bluuebunny/crossref_metadata_2025 huggingface dataset:
Adult and late adolescent complications of pediatric solid organ transplantation
Authors: Byeman Connor J. , Harshman Lyndsay A. , Engen Rachel M.
Published: April 2024

Background

There have been over 51 000 pediatric solid organ transplants since 1988 in the United States alone, leading to a growing population of long‐term survivors who face complications of childhood organ failure and long‐term immunosuppression.

Aims

This is an educational review of existing literature.

Results

Pediatric solid organ transplant recipients are at increased risk for risk for cardiovascular and kidney disease, skin cancers, and growth problems, though the severity of impact may vary by organ type. Pediatric recipients often are able to complete schooling, maintain a job, and form family and social networks in adulthood, though at somewhat lower rates than the general population, but face additional challenges related to neurocognitive deficits, mental health disorders, and discrimination.

Conclusions

Transplant centers and research programs should expand their focus to include long‐term well‐being. Increased collaboration between pediatric and adult transplant specialists will be necessary to better understand and manage long‐term complications.
Insights into biomimetic system–ligand interaction of substituted isophthalic acid: A functionality induced photophysical study
Authors: Jalan Neha , Das Tiasha , Sarkar Sumit , Ghosh Partha Pratim , Ganguly Sumi , Dutta Aparna , Mukhopadhyay Madhumita , Goswami Soumyabrata , Bose Debosreeta
Published: April 2024

The present article attempts to interpret the modulation of photophysical properties of isophthalic acid (IPA) through its amino [5‐amino isophthalic acid (5‐amino IPA)] and azido [5‐azido isophthalic acid (5‐azido IPA)] substituted derivatives which are chemically potent organic ligands. The ground state structure–reactivity correlation of 5‐amino IPA and 5‐azido IPA has been deciphered through computational studies. The computed energetics show significant interaction feasibility of the substituted ligand systems with the biomimetic systems which is further validated experimentally. The binding interaction of the probes with oppositely polarized functionalization is studied to be significant with cetyltrimethylammonium bromide (CTAB) and bovine serum albumin (BSA) with the amino functionalized derivative having a comparatively stronger binding constant value. The steady‐state absorption and fluorescence study establish significant modification of polarity of the heteronuclear probes. The micro polarity study in water–dioxane mixtures enables determination of polarity of 5‐amino IPA in CTAB and BSA unlike 5‐azido IPA. Presence of an overlapping region between the emission spectrum of BSA and the absorption spectrum of the probes as probable donor–acceptor pair are also scrutinized via the steady‐state fluorescence studies. The photophysical behavior of 5‐amino IPA is observed to be somewhat dissimilar to that of 5‐azido IPA.
Liberal democratic accountability standards and public administration
Authors: Koliba Christopher
Published: April 2024

This paper serves as a renewed call for public management scholars and public leaders in liberal democracies to be the champions of accountability standards that are explicitly and implicitly inherent to liberal democratic forms of governance. This call is particularly salient amid increasing populism, polarization, and democratic backsliding. Drawing from the historical and contemporary political and legal philosophies of small‐l liberalism and democracy advanced throughout the ages, we define a set of seven liberal democratic accountability standards focusing on matters of authority, rights, tolerance, truth claims, and professional deference. We then consider how these standards relate to some of public administration and management's ongoing considerations of the politics‐administration dichotomy, citizen engagement, and network governance, and make the case for more explicit focus on liberal democratic accountability standards in public management scholarship.
Trained immunity: Perspectives for disease control strategy in marine mollusc aquaculture
Authors: Montagnani Caroline , Morga Benjamin , Novoa Beatriz , Gourbal Benjamin , Saco Amaro , Rey‐Campos Magali , Bourhis Marion , Riera Fabien , Vignal Emmanuel , Corporeau Charlotte , Charrière Guillaume M. , Travers Marie‐Agnès , Dégremont Lionel , Gueguen Yannick , Cosseau Céline , Figueras Antonio
Published: April 2024

Recent evidence has demonstrated the unique properties of the innate immune system, known as innate immune memory, immune priming, or trained immunity. These properties have been described as the ability of the innate immune system to learn from previous microbial experiences, which improves survival after subsequent infection. In this review, we present the state of knowledge on trained immunity in invertebrates and provide a comprehensive overview of these capabilities in cultured marine molluscs, which are currently threatened by recurrent diseases. Studies have shown that exposure to environmental microbiota, pathogens, or derived elements, can provide a stronger response and protection against future infections. These studies highlight common and distinct features of protection, mechanisms, specificity, and duration that vary with immune markers, and methods of stimulation. While the cellular and molecular basis of these responses is only partially understood, effects on phagocytosis, haemocyte populations, apoptosis, oxidative stress, and immune gene expression have been suggested. Finally, we propose a framework for future research to go beyond the current evidence and address potential limitations in the implementation of trained immunity‐based strategies to control disease. Immune training may provide a unique opportunity to promote the sustainable development of marine mollusc aquaculture.
Drivers of natural disaster risk‐reduction actions and their temporal dynamics: Insights from surveys during an imminent hurricane threat and its aftermath
Authors: Botzen W. J. Wouter , Mol Jantsje M. , Robinson Peter J. , Czajkowski Jeffrey
Published: April 2024

