bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrafraction organ movement in adaptive MR-guided radiotherapy of abdominal lesions – dosimetric impact and how to detect its extent in advance
Authors: Buchele Carolin , Renkamp C. Katharina , Regnery Sebastian , Behnisch Rouven , Rippke Carolin , Schlüter Fabian , Hoegen-Saßmannshausen Philipp , Debus Jürgen , Hörner-Rieber Juliane , Alber Markus , Klüter Sebastian 
Published: June 2024

Abstract
Introduction
Magnetic resonance guided radiotherapy (MRgRT) allows daily adaptation of treatment plans to compensate for positional changes of target volumes and organs at risk (OARs). However, current adaptation times are relatively long and organ movement occurring during the adaptation process might offset the benefit gained by adaptation. The aim of this study was to evaluate the dosimetric impact of these intrafractional changes. Additionally, a method to predict the extent of organ movement before the first treatment was evaluated in order to have the possibility to compensate for them, for example by adding additional margins to OARs.

Materials & methods
Twenty patients receiving adaptive MRgRT for treatment of abdominal lesions were retrospectively analyzed. Magnetic resonance (MR) images acquired at the start of adaptation and immediately before irradiation were used to calculate adapted and pre-irradiation dose in OARs directly next to the planning target volume. The extent of organ movement was determined on MR images acquired during simulation sessions and adaptive treatments, and their agreement was evaluated. Correlation between the magnitude of organ movement during simulation and the duration of simulation session was analyzed in order to assess whether organ movement might be relevant even if the adaptation process could be accelerated in the future.

Results
A significant increase in dose constraint violations was observed from adapted (6.9%) to pre-irradiation (30.2%) dose distributions. Overall, OAR dose increased significantly by 4.3% due to intrafractional organ movement. Median changes in organ position of 7.5 mm (range 1.5–10.5 mm) were detected within a median time of 17.1 min (range 1.6–28.7 min). Good agreement was found between the range of organ movement during simulation and adaptation (66.8%), especially if simulation sessions were longer and multiple MR images were acquired. No correlation was determined between duration of simulation sessions and magnitude of organ movement.

Conclusion
Intrafractional organ movement can impact dose distributions and lead to violations of OAR tolerance doses, which impairs the benefit of daily on-table plan adaptation. By application of simulation images, the extent of intrafractional organ movement can be predicted, which possibly allows to compensate for them.
The safety and efficacy of volumetric modulated Arc therapy combined with computer tomography-guided adaptive brachytherapy for locally advanced cervical cancer: a single institution experience
Authors: Yang Tianyu , Zhao Tiandi , Ji Zhe , Lei Runhong , Qu Ang , jiang Weijuan , Deng Xiuwen , Jiang Ping 
Published: June 2024

Abstract
Background
Volumetric modulated arc therapy (VMAT) is a novel form of IMRT, which can deliver more accurate dose distribution and shorten treatment time. Compared to MRI-guided adaptive brachytherapy, which is recommended as gold standard imaging for cervical cancer contours, CT-guided adaptive brachytherapy (CTGAB) is more available, more widespread, and more affordable in many centers. This study aims to retrospectively analyze the efficacy and the safety of VMAT combined with CTGAB for patients with locally advanced cervical cancer.

Methods and materials
This study retrospectively analyzed 102 patients with locally advanced cervical cancer who underwent VMAT and CTGAB. Clinical outcomes including local control (LC), overall survival (OS) and progression-free survival (PFS), tumor response to treatment evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1), and toxicities including gastrointestinal toxicity, urinary toxicity and hematologic toxicity evaluated by the Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) were analyzed. The Kaplan-Meier method was used to calculate LC, OS, and PFS.

Results
Median follow-up time was 19 months. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) occurred in 68 (66.7%), 24 (23.5%), 4 (3.92%), and 6 (5.88%), respectively. The 2-year and 3-year OS were 89.6% and 83%, respectively. The 2-year and 3-year PFS were 84.2% and 74.3%, respectively. The 2-year and 3-year LC were 90.1% and 79.3%, respectively. The average cumulative D2cm3 in the rectum, the bladder, the colon, and the small intestine were 78.07 (SD: 0.46) Gy, 93.20 (SD: 0.63) Gy, 63.55 (SD: 1.03) Gy and 61.07 (SD: 0.75) Gy, respectively. The average cumulative D90% of the high-risk clinical target volume (HR-CTV) was 92.26 (SD: 0.35) Gy. Grade ≥ 3 gastrointestinal and urinary toxicities occurred in 4.9% and 0.98%, respectively. 1.96% of patients were observed grade ≥ 4 gastrointestinal toxicities and none of the patients observed grade ≥ 4 urinary toxicities.

