tbuckley/cabot-search huggingface dataset:
Spatial-resolved metabolomics reveals tissue-specific metabolic reprogramming in diabetic nephropathy by using mass spectrometry imaging
Authors: Zhonghua Wang, Wenqing Fu, Meiling Huo, Bingshu He, Yaqi Liu, Lu Tian, Wanfang Li, Zhi Zhou, Baili Wang, Jianzhen Xia, Yanhua Chen, Jinfeng Wei, Zeper Abliz
Journal: Acta Pharmaceutica Sinica B (2021)

Detailed knowledge on tissue-specific metabolic reprogramming in diabetic nephropathy (DN) is vital for more accurate understanding the molecular pathological signature and developing novel therapeutic strategies. In the present study, a spatial-resolved metabolomics approach based on air flow-assisted desorption electrospray ionization (AFADESI) and matrix-assisted laser desorption ionization (MALDI) integrated mass spectrometry imaging (MSI) was proposed to investigate tissue-specific metabolic alterations in the kidneys of high-fat diet-fed and streptozotocin (STZ)-treated DN rats and the therapeutic effect of astragaloside IV, a potential anti-diabetic drug, against DN. As a result, a wide range of functional metabolites including sugars, amino acids, nucleotides and their derivatives, fatty acids, phospholipids, sphingolipids, glycerides, carnitine and its derivatives, vitamins, peptides, and metal ions associated with DN were identified and their unique distribution patterns in the rat kidney were visualized with high chemical specificity and high spatial resolution. These region-specific metabolic disturbances were ameliorated by repeated oral administration of astragaloside IV (100 mg/kg) for 12 weeks. This study provided more comprehensive and detailed information about the tissue-specific metabolic reprogramming and molecular pathological signature in the kidney of diabetic rats. These findings highlighted the promising potential of AFADESI and MALDI integrated MSI based metabolomics approach for application in metabolic kidney diseases.
POS0574 RELATIONSHIP BETWEEN INVOLVED JOINT FOR REGION AND MODIFIED HEALTH ASSESSMENT QUESTIONNAIRE SCORE IN JAPANESE PATIENT WITH RHEUMATOID ARTHRITIS
Authors: I. Yoshii
Journal: Annals of the Rheumatic Diseases (2021)

Objectives: Rheumatoid arthritis (RA) is a chronic inflammatory disease that involves various joints in whole body. For evaluation of daily life activities (ADL), modified Health Assessment Questionnaire (mHAQ) is usually used. This index configures eight ADL functions these are separated by predominant extremities. This study aimed to evaluate how involved joint affect ADL predominantly in real world setting. Methods: A total of 24,450 times of consultation with RA patient were visited in the institute. Here, patient with RA was interviewed every another visit, and involved joint in whole body, pain score with visual analog scale (PS-VAS), and mHAQ were recorded. Involved joints were divided by four regions in accordance with joint size and part; small joint in upper extremities (US), large joint in upper extremities (UL), small joint in lower extremities (LS), and large joint in lower extremities (LL). mHAQ was also separately evaluated in accordance with predominant regions; upper extremities predominant mHAQ (mHAQ_UE), and lower extremities predominant mHAQ (mHAQ_LE). Adding to these parameters, as an index for disease activity monitoring, components of the simplified disease activity index score (SDAI) was also recorded. Relationship between mHAQ for each predominant extremities, and these parameters and sex, age, disease duration of RA, anti-cyclic citrullinated polypeptide antibodies (ACPA), rheumatoid factor (RF), and Sharp/van der Heijde score (SHS), were statistically evaluated using linear regression analysis. Results: mHAQ_UE significantly correlated with age, ACPA and RF titre, SHS, tenderness joint count (TJC), patient’s global assessment (PGA), evaluator’s global assessment (EGA), C-reactive protein (CRP), US, UL, LL, and PS-vas, whereas mHAQ-LE significantly correlated with all parameters that demonstrated significant correlation with mHAQ-UE and disease duration. mHAQ also correlated with all parameters those that demonstrated significant correlation with mHAQ-LE. Interestingly, all of mHAQ-UE, mHAQ-LE, and mHAQ did not correlated significantly with swollen joint count (SJC) and LS. Conclusion: mHAQ is influenced by various factors, however, SJC and involvement of small joint in lower extremities did not affect mHAQ. Disclosure of Interests: None declared
Integration of constraint-based modeling with fecal metabolomics reveals large deleterious effects of <i>Fusobacterium</i> spp. on community butyrate production
Authors: Johannes Hertel, Almut Heinken, Filippo Martinelli, Ines Thiele
Journal: Gut Microbes (2021)