To improve preparedness for natural disasters, it is imperative to understand the factors that enable individual risk‐reduction actions. This study offers such insights using innovative real‐time (N = 871) and repeated (N = 255) surveys of a sample of coastal residents in Florida regarding flood preparations and their drivers during an imminent threat posed by Hurricane Dorian and its aftermath. Compared with commonly employed cross‐sectional surveys, our methodology better represents relationships between preparedness actions undertaken during the disaster threat and their drivers derived from an extended version of Protection Motivation Theory (PMT). The repeated survey allows for examining temporal dynamics in these drivers. Our results confirm the importance of coping appraisals and show that risk perceptions relate more strongly to emergency protection decisions made during the period of the disaster threat than to decisions made well before. Moreover, we find that several personal characteristics that we add to the standard PMT framework significantly relate to undertaking preparedness actions, especially locus of control and social norms. Significant changes in key explanatory variables occur following the disaster threat, including a decline in risk perception, a potential learning effect in coping appraisals, and a decline in risk aversion. Our results confirm the advantage of the real‐time and repeated survey approach in understanding both short‐ and long‐term disaster preparedness actions.
Fair inheritance taxation
Authors: Decerf Benoit , Maniquet Francois
Published: April 2024

We study the optimal taxation of bequests in a successive‐generation model in which individuals have heterogeneous preferences over their consumption and the net‐of‐tax bequest received by their heir. We show that it is possible to reconcile the views that children should not be penalized by the lack of altruism of their parents, and parents should be free to choose their bequests. The resulting optimal non‐linear inheritance tax scheme collects money and redistributes it through a non‐negative demogrant, and does not tax, and, in some cases, subsidizes bequests lower than that of the poorest altruistic individual.
The novel HLA‐DPA1*02:86 allele was identified by next‐generation sequencing
Authors: Li Ying , Chen Chen , Zhao Shuoxian , Zhang Wei , Zhu Faming
Published: April 2024

HLA‐DPA1*02:86 differs from HLA‐DPA1*02:01:01 by a single nucleotide substitution at position 680 C > A in exon 4.
Characterisation of the novel HLA‐A*31:01:53 allele by next generation sequencing in a Chinese individual
Authors: Zou Hong‐Yan , Quan Zhan‐Rou
Published: April 2024

HLA‐A*31:01:53 differs from HLA‐A*31:01:02:01 by one nucleotide change at nucleotide 900 in exon 5 from G to A.
How much can heavy lines cover?
Authors: Dąbrowski Damian , Orponen Tuomas , Wang Hong
Published: April 2024

One formulation of Marstrand's slicing theorem is the following. Assume that , and is a Borel set with . Then, for almost all directions , almost all of is covered by lines parallel to with . We investigate the prospects of sharpening Marstrand's result in the following sense: in a generic direction , is it true that a strictly less than ‐dimensional part of is covered by the heavy lines , namely those with ? A positive answer for ‐regular sets was previously obtained by the first author. The answer for general Borel sets turns out to be negative for and positive for . More precisely, the heavy lines can cover up to a dimensional part of in a generic direction. We also consider the part of covered by the ‐heavy lines, namely those with for . We establish a sharp answer to the question: how much can the ‐heavy lines cover in a generic direction? Finally, we identify a new class of sets called sub‐uniformly distributed sets, which generalise Ahlfors‐regular sets. Roughly speaking, these sets share the spatial uniformity of Ahlfors‐regular sets, but pose no restrictions on uniformity across different scales. We then extend and sharpen the first author's previous result on Ahlfors‐regular sets to the class of sub‐uniformly distributed sets.
Adherence and Compliance of Different Delivery Methods of Home Exercise in Individuals With Nonspecific Low Back Pain
Authors: Devorski Luk , Suppiah Aravinthan , Fukuda David H. , Stout Jeffrey , Ingersoll Christopher D. , Mangum L. Colby
Published: April 2024

Autonomous exercise within nonspecific low back pain rehabilitation is a necessary tool to treat low back pain. The purpose of this study was to quantify adherence and compliance during two different 6-week home-exercise programs. Forty adults were randomly allocated to a gamified and packet group. Adherence, compliance, and system usability assessments occurred after 3 and 6 weeks. Packet group adherence was similar at 3 weeks and at 6 weeks. System usability was significantly greater at 6 weeks than at 3 weeks in the packet group. Adherence or compliance was not influenced. The usability of the intervention methodology was considered great by both groups.
Inhibition of Ironic Errors and Facilitation of Overcompensation Errors Under Pressure: An Investigation Including Perceived Weakness
Authors: Nakamoto Hiroki , Hashimoto Shoya , Kamei Mio , Murata Munenori , Ikudome Sachi , Karakida Kenta , Tanaka Yoshifumi
Published: April 2024

