bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of progression risk of monoclonal gammopathy of undetermined significance by method of detection
Authors: Visram Alissa , Larson Dirk , Norman Aaron , Dispenzieri Angela , Murray David , Kyle Robert , Rajkumar S. Vincent , Slager Susan , Kumar Shaji , Vachon Celine
Published: October 2024

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant disorder. The current standard of care is not to screen for MGUS, so it is often incidentally diagnosed in the clinic. It is unknown whether the outcomes of screened vs clinically detected MGUS differ. We compared the progression risk between screened vs clinical MGUS cohorts and assessed whether the MGUS detection method affected risk prediction of established clinical factors (score). We included 379 screened MGUS cases from the Olmsted County population-based study and 1384 patients with MGUS diagnosed during routine clinical evaluation at Mayo Clinic. Median follow-up time for the screened vs clinical cohort was 26.6 and 40.1 years, respectively. Accounting for death as a competing risk, the cumulative incidence of progression at 25 years was similar in the screened (11.1% [95% confidence interval [CI], 8.3-14.8]) vs clinical (10.1% [95% CI, 8.6-11.8]) MGUS cohorts, even when stratified by sex, age, or the baseline MGUS risk score. Overall, 0.9 (95% CI, 0.6-1.2) of patients with screened MGUS vs 1.0 (95% CI, 0.9-1.2) of those with clinically detected MGUS experienced disease progression for every 100 person-years of follow-up. MGUS detection method did not modify the association between MGUS risk score and progression risk (pinteraction = 0.217) and did not add to known risk factors for progression (likelihood ratio test; P = .839). Here, we show that progression risk among patients with screened vs clinically detected heavy-chain MGUS was similar. Future studies are needed to assess whether tailored follow-up of patients with screened MGUS affects clinical outcomes.
ASH living guidelines on use of anticoagulation for thromboprophylaxis in patients with COVID-19: executive summary
Authors: Siegal Deborah M , Tseng Eric K. , Schünemann Holger J. , Angchaisuksiri Pantep , Cuker Adam , Dane Kathryn E. , DeSancho Maria T , Diuguid David L , Griffin Daniel O. , Klok Frederikus A , Lee Alfred I , Neumann Ignacio , Pai Ashok , Righini Marc , Sanfilippo Kristen , Terrell Deirdra R , Akl Elie A. , Al Jabiri Reyad Nayif , Al Jabiri Yazan Nayif , Barbara Angela M , Bognanni Antonio , Bou Akl Imad , Boulos Mary , Brignardello-Petersen Romina , Chan Matthew , Charide Rana , Colunga-Lozano Luis E , Dearness Karin Lee , Darzi Andrea J. , Hussein Heba , Karam Samer G. , Kolb Philipp , Mansour Razan , Morgano Gian Paolo , Morsi Rami Z. , Muti Schuenemann Giovanna Elsa Ute , Nadim Menatalla K. , Noori Atefeh , Philip Binu A. , Piggott Thomas , Qiu Yuan , Benitez Yetiani Roldan , Schünemann Finn , Stevens Adrienne , Solo Karla , Wiercioch Wojtek , Mustafa Reem A. , Nieuwlaat Robby
Published: October 2024

COVID-19-related critical and acute illness are associated with an increased risk of venous thromboembolism (VTE). These evidence-based recommendations of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other healthcare professionals in decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19-related critical illness, acute illness, and those being discharged from the hospital, who do not have suspected or confirmed VTE. ASH formed a multidisciplinary panel, including three patient representatives, and applied a conflicts of interest management policy to minimize potential bias. The Michael G. DeGroote Cochrane Canada and MacGRADE Centres at McMaster University supported the guideline development process, including performing systematic evidence reviews (up to June 2023). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess certainty of the evidence and make recommendations, which were subject to public comment. This is an executive summary of three updated recommendations that have been published which concludes the living phase of the guidelines. For critically ill patients with COVID-19, the panel issued conditional recommendations in favor of (a) prophylactic-intensity over therapeutic-intensity anticoagulation and (b) prophylactic-intensity over intermediate-intensity anticoagulation. For acutely ill patients with COVID-19, conditional recommendations were made in favor of (a) prophylactic-intensity over intermediate-intensity anticoagulation and (b) therapeutic-intensity over prophylactic-intensity anticoagulation. The panel also issued a conditional recommendation against the use of post-discharge extended pharmacologic thromboprophylaxis. These three conditional recommendations were made based on low or very low certainty in the evidence, underscoring the need for additional, high-quality randomized controlled trials in patients with COVID-19-related illness.
Deformation Evolution and Perceptual Prediction for Additive Manufacturing of Lightweight Composite Driven by Hybrid Digital Twins
Authors: Xu Jinghua , Wang Linxuan , Gao Mingyu , Jia Chen , Chen Qianyong , Wang Kang , Zhang Shuyou , Tan Jianrong , Fei Shaomei
Published: October 2024

