bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteasome inhibition as a therapeutic target for the fungal pathogen
Cryptococcus neoformans
Authors: Caza Mélissa , Santos Daniel Assis , Burden Elizabeth , Brisland Anna , Hu Guanggan , Kronstad James W.
Published: September 2023

The current therapeutic challenges for treating fungal diseases demand new approaches and new drugs. A promising strategy involves combination therapy with agents of distinct mechanisms of action to increase fungicidal activity and limit the impact of mutations leading to resistance. In this study, we evaluated the antifungal potential of bortezomib by examining the inhibition of proteasome activity, cell proliferation, and capsule production by
Cryptococcus neoformans
, the causative agent of fungal meningoencephalitis. Chemical genetic screens with collections of deletion mutants identified potential druggable targets for combination therapy with bortezomib. In vitro assays of combinations of bortezomib with flucytosine, chlorpromazine, bafilomycin A1, copper sulfate, or hydroxyurea revealed antifungal effects against
C. neoformans
. Furthermore, combination treatment with bortezomib and flucytosine in a murine inhalation model of cryptococcosis resulted in the improvement of neurological functions and reduced fungal replication and dissemination, leading to a delay in disease progression. This study therefore highlights the utility of chemical genetic screens to identify new therapeutic approaches as well as the antifungal potential of proteasome inhibition.

IMPORTANCE

Fungal diseases of humans are difficult to treat, and there is a clear need for additional antifungal drugs, better diagnostics, effective vaccines, and new approaches to deal with emerging drug resistance. Fungi are challenging to control because they share many common biochemical functions with their mammalian hosts and it is therefore difficult to identify fungal-specific targets for drug development. One approach is to employ existing antifungal drugs in combination with agents that target common cellular processes at levels that are (ideally) not toxic for the host. We pursued this approach in this study by examining the potential of the clinically approved proteasome inhibitor bortezomib to influence the proliferation and virulence of
Cryptococcus neoformans
. We found that the combination of bortezomib with the anti-cryptococcal drug flucytosine improved the survival of infected mice, thus demonstrating the potential of this strategy for antifungal therapy.
Exploring the genetic background of the botulism neurotoxin BoNT/B2 in Spain
Authors: Valdezate Sylvia , Carrasco Gema , Medina María J. , Garrido Noelia , del Pino Silvia , Valiente Monica , Pallarés María P. , Villalon Pilar
Published: September 2023

To determine whether the neurotoxin BoNT/B2 causing botulism in Spain is clonal, the genetic diversity and phylogenetic relationships of
Clostridium botulinum
from food-borne episodes and infant cases of the condition were explored. The botulinum toxin gene (
bont
) subtype, the variable region of the flagellin gene (
fla
VR), and a seven-gene multi-locus sequence type were examined by sequencing 37 BoNT-positive cultures obtained over the period 2010 to 2022. Out of 37 botulism events, 16 food-borne episodes and 16 infant cases were associated with
bont/b
2. Eight
bont/b
2 alleles were detected [nucleotide distance range 0.0259–0.415%, Hunter and Gaston discrimination index (HGDI) 0.71]. The most common
bont/b
2 allele corresponded to that of strain Prevot 25 NCASE and its single and double locus variations (87.5%). Four known
fla
VR types were identified (HGDI 0.79), along with one previously unknown (
fla
VR-15). Sixteen sequence types (STs) (HGDI 0.89) were recorded including seven new STs (ST164–ST170; 10 new alleles) and five new STs (ST171–ST175; with new allele combinations) were also noted. Correlations among some STs and
fla
VR types were seen. Overall, the present results show that the combined analysis of
bont/b
2-
fla
VR-ST at the nucleotide level could be used to track botulism events in Spain. The neurotoxin BoNT/B2 has largely been responsible for human botulism in Spain. The polymorphism analysis of
bont/b2
,
fla
VR typing, and sequence type determinations, revealed a wide variety of clones to be responsible for human botulism, ruling out a common source of acquisition.

IMPORTANCE

Botulism, a potentially fatal disease, is classically characterized by a symmetrical descending flaccid paralysis, which if left untreated can lead to respiratory failure and death. Botulinum neurotoxin (BoNT), produced by certain species of Clostridium, is the most potent biological toxin known, and the direct cause of botulism. This study characterizes the acquisition in Spain of two forms of botulism, i.e., food-borne and infant botulism, which are largely caused by the main neurotoxin BoNT/B2. Polymorphism analysis of the bont/b2 gene, typing of the flagellin variable region sequence (flaVR), and multilocus sequence typing, were used to explore the genetic background of
Clostridium botulinum
group I. To our knowledge, this is the first phylogenetic and typing study of botulism undertaken in Spain.
Yearly variation coupled with social interactions shape the skin microbiome in free-ranging rhesus macaques
Authors: Roche Christina E. , Montague Michael J. , Wang JiCi , Dickey Allison N. , Ruiz-Lambides Angelina , Brent Lauren J. N. , Platt Michael L. , Horvath Julie E.
Published: September 2023

