bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychometric validation of the continuum beliefs of mental illness scale (CB-MIS) and its associations with stigma
Authors: Peter Lina-Jolien , McLaren Thomas , Tomczyk Samuel , Muehlan Holger , Schmidt Silke , Schomerus Georg
Published: February 2025

Background

Continuum beliefs of mental health and illness are robustly negatively correlated with mental illness stigma. However, there is a lack of multidimensional and validated measures, not entirely relying on vignettes.

Methods

To develop such a scale, a pool of 37 items adapted from other studies on continuum beliefs, was initially examined in expert discussions and a convenience sample (N = 227, M
age=32 years, 80.6% female). Items were selected based on theoretical tenability and assigned to pre-defined facets of “State”, “Person”, and nosological “Concept” in relation to mental illness. In a second sample (N = 1375; M
age=42 years; 65.2% female), the Continuum Beliefs of Mental Illness Scale (CB-MIS) was psychometrically tested (i.e. factorial, convergent, discriminant validity).

Results

The scale comprises three subscales with three items, and one optional vignette-based item each, rated on a 5-point Likert scale. It showed very good factorial and discriminant validity, associations with stigma were moderately negative. The scale exhibited good test-retest reliability over a period of six months.

Conclusions

A validated, practical, multifaceted measure is offered to evaluate beliefs regarding the continuum of mental health and illness. Future studies should conduct subgroup-specific investigations regarding sociodemographic and illness variables, and could apply this measure to anti-stigma interventions.

Trial registration

German Clinical Trials Register: DRKS00023557. Registered 11/12/2020. World Health Organization, Universal Trial Number: U1111–1264–9954. Registered 16/02/2021.
Sleep duration in adolescence buffers the impact of childhood trauma on anxiety and depressive symptoms
Authors: Coote Toni , Barrett Emma , Grummitt Lucinda
Published: February 2025

Background

Childhood trauma is a pervasive issue contributing to adverse mental health outcomes. Obtaining optimal sleep supports healthy development and protects against mood-related disorders. Whether sleep serves as a potential buffer between trauma and adverse mental health outcomes holds promise for informing targeted interventions and prevention for adolescents.

Methods

Data were drawn from the baseline assessment of a randomised controlled trial of a mental health prevention program. A total sample of 752 adolescents completed an online, self-report survey in 2023. Participants were students (Mage=13.8 years), attending independent schools in Australia and comprised of 37% girls and 60% boys. Australian sleep guidelines were used to dichotomise nightly sleep duration into whether adolescents met, or did not meet, the sleep guidelines for their age. Mixed-effects linear regression was used to examine whether sleep moderated the association between trauma and symptoms of anxiety, depression, and mental wellbeing.

Results

The majority of participants (82%) reported exposure to at least one traumatic event. The mean number of traumatic events was 1.8. Trauma was independently associated with higher depressive and anxiety symptoms and lower mental wellbeing scores. Those reporting exposure to one or more traumatic events were more likely to report difficulties falling asleep and less likely to report meeting nightly sleep duration guidelines. We found a significant interaction between meeting nightly sleep duration guidelines and any trauma exposure on depressive and anxiety scores, such that depression and anxiety symptoms were lower in trauma-exposed adolescents who met sleep duration guidelines compared to those who did not meet sleep guidelines.

Conclusions

Obtaining optimal amounts of sleep each night may help mitigate anxiety and depressive symptoms for non-clinical adolescents exposed to trauma, however, longitudinal research is needed to confirm the directionality of the relationships between trauma, sleep, and mental health symptoms. Future research should examine the effectiveness of public health interventions targeting sleep behaviours in adolescents to promote mental wellbeing.
Exploring the potential cost-effectiveness and societal burden implications of screening for fracture risk in a UK general radiography setting
Authors: Söreskog E. , Lopez B. , Bean T. , Lewis P. , Ashley N. , Da Palma Lopes J. , Meertens R. , Ratcliffe A.
Published: February 2025

Background

Fragility fractures lead to considerable societal costs and individual suffering. Despite the availability of cost-effective treatments for high-risk patients, a significant treatment gap exists, with many high-risk individuals remaining unidentified and untreated. The aim of this study was to explore the potential cost-effectiveness and societal impact of opportunistic screening for fracture risk with IBEX Bone Health (BH), a software solution that provides bone mineral density from wrist radiographs, in a UK general radiography setting.

Methods

The study used a health economic model that compared the health outcomes and costs of screening with IBEX BH versus usual care for men and women aged 50 and older who had a forearm radiograph for any reason. The model incorporated data on fracture incidence, fracture risk reduction, mortality, quality of life, and fracture and treatment costs from published sources and Royal Cornwall Hospitals NHS Trust. Costs and health outcomes in terms of quality-adjusted life years (QALYs) were simulated over the remaining lifetime of patients. The analysis took the perspective of the National Health Service (NHS) and Personal Social Services in the UK.

Results

The results showed that screening with IBEX BH was associated with a gain of 0.013 QALYs and a cost saving of £109 per patient compared with usual care, making it a dominant (cost-saving) strategy. Sensitivity analyses confirmed the robustness of the results under various assumptions. Widespread adoption of IBEX BH in the NHS was estimated to save 8,066 QALYs and £65,930,555 in healthcare costs over the lifetime of patients visiting hospitals for wrist radiographs each year.

