tbuckley/cabot-search huggingface dataset:
Response to faecal microbiota transplantation in ulcerative colitis is not sustained long term following induction therapy
Authors: Craig Haifer, Aiasha Saikal, Ramesh Paramsothy, Nadeem O Kaakoush, Rupert W Leong, Thomas J Borody, Michael A Kamm, Sudarshan Paramsothy
Journal: Gut (2020)

We read with interest the paper by Ng et al, 1 which discussed the need to optimise faecal microbiota transplantation (FMT) processes in order to increase its therapeutic potential, especially in inflammatory bowel disease (IBD). While there is randomised controlled trial evidence that FMT can be effective in the induction of remission in patients with ulcerative colitis (UC),2–5 the durability of therapeutic response following FMT cessation is unknown. Furthermore, there is limited long-term safety data following FMT, especially in patients with IBD. In the FOCUS study, FMT delivered via an initial colonoscopy infusion, followed by enema therapy for 8 weeks was effective in mild to moderate UC remission induction.2 Here, we report the long-term outcomes from the FOCUS study.

Enrolled study participants who received FMT (2013–2015) were contacted to assess time to disease relapse for patients in clinical remission following FMT induction (defined as worsening symptoms requiring escalation of medical therapy or surgery), disease progression and the development of adverse events or new medical conditions.

Long-term data were obtained from 87% (68/78) of participants who received FMT, with a median follow-up of …
ATRT-23. THE DUAL mTORC1/2 INHIBITOR SAPANISERTIB DISRUPTS THE NRF2-MEDIATED STRESS RESPONSE AND COMBINES SYNERGISTICALLY WITH THE BH3 MIMETIC OBATOCLAX TO EXTEND AT/RT SURVIVAL
Authors: Ashlyn Parkhurst, Sabrina Wang, Jesse Alt, Antje Arnold, Harpreet Kaur, Barbara Slusher, Charles Eberhart, Eric Raabe, Jeffrey Rubens
Journal: Neuro-Oncology (2020)

Abstract Atypical teratoid/rhabdoid tumors are aggressive infantile tumors highly resistant to intensive therapies. We aim to identify and target critical factors driving this therapy resistance to improve AT/RT survival. Analysis of publically available RNASeq on 32 AT/RT identified elevated expression of NRF2 (median expression 40.78, normal brain 18.81). NRF2 is a master regulator of cell’s stress response whose expression is correlated with therapy resistance and poor survival. NRF2 activation is sensitive to mTOR activity and is a biomarker predicting response to the dual mTORC1/2 inhibitor, Sapanisertib (TAK228, INK128). We performed RNASeq on 4 human-derived AT/RT cell models after Sapanisertib treatment. Pathway analysis reveals disruption of the NRF2-mediated stress response (-log p value 0.39, Z-score 1.0). As a result, Sapanisertib decreases ROS scavengers like glutathione (Metabolite analysis UHPLC-MS, t-test p&amp;lt;0.05) and induces a pro-death phenotype (decreased MCL-1 expression, western blot; gene-expression analysis, RNASeq). The brain-penetrant BH3 mimetic Obatoclax increases ROS generation and induces apoptosis (MUSE oxidative stress and ANNEXIN V assays, t-test p&amp;lt;0.05). These complementary mechanisms of action synergize to induce high rates of cell death (MUSE ANNEXIN V assay, ANOVA p&amp;lt;0.05, C-PARP western blot, Compusyn Synergy analysis CI&amp;lt;1.0) and slow cell growth (MUSE Cell viability, ANOVA p&amp;lt;0.05). Once-weekly treatments of Sapanisertib combined with Obatoclax in orthotopic mouse models of AT/RT are well tolerated, slow tumor growth (bioluminescence imaging) and significantly extend median survival from 35 to 55 days (Log-rank p&amp;lt;0.05). These findings support a new clinical trial aimed at improving AT/RT survival.
Covid-19 mass testing: throwing the baby out with the bathwater?
Authors: Julian Peto, David J Hunter, Elio Riboli
Journal: BMJ (2020)

