bluuebunny/crossref_metadata_2025_split huggingface dataset:
NT-proBNP for Predicting All-Cause Death and Heart Transplant in Children and Adults with Heart Failure
Authors: Schmitt Walter , Diedrich Christian , Hamza Taye H. , Meyer Michaela , Eissing Thomas , Breitenstein Stefanie , Rossano Joseph W. , Lipshultz Steven E. 
Published: May 2024

Abstract
Plasma N-terminal prohormone B-type natriuretic peptide (NT-proBNP) concentration is a heart failure (HF) biomarker in adults and children. Its prognostic value for HF-related events has been established only in adults. Therefore, we aimed to test the hypothesis that plasma NT-proBNP concentrations predicted the risk of heart transplantation or death in children with HF. We studied the medical records of 109 children with HF enrolled in the IBM Watson Explorys database and from 150 children enrolled in the Pediatric Cardiomyopathy Registry (PCMR). Nonlinear regression was used to assess the relationship between plasma NT-proBNP concentrations and the risk of events in the two cohorts. All children in the PCMR cohort had dilated cardiomyopathy. The Explorys cohort also included children with congenital cardiovascular malformations. Median plasma NT-proBNP concentrations were 1250 pg/mL and 184 pg/mL in the Explorys and PCMR cohorts, respectively. The percentage of deaths/heart transplantations was 7%/22%, over 2 years in the Explorys cohort and 3%/16% over 5 years in the PCMR cohort. Mean estimates of plasma NT-proBNP concentration indicative of half-maximum relative risk for events (EC50 values) at 2 and 5 years were 3730 pg/mL and 4199 pg/mL, respectively, values both close to the mean of 3880 pg/mL established for adults with HF. The plasma NT-proBNP concentration is suitable for estimating relative risk of mortality and heart transplantation in children with HF, independent of etiology and shows similar relations to clinical outcomes as in adults, indicating its likely value as a surrogate marker both for adult and pediatric HF.
ClinicalTrials.gov Identifiers: NCT00005391 (May 26, 2000), NCT01873976 (June 10, 2013).
Pre-therapy PET-based voxel-wise dosimetry prediction by characterizing intra-organ heterogeneity in PSMA-directed radiopharmaceutical theranostics
Authors: Xue Song , Gafita Andrei , Zhao Yu , Mercolli Lorenzo , Cheng Fangxiao , Rauscher Isabel , D’Alessandria Calogero , Seifert Robert , Afshar-Oromieh Ali , Rominger Axel , Eiber Matthias , Shi Kuangyu 
Published: May 2024

Abstract
Background and objective
Treatment planning through the diagnostic dimension of theranostics provides insights into predicting the absorbed dose of RPT, with the potential to individualize radiation doses for enhancing treatment efficacy. However, existing studies focusing on dose prediction from diagnostic data often rely on organ-level estimations, overlooking intra-organ variations. This study aims to characterize the intra-organ theranostic heterogeneity and utilize artificial intelligence techniques to localize them, i.e. to predict voxel-wise absorbed dose map based on pre-therapy PET.

Methods
23 patients with metastatic castration-resistant prostate cancer treated with [177Lu]Lu-PSMA I&T RPT were retrospectively included. 48 treatment cycles with pre-treatment PET imaging and at least 3 post-therapeutic SPECT/CT imaging were selected. The distribution of PET tracer and RPT dose was compared for kidney, liver and spleen, characterizing intra-organ heterogeneity differences. Pharmacokinetic simulations were performed to enhance the understanding of the correlation. Two strategies were explored for pre-therapy voxel-wise dosimetry prediction: (1) organ-dose guided direct projection; (2) deep learning (DL)-based distribution prediction. Physical metrics, dose volume histogram (DVH) analysis, and identity plots were applied to investigate the predicted absorbed dose map.

Results
Inconsistent intra-organ patterns emerged between PET imaging and dose map, with moderate correlations existing in the kidney (r = 0.77), liver (r = 0.5), and spleen (r = 0.58) (P < 0.025). Simulation results indicated the intra-organ pharmacokinetic heterogeneity might explain this inconsistency. The DL-based method achieved a lower average voxel-wise normalized root mean squared error of 0.79 ± 0.27%, regarding to ground-truth dose map, outperforming the organ-dose guided projection (1.11 ± 0.57%) (P < 0.05). DVH analysis demonstrated good prediction accuracy (R2 = 0.92 for kidney). The DL model improved the mean slope of fitting lines in identity plots (199% for liver), when compared to the theoretical optimal results of the organ-dose approach.

