bluuebunny/crossref_metadata_2025 huggingface dataset:
Recovery of walking after paralysis by regenerating characterized neurons to their natural target region
Authors: Squair Jordan W. , Milano Marco , de Coucy Alexandra , Gautier Matthieu , Skinnider Michael A. , James Nicholas D. , Cho Newton , Lasne Anna , Kathe Claudia , Hutson Thomas H. , Ceto Steven , Baud Laetitia , Galan Katia , Aureli Viviana , Laskaratos Achilleas , Barraud Quentin , Deming Timothy J. , Kohman Richie E. , Schneider Bernard L. , He Zhigang , Bloch Jocelyne , Sofroniew Michael V. , Courtine Gregoire , Anderson Mark A.
Published: September 2023

Axon regeneration can be induced across anatomically complete spinal cord injury (SCI), but robust functional restoration has been elusive. Whether restoring neurological functions requires directed regeneration of axons from specific neuronal subpopulations to their natural target regions remains unclear. To address this question, we applied projection-specific and comparative single-nucleus RNA sequencing to identify neuronal subpopulations that restore walking after incomplete SCI. We show that chemoattracting and guiding the transected axons of these neurons to their natural target region led to substantial recovery of walking after complete SCI in mice, whereas regeneration of axons simply across the lesion had no effect. Thus, reestablishing the natural projections of characterized neurons forms an essential part of axon regeneration strategies aimed at restoring lost neurological functions.
A novel bacterial sulfite dehydrogenase that requires three
c
-type cytochromes for electron transfer
Authors: Sun Weining , Xu Yuanyou , Liang Yawen , Yu Qingzi , Gao Haichun
Published: September 2023

c
-type Cytochromes (
c
-Cyts), primarily as electron carriers and oxidoreductases, play a key role in energy transduction processes in virtually all living organisms. Many bacteria, such as
Shewanella oneidensis
, are particularly rich in
c
-Cyts, supporting respiratory versatility not seen in eukaryotes. Unfortunately, a large number of
c
-Cyts are underexplored, and their biological functions remain unknown. In this study, we identify SorCABD of
S. oneidensis
as a novel sulfite dehydrogenase (SDH), which catalyzes the oxidation of sulfite to sulfate. In addition to catalytic subunit SorA, this enzymatic complex includes three
c
-Cyt subunits, which all together carry out electron transfer. The electrons extracted from sulfite oxidation are ultimately delivered to oxygen, leading to oxygen reduction, a process relying on terminal oxidase cyt
cbb
3
. Genomic analysis suggests that the homologs of this SDH are present in a small number of bacterial genera,
Shewanella
and
Vibrio
in particular. Because these bacteria are generally capable of reducing sulfite under anaerobic conditions, the co-existence of a sulfite oxidation system implies that they may play especially important roles in the transformation of sulfur species in natural environments.

Importance

c
-type Cytochromes (
c
-Cyts) endow bacteria with high flexibility in their oxidative/respiratory systems, allowing them to extracellularly transform diverse inorganic and organic compounds for survival and growth. However, a large portion of the bacterial
c
-Cyts remain functionally unknown. Here, we identify three
c
-Cyts that work together as essential electron transfer partners for the catalytic subunit of a novel SDH in sulfite oxidation in
Shewanella oneidensis
. This characteristic makes
S. oneidensis
the first organism known to be capable of oxidizing and reducing sulfite. The findings suggest that
Shewanella
, along with a small number of other aquatic bacteria, would serve as a particular driving force in the biogeochemical sulfur cycle in nature.
Proteomic survey of the DNA damage response in
Caulobacter crescentus
Authors: Tashjian Tommy F. , Zeinert Rilee D. , Eyles Stephen J. , Chien Peter
Published: September 2023

The bacterial DNA damage response is a critical, coordinated response to endogenous and exogenous sources of DNA damage. Response dynamics are dependent on coordinated synthesis and loss of relevant proteins. While much is known about its global transcriptional control, changes in protein abundance that occur upon DNA damage are less well characterized at the system level. Here, we perform a proteome-wide survey of the DNA damage response in
Caulobacter crescentus
. We find that while most protein abundance changes upon DNA damage are readily explained by changes in transcription, there are exceptions. The survey also allowed us to identify the novel DNA damage response factor, YaaA, which has been overlooked by previously published, transcription-focused studies. A similar survey in a ∆
lon
strain was performed to explore
lon’s
role in DNA damage survival. The ∆
lon
strain had a smaller dynamic range of protein abundance changes in general upon DNA damage compared to the wild-type strain. This system-wide change to the dynamics of the response may explain this strain’s sensitivity to DNA damage. Our proteome survey of the DNA damage response provides additional insight into the complex regulation of stress response and nominates a novel response factor that was overlooked in prior studies.