This paper proposes a deformation evolution and perceptual prediction methodology for additive manufacturing of lightweight composite driven by hybrid digital twins (HDT). In order to improve manufacturing quality of irregular lightweight composite through boosting conceptual design in aeronautic and aerospace engineering, the HDT meaning hybridization of physical and digital domains, including deformation and energy efficiency can be built, where the essential parameters can be perceptually predicted in advance, by virtue of the fusion of physical sensors and digital information. The long short term memory (LSTM) can be employed to void vanishing gradient problem and improve predicting precision via Recurrent Neural Networks, thereby laying a foundation for the HDT. The diverse manufacturing requirements of different regions are integrated into the parameters designing phase by attaching region weights confirmed via empiricism and in-service simulation. The effects of slicing strategy and external support structures on manufacturing quality are considered from the perspective of improving dimensional accuracy. The manufacturing efficiency and comprehensive costs are accounted as consideration factors, which are perceptually predicted via LSTM. The designed manufacturing parameters through HDT were virtually examined by evaluating the deformation and equivalent stress distributions of fabricated lightweight component with composite material through AM process simulation. The physical experiments were conducted to verify the HDT-based pre-designing and optimization method of manufacturing parameters via fused deposition modeling (FDM). The energy consumption of actual manufacturing process was measured via digital power meter and applied to evaluate accuracy of perceptual prediction outcomes. The dimensional accuracy and distortion distribution of the manufactured lightweight prototype made with composite material were measured through the coordinate measuring machine (CMM) and 3D optical scanner. The proposed method demonstrates effectiveness in improving manufacturing quality and accurately predicting energy consumption, which have been verified with a three-way solenoid valve element, in which the maximum deformation was reduced by 39.78% and the mean absolute percentage error for perceptual prediction was 3.76%.
Translation regulation by RNA stem-loops can reduce gene expression noise
Authors: Çelik Candan , Bokes Pavol , Singh Abhyudai
Published: October 2024

Background

Stochastic modelling plays a crucial role in comprehending the dynamics of intracellular events in various biochemical systems, including gene-expression models. Cell-to-cell variability arises from the stochasticity or noise in the levels of gene products such as messenger RNA (mRNA) and protein. The sources of noise can stem from different factors, including structural elements. Recent studies have revealed that the mRNA structure can be more intricate than previously assumed.

Results

Here, we focus on the formation of stem-loops and present a reinterpretation of previous data, offering new insights. Our analysis demonstrates that stem-loops that restrict translation have the potential to reduce noise.

Conclusions

In conclusion, we investigate a structured/generalised version of a stochastic gene-expression model, wherein mRNA molecules can be found in one of their finite number of different states and transition between them. By characterising and deriving non-trivial analytical expressions for the steady-state protein distribution, we provide two specific examples which can be readily obtained from the structured/generalised model, showcasing the model’s practical applicability.
Genomic dynamics of high-risk carbapenem-resistant Klebsiella pneumoniae clones carrying hypervirulence determinants in Egyptian clinical settings
Authors: Abdelsalam Nehal Adel , ElBanna Shahira A. , Mouftah Shaimaa F. , Cobo-Díaz José F. , Shata Ahmed H. , Shawky Sherine M. , Atteya Reham , Elhadidy Mohamed
Published: October 2024

Background

Ongoing studies have revealed the global prevalence of severe infections caused by the hypervirulent strains of Klebsiella pneumoniae (K. pneumoniae). Meanwhile, the World Health Organization and the Centers for Disease Control declared carbapenem-resistant K. pneumoniae as an urgent public health threat, requiring swift and effective action to mitigate its spread. Low- and middle-income countries are severely impacted by such devastating infectious diseases owing to the ill implementation of antimicrobial practices and infection control policies. Having both hypervirulence and carbapenemase gene determinants, the emergence of convergent hypervirulent carbapenem-resistant K. pneumoniae is now being reported worldwide.

Methods

In this study, we sequenced 19 carbapenemase-producing K. pneumoniae strains recovered from various clinical specimens. Additionally, we evaluated the phenotypic antimicrobial susceptibility to multiple antimicrobial classes using the VITEK2 automated system. Utilizing the sequencing data, we characterized the sequence types, serotypes, pangenome, resistance profiles, virulence profiles, and mobile genetic elements of the examined isolates. We highlighted the emergence of high-risk clones carrying hypervirulence genetic determinants among the screened isolates.

Results

Our findings revealed that all carbapenem-resistant isolates exhibited either extensive- or pan-drug resistance and harbored multiple variants of resistance genes spanning nearly all the antimicrobial classes. The most prevalent carbapenemase genes detected within the isolates were blaNDM−5 and blaOXA−48. We identified high-risk clones, such as ST383-K30, ST147-K64, ST11-K15, and ST14-K2, which may have evolved into putative convergent strains by acquiring the full set of hypervirulence-associated genetic determinants (iucABCD, rmpA and/ or rmpA2, putative transporter peg-344). Additionally, this study identified ST709-K9 as a high-risk clone for the first time and uncovered that capsule types K15 and K9 carried hypervirulence genetic determinants. The most frequent Inc types found in these isolates were Col440I, IncHI1B, and Inc FII(K).

