bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of pseudoaneurysm after follow‐up computed tomography for nonoperatively managed splenic injury: Systematic review
Authors: Aoki Makoto , Utsumi Shu , Terayama Takero , Katsura Morihiro , Matsushima Kazuhide 
Published: June 2024

AbstractBackgroundThe aim of this systematic review was to assess the estimated incidence of pseudoaneurysm (PSA) with follow‐up computed tomography (CT) for adult splenic injury with nonoperative management (NOM).MethodsA systematic literature search was conducted in MEDLINE, Central, CINAHL, Clinical Trials, and ICTRP databases between January 1, 2010, and December 31, 2023. Quality assessment was performed using the Risk of Bias in Non‐randomized Studies of Exposures (ROBINS‐E) tool. Adult splenic injury patients who were initially managed with NOM and followed‐up by protocolized CT were included. The primary outcome was the incidence of delayed PSA. Secondary outcome measures were delayed angiography and delayed splenectomy. Subgroup analyses were performed between NOM patients without initial splenic angioembolization (SAE) and NOM patients with initial SAE.ResultsTwelve studies were enrolled, including 11 retrospective studies and one prospective study, with 1746 patients in total. The follow‐up CT rate in the included patients was 94.9%. The estimated incidence of PSA was 14% (95% confidence interval (CI), 8%–21%). The estimated delayed angiography and delayed splenectomy incidence rates were 7% (95% CI, 4%–12%) and 2% (95% CI, 1%–6%), respectively. Subgroup analyses showed that the estimated PSA incidence was 12% in NOM patients without initial SAE (95% CI, 7%–20%) and was also 12% in NOM patients with SAE (95% CI, 5%–24%).ConclusionsThe estimated incidence of delayed PSA after follow‐up CT for adult splenic injury with NOM was 14%. The estimated incidence of PSA in NOM with initial SAE was similar to that in NOM without initial SAE.
Wigner analysis of fourier integral operators with symbols in the Shubin classes
Authors: Cordero Elena , Giacchi Gianluca , Rodino Luigi , Valenzano Mario 
Published: June 2024

AbstractWe study the decay properties of Wigner kernels for Fourier integral operators of types I and II. The symbol spaces that allow a nice decay of these kernels are the Shubin classes $$\Gamma ^m({\mathbb {R}^{2d}})$$

Γ
m

(

R

2
d

)

, with negative order m. The phases considered are the so-called tame ones, which appear in the Schrödinger propagators. The related canonical transformations are allowed to be nonlinear. It is the nonlinearity of these transformations that are the main obstacles for nice kernel localizations when symbols are taken in the Hörmander’s class $$S^{0}_{0,0}({\mathbb {R}^{2d}})$$

S

0
,
0

0

(

R

2
d

)

. Here we prove that Shubin classes overcome this problem and allow a nice kernel localization, which improves with the decreasing of the order m.
Tabak Harm Reduction: Die Notwendigkeit eines Paradigmenwechsels in der deutschen Tabakkontrollpolitik
Authors: Steimle Larissa , Grabski Meryem , Stöver Heino 
Published: June 2024

ZusammenfassungDer Konsum von Tabak ist nach wie vor das größte vermeidbare Gesundheitsrisiko in Deutschland. Jährlich sterben über 127.000 Menschen vorzeitig an den Folgen des Tabakkonsums – jede fünfte Krebsneuerkrankung ist eine Folge des Rauchens. Während Deutschland im internationalen Vergleich mit der derzeitigen Tabakkontrollpolitik bestehend aus Werbeverboten, einer Förderung von rauchfreien Umgebungen sowie einem alleinigen Abstinenzparadigma nur sehr schleppend eine Veränderung herbeiführt, zeigen uns andere Länder, wie durch eine Integration von „Harm Reduction“ (Konzept der Schadensminimierung) als ergänzende Maßnahme sowie eine deutlich aktivere Unterstützung von ausstiegswilligen Menschen die Zahl der Raucher*innen gesenkt und dadurch Todesfälle verhindert werden können. Dieser Beitrag stellt zunächst die aktuelle Lage sowie die aktuellen Maßnahmen in Deutschland vor. Aus einem Blick in das Vereinigte Königreich, das mit seiner Tabakkontrollpolitik europaweit als Vorreiter gilt, sowie einer Zusammenfassung des aktuellen Forschungsstandes werden Empfehlungen für Veränderungen der derzeitigen Tabakkontrollpolitik in Deutschland abgeleitet.
Identification of an HLA-A*11:01-restricted neoepitope of mutant PIK3CA and its specific T cell receptors for cancer immunotherapy targeting hotspot driver mutations
Authors: Shen Meiying , Chen Siyin , Han Xiaojian , Hao Yanan , Wang Junfan , Li Luo , Chen Tong , Wang Bozhi , Zou Lin , Zhang Tong , Zhang Wanli , Han Xiaxia , Wang Wang , Yu Haochen , Li Kang , Liu Shengchun , Jin Aishun 
Published: June 2024