Conclusions

IBEX BH could be a cost-effective tool for early identification and prevention of fragility fractures in the UK, addressing the current challenges of low provision and access to fracture risk assessment and treatment.
From awareness to action: investigating the impact of big-five teamwork model awareness on rationing of nursing care and patient-centered care
Authors: Ashour Heba Mohamed Al-Anwer Ali , Abou Hashish Ebtsam Aly Omer , Awad Nadia Hassan Ali
Published: February 2025

Background

Nurses are the cornerstone of healthcare delivery, playing a pivotal role in ensuring safe, high-quality, and patient-centered care. However, the significant demands on their time and resources often lead to the rationing or omission of essential nursing care activities, undermining patient outcomes. As frontline caregivers, nurses’ ability to collaborate effectively within teams is critical to overcoming these challenges. The Big Five Teamwork Model, which emphasizes trust, communication, and leadership, offers a transformative approach to strengthening teamwork and addressing barriers to comprehensive nursing care.

Aim

This study aimed to assess the impact of the Big Five Teamwork Awareness Sessions (Big 5TWAS) on the rationing of nursing care and patient-centered care.

Methods

A quasi-experimental pre-post-test design was conducted in critical care units at an Egyptian university hospital. A convenience sample of 60 nurses and 31 admitted patients participated in the study. Big 5TWAS interventions were implemented for nurses, and study variables were measured using nursing teamwork surveys, the Rationing of Nursing Care Observational Checklist (RONCO), and patient-centered care questionnaires before and after the intervention. Data were analyzed using descriptive and inferential statistics.

Results

The Big 5 Teamwork Awareness Sessions (Big 5TWAS) demonstrated a significant impact on the study variables. Post-sessions, there was a significant decrease in rationing of nursing care scores and significant increases in nursing teamwork and patient-centered care scores (p ≤ 0.001). In addition to the significant correlation values, regression analysis revealed that overall teamwork accounted for approximately 22% of the variance in rationing of nursing care (R² = 0.224, p = 0.015), with trust as the significant predictor. Furthermore, teamwork explained approximately 80% of the variance in patient-centered care (R² = 0.801, p < 0.001), with trust, backup, and team leadership emerging as significant predictors.

Conclusion and recommendations

The study underscores the critical role of teamwork in reducing the rationing of nursing care and enhancing patient-centered care in critical care units. The Big 5TWAS was effective in fostering improved team dynamics, trust, and leadership, which translated into better care delivery. These findings highlight the need for ongoing inter-professional training and teamwork-enhancing strategies led by nurse managers to sustain and amplify these improvements. By focusing on teamwork, healthcare institutions can ensure high-quality patient outcomes and minimize missed nursing care practices.
Health and social care use, costs, and satisfaction among key workers accessing Resilience Hub support during the COVID-19 pandemic
Authors: Rowlandson Aleix , Varese Filippo , Davies Linda M. , French Paul , Allsopp Kate , Carter Lesley-Anne , Hind Daniel , McGuirk Katherine , Barrett Alan , Bhutani Gita , Huntley Fay , Jordan Joanne , Sarsam May , Cate Hein Ten , Walker Holly , Watson Ruth , Wilkinson Jack , Willbourn Jenni , Shields Gemma E.
Published: February 2025

Key workers are vulnerable to adverse mental health. To ensure service sustainability during COVID-19, Resilience Hubs were established across England offering outreach, screening, and mental health support. This evaluation aimed to describe wider service use, associated costs, and satisfaction among Hub clients (key workers) accessing Hub support. Clients accessing support across four Hubs were invited to complete a service use questionnaire, between 5 and 8 months post referral, collecting satisfaction, wider service use and cost data. Exploratory linear regression assessed the relationship between demographic variables and service use. Most Hub clients reported Hub contact post referral (219/299, 73.2%), with many accessing mental health support (171/299, 57.2%) or on waitlists (34/299, 11.4%). Satisfaction was high, with median helpfulness rated 92 (out of 100), and many stating that Hubs either fully (148/299, 49.5%) or partially (54/299, 18.1%) met their needs. Mental health support accounted for most service use, with higher total service use and costs when including Hub services (£514 versus £213). Key workers have complex needs. Hub services helped clients to access support, with high reported satisfaction indicating that Hubs met clients needs. Further research is required to assess how service use varies according to occupation or demographic characteristics, and whether Hubs are clinically and cost-effective.
Moments that matter: childhood pain treatment shapes pain for life—we can do better every time in every child
Authors: Slater Rebeccah , Walker Suellen , Eccleston Christopher , Bellieni Carlo , Hirekodi Tanvi , Carbajal Ricardo , Smart Lucinda , Laughey William , Cobo Maria M. , Friedrichsdorf Stefan
Published: February 2025

Background

Needle procedures, such as vaccinations, blood draws, and intravenous cannulation, are the most frequent source of childhood pain, causing fear and reducing the uptake of medical procedures. Every child has the right to expect pain relief, and we have evidence-based tools to reduce needle procedure-related pain. Therefore, the lack of analgesic provision for needle pain is not justified. We argue that better informed and motivated healthcare professionals and families can advocate for appropriate pain relief in every child, every time.

Observations

Engaging communication campaigns are needed to educate our healthcare professionals. Evidence-based modalities such as topical anaesthesia, sucrose or breastfeeding, comfort positioning, and age-appropriate distractions should be available for every child during needle procedures. However, high-quality information is not enough to change behaviour—healthcare professionals need to be motivated, encouraged, and inspired. Parents and carers should be empowered to advocate for their children and be aware that their child has the right to receive pain relief during these procedures.

