bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do reflex comments on laboratory reports alter patient management?
Authors: Wilkinson Ben , Whitehead Simon J , George Elaine , Horton Sally , Bellaby Judith , Mohamed Sagal , Ford Clare , Min San San , Gama Rousseau 
Published: May 2020

Introduction Laboratory comments appended on clinical biochemistry reports are common in the UK. Although popular with clinicians and the public, there is little evidence that these comments influence the clinical management of patients. Methods We provided reflex automated laboratory comments on all primary care lipid results including, if appropriate, recommendation of direct referral to the West Midlands Familial Hypercholesterolaemia service (WMFHS). Over a two-year period, the number GP referrals from the Wolverhampton City Clinical Commissioning Group (CCG) to the WMFHS were compared with four comparator CCGs of similar population size, who were not provided with reflex laboratory comments. Results Over the study period, the WMFHS received more referrals from Wolverhampton GPs (241) than any other comparator CCG (range 8–65) and greater than the combined referrals (172) from all four comparator CCGs. Conclusion Targeted reflex laboratory comments may influence the clinical management of patients and may have a role in the identification of individuals with familial hypercholesterolaemia.
Frontal Ostium Grade (FOG): A New Computer Tomography Grading System for Endoscopic Frontal Sinus Surgery
Authors: Gheriani Heitham , Al‐Salman Rami , Habib Al‐Rahim R. , Javer Amin 
Published: May 2020

ObjectiveThe location and size of the frontal sinus ostium are critical in determining surgical difficulty. The more anterior the ostium, the more difficult is the surgical access. We propose a novel computed tomography (CT) grading specific to the anatomical position of the frontal ostium.Study DesignObservational study followed by a prospective part.SettingsTertiary rhinology practiceSubject and MethodsOn a specified sagittal CT cut, a vertical line was drawn through the posterior edge of the frontal process of the maxilla (frontal buttress/beak) along its vertical axis (reference [R‐] line). A second (S‐) line was placed at the point of upturn of the skull base. Based on if the S‐line was posterior or anterior to the R‐line, the frontal ostium was graded positive and more easily accessible or negative and thereby more challenging, respectively. If both lines overlapped, then a neutral (0) grading existed.ResultsA total of 297 CTs (594 ostia) were analyzed. In total, 394 (65%) ostia were grade positive, 52 (8.75%) were grade negative, and 103 (17.3%) were grade neutral. Ninety frontal sinusotomies were then performed using this grading system: 48 were positive, 21 negative, and 21 neutral. The average time to complete a frontal sinusotomy was 9.96 minutes for grade positive compared to 11.4 minutes for neutral and 16.05 minutes for grade negative (P <. 005).ConclusionThis novel anatomical CT grading system is designed to be useful in planning and predicting the level of difficulty in endoscopic frontal sinus surgery.
Sustaining Otolaryngology Services for the Long Haul during the COVID‐19 Pandemic: Experience from a Tertiary Health System
Authors: Tay Joshua K. , Lim Wei Sian , Loh Woei Shyang , Loh Kwok Seng 
Published: May 2020

The impact of the COVID‐19 pandemic has been far‐reaching and has profoundly affected the practice of otolaryngology in an unprecedented way. In this commentary, we draw from our experience in the first 90 days of the pandemic and discuss a set of workflow measures, personal protection equipment protocols, and strategic goals that can provide a safe environment for patients and staff to continue managing a significant proportion of patients in the otolaryngology service during the pandemic.
Process evaluation of ‘Brains Ahead!’: an intervention for children and adolescents with mild traumatic brain injury within a randomized controlled trial
Authors: Renaud M Irene , Klees Carina , van Haastregt Jolanda CM , Catsman-Berrevoets Coriene E , van de Port Ingrid GL , Lambregts Suzanne AM , van Heugten Caroline M 
Published: May 2020

