tbuckley/cabot-search huggingface dataset:
Indole alkaloid glycosides with a 1′-(phenyl)ethyl unit from Isatis indigotica leaves
Authors: Qinglan Guo, Dawei Li, Chengbo Xu, Chenggen Zhu, Ying Guo, Haibo Yu, Xiaoliang Wang, Jiangong Shi
Journal: Acta Pharmaceutica Sinica B (2019)

Seven indole alkaloid glycosides containing a 1′-(4″-hydroxy-3″,5″-dimethoxyphenyl)ethyl unit (1–7) were isolated from an aqueous extract of Isatis indigotica leaves (da qing ye). Their structures were determined by spectroscopic data analysis combined with enzymatic hydrolysis as well as comparison of their experimental CD (circular dichroism) and calculated ECD (electrostatic circular dichroism) spectra. Based on analysis of [α]D20 and/or Cotton effect (CE) data of 1–7, two simple roles to assign location and/or configuration of β-glycopyranosyloxy and 1′-(phenyl)ethyl units in the indole alkaloid glycosides are proposed. Stereoselectivity in plausible biosynthetic pathways of 1–7 is discussed. Compounds 3 and 4 and their mixture in a 3:2 ratio showed activity against KCNQ2 in CHO cells. The mixture of 5 and 6 (3:2) exhibited antiviral activity against influenza virus H1N1 PR8 with IC50 64.7 μmol/L (ribavirin, IC50 54.3 μmol/L), however, the individual 5 or 6 was inactive. Preliminary structure–activity relationships were observed.
TRAIL acts synergistically with iron oxide nanocluster-mediated magneto- and photothermia
Authors: Hanene Belkahla, Eva Mazarío, Anouchka Plan Sangnier, John S. Lomas, Tijani Gharbi, Souad Ammar, Olivier Micheau, Claire Wilhelm, Miryana Hémadi
Journal: Theranostics (2019)

Targeting TRAIL (Tumor necrosis factor (TNF)-Related Apoptosis-Inducing Ligand) receptors for cancer therapy remains challenging due to tumor cell resistance and poor preparations of TRAIL or its derivatives. Herein, to optimize its therapeutic use, TRAIL was grafted onto iron oxide nanoclusters (NCs) with the aim of increasing its pro-apoptotic potential through nanoparticle-mediated magnetic hyperthermia (MHT) or photothermia (PT). Methods: The nanovector, NC@TRAIL, was characterized in terms of size, grafting efficiency, and potential for MHT and PT. The therapeutic function was assessed on a TRAIL-resistant breast cancer cell line, MDA-MB-231, wild type (WT) or TRAIL-receptor-deficient (DKO), by combining complementary methylene blue assay and flow cytometry detection of apoptosis and necrosis. Results: Combined with MHT or PT under conditions of "moderate hyperthermia" at low concentrations, NC@TRAIL acts synergistically with the TRAIL receptor to increase the cell death rate beyond what can be explained by the mere global elevation of temperature. In contrast, all results are consistent with the idea that there are hotspots, close to the nanovector and, therefore, to the membrane receptor, which cause disruption of the cell membrane. Furthermore, nanovectors targeting other membrane receptors, unrelated to the TNF superfamily, were also found to cause tumor cell damage upon PT. Indeed, functionalization of NCs by transferrin (NC@Tf) or human serum albumin (NC@HSA) induces tumor cell killing when combined with PT, albeit less efficiently than NC@TRAIL. Conclusions: Given that magnetic nanoparticles can easily be functionalized with molecules or proteins recognizing membrane receptors, these results should pave the way to original remote-controlled antitumoral targeted thermal therapies.
Comparison of cerebral and cutaneous microvascular dysfunction with the development of type 1 diabetes
Authors: Wei Feng, Shaojun Liu, Chao Zhang, Qing Xia, Tingting Yu, Dan Zhu
Journal: Theranostics (2019)

