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[This corrects the article DOI: 10.1371/journal.pgen.1004747.].

The Banff Digital Pathology Working Group (DPWG) was established with the goal to establish a digital pathology repository; develop, validate, and share models for image analysis; and foster collaborations using regular videoconferencing. During the calls, a variety of artificial intelligence (AI)-based support systems for transplantation pathology were presented. Potential collaborations in a competition/trial on AI applied to kidney transplant specimens, including the DIAGGRAFT challenge (staining of biopsies at multiple institutions, pathologists’ visual assessment, and development and validation of new and pre-existing Banff scoring algorithms), were also discussed. To determine the next steps, a survey was conducted, primarily focusing on the feasibility of establishing a digital pathology repository and identifying potential hosts. Sixteen of the 35 respondents (46%) had access to a server hosting a digital pathology repository, with 2 respondents that could serve as a potential host at no cost to the DPWG. The 16 digital pathology repositories collected specimens from various organs, with the largest constituent being kidney (n = 12,870 specimens). A DPWG pilot digital pathology repository was established, and there are plans for a competition/trial with the DIAGGRAFT project. Utilizing existing resources and previously established models, the Banff DPWG is establishing new resources for the Banff community.

YT521-B homology (YTH) domain proteins act as readers of N6-methyladenosine (m6A) in mRNA. Members of the YTHDF clade determine properties of m6A-containing mRNAs in the cytoplasm. Vertebrates encode three YTHDF proteins whose possible functional specialization is debated. In land plants, the YTHDF clade has expanded from one member in basal lineages to eleven so-called EVOLUTIONARILY CONSERVED C-TERMINAL REGION1-11 (ECT1-11) proteins in Arabidopsis thaliana, named after the conserved YTH domain placed behind a long N-terminal intrinsically disordered region (IDR). ECT2, ECT3 and ECT4 show genetic redundancy in stimulation of primed stem cell division, but the origin and implications of YTHDF expansion in higher plants are unknown, as it is unclear whether it involves acquisition of fundamentally different molecular properties, in particular of their divergent IDRs. Here, we use functional complementation of ect2/ect3/ect4 mutants to test whether different YTHDF proteins can perform the same function when similarly expressed in leaf primordia. We show that stimulation of primordial cell division relies on an ancestral molecular function of the m6A-YTHDF axis in land plants that is present in bryophytes and is conserved over YTHDF diversification, as it appears in all major clades of YTHDF proteins in flowering plants. Importantly, although our results indicate that the YTH domains of all arabidopsis ECT proteins have m6A-binding capacity, lineage-specific neo-functionalization of ECT1, ECT9 and ECT11 happened after late duplication events, and involves altered properties of both the YTH domains, and, especially, of the IDRs. We also identify two biophysical properties recurrent in IDRs of YTHDF proteins able to complement ect2 ect3 ect4 mutants, a clear phase separation propensity and a charge distribution that creates electric dipoles. Human and fly YTHDFs do not have IDRs with this combination of properties and cannot replace ECT2/3/4 function in arabidopsis, perhaps suggesting different molecular activities of YTHDF proteins between major taxa.

Antibiotic resistance has become a serious threat to global public health and economic development. Rapid and accurate identification of a patient status for antimicrobial resistance (AMR) are urgently needed in clinical diagnosis. Here we describe the development of an assay method for activity fingerprinting of AMR β-lactamases using panels of 7 β-lactam antibiotics in 35 min. New Deli Metallo β-lactamase-1 (NDM-1) and penicillinase were demonstrated as two different classes of β-lactamases. The panel consisted of three classes of antibiotics, including: penicillins (penicillin G, piperacillin), cephalosporins (cefepime, ceftriaxone, cefazolin) and carbapenems (meropenem and imipenem). The assay employed a scheme combines the catalytic reaction of AMR β-lactamases on antibiotic substrates with a flow-injected thermometric biosensor that allows the direct detection of the heat generated from the enzymatic catalysis, and eliminates the need for custom substrates and multiple detection schemes. In order to differentiate classes of β-lactamases, characterization of the enzyme activity under different catalytic condition, such as, buffer composition, ion strength and pH were investigated. This assay could provide a tool for fast diagnosis of patient AMR status which makes possible for the future accurate treatment with selected antibiotics.