Objective: To investigate whether the ‘Brains Ahead! Intervention for children and adolescents with mild traumatic brain injury’ was implemented as intended. In addition, involvement in and satisfaction with the intervention among patients, caregivers and professionals delivering the intervention were studied. Design: Mixed methods, prospective study. Participants: Children with mild traumatic brain injury and their caregivers, allocated to the intervention group of the randomized controlled trial in the ‘Brains Ahead!’ study, and the two professionals providing the intervention. Intervention: The intervention consists of a standardized and individualized psychoeducational session with written take-home information, and follow-up telephone call(s). Main measures: Registration forms, evaluation questionnaires for patients and caregivers and semi-structured interviews for professionals. Data analysis: Qualitative data were categorized based on content. Quantitative data were reported as descriptive statistics. Results: Fifty-five patients and caregivers out of 60 study-participants attended both sessions. All elements of the intervention were delivered to 53 study-participants. Evaluation questionnaires were completed by 21 of the 31 patients aged 12 years and older, and by 41 caregivers. Overall, the sessions were considered useful by 19 patients, 40 caregivers and both professionals. Reassurance, creating a better understanding and recognition of symptoms were rated as important aspects. On a scale from 1 to 10, the intervention was rated by children, caregivers and professionals with 7.6 (SD 1.2), 8.1 (SD .9) and 8.0 (SD .0), respectively. Conclusion: The ‘Brains Ahead!’ intervention was largely implemented as intended and the process evaluation revealed that it is considered feasible according to patients, caregivers and professionals.
Awareness and Uptake of Maternal and Child Health Benefit Schemes Among the Women Attending a District Hospital in Coastal South India
Authors: Unnikrishnan Bhaskaran , Rathi Priya , Sequeira Renita Maria , Rao K Kshama , Kamath Swathi , K. Maria Alfam K. 
Published: May 2020

Introduction: Maternal and child health (MCH) benefit schemes were introduced to increase institutional deliveries, to reduce out of pocket expenditure, to provide quality care and nutrition to mother and baby and thereby reduce maternal mortality rate and infant mortality rate. Objective: To assess the awareness and estimate the uptake of benefits regarding various MCH benefit schemes among study participants. Methodology: A cross-sectional study was conducted at district hospital, Mangaluru, Karnataka, India, among 250 antenatal women and postnatal mothers. They were interviewed using a semi-structured–validated questionnaire. Data were analysed using Statistical Package for Social Science version 11.5. Result: Awareness for scheme varied, ranging from 94 per cent for Integrated Child Development Service and 0.8 per cent for Rashtriya Bal Swasthya Karyakram. Major source of information being accredited social health activist (40.41%), most of the study participants had a favourable opinion regarding the benefits of MCH schemes. Maximum uptake was seen for Janani Shishu Suraksha Karyakram (100%); however, none of them availed Prasoothi Araike. Conclusion: Our study showed that the awareness and uptake for different MCH-related schemes varied. Most of the study participants had a favourable opinion about the benefits of MCH schemes. Since awareness for some schemes were low, efforts should be made to increase awareness regarding all schemes by displaying the information. Uptake can be increased by proper channelising the resources.
Effectiveness of a Mindfulness-Based Retreat on Distress and Well-Being in Bereaved Parents
Authors: Thieleman Kara , Cacciatore Joanne 
Published: May 2020

Purpose: This study evaluated the effectiveness of a grief-focused mindfulness-based retreat on psychological distress (trauma, anxiety, and depression) and well-being (mindfulness and self-compassion) in bereaved parents. Method: A quasi-experimental design with two nonequivalent groups (intervention, comparison) and three observations was used. Results: Mixed-model repeated-measures analysis of variance showed significant reductions in distress at posttest in the intervention group, with significant group differences on four of the seven scales. While reductions were maintained at follow-up, group differences were only significant for one trauma subscale. The intervention group showed significant increases in two of the four mindfulness facets (describe and act with awareness) and self-compassion at posttest, although group differences were not significant and gains were not maintained at follow-up. A third mindfulness facet, nonjudge, increased significantly at follow-up, with significant group differences. Discussion: This approach shows promise for reducing some areas of distress and improving the nonjudging mindfulness facet in bereaved parents.
The novel role of IL-37 to enhance the anti-inflammatory response of regulatory T cells in patients with peripheral atherosclerosis
Authors: Lotfy Hassan , Moaaz Marwa , Moaaz Mai 
Published: May 2020