Conclusions and relevance

This is a call to action—we need collaboration between academics, healthcare professionals, industry and charities, to expedite behavioural change and parental advocacy through high-quality communication strategies. Effective pain management in infants and children can play a crucial role in promoting the uptake of vaccinations and medical procedures and can influence future attitudes to pain.
Visceral adipose tissue area and proportion provide distinct reflections of cardiometabolic outcomes in weight loss; pooled analysis of MRI-assessed CENTRAL and DIRECT PLUS dietary randomized controlled trials
Authors: Klein Hadar , Zelicha Hila , Yaskolka Meir Anat , Rinott Ehud , Tsaban Gal , Kaplan Alon , Chassidim Yoash , Gepner Yftach , Blüher Matthias , Ceglarek Uta , Isermann Berend , Stumvoll Michael , Shelef Ilan , Qi Lu , Li Jun , Hu Frank B. , Stampfer Meir J. , Shai Iris
Published: February 2025

Background

Visceral adipose tissue (VAT) is well established as a pathogenic fat depot, whereas superficial subcutaneous adipose tissue (SAT) is associated with either an improved or neutral cardiovascular state. However, it is unclear to what extent VAT area (VATcm2) and its proportion of total abdominal adipose tissue (VAT%) are distinguished in predicting cardiometabolic status and clinical outcomes during weight loss.

Methods

We integrated magnetic resonance imaging (MRI) measurements of VAT, deep-SAT, and superficial-SAT from two 18-month lifestyle weight loss clinical trials, CENTRAL and DIRECT PLUS (n = 572).

Results

At baseline, the mean VATcm2 was 144.8cm2 and VAT% = 28.2%; over 18 months, participants lost 28cm2 VATcm2 (− 22.5%), and 1.3 VAT% units. Baseline VATcm2 and VAT% were similarly associated with metabolic syndrome, hypertension, and diabetes status, while VAT% better classified hypertriglyceridemia. Conversely, higher VATcm2 was associated with elevated high-sensitivity C-reactive protein (hsCRP), while VAT% was not. After 18 months of lifestyle intervention, both VATcm2 and VAT% loss were significantly associated with decreased triglycerides, HbA1c, ferritin, and liver enzymes, and increased HDL-c levels beyond weight loss (FDR < 0.05). Only VATcm2 loss was correlated with decreased HOMA-IR, chemerin, and leptin levels.

Conclusions

MRI follow-up of 572 participants over 18 months of weight loss intervention suggests that although increased VATcm2 and VAT% exhibit similar clinical manifestations, it might be preferable to examine VAT% when exploring lipid status, while VATcm2 may better reflect inflammatory and glycemic states.

Trial registration

CENTRAL (Clinical-trials-identifier: NCT01530724); DIRECT PLUS (Clinical-trials-identifier: NCT03020186).
Exploration of treatment burden through examination of workload and patient capacity during transition onto kidney replacement therapy: a systematic review of qualitative research
Authors: Jones Catrin , Cairns Ross , Walker Heather , Welsh Silje , Edgar Benjamin , Stevenson Karen , Jani Bhautesh D. , Mark Patrick B. , Kingsmore David , Gallacher Katie I.
Published: February 2025

Background

Patients with advanced chronic kidney disease requiring initiation of kidney replacement therapy (KRT) are frequently asked to enact complex management plans. Treatment burden has been defined as the effect of healthcare workload and the capacity a person has to manage this workload has on wellbeing. The aim of this review is to examine the experience of healthcare workload and the factors that affect capacity to meet that workload for people transitioning onto KRT for the first time, using a framework synthesis of published literature informed by normalisation process theory (NPT) and theory of patient capacity (TPC).

Methods

Medline, Scopus and CINAHL were systematically searched with manual citation and reference searching. Studies were included if meeting the criteria of adults aged 18 or over transitioning for the first time onto any modality of KRT (haemodialysis, peritoneal dialysis or kidney transplantation), using qualitative methodologies to describe any aspect of experiences of healthcare workload or any factors that affect capacity to manage workload were included. Abstracts and full papers were independently screened by two reviewers and data extraction and quality appraisal were also independently conducted by two reviewers. Qualitative data were analysed using framework synthesis informed by NPT and TPC.

Results

A total of 24,380 studies were screened, 406 full texts were reviewed and 18 studies were included. There were four broad categories of workload described: making sense of KRT, working out what to do and how to do it, meeting the challenges of KRT, and reflecting on work done. Patient capacity influenced the experience of all types of workload and the treatment burden generated by the work.

Conclusions

Transitioning onto KRT is a period of very high healthcare workload and potentially high treatment burden. The relationship between healthcare workload and capacity to handle workload is complex, multifactorial and changes over time. By better understanding workload, capacity and burden during transition, we can develop better ways of measuring these important aspects of care and develop interventions to reduce treatment burden in those transitioning onto KRT.
PhantomAR: gamified mixed reality system for alleviating phantom limb pain in upper limb amputees—design, implementation, and clinical usability evaluation
Authors: Prahm Cosima , Eckstein Korbinian , Bressler Michael , Wang Zhixing , Li Xiaotong , Suzuki Takashige , Daigeler Adrien , Kolbenschlag Jonas , Kuzuoka Hideaki
Published: February 2025

Background

Phantom limb pain (PLP) is a restrictive condition in which patients perceive pain in a limb that is no longer present, greatly reducing their quality of life. Mirror Therapy, wherein patients observe a mirror reflection of their intact limb, has demonstrated efficacy in alleviating PLP. However, its unilateral and seated nature presents limitations. To address these constraints while still reducing PLP, and evaluating the impact of different virtual limb representations (anthropomorphic vs. non-anthropomorphic) on the user’s sense of ownership, agency, and embodiment, PhantomAR was developed. Leveraging wearable first-person augmented reality (AR) technology, PhantomAR extends traditional Mirror Therapy by enabling users to move freely and engage in bimanual tasks.