IMPORTANCE

The DNA damage response helps bacteria to react to and potentially survive DNA damage. The mutagenesis induced during this stress response contributes to the development of antibiotic resistance. Understanding how bacteria coordinate their response to DNA damage could help us to combat this growing threat to human health. While the transcriptional regulation of the bacterial DNA damage response has been characterized, this study is the first to our knowledge to assess the proteomic response to DNA damage in
Caulobacter
.
Representative measles virus infection requires appropriate airway epithelia culture conditions
Authors: Kaufman Justin W. , Singh Brajesh K. , Durnell Lorellin A. , Sinn Patrick L.
Published: September 2023

Despite an effective vaccine, measles virus (MeV) remains a critical health burden worldwide. Many fundamental questions remain about its unique biology. Because MeV is a human specific pathogen, research has largely relied on immortalized human cell lines with confirmatory studies in non-human primates or humanized mice. A critical challenge for MeV research is identification of representative
in vitro
model systems. To study infection, spread, and release in the airways, we utilize primary cultures of airway epithelia cells collected from human donor lungs. This cell culture model recapitulates the pseudostratified columnar epithelial structure and multiple cell types of the conducting airways. In this model, direct cell-to-cell spread of MeV results in well-defined foci termed infectious centers. Here, we demonstrate that infectious center formation following basolateral MeV infection is consistent between two primate species (human and macaque), between two university core facilities that provide primary human airway cultures, and between human primary cells and fresh human tracheal explants. Canine distemper virus infection of differentiated primary cultures of ferret airway epithelial cells also results in infectious center formation suggesting that this mechanism of infection and spread is shared between morbilliviruses. Importantly, the well-defined morphology of the pseudostratified columnar epithelial layer is lost when fetal bovine serum is included in the culture media or when primary cells are passaged twice. Both conditions lead to apical infection by MeV and loss of defined infectious centers. These results suggest that MeV-induced infectious center formation depends on appropriate differentiation, maintenance, and morphology of primary cultures.

Importance

For many years, measles virus (MeV) was assumed to first enter the host via the apical surface of airway epithelial cells and subsequently spread systemically. We and others reported that MeV has an overwhelming preference for entry at the basolateral surface of airway epithelial cells, which led to a fundamental new understanding of how MeV enters a human host. This unexpected observation using well-differentiated primary cultures of airway epithelia from human donors contradicted previous studies using immortalized cultured cells. Here, we show that appropriate differentiation and cell morphology of primary human airway epithelial cells are critical to recapitulate MeV infection patterns and pathogenesis of the
in vivo
airways. By simply culturing primary cells in media containing serum or passaging primary cultures, erroneous results quickly emerge. These results have broad implications for data interpretation related to respiratory virus infection, spread, and release from human airway epithelial cells.
Development of Cas13a-based assays for
Neisseria gonorrhoeae
detection and gyrase A determination
Authors: Allan-Blitz Lao-Tzu , Shah Palak , Adams Gordon , Branda John A. , Klausner Jeffrey D. , Goldstein Robert , Sabeti Pardis C. , Lemieux Jacob E.
Published: September 2023

Neisseria gonorrhoeae
is one of the most common bacterial sexually transmitted infections. The emergence of antimicrobial-resistant
N. gonorrhoeae
is an urgent public health threat. Currently, the diagnosis of
N. gonorrhoeae
infection requires expensive laboratory infrastructure, while antimicrobial susceptibility determination requires bacterial culture, both of which are infeasible in low-resource areas where the prevalence of infection is highest. Recent advances in molecular diagnostics, such as
s
pecific
h
igh-sensitivity
e
nzymatic
r
eporter un
lock
ing (SHERLOCK) using CRISPR-Cas13a and isothermal amplification, have the potential to provide low-cost detection of pathogen and antimicrobial resistance. We designed and optimized RNA guides and primer sets for SHERLOCK assays capable of detecting
N. gonorrhoeae
via the
por
A gene and of predicting ciprofloxacin susceptibility via a single mutation in the gyrase A (
gyr
A) gene. We evaluated their performance using both synthetic DNA and purified
N. gonorrhoeae
isolates. For
por
A
,
we created both a fluorescence-based assay and lateral flow assay using a biotinylated fluorescein reporter. Both methods demonstrated sensitive detection of 14
N
.
gonorrhoeae
isolates and no cross-reactivity with 3 non-gonococcal
Neisseria
isolates. For
gyr
A, we created a fluorescence-based assay that correctly distinguished between 20 purified
N. gonorrhoeae
isolates with phenotypic ciprofloxacin resistance and 3 with phenotypic susceptibility. We confirmed the
gyr
A genotype predictions from the fluorescence-based assay with DNA sequencing, which showed 100% concordance for the isolates studied. We report the development of Cas13a-based SHERLOCK assays that detect
N. gonorrhoeae
and differentiate ciprofloxacin-resistant isolates from ciprofloxacin-susceptible isolates.

IMPORTANCE

Neisseria gonorrhoeae,
the cause of gonorrhea, disproportionately affects resource-limited settings. Such areas, however, lack the technical capabilities for diagnosing the infection. The consequences of poor or absent diagnostics include increased disease morbidity, which, for gonorrhea, includes an increased risk for HIV infection, infertility, and neonatal blindness, as well as an overuse of antibiotics that contributes to the emergence of antibiotic resistance. We used a novel CRISPR-based technology to develop a rapid test that does not require laboratory infrastructure for both diagnosing gonorrhea and predicting whether ciprofloxacin can be used in its treatment, a one-time oral pill. With further development, that diagnostic test may be of use in low-resource settings.
Multi-environment ecogenomics analysis of the cosmopolitan phylum Gemmatimonadota
Authors: Mujakić Izabela , Cabello-Yeves Pedro J. , Villena-Alemany Cristian , Piwosz Kasia , Rodriguez-Valera Francisco , Picazo Antonio , Camacho Antonio , Koblížek Michal
Published: September 2023

