tbuckley/cabot-search huggingface dataset:
THU0139 The effect of increased air pressure on patients with active rheumatoid arthritis
Authors: LP Robertson, S Marshall, P Hickling
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> A pilot study to assess the effect of increased air pressure in a hyperbaric chamber on patients with active rheumatoid arthritis. <h3>Methods</h3> Seven out-patients with active rheumatoid arthritis (RA) and taking at least one disease modifying anti-rheumatic drug (DMARD) entered a hyperbaric chamber for 30 min. Patients were randomised to control and test groups and assessed in a double-blind fashion. The test group had the atmospheric pressure increased to 2 atmospheres. The control group did not have the pressure altered. Active disease was defined as a pain score on a 100 mm visual analogue scale (VAS) greater than 60 mm and 3 out of 4 from the following: – ESR &gt;28 mm/hr, &gt;6 swollen joints, &gt;6 tender joints and early morning stiffness &gt;45 min. The following were recorded or measured: pain score (by 100 mm VAS), number of swollen joints, number of tender joints, patients global score on a 100 mm VAS, ESR and CRP. The above measurements were repeated 30 min after leaving the hyperbaric chamber, the following day and 7 days later. Disease Activity Scores (DAS) were calculated using the DAS 28. <h3>Results</h3> Four female and three male patients participated. Mean age was 58.4 years (range:41–71 yrs), mean disease duration 10.86 yrs (4–20 yrs). In the test group the pain score of 1 patient was reduced by 60% and DAS by 38% at 24 hrs but had returned to the pre-test values by 7 days. Pain scores from the other 2 patients did not alter. In the control group the pain scores of 2 patients had fallen by 60% and 64% and at 30 mins post-test. This effect was maintained to 7 days for the latter patient whose DAS fell by 54% and at 24 hrs for the former patient whose DAS did not change, however, this patient's oral steroid dose was inadvertently altered between the 24 hr and 7 day assessment. All patients in the test group had reduced swollen joint counts at 30 mins and 24 hrs post-test, this was maintained at 7 days in 2 patients; the tender joint count was reduced in 1 patient at 24 hrs only. 3 out of the 4 control patients had reduced swollen joint counts from 30 mins post-test this was maintained at 24 hrs and 7 days, the same patients also had reduced tender joint counts. There was no change in the ESRs in either group. The CRP in 1 patient from the test group fell at 24 hrs and further decreased at 7 days. In the control group CRP decrease in 1 patient at 24 hrs only, neither of these 2 patients had reduced pain scores or DAS during the study. <h3>Conclusion</h3> In the small number of patients studied, increased atmospheric pressure does not appear to have any effect on active rheumatoid arthritis. There also appears to be a large placebo response.
Cathelicidin-mediated lipopolysaccharide signaling via intracellular TLR4 in colonic epithelial cells evokes CXCL8 production
Authors: Ravi Holani, Anshu Babbar, Graham A. D. Blyth, Fernando Lopes, Humberto Jijon, Derek M. McKay, Morley D. Hollenberg, Eduardo R. Cobo
Journal: Gut Microbes (2020)

We hypothesized that the antimicrobial peptide cathelicidin has a physiological role in regulating gut inflammatory homeostasis. We determined that cathelicidin synergizes with LPS to facilitate its internalization and signaling via endosomic TLR4 in colonic epithelium, evoking synthesis of the human neutrophil chemoattractant, CXCL8 (or murine homolog, CXCL1). Interaction of cathelicidin with LPS in the control of CXCL8/CXCL1 synthesis was assessed in human colon epithelial cells, murine colonoids and cathelicidin-null mice (Camp−/-). Mechanistically, human cathelicidin (LL-37), as an extracellular complex with LPS, interacted with lipid raft-associated GM1 gangliosides to internalize and activate intracellular TLR4. Two signaling pathways converged on CXCL8/CXCL1 production: (1) a p38MAPK-dependent pathway regulated by Src-EGFR kinases; and, (2) a p38MAPK-independent, NF-κB-dependent pathway, regulated by MEK1/2-MAPK. Increased cathelicidin-dependent CXCL8 secretion in the colonic mucosa activated human blood-derived neutrophils. These cathelicidin effects occurred in vitro at concentrations well below those needed for microbicidal function. The important immunomodulatory role of cathelicidins was evident in cathelicidin-null/Camp−/- mice, which had diminished colonic CXCL1 secretion, decreased neutrophil recruitment-activation and reduced bacterial clearance when challenged with the colitis-inducing murine pathogen, Citrobacter rodentium. We conclude that in addition to its known microbicidal action, cathelicidin has a unique pathogen-sensing role, facilitating LPS-mediated intestinal responses, including the production of CXCL8/CXCL1 that would contribute to an integrated tissue response to recruit neutrophils during colitis.
High grade dysplasia or esophageal adenocarcinoma in patients with a history of Roux-en-Y gastric bypass surgery: a case series
Authors: Omer Alaber, Emad Mansoor, Lady Katherine Mejia Perez, John Dumot, Amit Bhatt, Amitabh Chak
Journal: Endoscopy (2020)

