bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tools to assess the risk of bias of evidence syntheses: a scoping review protocol
Authors: Hasanoff Sabira , Pollock Danielle , Barker Timothy H. , Munn Zachary 
Published: December 2023

Objective:
The aim of this scoping review is to identify and examine risk of bias tools, critical appraisal tools, and/or assessment of methodological quality tools (including their items and domains) developed to assess all types of evidence syntheses.

Introduction:
Evidence synthesis is often the basis for policies, procedures, decisions, and evidence-based practice. It is imperative that evidence syntheses are of good quality, reproducible, and reliable. Despite methodological advancements, there remains a substantial risk that bias is present in the conduct of an evidence synthesis project, hindering the validity and reliability of the findings. One way to assess bias is through formal tools and assessments for assessing the risk of bias and/or methodological quality.

Inclusion criteria:
Published and unpublished papers presenting a risk of bias, critical appraisal, or methodological quality assessment tool for assessing an evidence synthesis will be included. Individual umbrella reviews proposing a de novo tool or modified tool will be excluded from the review, as will texts that do not present a tool.

Methods:
A 3-step search strategy will be conducted to locate both published and unpublished documents. An initial search of PubMed was developed with a librarian, which identified keywords and MeSH terms. A second search of MEDLINE (Ovid), CINAHL (EBSCOhost), Embase (Ovid), Scopus, and Compendex will follow. Websites and databases, including Google, Cochrane, and JBI, will be searched for difficult-to-locate and unpublished literature. Documents will be independently screened, selected, and extracted by 2 researchers, and the data will be presented narratively and in tables.

Review registration:
Open Science Framework osf.io/mjcfy
Cardiac nitric oxide scavenging: role of myoglobin and mitochondria
Authors: Giles Abigail V. , Edwards Lanelle , Covian Raul , Lucotte Bertrand M. , Balaban Robert S. 
Published: December 2023

AbstractVascular production of nitric oxide (NO) regulates vascular tone. However, highly permeable NO entering the cardiomyocyte would profoundly impact metabolism and signalling without scavenging mechanisms. The purpose of this study was to establish mechanisms of cardiac NO scavenging. Quantitative optical studies of normoxic working hearts demonstrated that micromolar NO concentrations did not alter mitochondria redox state or respiration despite detecting NO oxidation of oxymyoglobin to metmyoglobin. These data are consistent with proposals that the myoglobin/myoglobin reductase (Mb/MbR) system is the major NO scavenging site. However, kinetic studies in intact hearts reveal a minor role (∼9%) for the Mb/MbR system in NO scavenging. In vitro, oxygenated mitochondria studies confirm that micromolar concentrations of NO bind cytochrome oxidase (COX) and inhibit respiration. Mitochondria had a very high capacity for NO scavenging, importantly, independent of NO binding to COX. NO is also known to quickly react with reactive oxygen species (ROS) in vitro. Stimulation of NO scavenging with antimycin and its inhibition by substrate depletion are consistent with NO interacting with ROS generated in Complex I or III under aerobic conditions. Extrapolating these in vitro data to the intact heart supports the hypothesis that mitochondria are a major site of cardiac NO scavenging.
imageKey points
Cardiomyocyte scavenging of vascular nitric oxide (NO) is critical in maintaining normal cardiac function.
Myoglobin redox cycling via myoglobin reductase has been proposed as a major NO scavenging site in the heart.
Non‐invasive optical spectroscopy was used to monitor the effect of NO on mitochondria and myoglobin redox state in intact beating heart and isolated mitochondria.
These non‐invasive studies reveal myoglobin/myoglobin reductase plays a minor role in cardiac NO scavenging.
A high capacity for NO scavenging by heart mitochondria was demonstrated, independent of cytochrome oxidase binding but dependent on oxygen and high redox potentials consistent with generation of reactive oxygen species.
Identification of Spalling Fault Size of Ball Bearing Based on Modified Energy Value
Authors: Zhang Ke , Zhang Ru , Wang Zinan , Bai Xiaotian , Shi Huaitao 
Published: December 2023