Gemmatimonadota is a diverse bacterial phylum commonly found in environments such as soils, rhizospheres, fresh waters, and sediments. So far, the phylum contains just six cultured species (five of them sequenced), which limits our understanding of their diversity and metabolism. Therefore, we analyzed over 400 metagenome-assembled genomes (MAGs) and 5 culture-derived genomes representing Gemmatimonadota from various aquatic environments, hydrothermal vents, sediments, soils, and host-associated (with marine sponges and coral) species. The principal coordinate analysis based on the presence/absence of genes in Gemmatimonadota genomes and phylogenomic analysis documented that marine and host-associated Gemmatimonadota were the most distant from freshwater and wastewater species. A smaller genome size and coding sequences (CDS) number reduction were observed in marine MAGs, pointing to an oligotrophic environmental adaptation. Several metabolic pathways are restricted to specific environments. For example, genes for anoxygenic phototrophy were found only in freshwater, wastewater, and soda lake sediment genomes. There were several genomes from soda lake sediments and wastewater containing type IC/ID ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO). Various genomes from wastewater harbored bacterial type II RuBisCO, whereas RuBisCO-like protein was found in genomes from fresh waters, soil, host-associated, and marine sediments. Gemmatimonadota does not contain nitrogen fixation genes; however, the
nosZ
gene, involved in the reduction of N
2
O, was present in genomes from most environments, missing only in marine water and host-associated Gemmatimonadota. The presented data suggest that Gemmatimonadota evolved as an organotrophic species relying on aerobic respiration and then remodeled its genome inventory when adapting to particular environments.

IMPORTANCE

Gemmatimonadota is a rarely studied bacterial phylum consisting of a handful of cultured species. Recent culture-independent studies documented that these organisms are distributed in many environments, including soil, marine, fresh, and waste waters. However, due to the lack of cultured species, information about their metabolic potential and environmental role is scarce. Therefore, we collected Gemmatimonadota metagenome-assembled genomes (MAGs) from different habitats and performed a systematic analysis of their genomic characteristics and metabolic potential. Our results show how Gemmatimonadota have adapted their genomes to different environments.
The role of integration host factor in biofilm and virulence of high-alcohol-producing
Klebsiella pneumoniae
Authors: Fan Zheng , Fu Tongtong , Li Zhoufei , Du Bing , Cui Xiaohu , Zhang Rui , Feng Yanling , Zhao Hanqing , Xue Guanhua , Cui Jinghua , Yan Chao , Gan Lin , Feng Junxia , Xu Ziying , Yu Zihui , Tian Ziyan , Ding Zanbo , Chen Jinfeng , Chen Yujie , Yuan Jing
Published: September 2023

Klebsiella pneumoniae
is a well-known human nosocomial pathogen with an arsenal of virulence factors, including capsular polysaccharides (CPS), fimbriae, flagella, and lipopolysaccharides (LPS). Our previous study found that alcohol acted as an essential virulence factor for high-alcohol-producing
K. pneumoniae
(HiAlc
Kpn
). Integration host factor (IHF) is a nucleoid-associated protein that functions as a global virulence regulator in
Escherichia coli
. However, the regulatory role of IHF in
K. pneumoniae
remains unknown. In the present study, we found that deletion of
ihfA
or
ihfB
resulted in a slight defect in bacterial growth, a severe absence of biofilm formation and cytotoxicity, and a significant reduction in alcohol production. RNA sequencing differential gene expression analysis showed that compared with the wild-type control, the expression of many virulence factor genes was downregulated in Δ
ihfA
and Δ
ihfB
strains, such as those related to CPS (
rcsA
,
galF
,
wzi
, and
iscR
), LPS (
rfbABCD
), type I and type III fimbriae (
fim
and
mrk
operon), cellulose (
bcs
operon), iron transporter (
feoABC
,
fhuA
,
fhuF
,
tonB
,
exbB
, and
exbD
), quorum sensing (
lsr
operon and
sdiA
), type II secretion system (T2SS) and type VI secretion system (T6SS) (
tssG
,
hcp
, and
gspE
). Of these virulence factors, CPS, LPS, fimbriae, and cellulose are involved in biofilm formation. In addition, IHF could affect the alcohol production by regulating genes related to glucose intake (
ptsG
), pyruvate formate-lyase, alcohol dehydrogenase, and the tricarboxylic acid (TCA) cycle. Our data provided new insights into the importance of IHF in regulating the virulence of HiAlc
Kpn
.

