bluuebunny/crossref_metadata_2025_split huggingface dataset:
Big food and drink sponsorship of conferences and speakers: a case study of one multinational company’s influence over knowledge dissemination and professional engagement
Authors: Atli Gunnarsson Jónas , Ruskin Gary , Stuckler David , Steele Sarah 
Published: December 2022

AbstractObjectives:Research identifies that multinational corporations, including The Coca-Cola Company (‘Coca-Cola’), seek to influence public health research and policy through scientific events, such as academic and professional conferences. This study aims to understand how different forms of funding and sponsorship impact the relationship between Coca-Cola, academic institutions, public health organisations, academics and researchers.Design:The study was conducted using Freedom of Information (FOI) requests and systematic website searches.Setting:Data were collected by twenty-two FOI requests to institutions in the USA and UK, resulting in the disclosure of 11 488 pages, including emails and attachments relating to 239 events between 2009 and 2018. We used the Wayback Machine to review historical website data to evaluate evidence from 151 available official conference websites.Participants:N/AResults:Documents suggest that Coca-Cola provides direct financial support to institutions and organisations hosting events in exchange for benefits, including influence over proceedings. Coca-Cola also provided direct financial support to speakers and researchers, sometimes conditional on media interviews. Also, indirect financial support passed through Coca-Cola-financed non-profits. Often, such financial support was not readily identifiable, and third-party involvement further concealed Coca-Cola funding.Conclusion:Coca-Cola exerts direct influence on academic institutions and organisations that convene major public health conferences and events. These events offer Coca-Cola a vehicle for its messaging and amplifying viewpoints favourable to Coca-Cola’s interests. Such corporate-sponsored events should be viewed as instruments of industry marketing. Stronger rules and safeguards are needed to prevent hidden industry influence, such as complete disclosure of all corporate contributions for public health conferences and their speakers.
Monitoring CO2 Injection at the CaMI Field Research Station Using Microseismic Noise Sources
Authors: Li Tianyang , Gu Yu Jeffrey , Lawton Donald C. , Gilbert Hersh , Macquet Marie , Savard Genevieve , Wang Jingchuan , Innanen Kristopher A. , Yu Nian 
Published: November 2022

AbstractMonitoring subsurface velocity variations due to industrial activities using passive seismic imaging techniques has gained popularity in recent years. In this study, we examine the spatiotemporal variations of persistent, non‐ambient seismic noise during CO2 sequestration at the Containment and Monitoring Institute Field Research Station near Brooks, Alberta, Canada. Based on the temporal migration and power spectral density (PSD) analysis of continuous seismic records from both a dense geophone array and “X”‐shaped geophone lines operated from June to August 2019, we detect two non‐ambient local noise sources correlated with the local industrial activities during the two months: a dominant noise source (1–5 Hz) southeast of the study region and a slightly weaker noise source in the higher frequency range (5–15 Hz) around the injection well. The former noise source overlaps with the operations near a submersible disposal pump. The substantial diurnal variations in noise levels in PSD as a function of time of day, month and location are further evidence of these two noise sources. We propose that the persistent noise source around the injection well originated from the subsurface microtremors caused by the coupled interaction between the injected CO2 fluid and formation rocks. The proposed methods based on passive microseismic noise offer a potentially valuable strategy for long‐term evaluation of the safety of CO2 sequestration, which can be extended to future integrity monitoring of underground energy storage.
Shallow Ice‐Sheet Composite Structure Revealed by Seismic Imaging Near the West Antarctic Ice Sheet (WAIS) Divide Camp
Authors: Zhang Zhendong , Nakata Nori , Karplus Marianne , Kaip Galen , Yi Jia 
Published: November 2022

