tbuckley/cabot-search huggingface dataset:
Identifying the factors influencing outcome in probiotic studies in overweight and obese patients: host or microbiome?
Authors: Benjamin H Mullish, Daryn R Michael, Julie AK McDonald, Giulia Masetti, Sue F Plummer, Julian R Marchesi
Journal: Gut (2020)

We read with interest Rodriguez and colleagues’ study, using microbiota transfer from obese stool donors into inulin-treated hum-ob mice, to define a gut microbiome signature predicting response to prebiotic.1 However, the impact of other microbiome-based interventions (and particularly probiotics) on weight loss in humans is highly-variable between individuals.2 We were interested as to whether baseline gut microbiota, or aspects of host physiology, may predict weight loss during probiotic studies.

In our recent double-blind study (ISRCTN12562026), overweight/obese adults were randomised to either 6 months of Lab4P probiotic (containing lactobacilli and bifidobacteria) or placebo.3 A higher proportion of participants receiving probiotic lost weight compared with those receiving placebo, and the extent of weight loss in the probiotic arm was greater than the placebo group.3 We subsequently performed metataxonome and metabonome analysis on stool samples from study participants (using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry bile acid profiling, respectively, applying established protocols4 5).

We observed no difference in stool microbiota alpha-diversity at baseline between participants losing weight during the study versus those who did not (figure 1A); furthermore, no differences were observed in microbiota composition between groups at any taxonomic level. Conversely, on stool bile acid profiling, …
Abstract 248: Initiation and Assessment of Timekeeping Roles During In-Hospital Cardiac Arrests to Track Rhythm Checks and Epinephrine Dosing
Authors: Conor Crowley, Peter Clardy, Jessica McCannon, Rebecca Logiudice
Journal: Circulation (2019)

Introduction: Compliance to ACLS cardiac arrest algorithm is low and associated with worse outcomes from in-hospital cardiac arrests (IHCA). Reasons for non-compliance include reduced communication due to chaotic nature of IHCAs and difficulty timing epinephrine administration and rhythm check intervals. Hypothesis: Delegating two separate code team members for rhythm and epinephrine timing will increase adherence to ACLS algorithm during IHCAs. Methods: This is a pre-post interventional study of IHCAs at a single academic medical center. Two stopwatches were placed on all code carts and two new timekeeping roles were created. Education was provided to staff regarding the alteration of existing code team member roles for the use of stopwatches. Algorithm adherence was analyzed pre and post implementation of timekeeper roles. Deviation from the 2-minute rhythm check or 3-5-minute epinephrine administration was counted as one deviation. Anonymous surveys were delivered to evaluate providers perceived benefits of timekeeper roles for IHCAs. Results: Data from 13 pre intervention IHCAs were compared to 12 IHCAs post intervention. The initial rhythm was PEA/asystole in 69% pre-intervention vs 83% post intervention. Prior to implementation 82 deviations vs. 11 deviations post implementation occurred (p=0.006). The mean time until first dose of epinephrine was administered pre intervention was 2.3 ± 3.3 minutes vs 0.4 ±1 minute post. Pre-implementation ROSC rate was 53.8% vs. 66.7% post intervention. Surveys were delivered to 100% of code team members post intervention, with a 79% response rate. Surveys demonstrate providers felt time keeping roles made it easier to track epinephrine administration and rhythm checks. On a Likert scale, 78% of providers “strongly agree” that the use of timekeeping roles and devices improved code team communication. Conclusion: Two separate timekeeper roles during IHCAs improved algorithm compliance, code team function and communication, and was favored by code team members. Timekeeper roles may be associated with improved rates of ROSC and less time until the first dose of epinephrine is administered. This study is limited by its small sample size, single center and requires validation.
Abstract 16035: Diacylglycerol Lipase Beta (daglβ) Deletion Attenuates Western Diet-induced Cardiac Inflammation, Oxidative Stress And Dysfunction
Authors: Janos Paloczi, Varga V Zoltan, Cody Savage, Holovac David, Csaba Matyas, Trojnar Eszter, Mukhopadhyay Partha, van der Stelt M Mario, Cravatt F Benjamin, Pal Pacher
Journal: Circulation (2019)

