bluuebunny/crossref_metadata_2025 huggingface dataset:
Compressor Tip Leakage Mechanisms
Authors: Taylor James V. , Dickens Anthony M. J. , Simpson Harry
Published: December 2023

The over tip leakage flow in an unshrouded compressor blade row is highly three dimensional, yet in order for aerodynamicists to analyze and improve designs, they must be able to simplify the problem down to a limited number of mechanisms. In this article, the behaviors of the dominant loss mechanisms are investigated using a multi-order methodology that combines rapid experimental tests of different geometries, detailed measurements in a large rotating rig, large numbers of industry-standard 3D Reynolds-averaged Navier–Stokes (RANS) simulations, and a single direct numerical simulation (DNS) of the datum geometry. The three loss mechanisms identified are ultimately caused by mismatches in flow velocity: separation of the flow as it enters the gap, mixing of the leakage jet with the mainstream close to the suction surface, and endwall shear acting on the jet itself at mid passage. This article is presented in three sections: First, the loss mechanisms are visualized and examined in detail using experiment, simulation, and models. Second, the uncertainty in industry-standard predictions is analyzed and improvements to turbulence modeling are presented. Finally, a matrix of blades with different 3D designs is used to investigate the balance of loss mechanisms and a reduction in total loss generation.
Asymptotic Stress Field for the Blunt and Sharp Notches in Bi-Material Media Under Mode III Loading
Authors: Mirzaei Amir Mohammad , Sapora Alberto , Cornetti Pietro
Published: December 2023

This study introduces a novel approach to analyze the stress and displacement fields around blunt notches in bi-material media, focusing on mode III loading conditions. The eigenfunction expansion method is used to derive a simplified yet accurate solution, satisfying the boundary conditions for bi-material blunt V-notches. The robustness of the proposed asymptotic solution is validated through several finite element analyses, encompassing a range of notched geometries such as blunt V-notches, VO-notches, and circular holes. Notably, it is demonstrated that when the notch tip radius approaches zero, the solution coincides with the existing sharp V-notch model.
An adaptive algorithm for acoustic feedback compensation and secondary path identification of an active noise control system
Authors: Feng Zhu Jie , Lin Tian Ran , Cheng Li
Published: December 2023

An adaptive variable step-size algorithm is proposed in this paper to address the impact of the real-time acoustic feedback and the real-time secondary path identification on the overall noise reduction performance of an active noise control system. An automated adjustment weight factor is introduced in the algorithm to accelerate the convergence of the acoustic feedback path as well as the secondary path identification, and to prevent possible system divergence. It is shown in this study that the proposed algorithm can resolve the trade-off between a fast convergence and a low misalignment of the virtual and the actual control paths typically found in conventional algorithms. An optimized control structure is also proposed in the study by enabling an adaptive gain adjustment based on the output of the auxiliary filter to enhance the practicality of the control system. The effectiveness of the algorithm is tested using two simulated multi-component signals and a broadband noise signal, and the results confirm that the proposed algorithm can achieve a good noise reduction with only a few iterations.
TLR4 sensing of IsdB of
Staphylococcus aureus
induces a proinflammatory cytokine response via the NLRP3-caspase-1 inflammasome cascade
Authors: Gonzalez Juan José Izquierdo , Hossain Md Faruq , Neef Jolanda , Zwack Erin E. , Tsai Chih-Ming , Raafat Dina , Fechtner Kevin , Herzog Luise , Kohler Thomas P. , Schlüter Rabea , Reder Alexander , Holtfreter Silva , Liu George Y. , Hammerschmidt Sven , Völker Uwe , Torres Victor J. , van Dijl Jan Maarten , Lillig Christopher H. , Bröker Barbara M. , Darisipudi Murty N.
Published: December 2023

The iron-regulated surface determinant protein B (IsdB) of
Staphylococcus aureus
is involved in the acquisition of iron from hemoglobin. Moreover, IsdB elicits an adaptive immune response in mice and humans. Here, we show that IsdB also has impact on innate immunity. IsdB induces the release of proinflammatory cytokines, including IL-6 and IL-1β, in innate immune cells of humans and mice.
In silico
analysis and thermophoresis show that IsdB directly binds to TLR4 with high affinity. TLR4 sensing was essential for the IsdB-mediated production of IL-6, IL-1β, and other cytokines as it was abolished by blocking of TLR4-MyD88-IRAK1/4-NF-κB signaling. The release of IL-1β additionally required activation of the NLRP3 inflammasome. In human monocytes infected with live
S. aureus
, IsdB was necessary for maximal IL-1β release. Our studies identify
S. aureus
IsdB as a novel pathogen-associated molecular pattern that triggers innate immune defense mechanisms.