IMPORTANCE

Klebsiella pneumoniae
is a well-known human nosocomial pathogen that causes various infectious diseases, including urinary tract infections, hospital-acquired pneumonia, bacteremia, and liver abscesses. Our previous studies demonstrated that HiAlc
Kpn
mediated the development of nonalcoholic fatty liver disease by producing excess endogenous alcohol
in vivo
. However, the regulators regulating the expression of genes related to metabolism, biofilm formation, and virulence of HiAlc
Kpn
remain unclear. In this study, the regulator IHF was found to positively regulate biofilm formation and many virulence factors including CPS, LPS, type I and type III fimbriae, cellulose, iron transporter, AI-2 quorum sensing, T2SS, and T6SS in HiAlc
Kpn
. Furthermore, IHF positively regulated alcohol production in HiAlc
Kpn
. Our results suggested that IHF could be a potential drug target for treating various infectious diseases caused by
K. pneumoniae
. Hence, the regulation of different virulence factors by IHF in
K. pneumoniae
requires further investigation.
PeAP1-mediated oxidative stress response plays an important role in the growth and pathogenicity of
Penicillium expansum
Authors: Chen Yong , Zhang Yichen , Xu Dongying , Zhang Zhanquan , Li Boqiang , Tian Shiping
Published: September 2023

Penicillium expansum
is the causal agent of post-harvest blue mold in various fruits and serves as a model for understanding fungal pathogenicity and mycotoxin production. The relevance of oxidative stress response in the growth and virulence of
P. expansum
has been largely unexplored. Here, we identify the transcriptional factor PeAP1 as a regulator of oxidative stress response in
P. expansum
. Gene expression and protein abundance of PeAP1, as well as its nuclear localization, are specifically induced by H
2
O
2
. Deletion of
PeAP1
results in increased sensitivity to H
2
O
2
, and
PeAP1
mutants exhibit a variety of defects in hyphal growth and virulence. PeAP1 prevents the accumulation of both intracellular H
2
O
2
during vegetative growth and host-derived H
2
O
2
during biotrophic growth. Application of an antioxidant glutathione and a NADPH oxidase inhibitor, diphenylene iodonium, to the
PeAP1
mutant partially restored fungal growth and virulence. RNA sequencing analysis revealed 144 H
2
O
2
-induced PeAP1 target genes, including four antioxidant-related genes,
PeGST1
,
PePrx1
,
PePrx2
, and
PeTRX2
, that were also demonstrated to be involved in oxidative stress response and/or virulence. Collectively, our results demonstrate the global regulatory role of PeAP1 in response to oxidative stress and provide insights into the critical role of the PeAP1-mediated oxidative stress response to regulate growth and virulence of
P. expansum
.

IMPORTANCE

Reactive oxygen species are the core of host plant defense and also play a vital role in the successful invasion of host plants by pathogenic fungi. Despite its importance, the relevance of oxidative stress response in fungal growth and virulence is poorly understood in
P. expansum
. In this study, we reveal that the transcription factor PeAP1 acts as a central regulator of oxidative stress response in
P. expansum
and that there is a major link between PeAP1-mediated oxidative stress response and fungal growth and virulence. To explore the underlying mechanisms, we performed comparative transcriptomic studies and identified a number of H
2
O
2
-induced PeAP1 target genes, including four novel ones,
PePrx1
,
PePrx2
,
PeGST1
, and
PeTRX2
, whose functions were linked to PeAP1 and pathogenicity. These findings provide novel insights into the regulation mechanism of PeAP1 on growth and virulence, which might offer promising targets for control of blue mold and patulin contamination.
Formation of lower arc crust by magmatic underplating revealed by high-precision geochronology
Authors: Stirling Jack E. , Denyszyn Steven W. , Loucks Robert R. , Kemp Anthony I.S. , Hammerli Johannes , Fiorentini Marco L. , Vervoort Jeffrey D.
Published: September 2023

In modern plate tectonic regimes, continental crust is generated above subduction zones in magmatic island arcs. Models for continental growth—largely based on the modeling of geochemical processes that can transform mantle melts into the intermediate composition of bulk continental crust—have been hampered by a lack of definitive geochronology, which could clarify the temporal emplacement of igneous rocks at the base of island arc crust. The Kohistan Arc Complex (KAC) of Pakistan is a rare window into a nearly complete section of lower arc crust, revealing a sequence of igneous rocks representing discrete batches of magma underplated along the base of the arc crust. We present high-precision isotope dilution–thermal ionization mass spectrometry U-Pb geochronological data from zircon, and Lu-Hf and Sm-Nd isochron data from several mafic lower crustal cumulates within the KAC. These data establish a clear downward-younging age trend throughout this succession of cumulate complexes, demonstrating a total magmatic duration of ~20 m.y., corresponding to a rate of lower crust formation of up to 200–260 km3 km–1 Ma–1. These results provide the first direct evidence of a sequential process of underplating, revealing a fundamental mechanism responsible for building the root of island arc crust.
Endophthalmitis rates and risk factors following intraocular surgeries in the medicare population from 2016 to 2019
Authors: Chen Ariel , Dun Chen , Schein Oliver D , Srikumaran Divya , Zafar Sidra , Makary Martin , Woreta Fasika
Published: September 2023

Aims

To determine endophthalmitis rates and risk factors following intraocular surgeries in the Medicare population.

Methods

Retrospective, cross-sectional study from 2016 to 2019 in Medicare fee-for-service and Medicare Advantage beneficiaries. 100% Medicare claims were used to identify eyes that underwent intraocular surgery. Exclusion criteria included eyes that had intraocular surgery 42 days before or after and eyes in patients with a history of endophthalmitis within 12 months.