Abstract Background Roux-en-Y gastric bypass (RYGB) is the favored bariatric option in patients with gastroesophageal reflux and Barrett’s esophagus because it prevents reflux. Weight loss and decreased reflux following RYGB could theoretically minimize the risk of progression to cancer. We aimed to demonstrate the management of high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) developing in patients after RYGB. Methods A prospectively maintained database was searched to identify cases of HGD and cancer in RYGB patients. Charts were reviewed for past history, endoscopic findings, endoscopic therapy, and pathology findings. Results There were five cases where HGD/EAC developed several years after RYGB. The prior bariatric surgery precluded curative esophagectomy, illustrating the management challenges. All but one of the patients were uniquely and successfully managed with endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Conclusions RYGB patients are still at risk of developing esophageal cancer. Patients at risk should be screened prior to RYGB and those with Barret’s esophagus need to undergo rigorous endoscopic surveillance following surgery. If detected early, EMR and ESD are invaluable in managing those who progress.
A novel LncRNA transcript, RBAT1, accelerates tumorigenesis through interacting with HNRNPL and cis-activating E2F3
Authors: Xiaoyu He, Peiwei Chai, Fang Li, Leilei Zhang, Chuandi Zhou, Xiaoling Yuan, Yongyun Li, Jie Yang, Yingxiu Luo, Shengfang Ge, He Zhang, Renbing Jia, Xianqun Fan
Journal: Molecular Cancer (2020)

Abstract Background Long non-coding RNAs (lncRNAs) have been identified as important epigenetic regulators that play critical roles in human cancers. However, the regulatory functions of lncRNAs in tumorigenesis remains to be elucidated. Here, we aimed to investigate the molecular mechanisms and potential clinical application of a novel lncRNA, retinoblastoma associated transcript-1 (RBAT1), in tumorigenesis. Methods RBAT1 expression was determined by real-time PCR in both retinoblastoma (Rb) and bladder cancer (BCa) cell lines and clinical tissues. Chromatin isolation using RNA purification (ChIRP) assays were performed to identify RBAT1-interacting proteins. Patient-derived xenograft (PDX) retinoblastoma models were established to test the therapeutic potential of RBAT1-targeting GapmeRs. Results Here, we found that RBAT1 expression was significantly higher in Rb and BCa tissues than that in adjacent tissues. Functional assays revealed that RBAT1 accelerated tumorigenesis both in vitro and in vivo . Mechanistically, RBAT1 recruited HNRNPL protein to E2F3 promoter, thereby activating E2F3 transcription. Therapeutically, GapmeR-mediated RBAT1 silencing significantly inhibited tumorigenesis in orthotopic xenograft retinoblastoma models derived from Rb cell lines and Rb primary cells. Conclusions RBAT1 overexpression upregulates a known oncogene, E2F3, via directly recruiting HNPNPL to its promoter and cis-activating its expression. Our finding provides a novel mechanism of lncRNA biology and provides potential targets for diagnosis and treatment of Rb and BCa.
Author Correction: Meteorin-like facilitates skeletal muscle repair through a Stat3/IGF-1 mechanism
Authors: Gurpreet S. Baht, Akshay Bareja, David E. Lee, Rajesh R. Rao, Rong Huang, Janet L. Huebner, David B. Bartlett, Corey R. Hart, Jason R. Gibson, Ian R. Lanza, Virginia B. Kraus, Simon G. Gregory, Bruce M. Spiegelman, James P. White
Journal: Nature Metabolism (2020)
Abstract 13465: Precision Cardiovascular Medicine: A Rapid and Highly Sensitive Artificial Intelligence-Based Integrated Genetic-Epigenetic DNA Test for 3-Year Risk for Incident Coronary Heart Disease
Authors: Meesha Dogan, Stacey Knight, Amaury Lendasse, Kirk U Knowlton, Robert Philibert
Journal: Circulation (2019)