IMPORTANCE

The prevalence of multidrug-resistant
Staphylococcus aureus
is of global concern, and vaccines are urgently needed. The iron-regulated surface determinant protein B (IsdB) of
S. aureus
was investigated as a vaccine candidate because of its essential role in bacterial iron acquisition but failed in clinical trials despite strong immunogenicity. Here, we reveal an unexpected second function for IsdB in pathogen-host interaction: the bacterial fitness factor IsdB triggers a strong inflammatory response in innate immune cells via Toll-like receptor 4 and the inflammasome, thus acting as a novel pathogen-associated molecular pattern of
S. aureus
. Our discovery contributes to a better understanding of how
S. aureus
modulates the immune response, which is necessary for vaccine development against the sophisticated pathogen.
Sulfur metabolism-mediated fungal glutathione biosynthesis is essential for oxidative stress resistance and pathogenicity in the plant pathogenic fungus
Fusarium graminearum
Authors: Park Jiyeun , Han Jae Woo , Lee Nahyun , Kim Sieun , Choi Soyoung , Lee Hyun-Hee , Kim Jung-Eun , Seo Young-Su , Choi Gyung Ja , Lee Yin-Won , Kim Hun , Son Hokyoung
Published: December 2023

The oxidative stress response is required for plant pathogens to endure host-derived oxidative stress during infection. Previously, we identified the eight transcription factors (TFs) involved in the oxidative stress response in the plant pathogenic fungus
Fusarium graminearum
and found that of these TFs, the deletion of
FgbZIP007
caused hypersensitivity to oxidative stress. However, the underlying mechanisms of Fgbzip007 are not fully understood. Based on chromatin immunoprecipitation followed by sequencing (ChIP-seq) analysis, we found the regulons of Fgbzip007, and further genetic studies demonstrated that Fgbzip007 is a key regulator for sulfur assimilation. The deletion strains of
FgbZIP007
and its regulons exhibited low level of glutathione biosynthesis, which led to characterize glutathione biosynthesis. Fgbzip007-mediated sulfur assimilation is required for glutathione biosynthesis, which is essential for oxidative stress resistance and pathogenicity in
F. graminearum
. Although the reduced resistance of glutathione-deficient mutants against oxidative stress was restored by overexpression of
FCA7
, encoding a core peroxidase, but not on pathogenicity, suggesting that glutathione in pathogenesis is independent of antioxidant properties. This study characterized the function of genes of glutathione biosynthesis, provides specific insight into how Fgbzip007 regulates pathogenesis in
F. graminearum
, and establishes a genetic framework for the molecular dissection of a TF Fgbzip007 with the integration of pathogen responses to oxidative stress.

IMPORTANCE

Fusarium graminearum
is a destructive fungal pathogen that causes Fusarium head blight (FHB) on a wide range of cereal crops. To control fungal diseases, it is essential to comprehend the pathogenic mechanisms that enable fungi to overcome host defenses during infection. Pathogens require an oxidative stress response to overcome host-derived oxidative stress. Here, we identify the underlying mechanisms of the Fgbzip007-mediated oxidative stress response in
F. graminearum
. ChIP-seq and subsequent genetic analyses revealed that the role of glutathione in pathogenesis is not dependent on antioxidant functions in
F. graminearum
. Altogether, this study establishes a comprehensive framework for the Fgbzip007 regulon on pathogenicity and oxidative stress responses, offering a new perspective on the role of glutathione in pathogenicity.
Whole-genome sequence of
Proteus faecis
CR112, isolated from the gut of a healthy
Labeo rohita
Authors: Paul Sulav Indra , Khan Saif Uddin , Foysal Md Javed , Rahman Md Mahbubur
Published: December 2023

Bacteria of the genus
Proteus
are gram-negative bacilli.
Proteus faecis
CR112 was isolated from fish gut based on its antibacterial activity against fish pathogens. The genome sequence of CR112 provided valuable information about its secondary metabolite gene clusters.
A TetR family regulator of an RND efflux system that directs artemisinin resistance in
Vibrio cholerae
Authors: Chung In-Young , Choi Shin-Yae , Bae Hee-Won , Cho You-Hee
Published: December 2023

Artemisinin (ARS) displayed bactericidal activity against
Vibrio cholerae
. To assess the mechanistic details of its antibacterial action, we have isolated
V. cholerae
mutants with enhanced ARS resistance and identified a gene (VCA0767) whose loss-of-function resulted in the ARS resistance phenotypes. This gene (
atrR
) encodes a TetR family transcriptional regulator, and its deletion mutant displayed the reduction in ARS-induced ROS formation and DNA damage. Transcriptomic analysis revealed that the genes encoding a
r
esistance-
n
odulation-cell
d
ivision (RND) efflux pump operon (
vexRAB
) and the outer membrane component (
tolC
) were highly upregulated in the
artR
mutant, suggesting that AtrR might act as a negative regulator of this operon and
tolC
. Gene deletion of
vexR
,
vexB
, or
tolC
abrogated the ARS resistance of the
atrR
mutant, and more importantly, the ectopic expression of VexAB-TolC was sufficient for the ARS resistance, indicating that the increased expression of the VexAB-TolC efflux system is necessary and sufficient for the ARS resistance of the
atrR
mutant. The cytoplasmic accumulation of ARS was compromised in the
vexBtolC
mutant, suggesting that the VexAB-TolC might be the primary efflux system exporting ARS to reduce its toxicity inside of the bacterial cells. The
atrR
mutant displayed resistance to erythromycin as well in a VexR-dependent manner. This result suggests that AtrR may act as a global regulator responsible for preventing intracellular accumulation of toxic chemicals by enhancing the RND efflux system.

