tbuckley/cabot-search huggingface dataset:
Temporal Dynamics of Cortical Microinfarcts in Cerebral Small Vessel Disease
Authors: Annemieke ter Telgte, Kim Wiegertjes, Benno Gesierich, Brendon Sri Baskaran,, José P. Marques, Hugo J. Kuijf, David G. Norris, Anil M. Tuladhar, Marco Duering, Frank-Erik de Leeuw
Journal: JAMA Neurology (2020)

Neuropathology studies show a high prevalence of cortical microinfarcts (CMIs) in aging individuals, especially in patients with cerebrovascular disease and dementia. However, most, are invisible on T1- and T2-weighted magnetic resonance imaging (MRI), raising the question of how to explain this mismatch. Studies on small acute infarcts, detected on diffusion-weighted imaging (DWI), suggest that infarcts are largest in their acute phase and reduce in size thereafter. Therefore, we hypothesized that a subset of the CMI that are invisible on MRI can be detected on MRI in their acute phase. However, to our knowledge, a serial imaging study investigating the temporal dynamics of acute CMI (A-CMI) is lacking.To determine the prevalence of chronic CMI (C-CMI) and the cumulative incidence and temporal dynamics of A-CMI in individuals with cerebral small vessel disease (SVD).The RUN DMC-Intense study is a single-center hospital-based prospective cohort study on SVD performed between March 2016 and November 2017 and comprising 10 monthly 3-T MRI scans, including high-resolution DWI, 3-dimensional T1, 3-dimensional fluid-attenuated inversion recovery, and T2. One hundred six individuals from the previous longitudinal RUN DMC study were recruited based on the presence of progression of white matter hyperintensities on MRI between 2006 and 2015 and exclusion of causes of cerebral ischemia other than SVD. Fifty-four individuals (50.9%) participated. The median total follow-up duration was 39.5 weeks (interquartile range, 37.8-40.3). Statistical data analysis was performed between May and October 2019.We determined the prevalence of C-CMI using the baseline T1, fluid-attenuated inversion recovery, and T2 scans. Monthly high-resolution DWI scans (n = 472) were screened to determine the cumulative incidence of A-CMI. The temporal dynamics of A-CMI were determined based on the MRI scans collected during the first follow-up visit after A-CMI onset and the last available follow-up visit.The median age of the cohort at baseline MRI was 69 years (interquartile range, 66-74 years) and 34 participants (63%) were men. The prevalence of C-CMI was 35% (95% CI, 0.24-0.49). Monthly DWI detected 21 A-CMI in 7 of 54 participants, resulting in a cumulative incidence of 13% (95% CI, 0.06-0.24). All A-CMI disappeared on follow-up MRI.Acute CMI never evolved into chronically MRI-detectable lesions. We suggest that these A-CMI underlie part of the submillimeter C-CMI encountered on neuropathological examination and thereby provide a source for the high CMI burden on neuropathology.
The Magic of Randomization versus the Myth of Real-World Evidence
Authors: Rory Collins, Louise Bowman, Martin Landray, Richard Peto
Journal: New England Journal of Medicine (2020)

Nonrandomized observational analyses have been promoted as alternatives to randomized clinical trials. However, randomization ensures balance between groups, whereas nonrandomized studies are often biased by between-group differences. Efforts to reduce the cost and complexity of clinical trials are preferable to relying on observational studies.
Dimensionality changes actin network through lamin A/C and zyxin
Authors: Jip Zonderland, Ivan Lorenzo Moldero, Shivesh Anand, Carlos Mota, Lorenzo Moroni
Journal: Biomaterials (2020)