Conclusion
VMAT combined with CTGAB for locally advanced cervical cancer was an effective and safe treatment method, which showed satisfactory LC, OS, PFS, and acceptable toxicities.
Psychosocial interventions for depression among young people in Sub-Saharan Africa: a systematic review and meta-analysis
Authors: Olisaeloka Lotenna , Udokanma Echezona , Ashraf Asma 
Published: June 2024

Abstract
Background
Depression among young people is a global health problem due to its rising prevalence and negative physical and social outcomes. The prevalence of depression and the treatment gap among young people in Sub-Saharan Africa (SSA) is higher than global estimates. Most psychosocial interventions for adolescent and youth depression were developed in high-income countries and less is known about their effectiveness in SSA. Due to contextual differences, findings from High-Income Countries (HICs) are less applicable to SSA. Yet, no systematic review of psychosocial interventions for depression among young people in SSA has been conducted.

Methods
A systematic literature search of four databases (Medline, Web of Science, PsycInfo, and Cochrane library) was conducted. Experimental studies published before May 2024 that evaluated the effect of psychosocial interventions on depressive symptoms among young people (aged 10–24 years) in SSA were included in the systematic review. Effect sizes (Hedge’s g (g)) indicating differences between intervention and control groups were calculated using a random effects model.

Results
Twenty-two eligible studies were identified for the systematic review, of which eighteen randomized control trials (RCTs) involving 2338 participants were included in the meta-analysis. The findings revealed that psychosocial interventions significantly reduced depressive symptoms (g = −1.55, 95% CI −2.48, −0.63), although heterogeneity was high (I2 = 98.8%). Subgroup analysis revealed that efficacy differed significantly by intervention type, with Cognitive Behavioural Therapy (9 studies) showing the strongest effect (g = −2.84, 95% CI −4.29; −1.38). While Wise Interventions (a form of positive psychology interventions; 2 studies) had a moderate effect (g = −0.46, 95% C.I −0.53, −0.39), Interpersonal Psychotherapy (2 studies; g = −0.08, 95% CI −1.05, 0.88) and Creative Psychological Interventions (3 studies; g = −0.29, 95% CI −1.38, 0.79) showed smaller, non-significant effects. Sensitivity analysis excluding studies at high risk of bias strengthened the effect size. Few studies assessed factors affecting intervention efficacy and showed mixed effects of age, gender, and adherence levels.

Conclusion
Psychosocial interventions, particularly CBT, significantly reduced depressive symptoms among young people in SSA. However, it is crucial to acknowledge the high heterogeneity which likely stems from variations in study populations and intervention delivery modalities. This highlights the need for further research to identify the specific intervention components and delivery methods that work best for distinct subpopulations. Future research should also explore how long intervention effects are maintained and factors affecting efficacy.
Saliency-driven explainable deep learning in medical imaging: bridging visual explainability and statistical quantitative analysis
Authors: Brima Yusuf , Atemkeng Marcellin 
Published: June 2024

AbstractDeep learning shows great promise for medical image analysis but often lacks explainability, hindering its adoption in healthcare. Attribution techniques that explain model reasoning can potentially increase trust in deep learning among clinical stakeholders. In the literature, much of the research on attribution in medical imaging focuses on visual inspection rather than statistical quantitative analysis.In this paper, we proposed an image-based saliency framework to enhance the explainability of deep learning models in medical image analysis. We use adaptive path-based gradient integration, gradient-free techniques, and class activation mapping along with its derivatives to attribute predictions from brain tumor MRI and COVID-19 chest X-ray datasets made by recent deep convolutional neural network models.The proposed framework integrates qualitative and statistical quantitative assessments, employing Accuracy Information Curves (AICs) and Softmax Information Curves (SICs) to measure the effectiveness of saliency methods in retaining critical image information and their correlation with model predictions. Visual inspections indicate that methods such as ScoreCAM, XRAI, GradCAM, and GradCAM++ consistently produce focused and clinically interpretable attribution maps. These methods highlighted possible biomarkers, exposed model biases, and offered insights into the links between input features and predictions, demonstrating their ability to elucidate model reasoning on these datasets. Empirical evaluations reveal that ScoreCAM and XRAI are particularly effective in retaining relevant image regions, as reflected in their higher AUC values. However, SICs highlight variability, with instances of random saliency masks outperforming established methods, emphasizing the need for combining visual and empirical metrics for a comprehensive evaluation.The results underscore the importance of selecting appropriate saliency methods for specific medical imaging tasks and suggest that combining qualitative and quantitative approaches can enhance the transparency, trustworthiness, and clinical adoption of deep learning models in healthcare. This study advances model explainability to increase trust in deep learning among healthcare stakeholders by revealing the rationale behind predictions. Future research should refine empirical metrics for stability and reliability, include more diverse imaging modalities, and focus on improving model explainability to support clinical decision-making.
Doublecortin-like kinase is required for cnidocyte development in Nematostella vectensis
Authors: Kraus Johanna E. M. , Busengdal Henriette , Kraus Yulia , Hausen Harald , Rentzsch Fabian 
Published: June 2024