Abstract
The size of bearing outer ring spalling failures has a significant impact on the vibration and service life of rotating machinery. It is necessary to judge the size of the outer ring fault size. Most of the vibration analyses identify the bearing fault size only in terms of the shock interval. The decreasing impact of the shock on the vibration signal will be related to the identification accuracy of the shock interval. This study aims to identify some feasible vibration signal processing methods for the identification of outer ring spalling sizes of ball bearings based on a modified energy value. The method involves the influence of impact forces on the measured vibration characteristics. According to the simulation analysis, the mapping relationship between the vibration signals with different fault sizes and the modified energy value is obtained. Then, the size of the spalling failure size of the ball-bearing outer ring is determined. Compared to existing methods, the proposed method is less affected by impact forces. Simulation and experiment results have verified the accuracy of this fault size identification.
Regulation of chlamydial spreading from the small intestine to the large intestine by IL-22-producing CD4
+
T cells
Authors: Xu Ying , Wang Yihui , Winner Halah , Yang Huijie , He Rongze , Wang Jie , Zhong Guangming 
Published: December 2023

ABSTRACT

Following an oral inoculation,
Chlamydia muridarum
descends to the mouse large intestine for long-lasting colonization. However, a mutant
C. muridarum
that lacks the plasmid-encoded protein pGP3 due to an engineered premature stop codon (designated as CMpGP3S) failed to do so even following an intrajejunal inoculation. This was because a CD4
+
T cell-dependent immunity prevented the spread of CMpGP3S from the small intestine to the large intestine. In the current study, we found that mice deficient in IL-22 (IL-22
−/−
) allowed CMpGP3S to spread from the small intestine to the large intestine on day 3 after intrajejunal inoculation, indicating a critical role of IL-22 in regulating the chlamydial spread. The responsible IL-22 is produced by CD4
+
T cells since IL-22
−/−
mice were rescued to block the CMpGP3S spread by donor CD4
+
T cells from C57BL/6J mice. Consistently, CD4
+
T cells lacking IL-22 failed to block the spread of CMpGP3S in Rag2
−/−
mice, while IL-22-competent CD4
+
T cells did block. Furthermore, mice deficient in cathelicidin-related antimicrobial peptide (CRAMP) permitted the CMpGP3S spread, but donor CD4
+
T cells from CRAMP
−/−
mice were still sufficient for preventing the CMpGP3S spread in Rag2
−/−
mice, indicating a critical role of CRAMP in regulating chlamydial spreading, and the responsible CRAMP is not produced by CD4
+
T cells. Thus, the IL-22-producing CD4
+
T cell-dependent regulation of chlamydial spreading correlated with CRAMP produced by non-CD4
+
T cells. These findings provide a platform for further characterizing the subset(s) of CD4
+
T cells responsible for regulating bacterial spreading in the intestine.
An inhibitor/anti-inhibitor system controls the activity of lytic transglycosylase MltF in
Pseudomonas aeruginosa
Authors: Wang Michelle , Xiao Ma Sheya , Darwin Andrew J. 
Published: December 2023

ABSTRACT

Most bacterial cell envelopes contain a cell wall layer made of peptidoglycan. The synthesis of new peptidoglycan is critical for cell growth, division, and morphogenesis and is also coordinated with peptidoglycan hydrolysis to accommodate the new material. However, the enzymes that cleave peptidoglycan must be carefully controlled to avoid autolysis. In recent years, some control mechanisms have begun to emerge, although there are many more questions than answers for how most cell wall hydrolases are regulated. Here, we report a novel cell wall hydrolase control mechanism in
Pseudomonas aeruginosa
, which we discovered during our characterization of a mutant sensitive to the overproduction of a secretin protein. The mutation affected an uncharacterized Sel1-like repeat protein encoded by the PA3978 locus. In addition to the secretin-sensitivity phenotype, PA3978 disruption also increased resistance to a β-lactam antibiotic used in the clinic.
In vivo
and
in vitro
analyses revealed that PA3978 binds to the catalytic domain of the lytic transglycosylase MltF and inhibits its activity. ∆PA3978 mutant phenotypes were suppressed by deleting
mltF
, consistent with them having been caused by elevated MltF activity. We also discovered another interaction partner of PA3978 encoded by the PA5502 locus. The phenotypes of a ∆PA5502 mutant suggested that PA5502 interferes with the inhibitory function of PA3978 toward MltF, and we confirmed that activity for PA5502
in vitro
. Therefore, PA3978 and PA5502 form an inhibitor/anti-inhibitor system that controls MltF activity. We propose to name these proteins IltA (
i
nhibitor A of
l
ytic
t
ransglycosylase) and LiiA (
l
ytic transglycosylase
i
nhibitor A’s
i
nhibitor).

