tbuckley/cabot-search huggingface dataset:
Response letter to: letter to the editor: three-dimensional bioprinted hepatorganoids in liver failure
Authors: Huayu Yang, Lejia Sun, Yilei Mao
Journal: Gut (2020)

We thank Kaur et al 1 for their valuable comments on our three-dimensional bioprinted hepatorganoids (3DP-HO) published in Gut.2 We have read with care all the concerns raised by Kaur et al 1 and acknowledge the great contributions of Ghosh et al 3 to the field of 3D in vitro tumour cell cultures. We would like to discuss the issues in detail as below.

First, this study showed that after 7 days of differentiation in vitro, HepaRG cells in 3DP-HOs expressed hepatic marker genes and exhibited albumin secretion (figure 2). The relevant experimental methods were described in detail in the supplementary materials. …
8 Lower gastrointestinal symptoms in young patients: can symptoms and non-invasive tests be used systematically to avoid unnecessary colonoscopies?
Authors: A Alakkari, M Hussey, BM Ryan
Journal: Gut (2017)

Background  Colonoscopies in young patients presenting with lower GI symptoms are often normal. Avoidance of colonoscopy in such instances reduces patient risk exposure and rationalises limited resource utilisation.  Aim  To assess colonoscopy outcome, relevant faecal and blood tests in young symptomatic patients.  Method  Colonoscopies performed over 1 year were retrospectively identified from the ERS. Patient charts, faecal calprotectin (FC) and CRP were reviewed. A raised CRP or FC of ≥50 ug/g was considered abnormal. Inclusion and exclusion criteria are in table 1.  Results  242/2155 medical GI outpatient colonoscopies performed over 12 months met inclusion criteria for the study. Median age 34 years (range 16-45), 141 (58%) female. Indications; (Group A) diarrhoea 132/242 (55%), (Group B) constipation, abdominal pain/bloating 110/242 (45%). Colonoscopy was normal in 104 (79%) of Group A and 102 (93%) of Group B (p=0.002). 28/36 (78%) patients with mucosal inflammation confirmed on histology had diarrhoea (p=0.0001). FC was available in 36 patients, and CRP in 171. In group A the NPV, sensitivity and specificity of CRP/FC were 88%, 42% and 86%. In group B these figures were 95%, 38% and 95%. 21 patients had incidental early adenomatous polyps.  Conclusions  Colonoscopy has very low yield in young symptomatic patients, especially those with non–diarrhoeal symptoms. Non-invasive tests should be used systematically to better identify patients requiring colonoscopy. We are conducting a prospective study to explore non-invasive diagnostic paradigms. Implementation of these strategies will help reduce colonoscopy waiting times.
Phase III study of sustained release granisetron (APF530) compared to palonosetron for the prevention of chemotherapy-induced nausea and vomiting (CINV)
Authors: J. J. Grous, E. Riegel, N. Gabrail, V. Charu, R. Arevalo-Araujo, R. Yanagihara, A. Nguyen, P. Robertson, B. Cooper, E. O'Boyle, J. Barr
Journal: Journal of Clinical Oncology (2009)

