bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adipose-derived stem cells promote glycolysis and peritoneal metastasis via TGF-β1/SMAD3/ANGPTL4 axis in colorectal cancer
Authors: Zhu Chaojun , Teng Lan , Lai Yihong , Yao Xingxing , Fang Yuxin , Wang Zihuan , Lin Simin , Zhang Haonan , Li Qingyuan , Li Ye , Cai Jianqun , Zhang Yue , Wu Changjie , Huang Bing , Li Aimin , Liu Side , Lai Qiuhua 
Published: April 2024

AbstractPeritoneal metastasis, the third most common metastasis in colorectal cancer (CRC), has a poor prognosis for the rapid progression and limited therapeutic strategy. However, the molecular characteristics and pathogenesis of CRC peritoneal metastasis are poorly understood. Here, we aimed to elucidate the action and mechanism of adipose-derived stem cells (ADSCs), a prominent component of the peritoneal microenvironment, in CRC peritoneal metastasis formation. Database analysis indicated that ADSCs infiltration was increased in CRC peritoneal metastases, and high expression levels of ADSCs marker genes predicted a poor prognosis. Then we investigated the effect of ADSCs on CRC cells in vitro and in vivo. The results revealed that CRC cells co-cultured with ADSCs exhibited stronger metastatic property and anoikis resistance, and ADSCs boosted the intraperitoneal seeding of CRC cells. Furthermore, RNA sequencing was carried out to identify the key target gene, angiopoietin like 4 (ANGPTL4), which was upregulated in CRC specimens, especially in peritoneal metastases. Mechanistically, TGF-β1 secreted by ADSCs activated SMAD3 in CRC cells, and chromatin immunoprecipitation assay showed that SMAD3 facilitated ANGPTL4 transcription by directly binding to ANGPTL4 promoter. The ANGPTL4 upregulation was essential for ADSCs to promote glycolysis and anoikis resistance in CRC. Importantly, simultaneously targeting TGF-β signaling and ANGPTL4 efficiently reduced intraperitoneal seeding in vivo. In conclusion, this study indicates that tumor-infiltrating ADSCs promote glycolysis and anoikis resistance in CRC cells and ultimately facilitate peritoneal metastasis via the TGF-β1/SMAD3/ANGPTL4 axis. The dual-targeting of TGF-β signaling and ANGPTL4 may be a feasible therapeutic strategy for CRC peritoneal metastasis.
Old-age support policy and fertility with strategic bequest motives
Authors: Yakita Akira 
Published: April 2024

AbstractThis paper presents an analysis of the effects of public old-age support on individuals’ fertility decisions and on the long-term equilibrium in an overlapping generation economy with strategic bequest motives. Parents must pay their adult children at least the reservation wage to receive informal old-age support from them (individual rationality constraint). Formal old-age support is financed through wage taxes on children. The increased present value of formal old-age support tends to increase old-age utility, thereby decreasing the family support demand and decreasing savings for the old age. The increased wage tax reduces the opportunity cost of child-rearing time, thereby increasing the fertility rate. The effects of increased formal old-age support on per-worker capital and labor are indeterminate, as is the effect on the long-term lifetime utility of individuals. A strategic bequest motive might engender a higher fertility rate than that of the social optimum.
Segmentation in Measure Spaces
Authors: Moll Salvador , Pallardó-Julià Vicent , Solera Marcos 
Published: April 2024

AbstractWe consider an abstract concept of perimeter measure space as a very general framework in which one can properly consider two of the most well-studied variational models in image processing: the Rudin–Osher–Fatemi model for image denoising (ROF) and the Mumford–Shah model for image segmentation (MS). We show the linkage between the ROF model and the two phases piecewise constant case of MS in perimeter measure spaces. We show applications of our results to nonlocal image segmentation, via discrete weighted graphs, and to multiclass classification on high dimensional spaces.
Pharmacokinetic study of capivasertib and the CYP3A4 substrate midazolam in patients with advanced solid tumors
Authors: Miller Claire , Sommavilla Roberto , O’Bryant Cindy L. , Barve Minal , Dowlati Afshin , Luke Jason J. , Khatun Mahmuda , Morris Thomas , Cullberg Marie 
Published: April 2024

Abstract
Purpose
Capivasertib, a potent, selective inhibitor of all three AKT serine/threonine kinase (AKT) isoforms, is being evaluated in phase 3 trials in advanced breast and prostate cancer. This study evaluated the drug–drug interaction risk of capivasertib with the cytochrome P450 3A substrate midazolam in previously treated adults with advanced solid tumors.