AbstractHotspot driver mutations presented by human leukocyte antigens might be recognized by anti-tumor T cells. Based on their advantages of tumor-specificity and immunogenicity, neoantigens derived from hotspot mutations, such as PIK3CAH1047L, may serve as emerging targets for cancer immunotherapies. NetMHCpan V4.1 was utilized for predicting neoepitopes of PIK3CA hotspot mutation. Using in vitro stimulation, antigen-specific T cells targeting the HLA-A*11:01-restricted PIK3CA mutation were isolated from healthy donor-derived peripheral blood mononuclear cells. T cell receptors (TCRs) were cloned using single-cell PCR and sequencing. Their functionality was assessed through T cell activation markers, cytokine production and cytotoxic response to cancer cell lines pulsed with peptides or transduced genes of mutant PIK3CA. Immunogenic mutant antigens from PIK3CA and their corresponding CD8+ T cells were identified. These PIK3CA mutation-specific CD8+ T cells were subsequently enriched, and their TCRs were isolated. The TCR clones exhibited mutation-specific and HLA-restricted reactivity, demonstrating varying degrees of functional avidity. Identified TCR genes were transferred into CD8+ Jurkat cells and primary T cells deficient of endogenous TCRs. TCR-expressing cells demonstrated specific recognition and reactivity against the PIK3CAH1047L peptide presented by HLA-A*11:01-expressing K562 cells. Furthermore, mutation-specific TCR-T cells demonstrated an elevation in cytokine production and profound cytotoxic effects against HLA-A*11:01+ malignant cell lines harboring PIK3CAH1047L. Our data demonstrate the immunogenicity of an HLA-A*11:01-restricted PIK3CA hotspot mutation and its targeting therapeutic potential, together with promising candidates of TCR-T cell therapy.
USP47 deficiency in mice modulates tumor infiltrating immune cells and enhances antitumor immune responses in prostate cancer
Authors: Wang Qian-Lan , Lu Shun-Yuan , Xu Dan-Dan , Ma Jin-Xia , Guo Rui , Zhang Lu , Tang Ling-Yun , Shen Yan , Shen Chun-Ling , Wang Jin-Jin , Wu Ying-Li , Lu Li-Ming , Wang Zhu-Gang , Zhang Hong-Xin 
Published: June 2024

AbstractThis study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.
MB2033, an anti-PD-L1 × IL-2 variant fusion protein, demonstrates robust anti-tumor efficacy with minimal peripheral toxicity
Authors: Park Young Jin , Kim Suna , Bang Hyoju , Kang Seok Chan , Cho Sunjung , Park Jun-Eui , Jung Sungyoub , Kim Ha Hyung 
Published: June 2024

AbstractInterleukin-2 (IL-2), a cytokine with pleiotropic immune effects, was the first approved cancer immunotherapy agent. However, IL-2 is associated with systemic toxicity due to binding with its ligand IL-2Rα, such as vascular leakage syndrome, limiting its clinical applications. Despite efforts to extend the half-life of IL-2 and abolish IL-2Rα interactions, the risk of toxicity remains unresolved. In this study, we developed the bispecific fusion protein MB2033, comprising a novel IL-2 variant (IL-2v) connected to anti-programmed death ligand 1 (PD-L1) via a silenced Fc domain. The IL-2v of MB2033 exhibits attenuated affinity for IL-2Rβγ without binding to IL-2Rα. The binding affinity of MB2033 for PD-L1 is greater than that for IL-2Rβγ, indicating its preferential targeting of PD-L1+ tumor cells to induce tumor-specific immune activation. Accordingly, MB2033 exhibited significantly reduced regulatory T cell activation, while inducing comparable CD8+ T cell activation to recombinant human IL-2 (rhIL-2). MB2033 induced lower immune cell expansion and reduced cytokine levels compared with rhIL-2 in human peripheral blood mononuclear cells, indicating a decreased risk of peripheral toxicity. MB2033 exhibited superior anti-tumor efficacy, including tumor growth inhibition and complete responses, compared with avelumab monotherapy in an MC38 syngeneic mouse model. In normal mice, MB2033 was safer than non-α IL-2v and tolerable up to 30 mg/kg. These preclinical results provide evidence of the dual advantages of MB2033 with an enhanced safety and potent clinical efficacy for cancer treatment.
Analysis of PD-L1 promoter methylation combined with immunogenic context in pancreatic ductal adenocarcinoma
Authors: Chen Xinyuan , Yu Shuangni , Chen Jie , Chen Xianlong 
Published: June 2024