Students and researchers might have diverse ideas about and motivations for citizen science (CS) projects. To prevent uncertainty, we address ethical concerns emerging in CS projects and in CS in general, specifically, the transferability of the ethical skills and knowledge gained within academia (e.g. through studying and research conduct). We dedicate these Guidelines for Research Ethics and Research Integrity in Citizen Science primarily to Masters and Doctoral students and their supervisors, to facilitate CS-related research activities (i.e. mainstream CS) in line with the values of academic integrity. Using a pool of 85 papers, we identified nine topics covering 22 customised guidelines and supplemented them with further readings to build more in-depth knowledge.

Abstract Large epidemiological studies such as the UK Biobank (UKBB) or German National Cohort (NAKO) provide unprecedented health-related data of the general population aiming to better understand determinants of health and disease. As part of these studies, Magnetic Resonance Imaging (MRI) is performed in a subset of participants allowing for phenotypical and functional characterization of different organ systems. Due to the large amount of imaging data, automated image analysis is required, which can be performed using deep learning methods, e. g. for automated organ segmentation. In this paper we describe a computational pipeline for automated segmentation of abdominal organs on MRI data from 20,000 participants of UKBB and NAKO and provide results of the quality control process. We found that approx. 90% of data sets showed no relevant segmentation errors while relevant errors occurred in a varying proportion of data sets depending on the organ of interest. Image-derived features based on automated organ segmentations showed relevant deviations of varying degree in the presence of segmentation errors. These results show that large-scale, deep learning-based abdominal organ segmentation on MRI data is feasible with overall high accuracy, but visual quality control remains an important step ensuring the validity of down-stream analyses in large epidemiological imaging studies.

Abstract Even though each adolescent is unique, some ingredients for development may still be universal. According to Self-Determination Theory, every adolescent’s well-being should benefit when parents provide warmth and autonomy. To rigorously test this idea that each family has similar mechanisms, we followed 159 Dutch parent-adolescent dyads (parent: M age = 45.34, 79% mothers; adolescent: M age = 13.31, 62% female) for more than three months, and collected 100 consecutive daily reports of parental warmth, autonomy support, positive and negative affect. Positive effects of parental warmth and autonomy support upon well-being were found in 91–98% of the families. Preregistered analysis of 14,546 daily reports confirmed that effects of parenting differed in strength (i.e., some adolescents benefited more than others), but were universal in their direction (i.e., in fewer than 1% of families effects were in an unexpected direction). Albeit stronger with child-reported parenting, similar patterns were found with parent-reports. Adolescents who benefited most from need-supportive parenting in daily life were characterized by higher overall sensitivity to environmental influences. Whereas recent work suggests that each child and each family have unique developmental mechanisms, this study suggests that need-supportive parenting promotes adolescent well-being in most families.