Methods
Patients received oral capivasertib 400 mg twice daily (BID) on an intermittent schedule (4 days on/3 days off) starting on day 2 of cycle 1 (29 days) and on day 1 of each 28-day cycle thereafter. In cycle 1 only, patients received oral midazolam (1 mg) on day 1 (alone), and days 8 and 12 (3rd day off and 4th day on capivasertib, respectively). Midazolam pharmacokinetics on days 8 and 12 were analyzed versus day 1. Capivasertib, with or without standard-of-care treatment, was continued in patients deemed likely to benefit. Safety and exploratory efficacy analyses were conducted.

Results
Capivasertib–midazolam coadministration increased midazolam exposure (n = 21): geometric mean ratio (90% confidence interval) AUCinf and Cmax was 1.13 (0.97–1.32) and 1.15 (0.99–1.33) for day 8 versus day 1, and 1.75 (1.50–2.05) and 1.25 (1.08–1.46) for day 12 versus day 1. The capivasertib safety profile was manageable when administered with or without midazolam. Two patients had partial responses to treatment.

Conclusion
The up to 1.75-fold increase in midazolam exposure indicates capivasertib is a weak CYP3A inhibitor at 400 mg BID on an intermittent schedule. Capivasertib was well tolerated; exploratory efficacy analysis demonstrated evidence of clinical activity in this heavily pre-treated population.
ClinicalTrials.gov: NCT04958226.
Low light intensity increased survival of coral spat in aquaculture
Authors: Ramsby B. D. , Emonnot F. , Flores F. , Schipper S. , Diaz-Pulido G. , Abdul Wahab M. A. , Severati A. , Negri A. P. 
Published: April 2024

AbstractCoral reef ecosystems are declining and may not recover under future climate scenarios without intervention. Seeding reefs with corals bred in aquaculture is a promising restoration intervention; however, early coral recruits (spat) are vulnerable to overgrowth by benthic algae and maximizing their survival is essential for the feasibility of large-scale breeding operations. This study investigated the optimal light quality and intensity for spat survival and growth in the presence of algal communities typically used in coral aquaculture to induce larval settlement, but which might also outcompete spat and reduce survival during the grow-out period. Spat were exposed to two light spectra (blue and a full spectrum) at four light intensities (5–160 µmol m−2 s−1) over 12-week post-settlement. Survival was reduced under the highest intensity by nearly 40% compared to the lowest intensity. Light spectrum only affected survival at 60 µmol m−2 s−1—where survival was higher under blue compared to full spectrum light. Light treatments did not affect final spat size but spat were 33% smaller at the highest light intensity in weeks 6 and 8 due to overgrowth by crustose coralline algae (CCA), which was most abundant under these conditions. Low light intensity, on the other hand, favored green and brown algae, potentially due to their respective physiologies or less competition from crustose coralline algae. These results indicate that low light intensity presents several advantages for maintaining spat in coral aquaculture, including maximizing survival without significantly affecting growth, as well as minimizing husbandry and operating expenses.
The influence of Sargassum biomass and thallus density on the recruitment of coral reef fishes
Authors: Webber Kelsey , Fabricius Katharina , Wilson Shaun K. , Hoey Andrew S. 
Published: April 2024