9627 Background: APF530 is a polymeric formulation of granisetron providing sustained drug release over 5 days. Two doses (5 and 10 mg) of subcutaneous APF530 were evaluated in comparison to 0.25 mg intravenous palonosetron. Efficacy was evaluated in acute (0–24 hrs) and delayed (24–120 hrs) CINV among patients receiving moderate (MEC) or highly (HEC) emetogenic chemotherapy. Methods: Randomized, blinded patients (n=1,395) were stratified into MEC or HEC according to Hesketh et al 1999, and assigned to receive either dose of APF530 or palonosetron. Dexamethasone use was standardized based on the emetogenic strata. Patient diaries recorded emetic episodes, nausea and rescue medications over a 5-day period. Primary endpoint was Complete Response (CR), defined as no emetic episodes and no rescue medication. Non-inferiority to palonosetron was declared if the lower bound of the CI for the difference was above -15%. Results: APF530 was well tolerated. Adverse events were consistent with those previously reported for granisetron. For APF530 T max was observed about 24 hrs with sustained levels over 120 hrs. For MEC acute phase CR rates of 74.8% (n=214), 76.9% (n=212) and 75.0% (n=208) were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. Delayed phase CR rates of 51.4%, 59.0% and 57.7% were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. For HEC acute phase CR rates of 77.7% (n=229), 81.3% (n=240) and 80.7% (n=238) were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. Delayed phase CR rates of 64.6%, 68.3% and 66.4% were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. Efficacy was maintained with APF530 over multiple cycles (up to 4). Conclusions: Both doses of APF530 were non-inferior to palonosetron with respect to CR during the acute phase following MEC and HEC. Only the higher dose of APF530 (10 mg granisetron) was non-inferior to palonosetron during the delayed phase of MEC. Both doses of APF530 were comparable to the CR rates of palonosetron during the delayed phase of HEC. [Table: see text]
Absence of AGPAT2 impairs brown adipogenesis, increases IFN stimulated gene expression and alters mitochondrial morphology
Authors: Pablo J. Tapia, Ana-María Figueroa, Verónica Eisner, Lila González-Hódar, Fermín Robledo, Anil K. Agarwal, Abhimanyu Garg, Víctor Cortés
Journal: Metabolism (2020)
Peanut allergy diagnosis: A 2020 practice parameter update, systematic review, and GRADE analysis
Authors: Matthew Greenhawt, Marcus Shaker, Julie Wang, John J. Oppenheimer, Scott Sicherer, Corinne Keet, Keri Swaggart, Matthew Rank, Jay M. Portnoy, Jonathan Bernstein, Derek K. Chu, Chitra Dinakar, David Golden, Carolyn Horner, David M. Lang, Eddy S. Lang, David A. Khan, Jay Lieberman, David Stukus, Dana Wallace
Journal: Journal of Allergy and Clinical Immunology (2020)
Boosting NAD level suppresses inflammatory activation of PBMCs in heart failure
Authors: Bo Zhou, Dennis Ding-Hwa Wang, Yanhua Qiu, Sophia Airhart, Yaxin Liu, April Stempien-Otero, Kevin D. O’Brien, Rong Tian
Journal: Journal of Clinical Investigation (2020)

BACKGROUND. While mitochondria play an important role in innate immunity, the relationship between mitochondrial dysfunction and inflammation in heart failure (HF) is poorly understood. In this study we aimed to investigate the mechanistic link between mitochondrial dysfunction and inflammatory activation in peripheral blood mononuclear cells (PBMCs), and the potential antiinflammatory effect of boosting the NAD level.
Abstract 10539: Measurement of Left Atrial Appendage Orifice Perimeter Using Echocardiographic 3D Printed Model for the Guidance of LAmbreTM Occluder Selection
Authors: Binghong Zhang, Dan Jia, Hongning Song, Lan Zhang, Dane Mei
Journal: Circulation (2018)

Background: Optimal selection of device size before operation is critical in percutaneous left atrial appendage (LAA) occlusion. Currently, the size is determined by the largest diameter of the lan...
Long-Term Neurocognitive and Psychosocial Outcomes After Acute Myeloid Leukemia: A Childhood Cancer Survivor Study Report
Authors: Kristen J Stefanski, Julia S Anixt, Pamela Goodman, Katherine Bowers, Wendy Leisenring, K Scott Baker, Karen Burns, Rebecca Howell, Stella Davies, Leslie L Robison, Gregory T Armstrong, Kevin R Krull, Christopher Recklitis
Journal: JNCI Journal of the National Cancer Institute (2020)

