bluuebunny/crossref_metadata_2025_split huggingface dataset:
A bispecific Clec9A-PD-L1 targeted type I interferon profoundly reshapes the tumor microenvironment towards an antitumor state
Authors: Van Lint Sandra , Van Parys Alexander , Van Den Eeckhout Bram , Vandamme Niels , Plaisance Stephane , Verhee Annick , Catteeuw Dominiek , Rogge Elke , De Geest Jennifer , Vanderroost Nele , Roels Jana , Saeys Yvan , Uzé Gilles , Kley Niko , Cauwels Anje , Tavernier Jan 
Published: November 2023

AbstractDespite major improvements in immunotherapeutic strategies, the immunosuppressive tumor microenvironment remains a major obstacle for the induction of efficient antitumor responses. In this study, we show that local delivery of a bispecific Clec9A-PD-L1 targeted type I interferon (AcTaferon, AFN) overcomes this hurdle by reshaping the tumor immune landscape.Treatment with the bispecific AFN resulted in the presence of pro-immunogenic tumor-associated macrophages and neutrophils, increased motility and maturation profile of cDC1 and presence of inflammatory cDC2. Moreover, we report empowered diversity in the CD8+ T cell repertoire and induction of a shift from naive, dysfunctional CD8+ T cells towards effector, plastic cytotoxic T lymphocytes together with increased presence of NK and NKT cells as well as decreased regulatory T cell levels. These dynamic changes were associated with potent antitumor activity. Tumor clearance and immunological memory, therapeutic immunity on large established tumors and blunted tumor growth at distant sites were obtained upon co-administration of a non-curative dose of chemotherapy.Overall, this study illuminates further application of type I interferon as a safe and efficient way to reshape the suppressive tumor microenvironment and induce potent antitumor immunity; features which are of major importance in overcoming the development of metastases and tumor cell resistance to immune attack. The strategy described here has potential for application across to a broad range of cancer types.
Overcoming BCR::ABL1 dependent and independent survival mechanisms in chronic myeloid leukaemia using a multi-kinase targeting approach
Authors: Busch Caroline , Mulholland Theresa , Zagnoni Michele , Dalby Matthew , Berry Catherine , Wheadon Helen 
Published: November 2023

Abstract
Background
Despite improved patient outcome using tyrosine kinase inhibitors (TKIs), chronic myeloid leukaemia (CML) patients require life-long treatment due to leukaemic stem cell (LSC) persistence. LSCs reside in the bone marrow (BM) niche, which they modify to their advantage. The BM provides oncogene-independent signals to aid LSC cell survival and quiescence. The bone-morphogenetic pathway (BMP) is one pathway identified to be highly deregulated in CML, with high levels of BMP ligands detected in the BM, accompanied by CML stem and progenitor cells overexpressing BMP type 1 receptors- activin-like kinases (ALKs), especially in TKI resistant patients. Saracatinib (SC), a SRC/ABL1 dual inhibitor, inhibits the growth of CML cells resistant to the TKI imatinib (IM). Recent studies indicate that SC is also a potent ALK inhibitor and BMP antagonist. Here we investigate the efficacy of SC in overcoming CML BCR::ABL1 dependent and independent signals mediated by the BM niche both in 2D and 3D culture.

Methods
CML cells (K562 cell line and CML CD34+ primary cells) were treated with single or combination treatments of: IM, SC and the BMP receptors inhibitor dorsomorphin (DOR), with or without BMP4 stimulation in 2D (suspension) and 3D co-culture on HS5 stroma cell line and mesenchymal stem cells in AggreWell and microfluidic devices. Flow cytometry was performed to investigate apoptosis, cell cycle progression and proliferation, alongside colony assays following treatment. Proteins changes were validated by immunoblotting and transcriptional changes by Fluidigm multiplex qPCR.

Results
By targeting the BMP pathway, using specific inhibitors against ALKs in combination with SRC and ABL TKIs, we show an increase in apoptosis, altered cell cycle regulation, fewer cell divisions, and reduced numbers of CD34+ cells. Impairment of long-term proliferation and differentiation potential after combinatorial treatment also occurred.