IMPORTANCE

Drug efflux protein complexes or efflux pumps are considered as the major determinants of multiple antimicrobial resistance by exporting a wide range of structurally diverse antibiotics in bacterial pathogens. Despite the clinical significance of the increased expression of the efflux pumps, their substrate specificity and regulation mechanisms are poorly understood. Here, we demonstrated that VexAB-TolC, a
r
esistance-
n
odulation-cell
d
ivision (RND) efflux pump of
V. cholerae
, is responsible for the resistance to artemisinin (ARS), an antimalarial drug with bactericidal activity. Furthermore, we newly identified AtrR, a TetR family repressor, as a global regulator for VexRAB and the common outer membrane channel, TolC, where VexR functions as the pathway-specific regulator of the vexAB operon. Our findings will help improve our insight into a broad range of substrate specificity of the VexAB-TolC system and highlight the complex regulatory networks of the multiple RND efflux systems during
V. cholerae
pathogenesis.
Varying
Flavobacterium psychrophilum
shedding dynamics in three bacterial coldwater disease-susceptible salmonid (Family
Salmonidae
) species
Authors: Knupp Christopher , Soto Esteban , Loch Thomas P.
Published: December 2023

Flavobacterium psychrophilum
causes bacterial coldwater disease (BCWD) and is responsible for substantial losses in farm and hatchery-reared salmonids (Family
Salmonidae
). Although
F. psychrophilum
infects multiple economically important salmonids and is transmitted horizontally, the extent of knowledge regarding
F. psychrophilum
shedding rates and duration is limited to rainbow trout (
Oncorhynchus mykiss
). Concurrently, hundreds of
F. psychrophilum
sequence types (STs) have been described using multilocus sequence typing (MLST), and evidence suggests that some variants have distinct phenotypes, including differences in host associations. Whether shedding dynamics differ among
F. psychrophilum
variants and/or salmonids remains unknown. Thus, three
F. psychrophilum
isolates (e.g., US19, US62, and US87) in three MLST STs (e.g., ST13, ST277, and ST275) with apparent host associations for coho salmon (
O. kisutch
), Atlantic salmon (
Salmo salar
), or rainbow trout were intramuscularly injected into each respective fish species. Shedding rates of live and dead fish were determined by quantifying
F. psychrophilum
loads in water via quantitative PCR. Both live and dead Atlantic and coho salmon shed
F. psychrophilum
, as did live and dead rainbow trout. Regardless of salmonid species, dead fish shed
F. psychrophilum
at higher rates (e.g., up to ~10
8
–10
10
cells/fish/hour) compared to live fish (up to ~10
7
–10
9
cells/fish/hour) and for a longer duration (5–35 days vs 98 days); however, shedding dynamics varied by
F. psychrophilum
variant and/or host species, a matter that may complicate BCWD management. Findings herein expand knowledge on
F. psychrophilum
shedding dynamics across multiple salmonid species and can be used to inform future BCWD management strategies.

IMPORTANCE

Flavobacterium psychrophilum
causes bacterial coldwater disease (BCWD) and rainbow trout fry syndrome, both of which cause substantial losses in farmed and hatchery-reared salmon and trout populations worldwide. This study provides insight into
F. psychrophilum
shedding dynamics in rainbow trout (
Oncorhynchus mykiss
) and, for the first time, coho salmon (
O. kisutch
) and Atlantic salmon (
Salmo salar
). Findings revealed that live and dead fish of all fish species shed the bacterium. However, dead fish shed
F. psychrophilum
at higher rates than living fish, emphasizing the importance of removing dead fish in farms and hatcheries. Furthermore, shedding dynamics may differ according to
F. psychrophilum
genetic variant and/or fish species, a matter that may complicate BCWD management. Overall, study results provide deeper insight into
F. psychrophilum
shedding dynamics and will guide future BCWD management strategies.
Pharmacokinetic/pharmacodynamic integration of amphenmulin: a novel pleuromutilin derivative against
Mycoplasma gallisepticum
Authors: Wang Wenxiang , Yu Jiao , Ji Xuan , Xia Xirui , Ding Huanzhong
Published: December 2023

Amphenmulin is a novel pleuromutilin derivative with great anti-mycoplasma potential. The present study evaluated the action characteristics of amphenmulin against
Mycoplasma gallisepticum
using pharmacokinetic/pharmacodynamic (PK/PD) modeling approaches. Following intravenous administration, amphenmulin exhibited an elimination half-life of 2.13 h and an apparent volume of distribution of 3.64 L/kg in healthy broiler chickens, demonstrating PK profiles of extensive distribution and rapid elimination. The minimum inhibitory concentration (MIC) of amphenmulin against
M. gallisepticum
was determined to be 0.0039 µg/mL using the broth microdilution method, and the analysis of the static time–kill curves through the sigmoid
E
max
model showed a highly correlated relationship (R ≥ 0.9649) between the kill rate and drug concentrations (1–64 MIC). A one-compartment open model with first-order elimination was implemented to simulate the
in vivo
anti-mycoplasma effect of amphenmulin, and it was found that bactericidal levels were reached with continuous administration for 3 days at doses exceeding 0.8 µg/mL. Furthermore, the area under the concentration–time curve divided by MIC (AUC/MIC) correlated well with the anti-mycoplasma effect of amphenmulin within 24 h after each administration, with a target value of 904.05 h for predicting a reduction of
M. gallisepticum
by 1 Log
10
CFU/mL. These investigations broadened the antibacterial spectrum of amphenmulin and revealed its characteristics of action against
M. gallisepticum
, providing a theoretical basis for further clinical development.

