tbuckley/cabot-search huggingface dataset:
Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) markedly regulate tumor cell migration and invasion of three-dimensional collagen matrices
Authors: Kevin E. Fisher, Andreia Pop, Wonshill Koh, Nicholas J. Anthis, Kayla J. Bayless, George E. Davis
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

5638 

Tumor cell migration and invasion through three-dimensional (3D) extracellular matrices (ECMs) occurs via interactions between the cell and its environment. Here we describe two lipid signaling molecules, lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P). These compounds markedly stimulate cell migration and invasion and are more proficient at regulating tumor motility than growth factors (e.g. EGF, FGF, or HGF). Multiple tumor cell lines were tested for migratory ability in modified Boyden chamber assays using both LPA and S1P. Addition of toxins and adenovirally transfected cells helped identify downstream effectors. To assess invasive ability, cell lines were seeded on top of collagen matrices containing LPA and S1P. Invading cells were counted and visualized in cross-section. Nearly all cell lines tested strongly migrated in response to LPA and were inhibited by S1P. In contrast, the HT1080 fibrosarcoma migrated in response to both LPA and S1P. In most cases, pertussis toxin treatment inhibited cell migration in a dose dependent manner. Transfection with constitutively-active RhoA strongly reduced the migratory effect of LPA while dominant-negative RhoA reversed the inhibitory effect of S1P. C3-exoenzyme treatment also negated S1P inhibition and enhanced LPA-induced migration. In invasion assays in response to LPA, A2058 melanoma cells invaded moderately, while SKOV ovarian carcinoma and HEK293 showed little invasion- despite a marked ability of these cells to migrate in response to LPA. In contrast, HT1080 cells invaded dramatically into 3D collagen matrices in response to either LPA or S1P. Furthermore, S1P completely blocked invasion of A2058 melanoma cells. Treatment with matrix-metalloproteinase (MMP) inhibitors and the addition of tissue inhibitors of metalloproteinases (TIMP)-2, -3 and -4 fully inhibited LPA-induced invasion in HT1080 cells. TIMP-1 addition did not block LPA-induced invasion in HT1080 cells suggesting a critical role for membrane-type MMPs (MT-MMPs) in this process. In conclusion, we attribute a major role for both S1P and LPA in the regulation of tumor cell migration and invasion. In the latter case, the lipid-induced tumor invasive responses were entirely dependent on MT-MMPs as evidenced by blockade with TIMPs or synthetic MMP inhibitors (i.e. GM6001). We suggest that S1P and LPA act antagonistically, and a predominance of LPA or S1P will stimulate or inhibit migration, respectively. We believe that a loss of S1P inhibition may confer a pro-migratory or pro-invasive phenotype (e.g. HT1080 cells). Overall, our data suggests that LPA is a major stimulator of tumor cell migration and invasion of 3D ECMs, and in most cases, S1P inhibits these processes. We hypothesize that LPA stimulates MT-MMPs to coordinate the tumor invasion process.
T-DM1 in HER2-positive breast cancer brain metastases (BM).