Characterizing the metabolic functions of the gut microbiome in health and disease is pivotal for translating alterations in microbial composition into clinical insights. Two major analysis paradigms have been used to explore the metabolic functions of the microbiome but not systematically integrated with each other: statistical screening approaches, such as metabolome-microbiome association studies, and computational approaches, such as constraint-based metabolic modeling. To combine the strengths of the two analysis paradigms, we herein introduce a set of theoretical concepts allowing for the population statistical treatment of constraint-based microbial community models. To demonstrate the utility of the theoretical framework, we applied it to a public metagenomic dataset consisting of 365 colorectal cancer (CRC) cases and 251 healthy controls, shining a light on the metabolic role of Fusobacterium spp. in CRC. We found that (1) glutarate production capability was significantly enriched in CRC microbiomes and mechanistically linked to lysine fermentation in Fusobacterium spp., (2) acetate and butyrate production potentials were lowered in CRC, and (3) Fusobacterium spp. presence had large negative ecological effects on community butyrate production in CRC cases and healthy controls. Validating the model predictions against fecal metabolomics, the in silico frameworks correctly predicted in vivo species metabolite correlations with high accuracy. In conclusion, highlighting the value of combining statistical association studies with in silico modeling, this study provides insights into the metabolic role of Fusobacterium spp. in the gut, while providing a proof of concept for the validity of constraint-based microbial community modeling.
Effects of Tai Chi or Conventional Exercise on Central Obesity in Middle-Aged and Older Adults
Authors: Parco M. Siu, Angus P. Yu, Edwin C. Chin, Doris S. Yu, Stanley S. Hui, Jean Woo, Daniel Y. Fong, Gao X. Wei, Michael R. Irwin
Journal: Annals of Internal Medicine (2021)

Background: Central obesity is a major manifestation of metabolic syndrome, which is a common health problem in middle-aged and older adults. Objective: To examine the therapeutic efficacy of tai chi for management of central obesity. Design: Randomized, controlled, assessor-blinded trial. (ClinicalTrials.gov: NCT03107741) Setting: A single research site in Hong Kong between 27 February 2016 and 28 February 2019. Participants: Adults aged 50 years or older with central obesity. Intervention: 543 participants were randomly assigned in a 1:1:1 ratio to a control group with no exercise intervention (n = 181), conventional exercise consisting of aerobic exercise and strength training (EX group) (n = 181), and a tai chi group (TC group) (n = 181). Interventions lasted 12 weeks. Measurements: Outcomes were assessed at baseline, week 12, and week 38. The primary outcome was waist circumference (WC). Secondary outcomes were body weight; body mass index; high-density lipoprotein cholesterol (HDL-C), triglyceride, and fasting plasma glucose levels; blood pressure; and incidence of remission of central obesity. Results: The adjusted mean difference in WC from baseline to week 12 in the control group was 0.8 cm (95% CI, −4.1 to 5.7 cm). Both intervention groups showed reductions in WC relative to control (adjusted mean differences: TC group vs. control, −1.8 cm [CI, −2.3 to −1.4 cm]; P < 0.001; EX group vs. control: −1.3 cm [CI, −1.8 to −0.9 cm]; P < 0.001); both intervention groups also showed reductions in body weight (P < 0.05) and attenuation of the decrease in HDL-C level relative to the control group. The favorable changes in WC and body weight were maintained in both the TC and EX groups, whereas the beneficial effect on HDL-C was only maintained in the TC group at week 38. Limitations: High attrition and no dietary intervention. Conclusion: Tai chi is an effective approach to reduce WC in adults with central obesity aged 50 years or older. Primary Funding Source: Health and Medical Research Fund.
AB0065 HGF/C-MET SIGNALING PROMOTE ANGIOGENESIS THROUGH CXCL16 IN RHEUMATOID ARTHRITIS
Authors: M. Hosonuma, T. Isozaki, H. Furuya, Y. Yamazaki, Y. Ikari, S. Nishimi, S. Ishii, A. Maeoka, T. Tokunaga, K. Wakabayashi, N. Konishi, S. Fukuse, K. Ishikawa, N. Sakai, K. Inagaki, T. Kasama
Journal: Annals of the Rheumatic Diseases (2021)

