bluuebunny/crossref_metadata_2025_split huggingface dataset:
RUNX1 mutation has no prognostic significance in paediatric AML: a retrospective study of the AML-BFM study group
Authors: Sendker Stephanie , Awada Amani , Domagalla Sophia , Sendker Michael , Orhan Eser , Hoffmeister Lina Marie , Antoniou Evangelia , Niktoreh Naghmeh , Reinhardt Dirk , von Neuhoff Nils , Schneider Markus 
Published: May 2023

AbstractIn acute myeloid leukaemia (AML) RUNX1 mutation is characterised by certain clinicopathological features with poor prognosis and adverse risk by the European LeukemiaNet recommendation. Though initially considered as provisional category, the recent World Health Organisation (WHO) classification of 2022 removed RUNX1-mutated AML from the unique entity. However, the significance of RUNX1 mutation in paediatric AML remains unclear. We retrospectively analysed a German cohort of 488 paediatric patients with de novo AML, enroled in the AMLR12 or AMLR17 registry of the AML-BFM Study Group (Essen, Germany). A total of 23 paediatric AML patients (4.7%) harboured RUNX1 mutations, 18 of which (78%) had RUNX1 mutation at initial diagnosis. RUNX1 mutations were associated with older age, male gender, number of coexisting alterations and presence of FLT3-ITD but mutually exclusive of KRAS, KIT and NPM1 mutation. RUNX1 mutations did not prognostically impact overall or event-free survival. Response rates did not differ between patients with and without RUNX1 mutations. This comprehensive study, comprising the largest analysis of RUNX1 mutation in a paediatric cohort to date, reveals distinct but not unique clinicopathologic features, with no prognostic significance of RUNX1-mutated paediatric AML. These results broaden the perspective on the relevance of RUNX1 alterations in leukaemogenesis in AML.
SUMO specific peptidase 3 halts pancreatic ductal adenocarcinoma metastasis via deSUMOylating DKC1
Authors: Wu Xiao , Li Jian-Hui , Xu Long , Li Ya-Xiong , Zhu Xiao-Xu , Wang Xi-Yu , Wu Xingmei , Zhao Wei , Ni Xuhao , Yin Xiao-Yu 
Published: May 2023

AbstractIn the past few decades, advances in the outcomes of patients suffering from pancreatic ductal adenocarcinoma (PDAC) have lagged behind these gained in the treatment of many other malignancies. Although the pivotal role of the SUMO pathway in PDAC has been illustrated, the underlying molecule drivers have yet to be fully elucidated. In the present study, we identified SENP3 as a potential suppressor of PDAC progression through an in vivo metastatic model. Further studies revealed that SENP3 inhibited PDAC invasion in a SUMO system dependent fashion. Mechanistically, SENP3 interacted with DKC1 and, as such, catalyzed the deSUMOylation of DKC1, which accepted SUMO3 modifiers at three lysine residues. SENP3-mediated deSUMOylation caused DKC1 instability and disruption of the interaction between snoRNP proteins, which contributed to the impaired migration ability of PDAC. Indeed, overexpression of DKC1 abated the anti-metastasis effect of SENP3, and DKC1 was elevated in PDAC specimens and associated with a poor prognosis in PDAC patients. Collectively, our findings shed light on the essential role of SENP3/DKC1 axis in the progression of PDAC.
Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial
Authors: Nassiri Farshad , Patil Vikas , Yefet Leeor S. , Singh Olivia , Liu Jeff , Dang Rachel M. A. , Yamaguchi Takafumi N. , Daras Mariza , Cloughesy Timothy F. , Colman Howard , Kumthekar Priya U. , Chen Clark C. , Aiken Robert , Groves Morris D. , Ong Shirley S. , Ramakrishna Rohan , Vogelbaum Michael A. , Khagi Simon , Kaley Thomas , Melear Jason M. , Peereboom David M. , Rodriguez Analiz , Yankelevich Maxim , Nair Suresh G. , Puduvalli Vinay K. , Aldape Kenneth , Gao Andrew , López-Janeiro Álvaro , de Andrea Carlos E. , Alonso Marta M. , Boutros Paul , Robbins Joan , Mason Warren P. , Sonabend Adam M. , Stupp Roger , Fueyo Juan , Gomez-Manzano Candelaria , Lang Frederick F. , Zadeh Gelareh 
Published: May 2023