Introduction: The plasma levels of endocannabinoid 2-arachidonoylglycerol (2-AG) has been positively correlated with cardiovascular adverse events in obese subjects. 2-AG is biosynthesized by diacy...
Patients with paroxysmal nocturnal hemoglobinuria demonstrate a prothrombotic clotting phenotype which is improved by complement inhibition with eculizumab
Authors: Fraser L. Macrae, Barnaby Peacock‐Young, Polly Bowman, Stephen R. Baker, Sam Quested, Emma Linton, Peter Hillmen, Morag Griffin, Talha Munir, Daniel Payne, Claire McKinley, Deborah Clarke, Darren J Newton, Anita Hill, Robert A. S. Ariëns
Journal: American Journal of Hematology (2020)

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder, characterized by complement-mediated intravascular hemolysis and thrombosis. The increased incidence of PNH-driven thrombosis is still poorly understood, but unlike other thrombotic disorders, is thought to largely occur through complement-mediated mechanisms. Treatment with a C5 inhibitor, eculizumab, has been shown to significantly reduce the number of thromboembolic events in these patients. Based on previously described links between changes in fibrin clot structure and thrombosis in other disorders, our aim was to investigate clot structure as a possible mechanism of thrombosis in patients with PNH and the anti-thrombotic effects of eculizumab treatment on clot structure. Clot structure, fibrinogen levels and thrombin generation were examined in plasma samples from 82 patients from the National PNH Service in Leeds, UK. Untreated PNH patients were found to have increased levels of fibrinogen and thrombin generation, with subsequent prothrombotic changes in clot structure. No link was found between increasing disease severity and fibrinogen levels, thrombin generation, clot formation or structure. However, eculizumab treated patients showed decreased fibrinogen levels, thrombin generation and clot density, with increasing time spent on treatment augmenting these antithrombotic effects. These data suggest that PNH patients have a prothrombotic clot phenotype due to increased fibrinogen levels and thrombin generation, and that the antithrombotic effects of eculizumab are, in-part, due to reductions in fibrinogen and thrombin generation with downstream effects on clot structure.
CAL-101, a Specific Inhibitor of the p110δ Isoform of Phosphatidylinositide 3-Kinase Induces Cytotoxicity in Multiple Myeloma (MM)
Authors: Hiroshi Ikeda, Teru Hideshima, Yutaka Okawa, Sonia Vallet, Samantha Pozzi, Loredana Santo, Gullu Gorgun, Mariateresa Fulciniti, Noopur S. Raje, Giulia Perrone, Nikhil Munshi, Paul Richardson, Brian J Lannutti, Kamal D. Puri, Neill A. Giese, Kenneth C. Anderson
Journal: Blood (2008)
Bone Marrow Endothelial Cells Regulate Myelopoiesis in Diabetes Mellitus
Authors: Friedrich Felix Hoyer, Xinyi Zhang, Emilie Coppin, Sathish Babu Vasamsetti, Ganesh Modugu, Maximilian J. Schloss, David Rohde, Cameron S. McAlpine, Yoshiko Iwamoto, Peter Libby, Kamila Naxerova, Filip K. Swirski, Partha Dutta, Matthias Nahrendorf
Journal: Circulation (2020)