Diabetes can lead to cerebral and cutaneous vascular dysfunction. However, it is still unclear how vascular function changes with the development of diabetes and what differences exist between cerebral and cutaneous vascular dysfunction. Thus, it is very important to monitor changes in cerebral and cutaneous vascular function responses
Serum matrilysin (MMP7) levels are associated with progression, in curatively resected colorectal cancer (CRC) patients
Authors: A. Martinez-Fernandez, E. Pineda, L. Visa, X. Garcia-Albeniz, J. Auge, C. Nadal, A. Castells, A. Lacy, J. Maurel
Journal: Journal of Clinical Oncology (2007)

4124 Background: Matrilysin (MMP7) has been shown to be over-expressed in CRC, specially in liver metastases. Additionally MMP7 over-expression in primary tumor, predict metastatic potential in early-stage disease (Gut 12:1751;2005). As the activated pro-domain, could be detected in serum by ELISA method, we search if it could also identify a subgroup of non-metastatic CRC patients with a higher risk of relapse. Methods: Serum MMP7 (S-MMP7) was measured by commercially available ELISA, in 92 healthy controls and 175 consecutive patients before undergoing laparoscopy-assisted or open curative resection for CRC, between July 2003 to December 2004. Clinic- pathologic variables were tested for their effect on disease-free survival (DFS) in univariate and multivariate Cox regression analysis. Results: S-MMP7 levels were significantly higher in CRC patients than in controls (p=0.02). Mean age in CRC patients was 71 years (range 31–90). Median nodal retrieval was 14 (range 0–47). The median S-MMP7 (4.9 ng/ml) was chosen for cut-off value. After a median follow- up of 26 months, the rate of DFS was 72%. Univariate analysis identified high S-MMP7 levels, CEA concentration, age, extent of primary tumor and lymph-node metastases as variables associated with DFS. Multivariate analysis identified lymph-node metastases (OR.1,88, p=0.046) and S-MMP7 (OR.1,103, p=0.039) as independent prognostics factors. Conclusions: With a short follow-up, S-MMP7 levels predict recurrence in curatively resected CRC. As a subset of these patients could be managed with secondary liver resection, S-MMP7 determination would be particularly warranted for more intensive surveillance strategies. No significant financial relationships to disclose.
Cognitive gadgets and genetic accommodation
Authors: Eva Jablonka, Simona Ginsburg, Daniel Dor
Journal: Behavioral and Brain Sciences (2019)

Heyes argues that human metacognitive strategies (cognitive gadgets) evolved through cultural rather than genetic evolution. Although we agree that increased plasticity is the hallmark of human metacognition, we suggest cognitive malleability required the genetic accommodation of gadget-specific processes that enhanced the overall cognitive flexibility of humans.
What sentimentalists should say about emotion
Authors: Charlie Kurth
Journal: Behavioral and Brain Sciences (2019)

Abstract Recent work by emotion researchers indicates that emotions have a multilevel structure. Sophisticated sentimentalists should take note of this work – for it better enables them to defend a substantive role for emotion in moral cognition. Contra May's rationalist criticisms, emotions are not only able to carry morally relevant information, but can also substantially influence moral judgment and reasoning.
Progress in cancer survival, mortality, and incidence in seven high-income countries 1995–2014 (ICBP SURVMARK-2): a population-based study
Authors: Melina Arnold, Mark J Rutherford, Aude Bardot, Jacques Ferlay, Therese M-L Andersson, Tor Åge Myklebust, Hanna Tervonen, Vicky Thursfield, David Ransom, Lorraine Shack, Ryan R Woods, Donna Turner, Suzanne Leonfellner, Susan Ryan, Nathalie Saint-Jacques, Prithwish De, Carol McClure, Agnihotram V Ramanakumar, Heather Stuart-Panko, Gerda Engholm, Paul M Walsh, Christopher Jackson, Sally Vernon, Eileen Morgan, Anna Gavin, David S Morrison, Dyfed W Huws, Geoff Porter, John Butler, Heather Bryant, David C Currow, Sara Hiom, D Max Parkin, Peter Sasieni, Paul C Lambert, Bjørn Møller, Isabelle Soerjomataram, Freddie Bray
Journal: The Lancet Oncology (2019)
Non-invasive <i>In Vivo</i> Imaging of Cancer Using Surface-Enhanced Spatially Offset Raman Spectroscopy (SESORS)
Authors: Fay Nicolson, Bohdan Andreiuk, Chrysafis Andreou, Hsiao-Ting Hsu, Scott Rudder, Moritz F. Kircher
Journal: Theranostics (2019)