AbstractA habitat’s structural complexity is a key determinant of the recruitment and composition of associated communities. While the influence of the physical structure of corals on coral reef fish recruitment is well studied, the significance of other benthic components, like macroalgae, remains unclear. We used experimental patches of the canopy-forming macroalga Sargassum to assess the influence of macroalgal complexity, which was manipulated by altering thallus density and biomass, on coral reef fish recruitment. We established twenty-five 75 × 75 cm patches on the reef flat of Orpheus Island, (inshore, central Great Barrier Reef) during austral summer. Patches were randomly divided into five treatments of varying Sargassum thallus density (3–9 thalli) and/or biomass (177–779 g per patch) and surveyed daily for recruiting fishes for 18 d. We recorded 35 fish species recruiting to our patches, with Sargassum biomass having the greatest influence on fish recruits’ abundance and species richness. Comparisons between treatments with equal thallus density but varying biomass revealed a positive association between Sargassum biomass and fish species richness and abundance (up to ~ 2.5-fold differences). Additionally, treatments with similar total Sargassum biomass but different density revealed a negative relationship between density and fish species richness and abundance (20–30% reduction). These positive associations with Sargassum thallus biomass suggest that recruiting fishes favour the fine-scale complexity of intra-thallus spaces, rather than the larger, inter-thallus gaps. This study highlights that fine-scales of complexity within tropical macroalgal beds may influence the reef fish recruitment value of these often-underappreciated areas.
L1 slope: an overlooked spinal parameter
Authors: Iplikcioglu Ahmet Celal , Karabag Hamza 
Published: April 2024

Abstract
Objective
Lumbar lordosis can be divided into two parts by a horizontal line, creating the L1 slope and the sacral slope. Despite being a major spinopelvic parameter, the L1slope (L1S) is rarely reported. However, there is some evidence that L1S is a relatively constant parameter. This study aimed to analyze the L1 slope and its relationships with other spinopelvic parameters.

Methods
Standing lateral lumbosacral x-ray radiographies of 76 patients with low back pain and CT scans of 116 asymptomatic subjects were evaluated for spinal and spinopelvic parameters including L1 slope (L1S). The x-ray and CT groups were divided into subgroups according to mean sacral slope (SS) or pelvic incidence (PI) values. The mean values of the spinopelvic parameters and the correlations between them were investigated and compared.

Results
L1S was 19.70 and 18.15 in low SS and high SS subgroups of x-ray respectively. L1S was 7.95 and 9.36 in low and high PI subgroups of CT, respectively, and the differences were insignificant statistically. L1S was the only spinal parameter that did not change as SS or PI increased in standing and supine positions. L1S was correlated with lumbar lordosis (LL) proximal lumbar lordosis (PLL) and distal lumbar lordosis (DLL) in both x-ray and CT groups. L1S was also the strongest correlated parameter with pelvic incidence lumbar lordosis mismatch (PI-LL) mismatch in supine position.

Conclusions
L1S is a relatively constant parameter and is around 16°–18° and 8°–9° in the standing and supine positions, respectively. It was significantly correlated with LL, PLL, DLL, and PI-LL. In the standing position it was nearly equal to PLL while this equality was present in low PI subgroups of CT. There is strong evidence that L1S is significantly correlated with health-related quality of life scores.
Anti-infectious and anti-inflammatory effect of amniopatch in the treatment of spontaneous previable rupture of membranes
Authors: Alföldi Martin , Ferianec Vladimír 
Published: April 2024

AbstractSpontaneous previable rupture of membranes complicates approximately 0.4–0.7% of pregnancies and is associated with severe maternal and neonatal morbidity and mortality. Intra-amniotic inflammation is present in up to 94.4% of cases, most often caused by a bacterial infection. In comparison, the effectiveness of antibiotic therapy in its eradication reaches less than 17%. Inflammatory activity in the amniotic cavity disrupts the physiological development of the fetus with an increase in maternal, fetal, and neonatal inflammatory morbidity through the development of fetal inflammatory response syndrome, maternal chorioamnionitis, and neonatal sepsis. Amniopatch is an invasive therapeutic technique based on intra-amniotic administration of maternal hemoderivates in the form of thromboconcentrate and plasma cryoprecipitate to provide the temporary closure of the fetal membranes defect and secondary restitution of normohydramnios with correction of pressure–volume ratios. The supposed basis of this physical–mechanical action is the aggregation of coagulant components of amniopatch in the area of the defect with the formation of a valve cap. The background for the formulation of the hypothesis on the potential anti-infectious and anti-inflammatory action of non-coagulant components of amniopatch involved: i) clinical–academic and publishing outputs of the authors based on their many years’ experience with amniopatch application in the treatment of spontaneous previable rupture of membranes (2008–2019), ii) the documented absence of clinically manifested chorioamnionitis in patients treated this way with a simultaneously reduced incidence of neonatal respiratory distress syndrome compared to expectant management (tocolysis, corticotherapy, antibiotic therapy). The non-coagulant components of plasma cryoprecipitate include mainly naturally occurring isohemagglutinins, albumin, and soluble plasma fibrinogen. Although these components of the amniopatch have not been attributed a significant therapeutic role, the authors assume that due to their opsonizing and aggregative properties, they can significantly participate in optimizing the intrauterine environment through the reduction in bacterial and cytokine charge in the amniotic fluid. The authors think these facts constitute a vital stimulus to future research–academic activity and, at the same time, an idea for reconsidering the therapeutic role of amniopatch as a tool for improving perinatal results of spontaneous previable ruptures of membranes.
Amyotrophic lateral sclerosis stratification: unveiling patterns with virome, inflammation, and metabolism molecules
Authors: Niccolai Elena , Pedone Matteo , Martinelli Ilaria , Nannini Giulia , Baldi Simone , Simonini Cecilia , Di Gloria Leandro , Zucchi Elisabetta , Ramazzotti Matteo , Spezia Pietro Giorgio , Maggi Fabrizio , Quaranta Gianluca , Masucci Luca , Bartolucci Gianluca , Stingo Francesco Claudio , Mandrioli Jessica , Amedei Amedeo 
Published: April 2024

