bluuebunny/crossref_metadata_2025 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

Background

The 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).

Methods

A 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.

Results

Twelve 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%).

Conclusions

The 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

We 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

Der 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

Hotspot 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

This 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

Interleukin-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

Despite 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

A 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

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

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

We 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

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

A 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

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.
Training in the use of the water jet and cold atmospheric plasma jet for the decontamination of dental implants
Authors: Matthes Rutger , Jablonowski Lukasz , Pitchika Vinay , Holtfreter Birte , Eberhard Christian , Gerling Torsten , Wagner Juliane , Flörke Christian , Eisenbeiß Anne-Katrin , Cosgarea Raluca , Jepsen Karin , Bunke Jennifer , Ramanauskaite Ausra , Begić Amira , Obreja Karina , Mksoud Maria , Kocher Thomas
Published: June 2024

Objectives

Clinical trials testing new devices require prior training on dummies to minimize the "learning curve" for patients. Dentists were trained using a novel water jet device for mechanical cleaning of dental implants and with a novel cold plasma device for surface functionalisation during a simulated open flap peri-implantitis therapy. The hypothesis was that there would be a learning curve for both devices.

Materials and methods

11 dentists instrumented 44 implants in a dummy-fixed jaw model. The effect of the water jet treatment was assessed as stain removal and the effect of cold plasma treatment as surface wettability. Both results were analysed using photographs. To improve treatment skills, each dentist treated four implants and checked the results immediately after the treatment as feedback.

Results

Water jet treatment significantly improved from the first to the second implant from 62.7% to 75.3% stain removal, with no further improvement up to the fourth implant. The wettability with cold plasma application reached immediately a high level at the first implant and was unchanged to the 4th implant (mean scores 2.7 out of 3).

Conclusion

A moderate learning curve was found for handling of the water jet but none for handling of the cold plasma.

Clinical relevance

Scientific rational for study: Two new devices were developed for peri-implantitis treatment (Dental water jet, cold plasma). Dentists were trained in the use of these devices prior to the trial to minimize learning effects.

Principal findings: Experienced dentists learn the handling of the water jet very rapidly and for cold plasma they do not need much training.

Practical implications: A clinical study is in process. When the planned clinical study will be finished, we will find out, if this dummy head exercise really minimised the learning curve for these devices.
A unified framework for symmetry handling
Authors: van Doornmalen Jasper , Hojny Christopher
Published: June 2024

Handling symmetries in optimization problems is essential for devising efficient solution methods. In this article, we present a general framework that captures many of the already existing symmetry handling methods. While these methods are mostly discussed independently from each other, our framework allows to apply different methods simultaneously and thus outperforming their individual effect. Moreover, most existing symmetry handling methods only apply to binary variables. Our framework allows to easily generalize these methods to general variable types. Numerical experiments confirm that our novel framework is superior to the state-of-the-art symmetry handling methods as implemented in the solver on a broad set of instances.
Final analyses of the prospective controlled trial on the efficacy of uracil and tegafur/leucovorin as an adjuvant treatment for stage II colon cancer with risk factors for recurrence using propensity score-based methods (JFMC46-1201)
Authors: Ogata Yutaka , Sadahiro Sotaro , Sakamoto Kazuhiro , Tsuchiya Takashi , Takahashi Takao , Ohge Hiroki , Sato Toshihiko , Kondo Ken , Baba Hideo , Itabashi Michio , Ikeda Masataka , Hamada Madoka , Maeda Kiyoshi , Masuko Hiroyuki , Takahashi Keiichi , Kusano Mitsuo , Hyodo Ichinosuke , Sakamoto Junichi , Taguri Masataka , Morita Satoshi
Published: June 2024

Background

The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. Using propensity score matching, we previously reported that the 3-year disease-free survival (DFS) rate was significantly higher in patients treated with uracil and tegafur plus leucovorin (UFT/LV) against surgery alone. We report the final results, including updated 5-year overall survival (OS) rates and risk factor analysis outcomes.

Methods

In total, 1902 high-risk stage II CC patients with T4, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, and/or < 12 dissected lymph nodes were enrolled in this prospective, non-randomized controlled study based on their self-selected treatment. Oral UFT/LV therapy was administered for six months after surgery.

