNA uptake into the cytoplasm, but upstream of recombinational branch migration. Through mutational analysis, we show that SbcB promotes NT in a manner that does not rely on its exonuclease activity. Finally, we provide genetic evidence that SbcB directly interacts with the primary bacterial recombinase, RecA. Together, these data advance our molecular understanding of horizontal gene transfer in
V. cholerae
and reveal that SbcB promotes homologous recombination during NT in a manner that does not rely on its canonical exonuclease activity.

IMPORTANCE

Horizontal gene transfer by natural transformation contributes to the spread of antibiotic resistance and virulence factors in bacterial species. Here, we study how one protein, SbcB, helps facilitate this process in the facultative bacterial pathogen
Vibrio cholerae
. SbcB is a well-known for its exonuclease activity (i.e., the ability to degrade the ends of linear DNA). Through this study, we uncover that while SbcB is important for natural transformation, it does not facilitate this process using its exonuclease activity. Thus, this work helps further our understanding of the molecular events required for this conserved evolutionary process and uncovers a function for SbcB beyond its canonical exonuclease activity.
The
Campylobacter jejuni
BumS sensor phosphatase detects the branched short-chain fatty acids isobutyrate and isovalerate as direct cues for signal transduction
Authors: Ruiz Nestor , Xing Jiawei , Zhulin Igor B. , Brautigam Chad A. , Hendrixson David R. 
Published: December 2024

ABSTRACT

Two-component signal transduction systems (TCSs) are nearly ubiquitous across bacterial species and enable bacteria to sense and respond to specific cues for environmental adaptation. The
Campylobacter jejuni
BumSR TCS is unusual in that the BumS sensor exclusively functions as a phosphatase rather than a kinase to control phosphorylated levels of its cognate BumR response regulator (P-BumR). We previously found that BumSR directs a response to the short-chain fatty acid butyrate generated by resident microbiota so that
C. jejuni
identifies ideal lower intestinal niches in avian and human hosts for colonization. However, butyrate is an indirect cue for BumS and did not inhibit
in vitro
BumS phosphatase activity for P-BumR. In this work, we expanded the repertoire of lower intestinal metabolites that are cues sensed by BumS that modulate the expression of genes required for colonization to include the branched short-chain fatty acids isobutyrate and isovalerate. Unlike butyrate, isobutyrate and isovalerate inhibited
in vitro
BumS phosphatase activity for P-BumR, indicating that these metabolites are direct cues for BumS. Isobutyrate and isovalerate reduced the thermostability of BumS and caused a reorganization of protein structure to suggest how sensing these cues inhibits phosphatase activity. We also identified residues in the BumS sensory domain required to detect isobutyrate, isovalerate, and butyrate and for optimal colonization of hosts to reveal how gut bacteria can recognize these intestinal metabolites. Our work reveals how this unusual bacterial sensor phosphatase senses a repertoire of intestinal metabolites and how cues alter BumSR signal transduction to influence
C. jejuni
colonization of hosts.

IMPORTANCE

TCSs are prevalent in many bacteria, but the cues sensed by each are not actually known for many of these systems. Microbiota-generated butyrate in human and avian hosts is detected by the
Campylobacter jejuni
BumS sensor phosphatase so that the bacterium identifies ideal lower intestinal niches for colonization. However, BumS only indirectly senses butyrate to inhibit dephosphorylation of its cognate BumR response regulator. Here, we expanded the repertoire of cues sensed by BumS to the branched-short chain fatty acids isobutyrate and isovalerate that are also abundant in the lower intestines. Both isobutyrate and isovalerate are potent, direct cues for BumS, whereas butyrate is an indirect cue. Leveraging isobutyrate and isovalerate as direct cues, we reveal BumS structure is altered upon cue detection to inhibit its phosphatase activity. We provide an understanding of the mechanics of an unusual mode of signal transduction executed by BumSR and other bacterial sensor phosphatase-driven TCSs.
Complete genomes of
Salmonella
and draft genome of
Escherichia
isolates from oysters collected in Canada
Authors: Shutinoski Bojan , Flint Annika , Tamber Sandeep , Weedmark Kelly , Banerjee Swapan 
Published: December 2024