Results

9 744 400 intraocular surgeries were performed among Medicare beneficiaries from 2016 to 2019. A 42-day postoperative endophthalmitis rate was 0.09%. Endophthalmitis rate by surgery type was 0.43% for corneal transplant, 0.36% for secondary intraocular lens (IOL), 0.24% for retina, 0.16% for glaucoma, 0.11% for cataract combined with other procedures and 0.08% for cataract surgeries alone. On multivariable analysis, the risk of endophthalmitis was increased for all intraocular surgery types when compared with cataract surgeries; adjusted OR (aOR) 5.30 (p<0.01) for corneal transplant, aOR 4.50 (p<0.01) for secondary IOL, aOR 3.00 (p<0.01) for retina, aOR 1.93 (p<0.01) for glaucoma, aOR 1.45 (p<0.01) for combined cataract surgeries. Increased risk of developing endophthalmitis was associated with older age (≥85 vs 65–75 years: aOR 1.36; p<0.01), male sex (aOR 1.20; p<0.001) and greater Charlson Comorbidity Index (≥7 vs 0: aOR 1.79; p<0.01).

Conclusions

Postoperative endophthalmitis rate after intraocular surgeries was 0.09% between 2016 and 2019 for Medicare beneficiaries. Endophthalmitis rates were highest for corneal transplant surgeries followed by secondary IOL surgeries and lowest for cataract surgeries. Older age, male gender and higher comorbidity index were associated with risk of endophthalmitis.
Protocol of a randomised controlled phase II clinical trial investigating PREoperative endoscopic injection of BOTulinum toxin into the sphincter of Oddi to reduce bile leakage after hepatic resection: the PREBOT-II trial
Authors: Mack Claudia Eva , Klaiber Ulla , Sauer Peter , Kohlhas Laura , Baumann Lukas , Martin Eike , Mehrabi Arianeb , Buchler Markus W , Hackert Thilo
Published: September 2023

Introduction

Bile leakage represents a major cause of morbidity following hepatic resection. Although most patients can be managed non-operatively, this complication requires diagnostics and therapeutic interventions. Preoperative endoscopic injection of botulinum toxin (BTX) into the sphincter of Oddi represents an innovative approach to prevent bile leakage. The aim of the PREBOT-II trial is to generate the first randomised controlled trial data on the safety, feasibility and efficacy of preoperative endoscopic BTX injection into the sphincter of Oddi to prevent bile leakage following hepatic resection.

Methods and analysis

The PREBOT-II trial is an investigator-initiated, exploratory, multicentre, randomised, controlled, open-label, phase II clinical trial with two parallel study groups. 70 patients scheduled for hepatic resection will be randomised to either the intervention or the control group. Patients of the intervention group will undergo preoperative endoscopic injection of BTX into the sphincter of Oddi 3–10 days before surgery, whereas in the control group only hepatic resection will be performed. The primary endpoint is the occurrence of a postoperative bile leakage within 30 days after hepatic resection according to the definition of the International Study Group of Liver Surgery. The secondary endpoints comprise further postoperative morbidity parameters such as severity of postoperative bile leakage, post-hepatectomy haemorrhage or liver failure, mortality and quality of life up to 3 months after hepatic resection. Safety and feasibility of the procedure will also be recorded.

Ethics, funding and dissemination

The PREBOT-II trial has been approved by the German Federal Institute for Drugs and Medical Devices (reference number 4044932) and the Ethics Committee of Heidelberg University (reference number AFmu-558/2021). This trial is supported by the German Federal Ministry of Education and Research. The results will be presented at national and international conferences and published in a peer-reviewed journal.

Trial registration number

DRKS00024061, EudraCT: 2020-006001-35.
Patients’ experience of using colonoscopy as a diagnostic test after a positive FOBT/FIT: a systematic review of the quantitative literature
Authors: Kayal Ghalia , Kerrison Robert , Hirst Yasemin , von Wagner Christian
Published: September 2023

Objectives

Faecal occult blood testing (FOBT) and faecal immunochemical testing (FIT) are among the most used screening modalities for colorectal cancer (CRC). Colonoscopy is also widely used as a screening and diagnostic test for adults with a positive FOBT/FIT. Patient experience of colonoscopy is an important component for most CRC screening programmes. Individuals with negative experiences are less likely to engage with colonoscopy in the future and can deter others from attending colonoscopy when invited. This review synthesised data on patient experience with colonoscopy, following a positive result, to provide insights into how to improve patient experience within the English Bowel Cancer Screening Programme.

Methods

MEDLINE, EMBASE and PsycINFO were searched for quantitative questionnaire studies evaluating patient-reported experience with colonoscopy, following a positive screening FOB/FIT result. The search was limited to studies published between 2000 and 2021 (ie, when the first FOBT/FIT screening programmes for CRC were introduced). Data-driven and narrative summary techniques were used to summarise the literature.

Results

In total, six studies from the UK (n=4), Spain (n=1) and the Netherlands (n=1) were included in the review (total participants: 152 329; response rate: 68.0–79.3%). Patient experiences were categorised into three ‘stages’: ‘pre-colonoscopy’, ‘during the test’ and ‘post-colonoscopy’. Overall, patients reported a positive experience in all six studies. Bowel preparation was the most frequently endorsed issue experienced pre-test (experienced by 10.0–41.0% of individuals, across all studies), pain and discomfort for during the test (experienced by 10.0–21.0% of participants) and abdominal pain and discomfort after the test (these were experienced by 14.8–22% of patients).