Survivors of childhood acute myeloid leukemia (AML) are vulnerable to medical late effects of treatment; however, less is known about their psychosocial outcomes. This study evaluated neurocognitive and psychosocial outcomes in long-term AML survivors treated with bone marrow transplantation (BMT) or intensive chemotherapy (IC) without BMT.AML survivors (N = 482; median age at diagnosis = 8 [range = 0-20] years; median age at evaluation = 30 [range = 18-49] years) treated with BMT (n = 183) or IC (n = 299) and sibling controls (N = 3190; median age at evaluation = 32 [range = 18-58] years) from the Childhood Cancer Survivor Study were compared on emotional distress (Brief Symptom Inventory-18), neurocognitive problems (Childhood Cancer Survivor Study Neurocognitive Questionnaire), health-related quality of life (SF-36), and social attainment. Outcomes were dichotomized (impaired vs nonimpaired) using established criteria, and relative risks (RRs) were estimated with multivariable Poisson regression, adjusted for age at evaluation and sex.AML survivors were more likely than siblings to report impairment in overall emotional (RR = 2.19, 95% confidence interval [CI] = 1.51 to 3.18), neurocognitive (RR = 2.03, 95% CI = 1.47 to 2.79), and physical quality of life (RR = 2.71, 95% CI = 1.61 to 4.56) outcomes. Survivors were at increased risk for lower education (RR = 1.15, 95% CI = 1.03 to 1.30), unemployment (RR = 1.41, 95% CI = 1.16 to 1.71), lower income (RR = 1.39, 95% CI = 1.17 to 1.65), and not being married or having a partner (RR = 1.33, 95% CI = 1.17 to 1.51). BMT-treated survivors did not differ statistically significantly from IC-treated on any outcome measure.AML survivors are at increased risk for psychosocial impairment compared with siblings; however, BMT does not confer additional risk for psychosocial late effects compared with treatment without BMT.
Preferred reporting items for systematic review and meta-analysis of diagnostic test accuracy studies (PRISMA-DTA): explanation, elaboration, and checklist
Authors: Jean-Paul Salameh, Patrick M Bossuyt, Trevor A McGrath, Brett D Thombs, Christopher J Hyde, Petra Macaskill, Jonathan J Deeks, Mariska Leeflang, Daniël A Korevaar, Penny Whiting, Yemisi Takwoingi, Johannes B Reitsma, Jérémie F Cohen, Robert A Frank, Harriet A Hunt, Lotty Hooft, Anne W S Rutjes, Brian H Willis, Constantine Gatsonis, Brooke Levis, David Moher, Matthew D F McInnes
Journal: BMJ (2020)

Systematic reviews of diagnostic test accuracy (DTA) studies are fundamental to the decision making process in evidence based medicine. Although such studies are regarded as high level evidence, these reviews are not always reported completely and transparently. Suboptimal reporting of DTA systematic reviews compromises their validity and generalisability, and subsequently their value to key stakeholders. An extension of the PRISMA (preferred reporting items for systematic review and meta-analysis) statement was recently developed to improve the reporting quality of DTA systematic reviews. The PRISMA-DTA statement has 27 items, of which eight are unmodified from the original PRISMA statement. This article provides an explanation for the 19 new and modified items, along with their meaning and rationale. Examples of complete reporting are used for each item to illustrate best practices.
TGase‐Enhanced Microtissue Assembly in 3D‐Printed‐Template‐Scaffold (3D‐MAPS) for Large Tissue Defect Reparation
Authors: Hongsheng Yu, Zhifeng You, Xiaojun Yan, Wei Liu, Zhirui Nan, Dan Xing, Chenyu Huang, Yanan Du
Journal: Advanced Healthcare Materials (2020)