The conflicting predictions of ironic process theory and the implicit overcompensation hypothesis have been presented as a framework to explain the characteristics of errors that occur when a certain behavior is prohibited. The former predicts that instructions prohibiting a particular behavior will increase the likelihood of an outcome that should be avoided (ironic error), whereas the latter predicts that the likelihood of an outcome opposite of that to be avoided (overcompensation error) will increase. We examined how these errors, which negatively affect performance, are influenced by pressure and perceived weakness. Participants performed a tennis-stroke task, aiming to hit a ball toward a target zone while avoiding a discouraged zone. The results indicate that pressure decreases the ironic errors but increases the overcompensation errors that occur when a particular behavior is discouraged, while an increase in perceived weakness induces random errors.
Infection-associated gene regulation of L-tartrate metabolism in
Salmonella enterica
serovar Typhimurium
Authors: Rojas Vivian K. , Winter Maria G. , Jimenez Angel G. , Tanner Natasha W. , Crockett Stacey L. , Spiga Luisella , Hendrixson David R. , Winter Sebastian E.
Published: April 2024

Enteric pathogens such as
Salmonella enterica
serovar Typhimurium experience spatial and temporal changes to the metabolic landscape throughout infection. Host reactive oxygen and nitrogen species non-enzymatically convert monosaccharides to alpha hydroxy acids, including L-tartrate.
Salmonella
utilizes L-tartrate early during infection to support fumarate respiration, while L-tartrate utilization ceases at later time points due to the increased availability of exogenous electron acceptors such as tetrathionate, nitrate, and oxygen. It remains unknown how
Salmonella
regulates its gene expression to metabolically adapt to changing nutritional environments. Here, we investigated how the transcriptional regulation for L-tartrate metabolism in
Salmonella
is influenced by infection-relevant cues. L-tartrate induces the transcription of
ttdBAU
, genes involved in L-tartrate utilization. L-tartrate metabolism is negatively regulated by two previously uncharacterized transcriptional regulators TtdV (STM3357) and TtdW (STM3358), and both TtdV and TtdW are required for the sensing of L-tartrate. The electron acceptors nitrate, tetrathionate, and oxygen repress
ttdBAU
transcription via the two-component system ArcAB. Furthermore, the regulation of L-tartrate metabolism is required for optimal fitness in a mouse model of
Salmonella
-induced colitis. TtdV, TtdW, and ArcAB allow for the integration of two cues, i.e., substrate availability and availability of exogenous electron acceptors, to control L-tartrate metabolism. Our findings provide novel insights into how
Salmonella
prioritizes the utilization of different electron acceptors for respiration as it experiences transitional nutrient availability throughout infection.

IMPORTANCE

Bacterial pathogens must adapt their gene expression profiles to cope with diverse environments encountered during infection. This coordinated process is carried out by the integration of cues that the pathogen senses to fine-tune gene expression in a spatiotemporal manner. Many studies have elucidated the regulatory mechanisms of how
Salmonella
sense metabolites in the gut to activate or repress its virulence program; however, our understanding of how
Salmonella
coordinates its gene expression to maximize the utilization of carbon and energy sources found in transitional nutrient niches is not well understood. In this study, we discovered how
Salmonella
integrates two infection-relevant cues, substrate availability and exogenous electron acceptors, to control L-tartrate metabolism. From our experiments, we propose a model for how L-tartrate metabolism is regulated in response to different metabolic cues in addition to characterizing two previously unknown transcriptional regulators. This study expands our understanding of how microbes combine metabolic cues to enhance fitness during infection.
Epistasis, core-genome disharmony, and adaptation in recombining bacteria
Authors: Taylor Aidan J. , Yahara Koji , Pascoe Ben , Ko Seungwon , Mageiros Leonardos , Mourkas Evangelos , Calland Jessica K. , Puranen Santeri , Hitchings Matthew D. , Jolley Keith A. , Kobras Carolin M. , Bayliss Sion , Williams Nicola J. , van Vliet Arnoud H. M. , Parkhill Julian , Maiden Martin C. J. , Corander Jukka , Hurst Laurence D. , Falush Daniel , Keim Paul , Didelot Xavier , Kelly David J. , Sheppard Samuel K.
Published: April 2024

Recombination of short DNA fragments via horizontal gene transfer (HGT) can introduce beneficial alleles, create genomic disharmony through negative epistasis, and create adaptive gene combinations through positive epistasis. For non-core (accessory) genes, the negative epistatic cost is likely to be minimal because the incoming genes have not co-evolved with the recipient genome and are frequently observed as tightly linked cassettes with major effects. By contrast, interspecific recombination in the core genome is expected to be rare because disruptive allelic replacement is likely to introduce negative epistasis. Why then is homologous recombination common in the core of bacterial genomes? To understand this enigma, we take advantage of an exceptional model system, the common enteric pathogens
Campylobacter jejuni
and
C. coli
that are known for very high magnitude interspecies gene flow in the core genome. As expected, HGT does indeed disrupt co-adapted allele pairings, indirect evidence of negative epistasis. However, multiple HGT events enable recovery of the genome’s co-adaption between introgressing alleles, even in core metabolism genes (e.g., formate dehydrogenase). These findings demonstrate that, even for complex traits, genetic coalitions can be decoupled, transferred, and independently reinstated in a new genetic background—facilitating transition between fitness peaks. In this example, the two-step recombinational process is associated with
C. coli
that are adapted to the agricultural niche.