Conclusion

This study highlights the emergence of high-risk, extensively carbapenem-resistant K. pneumoniae strains co-carrying hypervirulence determinants in Egyptian clinical settings. This poses an imminent threat not only to Egypt but also to the global community, underscoring the urgent need for enhanced surveillance and control strategies to combat this pathogen.
The nexus between maternal antenatal care attendance, newborn postnatal care and neonatal mortality in India: a matched case-control study
Authors: Meitei Wahengbam Bigyananda , Singh Abhishek
Published: October 2024

Introduction

Our study examines the relationship between newborn postnatal care and neonatal mortality stratified by maternal antenatal care attendance under a matched case-control framework.

Methods

Data from the fifth round of the National Family Health Survey was used. A total of 172,079 recent births to eligible women (15–49 years) in five years preceding the survey were included in the study. We used the conditional logistic regression model, a commonly used regression model to fit matched case-control data to examine the effects of newborn postnatal care on neonatal mortality. The mother’s age at birth of the newborn, previous birth intervals, birth order of the newborn, and birthsize of the newborn were included as the matching variables.

Results

Newborns receiving postnatal care within two days or more than two days of birth are less likely to die during the neonatal period. Preferences for newborn postnatal care were also observed to increase with more maternal antenatal care visits. Our study also found a lower risk of neonatal mortality among those newborns whose umbilical cord was examined within two days of birth, regardless of the number of maternal antenatal care visits. Similarly, the risk of newborn deaths was lower among babies whose body temperature was measured within two days of birth. The tendency to breastfeed their newborns within an hour after delivery was considerably higher among those births that occurred to mothers who had a higher number of maternal antenatal care visits. The risk of newborn deaths was also observed to be lower among those born in public or private healthcare facilities.

Conclusion

Considering the cohesive nature of the relationship between neonatal mortality and maternal and child healthcare utilisation, strategic planning and management of the existing policies and programmes related to accessibility, availability, and affordability of maternal and child healthcare services is needed to achieve goal 3.2 of the Sustainable Development Goals. Promoting cost-effective measures such as continuous monitoring of the baby’s body temperature and umbilical cord care could also effectively help reduce neonatal mortality.
Social inequalities in child mental health trajectories: a longitudinal study using birth cohort data 12 countries
Authors: Cadman Tim , Avraam Demetris , Carson Jennie , Elhakeem Ahmed , Grote Veit , Guerlich Kathrin , Guxens Mònica , Howe Laura D. , Huang Rae-Chi , Harris Jennifer R. , Houweling Tanja A. J. , Hyde Eleanor , Jaddoe Vincent , Jansen Pauline W. , Julvez Jordi , Koletzko Berthold , Lin Ashleigh , Margetaki Katerina , Melchior Maria , Nader Johanna Thorbjornsrud , Pedersen Marie , Pizzi Costanza , Roumeliotaki Theano , Swertz Morris , Tafflet Muriel , Taylor-Robinson David , Wootton Robyn E. , Strandberg-Larsen Katrine
Published: October 2024

Background

Social inequalities in child mental health are an important public health concern. Whilst previous studies have examined inequalities at a single time point, very few have used repeated measures outcome data to describe how these inequalities emerge. Our aims were to describe social inequalities in child internalising and externalising problems across multiple countries and to explore how these inequalities change as children age.

Methods

We used longitudinal data from eight birth cohorts containing participants from twelve countries (Australia, Belgium, Denmark, France, Germany, Greece, Italy, Netherlands, Poland, Norway, Spain and the United Kingdom). The number of included children in each cohort ranged from N = 584 (Greece) to N = 73,042 (Norway), with a total sample of N = 149,604. Child socio‐economic circumstances (SEC) were measured using self‐reported maternal education at birth. Child mental health outcomes were internalising and externalising problems measured using either the Strengths and Difficulties Questionnaire or the Child Behavior Checklist. The number of data collection waves in each cohort ranged from two to seven, with the mean child age ranging from two to eighteen years old. We modelled the slope index of inequality (SII) using sex‐stratified multi‐level models.

Results

For almost all cohorts, at the earliest age of measurement children born into more deprived SECs had higher internalising and externalising scores than children born to less deprived SECs. For example, in Norway at age 2 years, boys born to mothers of lower education had an estimated 0.3 (95% CI 0.3, 0.4) standard deviation higher levels of internalising problems (SII) compared to children born to mothers with high education. The exceptions were for boys in Australia (age 2) and both sexes in Greece (age 6), where we observed minimal social inequalities. In UK, Denmark and Netherlands inequalities decreased as children aged, however for other countries (France, Norway, Australia and Crete) inequalities were heterogeneous depending on child sex and outcome. For all countries except France inequalities remained at the oldest point of measurement.

Conclusions

Social inequalities in internalising and externalising problems were evident across a range of EU countries, with inequalities emerging early and generally persisting throughout childhood.
High-cost users still came to hospitals during the COVID-19 pandemic during first wave data in Thailand: secondary data analysis
Authors: Karunayawong Picharee , Gaewkhiew Piyada , Sarajan Myka Harun , Boonma Chulathip , Butchon Rukmanee , Sukmanee Jarawee , Saeraneesopon Thanayut , Teerawattananon Yot , Isaranuwatchai Wanrudee
Published: October 2024

Background

The phenomenon of high-cost users (HCUs) in health care occurs when a small proportion of patients account for a large proportion of health care expenditures. By understanding this phenomenon during the COVID-19 pandemic, tailored interventions can be provided to ensure that patients receive the care they need and reduce the burden on the health system.