Background: Hepatocyte growth factor (HGF) binds to the receptor tyrosine kinase c-Met and is a multifunctional cytokine that promotes processes such as cell proliferation, survival, differentiation, migration and angiogenesis [1]. We previously reported that HGF is produced by inflammation in the RA synovium, and activates monocyte migration to the synovium and promotes bone destruction through its own chemotactic effect and enhanced chemokine production in the synovium [2]. Objectives: Therefore, we next aimed to determine the role of HGF in RA angiogenesis. Methods: The expression of HGF / c-Met in the serum and synovial tissues (STs) of RA patients and controls and human umbilical vein endothelial cells (HUVECs) was evaluated by ELISA and immunostaining. The effect of HGF/c-Met signaling on the promotion of CXCL16 production from HUVECs and RA fibroblast-like synoviocytes (FLSs) was determined by ELISA. To examine the role of HGF in angiogenesis, we performed in vitro Matrigel assays using HUVECs treated with HGF. Results: HGF in serum in treatment-naive RA patients was significantly higher than that in controls and HGF in serum in treatment-resistant RA showed a significant positive correlation with CXCL16. c-Met were expressed on vascular endothelial cells of RA STs and HUVECs. Stimulation of HUVECs with HGF dose-dependently increased CXCL16 production. c-Met signal inhibition by SU11274 suppressed TNF-α stimulation-enhanced CXCL16 production by RA FLSs in a dose-dependent manner. Furthermore, HGF induced HUVEC tube formation by 1.8-fold. Conclusion: HGF is produced by inflammation in the RA synovium, and activates angiogenesis through its own potent angiogenic effect and enhanced production of CXCL16 in the synovium. These results indicate that a strategy targeting c-Met signalling may be important for resolving treatment-resistant RA. References: [1]Nakamura T, Nishizawa T, Hagiya M, et al. Molecular cloning and expression of human hepatocyte growth factor. Nature. 1989 Nov 23;342(6248):440-3. [2]Hosonuma M, Sakai N, Furuya H, et al. Inhibition of hepatocyte growth factor/c-Met signalling abrogates joint destruction by suppressing monocyte migration in rheumatoid arthritis. Rheumatology (Oxford). 2021 Jan 5;60(1):408-419. Disclosure of Interests: None declared
Gemtuzumab Ozogamicin Improves Event-Free Survival and Reduces Relapse in Pediatric<i>KMT2A</i>-Rearranged AML: Results From the Phase III Children's Oncology Group Trial AAML0531
Authors: Jessica A. Pollard, Erin Guest, Todd A. Alonzo, Robert B. Gerbing, Mike R. Loken, Lisa Eidenschink Brodersen, E. Anders Kolb, Richard Aplenc, Soheil Meshinchi, Susana C. Raimondi, Betsy Hirsch, Alan S. Gamis
Journal: Journal of Clinical Oncology (2021)