IMPORTANCE

Genetic exchange among bacteria shapes the microbial world. From the acquisition of antimicrobial resistance genes to fundamental questions about the nature of bacterial species, this powerful evolutionary force has preoccupied scientists for decades. However, the mixing of genes between species rests on a paradox: 0n one hand, promoting adaptation by conferring novel functionality; on the other, potentially introducing disharmonious gene combinations (negative epistasis) that will be selected against. Taking an interdisciplinary approach to analyze natural populations of the enteric bacteria
Campylobacter
, an ideal example of long-range admixture, we demonstrate that genes can independently transfer across species boundaries and rejoin in functional networks in a recipient genome. The positive impact of two-gene interactions appears to be adaptive by expanding metabolic capacity and facilitating niche shifts through interspecific hybridization. This challenges conventional ideas and highlights the possibility of multiple-step evolution of multi-gene traits by interspecific introgression.
Complete genome sequence of
Pseudomonas canadensis
strain Pcan-CK-23 isolated from
Zophobas morio
larvae
Authors: Kundlacz Cindy , Aldeia Claudia , Eddoubaji Yasmine , Campos-Madueno Edgar I. , Endimiani Andrea
Published: April 2024

We present the complete genome sequence of
Pseudomonas canadensis
. The strain (Pcan-CK-23) was isolated from
Zophobas morio
(superworm) larvae. The genome consisted of a 6,424,469 bp chromosome with a GC content of 60.3% and 5,973 genes. Pcan-CK-23 can be used as a reference genome for further studies with
P. canadensis
.
Whole-genome sequence of the plant-associated bacterium
Pseudomonas granadensis
CT364 isolated in Seville, Spain
Authors: Cea-Torrescassana Eva , Howard Thomas P. , Stach Jem , Montero-Calasanz Maria del Carmen
Published: April 2024

Pseudomonas
sp. CT364 was isolated from olive tree rhizosphere in Seville (Spain). We report its complete genome sequence, acquired by co-assembling Illumina and Nanopore reads. The genome comprises a circular chromosome of 6.2 Mbp and a G + C content of 60.0%. Taxonomic analyses confirmed it to be
Pseudomonas granadensis
.
Draft genome sequence of
Magnusiomyces
sp. LA-1 isolated from a C6-C8 acid-producing bioreactor
Authors: Gemeinhardt Kurt , Park Hyojung , Won Jong In , Lee Jin Hyung , Hwang Ee Taek , Angenent Largus T. , Jeon Byoung Seung
Published: April 2024

Here, we report the draft genome of
Magnusiomyces
sp. LA-1, which was isolated from a C6-C8 carboxylic acid-producing bioreactor. The draft genome of
Magnusiomyces
sp. LA-1 is 19,829,165 bp in length, is divided into six contigs that comprise 6,557 CDS regions, and has a GC content of 34.5%.
The EH domain-containing protein, EdeA, is involved in endocytosis, cell wall integrity, and pathogenicity in
Aspergillus fumigatus
Authors: Dai Mengyao , Liu Xintian , Goldman Gustavo H. , Lu Ling , Zhang Shizhu
Published: April 2024

Endocytosis has been extensively studied in yeasts, where it plays crucial roles in growth, signaling regulation, and cell-surface receptor internalization. However, the biological functions of endocytosis in pathogenic filamentous fungi remain largely unexplored. In this study, we aimed to functionally characterize the roles of EdeA, an ortholog of the
Saccharomyces cerevisiae
endocytic protein Ede1, in
Aspergillus fumigatus
. EdeA was observed to be distributed as patches on the plasma membrane and concentrated in the subapical collar of hyphae, a localization characteristic of endocytic proteins. Loss of
edeA
caused defective hyphal polarity, reduced conidial production, and fewer sites of endocytosis initiations than that of the parental wild type. Notably, the
edeA
null mutant exhibited increased sensitivity to cell wall-disrupting agents, indicating a role for EdeA in maintaining cell wall integrity in
A. fumigatus
. This observation was further supported by the evidence showing that the thickness of the cell wall in the Δ
edeA
mutant increased, accompanied by abnormal activation of MpkA, a key component in the cell wall integrity pathway. Additionally, the Δ
edeA
mutant displayed increased pathogenicity in the
Galleria mellonella
wax moth infection model, possibly due to alterations in cell wall morphology. Site-directed mutagenesis identified the conserved residue E348 within the third EH (
E
ps15
h
omology) domain of EdeA as crucial for its subcellular localization and functions. In conclusion, our results highlight the involvement of EdeA in endocytosis, hyphal polarity, cell wall integrity, and pathogenicity in
A. fumigatus
.