The increasing number of technical equipment in the operating room (OR) is resulting in significantly higher noise levels. The more complex and sophisticated the surgical procedure is, the more essential it is for all team members of the OR to work together in a harmonious fashion to process and manage their demanding team tasks. With increasing noise in OR, the risk of more frequent errors also increases. The reduction of noise production in the OR is possible but limited. The aim of this study was to develop a device that reduces ambient noise for the operating team without hindering their ability to communicate. We developed a new communication technology set-up for the OR to meet all needed requirements. All members of the operating team are issued headsets with microphones. The headsets filter out background noises (active and passive noise cancelling) and the microphones enable interactive communication among and between OR subgroups through targeted information selection (signal selection). Any remaining background noise is overshadowed by music, which is quiesced by direct speech into the microphone (ducking). Information flow is programmed on a digital workstation, providing each team member a selection of acoustic signals from the OR on their bidirectional headset. A complex matrix of connections in this audio technology allows a predefined communication structure. These procedures were assembled in the Silent Operating Theatre Optimisation System (SOTOS). The technical specifications and user interface are described. A pilot study in 2015 using the SOTOS in cardiac surgery showed very positive feedback from the participating operating team members. Further studies focusing on communicational psychology perspective and physiological reaction are recommended.
Leveraging bile solubilization of poorly water-soluble drugs by rational polymer selection
Authors: Jonas Schlauersbach, Simon Hanio, Bettina Lenz, Sahithya P.B. Vemulapalli, Christian Griesinger, Ann-Christin Pöppler, Cornelius Harlacher, Bruno Galli, Lorenz Meinel
Journal: Journal of Controlled Release (2020)
Identifying Clear Cell Renal Cell Carcinoma Coexpression Networks Associated with Opioid Signaling and Survival
Authors: Joseph R. Scarpa, Renzo G. DiNatale, Roy Mano, Andrew W. Silagy, Fengshen Kuo, Takeshi Irie, Patrick J. McCormick, Gregory W. Fischer, A. Ari Hakimi, Joshua S. Mincer
Journal: Cancer Research (2020)

While opioids constitute the major component of perioperative analgesic regimens for surgery in general, a variety of evidence points to an association between perioperative opioid exposure and longer term oncologic outcomes. The mechanistic details underlying these effects are not well understood. In this study, we focused on clear cell renal cell carcinoma (ccRCC) and utilized RNA sequencing and outcome data from both The Cancer Genome Atlas, as well as a local patient cohort to identify survival-associated gene coexpression networks. We then projected drug-induced transcriptional profiles from in vitro cancer cells to predict drug effects on these networks and recurrence-free, cancer-specific, and overall survival. The opioid receptor agonist, leu-enkephalin, was predicted to have antisurvival effects in ccRCC, primarily through Th2 immune- and NRF2-dependent macrophage networks. Conversely, the antagonist, naloxone, was predicted to have prosurvival effects, primarily through angiogenesis, fatty acid metabolism, and hemopoesis pathways. Eight coexpression networks associated with survival endpoints in ccRCC were identified, and master regulators of the transition from the normal to disease state were inferred, a number of which are linked to opioid pathways. These results are the first to suggest a mechanism for opioid effects on cancer outcomes through modulation of survival-associated coexpression networks. While we focus on ccRCC, this methodology may be employed to predict opioid effects on other cancer types and to personalize analgesic regimens in patients with cancer for optimal outcomes. SIGNIFICANCE: This study suggests a possible molecular mechanism for opioid effects on cancer outcomes generally, with implications for personalization of analgesic regimens.
Environmental Cadmium and Mortality from Influenza and Pneumonia in U.S. Adults
Authors: Sung Kyun Park, Coralynn Sack, Matti J. Sirén, Howard Hu
Journal: Environmental Health Perspectives (2020)