Conclusion
BMP signalling pathway is important for CML cell survival. Targeting SRC, ABL and ALK kinases is more effective than ABL inhibition alone, the combination efficacy importantly being demonstrated in both 2D and 3D cell cultures highlighting the need for combinatorial therapies in contrast to standard of care single agents. Our study provides justification to target multiple kinases in CML to combat LSC persistence.
Lysyl oxidase inhibits BMP9-induced osteoblastic differentiation through reducing Wnt/β-catenin via HIF-1a repression in 3T3-L1 cells
Authors: Zhang Jie , Ye FangLin , Ye AiHua , He BaiCheng 
Published: November 2023

Abstract
Background
Bone morphogenetic protein 9 (BMP9) is a promising growth factor in bone tissue engineering, while the detailed molecular mechanism underlying BMP9-oriented osteogenesis remains unclear. In this study, we investigated the effect of lysyl oxidase (Lox) on the BMP9 osteogenic potential via in vivo and in vitro experiments, as well as the underlying mechanism.

Methods
PCR assay, western blot analysis, histochemical staining, and immunofluorescence assay were used to quantify the osteogenic markers level, as well as the possible mechanism. The mouse ectopic osteogenesis assay was used to assess the impact of Lox on BMP9-induced bone formation.

Results
Our findings suggested that Lox was obviously upregulated by BMP9 in 3T3-L1 cells. BMP9-induced Runx2, OPN, and mineralization were all enhanced by Lox inhibition or knockdown, while Lox overexpression reduced their expression. Additionally, the BMP9-induced adipogenic makers were repressed by Lox inhibition. Inhibition of Lox resulted in an increase in c-Myc mRNA and β-catenin protein levels. However, the increase in BMP9-induced osteoblastic biomarkers caused by Lox inhibition was obviously reduced when β-catenin knockdown. BMP9 upregulated HIF-1α expression, which was further enhanced by Lox inhibition or knockdown, but reversed by Lox overexpression. Lox knockdown or HIF-1α overexpression increased BMP9-induced bone formation, although the enhancement caused by Lox knockdown was largely diminished when HIF-1α was knocked down. Lox inhibition increased β-catenin levels and decreased SOST levels, which were almost reversed by HIF-1α knockdown.

Conclusion
Lox may reduce the BMP9 osteoblastic potential by inhibiting Wnt/β-catenin signaling via repressing the expression HIF-1α partially.

Graphical abstract
Development of a clinically useful multi‐segment kinetic foot model
Authors: Zhu Songlin , Jenkyn Thomas 
Published: November 2023

AbstractBackgroundTraditionally, gait analysis studies record the foot as a single rigid segment, leaving movements and loads within the foot undetected. In addition, very few data of multi‐segment foot kinetics have been represented in the literature due to measurement and equipment limitations. As a result, this study aims to develop a novel multi‐segment kinetic foot model that is clinically feasible and enables both kinematic and kinetic analysis of large patient groups.ResultsOutcome measurements include rotation angles of intersegmental dorsi/plantar flexion, inversion/eversion, and internal/external rotation, joint moments, joint powers and the medial longitudinal arch (MLA) height/length ratio. Repeatability of joint motions was calculated using coefficients of multiple correlation. Most joint motions measured by this foot model showed strong within‐subject reliability (R > 0.7) in healthy adults. Outcome measures were in agreement with other multi‐segment foot models found in the biomechanics literature.ConclusionsThis novel multi‐segment foot model is able to quantify intersegmental foot kinematics and kinetics and can be a useful tool for research and assessments on clinical populations.
Proteomic analysis of exosomes secreted during the epithelial-mesenchymal transition and potential biomarkers of mesenchymal high-grade serous ovarian carcinoma
Authors: Ferreira Germano Aguiar , Thomé Carolina Hassibe , Izumi Clarice , Grassi Mariana Lopes , Lanfredi Guilherme Pauperio , Smolka Marcus , Faça Vitor Marcel , Candido dos Reis Francisco José 
Published: November 2023

Abstract
Background
The epithelial-mesenchymal transition (EMT) promotes cell signaling and morphology alterations, contributing to cancer progression. Exosomes, extracellular vesicles containing proteins involved in cell-cell communication, have emerged as a potential source of biomarkers for several diseases.