IMPORTANCE

A peptidoglycan cell wall is an essential component of almost all bacterial cell envelopes, which determines cell shape and prevents osmotic rupture. Antibiotics that interfere with peptidoglycan synthesis have been one of the most important treatments for bacterial infections. Peptidoglycan must also be hydrolyzed to incorporate new material for cell growth and division and to help accommodate important envelope-spanning systems. However, the enzymes that hydrolyze peptidoglycan must be carefully controlled to prevent autolysis. Exactly how this control is achieved is poorly understood in most cases but is a highly active area of current research. Identifying hydrolase control mechanisms has the potential to provide new targets for therapeutic intervention. The work here reports the important discovery of a novel inhibitor/anti-inhibitor system that controls the activity of a cell wall hydrolase in the human pathogen
Pseudomonas aeruginosa
, which also affects resistance to an antibiotic used in the clinic.
Efficacy of EHEC gold nanoparticle vaccines evaluated with the Shiga toxin-producing
Citrobacter rodentium
mouse model
Authors: Bowser Sarah , Melton-Celsa Angela , Chapartegui-González Itziar , Torres Alfredo G. 
Published: December 2023

ABSTRACT

Enterohemorrhagic
Escherichia coli
(EHEC) is a group of pathogenic bacteria responsible for several foodborne-associated outbreaks of human diarrheal disease. Although EHEC is a major cause of morbidity as well as the condition known as hemolytic uremic syndrome, linked to the production of Shiga toxins (Stx), there are no licensed vaccines approved for human use. Fully assessing vaccine efficacy against EHEC infections is challenging because conventional adult mice are inherently resistant to EHEC infection and do not develop hallmark symptoms of the disease. Therefore, in this study, we utilized a strain of the murine pathogen
Citrobacter rodentium
that has been lysogenized to produce Stx2d, which consistently causes lethal infection and other measurable disease outcomes following oral challenge, to further evaluate the protective efficacy of our previously formulated EHEC gold nanoparticle (AuNP) vaccines. Using this model, along with a non-Stx2d-producing
C. rodentium
strain, we assessed the protection conferred by AuNPs conjugated to three EHEC antigens: EscC, LomW, and intimin (Eae). We demonstrated that intranasally immunizing mice with AuNP-Eae provides partial protection against mortality caused by Stx2d-producing
C. rodentium
and that AuNP-EscC and AuNP-Eae moderately reduce intestinal burden of the non-Stx2d-producing
C. rodentium
strain compared with adjuvant-only-treated mice. Additionally, the AuNP-protein vaccines induced antigen- and pathogen-specific serum IgG and fecal IgA against both EHEC and
C. rodentium
while
in vitro
functional assays indicate that the elicited antibodies are bactericidal and prevent adherence of
C. rodentium
to intestinal epithelial cells. We propose that
C. rodentium
murine data could translate into correlates of protection.

IMPORTANCE

Enterohemorrhagic
Escherichia coli
(EHEC) remains an important cause of diarrheal disease and complications worldwide, especially in children, yet there are no available vaccines for human use. Inadequate pre-clinical evaluation due to inconsistent animal models remains a major barrier to novel vaccine development. We demonstrate the usefulness of Stx2d-producing
Citrobacter rodentium
in assessing vaccine effectiveness because it more closely recapitulates human disease caused by EHEC.
Combined usage of serodiagnosis and O antigen typing to isolate Shiga toxin-producing
Escherichia coli
O76:H7 from a hemolytic uremic syndrome case and genomic insights from the isolate
Authors: Lee Kenichi , Iguchi Atsushi , Terano Chikako , Hataya Hiroshi , Isobe Junko , Seto Kazuko , Ishijima Nozomi , Akeda Yukihiro , Ohnishi Makoto , Iyoda Sunao ,   EHEC Working Group in Japan, Morimoto Yo , Ogawa Keiko , Ishiguro Makoto , Kikuchi Masayuki , Sampei Mika , Aoki Yoko , Seto Junji , Ishikawa Kanako , Sato Takashi , Kikuchi Koji , Tomari Kentaro , Ueno Hiroyuki , Hazama Kyoko , Kikuchi Takashi , Yajima Masayuki , Kanazawa Satoko , Kawase Masao , Kimata Keiko , Yuruzume Saya , Shiroza Mika , Kitagawa Emiko , Yoshikawa Misa , Yokoyama Koji , Ono Satoko , Furukawa Yumi , Matsuyama Miki , Furuta Ayako , Noda Makiko , Kameyama Yoshihiko , Aota Tatsuaki , Katamune Chiharu , Shimoda Yuko , Abe Yuri , Tamura Sawako , Furukawa Yurika , Obara Atsumi 
Published: December 2023