Environmental cadmium exposure is widespread. In humans, cadmium is poorly excreted, triggers pulmonary inflammation, reduces pulmonary function, and enhances lung injury by respiratory syncytial virus.We examined the association of cadmium burden with mortality related to influenza or pneumonia.This prospective analysis of the National Health and Nutrition Examination Survey (NHANES) included 7,173 and 8,678 participants ≥45 years of age enrolled in NHANES-III and NHANES 1999-2006, respectively. Associations were evaluated between cadmium and mortality from influenza or pneumonia during a median follow-up of 17.3 y (NHANES-III, based on creatinine-corrected urine cadmium) and 11.4 y (NHANES 1999-2006, based on blood cadmium). Survey-weighted Cox proportional hazard models were used to compute hazard ratios (HRs) comparing the mortality of individuals at the 80th vs. the 20th percentile of cadmium concentrations.In NHANES-III, after adjustment for sex, race/ethnicity, education, body mass index, serum cholesterol, hypertension, and NHANES phase (or cycle), the HR comparing influenza or pneumonia mortality among participants with creatinine-corrected urinary cadmium in the 80th vs. 20th percentile was 1.15 (95% CI: 1.05, 1.26; p=0.002) in the population as a whole and 1.27 (95% CI: 1.12, 1.43; p=0.002) among never smokers. In NHANES 1999-2006, adjusted HRs for the 80th vs. 20th percentile of blood cadmium were 1.14 (95% CI: 0.96, 1.36; p=0.15) for the overall population and 1.71 (95% CI: 0.95, 3.09; p=0.07) in never smokers.Among middle-aged and older adults in the United States, higher cadmium burdens are associated with higher mortality from influenza or pneumonia. This raises the possibility that cadmium may worsen outcomes from COVID-19 infections. https://doi.org/10.1289/EHP7598.
THER-02. EVALUATION OF THE ONCOLYTIC VIRUS DELTA24-RGD AS AN ANTI-TUMOR AGENT IN PRECLINICAL MODELS OF LOCALIZED AND DISSEMINATED AT/RT
Authors: Marc Garcia-Moure, Marisol González-Huarriz, Daniel de la Nava, Lucía Marrodán, Cande Gomez-Manzano, Juan Fueyo, Ana Patiño-García, Marta M Alonso
Journal: Neuro-Oncology (2020)

Abstract Current therapies for atypical teratoid/rhabdoid tumors (AT/RTs) are suboptimal, resulting in a 2-year OS below 20% and the development of severe side effects. Therefore, we need to explore alternative therapeutic approaches for this disease. Since the virus Delta24-RGD has already demonstrated its efficacy and safety as a therapeutic agent for brain tumors, including pediatric patients, here we propose to evaluate the anti-tumor effect of Delta24-RGD in AT/RT. In vitro, Delta24-RGD infects and replicates in AT/RT cultures followed by oncolysis, obtaining IC50 values below 1 PFU/cell. In vivo, a single local injection of Delta-24-RGD in three infratentorial AT/RT models (BT-12, CHLA-06 and CHLA-266) extended significantly the median OS (50 to 78 days BT-12; 21 to 31 days CHLA-06; 64 to 110 days CHLA-266). Delta-24-RGD also increased the survival of mice bearing supratentorial CHLA-266 tumors (from 93 to 132 days). Next, we evaluated the efficacy of Delta24-RGD in a model mimicking metastatic disease through intraventricular injection of BT-12-luciferase cells. Administration of Delta24-RGD inhibited tumor growth and development of metastases, leading to an increased OS and nearly 70% of long-term survivors. The interaction between Delta24-RGD and the immune system was evaluated in humanized mice models bearing CHLA-06. In this model, Delta24-RGD treatment extended OS (from 23 to 34 days) and we characterized the anti-tumor immune landscape in control and Delta24-RGD treated mice by transcriptional and functional analyses. These results underscore the potential of Delta24-RGD as a promising therapeutic choice for patients affected by AT/RT.
CLL Cell-Derived Exosomes Promote Bone Marrow Fibrosis and Inhibit Normal Hematopoietic Colony Proliferation
Authors: Uri Rozovski, David M. Harris, Ping Li, Zhiming Liu, Taghi Manshouri, Ivo Veletic, Carlos Bueso-Ramos, Preetesh Jain, Srdan Verstovsek, Alessandra Ferrajoli, Jan A. Burger, Prithviraj Bose, Philip A Thompson, Nitin Jain, William G Wierda, Michael J. Keating, Zeev Estrov
Journal: Blood (2017)
EPCO-33. MULTI-OMICS ANALYSIS REVEALS SUBTYPE-SPECIFIC ENHANCER-TARGET NETWORKS AND TUMOR CELL OF ORIGIN IN GROUPS 3 AND 4 MEDULLOBLASTOMA
Authors: Zhen You, L Frank Huang
Journal: Neuro-Oncology (2020)

