bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biosensors, Biomarkers and Biometrics: a Bootcamp Perspective
Authors: James Osian P , Robinson David B T , Hopkins Luke , Bowman Chris , Powell Arfon G M T , Brown Chris , Bailey Damian M , Egan Richard J , Lewis Wyn G 
Published: August 2020

IntroductionCompetitive physical performance is routinely monitored by wearable technology (biosensors), yet professional healthcare is not, despite high prevalence of trainee stress and burnout, notwithstanding the corresponding risk to patient safety. This study aimed to document the physiological stress response of UK Core Surgical Trainees (CSTs) during simulation training.MethodsCSTs (n=20, 10 male) were fitted with Vital Scout Wellness Monitors (VivaLNK, Campbell, California, USA) for an intensive 3-day training bootcamp. In addition to physiological parameters, CST demographics, event diaries and Maslach Burnout Inventory scores were recorded prospectively during exposure to three scenarios: interactive lectures, clinical skills simulation and non-technical (communication) training.ResultsBaseline heart rate (BHR, 60 bpm (range 39–81 bpm)) and baseline respiratory rate (14/min (11–18/min)) varied considerably and did not correlate (rho 0.076, p=0.772). BHR was associated with weekly exercise performed (66 bpm (<1 hour) vs 43 bpm (>5 hour), rho −0.663, p=0.004). Trainee response (standardised median heart rate vs BHR) revealed heart rate was related proportionately to lectures (71 bpm, p<0.001), non-technical skills training (79 bpm, p<0.001) and clinical skills simulation (88 bpm, p<0.001). Respiratory rate responded similarly (p<0.001 in each case). Heart rate during clinical skills simulation was associated with emotional exhaustion (rho 0.493, p=0.044), but maximum heart rate was unrelated to CSTs’ perceived peak stressors.DiscussionStress response, as derived from positive sympathetic heart rate drive varied over two-fold, with a direct implication on oxygen uptake and energy expenditure, and highlighting the daily physical demands placed upon clinicians.
Concurrent intracranial and extracranial artery stenosis and the prognosis of transient ischaemic symptoms or imaging-negative ischaemic stroke
Authors: Suo Yue , Jing Jing , Pan Yuesong , Chen Weiqi , Zhou Hongyu , Li Hao , Pu Yuehua , Liu Liping , Zhao Xingquan , Wang Yilong , Meng Xia , Wang Yongjun 
Published: August 2020

Background and purposeTransient ischaemic attack (TIA), transient symptoms with infarction (TSI) and diffusion-weighted imaging (DWI)-negative acute ischaemic stroke (AIS) share similar aetiologies but are considered to have a rather benign prognosis. We intended to investigate the association between intracranial atherosclerotic stenosis (ICAS), extracranial atherosclerotic stenosis (ECAS) and the prognosis of patients with TIA, TSI and DWI-negative AIS.MethodsClinical and imaging data of eligible participants were derived from the Chinese Intracranial Atherosclerosis study, according to symptom duration, acute infarction on DWI and discharge diagnosis. Based on the severity and location of arterial atherosclerosis, we categorised the study population into four groups: no or <50% ICAS and no ECAS; ≥50% ICAS but no ECAS; no or <50% ICAS with ECAS; and concurrent ≥50% ICAS and ECAS. Using multivariable Cox regression models, we analysed the relationship between the severity and distribution of large artery atherosclerosis and the prognosis of TIA, TSI and DWI-negative AIS.ResultsA total of 806 patients were included, 67.3% of whom were male. The median age of the study participants was 63 years. Patients in the concurrent ≥50% ICAS and ECAS subgroup had both a significantly higher 1-year recurrence rate (adjusted HR 3.4 (95% CI 1.15 to 10.04), p=0.027) and a higher risk of composite vascular events (adjusted HR 3.82 (95% CI 1.50 to 9.72), p=0.005).ConclusionsConcurrent ICAS and ECAS is associated with a higher possibility of 1-year recurrent stroke or composite vascular events. Large artery evaluation is necessary to assess patients with transient ischaemic symptoms or DWI-negative AIS. Progress in shortening the time interval between symptom onset and large vessel evaluation is needed.
Dynamics of the particle around de Sitter–Schwarzschild black hole surrounded by quintessence
Authors: Ali Khan Israr , Sultan Khan Amir , Islam Saeed 
Published: August 2020