Abstract Engineering large and functional tissue constructs with complex structures (e.g., external ear or nose) for reparation and reconstruction of tissue defects remains one of the major challenges in regenerative medicine, which demands abundant cell sources, advanced biofabrication schemes, and satisfactory integration with the host for long‐term efficacy post implantation. Here the ‘Microtissue Assembly in 3D‐Printed‐template‐Scaffold’ (3D‐MAPS), as a platform technology to rapidly fabricate centimeter‐sized functional tissue constructs with complex structures, is developed. 3D‐MAPS facilitates bottom‐up assembly of large‐scale manufactured microtissues within the 3D‐printed hollow polymeric templates with pre‐defined architectures. The assembly and fusion of 2×10 6 mesenchymal stem cell–based microtissues within the defined 3D‐printed template is further enhanced by addition of a natural protein crosslinker (i.e., transglutaminase (TGase)), and thereby achieves construction of centimeter‐sized tissue with high cell viability and mechanical stability in vitro within 30 min. Further in vivo implantation of the 3D‐MAPS‐fabricated ear‐like tissue construct in rabbit models assisted by flap prefabrication technique results in increased structural vascular support and strengthened functional survival. Thus, the TGase‐enhanced 3D‐MAPS demonstrates its potential and feasibility as a powerful biofabrication platform for tissue engineering application.
FRI0181 Skin manifestations in secondary antiphospholipid syndrome – analysis of forthy patients
Authors: MM Cirkovic, DV Mitrovic, DZ Stefanovic, BC Glisic, MR Petronijevic, MM Popovic
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Skin lesions are common kind of connective tissue disease manifestations. <h3>Objectives</h3> The aim of study was evaluation of skin involvement in clinical presentation of 40 patients with systemic lupus erythematosus (SLE) and secondary antiphospholipid syndrome (APS). <h3>Methods</h3> Examined group (34 women and 6 men) was represented by patients who fullfiled diagnostic ARA criteria for both, SLE and APS. Average duration of disease was 7.54 ± 7.53 (1–33) years and average age of patients was 31.45 ± 13.95 (8–65) years. Patients with SLE without APS represented control group. <h3>Results</h3> We noticed cutaneous ulcerations in 15/40 (37.5%) patients from examined group. They were predominantly located at lower legs and fingers of palms. Cutaneous ulcerations were significantly more frequently (p = 0.025) appeared in patients with both, SLE and APS than in control group. Livedo reticularis was observed in 9/40 (22.5%) patients from examined group, the most frequently at lower legs but one patient expressed livedo reticularis at skin of the torso. There was no significant difference in comparison to control group where prevalence of livedo reticularis was 10% (2/20). We observed palmar-plantar erythema in 12.5% (5/40) patients with APS as a part of SLE. In control group, palmar-plantar erythema was noticed in 10% patients (2/20). <h3>Conclusion</h3> Our study demonstrated that cutaneous ulcerations occurs more frequently in patients with both, SLE and APS than in patients with SLE alone, probably because of two present pathogenic mechanisms: vasculitis and thromophillia as a part od APS. On the other hand, livedo reticularis and palmar-plantar erythema were presented with the same frequency in both groups of patients.
Sex Differences in Coronary Artery Calcium and Mortality From Coronary Heart Disease, Cardiovascular Disease, and All Causes in Adults With Diabetes: The Coronary Calcium Consortium
Authors: Nathan D. Wong, Amber R. Cordola Hsu, Alan Rozanski, Leslee J. Shaw, Seamus P. Whelton, Matthew J. Budoff, Khurram Nasir, Michael D. Miedema, John Rumberger, Michael J. Blaha, Daniel S. Berman
Journal: Diabetes Care (2020)