While skin microbes are known to mediate human health and disease, there has been minimal research on the interactions between skin microbiota, social behavior, and year-to-year effects in non-human primates—important animal models for translational biomedical research. To examine these relationships, we analyzed skin microbes from 78 rhesus macaques living on Cayo Santiago Island, Puerto Rico. We considered age, sex, and social group membership, and characterized social behavior by assessing dominance rank and patterns of grooming as compared to nonsocial behaviors. To measure the effects of a shifting environment, we sampled skin microbiota (based on sequence analysis of the 16S rRNA V4 region) and assessed weather across sampling periods between 2013 and 2015. We hypothesized that, first, monkeys with similar social behavior and/or in the same social group would possess similar skin microbial composition due, in part, to physical contact, and, second, microbial diversity would differ across sampling periods. We found significant phylum-level differences between social groups in the core microbiome as well as an association between total grooming rates and alpha diversity in the complete microbiome, but no association between microbial diversity and measures of rank or other nonsocial behaviors. We also identified alpha and beta diversity differences in microbiota and differential taxa abundance across two sampling periods. Our findings indicate that social dynamics interact with yearly environmental changes to shape the skin microbiota in rhesus macaques, with potential implications for understanding the factors affecting the microbiome in humans, which share many biological and social characteristics with these animals.

IMPORTANCE

Primate studies are valuable for translational and evolutionary insights into the human microbiome. The majority of primate microbiome studies focus on the gut, so less is known about the factors impacting the microbes on skin and how their links affect health and behavior. Here, we probe the impact of social interactions and the yearly environmental changes on food-provisioned, free-ranging monkeys living on a small island. We expected animals that lived together and groomed each other would have more similar microbes on their skin, but surprisingly found that the external environment was a stronger influence on skin microbiome composition. These findings have implications for our understanding of the human skin microbiome, including potential manipulations to improve health and treat disease.
Structural biology and functional features of phage-derived depolymerase Depo32 on
Klebsiella pneumoniae
with K2 serotype capsular polysaccharides
Authors: Cai Ruopeng , Ren Zhuolu , Zhao Rihong , Lu Yan , Wang Xinwu , Guo Zhimin , Song Jinming , Xiang Wentao , Du Rui , Zhang Xiaokang , Han Wenyu , Ru Heng , Gu Jingmin
Published: September 2023

Hypervirulent
Klebsiella pneumoniae
with capsular polysaccharides (CPSs) causes severe nosocomial- and community-acquired infections. Phage-derived depolymerases can degrade CPSs from
K. pneumoniae
to attenuate bacterial virulence, but their antimicrobial mechanisms and clinical potential are not well understood. In the present study,
Klebsiella
phage GH-K3-derived depolymerase Depo32 (encoded by gene
gp32
) was identified to exhibit high efficiency in specifically degrading the CPSs of K2 serotype
K. pneumoniae
. The cryo-electron microscopy structure of trimeric Depo32 at a resolution up to 2.32 Å revealed potential catalytic centers in the cleft of each of the two adjacent subunits.
K. pneumoniae
subjected to Depo32 became more sensitive to phagocytosis by RAW264.7 cells and activated the cells by the mitogen-activated protein kinase signaling pathway. In addition, intranasal inoculation with Depo32 (a single dose of 200 µg, 20 µg daily for 3 days, or in combination with gentamicin) rescued all C57BL/6J mice infected with a lethal dose of
K. pneumoniae
K7 without interference from its neutralizing antibody. In summary, this work elaborates on the mechanism by which Depo32 targets the degradation of K2 serotype CPSs and its potential as an antivirulence agent.

IMPORTANCE

Depolymerases specific to more than 20 serotypes of
Klebsiella
spp. have been identified, but most studies only evaluated the single-dose treatment of depolymerases with relatively simple clinical evaluation indices and did not reveal the anti-infection mechanism of these depolymerases in depth. On the basis of determining the biological characteristics, the structure of Depo32 was analyzed by cryo-electron microscopy, and the potential active center was further identified. In addition, the effects of Depo32 on macrophage phagocytosis, signaling pathway activation, and serum killing were revealed, and the efficacy of the depolymerase (single treatment, multiple treatments, or in combination with gentamicin) against acute pneumonia caused by
Klebsiella pneumoniae
was evaluated. Moreover, the roles of the active sites of Depo32 were also elucidated in the
in vitro
and
in vivo
studies. Therefore, through structural biology, cell biology, and
in vivo
experiments, this study demonstrated the mechanism by which Depo32 targets K2 serotype
K
.
pneumoniae
infection.
Unique Structural Features of NbS3 Ribbon Whiskers
Authors: Martovitskii V. P. , Klokov A. Yu. , Pokrovskii V. Ya.
Published: September 2023

The X-ray diffraction analysis of NbS3 ribbon whiskers has revealed three structural features: (i) a fine-crystalline structure throughout the entire volume with the preferred orientation along the [001] direction perpendicular to the long b axis of the whisker, (ii) the combination of crystalline macroblocks with a length up to 0.5 mm with small crystallites of various orientations, and (iii) the combination of crystalline macroblocks with the left-hand twisting of planes around the b axis with a pitch angle of 1.25° per every 0.2 mm and with the return to the initial orientation in the next block. Structural features (ii) and (iii) of NbS3 whiskers have not yet been observed, and inorganic crystals with such properties are absent to the best of our knowledge. All crystallites have a unit cell with almost right angles and approximately the same lattice constant c (18.130 Å), whereas the lattice constants a and b are noticeably different in a single sample. All crystallites can be referred to phase IV rather than to phase I, as expected. The right angle between the a and c axes can be explained by the twinning of phase I along the c axis. Differences in the lattice constants in macroblocks indicate large stresses in structures. Such stresses near twins (and/or stacking faults) can significantly affect the free electron density and play a key role in the formation of charge density waves in various phases of NbS3.
Diffusive Modes of Two-Band Fermions Under Number-Conserving Dissipative Dynamics
Authors: Lyublinskaya A. A. , Burmistrov I. S.
Published: September 2023