Methods

The assistive mixed reality game application PhantomAR was deployed on the Microsoft HoloLens 2 and augmented the user’s residual limb by superimposing a virtual arm or tentacle that was controlled via residual muscles on their stump using an EMG electrode array. This setup allowed patients to engage in a first-person perspective and manipulate virtual objects with both the healthy and augmented limbs, free from the confines of a seated position. The study enrolled 10 able-bodied individuals and 8 individuals with unilateral, transradial amputation. All amputees experienced PLP. The usability of the PhantomAR application was evaluated using the System Usability Scale (SUS) and a user-centric survey. Additionally, the Game Experience was assessed on a 5-point Likert questionnaire (GEQ). Participants rated their phantom sensations using the Numerical Rating Scale and McGill Pain Questionnaire before, during, and after interaction with PhantomAR. The embodiment and agency of the virtual superimposed arm were evaluated with an altered Prosthesis Embodiment Scale. The study protocol included two sessions of 30 min each, during which participants experienced PhantomAR.

Results

Participants (n = 18) rated PhantomAR highly usable (SUS m = 90.8%, SD = 6.88). Feedback on the Game Experience Questionnaire was overwhelmingly positive, showing high immersion (m = 4.46, SD = 0.08) and positive affect (m = 4.97, SD = 0.05). PLP (n = 8) significantly decreased post-intervention (NRS and McGill Pain Questionnaire, p < .001). Skin temperature in the residual limb increased significantly post-intervention (p < .01) but did not correlate with PLP (r = − 0.08, p = 0.83). Tentacle overlay yielded mixed ownership but high agency ratings.

Conclusion

PhantomAR leverages mixed reality to significantly reduce Phantom Limb Pain, enhance user engagement, and alter perceptions of ownership and agency of their augmented limb through bi-manual, dynamic, full-body interactions.

Trial registration DRKS00033208 (Jan. 5th 2024)
UAV rice panicle blast detection based on enhanced feature representation and optimized attention mechanism
Authors: Lin Shaodan , Huang Deyao , Wu Libin , Cheng Zuxin , Ye Dapeng , Weng Haiyong
Published: February 2025

Background

Rice blast is one of the most destructive diseases in rice cultivation, significantly threatening global food security. Timely and precise detection of rice panicle blast is crucial for effective disease management and prevention of crop losses. This study introduces ConvGAM, a novel semantic segmentation model leveraging the ConvNeXt-Large backbone network and the Global Attention Mechanism (GAM). This design aims to enhance feature extraction and focus on critical image regions, addressing the challenges of detecting small and complex disease patterns in UAV-captured imagery. Furthermore, the model incorporates advanced loss functions to handle data imbalances effectively, supporting accurate classification across diverse disease severities.

Results

The ConvGAM model, leveraging the ConvNeXt-Large backbone network and the Global Attention Mechanism (GAM), achieves outstanding performance in feature extraction, crucial for detecting small and complex disease patterns. Quantitative evaluation demonstrates that the model achieves an overall accuracy of 91.4%, a mean IoU of 79%, and an F1 score of 82% on the test set. The incorporation of Focal Tversky Loss further enhances the model's ability to handle imbalanced datasets, improving detection accuracy for rare and severe disease categories. Correlation coefficient analysis across disease severity levels indicates high consistency between predictions and ground truth, with values ranging from 0.962 to 0.993. These results confirm the model’s reliability and robustness, highlighting its effectiveness in rice panicle blast detection under challenging conditions.

Conclusion

The ConvGAM model demonstrates strong qualitative advantages in detecting rice panicle blast disease. By integrating advanced feature extraction with the ConvNeXt-Large backbone and GAM, the model achieves precise detection and classification across varying disease severities. The use of Focal Tversky Loss ensures robustness against dataset imbalances, enabling accurate identification of rare disease categories. Despite these strengths, future efforts should focus on improving classification accuracy and adapting the model to diverse environmental conditions. Additionally, optimizing model parameters and exploring advanced data augmentation techniques could further enhance its detection capabilities and expand its applicability to broader agricultural scenarios.
Synthetic CT generation from CBCT and MRI using StarGAN in the Pelvic Region
Authors: Wongtrakool Paritt , Puttanawarut Chanon , Changkaew Pimolpun , Piasanthia Supakiet , Earwong Pareena , Stansook Nauljun , Khachonkham Suphalak
Published: February 2025

Rationale and objectives

This study evaluated StarGAN, a deep learning model designed to generate synthetic computed tomography (sCT) images from magnetic resonance imaging (MRI) and cone-beam computed tomography (CBCT) data using a single model. The goal was to provide accurate Hounsfield unit (HU) data for dose calculation to enable MRI simulation and adaptive radiation therapy (ART) using CBCT or MRI. We also compared the performance and benefits of StarGAN to the commonly used CycleGAN.

Materials and methods

StarGAN and CycleGAN were employed in this study. The dataset comprised 53 cases of pelvic cancer. Evaluation involved qualitative and quantitative analyses, focusing on synthetic image quality and dose distribution calculation.

