bluuebunny/crossref_metadata_2025 huggingface dataset:
Reinforcement learning–based framework for whale rendezvous via autonomous sensing robots
Authors: Jadhav Ninad , Bhattacharya Sushmita , Vogt Daniel , Aluma Yaniv , Tønnesen Pernille , Prabhakara Akarsh , Kumar Swarun , Gero Shane , Wood Robert J. , Gil Stephanie
Published: October 2024

Rendezvous with sperm whales for biological observations is made challenging by their prolonged dive patterns. Here, we propose an algorithmic framework that codevelops multiagent reinforcement learning–based routing (autonomy module) and synthetic aperture radar–based very high frequency (VHF) signal–based bearing estimation (sensing module) for maximizing rendezvous opportunities of autonomous robots with sperm whales. The sensing module is compatible with low-energy VHF tags commonly used for tracking wildlife. The autonomy module leverages in situ noisy bearing measurements of whale vocalizations, VHF tags, and whale dive behaviors to enable time-critical rendezvous of a robot team with multiple whales in simulation. We conducted experiments at sea in the native habitat of sperm whales using an “engineered whale”—a speedboat equipped with a VHF-emitting tag, emulating five distinct whale tracks, with different whale motions. The sensing module shows a median bearing error of 10.55° to the tag. Using bearing measurements to the engineered whale from an acoustic sensor and our sensing module, our autonomy module gives an aggregate rendezvous success rate of 81.31% for a 500-meter rendezvous distance using three robots in postprocessing. A second class of fielded experiments that used acoustic-only bearing measurements to three untagged sperm whales showed an aggregate rendezvous success rate of 68.68% for a 1000-meter rendezvous distance using two robots in postprocessing. We further validated these algorithms with several ablation studies using a sperm whale visual encounter dataset collected by marine biologists.
Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains
Authors: Zhu Biqing , Park Jae-Min , Coffey Sarah R. , Russo Anthony , Hsu I-Uen , Wang Jiawei , Su Chang , Chang Rui , Lam TuKiet T. , Gopal Pallavi P. , Ginsberg Stephen D. , Zhao Hongyu , Hafler David A. , Chandra Sreeganga S. , Zhang Le
Published: October 2024

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, and recent evidence suggests that pathogenesis may be in part mediated by inflammatory processes, the molecular and cellular architectures of which are largely unknown. To identify and characterize selectively vulnerable brain cell populations in PD, we performed single-nucleus transcriptomics and unbiased proteomics to profile the prefrontal cortex from postmortem human brains of six individuals with late-stage PD and six age-matched controls. Analysis of nearly 80,000 nuclei led to the identification of eight major brain cell types, including elevated brain-resident T cells in PD, each with distinct transcriptional changes in agreement with the known genetics of PD. By analyzing Lewy body pathology in the same postmortem brain tissues, we found that α-synuclein pathology was inversely correlated with chaperone expression in excitatory neurons. Examining cell-cell interactions, we found a selective abatement of neuron-astrocyte interactions and enhanced neuroinflammation. Proteomic analyses of the same brains identified synaptic proteins in the prefrontal cortex that were preferentially down-regulated in PD. By comparing this single-cell PD dataset with a published analysis of similar brain regions in Alzheimer’s disease (AD), we found no common differentially expressed genes in neurons but identified many shared differentially expressed genes in glial cells, suggesting that the disease etiologies, especially in the context of neuronal vulnerability, in PD and AD are likely distinct.
A kidney-specific fasting-mimicking diet induces podocyte reprogramming and restores renal function in glomerulopathy
Authors: Villani Valentina , Frank Camille Nicolas , Cravedi Paolo , Hou Xiaogang , Bin Sofia , Kamitakahara Anna , Barbati Cristiani , Buono Roberta , Da Sacco Stefano , Lemley Kevin V. , De Filippo Roger E. , Lai Silvia , Laviano Alessandro , Longo Valter D. , Perin Laura
Published: October 2024

Cycles of a fasting-mimicking diet (FMD) promote regeneration and reduce damage in the pancreases, blood, guts, and nervous systems of mice, but their effect on kidney disease is unknown. In addition, a FMD has not been tested in rats. Here, we show that cycles of a newly developed low-salt FMD (LS-FMD) restored normal proteinuria and nephron structure and function in rats with puromycin-induced nephrosis compared with that in animals with renal damage that did not receive the dietary intervention. LS-FMD induced modulation of a nephrogenic gene program, resembling renal developmental processes in multiple kidney structures. LS-FMD also activated podocyte-lineage reprogramming pathways and promoted a quiescent state in mature podocytes in the rat kidney damage model. In a pilot clinical study in patients with chronic kidney disease, FMD cycles of 5 days each month for 3 months promoted renoprotection, including reduction of proteinuria and improved endothelial function, compared with that in patients who did not receive the FMD cycles. These results show that FMD cycles, which promote the reprogramming of multiple renal cell types and lead to glomerular damage reversal in rats, should be tested further for the treatment of progressive kidney diseases.
Engineering CAR-T therapies for autoimmune disease and beyond
Authors: English Emily P. , Swingler Rachel N. , Patwa Simran , Tosun Mehmet , Howard Jr. James F. , Miljković Miloš D. , Jewell Christopher M.
Published: October 2024