AbstractThe complex morphology of neurons requires precise control of their microtubule cytoskeleton. This is achieved by microtubule-associated proteins (MAPs) that regulate the assembly and stability of microtubules, and transport of molecules and vesicles along them. While many of these MAPs function in all cells, some are specifically or predominantly involved in regulating microtubules in neurons. Here we use the sea anemone Nematostella vectensis as a model organism to provide new insights into the early evolution of neural microtubule regulation. As a cnidarian, Nematostella belongs to an outgroup to all bilaterians and thus occupies an informative phylogenetic position for reconstructing the evolution of nervous system development. We identified an ortholog of the microtubule-binding protein doublecortin-like kinase (NvDclk1) as a gene that is predominantly expressed in neurons and cnidocytes (stinging cells), two classes of cells belonging to the neural lineage in cnidarians. A transgenic NvDclk1 reporter line revealed an elaborate network of neurite-like processes emerging from cnidocytes in the tentacles and the body column. A transgene expressing NvDclk1 under the control of the NvDclk1 promoter suggests that NvDclk1 localizes to microtubules and therefore likely functions as a microtubule-binding protein. Further, we generated a mutant for NvDclk1 using CRISPR/Cas9 and show that the mutants fail to generate mature cnidocytes. Our results support the hypothesis that the elaboration of programs for microtubule regulation occurred early in the evolution of nervous systems.
Pain trajectories over 12 months following conservative care consultation in patients with lumbar spinal stenosis
Authors: Jensen Rikke K. , Hartvigsen Lisbeth , Kongsted Alice 
Published: June 2024

Abstract
Objective
To investigate symptom trajectories in chiropractic patients with lumbar spinal stenosis (LSS).

Methods
Patients diagnosed with LSS were recruited from chiropractic clinics and self-reported questionnaires were collected at baseline and 1-year follow-up. Patients received weekly text messages about low back pain (LBP) and leg symptoms for 1 year. Group-based trajectory modelling was performed to identify symptom trajectory groups. The groups were compared based on patient characteristics, LBP and leg pain intensity, Oswestry Disability Index (ODI) and Zurich Claudication Questionnaire (ZCQ).

Results
A total of 90 patients were included in the analysis. A three-group trajectory model was chosen: ‘improving’ (16%), ‘fluctuating/improving’ (30%), and ‘persistent’ (54%). The ‘persistent’ group had a higher proportion of women [71% (95% CI 57–82%)] than the ‘improving’ group 29% (95% CI 11–56%), and a higher ODI score at both baseline [34.2 (95% CI 29.7–38.8) vs. 22.8 (16.4–29.1)] and 1-year follow-up [28.1 (95% CI 23.2–33.0) vs. 4.8 (0.1–9.4)]. Similar differences were observed for ZCQ symptom and function scores.