Rationale:The goal of imaging tumors at depth with high sensitivity and specificity represents a significant challenge in the field of biomedical optical imaging.'Surface enhanced Raman scattering' (SERS) nanoparticles (NPs) have been employed as image contrast agents and can be used to specifically target cells in vivo.By tracking their unique "fingerprint" spectra, it becomes possible to determine their precise location.However, while the detection of SERS NPs is very sensitive and specific, conventional Raman spectroscopy imaging devices are limited in their inability to probe through tissue depths of more than a few millimetres, due to scattering and absorption of photons by biological tissues.Here, we combine the use of "Spatially Offset Raman spectroscopy" (SORS) with that of "surface-enhanced resonance Raman spectroscopy" (SERRS) in a technique known as "surface enhanced spatially offset resonance Raman spectroscopy" (SESO(R)RS) to image deep-seated glioblastoma multiforme (GBM) tumors in vivo in mice through the intact skull.Methods: A SORS imaging system was built in-house.Proof of concept SORS imaging was achieved using a PTFE-skull-tissue phantom.Imaging of GBMs in the RCAS-PDGF/N-tva transgenic mouse model was achieved through the use of gold nanostars functionalized with a resonant Raman reporter to create SERRS nanostars.These were then encapsulated in a thin silica shell and functionalized with a cyclic-RGDyK peptide to yield integrin-targeting SERRS nanostars.Non-invasive in vivo SORS image acquisition of the integrin-targeted nanostars was then performed in living mice under general anesthesia.Conventional non-SORS imaging was used as a direct comparison.Results: Using a low power density laser, GBMs were imaged via SESORRS in mice (n = 5) and confirmed using MRI and histopathology.The results demonstrate that via utilization of the SORS approach, it is possible to acquire clear and distinct Raman spectra from deep-seated GBMs in mice in vivo through the skull.SESORRS images generated using classical least squares outlined the tumors with high precision as confirmed via MRI and histology.Unlike SESORRS, conventional Raman imaging of the same areas did not provide a clear delineation of the tumor. Conclusion:To the best of our knowledge this is the first report of in vivo SESO(R)RS imaging.In a relevant brain tumor mouse model we demonstrate that this technique can overcome the limitations of conventional Raman imaging with regards to penetration depth.This work therefore represents a significant step forward in the potential clinical translation of SERRS nanoparticles for high precision cancer imaging.
Experimental pancreatic cancer develops in soft pancreas: novel leads for an individualized diagnosis by ultrafast elasticity imaging
Authors: Nicole Therville, Silvia Arcucci, Aurélie Vertut, Fernanda Ramos-Delgado, Dina Ferreira Da Mota, Marlène Dufresne, Céline Basset, Julie Guillermet-Guibert
Journal: Theranostics (2019)

Rapid, easy and early pancreatic cancer diagnosis and therapeutic follow up continue to necessitate an increasing attention towards the development of effective treatment strategies for this lethal disease. The non invasive quantitative assessment of pancreatic heterogeneity is limited. Here, we report the development of a preclinical imaging protocol using ultrasonography and shear wave technology in an experimental in situ pancreatic cancer model to measure the evolution of pancreatic rigidity. Methods: Intrapancreatic tumors were genetically induced by mutated Kras and p53 in KPC mice. We evaluated the feasiblity of a live imaging protocol by assessing pancreas evolution with Aixplorer technology accross 36 weeks. Lethality induced by in situ pancreatic cancer was heterogeneous in time. Results: The developed method successfully detected tumor mass from 26 weeks onwards at minimal 0.029 cm3 size. Elastography measurements using shear wave methodology had a wide detection range from 4.7kPa to 166.1kPa. Protumorigenic mutations induced a significant decrease of the rigidity of pancreatic tissue before tumors developed in correlation with the detection of senescent marker p16-positive cells. An intratumoral increased rigidity was quantified and found surprisingly heterogeneous. Tumors also presented a huge inter-individual heterogeneity in their rigidity parameters; tumors with low and high rigidity at detection evolve very heterogeneously in their rigidity parameters, as well as in their volume. Increase in rigidity in tumors detected by ultrafast elasticity imaging coincided with detection of tumors by echography and with the detection of the inflammatory protumoral systemic condition by non invasive follow-up and of collagen fibers by post-processing tumoral IHC analysis. Conclusion: Our promising results indicate the potential of the shear wave elastography to support individualization of diagnosis in this most aggressive disease.
An all-in-one homogeneous DNA walking nanomachine and its application for intracellular analysis of miRNA
Authors: Muren Hu, Dongsheng Mao, Xiaohao Liu, Lingjie Ren, Mengru Zhou, Xiaoxia Chen, Xiaoli Zhu
Journal: Theranostics (2019)

