bluuebunny/crossref_metadata_2025_split huggingface dataset:
Einsatz von T-Zelltherapien in der soliden Onkologie
Authors: Müller Philipp Jie , Kobold Sebastian 
Published: November 2023

AbstractLately, cellular immunotherapies have emerged as a powerful tool in treating hematological malignancies. However, these therapeutic advances have not demonstrated sustained efficacy in solid oncology yet. The reasons are multi-layered and can be brought down to the missing antigen specificity, lack of immune cell infiltration into the tumor and the hostile tumor microenvironment, rendering immune cells dysfunctional. Here, we give an overview of current problems and solutions for cellular immunotherapies in solid tumors.
O2-sensitive Mikrokavitätenarrays: 3D-Zellkultursystem mit Sensorfunktion
Authors: Gottwald Eric , Grün Christoph , Liebsch Gregor 
Published: November 2023

AbstractOxygen is a crucial parameter for organotypic in vitro-cultures which are still performed under ambient atmosphere supplemented with 5 % CO2. This can lead to hyperoxia with its associated effects on signaling cascades and their effects on cellular behavior. Here, we describe a platform that enables real-time, label-free, optical oxygen (gradient) measurements in organotypic 3D-/organoid cultures thus allowing for physioxic culture and assay conditions in e. g. mito stress tests and substance testing.
Erzeugung menschlicher Nervengewebe in der Kulturschale
Authors: Rockel Anna F. , Ergün Süleyman , Wörsdörfer Philipp 
Published: November 2023

AbstractMultiple protocols for organoid models of the human brain were developed over the last decade, representing different brain regions. Co-cultures of these organoids, referred to as assembloids, have further increased the complexity of these cultures. Our lab is working on neuro-mesodermal assembloids, which show incorporation of blood vessels and microglia-like cells into the nervous tissue. Moreover, these assembloids also contain neural crest cells and show peripheral nervous system development.
Assessment of stature in Iron Age populations of South Africa
Authors: Steyn Maryna 
Published: November 2023

AbstractWorldwide and in South African Stone Age contexts, much research has been done on the relationship between stature of past populations and general well-being, as well as trends and patterns in stature through time. This research is aimed at collating and assessing all available stature and long bone data for Bantu-speaker individuals living in the South African Iron Age. Data for only 25 female and 32 male individuals, dating from circa AD 550 to AD 1823, could be found. In general, methods used to reconstruct stature were inconsistent and data were poorly reported. From the available data, no clear trends or patterns in stature through time could be observed and stature seems to be on a par relative to those of early twentieth century individuals. Recommendations are made as to which methods to use in stature estimations in this context. The data provided in this research can serve as reference material for future similar studies and can assist in interpreting individual stature estimations from bioarcheological research in the region.
On the consistency of relative facts
Authors: Cavalcanti Eric G. , Di Biagio Andrea , Rovelli Carlo 
Published: November 2023

AbstractLawrence et al. have presented an argument purporting to show that “relative facts do not exist” and, consequently, “Relational Quantum Mechanics is incompatible with quantum mechanics”. The argument is based on a GHZ-like contradiction between constraints satisfied by measurement outcomes in an extended Wigner’s friend scenario. Here we present a strengthened version of the argument, and show why, contrary to the claim by Lawrence et al., these arguments do not contradict the consistency of a theory of relative facts. Rather, considering this argument helps clarify how one should not think about a theory of relative facts, like RQM.
RETRACTED ARTICLE: Dual Siamese Anchor Points Adaptive Tracker with Transformer for RGBT Tracking
Authors: Fan Liangsong , Kim Pyeoungkee 
Published: November 2023

