bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro
activity of sulbactam-durlobactam against colistin-resistant and/or cefiderocol-non-susceptible, carbapenem-resistant
Acinetobacter baumannii
collected in U.S. hospitals
Authors: Iovleva Alina , McElheny Christi L. , Fowler Erin L. , Cober Eric , Herc Erica S. , Arias Cesar A. , Hill Carol , Baum Keri , Fowler Vance G. , Chambers Henry F. , Greenwood-Quaintance Kerryl E. , Patel Robin , van Duin David , Bonomo Robert A. , Doi Yohei
Published: January 2024

The activity of a novel β-lactamase inhibitor combination, sulbactam-durlobactam (SUL-DUR), was tested against 87 colistin-resistant and/or cefiderocol-non-susceptible carbapenem-resistant
Acinetobacter baumannii
clinical isolates collected from U.S. hospitals between 2017 and 2019. Among them, 89% and 97% were susceptible to SUL-DUR and imipenem plus SUL-DUR, with MIC
50
/MIC
90
values of 2 µg/mL/8 µg/mL and 1 µg/mL/4 µg/mL, respectively. The presence of amino acid substitutions in penicillin-binding protein 3, including previously reported A515V or T526S, was associated with SUL-DUR non-susceptibility.
Transcriptional heterogeneity of catabolic genes on the plasmid pCAR1 causes host-specific carbazole degradation
Authors: Suzuki-Minakuchi Chiho , Yamamoto Natsumi , Takahira Saki , Yamaguchi Masataka , Takeda Yutaro , Okada Kazunori , Shigeto Shinsuke , Nojiri Hideaki
Published: January 2024

To elucidate why plasmid-borne catabolic ability differs among host bacteria, we assessed the expression dynamics of the P

ant

promoter on the carbazole-degradative conjugative plasmid pCAR1 in
Pseudomonas putida
KT2440(pCAR1) (hereafter, KTPC) and
Pseudomonas resinovorans
CA10. The P

ant

promoter regulates the transcription of both the
car
and
ant
operons, which are responsible for converting carbazole into anthranilate and anthranilate into catechol, respectively. In the presence of anthranilate, transcription of the P

ant

promoter is induced by the AraC/XylS family regulator AntR, encoded on pCAR1. A reporter cassette containing the P

ant

promoter followed by
gfp
was inserted into the chromosomes of KTPC and CA10. After adding anthranilate, GFP expression in the population of CA10 showed an unimodal distribution, whereas a small population with low GFP fluorescence intensity appeared for KTPC. CA10 has a gene,
antR
CA
, that encodes an iso-functional homolog of AntR on its chromosome. When
antR
CA
was disrupted, a small population with low GFP fluorescence intensity appeared. In contrast, overexpression of pCAR1-encoded AntR in KTPC resulted in unimodal expression under the P

ant

promoter. These results suggest that the expression of pCAR1-encoded AntR is insufficient to ameliorate the stochastic expression of the P

ant

promoter. Raman spectra of single cells collected using deuterium-labeled carbazole showed that the C–D Raman signal exhibited greater variability for KTPC than CA10. These results indicate that heterogeneity at the transcriptional level of the P

ant

promoter due to insufficient AntR availability causes fluctuations in the pCAR1-borne carbazole-degrading capacity of host bacterial cells.

IMPORTANCE

Horizontally acquired genes increase the competitiveness of host bacteria under selective conditions, although unregulated expression of foreign genes may impose fitness costs. The “appropriate” host for a plasmid is empirically known to maximize the expression of plasmid-borne traits. In the case of pCAR1-harboring
Pseudomonas
strains,
P. resinovorans
CA10 exhibits strong carbazole-degrading capacity, whereas
P. putida
KT2440 harboring pCAR1 exhibits low degradation capacity. Our results suggest that a chromosomally encoded transcription factor affects transcriptional and metabolic fluctuations in host cells, resulting in different carbazole-degrading capacities as a population. This study may provide a clue for determining appropriate hosts for a plasmid and for regulating the expression of plasmid-borne traits, such as the degradation of xenobiotics and antibiotic resistance.
Elucidating fungal decomposition of organic matter at sub-micrometer spatial scales using optical photothermal infrared (O-PTIR) microspectroscopy
Authors: Op De Beeck Michiel , Troein Carl , Peterson Carsten , Tunlid Anders , Persson Per
Published: January 2024

In microbiological studies, a common goal is to link environmental factors to microbial activities. Both environmental factors and microbial activities are typically derived from bulk samples. It is becoming increasingly clear that such bulk environmental parameters poorly represent the microscale environments microorganisms experience. Using infrared (IR) microspectroscopy, the spatial distribution of chemical compound classes can be visualized, making it a useful tool for studying the interactions between microbial cells and their microenvironments. The spatial resolution of conventional IR microspectroscopy has been limited by the diffraction limit of IR light. The recent development of optical photothermal infrared (O-PTIR) microspectroscopy has pushed the spatial resolution of IR microspectroscopy beyond this diffraction limit, allowing the distribution of chemical compound classes to be visualized at sub-micrometer spatial scales. To examine the potential and limitations of O-PTIR microspectroscopy to probe the interactions between fungal cells and their immediate environments, we imaged the decomposition of cellulose films by cells of the ectomycorrhizal fungus
Paxillus involutus
and compared O-PTIR results using conventional IR microspectroscopy. Whereas the data collected with conventional IR microspectroscopy indicated that
P. involutus
has only a very limited ability to decompose cellulose films, O-PTIR data suggested that the ability of
P. involutus
to decompose cellulose was substantial. Moreover, the O-PTIR method enabled the identification of a zone located outside the fungal hyphae where the cellulose was decomposed by oxidation. We conclude that O-PTIR can provide valuable new insights into the abilities and mechanisms by which microorganisms interact with their surrounding environments.