AbstractImmune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab in recurrent glioblastoma, first in a dose-escalation and then in a dose-expansion phase, in 49 patients. The primary endpoints were overall safety and objective response rate. The primary safety endpoint was met, whereas the primary efficacy endpoint was not met. There were no dose-limiting toxicities, and full dose combined treatment was well tolerated. The objective response rate was 10.4% (90% confidence interval (CI) 4.2–20.7%), which was not statistically greater than the prespecified control rate of 5%. The secondary endpoint of overall survival at 12 months was 52.7% (95% CI 40.1–69.2%), which was statistically greater than the prespecified control rate of 20%. Median overall survival was 12.5 months (10.7–13.5 months). Objective responses led to longer survival (hazard ratio 0.20, 95% CI 0.05–0.87). A total of 56.2% (95% CI 41.1–70.5%) of patients had a clinical benefit defined as stable disease or better. Three patients completed treatment with durable responses and remain alive at 45, 48 and 60 months. Exploratory mutational, gene-expression and immunophenotypic analyses revealed that the balance between immune cell infiltration and expression of checkpoint inhibitors may potentially inform on response to treatment and mechanisms of resistance. Overall, the combination of intratumoral DNX-2401 followed by pembrolizumab was safe with notable survival benefit in select patients (ClinicalTrials.gov registration: NCT02798406).
Design and experiments with a single spiral fixed depth ditching and fertilizing machine
Authors: Zhan Caixue , Ding Wenqin , Han Yu , Jiang Qinghai , Zhao Ying , Zhao Liang , Song Zhiyu 
Published: May 2023

AbstractAiming at the problems of low fertilization efficiency, mainly the process operation and inconsistent fertilization depth of domestic tea garden fertilizer machines, a single-spiral fixed depth ditching and fertilizing machine is appropriately designed. This machine is capable of performing the integrated operation of ditching, fertilization, and covering soil at the same time through the operation mode of single-spiral ditching and fertilization. The theoretical analysis and design of the structure of the main components are properly carried out. The fertilization depth can be adjusted through the established depth control system. The performance test reveals that the single-spiral ditching and fertilizing machine exhibits a maximum stability coefficient of 96.17% and a minimum of 94.29% in terms of trenching depth and a maximum of 94.23% and a minimum of 93.58% in terms of fertilization uniformity, meeting the production requirements of tea plantations.
Influence of the modifiers in polyol method on magnetically induced hyperthermia and biocompatibility of ultrafine magnetite nanoparticles
Authors: Radoń Adrian , Włodarczyk Agnieszka , Sieroń Łukasz , Rost-Roszkowska Magdalena , Chajec Łukasz , Łukowiec Dariusz , Ciuraszkiewicz Agnieszka , Gębara Piotr , Wacławek Stanisław , Kolano-Burian Aleksandra 
Published: May 2023

AbstractMagnetite nanoparticles (Fe3O4 NPs) are widely tested in various biomedical applications, including magnetically induced hyperthermia. In this study, the influence of the modifiers, i.e., urotropine, polyethylene glycol, and NH4HCO3, on the size, morphology, magnetically induced hyperthermia effect, and biocompatibility were tested for Fe3O4 NPs synthesized by polyol method. The nanoparticles were characterized by a spherical shape and similar size of around 10 nm. At the same time, their surface is functionalized by triethylene glycol or polyethylene glycol, depending on the modifiers. The Fe3O4 NPs synthesized in the presence of urotropine had the highest colloidal stability related to the high positive value of zeta potential (26.03 ± 0.55 mV) but were characterized by the lowest specific absorption rate (SAR) and intrinsic loss power (ILP). The highest potential in the hyperthermia applications have NPs synthesized using NH4HCO3, for which SAR and ILP were equal to 69.6 ± 5.2 W/g and 0.613 ± 0.051 nHm2/kg, respectively. Their application possibility was confirmed for a wide range of magnetic fields and by cytotoxicity tests. The absence of differences in toxicity to dermal fibroblasts between all studied NPs was confirmed. Additionally, no significant changes in the ultrastructure of fibroblast cells were observed apart from the gradual increase in the number of autophagous structures.
Dysbiosis of the gut microbiome in elderly patients with hepatocellular carcinoma
Authors: Zhang Weizheng , Xu Xiaosong , Cai Liping , Cai Xiangsheng 
Published: May 2023