IMPORTANCE

Aspergillus fumigatus
is a significant human pathogenic fungus known to cause invasive aspergillosis, a disease with a high mortality rate. Understanding the basic principles of
A. fumigatus
pathogenicity is crucial for developing effective strategies against this pathogen. Previous research has underscored the importance of endocytosis in the infection capacity of pathogenic yeasts; however, its biological function in pathogenic mold remains largely unexplored. Our characterization of EdeA in
A. fumigatus
sheds light on the role of endocytosis in the development, stress response, and pathogenicity of pathogenic molds. These findings suggest that the components of the endocytosis process may serve as potential targets for antifungal therapy.
Effects of short-term nitrogen and phosphorus addition on soil bacterial community of different halophytes
Authors: Zhang Zehao , Wang Lijie , Li Tian , Fu Zhanyong , Sun Jingkuan , Hu Rui , Zhang Yao
Published: April 2024

Soil microbial community composition and diversity are often affected by nutrient enrichment, which may influence soil microbes to affect nutrient cycling and plant community structure. However, the response of soil bacteria to nitrogen (N) and phosphorus (P) addition and whether it is influenced by plants remains unclear. By 16S rRNA sequencing, we investigated the response of the rhizosphere and bulk soil bacterial communities of different halophytes (salt-rejecting, salt-absorbing, and salt-secreting plant) in the Yellow River Delta to short-term N and P addition. The response of rhizosphere bacterial diversity to N and P addition was opposite in
Phragmites communis
and
Suaeda salsa
. N addition increased the rhizosphere soil bacterial α-diversity of
S. salsa
and
Aeluropus sinensis
, while P addition decreased the rhizosphere bacterial α-diversity bacteria of
S. salsa
. The N and P addition had a weak effect on the rhizosphere bacterial community composition and a significant effect on the bulk soil bacterial community composition of halophytes. The
S. salsa
and
P. communis
bulk soil bacterial community were mainly influenced by P addition, while it was influenced by N addition in
A. sinensis
. N and P addition reduced the difference in bacterial community composition between the two types of soil. N and P addition increased the eutrophic taxa (
Proteobacteria
and
Bacteroidetes
) and decreased the oligotrophic taxa (
Acidobacteria
). Redundancy analysis showed that soil organic matter, salt, and total N content had significant effects on the bacterial community composition. The results clarify that the response of soil bacterial communities to N and P additions is inconsistent across the three halophyte soils, and the effect of plant species on the bacterial community was stronger than short-term N and P addition.

IMPORTANCE

The bulk soil bacterial community was more affected by nutrient addition. Nitrogen (N) and phosphorus (P) have different effects on bacterial community. Soil organic matter is a key factor influencing the response of bacterial community to nutrient addition. N and P influence on bacterial community changes with plants.
A library of reporters of the global regulators of gene expression in
Escherichia coli
Authors: Dash Suchintak , Jagadeesan Rahul , Baptista Ines S. C. , Chauhan Vatsala , Kandavalli Vinodh , Oliveira Samuel M. D. , Ribeiro Andre S.
Published: April 2024

The topology of the transcription factor network (TFN) of
Escherichia coli
is far from uniform, with 22 global regulator (GR) proteins controlling one-third of all genes. So far, their production rates cannot be tracked by comparable fluorescent proteins. We developed a library of fluorescent reporters for 16 GRs for this purpose. Each consists of a single-copy plasmid coding for green fluorescent protein (GFP) fused to the full-length copy of the native promoter. We tracked their activity in exponential and stationary growth, as well as under weak and strong stresses. We show that the reporters have high sensitivity and specificity to all stresses tested and detect single-cell variability in transcription rates. Given the influence of GRs on the TFN, we expect that the new library will contribute to dissecting global transcriptional stress-response programs of
E. coli
. Moreover, the library can be invaluable in bioindustrial applications that tune those programs to, instead of cell growth, favor productivity while reducing energy consumption.

IMPORTANCE

Cells contain thousands of genes. Many genes are involved in the control of cellular activities. Some activities require a few hundred genes to run largely synchronous transcriptional programs. To achieve this, cells have evolved global regulator (GR) proteins that can influence hundreds of genes simultaneously. We have engineered a library of
Escherichia coli
strains to track the levels over time of these, phenotypically critical, GRs. Each strain has a single-copy plasmid coding for a fast-maturing green fluorescent protein whose transcription is controlled by a copy of the natural GR promoter. By allowing the tracking of GR levels, with sensitivity and specificity, this library should become of wide use in scientific research on bacterial gene expression (from molecular to synthetic biology) and, later, be used in applications in therapeutics and bioindustries.
Comparison of rectal swabs and fecal samples for the detection of
Clostridioides difficile
infections with a new in-house PCR assay
Authors: Huletsky Ann , Loo Vivian G. , Longtin Yves , Longtin Jean , Trottier Sylvie , Tremblay Cécile L. , Gilca Rodica , Lavallée Christian , Brochu Éliel , Bérubé Ève , Bastien Martine , Bernier Marthe , Gagnon Martin , Frenette Johanne , Bestman-Smith Julie , Deschênes Louise , Bergeron Michel G.
Published: April 2024

The detection of
Clostridioides difficile
infections (CDI) relies on testing the stool of patients by toxin antigen detection or PCR methods. Although PCR and antigenic methods have significantly reduced the time to results, delays in stool collection can significantly add to the turnaround time. The use of rectal swabs to detect
C. difficile
could considerably reduce the time to diagnosis of CDI. We developed a new rapid PCR assay for the detection of
C. difficile
and evaluated this PCR assay on both stool and rectal swab specimens. We recruited a total of 623 patients suspected of
C. difficile
infection. Stool samples and rectal swabs were collected from each patient and tested by our PCR assay. Stool samples were also tested by the cell cytotoxicity neutralization assay (CCNA) as a reference. The PCR assay detected
C. difficile
in 60 stool specimens and 61 rectal swabs for the 64 patients whose stool samples were positive for
C. difficile
by CCNA. The PCR assay detected an additional 35 and 36 stool and rectal swab specimens positive for
C. difficile
, respectively, for sensitivity with stools and rectal swabs of 93.8% and 95.3%, specificity of 93.7% and 93.6%, positive predictive values of 63.2% and 62.9%, and negative predictive values of 99.2% and 99.4%. Detection of
C. difficile
using PCR on stools or rectal swabs yielded reliable and similar results. The use of PCR tests on rectal swabs could reduce turnaround time for CDI detection, thus improving CDI management and control of
C. difficile
transmission.