IMPORTANCE

Infrared (IR) microspectroscopy allows the spatial distribution of chemical compound classes to be visualized. The use of conventional IR microspectroscopy in microbiological studies has been restricted by limited spatial resolution. Recent developments in laser technology have enabled a new class of IR microspectroscopy instruments to be developed, pushing the spatial resolution beyond the diffraction limit of IR light to approximately 500 nm. This improved spatial resolution now allows microscopic observations of changes in chemical compounds to be made, making IR microspectroscopy a useful tool to investigate microscale changes in chemistry that are caused by microbial activity. We show these new possibilities using optical photothermal infrared microspectroscopy to visualize the changes in cellulose substrates caused by oxidation by the ectomycorrhizal fungus
Paxillus involutus
at the interface between individual fungal hyphae and cellulose substrates.
Simultaneous glucose and xylose utilization by an
Escherichia coli
catabolite repression mutant
Authors: Kaplan Nicholas A. , Islam Khondokar Nowshin , Kanis Fiona C. , Verderber Jack R. , Wang Xin , Jones J. Andrew , Koffas Mattheos A. G.
Published: January 2024

As advances are made toward the industrial feasibility of mass-producing biofuels and commodity chemicals with sugar-fermenting microbes, high feedstock costs continue to inhibit commercial application. Hydrolyzed lignocellulosic biomass represents an ideal feedstock for these purposes as it is cheap and prevalent. However, many microbes, including
Escherichia coli
, struggle to efficiently utilize this mixture of hexose and pentose sugars due to the regulation of the carbon catabolite repression (CCR) system. CCR causes a sequential utilization of sugars, rather than simultaneous utilization, resulting in reduced carbon yield and complex process implications in fed-batch fermentation. A mutant of the gene encoding the cyclic AMP receptor protein,
crp*
, has been shown to disable CCR and improve the co-utilization of mixed sugar substrates. Here, we present the strain construction and characterization of a site-specific
crp*
chromosomal mutant in
E. coli
BL21 star (DE3). The
crp*
mutant strain demonstrates simultaneous consumption of glucose and xylose, suggesting a deregulated CCR system. The proteomics further showed that glucose was routed to the C5 carbon utilization pathways to support both
de novo
nucleotide synthesis and energy production in the
crp*
mutant strain. Metabolite analyses further show that overflow metabolism contributes to the slower growth in the
crp*
mutant. This highly characterized strain can be particularly beneficial for chemical production by simultaneously utilizing both C5 and C6 substrates from lignocellulosic biomass.

IMPORTANCE

As the need for renewable biofuel and biochemical production processes continues to grow, there is an associated need for microbial technology capable of utilizing cheap, widely available, and renewable carbon substrates. This work details the construction and characterization of the first B-lineage
Escherichia coli
strain with mutated cyclic AMP receptor protein, Crp*, which deregulates the carbon catabolite repression (CCR) system and enables the co-utilization of multiple sugar sources in the growth medium. In this study, we focus our analysis on glucose and xylose utilization as these two sugars are the primary components in lignocellulosic biomass hydrolysate, a promising renewable carbon feedstock for industrial bioprocesses. This strain is valuable to the field as it enables the use of mixed sugar sources in traditional fed-batch based approaches, whereas the wild-type carbon catabolite repression system leads to biphasic growth and possible buildup of non-preferential sugars, reducing process efficiency at scale.
Cell surface architecture of the cultivated DPANN archaeon
Nanobdella aerobiophila
Authors: Kato Shingo , Tahara Yuhei O. , Nishimura Yuki , Uematsu Katsuyuki , Arai Takahiro , Nakane Daisuke , Ihara Ayaka , Nishizaka Takayuki , Iwasaki Wataru , Itoh Takashi , Miyata Makoto , Ohkuma Moriya
Published: January 2024

The DPANN archaeal clade includes obligately ectosymbiotic species. Their cell surfaces potentially play an important role in the symbiotic interaction between the ectosymbionts and their hosts. However, little is known about the mechanism of ectosymbiosis. Here, we show cell surface structures of the cultivated DPANN archaeon
Nanobdella aerobiophila
strain MJ1
T
and its host
Metallosphaera sedula
strain MJ1HA, using a variety of electron microscopy techniques, i.e., negative-staining transmission electron microscopy, quick-freeze deep-etch TEM, and 3D electron tomography. The thickness, unit size, and lattice symmetry of the S-layer of strain MJ1
T
were different from those of the host archaeon strain MJ1HA. Genomic and transcriptomic analyses highlighted the most highly expressed MJ1
T
gene for a putative S-layer protein with multiple glycosylation sites and immunoglobulin-like folds, which has no sequence homology to known S-layer proteins. In addition, genes for putative pectin lyase- or lectin-like extracellular proteins, which are potentially involved in symbiotic interaction, were found in the MJ1T genome based on
in silico
3D protein structure prediction. Live cell imaging at the optimum growth temperature of 65°C indicated that cell complexes of strains MJ1
T
and MJ1HA were motile, but sole MJ1
T
cells were not. Taken together, we propose a model of the symbiotic interaction and cell cycle of
Nanobdella aerobiophila
.