Abstract Medulloblastoma (MB), one of the most common malignant childhood brain cancer, consists of heterogeneous subgroup of cerebellar tumors. Four molecular subgroups are classified, of which Groups3 and 4 are poorly characterized. Additionally, MB subtype tumorigenesis and cellular composition remain elusive. Here, we combined multi-omics data, including bulk ChIP-Seq, RNA-Seq data, and scRNA-Seq from medulloblastoma patients with primary tumors, and integrated with whole-genome sequencing data, to address the tumors development and cellular heterogeneity in MB subgroups. First, we identified subgroup-specific enhancers and their targets based on the differential accessibility of H3K27ac signatures and further acquired subgroup-enriched transcription factors. Three distinct transcriptional signatures were extracted from RNA-seq of groups 3 and 4 MB respectively using non-negative matrix factorization and consensus clustering. To illustrate the subtype-specific expressed genes in those subtypes, we applied the Shannon entropy approach to discover genes and lncRNAs that are exclusively active or quiescent in a certain subtype. Single-cell transcriptome analysis demonstrated that SHH subgroup mostly consisted of mature and proliferating GNPs; Group3 tumors contained divergent cells, e.g. GNPs, UBCs, and excitatory CN; while Group4 subgroup derived mainly from UBCs and GluCN. Moreover, deconvolution of bulk RNA-Seq revealed that Group3 subtype1 mostly resembled mitosis and mature GNPs; and subtype2 resembled mitosis GNPs, excitatory CN, and OPCs; while subtype3 resembled UBCs, mitosis and mature GNPs, indicating the cellular origin difference within Group3 tumorigenesis. Genes and lncRNAs specifically expressed in subtype and cell type linked to the subtype MB tumor development and intertumoral cellularity. Taken together, these data enabled us to constructed novel enhancers-target networks that give rise to MB subtyping and cellular heterogeneity and permits the discovery of novel driver genes and pathways in medulloblastoma.
Sesame Should Be on Food Labels to Warn Consumers With Allergy
Authors: Mary Chris Jaklevic
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Dietary iron restriction improves markers of disease severity in murine sickle cell anemia
Authors: Nermi L. Parrow, Pierre-Christian Violet, Nisha Ajit George, Faris Ali, Shivam Bhanvadia, Ryan Wong, John F. Tisdale, Courtney Fitzhugh, Mark Levine, Swee Lay Thein, Robert E. Fleming
Journal: Blood (2020)
<b>Correspondence on</b>‘<b>Haemodynamic phenotypes and survival in patients with systemic sclerosis: the impact of the new definition of pulmonary arterial hypertension’</b>
Authors: Michele Iudici, Danièle Allali, Raphaël Porcher
Journal: Annals of the Rheumatic Diseases (2020)

The 6th World Symposium of pulmonary hypertension has proposed to widen the definition of pulmonary arterial hypertension (PAH) identifying a lower cut-off for mean pulmonary arterial pressure (mPAP) from ≥25 mm Hg (as recommended by the actual guidelines) to >20 mm Hg, in combination with pulmonary vascular resistance (PVR) ≥3 Wood units (WU).