The study of particle dynamics in the vicinity of a black hole environed by dark energy and magnetic field has attracted researchers for their importance in astrophysics and cosmology. In this paper, we study the dynamics of neutral and charged particles in the vicinity of de Sitter–Schwarzschild black hole (DS–Sch-BH) surrounded by quintessence. The effect of the DS part is explored by virtue of effective potential, effective force, and escape velocity of the particle (neutral and charged) moving around DS–Sch-BH. Finally, a comparative study is also investigated.
Cancer Cell CD44 Mediates Macrophage/Monocyte-Driven Regulation of Head and Neck Cancer Stem Cells
Authors: Gomez Karina E. , Wu FangLong , Keysar Stephen B. , Morton J. Jason , Miller Bettina , Chimed Tugs-Saikhan , Le Phuong N. , Nieto Cera , Chowdhury Farshad N. , Tyagi Anit , Lyons Traci R. , Young Christian D. , Zhou Hongmei , Somerset Hilary L. , Wang Xiao-Jing , Jimeno Antonio 
Published: August 2020

Abstract

Tumor-associated macrophages (TAM) in the tumor microenvironment (TME) cooperate with cancer stem cells (CSC) to maintain stemness. We recently identified cluster of differentiation 44 (CD44) as a surface marker defining head and neck squamous cell carcinoma (HNSCC) CSC. PI3K–4EBP1–SOX2 activation and signaling regulate CSC properties, yet the upstream molecular control of this pathway and the mechanisms underlying cross-talk between TAM and CSC in HNSCC remain largely unknown. Because CD44 is a molecular mediator in the TME, we propose here that TAM-influenced CD44 signaling could mediate stemness via the PI3K–4EBP1–SOX2 pathway, possibly by modulating availability of hyaluronic acid (HA), the main CD44 ligand. HNSCC IHC was used to identify TAM/CSC relationships, and in vitro coculture spheroid models and in vivo mouse models were used to identify the influence of TAMs on CSC function via CD44. Patient HNSCC–derived TAMs were positively and negatively associated with CSC marker expression at noninvasive and invasive edge regions, respectively. TAMs increased availability of HA and increased cancer cell invasion. HA binding to CD44 increased PI3K–4EBP1–SOX2 signaling and the CSC fraction, whereas CD44–VCAM-1 binding promoted invasive signaling by ezrin/PI3K. In vivo, targeting CD44 decreased PI3K–4EBP1–SOX2 signaling, tumor growth, and CSC. TAM depletion in syngeneic and humanized mouse models also diminished growth and CSC numbers. Finally, a CD44 isoform switch regulated epithelial-to-mesenchymal plasticity as standard form of CD44 and CD44v8-10 determined invasive and tumorigenic phenotypes, respectively. We have established a mechanistic link between TAMs and CSCs in HNSCC that is mediated by CD44 intracellular signaling in response to extracellular signals.

Significance:
These findings establish a mechanistic link between tumor cell CD44, TAM, and CSC properties at the tumor–stroma interface that can serve as a vital area of focus for target and drug discovery.
Bubble Bubble, Senescent Cells Are a Cauldron of Tumor Trouble
Authors: Wiley Christopher D. 
Published: August 2020

Abstract
Senescent cells release a mélange of factors that drive multiple forms of pathology, including cancer aggressiveness. In this issue of Cancer Research, Han and colleagues show that small extracellular vesicles (sEV), membrane-enclosed bubbles that carry signaling molecules, from senescent stromal cells can promote tumorigenesis and multidrug resistance in prostate or breast cancer cells. They find that loss of SIRT1 activity drives senescence-associated sEV release, and treatment with a SIRT1 agonist prevented this effect. This adds another mechanism by which senescent cells can promote tumorigenesis and offers another activity of senescent cells that might be targeted to limit the spread of cancer.
See related article by Han et al., p. 3383
Abstract A21: TRIM29 promotes invasion and migration of bladder cancer cells by regulating myosin-intermediate filament network and focal adhesion
Authors: Wang Yin , Gumkowski Erica R. , Palmbos Phillip L. 
Published: August 2020