Objectives Regulatory T cells (Tregs) mediate immunomodulation and protect against atherosclerosis. It is considered that reducing the amount of pro-inflammatory mediators could be achieved by enhancing the anti-inflammatory response, and this may be considered one of the main targets for therapy development. The inhibitory cytokines secreted by Tregs mainly include interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β). Based on its known immunosuppressive involvement with other inflammatory disorders, we hypothesized that the newly characterized cytokine interleukin-37 (IL-37) might be associated with the inhibitory functions of Treg in atherosclerosis. Immune regulatory functions of IL-37 have not been completely clarified. Accordingly, we speculated that IL-37 might play a regulatory role in the immunosuppression of Tregs in atherosclerotic disease. Methods Real-time polymerase chain reaction and enzyme linked immunosorbent assay were used to test gene expression and protein levels of IL-37 in peripheral blood and localized freshly resected arterial tissues from 84 patients with peripheral arterial occlusive disease and 50 non-atherosclerotic subjects. Results were correlated to disease hallmarks. We also evaluated the ability of recombinant IL-37 to modulate Treg cytokine secretion and T cell inhibition in relation to atherosclerotic disorder in vitro. Results: Our results revealed that IL-37 was increased in patients with chronic lower limb atherosclerotic ischemia, compared to non-atherosclerotic controls. In addition, the expression levels of circulating IL-37 correlated with disease severity of chronic lower limb ischemia. Supplementation with rIL-37 augmented levels of released IL-10 and TGF-β in supernatants of T cells co-cultured with Tregs in the enrolled patients. Conclusions: Results suggest a role for IL-37 in mediating anti-inflammatory functions in the atherosclerotic process, potentially involving enhancement of Treg inhibitory function and anti-inflammatory cytokine secretion with a particularly marked direct response in severe disease.
The EMT modulator SNAI1 contributes to AML pathogenesis via its interaction with LSD1
Authors: Carmichael Catherine L. , Wang Jueqiong , Nguyen Thao , Kolawole Oluseyi , Benyoucef Aissa , De Mazière Charlotte , Milne Anna R. , Samuel Sona , Gillinder Kevin , Hediyeh-zadeh Soroor , Vo Anh N. Q. , Huang Yizhou , Knezevic Kathy , McInnes William R. L. , Shields Benjamin J. , Mitchell Helen , Ritchie Matthew E. , Lammens Tim , Lintermans Beatrice , Van Vlierberghe Pieter , Wong Nicholas C. , Haigh Katharina , Thoms Julie A. I. , Toulmin Emma , Curtis David J. , Oxley Ethan P. , Dickins Ross A. , Beck Dominik , Perkins Andrew , McCormack Matthew P. , Davis Melissa J. , Berx Geert , Zuber Johannes , Pimanda John E. , Kile Benjamin T. , Goossens Steven , Haigh Jody J. 
Published: May 2020

Abstract
Modulators of epithelial-to-mesenchymal transition (EMT) have recently emerged as novel players in the field of leukemia biology. The mechanisms by which EMT modulators contribute to leukemia pathogenesis, however, remain to be elucidated. Here we show that overexpression of SNAI1, a key modulator of EMT, is a pathologically relevant event in human acute myeloid leukemia (AML) that contributes to impaired differentiation, enhanced self-renewal, and proliferation of immature myeloid cells. We demonstrate that ectopic expression of Snai1 in hematopoietic cells predisposes mice to AML development. This effect is mediated by interaction with the histone demethylase KDM1A/LSD1. Our data shed new light on the role of SNAI1 in leukemia development and identify a novel mechanism of LSD1 corruption in cancer. This is particularly pertinent given the current interest surrounding the use of LSD1 inhibitors in the treatment of multiple different malignancies, including AML.
A hemophilia A mouse model for the in vivo assessment of emicizumab function
Authors: Ferrière Stephen , Peyron Ivan , Christophe Olivier D. , Kawecki Charlotte , Casari Caterina , Muczynski Vincent , Nathwani Amit , Kauskot Alexandre , Lenting Peter J. , Denis Cécile V. 
Published: May 2020

Abstract
The bispecific antibody emicizumab is increasingly used for hemophilia A treatment. However, its specificity for human factors IX and X (FIX and FX) has limited its in vivo functional analysis to primate models of acquired hemophilia. Here, we describe a novel mouse model that allows emicizumab function to be examined. Briefly, FVIII-deficient mice received IV emicizumab 24 hours before tail-clip bleeding was performed. A second infusion with human FIX and FX, administered 5 minutes before bleeding, generated consistent levels of emicizumab (0.7-19 mg/dL for 0.5-10 mg/kg doses) and of both FIX and FX (85 and 101 U/dL, respectively, after dosing at 100 U/kg). Plasma from these mice display FVIII-like activity in assays (diluted activated partial thromboplastin time and thrombin generation), similar to human samples containing emicizumab. Emicizumab doses of 1.5 mg/kg and higher significantly reduced blood loss in a tail-clip–bleeding model using FVIII-deficient mice. However, reduction was incomplete compared with mice treated with human FVIII concentrate, and no difference in efficacy between doses was observed. From this model, we deducted FVIII-like activity from emicizumab that corresponded to a dose of 4.5 U of FVIII per kilogram (ie, 9.0 U/dL). Interestingly, combined with a low FVIII dose (5 U/kg), emicizumab provided enough additive activity to allow complete bleeding arrest. This model could be useful for further in vivo analysis of emicizumab.
Risk stratification in pulmonary arterial hypertension using Bayesian analysis
Authors: Kanwar Manreet K. , Gomberg-Maitland Mardi , Hoeper Marius , Pausch Christine , Pittrow David , Strange Geoff , Anderson James J. , Zhao Carol , Scott Jacqueline V. , Druzdzel Marek J. , Kraisangka Jidapa , Lohmueller Lisa , Antaki James , Benza Raymond L. 
Published: May 2020