ABSTRACT

Minor O-serogroups of Shiga toxin-producing
Escherichia coli
(STEC) can cause severe clinical complications in humans, including hemolytic uremic syndrome (HUS). However, detection and isolation of these minor serogroups of STEC are challenging due to the lack of specific isolation methods. Here, we present a case of HUS in which STEC was not isolated by routine diagnostic tests for the major serotypes. Therefore, we tried a new diagnostic and isolation method that combines PCR screening, immunomagnetic bead separation, and serum agglutination tests and successfully isolated STEC O76. Subsequent genomic analyses of the STEC O76 isolates revealed that several isolates of this serogroup carrying
stx2
were related to severe infections. The complete genome of the HUS-derived isolates provided two important implications. First, using a complete genome as a reference in core genome single nucleotide polymorphism analysis leads to the highest resolution of the analysis. Second, the HUS-derived STEC O76:H7 possessed two copies of Stx2a prophages, and one of them showed a “prophage integrating into prophage” structure, as described in STEC O145:H28. These results demonstrate that our detection methods contribute to the diagnosis and isolation of minor serogroups of STECs and complete genomic analyses can illuminate the pathogenic potential of STECs.

IMPORTANCE

Hemolytic uremic syndrome (HUS) is a life-threatening disease caused by Shiga toxin-producing
Escherichia coli
(STEC) infection. The treatment approaches for STEC-mediated typical HUS and atypical HUS differ, underscoring the importance of rapid and accurate diagnosis. However, specific detection methods for STECs other than major serogroups, such as O157, O26, and O111, are limited. This study focuses on the utility of PCR-based O-serotyping, serum agglutination tests utilizing antibodies against the identified Og type, and isolation techniques employing antibody-conjugated immunomagnetic beads for STEC isolation. By employing these methods, we successfully isolated a STEC strain of a minor serotype, O76:H7, from a HUS patient.
Nanosecond pulsed electric fields increase antibiotic susceptibility in methicillin-resistant
Staphylococcus aureus
Authors: Chittams-Miles Alexandra E. , Malik Areej , Purcell Erin B. , Muratori Claudia 
Published: December 2023

ABSTRACT

Staphylococcus aureus
is the leading cause of skin and soft-tissue infections (SSTIs). SSTIs caused by bacteria resistant to antimicrobials, such as methicillin-resistant
S. aureus
(MRSA), are increasing in incidence and have led to higher rates of hospitalization. In this study, we measured MRSA inactivation by nanosecond pulsed electric fields (nsPEF), a promising new cell ablation technology. Our results show that treatment with 120 pulses of 600 ns duration (28 kV/cm, 1 Hz), caused modest inactivation, indicating cellular damage. We anticipated that the perturbation created by nsPEF could increase antibiotic efficacy if nsPEF were applied as a co-treatment. To test this hypothesis, we used three antibiotics approved to treat SSTI, daptomycin, doxycycline, and vancomycin, and compared the cytotoxic effects of these antibiotics administered either before or after nsPEF. Co-treatment with nsPEF and daptomycin greatly potentiated the effects of each monotherapy regardless of their order. Conversely, the sensitivity of MRSA to both doxycycline and vancomycin was increased only when nsPEF preceded the antibiotic incubation. Finally, MRSA cells grown in biofilms were efficiently killed by co-treatment with nsPEF/vancomycin, suggesting that their mutual enhancement is maintained even when treating sessile communities known for their inherent antimicrobial resistance. Altogether our results show that MRSA perturbation by nsPEF potentiates the effect of multiple antibiotics and that the order of the combined treatment can have a major impact on efficacy. Since SSTIs are accessible for physical interventions such as nsPEF stimulus, combinatorial treatments could be used to increase the efficacy of antibiotics used to treat such infections.

IMPORTANCE

We have found that treatment with short electric pulses potentiates the effects of multiple antibiotics against methicillin-resistant
Staphylococcus aureus
. By reducing the dose of antibiotic necessary to be effective, co-treatment with electric pulses could amplify the effects of standard antibiotic dosing to treat
S. aureus
infections such as skin and soft-tissue infections (SSTIs). SSTIs are accessible to physical intervention and are good candidates for electric pulse co-treatment, which could be adopted as a step-in wound and abscess debridement.
Lactococcus lactis
mutants resistant to lactococcin A and garvicin Q reveal missense mutations in the sugar transport domain of the mannose phosphotransferase system
Authors: van Belkum Marco J. , Aleksandrzak-Piekarczyk Tamara , Lamer Tess , Vederas John C. 
Published: December 2023