Abstract
Development of invasive progression in human bladder cancer is a key determinant of patient outcomes. Therefore, understanding the drivers of bladder cancer invasive progression is critical to improving patient care. We have previously shown that TRIM29 (also known as ataxia-telangiectasia group D complementing gene, ATDC) is highly expressed in muscle-invasive bladder cancer and plays an important role in driving tumor formation and invasion in vitro and in vivo. TRIM29 is upregulated by TP63 in basal subtype tumors, but the mechanism by which TRIM29 promotes tumor invasion was unknown. To elucidate the mechanism by which TRIM29 drives bladder cancer invasion, we developed a 3-D bladder cancer spheroid invasion assay that allows observation of the invasive process of cancer spheroids in a real-time fashion and observation of protein expression using confocal microscopy. Using this system, we confirmed that TRIM29 is required for bladder cancer stromal invasion. To determine if TRIM29 is specifically required for cell migration, which is an important ability contributing to invasive behavior, scratch assays were performed and we found TRIM29 is required for migration. Cancer cell migration requires modulation of cell adhesion and actin/myosin activation. To examine the role of TRIM29 in cell adhesion and motility, gene knockout or knockdowns of TRIM29 were generated in human bladder cancer cell lines (UM-UC5, UC9, UC13, UC14). Interestingly, TRIM29 KO/KD downregulates the expression of keratin 14 (KRT14), a member of type I keratin family that constitutes intermediate filament (IF) network, as well as myosin IIA (MYH9), a non-muscle motor protein that is essential for cell adhesion and migration. Using immunofluorescent confocal microscopy, we found that TRIM29 also modulates formation of focal adhesion plaques in bladder cancer during cell migration. Taken together, these findings suggest a novel mechanism by which TRIM29 regulates bladder cancer cell motility and invasion.
Citation Format: Yin Wang, Erica R. Gumkowski, Phillip L. Palmbos. TRIM29 promotes invasion and migration of bladder cancer cells by regulating myosin-intermediate filament network and focal adhesion [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr A21.
Abstract B13: Characterization of the global proteome and phosphoproteome in cisplatin-resistant bladder cancers revealed the CDK2 network as a potential therapeutic target
Authors: Jung Jae Hun , You Sungyong , Oh Jae Won , Yoon Junhee , Yeon Austin , Shahid Muhammad , Cho Eunho , Sairam Vikram , Park Taeeun , Kim Kwang Pyo , Kim Jayoung 
Published: August 2020

Abstract
Introduction and Objective: Cisplatin-based chemotherapy is currently part of the standard of care for bladder cancer (BC). Unfortunately, some patients respond poorly to chemotherapy and have acquired or developed resistance. The molecular mechanisms underlying this resistance remain unclear. Here, we introduce a multidimensional proteomic analysis of a cisplatin-resistant BC model that provides different levels of protein information, including that of the global proteome and phosphoproteome.
Methods: To characterize the global proteome and phosphoproteome in cisplatin-resistant BC cells, liquid chromatography-mass spectrometry/mass spectrometry experiments combined with comprehensive bioinformatics analysis were performed. Perturbed expression and phosphorylation levels of key kinases associated with cisplatin resistance were further studied using various cell biology assays, including Western blot analysis.
Results: Analyses of protein expression and phosphorylation identified significantly altered proteins, which were also EGF dependent and independent. This suggests that protein phosphorylation plays a significant role in cisplatin-resistant BC. Additional network analysis of significantly altered proteins revealed CDK2, CHEK1, and ERBB2 as central regulators mediating cisplatin resistance. In addition to this, we identified the CDK2 network, which consists of CDK2 and its five substrates, as being significantly associated with poor survival after cisplatin chemotherapy.
Conclusions: Collectively, these findings potentially provide a novel way of classifying higher-risk patients and may guide future research in developing therapeutic targets.
Citation Format: Jae Hun Jung, Sungyong You, Jae Won Oh, Junhee Yoon, Austin Yeon, Muhammad Shahid, Eunho Cho, Vikram Sairam, Taeeun Park, Kwang Pyo Kim, Jayoung Kim. Characterization of the global proteome and phosphoproteome in cisplatin-resistant bladder cancers revealed the CDK2 network as a potential therapeutic target [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr B13.
Abstract IA04: Molecular alterations in variant morphology
Authors: Hansel Donna E. 
Published: August 2020