Chimeric antigen receptor–T cell (CAR-T) therapy has transformed the management of refractory hematological malignancies. Now that targeting pathogenic cells of interest with antigen-directed cytotoxic T lymphocytes is possible, the field is expanding the reach of CAR-T therapy beyond oncology. Recently, breakthrough progress has been made in the application of CAR-T technology to autoimmune diseases, exploiting the same validated targets that were used by pioneering CAR-T therapies in hematology. Here, we discuss recent advances and outcomes that are paving the way for extension to new therapeutic areas, including autoimmunity.
Pangenome analysis of
Paenibacillus polymyxa
strains reveals the existence of multiple and functionally distinct
Paenibacillus
species
Authors: Maggi Federica , Giuliodori Anna Maria , Brandi Anna , Cimarelli Lucia , Alcántara Roberto , Pallotti Stefano , Amantini Consuelo , Petrelli Dezemona , Fabbretti Attilio , Spurio Roberto , Napolioni Valerio
Published: October 2024

Paenibacillus polymyxa
, a Gram-positive bacterium commonly found in soil and plant roots, plays an important role in the environment due to its nitrogen-fixing ability and is renowned for producing antibiotics like polymyxin. In this study, we present a robust framework for investigating the evolutionary and taxonomic connections of strains belonging to
P. polymyxa
available at the National Center for Biotechnology Information, as well as five new additional strains isolated at the University of Camerino (Italy), through pangenome analysis. These strains can produce secondary metabolites active against
Staphylococcus aureus
and
Klebsiella pneumoniae
. Employing techniques such as digital DNA-DNA hybridization (dDDH), average nucleotide identity (ANI) estimation, OrthoFinder, and ribosomal multilocus sequence typing, we consistently divided these
P. polymyxa
strains into four clusters, which differ significantly in terms of ANI and dDDH percentages, both considered as reference indices for separating bacterial species. Moreover, the strains of Cluster 2 were re-classified as belonging to the
Paenibacillus ottowii
species. By comparing the pangenomes, we identified the core genes of each cluster and analyzed them to recognize distinctive features in terms of biosynthetic/metabolic potential. The comparison of pangenomes also allowed us to pinpoint differences between clusters in terms of genetic variability and the percentage of the genome dedicated to core and accessory genes. In conclusion, the data obtained from our analyses of strains belonging to the
P. polymyxa
species converge toward a necessary reclassification, which will require a fundamental contribution from microbiologists in the near future.

IMPORTANCE

The development of sequencing technologies has led to an exponential increase in microbial sequencing data. Accurately identifying bacterial species remains a challenge because of extensive intra-species variability, the need for multiple identification methods, and the rapid rate of taxonomic changes. A substantial contribution to elucidating the relationships among related bacterial strains comes from comparing their genomic sequences. This comparison also allows for the identification of the “pangenome,” which is the set of genes shared by all individuals of a species, as well as the set of genes that are unique to subpopulations. Here, we applied this approach to
Paenibacillus polymyxa
, a species studied for its potential as a biofertilizer and biocontrol agent and known as an antibiotic producer. Our work highlights the need for a more efficient classification of this bacterial species and provides a better delineation of strains with different properties.
Bacterial acquisition of host fatty acids has far-reaching implications on virulence
Authors: Waters Jack K. , Eijkelkamp Bart A.
Published: October 2024

The lipid homeostasis pathways of bacterial pathogens have been studied comprehensively for their biochemical functionality. However, new and refined technologies have supported the interrogation of bacterial lipid and fatty acid homeostasis mechanisms in more complex environments, such as mammalian host niches. In particular, emerging findings on the breadth and depth of host fatty acid uptake have demonstrated their importance beyond merely fatty acid utilization for membrane synthesis, as they can contribute to virulence factor regulation, pathogenesis, and group-based behaviors. Lipid homeostasis is also intertwined with other metabolic and physiological processes in the bacterial cells, which appear to be largely unique per species, but overarching themes can be derived. This review combines the latest biochemical and structural findings and places these in the context of bacterial pathogenesis, thereby shedding light on the far-reaching implications of lipid homeostasis on bacterial success.
In vivo
RNA sequencing reveals a crucial role of Fus3-Kss1 MAPK pathway in
Candida glabrata
pathogenicity
Authors: Mo Xinreng , Yu Xiangtai , Cui Hao , Xiong Kang , Yang Shan , Su Chang , Lu Yang
Published: October 2024

Candida glabrata
is an important and increasingly common pathogen of humans, particularly in immunocompromised hosts. Despite this, little is known about how this fungus causes disease. Here, we applied RNA sequencing and an
in vivo
invasive infection model to identify the attributes that allow this organism to infect hosts. Fungal transcriptomes show a dramatic increase in the expression of Fus3 and Kss1, two mitogen-activated protein kinases (MAPKs), during invasive infection. We further demonstrate that they are both highly induced under a combination of serum and high CO
2
conditions. Deletion of both
FUS3
and
KSS1
, but neither gene alone, results in a reduced fungal burden in organs, as well as in the gastrointestinal tract in the DSS (Dextran Sulfate Sodium)-induced colitis model. Similarly, the defect in persistence in macrophages and attenuated adhesion to epithelial cells are observed when
FUS3
and
KSS1
are both disrupted. The
fus3 kss1
double mutant also displays defects in the induction of virulence attributes such as genes required for iron acquisition and adhesion and in the anti-fungal drug tolerance. The putative downstream transcription factors Ste12 (1), Ste12 (2), Tec1, and Tec2 are found to be involved in the regulation of these virulence attributes. Collectively, our study indicates that an evolutionary conserved MAPK pathway, which regulates mating and filamentous growth in
Saccharomyces cerevisiae
, is critical for
C. glabrata
pathogenicity.