Mechanosensing proteins have mainly been investigated in 2D culture platforms, while understanding their regulation in 3D enviroments is critical for tissue engineering. Among mechanosensing proteins, the actin cytoskeleton plays a key role in human mesenchymal stromal cells (hMSCs) activity, but its regulation in 3D tissue engineered scaffolds remains poorly studied. Here, we show that human mesenchymal stromal cells (hMSCs) cultured on 3D electrospun scaffolds made of a stiff material do not form actin stress fibers, contrary to hMSCs on 2D films of the same material. On 3D electrospun and additive manufactured scaffolds, hMSCs also displayed fewer focal adhesions, lower lamin A and C expression and less YAP1 nuclear localization and myosin light chain phosphorylation. Together, this strongly suggests that dimensionality prevents the build-up of cellular tension, even on stiff materials. Knock down of either lamin A and C or zyxin resulted in fewer stress fibers in the cell center. Zyxin knock down reduced lamin A and C expression, but not vice versa, showing that this signal chain starts from the outside of the cell. Lineage commitment was not affected by the lack of these important osteogenic proteins in 3D, as all cells committed to osteogenesis in bi-potential medium. Our study demonstrates that dimensionality changes the actin cytoskeleton through lamin A and C and zyxin, and highlights the difference in the regulation of lineage commitment in 3D enviroments. Together, these results can have important implications for future scaffold design for both stiff- and soft tissue engineering constructs.
Australian consensus statements for the regulation, production and use of faecal microbiota transplantation in clinical practice
Authors: Craig Haifer, Colleen R Kelly, Sudarshan Paramsothy, David Andresen, Lito E Papanicolas, Genevieve L McKew, Thomas J Borody, Michael Kamm, Samuel P Costello, Jane M Andrews, Jakob Begun, Hiu Tat Chan, Susan Connor, Simon Ghaly, Paul DR Johnson, Daniel A Lemberg, Ramesh Paramsothy, Andrew Redmond, Harsha Sheorey, David van der Poorten, Rupert W Leong
Journal: Gut (2020)

Objective Faecal microbiota transplantation (FMT) has proved to be an extremely effective treatment for recurrent Clostridioides difficile infection, and there is interest in its potential application in other gastrointestinal and systemic diseases. However, the recent death and episode of septicaemia following FMT highlights the need for further appraisal and guidelines on donor evaluation, production standards, treatment facilities and acceptable clinical indications. Design For these consensus statements, a 24-member multidisciplinary working group voted online and then convened in-person, using a modified Delphi approach to formulate and refine a series of recommendations based on best evidence and expert opinion. Invitations to participate were directed to Australian experts, with an international delegate assisting the development. The following issues regarding the use of FMT in clinical practice were addressed: donor selection and screening, clinical indications, requirements of FMT centres and future directions. Evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Results Consensus was reached on 27 statements to provide guidance on best practice in FMT. These include: (1) minimum standards for donor screening with recommended clinical selection criteria, blood and stool testing; (2) accepted routes of administration; (3) clinical indications; (4) minimum standards for FMT production and requirements for treatment facilities acknowledging distinction between single-site centres (eg, hospital-based) and stool banks; and (5) recommendations on future research and product development. Conclusions These FMT consensus statements provide comprehensive recommendations around the production and use of FMT in clinical practice with relevance to clinicians, researchers and policy makers.
Endoscopic grading of gastric intestinal metaplasia on risk assessment for early gastric neoplasia: can we replace histology assessment also in the West?
Authors: Pedro Marcos, Gisela Brito-Gonçalves, Diogo Libânio, Inês Pita, Rui Castro, Inês Sá, Mário Dinis-Ribeiro, Pedro Pimentel-Nunes
Journal: Gut (2020)

