tbuckley/cabot-search huggingface dataset:
A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma
Authors: Ankit Singh Tomar, Paul T. Finger, Brenda Gallie, Ashwin Mallipatna, Tero T. Kivelä, Chengyue Zhang, Junyang Zhao, Matthew W. Wilson, Rachel C. Brenna, Michala Burges, Jonathan Kim, Vikas Khetan, Suganeswari Ganesan, Andrey Yarovoy, Vera Yarovaya, Elena Kotova, Yacoub A. Yousef, Kalle Nummi, Tatiana L. Ushakova, Olga V. Yugay, Vladimir G. Polyakov, Marco A. Ramirez-Ortiz, Elizabeth Esparza-Aguiar, Guillermo Chantada, Paula Schaiquevich, Adriana Fandino, Jason C. Yam, Winnie W. Lau, Carol P. Lam, Phillipa Sharwood, Sonia Moorthy, Quah Boon Long, Vera Adobea Essuman, Lorna A. Renner, Ekaterina Semenova, Jaume Català, Genoveva Correa-Llano, Elisa Carreras
Journal: Ophthalmology (2020)

To evaluate the ability of the American Joint Committee on Cancer (AJCC) 8th edition to predict local tumor control and globe salvage for children with retinoblastoma (RB).International, multicenter, registry-based retrospective case series.A total of 2854 eyes of 2097 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents.International, multicenter, registry-based data were pooled from patients enrolled between January 2001 and December 2013. All RB eyes with adequate records to allow tumor staging by the AJCC 8th edition criteria and follow-up to ascertain treatment outcomes were included.Globe-salvage rates were estimated by AJCC clinical (cTNMH) categories and tumor laterality. Local treatment failure was defined as use of enucleation or external beam radiation therapy (EBRT), with or without plaque brachytherapy or intra-arterial chemotherapy (IAC).Unilateral RB occurred in 1340 eyes (47%). Among the 2854 eyes, tumor categories were cT1 to cT4 in 696 eyes (24%), 1334 eyes (47%), 802 eyes (28%), and 22 eyes (1%), respectively. Of these, 1275 eyes (45%) were salvaged, and 1179 eyes (41%) and 400 eyes (14%) underwent primary and secondary enucleation, respectively. The 2- and 5-year Kaplan-Meier cumulative globe-salvage rates without the use of EBRT by cTNMH categories were 97% and 96% for category cT1a tumors, 94% and 88% for cT1b tumors, 68% and 60% for cT2a tumors, 66% and 57% for cT2b tumors, and 32% and 25% for cT3 tumors, respectively. Risk of local treatment failure increased with increasing cT category (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of local treatment failure in categories cT1b (hazard ratio [HR], 3.5; P = 0.004), cT2a (HR, 15.1; P < 0.001), cT2b (HR, 16.4; P < 0.001), and cT3 (HR, 45.0; P < 0.001) compared with category cT1a. Use of plaque brachytherapy and IAC improved local tumor control in categories cT1a (P = 0.031) and cT1b (P < 0.001).Multicenter, international, internet-based data sharing validated the 8th edition AJCC RB staging to predict globe-salvage in a large, heterogeneous, real-world patient population with RB.
Immune status could determine efficacy of COVID-19 therapies
Authors: Megan Cully
Journal: Nature Reviews Drug Discovery (2020)