Wenjia Chen,1 Mohsen Sadatsafavi,2 Trung N Tran,3 Ruth B Murray,4 Chong Boon Nigel Wong,1 Nasloon Ali,4,5 Cono Ariti,4,5 Esther Garcia Gil,6 Anthony Newell,5,7 Marianna Alacqua,8 Mona Al-Ahmad,9 Alan Altraja,10 Riyad Al-Lehebi,11,12 Mohit Bhutani,13 Leif Bjermer,14 Anne Sofie Bjerrum,15 Arnaud Bourdin,16 Lakmini Bulathsinhala,4,5 Anna von Bülow,17 John Busby,18 Giorgio Walter Canonica,19,20 Victoria Carter,4,5 George C Christoff,21 Borja G Cosio,22 Richard W Costello,23 J Mark FitzGerald,24 João A Fonseca,25 Kwang Ha Yoo,26 Liam G Heaney,27 Enrico Heffler,19,20 Mark Hew,28,29 Ole Hilberg,30 Flavia Hoyte,31,32 Takashi Iwanaga,33 David J Jackson,34,35 Rupert C Jones,36 Mariko Siyue Koh,37,38 Piotr Kuna,39 Désirée Larenas-Linnemann,40 Sverre Lehmann,41 Lauri A Lehtimäki,42,43 Juntao Lyu,5,7 Bassam Mahboub,44,45 Jorge Maspero,46,47 Andrew N Menzies-Gow,48 Concetta Sirena,49 Nikolaos Papadopoulos,50,51 Andriana I Papaioannou,52 Luis Pérez de Llano,53,54 Diahn-Warng Perng,55,56 Matthew Peters,57 Paul E Pfeffer,58,59 Celeste M Porsbjerg,17 Todor A Popov,60 Chin Kook Rhee,61 Sundeep Salvi,62 Camille Taillé,63 Christian Taube,64 Carlos A Torres-Duque,65 Charlotte S Ulrik,66 Seung Won Ra,67 Eileen Wang,31,32 Michael E Wechsler,68 David B Price4,5,69 1Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore; 2Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada; 3AstraZeneca, Gaithersburg, MD, USA; 4Optimum Patient Care, Cambridge, UK; 5Observational and Pragmatic Research Institute, Singapore, Singapore; 6AstraZeneca, Barcelona, Spain; 7Optimum Patient Care, Queensland, VIC, Australia; 8AstraZeneca, Cambridge, UK; 9Microbiology Department, Faculty of Medicine, Kuwait University, Al-Rashed Allergy Center, Ministry of Health, Kuwait City, Kuwait; 10Department of Pulmonology, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia; 11Department of Pulmonology, King Fahad Medical City, Riyadh, Saudi Arabia; 12College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; 13Department of Medicine, Division of Pulmonary Medicine, University of Alberta, Western Canada, AB, Canada; 14Department of Clinical Sciences, Respiratory Medicine and Allergology, Skåne University Hospital, Lund University, Lund, Sweden; 15Department of Respiratory Medicine and Allergy, Aarhus University Hospital, Jutland, Aarhus, Denmark; 16PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France; 17Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark; 18Centre for Public Health, Queen’s University Belfast, Belfast, Northern Ireland; 19Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center IRCCS, Milan, Italy; 20Department of Biomedical Sciences, Humanitas University, Milan, Italy; 21Medical University-Sofia, Faculty of Public Health, Sofia, Bulgaria; 22Son Espases University Hospital-IdISBa-Ciberes, Mallorca, Spain; 23Department of Respiratory Medicine, Clinical Research Centre, Smurfit Building Beaumont Hospital, RCSI, Dublin, Ireland; 24Department of Medicine, the University of British Columbia, Vancouver, BC, Canada; 25Comunity Health, Information and Decision Sciences Department (MEDCIDS) & Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine of University of Porto, Porto, Portugal; 26KonKuk University School of Medicine in Seoul, Seoul, Korea; 27Wellcome-Wolfson Centre for Experimental Medicine, Queen’s University Belfast, Belfast, Northern Ireland; 28Allergy, Asthma & Clinical Immunology Service, Alfred Health, Melbourne, VIC, Australia; 29Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; 30Medical Department, Vejle University Hospital, Jutland, Vejle, Denmark; 31Department of Medicine, Division of Allergy and Clinical Immunology, National Jewish Health, Denver, CO, USA; 32Department of Internal Medicine, Division of Allergy & Clinical Immunology, University of Colorado School of Medicine, Aurora, CO, USA; 33Center for General Medical Education and Clinical Training, Kindai University Hospital, Osakasayama, Japan; 34UK Severe Asthma Network and National Registry, Guy’s and St Thomas’ NHS Trust, London, UK; 35School of Immunology & Microbial Sciences, King’s College London, London, UK; 36Research and Knowledge Exchange, Plymouth Marjon University, Plymouth, UK; 37Respiratory & Critical Care Medicine, Singapore General Hospital, Singapore, Singapore; 38SingHealth Duke-NUS Lung Centre, Singapore, Singapore; 39Division of Internal Medicine, Asthma and Allergy Medical University of &Lstrok;ód&zacute;, &Lstrok;ód&zacute;, Poland; 40Directora Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico; 41Section of Thoracic Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway; 42Allergy Centre, Tampere University Hospital, Tampere, Finland; 43Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 44College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; 45Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates; 46Clinical Research for Allergy and Respiratory Medicine, CIDEA Foundation, Buenos Aires, Argentina; 47University Career of Specialists in Allergy and Clinical Immunology at the Buenos Aires University School of Medicine, Buenos Aires, Argentina; 48Royal Brompton & Harefield Hospitals, London, UK; 49Severe Asthma Network in Italy (SANI), Milano, Italy; 50Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK; 51Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece; 52 2nd Respiratory Medicine Department, National and Kapodistrian University of Athens Medical School, Attikon University Hospital, Athens, Greece; 53Pneumology Service, Lucus Augusti University Hospital, EOXI Lugo, Lugo, Spain; 54Biodiscovery Research Group, Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain; 55Division of Clinical Respiratory Physiology Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan; 56COPD Assembly of the Asian Pacific Society of Respirology Hongo, Bunkyo-ku, Tokyo, Japan; 57Department of Thoracic Medicine, Concord Hospital, Sydney, NSW, Australia; 58Department of Respiratory Medicine, Barts Health NHS Trust, London, UK; 59Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; 60University Hospital ”sv. Ivan Rilski”, Sofia, Bulgaria; 61Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, South Korea; 62Pulmocare Research and Education Foundation, Pune, India; 63Department of Respiratory Diseases, Bichat Hospital, AP-HP Nord-Université de Paris, Paris, France; 64Department of Pulmonary Medicine, University Medical Center Essen-Ruhrlandklinik, Essen, Germany; 65CINEUMO, Respiratory Research Center, Fundación Neumológica Colombiana, Bogotá, Colombia; 66Department of Respiratory Medicine, Copenhagen University Hospital-Hvidovre, Hvidovre, Denmark; 67Department of Internal Medicine, Division of Pulmonology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea; 68Department of Medicine, NJH Cohen Family Asthma Institute, National Jewish Health, Denver, CO, USA; 69Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David B Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, &num;06 Midview City, Singapore, Singapore, 573969, Tel +65 3105 1489, Email dprice@opri.sgBackground: Many severe asthma patients with high oral corticosteroid exposure (HOCS) often do not initiate biologics despite being eligible. This study aimed to compare the characteristics of severe asthma patients with HOCS who did and did not initiate biologics.Methods: Baseline characteristics of patients with HOCS (long-term maintenance OCS therapy for at least 1 year, or ≥ 4 courses of steroid bursts in a year) from the International Severe Asthma Registry (ISAR; https://isaregistries.org/), who initiated or did not initiate biologics (anti-lgE, anti-IL5/5R or anti-IL4R), were described at the time of biologic initiation or registry enrolment. Statistical relationships were tested using Pearson’s chi-squared tests for categorical variables, and t-tests for continuous variables, adjusting for potential errors in multiple comparisons.Results: Between January 2015 and February 2021, we identified 1412 adult patients with severe asthma from 19 countries that met our inclusion criteria of HOCS, of whom 996 (70.5%) initiated a biologic and 416 (29.5%) did not. The frequency of biologic initiation varied across geographical regions. Those who initiated a biologic were more likely to have higher blood eosinophil count (483 vs 399 cells/μL, p=0.003), serious infections (49.0% vs 13.3%, p< 0.001), nasal polyps (35.2% vs 23.6%, p< 0.001), airflow limitation (56.8% vs 51.8%, p=0.013), and uncontrolled asthma (80.8% vs 73.2%, p=0.004) despite greater conventional treatment adherence than those who did not start a biologic. Both groups had similar annual asthma exacerbation rates in the previous 12 months (5.7 vs 5.3, p=0.147).Conclusion: Around one third of severe HOCS asthma patients did not receive biologics despite a similar high burden of asthma exacerbations as those who initiated a biologic therapy. Other disease characteristics such as eosinophilic phenotype, serious infectious events, nasal polyps, airflow limitation and lack of asthma control appear to dictate biologic use.Keywords: severe asthma, biologics, real-world, treatment pattern, patient characteristics