ABSTRACT

Human enteric pathogens in fresh uncooked seafood are of concern to human health. Here, we report the complete genomes of bacteria not commonly found in freshly harvested seafood, two
Salmonella
Typhimurium strains and one draft
Escherichia coli
genome, isolated from harvested oysters grown in Canada.
Draft genome of a
Bacillus subtilis
ICS isolated from an okra (
Abelmoschus esculentus
) extract exhibited genes related to plant growth-promoting potential
Authors: Gloria Paul Christian T. , Luague Ma. Jhanessa A. , Siringan Maria Auxilia T. , Argayosa Vina B. 
Published: December 2024

ABSTRACT

Here, we report the draft genome of
Bacillus subtilis
ICS isolated from the aqueous extract of
Abelmoschus esculentus
. The isolate has a genome size of 4.15 Mb, 43.07% GC, 99.8% BUSCO completeness, and 91.15% CheckM completeness. The genome exhibited genes related to plant growth promotion and secondary metabolite production.
Draft genomes of two contemporary strains of
Babesia divergens
Authors: Apaa Ternenge T. , Jones Ben P. , Blanchard Adam M. , Johnson Nicholas 
Published: December 2024

ABSTRACT

Babesia divergens
,
a
major cause of bovine babesiosis with zoonotic potential, was analyzed through genomes Bdiv23B and Bdiv24B following Illumina sequencing of DNA extracted from PCR-positive cattle blood. The genomes comprised 3888 and 4032 predicted coding sequences, respectively, comparable to the reference genome, Rouen 1987, highlighting genomic consistency across isolates.
Human adenovirus species B knob proteins as immunogens for inducing cross-neutralizing antibody responses
Authors: Liu Zhenwei , Xian Yuting , Lan Jixian , Zhou Zhichao , Li Xiao , Zhou Rong , Chen Dehui , Tian Xingui 
Published: December 2024

ABSTRACT

The re-emerging human adenovirus (HAdV) types 3, 7, 14, and 55 of species B have caused severe or even fatal acute respiratory disease. Therefore, the development of multivalent vaccines against HAdV types 3, 7, 14, and 55 remains an important goal. In our previous study, we identified a cross-neutralizing epitope that induced broadly reactive monoclonal neutralizing antibodies against the knob proteins of HAdV types 7, 11, 14, and 55. To study the immunogenicity of HAdV species B knob proteins, we evaluated humoral immune responses to the knob proteins
in vivo
and
in vitro
. We found that the knob proteins elicited robust binding and neutralizing antibody responses after three immunizations of mice. In addition, mouse antisera raised against the knob proteins exhibited cross-neutralizing activity against original species B members. Furthermore, immunization with a mix of HAdV-3, 7, and 55 knob proteins protected Chinese tree shrews against an experimental HAdV challenge. Our results provide insight into the immunogenicity of HAdV species B knob proteins.

IMPORTANCE
Human adenovirus (HAdV) species B are common pathogens causing severe pneumonia in children, and there is currently no vaccine available. Because there are many HAdV species B types, developing broad-spectrum vaccines against HAdV species B is an important research goal. Our study revealed that immunization with recombinant HAdV species B knob proteins effectively elicited cross-neutralizing antibody responses against original species B members with protective immunity. This study provides a novel insight into the immunogenicity of HAdV species B knob proteins.
Exploring the genomic and antimicrobial resistance tapestry: comparative insights into
Salmonella enterica
serotypes Agona, Braenderup, Muenchen, and Panama in Latin American surface waters
Authors: Chen Zhao , Delgado Suárez Enrique J. , Bonelli Raquel R. , Oliveira Celso J. B. , Moreno-Switt Andrea I. , Adell Aiko D. , Reyes-Jara Angélica , Grim Christopher J. , Allard Marc W. , Tallent Sandra M. , Brown Eric W. , Bell Rebecca L. , Toro Magaly , Meng Jianghong 
Published: December 2024