Objectives To assess the value of endoscopic grading of gastric intestinal metaplasia (EGGIM), operative link on gastritis assessment (OLGA) and operative link on gastric intestinal metaplasia (OLGIM) on risk stratification for early gastric neoplasia (EGN) and to investigate other factors possibly associated with its development. Design Single centre, case–control study including 187 patients with EGN treated endoscopically and 187 age-matched and sex-matched control subjects. Individuals were classified according to EGGIM, OLGA and OLGIM systems. EGN risk according to gastritis stages and other clinical parameters was further evaluated. Results More patients with EGN had EGGIM of ≥5 than control subjects (68.6% vs 13.3%, p&lt;0.001). OLGA and OLGIM stages III/IV were more prevalent in patients with EGN than in control subjects (68% vs 11%, p&lt;0.001, and 61% vs 3%, p&lt;0.001, respectively). The three systems were the only parameters significantly related to the risk of EGN in multivariate analysis: for EGGIM 1–4 (adjusted OR (AOR) 12.9, 95% CI 1.4 to 118.6) and EGGIM 5–10 (AOR 21.2, 95% CI 5.0 to 90.2); for OLGA I/II (AOR 5.0, 95% CI 0.56 to 44.5) and OLGA III/IV (AOR 11.1, 95% CI 3.7 to 33.1); for OLGIM I/II (AOR 11.5, 95% CI 4.1 to 32.3) and OLGIM III/IV (AOR 16.0, 95% CI 7.6 to 33.4). Conclusion This study confirms the role of histological assessment as an independent risk factor for gastric cancer (GC), but it is the first study to show that an endoscopic classification of gastric intestinal metaplasia is highly associated with that outcome. After further prospective validation, this classification may be appropriate for GC risk stratification and may simplify every day practice by reducing the need for biopsies.
Emotions, Common Sense, and Evidence in Operating Room Attire
Authors: Radwan Dipp Ramos, Kamal M. F. Itani
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Visualizing Synaptic Transfer of Tumor Antigens among Dendritic Cells
Authors: Megan K. Ruhland, Edward W. Roberts, En Cai, Adriana M. Mujal, Kyle Marchuk, Casey Beppler, David Nam, Nina K. Serwas, Mikhail Binnewies, Matthew F. Krummel
Journal: Cancer Cell (2020)

Generation of tumor-infiltrating lymphocytes begins when tumor antigens reach the lymph node (LN) to stimulate T cells, yet we know little of how tumor material is disseminated among the large variety of antigen-presenting dendritic cell (DC) subsets in the LN. Here, we demonstrate that tumor proteins are carried to the LN within discrete vesicles inside DCs and are then transferred among DC subsets. A synapse is formed between interacting DCs and vesicle transfer takes place in the absence of free exosomes. DCs -containing vesicles can uniquely activate T cells, whereas DCs lacking them do not. Understanding this restricted sharing of tumor identity provides substantial room for engineering better anti-tumor immunity.
An immune-cell signature of bacterial sepsis
Authors: Miguel Reyes, Michael R. Filbin, Roby P. Bhattacharyya, Kianna Billman, Thomas Eisenhaure, Deborah T. Hung, Bruce D. Levy, Rebecca M. Baron, Paul C. Blainey, Marcia B. Goldberg, Nir Hacohen
Journal: Nature Medicine (2020)
Type 1 diabetes progression is associated with loss of CD3+CD56+ regulatory T cells that control CD8+ T-cell effector functions
Authors: Giuseppe Terrazzano, Sara Bruzzaniti, Valentina Rubino, Marianna Santopaolo, Anna Teresa Palatucci, Angela Giovazzino, Claudia La Rocca, Paola de Candia, Annibale Puca, Francesco Perna, Claudio Procaccini, Veronica De Rosa, Chiara Porcellini, Salvatore De Simone, Valentina Fattorusso, Antonio Porcellini, Enza Mozzillo, Riccardo Troncone, Adriana Franzese, Johnny Ludvigsson, Giuseppe Matarese, Giuseppina Ruggiero, Mario Galgani
Journal: Nature Metabolism (2020)
A Clinical Practice Guideline for Treating Tobacco Use and Dependence: A US Public Health Service Report
Authors: None The Tobacco Use and Dependence Clinical Practice Guideline Panel, Staff, and Consortium Representatives
Journal: JAMA (2000)