Authors: Rupert Bartsch, Anna Sophie Berghoff, Margareta Rudas, Elisabeth Bergen, Michael Gnant, Karin Dieckmann, Katja Pinker, Christoph Zielinski, Guenther G. Steger, Matthias Preusser
Journal: Journal of Clinical Oncology (2014)

650 Background: Local treatment options such as radiotherapy or neurosurgery are the mainstay of BM management. Whole brain radiotherapy (WBRT), however, is associated with severe late-toxicity. The LANDSCAPE trial established lapatinib plus capecitabine (LapCap) as primary systemic treatment in oligosymptomatic patients (pts) with multiple Her2-positive BM. Limited evidence exists regarding the activity of antibodies in BM. T-DM1 is an antibody-drug conjugate linking trastuzumab (T) to an anti-microtubule agent. T-DM1 provides activity in pts progressing upon T and has lower toxicity as compared to LapCap. Here, we investigated the activity of T-DM1 in newly diagnosed or progressive BM. Methods: A total of six consecutive pts (median age 55 years) with Her2-positive breast cancer and BM were treated with T-DM1. In two asymptomatic pts, T-DM1 was administered as primary systemic therapy, while four subjects had already received local therapy and had documented CNS progression. T-DM1 was administered intravenously at a dose of 3.6 mg/kg body weight every three weeks; re-assessment of disease status was performed every three cycles. At baseline and restaging, MRI was performed. CNS response was defined as a reduction of lesion size of ≥50%. Results: Median follow-up was 6 months (m) and median brain metastases-free survival 11 m, respectively. All pts had received prior T, three (50%) had already received LapCap, and two (33.3%) pertuzumab. Currently, 4/6 pts (1 with primary treatment and 3 receiving T-DM1 upon CNS progression) are assessable for CNS response. 2/4 pts (50%) had partial remission, while one patient progressing upon prior local therapy had stable disease lasting for 15 cycles. One patient had minor response on MRI but no reduction of pre-existing brain oedema and increasing cortisol doses and was therefore deemed PD. A significant LVEF drop was observed in one heavily pretreated patient. Conclusions: This prospective case series again indicates that systemic therapy offers activity in Her2-positive BM. Currently, LapCap remains the standard of care. Still, T-DM1 offers relevant clinical activity; therefore, the role of T-DM1 in BM should be investigated in larger studies.
Neutralizing activity of non-polyreactive monoclonal antibodies directed against the Hepatitis C virus E2 glycoprotein isolated from patients with spontaneous resolution
Authors: A. Olbrich, C. Colpitts, H. Wardemann, S. Böhm, B. Michling, T.F. Baumert, T. Berg, J. Benckert
Journal: Journal of Hepatology (2017)
The Overall Survival of Patients with Hepatocellular Carcinoma Correlates with the Newly Defined Time to Progression after Transarterial Chemoembolization
Authors: Tadaaki Arizumi, Kazuomi Ueshima, Mina Iwanishi, Tomohiro Minami, Hirokazu Chishina, Masashi Kono, Masahiro Takita, Norihisa Yada, Satoru Hagiwara, Yasunori Minami, Hiroshi Ida, Yoriaki Komeda, Mamoru Takenaka, Toshiharu Sakurai, Tomohiro Watanabe, Naoshi Nishida, Masatoshi Kudo
Journal: Liver Cancer (2017)

The ultimate aim of any treatment for hepatocellular carcinoma (HCC) is to improve overall survival (OS); however, the clinical significance of time to progression (TTP) after transarterial chemoembolization (TACE) is unclear. This retrospective study examined the association between OS and the newly defined time to TACE progression (TTTP) to assess whether TTTP can be an alternative to OS in HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage B.Between January 2006 and December 2013, 592 patients with HCC (BCLC B1, n = 118; BCLC B2, n = 170) underwent TACE. TTTP was then redefined as time to progression from the first image taken after TACE. The relationship between TTTP and OS was then examined based on survival time.Survival analysis revealed significant differences in the OS of patients with BCLC B1 and those with BCLC B2 (median OS: 42.3 months, 95% confidence interval [CI] 34.4-50.7; and 29.3 months, 95% CI 26.1-37.6, respectively, p = 0.0348). The median TTTP values were 9.5 months (95% CI 7.0-10.9) and 5.3 months (95% CI 4.6-6.7), respectively (p = 0.0078). There was a moderate positive correlation between OS and TTTP for both B1 (R2 = 0.6563, p = 0.0045) and B2 (R2 = 0.6433, p = 0.0052) substages. There was also a positive correlation between OS and TTTP for the combined B1 and B2 substages (R2 = 0.6590, p = 0.0024).There was a moderate correlation between the TTTP and OS of patients with HCC after TACE therapy, where the patients with short TTTP represented short OS, indicating that TTTP is an alternative parameter for survival analysis of HCC patients with BCLC stage B tumors who undergo TACE.