ABSTRACT

Lactococcin A is a bacteriocin from
Lactococcus lactis
that permeabilizes the membrane of sensitive lactococcal cells and requires the presence of the membrane-bound components IIC and IID of the mannose phosphotransferase system (man-PTS). Recently, it was reported through cryo-electron microscopy analyses of man-PTS and several bacteriocins fused to a maltose-binding protein, including lactococcin A, that these bacteriocins create pores by inserting themselves between the Core and Vmotif domains of man-PTS. In our study, we obtained a dozen spontaneous mutants of
L. lactis
IL1403 resistant to lactococcin A. All but one of the mutants of IL1403 have mutations located in the genes encoding the IIC or IID proteins. These mutations also resulted in resistance to garvicin Q, a bacteriocin from
Lactococcus garvieae
with a broad inhibition spectrum and very little sequence homology to lactococcin A. Missense mutations were found in the sugar transport domain of man-PTS of bacteriocin-resistant IL1403 mutants, which also impeded the uptake of mannose. When lactococcin A, garvicin Q, or pediocin PA-1, an anti-listerial bacteriocin, were fused to a maltose-binding protein, we observed reduced or no antibacterial activity. Taken together, the precise mechanism of action of bacteriocins using the man-PTS remains to be fully understood.

IMPORTANCE
Many bacteriocins target the sugar transporter mannose phosphotransferase system (man-PTS) to exert their antibacterial activity. The elucidation in recent years of the structure of man-PTS has facilitated our understanding of how bacteriocins might interact with the receptor and which domains of the transporter are involved in bacteriocin resistance. Here, we show that missense mutations in the sugar-binding domain of the man-PTS not only impede the uptake of sugars but also prevent the antibacterial activity of the bacteriocins lactococcin A and garvicin Q.
A Generator of Nanosecond High-Voltage Pulses Based on Shock-Ionized Dynistors
Authors: Korotkov S. V. , Zhmodikov A. L. , Korotkov D. A. 
Published: December 2023

Abstract—
A generator of high-power nanosecond pulses consisting of four stages that are switched on in a relay-race mode is described. Each stage contains a storage capacitor with an operating voltage of 8 kV and an assembly of series-connected shock-ionized dynistors. The possibility of switching current pulses with an amplitude of 800 А to a load of 30 Ω a rise time of 4 ns, and a repetition rate of 100 Hz is demonstrated. The prospects for increasing the output voltage and the output energy of the generator are determined.
Consensus statement on the interhospital transfer of patients with acute aortic syndrome: TRAVERSING Delphi study
Authors: Staniszewska Aleksandra , Gaba Kamran , Patterson Benjamin , Wilson Sarah , Bell Rachel , Bicknell Colin , Brooks Marcus , Callaway Mark , Goode Stephen , Grier Scott , Hobson Alex , Mouton Ronelle , Neequaye Simon , Owens Gareth , Rajakaruna Cha , Redfern Emma , Tsang Geoffrey , Hinchliffe Robert 
Published: December 2023

BackgroundStandardisation of referral pathways and the transfer of patients with acute aortic syndromes (AAS) to regional centres are recommended by NHS England in the Acute Aortic Dissection Toolkit. The aim of the Transfer of Thoracic Aortic Vascular Emergencies to Regional Specialist INstitutes Group study was to establish an interdisciplinary consensus on the interhospital transfer of patients with AAS to specialist high-volume aortic centres.MethodsConsensus on the key aspects of interhospital transfer of patients with AAS was established using the Delphi method, in line with Conducting and Reporting of Delphi Studies guidelines. A national patient charity for aortic dissection was involved in the design of the Delphi study. Vascular and cardiothoracic surgeons, emergency physicians, interventional radiologists, cardiologists, intensivists and anaesthetists in the United Kingdom were invited to participate via their respective professional societies.ResultsThree consecutive rounds of an electronic Delphi survey were completed by 212, 101 and 58 respondents, respectively. Using predefined consensus criteria, 60 out of 117 (51%) statements from the survey were included in the consensus statement. The study concluded that patients can be taken directly to a specialist aortic centre if they have typical symptoms of AAS on the background of known aortic disease or previous aortic intervention. Accepted patients should be transferred in a category 2 ambulance (response time <18 min), ideally accompanied by transfer-trained personnel or Adult Critical Care Transfer Services. A clear plan should be agreed in case of a cardiac arrest occurring during the transfer. Patients should reach the aortic centre within 4 hours of the initial referral from their local hospital.ConclusionsThis consensus statement is the first set of national interdisciplinary recommendations on the interhospital transfer of patients with AAS. Its implementation is likely to contribute to safer and more standardised emergency referral pathways to regional high-volume specialist aortic units.