AbstractAmyotrophic lateral sclerosis (ALS) is an untreatable and clinically heterogeneous condition primarily affecting motor neurons. The ongoing quest for reliable biomarkers that mirror the disease status and progression has led to investigations that extend beyond motor neurons’ pathology, encompassing broader systemic factors such as metabolism, immunity, and the microbiome. Our study contributes to this effort by examining the potential role of microbiome-related components, including viral elements, such as torque tenovirus (TTV), and various inflammatory factors, in ALS. In our analysis of serum samples from 100 ALS patients and 34 healthy controls (HC), we evaluated 14 cytokines, TTV DNA load, and 18 free fatty acids (FFA). We found that the evaluated variables are effective in differentiating ALS patients from healthy controls. In addition, our research identifies four unique patient clusters, each characterized by distinct biological profiles. Intriguingly, no correlations were found with site of onset, sex, progression rate, phenotype, or C9ORF72 expansion. A remarkable aspect of our findings is the discovery of a gender-specific relationship between levels of 2-ethylhexanoic acid and patient survival. In addition to contributing to the growing body of evidence suggesting altered peripheral immune responses in ALS, our exploratory research underscores metabolic diversity challenging conventional clinical classifications. If our exploratory findings are validated by further research, they could significantly impact disease understanding and patient care customization. Identifying groups based on biological profiles might aid in clustering patients with varying responses to treatments.
Graphical abstract
Age-specific prevalence of the different clinical presentations of AD and FTD in young-onset dementia
Authors: Zamboni Giovanna , Maramotti Riccardo , Salemme Simone , Tondelli Manuela , Adani Giorgia , Vinceti Giulia , Carbone Chiara , Filippini Tommaso , Vinceti Marco , Pagnoni Giuseppe , Chiari Annalisa 
Published: April 2024

Abstract
Background
Studies have shown that the prevalence of all-variants Alzheimer’s disease (AD) and frontotemporal dementia (FTD) both increase with age, even before the age of 65. However, it is not known whether their different clinical presentations all increase in prevalence with age in the same way.

Methods
We studied the prevalence of the different clinical presentations of young-onset AD and FTD by 5-year age groups in a population-based study identifying all dementia patients with a diagnosis of AD and FTD and symptoms onset before age 65 in the Modena province, Italy. By using regression models of cumulative occurrences, we also estimated age-specific prevalence and compared the growth curves of the clinical presentations.

Results
The prevalence of all-variants AD increased with age, from 18/1,000,000 in the 40–44 age group to 1411/1,000,000 in the 60–64 age group. The prevalence of all-variants FTD also increased with age, from 18/1,000,000 to 866/1,000,000. An estimation of age-specific prevalence functions of each clinical presentation showed that atypical non-amnestic AD and aphasic FTD grew the most in early ages, followed by the behavioural variant of FTD (bvFTD). Then, around the age of 60, amnestic AD took over and its age-specific prevalence continued to increase disproportionally compared to all the other clinical variants of AD and FTD, which, instead, started to decrease in prevalence.