AbstractDue to environmental conditions, such as rainy days, foggy days, and dim lighting, objects in visible light images are not prominently displayed, leading to an easy loss of targets during tracking. In recent years, many RGB visible light trackers have achieved significant success in addressing visual tracking challenges. However, these trackers perform poorly when tracking targets under special conditions, such as occlusions and low-light scenarios. In contrast, objects in thermal infrared images are more distinct in poor lighting conditions. Given this characteristic, researchers have shown increased interest in the development of trackers that combine thermal infrared and visible light imagery. However, some mainstream RGBT (red–green–blue and thermal) algorithms, such as MANET and ADNET, are based on the anchor-based theory, requiring consideration of anchor box sizes and introducing a substantial number of hyperparameters. This can lead to suboptimal performance when tracking dynamically changing targets. Moreover, these models rely on convolutional neural networks for feature extraction, which have limitations in capturing global features. In this paper, we introduce a novel training network model called DAPAT, which combines the anchor-free concept with Transformer theory. DAPAT differs from previous models in several ways. Specifically, we have designed a straightforward model to extract precise global features from template and search images. We have also incorporated two enhancement modules into the model to improve template and search images of different sizes while suppressing the impact of non-target images. We employ a dual-stream feature fusion network to reduce the loss of image feature information due to feature correlation operations. Finally, we compare the performance of the tracking model proposed in this paper with some advanced RGBT trackers on three data sets (RGBT234, RGBT210, and GTOT). The test results demonstrate that our tracker exhibits improvements in robustness and success rate, among other performance aspects.
Customized Career Development Platform (CCDP) for clinical and translational researchers: A pragmatic cluster-randomized controlled trial
Authors: Rubio Doris M. , Mayowski Colleen , Meagher Emma A. , Patino Cecilia M. , Thakar Maya S. , Welch Julie L. , White Gretchen E. 
Published: November 2023

Abstract

Introduction:
Early-stage clinical and translational researchers who set and track career goals, milestones, and progress are successful in career development. We aimed to determine the effectiveness of the Customized Career Development Platform (CCDP), an online individual development plan (IDP), versus the traditional IDP template in improving research success and career satisfaction.

Methods:
We conducted a pragmatic cluster-randomized controlled trial of 340 scholars and trainees at 27 US academic healthcare institutions. The primary outcome was number of published manuscripts 24 months post-intervention. Secondary outcomes included the number of grant proposals submitted and funded, job satisfaction, and level of communication with mentors. An analysis of CCDP participants assessed proficiency level for the 14 Clinical and Translational Science Award (CTSA) competencies. Data were analyzed using intention-to-treat.

Results:
Participants were mostly female (60.3%) and Caucasian (67.2%); mean age was 34 years. Twenty-four months following the intervention, the CCDP versus traditional IDP groups showed a similar number of publications (9.4 vs 8.6), grants submitted (4.1 vs 4.4) and funded (1.3 vs 2.0), and job satisfaction score (3.6 vs 3.7). The CCDP group had higher odds of discussing communication (OR = 2.08) and leadership skills (OR = 2.62) and broadening their network (2.31) than the traditional IDP group. The CCDP arm reported improvements in 9 of the 14 CTSA competencies.

Conclusion:
The CCDP offers CTSA hubs an innovative alternative to traditional IDP tools. Future studies are needed to elucidate why the CCDP users did not fully appreciate or adopt the functionality of the online platform.
Is there really a healthy context paradox for victims of bullying? A longitudinal test of bidirectional within-and between-person associations between victimization and psychological problems
Authors: Laninga-Wijnen Lydia , Yanagida Takuya , Garandeau Claire F. , Malamut Sarah T. , Veenstra René , Salmivalli Christina 
Published: November 2023

AbstractThe finding that victims’ psychological problems tend to be exacerbated in lower-victimization classrooms has been referred to as the “healthy context paradox.” The current study has put the healthy context paradox to a strict test by examining whether classroom-level victimization moderates bidirectional within- and between-person associations between victimization and psychological adjustment. Across one school year, 3,470 Finnish 4th to 9th graders (Mage = 13.16, 46.1% boys) reported their victimization, depressive symptoms, anxiety, and self-esteem. Three types of multilevel models (cross-lagged panel, latent change score, and random-intercept cross-lagged panel) were estimated for each indicator of psychological adjustment. Findings indicated that the healthy context paradox emerges because classroom-level victimization moderates the prospective effect of victimization on psychological problems, rather than the effect of psychological problems on victimization. In classrooms with lower victimization, victims not only experience worse psychological maladjustment over time compared to others (between-person changes), but also higher maladjustment than before (absolute within-person changes).
“Baked bread to the people”: bread distribution and social and political networks at Pompeii
Authors: Tuck Steven L. 
Published: November 2023