IMPORTANCE

DPANN archaea are widely distributed in a variety of natural and artificial environments and may play a considerable role in the microbial ecosystem. All of the cultivated DPANN archaea so far need host organisms for their growth, i.e., obligately ectosymbiotic. However, the mechanism of the ectosymbiosis by DPANN archaea is largely unknown. To this end, we performed a comprehensive analysis of the cultivated DPANN archaeon,
Nanobdella aerobiophila
, using electron microscopy, live cell imaging, transcriptomics, and genomics, including 3D protein structure prediction. Based on the results, we propose a reasonable model of the symbiotic interaction and cell cycle of
Nanobdella aerobiophila
, which will enhance our understanding of the enigmatic physiology and ecological significance of DPANN archaea.
Crystal structure and biochemical activity of the macrodomain from rubella virus p150
Authors: Stoll Guido A. , Nikolopoulos Nikos , Zhai Haoming , Zhang Liao , Douse Christopher H. , Modis Yorgo
Published: January 2024

Rubella virus remains a global health threat. Rubella infections during pregnancy can cause serious congenital pathology, for which no antiviral treatments are available. Our work demonstrates that, like alpha- and coronaviruses, rubiviruses encode a mono-ADP-ribosylhydrolase with a structurally conserved macrodomain fold to counteract MARylation by poly (ADP–ribose) polymerases (PARPs) in the host innate immune response. Our structural data will guide future efforts to develop novel antiviral therapeutics against rubella or infections with related viruses.
Multifaceted interactions between host ESCRT-III and budded virus-related proteins involved in entry and egress of the baculovirus Autographa californica multiple nucleopolyhedrovirus
Authors: Bai Lisha , Sun Yu , Yue Xiaorong , Ji Ning , Yan Fanye , Yang Tian , Feng Guozhong , Guo Ya , Li Zhaofei
Published: January 2024

From archaea to eukaryotes, the endosomal sorting complex required for transport (ESCRT)-III complex is hijacked by many enveloped and nonenveloped DNA or RNA viruses for efficient replication. However, the mechanism of ESCRT-III recruitment, especially for that of large enveloped DNA viruses, remains elusive. Recently, we found the ESCRT-III components Vps2B, Vps20, Vps24, Snf7, Vps46, and Vps60 are necessary for the entry and/or egress of budded viruses (BVs) of Autographa californica multiple nucleopolyhedrovirus. Here, we demonstrated that the other three ESCRT-III components Chm7, Ist1, and Vps2A play similar roles in BV infection. By determining the subcellular localization of ESCRT-III components in infected cells and mapping the interaction of nine ESCRT-III components and 64 BV-related proteins, we built the interaction networks of ESCRT-III and the viral protein complexes involved in BV entry and egress. These studies provide a fundamental basis for understanding the mechanism of the ESCRT-mediated membrane remodeling for replication of baculoviruses.
SARS-CoV-2 and oncolytic EV-D68-encoded proteases differentially regulate pyroptosis
Authors: Shen Siyu , Guo Haoran , Li Yan , Zhang Lili , Tang Yubin , Li Huili , Li Xiaohan , Wang Pei-Hui , Yu Xiao-Fang , Wei Wei
Published: January 2024

Pyroptosis plays a crucial role in the pathogenesis of coronavirus disease 2019, and comprehending its function may facilitate the development of novel therapeutic strategies. This study aims to explore how viral-encoded proteases modulate pyroptosis. We investigated the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory enterovirus D68 (EV-D68) proteases on host cell pyroptosis. We found that SARS-CoV-2-encoded proteases NSP5 and NSP3 inactivate gasdermin D (GSDMD) but initiate gasdermin E (GSDME)-mediated pyroptosis, respectively. We also discovered that another respiratory virus EV-D68 encodes two distinct proteases 2A and 3C that selectively trigger GSDME-mediated pyroptosis while suppressing the function of GSDMD. Based on these findings, we further noted that EV-D68 infection triggers pyroptosis and produces oncolytic effects in human carcinoma cells. Our study provides new insights into the molecular mechanisms underlying virus-modulated pyroptosis and identifies potential targets for the development of antiviral and cancer therapeutics.
Development of reverse genetics system for Guanarito virus: substitution of E1497K in the L protein of Guanarito virus S-26764 strain changes plaque phenotype and growth kinetics
Authors: Taniguchi Satoshi , Maruyama Junki , Saito Takeshi , Littlefield Kirsten , Reyna Rachel A. , Manning John T. , Huang Cheng , Saijo Masayuki , Paessler Slobodan
Published: January 2024

Guanarito virus (GTOV) is a rodent-borne virus. GTOV causes fever, prostration, headache, arthralgia, cough, sore throat, nausea, vomiting, diarrhea, epistaxis, bleeding gums, menorrhagia, and melena in humans. The lethality rate is 23.1% or higher. Vero cell-adapted GTOV S-26764 shows a clear cytopathic effect (CPE), whereas the parental virus shows unclear CPE in Vero cells. We generated a reverse genetics system to rescue recombinant GTOVs and found that E1497K in the L protein was responsible for the formation of clear plaques as well as enhanced viral RNA replication and transcription efficiency. This reverse genetic system will accelerate vaccine and antiviral drug developments, and the findings of this study contribute to the understanding of the function of GTOV L as an RNA polymerase.
Genetic characterization and pathogenicity in a mouse model of newly isolated bat-originated mammalian orthoreovirus in South Korea
Authors: Do Hai Quynh , Yeom Minjoo , Moon Suyun , Lee Hanbyeul , Chung Chul-un , Chung Hee-chun , Park Jun Won , Na Woonsung , Song Daesub
Published: January 2024