Ileo-anal pouch anastomosis negatively impacts graft survival following liver transplantation for primary sclerosing cholangitis
Authors: P.J. Trivedi, J. Reece, R.W. Laing, E. Slaney, R. Cooney, T. Iqbal, B. Gunson, F. Thompson, P. Mueisan, G.M. Hirschfield, J. Ferguson
Journal: Journal of Hepatology (2017)
Involvement of TA and ΔN p63 and p73 isoforms on the regulation of cell death and tumour recurrence in patients with hepatocarcinoma submitted to liver transplantation
Authors: R. González, Á.J. De la Rosa, A. Rufini, M.Á. Rodríguez-Hernández, E. Navarro-Villarán, T. Marchal, S. Pereira, M. De la Mata, M. Müller-Schilling, J.M. Pascasio-Acevedo, M.T. Ferrer-Ríos, M.Á. Gómez-Bravo, F.J. Padillo, J. Muntané
Journal: Journal of Hepatology (2017)
DAA treatment scale-up in HIV/HCV co-infection: characterisinga population at risk for reinfection
Authors: M. Martinello, G.J. Dore, R.I. Bopage, R. Finlayson, D. Baker, M. Bloch, A. Wilcox, E. Filep, M. Hellard, G.V. Matthews
Journal: Journal of Hepatology (2017)
Mucosal-associated invariant T cells are functionally impaired during chronic liver diseases and promote fibrosis
Authors: P. Hegde, E. Weiss, J. Wan, V. Paradis, P.-E. Rautou, M. Mabire, G. Ferrere, A. Gupta, P. Letteron, B. Kiaf, A. Toubal, R. Moreau, A. Lehuen, S. Lotersztajn
Journal: Journal of Hepatology (2017)
The impact of esophageal varices on the prognosis of patients with hepatocellular carcinoma after surgical resection: a propensity score matching analysis
Authors: C.-Y. Chang, C.-W. Su, W.-Y. Hsieh, G.-Y. Chau, M.-C. Hou, P.-H. Chen, P.-C. Lee, T.-I. Huo, Y.-H. Huang, H.-C. Lin, J.-C. Wu
Journal: Journal of Hepatology (2017)
Open label, multi-center, prospective study to investigate the efficacy and safety of osimertinib in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI (APOLLO Study, NCT02972333)
Authors: L. Wang, L. Xing, L. Cao, L. Wang, X. Wang, J. Feng, Y. Shu, Y. Shi, Y. Song, J. Yu
Journal: Annals of Oncology (2017)
PREVALENCE OF PATELLAR TENDON PAIN HISTORY IN BRAZILIAN VOLLEYBALL AND BASKETBALL ATHLETES
Authors: Luciana Mendonça, Natália Bittencourt, Juliana Ocarino, Sérgio Fonseca
Journal: British Journal of Sports Medicine (2017)

Background Patellar tendinopathy is a clinically identified overload injury associated to jumping activities. The symptoms may last for years, affect sports participation and even lead to the end of a sport career. Therefore, is necessary to understand the profile of injury/complain in a sports team in order to plan preventive strategies. Objective The purpose of this study was to identify the prevalence of patellar tendon pain history in Brazilian volleyball and basketball athletes. Design Cross-sectional . Setting Sports Science Laboratory in the Universidade Federal de Minas Gerais. Patients (or Participants) One-hundred and ninety and one volleyball and basketball athletes with a mean age of 18.29 (+4.9) years, body mass of 76.50 (+13.8) kilograms and height of 1.85 (0,11) meters participated in this study. Interventions (or Assessment of Risk Factors) The athletes were questioned by the examiner about patellar tendon pain history related to sports practice. If the athlete had history of other knee complains (as patellofemoral pain and bursitis) and/or Osgood-Schlatter, he/she was excluded. Main Outcome Measurements History of pain, in the last 6 months, localized at the patellar tendon, which compromised the sports participation and/or sports performance. Results The prevalence of patellar tendon pain history was 22.5% (n=43) in the athletes participating in this study. Fifteen were female and 28 male, 25 were juvenile and 18 adult and 34 practiced volleyball and 9 basketball. Ten athletes reported patellar tendon pain in left lower limb, 14 in right lower limb and 19 bilaterally. Therefore, 147 athletes did not had patellar tendon pain history in the last 6 months. Conclusions The prevalence of patellar tendon pain history in this study was 22.5%. The major occurrence was bilateral pain history and the results suggest that male volleyball athletes had higher prevalence.