Nearly as soon as the SARS-CoV-2 virus was identified, clinicians started working with repurposed antivirals such as Gilead's remdesivir and the HIV drug combo lopinavir-ritonavir to establish whether these agents had activity against the coronavirus.As ICUs filled up with infected patients who had acute respiratory distress syndrome (ARDS), seemingly caused by runaway immune responses and the resulting cytokine storms, clinicians set about assessing whether approved anti-inflammatory agents could be used to keep immune responses in check and avoid collateral damage.Several months on, the COVID-19 pipeline -spanning more than 1,100 interventional trials on ClinicalTrials.gov,as of mid-June -remains dominated by these two strategies.But a growing number of front-line intensivists are advocating a more nuanced approach to immune modulation in COVID-19.Dampening the immune system when patients are fighting off infections can be a dangerous approach, says Richard Hotchkiss, an intensivist at Washington University in St Louis.Instead, patients might need immune-boosting agents to help fend off infection."I'm personally tired of reading about the cytokine storm, " says Hotchkiss."That's the predominant theory, but I believe that's not correct."Oncologists Santosh Vardhana and Jedd Wolchok, both at the Memorial Sloan Kettering Cancer Center, recently outlined their case for immunotherapies for the treatment of COVID-19 in the Journal of Experimental Medicine, based on their experience with cancer patients who became infected with SARS-CoV-2.The immune system takes on different forms with COVID-19, they wrote.While many patients have hallmarks of inflammation early on in the infection, the virus can outlive the initial burst of immune activity.
Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study
Authors: Andrew Clark, Mark Jit, Charlotte Warren-Gash, Bruce Guthrie, Harry H X Wang, Stewart W Mercer, Colin Sanderson, Martin McKee, Christopher Troeger, Kanyin L Ong, Francesco Checchi, Pablo Perel, Sarah Joseph, Hamish P Gibbs, Amitava Banerjee, Rosalind M Eggo, Emily S Nightingale, Kathleen O'Reilly, Thibaut Jombart, W John Edmunds, Alicia Rosello, Fiona Yueqian Sun, Katherine E Atkins, Nikos I Bosse, Samuel Clifford, Timothy W Russell, Arminder K Deol, Yang Liu, Simon R Procter, Quentin J Leclerc, Graham Medley, Gwen Knight, James D Munday, Adam J Kucharski, Carl A B Pearson, Petra Klepac, Kiesha Prem, Rein M G J Houben, Akira Endo, Stefan Flasche, Nicholas G Davies, Charlie Diamond, Kevin van Zandvoort, Sebastian Funk, Megan Auzenbergs, Eleanor M Rees, Damien C Tully, Jon C Emery, Billy J Quilty, Sam Abbott, Ch Julian Villabona-Arenas, Stéphane Hué, Joel Hellewell, Amy Gimma, Christopher I Jarvis
Journal: The Lancet Global Health (2020)
Microbiomics, Metabolomics, Predicted Metagenomics, and Hepatic Steatosis in a Population‐Based Study of 1,355 Adults
Authors: Louise J.M. Alferink, Djawad Radjabzadeh, Nicole S. Erler, Dina Vojinovic, Carolina Medina‐Gomez, André G. Uitterlinden, Robert J. de Knegt, Najaf Amin, M. Arfan Ikram, Harry L.A. Janssen, Jessica C. Kiefte‐de Jong, Herold J. Metselaar, Cornelia M. van Duijn, Robert Kraaij, Sarwa Darwish Murad
Journal: Hepatology (2020)