Driven-dissipative protocols are proposed to control and create nontrivial quantum many-body correlated states. Protocols conserving the number of particles stand apart. As well-known, in quantum systems with the unitary dynamics the particle number conservation and random scattering yield diffusive behavior of two-particle excitations (diffusons and cooperons). Existence of diffusive modes in the particle-number-conserving dissipative dynamics is not well studied yet. We explicitly demonstrate the existence of diffusons in a paradigmatic model of a two-band system, with dissipative dynamics aiming to empty one fermion band and to populate the other one. The studied model is generalization of the model introduced in F. Tonielli, J.C. Budich, A. Altland, and S. Diehl, Phys. Rev. Lett. 124, 240404 (2020). We find how the diffusion coefficient depends on details of a model and the rate of dissipation. We discuss how the existence of diffusive modes complicates engineering of macroscopic many-body correlated states.
Potential benefits of prenatal diagnosis of TGA in Australia may be outweighed by the adverse effects of earlier delivery: likely causation and potential solutions
Authors: Namachivayam Siva P , Butt Warwick , Brizard Christian , Millar Johnny , Thompson Jenny , Walker Susan P , Cheung Michael M H
Published: September 2023

Objective

Prenatal diagnosis of transposition of great arteries (TGA) is expected to improve postoperative outcomes after neonatal arterial switch operation (ASO); however, published reports give conflicting results. We aimed to determine the association between prenatal diagnosis and early postoperative outcomes after neonatal ASO.

Methods

Cohort study involving 243 newborns who underwent ASO (70% prenatally diagnosed) between 2010 and 2019. Multivariable regression was used to determine the association between prenatal diagnosis and (a) birth characteristics and (b) postoperative outcomes.

Results

Gestational age and birthweight centile were lower and small-for-gestational-age more common (11.8% vs 1.4%) in those diagnosed prenatally. Among births which followed labour induction or prelabour caesarean, prenatal diagnosis was associated with earlier gestation at birth (mean (SD), 38.5 (1.6) vs 39.2 (1.4), p=0.01). Among births which followed spontaneous labour, prenatal diagnosis was associated with earlier gestation at labour onset (38.2 (1.8) vs 39.2 (1.4), p=0.01). Prenatal diagnosis was associated with longer postoperative mechanical ventilation (incidence rate ratio 1.74, 95% CI 1.37 to 2.21), intensive care (1.70, 1.31 to 2.21) and hospital length of stay (1.37, 1.14 to 1.66) after ASO. Gestational age mediated up to 60% of the effect of prenatal diagnosis on postoperative outcomes.

Conclusion

Among newborns undergoing ASO for TGA, prenatal diagnosis is associated with poorer early postoperative outcomes. In addition to minimising iatrogenic factors (such as planned births) resulting in earlier births, evaluation of other dynamics following a prenatal diagnosis which may result in poor fetal growth and earlier onset of spontaneous labour is important.
Localised intestinal Kaposi sarcoma in a patient with non-coeliac seronegative villous atrophy
Authors: Norton Benjamin , Pelkonen Otso , Watkins Jennifer , Mann Steven
Published: September 2023

Seronegative villous atrophy (SNVA) is a diagnostic challenge for gastroenterologists, which is defined by villous atrophy and negative coeliac serology. Non-coeliac forms of SNVA, such as autoimmune enteropathy, can be life-threatening leading to intractable diarrhoea and severe malabsorption that require systemic immunosuppression. When all known causes have been excluded, it is termed idiopathic villous atrophy (IVA). We present a case of non-coeliac SNVA complicated by Kaposi sarcoma (KS). A previously well HIV-negative man in his 30s presented with a 4-month history of watery diarrhoea and 25 kg weight loss. After prolonged investigation, he was diagnosed with non-coeliac SNVA without an identified aetiology that would be consistent with IVA. Clinical recovery was achieved with parenteral nutrition for type II intestinal failure and immunosuppression using high-dose corticosteroids. On subsequent gastroscopy, he was diagnosed with localised intestinal KS prompting cessation of all immunosuppression but remained in clinical remission.
Clinical effects of tranexamic acid on bleeding tendency due to fibrinolytic activation of AL amyloidosis
Authors: Matsumoto Gaku , Mori Hideki , Mori Takahiro , Sakaki Chika
Published: September 2023