PURPOSE We investigated the impact of the CD33-targeted agent gemtuzumab ozogamicin (GO) on survival in pediatric patients with KMT2A-rearranged ( KMT2A-r) acute myeloid leukemia (AML) enrolled in the Children's Oncology Group trial AAML0531 ( NCT01407757 ). METHODS Patients with KMT2A-r AML were identified and clinical characteristics described. Five-year overall survival (OS), event-free survival (EFS), disease-free survival (DFS), and relapse risk (RR) were determined overall and for higher-risk versus not high-risk translocation partners. GO's impact on response was determined and outcomes based on consolidation approach (hematopoietic stem cell transplant [HSCT] v chemotherapy) described. RESULTS Two hundred fifteen (21%) of 1,022 patients enrolled had KMT2A-r AML. Five-year EFS and OS from study entry were 38% and 58%, respectively. EFS was superior with GO treatment (EFS 48% with GO v 29% without, P = .003), although OS was comparable (63% v 53%, P = .054). For patients with KMT2A-r AML who achieved complete remission, GO was associated with lower RR (40% GO v 66% patients who did not receive GO [No-GO], P = .001) and improved 5-year DFS (GO 57% v No-GO 33%, P = .002). GO benefit was observed in both higher-risk and not high-risk KMT2A-r subsets. For patients who underwent HSCT, prior GO exposure was associated with decreased relapse (5-year RR: 28% GO and HSCT v 73% No-GO and HSCT, P = .006). In multivariable analysis, GO was independently associated with improved EFS, improved DFS, and reduced RR. CONCLUSION GO added to conventional chemotherapy improved outcomes for KMT2A-r AML; consolidation with HSCT may further enhance outcomes. Future clinical trials should study CD33-targeted agents in combination with HSCT for pediatric KMT2A-r AML.
Abstract 10871: Serum Dickkopf-1 Signaling and Calcium Deposition in the Aortic Valve Are Significantly Related to the Presence of Concomitant Coronary Atherosclerosis in Patients with Symptomatic Calcified Aortic Stenosis
Authors: Zuzana Motovska, Teodora Vichova, Magdalena Doktorova, Marek Labos, Petr Widimsky
Journal: Circulation (2012)

Background: The osteoprotegerin (OPG) / RANKL / RANK axis and Dickkopf-1 (Dkk-1) signaling have been linked to the development of atherosclerosis and might be part of the causal pathway in the regu...
Disruption of a GATA2-TAL1-ERG regulatory circuit promotes erythroid transition in healthy and leukemic stem cells
Authors: Julie A. I. Thoms, Peter Truong, Shruthi Subramanian, Kathy Knezevic, Gregory Harvey, Yizhou Huang, Janith A. Seneviratne, Daniel R. Carter, Swapna Joshi, Joanna Skhinas, Diego Chacon, Anushi Shah, Ineke de Jong, Dominik Beck, Berthold Göttgens, Jonas Larsson, Jason W. H. Wong, Fabio Zanini, John E. Pimanda
Journal: Blood (2021)
Reply to the letter to the editor: adjuvant nivolumab for the management of the pathological residual disease in esophageal or junctional tumors: a word of caution by P.K. Garg, R. Kumar and P. Dixit
Authors: E.C. Smyth, V. Gambardella, A. Cervantes, T. Fleitas
Journal: Annals of Oncology (2021)
Platelets instruct T reg cells and macrophages in the resolution of lung inflammation
Authors: Rick Kapur, John W. Semple
Journal: The Journal of Experimental Medicine (2021)