Background and Aims Previous small studies have appraised the gut microbiome (GM) in steatosis, but large‐scale studies are lacking. We studied the association of the GM diversity and composition, plasma metabolites, predicted functional metagenomics, and steatosis. Approach and Results This is a cross‐sectional analysis of the prospective population‐based Rotterdam Study. We used 16S ribosomal RNA gene sequencing and determined taxonomy using the SILVA reference database. Alpha diversity and beta diversity were calculated using the Shannon diversity index and Bray–Curtis dissimilarities. Differences were tested across steatosis using permutational multivariate analysis of variance. Hepatic steatosis was diagnosed by ultrasonography. We subsequently selected genera using regularized regression. The functional metagenome was predicted based on the GM using Kyoto Encyclopedia of Genes and Genomes pathways. Serum metabolomics were assessed using high‐throughput proton nuclear magnetic resonance. All analyses were adjusted for age, sex, body mass index, alcohol, diet, and proton‐pump inhibitors. We included 1,355 participants, of whom 472 had steatosis. Alpha diversity was lower in steatosis ( P = 1.1∙10 −9 ), and beta diversity varied across steatosis strata ( P = 0.001). Lasso selected 37 genera of which three remained significantly associated after adjustment ( Coprococcus3 : β = −65; Ruminococcus Gauvreauiigroup : β = 62; and Ruminococcus Gnavusgroup : β = 45, Q ‐value = 0.037). Predicted metagenome analyses revealed that pathways of secondary bile‐acid synthesis and biotin metabolism were present, and D‐alanine metabolism was absent in steatosis. Metabolic profiles showed positive associations for aromatic and branched chain amino acids and glycoprotein acetyls with steatosis and R. Gnavusgroup , whereas these metabolites were inversely associated with alpha diversity and Coprococcus3 . Conclusions We confirmed, on a large‐scale, the lower microbial diversity and association of Coprococcus and Ruminococcus Gnavus with steatosis. We additionally showed that steatosis and alpha diversity share opposite metabolic profiles.
Association of Long-term Change and Variability in Glycemia With Risk of Incident Heart Failure Among Patients With Type 2 Diabetes: A Secondary Analysis of the ACCORD Trial
Authors: Matthew W. Segar, Kershaw V. Patel, Muthiah Vaduganathan, Melissa C. Caughey, Javed Butler, Gregg C. Fonarow, Justin L. Grodin, Darren K. McGuire, Ambarish Pandey
Journal: Diabetes Care (2020)

To evaluate the associations between long-term change and variability in glycemia with risk of heart failure (HF) among patients with type 2 diabetes mellitus (T2DM).Among participants with T2DM enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, variability in HbA1c was assessed from stabilization of HbA1c following enrollment (8 months) to 3 years of follow-up as follows: average successive variability (ASV) (average absolute difference between successive values), coefficient of variation (SD/mean), and SD. Participants with HF at baseline or within 3 years of enrollment were excluded. Adjusted Cox models were used to evaluate the association of percent change (from baseline to 3 years of follow-up) and variability in HbA1c over the first 3 years of enrollment and subsequent risk of HF.The study included 8,576 patients. Over a median follow-up of 6.4 years from the end of variability measurements at year 3, 388 patients had an incident HF hospitalization. Substantial changes in HbA1c were significantly associated with higher risk of HF (hazard ratio [HR] for ≥10% decrease 1.32 [95% CI 1.08-1.75] and for ≥10% increase 1.55 [1.19-2.04]; reference <10% change in HbA1c). Greater long-term variability in HbA1c was significantly associated with higher risk of HF (HR per 1 SD of ASV 1.34 [95% CI 1.17-1.54]) independent of baseline risk factors and interval changes in cardiometabolic parameters. Consistent patterns of association were observed with use of alternative measures of glycemic variability.Substantial long-term changes and variability in HbA1c were independently associated with risk of HF among patients with T2DM.
AB0053 BERGENIN, ACTING AS AN AGONIST OF SIRT1, REDUCE SERUM URATE IN MICE THROUGH THE UPREGULATION OF ABCG2
Authors: M. Chen, X. Lu, H. Wu
Journal: Annals of the Rheumatic Diseases (2020)