AbstractFecal samples from participants aged 60–80 were collected and sequenced by a high-throughput second-generation sequencer to explore the structural composition of gut microbiota in elderly patients with hepatocellular carcinoma(HCC). Comparison of gut microbiota between patients with hepatocellular carcinoma and healthy controls, α diversity and β diversity were statistically different. At the genus level, compared with the normal group, the abundance of A Blautia, Fusicatenibacter, Anaerostipes, Lachnospiraceae_ND3007_group, CAG-56, Eggerthella, Lachnospiraceae_FCS020_group and Olsenella were decreased significantly in the LC group. In contrast, the abundance of Escherichia-Shigella, Fusobacterium, Megasphaera, Veillonella, Tyzzerella_4, Prevotella_2 and Cronobacter increased significantly. The KEGG and COG pathway analyses showed that the dysbiosis of gut bacteria in primary liver carcinoma is associated with several pathways, including amino acid metabolism, replication and repair, nucleotide metabolism, cell motility, cell growth and death, and transcription. Age is negatively associated with the abundance of Bifidobacterium. Lachnospiraceae_ ND3007_ group, [Eubacterium]_hallii_group, Blautia, Fuscatenibacter and Anaerostipes are negatively correlated with ALT, AST and GGT levels (p < 0.05), respectively. Alpha-fetoprotein (AFP) is positively associated with the abundance of Erysipelatoclostridium, Magasphaera, Prevotella 2, Escherichia-Shigella, Streptococcus and [Eubacterium]_eligens_group (p < 0.05), respectively. A random forest model showed that the genera Eggerthella, Anaerostipes, and Lachnospiraceae_ ND3007_ group demonstrated the best predictive capacity. The area under the Receiver Operating Characteristic Curve of Eggerthella, Anaerostipes and Lachnospiraceae_ ND3007_ group are 0.791, 0.766 and 0.730, respectively. These data are derived from the first known gut microbiome study in elderly patients with hepatocellular carcinoma. Potentially, specific microbiota can be used as a characteristic index for screening, diagnosis, and prognosis of gut microbiota changes in elderly patients with hepatocellular carcinoma and even as a therapeutic clinical target.
Computer-assisted diagnosis for an early identification of lung cancer in chest X rays
Authors: Juan Judith , Monsó Eduard , Lozano Carme , Cufí Marta , Subías-Beltrán Paula , Ruiz-Dern Laura , Rafael-Palou Xavier , Andreu Marta , Castañer Eva , Gallardo Xavier , Ullastres Anna , Sans Carles , Lujàn Manel , Rubiés Carles , Ribas-Ripoll Vicent 
Published: May 2023

AbstractComputer-assisted diagnosis (CAD) algorithms have shown its usefulness for the identification of pulmonary nodules in chest x-rays, but its capability to diagnose lung cancer (LC) is unknown. A CAD algorithm for the identification of pulmonary nodules was created and used on a retrospective cohort of patients with x-rays performed in 2008 and not examined by a radiologist when obtained. X-rays were sorted according to the probability of pulmonary nodule, read by a radiologist and the evolution for the following three years was assessed. The CAD algorithm sorted 20,303 x-rays and defined four subgroups with 250 images each (percentiles ≥ 98, 66, 33 and 0). Fifty-eight pulmonary nodules were identified in the ≥ 98 percentile (23,2%), while only 64 were found in lower percentiles (8,5%) (p < 0.001). A pulmonary nodule was confirmed by the radiologist in 39 out of 173 patients in the high-probability group who had follow-up information (22.5%), and in 5 of them a LC was diagnosed with a delay of 11 months (12.8%). In one quarter of the chest x-rays considered as high-probability for pulmonary nodule by a CAD algorithm, the finding is confirmed and corresponds to an undiagnosed LC in one tenth of the cases.
Characterization of Duffy Binding Protein II-specific CD4+T cell responses in Plasmodium vivax patients
Authors: Thawornpan Pongsakorn , Malee Chayapat , Kochayoo Piyawan , Wangriatisak Kittikorn , Leepiyasakulchai Chaniya , Ntumngia Francis B. , De Sai Lata , Adams John H. , Chootong Patchanee 
Published: May 2023