We report a case where tranexamic acid, which is an antifibrinolytic agent, was used to effectively treat bleeding tendency in a patient with immunoglobulin light chain (AL) amyloidosis. A male patient in his 80s without a history of bleeding disorders was admitted to our hospital for the examination of bleeding tendency and was diagnosed with a bleeding disorder due to AL amyloidosis. Blood tests revealed elevated plasmin-α2-plasmin inhibitor complex levels, suggesting fibrinolytic activation. Managing the bleeding was difficult; however, we suspected fibrinolytic activation associated with AL amyloidosis and initiated treatment with oral tranexamic acid, which markedly improved the bleeding disorder and abnormalities of the fibrinolytic system. Therefore, in cases of bleeding due to fibrinolytic activation of AL amyloidosis, tranexamic acid administration can be an effective treatment.
Incidental DCIS within a fibroadenoma
Authors: Chen Arnold , Kanakaratne Shaveen , Britten-Jones Philip , Bingham Janne
Published: September 2023

A female in her early 20s was referred to the breast-endocrine surgeons with a self-detected tender left breast lump on the background of a family history of breast cancer. A physical examination revealed a rubbery and mobile mass in the left upper breast. Ultrasound demonstrated a solid hypoechoic mass with a likely differential diagnosis of fibroadenoma, with a subsequent core needle biopsy (CNB) confirming a fibroadenoma. Given the size and tenderness of the lump, an excisional biopsy was performed. Histology revealed a fibroadenoma with components of low-grade ductal carcinoma in situ, contained within the fibroadenoma and excised with clear margins.

Following surgical excision, a multidisciplinary review determined that no further local therapy was required and recommended a genetics referral. This case was interesting as it raised important questions, including what the best surveillance strategies are for female patients with breast cancer within fibroadenoma and determining the risk and probability of missing epithelial atypia via CNB.
Recurrent episodes of febrile dyspnoea: hypersensitivity pneumonitis caused by a household ultrasonic humidifier
Authors: Kurian George Karun , Simonin Valentin , Colombé Jessica , Duplain Hervé
Published: September 2023

Hypersensitivity pneumonitis is an immune-mediated interstitial lung disease that presents with respiratory symptoms, with or without systemic symptoms, following exposure to an identified or unidentified external factor. It can be caused by extrinsic factors including household items such as ultrasonic humidifiers.

We present an intriguing case of a previously healthy 50-year-old man who displayed recurrent episodes of progressive dyspnoea and fever after repeated exposure to his household ultrasonic humidifier. He was treated with corticosteroids, followed by the removal of the humidifier, resulting in total recovery and absence of recurrence of further episodes.

The clinical presentation of hypersensitivity pneumonitis can be dramatic, and the differential diagnosis is broad. The correct diagnosis is achieved by combining clinical, radiological and histopathological patterns. The key to finding the aetiology lies in a thorough history, with an important role for household investigations to identify the external factor.
Small bowel obstruction: a rare presentation of systemic mastocytosis
Authors: Babu Basil , Subbiah Nagaraj Satish , Gopalam Vivek , Vaiphei Kim
Published: September 2023

Mastocytosis (MC) is a heterogeneous group of disorders characterised by abnormal growth, neoplastic proliferation and accumulation of mast cells. Approximately, 80% of patients with MC have evidence of skin involvement, while the rest may involve the gastrointestinal tract, liver, spleen or bone. Isolated gastrointestinal presentation of aggressive MC without bone marrow involvement and cutaneous symptoms is rare. Isolated MC with tumour cells infiltrating the ileum presenting with mechanical obstruction has not been reported in the literature to date. Here, we present a case of a patient in his late 50s who presented with malignant MC of the small bowel with obstruction in the emergency surgical outpatient department. The patient underwent surgical resection of the affected bowel. Histopathological examination along with immunohistochemistry revealed malignant MC. The further evaluation consisted of bone marrow biopsies, PET CT and other mutation analyses. However, the patient succumbed to death during the further course of treatment. The differential of MC must be kept in mind when there is the presence of abnormal hematopoietic cells in gastrointestinal biopsies even in the absence of cutaneous manifestations and bone marrow abnormalities.
Haemolytic uraemic syndrome managed with subtotal colectomy
Authors: Adachi Toshiyuki , Inoue Yusuke , Okada Satomi , Eguchi Susumu
Published: September 2023

A man in his early 70s was transferred to our hospital due to rapid decline in renal function and inflammation throughout the colon, indicating severe ischaemic enteritis. On the day following the start of intensive care, a stool specimen tested positive for verotoxin, and haemolytic uraemic syndrome (HUS) was diagnosed. On the same day, his vital signs deteriorated suddenly, and emergency surgery was performed due to the possibility of intestinal necrosis and perforation. Severe inflammation extending to the serosal surface of the whole colon was observed, but there was no obvious intestinal necrosis or perforation. Advanced mucosal necrosis of the entire colon suggested sepsis due to bacterial translocation, and subtotal colectomy was performed to remove the infection source. Postoperative management was successful. This case demonstrates the importance of considering HUS in patients with severe renal dysfunction and bloody stools, as well as the significance of colectomy in such patients.
New insights on the role of microRNAs in retinal Müller glial cell function
Authors: Jiang Weijie , He Siqi , Liu Logen , Meng Xia , Lu Jing , Li Juan , Chen Tuo , Xu Ying , Xiao Qiguo , Qi Ling , Zhang Jia
Published: September 2023

