tbuckley/cabot-search huggingface dataset:
Abstract 1486: Exosomal miR-141 promoted tumor angiogenesis via KLF12 in small cell lung cancer
Authors: Shuangshuang Mao, Zhiliang Lu, Sufei Zheng, Guochao Zhang, Jianbing Huang, Nan Sun, Jie He
Journal: Cancer Research (2020)

Abstract Background: Angiogenesis, the basic requirement for the survival of tumor cells, has been considered to be one of the malignant characteristics of small cell lung cancer (SCLC) and was closely related to the poor outcomes of SCLC patients. MiR-141 has been found to play a pro- or anti-angiogenetic role in different cancers while its role in SCLC angiogenesis has never been explored. Methods: We isolate total RNA from plasm exosomes and serum samples from two cohorts of SCLC patients respectively to detect the expression of circulating miR-141 in SCLC patients using qRT-PCR. miR-141 was overexpressed in SCLC cell-secreted exosomes to investigate its effects on cell migration, tube formation and microvessel sprouting capabilities of human umbilical vein vascular endothelial cells (HUVECs) both in vitro and in vivo. A dual-luciferase assay was conducted to validate the direct target gene of miR-141. Results: We showed that the level of circulating miR-141 was significantly upregulated in a total of 116 SCLC patients compared with normal volunteers, and the increased miR-141 was revealed to be associated with advanced patient TNM stages which implying the potential oncogenic role of miR-141 in SCLC malignances. In vitro experiments indicated that miR-141 was packaged into SCLC cell-secreted exosomes and was delivered to HUVECs via exosomes to strengthen the migration, invasion, tube formation and microvessel sprouting capabilities of HUVECs. Moreover, mouse models demonstrated that exosomal miR-141 derived from SCLC cells induced neo-angiogenesis in vivo and subcutaneous tumor nodules developed from SCLC cells with miR-141 overexpression showed higher microvessel densities and faster tumor growth than which developed from negative control cells. Combining miRNA target prediction tools with a dual-luciferase assay, we identified that KLF12 was the direct target gene of miR-141 and the angiogenetic promotion effect of miR-141 on HUVECs was abrogated by overexpressing KLF12. Conclusions: Our results elaborated the specific function of exosomal miR-141/KLF12 pathway in SCLC angiogenesis for the first time and provided potential novel targets for anti-angiogenetic therapies in SCLC patients. Our study highlighted the critical role of exosomal miRNAs in SCLC microenvironments and cell communications which offered novel clues for the future exploration of molecular mechanisms of SCLC malignances. Citation Format: Shuangshuang Mao, Zhiliang Lu, Sufei Zheng, Guochao Zhang, Jianbing Huang, Nan Sun, Jie He. Exosomal miR-141 promoted tumor angiogenesis via KLF12 in small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1486.
HP0004 Hand’s rehabilitation in rheumatoid arthritis
Authors: JD Petit, RC Camp, AR De la Serna
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Objective</h3> Decrease of pain and inflammation, maintenance articular mobility, muscular power and prevention of tendons rupture. <h3>Material</h3> We conducted a prospective study in 530 rheumatoid arthritis female patients suffering from bilateral hand sinovitis with an average of 45 years old (range 25–69 years old). <h3>Method</h3> The following treatment was used during 2–3 sessions/week for six months. Acute phase: cryotherapy and rest with orthesis in functional position. Chronic phase: thermotherapy; paraffin bath and passive and active exercise alternating with rest; ring orthesis; articular saveness and healthy education. We have measured the results through followings items: Pain: visual analogic scalee (VAS) Hand grip strength: mm. Hg Functional capacity: health assessment questionary (HAQ) <h3>Results</h3> Table 1. <h3>Conclusions</h3> Rheumatoid arthritis hand's physiotherapy increase quality of life and articular movility, and decrease of pain. This treatment in not able to stop the progression of the illness.
Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial
Authors: Othman Al-Sawaf, Can Zhang, Maneesh Tandon, Arijit Sinha, Anna-Maria Fink, Sandra Robrecht, Olga Samoylova, Anna M Liberati, Javier Pinilla-Ibarz, Stephen Opat, Liliya Sivcheva, Katell Le Dû, Laura M Fogliatto, Carsten U Niemann, Robert Weinkove, Sue Robinson, Thomas J Kipps, Eugen Tausch, William Schary, Matthias Ritgen, Clemens-Martin Wendtner, Karl-Anton Kreuzer, Barbara Eichhorst, Stephan Stilgenbauer, Michael Hallek, Kirsten Fischer
Journal: The Lancet Oncology (2020)
Activation of TRPA1 nociceptor promotes systemic adult mammalian skin regeneration
Authors: Jenny J. Wei, Hali S. Kim, Casey A. Spencer, Donna Brennan-Crispi, Ying Zheng, Nicolette M. Johnson, Misha Rosenbach, Christopher Miller, Denis H. Leung, George Cotsarelis, Thomas H. Leung
Journal: Science Immunology (2020)