Mammalian orthoreoviruses (MRVs) infect a wide range of hosts, including humans, livestock, and wildlife. In the present study, we isolated a novel
Mammalian orthoreovirus
from the intestine of a microbat (
Myotis aurascens
) and investigated its biological and pathological characteristics. Phylogenetic analysis indicated that the new isolate was serotype 2, sharing the segments with those from different hosts. Our results showed that it can infect a wide range of cell lines from different mammalian species, including human, swine, and non-human primate cell lines. Additionally, media containing trypsin, yeast extract, and tryptose phosphate broth promoted virus propagation in primate cell lines and most human cell lines, but not in A549 and porcine cell lines. Mice infected with this strain via the intranasal route, but not via the oral route, exhibited weight loss and respiratory distress. The virus is distributed in a broad range of organs and causes lung damage.
In vitro
and
in vivo
experiments also suggested that the new virus could be a neurotropic infectious strain that can infect a neuroblastoma cell line and replicate in the brains of infected mice. Additionally, it caused a delayed immune response, as indicated by the high expression levels of cytokines and chemokines only at 14 days post-infection (dpi). These data provide an important understanding of the genetics and pathogenicity of mammalian orthoreoviruses in bats at risk of spillover infections.

IMPORTANCE

Mammalian orthoreoviruses (MRVs) have a broad range of hosts and can cause serious respiratory and gastroenteritis diseases in humans and livestock. Some strains infect the central nervous system, causing severe encephalitis. In this study, we identified BatMRV2/SNU1/Korea/2021, a reassortment of MRV serotype 2, isolated from bats with broad tissue tropism, including the neurological system. In addition, it has been shown to cause respiratory syndrome in mouse models. The given data will provide more evidence of the risk of mammalian orthoreovirus transmission from wildlife to various animal species and the sources of spillover infections.
Antimicrobial properties of tomato juice and peptides against typhoidal
Salmonella
Authors: Kwon Ryan S. , Lee Gi Young , Lee Sohyoung , Song Jeongmin
Published: January 2024

Tomatoes are readily available and affordable vegetables that offer a range of health benefits due to their bioactive molecules, such as antioxidants and antimicrobials. In contrast to the widely recognized antioxidant properties of tomatoes, their antimicrobial properties remain largely unexplored. Here, we present our findings on the antimicrobial properties of tomato juice and peptides, namely, tomato-derived antimicrobial peptides (tdAMPs), in relation to their effectiveness against typhoidal
Salmonella
. Our research has revealed that tomato juice demonstrates significant antimicrobial properties against
Salmonella
Typhi, a pathogen that specifically affects humans and is responsible for causing typhoid fever. By employing computational analysis of the tomato genome sequence, conducting molecular dynamics simulation, and performing functional analyses, we have successfully identified two tdAMPs, namely, tdAMP-1 and tdAMP-2. These tdAMPs have demonstrated potent antimicrobial properties by effectively disrupting bacterial membranes. The efficacy of tdAMP-2 is shown to be more effective than tdAMP-1. The efficacy of tdAMP-1 and tdAMP-2 has been demonstrated against drug-resistant
S
. Typhi, as well as hyper-capsular
S
. Typhi variants that possess hypervirulent characteristics, which are presently circulating in countries with endemicity. Tomato juice, along with the two tdAMPs, has demonstrated effectiveness against uropathogenic
Escherichia coli
as well. This underscores their potential as viable agents in combating certain Gram-negative pathogens. This study provides valuable insights into the development of effective and sustainable public health strategies that utilize tomato and its derivatives as lifestyle interventions.

IMPORTANCE

In this study, we investigate the antimicrobial properties of tomato juice, the most widely consumed affordable vegetables, as well as tomato-derived antimicrobial peptides, in relation to their effectiveness against foodborne pathogens with an emphasis on
Salmonella
Typhi, a deadly human-specific pathogen.
Erratum to: Tunable Diode Lasers for Analytics and Diagnostics
Authors: Bolshov M. A. , Kuritsyn Yu. A. , Liger V. V. , Mironenko V. R. , Ponurovskii Ya. Ya.
Published: January 2024

An Erratum to this paper has been published: https://doi.org/10.1134/S1061934823440028
Erratum to: Biohybrid Technology for the Detection of Ultralow Concentrations of Trinitrotoluene in Air
Authors: Kiroy V. N. , Kosenko P. O. , Shepelev I. E. , Shcherban I. V. , Smolikov A. B. , Arsenyev F. V. , Zaborovsky A. V. , Aksenov V. A. , Tivileva M. I. , Gruznov V. M. , Zasypkina I. I.
Published: January 2024

An Erratum to this paper has been published: https://doi.org/10.1134/S1061934823440041
Erratum to: Nanoobjects for the Luminescence Determination of Fluoroquinolones
Authors: Shtykov S. N. , Smirnova T. D. , Rusanova T. Yu.
Published: January 2024

An Erratum to this paper has been published: https://doi.org/10.1134/S1061934823440065
Description of maternal and neonatal adverse events in pregnant people immunised with COVID-19 vaccines during pregnancy in the CLAP NETWORK of sentinel sites: nested case–control analysis of the immunization-associated risk – a study protocol
Authors: Macías Saint-Gerons Diego , Castro José Luis , Colomar Mercedes , Rojas-Cortés Robin , Sosa Claudio , Ropero Alba Maria , Serruya Suzanne Jacob , Pastor Desiré , Chiu Monica , Velandia-Gonzalez Martha , Abalos Edgardo , Durán Pablo , Gomez Ponce de León Rodolfo , Tomasso Giselle , Mainero Luis , Rubino Marcelo , De Mucio Bremen
Published: January 2024

Introduction

COVID-19 is associated with higher morbimortality in pregnant people compared with non-pregnant people. At present, the benefits of maternal immunisation are considered to outweigh the risks, and therefore, vaccination is recommended during pregnancy. However, additional information is needed on the safety of the vaccines in this population.