Conclusion
Our results demonstrated the intra-organ heterogeneity of pharmacokinetics may complicate pre-therapy dosimetry prediction. DL has the potential to bridge this gap for pre-therapy prediction of voxel-wise heterogeneous dose map.
The impact of PET/CT and brain MRI for metastasis detection among patients with clinical T1-category lung cancer: Findings from a large-scale cohort study
Authors: Feng Yi , Cheng Bo , Zhan Shuting , Liu Haiping , Li Jianfu , Chen Peiling , Wang Zixun , Huang Xiaoyan , Fu Xiuxia , Ye Wenjun , Wang Runchen , Wang Qixia , Xiang Yang , Wang Huiting , Zhu Feng , Zheng Xin , Fu Wenhai , Hu Guodong , Chen Zhuxing , He Jianxing , Liang Wenhua 
Published: May 2024

Abstract
Purpose
[18F]-FDG PET/CT and brain MRI are common approaches to detect metastasis in patients of lung cancer. Current guidelines for the use of PET/CT and MRI in clinical T1-category lung cancer lack risk-based stratification and require optimization. This study stratified patients based on metastatic risk in terms of the lesions' size and morphological characteristics.

Methods
The detection rate of metastasis was measured in different sizes and morphological characteristics (solid and sub-solid) of tumors. To confirm the cut-off value for discriminating metastasis and overall survival (OS) prediction, the receiver operating characteristic (ROC) analysis was performed based on PET/CT metabolic parameters (SUVmax/SUVmean/SULpeak/MTV/TLG), followed by Kaplan–Meier analysis for survival in post-operation patients with and without PET/CT plus MRI.

Results
2,298 patients were included. No metastasis was observed in patients with solid nodules < 8.0 mm and sub-solid nodules < 10.0 mm. The cut-off of PET/CT metabolic parameters on discriminating metastasis were 1.09 (SUVmax), 0.26 (SUVmean), 0.31 (SULpeak), 0.55 (MTV), and 0.81 (TLG), respectively. Patients undergoing PET/CT plus MRI exhibited longer OS compared to those who did not receive it in solid nodules ≥ 8.0 mm & sub-solid nodules ≥ 10.0 mm (HR, 0.44; p < 0.001); in solid nodules ≥ 8.0 mm (HR, 0.12; p<0.001) and in sub-solid nodules ≥ 10.0 mm (HR; 0.61; p=0.075), respectively. Compared to patients with metabolic parameters lower than cut-off values, patients with higher metabolic parameters displayed shorter OS: SUVmax (HR, 12.94; p < 0.001), SUVmean (HR, 11.33; p <0.001), SULpeak (HR, 9.65; p < 0.001), MTV (HR, 9.16; p = 0.031), and TLG (HR, 12.06; p < 0.001).

Conclusion
The necessity of PET/CT and MRI should be cautiously evaluated in patients with solid nodules < 8.0 mm and sub-solid nodules < 10.0 mm, however, these examinations remained essential and beneficial for patients with solid nodules ≥ 8.0 mm and sub-solid nodules ≥ 10.0 mm.
A Novel Approach for Treating Lipomas: Percutaneous Microwave Ablation Combined with Liposuction
Authors: Chen Shuxun , Qiu Yinrong , Lin Li , Lin Jianhuang , Lu Yizhuo 
Published: May 2024

AbstractLipomas, benign adipose tissue tumors, are a common occurrence but currently, the options for their treatment are limited, with surgical excision being the most frequently used management pathway. This scenario can often lead to unsatisfactory cosmetic results and significant patient discomfort. This paper introduces a novel technique, percutaneous microwave ablation with liposuction, to address these challenges. The innovative procedure aims to enhance patient satisfaction, minimize post-operative discomfort, and improve aesthetic outcomes. The technique involves two key steps: (1) the application of percutaneous microwave ablation to selectively disrupt the lipoma cells, followed by (2) a targeted liposuction procedure to remove the ablated lipoma tissue. Our approach optimizes the removal of the lipoma and preserves the surrounding healthy tissue, reducing the risk of local recurrence and improving the cosmetic result. The use of preoperative ultrasound imaging allows for precise localization and delineation of the lipoma, aiding in the planning and execution of the procedure. This novel approach to lipoma treatment is reliable, associated with minimal morbidity, and consistently yields effective results. Additionally, it provides a new perspective on lipoma management, potentially changing the paradigm of current treatment approaches.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Copper tantalum nitride (CuTaN2) thin films prepared by reactive radio-frequency magnetron sputtering
Authors: Islam Md Maidul , Ranga Abhishek Goud , Borra Vamsi , Georgiev Daniel G. 
Published: May 2024