IMPORTANCE

Clostridioides difficile
infection (CDI) is the leading cause of healthcare-associated diarrhea, resulting in high morbidity, mortality, and economic burden. In clinical laboratories, CDI testing is currently performed on stool samples collected from patients with diarrhea. However, the diagnosis of CDI can be delayed by the time required to collect stool samples. Barriers to sample collection could be overcome by using a rectal swab instead of a stool sample. Our study showed that CDI can be identified rapidly and reliably by a new PCR assay developed in our laboratory on both stool and rectal swab specimens. The use of PCR tests on rectal swabs could reduce the time for the detection of CDI and improve the management of this infection. It should also provide a useful alternative for infection-control practitioners to better control the spread of
C. difficile
.
What is the role of out of programme clinical fellowships in the era of Shape of Training? A single-centre cohort study
Authors: Raju Suneil A , Bowker-Howell Freya J , Aziz Imran , Thoufeeq Mo , Lobo Alan J , Gleeson Dermot C , Al-Joudeh Amer , McAlindon Mark E , Hopper Andrew D , Kumar Sampath , Sidhu Reena , Sanders David S
Published: April 2024

Background

The updated Shape of Training curriculum has shortened the duration of specialty training. We present the potential role of out of programme clinical fellowships.

Method

An electronic online survey was sent to all current fellows to understand their experiences, training opportunities and motivations.

Data were collected on fellows’ endoscopic experiences and publications using PubMed for all previous doctors who have completed the Sheffield Fellowship Programme.

Results

Since 2004, 39 doctors have completed the Sheffield Fellowship.

Endoscopic experience: current fellows completed a median average of 350 (IQR 150–500) gastroscopies and 150 (IQR 106–251) colonoscopies per year. Fellows with special interests completed either 428 hepato-pancreato-biliary procedures or 70 endoscopic mucosal resections per year.

Medline publications: Median average 9 publications(IQR 4–17). They have also received multiple national or international awards and 91% achieved a doctoral degree.

The seven current fellows in the new Shape of Training era (57% male, 29% Caucasian, aged 31–40 years) report high levels of enjoyment due to their research projects, supervisory teams and social aspects. The most cited reasons for undertaking the fellowship were to develop a subspecialty interest, take time off the on-call rota and develop endoscopic skills. The most reported drawback was a reduced income.

All current fellows feel that the fellowship has enhanced their clinical confidence and prepared them to become consultants.

Conclusion

Out of programme clinical fellowships offer the opportunity to develop the required training competencies, subspecialty expertise and research skills in a supportive environment.
Rapid diagnostic test: a critical need for outbreak preparedness and response for high priority pathogens
Authors: Yimer Solomon Abebe , Booij Birgitte Boonstra , Tobert Gwen , Hebbeler Andrew , Oloo Paul , Brangel Polina , L'Azou Jackson Maïna , Jarman Richard , Craig Danielle , Avumegah Michael Selorm , Mandi Henshaw , Endy Timothy , Wooden Stacey , Clark Carolyn , Bernasconi Valentina , Shurtleff Amy , Kristiansen Paul A
Published: April 2024

Rapid diagnostic tests (RDTs) are critical for preparedness and response against an outbreak or pandemic and have been highlighted in the 100 Days Mission, a global initiative that aims to prepare the world for the next epidemic/pandemic by driving the development of diagnostics, vaccines and therapeutics within 100 days of recognition of a novel Disease X threat.

RDTs play a pivotal role in early case identification, surveillance and case management, and are critical for initiating deployment of vaccine and monoclonal antibodies. Currently available RDTs, however, have limited clinical sensitivity and specificity and inadequate validation. The development, validation and implementation of RDTs require adequate and sustained financing from both public and private sources. While the World Health Assembly recently passed a resolution on diagnostic capacity strengthening that urges individual Member States to commit resources towards this, the resolution is not binding and implementation will likely be impeded by limited financial resources and other competing priorities, particularly in low-income countries. Meanwhile, the diagnostic industry has not sufficiently invested in RDT development for high priority pathogens.

Currently, vaccine development projects are getting the largest funding support among medical countermeasures. Yet vaccines are insufficient tools in isolation, and pandemic preparedness will be incomplete without parallel investment in diagnostics and therapeutics.

The Pandemic Fund, a global financing mechanism recently established for strengthening pandemic prevention, preparedness and response, may be a future avenue for supporting diagnostic development.