Coronary heart disease (CHD) associated morbidity and mortality are largely preventable. Primary prevention of CHD includes the estimation of risk using a risk estimator as a basis to recommend tre...
Time in Range for Multiple Technologies in Type 1 Diabetes: A Systematic Review and Network Meta-analysis
Authors: Anthony Pease, Clement Lo, Arul Earnest, Velislava Kiriakova, Danny Liew, Sophia Zoungas
Journal: Diabetes Care (2020)

BACKGROUND Time in range is a key glycemic metric, and comparisons of management technologies for this outcome are critical to guide device selection. PURPOSE We conducted a systematic review and network meta-analysis to compare and rank technologies for time in glycemic ranges. DATA SOURCES We searched Evidenced-Based Medicine Reviews, CINAHL, Embase, MEDLINE, MEDLINE In-Process &amp; Other Non-Indexed Citations, PROSPERO, PsycInfo, PubMed, and Web of Science until 24 April 2019. STUDY SELECTION We included randomized controlled trials ≥2 weeks’ duration comparing technologies for management of type 1 diabetes in adults (≥18 years of age), excluding pregnant women. DATA EXTRACTION Data were extracted using a predefined template. Outcomes were percent time with sensor glucose levels 3.9–10.0 mmol/L (70–180 mg/dL), &amp;gt;10.0 mmol/L (180 mg/dL), and &amp;lt;3.9 mmol/L (70 mg/dL). DATA SYNTHESIS We identified 16,772 publications, of which 14 eligible studies compared eight technologies comprising 1,043 participants. Closed-loop systems led to greater percent time in range than any other management strategy, and mean percent time in range was 17.85 (95% predictive interval 7.56–28.14) longer than with usual care of multiple daily injections with capillary glucose testing. Closed-loop systems ranked best for percent time in range or above range with use of Surface Under the Cumulative RAnking curve (SUCRA) (98.5% and 93.5%, respectively). Closed-loop systems also ranked highly for time below range (SUCRA 62.2%). LIMITATIONS Overall risk of bias ratings were moderate for all outcomes. Certainty of evidence was very low. CONCLUSIONS In the first integrated comparison of multiple management strategies considering time in range, we found that the efficacy of closed-loop systems appeared better than all other approaches.
The environmental footprint of health care: a global assessment
Authors: Manfred Lenzen, Arunima Malik, Mengyu Li, Jacob Fry, Helga Weisz, Peter-Paul Pichler, Leonardo Suveges Moreira Chaves, Anthony Capon, David Pencheon
Journal: The Lancet Planetary Health (2020)

BackgroundHealth-care services are necessary for sustaining and improving human wellbeing, yet they have an environmental footprint that contributes to environment-related threats to human health. Previous studies have quantified the carbon emissions resulting from health care at a global level. We aimed to provide a global assessment of the wide-ranging environmental impacts of this sector.MethodsIn this multiregional input-output analysis, we evaluated the contribution of health-care sectors in driving environmental damage that in turn puts human health at risk. Using a global supply-chain database containing detailed information on health-care sectors, we quantified the direct and indirect supply-chain environmental damage driven by the demand for health care. We focused on seven environmental stressors with known adverse feedback cycles: greenhouse gas emissions, particulate matter, air pollutants (nitrogen oxides and sulphur dioxide), malaria risk, reactive nitrogen in water, and scarce water use.FindingsHealth care causes global environmental impacts that, depending on which indicator is considered, range between 1% and 5% of total global impacts, and are more than 5% for some national impacts.InterpretationEnhancing health-care expenditure to mitigate negative health effects of environmental damage is often promoted by health-care practitioners. However, global supply chains that feed into the enhanced activity of health-care sectors in turn initiate adverse feedback cycles by increasing the environmental impact of health care, thus counteracting the mission of health care.FundingAustralian Research Council, National eResearch Collaboration Tools and Resources project.
FMT in IBS: how cautious should we be?
Authors: Magdy El-Salhy
Journal: Gut (2020)

We agree with the comments1 2 on the recently reported randomised double-blind, placebo-controlled trial from our group on the efficacy of faecal microbiota transplantation (FMT) in patients with IBS3 that caution is required when using FMT to treat this condition. However, we have some further comments concerning the efficacy and safety of FMT in IBS.