Adult mammalian wounds, with rare exception, heal with fibrotic scars that severely disrupt tissue architecture and function. Regenerative medicine seeks methods to avoid scar formation and restore the original tissue structures. We show in three adult mouse models that pharmacologic activation of the nociceptor TRPA1 on cutaneous sensory neurons reduces scar formation and can also promote tissue regeneration. Local activation of TRPA1 induces tissue regeneration on distant untreated areas of injury, demonstrating a systemic effect. Activated TRPA1 stimulates local production of interleukin-23 (IL-23) by dermal dendritic cells, leading to activation of circulating dermal IL-17-producing γδ T cells. Genetic ablation of TRPA1, IL-23, dermal dendritic cells, or γδ T cells prevents TRPA1-mediated tissue regeneration. These results reveal a cutaneous neuroimmune-regeneration cascade triggered by topical TRPA1 activators that promotes adult mammalian tissue regeneration, presenting a new avenue for research and development of therapies for wounds and scars.
Abstract 2483: NELFE modulates chromatin accessibility to amplify the transcription of MYC-associated genes in hepatocellular carcinoma
Authors: Kai Zhang, Hien Dang, Anna Barry
Journal: Cancer Research (2020)

Abstract Global transcriptomic alterations are often observed in cancers, including hepatocellular carcinoma (HCC). How these large changes are modulated remain elusive. We have previously demonstrated that the overexpression of Negative elongation factor E (NELFE) contributes to the transcriptomic imbalance in HCC through MYC signaling, which regulates more than 15% of the genome. However, how NELFE modulates MYC to enhance the transcription of pro-oncogenic mRNAs is unknown. It is known that the status of the chromatin is essential for gene expression. Previous studies have shown that NELF-mediated stalling of Pol II can enhance gene expression by blocking promoter-proximal nucleosome assembly in Drosophila. Here, we propose that NELFE modulates the status of the chromatin to regulate gene expression to promote hepatocarcinogenesis. Accordingly, the overexpression of NELFE and MYC in the h-TERT immortalized hepatocyte cells, HHT4, significantly enhanced cancer associated phontypes, including proliferation and colony and spheroid formation. NELFE and MYC ChIP-PCR demonstrated that both NELFE and MYC co-occupy the promoter regions of two proliferative genes, cyclin E2 and PA2G4. Furthermore, the signals of MYC and H3K27ac, a histone marker associated with open and active promoter and enhancer elements, were decreased in these regions by NELFE-depletion. These results provide a possible mechanism whereby NELFE plays an essential role in modulating the status of the chromatin to regulate MYC-induced gene expression. Current studies include the use of CRISPR/Cas9 tools to generate NELFE mutants and ATAC-seq and ChIP-seq (MYC and NELFE) to explore NELFE's role in chromatin modulation genome-wide. These assays will allow us to determine the dynamic function and pro-oncogenic roles of NELFE and their effect on the MYC targets, including cyclin E2 and PA2G4 transcripts. Key words: NELFE, chromatin, transcription, HCC, liver, MYC. Citation Format: Kai Zhang, Hien Dang, Anna Barry. NELFE modulates chromatin accessibility to amplify the transcription of MYC-associated genes in hepatocellular carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2483.
Neighbourhood unemployment and other socio-demographic predictors of emergency hospitalisation for infectious intestinal disease in England: A longitudinal ecological study
Authors: Tanith C. Rose, Natalie L. Adams, Margaret Whitehead, Sophie Wickham, Sarah J. O'Brien, Jeremy Hawker, David C. Taylor-Robinson, Mara Violato, Benjamin Barr
Journal: Journal of Infection (2020)