Objectives

This study aimed to determine (1) whether the HCUs phenomenon occurred during the pandemic in Thailand by exploring the pattern of inpatient health expenditures over time from 2016 to 2021; (2) the patient characteristics of HCUs; (3) the top 5 primary diagnoses of HCUs; and (4) the potential predictors associated with being an HCU.

Methods

The secondary data analysis was conducted via inpatient department (IPD) e-Claim data from the National Health Security Office for the Universal Coverage Scheme, which provides health care to ~ 80% of the Thai population. Health care expenditure over time was calculated, and the characteristics of the population were examined via descriptive analysis. Multinomial logistic regression was applied to explore the potential predictors associated with being an HCU.

Results

The characteristics of HCUs remained relatively the same from 2016 to 2021. In terms of the proportion of male (55%) to female patients (45%), the age ranged from 55 to 57 years, with an estimated 8-day length of hospital stay and 7 admissions per year, and the average health care cost per patient was ≥ USD 2,860 (100,000 THB). The low-cost users (LCUs) group (the bottom 50% of the population), had more female patients (55%), a younger age ranging from 27 to 33 years, a 3-day length of stay, 1‒2 admissions per year, and a lower average health care cost per patient, which was less than USD 315 (≤ 11,000 THB).

Conclusion

The HCUs phenomenon still existed even with limited health care accessibility or lockdown measures implemented during the COVID-19 pandemic. This finding could indicate the uniqueness of the need for health services by HCUs, which differ from those of other population groups. By understanding the trends of health care utilization and expenditure, along with potential predictors associated with being an HCU, policies can be introduced to ensure the appropriate allocation of health resources to the right people in need of the right care during future pandemics.
Machine learning predictive models and risk factors for lymph node metastasis in non-small cell lung cancer
Authors: Wu Bo , Zhu Yihui , Hu Zhuozheng , Wu Jiajun , Zhou Weijun , Si Maoyan , Cao Xiying , Wu Zhicheng , Zhang Wenxiong
Published: October 2024

Background

The prognosis of non-small cell lung cancer (NSCLC) is substantially affected by lymph node metastasis (LNM), but there are no noninvasive, inexpensive methods of relatively high accuracy available to predict LNM in NSCLC patients.

Methods

Clinical data on NSCLC patients were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Risk factors for LNM were recognized LASSO and multivariate logistic regression. Six predictive models were constructed with machine learning based on risk factors. The area under the receiver operating characteristic curve (AUC) was used to assess the performance of the model. Subgroup analysis with different T-stages was performed on an optimal model. A webpage LNM risk calculator for optimal model was built using the Shinyapps.io platform.

Results

We enrolled 64,012 NSCLC patients, of whom 26,611 (41.57%) had LNM. Using multivariate logistic regression, we finally identified 10 independent risk factors for LNM: age, sex, race, histology, primary site, grade, T stage, M stage, tumor size, and bone metastases. GLM is the optimal model among all six machine learning models in both the training and validation cohorts. Subgroup analyses revealed that GLM has good predictability for populations with different T staging. A webpage LNM risk calculator based on GLM was posted on the shinyapps.io platform (https://wubopredict.shinyapps.io/dynnomapp/).

Conclusion

The predictive model based on GLM can be used to precisely predict the probability of LNM in NSCLC patients, which was proven effective in all subgroup analyses according to T staging.
The relationship between cyberchondria and health literacy among first-year nursing students: the mediating effect of health anxiety
Authors: Ali Samira Saad , Hendawi Nourhan Essam , El-Ashry Ayman Mohamed , Mohammed Manal Saeed
Published: October 2024

Background

First-year nursing students are at a critical juncture in their education. They are transitioning from laypersons to healthcare professionals, and students are frequently exposed to medical information in academic settings and through personal research. This exposure can sometimes lead to cyberchondria; improving health literacy and managing health anxiety are critical strategies for reducing the incidence of cyberchondria.

Aim

Investigate the mediating effect of health anxiety on cyberchondria and health literacy among first-year nursing students.

Methods

A cross-sectional correlational research design was used in this study. The study was conducted with 475 students in October 2023 during the first semester of the academic year 2023–2024.

Results

Cyberchondria and health literacy levels were both moderate. In addition, the degree of health anxiety among first-year Nursing Students was mild, too. The results showed that the association between Cyberchondria and Health Literacy was partially mediated by health anxiety.

Conclusion and implications

This study highlights the sophisticated relationship between cyberchondria, health literacy, and anxiety among first-year nursing students. It demonstrates that lower health literacy can lead to increased health anxiety, which in turn exacerbates cyberchondria. To mitigate these issues, it is essential to enhance health literacy and provide support for managing health anxiety within nursing education programs. By doing so, we can help nursing students navigate online health information effectively and reduce unnecessary health-related anxieties, promoting better educational outcomes and overall well-being.
Employer support for health and social care registered professionals, their patients and service users involved in regulatory fitness to practise regulatory proceedings
Authors: Wallace Louise M , Greenfield Mari
Published: October 2024

Background

Health and social care employees may be involved in professional regulatory proceedings because their alleged behaviour raises health or conduct concerns. Employees, patients or service users may also be involved in a regulatory tribunal as witnesses. This study is about the role of employers in supporting them in this process.