Platelets convey important nonhemostatic immune functions; however, their potential role in resolving pulmonary inflammation remains to be determined. In this issue of JEM, Rossaint et al. (2021. J. Exp. Med. https://doi.org/10.1084/jem.20201353) reveal that platelets contribute to the resolution of pulmonary inflammation by directly recruiting T regulatory (T reg) cells to the lungs and by transcriptionally reprogramming alveolar macrophages toward an anti-inflammatory phenotype.
Neurotensin is an anti-thermogenic peptide produced by lymphatic endothelial cells
Authors: Jin Li, Erwei Li, Rafael S. Czepielewski, Jingyi Chi, Xiao Guo, Yong-Hyun Han, Daqing Wang, Luhong Wang, Bo Hu, Brian Dawes, Christopher Jacobs, Danielle Tenen, Samuel J. Lin, Bernard Lee, Donald Morris, Adam Tobias, Gwendalyn J. Randolph, Paul Cohen, Linus Tsai, Evan D. Rosen
Journal: Cell Metabolism (2021)
Mild COVID-19 despite autoantibodies against type I IFNs in autoimmune polyendocrine syndrome type 1
Authors: Christian Meisel, Bengisu Akbil, Tim Meyer, Erwin Lankes, Victor M. Corman, Olga Staudacher, Nadine Unterwalder, Uwe Kölsch, Christian Drosten, Marcus A. Mall, Tilmann Kallinich, Dirk Schnabel, Christine Goffinet, Horst von Bernuth
Journal: Journal of Clinical Investigation (2021)

Autoantibodies against IFN-α and IFN-ω (type I IFNs) were recently reported as causative for severe COVID-19 in the general population. Autoantibodies against IFN-α and IFN-ω are present in almost all patients with autoimmune polyendocrine syndrome type 1 (APS-1) caused by biallelic deleterious or heterozygous dominant mutations in AIRE. We therefore hypothesized that autoantibodies against type I IFNs also predispose patients with APS-1 to severe COVID-19. We prospectively studied 6 patients with APS-1 between April 1, 2020 and April 1, 2021. Biobanked pre-COVID-19 sera of APS-1 subjects were tested for neutralizing autoantibodies against IFN-α and IFN-ω. The ability of the patients' sera to block recombinant human IFN-α and IFN-ω was assessed by assays quantifying phosphorylation of signal transducer and activator of transcription 1 (STAT1) as well as infection-based IFN-neutralization assays. We describe 4 patients with APS-1 and preexisting high titers of neutralizing autoantibodies against IFN-α and IFN-ω who contracted SARS-CoV-2, yet developed only mild symptoms of COVID-19. None of the patients developed dyspnea, oxygen requirement, or high temperature. All infected patients with APS-1 were females and younger than 26 years of age. Clinical penetrance of neutralizing autoantibodies against type I IFNs for severe COVID-19 is not complete.
Sofosbuvir/velpatasvir for 12 vs. 6 weeks for the treatment of recently acquired hepatitis C infection
Authors: Gail V. Matthews, Sanjay Bhagani, Marc Van der Valk, Juergen Rockstroh, Jordan J. Feld, Andri Rauch, Christine Thurnheer, Julie Bruneau, Arthur Kim, Margaret Hellard, David Shaw, Ed Gane, Mark Nelson, Patrick Ingiliz, Tanya L. Applegate, Jason Grebely, Phillipa Marks, Marianne Martinello, Kathy Petoumenos, Gregory J. Dore, Marc van der Valk, Margaret Hellard, Ed Gane, Andri Rauch, Julie Bruneau, Arthur Kim, Sanjay Bhagani, Greg Dore, Pip Marks, Gail Matthews, Jason Grebely, Kathy Petoumenos, Marianne Martinello, Tanya Applegate, Jordan Feld, Jürgen Rockstroh, Gail Matthews, Pip Marks, Sophia Amjad, Elise Tu, Kathy Petoumenos, Mahshid Tamaddoni, Marc van der Valk, Margaret Hellard, Ed Gane, Maria Christine Thurnheer, Yvonne Gilleece, Julie Bruneau, Mark Nelson, Chris Fraser, Alberto Moriggia, Thomas Lutz, Juhi Moon, Phillip Read, Arthur Y. Kim, Andrew Ustianowski, Christiane Cordes, David Shaw, Sanjay Bhagani, Joe Sasadeusz, Mark Hull, Greg Dore, Jordan Feld, Jürgen Rockstroh, Dominique Braun, Patrick Ingiliz
Journal: Journal of Hepatology (2021)
Personalized Single-Cell Proteogenomics to Distinguish Acute Myeloid Leukemia from Nonmalignant Clonal Hematopoiesis
Authors: Laura W. Dillon, Jack Ghannam, Chidera Nosiri, Gege Gui, Meghali Goswami, Katherine R. Calvo, Katherine E. Lindblad, Karolyn A. Oetjen, Matthew D. Wilkerson, Anthony R. Soltis, Gauthaman Sukumar, Clifton L. Dalgard, Julie Thompson, Janet Valdez, Christin B. DeStefano, Catherine Lai, Adam Sciambi, Robert Durruthy-Durruthy, Aaron Llanso, Saurabh Gulati, Shu Wang, Aik Ooi, Pradeep K. Dagur, J. Philip McCoy, Patrick Burr, Yuesheng Li, Christopher S. Hourigan
Journal: Blood Cancer Discovery (2021)