Methods
Our aim was to assess the proteome content of exosomes secreted after EMT-induction to identify potential biomarkers for ovarian cancer classification. EMT was induced in the ovarian cancer cell line CAOV3 by treating it with EGF (10 ng/mL) for 96 h following 24 h of serum deprivation. Subsequently, exosomes were isolated from the supernatant using selective centrifugation after decellularization, and their characteristics were determined. The proteins present in the exosomes were extracted, identified, and quantified using Label-Free-Quantification (LFQ) via Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). To identify potential biomarkers, the obtained proteomic data was integrated with the TGGA database for mRNA expression using principal component analysis and a conditional inference tree.

Results
The exosomes derived from CAOV3 cells exhibited similar diameter and morphology, measuring approximately 150 nm, regardless of whether they were subjected to EMT stimulation or not. The proteomic analysis of proteins from CAOV3-derived exosomes revealed significant differential regulation of 157 proteins, with 100 showing upregulation and 57 downregulation upon EMT induction. Further comparison of the upregulated proteins with the TCGA transcriptomic data identified PLAU, LAMB1, COL6A1, and TGFB1 as potential biomarkers of the mesenchymal HGSOC subtype.

Conclusions
The induction of EMT, the isolation of exosomes, and the subsequent proteomic analysis highlight potential biomarkers for an aggressive ovarian cancer subtype. Further investigation into the role of these proteins is warranted to enhance our understanding of ovarian cancer outcomes.
EZH2 K63-polyubiquitination affecting migration in extranodal natural killer/T-cell lymphoma
Authors: Li Boheng , Zhou Qidi , Wan Qin , Qiao Xuan , Chen Shangying , Zhou Jianbiao , Wuxiao Zhijun , Luo Lei , Ng Siok-Bian , Li Jieping , Chng Wee-Joo 
Published: November 2023

Abstract
Background
Overexpressed EZH2 is oncogenically involved in the pathogenesis of different cancerous contexts including extranodal natural killer/T cell lymphoma (ENKTL). However, the underlying mechanisms of EZH2 upregulation have not been fully clarified and it is still difficult to target EZH2 in ENKTL.

Results
Current study identifies an E3 ligase TRIP12 that triggers K63-linked polyubiquitination of EZH2 in ENKTL and unexpectedly, stabilizes EZH2. As determined by gene expression profiling (GEP), TRIP12 and EZH2 levels correlate with each other in ENKTL patient samples. Aided by quantitative mass spectrometry (MS) and follow-up analysis, we identify K634 as the ubiquitination site of EZH2. Further study confirms that TRIP12-mediated EZH2 K634 ubiquitination enhances the interaction between EZH2 and SUZ12 or CDK1 and increases the level of EZH2 T487 phosphorylation. This study further demonstrates the TRIP12-EZH2 signaling might be regulated by cytoplasmic HSP60. Importantly, the TRIP12-EZH2 axis mediates ENKTL cell migration via accelerating epithelial-mesenchymal transition (EMT). Moreover, our study finds out dexamethasone treatment manipulates TRIP12-EZH2 signaling and may represent a novel therapeutic strategy against ENKTL metastasis.

Conclusions
Altogether, TRIP12 induces K63-linked site-specific polyubiquitination of EZH2 for stabilization, which promotes ENKTL cell migration and could be targeted by dexamethasone treatment.
Numerical and Experimental Behavior of Two-Story Confined Masonry Structure Subjected to Cyclic Loads
Authors: El-Diasity Mosaad , Salah Sayed , El-Hariri Mohamed O. R. , Gamal Amr A. , Elsalakawy Tarik S. 
Published: November 2023

AbstractThis research presents the numerical and experimental results of lateral cyclic loading applied on a two-story confined masonry structure utilizing local materials and standards. Two half-scale confined masonry structures were constructed using clay masonry units, confining columns, tie beams, and reinforced concrete slabs. The assemblies were tested up to failure using a displacement controlled loading methodology under vertical self-weight and lateral reversed cyclic loading. The walls of the assemblies have varying perforations (solid / windows / doors) to examine the influence of perforation on in-plane and out-of-plane performance. A strengthened assembly with an exterior layer of ferrocement has been used and this suggested upgrading approach enhanced the lateral resistance of the confined assembly by about (61–95%) while improving ductility and total energy absorbed by 27%. The maximum lateral drift at failure have been decreased to (23–31%), however the corresponding load for the first visible fracture have been raised by (150–175%). Furthermore, total failure has been delayed for the strengthened walls (all sides, particularly the perforated sides). Comparing distorted forms, fracture patterns, and capacity curves of finite element models included in this research yielded excellent agreement.
Koryŏ inlay celadon from Taicang Port of the Yuan Dynasty, China
Authors: Chang Dongxue , Zhang Zhiqing , Li Xiaoshuang , Zhang Liangren 
Published: November 2023