Methods

Taking an organisational support perspective, we interviewed 25 senior employees in health and social care organisations in the UK who are responsible for managing the employer’s role in the proceedings. Template analysis was used to analyse the transcripts.

Results

Support for patients was limited to that offered during an employer’s complaints process, and only one employer gave some support during the regulatory process if the patient or service user initiated regulatory proceedings. Support for employees in tribunals was little different to that offered during an initial investigation by the employer. However, where additional support for being involved in a regulatory tribunal was offered to employees, it most often came from the senior employees’ own experience of the stressfulness of being a witness in these proceedings. Employers were not aware of training resources that would better support their employees to engage with professional regulatory proceedings.

Conclusions

Employers offer limited support to employees who are involved in professional regulatory proceedings, and the support offered may depend more on senior employee’s individual experience of involvement in regulatory proceedings to exercise this discretion. Patients, service users and other public witnesses receive almost no support from health and social care employers during professional regulatory proceedings.
Comprehensive neurosurgical and visceral surgical therapy of retroperitoneal nerve tumors: a descriptive and retrospective analysis
Authors: Petkov Martin , Kornmann Marko , Bäzner Ute Marlies , Minzenmay Lena , Pala Andrej , Pedro Maria Teresa , Wirtz Christian Rainer , Antoniadis Gregor
Published: October 2024

Nerve tumors in the retroperitoneal space are a rarity. Radical surgery according to soft tissue tumors can lead to persistent pain and neurological deficits. This study aims to evaluate clinical outcomes of patients treated by a visceral- / neurosurgical approach. 33 patients with a retroperitoneal nerve tumor underwent surgery between 01/2002 and 12/2022 at our department. A visceral surgeon provided access to the retroperitoneal space, followed by micro-neurosurgical tumor preparation under neuromonitoring. Clinical examination and MRI were performed 12 weeks after surgery and further 3 months (WHO grade > 1) or 12 months (WHO grade 1). Further examinations were based on MRI findings and residual symptoms with median follow-up time of 24 months. One patient was treated for two distinct masses resulting in a total of 34 histological findings. Schwannomas (n = 15; 44.1%) and neurofibromas (n = 10; 29.4%) were the most common tumors. Long-term improvements were noted in radicular pain (15/18 patients; 83.3%), motor deficits (7/16 patients; 43.8%), abdominal discomfort and pain (5/7 patients; 71.4%). Recurrences were observed in 3/33 (9,1%) patients. This study represents the largest series of retroperitoneal BPNSTs treated with microsurgical techniques. Prospective multicenter studies are warranted to establish standardized treatment guidelines.
The effectiveness and acceptability of physical activity interventions amongst older adults with lower socioeconomic status: a mixed methods systematic review
Authors: Harris Danielle , Dlima Schenelle Dayna , Gluchowski Ashley , Hall Alex , Elliott Emma , Munford Luke
Published: October 2024

Background

Older adults with lower socioeconomic status are less likely to be physically active than those with higher socioeconomic status. To inform future intervention development, this review explored: [i] how effective are physical activity interventions at increasing levels of physical activity amongst older adults with lower socioeconomic status?; [ii] what factors are associated with the acceptability of physical activity interventions amongst older adults with lower socioeconomic status?; [iii] what are the implications for developing physical activity interventions for older adults with lower socioeconomic status?

Methods

This mixed methods systematic review followed PRISMA guidelines. MEDLINE, CENTRAL, Embase, Scopus, Web of Science, PsycINFO, CINAHL, ASSIA and Sports Medicine and Education Index were searched up to May 2023, to identify quantitative, qualitative and mixed methods primary research studies measuring the effectiveness of and/or experiences of physical activity interventions for older adults (aged ≥ 65 years) with lower socioeconomic status. No limits on country were applied. Included studies were assessed for methodological quality using the Mixed Methods Appraisal Tool. Results were synthesised using a results-based convergent synthesis approach with narrative synthesis of quantitative findings and thematic synthesis of qualitative findings.

Results

Thirty studies were included. Mixed effects were found for the effectiveness of physical activity interventions, with positive effects for increases in utilitarian walking (i.e. for transport) but not for leisure, mixed effects for objectively measured physical activity and no effects for self-reported total physical activity or muscle strengthening and flexibility activities. Engaging in physical activity interventions was perceived as offering many benefits, social familiarity was important to intervention acceptability and interventions were seen as more acceptable when they were compatible with the lifestyles of older adults with lower socioeconomic status.

Conclusions

Future development of physical activity interventions for older adults with lower socioeconomic status should foster social connections, emphasise health benefits of physical activity, hold interventions in locations that are accessible and familiar to older adults with lower socioeconomic status, minimise costs to participants, employ individuals who share participant characteristics to lead interventions, and combine physical activity with other activities older adults with lower socioeconomic status already do to make more efficient use of time.