AbstractSmall‐scale polar ice‐sheet composite structures can influence coarse‐grained climate models. For example, surface melting can hydro‐fracture the ice and may eventually lubricate the base. The drainage process will change the petrophysical properties of the subsurface and is predictable from high‐resolution seismic imaging. Ray‐based imaging methods, though limited by the approximations made, have mapped seismic velocities in 1D, but have yet to offer definitive information about the lateral heterogeneity. Here we use the wave‐equation‐based seismic imaging method to estimate shear‐wave velocities and to image an englacial reflector in 2D. We use 7‐day ambient‐noise data recorded by a linear array near the West Antarctic Ice Sheet (WAIS) Divide drilling site to perform the study. We obtain 2D vertical and horizontal shear‐wave velocity models and observe a lateral variation of the radial anisotropy along the acquisition line. The inverted velocity model is further used to estimate the thicknesses of firn‐air and firn layers. We also observe evident SH reflections and calculate the reflector image using robust zero‐offset imaging and a more precise reverse time migration imaging method. The imaged reflector is at about 1,700 m depth and is dipping to the southwest. We anticipate that a porosity change at that depth may cause this englacial seismic discontinuity near WAIS Divide. Our results demonstrate the feasibility of estimating the petrophysical properties of polar ice using seismic methods. We anticipate our work to be further used for understanding ice dynamics and thermodynamics, such as the stability of ice shelves, the retreat of the Antarctic ice sheet, and restoring the paleo‐sedimentary environment.
Diagnostics in Waldenström’s macroglobulinemia: a consensus statement of the European Consortium for Waldenström’s Macroglobulinemia
Authors: Dogliotti Irene , Jiménez Cristina , Varettoni Marzia , Talaulikar Dipti , Bagratuni Tina , Ferrante Martina , Pérez José , Drandi Daniela , Puig Noemí , Gilestro Milena , García-Álvarez María , Owen Roger , Jurczak Wojciech , Tedeschi Alessandra , Leblond Veronique , Kastritis Efstathios , Kersten Marie José , D’Sa Shirley , Kaščák Michal , Willenbacher Wolfgang , Roccaro Aldo M. , Poulain Stephanie , Morel Pierre , Kyriakou Charalampia , Fend Falko , Vos Josephine M. I. , Dimopoulos Meletios A. , Buske Christian , Ferrero Simone , García-Sanz Ramón 
Published: November 2022

AbstractThe diagnosis of Waldenström’s macroglobulinemia (WM), an IgM-associated lymphoplasmacytic lymphoma, can be challenging due to the different forms of disease presentation. Furthermore, in recent years, WM has witnessed remarkable progress on the diagnostic front, as well as a deeper understanding of the disease biology, which has affected clinical practice. This, together with the increasing variety of tools and techniques available, makes it necessary to have a practical guidance for clinicians to perform the initial evaluation of patients with WM. In this paper, we present the consensus recommendations and laboratory requirements for the diagnosis of WM developed by the European Consortium of Waldenström’s Macroglobulinemia (ECWM), for both clinical practice as well as the research/academical setting. We provide the procedures for multiparametric flow cytometry, fluorescence in situ hybridization and molecular tests, and with this offer guidance for a standardized diagnostic work-up and methodological workflow of patients with IgM monoclonal gammopathy of uncertain significance, asymptomatic and symptomatic WM.
Activation of orphan receptor GPR132 induces cell differentiation in acute myeloid leukemia
Authors: Yi Chunyang , He Jiacheng , Huang Dan , Zhao Yumiao , Zhang Chan , Ye Xiyun , Huang Ying , Nussinov Ruth , Zheng Junke , Liu Mingyao , Lu Weiqiang 
Published: November 2022

AbstractBlocked cellular differentiation is a critical pathologic hallmark of acute myeloid leukemia (AML). Here, we showed that genetic activation of the orphan GPCR GPR132 significantly induced cell differentiation of AML both in vitro and in vivo, indicating that GPR132 is a potential trigger of myeloid differentiation. To explore the therapeutic potential of GPR132 signaling, we screened and validated a natural product 8-gingerol (8GL) as a GPR132 agonist. Notably, GPR132 activation by 8GL promoted differentiation and reduced colony formation in human AML cell lines with diverse genetic profiles. Mechanistic studies revealed that 8GL treatment inhibits the activation of the mammalian target of rapamycin (mTOR), a regulator of AML cell differentiation blockade, via activating GPR132-Gs-PKA pathway. We further showed that the combination of 8GL and an mTOR inhibitor synergistically elicited AML cell differentiation in vitro. Importantly, 8GL alone or in combination with an mTOR inhibitor remarkably impaired tumor growth and extended mouse survival in an AML xenograft model accompanied by enhanced cell differentiation. Notably, genetic or pharmacological activation of GPR132 triggered the differentiation of human primary AML cells. In summary, this study demonstrated that activation of orphan GPR132 represents a potential strategy for inducing myeloid differentiation in AML patients.
High-confidence cancer patient stratification through multiomics investigation of DNA repair disorders
Authors: Mkrtchyan Garik V. , Veviorskiy Alexander , Izumchenko Evgeny , Shneyderman Anastasia , Pun Frank W. , Ozerov Ivan V. , Aliper Alex , Zhavoronkov Alex , Scheibye-Knudsen Morten 
Published: November 2022