<h2>Summary</h2><h3>Background</h3> Previous studies have observed that infectious intestinal disease (IID) related hospital admissions are higher in more deprived neighbourhoods. These studies have mainly focused on paediatric populations and are cross-sectional in nature. This study examines recent trends in emergency IID admission rates, and uses longitudinal methods to investigate the effects of unemployment (as a time varying measure of neighbourhood deprivation) and other socio-demographic characteristics on IID admissions for adults and children in England. <h3>Methods</h3> A longitudinal ecological analysis was performed using Hospital Episode Statistics on emergency hospitalisations for IID, collected over the time period 2012–17 across England. Analysis was conducted at the neighbourhood (Lower-layer Super Output Area) level for three age groups (0–14; 15–64; 65+ years). Mixed-effect Poisson regression models were used to assess the relationship between trends in neighbourhood unemployment and emergency IID admission rates, whilst controlling for measures of primary and secondary care access, underlying morbidity and the ethnic composition of each neighbourhood. <h3>Results</h3> From 2012–17, declining trends in emergency IID admission rates were observed for children and older adults overall, while rates increased for some sub-groups in the population. Each 1 percentage point increase in unemployment was associated with a 6.3, 2.4 and 4% increase in the rate of IID admissions per year for children [IRR=1.06, 95%CI 1.06–1.07], adults [IRR=1.02, 95%CI 1.02–1.03] and older adults [IRR=1.04, 95%CI 1.036–1.043], respectively. Increases in poor primary care access, the percentage of people from a Pakistani ethnic background, and the prevalence of long-term health problems, in a neighbourhood, were also associated with increases in IID admission rates. <h3>Conclusions</h3> Increasing trends in neighbourhood deprivation, as measured by unemployment, were associated with increases in emergency IID admission rates for children and adults in England, despite controlling for measures of healthcare access, underlying morbidity and ethnicity. Research is needed to improve understanding of the mechanisms that explain these inequalities, so that effective policies can be developed to reduce the higher emergency IID admission rates experienced by more disadvantaged communities.
Abstract 3346: Changes of gut microbiota in FAP and UC that might harbor colorectal cancer carcinogenesis
Authors: Atil Bisgin, Abdullah Hanta, Ahmet Rencuzogullari, Ibrahim Boga
Journal: Cancer Research (2020)

Abstract Inflammatory bowel diseases, Familial adenomatous polyposis(FAP) and colorectal cancer(CRC) are associated with alterations of the intestinal microbiota. However, few data are available on the perpetuation of FAP and Ulcerative Colitis(UC) in relation to microbial dysbiosis. This study evaluated the UC and genetically confirmed FAP patients' gut microbial balance in concordance to clinical outcome. Fecal materials (average mass of 0.54 g) were collected from three FAP and five UC patients to compare with healthy individuals as control group. Genomic materials of microbiota were isolated via QIAamp PowerFecal DNA kit according to manufacturer instructions. Next generation sequencing of 16S rRNA was performed by using QIAseq 16S/ITS panel in Illumina Miseq Platform. Data processing and bioinformatics analysis were performed via CLC Genomic Workbench bioinformatics tool. The comparison between FAP subjects, UC patients and control group revealed an alteration in the intestinal microbial composition. More in details, relative abundance of class levels showing statistical significance differences among FAP, UC and control group was given in Table 1, in which the sample groups are reported in column while class levels are in row. Our preliminary data focused on the explanation of how dysbiosis can lead to inflammation and drive processes together with host genetic profile that leads to colorectal carcinogenesis. Abundance table of class levels compared between FAP, UC and control groupClass (Aggregated)Cont AbundanceUlc. Col. AbundanceFAP AbundanceActinobacteria65847688013162Alphaproteobacteria899923560Bacilli4806197740237684Bacteroidia13247361374676321973Campylobacteria0730Clostridia748894613039897452Coriobacteriia5684586513543Deltaproteobacteria493780Erysipelotrichia6787833346228289Fusobacteriia18374510Gammaproteobacteria328501859739269883Halanaerobiia27000Kiritimatiellae700Lentisphaeria75400Melainabacteria201100Methanobacteria65600Mollicutes29069949Negativicutes578632230683666Oligosphaeria1700Oxyphotobacteria21150Saccharimonadia048360Stramenopiles200Verrucomicrobiae32065733252 Citation Format: Atil Bisgin, Abdullah Hanta, Ahmet Rencuzogullari, Ibrahim Boga. Changes of gut microbiota in FAP and UC that might harbor colorectal cancer carcinogenesis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3346.
Cardiovascular effects of biological versus conventional synthetic disease-modifying antirheumatic drug therapy in treatment-naïve, early rheumatoid arthritis
Authors: Sven Plein, Bara Erhayiem, Graham Fent, Sarah Horton, Raluca Bianca Dumitru, Jacqueline Andrews, John P Greenwood, Paul Emery, Elizabeth MA Hensor, Paul Baxter, Sue Pavitt, Maya H Buch
Journal: Annals of the Rheumatic Diseases (2020)