Trial registration

PROSPERO CRD42023417312; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=417312.
Combining ERAP1 silencing and entinostat therapy to overcome resistance to cancer immunotherapy in neuroblastoma
Authors: Tempora Patrizia , D’Amico Silvia , Gragera Paula , Damiani Verena , Krol Kamila , Scaldaferri Valentina , Pandey Kirti , Chung Shanzou , Lucarini Valeria , Giorda Ezio , Scarsella Marco , Volpe Gabriele , Pezzullo Marco , De Stefanis Cristiano , D’Oria Valentina , De Angelis Lorenzo , Giovannoni Roberto , De Ioris Maria Antonietta , Melaiu Ombretta , Purcell Anthony W. , Locatelli Franco , Fruci Doriana
Published: October 2024

Background

Checkpoint immunotherapy unleashes tumor control by T cells, but it is undermined in non-immunogenic tumors, e.g. with low MHC class I expression and low neoantigen burden, such as neuroblastoma (NB). Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an enzyme that trims peptides before loading on MHC class I molecules. Inhibition of ERAP1 results in the generation of new antigens able of inducing potent anti-tumor immune responses. Here, we identify a novel non-toxic combinatorial strategy based on genetic inhibition of ERAP1 and administration of the HDAC inhibitor (HDACi) entinostat that increase the immunogenicity of NB, making it responsive to PD-1 therapy.

Methods

CRISPR/Cas9-mediated gene editing was used to knockout (KO) the ERAP1 gene in 9464D NB cells derived from spontaneous tumors of TH-MYCN transgenic mice. The expression of MHC class I and PD-L1 was evaluated by flow cytometry (FC). The immunopeptidome of these cells was studied by mass spectrometry. Cocultures of splenocytes derived from 9464D bearing mice and tumor cells allowed the assessment of the effect of ERAP1 inhibition on the secretion of inflammatory cytokines and activation and migration of immune cells towards ERAP1 KO cells by FC. Tumor cell killing was evaluated by Caspase 3/7 assay and flow cytometry analysis. The effect of ERAP1 inhibition on the immune content of tumors was analyzed by FC, immunohistochemistry and multiple immunofluorescence.

Results

We found that inhibition of ERAP1 makes 9464D cells more susceptible to immune cell-mediated killing by increasing both the recall and activation of CD4+ and CD8+ T cells and NK cells. Treatment with entinostat induces the expression of MHC class I and PD-L1 molecules in 9464D both in vitro and in vivo. This results in pronounced changes in the immunopeptidome induced by ERAP1 inhibition, but also restrains the growth of ERAP1 KO tumors in vivo by remodelling the tumor-infiltrating T-cell compartment. Interestingly, the absence of ERAP1 in combination with entinostat and PD-1 blockade overcomes resistance to PD-1 immunotherapy and increases host survival.

Conclusions

These findings demonstrate that ERAP1 inhibition combined with HDACi entinostat treatment and PD-1 blockade remodels the immune landscape of a non-immunogenic tumor such as NB, making it responsive to checkpoint immunotherapy.
Uptake of health economic evaluations alongside clinical trials in Australia: an observational study
Authors: Carrandi Alayna , Wells Cynthia , Morton Rachael L. , Norman Richard , Skouteris Helen , Grove Amy , Higgins Alisa M.
Published: October 2024

Background

Australia’s clinical trials sector is highly productive with continued sector investment needed to enhance research impact. Generating economic evidence alongside trials has the potential to facilitate the implementation of trial results into practice. Ascertaining the use of health economic evaluations alongside clinical trials can assist in determining whether clinical trials fully realize and operationalize their potential to change policy and practice. The aims of this study were to ascertain the uptake of health economic evaluations alongside Australian-led clinical trials and explore associations between uptake and trial characteristics.

Methods

This observational study comprised a descriptive analysis of clinical trials registries, a cross-sectional survey of Australian Clinical Trials Alliance (ACTA) networks, and a subgroup analysis of completed acute care trials. Descriptive analyses of trial registrations were conducted, with logistic regressions used to identify predictors of proposing and subsequently publishing a health economic evaluation alongside acute care trials.

Results

Few randomized Australian-led clinical trials (11% of 9251) and ACTA network trials (43% of 227) proposed a health economic evaluation. In the subgroup analysis, 22% of the 324 acute care trials and 53% of the 38 ACTA network acute care trials proposed a health economic evaluation. Acute care trials funded by government bodies were significantly more likely to propose and publish a health economic evaluation than those funded by hospitals, universities, and other funders, after adjusting for phase, registration year, primary sponsor type, and comparator.