Conclusion

This review highlighted that patient-reported experiences associated with colonoscopy were generally positive. To improve the colonoscopy experience, bowel screening centres should investigate means to: make bowel preparation more acceptable, make colonoscopy less painful and reduce post-colonoscopy symptoms.
Prevalence and risk factors of stroke in high-altitude areas: a systematic review and meta-analysis
Authors: Zheng Bo , Luo Yuding , Li Yan , Gu Gangfeng , Jiang Junyao , Chen Chuanli , Chen Zhao , Wang Jian
Published: September 2023

Objective

The primary objective of this study is to investigate the prevalence and risk factors of stroke in high-altitude areas through a comprehensive systematic review and meta-analysis.

Design

This study adopts a systematic review and meta-analysis design.

Data sources

A thorough search was conducted on databases including PubMed, Web of Science, Embase, Cochrane Library, MEDLINE and SCOPUS, covering the period up to June 2023.

Eligibility criteria

Studies reporting the prevalence of stroke in high-altitude areas and exploring related risk factors were included, regardless of whether they involved clinical samples or the general population. Studies with incomplete, outdated or duplicate data were excluded.

Data extraction and synthesis

We performed eligibility screening, data extraction and quality evaluation of the retrieved articles. Meta-analysis was employed to estimate the prevalence and risk factors of stroke in high-altitude areas. The Newcastle-Ottawa Scale was used to assess the risk of bias.

Results

A total of 17 studies encompassing 8 566 042 participants from four continents were included, with altitudes ranging from 1500 m to nearly 5000 m. The pooled prevalence of stroke in high-altitude areas was found to be 0.5% (95% CI 0.3%–7%). Notably, the prevalence was higher in clinical samples (1.2%; 0.4%–2.5%) compared with the general population (0.3%; 95% CI 0.1%–0.6%). When considering geographic regions, the aggregated data indicated that stroke prevalence in the Eurasia plate was 0.3% (0.2%–0.4%), while in the American region, it was 0.8% (0.4%–1.3%). Age (OR, 14.891), gender (OR, 1.289), hypertension (OR, 3.158) and obesity (OR, 1.502) were identified as significant risk factors for stroke in high-altitude areas.

Conclusions

The findings of this study provide insights into the pooled prevalence of stroke in high-altitude areas, highlighting variations based on geographic regions and sampling type. Moreover, age, gender, hypertension and obesity were found to be associated with the occurrence of stroke.

PROSPERO registration number

CRD42022381541.
Development of a patient-centred medication management model for polymedicated home-dwelling older adults after hospital discharge: results of a mixed methods study
Authors: Pereira Filipa , Meyer-Massetti Carla , del Río Carral María , von Gunten Armin , Wernli Boris , Verloo Henk
Published: September 2023

Objective

This study aimed to investigate medication management among polymedicated, home-dwelling older adults after discharge from a hospital centre in French-speaking Switzerland and then develop a model to optimise medication management and prevent adverse health outcomes associated with medication-related problems (MRPs).

Design

Explanatory, sequential, mixed methods study based on detailed quantitative and qualitative findings reported previously.

Setting

Hospital and community healthcare in the French-speaking part of Switzerland.

Participants

The quantitative strand retrospectively examined 3 years of hospital electronic patient records (n=53 690 hospitalisations of inpatients aged 65 years or older) to identify the different profiles of those at risk of 30-day hospital readmission and unplanned nursing home admission. The qualitative strand explored the perspectives of older adults (n=28), their informal caregivers (n=17) and healthcare professionals (n=13) on medication management after hospital discharge.

Results

Quantitative results from older adults’ profiles, affected by similar patient-related, medication-related and environment-related factors, were enhanced and supported by qualitative findings. The combined findings enabled us to design an interprofessional, collaborative medication management model to prevent MRPs among home-dwelling older adults after hospital discharge. The model comprised four interactive fields of action: listening to polymedicated home-dwelling older adults and their informal caregivers; involving older adults and their informal caregivers in shared, medication-related decision-making; empowering older adults and their informal caregivers for safe medication self-management; optimising collaborative medication management practices.

Conclusion

By linking the retrospective and prospective findings from our explanatory sequential study involving multiple stakeholders’ perspectives, we created a deeper comprehension of the complexities and challenges of safe medication management among polymedicated, home-dwelling older adults after their discharge from hospital. We subsequently designed an innovative, collaborative, patient-centred model for optimising medication management and preventing MRPs in this population.
Physical activity and physical fitness among children and adolescents after the onset of the COVID-19 pandemic in the WHO European Region: a systematic review protocol
Authors: Ludwig-Walz Helena , Siemens Waldemar , Heinisch Sarah , Dannheim Indra , Loss Julika , Bujard Martin
Published: September 2023

Introduction

The implementation of COVID-19 pandemic-related restrictions resulted in limitations for physical activity (PA) opportunities, which may have initiated a longer-term behavioural change. The protocol describes the methodology for a planned systematic review that aims to summarise changes in PA and physical fitness (PF) in children and adolescents in the WHO European Region after the onset of the COVID-19 pandemic.