Abstract
Bladder cancer can be divided into several major subtypes that include urothelial carcinoma, squamous cell carcinoma, adenocarcinoma and neuroendocrine carcinoma. Urothelial carcinoma, the most common form of bladder cancer, is further subdivided into numerous histologic variants based on distinct morphologic features. While histologic characterization remains the most important factor in diagnosis and patient management, emerging molecular data across bladder cancer subtypes and variants may potentially alter how bladder cancer is classified. Large scale -omic analytics have uncovered unique signatures within major bladder cancer subtypes. In addition, molecular groupings and unique single-gene alterations have been identified within urothelial carcinoma and its many morphologic variants, including plasmacytoid urothelial carcinoma and micropapillary urothelial carcinoma. We will review molecular alterations in major categories of bladder cancer and urothelial carcinoma variants. Many of these molecular alterations could potentially be used in revised classification, diagnosis, and therapy of bladder cancer.
Citation Format: Donna E. Hansel. Molecular alterations in variant morphology [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr IA04.
Abstract IA09: Collagen microenvironment in the modulation of local invasion and distal metastasis
Authors: Cheng Yu , Chan Keith Syson 
Published: August 2020

Abstract
Metastasis is a multistep process that includes, but is not limited to, local invasion, intravasation of tumor cells into the circulation, and extravasation of circulating tumor cells from the circulation into distal organs for metastatic colonization. The 5-year survival rate of patients diagnosed with metastatic bladder urothelial carcinomas is less than 10%, posing a major clinical challenge. Previous studies in human bladder urothelial carcinomas have elegantly investigated the mechanistic contribution of tumor cell intrinsic properties that promote metastasis. However, the contribution of tumor microenvironments at both the primary tumor and metastatic sites to the metastatic process is not as well characterized.
Historically, the extracellular matrix (ECM) was considered a passive scaffold, enclosing neighboring cancer cells and other cell types to support tissue architecture. Intriguingly, recent studies, including ours, revealed the emerging roles of ECMs as a dynamic component of the tumor microenvironment, which crosstalks with cancer cells. Here, we showed that bladder cancer cells expressing the collagen receptor CD167a or discoidin domain receptor 1 responded to collagen stimulation at the primary tumor to promote local invasion and utilized the same receptor to preferentially colonize at airway smooth muscle cells—another rich source of collagen and a newly identified metastatic niche in lung. Morphologically, these collagen-CD167a-driven metastatic foci are uniquely distinct from typical lung alveolar metastatic lesions and exhibited activation of the CD167a-HSP90-Stat3 axis. Interestingly, metastatic lung colonization could be abrogated using an investigational drug that attenuates Stat3 activity, implicating this seed-and-soil interaction as a therapeutic target for abrogating lung metastases.
Together with our recent study demonstrating prevalent Stat3 expression in the primary basal bladder carcinomas (J Natl Cancer Inst 2018 May 1;110[5]:448-59), these findings implicate Stat3 as a valid target for metastatic bladder carcinoma patients with a basal molecular subtype, thus opening a new avenue for potential clinical intervention.
Citation Format: Yu Cheng, Keith Syson Chan. Collagen microenvironment in the modulation of local invasion and distal metastasis [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr IA09.
Abstract IA17: Patient-derived organoid models of bladder cancer
Authors: Shen Michael M. 
Published: August 2020

Abstract
The molecular mechanisms of bladder tumorigenesis are poorly understood, in part due to the lack of suitable model systems that reflect the biology of human bladder cancer. In our studies, we have used three-dimensional culture approaches to establish a novel biobank of human patient-derived organoids from primary bladder tumors. These organoid lines recapitulate the histopathologic and molecular diversity of non-muscle invasive bladder cancer as well as muscle-invasive bladder cancer, and can be readily converted into xenografts by orthotopic transplantation. These organoid lines can be propagated by serial passaging in culture while maintaining their tumor properties and display mutational profiles that are highly concordant with their parental tumors. Notably, organoid lines often retain parental tumor heterogeneity and exhibit a spectrum of genomic changes that are consistent with tumor evolution in culture. Furthermore, we have shown that these organoid lines are highly amenable for analyses of drug response, which can be validated in vivo using orthotopic xenografts.
I will discuss our recent findings using patient-derived tumor organoid lines to investigate bladder cancer biology and drug response, including ongoing analyses of tumor plasticity and the basis for tumor recurrence.
Citation Format: Michael M. Shen. Patient-derived organoid models of bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr IA17.
Adenomegalia dolorosa: doença de kikuchi entre os diagnósticos diferenciais
Authors: Oliveira Dagna Karen , Lehmann Kenny Regina , Kreuz Raquel Laís , Romero Frederico Ramalho 
Published: August 2020