Abstract Background In acute pancreatitis, secondary infection of pancreatic necrosis is a complication that mostly necessitates interventional therapy. A reliable prediction of infected necrotizing pancreatitis would enable an early identification of patients at risk, which however, is not possible yet. Methods This study aims to identify parameters that are useful for the prediction of infected necrosis and to develop a prediction model for early detection. We conducted a retrospective analysis from the hospital information and reimbursement data system and screened 705 patients hospitalized with diagnosis of acute pancreatitis who underwent contrast-enhanced computed tomography and additional diagnostic puncture or drainage of necrotic collections. Both clinical and laboratory parameters were analyzed for an association with a microbiologically confirmed infected pancreatic necrosis. A prediction model was developed using a logistic regression analysis with stepwise inclusion of significant variables. The model quality was tested by receiver operating characteristics analysis and compared to single parameters and APACHE II score. Results We identified a total of 89 patients with necrotizing pancreatitis, diagnosed by computed tomography, who additionally received biopsy or drainage. Out of these, 59 individuals had an infected necrosis. Eleven parameters showed a significant association with an infection including C-reactive protein, albumin, creatinine, and alcoholic etiology, which were independent variables in a predictive model. This model showed an area under the curve of 0.819, a sensitivity of 0.692 (95%-CI [0.547–0.809]), and a specificity of 0.840 (95%-CI [0.631–0.947]), outperforming single laboratory markers and APACHE II score. Even in cases of missing values predictability was reliable. Conclusion A model consisting of a few single blood parameters and etiology of pancreatitis might help for differentiation between infected and non-infected pancreatic necrosis and assist medical therapy in acute necrotizing pancreatitis.