AbstractRF reactive sputtering was used to deposit copper tantalum nitride (CuTaN2) films from a Cu/Ta target in an environment containing a mixture of argon and nitrogen at two different substrate temperatures: room temperature and 200 °C. The films were studied by SEM, EDS, XRD, Raman spectroscopy, spectrophotometry, and resistivity measurements. The deposition conditions significantly impacted the morphology of the films, which varied from smooth, void-free films at high nitrogen concentrations and at room temperature substrates to cauliflower-like grains with voids at low nitrogen contents and elevated substrate temperatures. Despite the target’s 1:1 Cu: Ta ratio, the stoichiometric analysis showed a lower Ta content in the deposited film. The films produced on silicon substrates were polycrystalline, whereas those deposited on glass substrates were amorphous. The band gap (0.9 eV to 1.55 eV) and film resistivity (20 kΩ-cm to 76 kΩ-cm) are strongly affected by the nitrogen fraction in the sputtering gas. Increasing the nitrogen percentage in semiconductor films results in smoother films with larger bandgaps (approximately 1.5 eV), higher resistivity, and compositions closest to those of stoichiometric CuTaN2.
Physiological aging and inflammation-induced cellular senescence may contribute to oligodendroglial dysfunction in MS
Authors: Windener Farina , Grewing Laureen , Thomas Christian , Dorion Marie-France , Otteken Marie , Kular Lara , Jagodic Maja , Antel Jack , Albrecht Stefanie , Kuhlmann Tanja 
Published: May 2024

AbstractAging affects all cell types in the CNS and plays an important role in CNS diseases. However, the underlying molecular mechanisms driving these age-associated changes and their contribution to diseases are only poorly understood. The white matter in the aging brain as well as in diseases, such as Multiple sclerosis is characterized by subtle abnormalities in myelin sheaths and paranodes, suggesting that oligodendrocytes, the myelin-maintaining cells of the CNS, lose the capacity to preserve a proper myelin structure and potentially function in age and certain diseases. Here, we made use of directly converted oligodendrocytes (dchiOL) from young, adult and old human donors to study age-associated changes. dchiOL from all three age groups differentiated in an comparable manner into O4 + immature oligodendrocytes, but the proportion of MBP + mature dchiOL decreased with increasing donor age. This was associated with an increased ROS production and upregulation of cellular senescence markers such as CDKN1A, CDKN2A in old dchiOL. Comparison of the transcriptomic profiles of dchiOL from adult and old donors revealed 1324 differentially regulated genes with limited overlap with transcriptomic profiles of the donors’ fibroblasts or published data sets from directly converted human neurons or primary rodent oligodendroglial lineage cells. Methylome analyses of dchiOL and human white matter tissue samples demonstrate that chronological and epigenetic age correlate in CNS white matter as well as in dchiOL and resulted in the identification of an age-specific epigenetic signature. Furthermore, we observed an accelerated epigenetic aging of the myelinated, normal appearing white matter of multiple sclerosis (MS) patients compared to healthy individuals. Impaired differentiation and upregulation of cellular senescence markers could be induced in young dchiOL in vitro using supernatants from pro-inflammatory microglia. In summary, our data suggest that physiological aging as well as inflammation-induced cellular senescence contribute to oligodendroglial pathology in inflammatory demyelinating diseases such as MS.
NRN1 epistasis with BDNF and CACNA1C: mediation effects on symptom severity through neuroanatomical changes in schizophrenia
Authors: Almodóvar-Payá Carmen , Guardiola-Ripoll Maria , Giralt-López Maria , Oscoz-Irurozqui Maitane , Canales-Rodríguez Erick Jorge , Madre Mercè , Soler-Vidal Joan , Ramiro Núria , Callado Luis F. , Arias Bárbara , Gallego Carme , Pomarol-Clotet Edith , Fatjó-Vilas Mar 
Published: May 2024