DNA walker is a powerful type of DNA nanomachine that can produce amplified signals during the "burnt-bridge"-like walking process. Despite their successful application in extracellular bioanalysis, the heterogeneity of the existing DNA walkers makes it difficult to guarantee the consistency of the results during the analysis of different cells. Methods: Here, an all-in-one homogeneous DNA walking nanomachine is reported that can be delivered into living cells for intracellular bioanalysis of miRNA without auxiliary materials. Results: This DNA walking nanomachine is constructed of gold nanoparticles on which two types of interrelated DNA tracks are assembled. The target miRNA, cancer-related miR-21, can be captured by one of the tracks (track 1) and then walk to the other track (track 2), releasing the hybrid of track 1 and track 2 from the nanoparticle to produce a signal. The walking process can proceed in a cyclic 1-2-1-2 manner and thereby produce amplified signals. Thus, sensitive imaging of the miRNA in situ can be achieved. Conclusion: Benefiting from the homogeneity of the detection system, the method can be applied for intracellular analysis without interference induced by the fluctuations of stimuli or accessorial contents.
Endoscopic removal of a lumen-apposing metal stent that migrated into the walled-off necrosis during the first drainage procedure
Authors: Nao Fujimori, Yosuke Minoda, Masatoshi Murakami, Yuta Suehiro, Takamasa Oono, Eikichi Ihara, Yoshihiro Ogawa
Journal: Endoscopy (2019)

A 43-year-old man with severe alcoholic acute pancreatitis complicated by infected walled-off necrosis (WON) ([Fig. 1]) was referred to our hospital. An endoscopic ultrasound (EUS)-guided transluminal drainage was performed using a GF-UCT260 echoendoscope (Olympus Medical Systems, Tokyo, Japan) and a 15-mm lumen-apposing metal stent (LAMS; Hot AXIOS; Boston Scientific, Marlborough, Massachusetts, USA) was inserted. Although we used the intrascope channel release technique, the LAMS migrated into the WON ([Fig. 2 a]). After insertion of a 0.025-inch guidewire (VisiGlide 2; Olympus Medical Systems), the migrated LAMS was moved further into the WON using a balloon catheter ([Fig. 2 b]) to provide interspace for insertion of an additional 20-mm LAMS (Hot AXIOS; Boston Scientific), which was inserted along the guidewire and carefully deployed under endoscopic and fluoroscopic guidance ([Fig. 2 c]).
ILC2s mediate systemic innate protection by priming mucus production at distal mucosal sites
Authors: Laura Campbell, Matthew R. Hepworth, Jayde Whittingham-Dowd, Seona Thompson, Allison J. Bancroft, Kelly S. Hayes, Tovah N. Shaw, Burton F. Dickey, Anne-Laure Flamar, David Artis, David A. Schwartz, Christopher M. Evans, Ian S. Roberts, David J. Thornton, Richard K. Grencis
Journal: The Journal of Experimental Medicine (2019)