Comparison of cytokine profiles in idiosyncratic drug-induced liver injury, acute non-drug-induced hepatitis and controls
Authors: C. Stephens, R. Sanjuan-Jiménez, J.A. Sanabria-Cabrera, B. Battikhi, A. Ortega-Alonso, M. Robles-Díaz, M. Jiménez-Pérez, I. Medina-Cáliz, F. Ruiz-Cabello, M.I. Lucena, R.J. Andrade
Journal: Journal of Hepatology (2017)
Safety and efficacy of ombitasvir/paritaprevir/ritonavir ± dasabuvir and ± ribavirin in adult renal or liver transplant recipients with HCV infection (CORAL-I: cohorts 3–6)
Authors: K. Agarwal, R.S. Brown, E.O. Dumas, G.W. McCaughan, D. Samuel, N. Terrault, K.A. Brown, P.S. Mantry, M. Berenguer, P.Y. Kwo, J. O’leary, M. Charafeddine, T.J. Pilot-Matias, D.L. Shuster, W. Lu, J.V. Enejosa, D.E. Cohen, Z. Mariño, X. Forns
Journal: Journal of Hepatology (2017)
Case Series of Pediatric Sickle Retinopathy By Sensitive Clinical Imaging Technologies Suggests Frequent Early Pathology
Authors: Pahl A. Daniel, Nancy S. Green, Monica Bhatia, Maureen Licursi, Courtney Briamonte, Elana Smilow, Jonathan S. Chang, Margaret T. Lee, Royce W.S. Chen
Journal: Blood (2016)
Characterisation of the immune response in patients with drug induced liver injury
Authors: C. Bergamo, G. Germani, D. Bizzaro, C. Frasson, G. Basso, A. Ferrarese, A. Zanetto, S. Shalaby, I. Bortoluzzi, M. Senzolo, M. Gambato, F.P. Russo, P. Burra
Journal: Journal of Hepatology (2017)
Efficacy and safety of simtuzumab for the treatment of nonalcoholic steatohepatitis with bridging fibrosis or cirrhosis: results of two phase 2b, dose-ranging, randomized, placebo-controlled trials
Authors: A. Sanyal, M.F. Abdelmalek, A.M. Diehl, S. Caldwell, M.L. Shiffman, R. Ghalib, E. Lawitz, D.C. Rockey, R.A. Schall, C. Jia, B.J. McColgan, R. Myers, G.M. Subramanian, J.G. McHutchison, V. Ratziu, N. Afdhal, Z. Goodman, S.A. Harrison, J. Bosch
Journal: Journal of Hepatology (2017)
CNS activity of ensartinib in ALK+ non-small cell lung cancer (NSCLC) patients (pts)
Authors: K.L. Reckamp, H.A. Wakelee, S. Patel, G. Blumenschein, J.W. Neal, B. Gitlitz, S.N. Waqar, F. Tan, K. Harrow, L. Horn
Journal: Annals of Oncology (2017)
Nasotracheal prolonged safe extubation in acute respiratory failure post-thyroidectomy: An efficacious technique to avoid tracheotomy? A retrospective analysis of a large case series
Authors: F. Ferraro, C. Gambardella, D. Testa, L. Santini, R. Marfella, P. Fusco, C.P. Lombardi, A. Polistena, A. Sanguinetti, N. Avenia, G. Conzo
Journal: International Journal of Surgery (2017)
Paired biopsy analysis of human liver transcriptome before and 1 year after bariatric surgery identifies a restricted set of inflammation- and extracellular matrix-related genes as pivotal in NASH and fibrosis pathogenesis
Authors: S.M. Francque, P. Lefebvre, F. Lalloyer, M. Pawlak, E. Baugé, C. Gheeraert, H. Dehondt, J. Vanhoute, N. Hennuyer, C. Mazuy, B. Derudas, A. Driessen, G. Hubens, L. Vonghia, W. Kwanten, P. Michielsen, T. Vanwolleghem, J. Eeckhoute, A. Verrijken, L. Van Gaal, B. Staels
Journal: Journal of Hepatology (2017)
A national survey of support and information needs of Australian women living with advanced breast cancer.