Results

Of the 1880 eligible patients, 402 in Group A (surgery alone) and 804 in Group B (UFT/LV) were propensity score-matched. The 5-year DFS rate was significantly higher in Group B than in Group A (P = 0.0008). The 5-year OS rates were not significantly different between groups. The inverse probability of treatment weighting revealed significantly higher 5-year DFS (P = 0.0006) and 5-year OS (P = 0.0122) rates in group B than in group A. Multivariate analyses revealed that male sex, age ≥ 70 years, T4, < 12 dissected lymph nodes, and no adjuvant chemotherapy were significant risk factors for DFS and/or OS.

Conclusion

The follow-up data from our prospective non-randomized controlled study revealed a considerable survival advantage in DFS offered by adjuvant chemotherapy with UFT/LV administered for six months over surgery alone in individuals with high-risk stage II CC.

Trial registration

Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019), UMIN Clinical Trials Registry: UMIN000007783 (date of registration: 18/04/2012).
Carleman estimates for third order operators of KdV and non KdV-type and applications
Authors: Federico Serena
Published: June 2024

In this paper we study a class of variable coefficient third order partial differential operators on $${\mathbb {R}}^{n+1}$$

R

n
+
1

, containing, as a subclass, some variable coefficient operators of KdV-type in any space dimension. For such a class, as well as for the adjoint class, we obtain a Carleman estimate and the local solvability at any point of $${\mathbb {R}}^{n+1}$$

R

n
+
1

. A discussion of possible applications in the context of dispersive equations is provided.
Simultaneously learning intentions and preferences during physical human-robot cooperation
Authors: van der Spaa Linda , Kober Jens , Gienger Michael
Published: June 2024

The advent of collaborative robots allows humans and robots to cooperate in a direct and physical way. While this leads to amazing new opportunities to create novel robotics applications, it is challenging to make the collaboration intuitive for the human. From a system’s perspective, understanding the human intentions seems to be one promising way to get there. However, human behavior exhibits large variations between individuals, such as for instance preferences or physical abilities. This paper presents a novel concept for simultaneously learning a model of the human intentions and preferences incrementally during collaboration with a robot. Starting out with a nominal model, the system acquires collaborative skills step-by-step within only very few trials. The concept is based on a combination of model-based reinforcement learning and inverse reinforcement learning, adapted to fit collaborations in which human and robot think and act independently. We test the method and compare it to two baselines: one that imitates the human and one that uses plain maximum entropy inverse reinforcement learning, both in simulation and in a user study with a Franka Emika Panda robot arm.
Efficiency analysis of discontinuous Galerkin approaches for the application onto quantum Liouville-type equations
Authors: Ganiu Valmir , Schulz Dirk
Published: June 2024

The simulation of nanodevices is computationally inefficient with current algorithms. The discontinuous Galerkin approach has been demonstrated in the field of computational fluid dynamics to deliver high order accuracy and efficiency due to its reliance on matrix–vector multiplications. Previously, the discontinuous Galerkin approach was successfully used in conjunction with the finite volume technique to solve the Liouville–von Neumann equation in center-mass coordinates and thus simulate nanodevices. To exploit its full potential regarding high-performance computing, this work aims to substitute the aforementioned finite volume technique with the discontinuous Galerkin method. To arrive at the said formalism, a finite element method is implemented as an intermediate step.
Photosensitive iron–aluminum oxide gas sensor
Authors: Turgut Erdal
Published: June 2024