AbstractMultiple cancer types have limited targeted therapeutic options, in part due to incomplete understanding of the molecular processes underlying tumorigenesis and significant intra- and inter-tumor heterogeneity. Identification of novel molecular biomarkers stratifying cancer patients with different survival outcomes may provide new opportunities for target discovery and subsequent development of tailored therapies. Here, we applied the artificial intelligence-driven PandaOmics platform (https://pandaomics.com/) to explore gene expression changes in rare DNA repair-deficient disorders and identify novel cancer targets. Our analysis revealed that CEP135, a scaffolding protein associated with early centriole biogenesis, is commonly downregulated in DNA repair diseases with high cancer predisposition. Further screening of survival data in 33 cancers available at TCGA database identified sarcoma as a cancer type where lower survival was significantly associated with high CEP135 expression. Stratification of cancer patients based on CEP135 expression enabled us to examine therapeutic targets that could be used for the improvement of existing therapies against sarcoma. The latter was based on application of the PandaOmics target-ID algorithm coupled with in vitro studies that revealed polo-like kinase 1 (PLK1) as a potential therapeutic candidate in sarcoma patients with high CEP135 levels and poor survival. While further target validation is required, this study demonstrated the potential of in silico-based studies for a rapid biomarker discovery and target characterization.
GOLPH3 protein controls organ growth by interacting with TOR signaling proteins in Drosophila
Authors: Frappaolo Anna , Karimpour-Ghahnavieh Angela , Cesare Giuliana , Sechi Stefano , Fraschini Roberta , Vaccari Thomas , Giansanti Maria Grazia 
Published: November 2022

AbstractThe oncoprotein GOLPH3 (Golgi phosphoprotein 3) is an evolutionarily conserved phosphatidylinositol 4-phosphate effector, mainly localized to the Golgi apparatus, where it supports organelle architecture and vesicular trafficking. Overexpression of human GOLPH3 correlates with poor prognosis in several cancer types and is associated with enhanced signaling downstream of mTOR (mechanistic target of rapamycin). However, the molecular link between GOLPH3 and mTOR remains elusive. Studies inDrosophila melanogasterhave shown that Translationally controlled tumor protein (Tctp) and 14-3-3 proteins are required for organ growth by supporting the function of the small GTPase Ras homolog enriched in the brain (Rheb) during mTORC1 (mTOR complex 1) signaling. Here we demonstrate thatDrosophilaGOLPH3 (dGOLPH3) physically interacts with Tctp and 14-3-3ζ. RNAi-mediated knockdown of dGOLPH3 reduces wing and eye size and enhances the phenotypes ofTctpRNAi. This phenotype is partially rescued by overexpression of Tctp, 14-3-3ζ, or Rheb. We also show that the Golgi localization of Rheb inDrosophilacells depends on dGOLPH3. Consistent with dGOLPH3 involvement in Rheb-mediated mTORC1 activation, depletion of dGOLPH3 also reduces levels of phosphorylated ribosomal S6 kinase, a downstream target of mTORC1. Finally, the autophagy flux and the expression of autophagic transcription factors of the TFEB family, which anti correlates with mTOR signaling, are compromised upon reduction of dGOLPH3. Overall, our data provide the first in vivo demonstration that GOLPH3 regulates organ growth by directly associating with mTOR signaling proteins.
Identification of a group of bisbenzylisoquinoline (BBIQ) compounds as ferroptosis inhibitors
Authors: Fan Yipu , Zhang Yihan , Shi Kunyu , Cheng Shan , Pei Duanqing , Shu Xiaodong 
Published: November 2022