AbstractIn 2017, archaeologists at Pompeii discovered by far the longest tomb inscription ever found at the city on a monumental tomb. This elogium provided insight into many aspects of the city's social, economic, and political world. One clause attests to the distribution of baked bread in the city. This note argues that the passage provides new evidence from Pompeii that answers two longstanding questions. The first is that of the subject of an often-reproduced Pompeian fresco. The identity of the main figure in the painting is debated: either a baker or a politician. The second is the status, political rank, and network of the owner of the property on which the fresco was discovered. Supported by the evidence of an electoral programma, the painting and inscription illuminate the mechanics of beneficence at Pompeii and serve to identify the residence of someone who operated in the political networks of the 1st-c. CE city at a sub-elite level.
γδ T cells: origin and fate, subsets, diseases and immunotherapy
Authors: Hu Yi , Hu Qinglin , Li Yongsheng , Lu Ligong , Xiang Zheng , Yin Zhinan , Kabelitz Dieter , Wu Yangzhe 
Published: November 2023

AbstractThe intricacy of diseases, shaped by intrinsic processes like immune system exhaustion and hyperactivation, highlights the potential of immune renormalization as a promising strategy in disease treatment. In recent years, our primary focus has centered on γδ T cell-based immunotherapy, particularly pioneering the use of allogeneic Vδ2+ γδ T cells for treating late-stage solid tumors and tuberculosis patients. However, we recognize untapped potential and optimization opportunities to fully harness γδ T cell effector functions in immunotherapy. This review aims to thoroughly examine γδ T cell immunology and its role in diseases. Initially, we elucidate functional differences between γδ T cells and their αβ T cell counterparts. We also provide an overview of major milestones in γδ T cell research since their discovery in 1984. Furthermore, we delve into the intricate biological processes governing their origin, development, fate decisions, and T cell receptor (TCR) rearrangement within the thymus. By examining the mechanisms underlying the anti-tumor functions of distinct γδ T cell subtypes based on γδTCR structure or cytokine release, we emphasize the importance of accurate subtyping in understanding γδ T cell function. We also explore the microenvironment-dependent functions of γδ T cell subsets, particularly in infectious diseases, autoimmune conditions, hematological malignancies, and solid tumors. Finally, we propose future strategies for utilizing allogeneic γδ T cells in tumor immunotherapy. Through this comprehensive review, we aim to provide readers with a holistic understanding of the molecular fundamentals and translational research frontiers of γδ T cells, ultimately contributing to further advancements in harnessing the therapeutic potential of γδ T cells.
Vulnerability and resilience to prenatal stress exposure: behavioral and molecular characterization in adolescent rats
Authors: Creutzberg Kerstin Camile , Begni Veronica , Orso Rodrigo , Lumertz Francisco Sindermann , Wearick-Silva Luis Eduardo , Tractenberg Saulo Gantes , Marizzoni Moira , Cattaneo Annamaria , Grassi-Oliveira Rodrigo , Riva Marco Andrea 
Published: November 2023

AbstractExposure to stress can lead to long lasting behavioral and neurobiological consequences, which may enhance the susceptibility for the onset of mental disorders. However, there are significant individual differences in the outcome of stress exposure since only a percentage of exposed individuals may show pathological consequences, whereas others appear to be resilient. In this study, we aimed to characterize the effects of prenatal stress (PNS) exposure in rats at adolescence and to identify subgroup of animals with a differential response to the gestational manipulation. PNS adolescent offspring (regardless of sex) showed impaired emotionality in different pathological domains, such as anhedonia, anxiety, and sociability. However, using cluster analysis of the behavioral data we could identify 70% of PNS-exposed animals as vulnerable (PNS-vul), whereas the remaining 30% were considered resilient (PNS-res). At the molecular level, we found that PNS-res males show a reduced basal activation of the ventral hippocampus whereas other regions, such as amygdala and dorsal hippocampus, show significant PNS-induced changes regardless from vulnerability or resilience. Taken together, our results provide evidence of the variability in the behavioral and neurobiological effects of PNS-exposed offspring at adolescence. While these data may advance our understanding of the association between exposure to stress during gestation and the risk for psychopathology, the investigation of the mechanisms associated to stress vulnerability or resilience may be instrumental to develop novel strategies for therapeutic intervention.
PDPN+ CAFs facilitate the motility of OSCC cells by inhibiting ferroptosis via transferring exosomal lncRNA FTX
Authors: Li Yaoyin , Ma Zeyi , Li Weiyu , Xu Xiaoqing , Shen Peiqi , Zhang Si-en , Cheng Bin , Xia Juan 
Published: November 2023