ObjectiveTo summarize the recently published US Public Health Service report Treating Tobacco Use and Dependence: A Clinical Practice Guideline, which provides recommendations for brief clinical interventions, intensive clinical interventions, and system changes to promote the treatment of tobacco dependence.ParticipantsAn independent panel of 18 scientists, clinicians, consumers, and methodologists selected by the US Agency for Healthcare Research and Quality. A consortium of 7 governmental and nonprofit organizations sponsored the update.EvidenceApproximately 6000 English-language, peer-reviewed articles and abstracts, published between 1975 and 1999, were reviewed for data that addressed assessment and treatment of tobacco dependence. This literature served as the basis for more than 50 meta-analyses.Consensus ProcessOne panel meeting and numerous conference calls and staff meetings were held to evaluate meta-analytic and other results, to synthesize the results, and to develop recommendations. The updated guideline was then externally reviewed by more than 70 experts and revised.ConclusionsThis evidence-based, updated guideline provides specific recommendations regarding brief and intensive tobacco cessation interventions as well as system-level changes designed to promote the assessment and treatment of tobacco use. Brief clinical approaches for patients willing and unwilling to quit are described. Major conclusions and recommendations include: (1) Tobacco dependence is a chronic condition that warrants repeated treatment until long-term or permanent abstinence is achieved. (2) Effective treatments for tobacco dependence exist and all tobacco users should be offered those treatments. (3) Clinicians and health care delivery systems must institutionalize the consistent identification, documentation, and treatment of every tobacco user at every visit. (4) Brief tobacco dependence treatment is effective, and every tobacco user should be offered at least brief treatment. (5) There is a strong dose-response relationship between the intensity of tobacco dependence counseling and its effectiveness. (6) Three types of counseling were found to be especially effective—practical counseling, social support as part of treatment, and social support arranged outside of treatment. (7) Five first-line pharmacotherapies for tobacco dependence—sustained-release bupropion hydrochloride, nicotine gum, nicotine inhaler, nicotine nasal spray, and nicotine patch—are effective, and at least 1 of these medications should be prescribed in the absence of contraindications. (8) Tobacco dependence treatments are cost-effective relative to other medical and disease prevention interventions; as such, all health insurance plans should include as a reimbursed benefit the counseling and pharmacotherapeutic treatments identified as effective in the updated guideline.
Vaginal bleeding and spotting in transgender men after initiation of testosterone therapy: A prospective cohort study (ENIGI)
Authors: Justine Defreyne, Yuran Vanwonterghem, Sarah Collet, Sean J. Iwamoto, Chantal M. Wiepjes, Alessandra D. Fisher, Thomas Schreiner, Martin Den Heijer, Guy T’Sjoen
Journal: International Journal of Transgender Health (2020)

Background: Previous studies have cross-sectionally described amenorrhea in cohorts of transgender men on intramuscular or subcutaneous testosterone injections. It remains uncertain which testosterone preparations most effectively suppress vaginal bleeding and when amenorrhea occurs after testosterone initiation.Aim:To investigate the clinical effects of various testosterone preparations on vaginal bleeding and spotting in transgender men.Methods: This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence (ENIGI). Data on the persistence and intensity of vaginal bleeding and spotting, serum sex steroid levels and body composition were prospectively and cross-sectionally assessed in 267 transgender men during a three-year follow-up period, starting at the initiation of various testosterone preparations.Results: After three months of testosterone, 17.9% of transgender men reported persistent vaginal bleeding and 26.8% reported spotting. The percentages reporting vaginal bleeding and spotting decreased over the first year of testosterone (bleeding 4.7% and spotting 6.9% at 12 months, respectively), with no participants reporting vaginal bleeding or spotting after 18 months of testosterone. Factors associated with vaginal bleeding or spotting included lower serum testosterone levels and being on testosterone gel as compared to injections (e.g., esters or undecanoate preparations). If vaginal bleeding persisted, starting progestogens at three months resulted in a decrease in the intensity of vaginal bleeding and spotting.Discussion: Transgender men and hormone-prescribing providers can be reassured that vaginal bleeding and spotting usually stop within three months after testosterone initiation. If not, serum testosterone levels should be measured and testosterone dose adjusted to achieve serum testosterone levels in the physiologic male range. Adding a progestin can be considered after three to six months if bleeding persists. Providers should be aware that cessation of bleeding can be more difficult to achieve in transgender men with lower serum testosterone levels or those on testosterone gel.
Immune-mediated necrotizing myopathies and interstitial lung disease are predominant characteristics in anti-Ku positive patients with idiopathic inflammatory myopathies
Authors: Hongxia Yang, Wenli Li, Xiaolan Tian, Guochun Wang, Xiaoming Shu, Qinglin Peng, Xin Lu
Journal: Annals of the Rheumatic Diseases (2020)