AbstractPlasmodium vivax Duffy Binding Protein region II (PvDBPII) is a leading vaccine candidate against blood-stage vivax malaria. Anti-PvDBPII antibodies potentially block parasite invasion by inhibition of erythrocyte binding. However, knowledge of PvDBPII-specific T cell responses is limited. Here, to assess the responses of PvDBPII-specific CD4+T cells in natural P. vivax infection, three cross-sectional studies were conducted in recovered subjects. In silico analysis was used for potential T cell epitope prediction and selection. PBMCs from P. vivax subjects were stimulated with selected peptides and examined for cytokine production by ELISPOT or intracellular cytokine staining. Six dominant T cell epitopes were identified. Peptide-driven T cell responses showed effector memory CD4+T cell phenotype, secreting both IFN-γ and TNF-α cytokines. Single amino acid substitutions in three T cell epitopes altered levels of IFN-γ memory T cell responses. Seropositivity of anti-PvDBPII antibodies were detected during acute malaria (62%) and persisted up to 12 months (11%) following P. vivax infection. Further correlation analysis showed four out of eighteen subjects had positive antibody and CD4+T cell responses to PvDBPII. Altogether, PvDBPII-specific CD4+T cells were developed in natural P. vivax infections. Data on their antigenicity could facilitate development of an efficacious vivax malaria vaccine.
Time domain self-bending photonic hook beam based on freezing water droplet
Authors: Minin Oleg V. , Minin Igor V. , Cao Yinghui 
Published: May 2023

AbstractTunable optical devices are of great interest as they offer adjustability to their functions. Temporal optics is a fast-evolving field, which may be useful both for revolutionizing basic research of time-dependent phenomena and for developing full optical devices. With increasing focus on ecological compatibility, bio-friendly alternatives are a key subject matter. Water in its various forms can open up new physical phenomena and unique applications in photonics and modern electronics. Water droplets freezing on cold surfaces are ubiquitous in nature. We propose and demonstrate the effectual generation of time domain self-bending photonic hook (time–PH) beams by using mesoscale freezing water droplet. The PH light bends near the shadow surface of the droplet into large curvature and angles superior to a conventional Airy beam. The key properties of the time–PH (length, curvature, beam waist) can be modified flexibly by changing the positions and curvature of the water–ice interface inside the droplet. Due to the modifying internal structure of freezing water droplets in real time, we showcase the dynamical curvature and trajectory control of the time–PH beams. Compared with the traditional methods, our phase-change- based materials (water and ice) of the mesoscale droplet have advantages of easy fabrication, natural materials, compact structure and low cost. Such PHs may have applications in many fields, including temporal optics and optical switching, microscopy, sensors, materials processing, nonlinear optics, biomedicine, and so on.
Projecting malaria elimination in Thailand using Bayesian hierarchical spatiotemporal models
Authors: Rotejanaprasert Chawarat , Lawpoolsri Saranath , Sa-angchai Patiwat , Khamsiriwatchara Amnat , Padungtod Chantana , Tipmontree Rungrawee , Menezes Lynette , Sattabongkot Jetsumon , Cui Liwang , Kaewkungwal Jaranit 
Published: May 2023

AbstractThailand has set a goal of eliminating malaria by 2024 in its national strategic plan. In this study, we used the Thailand malaria surveillance database to develop hierarchical spatiotemporal models to analyze retrospective patterns and predict Plasmodium falciparum and Plasmodium vivax malaria incidences at the provincial level. We first describe the available data, explain the hierarchical spatiotemporal framework underlying the analysis, and then display the results of fitting various space–time formulations to the malaria data with the different model selection metrics. The Bayesian model selection process assessed the sensitivity of different specifications to obtain the optimal models. To assess whether malaria could be eliminated by 2024 per Thailand’s National Malaria Elimination Strategy, 2017–2026, we used the best-fitted model to project the estimated cases for 2022–2028. The study results based on the models revealed different predicted estimates between both species. The model for P. falciparum suggested that zero P. falciparum cases might be possible by 2024, in contrast to the model for P. vivax, wherein zero P. vivax cases might not be reached. Innovative approaches in the P. vivax-specific control and elimination plans must be implemented to reach zero P. vivax and consequently declare Thailand as a malaria-free country.
Predictive network analysis identifies JMJD6 and other potential key drivers in Alzheimer’s disease
Authors: Merchant Julie P. , Zhu Kuixi , Henrion Marc Y. R. , Zaidi Syed S. A. , Lau Branden , Moein Sara , Alamprese Melissa L. , Pearse Richard V. , Bennett David A. , Ertekin-Taner Nilüfer , Young-Pearse Tracy L. , Chang Rui 
Published: May 2023