Conclusions

Current uptake of health economic evaluations alongside Australian-led clinical trials is low, with uptake higher among the subset of ACTA network trials. This is despite economic evidence playing an increasingly prominent role in health system management, as well as rising health expenditure, limited budgets, and competing demands. There is significant opportunity to embed health economic evaluations alongside clinical trials, particularly phase 3 trials, to increase research outputs and optimize research translation. Investing in clinical trial networks that support funding for a health economist or a health economic evaluation may be an effective strategy to increase the uptake of health economic evaluations alongside trials.
Strengthening lung cancer screening in Europe: fostering participation, improving outcomes, and addressing health inequalities through collaborative initiatives in the SOLACE consortium
Authors: Kauczor Hans-Ulrich , von Stackelberg Oyunbileg , Nischwitz Emily , Chorostowska-Wynimko Joanna , Hierath Monika , Mathonier Coline , Prosch Helmut , Zolda Pamela , Revel Marie-Pierre , Horváth Ildikó , Vašáková Martina Koziar , Powell Pippa , Samarzija Miroslav , Blum Torsten Gerriet ,   and SOLACE Consortium
Published: October 2024

The Strengthening the Screening of Lung Cancer in Europe (SOLACE) initiative, supported by Europe’s Beating Cancer Plan, is dedicated to advancing lung cancer screening. This initiative brings together the most extensive pan-European network of respiratory and radiology experts, involving 37 partners from 15 countries. SOLACE aims to enhance equitable access to lung cancer screening by developing targeted recruitment strategies for underrepresented and high-risk populations. Through comprehensive work packages, SOLACE integrates scientific research, pilot studies, and sustainability efforts to bolster regional and national screening efforts across EU member states.

Critical relevance statement

The SOLACE project aims to facilitate the optimization and implementation of equitable lung cancer screening programs across the heterogeneous healthcare landscape in EU member states.

Key Points

The effectiveness of lung cancer screening is supported by both scientific evidence and now increasing legislative support.

SOLACE aims to develop, test, and disseminate tools to facilitate the realization of lung cancer screening at both a national and regional level.

Previously underrepresented populations in lung cancer screening will be targeted by tailored recruitment strategies.

SOLACE forms the first pan-European network of experts poised to drive real-world implementation of lung cancer screening.
Reproducibility of ultrasound-derived fat fraction in measuring hepatic steatosis
Authors: Song Danlei , Wang Pingping , Han Jiahao , Chen Huihui , Gao Ruixia , Li Ling , Li Jia
Published: October 2024

Purpose

Steatotic liver disease (SLD) has become the most common cause of chronic liver disease. Nevertheless, the non-invasive quantitative diagnosis of steatosis is still lacking in clinical practice. This study aimed to evaluate the reproducibility of the new parameter for steatosis quantification named ultrasound-derived fat fraction (UDFF).

Materials and methods

The UDFF values were independently executed by two operators in two periods. In the process, repeated measurements of the same patient were performed by the same operator under different conditions (liver segments, respiration, positions, and dietary). Finally, the results of some subjects (28) were compared with the MRI-derived proton density fat fraction (PDFF). The concordance analysis was mainly achieved by the intraclass correlation coefficient (ICC) and Bland–Altman.

Results

One hundred-five participants were included in the study. UDFF had good reliability in measuring the adult liver (ICCintra-observer = 0.96, ICCinter-observer = 0.94). Meanwhile, the ICC of the two operators increased over time. The variable measurement states did not influence the UDFF values on the surface, but they affected the coefficient of variation (Cov) of the results. Segment 8 (S8), end-expiratory, supine, and fasting images had the most minor variability. On the other hand, the UDFF value of S8 displayed satisfied consistency with PDFF (mean difference, −0.24 ± 1.44), and the results of both S5 (mean difference: −0.56 ± 3.95) and S8 (mean difference: 0.73 ± 1.87) agreed well with the whole-liver PDFF.

Conclusion

UDFF measurements had good reproducibility. Furthermore, the state of S8, end-expiration, supine, and fasting might be the more stable measurement approach.

Critical relevance statement

UDFF is the quantitative ultrasound parameter of hepatic steatosis and has good reproducibility. It can show more robust performance under specific measurement conditions (S8, end-expiratory, supine, and fasting).

Trial registration

The research protocol was registered at the Chinese Clinical Trial Registry on October 9, 2023 (http://www.chictr.org.cn/). The registration number is ChiCTR 2300076457.

Key Points

There is a lack of non-invasive quantitative measurement options for hepatic steatosis.

UDFF demonstrated excellent reproducibility in measuring hepatic steatosis.

S8, end-expiratory, supine, and fasting may be the more stable measuring condition.

Training could improve the operators’ measurement stability.

Variable measurement state affects the repeatability of the UDFF values (Cov).

Graphical Abstract
Optimizing CD8+ T cell-based immunotherapy via metabolic interventions: a comprehensive review of intrinsic and extrinsic modulators
Authors: Zhou Zihao , Zheng Jiarong , Lu Ye , Mai Zizhao , Lin Yunfan , Lin Pei , Zheng Yucheng , Chen Xu , Xu Rongwei , Zhao Xinyuan , Cui Li
Published: October 2024