IMPORTANCE

The MAPK signaling pathway, mediated by closely related kinases Fus3 and Kss1, is crucial for controlling mating and filamentous growth in
Saccharomyces cerevisiae
, but this pathway does not significantly impact hyphal development and pathogenicity in
Candida albicans
, a commensal-pathogenic fungus of humans. Furthermore, deletion of Cpk1, the ortholog of Fus3 in pathogenic fungus
Cryptococcus neoformans
, has no effect on virulence. Here, we demonstrate that the MAPK pathway is crucial for the pathogenicity of
Candida glabrata
, a fungus that causes approximately one-third of cases of hematogenously disseminated candidiasis in the United States. This pathway regulates multiple virulence attributes including the induction of iron acquisition genes and adhesins, as well as persistence in macrophages and organs. Our work provides insights into
C. glabrata
pathogenesis and highlights an example in which regulatory rewiring of a conserved pathway confers a virulent phenotype in a pathogen.
Cyclooxygenase-2/prostaglandin E2 pathway orchestrates the replication of infectious bronchitis virus in chicken tracheal explants
Authors: Mahmoud Motamed Elsayed , Ali Ahmed , Farooq Muhammad , Isham Ishara M. , Suhail Sufna M. , Herath-Mudiyanselage Heshanthi , Rahimi Ryan , Abdul-Careem Mohamed Faizal
Published: October 2024

In this study, we investigated the localized pathogenesis of infectious bronchitis virus (IBV) in chicken tracheal organ cultures (TOCs), focusing on the role of inducible cyclooxygenase (COX-2). Two divergent IBV strains, respiratory Connecticut (Conn) A5968 and nephropathogenic Delmarva (DMV)/1639, were studied at 6, 12, 24, and 48 hours post-infection (hpi). Various treatments including exogenous prostaglandin (PGE)2, a selective COX-2 antagonist (SC-236), and inhibitors of PGE2 receptors and Janus kinase (JAK) were administered. IBV genome load and antigen expression were quantified using real-time quantitative PCR and immunohistochemistry. COX-2, interferon (IFN)-α, IFN-β, interleukin (IL)−1β, IL-6, and inducible nitric oxide synthase (iNOS) expressions were measured, along with PGE2 and COX-2 concentrations. IBV genome load and protein expression peaked at 12 and 24 hpi, respectively. Conn A5968-infected TOCs exhibited continuous COX-2 expression for up to 24 hpi, extended PGE2 production up to 48 hpi, and reduced inflammatory cytokine expression. In contrast, DMV/1639-infected TOCs displayed heightened inflammatory cytokine expression, brief COX-2 expression, and PGE2 production. Treatment with IFN-γ, SC-236, PGE2 receptor inhibitors, or JAK inhibitors reduced IBV infection and lesion scores, whereas exogenous PGE2 or IFN-γ pretreatment with a JAK-2 inhibitor augmented infection. These findings shed light on the innate immune regulation of IBV infection in the trachea, highlighting the involvement of the COX-2/PGE2 pathway.

IMPORTANCE

Understanding the localized pathogenesis of infectious bronchitis virus (IBV) within the trachea of chickens is crucial for developing effective control strategies against this prevalent poultry pathogen. This study sheds light on the role of inducible cyclooxygenase (COX-2) and prostaglandin (PGE)2 in IBV pathogenesis using chicken tracheal organ culture (TOC) models. The findings reveal distinct patterns of COX-2 expression, PGE2 production, and immune responses associated with different IBV strains, highlighting the complexity of host-virus interactions. Furthermore, the identification of specific inhibitors targeting the COX-2/PGE2 pathway and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway provides potential therapeutic avenues for mitigating IBV infection in poultry. Overall, this study contributes to our understanding of the innate immune regulation of IBV infection within the trachea, laying the groundwork for the development of targeted interventions to control IBV outbreaks in poultry populations.
Variation in the metagenomic analysis of fecal microbiome composition calls for a standardized operating approach
Authors: Xu Zhilu , Yeoh Yun Kit , Tun Hein M. , Fei Na , Zhang Jingwan , Morrison Mark , Kamm Michael A. , Yu Jun , Chan Francis Ka Leung , Ng Siew C.
Published: October 2024

The reproducibility in microbiome studies is limited due to the lack of one gold-standard operating procedure. The aim of this study was to examine the impact of protocol variations on microbiome composition using metagenomic data sets from a single center. We assessed the variation in a data set consisted of 2,722 subjects, including 9 subcohorts harboring healthy subjects and patients with various disorders, such as inflammatory bowel disease, colorectal cancer, and type 2 diabetes. Two different DNA extraction kits, with or without lyticase, and two sample storage methods were compared. Our results indicated that DNA extraction had the largest impact on gut microbiota diversity among all host factors and sample operating procedures. Healthy subjects matched by age, body mass index, and sample operating methods exhibited reduced, yet significant differences (PERMANOVA,
P
< 0.05) in gut microbiota composition across studies. The variations contributed by DNA extraction were primarily driven by different recovery efficiency of gram-positive bacteria, e.g., phyla Firmicutes and Actinobacteria. This was further confirmed by a parallel comparison of fecal samples from five healthy subjects and a standard mock community. In addition, the DNA extraction method influenced DNA biomass, quality, and the detection of specific lineage-associated diseases. Sample operating approach and batch effects should be considered for cohorts with large sample size or longitudinal cohorts to ensure that source data were appropriately generated and analyzed. Comparison between samples processed with inconsistent methods should be dealt with caution. This study will promote the establishment of a sample operating standard to enhance our understanding of microbiome and translating in clinical practice.