IMPORTANCE

Mycoplasma
has long been recognized as a significant pathogen causing global livestock production losses and public health concerns, and the use of antimicrobial agents is currently one of the mainstream strategies for its prevention and control. Amphenmulin is a promising candidate pleuromutilin derivative that was designed, synthesized, and screened by our laboratory in previous studies. Moreover, this study further confirms the excellent antibacterial activity of amphenmulin against
Mycoplasma gallisepticum
and reveals its action characteristics and model targets on
M. gallisepticum
by establishing an
in vitro
pharmacokinetic/pharmacodynamic synchronization model. These findings can further broaden the pharmacological theoretical basis of amphenmulin and serve as data support for its clinical development, which is of great significance for the discovery of new antimicrobial drugs and the control of bacterial diseases in humans and animals.
Supplemental Material: Copper skarn mineralization related to reduced monzodioritic magma at the Huanren deposit, northeastern China
Authors: Ouyang Hegen , et al.
Published: December 2023

All data mentioned in the text and required to create all figures (i.e., Table S1-S9), as well as four supplementary figures (i.e., Figure S1-S4).
Unexpected pulmonary sequestration in a pregnant patient
Authors: Alsararatee Hasan Hazim , Munje Muhit
Published: December 2023

A pregnant woman in her early 30s, at 20 weeks of gestational age, presented with recurrent haemoptysis, pleuritic chest pain and a productive cough of 6 months duration. She underwent CT pulmonary angiogram which demonstrated right pulmonary sequestration and right-sided consolidation. Pre-existing pulmonary comorbidities such as chronic inflammation, structural abnormalities or weakened blood vessels within the lungs can encourage the growth of abnormal blood vessels. During pregnancy, these dynamics can be further aggravated by increasing cardiac output to promote blood flow to the placenta and increasing oxygen delivery to the developing foetus. These changes likely cause increased blood flow to the pulmonary sequestration, resulting in haemoptysis. The patient was treated conservatively for community-acquired pneumonia with a course of oral amoxicillin 500 mg three times a day for 5 days, and she is doing well on follow-up.
Expert guidance on target product profile development for AMR diagnostic tests
Authors: Bachmann Till T , Mitsakakis Konstantinos , Hays John P , van Belkum Alex , Russom Aman , Luedke Gerd , Simonsen Gunnar Skov , Abel Gyorgy , Peter Harald , Goossens Herman , Moran-Gilad Jacob , Vila Jordi , Becker Karsten , Moons Pieter , Sampath Rangarajan , Peeling Rosanna W , Luz Saturnino , van Staa Tjeerd , Di Gregori Valentina
Published: December 2023

Diagnostics are widely considered crucial in the fight against antimicrobial resistance (AMR), which is expected to kill 10 million people annually by 2030. Nevertheless, there remains a substantial gap between the need for AMR diagnostics versus their development and implementation. To help address this problem, target product profiles (TPP) have been developed to focus developers’ attention on the key aspects of AMR diagnostic tests. However, during discussion between a multisectoral working group of 51 international experts from industry, academia and healthcare, it was noted that specific AMR-related TPPs could be extended by incorporating the interdependencies between the key characteristics associated with the development of such TPPs. Subsequently, the working group identified 46 characteristics associated with six main categories (ie, Intended Use, Diagnostic Question, Test Description, Assay Protocol, Performance and Commercial). The interdependencies of these characteristics were then identified and mapped against each other to generate new insights for use by stakeholders. Specifically, it may not be possible for diagnostics developers to achieve all of the recommendations in every category of a TPP and this publication indicates how prioritising specific TPP characteristics during diagnostics development may influence (or not) a range of other TPP characteristics associated with the diagnostic. The use of such guidance, in conjunction with specific TPPs, could lead to more efficient AMR diagnostics development.
Cost-effectiveness of camrelizumab combined with chemotherapy in the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma in China
Authors: Zhao Ziying , Chen Tongfeng , Zhou Zhen , Guo Rui , Liu Qiao
Published: December 2023

Objective

This study aimed to investigate the cost-effectiveness of adding Chinese-developed anti-PD-1 antibody camrelizumab to first-line platinum-doublet chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma (L/M NPC) from the perspective of Chinese healthcare system.

Design

A Markov model consisting of four health states, progression-free survival, first progression survival, second progression survival and death, was built to simulate 3-week patient transitions over a 20-year horizon. A direct comparison between first-line camrelizumab in combination with gemcitabine plus cisplatin and gemcitabine plus cisplatin was performed by calculating transition probabilities from the CAPTAIN-1st trial. Costs and utilities were collected from the local public database and literature. One-way and probabilistic sensitivity analyses were employed to evaluate the robustness of the model.

Setting

The Chinese healthcare system perspective.

Participants

A hypothetical cohort of Chinese patients with pathologically diagnosed L/M NPC who had an Eastern Cooperative Oncology Group performance status of 0 or 1.

Interventions

First-line camrelizumab in combination with camrelizumab and gemcitabine plus cisplatin (CGP) versus gemcitabine plus cisplatin (GP).

Primary outcome measure

Cost, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER).

Results

The baseline analysis demonstrated that, compared with first-line GP, first-line CGP yields an effectiveness increase of 0.26 QALY, accompanied by an increment of US$6137.59 in healthcare cost. This results in an ICER of US$23 482.32/QALY. With the willingness-to-pay (WTP) threshold for a QALY set at US$37 654.50, first-line CGP proves to be cost-effective in 97.20% of the iterations. Deterministic sensitivity analyses indicated that the uncertainty in model parameters had no substantial effect on our results. Probability sensitivity analysis indicated that CGP was cost-effective at the assumed WTP threshold.