Methods and analysis

This a retrospective cohort nested case–control study in pregnant people who attended maternity hospitals from eight Latin American and Caribbean countries. A perinatal electronic clinical history database with neonatal and obstetric information will be used. The proportion of pregnant people immunised with COVID-19 vaccines of the following maternal and neonatal events will be described: preterm infant, small for gestational age, low birth weight, stillbirth, neonatal death, congenital malformations, maternal near miss and maternal death. Moreover, the risk of prematurity, small for gestational age and low birth weight associated with exposure to COVID-19 vaccines will be estimated. Each case will be matched with two groups of three randomly selected controls. Controls will be matched by hospital and mother’s age (±3 years) with an additional matching by delivery date and conception time in the first and second control groups, respectively. The estimated required sample size for the main analysis (exposure to any vaccine) concerning ‘non-use’ is at least 1009 cases (3027 controls) to detect an increased probability of vaccine-associated event risk of 30% and at least 650 cases (1950 controls) to detect 30% protection. Sensitivity and secondary analyses considering country, type of vaccine, exposure windows and completeness of immunisation will be reported.

Ethics

The study protocol was reviewed by the Ethical Review Committee on Research of the Pan American Health Organization. Patient informed consent was waived due to the retrospective design and the utilisation of anonymised data (Ref. No: PAHOERC.0546.01). Results will be disseminated in open access journals.
Improving our understanding of the social determinants of mental health: a data linkage study of mental health records and the 2011 UK census
Authors: Cybulski Lukasz , Chilman Natasha , Jewell Amelia , Dewey Michael , Hildersley Rosanna , Morgan Craig , Huck Rachel , Hotopf Matthew , Stewart Robert , Pritchard Megan , Wuerth Milena , Das-Munshi Jayati
Published: January 2024

Objectives

To address the lack of individual-level socioeconomic information in electronic healthcare records, we linked the 2011 census of England and Wales to patient records from a large mental healthcare provider. This paper describes the linkage process and methods for mitigating bias due to non-matching.

Setting

South London and Maudsley NHS Foundation Trust (SLaM), a mental healthcare provider in Southeast London.

Design

Clinical records from SLaM were supplied to the Office of National Statistics for linkage to the census through a deterministic matching algorithm. We examined clinical (International Classification of Disease-10 diagnosis, history of hospitalisation, frequency of service contact) and socio-demographic (age, gender, ethnicity, deprivation) information recorded in Clinical Record Interactive Search (CRIS) as predictors of linkage success with the 2011 census. To assess and adjust for potential biases caused by non-matching, we evaluated inverse probability weighting for mortality associations.

Participants

Individuals of all ages in contact with SLaM up until December 2019 (N=459 374).

Outcome measures

Likelihood of mental health records’ linkage to census.

Results

220 864 (50.4%) records from CRIS linked to the 2011 census. Young adults (prevalence ratio (PR) 0.80, 95% CI 0.80 to 0.81), individuals living in more deprived areas (PR 0.78, 95% CI 0.78 to 0.79) and minority ethnic groups (eg, Black African, PR 0.67, 0.66 to 0.68) were less likely to match to census. After implementing inverse probability weighting, we observed little change in the strength of association between clinical/demographic characteristics and mortality (eg, presence of any psychiatric disorder: unweighted PR 2.66, 95% CI 2.52 to 2.80; weighted PR 2.70, 95% CI 2.56 to 2.84).

Conclusions

Lower response rates to the 2011 census among people with psychiatric disorders may have contributed to lower match rates, a potential concern as the census informs service planning and allocation of resources. Due to its size and unique characteristics, the linked data set will enable novel investigations into the relationship between socioeconomic factors and psychiatric disorders.
Determinants and acceptability of HIV self-testing among vulnerable groups in sub-Saharan Africa: A scoping review protocol
Authors: Anyiam Felix Emeka , Sibiya Maureen Nokuthula , Oladimeji Olanrewaju
Published: January 2024

Introduction

HIV self-testing (HIVST) is where individuals collect their specimens and perform the HIV test privately. HIVST has improved testing uptake and coverage, especially among vulnerable groups of sub-Saharan Africa (SSA). Vulnerable groups include key populations such as men who have sex with men, sex workers, people who inject drugs, lesbian, gay, bisexual and transgender persons and young women. However, little is known about the determinants and acceptability of HIVST among these groups in SSA. Therefore, this scoping review aims to explore the determinants and acceptability of HIVST among vulnerable groups in SSA.