Correspondence patients, respectively.In addition, 1 patient with coexistence of anti-Ku and anti-Jo-1 was diagnosed with non-specific myositis according to the 2004 ENMC classification criteria for IIM(table 1, figure 1). 7n conclusion, the presence of anti-Ku autoantibodies is rare among IIM patients.Concomitant ILD and elevated CK level are common features of anti-Ku positive patients.However, the clinical and pathological characteristics are distinct in patients with isolated anti-Ku and those with coexistence of anti-Ku and MSA.Skin rash is more common in patients with coexistence of anti-Ku and MSA, while severe ILD and IMNM are common in patients with isolated anti-Ku.Further studies on the characteristics of anti-Ku-positive IIM using larger cohorts are warranted.
Developing your career as a haematologist
Authors: Jacqui Wise
Journal: BMJ (2020)

Haematology is a flexible specialty that offers the opportunity to develop special interests in a variety of clinical and laboratory areas. It is also possible to combine a clinical and academic career.

A certificate of completion of training is awarded by the General Medical Council once a trainee successfully completes specialist training, has passed the Fellow of the Royal College of Pathologists examination, and is deemed competent by the specialist advisory committee. They will then be placed on the specialist register and allowed to apply for consultant posts.

The Royal College of Pathologists 2017 census showed there were 1035 consultant haematologists across the UK. The 2018 workforce survey identified 76 consultants working in paediatric haematology with a further eight vacant consultant posts in that area

Haematologists are responsible for the management of acute and chronic haematological conditions in NHS hospitals; in addition, they provide clinical oversight for haematology laboratory services and a liaison service which supports all other areas of the hospital and community medical services. Haematology consultant posts range from general hospital posts which cover all areas of haematology to more specialist posts in larger …
Structure of intact IgE and the mechanism of ligelizumab revealed by electron microscopy
Authors: Rasmus K. Jensen, Frederic Jabs, Michaela Miehe, Brian Mølgaard, Wolfgang Pfützner, Christian Möbs, Edzard Spillner, Gregers R. Andersen
Journal: Allergy (2020)

Abstract Background IgE is the central antibody isotype in TH2‐biased immunity and allergic diseases. The structure of intact IgE and the impact of IgE‐targeting molecules on IgE however remain elusive. In order to obtain insights into IgE biology and the clinical impact, we aimed for structure determination of IgE and the complex of IgE with the anti‐IgE antibody ligelizumab. Methods Structures of two distinct intact IgE with specificity for cross‐reactive carbohydrate determinants and Der p 2 as well as complexes of ligelizumab‐Fab with IgE and IgE Fc were assessed by negative stain electron microscopy and solution scattering. Inhibition of IgE binding and displacement of receptor‐bound IgE were assessed using cellular assays, basophil activation testing and ELIFAB assays. Results Our data reveal that the investigated IgE molecules share an overall rigid conformation. In contrast to the IgE Fc fragment, the IgE Fc in intact IgE is significantly less asymmetrically bent. The proximal and the distal Fabs are rigidly tethered to the Fc. Binding of ligelizumab to IgE in a 2:1 stoichiometry induces an extended and twofold symmetrical conformation of IgE, which retains a rigid Fab‐Fc architecture. Analyses of effector cell activation revealed that ligelizumab inhibits IgE binding without displacing receptor‐bound IgE. Together with an interference of CD23 binding, the data underline a functional activity similar to omalizumab. Conclusions Our data reveal the first structures of intact IgE suggesting that the IgE Fab is fixed relative to the Fc. Furthermore, we provide a structural rationale for the inhibitory mechanism of ligelizumab.