Conclusion

For Chinese patients with L/M NPC, adding Chinese-developed anti-PD-1 antibody camrelizumab to the first-line GP chemotherapy may be cost-effective.
Developing a model for decision-making around antibiotic prescribing for patients with COVID-19 pneumonia in acute NHS hospitals during the first wave of the COVID-19 pandemic: qualitative results from the Procalcitonin Evaluation of Antibiotic use in COVID-19 Hospitalised patients (PEACH Study)
Authors: Henley Josie , Brookes-Howell Lucy , Euden Joanne , Pallmann Philip , Llewelyn Martin , Howard Philip , Powell Neil , Dark Paul , Szakmany Tamas , Hellyer Thomas P , Albur Mahableshwar , Hamilton Ryan , Prestwich Graham , Ogden Margaret , Maboshe Wakunyambo , Sandoe Jonathan , Thomas-Jones Emma , Carrol Enitan
Published: December 2023

Objective

To explore and model factors affecting antibiotic prescribing decision-making early in the pandemic.

Design

Semistructured qualitative interview study.

Setting

National Health Service (NHS) trusts/health boards in England and Wales.

Participants

Clinicians from NHS trusts/health boards in England and Wales.

Method

Individual semistructured interviews were conducted with clinicians in six NHS trusts/health boards in England and Wales as part of the Procalcitonin Evaluation of Antibiotic use in COVID-19 Hospitalised patients study, a wider study that included statistical analysis of procalcitonin (PCT) use in hospitals during the first wave of the pandemic. Thematic analysis was used to identify key factors influencing antibiotic prescribing decisions for patients with COVID-19 pneumonia during the first wave of the pandemic (March to May 2020), including how much influence PCT test results had on these decisions.

Results

During the first wave of the pandemic, recommendations to prescribe antibiotics for patients with COVID-19 pneumonia were based on concerns about secondary bacterial infections. However, as clinicians gained more experience with COVID-19, they reported increasing confidence in their ability to distinguish between symptoms and signs caused by SARS-CoV-2 viral infection alone, and secondary bacterial infections. Antibiotic prescribing decisions were influenced by factors such as clinician experience, confidence, senior support, situational factors and organisational influences. A decision-making model was developed.

Conclusion

This study provides insight into the decision-making process around antibiotic prescribing for patients with COVID-19 pneumonia during the first wave of the pandemic. The importance of clinician experience and of senior review of decisions as factors in optimising antibiotic stewardship is highlighted. In addition, situational and organisational factors were identified that could be optimised. The model presented in the study can be used as a tool to aid understanding of the complexity of the decision-making process around antibiotic prescribing and planning antimicrobial stewardship support in the context of a pandemic.

Trial registration number

ISRCTN66682918.
Childhood and adolescent factors shaping vulnerability to underage entry into sex work: a quantitative hierarchical analysis of female sex workers in Nairobi, Kenya
Authors: Shah Pooja , Kabuti Rhoda , Beksinska Alicja , Nyariki Emily , Babu Hellen , Kungu Mary , Jama Zaina , Ngurukiri Pauline ,   The Maisha Fiti Study Champions, Kaul Rupert , Kyegombe Nambusi , Medley Graham F , Devries Karen , Seeley Janet , Weiss Helen Anne , Beattie Tara S , Kimani Joshua
Published: December 2023

Objective

To explore factors associated with early age at entry into sex work, among a cohort of female sex workers (FSWs) in Nairobi, Kenya.

Background

Younger age at sex work initiation increases the risk of HIV acquisition, condom non-use, violence victimisation and alcohol and/or substance use problems. This study aimed to understand factors in childhood and adolescence that shape the vulnerability to underage sex work initiation.

Design

Building on previous qualitative research with this cohort, analysis of behavioural–biological cross-sectional data using hierarchical logistic regression.

Participants and measures

FSWs aged 18–45 years were randomly selected from seven Sex Workers Outreach Programme clinics in Nairobi, and between June and December 2019, completed a baseline behavioural–biological survey. Measurement tools included WHO Adverse Childhood Experiences, Alcohol, Smoking and Substance Involvement Screening Test and questionnaires on sociodemographic information, sexual risk behaviours and gender-based violence. Descriptive statistics and logistic regression were conducted using hierarchical modelling.

Results

Of the 1003 FSWs who participated in the baseline survey (response rate 96%), 176 (17.5%) initiated sex work while underage (<18 years). In the multivariable analysis, factors associated with entering sex work while underage included incomplete secondary school education (aOR=2.82; 95% CI=1.69 to 4.73), experiencing homelessness as a child (aOR=2.20; 95% CI=1.39 to 3.48), experiencing childhood physical or sexual violence (aOR=1.85; 95% CI=1.09 to 3.15), young age of sexual debut (≤15 years) (aOR=5.03; 95% CI=1.83 to 13.79) and being childless at time of sex work initiation (aOR=9.80; 95% CI=3.60 to 26.66).