Abstract
Inlay celadon was a type of high-end ceramics of the Koryŏ dynasty (918–1392 AD) produced in the Korean Peninsula. It was conveyed to China during the Yuan dynasty (1279–1368 AD) as tribute or trade goods. In this study, the authors analyzed six samples of inlay celadon recently discovered at the prosperous Taicang Port of the Yuan and Ming dynasties in the lower Yangtze River, China. With scanning electron microscopy coupled with energy dispersive spectroscopy (SEM–EDS) and X-ray diffraction (XRD), the authors investigated the production technique, and compositional characteristics of these samples for the purpose of tracking their provenances. While the bodies are made of porcelain stone, the glazes are of porcelain stone and calcium-rich flux. The white inlay material in these samples is kaolinite-dominant, and the black one is made of quartz with high Fe content or a compound of quartz and raw materials with high Fe content. The results link the samples uncovered at the Taicang Port to the Samhǔngni Kiln in Kangjin-gun and the Uch'ǒlli and Chinsǒri Kilns in Buan-gun in Southern Korea. The products from these kilns were shipped to China in several shipments.
Corrosion of carbon steel rebar in binary blended concrete with accelerated chloride transport
Authors: Hoque Kazi Naimul , Presuel-Moreno Francisco , Nazim Manzurul 
Published: November 2023

AbstractSamples with two different binary blended concrete mixes were prepared, one containing cement replacement of 50% slag (referred here as SL mix) and the other containing cement replacement of 20% fly ash (termed here as FA mix). The water to cementitious ratio used to produce concrete specimens was 0.41. On the top surface of each specimen, various reservoir lengths that ranged from 2.5 cm to 17.5 cm were fitted, and these reservoirs were filled with a 10% NaCl solution. Electromigration was used to accelerate the transport of chlorides, with an applied potential of 9 V at first, and subsequently reduced to 3 V after about a week. The electromigration was applied for a short period (few weeks to a couple of months). For a period of about 1100 days, the corrosion related parameters such as concrete solution resistance, rebar potential, and corrosion current were monitored via the rebar potential measurements, linear polarization resistance (LPR) and electrochemical impedance spectroscopy (EIS) measurements, the latter used only to obtain the solution resistance. The corrosion current values determined through experimental observations were then converted to mass loss using Faraday’s law. The readings of corrosion current values (last 7 sets of readings) as well as the calculated mass loss values were found to be larger for the rebars embedded in specimens prepared with SL mix, followed by rebars embedded in specimens prepared with FA mix. Corrosion current and calculated mass loss values in general tended to increase with increasing solution reservoir lengths. No cracks or corrosion products that reached the surface of the concrete were observed on the specimens for the duration of the reported monitored propagation period. This study offers a framework for future studies on accelerated steel corrosion in concrete.
NoOnesRose: An Interview with Pierre Joris
Authors: Bernstein Charles 
Published: November 2023

Abstract
Pierre Joris discusses his literary journey from Luxembourg to Bard College to Algeria to Paris and London and finally New York. Joris focuses on his translation of Paul Celan, his engagement with the poetry of the Maghreb (culminating in his coediting of The University of California Book of North African Literature, volume 4 of Poems for the Millennium), and the importance of French poet Edmond Jabès. He goes on to address his choice to write in his fourth language, English, and the formative readings of American poetry and his connection to some of the New American Poets of the generation older than him. In the course of the interview, Joris discusses his sense of a nomadic community—or perhaps better to say “negative” or “inoperable” community. Throughout, he comes back to his commitments to writing poetry and to translation as the core the practice of poetry.
The Darkness in the Poem, and the Light: Beyond Witness—the Visionary, Non-Soteriological Poetics of Paul Celan
Authors: Joris Pierre 
Published: November 2023