In this paper, we discuss why RDTs are critical for preparedness and response. We also discuss RDT investment challenges and reflect on the way forward.
Policy uptake and implementation of the RTS,S/AS01 malaria vaccine in sub-Saharan African countries: status 2 years following the WHO recommendation
Authors: Osoro Caroline Bonareri , Ochodo Eleanor , Kwambai Titus K , Otieno Jenifer Akoth , Were Lisa , Sagam Caleb Kimutai , Owino Eddy Johnson , Kariuki Simon , ter Kuile Feiko O , Hill Jenny
Published: April 2024

In October 2021, the WHO recommended the world’s first malaria vaccine—RTS,S/AS01—to prevent malaria in children living in areas with moderate-to-high transmission in sub-Saharan Africa (SSA). A second malaria vaccine, R21/Matrix-M, was recommended for use in October 2023 and added to the WHO list of prequalified vaccines in December 2023. This study analysis assessed the country status of implementation and delivery strategies for RTS,S/AS01 by searching websites for national malaria policies, guidelines and related documents. Direct contact with individuals working in malaria programmes was made to obtain documents not publicly available. 10 countries had documents with information relating to malaria vaccine implementation, 7 referencing RTS,S/AS01 and 3 (Burkina Faso, Kenya and Nigeria) referencing RTS,S/AS01 and R21/Matrix-M. Five other countries reported plans for malaria vaccine roll-out without specifying which vaccine. Ghana, Kenya and Malawi, which piloted RTS,S/AS01, have now integrated the vaccine into routine immunisation services. Cameroon and Burkina Faso are the first countries outside the pilot countries to incorporate the vaccine into national immunisation services. Uganda plans a phased RTS,S/AS01 introduction, while Guinea plans to first pilot RTS,S/AS01 in five districts. The RTS,S/AS01 schedule varied by country, with the first dose administered at 5 or 6 months in all countries but the fourth dose at either 18, 22 or 24 months. SSA countries have shown widespread interest in rolling out the malaria vaccine, the Global Alliance for Vaccines and Immunization having approved financial support for 20 of 30 countries which applied as of March 2024. Limited availability of RTS,S/AS01 means that some approved countries will not receive the required doses. Vaccine availability and equity must be addressed even as R21/Matrix-M becomes available.
Association between daily step counts and healthy life years: a national cross-sectional study in Japan
Authors: Nishi Masahiro , Nagamitsu Reo , Matoba Satoaki
Published: April 2024

Background

Despite accumulating evidence concerning the association between daily step counts and mortality or disease risks, it is unclear whether daily step counts are associated with healthy life years.

Methods

We used the combined dataset of the Comprehensive Survey of Living Conditions and the National Health and Nutrition Survey conducted for a randomly sampled general population in Japan, 2019. Daily step counts were measured for 4957 adult participants. The associations of daily step counts with activity limitations in daily living and self-assessed health were evaluated using a multivariable logistic regression model. The bootstrap method was employed to mitigate uncertainties in estimating the threshold of daily step counts.

Results

The median age was 60 (44–71) years, and 2592 (52.3%) were female. The median daily step counts were 5650 (3332–8452). The adjusted OR of activity limitations in daily living for the adjacent daily step counts was 0.27 (95% CI 0.26 to 0.27) for all ages and 0.25 (95% CI 0.25 to 0.26) for older adults at the lowest, with the thresholds of significant association at 9000 step counts. The OR of self-assessed unhealthy status was 0.45 (95% CI 0.44 to 0.46) for all ages and 0.42 (95% CI 0.41 to 0.43) for older adults at the lowest, with the thresholds at 11 000 step counts.

Conclusion

Daily step counts were significantly associated with activity limitations in daily living and self-assessed health as determinants of healthy life years, up to 9000 and 11 000 step counts, respectively. These results suggest a target of daily step counts to prolong healthy life years within health initiatives.
Rationale and design of OPtimising thERapy to prevent Avoidable hospital
admissions in Multimorbid older people (OPERAM): a cluster randomised
controlled trial
Authors: Adam Luise , Moutzouri Elisavet , Baumgartner Christine , Loewe Axel Lennart , Feller Martin , M’Rabet-Bensalah Khadija , Schwab Nathalie , Hossmann Stefanie , Schneider Claudio , Jegerlehner Sabrina , Floriani Carmen , Limacher Andreas , Jungo Katharina Tabea , Huibers Corlina Johanna Alida , Streit Sven , Schwenkglenks Matthias , Spruit Marco , Van Dorland Anette , Donzé Jacques , Kearney Patricia M , Jüni Peter , Aujesky Drahomir , Jansen Paul , Boland Benoit , Dalleur Olivia , Byrne Stephen , Knol Wilma , Spinewine Anne , O’Mahony Denis , Trelle Sven , Rodondi Nicolas
Published: April 2024

Introduction

Multimorbidity and polypharmacy are important risk factors for
drug-related hospital admissions (DRAs). DRAs are often linked to
prescribing problems (overprescribing and underprescribing), as well as
non-adherence with drug regimens for different reasons. In this trial,
we aim to assess whether a structured medication review compared with
standard care can reduce DRAs in multimorbid older patients with
polypharmacy.