To determine whether patients with early rheumatoid arthritis (ERA) have cardiovascular disease (CVD) that is modifiable with disease-modifying antirheumatic drug (DMARD) therapy, comparing first-line etanercept (ETN) + methotrexate (MTX) with MTX strategy.Patients from a phase IV ERA trial randomised to ETN+MTX or MTX strategy±month 6 escalation to ETN+MTX, and with no CVD and maximum one traditional risk factor underwent cardiovascular magnetic resonance (CMR) at baseline, years 1 and 2. Thirty matched controls underwent CMR. Primary outcome measure was aortic distensibility (AD) between controls and ERA, and baseline to year 1 AD change in ERA. Secondary analyses between and within ERA groups performed. Additional outcome measures included left ventricular (LV) mass and myocardial extracellular volume (ECV).Eighty-one patients recruited. In ERA versus controls, respectively, baseline (geometric mean, 95% CI) AD was significantly lower (3.0×10-3 mm Hg-1 (2.7-3.3) vs 4.4×10-3 mm Hg-1 (3.7-5.2), p<0.001); LV mass significantly lower (78.2 g (74.0-82.7), n=81 vs 92.9 g (84.8-101.7), n=30, p<0.01); and ECV increased (27.1% (26.4-27.9), n=78 vs 24.9% (23.8-26.1), n=30, p<0.01). Across all patients, AD improved significantly from baseline to year 1 (3.0×10-3 mm Hg-1 (2.7-3.4) to 3.6×10-3 mm Hg-1 (3.1-4.1), respectively, p<0.01), maintained at year 2. The improvement in AD did not differ between the two treatment arms and disease activity state (Disease Activity Score with 28 joint count)-erythrocyte sedimentation rate-defined responders versus non-responders.We report the first evidence of vascular and myocardial abnormalities in an ERA randomised controlled trial cohort and show improvement with DMARD therapy. The type of DMARD (first-line tumour necrosis factor-inhibitors or MTX) and clinical response to therapy did not affect CVD markers.ISRCTN: ISRCTN89222125; ClinicalTrials.gov: NCT01295151.
Disruptive Behavior Disorders: The Challenge of Delineating Mechanisms in the Face of Heterogeneity
Authors: Essi Viding, Eamon McCrory
Journal: American Journal of Psychiatry (2020)

Causal pathways to disruptive behavior disorders, even within the same diagnostic category, are varied. Both equifinality and multifinality pose considerable challenges to uncovering underlying mechanisms and understanding varied developmental trajectories associated with disruptive behavior disorders. Uncovering genetic causes requires improved granularity in how we operationalize presentation and developmental trajectories associated with disruptive behavior disorders. If we want to integrate the study of genetic, environmental, and neurocognitive factors within a longitudinal framework, we need to improve measurement. Furthermore, brain changes associated with disruptive behavior disorders should not simply be understood as outcomes of genetic and environmental influences, but also as factors that reciprocally influence future social environments over time in ways that are important in contributing to risk and resilience. Advancing the field with regard to these challenges will result in more truly integrated investigation of disruptive behavior disorders, which holds the promise of improving our ability to develop more effective preventive and intervention approaches.
Western-type diet influences mortality from necrotising pancreatitis and demonstrates a central role for butyrate
Authors: Fons F van den Berg, Demi van Dalen, Sanjiv K Hyoju, Hjalmar C van Santvoort, Marc G Besselink, Willem Joost Wiersinga, Olga Zaborina, Marja A Boermeester, John Alverdy
Journal: Gut (2020)

The gut microbiota are the main source of infections in necrotising pancreatitis. We investigated the effect of disruption of the intestinal microbiota by a Western-type diet on mortality and bacterial dissemination in necrotising pancreatitis and its reversal by butyrate supplementation.C57BL/6 mice were fed either standard chow or a Western-type diet for 4 weeks and were then subjected to taurocholate-induced necrotising pancreatitis. Blood and pancreas were collected for bacteriology and immune analysis. The cecum microbiota composition of mice was analysed using 16S rRNA gene amplicon sequencing and cecal content metabolites were analysed by targeted (ie, butyrate) and untargeted metabolomics. Prevention of necrotising pancreatitis in this model was compared between faecal microbiota transplantation (FMT) from healthy mice, antibiotic decontamination against Gram-negative bacteria and oral or systemic butyrate administration. Additionally, the faecal microbiota of patients with pancreatitis and healthy subjects were analysed.Mortality, systemic inflammation and bacterial dissemination were increased in mice fed Western diet and their gut microbiota were characterised by a loss of diversity, a bloom of Escherichia coli and an altered metabolic profile with butyrate depletion. While antibiotic decontamination decreased mortality, Gram-positive dissemination was increased. Both oral and systemic butyrate supplementation decreased mortality, bacterial dissemination, and reversed the microbiota alterations. Paradoxically, mortality and bacterial dissemination were increased with FMT administration. Finally, patients with acute pancreatitis demonstrated an increase in Proteobacteria and a decrease of butyrate producers compared with healthy subjects.Butyrate depletion and its repletion appear to play a central role in disease progression towards necrotising pancreatitis.
Abstract 586: Anti-leukemia activities of selenium nanoparticles embedded in nanotube consisted of triple-helix β-D-glucan
Authors: Yanxia Jin, Liqin Cai, Qian Yang, Ziyi Luo, Lina Zhang, Fuling Zhou
Journal: Cancer Research (2020)