MicroRNAs belong to the family of non-coding RNAs that participate in cell proliferation, cell death and development. The Müller glial cells are the inherent and specific neuroglia cells in the retinal organisation and play significant roles in retinal neuroprotection, organisational maintenance, inflammation and immunity, regeneration, and the occurrence and development of retinal diseases. However, only a few studies report the underlying mechanism of how miRNAs drive the function of Müller glial cells in the development of retinal diseases. This review aims to summarise the roles of miRNAs in retinal Müller glial cell function, including gliogenesis, inflammation and immunity, regeneration, the development of retinal diseases, and retinal development. This review may point out a novel miRNA-based insight into retinal repair and regeneration. MiRNAs in Müller glial cells may be considered a diagnostic and therapeutic target in the process of retinal repair and regeneration.
Motivational simulated teaching of clinical skills using formative assessment methods for medical undergraduate students: between-group evaluation of a simulated course in a Chinese medical college
Authors: Yang Wen , Ruan Manzhen , Gong Jie , Peng Miao , Wang Zhen , Xia Wenfang , Liu Xianzhe , Yang Guangyao
Published: September 2023

Objectives

Teaching clinical skills is an important component of educational programmes for medical undergraduates. However, the extension of the interval between the completion of the course and qualification examination affects the performance of students in the skill examination. This study established a multisource evaluation system to determine whether formative assessment can enhance the instruction of clinical skills.

Methods

Formative assessment was introduced to the entire training course on clinical skills, in which diversified methods were used to observe the performance of students during training. Students in the experimental group received training for clinical skills using formative assessment (class of 2019, n=128), while students in the control group received traditional training without formative assessment (class of 2018, n=123). Both groups participated in the Objective Structured Clinical Examination (OSCE) conducted by Tongji Medical College, and the exam scores were taken as the objective measure of course outcome. After completing the course, all students in the experimental group were instructed to fill in a questionnaire to evaluate their experience in the training programme, as a subjective measure of course outcome.

Results

Compared with the control group, students in the experimental group received significantly better practical scores in the four clinical skills tested by the OSCE. The questionnaire results revealed that the majority of students who were trained using formative assessment methods considered the course helpful for learning, and appreciated the course for the clinical skills they had gained, and the opportunity to receive and give feedback to the instructors.

Conclusions

The findings of this study suggest that formative assessment methods are beneficial for learning clinical skills through simulated teaching, as shown by the improved objective clinical skills evaluated by the structured clinical examination, and the self-reported satisfaction with the learning process.
Scoping review of modelling studies assessing the impact of disruptions to essential health services during COVID-19
Authors: Veettil Sajesh K , Schwerer Luke , Kategeaw Warittakorn , Toth Damon , Samore Matthew H , Hutubessy Raymond , Chaiyakunapruk Nathorn
Published: September 2023

Background

Studies assessing the indirect impact of COVID-19 using mathematical models have increased in recent years. This scoping review aims to identify modelling studies assessing the potential impact of disruptions to essential health services caused by COVID-19 and to summarise the characteristics of disruption and the models used to assess the disruptions.

Methods

Eligible studies were included if they used any models to assess the impact of COVID-19 disruptions on any health services. Articles published from January 2020 to December 2022 were identified from PubMed, Embase and CINAHL, using detailed searches with key concepts including COVID-19, modelling and healthcare disruptions. Two reviewers independently extracted the data in four domains. A descriptive analysis of the included studies was performed under the format of a narrative report.

Results

This scoping review has identified a total of 52 modelling studies that employed several models (n=116) to assess the potential impact of disruptions to essential health services. The majority of the models were simulation models (n=86; 74.1%). Studies covered a wide range of health conditions from infectious diseases to non-communicable diseases. COVID-19 has been reported to disrupt supply of health services, demand for health services and social change affecting factors that influence health. The most common outcomes reported in the studies were clinical outcomes such as mortality and morbidity. Twenty-five studies modelled various mitigation strategies; maintaining critical services by ensuring resources and access to services are found to be a priority for reducing the overall impact.

Conclusion

A number of models were used to assess the potential impact of disruptions to essential health services on various outcomes. There is a need for collaboration among stakeholders to enhance the usefulness of any modelling. Future studies should consider disparity issues for more comprehensive findings that could ultimately facilitate policy decision-making to maximise benefits to all.
Integrating equity, diversity and inclusion throughout the lifecycle of AI within healthcare: a scoping review protocol
Authors: Nyariro Milka , Emami Elham , Caidor Pascale , Abbasgholizadeh Rahimi Samira
Published: September 2023

Introduction

Artificial intelligence (AI) has the potential to improve efficiency and quality of care in healthcare settings. The lack of consideration for equity, diversity and inclusion (EDI) in the lifecycle of AI within healthcare settings may intensify social and health inequities, potentially causing harm to under-represented populations. This article describes the protocol for a scoping review of the literature relating to integration of EDI in the AI interventions within healthcare setting. The objective of the review is to evaluate what has been done on integrating EDI concepts, principles and practices in the lifecycles of AI interventions within healthcare settings. It also aims to explore which EDI concepts, principles and practices have been integrated into the design, development and implementation of AI in healthcare settings.