OBJECTIVE While diabetes has been previously noted to be a stronger risk factor for cardiovascular disease (CVD) in women compared with men, whether this is still the case is not clear. Coronary artery calcium (CAC) predicts coronary heart disease (CHD) and CVD in people with diabetes; however, its sex-specific impact is less defined. We compared the relation of CAC in women versus men with diabetes for total, CVD, and CHD mortality. RESEARCH DESIGN AND METHODS We studied adults with diabetes from a large registry of patients with CAC scanning with mortality follow-up over 11.5 years. Cox regression examined the relation of CAC with mortality end points. RESULTS Among 4,503 adults with diabetes (32.5% women) aged 21–93 years, 61.2% of women and 80.4% of men had CAC &amp;gt;0. Total, CVD, and CHD mortality rates were directly related to CAC; women had higher total and CVD death rates than men when CAC &amp;gt;100. Age- and risk factor–adjusted hazard ratios (HRs) per log unit CAC were higher among women versus men for total mortality (1.28 vs. 1.18) (interaction P = 0.01) and CVD mortality (1.47 vs. 1.27) (interaction P = 0.04) but were similar for CHD mortality (1.48 and 1.48). For CVD mortality, HRs with CAC scores of 101–400 and &amp;gt;400 were 3.67 and 6.27, respectively, for women and 1.63 and 3.48, respectively, for men (interaction P = 0.04). For total mortality, HRs were 2.56 and 4.05 for women, respectively, and 1.88 and 2.66 for men, respectively (interaction P = 0.01). CONCLUSIONS CAC predicts CHD, CVD, and all-cause mortality in patients with diabetes; however, greater CAC predicts CVD and total mortality more strongly in women.
Abstract 8299: Loss of Apelin Exacerbates Post-Myocardial Infarction Remodeling and Myocardial Ischemia-Reperfusion Injury
Authors: Wang Wang, Sreedhar Bodiga, Zamaneh Kassiri, Josef M Penninger, Gavin Oudit
Journal: Circulation (2011)

Objectives: Apelin (APLN), the endogenous peptide ligand of the APJ receptor, improves heart function in patients with heart failure and apelin peptides mediate positive inotropic effects and vasodilation. We hypothesize that there is an exacerbated myocardial ischemic injury in APLN knockout (KO) mice compared to littermate WT. Methods: Male WT (C57Bl/6) and APLN knockout mice were subjected to myocardial infarction (MI) using the LAD ligation technique and mortality and heart function were monitored. Langendorff perfused ex vivo hearts from WT and APLN KO mice were subjected to 30 min global ischemia followed by 40 min reperfusion. Results: LAD ligation in APLN KO mice resulted in greater mortality based on Kaplan-Meir survival analysis (76% vs 48%; p&lt;0.01) at 1 week post-MI. Echocardiography showed greater reduction in ejection fraction in APLN KO mice (18.1±3.5 vs 29.3±3.1%; p&lt;0.05) with greater LV dilation (LV end-diastolic volume=196±14.2 vs 161±13.1 μ L; p&lt;0.05; n=8) at 1 week post-MI. In response to global ischemia-reperfusion (I/R) injury, functional recovery was significantly decreased in APLN KO hearts with LV developed pressure=19.5±2.8 vs 33.8±4.1 mmHg (WT; p&lt;0.05; n=5) at the end of 40 min of reperfusion with significant lowering of the dP/dtmax=1289±65 mmHg/s (WT) versus 610±65 mmHg/s (APLN KO; p&lt;0.05) and dP/dtmin=-657±34 mmHg/s (WT) versus -329±25 mmHg/s (APLN KO; p&lt;0.05) and the rate-pressure product averaging 9975±253 bpm*mmHg (WT) versus 4208±212 bpm*mmHg (APLN KO; p&lt;0.05). Creatine kinase in the coronary perfusate showed a greater increase in APLN KO compared to WT (102.7±17.7 vs 57.5±8.9 U/L; p&lt;0.05) mice in response to I/R injury. Western blot analysis showed reduced phosphorylation of Akt, GSK3β and ERK1/2 in the ischemic-reperfused APLN KO hearts compared with WT hearts. Conclusions: Loss of apelin increases MI-induced mortality, exacerbates post-MI adverse modeling and enhances the susceptibility to I/R injury. Enhancing apelin function may represent a novel therapy for minimizing the myocardial damage in patients with heart disease.
FRI0065 Anti-tnf alpha monoclonal antibodies alter the activation and differentiation pattern of monocytes in patients with rheumatoid arthritis
Authors: R Müller, A Skapenko, J Wendler, M Grünke, JR Kalden, H Schulze-Koops
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Anti-TNFα monoclonal antibodies (mAbs) have recently been introduced as a treatment for rheumatoid arthritis (RA). Whereas anti-TNFα mAbs are potent inhibitors of inflammation, their effect on the activation and differentiation of myeloid cells has not been elucidated. <h3>Objectives</h3> To investigate the function and the phenotype of monocytes from RA patients during their differentiation to macrophages <i>in vitro</i> before and 4 weeks after a single administration of mAbs to TNFα. <h3>Methods</h3> Patients with highly active disease who were resistant to treatment with disease modifying antirheumatic drugs and corticosteroids were included into the study. Monocytes were isolated from the peripheral blood by negative selection, and their phenotype was analysed directly after isolation and during differentiation to macrophages. <h3>Results</h3> Treatment was effective as 4 weeks after mAb application the inflammatory activity, as assesed by DAS 28, and the sedimentation rate were significantly reduced. Whereas the &nbsp;expression of HLA-DR, CD40, CD25, CD80, CD86, CD14 and CD68 in freshly isolated monocytes was similar before and after treatment with anti-TNFα, marked differences were found during maturation. After treatment, upregulation of HLA-DR and CD80 was markedly enhanced during macrophage differentiation. In contrast, the expression of CD40 was decreased after treatment. <h3>Conclusion</h3> The results demonstrate that a single therapy with anti-TNFα mAbs alters the ability of macrophages to upregulate molecules involved in cellular inflammation even 4 weeks after treatment. However, as those changes were associated with clinical benefit, the data suggest that the clinical effect of anti-TNFα mAbs treatment is not restricted to neutralising TNFα but may be due to long lasting anti-inflammatory alterations that remain active even after the mAb has been cleared from the circulation.
Abstract B12: Acetate metabolism mediated by acetyl-CoA synthetase 2 in cisplatin-resistant bladder cancer
Authors: He Wen, Sujin Lee, Wei-Guo Zhu, Ok-Jun Lee, Seok Joong Yun, Jayoung Kim, Sunghyouk Park
Journal: Clinical Cancer Research (2020)