Abstract Background Renal hypoperfusion has been suggested to contribute to the development of acute kidney injury (AKI) in critical COVID-19. However, limited data exist to support this. We aim to investigate the differences in renal perfusion, oxygenation and water diffusion using multiparametric magnetic resonance imaging in critically ill COVID-19 patients with and without AKI. Methods A prospective case–control study where patients without prior kidney disease treated in intensive care for respiratory failure due to COVID-19 were examined. Kidney Disease: Improving Global Outcomes Creatinine criteria were used for group allocation. Main comparisons were tested using Mann–Whitney U test. Results Nineteen patients were examined, ten with AKI and nine without AKI. Patients with AKI were examined in median 1 [0–2] day after criteria fulfillment. Age and baseline Plasma-Creatinine were similar in both groups. Total renal blood flow was lower in patients with AKI compared with patients without (median 645 quartile range [423–753] vs. 859 [746–920] ml/min, p = 0.037). Regional perfusion was reduced in both cortex (76 [51–112] vs. 146 [123–169] ml/100 g/min, p = 0.015) and medulla (28 [18–47] vs. 47 [38–73] ml/100 g/min, p = 0.03). Renal venous saturation was similar in both groups (72% [64–75] vs. 72% [63–84], ns.), as was regional oxygenation (R 2*) in cortex (17 [16–19] vs. 17 [16–18] 1/s, ns.) and medulla (29 [24–39] vs. 27 [23–29] 1/s, ns.). Conclusions In critically ill COVID-19 patients with AKI, the total, cortical and medullary renal blood flows were reduced compared with similar patients without AKI, whereas no differences in renal oxygenation were demonstrable in this setting. Trial registration ClinicalTrials ID: NCT02765191 , registered May 6 2014 and updated May 7 2020. Graphic Abstract