BackgroundCurrent risk stratification tools in pulmonary arterial hypertension (PAH) are limited in their discriminatory abilities, partly due to the assumption that prognostic clinical variables have an independent and linear relationship to clinical outcomes. We sought to demonstrate the utility of Bayesian network-based machine learning in enhancing the predictive ability of an existing state-of-the-art risk stratification tool, REVEAL 2.0.MethodsWe derived a tree-augmented naïve Bayes model (titled PHORA) to predict 1-year survival in PAH patients included in the REVEAL registry, using the same variables and cut-points found in REVEAL 2.0. PHORA models were validated internally (within the REVEAL registry) and externally (in the COMPERA and PHSANZ registries). Patients were classified as low-, intermediate- and high-risk (<5%, 5–20% and >10% 12-month mortality, respectively) based on the 2015 European Society of Cardiology/European Respiratory Society guidelines.ResultsPHORA had an area under the curve (AUC) of 0.80 for predicting 1-year survival, which was an improvement over REVEAL 2.0 (AUC 0.76). When validated in the COMPERA and PHSANZ registries, PHORA demonstrated an AUC of 0.74 and 0.80, respectively. 1-year survival rates predicted by PHORA were greater for patients with lower risk scores and poorer for those with higher risk scores (p<0.001), with excellent separation between low-, intermediate- and high-risk groups in all three registries.ConclusionOur Bayesian network-derived risk prediction model, PHORA, demonstrated an improvement in discrimination over existing models. This is reflective of the ability of Bayesian network-based models to account for the interrelationships between clinical variables on outcome, and tolerance to missing data elements when calculating predictions.
Early childhood respiratory morbidity and antibiotic use in ex-preterm infants: a primary care population-based cohort study
Authors: Tan Shin , Szatkowski Lisa , Moreton William , Fiaschi Linda , McKeever Tricia , Gibson Jack , Sharkey Don 
Published: May 2020

BackgroundGlobally, bronchopulmonary dysplasia (BPD) continues to increase in preterm infants. Recent studies exploring subsequent early childhood respiratory morbidity have been small or focused on hospital admissions.AimsTo examine early childhood rates of primary care consultations for respiratory tract infections (RTI), lower respiratory tract infections (LRTI), wheeze and antibiotic prescriptions in ex-preterm and term children. A secondary aim was to examine differences between preterm infants discharged home with or without oxygen.MethodsRetrospective cohort study using linked electronic primary care and hospital databases of children born between 1997 and 2014. We included 253 277 eligible children, with 1666 born preterm at <32 weeks' gestation, followed-up from primary care registration to age 5 years. Adjusted incidence rate ratios (aIRRs) were calculated.ResultsEx-preterm infants had higher rates of morbidity across all respiratory outcomes. After adjusting for confounders, aIRRs for RTI (1.37, 95% CI 1.33–1.42), LRTI (2.79, 95% CI 2.59–3.01), wheeze (3.05, 95% CI 2.64–3.52) and antibiotic prescriptions (1.49, 95% CI 1.44–1.55) were higher for ex-preterm infants. Ex-preterm infants discharged home on oxygen had significantly greater morbidity across all respiratory diagnoses and antibiotic prescriptions compared to those without home oxygen. The highest rates of respiratory morbidity were observed in children from the most deprived socioeconomic groups.ConclusionEx-preterm infants, particularly those with BPD requiring home oxygen, have significant respiratory morbidity and antibiotic prescriptions in early childhood. With the increasing prevalence of BPD, further research should focus on strategies to reduce the burden of respiratory morbidity in these high-risk infants after hospital discharge.
Comparison of personal and shared frameshift neoantigen vaccines in a mouse mammary cancer model
Authors: Peterson Milene , Murphy Sierra Nicole , Lainson John , Zhang Jian , Shen Luhui , Diehnelt Chris W. , Johnston Stephen Albert 
Published: May 2020