Conclusions
Pain symptoms in people with LSS followed distinctly different trajectories. Half of the sample had a pattern of consistently severe symptoms over a year, while the other half either improved rapidly or experienced fluctuating symptoms with some improvement.
Methylome analysis in girls with idiopathic central precocious puberty
Authors: Palumbo Stefania , Palumbo Domenico , Cirillo Grazia , Giurato Giorgio , Aiello Francesca , Miraglia del Giudice Emanuele , Grandone Anna 
Published: June 2024

Abstract
Background
Genetic and environmental factors are implicated in many developmental processes. Recent evidence, however, has suggested that epigenetic changes may also influence the onset of puberty or the susceptibility to a wide range of diseases later in life. The present study aims to investigate changes in genomic DNA methylation profiles associated with pubertal onset analyzing human peripheral blood leukocytes from three different groups of subjects: 19 girls with central precocious puberty (CPP), 14 healthy prepubertal girls matched by age and 13 healthy pubertal girls matched by pubertal stage. For this purpose, the comparisons were performed between pre- and pubertal controls to identify changes in normal pubertal transition and CPP versus pre- and pubertal controls.

Results
Analysis of methylation changes associated with normal pubertal transition identified 1006 differentially methylated CpG sites, 86% of them were found to be hypermethylated in prepubertal controls. Some of these CpG sites reside in genes associated with the age of menarche or transcription factors involved in the process of pubertal development. Analysis of methylome profiles in CPP patients showed 65% and 55% hypomethylated CpG sites compared with prepubertal and pubertal controls, respectively. In addition, interestingly, our results revealed the presence of 43 differentially methylated genes coding for zinc finger (ZNF) proteins. Gene ontology and IPA analysis performed in the three groups studied revealed significant enrichment of them in some pathways related to neuronal communication (semaphorin and gustation pathways), estrogens action, some cancers (particularly breast and ovarian) or metabolism (particularly sirtuin).

Conclusions
The different methylation profiles of girls with normal and precocious puberty indicate that regulation of the pubertal process in humans is associated with specific epigenetic changes. Differentially methylated genes include ZNF genes that may play a role in developmental control. In addition, our data highlight changes in the methylation status of genes involved in signaling pathways that determine the migration and function of GnRH neurons and the onset of metabolic and neoplastic diseases that may be associated with CPP in later life.
Effects of time of the day at sampling on CSF and plasma levels of Alzheimer’ disease biomarkers
Authors: Orduña Dolado Anna , Stomrud Erik , Ashton Nicholas J. , Nilsson Johanna , Quijano-Rubio Clara , Jethwa Alexander , Brum Wagner S. , Brinkmalm Westman Ann , Zetterberg Henrik , Blennow Kaj , Janelidze Shorena , Hansson Oskar 
Published: June 2024

Abstract
Background
Studies suggest that cerebrospinal fluid (CSF) levels of amyloid-β (Aβ)42 and Aβ40 present a circadian rhythm. However sustained sampling of large volumes of CSF with indwelling intrathecal catheters used in most of these studies might have affected CSF dynamics and thereby confounded the observed fluctuations in the biomarker levels.

Methods
We included 38 individuals with either normal (N = 20) or abnormal (N = 18) CSF Aβ42/Aβ40 levels at baseline. CSF and plasma were collected at two visits separated by an average of 53 days with lumbar punctures and venipunctures performed either in the morning or evening. At the first visit, sample collection was performed in the morning for 17 participants and the order was reversed for the remaining 21 participants. CSF and plasma samples were analyzed for Alzheimer’ disease (AD) biomarkers, including Aβ42, Aβ40, GFAP, NfL p-tau181, p-tau217, p-tau231 and t-tau. CSF samples were also tested using mass spectrometry for 22 synaptic and endo-lysosomal proteins.

Results
CSF Aβ42 (mean difference [MD], 0.21 ng/mL; p = 0.038), CSF Aβ40 (MD, 1.85 ng/mL; p < 0.001), plasma Aβ42 (MD, 1.65 pg/mL; p = 0.002) and plasma Aβ40 (MD, 0.01 ng/mL, p = 0.002) were increased by 4.2-17.0% in evening compared with morning samples. Further, CSF levels of 14 synaptic and endo-lysosomal proteins, including neurogranin and neuronal pentraxin-1, were increased by 4.5-13.3% in the evening samples (MDrange, 0.02-0.56 fmol/µl; p < 0.042). However, no significant differences were found between morning and evening levels for the Aβ42/Aβ40 ratio, different p-tau variants, GFAP and NfL. There were no significant interaction between sampling time and Aβ status for any of the biomarkers, except that CSF t-tau was increased (by 5.74%) in the evening samples compared to the morning samples in Aβ-positive (MD, 16.46 ng/ml; p = 0.009) but not Aβ-negative participants (MD, 1.89 ng/ml; p = 0.47). There were no significant interactions between sampling time and order in which samples were obtained.