Conclusions
Amnestic AD is the clinical presentation that increases the most with advancing age, followed by bvFTD, suggesting that there is a differential vulnerability to the effect of ageing within the same neurodegenerative disease.
Modelling multidecadal variability in flood frequency using the Two-Component Extreme Value distribution
Authors: Totaro Vincenzo , Gioia Andrea , Kuczera George , Iacobellis Vito 
Published: April 2024

AbstractThe Two-Component Extreme Value (TCEV) distribution is traditionally known as the exact distribution of extremes arising from Poissonian occurrence of a mixture of two exponential exceedances. In some regions, flood frequency is affected by low-frequency (decadal) climate fluctuations resulting in wet and dry epochs. We extend the exact distribution of extremes approach to such regions to show that the TCEV arises as the distribution of annual maximum floods for Poissonian occurrences and (at least two) exponential exceedances. A case study using coastal basins in Queensland and New South Wales (Australia) affected by low-frequency climate variability, shows that the TCEV produces good fits to the marginal distribution over the entire range of observed values without the explicit need to resort to climate covariates and removal of potentially influential low values. Moreover, the TCEV reproduces the observed dog-leg, a key signature of different flood generation processes. A literature review shows that the assumptions underpinning the TCEV are conceptually consistent with available evidence on climate and flood mechanisms in these basins. We provide an extended domain of the TCEV distribution in the L-moment ratio diagram to account for the wider range of parameter values encountered in the case study and show that for all basins, L-skew and L-kurtosis fall within the extended domain of the TCEV.
Hierarchical reinforcement Thompson composition
Authors: Tanık Güven Orkun , Ertekin Şeyda 
Published: April 2024

AbstractModern real-world control problems call for continuous control domains and robust, sample efficient and explainable control frameworks. We are presenting a framework for recursively composing control skills to solve compositional and progressively complex tasks. The framework promotes reuse of skills, and as a result quick adaptability to new tasks. The decision tree can be observed, providing insight into the agents’ behavior. Furthermore, the skills can be transferred, modified or trained independently, which can simplify reward shaping and increase training speeds considerably. This paper is concerned with efficient composition of control algorithms using reinforcement learning and soft attention. Compositional and temporal abstraction is the key to improving learning and planning in reinforcement learning. Our Thompson sampling inspired soft-attention model is demonstrated to efficiently solve the composition problem.
Intramedullary versus plate fixation of both bone forearm fractures in skeletally immature patients: a systematic review and meta-analysis
Authors: Ahmed Ahmed Mohamed , Said Elsayed , Addosooki Ahmad , Attya Hossam Ahmed , Awad Ahmad Khairy , Ahmed Emad Hamdy , Tammam Hamdy 
Published: April 2024

Abstract
Background
Both bone forearm fractures (BBFFs) are a common injury amongst the pediatric population. The main indications of surgical fixation are open, irreducible, or unstable fractures. The two most commonly used surgical techniques are closed or open reduction with intramedullary fixation (IMF) and open reduction with plate fixation (PF). The aim of this systematic review and meta-analysis was to determine which fixation method is superior for BBFFs.

Methods
PubMed, Scopus, Web of Science, and CENTRAL were searched to identify studies comparing IMF and PF. We extracted data on union rates, complications, early hardware removal rates, reoperation rates, and radiographic, clinical, and perioperative outcomes.

Results
Sixteen studies were included in the analysis, with a total of 922 patients (539 IMF and 383 PF). Similar union rates were achieved by both fixation technique. IMF was associated with a higher incidence of symptomatic hardware, and early hardware removal. Better restoration of the radial bow was observed with the PF group, especially in older children and adolescents. The rate of excellent function was comparable between groups, whereas better cosmesis was reported with the IMF group. Despite shorter fluoroscopy time and immobilization time, PF demonstrated longer tourniquet time, operating time, and hospital stay compared to IMF.

Conclusions
We found no significant difference between IMF and PF in terms of union rates and functional outcomes taking in consideration the merits and demerits of each technique. High-quality randomized controlled trials are, therefore, necessary to determine the superiority of one fixation technique over the other.

Level of evidence
III.