Method and analysis

The scoping review will be guided by the six-step methodological framework developed by Arksey and O’Malley supplemented by Levac et al, and Joanna Briggs Institute methodological framework for scoping reviews. Relevant literature will be identified by searching seven electronic databases in engineering/computer science and healthcare, and searching the reference lists and citations of studies that meet the inclusion criteria. Studies on AI in any healthcare and geographical settings, that have considered aspects of EDI, published in English and French between 2005 and present will be considered. Two reviewers will independently screen titles, abstracts and full-text articles according to inclusion criteria. We will conduct a thematic analysis and use a narrative description to describe the work. Any disagreements will be resolved through discussion with the third reviewer. Extracted data will be summarised and analysed to address aims of the scoping review. Reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews. The study began in April 2022 and is expected to end in September 2023. The database initial searches resulted in 5,745 records when piloted in April 2022.

Ethics and dissemination

Ethical approval is not required. The study will map the available literature on EDI concepts, principles and practices in AI interventions within healthcare settings, highlight the significance of this context, and offer insights into the best practices for incorporating EDI into AI-based solutions in healthcare settings. The results will be disseminated through open-access peer-reviewed publications, conference presentations, social media and 2-day workshops with relevant stakeholders.
Perioperative sleep disorders in gynaecological daycase surgery patients and analysis of risk factors: protocol for a cross-sectional study
Authors: Zhang Wensi , Gao Teng , Liu Fanglin , Zhang Haijing , Wang Shaoheng
Published: September 2023

Introduction

Sleep disorders are clinical syndromes of disturbed sleep-wake rhythms and abnormal sleep quality. They have various causes, but their main manifestations are difficulty falling asleep, sleep disruption and daytime fatigue. These are common clinical symptoms in perioperative patients, especially in gynaecological patients. There is a lack of research on the factors influencing perioperative sleep disorders in gynaecological patients. The aim of this study is to assess the prevalence of sleep disorders in gynaecological surgery patients and to analyse the possible factors influencing them to provide new ideas for improving sleep disorders in this patient population.

Methods and analysis

This cross-sectional, descriptive and observational survey is planned to include 480 gynaecological day surgery patients. All patients who meet the inclusion criteria are eligible to join the study. The study will record preoperative diagnosis, surgical procedure, duration of surgery, type of anaesthesia, anaesthetic drugs, sleep quality, anxiety and depression levels and pain indices 30 days before and 1, 2, 3 and 30 days after surgery.

Ethics and dissemination

The study was approved by the Ethics Committee of Beijing Shijitan Hospital Affiliated with Capital Medical University (Approval Number: sjtkyll-lx-2022(109)) before the start of recruitment. The results of the study will be disseminated through peer-reviewed publications and conference presentations.

Trial registration number

ChiCTR2200064533.
Integration of the social determinants of health into quality indicators for colorectal cancer surgery: a scoping review protocol
Authors: Bondzi-Simpson Adom , Ribeiro Tiago , Benipal Harsukh , Barabash Victoria , Lofters Aisha , Sutradhar Rinku , Snyder Rebecca A , Clarke Callisia , Coburn Natalie G , Hallet Julie
Published: September 2023

Introduction

Quality monitoring is a critical component of high-performing cancer care systems. Quality indicators (QIs) are standardised, evidence-based measures of healthcare quality that allow healthcare systems to track performance, identify gaps in healthcare delivery and inform areas of priority for strategic planning. Social structures and economic systems that allow for unequal access to power and resources that shape health and health inequities can be described through the social determinants of health (SDoH) framework. Therefore, granular analysis of healthcare quality through SDoH frameworks is required to identify patient subgroups who may experience health inequity. Given the high burden of disease of colorectal cancer (CRC) and well-defined cancer care pathways, CRC is often the first disease site targeted by health systems for quality improvement. The objective of this review is to examine how SDoH have been integrated into QIs for CRC surgery. This review aims to address three primary questions: (1) Have SDoH been integrated into the development, reporting and assessment of CRC surgery QIs? (2) When integrated, what measures and statistical methods have been applied? (3) In which direction do individual SDoH influence QIs outputs?

Methods

This review will follow Arksey and O’Malley frameworks for scoping reviews. We will search MEDLINE, EMBASE, HealthSTAR databases for papers that examine QIs for CRC surgery applicable to healthcare systems from database inception until January 2023. Interventional trials, prospective and retrospective observational studies, reviews, case series and qualitative study designs will be included. Two authors will independently review all titles, abstracts and full texts to determine which studies meet the inclusion criteria.

Ethics & dissemination

No ethics approval is required for this review. Results will be disseminated through scientific presentation and relevant conferences targeted for researchers examining healthcare quality and equity in cancer care.

Registration details

osf.io/vfzd3-Open Science Framework.
Does a Community Care programme reach a high health need population and high users of acute care hospital services in Melbourne, Australia? An observational cohort study
Authors: Shannon Brendan , Bowles Kelly-Ann , Williams Cylie , Ravipati Tanya , Deighton Elise , Andrew Nadine
Published: September 2023

Objective

The Community Care programme is an initiative aimed at reducing hospitalisations and emergency department (ED) presentations among patients with complex needs. We aimed to describe the characteristics of the programme participants and identify factors associated with enrolment into the programme.