IMPORTANCE

The reproducibility of human gut microbiome studies has been suboptimal across cohorts and study design choices. One possible reason for the disagreement is the introduction of systemic biases due to differences in methodologies. In our study, we utilized microbial metagenomic data sets from 2,722 fecal samples generated from a single research center to examine the extent to which sample storage and DNA extraction influence the quantification of microbial composition and compared this variable with other sources of technical and biological variation. Our research highlights the impact of DNA extraction methods when analyzing microbiome data and suggests that the microbiome profile may be influenced by differences in the extraction efficiency of bacterial species. With metagenomics sequencing being increasingly used in clinical biology, our findings provide insight into the challenges using metagenomics sequencing in clinical diagnostics, where the detection of certain species and its abundance relative to a “healthy reference” is key.
Giant plagioclase in the Steens Basalt, southeast Oregon, USA: Tracking the balance of differentiation processes in continental flood basalt evolution
Authors: Moore N.E. , Toth C. , Bohrson W.A. , Grunder A.L. , Clark N.
Published: October 2024

Giant plagioclase basalts (GPBs), flows that contain abundant and conspicuous plagioclase crystals ≥1 cm in length, exist at many continental flood basalt provinces, and their presence can provide a window into the crustal differentiation processes and storage conditions that produced the magmas prior to eruption. GPB flows occur in the Steens Basalt of southeast Oregon, USA, one of the earliest members of the Columbia River Flood Basalt Group, but their origin in this province has not been studied in detail. We conducted quantitative textural analysis utilizing crystal size distributions (CSDs) at the outcrop and thin section scale, as well as in situ plagioclase trace element and isotopic compositional analysis, in order to elucidate the processes responsible for generating two end-member textural types of GPB found in the Steens Basalt: daisy stone glomerocryst clusters composed of radiating plagioclase laths and single isolated plagioclase. CSD patterns suggest a changing balance of multiple differentiation processes affected the magmas that created each GPB textural type. In the daisy stone plagioclase, crystals rarely exhibit resorption textures, trace element abundances are comparatively low with minimal variability, and Sr isotopes are commonly in equilibrium with groundmass. In the single isolated plagioclase, resorption textures are common, trace element abundances are generally higher and display within crystal variation, and Sr isotopes are typically not in equilibrium with groundmass. These distinctive characteristics require separate mechanisms to generate each end-member GPB texture. Daisy stone GPBs form by growth of large crystals following mafic recharge events that completely resorb entrained cumulate plagioclase. A large amount of plagioclase may then grow with minimal cooling following recharge due to saturation in plagioclase components. In contrast, single isolated GPBs are the result of partial resorption of both entrained and resident plagioclase following less voluminous and less primitive recharge events; regrowth then occurs on the partially resorbed cores when cooling resumes. Both GPB types are formed by thermal cycling, but each texture reflects the differentiation processes that were prevalent during different eruptive stages of the Steens Basalt, as the balance between recharge, crystal fractionation, and assimilation varied in time.
Petrogenetic relationship of the variably Ni–Cu–platinum-group element (PGE)-mineralized intrusions of the Thunder Bay North Intrusive Complex, Midcontinent Rift, Canada: Implications for mineral exploration in mafic–ultramafic complexes
Authors: Brzozowski Matthew J. , Hollings Pete , Hamilton Mike , Heggie Geoff , Caglioti Connor , Yahia Khalid , Bravo Andrea Corredor
Published: October 2024

The Thunder Bay North Intrusive Complex (TBNIC) of Canada comprises six variably Ni–Cu–platinum-group element (PGE)-mineralized mafic–ultramafic intrusions that intruded the Archean Quetico Subprovince. These are the Current, Escape, Lone Island, Greenwich, and 025 intrusions, with the former three aligned along an east–west-trending intrusion termed the East–West Corridor. These intrusions have a consistent igneous stratigraphy comprising, from bottom to top, peridotite, gabbros, and quartz gabbro. Only the Current and Escape intrusions are known to host sulfide mineralization in the peridotite. Despite the economic significance of the TBNIC, little work has been done to characterize its petrogenetic evolution and the causes of the apparent variable fertility. Our new ages for Escape (1107.6 ± 0.9 Ma) and Greenwich (1105.7 ± 0.9 Ma), combined with previously determined ages for Current (1106.6 ± 1.6 Ma) and Lone Island (1106.3 ± 2.1 Ma), demonstrate that the TBNIC was emplaced as part of the ca. 1.1 Ga Midcontinent Rift event. The similarities in their rare earth element geochemistry and consistently low Th/La–Sri values indicate that the intrusions crystallized from genetically related magmas that did not assimilate significant amounts of crustal material. Accordingly, their systematically negative εNdt values and Nb anomalies likely reflect that their parent magmas were largely sourced from the subdcontinental lithospheric mantle and not the Keweenaw Plume. Given their genetic relationship, the variable fertility of the intrusions cannot be related to processes that occurred in their mantle sources. Since the gabbros have systematically depleted Cu/Zr–Cu/Pd ratios and the peridotites have enriched ratios, the apparent variable fertility is likely related to the timing and location of sulfide segregation and accumulation, with the barren gabbros preserving magmas that lost sulfide liquid during transport to shallow crustal levels, and the mineralized peridotites recording accumulation of sulfide liquid. This interpretation has important implications for exploration as it implies that sulfide mineralization in the apparently barren intrusions may be located at depth in undiscovered ultramafic cumulates.
Complications of excess weight seen in two tier 3 paediatric weight management services: an observational study
Authors: Hawton Katherine , Apperley Louise , Parkinson Jennifer , Owens Meghan , Semple Claire , Canvin Lauren , Holt Alanna , Easter Shelley , Clark Kate , Lund Kim , Clarke Ellie , O’Brien James , Giri Dinesh , Senniappan Senthil , Shield Julian P H
Published: October 2024