AbstractCancer-associated fibroblasts (CAFs) are abundant and heterogeneous in tumor microenvironment (TME). Cross-talk between cancer cells and CAFs results in cancer progression. Here, we demonstrated that a distinct cancer-associated fibroblasts subset with podoplanin (PDPN) positive expression (PDPN+ CAFs) was correlated with poor survival in oral squamous cell carcinoma (OSCC). PDPN+ CAFs promoted the progression of OSCC by transferring exosomal lncRNA FTX to OSCC cells. Mechanically, FTX bound to flap endonuclease-1 (FEN1), forming an RNA‒protein complex. FTX enhanced promoter demethylation of FEN1 by recruiting ten-eleven translocation-2 (TET2). In addition, FTX/FEN1 axis promoted OSCC cells motility by inhibiting ferroptosis. In xenograft experiments, RSL-3, a ferroptosis-inducing agent, suppressed the tumorigenesis potential of FEN1-overexpressed OSCC cells. Furthermore, Acyl-CoA synthetase long-chain family member 4 (ACSL4) was confirmed to participate in the motility promotion induced by FEN1 overexpression. FEN1 could bind to promoter region of ACSL4 and then inhibit ferroptosis in OSCC cells. Our study reveals that PDPN+ CAFs promote the invasiveness of OSCC cells by inhibiting ferroptosis through FTX/FEN1/ACSL4 signaling cascade. PDPN+ CAFs may serve as a novel potential therapeutic target for OSCC.
3,4-dimethoxychalcone induces autophagy and reduces neointimal hyperplasia and aortic lesions in mouse models of atherosclerosis
Authors: Cerrato Giulia , Alvarez-Lucena Carlota , Sauvat Allan , Hu Yanhua , Forveille Sabrina , Chen Guo , Durand Sylvère , Aprahamian Fanny , Leduc Marion , Motiño Omar , Boscá Lisardo , Xu Qingbo , Kepp Oliver , Kroemer Guido 
Published: November 2023

AbstractAutophagy inducers can prevent cardiovascular aging and age-associated diseases including atherosclerosis. Therefore, we hypothesized that autophagy-inducing compounds that act on atherosclerosis-relevant cells might have a protective role in the development of atherosclerosis. Here we identified 3,4-dimethoxychalcone (3,4-DC) as an inducer of autophagy in several cell lines from endothelial, myocardial and myeloid/macrophagic origin, as demonstrated by the aggregation of the autophagosome marker GFP-LC3 in the cytoplasm of cells, as well as the downregulation of its nuclear pool indicative of autophagic flux. In this respect, 3,4-DC showed a broader autophagy-inducing activity than another chalcone (4,4- dimethoxychalcone), spermidine and triethylene tetramine. Thus, we characterized the potential antiatherogenic activity of 3,4-DC in two different mouse models, namely, (i) neointima formation with smooth muscle expansion of vein segments grafted to the carotid artery and (ii) genetically predisposedApoE−/−mice fed an atherogenic diet. In the vein graft model, local application of 3,4-DC was able to maintain the lumen of vessels and to reduce neointima lesions. In the diet-induced model, intraperitoneal injections of 3,4-DC significantly reduced the number of atherosclerotic lesions in the aorta. In conclusion, 3,4-DC stands out as an autophagy inducer with potent antiatherogenic activity.
USP35 promotes HCC development by stabilizing ABHD17C and activating the PI3K/AKT signaling pathway
Authors: Wang Linpei , Wang Jiawei , Ma Xiaoqiu , Ju Guomin , Shi Chunfeng , Wang Wei , Wu Jian 
Published: November 2023