AbstractDespite the successful application of programmed cell death ligand 1 (PD-L1)-blocking strategies in some types of cancers and well-established prognostic indicators in pancreatic ductal adenocarcinoma (PDAC), the biological and clinical implications of the methylation status of PD-L1/PD-L2 in PDAC remain largely unknown. Therefore, this study aimed to explore the biological role of PD-L1/PD-L2 methylation and its association with clinicopathological features, clinical outcomes, and the immune microenvironment by analyzing the data on PD-L1/PD-L2 methylation and mRNA expression in PDAC cohorts obtained from the Cancer Genome Atlas and International Cancer Genome Consortium. The correlation between PD-L1 promoter methylation and PD-L1 expression and survival was further validated in an independent validation cohort (Peking Union Medical College Hospital [PUMCH] cohort) using pyrosequencing and immunohistochemistry. These results demonstrated that hypomethylation of the PD-L1 promoter was strongly associated with upregulated PD-L1 expression and shorter overall survival in PDAC. Multivariate Cox regression analyses revealed that the PD-L1 promoter methylation was an independent prognostic factor. PD-L1 promoter hypomethylation and high expression were related to aggressive clinical phenotypes. Moreover, both PD-L1 and PD-L2 methylation correlated with immune cell infiltration and the expression of immune checkpoint genes. PD-L1 promoter methylation status was further validated as an independent prognostic biomarker in patients with PDAC using the PUMCH cohort. The prognostic significance of PD-L1 promoter methylation was more discriminative in tumors with perineural/lymphovascular invasion and distant metastasis than in those without perineural/lymphovascular invasion and distant metastasis. In summary, the methylation status of the PD-L1 promoter is a promising biomarker for survival outcomes, immune infiltration, and the potential immune benefits of immunotherapy in PDAC.
Alteration of gene expression and protein solubility of the PI 5-phosphatase SHIP2 are correlated with Alzheimer’s disease pathology progression
Authors: Ando Kunie , Küçükali Fahri , Doeraene Emilie , Nagaraj Siranjeevi , Antonelli Eugenia Maria , Thazin Htut May , Yilmaz Zehra , Kosa Andreea-Claudia , Lopez-Guitierrez Lidia , Quintanilla-Sánchez Carolina , Aydin Emmanuel , Ramos Ana Raquel , Mansour Salwa , Turbant Sabrina , Schurmans Stéphane , Sleegers Kristel , Erneux Christophe , Brion Jean-Pierre , Leroy Karelle ,   Brain Bank NeuroCEB Neuropathology Network
Published: June 2024

AbstractA recent large genome-wide association study has identified EGFR (encoding the epidermal growth factor EGFR) as a new genetic risk factor for late-onset AD. SHIP2, encoded by INPPL1, is taking part in the signalling and interactome of several growth factor receptors, such as the EGFR. While INPPL1 has been identified as one of the most significant genes whose RNA expression correlates with cognitive decline, the potential alteration of SHIP2 expression and localization during the progression of AD remains largely unknown. Here we report that gene expression of both EGFR and INPPL1 was upregulated in AD brains. SHIP2 immunoreactivity was predominantly detected in plaque-associated astrocytes and dystrophic neurites and its increase was correlated with amyloid load in the brain of human AD and of 5xFAD transgenic mouse model of AD. While mRNA of INPPL1 was increased in AD, SHIP2 protein undergoes a significant solubility change being depleted from the soluble fraction of AD brain homogenates and co-enriched with EGFR in the insoluble fraction. Using FRET-based flow cytometry biosensor assay for tau-tau interaction, overexpression of SHIP2 significantly increased the FRET signal while siRNA-mediated downexpression of SHIP2 significantly decreased FRET signal. Genetic association analyses suggest that some variants in INPPL1 locus are associated with the level of CSF pTau. Our data support the hypothesis that SHIP2 is an intermediate key player of EGFR and AD pathology linking amyloid and tau pathologies in human AD.
Average and Expected Distortion of Voronoi Paths and Scapes
Authors: Edelsbrunner Herbert , Nikitenko Anton 
Published: June 2024