Discussion
Our findings provide evidence for diurnal fluctuations in Aβ peptide levels, both in CSF and plasma, while CSF and plasma p-tau, GFAP and NfL were unaffected. Importantly, Aβ42/Aβ40 ratio remained unaltered, suggesting that it is more suitable for implementation in clinical workup than individual Aβ peptides. Additionally, we show that CSF levels of many synaptic and endo-lysosomal proteins presented a diurnal rhythm, implying a build-up of neuronal activity markers during the day. These results will guide the development of unified sample collection procedures to avoid effects of diurnal variation for future implementation of AD biomarkers in clinical practice and drug trials.
Lifetime assessment of semi-submersible wind turbines by Gaidai risk evaluation method
Authors: Gaidai Oleg , Ashraf Alia , Cao Yu , Sheng Jinlu , Zhu Yan , Liu Zirui 
Published: June 2024

AbstractAs the global agenda turns more towards the so-called challenge of climate change and lowering carbon emissions, research into green, renewable energy sources becoming nowadays more and more popular. Offshore wind power, produced by FOWTs (i.e., Floating Offshore Wind Turbines), is one such substitute. It is a significant industrial part of the contemporary offshore wind energy industry and produces clean, renewable electricity. Accurate operational lifetime assessment for FOWTs is an important technical safety issue, as environmental in situ loads can lead to fatigue damage as well as extreme structural dynamics, which can cause structural damage. In this study, in situ environmental hydro and aerodynamic environmental loads, that act on FOWT, given actual local sea conditions have been numerically assessed, using the FAST coupled nonlinear aero-hydro-servo-elastic software package. FAST combines aerodynamics and hydrodynamics models for FOWTs, control and electrical system dynamics models, along with structural dynamics models, enabling coupled nonlinear MC simulation in the real time. The FAST software tool enables analysis of a range of FOWT configurations, including 2- or 3-bladed horizontal-axis rotor, pitch and stall regulation, rigid and teetering hub, upwind and downwind rotors. FAST relies on advanced engineering models—derived from the fundamental laws, however with appropriate assumptions and simplifications, supplemented where applicable with experimental data. Recently developed Gaidai reliability lifetime assessment method, being well suitable for risks evaluation of a variety of sustainable energy systems, experiencing nonlinear, potentially extreme in situ environmental loads, throughout their designed service life. The main advantage of the advocated Gaidai risks evaluation methodology being its ability to tackle simultaneously a large number of dynamic systems' degrees of freedom, corresponding to the system's critical components.
Metagenomic insights into Heimdallarchaeia clades from the deep-sea cold seep and hydrothermal vent
Authors: Liu Rui , Cai Ruining , Wang Minxiao , Zhang Jing , Zhang Huan , Li Chaolun , Sun Chaomin 
Published: June 2024

AbstractHeimdallarchaeia is a class of the Asgardarchaeota, are the most probable candidates for the archaeal protoeukaryote ancestor that have been identified to date. However, little is known about their life habits regardless of their ubiquitous distribution in diverse habitats, which is especially true for Heimdallarchaeia from deep-sea environments. In this study, we obtained 13 metagenome-assembled genomes (MAGs) of Heimdallarchaeia from the deep-sea cold seep and hydrothermal vent. These MAGs belonged to orders o_Heimdallarchaeales and o_JABLTI01, and most of them (9 MAGs) come from the family f_Heimdallarchaeaceae according to genome taxonomy database (GTDB). These are enriched for common eukaryote-specific signatures. Our results show that these Heimdallarchaeia have the metabolic potential to reduce sulfate (assimilatory) and nitrate (dissimilatory) to sulfide and ammonia, respectively, suggesting a previously unappreciated role in biogeochemical cycling. Furthermore, we find that they could perform both TCA and rTCA pathways coupled with pyruvate metabolism for energy conservation, fix CO2 and generate organic compounds through an atypical Wood-Ljungdahl pathway. In addition, many genes closely associated with bacteriochlorophyll and carotenoid biosynthesis, and oxygen-dependent metabolic pathways are identified in these Heimdallarchaeia MAGs, suggesting a potential light-utilization by pigments and microoxic lifestyle. Taken together, our results indicate that Heimdallarchaeia possess a mixotrophic lifestyle, which may give them more flexibility to adapt to the harsh deep-sea conditions.