Authors: Linda R. Mileshkin, Lisa Sheeran, Kate Robins-Browne, Michelle Marven, Karla Gough, Sanchia Aranda
Journal: Journal of Clinical Oncology (2012)

9124 Background: Improved treatments mean women with advanced breast cancer (ABC) are living longer, sometimes for many years. As a result, these women may experience chronic needs that are different from those with early breast cancer. We aimed to assess the support and information needs of women living with ABC. Methods: A national postal survey was sent to 2,345 women with ABC registered as members of the consumer organizations BCNA and/or BreaCan. Women were asked about their disease, treatment, experiences of care, and to complete the Supportive Care Needs Survey. Results: The response rate was 34% (792 valid responses). Mean age was 57 (range 25-99) with 21% living alone and 27% working. 18% reported living with ABC for &gt;7 years. 656 (85%) were having current treatment: chemotherapy (43%), hormonal therapy (46%), bisphosphonates (49%), and/or trastuzumab (Herceptin) (19%) respectively. 49% of women reported having access to a Breast Care Nurse (BCN) since diagnosis of ABC but only 3% cited a BCN or cancer nurse as their main contact. The majority (76%) cited their medical oncologist as their main contact, 8% cited their family doctor. Women wanted information about: treatment options (84.2%), new treatments (79.2%), symptoms/side effects (78.9%), clinical trials (60.8%), managing pain (57.2%) and financial assistance (38%). Women ≤ 65 had significantly higher levels of unmet needs than those &gt;65 for the 7 items below, including all items from the sexual domain. Conclusions: Women with ABC have many unmet needs with younger women particularly needing more support with sexual needs and anxiety. Women are heavily reliant on their medical oncologist, who may not be equipped or best placed to meet these needs. Models of care need to be developed to address the unmet supportive care needs of women living with ABC. [Table: see text]
Serum HBV pgRNA can serve as clinical marker for cccDNA activity in patients with HBV mono and HBV/HDV co-infection
Authors: L. Allweiss, K. Giersch, T. Nuurei, S. Polywka, T. Volz, A.W. Lohse, J.-H. Bockmann, M. Dandri, M. Lütgehetmann
Journal: Journal of Hepatology (2017)
Clinical Activity of Bosutinib by Mutational Status In Patients with Previously Treated Philadelphia Chromosome–positive Leukemias.
Authors: Carlo Gambacorti-Passerini, H. Jean Khoury, Helio Pinczowski, Tamas Masszi, Dong-Wook Kim, Maria Zanichelli, Giovanni Martinelli, Virginia Kelly, Nadine Besson, Trevor McMullan, Tim H. Brummendorf, Jorge E. Cortes
Journal: Blood (2010)
Blood Oxygen Measurement: Epidermal Inorganic Optoelectronics for Blood Oxygen Measurement (Adv. Healthcare Mater. 9/2017)
Authors: Haicheng Li, Yun Xu, Xiaomin Li, Ying Chen, Yu Jiang, Changxing Zhang, Bingwei Lu, Jian Wang, Yinji Ma, Yihao Chen, Yin Huang, Minquang Ding, Honghong Su, Guofeng Song, Yi Luo, X. Feng
Journal: Advanced Healthcare Materials (2017)

In article number 1601013, Xue Feng and co-workers report a systematic strategy to design an epidermal inorganic optoelectronic device by using specific strain-isolation design, nano-diamond thinning and hybrid transfer printing. This device has similar mechanical properties to epidermis and it is totally conformal to skin and keeps the constant light transmission between emitting element and photodetector as well as the signal stability due to skin deformation. It is also utilized to quantitatively detect human peripheral capillary oxygen saturation and cardiac pulse rate in vitro experiment. This strategy opens a route for traditional inorganic optoelectronics to achieve flexibility and stretchability and improve the performance of optoelectronics for biomedical application.
