The history of the Connell Stitch begins at the Milwaukee County Hospital in 1887 and continues across two generations of surgeons, Dr. M.E. Connell and Dr. F Gregory Connell. With this historical ...article, we review the evolution of the Connell stitch in context of the surgeons responsible for the stitch’s development and evolution. Understanding the history of the Connell stitch facilitates a better appreciation for the Connell Stitch that we know and use today.
Patients with B-cell lymphomas have altered cellular components of vaccine responses due to malignancy and therapy, and the optimal timing of vaccination relative to therapy remains unknown. ...SARS-CoV-2 vaccines created an opportunity for new insights in vaccine timing because patients were challenged with a novel antigen across multiple phases of treatment. We studied serologic mRNA vaccine response in retrospective and prospective cohorts with lymphoma and CLL, paired with clinical and research immune parameters. Reduced serologic response was observed more frequently during active therapies, but non-response was also common within observation and post-treatment groups. Total IgA and IgM correlated with successful vaccine response. In individuals treated with CART-19, non-response was associated with reduced B and T follicular helper cells. Predictors of vaccine response varied by disease and therapeutic group, and therefore further studies of immune health during and after cancer therapies are needed to allow individualized vaccine timing.
Abstract Patients with B-cell lymphomas have altered cellular components of vaccine responses due to malignancy and therapy, and the optimal timing of vaccination relative to therapy remains unknown. ...Severe acute respiratory syndrome coronavirus 2 vaccines created an opportunity for new insights in vaccine timing because patients were challenged with a novel antigen across multiple phases of treatment. We studied serologic messenger RNA vaccine response in retrospective and prospective cohorts with lymphoma and chronic lymphocytic leukemia, paired with clinical and research immune parameters. Reduced serologic response was observed more frequently during active treatment, but nonresponse was also common within observation and posttreatment groups. Total immunoglobulin A and immunoglobulin M correlated with successful vaccine response. In individuals treated with anti-CD19–directed chimeric antigen receptor–modified T cells, nonresponse was associated with reduced B and T follicular helper cells. Predictors of vaccine response varied by disease and therapeutic group, and therefore further studies of immune health during and after cancer therapies are needed to individualize vaccine timing.
How many human proteoforms are there? Aebersold, Ruedi; Agar, Jeffrey N; Amster, I Jonathan ...
Nature chemical biology,
02/2018, Letnik:
14, Številka:
3
Journal Article
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Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One ...of the most fundamental queries is the extent to which the combinations of DNA-, RNA- and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype.
The 2017 EULAR/ACR classification criteria for adult/juvenile idiopathic inflammatory myopathies (IIM) were established using a data-driven approach by an international group of myositis experts to ...allow classification of IIM and its major subtypes. Since their publication, the performance of the criteria has been tested in multiple cohorts worldwide and significant limitations have been identified. Moreover, the understanding and classification of IIM have evolved since 2017. This scoping review was undertaken as part of a large international project to revise the EULAR/ACR criteria and aims to i) summarise the evidence from the current literature on the performance characteristics of the 2017 EULAR/ACR classification criteria in various cohorts and IIM subtypes, and ii) delineate the factors that need to be considered in the revision of the classification criteria. A systematic search of Medline (via PubMed), Cumulative Index to Nursing and Allied Health Literature, and conference abstract archives was conducted independently by three investigators for studies on the EULAR/ACR criteria published between October 2017 and January 2023. This scoping review of 19 articles and 13 abstracts revealed overall good performance characteristics of the EULAR/ACR criteria for IIM, yet deficiencies in lack of inclusion of certain IIM subtypes, such as immune mediated necrotising myopathy, amyopathic dermatomyositis, antisynthetase syndrome and overlap myositis. Published modifications that may improve the performance characteristics of the criteria for classification of IIM subtypes were also summarised. The results of this review suggest that a revision of the EULAR/ACR criteria is warranted.