In this study, the structural, topographic, and optical properties of iron–aluminum oxide (AlxFe2−xO3, 1 > x > 0) thin film grown by co-sputtering method were investigated. Firstly, AlxFe2−xO3 films grown by magnetron RF–DC co-sputtering method were annealed at 540 °C and then XRD analyses were performed. The absorption measurement, Raman shift, XPS, gas sensor measurements, and SEM images were taken, respectively. The band gap energy of the AlxFe2−xO3 samples was obtained and measured as approximately 2.41 eV, and different peaks at various intensities were seen in the XRD analysis. According to the XRD analysis of the AlxFe2−xO3 semiconductor, the peaks occurred at 33.42°, 41.16°, and 54.43° and the XRD analysis results show that the structure is polycrystalline. As seen in the measurement of the AlxFe2−xO3 gas sensors, acoustic gas sensorsgas sensor, the current value increased with the flow of hydrogen gas. This means that the oxygen that hydrogen detached from the thin film surface contributes to the conductivity of the remaining electrons in the structure, which means that the thin film was an n-type semiconductor. It was seen that the AlxFe2−xO3 gas sensor was very sensitive to light. During the feature measurement, it was seen that the current value measured under the light increases considerably.
In silico assessment of biocompatibility and toxicity: molecular docking and dynamics simulation of PMMA-based dental materials for interim prosthetic restorations
Authors: Saini Ravinder S. , Binduhayyim Rayan Ibrahim H. , Gurumurthy Vishwanath , Alshadidi Abdulkhaliq Ali F. , Bavabeedu Shashit Shetty , Vyas Rajesh , Dermawan Doni , Naseef Punnoth Poonkuzhi , Mosaddad Seyed Ali , Heboyan Artak
Published: June 2024

Aim: This study aimed to comprehensively assess the biocompatibility and toxicity profiles of poly(methyl methacrylate) (PMMA) and its monomeric unit, methyl methacrylate (MMA), crucial components in dental materials for interim prosthetic restorations. Methodology: Molecular docking was employed to predict the binding affinities, energetics, and steric features of MMA and PMMA with selected receptors involved in bone metabolism and tissue development, including RANKL, Fibronectin, BMP9, NOTCH2, and other related receptors. The HADDOCK standalone version was utilized for docking calculations, employing a Lamarckian genetic algorithm to explore the conformational space of ligand-receptor interactions. Furthermore, molecular dynamics (MD) simulations over 100 nanoseconds were conducted using the GROMACS package to evaluate dynamic actions and structural stability. The LigandScout was utilized for pharmacophore modeling, which employs a shape-based screening approach to identify potential ligand binding sites on protein targets. Results: The molecular docking studies elucidated promising interactions between PMMA and MMA with key biomolecular targets relevant to dental applications. MD simulation results provided strong evidence supporting the structural stability of PMMA complexes over time. Pharmacophore modeling highlighted the significance of carbonyl and hydroxyl groups as pharmacophoric features, indicating compounds with favorable biocompatibility profiles. Conclusion: This study underscores the potential of PMMA in dental applications, emphasizing its structural stability, molecular interactions, and safety considerations. These findings lay a foundation for future advancements in dental biomaterials, guiding the design and optimization of materials for enhanced biocompatibility. Future directions include experimental validation of computational findings and the development of PMMA-based dental materials with improved biocompatibility and clinical performance.

Graphical Abstract
A survey of isatin hybrids and their biological properties
Authors: Shu Vanessa Asoh , Eni Donatus Bekindaka , Ntie-Kang Fidele
Published: June 2024

The emergence of diverse infections worldwide, which is a serious global threat to human existence, necessitates the urgent development of novel therapeutic candidates that can combat these diseases with efficacy. Molecular hybridization has been established as an efficient technique in designing bioactive molecules capable of fighting infections. Isatin, a core nucleus of an array of compounds with diverse biological properties can be modified at different positions leading to the creation of novel drug targets, is an active area of medicinal chemistry. This review containing published articles from 2005 to 2022 highlights isatin hybrids which have been synthesized and reported in the literature alongside a discussion on their biological properties. The enriched structure–activity relationship studies discussed provides insights for the rational design of novel isatin hybrids with tailored biological properties as effective therapeutic candidates inspired by nature.
Tree root-mediated soil metabolome in agroforestry enhancing the growth and quality of Panax notoginseng
Authors: Wang Cuiying , Mao Guomin , Li Yingbin , Zi Wenjing , Wang Qingying , Huang Huichuan , Yang Min , Du Fei , Mei Xinyue , Deng Weiping , Lu Jian , Zhu Shusheng , Ye Chen , Liu Yixiang
Published: June 2024

Purpose

The ecological cultivation of Panax notoginseng under a forest canopy relies on the coupling of the P. notoginseng growth environment and the forest ecosystem

Methods

In this study, six tree species, such as Platycladus orientalis (L.) Franco, were chosen to research the effects of species interactions on the growth, quality, and disease occurrence under intercropping with P. notoginseng, with single P. notoginseng serving as the control.