AbstractThe expression of Neuritin-1 (NRN1), a neurotrophic factor crucial for neurodevelopment and synaptic plasticity, is enhanced by the Brain Derived Neurotrophic Factor (BDNF). Although the receptor of NRN1 remains unclear, it is suggested that NRN1’s activation of the insulin receptor (IR) pathway promotes the transcription of the calcium voltage-gated channel subunit alpha1 C (CACNA1C). These three genes have been independently associated with schizophrenia (SZ) risk, symptomatology, and brain differences. However, research on how they synergistically modulate these phenotypes is scarce. We aimed to study whether the genetic epistasis between these genes affects the risk and clinical presentation of the disorder via its effect on brain structure. First, we tested the epistatic effect of NRN1 and BDNF or CACNA1C on (i) the risk for SZ, (ii) clinical symptoms severity and functionality (onset, PANSS, CGI and GAF), and (iii) brain cortical structure (thickness, surface area and volume measures estimated using FreeSurfer) in a sample of 86 SZ patients and 89 healthy subjects. Second, we explored whether those brain clusters influenced by epistatic effects mediate the clinical profiles. Although we did not find a direct epistatic impact on the risk, our data unveiled significant effects on the disorder’s clinical presentation. Specifically, the NRN1-rs10484320 x BDNF-rs6265 interplay influenced PANSS general psychopathology, and the NRN1-rs4960155 x CACNA1C-rs1006737 interaction affected GAF scores. Moreover, several interactions between NRN1 SNPs and BDNF-rs6265 significantly influenced the surface area and cortical volume of the frontal, parietal, and temporal brain regions within patients. The NRN1-rs10484320 x BDNF-rs6265 epistasis in the left lateral orbitofrontal cortex fully mediated the effect on PANSS general psychopathology. Our study not only adds clinical significance to the well-described molecular relationship between NRN1 and BDNF but also underscores the utility of deconstructing SZ into biologically validated brain-imaging markers to explore their mediation role in the path from genetics to complex clinical manifestation.
RRP8, associated with immune infiltration, is a prospective therapeutic target in hepatocellular carcinoma
Authors: You Kai , Du Xingxing , Zhao Yunzheng , Wen Fukai , Lu Zhaoyang , Fan Huitao 
Published: May 2024

Abstract
Background
Ribosomal RNA Processing 8 (RRP8) is a nucleolar Rossman fold-like methyltransferase that exhibits increased expression in many malignant tumours. However, the role of RRP8 in hepatocellular carcinoma (HCC) is still uncertain. We explored the relationships between RRP8 and prognosis and immune infiltration, as well as the putative pathological function and mechanism of RRP8 in HCC.

Methods
Analysis of RRP8 expression across cancers was performed by using multiple databases. Associations between RRP8 expression and clinicopathological factors were further examined. Gene enrichment analysis was used to identify various putative biological activities and regulatory networks of RRP8 in HCC. The relationship between RRP8 expression and immune infiltration was confirmed by single-sample gene set enrichment analysis (ssGSEA). Univariate and multivariate Cox regression analyses were conducted to assess the impact of clinical variables on patient outcomes. Furthermore, a nomogram was constructed to estimate survival probability based on multivariate Cox regression analysis. Functional validation of RRP8 in HCC was performed with two different systems: doxycycline-inducible shRNA knockdown and CRISPR-Cas9 knockout.

Results
RRP8 was markedly overexpressed in HCC clinical specimens compared to adjacent normal tissues. Further analysis demonstrated that RRP8 was directly connected to multiple clinical characteristics and strongly associated with various immune markers in HCC. Moreover, elevated RRP8 expression indicated an unfavourable prognosis. Our functional studies revealed that both knockdown and knockout of RRP8 dramatically attenuated liver cancer cells to proliferate and migrate. Knockout of RRP8 decreased the phosphorylation of MEK1/2 and β-catenin-(Y654) signalling pathway components; downregulated downstream signalling effectors, including Cyclin D1 and N-cadherin; and upregulated E-cadherin.

Conclusions
RRP8 is strongly implicated in immune infiltration and could be a potential therapeutic target in HCC.
Comprehensive molecular analyses of cuproptosis-related genes with regard to prognosis, immune landscape, and response to immune checkpoint blockers in lung adenocarcinoma
Authors: Li Ruixia , Tong Run , Zhang Jasmine Lin , Zhang Zhe , Deng Mingming , Hou Gang 
Published: May 2024

Abstract
Background
Recent studies have emphasized the importance of the biological processes of different forms of cell death in tumor heterogeneity and anti-tumor immunity. Nonetheless, the relationship between cuproptosis and lung adenocarcinoma (LUAD) remains largely unexplored.

Methods
Data for 793 LUAD samples and 59 normal lung tissues obtained from TCGA-LUAD cohort GEO datasets were used in this study. A total of 165 LUAD tissue samples and paired normal lung tissue samples obtained from our hospital were used to verify the prognostic value of dihydrolipoamide S-acetyltransferase (DLAT) and dihydrolipoamide branched chain transacylase E2 (DBT) for LUAD. The cuproptosis-related molecular patterns of LUAD were identified using consensus molecular clustering. Recursive feature elimination with random forest and a tenfold cross-validation method was applied to construct the cuproptosis score (CPS) for LUAD.