Methods

A scoping review will be conducted using the Arksey and O’Malley framework and further refined by Levac framework. The review will follow a six-step approach: (1) identifying the research question, (2) identifying relevant studies, (3) study selection eligibility, (4) charting the data, (5) collating, summarising and reporting the results and (6) consultation. A comprehensive search strategy will be developed, and the following electronic databases will be searched: MEDLINE, Embase, Global Health and the Cochrane Library. Grey literature will also be searched, including conference abstracts and reports. Eligibility criteria will include studies conducted in SSA, published between 2010 and 2023, focusing on vulnerable groups and exploring the determinants and acceptability of HIVST. Two independent reviewers will screen identified studies’ titles, abstracts and full texts. Any disagreements will be resolved through discussion or consultation with a third reviewer. Data extraction will be conducted using a standardised form.

Ethics and dissemination

This review, not requiring ethical approval, aims to inform policy and intervention design to boost HIV testing adoption within vulnerable communities. We plan to disseminate our findings via a peer-reviewed journal, policy briefs, conference presentations and stakeholder engagement.
Association between N-terminal pro-B-type natriuretic peptide and clinical outcomes in bedridden patients with stroke: a cross-sectional study
Authors: Li Dongxia , Zhou Mingchao , Zha Fubing , Long Jianjun , Wang Yulong
Published: January 2024

Objectives

Patients with stroke often remain bedridden despite rehabilitation. Serum N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels increase after stroke. Our study aimed to investigate the difference in NT-pro-BNP levels between bedridden and non-bedridden patients with stroke and to explore the factors influencing NT-pro-BNP levels in bedridden patients.

Design

A single-centre, cross-sectional study.

Setting

This study was conducted in a hospital, Shenzhen, China.

Participants

Between January 2019 and December 2022, 465 participants were included in this study.

Outcome measures

The collected data included basic information, laboratory data and echocardiographic parameters. Binary logistic regression analysis and receiver operating characteristic curves were used to identify factors associated with high NT-pro-BNP levels.

Results

Bedridden patients with stroke had higher levels of NT-pro-BNP, D-dimer, high-sensitivity C reactive protein (hs-CRP) and lower levels of creatinine, high-density lipoprotein cholesterol, albumin and haemoglobin, as well as lower left ventricular ejection fraction, fractional shortening and the ratio between the peak velocities of early and late diastolic filling than non-bedridden patients. In bedridden patients, age ≥75 years, high levels of hs-CRP and creatinine, and low levels of albumin were associated with high NT-pro-BNP levels. In non-bedridden patients, age ≥75 years and high creatinine levels were associated with high NT-pro-BNP levels. In bedridden patients with stroke, the area under the curve (AUC) of hs-CRP was 0.700 (p<0.001, 95% CI 0.638 to 0.762) with a cut-off value of 5.12 mg/L. The AUC of albumin was 0.671 (p<0.001, 95% CI 0.606 to 0.736) with a cut-off value of 37.15 g/L.

Conclusions

NT-pro-BNP levels were higher in bedridden patients with stroke than in non-bedridden patients. Decreased albumin and elevated hs-CRP levels were associated with high levels of NT-pro-BNP in bedridden patients. Further studies are needed to explore the risk stratification and potential treatments for elevated NT-pro-BNP in bedridden patients with stroke.
Effects of 6 weeks of cryotherapy plus compression therapy after total or unicompartmental knee arthroplasty: protocol for a single-centre, single-blind randomised controlled trial
Authors: de Vries Astrid J , Aksakal Haci K , Brouwer Reinoud W
Published: January 2024

Introduction

Effective rehabilitation after total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA) is often impeded by pain and swelling. Beneficial short-term effects in terms of pain and opioid use after a short period of cryotherapy (±compression therapy) have been demonstrated. The effectiveness of a longer intervention period on longer-term postoperative outcomes is unclear. This study aims to assess the effects of 6 weeks of cryotherapy plus compression therapy on pain, functioning and patient satisfaction after TKA or UKA.

Methods and analysis

A single-centre, single-blind randomised controlled trial will be conducted at a teaching hospital in the Netherlands. Patients over age 18 with end-stage osteoarthritis planned for a TKA or UKA are eligible; 104 UKA and 104 TKA patients will be included. Both groups will be randomly allocated (1:1) into an intervention group receiving 6 weeks of cryotherapy plus compression therapy (commencing after discharge from hospital) or a control group (usual care). The primary endpoint is perceived pain at rest at 6 weeks postoperatively. Secondary outcomes include compliance with cold protocol, pain at rest during the first six postoperative weeks and at 6 and 12 months postoperatively, pain on weight bearing, opioid use, functioning, patient satisfaction and complications.

Ethics and dissemination

The local medical ethics committee MEC-U approved the study protocol (R22.095/NL-number NL81956.100.22). The study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice regulations, and personal data will be handled in agreement with the Dutch Personal Data Protection Act (AGV). Written informed consent will be obtained prior to performing any of the study procedures. We will disseminate study results through multiple peer-reviewed publications and through conference presentations.

Trial registration number

NCT05572359.
Exploring the value of structured narrative feedback within the Serious Illness Conversation-Evaluation Exercise (SIC-Ex): a qualitative analysis
Authors: Ko Jenny , Roze des Ordons Amanda , Ballard Mark , Shenkier Tamara , Simon Jessica E , Fyles Gillian , Lefresne Shilo , Hawley Philippa , Chen Charlie , McKenzie Michael , Sanders Justin , Bernacki Rachelle
Published: January 2024

Objectives

The Serious Illness Conversation Guide (SICG) has emerged as a framework for conversations with patients with a serious illness diagnosis. This study reports on narratives generated from open-ended questions of a novel assessment tool, the Serious Illness Conversation-Evaluation Exercise (SIC-Ex), to assess resident-led conversations with patients in oncology outpatient clinics.