Abstract
Background
It is widely hoped that personal cancer vaccines will extend the number of patients benefiting from checkpoint and other immunotherapies. However, it is clear creating such vaccines will be challenging. It requires obtaining and sequencing tumor DNA/RNA, predicting potentially immunogenic neoepitopes and manufacturing a one-use vaccine. This process takes time and considerable cost. Importantly, most mutations will not produce an immunogenic peptide and many patient’s tumors do not contain enough DNA mutations to make a vaccine. We have discovered that frameshift peptides (FSP) created from errors in the production of RNA rather than from DNA mutations are potentially a rich source of neoantigens for cancer vaccines. These errors are predictable, enabling the production of a FSP microarray. Previously we found that these microarrays can identify both personal and shared neoantigens. Here, we compared the performance of personal cancer vaccines (PCVs) with that of a shared antigen vaccine, termed Frameshift Antigen Shared Therapeutic (FAST) vaccine, using the 4 T1 breast cancer model. Sera from 4 T1-tumor bearing mice were assayed on the peptide microarray containing 200 Fs neoantigens, for the PCV, the top 10 candidates were select and personal vaccines constructed and administrated to the respective mice. For the FAST, we selected the top 10 candidates with higher prevalence among all the mice challenged. Seven to 12 days challenged mice were immunized, combined or not with immune checkpoint inhibitor (ICI) (αPD-L1 and αCTLA-4). Primary and secondary tumor clearance and growth were evaluated as well as cellular and humoral immune response against the vaccine targets by IFN-γ ELISPOT and ELISA. Lastly, we analyzed the immune response of the FAST-vaccinated mice by flow cytometry in comparison to the control group.

Results
We found that PCVs and FAST vaccines both reduced primary tumor incidence and growth as well as lung metastases when delivered as monotherapies or in combination with ICI. Additionally, the FAST vaccine induces a robust and effective T-cell response.

Conclusions
These results suggest that FSPs produced from RNA-based errors are potent neoantigens that could enable production of off-the-shelf shared antigen vaccines for solid tumors with efficacy comparable to that of PCVs.
Evaluating the effects of a risk-adapted screening program for familial colorectal cancer in individuals between 25 and 50 years of age: study protocol for the prospective population-based intervention study FARKOR
Authors: Hoffmann Sabine , Crispin Alexander , Lindoerfer Doris , Sroczynski Gaby , Siebert Uwe , Mansmann Ulrich , Consortium FARKOR 
Published: May 2020

Abstract
Background
Colorectal cancer (CRC) is the second most common malignant disease and the second most common cause of cancer death in Germany. Official CRC screening starts at age 50. As there is evidence that individuals with a family history of CRC have an increased risk of developing CRC before age 50, there are recommendations to start screening for this group earlier. This study aims to evaluate the clinical and economic effects of a risk-adapted screening program for CRC in individuals between 25 and 50 years of age with potentially increased familial CRC risk.

Methods
FARKOR (Familiäres Risiko für das Kolorektale Karzinom) is a population-based prospective intervention study. All members of cooperating statutory health insurance companies between 25 and 50 years of age living in a model region in Germany (federal state of Bavaria, 3.5 million inhabitants in this age group) can participate in the program between October 2018 and March 2020. Recruitment takes place through physicians and through a public campaign. Additionally, insurances contact recently diagnosed CRC patients in order to encourage their relatives to participate in the program. Physicians assess a participant’s familial history of CRC using a short questionnaire. All participants with a family history of CRC are invited to a shared decision making process to decide on further screening options consisting of either undergoing an immunological test for fecal occult blood or colonoscopy. Comprehensive data collection based on self-reported lifestyle information, medical documentation and health administrative databases accompanies the screening program. Longterm benefits, harms and the cost-effectiveness of the risk-adapted CRC screening program will be assessed by decision analytic modeling.

Discussion
The data collected in this study will add important pieces of information that are still missing in the evaluation of the effects and the cost-effectiveness of a risk-adapted CRC screening strategy for individuals under 50 years of age.

Trial registration
German Clinical Trials Register, DRKS-IDDRKS00015097.