Results

For sCT generated from CBCT, StarGAN demonstrated superior anatomical preservation based on qualitative evaluation. Quantitatively, CycleGAN exhibited a lower mean absolute error (MAE) for the body (42.8 ± 4.3 HU) and bone (138.2 ± 20.3), whereas StarGAN produced a higher MAE for the body (50.8 ± 5.2 HU) and bone (153.4 ± 27.7 HU). Dosimetric evaluation showed a mean dose difference (DD) within 2% for the planning target volume (PTV) and body, with a gamma passing rate (GPR) > 90% under the 2%/2 mm criteria. For sCT generated from MRI, qualitative evaluation also favored the anatomical preservation provided by StarGAN. CycleGAN recorded a lower MAE (79.8 ± 14 HU for the body and 253.6 ± 30.9 HU for bone) compared with StarGAN (94.7 ± 7.4 HU for the body and 353.6 ± 34.9 HU for bone). Both models achieved a mean DD within 2% in the PTV and body, and GPR > 90%.

Conclusion

While CycleGAN exhibited superior quantitative metrics, StarGAN was better in anatomical preservation, highlighting its potential for sCT generation in radiotherapy.
Intravenous leiomyomatosis presenting as Budd–Chiari syndrome: a case report and literature review
Authors: Gan Jingwen , Ma Xiao , Shao Jiang , Wang Jinhui , Cao Dongyan
Published: February 2025

Background

Budd–Chiari syndrome (BCS) caused by intravenous leiomyomatosis (IVL) is rare. Further reports and thorough evaluation are needed to identify and manage this disease.

Method

We described the case of a 49-year-old lady, exhibiting features of BCS secondary to IVL, and reviewed three other previous cases of BCS caused by IVL.

Results

The mean onset age of these four patients was 54.8 years. All but one (Patient No. 2) had a history of myoma, myomectomy, or hysterectomy. Abdominal pain, bloating or increasing abdominal circumference, and bilateral lower extremity edema were common symptoms. The establishment of clinical diagnoses of IVL and BCS mainly depends on clinical presentations and imaging, such as ultrasonography, computed tomography, and magnetic resonance imaging. Surgical intervention to alleviate the hepatic veins outflow obstruction is the most important treatment.

Conclusions

BCS caused by IVL should be considered when the inferior vena cava and right atrium lesions were detected in a patient with characteristics of BCS and a history of uterine myoma or hysterectomy. Complete tumor resection is the only curative treatment and should be performed as soon as possible.
The effect of GM-CSF and predictors of treatment outcome in pediatric septic shock patients
Authors: Yu Zhen-Hao , Tian Gui-Xiang , Wang Yao-Dong , Liu Ting-Yan , Shi Peng , Ying Jia-Yun , Chen Wei-Ming , Zhou Yu-Feng , Lu Guo-Ping , Zhang Cai-Yan
Published: February 2025

Background

Pediatric septic shock is a critical condition associated with high mortality rates, largely due to sepsis-induced immunosuppression. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been explored as a therapeutic intervention to counteract this immunosuppression. Despite its potential, the efficacy of GM-CSF in pediatric septic shock has not been clearly established. This study aims to investigate the impact of GM-CSF administration on survival rates and to identify key predictors of treatment outcomes in pediatric septic shock patients.

Methods

We conducted a retrospective cohort study at the Pediatric Intensive Care Unit (PICU) of Children’s Hospital of Fudan University, Shanghai, from January 1, 2019, to December 31, 2023. The study included pediatric patients diagnosed with septic shock, analyzing their demographic data, GM-CSF and adjunctive therapies, laboratory results, and clinical outcomes. We employed univariate and multivariate logistic regression models to assess the influence of GM-CSF on 28-day mortality and identify significant predictors of treatment outcomes.

Results

The study included 200 pediatric patients, with 66 receiving GM-CSF treatment and 134 not treated with GM-CSF. The initial comparison showed a higher 28-day mortality in the GM-CSF group (59.1%) compared to the non-GM-CSF group (35.1%, P = 0.001). Notably, after adjustment for confounding factors, multivariate analysis revealed that the effect of GM-CSF treatment on 28-day mortality among pediatric septic shock patients did not reach statistical significance, with an odds ratio (OR) of 0.472 and a 95% confidence interval (CI) ranging from 0.153 to 1.457 (P = 0.192). However, the analysis indicated a potential trend suggesting that GM-CSF treatment may contribute to a reduction in 28-day mortality. In addition, significant predictors of treatment outcomes included hematopoietic stem cell transplantation (HSCT), lactic acid (LAC) levels, hospital-acquired septic shock (HASS), red blood cell (RBC) count, and platelet (PLT) count.

Conclusions

GM-CSF treatment may benefit pediatric septic shock patients, especially those with higher lactic acid, and lower RBC and platelet counts. These factors, which are significant predictors of outcomes, should be monitored during therapy.
Quantifying the tumour vasculature environment from CD-31 immunohistochemistry images of breast cancer using deep learning based semantic segmentation
Authors: Whitmarsh Tristan , Cope Wei , Carmona-Bozo Julia , Manavaki Roido , Sammut Stephen-John , Woitek Ramona , Provenzano Elena , Brown Emma L. , Bohndiek Sarah E. , Gallagher Ferdia A. , Caldas Carlos , Gilbert Fiona J. , Markowetz Florian
Published: February 2025

Background

Tumour vascular density assessed from CD-31 immunohistochemistry (IHC) images has previously been shown to have prognostic value in breast cancer. Current methods to measure vascular density, however, are time-consuming, suffer from high inter-observer variability and are limited in describing the complex tumour vasculature morphometry.