CD8+ T cells are integral to the effective management of cancer and infectious diseases due to their cytotoxic functions. The efficacy of these cells is profoundly influenced by their metabolic state, which regulates their activation, differentiation, and longevity. Accordingly, the modulation of metabolic pathways within CD8+ T cells is crucial for enhancing the effectiveness of T cell-based immunotherapy. Precise metabolic control is paramount in optimizing therapeutic outcomes and minimizing potential toxicities associated with treatment. Importantly, the potential of exogenous metabolites to augment CD8+ T cell responses is critically evaluated, especially through in vivo evidence that underscores their therapeutic promise. This review also addresses current challenges, including the need for precise control of metabolic modulation to avoid adverse effects, the development of targeted delivery systems to ensure efficient metabolite delivery to CD8+ T cells, and the inherent variability of metabolic states among patients that may influence treatment outcomes. Addressing these hurdles will be crucial for the successful integration of metabolic interventions into established immunotherapeutic regimens.
Oviduct epithelial spheroids during in vitro culture of bovine embryos mitigate oxidative stress, improve blastocyst quality and change the embryonic transcriptome
Authors: Pranomphon Thanya , López-Valiñas Álvaro , Almiñana Carmen , Mahé Coline , Brair Viviane Lopes , Parnpai Rangsun , Mermillod Pascal , Bauersachs Stefan , Saint-Dizier Marie
Published: October 2024

Background

In vitro embryo production is increasingly used for genetic improvement in cattle but bypasses the oviduct environment and exposes the embryos to oxidative stress with deleterious effects on further development. Here we aimed to examine the effect of oviduct epithelial spheroids (OES) on embryo development and quality in terms of morphology and gene expression during two co-culture times (4 days: up to embryonic genome activation at 8–16 cell stage vs. 7 days: up to blastocyst stage) and under two oxygen levels (5% vs. 20%).

Methods

Bovine presumptive zygotes produced by in vitro fertilization (day 0) using in-vitro matured oocytes were cultured in droplets of synthetic oviductal fluid (SOF) medium with or without (controls) OES for 4 or 7 days under 5% or 20% oxygen (4 treated and 2 control groups). Cleavage rates were evaluated on day 2 and blastocyst rates on days 7–8. Expanded blastocysts on days 7–8 were evaluated for total cell numbers and gene expression analysis by RNA-sequencing.

Results

Under 20% oxygen, blastocyst rates and total cell numbers were significantly higher in the presence of OES for 4 and 7 days compared to controls (P < 0.05), with no difference according to the co-culture time. Under 5% oxygen, the presence of OES did not affect blastocyst rates but increased the number of cells per blastocyst after 7 days of co-culture (P < 0.05). Both oxygen level and OES co-culture had a significant impact on the embryonic transcriptome. The highest number of differentially expressed genes (DEGs) was identified after 7 days of co-culture under 20% oxygen. DEGs were involved in a wide range of functions, including lipid metabolism, membrane organization, response to external signals, early embryo development, and transport of small molecules among the most significantly impacted.

Conclusion

OES had beneficial effects on embryo development and quality under both 5% and 20% oxygen, mitigating oxidative stress. Stronger effects on embryo quality and transcriptome were obtained after 7 than 4 days of co-culture. This study shows the impact of OES on embryo development and reveals potential molecular targets of OES-embryo dialog involved in response to stress and early embryonic development.
Assessment of gestational diabetes mellitus knowledge, attitudes, and practices and associated factors among pregnant women at a district hospital in Coastal Kenya
Authors: Siuluta Nanyangwe , Sato Miho , Linh Le Khac , Wanjihia Violet , Changoma Mwatasa Salim , Huy Nguyen Tien , Kaneko Satoshi
Published: October 2024

Background

Gestational diabetes mellitus (GDM) is any degree of glucose intolerance first recognized during pregnancy. GDM awareness among pregnant women translates into GDM prevention and early diagnosis.

Objective

To establish the underlying factors influencing GDM Knowledge Attitude and Practices (KAP) among pregnant women at Kinango District Hospital.

Method

An explanatory mixed-methods design was implemented by initially assessing GDM KAP quantitatively [QUAN], followed by the qualitative [qual] exploration of contextual factors behind quantitative results. In the [QUAN] strand, 354 pregnant women were interviewed from January to February 2019. Thereafter, in the [qual] strand, key informant interviews were conducted among four pregnant women and three healthcare workers; a focus group discussion was held among nine pregnant women, from May to June 2019. STATA V15 software package was used to analyze the quantitative data. Qualitative data were analyzed manually using thematic analysis.

Result

Among 354 pregnant women, 29.0% were knowledgeable, 46.98% had good attitude and 60.17% had good practice. Attending at least one antenatal clinic visit and having heard about diabetes mellitus were associated with good GDM attitude and practices. Among the knowledgeable pregnant women, one-third (33.33%) obtained GDM information from a health facility. Discussions with pregnant women and the interviews with healthcare workers highlighted that daily health talks during antenatal clinic, included GDM and diabetes mellitus information. Furthermore, attendance of at least one antenatal clinic visit was low (85.88%), among pregnant women (87.86%) who were expected to have attended at least one antenatal clinic visits.

Conclusion

Despite low GDM knowledge, pregnant women had relatively good GDM attitudes and good GDM practices. Daily health talks conducted during antenatal clinic as well as indigenous knowledge among pregnant women, influenced the latter. Hence, GDM information dissemination needs to be enhanced for the improvement of GDM KAP among pregnant women for GDM prevention.