Methods and analysis

The protocol adheres to the ‘Preferred Reporting Items for Systematic Review and Meta-Analysis for Protocols’ (PRISMA-P) statement. Using a peer-reviewed search strategy according to the evidence-based checklist ‘Peer Review of Electronic Search Strategies’ (PRESS), we will perform a systematic literature search in seven databases. Inclusion criteria are all primary studies that gathered data on children and adolescents ≤19 years living in the WHO European Region and made a comparison to pre-pandemic data. Primary outcomes are PA and PF. We will assess the risk of bias with the ‘Risk of Bias Instrument for Non-Randomized Studies of Exposures’ (ROBINS-E). The ‘Grading of Recommendations Assessment, Development and Evaluation’ (GRADE) approach will be used for the evaluation of the certainty of evidence. Also, subgroup analyses will be performed (eg, for gender, age, stringency of pandemic restrictions).

Ethics and dissemination

Ethical approval is not required, as primary data will not be collected in this study. The results will be presented in a peer-reviewed publication and at congresses relevant to the research field.

PROSPERO registration number

CRD42023395871.
Efficacy of TTFields in high-grade gliomas: a protocol for systematic review and meta-analysis
Authors: Li Xinlong , Wang Juncheng , Yuan Guoqiang , Pan Yawen
Published: September 2023

Introduction

Despite their recent FDA(Food and Drug Administration) approval, tumour treatment fields (TTFields) have not seen acceptance as part of standard of care (SOC) for the treatment of high-grade gliomas (HGGs). Few studies have reported the clinical effect of simultaneous or sequential use of TTFields with the current SOC. However, whether TTFields are beneficial over the standard treatment remains to be established with a meta-analysis. Therefore, we here performed a systematic review and meta-analysis to understand the benefit of TTFields for patients with HGGs.

Methods and analysis

We registered this systematic review with the PROSPERO network (registration number: CRD42023398972) and aimed to follow the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines in the study. All articles related to TTFields in glioma will be systematically searched for in the following databases since their inception until November 2023: the China National Knowledge Infrastructure, Embase, Cochrane Library, Wanfang Database, China Science Journal Database, China Biomedical Documentation Database, VIP database, Web of Science and PubMed. Article screening and data extraction will be done independently by the authors and cross-checked by two of the authors on completion. The Cochrane risk of bias assessment tool will be used for quality assessment of the included studies. Review Manager V.5.3 (Cochrane Collaboration) will be used to perform the meta-analysis.

Ethics and dissemination

Ethical approval is not required because the data used will be obtained from published studies, and there will be no concerns about privacy. The results of this study will be published in a peer-reviewed journal.

PROSPERO registration number

CRD42023398972.
Relationship between household financial debt and depressive symptoms: a longitudinal study in China
Authors: Hu Mingzheng , Nie Weihao , Song Jiru , Wang Ting , Ye Xin
Published: September 2023

Objectives

To examine the impacts of household financial debt on depressive symptoms and its possible mediating mechanisms.

Design

A nationally representative longitudinal study using the ordinary least squares regression model, fixed-effects model, and instrumental variable approach to explore the relationship between household financial debt and depressive symptoms and further using structural equation models and the Bootstrap method to analyse the mediating effects.

Setting

The China Family Panel Studies (CFPS) database.

Participants

Three waves of longitudinal data in 2012, 2016, and 2018 from CFPS were used. A total of 103,247 individuals over the age of 18 were included in our study sample.

Outcome measures

Depression symptoms were assessed using an eight-item version of the Center for Epidemiologic Studies Depression Scale (CES-D8). We summed these eight items to conduct a depressive symptoms index to measure depressive symptoms.

Results

Among the sample, 35.3% of the households have financial debt, 49.7% of the sample are male, 73.2% of them have rural hukou, and the average age was 46.6. Regression results showed that household financial debt had a negative effect on depressive symptoms (β=0.655, 95% CI 0.602 to 0.707, p<0.01). This result remained robust after using instrumental variables with fixed effects (β=0.483, 95% CI 0.311 to 0.656, p<0.01). Household financial debt could affect depressive symptoms through mediating variables such as working pressure (p<0.05) and life happiness (p<0.01).

Conclusion

Our study showed that household indebtedness in China had a negative effect on depressive symptoms. Also, we found some mediating mechanisms for this effect, which might help provide new guidance for psychological interventions to promote the mental health of indebted residents.
Association between ethnic background and COVID-19 morbidity, mortality and vaccination in England: a multistate cohort analysis using the UK Biobank
Authors: Urdiales Tomás , Dernie Francesco , Català Martí , Prats-Uribe Albert , Prats Clara , Prieto-Alhambra Daniel
Published: September 2023

Objectives

Despite growing evidence suggesting increased COVID-19 mortality among people from ethnic minorities, little is known about milder forms of SARS-CoV-2 infection. We sought to explore the association between ethnic background and the probability of testing, testing positive, hospitalisation, COVID-19 mortality and vaccination uptake.

Design

A multistate cohort analysis. Participants were followed between 8 April 2020 and 30 September 2021.

Setting

The UK Biobank, which stores medical data on around half a million people who were recruited between 2006 and 2010.

Participants

405 541 subjects were eligible for analysis, limited to UK Biobank participants living in England. 23 891 (6%) of participants were non-white.

Primary and secondary outcome measures

The associations between ethnic background and testing, testing positive, hospitalisation and COVID-19 mortality were studied using multistate survival analyses. The association with single and double-dose vaccination was also modelled. Multistate models adjusted for age, sex and socioeconomic deprivation were fitted to estimate adjusted HRs (aHR) for each of the multistate transitions.