Abstract Genetic mutations associated with acute myeloid leukemia (AML) also occur in age-related clonal hematopoiesis, often in the same individual. This makes confident assignment of detected variants to malignancy challenging. The issue is particularly crucial for AML posttreatment measurable residual disease monitoring, where results can be discordant between genetic sequencing and flow cytometry. We show here that it is possible to distinguish AML from clonal hematopoiesis and to resolve the immunophenotypic identity of clonal architecture. To achieve this, we first design patient-specific DNA probes based on patient's whole-genome sequencing and then use them for patient-personalized single-cell DNA sequencing with simultaneous single-cell antibody–oligonucleotide sequencing. Examples illustrate AML arising from DNMT3A- and TET2-mutated clones as well as independently. The ability to personalize single-cell proteogenomic assessment for individual patients based on leukemia-specific genomic features has implications for ongoing AML precision medicine efforts. Significance: This study offers a proof of principle of patient-personalized customized single-cell proteogenomics in AML including whole-genome sequencing–defined structural variants, currently unmeasurable by commercial “off-the-shelf” panels. This approach allows for the definition of genetic and immunophenotype features for an individual patient that would be best suited for measurable residual disease tracking.
Procurement Biopsies in Kidney Transplantation: More Information May Not Lead to Better Decisions
Authors: Krista L. Lentine, Bertram Kasiske, David A. Axelrod
Journal: Journal of the American Society of Nephrology (2021)

The ongoing shortage of organs available for transplant contributes to prolonged waiting times, death on the waiting list, and higher costs of care for patients with ESKD. Although the total number of deceased donors has risen nationally, the waiting list remains large, with nearly 100,000
Pain in right buttock after carbon monoxide poisoning
Authors: Huijun Hu, Qiang Sun
Journal: BMJ (2021)

A woman in her 30s, eight weeks into her second pregnancy, was found disorientated at home. She had been lying on her right side in bed for about six hours in an airtight room with a coal stove that had nearly burnt out. On admission to the emergency department, she had a Glasgow coma scale score of 8 and her serum carboxyhaemoglobin level was 25%. Acute carbon monoxide poisoning was diagnosed.

The patient was assessed by a gynaecologist on admission. No fetal heart beat was detected on ultrasonography.

Chest computed tomography was requested to rule out pneumothorax before hyperbaric oxygen therapy was initiated for carbon monoxide poisoning.1

After 10 hours of hyperbaric oxygen therapy the woman regained full consciousness, and she mentioned pain in her right buttock. Examination revealed mild swelling and tenderness over the area. She had reduced sensation over her right thigh, but nothing else was found on neurological examination.

Her urine was dark.

Table 1 shows the results of other relevant investigations.

View this table:

Table 1 
Results of laboratory tests



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