A doença de Kikuchi-Fujimoto ou linfadenite histiocítica necrosante, de curso benigno, é prevalente em mulheres jovens, e associada à febre e leucopenia. Estudos recentes têm demostrado que sua etiologia ainda é incerta, sendo uma doença rara, com incidência de 0,5 a 5% de todas as adenopatias analisadas histologicamente. O diagnóstico diferencial por imunohistoquímica foi decisivo, descartando outras hipóteses diagnósticas como: linfoma, tuberculose ganglionar e lúpus eritematoso sistêmico. Este relato de caso mostra as características da apresentação da doença em uma mulher, caucasiana e todas as etapas da investigação, destacando a importância dos diagnósticos diferenciais em adenopatias dolorosas e as dificuldades quando avaliamos portadores de doenças raras.
Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus
Authors: van Zuydam Natalie R. , Ladenvall Claes , Voight Benjamin F. , Strawbridge Rona J. , Fernandez-Tajes Juan , Rayner N. William , Robertson Neil R. , Mahajan Anubha , Vlachopoulou Efthymia , Goel Anuj , Kleber Marcus E. , Nelson Christopher P. , Kwee Lydia Coulter , Esko Tõnu , Mihailov Evelin , Mägi Reedik , Milani Lili , Fischer Krista , Kanoni Stavroula , Kumar Jitender , Song Ci , Hartiala Jaana A. , Pedersen Nancy L. , Perola Markus , Gieger Christian , Peters Annette , Qu Liming , Willems Sara M. , Doney Alex S.F. , Morris Andrew D. , Zheng Yan , Sesti Giorgio , Hu Frank B. , Qi Lu , Laakso Markku , Thorsteinsdottir Unnur , Grallert Harald , van Duijn Cornelia , Reilly Muredach P. , Ingelsson Erik , Deloukas Panos , Kathiresan Sek , Metspalu Andres , Shah Svati H. , Sinisalo Juha , Salomaa Veikko , Hamsten Anders , Samani Nilesh J. , März Winfried , Hazen Stanley L. , Watkins Hugh , Saleheen Danish , Morris Andrew P. , Colhoun Helen M. , Groop Leif , McCarthy Mark I. , Palmer Colin N.A. , Danesh John , Erdmann Jeanette , Gu Dongfeng , Kooner Jaspal S. , Roberts Robert , Schunkert Heribert , Assimes Themistocles L. , Blankenberg Stefan , Boehm Bernhard O. , Chambers John C. , Clarke Robert , Collins Rory , Dedoussis George , Franks Paul W. , Hovingh G. Kees , Kim Bong-Jo , Lehtimäki Terho , McPherson Ruth , Nieminen Markku S , O’Donnell Christopher , Ripatti Samuli , Sandhu Manjinder S , Schreiber Stefan , Siegbahn Agneta , Willer Cristen J. , Zalloua Pierre A. , Mark Michael , Kanninen Timo , Thorand Barbara , Remuzzi Giuseppe , Dunger David , Shore Angela , Smith Ulf , Groop Per-Henrik , Ylä-Herttuala Seppo , Cobelli Claudio , Bellazzi Riccardo , Ferrannini Ele , Patrono Carlo , Nuutila Pirjo , McKeague Paul , Steckel-Hamann Birgit , Gan Li-ming , Nogoceke Everson , Tortoli Piero , Jablonka Bernd , Brosnan Mary-Julia 
Published: August 2020

Background:
Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D).

Methods:
To test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D).

Results:
None of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background.

Conclusions:
This study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.