Abstract Background: Acute myeloid leukemia (AML) is a hematological malignant tumor. The common chemotherapy results in various side-effect and drug-resistance for AML, so it is urgent to find a non-toxic natural drug for AML therapy. Herein, for the first time, the Se nanoparticles embedded in nanotube consisted of triple helix β-D-glucan (BFP) exhibit the high anti-leukemia effects. Methods: A triple helix β-(1, 3)-D-glucan (BFP) extracted from the black fungus was self-assembled into nanotube in water, and Se nanoparticles (SeNPs) were wrapped to form stable inclusion complex BFP-Se. The CCK8 assays, lactose dehydrogenase release assays, optofluidics chips and flow cytometry were used to test the anti-leukemia effects of BFP-Se in vitro and in vivo. Results: The SeNPs embedded in the BFP nanotubes exhibited high stability in water, avoiding aggregation and dispersion to out. In vitro, the BFP-Se significantly inhibited the proliferation of AML cell lines and patient cells and markedly increased the cytotoxicity on AML cells. BFP-Se slowed the Molm-13 GFP+ cells growth. On single-cell levels, the U937 cells were gradually swelled and lysed with BFP-Se treatment. In addition, BFP-Se had little toxic to hematopoietic stem cells (HSC) and T cells compared to Ara-c. Flow cytometry indicated that BFP-Se promoted the cell apoptosis and blocked cell cycle of AML cells. Further, after injection of BFP-Se, the survival was longer on AML PDX model constructed with B-NSG mice. The blood and bone marrow analysis indicated the anti-leukemia effects of BFP-Se in vivo. Moreover, BFP-Se extremely increased the total antioxidant capacity (T-AOC) of AML cells, and decreased the expression of c-Jun activation domain-binding protein-1 (Jab1) and thioredoxin 1 (Trx1). Conclusion: This biocompatible polysaccharide nanotube containing Se nanoparticles - against AML would provide a novel strategy for AML therapy. Citation Format: Yanxia Jin, Liqin Cai, Qian Yang, Ziyi Luo, Lina Zhang, Fuling Zhou. Anti-leukemia activities of selenium nanoparticles embedded in nanotube consisted of triple-helix β-D-glucan [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 586.
Dapagliflozin Improves Left Ventricular Myocardial Longitudinal Function in Patients With Type 2 Diabetes
Authors: Alexander Brown, Stephen Gandy, Ify R. Mordi, Rory McCrimmon, Prasad G. Ramkumar, J. Graeme Houston, Allan D. Struthers, Chim C. Lang
Journal: JACC. Cardiovascular imaging (2020)
Novel Targets for Alzheimer's Disease: A View Beyond Amyloid
Authors: William J. Ray, Virginie Buggia-Prevot
Journal: Annual Review of Medicine (2020)

Genetic studies of autosomal dominant Alzheimer's disease (AD) revealed that β-amyloid is central to disease pathogenesis. However, amyloid-targeted therapies have generally failed to slow progression in patients with symptomatic disease. This result suggests a transition from an early amyloid-dependent phase to a later amyloid-independent one, during which neurodegeneration occurs and symptoms arise. Microglia, the brain's resident myeloid cells, envelop amyloid and express the majority of genes linked to risk for sporadic late-onset AD. Their activation is associated spatially and temporally with the accumulation of pathological tau. Microglial facilitation of tau pathology may involve apolipoprotein E, the most important genetic risk factor for AD. Once formed, pathological tau spreads between connected neurons, eventually accumulating in the somatic compartment where catastrophic nuclear damage ensues. This emerging understanding of the postamyloid processes leading to neurodegeneration affords the opportunity to develop therapeutics that interrupt this pathological cascade and prevent or delay dementia, even after amyloid deposition.