Results

Intercropping P. notoginseng with PO (Platycladus orientalis, a coniferous tree species) or with SW (Schima wallichii Choisy, a broad-leaved tree species) promoted the accumulation of P. notoginseng biomass, reduced the occurrence of root rot, improved the contents of nitrogen, phosphorus and potassium in P. notoginseng, and increased the saponin concentration. Then, 43 differentially abundant metabolites were screened in the P. notoginseng-tree intercropping system by soil metabolism analysis and compared with those in the monocropped system. Indole-3-carboxaldehyde showed a significant negative relationship with the occurrence of root rot disease and inhibited Fusarium oxysporum. In addition, 2-naphthalenesulfonic acid was significantly positively correlated with biomass and increased the dry weight in the underground part of P. notoginseng in the pot experiments. 

Conclusions

Thus, the coniferous tree species PO and the broad-leaved tree species SW are potentially good neighbours of P. notoginseng, and soil metabolic changes may be important mechanisms for the growth and disease resistance benefits observed in the understorey of P. notoginseng.
An alternative bounded distribution: regression model and applications
Authors: Sağlam Şule , Karakaya Kadir
Published: June 2024

In this paper, a new bounded distribution is introduced and some distributional properties of the new distribution are discussed. Moreover, the new distribution is implemented in the field of engineering to the Cpc process capability index. Three unknown parameters of the distribution are estimated with several estimators, and the performances of the estimators are evaluated with a Monte Carlo simulation. A new regression model is introduced based on this new distribution as an alternative to beta and Kumaraswamy models. Furthermore, it is considered one of the first studies where regression model parameters are estimated using least squares, weighted least squares, Cramér–von Mises, and maximum product spacing estimators other than the maximum likelihood. The efficiency of the estimators for the parameters of the regression model is further assessed through a simulation. Real datasets are analyzed to demonstrate the applicability of the new distribution and regression model.
Fungi associated with ambrosia beetle Xylosandrus germanus in Slovakia
Authors: Pastirčáková Katarína , Baková Katarína , Adamčíková Katarína , Barta Marek , Lalík Michal , Pavlík Martin , Kunca Andrej , Galko Juraj , Pastirčák Martin
Published: June 2024

The black timber bark beetle (Xylosandrus germanus) is a strongly invasive ambrosia beetle and an important forest pest in Slovakia. This pest is closely associated with symbiotic fungi used as its food source. We investigated the fungi associated with X. germanus adults in Slovakia. In this study, Beauveria bassiana, B. pseudobassiana, Clonostachys rosea, Fusarium oxysporum, Ophiostoma quercus, Phaeoacremonium scolyti, and Talaromyces amestolkiae were isolated and identified by morphological and molecular analyses. The fungus Ophiostoma quercus was most frequently isolated from living beetles, while the entomopathogenic Beauveria bassiana was the most commonly isolated from dead beetles. The morphological descriptions of fungi based on isolates from the surface of X. germanus adults are provided.
Preliminary investigation of the regulatory loop of loneliness and the protective role of self-esteem – a cross-sectional study
Authors: Skoko Andrej , Kaeser Janko , Seewer Noëmi , Krieger Tobias
Published: June 2024

As a major public health issue, chronic loneliness has been associated with increased mortality and impaired physical and mental health. The proposed model by Cacioppo and Hawkley (Trends in Cognitive Sciences, 13(10), 447–454, 2009) pictures the emergence and maintenance of chronic loneliness as a vicious cycle containing cognitive and behavioral aspects. As a potential source of resilience, self-esteem has been shown to have buffering effects on loneliness. This study aimed to investigate the central relationships between the components within the regulatory loop of loneliness and the potential buffering effect of self-esteem. In this study, a community sample of 436 adult participants completed measures of loneliness, interpretation bias in social situations, social avoidance behavior, self-esteem, and important covariates (including depressive and social anxiety symptoms and social network size). First, we tested bivariant correlations. Subsequently, we tested three mediation models representing the regulatory loop of loneliness. Lastly, we tested moderated mediation models with self-esteem as a moderator. Loneliness was positively associated with interpretation bias and social avoidance and negatively with self-esteem. Indirect effects in all three mediation models testing the regulatory loop were positive and strongly significant. Self-esteem was a significant moderator in the mediation models, with higher levels of self-esteem attenuating the indirect effect of loneliness on interpretation bias. These effects held even when controlled for relevant covariates, such as depressive and social anxiety symptoms. This study gives preliminary empirical support for the proposed model of chronic loneliness by Cacioppo and Hawkley (Trends in Cognitive Sciences, 13(10), 447–454, 2009) and the potential buffering effect of self-esteem. Hence, our results support the notion of addressing maladaptive social cognitions and maladaptive social behavior to effectively reduce chronic loneliness and strengthen self-esteem as a protective factor.
Subjective Well-Being and Bullying Victimisation: A Cross-National Study of Adolescents in 64 Countries and Economies
Authors: Katsantonis Ioannis , Barrado Beatriz , McLellan Ros , Gimenez Gregorio
Published: June 2024