AbstractFerroptosis induced by detrimental accumulation of lipid peroxides has been recently linked to a variety of pathological conditions ranging from acute tissue injuries to chronic degenerative diseases and suppression of ferroptosis by small chemical inhibitors is beneficial to the prevention and treatment of these diseases. However, in vivo applicable small chemical ferroptosis inhibitors are limited currently. In this study, we screened an alkaloid natural compound library for compounds that can inhibit RSL3-induced ferroptosis in HT1080 cells and identified a group of bisbenzylisoquinoline (BBIQ) compounds as novel ferroptosis-specific inhibitors. These BBIQ compounds are structurally different from known ferroptosis inhibitors and they do not appear to regulate iron homeostasis or lipid ROS generation pathways, while they are able to scavenge 1,1-diphenyl-2-picryl-hydrazyl (DPPH) in cell-free reactions and prevent accumulation of lipid peroxides in living cells. These BBIQ compounds demonstrate good in vivo activities as they effectively protect mice from folic acid-induced renal tubular ferroptosis and acute kidney injury. Several BBIQ compounds are approved drugs in Japan and China for traditional uses and cepharanthine is currently in clinical trials against SARS-CoV-2, our discovery of BBIQs as in vivo applicable ferroptosis inhibitors will expand their usage to prevent ferroptotic tissue damages under various pathological conditions.
Mutual regulation between phosphofructokinase 1 platelet isoform and VEGF promotes glioblastoma tumor growth
Authors: Lim Je Sun , Shi YuJie , Park Su Hwan , Jeon So Mi , Zhang Chuanbao , Park Yun-Yong , Liu Rui , Li Jing , Cho Wan-Seob , Du Linyong , Lee Jong-Ho 
Published: November 2022

AbstractGlioblastoma (GBM) is a highly vascular malignant brain tumor that overexpresses vascular endothelial growth factor (VEGF) and phosphofructokinase 1 platelet isoform (PFKP), which catalyzes a rate-limiting reaction in glycolysis. However, whether PFKP and VEGF are reciprocally regulated during GBM tumor growth remains unknown. Here, we show that PFKP can promote EGFR activation-induced VEGF expression in HIF-1α-dependent and -independent manners in GBM cells. Importantly, we demonstrate that EGFR-phosphorylated PFKP Y64 has critical roles in both AKT/SP1-mediated transcriptional expression ofHIF-1αand in the AKT-mediated β-catenin S552 phosphorylation, to fully enhanceVEGFtranscription, subsequently promoting blood vessel formation and brain tumor growth. Levels of PFKP Y64 phosphorylation in human GBM specimens are positively correlated with HIF-1α expression, β-catenin S552 phosphorylation, and VEGF expression. Conversely, VEGF upregulates PFKP expression in a PFKP S386 phosphorylation-dependent manner, leading to increased PFK enzyme activity, aerobic glycolysis, and proliferation in GBM cells. These findings highlight a novel mechanism underlying the mutual regulation that occurs between PFKP and VEGF for promoting GBM tumor growth and also suggest that targeting the PFKP/VEGF regulatory loop might show therapeutic potential for treating GBM patients.
Metabolic regulation of cholestatic liver injury by D-2-hydroxyglutarate with the modulation of hepatic microenvironment and the mammalian target of rapamycin signaling
Authors: Tian Xinbei , Wang Ying , Lu Ying , Wu Bo , Chen Shanshan , Du Jun , Cai Wei , Xiao Yongtao 
Published: November 2022

AbstractBiliary atresia (BA) is a cholestatic liver disease in neonates with devastating obstructive intrahepatic and extrahepatic biliary ducts. Owing to the lack of an early diagnostic marker and limited understanding of its pathogenesis, BA often leads to death within 2 years. Therefore, this study aimed to develop early diagnostic methods and investigate the underlying pathogenesis of liver injury in BA using metabolomics. Metabolomics and organoid combined energy metabolism analysis was used to obtain new insights into BA diagnosis and pathobiology using patient samples, mice liver organoids, and a zebrafish model. Metabolomics revealed that D-2-hydroxyglutarate (D-2-HG) levels were significantly elevated in the plasma and liver of patients with BA and closely correlated with liver injuries and impaired liver regeneration. D-2-HG suppressed the growth and expansion of liver organoids derived from the intrahepatic biliary ducts. The energy metabolism analysis demonstrated that D-2-HG inhibited mitochondrial respiration and ATP synthase; however, it increased aerobic glycolysis in organoids. In addition, D-2-HG exposure caused liver degeneration in zebrafish larvae. Mechanistically, D-2-HG inhibited the activation of protein kinase B and the mammalian target of rapamycin signaling. These findings reveal that D-2-HG may represent a novel noninvasive diagnostic biomarker and a potential therapeutic target for infants with BA.
Extrinsic cell death pathway plasticity: a driver of clonal evolution in cancer?
Authors: Seidel Eric , von Karstedt Silvia 
Published: November 2022