Methods and analysis

OPtimising thERapy to prevent Avoidable hospital admissions in
Multimorbid older people is a European multicentre, cluster randomised,
controlled trial. Hospitalised patients ≥70 years with ≥3 chronic
medical conditions and concurrent use of ≥5 chronic medications are
included in the four participating study centres of Bern (Switzerland),
Utrecht (The Netherlands), Brussels (Belgium) and Cork (Ireland).
Patients treated by the same prescribing physician constitute a cluster,
and clusters are randomised 1:1 to either standard care or Systematic
Tool to Reduce Inappropriate Prescribing (STRIP) intervention with the
help of a clinical decision support system, the STRIP Assistant. STRIP
is a structured method performing customised medication reviews, based
on Screening Tool of Older People’s Prescriptions/Screening  Tool to
Alert to Right Treatment criteria to detect potentially inappropriate
prescribing. The primary endpoint is any DRA where the main reason or a
contributory reason for the patient’s admission is caused by
overtreatment or undertreatment, and/or inappropriate treatment.
Secondary endpoints include number of any hospitalisations, all-cause
mortality, number of falls, quality of life, degree of polypharmacy,
activities of daily living, patient’s drug compliance, the number of
significant drug–drug interactions, drug overuse and underuse and
potentially inappropriate medication.

Ethics and dissemination

The local Ethics Committees in Switzerland, Ireland, The Netherlands
and Belgium approved this trial protocol. We will publish the results of
this trial in a peer-reviewed journal.

Main funding

European Union’s Horizon 2020 programme.

Trial registration number

NCT02986425,
NCT000002183,NCT6012,
U1111-1181-9400.
Prevalence of modern contraceptive discontinuation and associated factors among married reproductive age group women in Debre Berhan town, Ethiopia: a community-based cross-sectional study
Authors: Ayele Siraye Genzeb , Mekonnen Baze , Deribe Leul , Tsige Abate Wondesen
Published: April 2024

Objective

To assess the prevalence of modern contraceptive discontinuation and associated factors among married reproductive age (15–49 years) group women.

Study design, setting and participants

A community-based cross-sectional study was conducted in Debre Berhan town among 500 reproductive age group women. Study participants were selected using two-stage sampling procedures. Data were collected using a semistructured face-to-face interview questionnaire. The data were entered in EpiData V.4.2.0 and then exported to SPSS V.25 software for data analysis. Descriptive statistics such as mean, per cent and frequency were used to summarise women’s characteristics. Binary logistic regression analysis was used to identify predictors’ variables with modern contraceptive discontinuation and p<0.05 was used to declare association.

Results

The prevalence of modern contraceptive discontinuation among married reproductive age group women was 35.2% with a mean duration of use of 2.6±2.1 months. This study also revealed that the discontinuation rate was 12.6% within the first year of use. In the current study, those living with their husband (adjusted OR (AOR)=3.81, p<0.001), experiencing side effects while using modern contraceptives (AOR=2.45, p=0.02), getting counselling service (AOR=5.51, p<0.001) and respondent husband acceptance of her modern contraceptive use (AOR=3.85, p=0.01) were significantly associated with modern contraceptive discontinuation.

Conclusion

The findings of this study showed that the prevalence of modern contraceptive discontinuation rate of all methods among married reproductive age group women was 35.2%. To reduce modern contraceptive discontinuation, mutually, it is important to create community awareness about the importance of the continued use of modern contraceptives, improve the quality of family planning service in the health institution, strengthen family planning counselling service and give adequate counselling on details of effectiveness and side effects.
Trade-offs between overall survival and side effects in the treatment of metastatic breast cancer: eliciting preferences of patients with primary and metastatic breast cancer using a discrete choice experiment
Authors: Bullen Alistair , Ryan Mandy , Ennis Holly , Gray Ewan , Loría-Rebolledo Luis Enrique , McIntyre Morag , Hall Peter
Published: April 2024

Objectives

There has been a recent proliferation in treatment options for patients with metastatic breast cancer. Such treatments often involve trade-offs between overall survival and side effects. Our study aims to estimate the trade-offs that could be used to inform decision-making at the individual and policy level.

Design

We designed a discrete choice experiment (DCE) to look at preferences for avoiding severity levels of side effects when choosing treatment for metastatic breast cancer. Treatment attributes were: fatigue, nausea, diarrhoea, other side effects (peripheral neuropathy, hand–foot syndrome and mucositis) and urgent hospital admission and overall survival. Responses were analysed using an error component logit model. We estimated the relative importance of attributes and minimum acceptable survival for improvements in side effects.

Setting

The DCE was completed online by UK residents with self-reported diagnoses of breast cancer.

Participants

105 respondents participated, of which 72 patients had metastatic breast cancer and 33 patients had primary breast cancer.

Results

Overall survival had the largest relative importance, followed by other side effects, diarrhoea, nausea and fatigue. The risk of urgent hospital admission was not significant. While overall survival was the most important attribute, respondents were willing to forgo some absolute probability of overall survival for reductions in all Grade 2 side effects (12.02% for hand–foot syndrome, 11.01% for mucositis, 10.42% for peripheral neuropathy, 6.33% for diarrhoea and 3.62% for nausea). Grade 1 side effects were not significant, suggesting respondents have a general tolerance for them.

Conclusions

Patients are willing to forgo overall survival to avoid particular severity levels of side effects. Our results have implications for data collected in research studies and can help inform person-centred care and shared decision-making.