Methods

We propose a method for automatically measuring a range of vascular parameters from CD-31 IHC images, which together provide a detailed description of the vasculature morphology. We first used a U-Net based convolutional neural network, trained and validated using 36 partially annotated whole slide images from 27 patients, to segment vessel structures and tumour regions from which the measurements are taken. The model also segments the vascular smooth muscle, benign epithelium, adipose tissue, stroma, lymphocyte clusters, nerves and CD-31 positive leukocytes, and we applied it to an additional 21 images from 15 patients. Using these segmentations, we investigated the relationship between the various tissue types and the vasculature and studied the relationship of various vascular parameters with clinical parameters. We also performed a 3D histology analysis on a separate tumour sample as a proof of principle, providing a more comprehensive visualization of vasculature morphology compared to the standard 2D cross-section of a tissue sample.

Results

Using two-way cross-validation, we show that vessels were accurately segmented, with Dice scores of 0.875 and 0.856, and were accurately identified, with F1 scores of 0.777 and 0.748. All vascular parameters exhibit strong (

$$r>0.7$$

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>
0.7

) and significant (p<0.001) correlations with measurements taken from the manual ground truth vessel segmentations. A significant relationship between the major/minor axis ratio, a measure of elongation, and the tumour grade was found.

Conclusion

Our proposed method shows promise as a tool for studying the tumour vasculature and its relationship with surrounding cells and tissue types. Furthermore, the correlation with tumour grade highlights the clinical relevance of our approach. These findings suggest that our method could have substantial implications for improving prognostic assessments and personalizing therapeutic strategies in breast cancer treatment.
ZBiotics ameliorates T2DM-induced histopathological damage in liver, kidney and adipose tissues by modulating the NOD-like receptor signaling in Wistar rats
Authors: Esawie Mohammed , Matboli Marwa , Bushra Mariam Sameh , Hasanin Amany H. , Habib Eman Kamal , Mohamed Reham Hussein , Ali Hebatalla Said
Published: February 2025

Probiotics serve as promising candidates in type 2 diabetes mellitus (T2DM) therapy. Not only they presumably reduce the T2DM prevalence, but also keep down its complications. In the present study, we explored the beneficial impact of ZBiotics, an engineered probiotic, on T2DM Wistar rats. In silico analysis was performed to construct a genetic-epigenetic network linked to STING-NOD pathway and autophagy signaling. Then, 30 Wistar rats were divided into 5 groups (each n = 6); normal group, diabetic model, B. subtilis, and ZBiotics treated rats at high and low doses. Experimental procedures were carried out including biochemical and histopathologic analyses. Samples were extracted from rats’ blood, liver, kidney and adipose tissues. At the molecular aspect, the molecular players, chosen by the in silico analysis, were assessed using 2–ΔΔCt to estimate their relative quantification. With immunohistochemistry, TNF-alpha and LC3B were assessed as reflectors for inflammation and autophagy respectively. ZBiotics was reported to ameliorate the T2DM-induced histological damage. Besides, it downregulated TNF-alpha and upregulated LC3B expression levels. At the biochemical aspect, ZBiotics corrected LDL-c and improved serum creatinine and CK-MB levels. Inflammation relevant genes have been downregulated regarding CHUK, NFKB1 and miR-611. Therefore, ZBiotics is speculated to operate by modulating the genetic-epigenetic network linked to inflammatory cGAS-STING and autophagy signaling. ZBiotics is recommended for clinical trials as a separate candidate or as an adjuvant to the conventional T2DM therapy.
Exploring the intricacies of plant growth promoting rhizobacteria interactions: an omics review
Authors: Mmotla Kamogelo , Sibanyoni Nompumelelo R. , Allie Farhahna , Sitole Lungile , Mafuna Thendo , Mashabela Manamele D. , Mhlongo Msizi I.
Published: February 2025

Background

Plant growth-promoting rhizobacteria (PGPR) are beneficial microorganisms that inhabit the rhizosphere. PGPR play a role in stimulating plant growth and development and enhancing plant resistance and tolerance to biotic and abiotic stresses. To effectively fulfil their roles, PGPR engage in intricate interactions with one another, a phenomenon that occurs within the rhizosphere.

Mainbody.

This collaborative synergy among PGPR species within the rhizosphere is essential for them to perform their functions optimally. Nonetheless, the precise mechanisms and dynamics of PGPR-PGPR interactions, particularly at the transcriptomic level, remain the subject of ongoing research. Scientists are actively exploring and studying how these microorganisms interact and coordinate their activities within the rhizosphere, shedding light on the molecular processes underpinning their cooperative efforts. In this review, we undertake a thorough examination centred on the communication systems that regulate interactions among PGPR in the rhizosphere. Our examination delves into the mechanisms by which this communication triggers alterations at both the transcriptomic and metabolomic levels. Additionally, we assess the cutting-edge omics technologies currently available to study these intricate processes.