The patients with IBS included in our randomised controlled trial (RCT)3 were only those with moderate symptom severity (IBS Symptom Severity Score (IBS-SSS) score between 175 and 300)2 and severe symptom severity (IBS-SSS score of ≥300).4 One way to evaluate the efficacy of FMT when using the IBS-SSS, as pointed out by Camilleri, is to look at the proportions of patients with moderate symptom severity and severe symptom severity at different time intervals after FMT.2 The raw results for our RCT from the IBS-SSS …
Tackling corruption in global health
Authors: Maimouna Bah, Ludmilla Charlier, Camilla Davila, Sophie Descousse, Benoît Frimon-Richard, Sameh Hashem, Clara Leroy, Marie Minault, Violette Mouro, Rajiv Nillameyom, Louise Schlüter, Manon Wailly
Journal: The Lancet (2020)
Evolutionary Genomics of Structural Variation in Asian Rice (<i>Oryza sativa</i>) Domestication
Authors: Yixuan Kou, Yi Liao, Tuomas Toivainen, Yuanda Lv, Xinmin Tian, J J Emerson, Brandon S Gaut, Yongfeng Zhou
Journal: Molecular Biology and Evolution (2020)

Abstract Structural variants (SVs) are a largely unstudied feature of plant genome evolution, despite the fact that SVs contribute substantially to phenotypes. In this study, we discovered SVs across a population sample of 347 high-coverage, resequenced genomes of Asian rice (Oryza sativa) and its wild ancestor (O. rufipogon). In addition to this short-read data set, we also inferred SVs from whole-genome assemblies and long-read data. Comparisons among data sets revealed different features of genome variability. For example, genome alignment identified a large (∼4.3 Mb) inversion in indica rice varieties relative to japonica varieties, and long-read analyses suggest that ∼9% of genes from the outgroup (O. longistaminata) are hemizygous. We focused, however, on the resequencing sample to investigate the population genomics of SVs. Clustering analyses with SVs recapitulated the rice cultivar groups that were also inferred from SNPs. However, the site-frequency spectrum of each SV type—which included inversions, duplications, deletions, translocations, and mobile element insertions—was skewed toward lower frequency variants than synonymous SNPs, suggesting that SVs may be predominantly deleterious. Among transposable elements, SINE and mariner insertions were found at especially low frequency. We also used SVs to study domestication by contrasting between rice and O. rufipogon. Cultivated genomes contained ∼25% more derived SVs and mobile element insertions than O. rufipogon, indicating that SVs contribute to the cost of domestication in rice. Peaks of SV divergence were enriched for known domestication genes, but we also detected hundreds of genes gained and lost during domestication, some of which were enriched for traits of agronomic interest.
Peroral endoscopic myotomy in a case of recurrent epiphrenic diverticulum after surgery
Authors: Margherita Pizzicannella, Andrea Spota, Bernard Dallemagne, Lee Swanström, Jacques Marescaux, Silvana Perretta
Journal: Endoscopy (2020)

Epiphrenic diverticula are pulsion-type diverticula most commonly located in the distal esophagus. They are classed as “pseudo-diverticula” and are usually associated with esophageal motility disorders (EMD) [1].
The Cutoff Value of Serum Ferritin for the Diagnosis of Iron Deficiency in the Community-Residing Older Persons.
Authors: Chul Won Choi, Soo-Young Yoon, Kyong Hwa Park, In Keun Choi, Seok Jin Kim, Jae Hong Seo, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim, Juneyoung Lee
Journal: Blood (2004)
Total Body Irradiation and Risk of Breast Cancer After Blood or Marrow Transplantation: A Blood or Marrow Transplantation Survivor Study Report
Authors: Andrew M. McDonald, Yanjun Chen, Jessica Wu, Lindsey Hageman, Liton Francisco, Michelle Kung, F. Lennie Wong, Emily Ness, Wendy Landier, Kevin Battles, Donna Salzman, Daniel J. Weisdorf, Stephen J. Forman, Mukta Arora, Saro H. Armenian, Smita Bhatia
Journal: Journal of Clinical Oncology (2020)