Background: Diabetes mellitus is a prevalent public health problem that affects about one-third of the US population and leads to serious vascular complications with increased risk for coronary artery disease. How bone marrow hematopoiesis contributes to diabetes mellitus complications is incompletely understood. We investigated the role of bone marrow endothelial cells in diabetic regulation of inflammatory myeloid cell production. Methods: In 3 types of mouse diabetes mellitus, including streptozotocin, high-fat diet, and genetic induction using leptin-receptor-deficient db/db mice, we assayed leukocytes, hematopoietic stem and progenitor cells (HSPC). In addition, we investigated bone marrow endothelial cells with flow cytometry and expression profiling. Results: In diabetes mellitus, we observed enhanced proliferation of HSPC leading to augmented circulating myeloid cell numbers. Analysis of bone marrow niche cells revealed that endothelial cells in diabetic mice expressed less Cxcl12 , a retention factor promoting HSPC quiescence. Transcriptome-wide analysis of bone marrow endothelial cells demonstrated enrichment of genes involved in epithelial growth factor receptor (Egfr) signaling in mice with diet-induced diabetes mellitus. To explore whether endothelial Egfr plays a functional role in myelopoiesis, we generated mice with endothelial-specific deletion of Egfr ( Cdh5 Cre Egfr fl/fl ). We found enhanced HSPC proliferation and increased myeloid cell production in Cdh5 Cre Egfr fl/fl mice compared with wild-type mice with diabetes mellitus. Disrupted Egfr signaling in endothelial cells decreased their expression of the HSPC retention factor angiopoietin-1. We tested the functional relevance of these findings for wound healing and atherosclerosis, both implicated in complications of diabetes mellitus. Inflammatory myeloid cells accumulated more in skin wounds of diabetic Cdh5 Cre Egfr fl/fl mice, significantly delaying wound closure. Atherosclerosis was accelerated in Cdh5 Cre Egfr fl/fl mice, leading to larger and more inflamed atherosclerotic lesions in the aorta. Conclusions: In diabetes mellitus, bone marrow endothelial cells participate in the dysregulation of bone marrow hematopoiesis. Diabetes mellitus reduces endothelial production of Cxcl12, a quiescence-promoting niche factor that reduces stem cell proliferation. We describe a previously unknown counterregulatory pathway, in which protective endothelial Egfr signaling curbs HSPC proliferation and myeloid cell production.
Hydroxychloroquine reduces the risk of covid-19 in patients with rheumatic diseases: myth or reality?
Authors: Wenhui Xie, Yu Wang, Zhuoli Zhang
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the article by Figueroa-Parra et al illustrating whether patients with rheumatic diseases are at higher risk of the coronavirus disease 2019 (covid-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1 In this study, the authors mentioned the potential benefit of antimalarial drugs for patients with rheumatic diseases in the context of covid-19 pandemic. At present, that is the really pivotal question, whether the antimalarial drugs could reduce the risk of SARS-CoV-2 infection in patients with rheumatic diseases.

Hydroxychloroquine (HCQ) and chloroquine, as antimalarial drugs for more than 70 years, have been successfully used to treat variety of rheumatic diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. Both drugs have a flat aromatic core structure and share nearly identical mechanism of action, but HCQ has replaced chloroquine in most …
Flavopiridol (Alvocidib) Induces Durable Responses in Relapsed Chronic Lymphocytic Leukemia (CLL) Patients with High-Risk Cytogenetic Abnormalities
Authors: Thomas S. Lin, Nyla A. Heerema, Gerard Lozanski, Beth Fischer, Kristie A. Blum, Leslie A. Andritsos, Jeffrey A. Jones, Joseph M. Flynn, Mollie E. Moran, Sarah Mitchell, Amy J. Johnson, Mitch A. Phelps, Michael R. Grever, John C. Byrd
Journal: Blood (2008)
Th1-Th2 Cross-Regulation Controls Early Leishmania Infection in the Skin by Modulating the Size of the Permissive Monocytic Host Cell Reservoir
Authors: Matheus Batista Carneiro, Mateus Eustáquio Lopes, Leah S. Hohman, Audrey Romano, Bruna Araujo David, Rachel Kratofil, Paul Kubes, Matthew L. Workentine, Alexandre C. Campos, Leda Quercia Vieira, Nathan C. Peters
Journal: Cell Host & Microbe (2020)
Case 13-2020: A 29-Year-Old Man with High Blood Pressure, Renal Insufficiency, and Hematuria
Authors: Andrew L. Lundquist, Sahir Kalim, Amirkasra Mojtahed, Kristen J. Tomaszewski
Journal: New England Journal of Medicine (2020)

A 29-year-old man was evaluated because of hypertension, renal insufficiency, and hematuria. He had a blood pressure of 160/102 mm Hg, a urea nitrogen level of 48 mg per deciliter, and a creatinine level of 3.93 mg per deciliter. Examination of urine sediment revealed fine granular casts, dysmorphic red cells, and rare white-cell casts. Diagnostic tests were performed.
Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010 (vol 380, pg 2095, 2012)
Authors: R Lozano, M Naghavi, K Foreman, Mohammad A AlMazroa, Ziad A Memish
Journal: The Lancet (2013)
The Prognostic Value of 99mTc-HMPAO-Labeled Leucocyte SPECT/CT in Cardiac Device-Related Infective Endocarditis
Authors: Katarzyna Holcman, Paweł Rubiś, Andrzej Ząbek, Bogdan Ćmiel, Wojciech Szot, Krzysztof Boczar, Sylwia Wiśniowska-Śmiałek, Agnieszka Stępień, Barbara Małecka, Piotr Podolec, Magdalena Kostkiewicz
Journal: JACC. Cardiovascular imaging (2020)
A20 and RBX1 Regulate Brentuximab Vedotin Sensitivity in Hodgkin Lymphoma Models
Authors: Wei Wei, Yuquan Lin, Zhihui Song, Wenming Xiao, Liqi Chen, Jiejing Yin, Yan Zhou, Stefan K. Barta, Michael Petrus, Thomas A. Waldmann, Yibin Yang
Journal: Clinical Cancer Research (2020)

Abstract Purpose: For patients with refractory/relapsed Hodgkin lymphoma (roughly 20% of total cases), few effective therapeutic options exist. Currently, brentuximab vedotin (BV), a drug-conjugated anti-CD30 antibody, is one of the most effective approved therapy agents for these patients. However, many patients do not achieve complete remission and ultimately develop BV-resistant disease, necessitating a more detailed understanding of the molecular circuitry that drives BV sensitivity and the mechanism of BV resistance. Experimental Design: Here, we established a ubiquitin regulator–focused CRISPR library screening platform in Hodgkin lymphoma and carried out a drug sensitization screen against BV to identify genes regulating BV treatment sensitivity. Results: Our CRISPR library screens revealed the ubiquitin-editing enzymes A20 and RBX1 as key molecule effectors that regulate BV sensitivity in Hodgkin lymphoma line L428. A20 negatively regulates NF-κB activity which is required to prevent BV cytotoxicity. In line with these results, the RNA-seq analysis of the BV-resistant single-cell clones demonstrated a consistent upregulation of NF-κB signature genes, as well as the ABC transporter gene ABCB1. Mechanically, NF-κB regulates BV treatment sensitivity through mediating ABCB1 expression. Targeting NF-κB activity synergized well with BV in killing Hodgkin lymphoma cell lines, augmented BV sensitivity, and overcame BV resistance in vitro and in Hodgkin lymphoma xenograft mouse models. Conclusions: Our identification of this previously unrecognized mechanism provides novel knowledge of possible BV responsiveness and resistance mechanisms in Hodgkin lymphoma, as well as leads to promising hypotheses for the development of therapeutic strategies to overcome BV resistance in this disease.
Development and Assessment of the Wisconsin Surgical Coaching Rubric
Authors: Kara A. Vande Walle, Sudha R. Pavuluri Quamme, Heather L. Beasley, Glen E. Leverson, Hala N. Ghousseini, Janet C. Dombrowski, Brian T. Fry, Justin B. Dimick, Douglas A. Wiegmann, Caprice C. Greenberg
Journal: JAMA Surgery (2020)

<h3>Importance</h3> Surgical coaching continues to gain momentum as an innovative method for continuous professional development. A tool to measure the performance of a surgical coach is needed to provide formative feedback to coaches for continued skill development and to assess the fidelity of a coaching intervention for future research and dissemination. <h3>Objective</h3> To evaluate the validity of the Wisconsin Surgical Coaching Rubric (WiSCoR), a novel tool to assess the performance of a peer surgical coach. <h3>Design, Setting, and Participants</h3> Surgical coaching sessions from November 2014 through February 2018 conducted by 2 statewide peer surgical coaching programs were audio recorded and transcribed. Twelve raters used WiSCoR to rate the performance of the surgical coach for each session. The study included peer surgical coaches in the Wisconsin Surgical Coaching Program (n = 8) and the Michigan Bariatric Surgery Collaborative coaching program (n = 15). The data were analyzed in 2019. <h3>Interventions or Exposures</h3> Use of WiSCoR to rate peer surgical coaching sessions. <h3>Main Outcomes and Measures</h3> There were 282 WiSCoR ratings from the 106 coaching sessions included in the study. WiSCoR was evaluated using a framework, including inter-rater reliability assessed with Gwet weighted agreement coefficent. Descriptive statistics of WiSCoR were calculated. <h3>Results</h3> Eight coaches (35%) and 11 coachees (29%) were from the Wisconsin Surgical Program and 15 coaches (65%) and 27 coachees (71%) were from the Michigan Bariatric Surgery Collaborative. The validity of WiSCoR is supported by high interrater reliability (Gwet weighted agreement coefficient, 0.87) as well as a weakly positive correlation of WiSCoR to coachee ratings of coaches (<i>r</i> = 0.22;<i>P</i> = .04), rigorous content development, consistent rater training, and the association of WiSCoR with coach and coaching program development. The mean (SD) overall coach performance rating using WiSCoR was 3.23 (0.82; range, 1-5). <h3>Conclusions and Relevance</h3> WiSCoR is a reliable measure that can assess the performance of a surgical coach, inform fidelity to coaching principles, and provide formative feedback to surgical coaches. While coachee ratings may reflect coachee satisfaction, they are not able to determine the quality of a coach.
Neighbourhood disadvantage and child behaviour in Montevideo, Uruguay: a mixed methods study
Authors: Seth Frndak, Yanina Gallo, Elena Quierolo, Gabriel Barg, Nelly Mañay, Katarzyna Kordas
Journal: The Lancet Global Health (2020)

BackgroundThe neighbourhood context is important for child development, but little evidence exists on neighbourhood-based challenges and resources in South American cities. We used a mixed methods approach to quantify the effect of neighbourhood disadvantage on child behaviour and to empower parents to explain life in disadvantaged neighbourhoods in Montevideo, Uruguay.MethodsA study within the Salud Ambiental Montevideo (SAM) longitudinal cohort yielded a cross-sectional sample of 225 (63% of total) children aged 6–8 years with complete data. Teacher ratings of child behaviour were collected using the Connors' Teacher Rating Scale—Revised (CTRS-R) and Behavior Rating Inventory of Executive Function (BRIEF). Five indicators of neighbourhood disadvantage were collected from Montevideo census data, and combined into to a single neighbourhood disadvantage factor. In the analyses of the relation between neighbourhood disadvantage and child behaviour scores we controlled for individual-level socioeconomic indicators, child IQ, and concentrations of lead in blood. In a nested study, we conducted semi-structured interviews with ten caregivers of SAM children in low-income neighbourhoods. Parents discussed what neighbourhood means to them and what they liked and disliked about their neighbourhood, perceptions of community services, and raising children in their neighbourhood. Parents were also asked to photograph their neighbourhoods and to discuss the meaning of at least four of their photographs during the interview.FindingsOne SD increase in neighbourhood disadvantage was related to a 1% increase in prevalence ratio on scores of oppositional behaviour (p=0·048) and a 4% increase in prevalence ratio on emotional control problem ratings (p=0·006). Neighbourhood disadvantage was unrelated to hyperactive behaviours and inhibitory control scores. From the interviews, common themes emerged on the importance of playgrounds, neighbourhood disorder, fears over crime, and lack of infrastructure. Many interviewees perceived that their neighbourhoods had been safer in the past. Suggestions for improving neighbourhoods included: better waste management, increased policing, traffic regulation, and improved local clinics.InterpretationNeighbourhood disadvantage is related to child behaviour beyond the influences of individual-level socioeconomic factors. Low-income neighbourhoods in Montevideo face challenges related to local infrastructure and services. Parents advocated for improved infrastructure, health services, transportation, and safety. Future studies should test specific mechanisms behind the effects of neighbourhood disadvantage and child behaviour in Montevideo.FundingUS National Institute of Environmental Health Sciences (NIEHS) and Fogarty International (FI) Institute under grant number R21ES16523, and by NIEHS grant R21ES019949.
Willebrand in the Netherlands: WiN Study. Background and Study Design
Authors: Eva M. De Wee, Eveline P. Mauser-Bunschoten, Anske G. Van der Bom, Jeroen C.J. Eikenboom, Karin J. Fijn van Draat, Arja De Goede-Bolder, Karina Meijer, Irena Nováková, Iris Plug, Frank W.G. Leebeek
Journal: Blood (2008)
Bicalutamide: A potential new oral antiandrogenic drug for female pattern hair loss
Authors: Diego Fernandez-Nieto, David Saceda-Corralo, Juan Jimenez-Cauhe, Oscar Muñoz Moreno-Arrones, Rita Rodrigues-Barata, Angela Hermosa-Gelbard, Sergio Vano-Galvan
Journal: Journal of the American Academy of Dermatology (2020)
Abstract 15278: Empagliflozin, a SGLT2 Inhibitor, Directly Protects Cardiomyocytes by Off-Target Effect-Mediated Promotion of Mitophagy
Authors: Yasuhiro Maejima
Journal: Circulation (2019)

Introduction: Growing body of evidence, including EMPA-REG OUTCOME, suggest that administration of sodium glucose co-transporter 2 (SGLT2) inhibitor effectively alleviates heart failure in patients...
The Impact of Age on the Efficacy and Safety of Extended-Duration Thromboprophylaxis in Acutely Ill Medical Patients with Recent Immobility: A Sub-Group Analysis from the EXCLAIM Study
Authors: Roger D Yusen, Russell D Hull, Sebastian M Schellong, Victor F Tapson, Manuel Monreal, Michel Meyer Samama, Min Chen, Alexander GG Turpie
Journal: Blood (2008)
Covid-19: Government cannot say whether NHS will run out of protective gowns this weekend
Authors: Gareth Iacobucci
Journal: BMJ (2020)

NHS staff may not have enough protective gowns this weekend because of a severe shortage in supplies, the health secretary has admitted.

Matt Hancock told MPs on the health select committee on 17 April that recent changes to UK clinical guidance on personal protective equipment (PPE)1 had increased demand for all such equipment at a time when there was a serious shortage.

When asked by the select committee chair, Jeremy Hunt, whether there would be enough gowns to see NHS staff through this weekend, Hancock said, “The challenge of getting protective equipment out to everybody who needs it is an incredibly difficult one. We are tight on gowns, that is the pressure point at the moment.

“We …
Covid-19: Government appoints former Olympics chief to lead PPE production drive
Authors: Abi Rimmer
Journal: BMJ (2020)

The former head of the 2012 Summer Olympics and Paralympics has been appointed to lead the UK’s effort to produce personal protective equipment (PPE) for NHS staff.

Paul Deighton will lead a campaign to scale up domestic PPE manufacturing, said the Department of Health and Social Care.

Matt Hancock, England’s health and social care secretary, said, “Lord Deighton led the delivery of the Olympics. Now he will lead a singular and relentless focus on PPE as the country’s top manufacturing priority, with the full weight of the government behind him.”

The government said that it had issued a “call to …