Abstract
Reflecting on a question posed to the author by the poet Gerrit Lansing concerning a possible soteriological dimension of Paul Celan's thought, this essay argues for Celan as a radically secular figure—revolutionary both politically and poetically—whose Jewishness was and remained an absolute for him, without this, however, having led to a retro-assimilation within a, or any, religious or theological stance. Using certain core images of Celan's poetry—his doors—and thinking their metaphoricity and polysemanticism through with the help of the painter Irving Petlin's series of works inspired by and reflecting on Celan's doors, the essay, after examining a range of critical takes on Celan—by the likes of Otto Pöggeler, George Steiner, Hans-Georg Gadamer, Jean Bollack, and others—comes to the conclusion that probably the only salvific quality for Celan lay in the act of writing itself, and was thus not a transcendental reach.
Computer Center Sabotage, 1968–1971: Luddism, Black Studies, and the Diversion of Technological Progress
Authors: Larson Max 
Published: November 2023

AbstractThroughout the late 1960s and early 1970s students across the United States repeatedly seized and in some cases destroyed university computer centers. Supporters and detractors alike have tended to frame these incidents narrowly, in terms of a generalized war against technology. This essay offers a more expansive account, demonstrating that this brief yet intense rash of computer center sabotage was more complex and, frankly, more interesting than a bad case of technophobia. While it was clearly directed against computers, sabotage often had less to do with computerization itself than with imperialism and racial injustice. Saboteurs targeted computational collaborations with the Department of Defense, and they held computers hostage in exchange for increased support for Black students. This does not mean that computers themselves were irrelevant to computer center sabotage. Rather, it pushes us to rethink how computers and other technical devices become political objects.
Not All Shocks Are Created Equal: Assessing Heterogeneity in the Bank Lending Channel
Authors: Nogueira Gil , Farinha Luísa , Blattner Laura 
Published: November 2023

We provide evidence that the yield impact of unconventional monetary policy is not a sufficient statistic to measure the strength of the bank lending channel of unconventional monetary policy. As a laboratory, we study three major positive events in the European sovereign debt crisis—the Greek debt restructuring (private sector involvement (PSI)), outright monetary transactions (OMT), and quantitative easing (QE)—using credit registry and security-level bank balance sheet data from Portugal, a country that was directly exposed to all three events. Even though the price of sovereign debt increased by substantially more after the PSI and OMT announcements, only QE led banks to reduce their net sovereign debt holdings and had statistically and economically significant effects on lending to firms and households. The differential effect on banks’ behavior reflects two forces. First, lower bank capitalization levels during the PSI and OMT episodes as well as disincentives to sell sovereign bonds because of their collateral value in the European Central Bank’s long-term refinancing operation facilities reduce the effectiveness of the recapitalization channel. Second, only QE involved direct asset purchases by the central bank and thereby induced a portfolio rebalancing channel from sovereign debt to loans. This paper was accepted by Victoria Ivashina, finance. Funding: The contribution by G. Nogueira to this paper has been prepared under the Lamfalussy Fellowship Program sponsored by the European Central Bank. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2023.00104 .
Tele-Health Psychological Interventions in Breast Cancer at the Time of Coronavirus: A Narrative Review
Authors: Bertolucci Ilaria 
Published: November 2023

Introduction: During the recent pandemic-related health emergency of COVID-19, the health system care has undergone several substantial and sudden changes to benefit the populations of patients affected by COVID-19 delaying the diagnosis and treatment of all other patients. One of the most vulnerable populations during this period was the oncological population. The use of telemedicine has become necessary to compensate for all this by forging medical and psychological support at a distance.
Objectives: The purpose of this narrative review is to offer an overview of the literature on present scientific papers regarding tele-health psychological interventions aimed at breast cancer patients during the pandemic period of COVID-19 and discussing the reported effects.
Methods: This narrative review has been realized through a revision of the scientific literature conducted from August to October 2023 using the following electronic databases: “PubMed”, “Science Direct” and “Google Scholar” typing keywords related to the pandemic period, breast cancer population and telehealth psychological interventions. For the evaluation of the effects of the interventions, the statistical indices of p-value and effect size measures were considered.
Results: Online mindfulness-based interventions have been found to be significant in reducing anxiety, depression and sleep problems, and in improving self-perception of body image, quality of life, and self-efficacy. No significant results are detected in the reduction of depression symptoms and stress levels between groups.
Discussions: Very limited studies investigated the topic. Further research is needed to better understand the efficacy of telepsychology during the pandemic period and deepen research in terms of other therapeutic approaches and other methods of treatment delivery. In addition, interventions based on a systemic approach, that involve both health care workers and caregivers, can be more effective for the overall well-being of breast cancer patients.