Background

Children and young people living with severe obesity experience a range of complications of excess weight (CEW); however the prevalence of complications is not well defined. We have evaluated baseline characteristics and CEW of patients from two UK tier 3 paediatric weight management services.

Methods

All new patients aged 2–17 years seen from March 2022 to February 2023 were included. Baseline demographic data was collected, and patients screened for CEW. PedsQL-4.0 questionnaires were used to assess health-related quality of life (HRQL).

Results

185 patients were included, median age 14.3 years (range 3.3–18.0), 50.8% were girls. Of the patients, 73.8% were white British, with a significant excess of patients living in the most deprived decile (41.4%). Median body mass index SD score was +3.55 (IQR 3.11–3.90) and median body fat was 49.3% (IQR 42.3%–55.1%). Autistic spectrum disorder, attention deficit hyperactivity disorder and learning difficulties were vastly over-represented.

Dyslipidaemia was the most common (51.6%) complication, followed by hypertension (28.9%), metabolic dysfunction-associated steatotic liver disease (17.8%), obstructive sleep apnoea (9.0%) and idiopathic intracranial hypertension (4.3%). Mean glycated haemoglobin was 35.0 mmol/mol (IQR 33–38). 8.1% had type 2 diabetes mellitus. Many of these complications were detected through screening in CEW clinics.

Both child-reported (mean 51.9/100) and parented-reported (47.8/100) HRQL scores were low. Mental health problems were common: 26.2% with anxiety and 7.7% with depression.

Conclusions

This study demonstrates the significant and profound mental and organ-specific pathology resulting from severe obesity in childhood, highlighting the clinical necessity for CEW clinics. A rigorous approach to identify complications at an early stage is essential to improve long-term health outcomes.
Mixed-method Irish study exploring the role of diet in IBD based on an online questionnaire and a patient panel opinion
Authors: Hanrahan Naomi , Spillane Victoria , Moore Kevin , Dineen Mick , Murphy Aoife , Velikonja Ana , Hurley Margot , O’Keeffe Majella , Melgar Silvia
Published: October 2024

Objective

Diet is a risk factor in inflammatory bowel diseases (IBD) pathogenesis. This study aims to examine the dietary patterns and beliefs of Irish patients living with IBD through an online questionnaire and subsequent open discussions with an IBD patient collaborator panel (PCP). All data presented here are selected and presented following the PCP’s suggestions and views.

Design

This mixed-method study included an online questionnaire using a short food frequency questionnaire examining dietary patterns, dietary opinions, beliefs and behaviours (phase I). Six in-person PCP sessions were conducted, where findings from the online questionnaire, diet and lifestyle in the context of IBD were discussed in depth (phase II).

Results

The questionnaire revealed that respondents with active IBD are associated with the consumption of high-sugar, processed and meat-based foods while reducing their consumption of high-fibre foods. Individuals with active Crohn’s disease have a decrease in overall daily energy consumption and a significant reduction in intake of fibre, non-starch polysaccharides, micronutrients [B vitamins (B1, B2, and B9), vitamin C, calcium] and trace elements (iron, zinc, copper and manganese). The PCP reported that food tolerability is limited during relapse, leading patients to prefer simple carbohydrates for energy, consistent with the dietary intake data. The PCP reported that most dietary advice was received during hospitalisation (relapse), focused on food avoidance, with little follow-up during remission. The consensus among the PCP was that factors, such as disease type, psychological aspects, dietary understanding and support, can influence peoples’ dietary choices.

Conclusion

In summary, we show that dietary intake in people with IBD varies and may depend on several factors, not just the disease itself. This PCP desires more dietary information and professional support outside of hospitalisation to assist with disease management.
Association between cannabis use and brain structure and function: an observational and Mendelian randomisation study
Authors: Ishrat Saba , Levey Daniel F , Gelernter Joel , Ebmeier Klaus , Topiwala Anya
Published: October 2024

Background

Cannabis use during adolescence and young adulthood has been associated with brain harm, yet despite a rapid increase in cannabis use among older adults in the past decade, the impact on brain health in this population remains understudied.

Objective

To explore observational and genetic associations between cannabis use and brain structure and function.