Results
Bioinformatic and immunohistochemistry (IHC) analyses revealed that 13 core genes of cuproptosis were all significantly elevated in LUAD tissues, among which DBT and DLAT were associated with poor prognosis (DLAT, HR = 6.103; DBT, HR = 4.985). Based on the expression pattern of the 13 genes, two distinct cuproptosis-related patterns have been observed in LUAD: cluster 2 which has a relatively higher level of cuproptosis was characterized by immunological ignorance; conversely, cluster 1 which has a relatively lower level of cuproptosis is characterized by TILs infiltration and anti-tumor response. Finally, a scoring scheme termed the CPS was established to quantify the cuproptosis-related pattern and predict the prognosis and the response to immune checkpoint blockers of each individual patient with LUAD.

Conclusion
Cuproptosis was found to influence tumor microenvironment (TME) characteristics and heterogeneity in LUAD. Patients with a lower CPS had a relatively better prognosis, more abundant immune infiltration in the TME, and an enhanced response to immune checkpoint inhibitors.
Groundwater salinization risk in coastal regions triggered by earthquake-induced saltwater intrusion
Authors: Kuriqi Alban , Abd-Elaty Ismail 
Published: May 2024

AbstractAnthropogenic factors such as over-pumping and natural events such as earthquakes impact coastal aquifers by reducing freshwater recharge, aquifer water budgets, and increasing saltwater intrusion (SWI). This study investigates the impact of hydrodynamic forces induced by earthquakes on SWI in one hypothetical case, namely, the Henry problem, and a real case of the Biscayne aquifer located in Florida, USA. The analysis was carried out using the analytical solution of estimating the earthquake’s induced hydrodynamic pressure and applying the SEAWAT code to investigate the SWI for the base case and three scenarios, namely for the horizontal acceleration (αh) by 0.10 g, 0.20 g, and 0.30 g. The results show that earthquakes might considerably increase the SWI in coastal aquifers. Moreover, the rise in salinity across expansive land areas significantly threatens agricultural productivity and jeopardizes food security. Namely, in the case of Biscayne aquifer, salinity was increased by 12.10%, 21.90%, and 45.70% for the horizontal seismic acceleration of 0.1 g, 0.20 g, and 0.30 g, respectively. Hence, the conclusions drawn from this study underscore the need for carefull consideration of earthquake impacts in future planning and water management strategies for coastal regions. This proactive approach is crucial to preemptively address and mitigate the groundwater salinization hazard associated with SWI fluctuations due to earthquakes.
Design and characterization of a silicon MEMS microvalve for proportional flow control based on electrostatic bending actuators
Authors: Jongmanns Marcel , Kaiser Bert , Ruffert Christine , Langa Sergiu 
Published: May 2024

Abstract
We designed a MEMS microvalve based on the nanoscopic electrostatic drive (NED) technology (Nat Commun 6:10078, 2015). NED actuators, electrostatically controlled bending beams, are implemented in a clamped-clamped configuration. A normally open plunger valve was designed and characterized. The device is manufactured from silicon. Gas flow rates of up to 37 SCCM can be proportionally controlled between 10% and 100%. A 10% leakage is always present at low backpressures (< 10 kPa) and increases to roughly 20% at 75 kPa backpressure. The structure has been tested up to backpressures of 300 kPa without damage to the structures, but the leakage increases to over 95%. Our unprecedented microvalve concept shows that it is possible to manufacture all-silicon MEMS microvalves with proportional control of the flow rate. The presented work is a proof of concept to test the capabilities of the NED technology for the use in microvalves. There are plans to decrease the leakage in future designs by introducing an additional sealing layer as well as manufacturing a shutter instead of a plunger design.
The stock market reaction to political and economic changes: the Spanish case
Authors: Castaño Leticia , Farinós José E. , Ibáñez Ana M. 
Published: May 2024

AbstractAs other European countries, Spain has experienced a turmoil in which new political parties emerged with force after the global financial crisis in 2008. In this context, we analyze whether the empirical implications of the opportunistic and partisan theories, as well as the Uncertain Information Hypothesis, are met in the Spanish stock market, considering the size and the industry of the companies. The horizon of our study takes into account the seven general elections, 24 regional elections and 4 European elections held from 2002 to 2019, period in which Spain is fully integrated in the economic and monetary union and under the macroeconomic imbalance procedure. Our results do not support the opportunistic and partisan theories, or the Uncertain Information Hypothesis. Our evidence suggests that the short-term negative market reaction to the general elections is linked to the uncertainty with a change in the political sign of the incumbent. Besides, it is not related to size or industry characteristics.