Background: About 20% of individuals in the USA have asymptomatic hyperuricaemia [1] . However, Urate-lowering therapy in asymptomatic hyperuricaemia condition is still controversial considering the benefit and side effects [2] . Therefore, safe and effective anti-hyperuricemia therapies are necessary. Objectives: Bergenin, the major bioactive ingredient isolated from Saxifraga stolonifera, could activate SIRT1. In this study, we identify the effect of bergenin on hyperuricemia, and explored the related mechanisms. Methods: Significant hyperuricemia was established in C57BL/6N mice treated with oxonate and yeast polysaccharide. Bergenin was administered to the mice at the same time. The serum uric acid and creatinine levels, clearance of uric acid and creatinine, the intestinal uric acid excretion, and renal pathological lesions were determined were used to evaluate the anti-hyperuricemic effects. The location and expression levels of ABCG2 in the kidney and intestine were analyzed. HK-2 and Caco-2 cell lines were exposed to soluble uric acid with or without the treatment of Bergenin. Then the expression of ABCG2 and underlying mechanisms were explored. Results: The administration of bergenin decreased serum uric acid in hyperuricemic mice by the promotion of uric acid excretion both in kidney and intestine. Bergenin recued the downregulation of ABCG2 in the kidney of hyperuricemic mice and upregulated the expression of ABCG2 in the jejunum and ileum. In vitro, Bergenin significantly increased the expression of ABCG2 as well as activated SIRT1, which was reversed by addition of PPARg antagonist GW9662 and siPPARg. Conclusion: These findings suggest bergenin increases uric acid excretion both in the kidney and intestines, which may be related to the upregulation of ABCG2 via SIRT1- PPARg pathway. References: [1]Zhu, Y., Pandya, B. J. &amp; Choi, H. K. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007–2008. Arthritis Rheum. 63, 3136–3141 (2011). [2]Joosten LAB, Crisan TO, Bjornstad P, Johnson RJ: Asymptomatic hyperuricaemia: a silent activator of the innate immune system. Nature reviews Rheumatology 2020, 16(2):75-86. Disclosure of Interests: None declared
Osteoclast-derived apoptotic bodies show extended biological effects of parental cell in promoting bone defect healing
Authors: Qinyu Ma, Mengmeng Liang, Nathachit Limjunyawong, Yang Dan, Junchao Xing, Jianmei Li, Jianzhong Xu, Ce Dou
Journal: Theranostics (2020)

Apoptotic bodies (ABs) traditionally considered as garbage bags that enclose residual components of dead cells are gaining increasing attentions due to their potential roles in intercellular communications. In bone turn over, at the end of bone resorption phase, most osteoclasts undergo apoptosis, generating large amounts of ABs. However, it remains unclear of the role of osteoclast-derived ABs in bone remodeling. Methods: Staurosporine (STS) was used to apoptotic induction and differential centrifugation was used to isolate ABs. Western blotting, flowcytometry and Transmission electron microscopy (TEM) were performed for ABs identification, while whole transcriptome of ABs from osteoclasts at different stages was detected by RNA-seq. VENN analysis and gene set enrichment analysis (GSEA) were performed to compare the profile similarities between ABs and parental cells. In vitro efficacy of ABs on angiogenesis and osteogenesis were evaluated by tube formation assay and ALP staining. In vivo, calvarial defect mice model was used to assess the effects of ABs-modified decalcified bone matrix (DBM) scaffolds on angiogenesis and osteogenesis. Results: Here we mapped the whole transcriptome paralleled with small RNA profiling of osteoclast derived ABs at distinct differentiation stages. Whole transcriptome analysis revealed significant differences in RNA signatures among the ABs generated from osteoclasts at different stages. By comparing with parental osteoclast RNA profiles, we found that the transcriptome of ABs exhibited high similarities with the corresponding parental cells. Functionally, in vitro and in vivo studies showed that similar with the parental cells, pOC-ABs potentiated endothelial progenitor cell proliferation and differentiation, whereas mOC-ABs promoted osteogenic differentiation. The inherited biological effects of ABs were shown mediated by several enriched lncRNAs of which the interference abolished AB functions. Conclusions: Our study revealed the total RNA profiles of osteoclast derived ABs and demonstrated their biological functions. Both gene set and functional analysis indicated that osteoclast derived ABs are biologically similar with the parental cells suggesting their bridging role in osteoclast-osteoblast coupling in bone remodeling.
Therapy-Related Myeloid Neoplasms Are Not Always Dismal If They Have Better Cytogenetic Profile and Longer Latency Period from Preceding Anti-Cancer Treatment
Authors: Junshik Hong, Ji Yun Lee, Ja Min Byun, Dong-Yeop Shin, Youngil Koh, Inho Kim, Sung-Soo Yoon
Journal: Blood (2017)
Application of Diagnostic Algorithms for Heart Failure With Preserved Ejection Fraction to the Community
Authors: Senthil Selvaraj, Peder L. Myhre, Muthiah Vaduganathan, Brian L. Claggett, Kunihiro Matsushita, Dalane W. Kitzman, Barry A. Borlaug, Amil M. Shah, Scott D. Solomon
Journal: JACC Heart Failure (2020)
Abstract 16595: The Impact of Aortic Valve Replacement on the Intermediate Survival of Patients With Severe Aortic Stenosis
Authors: Amjad I Hussain, Andreas Auensen, Cathrine Brunborg, Svend Aakhus, Arnt Fiane, Kjell I Pettersen, Lars Gullestad
Journal: Circulation (2016)