ABSTRACT

Surface waters function as ecological niches where
Salmonella enterica
can persist and disseminate to fresh produce production systems. We examined the genomic characteristics of
S. enterica
serotypes Agona (
n
= 86), Braenderup (
n
= 47), Muenchen (
n
= 53), and Panama (
n
= 69) isolates from surface waters in Chile, Mexico, and Brazil between 2019 and 2022. Mexican isolates consistently displayed a higher occurrence of genotypic antimicrobial resistance (AMR) than Chilean and Brazilian isolates. All
S
. Agona isolates exhibited the presence of
fosA7.2
, while
qnrB19
emerged as the predominant AMR gene (ARG) among
S
. Braenderup isolates.
S
. Muenchen isolates from Chile displayed an absence of any ARGs, while those from Mexico and Brazil predominantly carried
qnrB19
. Among
S
. Panama isolates from Chile,
aadA1
,
floR
,
sat2
, and
tet(B
) were the most prevalent ARGs, whereas those from Mexico and Brazil harbored
tet(A
), and
floR
and
tet(A
) as the leading ARGs, respectively. ARG sharing among isolates and ARG co-occurrence within individual isolates were prevalent across countries and serotypes. All isolates containing integrons exhibited genotypic multidrug resistance. The principal coordinates analysis reveals distinct clustering patterns based on country, serotype, number of ARGs per isolate, and plasmid and integron presence/absence. The whole-genome phylogenetic analysis demonstrates clear clusters, each associated with their respective countries. However, a notable exception was observed with one
S
. Agona isolate from Brazil closely related to two isolates from Chile, differing by only 18 and 19 single-nucleotide polymorphisms, respectively.

IMPORTANCE

This comprehensive study explored the intricate genomic landscapes of
S
. Agona, Braenderup, Muenchen, and Panama isolates from surface waters across Chile, Mexico, and Brazil. By filling important knowledge gaps related to the genomic characteristics of these serotypes, the research offers a nuanced understanding of these serotypes as potential reservoirs for multidrug resistance. Our findings emphasize the urgency of targeted interventions to mitigate the emergence and dissemination of multidrug-resistant
Salmonella enterica
. This work underscores the need for informed policies and collaborative efforts to address the risks posed by
S. enterica
in Latin American surface waters.
Inferior rectus muscle detachment during strabismus surgery has a major effect on anterior segment perfusion, as shown by LSCI perfusion monitoring
Authors: Engqvist Linn , Öhnell HannaMaria , Nygren Ella , Merdasa Aboma , Sheikh Rafi , Dahlstrand Ulf , Malmsjö Malin 
Published: December 2024

BackgroundAnterior segment ischaemia (ASI) is a rare but feared complication associated with strabismus surgery, arising from damage of the anterior ciliary arteries that run along the extraocular rectus muscles. It has been reported that the risk of ASI following strabismus surgery increases when the vertical rectus muscles are involved. The aim of the present study was to monitor anterior segment perfusion in real time during inferior rectus muscle surgery.Methods17 eyes in 16 patients undergoing surgery on the inferior rectus muscle were included. Perfusion was measured in the adjacent paralimbal and iris tissue, before and after inferior rectus muscle detachment, using laser speckle contrast imaging.ResultsThe paralimbal vascular network was clearly visualised in the perfusion images, whereas the signals from the iris were lower. Detachment of the inferior rectus muscle resulted in a reduction in paralimbal and iris perfusion by a median of 33% (p<0.0001) and 11% (p=0.0174), respectively.ConclusionStrabismus surgery involving the inferior rectus muscle significantly affects perfusion to the anterior segment, and to a greater extent than previously observed following surgery on horizontal rectus muscles (where the decrease was only 23% and 5%).