ObjectiveDigital symptom-checkers (SCs) have potential to improve rheumatology triage and reduce diagnostic delays. In addition to being accurate, SCs should be user friendly and meet patient’s ...needs. Here, we examined usability and acceptance of Rheumatic?—a new and freely available online SC (currently with >44 000 users)—in a real-world setting.MethodsStudy participants were recruited from an ongoing prospective study, and included people ≥18 years with musculoskeletal complaints completing Rheumatic? online. The user experience survey comprised five usability and acceptability questions (11-point rating scale), and an open-ended question regarding improvement of Rheumatic? Data were analysed in R using t-test or Wilcoxon rank test (group comparisons), or linear regression (continuous variables).ResultsA total of 12 712 people completed the user experience survey. The study population had a normal age distribution, with a peak at 50–59 years, and 78% women. A majority found Rheumatic? useful (78%), thought the questionnaire gave them an opportunity to describe their complaints well (76%), and would recommend Rheumatic? to friends and other patients (74%). Main shortcoming was that 36% thought there were too many questions. Still, 39% suggested more detailed questions, and only 2% suggested a reduction of questions.ConclusionBased on real-world data from the largest user evaluation study of a digital SC in rheumatology, we conclude that Rheumatic? is well accepted by women and men with rheumatic complaints, in all investigated age groups. Wide-scale adoption of Rheumatic?, therefore, seems feasible, with promising scientific and clinical implications on the horizon.
Plasma-derived polyclonal antibody therapeutics, such as intravenous immunoglobulin, have multiple drawbacks, including low potency, impurities, insufficient supply and batch-to-batch variation. Here ...we describe a microfluidics and molecular genomics strategy for capturing diverse mammalian antibody repertoires to create recombinant multivalent hyperimmune globulins. Our method generates of diverse mixtures of thousands of recombinant antibodies, enriched for specificity and activity against therapeutic targets. Each hyperimmune globulin product comprised thousands to tens of thousands of antibodies derived from convalescent or vaccinated human donors or from immunized mice. Using this approach, we generated hyperimmune globulins with potent neutralizing activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in under 3 months, Fc-engineered hyperimmune globulins specific for Zika virus that lacked antibody-dependent enhancement of disease, and hyperimmune globulins specific for lung pathogens present in patients with primary immune deficiency. To address the limitations of rabbit-derived anti-thymocyte globulin, we generated a recombinant human version and demonstrated its efficacy in mice against graft-versus-host disease.
Voices in methods development Anikeeva, Polina; Boyden, Edward; Brangwynne, Clifford ...
Nature methods,
10/2019, Letnik:
16, Številka:
10
Journal Article
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To mark the 15th anniversary of Nature Methods, we asked scientists from across diverse fields of basic biology research for their views on the most exciting and essential methodological challenges ...that their communities are poised to tackle in the near future.
IntroductionLung cancer is a significant burden on societies worldwide, and the most common cause of death in patients with cancer overall. Exercise intervention studies in patients with lung cancer ...have consistently shown benefits with respect to physical and emotional functioning. However, to date, exercise training has not been consistently implemented into clinical practice given that interventions have been costly and not aligned with clinical care.Methods/designThe Precision-Exercise-Prescription (PEP) study is a prospective randomised controlled trial comparing the effectiveness and feasibility of a personalised intervention exercise programme among patients with lung cancer undergoing surgery. Two-hundred patients who are diagnosed with stage primary or secondary lung cancer and are eligible to undergo surgical treatment at Huntsman Cancer Institute comprise the target population. Patients are randomised to either the (1) outpatient precision-exercise intervention group or (2) delayed intervention group. The intervention approach uses Motivation and Problem Solving, a hybrid behavioural treatment based on motivational interviewing and practical problem solving. The dosage of the exercise intervention is personalised based on the individual’s Activity Measure for Post-Acute-Care outpatient basic mobility score, and incorporates four exercise modes: mobility, callisthenics, aerobic and resistance. Exercise is implemented by physical therapists at study visits from presurgery until 6 months postsurgery. The primary endpoint is the level of physical function assessed by 6 min walk distance at 2 months postsurgery. Secondary outcomes include patient-reported outcomes (eg, quality of life, fatigue and self-efficacy) and other clinical outcomes, including length of stay, complications, readmission, pulmonary function and treatment-related costs up to 6 months postsurgery.Ethics/disseminationThe PEP study will test the clinical effectiveness and feasibility of a personalised exercise intervention in patients with lung cancer undergoing surgery. Outcomes of this clinical trial will be presented at national and international conferences and symposia and will be published in international, peer-reviewed journals. Ethics approval was obtained at the University of Utah (IRB 00104671).Trial registration number NCT03306992.
The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- ...these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.
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