Introduction: Recently more comorbid, elderly and frail patients with severe aortic stenosis are being eligible for aortic valve replacement (AVR) due to emerging new techniques. However, there is ...
Genomic Characterization of HIV-Associated Plasmablastic Lymphoma Identifies Pervasive Mutations in the JAK–STAT Pathway
Authors: Zhaoqi Liu, Ioan Filip, Karen Gomez, Dewaldt Engelbrecht, Shabnum Meer, Pooja N. Lalloo, Pareen Patel, Yvonne Perner, Junfei Zhao, Jiguang Wang, Laura Pasqualucci, Raul Rabadan, Pascale Willem
Journal: Blood Cancer Discovery (2020)

Plasmablastic lymphoma (PBL) is an aggressive B-cell non-Hodgkin lymphoma associated with immunodeficiency in the context of human immunodeficiency virus (HIV) infection or iatrogenic immunosuppression. While a rare disease in general, the incidence is dramatically increased in regions of the world with high HIV prevalence. The molecular pathogenesis of this disease is poorly characterized. Here, we defined the genomic features of PBL in a cohort of 110 patients from South Africa (15 by whole-exome sequencing and 95 by deep targeted sequencing). We identified recurrent mutations in genes of the JAK–STAT signaling pathway, including STAT3 (42%), JAK1 (14%), and SOCS1 (10%), leading to its constitutive activation. Moreover, 24% of cases harbored gain-of-function mutations in RAS family members (NRAS and KRAS). Comparative analysis with other B-cell malignancies uncovered PBL-specific somatic mutations and transcriptional programs. We also found recurrent copy number gains encompassing the CD44 gene (37%), which encodes for a cell surface receptor involved in lymphocyte activation and homing, and was found expressed at high levels in all tested cases, independent of genetic alterations. These findings have implications for the understanding of the pathogenesis of this disease and the development of personalized medicine approaches.
Toward Inclusion of Youths With Psychiatric Disorders in Brain-Body Research—Reply
Authors: Jennifer S. Laurent, Richard Watts, Scott Mackey
Journal: JAMA Pediatrics (2020)

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AB0886 INCIDENCE OF FRACTURES IN A BARIATRIC SURGERY COHORT
Authors: M. D. P. Ahijado Guzman, R. M. Veiga Cabello, M. Cantalejo Moreira, J. Ruiz Ruiz, A. Zapatero Gaviria
Journal: Annals of the Rheumatic Diseases (2020)