Design

Qualitative study using template analysis.

Setting

Three academic cancer centres in Canada.

Participants

7 resident physicians (trainees), 7 patients from outpatient cancer clinics, 10 preceptors (raters) consisting of medical oncologists, palliative care physicians and radiation oncologists.

Interventions

Each trainee conducted an SIC with a patient, which was videotaped. The raters watched the videos and evaluated each trainee using the novel SIC-Ex and the reference Calgary-Cambridge Guide (CCG) initially and again 3 months later. Two independent coders used template analysis to code the raters’ narrative comments and identify themes/subthemes.

Outcome measures

How narrative comments aligned with elements of the CCG and SICG.

Results

Template analysis yielded four themes: adhering to SICG, engaging patients and family members, conversation management and being mindful of demeanour. Narrative comments identified numerous verbal and non-verbal elements essential to SICG. Some comments addressing general skills in engaging patients/families and managing the conversation (eg, setting agenda, introduction, planning, exploring, non-verbal communication) related to both the CCG and SICG, whereas other comments such as identifying substitute decision maker(s), affirming commitment and introducing Advance Care Planning were specific to the SICG.

Conclusions

Narrative comments generated by SIC-Ex provided detailed and nuanced insights into trainees’ competence in SIC, beyond the numerical ratings of SIC-Ex and the general communication skills outlined in the CCG, and may contribute to a more fulsome assessment of SIC skills.
Developing and testing culturally relevant bolt-on items for EQ-5D-5L in Chinese populations: a mixed-methods study protocol
Authors: Mao Zhuxin , Fan Jingzhi , Rencz Fanni , Yang Zhihao , Luo Nan , Wang Pei
Published: January 2024

Introduction

EQ-5D is one of the most frequently used health-related quality of life (HRQoL) measures but has been found to be insensitive in detecting differences in health status in some general populations and disease groups. For example, the appropriateness of applying EQ-5D in the Chinese cultural setting has been widely discussed. Adding additional HRQoL dimensions (bolt-on items) can be a solution to both retain the original descriptive system of EQ-5D, while enhancing its sensitivity to the local context. To date, no studies have proposed culturally relevant bolt-ons for China or examined the psychometric properties of such bolt-on items. This protocol documents the identification, development, selection and psychometric testing of culturally relevant bolt-on items for EQ-5D-5L in China.

Methods and analysis

We will identify and develop candidate bolt-on items that are most relevant in the Chinese culture, through former literature reviews on health concepts important for the Chinese population, conducting expert consultations and qualitative interviews. We will quantitatively test the acceptability and measurement properties (including distributional characteristics and construct validity) of the candidate items in both general and disease populations in a cross-sectional setting. The patient group will be followed up to collect two-time-point data to assess test–retest reliability of the candidate items. Bolt-on item selection will consider both the qualitative and quantitative evidence gathered. This protocol outlines a comprehensive mixed-methods process for identifying, developing, selecting and testing bolt-on items that are relevant and culturally appropriate in China. This study may serve as a guide for similar initiatives in other cultural contexts.

Ethics and dissemination

This study received ethics approval from the Institutional Review Board of School of Public Health, Fudan University (IRB number: 2022-TYSQ-03-154). Study findings will be disseminated through international peer-reviewed journal articles as well as public, academic presentations at national and international conferences.
Expanding the phenotype of Kleefstra syndrome: speech, language and cognition in 103 individuals
Authors: Morison Lottie D. , Kennis Milou G.P. , Rots Dmitrijs , Bouman Arianne , Kummeling Joost , Palmer Elizabeth , Vogel Adam P. , Liegeois Frederique , Brignell Amanda , Srivastava Siddharth , Frazier Zoe , Milnes Di , Goel Himanshu , Amor David J. , Scheffer Ingrid E. , Kleefstra Tjitske , Morgan Angela T.
Published: January 2024

Objectives

Speech and language impairments are core features of the neurodevelopmental genetic condition Kleefstra syndrome. Communication has not been systematically examined to guide intervention recommendations. We define the speech, language and cognitive phenotypic spectrum in a large cohort of individuals with Kleefstra syndrome.

Method

103 individuals with Kleefstra syndrome (40 males, median age 9.5 years, range 1–43 years) with pathogenic variants (52 9q34.3 deletions, 50 intragenic variants, 1 balanced translocation) were included. Speech, language and non-verbal communication were assessed. Cognitive, health and neurodevelopmental data were obtained.

Results

The cognitive spectrum ranged from average intelligence (12/79, 15%) to severe intellectual disability (12/79, 15%). Language ability also ranged from average intelligence (10/90, 11%) to severe intellectual disability (53/90, 59%). Speech disorders occurred in 48/49 (98%) verbal individuals and even occurred alongside average language and cognition. Developmental regression occurred in 11/80 (14%) individuals across motor, language and psychosocial domains. Communication aids, such as sign and speech-generating devices, were crucial for 61/103 (59%) individuals including those who were minimally verbal, had a speech disorder or following regression.