AbstractS-palmitoylation is a reversible protein lipidation that controls the subcellular localization and function of targeted proteins, including oncogenes such as N-RAS. The depalmitoylation enzyme family ABHD17s can remove the S-palmitoylation from N-RAS to facilitate cancer development. We previously showed that ABHD17C has oncogenic roles in hepatocellular carcinoma (HCC) cells, and its mRNA stability is controlled by miR-145-5p. However, it is still unclear whether ABHD17C is regulated at the post-translational level. In the present study, we identified multiple ubiquitin-specific proteases (USPs) that can stabilize ABHD17C by inhibiting the ubiquitin-proteasome-mediated degradation. Among them, USP35 is the most potent stabilizer of ABHD17C. We found a positive correlation between the elevated expression levels of USP35 and ABHD17C, together with their association with increased PI3K/AKT pathway activity in HCCs. USP35 knockdown caused decreased ABHD17C protein level, impaired PI3K/AKT pathway, reduced proliferation, cell cycle arrest, increased apoptosis, and mitigated migration and invasion. USP35 can interact with and stabilize ABHD17C by inhibiting its ubiquitination. Overexpression of ABHD17C can rescue the defects caused by USP35 knockdown in HCC cells. In support of these in vitro observations, xenograft assay data also showed that USP35 deficiency repressed HCC development in vivo, characterized by reduced proliferation and disrupted PI3K/AKT signaling. Together, these findings demonstrate that USP35 may promote HCC development by stabilization of ABHD17C and activation of the PI3K/AKT pathway.
Distinct transcriptomic profiles in children prior to the appearance of type 1 diabetes-linked islet autoantibodies and following enterovirus infection
Authors: Lin Jake , Moradi Elaheh , Salenius Karoliina , Lehtipuro Suvi , Häkkinen Tomi , Laiho Jutta E. , Oikarinen Sami , Randelin Sofia , Parikh Hemang M. , Krischer Jeffrey P. , Toppari Jorma , Lernmark Åke , Petrosino Joseph F. , Ajami Nadim J. , She Jin-Xiong , Hagopian William A. , Rewers Marian J. , Lloyd Richard E. , Rautajoki Kirsi J. , Hyöty Heikki , Nykter Matti ,   the TEDDY Study Group
Published: November 2023

AbstractAlthough the genetic basis and pathogenesis of type 1 diabetes have been studied extensively, how host responses to environmental factors might contribute to autoantibody development remains largely unknown. Here, we use longitudinal blood transcriptome sequencing data to characterize host responses in children within 12 months prior to the appearance of type 1 diabetes-linked islet autoantibodies, as well as matched control children. We report that children who present with insulin-specific autoantibodies first have distinct transcriptional profiles from those who develop GADA autoantibodies first. In particular, gene dosage-driven expression of GSTM1 is associated with GADA autoantibody positivity. Moreover, compared with controls, we observe increased monocyte and decreased B cell proportions 9-12 months prior to autoantibody positivity, especially in children who developed antibodies against insulin first. Lastly, we show that control children present transcriptional signatures consistent with robust immune responses to enterovirus infection, whereas children who later developed islet autoimmunity do not. These findings highlight distinct immune-related transcriptomic differences between case and control children prior to case progression to islet autoimmunity and uncover deficient antiviral response in children who later develop islet autoimmunity.
Structure of the DDB1-AMBRA1 E3 ligase receptor complex linked to cell cycle regulation
Authors: Liu Ming , Wang Yang , Teng Fei , Mai Xinyi , Wang Xi , Su Ming-Yuan , Stjepanovic Goran 
Published: November 2023

AbstractAMBRA1 is a tumor suppressor protein that functions as a substrate receptor of the ubiquitin conjugation system with roles in autophagy and the cell cycle regulatory network. The intrinsic disorder of AMBRA1 has thus far precluded its structural determination. To solve this problem, we analyzed the dynamics of AMBRA1 using hydrogen deuterium exchange mass spectrometry (HDX-MS). The HDX results indicated that AMBRA1 is a highly flexible protein and can be stabilized upon interaction with DDB1, the adaptor of the Cullin4A/B E3 ligase. Here, we present the cryo-EM structure of AMBRA1 in complex with DDB1 at 3.08 Å resolution. The structure shows that parts of the N- and C-terminal structural regions in AMBRA1 fold together into the highly dynamic WD40 domain and reveals how DDB1 engages with AMBRA1 to create a binding scaffold for substrate recruitment. The N-terminal helix-loop-helix motif and WD40 domain of AMBRA1 associate with the double-propeller fold of DDB1. We also demonstrate that DDB1 binding-defective AMBRA1 mutants prevent ubiquitination of the substrate Cyclin D1 in vitro and increase cell cycle progression. Together, these results provide structural insights into the AMBRA1-ubiquitin ligase complex and suggest a mechanism by which AMBRA1 acts as a hub involved in various physiological processes.