AbstractDespite decades of genetic studies on late-onset Alzheimer’s disease, the underlying molecular mechanisms remain unclear. To better comprehend its complex etiology, we use an integrative approach to build robust predictive (causal) network models using two large human multi-omics datasets. We delineate bulk-tissue gene expression into single cell-type gene expression and integrate clinical and pathologic traits, single nucleotide variation, and deconvoluted gene expression for the construction of cell type-specific predictive network models. Here, we focus on neuron-specific network models and prioritize 19 predicted key drivers modulating Alzheimer’s pathology, which we then validate by knockdown in human induced pluripotent stem cell-derived neurons. We find that neuronal knockdown of 10 of the 19 targets significantly modulates levels of amyloid-beta and/or phosphorylated tau peptides, most notablyJMJD6. We also confirm our network structure by RNA sequencing in the neurons following knockdown of each of the 10 targets, which additionally predicts that they are upstream regulators of REST and VGF. Our work thus identifies robust neuronal key drivers of the Alzheimer’s-associated network state which may represent therapeutic targets with relevance to both amyloid and tau pathology in Alzheimer’s disease.
Content aware image restoration improves spatiotemporal resolution in luminescence imaging
Authors: Boothe Tobias , Ivanković Mario , Grohme Markus A. , Markus M. Andrea , Dullin Christian , Xu Xingbo , Rink Jochen C. 
Published: May 2023

AbstractLuminescent reporters are due to their intrinsically high signal-to-noise ratio a powerful labelling tool for microscopy and macroscopic in vivo imaging in biomedical research. However, luminescence signal detection requires longer exposure times than fluorescence imaging and is consequently less suited for applications requiring high temporal resolution or throughput. Here we demonstrate that content aware image restoration can drastically reduce the exposure time requirements in luminescence imaging, thus overcoming one of the major limitations of the technique.
Mental health penalties of having a child: findings from the China family panel studies
Authors: Shi Xinjie , Shen Yu 
Published: May 2023

AbstractIn recent years, the birth rate in China has rapidly declined. While much research has been done on the penalties in earnings that women incur when they fall behind men in the labor market due to childbirth, there has been little to no research on the mental health effects. This study addresses the gap in current literature by examining the mental health penalties that women experience after having a child in comparison to men. We applied econometric modeling to data collected from China Family Panel Studies (CFPS) and found that women experienced a significant, immediate, and long-run decline (4.3%) in life satisfaction after their first child, while men were unaffected. We also found that women experienced a significant increase in depression after their first child. This suggests mental health penalties since the mental health risk proxied by these two measurements is only significant for women. This is likely related to child penalties in labor market performance and childbirth-related physical health issues. When countries adopt multiple tools to stimulate the birth rate for economic growth, they must consider the implicit burden on women—especially the long-term negative effects on mental health.
RF characteristics of 150‐nm AlGaN/GaN high electron mobility transistors fabricated using i‐line stepper lithography
Authors: Ando Yuji , Takahashi Hidemasa , Makisako Ryutaro , Wakejima Akio , Suda Jun 
Published: May 2023

AbstractThis article reports radio frequency characteristics of 150‐nm gate aluminum gallium nitride (AlGaN)/gallium nitride (GaN) high electron mobility transistors (HEMTs) fabricated using i‐line stepper lithography and a thermal reflow technique. The authors have developed two different gate structures that were a field‐plated gate using the lift‐off process and a Y‐shaped gate using the ion‐milling process. Fabricated HEMTs using these different gate structures exhibited nearly equivalent DC characteristics. The field‐plated gate device showed a unity current gain cutoff frequency (fT) of 35 GHz and a maximum oscillation frequency (fmax) of 106 GHz, while the Y‐shaped gate device showed fT of 36 GHz and fmax of 115 GHz. The equivalent circuit analysis indicated a decrease in the gate‐drain capacitance and the drain conductance is responsible for the improved fmax in the Y‐shaped gate device.