Conclusions

Lower education level and childhood homelessness, combined with sexual violence and sexual risk behaviours in childhood, create pathways to underage initiation into sex work. Interventions designed for girls and young women at these pivotal points in their lives could help prevent underage sex work initiation and their associated health, social and economic consequences.
Supporting High-impAct useRs in Emergency Departments (SHarED) quality improvement: a mixed-method evaluation
Authors: Sillero-Rejon Carlos , Kirbyshire Megan , Thorpe Rebecca , Myring Gareth , Evans Clare , Lloyd-Rees Johanna , Bezer Angela , McLeod Hugh
Published: December 2023

Background

The need to better manage frequent attenders or high-impact users (HIUs) in hospital emergency departments (EDs) is widely recognised. These patients often have complex medical needs and are also frequent users of other health and care services. The West of England Academic Health Science Network launched its Supporting High impAct useRs in Emergency Departments (SHarED) quality improvement programme to spread a local HIU intervention across six other EDs in five Trusts.

Aim

SHarED aimed to reduce ED attendance and hospital admissions by 20% for enrolled HIUs. To evaluate the implementation of SHarED, we sought to learn about the experience of staff with HIU roles and their ED colleagues and assess the impact on HIU attendance and admissions.

Methods

We analysed a range of data including semistructured interviews with 10 HIU staff; the number of ED staff trained in HIU management; an ED staff experience survey; and ED attendances and hospital admissions for 148 HIUs enrolled in SHarED.

Results

Staff with HIU roles were unanimously positive about the benefits of SHarED for both staff and patients. SHarED contributed to supporting ED staff with patient-centred recommendations and provided the basis for more integrated case management across the health and care system. 55% of ED staff received training. There were improvements in staff views relating to confidence, support, training and HIUs receiving more appropriate care. The mean monthly ED attendance per HIU reduced over time. Follow-up data for 86% (127/148) of cases showed a mean monthly ED attendances per HIU reduced by 33%, from 2.1 to 1.4, between the 6 months pre-enrolment and post-enrolment (p<0.001).

Conclusion

SHarED illustrates the considerable potential for a quality improvement programme to promote more integrated case management by specialist teams across the health and care system for particularly vulnerable individuals and improve working arrangements for hard-pressed staff.
Factors associated with the response to postnatal dexamethasone use in very low birthweight infants: a nationwide cohort study
Authors: Baek Seung Hwan , Shin Jeong Eun , Han Jungho , Song In Gyu , Park Joonsik , Lee Su Min , Shim Sungbo , Eun Ho Seon , Lee Soon Min , Lim Joohee , Yoon So Jin , Chang Wook , Park Min Soo
Published: December 2023

Background

Dexamethasone is widely used as a systemic corticosteroid to treat and prevent bronchopulmonary dysplasia (BPD) in preterm infants. We evaluated the current epidemiology of dexamethasone use to prevent BPD and analyse the factors associated with the response to dexamethasone in very low birthweight infants using a nationwide database.

Methods

We included very low birthweight infants born between January 2013 and December 2020 with a gestational age of 23–31 weeks using data from the Korean Neonatal Network registry. Patients were grouped based on their dexamethasone use into ‘Dex’ or ‘No Dex’ groups. Clinical variables and data were collected, and the annual trends of dexamethasone use and the proportion of patients who received dexamethasone according to gestational age were analysed. Respiratory outcomes were compared between the groups. Univariate and multivariate analyses were performed to analyse factors associated with the response to dexamethasone in BPD.

Results

Of 11 261 eligible infants, 2313 (20.5%) received dexamethasone, and 1714 (74.1%) of them were diagnosed with moderate-to-severe BPD. The 8-year annual prevalence of dexamethasone use was 17.7–22.3%. The ‘Dex’ group had more moderate-to-severe BPD, more frequent invasive ventilation use at a postmenstrual age of 36 weeks and longer ventilator duration. Birth weight, 5-minute APGAR score, pulmonary hypertension within the first 28 days, surgical treatment of patent ductus arteriosus, medical treatment of patent ductus arteriosus, pathological chorioamnionitis, hydrocortisone or budesonide use, surgical management of necrotising enterocolitis and fungal sepsis were associated with BPD after dexamethasone use.

Conclusions

Approximately 20.5% of preterm infants received dexamethasone, and the frequency increased as gestational age decreased. Poor response to dexamethasone was associated with antenatal and postnatal inflammation, low birth weight and early pulmonary hypertension.
Case series of anifrolumab for treatment of cutaneous lupus erythematosus and lupus-related mucocutaneous manifestations in patients with SLE
Authors: Bao Aaron , Petri Michelle A , Fava Andrea , Kang Jun
Published: December 2023

Objective

To assess the efficacy of anifrolumab, a type-1 interferon receptor subunit-1 monoclonal antibody, in treating refractory cutaneous lupus erythematosus (CLE) and lupus non-specific mucocutaneous manifestations in patients with systemic lupus erythematosus (SLE).

Methods

A case series comprising four SLE patients with refractory CLE received anifrolumab (300mg) as add-on therapy. Medical history, serological markers and images were collected. Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) was assessed at baseline and post-treatment visits.

Results

Patient 1:Anifrolumab effectively treated refractory chronic cutaneous lupus erythematosus with lupus panniculitis and calcinosis cutis.

Patient 2:Anifrolumab demonstrated rapid improvement in generalised discoid lupus, achieving a substantial reduction in CLASI-A from 40 to 8.

Patient 3:Switching from belimumab to anifrolumab led to notable improvement in photosensitivity and tumid lupus.

Patient 4:Anifrolumab effectively managed refractory subacute cutaneous lupus erythematosus, resulting in remarkable cutaneous improvement and successful tapering of prednisone and mycophenolate mofetil.