Bullying is a recognised serious public problem affecting many students worldwide. Despite the well-established empirical evidence for the negative consequences of bullying on adolescents? mental and physical health and educational outcomes, little is known about the link between bullying victimisation and adolescents? subjective well-being. Moreover, empirical studies using comparative large-scale survey data are particularly scarce. This study explores this question using nationally-representative data from 329,015 adolescents across 64 high and middle-income countries and economies from the 2018 PISA survey. Two measures of subjective well-being were considered: overall life satisfaction and positive affect. Multilevel regressions were estimated at three levels (student, school, and country). Results showed that bullying victimisation was negatively and significantly related to overall life satisfaction and positive affect after controlling for a wide set of factors affecting subjective well-being. Moreover, this negative relationship was more pronounced for top performing students. Locally adapted intervention programmes are needed to tackle the issue of school bullying and foster positive school climate and student well-being. Practical and policy implications are discussed in detail.
Individual and regional determinants of women’s participation in the European labour market: a Labour Force Survey empirical study
Authors: Lovaglio Pietro Giorgio , Perrelli Adalgisa
Published: June 2024

In line with the existing literature, the primary focus of the present paper is on understanding the multifaceted factors contributing to unequal employment opportunities for women and the potential implications for both individuals and society. Specifically, the objective is to identify meaningful risk factors that affect the probability of being employed for women in the 20–49 age group, exploring possible demographic, educational, social, and family factors, as well as territorial context factors. The analysis is conducted on the three most populous European countries (Italy, France, and Germany) as representatives of different welfare regimes. The analysis exploits the rich information available in the micro-data of the Labour Force Survey (2021) as well as Eurostat regional statistics considering individuals nested in regions (NUTS 2). A deep analysis of empirical findings sheds light on employment determinants and motivations for not working, which appear to be essentially related to family and demographic factors. These results reveal the country-specific profiles that indicate greater risk of non-employment and also provide a basis for suggesting different policy implications.
VNIR–SWIR reflectance spectroscopy as a nondestructive technique for compositional determination of archaeological talc samples with a machine learning approach
Authors: Ferrer-Julià M. , Quirós A. , Herrero-Alonso D. , González E. , García-Meléndez E.
Published: June 2024

The material from which an archaeological piece is made provides a great deal of information regarding the society in which it was made; thus, any misidentification can lead to erroneous conclusions. The uniqueness of many of these pieces hinders their mineralogical analysis because the pieces cannot be damaged for sampling; therefore, errors in the classification of these materials are common. In the present study, we evaluate the suitability of the spectroradiometry technique in the analysis of two archaeological talc pieces. Both came from the Iron Age archaeological site of Peña del Castro (La Ercina, León) in the northwestern Iberian Peninsula. We compared the spectral curves of these 2 pieces with the spectral curves from 50 talc geological samples from different geographical sources, combining bulk and powdered samples. Our results show that spectral curves enabled the identification of the talc material in the powdered and bulk samples. Moreover, the absence of the talc characteristic features in other soft materials also used in antiquity enabled the detection of incorrect identification of the classified pieces. Even though our results cannot be used to define any absorption feature characteristic to establish the provenance of the material, in the present study, spectral analysis has been shown to be suitable as a nondestructive technique to mineralogically identify archaeological pieces.