Design

This observational cohort study was conducted using routinely collected data from the National Centre for Healthy Ageing data platform.

Setting

The study was carried out at Peninsula Health, a health service provider serving a population in Melbourne, Victoria, Australia.

Participants

We included all adults with unplanned ED presentation or hospital admission to Peninsula Health between 1 November 2016 and 31 October 2017, the programme’s first operational year.

Outcome measures

Community Care programme enrolment was the primary outcome. Participants’ demographics, health factors and enrolment influences were analysed using a staged multivariable logistic regression.

Results

We included 47 148 adults, of these, 914 were enrolled in the Community Care programme. Participants were older (median 66 vs 51 years), less likely to have a partner (34% vs 57%) and had more frequent hospitalisations and ED visits. In the multivariable analysis, factors most strongly associated with enrolment included not having a partner (adjusted OR (aOR) 1.83, 95% CI 1.57 to 2.12), increasing age (aOR 1.01, 95% CI 1.01 to 1.02), frequent hospitalisations (aOR 7.32, 95% CI 5.78 to 9.24), frequent ED visits (aOR 2.0, 95% CI 1.37 to 2.85) and having chronic diseases, such as chronic pulmonary disease (aOR 2.48, 95% CI 2.06 to 2.98), obesity (aOR 2.06, 95% CI 1.39 to 2.99) and diabetes mellitus (complicated) (aOR 1.75, 95% CI 1.44 to 2.13). Residing in aged care home and having high socioeconomic status) independently associated with reduced odds of enrolment.

Conclusions

The Community Care programme targets patients with high-readmission risks under-representation of individuals residing in residential aged care homes warrants further investigation. This study aids service planning and offers valuable feedback to clinicians about programme beneficiaries
Reducing hospital admissions in patients with malignant pleural effusion: a quality improvement study
Authors: Cloyes Rebecca R , Josan Enambir , Pastis Nicholas , Ma Jianing , Palettas Marilly , Peng Jing , Vasko-Wood Susan , Mohrman Chelsea , Ghattas Christian , Presley Carolyn , Revelo Alberto , Pannu Jasleen
Published: September 2023

Background

Malignant pleural effusions (MPE) can cause severe dyspnoea leading to greater than 125 000 hospitalisations per year and cost greater than US$5 billion per year in the USA. Timely insertion of tunnelled pleural catheters (TPCs) is associated with fewer inpatient days and emergency department visits. We conducted a quality improvement study to reduce hospital admissions of patients with MPE.

Methods

Key stakeholders were surveyed, including thoracic and breast oncology teams, general pulmonary and interventional pulmonology (IP) to help identify the underlying causes and solutions. Our preintervention group consisted of 51 patients who underwent TPC placement by our IP service. In our first intervention, we reviewed referrals for MPE with the scheduling team and triaged them based on urgency. In the second intervention, we added a follow-up phone call 1 week after the initial thoracentesis performed by IP to assess for the recurrence of symptoms.

Results

Demographic and clinical characteristics were summarised across the three groups. We evaluated the rate ratio (RR) of admissions in the intervention groups with the multivariable Poisson regression and adjusted for race, gender and cancer. Compared with the preintervention group, intervention I showed trends towards a 41% lower hospital admission rate (RR 0.59 (0.33–1.07), p=0.11). Compared with the preintervention group, intervention II showed trends towards a 40% lower hospital admission rate (RR 0.6 (0.36–0.99), p=0.07). The results did not reach statistical significance. Exploratory comparisons in readmission rates between interventions I and II showed no difference (RR 0.89 (0.43–1.79), p=0.75).

Conclusions

Both interventions showed trends toward fewer hospital readmissions although they were not statistically significant. Larger-size prospective studies would be needed to demonstrate the continued effectiveness of these interventions.
Population mortality impacts of the rising cost of living in Scotland: scenario modelling study
Authors: Richardson Elizabeth , McCartney Gerry , Taulbut Martin , Douglas Margaret , Craig Neil
Published: September 2023

Introduction

To inform policymaking, it is important to understand the population health impacts of recent increased inflation, and of measures implemented to mitigate these.

Methods

We used scenario modelling to estimate (a) how recent increased inflation would affect household incomes in Scotland, (b) how mitigation measures would modify these effects and (c) how mortality outcomes and inequalities in these would change as a result. Against a long-term average inflation scenario (baseline), we compared unmitigated recent inflation and inflation mitigated by UK Government support policies. We estimated differential price inflation by income quintile, based on the proportion of household spending on different goods and services. Using differential inflation rates, we estimated change in spending power (real income) for 2704 Scottish households in the 2015/16 Family Resources Survey, both with and without mitigating UK Government policies, and scaled these to the Scottish population. We estimated mortality effects using a cross-sectional relationship between household income and mortality, by deprivation quintile.

Results

Unmitigated price inflation was 14.9% for the highest income quintile and 22.9% for the lowest. UK Government policies partially mitigated impacts of the rising cost of living on real incomes, although households in the most deprived areas of Scotland would still be £1400 per year worse off than at baseline. As a result, even with mitigating measures in place, premature mortality was estimated to increase by up to 6.4%, and life expectancy to decrease by up to 0.9%. Effects would be greater in more deprived areas, and health inequalities would increase as a result.