Conclusion

Understanding the modes of communication and molecular mechanisms underlying these interactions is crucial for harnessing their full potential, particularly in sustainable agriculture. By exploring transcriptomic and metabolomic alterations driven by these interactions, as well as the integration of advanced omics technologies, researchers can uncover new insights into decoding these complex processes, paving the way for innovative strategies to enhance sustainable agriculture.
Targeting AI-2 quorum sensing: harnessing natural products against Streptococcus suis biofilm infection
Authors: Gao Shuji , Yuan Shuo , Quan Yingying , Jin Wenjie , Shen Yamin , Li Rishun , Liu Baobao , Wang Yuxin , Yi Li , Wang Shaohui , Hou Xiaogai , Wang Yang
Published: February 2025

The biofilm acts as a protective layer for Streptococcus suis (S. suis), contributing to the development of drug resistance and chronic infections. Autoinducer 2 (AI-2) quorum sensing represents the primary regulatory pathway governing biofilm formation in S. suis. Consequently, targeting AI-2 quorum sensing to inhibit biofilm formation represents a promising strategy for preventing and managing drug resistance and chronic infections caused by S. suis. This study established a small natural product library by integrating commercial drug molecules with Chinese herbal medicine molecules. Consequently, two natural products, salvianolic acid A (SAA) and rhapontin (RH), which target S. suis AI-2 via quorum sensing, were identified. SAA and RH inhibit AI-2 synthesis through noncompetitive and competitive binding to S-ribosylhomocysteinase (LuxS). By inhibiting S. suis AI-2 quorum sensing, these compounds modulate the expression of adhesion genes and the synthesis of extracellular polysaccharides (EPS), reducing the adhesion ability of S. suis and ultimately inhibiting biofilm formation. Using LC‒MS/MS, we further analysed the impact of SAA and RH on the metabolic activity of S. suis, revealing the potential medicinal value of these compounds. Finally, the efficacy of SAA and RH against S. suis infection was validated in Galleria mellonella larvae, confirming their significant anti-infection effects.
Regulatory signatures involved in the cell cycle pathway contribute to egg production heterosis in chicken
Authors: Yuan Jingwei , Wang Yuanmei , Sun Yanyan , Li Yunlei , Ni Aixin , Li Qin , Yang Hanhan , Xu Xinying , Zong Yunhe , Ma Hui , Chen Jilan
Published: February 2025

Background

Crossbreeding is widely promoted as an efficient strategy to improve the productivity in agriculture. The molecular mechanism underlying heterosis for egg production is always intriguing in chicken. The transcriptional dynamic changes play a crucial role in the formation of heterosis, but little is known for the egg production traits.

Results

In present study, we measured the continuous manifestation of heterosis ranging from 2.67% to 10.24% for egg number in the crossbreds generated by reciprocal crossing White Leghorn and Beijing You chicken. The high-quality transcriptomes of ovary for purebreds (WW and YY) and crossbreds (WY and YW) in 5 laying stages were sequenced and integrated to identify regulatory networks relevant to the heterosis. We found highly conserved transcriptional features among 4 genetic groups. By using weighted gene co-expression network analysis (WGCNA), we obtained multiple gene co-expression modules that were significantly correlated with egg number for each group. The common KEGG pathways including apelin signaling pathway, cell cycle, ribosome, spliceosome and oxidative phosphorylation, were screened for the 2 crossbreds. Then, we identified consensus co-expression modules (CMs) that showed divergent expression pattern among crossbred (WY or YW) and purebreds (WW and YY). The hub genes of CMs were again overrepresented in the cell cycle pathway, and the crossbreds exhibited temporally complementary dominance of hub genes in the 5 laying stages. These results suggested that the crossbreds inherited from both parents to maintain the ovary function by cell cycle-related genes, contributing to the persistent heterosis for egg production. Furthermore, the dominant genes including MAD2L1, CHEK2 and E2F1 were demonstrated to function in ovarian follicle development and maturation and could be the candidate genes for egg production heterosis.

Conclusion

Our study characterized the dynamic profile of genome-wide gene expression in ovary and highlighted the role of dominant expression of cell cycle pathway genes in heterosis. These findings provided new insights for the molecular mechanism of egg production heterosis, which would facilitate the rational choice of suitable parents for producing crossbred chickens with higher egg production.
De-biasing microbiome sequencing data: bacterial morphology-based correction of extraction bias and correlates of chimera formation
Authors: Rauer Luise , De Tomassi Amedeo , Müller Christian L. , Hülpüsch Claudia , Traidl-Hoffmann Claudia , Reiger Matthias , Neumann Avidan U.
Published: February 2025

Introduction

Microbiome amplicon sequencing data are distorted by multiple protocol-dependent biases from bacterial DNA extraction, contamination, sequence errors, and chimeras, hindering clinical microbiome applications. In particular, extraction bias is a major confounder in sequencing-based microbiome analyses, with no correction method available to date. Here, we suggest using mock community controls to computationally correct extraction bias based on bacterial morphological properties.

Methods

We compared dilution series of 3 cell mock communities with an even or staggered composition. DNA of these mock, and additional skin microbiome samples, was extracted with 8 different extraction protocols (2 buffers, 2 extraction kits, 2 lysis conditions). Extracted DNA was sequenced (V1–V3 16S rRNA gene) together with corresponding DNA mocks.

Results

Microbiome composition was significantly different between extraction kits and lysis conditions, but not between buffers. Independent of the extraction protocol, chimera formation increased with higher input cell numbers. Contaminants originated mostly from buffers, and considerable cross-contamination was observed in low-input samples. Comparing the microbiome composition of the cell mocks to corresponding DNA mocks revealed taxon-specific protocol-dependent extraction bias. Strikingly, this extraction bias per species was predictable by bacterial cell morphology. Morphology-based computational correction of extraction bias significantly improved resulting microbial compositions when applied to different mock samples, even with different taxa. Equivalent correction of the skin samples showed a substantial impact on microbiome compositions.