Host immunity to parasitic nematodes requires the generation of a robust type 2 cytokine response, characterized by the production of interleukin 13 (IL-13), which drives expulsion. Here, we show that infection with helminths in the intestine also induces an ILC2-driven, IL-13–dependent goblet cell hyperplasia and increased production of mucins (Muc5b and Muc5ac) at distal sites, including the lungs and other mucosal barrier sites. Critically, we show that type 2 priming of lung tissue through increased mucin production inhibits the progression of a subsequent lung migratory helminth infection and limits its transit through the airways. These data show that infection by gastrointestinal-dwelling helminths induces a systemic innate mucin response that primes peripheral barrier sites for protection against subsequent secondary helminth infections. These data suggest that innate-driven priming of mucus barriers may have evolved to protect from subsequent infections with multiple helminth species, which occur naturally in endemic areas.
Early-Phase 18F-Florbetaben PET as an Alternative Modality for 18F-FDG PET
Authors: Seung Hyun Son, Kyunghun Kang, Pan-Woo Ko, Ho-Won Lee, Sang-Woo Lee, Byeong-Cheol Ahn, Jaetae Lee, Uicheul Yoon, Shin Young Jeong
Journal: Clinical Nuclear Medicine (2019)

Purpose Based on the possibility that early-phase florbetaben (E-FBB) brain PET can be a surrogate for brain perfusion imaging, we conducted this study to investigate the clinical utility of E-FBB PET instead of 18 F-FDG brain PET. Materials and Methods This prospective study included 35 patients with clinical suspicion of cognitive decline or dementia and 5 healthy controls. Brain MRI, E-FBB PET, late-phase FBB PET, and FDG PET were acquired. The regional SUV ratios (SUVRs) were calculated by cortical surface region of interest analysis using individual MRI, and relationship between E-FBB and FDG PET was analyzed. All PET scans were scored and analyzed as per visual scoring system, which represent tracer uptake abnormality. Moreover, uptake patterns were analyzed to determine the disease. Results Among the 40 subjects, 19 were amyloid-positive and 21 were amyloid-negative on late-phase FBB PET. Cortical surface region of interest analysis conducted for comparing between E-FBB and FDG PET revealed significant correlations ( P &lt; 0.0001) for regional SUVR among all brain regions; however, the SUVR values of FDG PET were statistically higher than those of E-FBB PET. Similarly, although the visually rated scores for E-FBB and FDG PET showed significant correlation ( P &lt; 0.0001), it was considered that the tracer uptake was more severely decreased for FDG PET. The disease types, specified by E-FBB and FDG PET, were statistically correlated. Conclusions E-FBB PET could potentially be a useful biomarker for the diagnosis of dementia in place of FDG PET. Nevertheless, the severity of the disease was more accurately determined by FDG PET.
Atypical Parkinson Syndrome Hiding a Meningioma
Authors: Caroline Bund, Eric Ouvrard, Mathilde Renaud, Christine Tranchant, Izzie-Jacques Namer
Journal: Clinical Nuclear Medicine (2019)

Abstract A 59-year-old man had developed within a few months walking disorders and rigidity of the left upper limb. 123 I-FP-CIT SPECT/CT was performed in response to the suspicion of atypical parkinsonian syndrome. It showed an anomaly in presynaptic dopaminergic transmission on the right striatum and a voluminous expansive process on CT. MRI revealed an atypical meningioma. The patient had surgery for tumor removal. Later 123 I-FP-CIT SPECT/CT showed normalization of presynaptic dopaminergic transmission on the right striatum.
MUC1-C Activates the NuRD Complex to Drive Dedifferentiation of Triple-Negative Breast Cancer Cells
Authors: Tsuyoshi Hata, Hasan Rajabi, Hidekazu Takahashi, Yota Yasumizu, Wei Li, Caining Jin, Mark D. Long, Qiang Hu, Song Liu, Atsushi Fushimi, Nami Yamashita, Ling Kui, Deli Hong, Masaaki Yamamoto, Masaaki Miyo, Masayuki Hiraki, Takahiro Maeda, Yozo Suzuki, Mehmet K. Samur, Donald Kufe
Journal: Cancer Research (2019)