Abstract Introduction and Objective: Cisplatin is an important chemotherapeutic agent against metastatic bladder cancer, but resistance often limits its usage. With the recent recognition of lipid metabolic alterations in bladder cancers, we studied the metabolic implications of cisplatin resistance using cisplatin-sensitive (T24S) and -resistant (T24R) bladder cancer cells. Methods: To test whether there should be differences in metabolism and metabolism-associated pathways between cisplatin-sensitive and resistant bladder cancer cells, we applied the live metabolomics approach that we recently developed to isogenic bladder cancer cell lines T24S (cisplatin sensitive) and T24R (cisplatin resistant). The metabolites generated from 13C-glucose tracer were monitored with 2D 1H-13C HSQC NMR in real time. Results: Real-time live metabolomics revealed that T24R cells consume more glucose, leading to higher production of glucose-derived acetate and fatty acids. Along with the activation of general metabolic regulators, enzymes involved in acetate usage (ACSS2) and fatty acid synthesis (ACC) and a precursor for fatty acid synthesis (acetyl-CoA) were elevated in T24R cells. Consistently, metabolic analysis with 13C isotope revealed that T24R cells preferred glucose to acetate as the exogenous carbon source for the increased fatty acid synthesis, contrary to T24S cells. In addition, ACSS2, rather than the well-established ACLY, was the key enzyme that supplies acetyl-CoA in T24R cells through glucose-derived endogenous acetate. The relevance of ACSS2 in cisplatin resistance was further confirmed by the abrogation of resistance by an ACSS2 inhibitor and, finally, by the higher expression of ACSS2 in the patient tissues with cisplatin resistance. Conclusions: Our results may help improve the treatment options for chemoresistant bladder cancer patients and provide possible vulnerability targets to overcome the resistance. Citation Format: He Wen, Sujin Lee, Wei-Guo Zhu, Ok-Jun Lee, Seok Joong Yun, Jayoung Kim, Sunghyouk Park. Acetate metabolism mediated by acetyl-CoA synthetase 2 in cisplatin-resistant bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr B12.