Background: Bariatric surgery is the set of surgical techniques whose objective is weight reduction, and it could have complications. One of them may be the increase in the incidence of fractures (1), secondary to nutritional defects (2), among others, that could modify bone metabolism with an increase in remodeling (3). Objectives: To carry out a retrospective observational pilot analysis of a cohort of 140 morbidly obese patients after bariatric surgery, of a total of 304, descriptive of axial and peripheral fractures, among other variables. Methods: Data were collected from the University Hospital of Fuenlabrada of a cohort of morbidly obese people who underwent bariatric surgery from 2009 to the present. Were included as variables age in years, sex, body mass index (BMI) before surgery, evolution time since surgery in years, incidence of sleep apnea syndrome (OSAS), incidence and type of fracture, osteoporotic or not, and axial or peripheral. A descriptive and frequency analysis, and a chi-square contingency table between incidence of fracture, and gender, OSAS, or childhood obesity, were performed. Results: A 48.76 years old cohort was observed, 25.7% men/74.3% women, 30.8% childhood obesity, BMI of 45.65 kg / m2, and 45% with a diagnosis of OSAS. A 15% of fractures were noted: 66.66% considered as osteoporotics (40.76% axial, 50.31% peripheral, and 8.93% of both) in a time of evolution of 5.81 years, and without relationship with gender, OSAS or childhood obesity (p = 0.7, p = 0.15, p = 0.16). Conclusion: It is a study that higlights that bariatric surgery in Fuenlabrada area is mainly performed on morbidly obese women in adulthood. There is a high rate of OSAS, and an increase in the incidence of fractures unrelated to gender, OSAS or childhood obesity, despite the fact that in the bariatric surgery protocol densitometric osteoporosis is an exclusion criterion. References: [1]Rousseau C, Jean S, Gamache P, Lebel S, Mac-Way F, Biertho L, et al. Change in fracture risk and fracture pattern after bariatric surgery: nested case-control study. BMJ. 27 july 2016;354:i3794. [2]Scibora LM. Skeletal effects of bariatric surgery: examining bone loss, potential mechanisms and clinical relevance. Diabetes Obes Metab2014;16:1204-13. doi:10.1111/dom.12363 pmid:25132010. [3]Coates PS, Fernstrom JD, Fernstrom MH, Schauer PR, Greenspan SL. Gastric bypass surgery for morbid obesity leads to an increase in bone turnover and a decrease in bone mass. J Clin Endocrinol Metab2004;89:1061-5. doi:10.1210/jc.2003-031756 pmid:15001587. Disclosure of Interests: None declared
Viral-bacterial (co-)occurrence in the upper airways and the risk of childhood pneumonia in resource-limited settings
Authors: James S. Ngocho, Linda Minja, Christa E. van der Gaast – de Jongh, Janette C. Rahamat-Langendoen, Jeroen D. Langereis, Blandina T. Mmbaga, Marien I. de Jonge
Journal: Journal of Infection (2020)

To examine the association between bacterial-viral co-occurrence in the nasopharynx and the risk of community acquired pneumonia (CAP) in young children living in resource-limited settings.A case-control study was conducted between January and December 2017 in Moshi, Tanzania. Children 2-59 months with CAP and healthy controls were enrolled. RSV and Influenza A/B were detected with a standardized polymerase chain reaction (PCR) method, and a simplified real-time quantitative PCR method, without sample pre-processing, was developed to detect bacterial pathogens in nasopharyngeal samples.A total of 109 CAP patients and 324 healthy controls were enrolled. Co-detection of H. influenzae and S. pneumoniae in nasopharyngeal swabs was linked with higher odds of CAP (aOR=3.2, 95% CI=1.1-9.5). The majority of the H. influenzae isolated in cases and controls (95.8%) were non-typeable. Of the viruses examined, respiratory syncytial virus (RSV) was most common (n = 31, 7.2%) in cases and controls. Children with RSV had 8.4 times higher odds to develop pneumonia than healthy children (aOR=8.4, 95%CI= 3.2 - 22.1).Co-occurence of H. influenzae and S. pneumoniae in the nasopharynx was strongly associated with CAP. The high prevalence of non-typeable H. influenzae might be a sign of replacement as a consequence of Haemophilus influenzae type b vaccination.