Conclusions

The speech, language and cognitive profile of Kleefstra syndrome is broad, ranging from severe impairment to average ability. Genotype and age do not explain the phenotypic variability. Early access to communication aids may improve communication and quality of life.
Cardiometabolic risk factors and neurodegeneration: a review of the mechanisms underlying diabetes, obesity and hypertension in Alzheimer’s disease
Authors: Patel Vijay , Edison Paul
Published: January 2024

A growing body of evidence suggests that cardiometabolic risk factors play a significant role in Alzheimer’s disease (AD). Diabetes, obesity and hypertension are highly prevalent and can accelerate neurodegeneration and perpetuate the burden of AD. Insulin resistance and enzymes including insulin degrading enzymes are implicated in AD where breakdown of insulin is prioritised over amyloid-β. Leptin resistance and inflammation demonstrated by higher plasma and central nervous system levels of interleukin-6 (IL-6), IL-1β and tumour necrosis factor-α, are mechanisms connecting obesity and diabetes with AD. Leptin has been shown to ameliorate AD pathology and enhance long-term potentiation and hippocampal-dependent cognitive function. The renin-aldosterone angiotensin system, involved in hypertension, has been associated with AD pathology and neurotoxic reactive oxygen species, where angiotensin binds to specific angiotensin-1 receptors in the hippocampus and cerebral cortex. This review aims to consolidate the evidence behind putative processes stimulated by obesity, diabetes and hypertension, which leads to increased AD risk. We focus on how novel knowledge can be applied clinically to facilitate recognition of efficacious treatment strategies for AD.
Prevalence and burden of pain across the entire spectrum of Huntington’s disease
Authors: Sprenger Gregory P , van Zwet Erik W , Bakels Hannah S , Achterberg Wilco P , Roos Raymund A , de Bot Susanne T
Published: January 2024

Background

Pain is an important symptom in Huntington’s disease (HD), however, not systematically studied and understood. The objective of the current study is to assess the prevalence of pain, pain interference in daily activities, painful conditions, analgesic use and the severity of the pain burden across different disease stages and ‘Age at symptom Onset’ groups. Additionally, the association between pain and disease burden was investigated.

Methods

A cross-sectional analysis was conducted within two large data sets, which included different types of pain scales. Multivariable logistic regression analyses and analyses of variance were performed to compare the pain levels with those in the general population. The analyses were adjusted for sex and age. Locally Estimated Scatterplot Smoothing was used to test the association between pain and the HD pathology score: a measure of disease burden.

Results

The mean prevalence of pain in the HD population was 40% and for pain interference around 35% in both data sets. Patients in the early, middle and late stage of HD experience more pain burden compared with what is reported in patients with chronic pain (p<0.01). A positive and significant association was demonstrated between pain and disease burden. Patients in late stage HD with pain use significantly less analgesics compared with the general population (5% vs 13%, respectively (p<0.01)).

Conclusions

Pain is a prevalent and important symptom in HD. Severe pain burden in the HD population is present and positively associated with disease burden. Risk for undertreatment with analgesics is nevertheless present. Awareness of pain in HD needs to be increased, both clinically and scientifically.
Penetration characteristics of suction caisson for offshore wind power: a field study
Authors: Zhu Xun , Chen Zheng , Guan Yun-Fei , Ni Pengpeng , Liu Yong-Gang , Li Wen-Xuan , Han Xun , Fan Kai-Fang
Published: January 2024

Suction caisson is a new offshore wind power foundation structure developed in recent years. Understanding its penetration characteristics is crucial to the successful application. A field test was conducted in the eastern waters of Rudong, Jiangsu Province, China, to investigate the penetration process of suction caisson. The test results demonstrate that suction caisson can penetrate smoothly to a predetermined elevation of seabed soil under the complex environmental loads, such as natural wind and wave currents. The inclination of the caisson is only 0.018° once the penetration process is complete. The pore water pressure at the outer skirt is primarily influenced by the tide level and drainage conditions of the contact soil layer during penetration, and the peak effective interface pressure at the skirt-soil interface decreases by about 46.7% due to negative pressure inside the skirt. Frictional fatigue effects are found at the skirt-soil interfaces. Meanwhile, the seepage reduction and squeezing induced resistance effects at the skirt-soil interface are the leading causes for the different distributions of effective interface pressure between the inner and outer skirts of the caisson. The findings of this study can guide the future penetration of suction caisson under challenging geological circumstances.
Regression analysis of factors impacting interest rates
Authors: Wang Guizhou , Hausken Kjell
Published: January 2024

This paper investigates the factors that interact with interest rates. The results show that interest rates positively correlate with deviations in inflation, the logarithm of the real GDP (gross domestic product) ratio, the logarithm of the money supply ratio, deviations in unemployment rates, money velocity, deficit, and the dollar index. The interest rates negatively correlate with debt, the Dow Jones Industrial Average (DJIA), debt to GDP ratio, and real GDP growth rate. Regression analysis shows with statistical significance an increase in interest rates with deviations in inflation, money velocity, the dollar index, and a decrease with the DJIA. The analysis is refined by removing insignificant variables and addressing a multicollinearity problem. The results could provide governments and central banks with focal points for developing interest rate policies.
Can AMH Replace Ultrasound in the Diagnosis of PCOS
Authors: Norman Robert
Published: January 2024

AMH is a hormone released by the developing and small follicles in the ovary. It circulates in the blood and has actions in the hypothalamus as well as in the ovary. Measurement of AMH is now well established and is routine in women who will undergo ovarian stimulation.

AMH is also a measure of the number of small follicles in the ovary and correlates well with the ultrasound assessment of follicle numbers. It is now part of the recommended diagnostic criteria contributing to determination of polycystic morphology and can replace the need for a diagnostic ultrasound. Values are age dependant, affected by the oral contraceptive pill and weight and variable depending on the immunoassay used.

In this talk I will discuss the latest development in AMH as a diagnostic tool contributing to the diagnosis of PCOS.