Abstract
The approximation of a circle with the edges of a fine square grid distorts the perimeter by a factor about

$$\tfrac{4}{\pi }$$

4
π

. We prove that this factor is the same on average (in the ergodic sense) for approximations of any rectifiable curve by the edges of any non-exotic Delaunay mosaic (known as Voronoi path), and extend the results to all dimensions, generalizing Voronoi paths to Voronoi scapes.
The extent of kidney involvement in paediatric tuberous sclerosis complex
Authors: Limavady Andrew , Marlais Matko 
Published: June 2024

Abstract
Background
Tuberous sclerosis (TSC)–associated kidney disease is a leading cause of mortality in adults with TSC. This study aimed to understand TSC features in children, particularly kidney involvement, to inform clinical care for this specific group.

Methods
This retrospective cohort study included all paediatric (< 19 years) TSC cases at a large tertiary paediatric nephrology centre. Relevant data were collected from patients’ records, statistical analyses were performed to identify associations between variables, survival probabilities were estimated with Kaplan‒Meier curves, and log-rank tests were conducted to assess survival differences among genetic mutations.

Results
A total of 182 children with TSC were included. Among the 145 children with available kidney imaging data, 78.6% (114/145) exhibited kidney lesions. Angiomyolipomas (AMLs) were significantly more prevalent in the TSC2 mutation group (p = 0.018). Children with TSC2 mutations generally had poorer lesion-free survival than those with TSC1 mutations, but this difference was only significant for AMLs (p = 0.030). The change in size of largest AMLs increased with age and doubled in children above 9 years; a similar pattern was observed when stratified by genetic mutation. In contrast, kidney cysts exhibited two peaks: one in children under 5 years (2.31 mm/year) and the second in children between 15–19 years (2.82 mm/year). Chronic kidney disease was observed in 12.3% (10/81) of children, and high-risk AMLs above 3 cm were observed in 9% (13/145).

Conclusions
While TSC kidney disease emerges later in the disease course than neurological features, our findings emphasise the importance of kidney surveillance during childhood, including routine kidney imaging, kidney function, and blood pressure monitoring.

Graphical abstract
Exploring how a generative AI interprets music
Authors: Barenboim Gabriela , Debbio Luigi Del , Hirn Johannes , Sanz Verónica 
Published: June 2024

AbstractWe aim to investigate how closely neural networks (NNs) mimic human thinking. As a step in this direction, we study the behavior of artificial neuron(s) that fire most when the input data score high on some specific emergent concepts. In this paper, we focus on music, where the emergent concepts are those of rhythm, pitch and melody as commonly used by humans. As a black box to pry open, we focus on Google’s MusicVAE, a pre-trained NN that handles music tracks by encoding them in terms of 512 latent variables. We show that several hundreds of these latent variables are “irrelevant” in the sense that can be set to zero with minimal impact on the reconstruction accuracy. The remaining few dozens of latent variables can be sorted by order of relevance by comparing their variance. We show that the first few most relevant variables, and only those, correlate highly with dozens of human-defined measures that describe rhythm and pitch in music pieces, thereby efficiently encapsulating many of these human-understandable concepts in a few nonlinear variables.
Surgical vs ultrasound-guided lumbar erector spinae plane block for pain management following lumbar spinal fusion surgery
Authors: Kaciroglu Ahmet , Ekinci Mursel , Gurbuz Hande , Ulusoy Emre , Ekici Mehmet Ali , Dogan Özgür , Golboyu Birzat Emre , Alver Selcuk , Ciftci Bahadir 
Published: June 2024

Abstract
Purpose
Spinal surgery is associated with severe diffuse pain in the postoperative period. Effective pain management plays an essential role in reducing morbidity and mortality. This study is designed to compare the ultrasound-guided erector spinae plane (ESP) block and surgical infiltrative ESP block for postoperative analgesia management after lumbar spinal fusion surgery.

Methods
The patients who underwent two or three levels of posterior lumbar spinal fusion surgery were randomly allocated into one of three groups with 30 patients each (Group SE = Surgical ESP block; Group UE = ultrasound-guided ESP block; Group C = Controls). The primary aim was to compare postoperative opioid consumption, and the secondary aim was to evaluate postoperative dynamic and static pain scores and the incidence of opioid-related adverse effects.