Conclusion

Anifrolumab demonstrates efficacy in treating refractory CLE subtypes and lupus non-specific mucocutaneous manifestations in SLE patients. Further studies are needed to establish response rates, optimal dosing, and long-term outcomes.
Gut-joint axis in knee synovitis: gut fungal dysbiosis and altered fungi–bacteria correlation network identified in a community-based study
Authors: Jiang Ting , Liu Ke , Li Jiatian , Zhang Yuqing , Zhang Weiya , Doherty Michael , Yang Zidan , Yang Tuo , Yang Yuanheng , Weng Qianlin , Luo Xianghang , Xie Hui , Li Changjun , Ai Kelong , Wei Jie , Lei Guanghua , Zeng Chao
Published: December 2023

Objectives

Knee synovitis is a highly prevalent and potentially curable condition for knee pain; however, its pathogenesis remains unclear. We sought to assess the associations of the gut fungal microbiota and the fungi–bacteria correlation network with knee synovitis.

Methods

Participants were derived from a community-based cross-sectional study. We performed an ultrasound examination of both knees. A knee was defined as having synovitis if its synovium was ≥4 mm and/or Power Doppler (PD) signal was within the knee synovium area (PD synovitis). We collected faecal specimens from each participant and assessed gut fungal and bacterial microbiota using internal transcribed spacer 2 and shotgun metagenomic sequencing. We examined the relation of α-diversity, β-diversity, the relative abundance of taxa and the interkingdom correlations to knee synovitis.

Results

Among 977 participants (mean age: 63.2 years; women: 58.8%), 191 (19.5%) had knee synovitis. β-diversity of the gut fungal microbiota, but notα-diversity, was significantly associated with prevalent knee synovitis. The fungal genusSchizophyllumwas inversely correlated with the prevalence and activity (ie, control, synovitis without PD signal and PD synovitis) of knee synovitis. Compared with those without synovitis, the fungi–bacteria correlation network in patients with knee synovitis was smaller (nodes: 93 vs 153; edges: 107 vs 244), and the average number of neighbours was fewer (2.3 vs 3.2).

Conclusion

Alterations of gut fungal microbiota and the fungi–bacteria correlation network are associated with knee synovitis. These novel findings may help understand the mechanisms of the gut-joint axis in knee synovitis and suggest potential targets for future treatment.
Differences in treatment response between female and male psoriatic arthritis patients during IL-12/23 therapy with or without methotrexate: post hoc analysis of results from the randomised MUST trial
Authors: Koehm Michaela , Foldenauer Ann C , Rossmanith Tanja , Kellner Herbert , Kiltz Uta , Burmester Gerd R , Kofler David M , Brandt Jan , Finzel Stephanie , Bergner Raoul , Sieburg Maren , Behrens Frank
Published: December 2023

Background

The influence of sex on treatment outcomes during interleukin-12/23 therapy in patients with psoriatic arthritis (PsA) has not been explored.

Objective

To conduct exploratory post hoc analyses of sex-stratified data from the MUST trial, an investigator-initiated, multicentre, phase 3b study in which patients with active PsA initiating treatment with open-label ustekinumab were randomised to treatment with placebo or methotrexate (MTX).

Methods

We evaluated baseline characteristics, key treatment outcomes and adverse events stratified by sex, with a focus on outcomes that did not include erythrocyte sedimentation rate (ESR) as a component due to the known elevation of ESR in females.

Results

A total of 166 patients were treated with ustekinumab+MTX (37 female, 50 male) or ustekinumab+placebo (32 female, 47 male). At baseline, females had a significantly longer time since PsA diagnosis and greater impairment in physical function, but similar joint counts. At week 24, both females and males showed marked improvements to ustekinumab with or without MTX. Females generally had numerically reduced treatment responses compared with males, although differences did not achieve statistical significance. MTX did not show an overall effect on treatment outcomes, but was associated with faster enthesitis responses in males only. Adverse events were generally comparable, but females in the ustekinumab+MTX group had higher levels of gastrointestinal disorders.

Conclusion

Females and males with PsA had differences in baseline characteristics, treatment responses and adverse events during therapy. A better understanding of sex-based differences in PsA may help optimise treatment.
Anti-IL-5 biologics and rheumatoid arthritis: a single-centre 500 patient year exposure analysis
Authors: Dean Nathan J , Clifton Ian J , Salman Rashad , Bridgewood Charles , Nam Jacquie , Macleod Tom , McGonagle Dennis G
Published: December 2023

Objective

The increasing use of biological therapies has led to the paradoxical finding that monoclonal antibody therapy for one inflammatory disease can sometimes induce another inflammatory disease. Recently, the use of anti-IL-5 (IL, interleukin) antibody therapies for severe asthma has been associated with the onset of rheumatoid arthritis (RA) and other inflammatory rheumatological disease. We undertook this audit to identify the prevalence of this finding across a large clinical cohort of patients receiving anti-IL-5 therapy.

Methods

All patients currently receiving mepolizumab or benralizumab for severe asthma across the Leeds Teaching Hospitals NHS Trust’s (LTHT) Respiratory Service were included. Electronic records for each patient were searched to identify clinical and biochemical manifestations of inflammatory rheumatological disease following the initiation of anti-IL-5 therapy.

Results

142 patients, with a mean duration of 3.5 years on therapy, were included (89 mepolizumab, 53 benralizumab). 17 patients developed new arthralgias (nine mepolizumab, eight benralizumab), however only one of these patients (on mepolizumab) had raised acute phase reactants and newly positive anti-CCP antibody (ACPA) and rheumatoid factor and was the only patient to receive a formal diagnosis of RA.