Methods

We examined 3641 lifetime cannabis users (mean (SD) age 61.0 (7.1) years) and 12 255 controls (mean (SD) age 64.5 (7.5) years) from UK Biobank. Brain structure and functional connectivity were measured using multiple imaging-derived phenotypes. Associations with cannabis use were assessed using multiple linear regression controlling for potential confounds. Bidirectional two-sample Mendelian randomisation analyses were used to investigate potential causal relationships.

Findings

Cannabis use was associated with multiple measures of brain structure and function. Participants with a history of cannabis use had poorer white matter integrity, as assessed by lower fractional anisotropy and higher mean diffusivity in the genu of the corpus callosum, as well as weaker resting-state functional connectivity in brain regions underlying the default mode and central executive networks. Mendelian randomisation analyses found no support for causal relationships underlying associations between cannabis use and brain structure or function.

Conclusions

Associations between lifetime cannabis use and brain structure and function in later life are probably not causal in nature and might represent residual confounding.

Clinical implications

Cannabis use is associated with differences in brain structure and function. Further research is needed to understand the mechanisms underlying these associations, which do not appear to be causal.
Knowledge and acceptability of the human papillomavirus vaccine and associated factors among adolescent girls in public primary schools in Dessie Town, South Wollo, Northeast Ethiopia, 2020: A cross-sectional study
Authors: Negesse Simegn Yezbalem , Wossen Samuel Alemtsehay , Gebresilasie Kelelew Rediet , Mohammed Lubaba Ahmed , Liyew Atrsaw Dessie , Abate Belay Mengistu
Published: October 2024

Objective

To assess the knowledge and acceptability of the human papillomavirus (HPV) vaccine and the associated factors among adolescent girls in public primary schools in Dessie Town, South Wollo, Northeast Ethiopia in 2020.

Design, participants and methods

This was an institutional cross-sectional study conducted from 1 November to 30 November 2020 among 844 adolescent girls. A systematic random sampling method was used to select participants, who completed a pretested, self-administered questionnaire. Data were entered into EpiData V.4.6 and exported to SPSS V.25 for analysis. A binary logistic regression model identified the contributing factors to HPV vaccine knowledge and acceptance. Adjusted OR (AOR) and 95% CI computed at p<0.05 were used to assess significance levels.

Main outcome measures

The primary outcomes of interest were knowledge and acceptability of the HPV vaccine.

Results

The HPV vaccine is known and acceptable to 47% and approximately 43% of the respondents, respectively. Age (AOR=3.51, 95% CI 1.62 to 7.6), father’s educational level (AOR=2.62, 95% CI 1.57 to 4.38) and parent–child communication about sex and reproductive health (AOR=1.94, 95% CI 1.36 to 2.76) were associated with knowledge of the HPV vaccine. Acceptance of the HPV vaccine was significantly influenced by fathers’ educational level (AOR=1.88, 95% CI:1.02 to 3.29), knowledge of Pap smear tests (AOR=2.54, 95% CI 1.79 to 3.62) and knowledge of the HPV vaccine (AOR=5.30, 95% CI 3.77 to 7.73).

Conclusion

In this study, there was generally good and high acceptance of the HPV vaccine, respectively, compared with a study conducted in Southwest Ethiopia. The study, however, had limitations in terms of recall bias, assessment of coverage/effectiveness over time and generalisability due to the institutional sample used.
Grading carcinoembryonic antigen levels can enhance the effectiveness of prognostic stratification in patients with colorectal cancer: a single-centre retrospective study
Authors: Xie Hailun , Wei Lishuang , Wang Qiwen , Tang Shuangyi , Gan Jialiang
Published: October 2024

Objectives

This study developed a refined carcinoembryonic antigen (CEA) grading system using CEA cut-off points of 5, 20 and 50 ng/mL and to explore the prognostic value of CEA grading in predicting the progression-free survival (PFS) and overall survival (OS) of colorectal cancer (CRC) patients.

Design

A retrospective cohort study.

Setting

First Affiliated Hospital of Guangxi Medical University.

Participants

1107 CRC patients who received surgical treatment.

Materials and methods

Survival analysis was conducted using the Kaplan-Meier method and compared using the log-rank test. A Cox regression model with a 95% CI was used to evaluate the independent prognostic risk factors for CRC. Prognostic nomograms were constructed to predict the 1–5-year PFS/OS.

Results

Elevated serum CEA levels are often indicative of recurrence and death in CRC patients. Higher CEA levels were significantly associated with more aggressive tumour phenotypes. The CEA grading system was an independent predictor of prognosis in CRC patients and effectively stratified PFS (62.0% vs 51.2% vs 33.7% vs 20.2%, p<0.001) and OS (64.7% vs 54.4% vs 36.6% vs 22.5%, p<0.001) in CRC patients. As the CEA grade increased, the risk of poor prognosis gradually increased in a gradient manner, with an approximately 10% difference in risk grade between each CEA grade. The internal validation cohort further confirmed that CEA grade remains an effective prognostic factor for the survival of CRC patients. Prognostic nomograms, which integrate individual characteristics, tumour features and CEA grading, provide a more comprehensive prognostic evaluation for CRC patients.