Background and purpose: Antibiotic-loaded bone cement (ALBC) and systemic antibiotic prophylaxis (SAP) have been used to reduce periprosthetic joint infection (PJI) rates. We investigated the use of ALBC and SAP in primary total knee arthroplasty (TKA). Patients and methods: This observational study is based on 2,971,357 primary TKAs reported in 2010–2020 to national/regional joint arthroplasty registries in Australia, Denmark, Finland, Germany, Italy, the Netherlands, New Zealand, Norway, Romania, South Africa, Sweden, Switzerland, the UK, and the USA. Aggregate-level data on trends and types of bone cement, antibiotic agents, and doses and duration of SAP used was extracted from participating registries. Results: ALBC was used in 77% of the TKAs with variation ranging from 100% in Norway to 31% in the USA. Palacos R+G was the most common (62%) ALBC type used. The primary antibiotic used in ALBC was gentamicin (94%). Use of ALBC in combination with SAP was common practice (77%). Cefazolin was the most common (32%) SAP agent. The doses and duration of SAP used varied from one single preoperative dosage as standard practice in Bolzano, Italy (98%) to 1-day 4 doses in Norway (83% of the 40,709 TKAs reported to the Norwegian arthroplasty register). Conclusion: The proportion of ALBC usage in primary TKA varies internationally, with gentamicin being the most common antibiotic. ALBC in combination with SAP was common practice, with cefazolin the most common SAP agent. The type of ALBC and type, dose, and duration of SAP varied among participating countries.

BackgroundTrauma causes disability and mortality globally, leading to fractures and hemorrhagic shock. This can trigger an irregular inflammatory response that damages remote organs, including liver. Aging increases the susceptibility to dysregulated immune responses following trauma, raising the risk of organ damage, infections, and higher morbidity and mortality in elderly patients. This study investigates how aging affects liver inflammation and damage post-trauma.Methods24 male C57BL/6J mice were randomly divided into four groups. Twelve young (17-26 weeks) and 12 aged (64-72 weeks) mice were included. Mice further underwent either hemorrhagic shock (trauma/hemorrhage, TH), and femoral fracture (osteotomy) with external fixation (Fx) (THFx, n=6) or sham procedures (n=6). After 24 hours, mice were sacrificed. Liver injury and apoptosis were evaluated using hematoxylin-eosin staining and activated caspase-3 immunostaining. CXCL1 and infiltrating polymorphonuclear leukocytes (PMNL) in the liver were assessed by immunostaining, and concentrations of CXCL1, TNF, IL-1β, and IL-10 in the liver tissue were determined by ELISA. Gene expression of Tnf, Cxcl1, Il-1β, and Cxcl2 in the liver tissue was determined by qRT-PCR. Finally, western blot was used to determine protein expression levels of IκBα, Akt, and their phosphorylated forms.ResultsTHFx caused liver damage and increased presence of active caspase-3-positive cells compared to the corresponding sham group. THFx aged group had more severe liver injury than the young group. CXCL1 and PMNL levels were significantly higher in both aged groups, and THFx caused a greater increase in CXCL and PMNL levels in aged compared to the young group. Pro-inflammatory TNF and IL-1β levels were elevated in aged groups, further intensified by THFx. Anti-inflammatory IL-10 levels were lower in aged groups. Tnf and Cxcl1 gene expression was enhanced in the aged sham group. Phosphorylation ratio of IκBα was significantly increased in the aged sham group versus young sham group. THFx-induced IκBα phosphorylation in the young group was significantly reduced in the aged THFx group. Akt phosphorylation was significantly reduced in the THFx aged group compared to the THFx young group.ConclusionThe findings indicate that aging may lead to increased vulnerability to liver injury and inflammation following trauma due to dysregulated immune responses.

Chronic pulmonary infection is a hallmark of cystic fibrosis (CF) and requires continuous antibiotic treatment. In this context, Pseudomonas aeruginosa (Pa) is of special concern since colonizing strains frequently acquire multiple drug resistance (MDR). Bactericidal/permeability-increasing protein (BPI) is a neutrophil-derived, endogenous protein with high bactericidal potency against Gram-negative bacteria. However, a significant range of people with CF (PwCF) produce anti-neutrophil cytoplasmic antibodies against BPI (BPI-ANCA), thereby neutralizing its bactericidal function. In accordance with literature, we describe that 51.0% of a total of 39 PwCF expressed BPI-ANCA. Importantly, an orthologous protein to human BPI (huBPI) derived from the scorpionfish Sebastes schlegelii (scoBPI) completely escaped recognition by these autoantibodies. Moreover, scoBPI exhibited high anti-inflammatory potency towards Pa LPS and was bactericidal against MDR Pa derived from PwCF at nanomolar concentrations. In conclusion, our results highlight the potential of highly active orthologous proteins of huBPI in treatment of MDR Pa infections, especially in the presence of BPI-ANCA.