Conclusion

Although ACPA positive RA has now been reported in a handful of case reports, we noted a very low rate of evolution into RA or inflammatory arthritis, at least in the short-medium term under anti-IL-5 therapy. This challenges the emerging suggestion that anti-IL-5 biologics may be triggering RA.
Moderately non-local $$\eta {\bar{\eta }}$$ vertices in the $$AdS_4$$ higher-spin gauge theory
Authors: Gelfond O. A.
Published: December 2023

A new concept of moderate non-locality in higher-spin gauge theory is introduced. Based on the recently proposed differential homotopy approach, a moderately non-local scheme, that is softer than those resulting from the shifted homotopy approach available in the literature so far, is worked out in the mixed $$\eta {\bar{\eta }}$$

η

η

¯

sector of the Vasiliev higher-spin theory. To calculate moderately non-local vertices $$\Upsilon ^{\eta \bar{\eta }}(\omega , C,C,C)$$

Υ

η

η

¯

(
ω
,
C
,
C
,
C
)

for all ordering of the fields $$\omega $$
ω
and C we apply an interpolating homotopy, that respects the moderate non-locality in the perturbative analysis of the higher-spin equations.
A Process Mining Method for Inter-organizational Business Process Integration
Authors: Aouachria Moufida , Leshob Abderrahmane , Ghomari Abdessamed Réda , Aouache Mustapha
Published: December 2023

Business process integration (BPI) allows organizations to connect and automate their business processes in order to deliver the right economic resources at the right time, place, and price. BPI requires the integration of business processes and their supporting systems across multiple autonomous organizations. However, such integration is complex and can face coordination complexities that occur during the resource exchanges between the partners’ processes. This article proposes a new method called Process Mining for Business Process Integration (PM4BPI) that helps process designers to perform BPI by creating new process models that cross the boundaries of multiple organizations from a collection of process event logs. PM4BPI uses federated process mining techniques to detect incompatibilities before the integration of the partners’ processes. Then, it applies process adaptation patterns to solve detected incompatibilities. Finally, organizations’ processes are merged to build a collaborative process model that crosses the organizations’ boundaries. Adapt

WF_Net

, an extension of a Petri net, is used to design inter-organizational business processes and adaptation patterns. An integrated care pathway is used as a case study to assess the applicability and effectiveness of the proposed method.
Dynamic Response and Parameter Analysis of Electromagnetic Railguns under Time Varying Moving Loads
Authors: Liu Lilan , Zhang Xukai , Wang Jiayi
Published: December 2023

During the launch process of an electromagnetic railgun, the armature is subjected to the ampere force and moves along the rail with variable acceleration. In this period, the rail is excited by time varying moving loads and generates lateral vibration. For analysis, the rail is simplified as an Euler–Bernoulli beam, and the nonlinear dynamic equation of the beam under time varying moving loads is established. The electromagnetic repulsive force between rails, the contact pressure between the armature and the rail, and the thermal expansion pressure acting on the rail are taken into account. The lateral vibration response of the rail is achieved by using the analytical method combined with numerical integration. The variable motion of the armature during launch is also illustrated. Furthermore, the study of the effects of structure parameters on the vibration amplitude of the rail is performed. The research results can provide a theoretical basis for the structural optimization and vibration reduction of electromagnetic railguns.
Evaluation of Contralateral Limb Cross Education and High-Frequency Repetitive Transcranial Magnetic Stimulation on Functional Indices of the Affected Upper Limb in Subacute Phase of Stroke
Authors: Rezaei Katayoon , Kordi Yoosefinejad Amin , Moslemi Haghighi Farzaneh , Razeghi Mohsen
Published: December 2023

Background. Stroke is one of the causes of long-term morbidity. Despite rehabilitation strategies, most survivors live with motor deficits in the upper limbs. Objectives. The aim of the study was to compare the effect of contralateral cross education (CE) and high-frequency repetitive magnetic stimulation (HF-rTMS) on the function of upper extremity in subacute phase of stroke. Methods. Forty patients were randomly assigned into 4 groups. Group “A” received physical therapy (PT) for 10 sessions, 3 times per week. Group “B” received PT and HF-rTMS as follows: stimulation of 20 Hz for 5 s, intertrain interval for 50 s, 20 trains, 2000 pulses at 90% resting motor threshold, and conventional PT. Group “C” was treated with CE and PT. In group “D,” HF-rTMS, CE, and PT were administered. Results. Significant differences were found in the Fugl-Meyer scale between “A” and “C” (

P
=
0.01

), “A” and “D” (

P
=
0.02

), and “B” and “C” groups (

P
=
0.01

). In the box-block test, there were significant differences between “A” and “B” (

P
=
0.01

), “A” and “C” (

P
<
0.001

), “B” and “D” (

P
=
0.001

), and “B” and “C” groups (

P
=
0.01

). Statistical differences were observed in grip strength between “A” and “B” (

P
=
0.01

) and “A” and “C” groups (

P
=
0.02

). Conclusions. It is suggested that clinicians select the therapeutic methods in line with their expected goal. When the goal is to improve upper extremity function, CE+PT could be more effective than HF-rTMS+PT. Also, CE+PT and HF-rTMS+PT were more effective than CE+HF-rTMS+PT at improving grip strength. Therefore, combining several methods would not always lead to better results.