Conclusions

The CEA grading system is an independent predictor of prognosis for CRC patients and can effectively stratify PFS and OS.
Application of ICU electronic diary platform based on co-design concept in Chinese critically ill patients: a mixed methods study protocol
Authors: Li Li , Pan Xiaoying , Tong Qingqing , Gao Huiming , Yuan You , Zhang Xia , Chen Junxi , Chang Yonghu , Zhang Tianxi , Hu Rujun
Published: October 2024

Introduction

Critically ill patients are at a heightened risk for post-traumatic stress disorder (PTSD). While the intensive care unit (ICU) diary has been shown to improve the mental health and quality of life of ICU patients, the handwritten version still has some limitations such as a lack of support for multimedia content and writing by remote family members, as well as being time-consuming and labour-intensive. We hypothesise that constructing an ICU electronic diary platform based on a co-design approach and verifying its applicability could alleviate these limitations, making the ICU diary more convenient for users.

Methods and analysis

This sequential exploratory mixed-methods study will consist of four consecutive phases: understanding the ICU diary research content and implementation, developing an ICU electronic diary platform after conducting qualitative interviews with stakeholders, verifying the applicability of the platform and verifying its effectiveness.

Ethics and dissemination

Ethics approval was obtained from the Biomedical Research Ethics Committee of the Affiliated Hospital of Zunyi Medical University (approval number: KLL-2023–602). The results of this study will be distributed through peer-reviewed journals.

Trial registration number

Chinese Clinical Trial Register (ChiCTR2400079903).
Minimal clinically important difference for acupuncture for patients with chronic spontaneous urticaria: secondary analysis from a multicentre randomised controlled trial in China
Authors: Xiao Xianjun , Cao Wei , Zou Zihao , Chen Sijue , Yang Qian , Qin Di , Xue Peiwen , Wang Lu , Xi Menghan , Li Ying , Qin Haiyan , Shi Yunzhou
Published: October 2024

Objectives

To evaluate the minimal clinically important difference (MCID) value for acupuncture treatment in chronic spontaneous urticaria (CSU), providing guidance for its application in CSU management.

Design

Secondary analysis of data from a multicentre randomised controlled trial.

Setting

Three tertiary hospitals across three cities in China.

Participants

103 CSU patients (78.7% female) with an average age of 39.97 years.

Interventions

Participants received acupuncture treatment for 4 weeks in the original study.

Outcome measures

MCID and minimal detectable change (MDC) for the Urticaria Activity Score over 7 days (UAS7) in acupuncture treatment of CSU. Convergent validity assessed by intraclass correlation coefficient (ICC). Responsiveness evaluated through Spearman correlation between UAS7 improvements and anchor tools (physician’s and patient’s assessments). MDC calculated using SE of measurement of changes in UAS7 scores. MCID estimated using distribution-based and anchor-based methods.

Results

The ICC for UAS7 was 0.86. Improvements in UAS7 scores were significantly correlated with patient (r=0.44, p<0.01) and physician (r=0.85, p<0.01) assessments of CSU activity shifts. The MDC for UAS7 was 5.08. The MCID for acupuncture treatment in CSU was 8.3.

Conclusions

This study provides the first MCID value for acupuncture treatment in CSU. These findings contribute to the understanding of acupuncture’s effects in treating CSU and may inform future research and clinical practice in the management of this condition.

Trial registration number

ChiCTR1900022994.
Demographic and clinical characteristics of New York City Health + Hospitals HIV Heart Failure (NYC4H cohort): cohort profile
Authors: Chen Yi-Yun , Borkowski Pawel , Nazarenko Natalia , Biavati Luca , Parker Matthew , Chowdhury Ishmum , Vargas-Pena Coral , Bhakta Shivang , Garg Vibhor , Bock Joshua , Faillace Robert T , Palaiodimos Leonidas
Published: October 2024

Purpose

Studies have elucidated that heart failure (HF) in people living with HIV manifests differently when compared with HF cases in the general population. This cohort aimed to examine the mortality risk factors, including biological and social factors, as well as suitable medical interventions to prevent death in this population.

Participants

The New York City Health+Hospitals HIV Heart Failure (NYC4H) cohort encompassed records from 11 major hospital sites. Adult individuals with confirmed HIV and HF were recruited from either inpatient or clinic hospital visits between July 2017 and June 2022. The first follow-up period began on the date of the first clinical encounter until June 2023, and the second follow-up period extended between July 2022 and October 2023.

Findings to date

In total, 1044 patients were enrolled in the study. The cohort comprised 657 (62.9%) males and 387 (37.1%) females. The average age was 61.6 years at baseline and the average follow-up time was 3.8 years. Overall, a total of 259 (24.8%) deaths were identified, of which 193 occurred in the first follow-up period (enrolling date to June 2022) and 66 during the second follow-up period (June 2022 to October 2023). The most common comorbidities within this population were hypertension (75.3%), chronic obstructive pulmonary disease (39.2%), type II diabetes mellitus (40%) and hyperlipidaemia (35.7%). The most common social adversities were polysubstance use (31.13%), mental health-related issues (20.7%) and lack of family support (14.5%). 601 (57.6%) patients had encountered at least one and more than one social adversity in their lifetime.