The NuRD chromatin remodeling and deacetylation complex, which includes MTA1, MBD3, CHD4, and HDAC1 among other components, is of importance for development and cancer progression. The oncogenic mucin 1 (MUC1) C-terminal subunit (MUC1-C) protein activates EZH2 and BMI1 in the epigenetic reprogramming of triple-negative breast cancer (TNBC). However, there is no known link between MUC1-C and chromatin remodeling complexes. Here, we showed that MUC1-C binds directly to the MYC HLH-LZ domain and identified a previously unrecognized MUC1-C→MYC pathway that regulates the NuRD complex. MUC1-C/MYC complexes selectively activated the MTA1 and MBD3 genes and posttranscriptionally induced CHD4 expression in basal- but not luminal-type BC cells. In turn, MUC1-C formed complexes with these NuRD components on the ESR1 promoter. Downregulating MUC1-C decreased MTA1/MBD3/CHD4/HDAC1 occupancy and increased H3K27 acetylation on the ESR1 promoter, with induction of ESR1 expression and downstream estrogen response pathways. Targeting MUC1-C and these NuRD components also induced expression of FOXA1, GATA3, and other markers associated with the luminal phenotype. These findings support a model in which MUC1-C activates the NuRD complex to drive dedifferentiation and reprogramming of TNBC cells. SIGNIFICANCE: MUC1-C directly interacts with MYC to activate the NuRD complex, mediating regulation of the estrogen receptor in triple-negative breast cancer cells.
MARS: Mutation-Adjusted Risk Score for Advanced Systemic Mastocytosis
Authors: Mohamad Jawhar, Juliana Schwaab, Iván Álvarez-Twose, Khalid Shoumariyeh, Nicole Naumann, Johannes Lübke, Cecelia Perkins, Javier I. Muñoz-González, Manja Meggendorfer, Vanessa Kennedy, Georgia Metzgeroth, Alice Fabarius, Dietmar Pfeifer, Karl Sotlar, Hans-Peter Horny, Nikolas von Bubnoff, Torsten Haferlach, Nicholas C.P. Cross, Wolf-Karsten Hofmann, Wolfgang R. Sperr, Andrés C. García-Montero, Peter Valent, Jason Gotlib, Alberto Orfao, Andreas Reiter
Journal: Journal of Clinical Oncology (2019)

To develop a risk score for patients with advanced systemic mastocytosis (AdvSM) that integrates clinical and mutation characteristics. The study included 383 patients with AdvSM from the German Registry on Disorders of Eosinophils and Mast Cells (training set; n = 231) and several centers for mastocytosis in the United States and Europe, all within the European Competence Network on Mastocytosis (validation set; n = 152). A Cox multivariable model was used to select variables that were predictive of overall survival (OS). In multivariable analysis, the following risk factors were identified as being associated with OS: age greater than 60 years, anemia (hemoglobin < 10 g/dL), thrombocytopenia (platelets < 100 × 109/L), presence of one high molecular risk gene mutation (ie, in SRSF2, ASXL1, and/or RUNX1), and presence of two or more high molecular risk gene mutations. By assigning hazard ratio-weighted points to these variables, the following three risk categories were defined: low risk (median OS, not reached), intermediate risk (median OS, 3.9 years; 95% CI, 2.1 to 5.7 years), and high risk (median OS, 1.9 years; 95% CI, 1.3 to 2.6 years; P < .001). The mutation-adjusted risk score (MARS) was independent of the WHO classification and was confirmed in the independent validation set. During a median follow-up time of 2.2 years (range, 0 to 23 years), 63 (16%) of 383 patients experienced a leukemic transformation to secondary mast cell leukemia (32%) or secondary acute myeloid leukemia (68%). The MARS was also predictive for leukemia-free survival (P < .001). The MARS is a validated, five-parameter, WHO-independent prognostic score that defines three risk groups among patients with AdvSM and may improve up-front treatment stratification for these rare hematologic neoplasms.
Fusion driven JMML: a novel CCDC88C–FLT3 fusion responsive to sorafenib identified by RNA sequencing
Authors: Alexander K. Chao, Julia A. Meyer, Alex G. Lee, Anna Hecht, Theodore Tarver, Jessica Van Ziffle, Ashley K. Koegel, Carla Golden, Benjamin S. Braun, E. Alejandro Sweet-Cordero, Catherine C. Smith, Christopher C. Dvorak, Mignon L. Loh, Elliot Stieglitz
Journal: Leukemia (2019)