To examine the association between total body irradiation (TBI) and subsequent breast cancer in women treated with blood or marrow transplantation (BMT) for hematologic malignancies.Participants were drawn from the BMT Survivor Study (BMTSS), a retrospective cohort study that included patients who underwent transplantation between 1974 and 2014 and survived for ≥ 2 years after BMT. Patients with pre-BMT chest radiation or a history of breast cancer were excluded. Participants completed the BMTSS survey, which included details regarding breast cancer diagnosis. Subsequent breast cancer was confirmed by pathology report review or physician notes. Cox proportional hazards models assessed the association between TBI and subsequent breast cancer. Standardized incidence ratios were calculated to determine the excess risk of subsequent breast cancer compared with that in the general population.A total of 1,464 female BMT survivors (allogeneic: n = 788; autologous: n = 676) participated, with a median follow-up of 9.3 years from BMT. TBI was used in 660 patients (46%). Thirty-seven women developed subsequent breast cancer (allogeneic: n = 19; autologous: n = 18). Multivariable analysis revealed that exposure to TBI was associated with an increased risk of subsequent breast cancer among allogeneic BMT survivors (hazard ratio [HR], 3.7 [95% CI, 1.2 to 11.8]; P = .03) and autologous BMT survivors (HR, 2.6 [95% CI, 1.0 to 6.8]; P = .048). Pre-BMT exposure to alkylating agents was associated with an increased risk of subsequent breast cancer among autologous BMT survivors (HR, 3.3 [95% CI, 1.0 to 9.0]; P = .05). Compared with that in the general population, exposure to TBI at age < 30 years was associated with a 4.4-fold higher risk of subsequent breast cancer in allogeneic BMT survivors and a 4.6-fold higher risk in autologous BMT survivors.The association between TBI and subsequent breast cancer, especially among those exposed at a young age, as well as pre-BMT exposure to alkylating agents, should inform breast cancer screening for early detection.
Na<b>2</b>CO<b>3</b> <i>-</i>Responsive Photosynthetic and ROS Scavenging Mechanisms in Chloroplasts of Alkaligrass Revealed by Phosphoproteomics
Authors: Jinwei Suo, Heng Zhang, Qi Zhao, Nan Zhang, Yongxue Zhang, Ying Li, Baohua Song, Juanjuan Yu, Jianguo Cao, Tai Wang, Ji Luo, Lihai Guo, Jun Ma, Xumin Zhang, Yimin She, Lianwei Peng, Weimin Ma, Siyi Guo, Yuchen Miao, Sixue Chen, Zhi Qin, Shaojun Dai
Journal: Genomics Proteomics & Bioinformatics (2020)

Alkali-salinity exerts severe osmotic, ionic, and high-pH stresses to plants. To understand the alkali-salinity responsive mechanisms underlying photosynthetic modulation and reactive oxygen species (ROS) homeostasis, physiological and diverse quantitative proteomics analyses of alkaligrass (Puccinellia tenuiflora) under Na2CO3 stress were conducted. In addition, Western blot, real-time PCR, and transgenic techniques were applied to validate the proteomic results and test the functions of the Na2CO3-responsive proteins. A total of 104 and 102 Na2CO3-responsive proteins were identified in leaves and chloroplasts, respectively. In addition, 84 Na2CO3-responsive phosphoproteins were identified, including 56 new phosphorylation sites in 56 phosphoproteins from chloroplasts, which are crucial for the regulation of photosynthesis, ion transport, signal transduction, and energy homeostasis. A full-length PtFBA encoding an alkaligrass chloroplastic fructose-bisphosphate aldolase (FBA) was overexpressed in wild-type cells of cyanobacterium Synechocystis sp. Strain PCC 6803, leading to enhanced Na2CO3 tolerance. All these results indicate that thermal dissipation, state transition, cyclic electron transport, photorespiration, repair of photosystem (PS) II, PSI activity, and ROS homeostasis were altered in response to Na2CO3 stress, which help to improve our understanding of the Na2CO3-responsive mechanisms in halophytes.
Enhanced Quality and Effectiveness of Transurethral Resection of Bladder Tumour in Non–muscle-invasive Bladder Cancer: A Multicentre Real-world Experience from Scotland’s Quality Performance Indicators Programme
Authors: Paramananthan Mariappan, Allan Johnston, Luisa Padovani, Eilidh Clark, Matthew Trail, Sami Hamid, Graham Hollins, Helen Simpson, Benjamin G. Thomas, Rami Hasan, Jaimin Bhatt, Imran Ahmad, Ghulam M. Nandwani, Ian D.C. Mitchell, David Hendry
Journal: European Urology (2020)