In this paper, various dimensions of care involved in mathematics education are linked to the need to develop classroom activities that connect mathematics and social justice issues. Drawing from literature that shows cognition is situated and embodied, the importance of meaningful contextualization and social interaction when learning mathematics is highlighted. The concept of “simulation-based mathematics and social justice activities” is presented as an approach for the work of bringing social justice issues that have mathematics at their core to the classroom. Theoretical constructs and examples are discussed, to illustrate what such simulations may entail and what may be learned from scholars, in different educational fields, who use simulations in classroom activities. Potentially beneficial features of social justice simulations are related to various educational goals, such as: decreasing arbitrary boundaries between mathematical sub-areas and between mathematics and other disciplines; providing opportunities for choice and the embodiment of different perspectives; and offering opportunities for inter-personal learning. I report on a simulation-based mathematics and social justice activity, conducted in a teacher education classroom. Students—in this case future teachers—were prompted to write reflectively about their participation in the activity. My interest lies in finding out what, if any, cognitive and affective benefits these prospective teachers connect with their experience of mathematics in the activity. To investigate this, I analyze six themes that are present in the data and illustrate each theme using excerpts of student writing. The thematic analysis allows us to learn about connections made by these students, between mathematics, in the context of the activity, and issues that are personally meaningful to them, such as: their own future teaching practice, learning and interacting with peers, beliefs and feelings about mathematics and the learning of mathematics, and different perspectives on complex decisions, involving cooperation or lack thereof, that are encountered in real life situations.

Globins are usually associated with oxygen carriage in vertebrates. However, plants also contain similar heme-containing proteins, called phytoglobins (Pgbs). Unlike conventional hemoglobin, these proteins are often linked to nitric oxide metabolism, energy metabolism and redox maintenance under hypoxic and related abiotic and biotic stress conditions. Class I and II non-symbiotic Pgbs (nsPgbs) have different degrees of heme hexacoordination. This involves direct interaction of the distal histidine in the E-helix with the sixth coordination site of the central iron, resulting in increased stability, in contrast to the oxygen storage linked to pentacoordinated globins, such as myoglobin (Mb). Due to their robustness, nsPgbs have substantial potential for various biomedical applications, particularly for iron supplementation. In this study, a class I nsPgb from sugar beet (Beta vulgaris ssp. vulgaris) was encapsulated in a lipid sponge phase system for potential protein delivery purposes and compared to a similar system of Mb containing nanoparticles. Bulk phases and dispersions were made with two lipid compositions (30/45/25 diglycerol monooleate (DGMO)/Capmul GMO-50/sorbitan monooleate (P80) and 28/42/30 DGMO/GMO-50/P80, where the DGMO/GMO-50 ratio was kept constant at 40/60). In addition, buffer effects on protein loading and particle formation were investigated. High concentrations of BvPgb1.2 (60 mg/mL) showed higher aggregation tendencies than Mb but these appeared to be transient. This property could be coupled to the higher isoelectric point (pI) of the BvPgb1.2 (7.85, compared to 6.8 for Mb), which make it more sensitive to small pH changes. In addition, excess protein/leakage was observed with Mb from the nanoparticles when analysed with size exclusion chromatography. This work highlighted the encapsulation efficiency of these proteins, which might be directly linked to difference in iron coordination and therefore, reactivity and lipid peroxidation. The interactions between the bulk phases and dispersion of the hemeproteins are complex, more research is needed to proper elucidate these relations in more detail, in order to facilitate the encapsulation capacity for heme-containing proteins in similar lipid-based systems.