AbstractHuman cancers are known to adhere to basic evolutionary principles. During their journey from early transformation to metastatic disease, cancer cell populations have proven to be remarkably adaptive to different forms of intra- and extracellular selective pressure, including nutrient scarcity, oxidative stress, and anti-cancer immunity. Adaption may be achieved via the expansion of clones bearing driver mutations that optimize cellular fitness in response to the specific selective scenario, e.g., mutations facilitating evasion of cell death, immune evasion or increased proliferation despite growth suppression, all of which constitute well-established hallmarks of cancer. While great progress concerning the prevention, diagnosis and treatment of clinically apparent disease has been made over the last 50 years, the mechanisms underlying cellular adaption under selective pressure via the immune system during early carcinogenesis and its influence on cancer cell fate or disease severity remain to be clarified. For instance, evasion of cell death is generally accepted as a hallmark of cancer, yet recent decades have revealed that the extrinsic cell death machinery triggered by immune effector cells is composed of an astonishingly complex network of interacting—and sometimes compensating—modes of cell death, whose role in selective processes during early carcinogenesis remains obscure. Based upon recent advances in cell death research, here we propose a concept of cell death pathway plasticity in time shaping cancer evolution prior to treatment in an effort to offer new perspectives on how cancer cell fate may be determined by cell death pathway plasticity during early carcinogenesis.
Proteomic and functional profiling of platelet-derived extracellular vesicles released under physiological or tumor-associated conditions
Authors: Vismara Mauro , Manfredi Marcello , Zarà Marta , Trivigno Silvia Maria Grazia , Galgano Luca , Barbieri Silvia Stella , Canobbio Ilaria , Torti Mauro , Guidetti Gianni Francesco 
Published: November 2022

AbstractDuring hemostasis, thrombosis, and inflammation, activated blood platelets release extracellular vesicles (PEVs) that represent biological mediators of physiological and pathological processes. We have recently demonstrated that the activation of platelets by breast cancer cells is accompanied by a massive release of PEVs, evidence that matches with the observation that breast cancer patients display increased levels of circulating PEVs. A core concept in PEVs biology is that their nature, composition and biological function are strongly influenced by the conditions that induced their release. In this study we have performed a comparative characterization of PEVs released by platelets upon activation with thrombin, a potent thrombotic stimulus, and upon exposure to the breast cancer cell line MDA-MB-231. By nanoparticle tracking analysis and tandem mass spectrometry we have characterized the two populations of PEVs, showing that the thrombotic and tumoral stimuli produced vesicles that largely differ in protein composition. The bioinformatic analysis of the proteomic data led to the identification of signaling pathways that can be differently affected by the two PEVs population in target cells. Specifically, we have demonstrated that both thrombin- and cancer-cell-induced PEVs reduce the migration and potentiate Ca2+-induced apoptosis of Jurkat cells, but only thrombin-derived PEVs also potentiate cell necrosis. Our results demonstrate that stimulation of platelets by thrombotic or tumoral stimuli induces the release of PEVs with different protein composition that, in turn, may elicit selective biological responses in target cells.
Mesenchymal stem cells alleviate systemic sclerosis by inhibiting the recruitment of pathogenic macrophages
Authors: Gong Pixia , Ding Yayun , Sun Rongrong , Jiang Zishan , Li Wen , Su Xiao , Tian Ruifeng , Zhou Yipeng , Wang Tingting , Jiang Junjie , Li Peishan , Shao Changshun , Shi Yufang 
Published: November 2022

AbstractSystemic sclerosis (SSc) is a recalcitrant autoimmune disease for which there is no cure. Mesenchymal stem cell (MSC)-based treatment has emerged as a promising therapeutic option for several autoimmune diseases. Previously, we found that the immunoregulatory potential of MSCs can be greatly enhanced by IFN-γ and TNF-α. Here, we found that IFN-γ- and TNF-α-pretreated MSCs significantly alleviated skin fibrosis in a bleomycin (BLM)-induced SSc model. Macrophages were found to be the predominant profibrotic immune cell population in the pathogenesis of SSc. The accumulation of macrophages was significantly decreased by MSC treatment. Importantly, MSCs primarily reduced the population of maturing macrophages with high CCR2 expression by inhibiting the generation of CCL2 from fibroblasts and macrophages. This finding may help to improve MSC-based clinical treatments for SSc patients.