Rapid liver fibrosis regression after sustained virological response in HCV patients treated with direct acting antivirals
Authors: G.M. Lledó Ibáñez, A. Arias, L.M. Benítez-Gutiérrez, M.J. Cítores, I. Carrasco, V. Cuervas-Mons, C. De Mendoza
Journal: Journal of Hepatology (2017)
Coverage of Magnetic Resonance Imaging for Patients With Cardiac Devices
Authors: Daniel B. Kramer, Aaron S. Kesselheim
Journal: JAMA Cardiology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Preoperative intra-platelet serotonin levels are associated with early disease recurrence after liver resection in humans
Authors: D. Pereyra, R. Padickakudy, S. Haegele, F. Offensperger, L. Oehlberger, C. Schwarz, A. Assinger, C. Brostjan, T. Gruenberger, P. Starlinger
Journal: Journal of Hepatology (2017)
Human leukocyte antigen and IL28B polymorphisms independently associated with hepatitis C virus RNA spontaneous clearance: a study from REVEAL-HCV cohort
Authors: Y.-H. Huang, Y.-J. Lin, C.-L. Jen, S.-N. Lu, L.-Y. Wang, G. L’Italien, Y. Yuan, H.-I. Yang, C.-J. Chen, M.-H. Lee
Journal: Journal of Hepatology (2017)
Neutrophil extracellular traps are associated with disease severity and microbiota diversity in patients with chronic obstructive pulmonary disease
Authors: Alison J. Dicker, Megan L. Crichton, Eleanor G. Pumphrey, Andrew J. Cassidy, Guillermo Suarez-Cuartin, Oriol Sibila, Elizabeth Furrie, Christopher J. Fong, Wasyla Ibrahim, Gill Brady, Gisli G. Einarsson, J. Stuart Elborn, Stuart Schembri, Sara E. Marshall, Colin N.A. Palmer, James D. Chalmers
Journal: Journal of Allergy and Clinical Immunology (2017)

BackgroundNeutrophil extracellular traps (NETs) have been observed in the airway in patients with chronic obstructive pulmonary disease (COPD), but their clinical and pathophysiologic implications have not been defined.ObjectiveWe sought to determine whether NETs are associated with disease severity in patients with COPD and how they are associated with microbiota composition and airway neutrophil function.MethodsNET protein complexes (DNA-elastase and histone-elastase complexes), cell-free DNA, and neutrophil biomarkers were quantified in soluble sputum and serum from patients with COPD during periods of disease stability and during exacerbations and compared with clinical measures of disease severity and the sputum microbiome. Peripheral blood and airway neutrophil function were evaluated by means of flow cytometry ex vivo and experimentally after stimulation of NET formation.ResultsSputum NET complexes were associated with the severity of COPD evaluated by using the composite Global Initiative for Obstructive Lung Disease scale (P < .0001). This relationship was due to modest correlations between NET complexes and FEV1, symptoms evaluated by using the COPD assessment test, and higher levels of NET complexes in patients with frequent exacerbations (P = .002). Microbiota composition was heterogeneous, but there was a correlation between NET complexes and both microbiota diversity (P = .009) and dominance of Haemophilus species operational taxonomic units (P = .01). Ex vivo airway neutrophil phagocytosis of bacteria was reduced in patients with increased sputum NET complexes. Consistent results were observed regardless of the method of quantifying sputum NETs. Failure of phagocytosis could be induced experimentally by incubating healthy control neutrophils with soluble sputum from patients with COPD.ConclusionNET formation is increased in patients with severe COPD and associated with more frequent exacerbations and a loss of microbiota diversity.Graphical abstract