Future plans

Currently, nutritional notes from licensed dietitians and right and left heart catheterisation reports are under review. We are scheduled to complete the data collection for the comprehensive third follow-up period, which includes follow-up psychosocial evaluations, by the end of 2025. In addition, we intend to conduct annual follow-ups for specific high-risk groups, such as individuals with pulmonary hypertension, those facing higher social adversities and participants with poor HIV control.
Evaluation of childbirth readiness and its associated factors and consequences in pregnant women referring to health centers in Tabriz, Iran and providing strategies to promote childbirth readiness: a sequential explanatory mixed method study protocol
Authors: Alizadeh-Dibazari Zohreh , Abbasalizadeh Fatemeh , Mohammad-Alizadeh-Charandabi Sakineh , Mirghafourvand Mojgan
Published: October 2024

Background

Childbirth readiness encompasses interventions conducted during pregnancy that encourage pregnant women, their families and communities to plan for a healthy pregnancy, childbirth and postpartum period. It enhances women’s childbirth experience and diminishes maternal mortality rates. This study seeks to assess the level of childbirth readiness, relevant factors and outcomes among pregnant women who have completed 37 or more weeks of gestational age and are attending health centres in Tabriz, Iran. The objective is to offer strategies for enhancing childbirth readiness.

Methods and analysis

This sequential explanatory mixed-method study comprises three phases. The initial quantitative phase involves a descriptive-analytical longitudinal study focusing on pregnant women at 37 weeks of gestation or beyond. The quantitative data will be gathered by the sociodemographic and obstetric information questionnaire, the childbirth readiness scale, the pregnancy experience scale, the Wijma delivery expectancy/experience questionnaire (version A) (W-DEQ-Version A), the childbirth experience questionnaire-2, the childbirth outcome checklist, the Edinburgh’s postnatal depression scale (EPDS), the postpartum specific anxiety scale research short-form, the next pregnancy desire questionnaire and the exclusive breastfeeding checklist. In the subsequent qualitative phase, purposive sampling will be employed, and data will be collected through individual, in-depth and semi-structured interviews featuring open-ended questions. Data analysis will be conducted using conventional content analysis techniques. In the final mixed-method phase, strategies to enhance childbirth readiness will be formulated by integrating findings from the quantitative and qualitative studies, a comprehensive literature review, and employing the Delphi method.

Ethics and dissemination

This study has received approval from the Ethics Committee of Tabriz University of Medical Sciences in Tabriz, Iran (code number: IR.TBZMED.REC.1401.557). All participants will provide written informed consent before taking part in the study. The outcomes will be shared through articles published in journals, presentations at medical conferences, the validation of a reliable scale for assessing the level of childbirth readiness in pregnant women and the development of a policy brief outlining supportive strategies to improve childbirth readiness. These resources will be valuable for healthcare providers.
Understanding street-exposure and abuse among street-involved children and youth in Kenya: structural intervention insights from routinely collected program data
Authors: Goodman Michael , Munene Kelvin , Gardner Nora , Gitari Stanley
Published: October 2024

Background

Street-involved children and youth (SICY) face significant challenges, including structural and social exclusion, and multiple forms of abuse. Global estimates indicate there are 10–15 million SICY worldwide, with over 250 000 in Kenya alone. There is limited understanding of the timing of these abuse experiences, which may inform interventional efforts.

Methods

This study analysed relationships between the duration of street exposure, sleep location and experiences of abuse among formerly SICY (aged 6–19 years) in Kenya. Data were collected from participants in the Watoto wa Ahadi Rescue Center programme over a 6-year period (2016–2022). Abuse experiences were categorised into physical, emotional, economic and sexual abuse. Statistical analyses, including Lowess-curve plots and piecewise logit regression, were used to explore the relationships between street exposure duration, sleep location and reported abuse experiences.

Results

The sample consisted of 228 unique children, predominantly male, with a mean age of 13.2 years. Physical abuse (37%), emotional abuse (36%), economic abuse (28%) and any abuse (69%) were common, while sexual abuse (5.7%) was less frequently reported. The probability of experiencing abuse varied with the duration of street exposure, with significant increases observed for those on the street for 3 weeks or more. Sleeping under verandas was associated with higher odds of economic abuse and any type of abuse. Longer street exposure did not further increase the odds of physical, economic or any abuse beyond 10 months.

Conclusions

Children and youth living on the streets experience high levels of abuse, underscoring the need for data-informed, trauma-informed approaches to support their reintegration. The findings highlight the importance of early intervention and tailored strategies that address the specific timing and types of abuse experienced by SICY. Policy and funding should focus on preventing street migration, providing alternative living locations and supporting long-term reintegration efforts to protect and empower SICY.
Achalasia: beyond the basics
Authors: Mari Amir , Khoury Tawfik , Sweis Rami
Published: October 2024

Achalasia is a rare oesophageal disease characterised by an unrelaxing lower oesophageal sphincter and abnormal peristalsis of the oesophageal body. Achalasia symptoms include dysphagia to solid and liquid, chest pain, regurgitation and weight loss. Achalasia diagnosis might be delayed for many years when atypical symptoms dominate. Significant progress has been made over the last two decades regarding our understanding of pathophysiology, methods of evaluation and management. The development of high-resolution manometry in particular has improved the diagnosis of achalasia, as well as other major motility disorders. Subtyping achalasia into manometric patterns has pathophysiological and therapeutic implications. Furthermore, complementary tests such as timed barium swallow and the functional lumen imaging probe (EndoFLIP; Crospon Medical Devices, Galway, Ireland) have significantly added to achalasia diagnosis algorithm and management decision-making. Progression in management has helped optimise established therapy (pneumatic dilatation and Heller myotomy) and introduced new endoscopic treatments (peroral endoscopic myotomy) and surgical techniques (surgical robotic Heller myotomy). This review will aim to shed light on the most recent advances in achalasia diagnosis, classification and management.