Results
There was a significant difference in terms of opioid consumption, rescue analgesia on demand, and both static and dynamic pain scores between groups at all time periods (p < 0.05). Group SE and Group UE had lower pain scores and consumed fewer opioids than the controls (p < 0.05). However, the Group UE had lower pain scores and opioid consumption than the Group SE. The sedation level of patients was significantly higher in the control group than in the other two groups. Also, nausea was more common in controls than in the other groups.

Conclusion
While both surgical and ultrasound-guided ESP blocks reduced opioid consumption compared to the controls, the patients who received ultrasound-guided ESP blocks experienced better postsurgical pain relief than those in the other groups (surgical ESP and controls).
Contributing to the management of viral infections through simple immunosensing of the arachidonic acid serum level
Authors: Torrente-Rodríguez Rebeca M. , Ruiz-Valdepeñas Montiel Víctor , Iftimie Simona , Montero-Calle Ana , Pingarrón José M. , Castro Antoni , Camps Jordi , Barderas Rodrigo , Campuzano Susana , Joven Jorge 
Published: June 2024

AbstractA trendsetting direct competitive-based biosensing tool has been developed and implemented for the determination of the polyunsaturated fatty acid arachidonic acid (ARA), a highly significant biological regulator with decisive roles in viral infections. The designed methodology involves a competitive reaction between the target endogenous ARA and a biotin-ARA competitor for the recognition sites of anti-ARA antibodies covalently attached to the surface of carboxylic acid-coated magnetic microbeads (HOOC-MµBs), followed by the enzymatic label of the biotin-ARA residues with streptavidin-horseradish peroxidase (Strep-HRP) conjugate. The resulting bioconjugates were magnetically trapped onto the sensing surface of disposable screen-printed carbon transducers (SPCEs) to monitor the extent of the biorecognition reaction through amperometry. The operational functioning of the exhaustively optimized and characterized immunosensing bioplatform was highly convenient for the quantitative determination of ARA in serum samples from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2-) and respiratory syncytial virus (RSV)-infected individuals in a rapid, affordable, trustful, and sensitive manner.
Graphical Abstract
Arbeitszufriedenheit unter österreichischen Pädiaterinnen und Pädiatern
Authors: Kohlfürst Daniela S. , Zöggeler Thomas , Karall Daniela , Kerbl Reinhold 
Published: June 2024

Zusammenfassung

Hintergrund
Die pädiatrische Mangelversorgung vor allem in ländlichen Gebieten spitzt sich immer mehr zu, denn 12 % (34/288) der Kassenarztstellen für Kinder- und Jugendheilkunde sind derzeit österreichweit unbesetzt. Ziel dieser Studie war die Evaluierung verschiedener Faktoren, die hinsichtlich Arbeitsbelastung und Arbeitszufriedenheit eine Rolle spielen.

Methoden
Im Februar 2020 erfolgte unter den Mitgliedern der Österreichischen Gesellschaft für Kinder- und Jugendheilkunde (ÖGKJ) mittels Survey Monkey eine aus 16 Fragen bestehende Online-Umfrage.

Ergebnisse
Insgesamt nahmen 375 Personen teil, davon 61 % Frauen und 39 % Männer. 61 % arbeiteten im Spital, 21 % in der Kassenpraxis und 12 % in der Privatpraxis. In der Kassenpraxis wurde über eine signifikant höhere durchschnittliche Patient:innenenzahl pro Tag berichtet als in der Privatpraxis (> 51 vs. < 30; p < 0,01), während im Spital signifikant häufiger eine höhere durchschnittliche Wochenarbeitszeit als in der Kassenpraxis bzw. Privatpraxis (> 40 vs. < 40 h; p = 0,00) angegeben wurde.
Die höhere Arbeitsbelastung korrelierte signifikant mit niedrigerer Arbeitszufriedenheit (p = 0,00). Die mittlere Arbeitszufriedenheit war in einer Kassenpraxis (5,8 ± 0,3) und im Spital (5,6 ± 0,2) signifikant niedriger als in einer Privatpraxis (7,7 ± 0,3; p < 0,000).

Diskussion
Diese Studie zeigt, dass die relativ höhere Arbeitsbelastung im Spital und in der Kassenpraxis mit einer Einschränkung der Arbeitszufriedenheit einhergeht. Um die weitere pädiatrische Primärversorgung aufrechtzuerhalten, müssen neue Arbeitsmodelle angedacht und umgesetzt werden. Eine Reduktion des Arbeitsausmaßes und des Administrationsaufwandes erscheinen dabei ähnlich wichtig zu sein wie „mehr Zeit“ pro Patient:in und eine verbesserte Zusammenarbeit zwischen intramuralem und extramuralem Bereich.