Conclusions

Our results indicate that higher DNA density increases chimera formation during PCR amplification. Furthermore, we show that computational correction of extraction bias based on bacterial cell morphology would be feasible using appropriate positive controls, thus constituting an important step toward overcoming protocol biases in microbiome analysis.
Machine learning for predicting severe dengue in Puerto Rico
Authors: Madewell Zachary J. , Rodriguez Dania M. , Thayer Maile B. , Rivera-Amill Vanessa , Paz-Bailey Gabriela , Adams Laura E. , Wong Joshua M.
Published: February 2025

Background

Distinguishing between non-severe and severe dengue is crucial for timely intervention and reducing morbidity and mortality. World Health Organization (WHO)-recommended warning signs offer a practical approach for clinicians but have limited sensitivity and specificity. This study aims to evaluate machine learning (ML) model performance compared to WHO-recommended warning signs in predicting severe dengue among laboratory-confirmed cases in Puerto Rico.

Methods

We analyzed data from Puerto Rico’s Sentinel Enhanced Dengue Surveillance System (May 2012–August 2024), using 40 clinical, demographic, and laboratory variables. Nine ML models, including Decision Trees, K-Nearest Neighbors, Naïve Bayes, Support Vector Machines, Artificial Neural Networks, AdaBoost, CatBoost, LightGBM, and XGBoost, were trained using fivefold cross-validation and evaluated with area under the receiver operating characteristic curve (AUC-ROC), sensitivity, and specificity. A subanalysis excluded hemoconcentration and leukopenia to assess performance in resource-limited settings. An AUC-ROC value of 0.5 indicates no discriminative power, while values closer to 1.0 reflect better performance.

Results

Among the 1708 laboratory-confirmed dengue cases, 24.3% were classified as severe. Gradient boosting algorithms achieved the highest predictive performance, with an AUC-ROC of 97.1% (95% CI: 96.0–98.3%) for CatBoost using the full 40-variable feature set. Feature importance analysis identified hemoconcentration (≥ 20% increase during illness or ≥ 20% above baseline for age and sex), leukopenia (white blood cell count < 4000/mm3), and timing of presentation at 4–6 days post-symptom onset as key predictors. When excluding hemoconcentration and leukopenia, the CatBoost AUC-ROC was 96.7% (95% CI: 95.5–98.0%), demonstrating minimal reduction in performance. Individual warning signs like abdominal pain and restlessness had sensitivities of 79.0% and 64.6%, but lower specificities of 48.4% and 59.1%, respectively. Combining ≥ 3 warning signs improved specificity (80.9%) while maintaining moderate sensitivity (78.6%), resulting in an AUC-ROC of 74.0%.

Conclusions

ML models, especially gradient boosting algorithms, outperformed traditional warning signs in predicting severe dengue. Integrating these models into clinical decision-support tools could help clinicians better identify high-risk patients, guiding timely interventions like hospitalization, closer monitoring, or the administration of intravenous fluids. The subanalysis excluding hemoconcentration confirmed the models’ applicability in resource-limited settings, where access to laboratory data may be limited.

Graphical Abstract
Repeated positron emission tomography tracing neutrophil elastase in a porcine intensive-care sepsis model
Authors: Wilske Frida , Eriksson Olof , Amini Rose-Marie , Estrada Sergio , Janols Helena , Khalil Amina , Larsson Anders , Lipcsey Miklós , Mangsbo Sara , Sigfridsson Jonathan , Sjölin Jan , Skorup Paul , Wall Anders , Wilson Viola , Castegren Markus , Antoni Gunnar
Published: February 2025

Background

Neutrophil granulocytes are important parts of the defence against bacterial infections. Their action is a two-edged sword, the mediators killing the intruding bacteria are at the same time causing tissue damage. Neutrophil activation is part of the dysregulated immune response to infection defining sepsis and neutrophil elastase is one of the powerful proteases causing both effects and damage. Inhibition of neutrophil elastase has been tried in sepsis and ARDS, so far with inconclusive results.

Methods

We used positron emission tomography (PET) combined with computed tomography (CT) and the selective and specific neutrophil elastase inhibitor PET-tracer [11C]GW457427 ([11C]NES), in an intensive care unit porcine Escherichia coli sepsis model with the primary aim to visualise the biodistribution of neutrophil elastase in the initial acute phase of the septic reaction. Repeated PET–CT investigations were performed before and after induction of sepsis.

Results

At baseline [11C]NES uptake was found in the bone marrow, spleen and liver. The uptake in the bone marrow was markedly increased two hours into the sepsis, whereas in spleen and liver the uptake was not as markedly changed compared to baseline. At 4 h after the sepsis induction [11C]NES in the bone marrow decreased while the uptake increased in the spleen, liver and lungs.

Conclusion

The neutrophil elastase PET-tracer [11C]NES is a novel and unique instrument to study the acute innate neutrophil immune response in sepsis and associated vital organ failure. We here present images and quantitative data of the neutrophil elastase distribution the first hours of acute experimental sepsis. Surprisingly, a pronounced increase of neutrophil elastase was found in the bone marrow 2 h into the sepsis reaction followed at 4 h by increase in the liver, spleen and lungs and a concomitant reduction of the tracer uptake in bone marrow.