In general, a change in the formal definition of a disease can impact in many different ways how the patients are identified, treated, and their prognosis. One of the consequence of such redefinition in patients with systemic sclerosis (SSc) has been addressed by Xanthouli et al , in their very interesting and original paper.1 The authors have shown that since most patients with SSc with an mPAP 21–24 mm Hg have PVR <3 WU, if left unmodified, the new criteria could allow to reclassify as PAH only 8% of mPAP 21–24 mm Hg patients, despite they display a pulmonary vascular disease and a poor prognosis. This paper, focusing on one aspect related to disease redefinition, has prompted us to add further general comments on what we should consider when future observational research will compare samples …
RADT-08. ADJUVANT SBRT FOR RESECTED BRAIN METASTASES: THE EFFECT OF TIMING ON LONG-TERM INTENDED-FIELD CONTROL
Authors: Evan Bander, Melissa Yuan, Anne Reiner, Katherine Panageas, Cameron Brennan, Kathryn Beal, Viviane Tabar, Nelson Moss
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Adjuvant stereotactic body radiation therapy (SBRT) improves the local control of resected brain metastases (BrM). However, the dependency of long-term outcomes on SBRT timing relative to surgery remains unclear. METHODS Retrospective analysis of metastasectomy-plus-adjuvant-SBRT patients at Memorial Sloan Kettering (MSK) between 2013-2016 was conducted. Kaplan-Meier methodology was used to describe overall survival (OS) and cumulative incidence in a competing-risks setting recurrence at the surgical site, other SBRT-treated sites, and elsewhere in the brain as defined by RANO-BM criteria. Recursive partitioning analysis (RPA) and competing-risks regression modeling assessed prognostic variables and associated events of interest. RESULTS Two hundred eighty-two patients with BrM including non-small cell lung (34%), breast (16%), melanoma (13%), and other cancers were included. Median time-to-adjuvant-SBRT (TT-SBRT) was 34 days (IQR: 27-39). Median overall survival (OS) from SBRT was 1.5 years (95% CI: 1.2-2.1) with median follow-up of 49.8 months for survivors. Local surgical recurrence, other irradiated-site, and distant progression rates were 14.3% (95%CI: 10.1-18.5), 4.9% (95%CI: 2.3-7.5), and 47.5% (95%CI: 41.4-53.6) at 5 years, respectively. TT-SBRT as a continuous variable significantly associated with surgical-site recurrence (HR 1.05 [1.02-1.07], p=0.0003), but not with distant or other irradiated-site recurrence nor OS. RPA analysis demonstrated the greatest control rate advantage with TT-SBRT &amp;lt; 39 days (HR for 39+ days: 2.81 [1.50-5.27], p=0.001). No association of TT-SBRT with radiation necrosis, wound complication, or development of leptomeningeal dissemination was identified. CONCLUSIONS Delays in initiation of post-operative SBRT can decrease its efficacy. Efforts must be made to minimize logistical, procedural, and socioeconomic factors responsible for these delays.
Intracellular Activation of Anticancer Therapeutics Using Polymeric Bioorthogonal Nanocatalysts
Authors: Xianzhi Zhang, Ryan F. Landis, Puspam Keshri, Roberto Cao‐Milán, David C. Luther, Sanjana Gopalakrishnan, Yuanchang Liu, Rui Huang, Gengtan Li, Morgane Malassiné, Imad Uddin, Brayan Rondon, Vincent M. Rotello
Journal: Advanced Healthcare Materials (2020)

Abstract Bioorthogonal catalysis provides a promising strategy for imaging and therapeutic applications, providing controlled in situ activation of pro‐dyes and prodrugs. In this work, the use of a polymeric scaffold to encapsulate transition metal catalysts (TMCs), generating bioorthogonal “polyzymes,” is presented. These polyzymes enhance the stability of TMCs, protecting the catalytic centers from deactivation in biological media. The therapeutic potential of these polyzymes is demonstrated by the transformation of a nontoxic prodrug to an anticancer drug (mitoxantrone), leading to the cancer cell death in vitro.
The Treatment of Patients With Unbearable Suffering—The Slippery Slope Is Real
Authors: Diane E. Meier
Journal: JAMA Internal Medicine (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal