tbuckley/cabot-search huggingface dataset:
The combined use of end-tidal carbon dioxide and alveolar dead space fraction values in the diagnosis of pulmonary embolism
Authors: Ziba Songur Yücel, Nalan Metin aksu, Meltem Akkaş
Journal: Pulmonology (2020)

Several studies have reported that computed tomography pulmonary angiography is the best method for diagnosing pulmonary embolism (PE). This study, however, aimed to predict or exclude PE using the end-tidal carbon dioxide (ETCO2) value and alveolar dead space fraction (AVDSf) together. One-hundred patients were included in the present study. Patients with suspected PE were evaluated using clinical prediction rules proposed by the Wells and the Modified Geneva scoring systems. PE was ruled out in patients with normal d-dimer concentrations (< 0.55 mg/dl). Patient ETCO2 values were recorded using time versus waveform capnography before performing imaging studies. Capnography was performed for 2 min; however, the average ETCO2 values measured over the final 1 min were recorded in "full continuous" mode. Arterial puncture was performed simultaneously for arterial blood gas analysis. Additionally, AVDSf was calculated according to the Bohr equation. PE was detected in 36 % of patients. Patients were classified into high-, moderate, and low-risk groups according to the Wells and Modified Geneva scores. PE was excluded in 95 % and 100 % of patients with low Wells and Modified Geneva system scores, respectively, when ETCO2 was > 28.5 mmHg. The diagnosis of PE was excluded in 100 % of patients with low Wells and Modified Geneva scoring system scores with AVDSf < 0.128. High wells and Modified Geneva system scores were helpful in diagnosing of PE (100 %) when AVDSf was > 0.128. It was possible to exclude/predict PE based on ETCO2 and AVDSf values calculated using capnography when evaluated with clinical prediction rules and d-dimer test using an algorithm.
Feeling Things Out: Bidirectional Signaling of the Cell–ECM Interface, Implications in the Mechanobiology of Cell Spreading, Migration, Proliferation, and Differentiation
Authors: Andrew E. Miller, Ping Hu, Thomas H. Barker
Journal: Advanced Healthcare Materials (2020)

Abstract Biophysical cues stemming from the extracellular environment are rapidly transduced into discernible chemical messages (mechanotransduction) that direct cellular activities–placing the extracellular matrix (ECM) as a potent regulator of cell behavior. Dynamic reciprocity between the cell and its associated matrix is essential to the maintenance of tissue homeostasis and dysregulation of both ECM mechanical signaling, via pathological ECM turnover, and internal mechanotransduction pathways contribute to disease progression. This review covers the current understandings of the key modes of signaling used by both the cell and ECM to coregulate one another. By taking an outside‐in approach, the inherent complexities and regulatory processes at each level of signaling (ECM, plasma membrane, focal adhesion, and cytoplasm) are captured to give a comprehensive picture of the internal and external mechanoregulatory environment. Specific emphasis is placed on the focal adhesion complex which acts as a central hub of mechanical signaling, regulating cell spreading, migration, proliferation, and differentiation. In addition, a wealth of available knowledge on mechanotransduction is curated to generate an integrated signaling network encompassing the central components of the focal adhesion, cytoplasm and nucleus that act in concert to promote durotaxis, proliferation, and differentiation in a stiffness‐dependent manner.
Hepatitis C Vaccine: 10 Good Reasons for Continuing
Authors: Philippe Roingeard, Elodie Beaumont
Journal: Hepatology (2020)

1Faculté de MédecineINSERM U1259Université de Tours and CHRU de ToursToursFrance *Address Correspondence and Reprint Requests to: Philippe Roingeard, Pharm.D., Ph.D. INSERM U1259, Faculté de Médecine, Université de Tours 10 Boulevard Tonnellé, 37032 Tours, France E‐mail: [email protected] Tel.: +1‐33‐02‐34‐37‐96‐46
Health ministers condemn Novartis lottery for Zolgensma, the world’s most expensive drug
Authors: Owen Dyer
Journal: BMJ (2020)

Novartis has held the first draw to choose four babies who will receive its one-shot treatment for the genetic disease spinal muscular atrophy, Zolgensma (onasemnogene abeparvovec), amid criticism of its lottery programme from patient groups and EU health ministers.

Priced in the United States at $2.1m (£1.6m; €1.9m), the most expensive drug course of treatment ever, Zolgensma is not yet approved elsewhere. In December the company announced a plan to give away 50 treatments in other countries over the next six months, the recipients to be chosen randomly from among applicants every two weeks. 

Recipients must be …
Hung-up Knee Jerk in Huntington’s Disease
Authors: Tatsuya Fukumoto, Ryosuke Miyamoto
Journal: New England Journal of Medicine (2020)

A 54-year-old woman presented with progressively worsening gait disturbance. Physical examination revealed persistent leg extension on stimulation of the patellar tendon, shown in a video. A diagnosis of Huntington’s disease was made.
Abstract P5-05-16: Quantitative regression of estrogen receptor alpha positive breast cancer
Authors: Matthew W Boudreau, Paul J Hergenrother, Darjan Duraki, Lawrence Wang, Chengjian Mao, Ben H Park, Tim M Fan, Eric R Nelson, David J Shapiro, Ramon Moreno, Elizabeth Bruckheimer, Jeffrey Kiefer, Theodore M Tarasow
Journal: Cancer Research (2020)

Abstract Treatment of advanced ERα-positive breast cancer remains a major clinical challenge, as the standard therapeutics are mostly cytostatic agents, ultimately leading to drug resistance. Resistant ERα-positive tumors typically retain ERα expression, suggesting an opportunity to develop new therapeutics that move beyond inhibition of this nuclear receptor. Through a medicinal chemistry campaign, we have discovered an estrogen receptor selective activator, the compound ErSO, that – in stark contrast to current ERα modulators – potently kills ERα-positive breast cancer cells. ErSO is effective even against breast cancer cell lines with known mutations in ERα that confer drug resistance. ErSO hyperactivates the anticipatory unfolded protein response, leading to quantitative cell death. ErSO is well-tolerated in mice, orally bioavailable, blood-brain-barrier penetrant. Using sensitive tumor imaging, ErSO often leads to quantitative tumor eradication (without recurrence) in multiple mouse models of ERα-positive breast cancer, including those utilizing breast cancer cell lines harboring mutant ERα. This potent activity against advanced primary and metastatic ERα-positive breast cancers represents a paradigm shift in leveraging of ERα for anticancer efficacy. Citation Format: Matthew W Boudreau, Paul J Hergenrother, Darjan Duraki, Lawrence Wang, Chengjian Mao, Ben H Park, Tim M Fan, Eric R Nelson, David J Shapiro, Ramon Moreno, Elizabeth Bruckheimer, Jeffrey Kiefer, Theodore M Tarasow. Quantitative regression of estrogen receptor alpha positive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-05-16.
Annals Story Slam - Voices of Medical Students and Residents: What Can Be Done to Build Trust
Authors: Candice Kim
Journal: Annals of Internal Medicine (2020)

Web Exclusives18 February 2020Annals Story Slam - Voices of Medical Students and Residents: What Can Be Done to Build TrustFREECandice KimCandice KimStanford University, Stanford, California (C.K.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W20-0013 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Voices of Medical Students and Residents: What Can Be Done to Build Trust "Voices of Medical Students and Residents: What Can Be Done to Build Trust," by Candice Kim (Duration 3:59)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Stanford University, Stanford, California (C.K.)Current Author Address: Candice Kim; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 February 2020Volume 172, Issue 4Page: SS1 ePublished: 18 February 2020 Issue Published: 18 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.Loading ...
Ethnic minority staff: trust boards still do not reflect NHS workforce
Authors: Abi Rimmer
Journal: BMJ (2020)

Black and ethnic minority staff continue to be underrepresented in the most senior jobs in NHS trusts, although there are signs of some improvement, new data show.

In 2019, black and ethnic minority staff made up 19.7% of the NHS trust workforce in England but only 8.4% of them were members of trust boards, an increase from 7.4% in 2018 and 7.0% in 2017.

The figures are compiled in the latest Workforce Race Equality Standard (WRES) report1 which uses nine key indicators to measure the experience and opportunities of white and ethnic minority people working in the NHS. They were published to coincide with the publication of The BMJ ’s special issue on racism in medicine.2

They show that in London—which at 45% has the highest proportion of ethnic minority NHS staff—all 36 trusts had at least one board member from an ethnic minority background in 2019, up from 16 in 2014. But even this increase means that ethnic minority board members made up just 17.1% of boards …
A native function for RAN translation and CGG repeats in regulating fragile X protein synthesis
Authors: Caitlin M. Rodriguez, Shannon E. Wright, Michael G. Kearse, Jill M. Haenfler, Brittany N. Flores, Yu Liu, Marius F. Ifrim, Mary R. Glineburg, Amy Krans, Paymaan Jafar-Nejad, Michael A. Sutton, Gary J. Bassell, Jack M. Parent, Frank Rigo, Sami J. Barmada, Peter K. Todd
Journal: Nature Neuroscience (2020)
Floating the invisible swan: noninvasive prediction of haemodynamics
Authors: Vineet Agrawal, Evan L. Brittain
Journal: European Respiratory Journal (2020)

<b>The study by Obokata and co-workers published in this issue of the <i>European Respiratory Journal</i> significantly contributes to the field of noninvasive prediction of haemodynamics during exercise</b>http://bit.ly/2svY7TP
Government orders urgent review of maternity services at East Kent Hospitals
Authors: Clare Dyer
Journal: BMJ (2020)

NHS England and NHS Improvement will commission an urgent independent review of maternity services at East Kent Hospitals University NHS Foundation Trust, where several babies have died preventable deaths.

An independent support team has already been sent to the trust, which has been under the spotlight since failings in care emerged during an inquest into the death of baby Harry Richford.1 He died in November 2017, a week after his birth at Queen Elizabeth the Queen Mother Hospital in Margate. The coroner concluded that Harry’s death had been “wholly avoidable.”

The coroner criticised the trust for initially categorising the death as “expected,” meaning that he was not informed, …
Abstract 193: CRISPR-mediated Introduction of the Sodium-iodide Symporter to Enable Non-invasive Monitoring of Macaque Induced-pluripotent Stem Cell-derived Cardiomyocytes
Authors: John Ostrominski, Ravi Chandra Yada, Noriko Sato, Maryknoll Palisoc, Stefania Pittaluga, Yongshun Lin, Jizhong Zou, Kah-Whye Peng, So Gun Hong, Cynthia Dunbar
Journal: Circulation Research (2017)

Due to the limited regenerative capacity of mature cardiomyocytes, cardiac cell therapies constitute an exciting strategy for myocardial repair. However, there is limited understanding of the spatio-temporal distribution and survival of transplanted cells. Hence, there is demand for technologies enabling long-term non-invasive tracking of transplanted cellular therapeutics. Sodium-iodide symporter (NIS)-based in vivo imaging has many potential advantages, including predicted safety and immunotolerance due to reliance on an endogenous species-specific gene and on widely available imaging technologies. We believe that non-human primates represent ideal models for investigating the biology of allogenic or autologous cellular grafts, because of close physiologic similarity to humans. We report the development of NIS-based in vivo imaging to detect and track rhesus induced pluripotent stem cell (RhiPSC)-derived teratomas as a proof-of-concept model tested in mice, and characterization of NIS-positive RhiPSC (NIS-RhiPSC)-derived cardiomyocytes (CM). NIS-RhiPSCs were generated by CRISPR/Cas9-mediated integration of the rhesus NIS cDNA within the AAVS1 safe harbor locus. NIS was stably expressed and radiotracer uptake by NIS-RhiPSCs was demonstrated in vitro . To evaluate viability of NIS-mediated imaging in RhiPSCs, undifferentiated NIS-RhiPSCs were introduced intramuscularly into immunodeficient mice, and NIS imaging was performed via PET/CT at 2, 4, and 6-weeks post-injection. NIS-positive teratomas were readily detectable as early as 2 weeks post-injection, prior to development of any palpable mass. Using our previously established differentiation protocol, NIS-RhiPS-CMs were derived with high purity, exhibited spontaneous beating in culture, and were similar in all aspects to parental RhiPS-CMs. NIS-RhiPS-CMs maintained stable NIS expression that was comparable to undifferentiated NIS-RhiPSCs, suggesting that in vivo imaging of transplanted NIS-RhiPS-CMs should be feasible. Further functional characterization of NIS-RhiPS-CMs, including in vitro radiotracer uptake, post-transplantation imaging in a mouse myocardial infarction model, and electrophysiologic analysis is ongoing and data will be presented.
Abstract 21347: Percutaneous Coronary Intervention With Drug Eluting Stents is as Efficacious as Coronary Artery Bypass Grafting in Unprotected Left Main Disease: A Meta Analysis
Authors: Senthil S Balasubramanian, Aviral Vij, Sisir Siddamsetti, Ankur Sethi, Vamsi Kodumuri
Journal: Circulation (2017)

Background: CABG is the preferred revascularization strategy for unprotected left main disease. Multiple small scale trials and registry data showed that PCI with Drug Eluting Stents is a non-inferior strategy and is a Class IIa ACC/AHA recommendation in a high surgical risk patient with favorable anatomy. However, two recent large scale randomized trials have shown conflicting evidence. We conducted a meta-analysis of the existing data to compare the long term outcomes of PCI with DES vs CABG for left main stenosis. Methods: 4 randomized and 8 non-randomized studies involving 10,284 patients were included. The primary endpoint was a composite of death, stroke or MI at three years or longer. Secondary end points were MACCE (death, stroke, MI or repeat revascularization) and it's individual components. Heterogeneity of the studies was analyzed by Cochran’s Q statistics. The Mantel-Haenszel random effects model was used to calculate the combined odds ratio for outcomes. An independent analysis was performed for the randomized data only. Results: There was no significant difference in the primary composite outcome between PCI and CABG at long term follow up. However the MACCE was significantly higher in PCI, primarily driven by significantly high repeat revascularization. The stroke rate was lower in PCI, although not significant. Analysis of randomized data also yielded similar results. A subgroup analysis stratified by SYNTAX score showed that MACCE and repeat revascularization were not significantly different between PCI and CABG in low to intermediate SYNTAX score (&lt;33) while they were significantly higher in PCI in high SYNTAX score. Conclusion: There was no significant difference in the primary composite outcome between PCI with DES and CABG at long term follow up. Repeat Revascularization in PCI was also not different from CABG in left main stenosis with low SYNTAX score. PCI with DES can be considered as a reasonable alternate strategy in isolated left main stenosis.
Addition of Maraviroc Versus Placebo to Standard Antiretroviral Therapy for Initial Treatment of Advanced HIV Infection
Authors: Yves Lévy, Jean-Daniel Lelièvre, Lambert Assoumou, Esther Aznar, Federico Pulido, Giuseppe Tambussi, Manuel Crespo, Agnès Meybeck, Jean-Michel Molina, Constance Delaugerre, Jacques Izopet, Gilles Peytavin, Fanny Cardon, Alpha Diallo, Rémi Lancar, Lydie Béniguel, Dominique Costagliola
Journal: Annals of Internal Medicine (2020)

Background: Patients diagnosed with advanced HIV infection have a poor prognosis despite initiation of combined antiretroviral therapy (c-ART). Objective: To assess the benefit of adding maraviroc, an antiretroviral drug with immunologic effects, to standard c-ART for patients with advanced disease at HIV diagnosis. Design: Randomized controlled trial. (ClinicalTrials.gov: NCT01348308) Setting: Clinical sites in France (n = 25), Italy (n = 5), and Spain (n = 20). Participants: 416 HIV-positive, antiretroviral-naive adults with CD4 counts less than 0.200 × 109 cells/L and/or a previous AIDS-defining event (ADE). Intervention: C-ART plus placebo or maraviroc (300 mg twice daily with dose modification) for 72 weeks. Measurements: The primary end point was first occurrence of severe morbidity (new ADE, selected serious infections, serious non-ADE, immune reconstitution inflammatory syndrome, or death). Prespecified secondary outcomes included primary outcome components, biological and pharmacokinetic measures, and adverse events graded 2 or higher. Results: 409 randomly assigned participants (207 in the placebo group and 202 in the maraviroc group) who received more than 1 dose were included in the analysis. During 72 weeks of follow-up, incidence of severe morbidity was 11.1 per 100 person-years in the maraviroc group and 11.2 per 100 person-years in the placebo group (hazard ratio, 0.97 [95% CI, 0.57 to 1.67]). Incidence of adverse events graded 2 or higher was 36.1 versus 41.5 per 100 person-years (incidence rate ratio, 0.87 [CI, 0.65 to 1.15]). Limitations: Sixty-four participants discontinued therapy during follow-up. The study was not designed to evaluate time-dependent outcomes or effect modification. Conclusion: Addition of maraviroc to standard c-ART does not improve clinical outcomes of patients initiating therapy for advanced HIV infection. Primary Funding Source: INSERM-ANRS (French National Agency for Research on AIDS).
Partha Kar: Sadda haq, aithe rakh
Authors: Partha Kar
Journal: BMJ (2020)

We live in a world where discussion around the issue of race gets caught up in a maze of debates about what’s politically correct, what’s part of “woke” culture, and what’s simply unacceptable in 2020. In this febrile environment, it’s not always easy to be a doctor from an ethnic minority in the NHS.

Whatever your view on Brexit, it’s clear that the 2016 referendum has opened wounds that will take decades to heal. And many doctors from ethnic minorities feel a sense of deja vu as controversies erupt about immigrants, race, ethnicity, and religion. It’s not easy to say whether the UK is racist or not: there’s no doubt that it’s largely more accepting than other countries, but, as a qualifying argument, that holds little …
Effect of salt substitution on community-wide blood pressure and hypertension incidence
Authors: Antonio Bernabe-Ortiz, Víctor G. Sal y Rosas, Vilarmina Ponce-Lucero, María K. Cárdenas, Rodrigo M. Carrillo-Larco, Francisco Diez-Canseco, M. Amalia Pesantes, Katherine A. Sacksteder, Robert H. Gilman, J. Jaime Miranda
Journal: Nature Medicine (2020)
Cholesterol-modified DP7 enhances the effect of individualized cancer immunotherapy based on neoantigens
Authors: Rui Zhang, Lin Tang, Yaomei Tian, Xiao Ji, Qiuyue Hu, Bailing Zhou, Ding Zhenyu, Xu Heng, Li Yang
Journal: Biomaterials (2020)

Personalized cancer vaccines based on neoantigens have become an important research direction in cancer immunotherapy. However, their therapeutic effects are limited by the efficiency of antigen uptake and presentation by antigen presenting cells. Here, the low-toxicity cholesterol-modified antimicrobial peptide (AMP) DP7 (DP7-C), which has dual functions as a carrier and an immune adjuvant, improved the dendritic cell (DC)-based vaccine efficacy. As a delivery carrier, DP7-C can efficiently delivery various antigen peptides into 75-95% of DCs via caveolin- and clathrin-dependent pathways. As an immune adjuvant, DP7-C can induce DC maturation and proinflammatory cytokine release via the TLR2-MyD88-NF-κB pathway and effectively increase antigen presentation efficiency. In addition, DP7-C enhanced the efficacy of DC-based individualized cancer immunotherapy and achieved excellent antitumor effects on mouse tumor models using the OVA antigen peptides and LL2-neoantigens. Excitingly, after DP7-C stimulation, the antigen uptake efficiency of monocytes-derived DCs (MoDCs) in patients with advanced lung cancer increased from 14-40% to 88-98%, the presentation efficiency increased from approximately 15% to approximately 65%, and the proportion of mature MoDCs increased from approximately 20% to approximately 60%. These findings suggest that our approach may be a potentially alternative strategy to produce cancer vaccines designed for individual patients.
Tumor cell-derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs
Authors: Li Qiao, Shiqi Hu, Ke Huang, Teng Su, Zhenhua Li, Adam Vandergriff, Jhon Cores, Phuong-Uyen Dinh, Tyler Allen, Deliang Shen, Hongxia Liang, Yongjun Li, Ke Cheng
Journal: Theranostics (2020)

Cancer is the second leading cause of death worldwide and patients are in urgent need of therapies that can effectively target cancer with minimal off-target side effects.Exosomes are extracellular nano-shuttles that facilitate intercellular communication between cells and organs.It has been established that tumor-derived exosomes contain a similar protein and lipid composition to that of the cells that secrete them, indicating that exosomes might be uniquely employed as carriers for anti-cancer therapeutics.Methods: We isolated exosomes from two cancer cell lines, then co-cultured each type of cancer cells with these two kinds of exosomes and quantified exosome.HT1080 or Hela exosomes were systemically injected to Nude mice bearing a subcutaneous HT1080 tumor to investigate their cancer-homing behavior.Moreover, cancer cell-derived exosomes were engineered to carry Doxil (a common chemotherapy drug), known as D-exo, were used to detect their target and therapeutic efficacy as anti-cancer drugs.Exosome proteome array analysis were used to reveal the mechanism underly this phenomenon.Results: Exosomes derived from cancer cells fuse preferentially with their parent cancer cells, in vitro.Systemically injected tumor-derived exosomes home to their original tumor tissues.Moreover, compared to Doxil alone, the drug-loaded exosomes showed enhanced therapeutic retention in tumor tissues and eradicated them more effectively in nude mice.Exosome proteome array analysis revealed distinct integrin expression patterns, which might shed light on the underlying mechanisms that explain the exosomal cancer-homing behavior. Conclusion:Here we demonstrate that the exosomes' ability to target the parent cancer is a phenomenon that opens up new ways to devise targeted therapies to deliver anti-tumor drugs.