Conclusions

Large and inequitable impacts on mortality in Scotland are predicted if real-terms income reductions are sustained. Progressive Cost of Living Support payments are not sufficient to offset the mortality impacts of the greater real income reductions in deprived areas.
Precancerous nature of intestinal metaplasia with increased chance of conversion and accelerated DNA methylation
Authors: Takeuchi Chihiro , Yamashita Satoshi , Liu Yu-Yu , Takeshima Hideyuki , Sasaki Akiko , Fukuda Masahide , Hashimoto Taiki , Naka Tomoaki , Ishizu Kenichi , Sekine Shigeki , Yoshikawa Takaki , Hamada Akinobu , Yamamichi Nobutake , Fujishiro Mitsuhiro , Ushijima Toshikazu
Published: September 2023

Objective

The presence of intestinal metaplasia (IM) is a risk factor for gastric cancer. However, it is still controversial whether IM itself is precancerous or paracancerous. Here, we aimed to explore the precancerous nature of IM by analysing epigenetic alterations.

Design

Genome-wide DNA methylation analysis was conducted by EPIC BeadArray using IM crypts isolated by Alcian blue staining. Chromatin immunoprecipitation sequencing for H3K27ac and single-cell assay for transposase-accessible chromatin by sequencing were conducted using IM mucosa.NOS2was induced using Tet-on gene expression system in normal cells.

Results

IM crypts had a methylation profile unique from non-IM crypts, showing extensive DNA hypermethylation in promoter CpG islands, including those of tumour-suppressor genes. Also, the IM-specific methylation profile, namely epigenetic footprint, was present in a fraction of gastric cancers with a higher frequency than expected, and suggested to be associated with good overall survival. IM organoids had remarkably highNOS2expression, andNOS2induction in normal cells led to accelerated induction of aberrant DNA methylation, namely epigenetic instability, by increasing DNA methyltransferase activity. IM mucosa showed dynamic enhancer reprogramming, including the regions involved in higherNOS2expression.NOS2had open chromatin in IM cells but not in gastric cells, and IM cells had frequent closed chromatin of tumour-suppressor genes, indicating their methylation-silencing.NOS2expression in IM-derived organoids was upregulated by interleukin-17A, a cytokine secreted by extracellular bacterial infection.

Conclusions

IM cells were considered to have a precancerous nature potentially with an increased chance of converting into cancer cells, and an accelerated DNA methylation induction due to abnormalNOS2expression.
Early palliative care versus usual haematological care in multiple myeloma: retrospective cohort study
Authors: Giusti Davide , Colaci Elisabetta , Pioli Valeria , Banchelli Federico , Maccaferri Monica , Leonardi Giovanna , Marasca Roberto , Morselli Monica , Forghieri Fabio , Bettelli Francesca , Cuoghi Angela , Bresciani Paola , Messerotti Andrea , Gilioli Andrea , Candoni Anna , Cassanelli Luca , Sbadili Elena , Bassoli Ilaria , Longo Giuseppe , Gilioli Fabio , Borelli Eleonora , Bigi Sarah , D'Amico Roberto , Porro Carlo Adolfo , Odejide Oreofe , Zimmermann Camilla , Efficace Fabio , Bruera Eduardo , Luppi Mario , Bandieri Elena , Potenza Leonardo
Published: September 2023

Objectives

Although early palliative care (EPC) is beneficial in acute myeloid leukaemia, little is known about EPC value in multiple myeloma (MM). We compared quality indicators for palliative and end-of-life (EOL) care in patients with MM receiving EPC with those of patients who received usual haematological care (UHC).

Methods

This observational, retrospective study was based on 290 consecutive patients with MM. The following indicators were abstracted: providing psychological support, assessing/managing pain, discussing goals of care, promoting advance care plan, accessing home care services; no anti-MM treatment within 14 and 30 days and hospice length of stay >7 days before death; no cardiopulmonary resuscitation, no intubation, <2 hospitalisations and emergency department visits within 30 days before death. Comparisons were performed using unadjusted and confounder-adjusted regression models.

Results

55 patients received EPC and 231 UHC. Compared with UHC patients, EPC patients had a significantly higher number of quality indicators of care (mean 2.62±1.25 vs 1.12±0.95; p<0.0001)); a significant reduction of pain intensity over time (p<0.01) and a trend towards reduced aggressiveness at EOL, with the same survival (5.3 vs 5.46 years; p=0.74)).

Conclusions

Our data support the value of integrating EPC into MM routine practice and lay the groundwork for future prospective comparative studies.
Tides across thin-shells: differences between spacetimes with one and two asymptotic regions
Authors: Rubín de Celis E. , Simeone C.
Published: September 2023

Traversability across thin shells is investigated, with special attention devoted to the difference in tides related with different global properties of the geometries. While we have recently associated curvature jumps across infinitely thin shells to troublesome tides and consequent very restrictive conditions for a safe travel across a throat satisfying the flare-out condition in spacetimes with two asymptotic regions, now we find that analogous problems can be significantly reduced or even cancelled across shells joining an inner with an outer submanifold of spacetimes with one asymptotic region. We also show that, within this framework, cylindrical shells present an advantage over spherical shells.