Results

18 172 (4.5%) individuals tested positive, 3285 (0.8%) tested negative and then positive, 1490 (6.9% of those tested positive) were hospitalised, and 129 (0.6%) tested positive at the moment of hospital admission (ie, direct hospitalisation). Finally, 662 (17.4%) died after admission. Compared with white participants, Asian participants had an increased risk of negative to positive transition (aHR 1.24 (95% CI 1.02 to 1.52)), testing positive (95% CI 1.44 (1.33 to 1.55)) and direct hospitalisation (1.61 (95% CI 1.28 to 2.03)). Black participants had an increased risk of hospitalisation following a positive test (1.71 (95% CI 1.29 to 2.27)) and direct hospitalisation (1.90 (95% CI 1.51 to 2.39)). Although not the case for Asians (aHR 1.00 (95% CI 0.98 to 1.02)), black participants had a reduced vaccination probability (0.63 (95% CI 0.62 to 0.65)). In contrast, Chinese participants had a reduced risk of testing negative (aHR 0.64 (95% CI 0.57 to 0.73)), of testing positive (0.40 (95% CI 0.28 to 0.57)) and of vaccination (0.78 (95% CI 0.74 to 0.83)).

Conclusions

We identified inequities in testing, vaccination and COVID-19 outcomes according to ethnicity in England. Compared with whites, Asian participants had increased risks of infection and admission, and black participants had almost double hospitalisation risk, and a 40% lower vaccine uptake.
Incidence of vasa praevia: a systematic review and meta-analysis
Authors: Zhang Weiyu , Giacchino Tara , Chanyarungrojn Pannapat Amy , Ionescu Olivia , Akolekar Ranjit
Published: September 2023

Objectives

To derive accurate estimates of the incidence of vasa praevia (VP) in a routine population of unselected pregnancies.

Design

Systematic review and meta-analysis.

Data sources

A search of MEDLINE, EMBASE, CINAHL and the Cochrane database was performed to review relevant citations reporting outcomes in pregnancies with VP from January 2000 until 5 April 2023.

Eligibility criteria for selection of studies

Prospective or retrospective cohort or population studies that provided data regarding VP cases in routine unselected pregnancies during the study period. We included studies published in the English language after the year 2000 to reflect contemporary obstetric and neonatal practice.

Data extraction and synthesis

Two reviewers independently screened the retrieved citations and extracted data. The methodological quality of studies was assessed using the Newcastle–Ottawa Scale, and Preferred Reporting Items for Systematic reviews and Meta-Analyses was used to ensure standardised reporting of studies.

Results

A total of 3847 citations were screened and 82 full-text manuscripts were retrieved for analysis. There were 24 studies that met the inclusion criteria, of which 12 studies reported prenatal diagnosis with a systematic protocol of screening. There were 1320 pregnancies with VP in a total population of 2 278 561 pregnancies; the weighted pooled incidence of VP was 0.79 (95% CI: 0.59 to 1.01) per 1000 pregnancies, corresponding to 1 case of VP per 1271 (95% CI: 990 to 1692) pregnancies. Nested subanalysis of studies reporting screening for VP based on a specific protocol identified 395 pregnancies with VP in a population of 732 654 pregnancies with weighted pooled incidence of 0.82 (95% CI: 0.53 to 1.18) per 1000 pregnancies (1 case of VP per 1218 (95% CI: 847 to 1901) pregnancies).

Conclusion

The incidence of VP in unselected pregnancies is 1 in 1218 pregnancies. This is higher than is previously reported and can be used as a basis to assess whether screening for this condition should be part of routine clinical practice. Incorporation of strategies to screen for VP in routine clinical practice is likely to prevent 5% of stillbirths.

PROSPERO registration number

CRD42020125495.
Decreasing appointment waiting days for first consultation for patients attending adult weight management clinic in a tertiary hospital
Authors: Lulla Dypti , Neo Jeslyn Hwee Teng , Cheah Rui En Lynette , Soedar Zaiton Bte , Puvanendran Rukshini
Published: September 2023

Adult weight management (AWM) clinic at our tertiary institution is a clinical service run for overweight or obese adult women, who are also under the care of gynaecologists for subfertility or menstrual irregularities. Unfortunately, the appointment waiting days for the first consultation at AWM clinic were long, which affected the timeliness of care given to our patients. We suspect that the referred patients are more likely to forget or lose motivation during the long waiting days, resulting in higher non-attendance rates.

Baseline data confirmed that average of median appointment waiting days for the first consultation was 74 days. A multidisciplinary team of weight management clinic stakeholders was created to address this issue. Following a root cause analysis, the team implemented two interventions to improve appointment waiting days.

The first intervention was offering video consultation to new cases for AWM clinic. This increased the clinic capacity without requiring additional physical clinic space. The referral criteria were refined to target patients who are most likely to benefit from the services provided at our institution. The second intervention was creating AWM clinic appointments only after patients completed the required laboratory investigations for obesity workup.

A run chart demonstrated average of median appointment waiting days decreased from 74 days to 34 days after implementation of the second intervention (p=0.0104). The team successfully decreased and sustained the lower appointment waiting days through innovative interventions that increased clinic capacity and improved patient selection, with the potential to further increase clinic capacity if the demand surges.