bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shared leadership in tertiary care: design of a simulation for patient safety decision-making in healthcare management teams
Authors: Aufegger Lisa , Soane Emma , Darzi Ara , Bicknell Colin 
Published: September 2020

IntroductionSimulation-based training (SBT) on shared leadership (SL) and group decision-making (GDM) can contribute to the safe and efficient functioning of a healthcare system, yet it is rarely incorporated into healthcare management training. The aim of this study was design, develop and validate a robust and evidence-based SBT to explore and train SL and GDM.MethodUsing a two-stage iterative simulation design approach, 103 clinical and non-clinical managerial students and healthcare professionals took part in an SBT that contained real-world problems and opportunities to improve patient safety set within a fictional context. Self-report data were gathered, and a focus group was conducted to address the simulation’s degree of realism, content, relevance, as well as areas for improvement.ResultsParticipants experienced the simulation scenario, the material and the role assignment as realistic and representative of real-world tasks and decision contexts, and as a good opportunity to identify and enact relevant tasks, behaviours and knowledge related to SL and GDM. Areas for improvement were highlighted with regard to involving an actor who challenges SL and GDM; more preparatory time to allow for an enhanced familiarisation of the content; and, video debriefs to reflect on relevant behaviours and team processes.ConclusionsOur simulation was perceived as an effective method to develop SL and GDM within the context of patient safety and healthcare management. Future studies could extend this scenario method to other areas of healthcare service and delivery, and to different sectors that require diverse groups to make complex decisions.
Neoantigen-specific CD4+T-cell response is critical for the therapeutic efficacy of cryo-thermal therapy
Authors: Peng Peng , Hu Hongming , Liu Ping , Xu Lisa X 
Published: September 2020

BackgroundTraditional tumor thermal ablations, such as radiofrequency ablation (RFA) and cryoablation, can result in good local control of tumor, but traditional tumor thermal ablations are limited by poor long-term survival due to the failure of control of distal metastasis. Our previous studies developed a novel cryo-thermal therapy to treat the B16F10 melanoma mouse model. Long-term survival and T-cell-mediated durable antitumor immunity were achieved after cryo-thermal therapy, but whether tumor antigen-specific T-cells were augmented by cryo-thermal therapy was not determined.MethodsThe long-term antitumor therapeutic efficacy of cryo-thermal therapy was performed in B16F10 murine melanoma models. Splenocytes derived from mice treated with RFA or cryo-thermal therapy were coincubated with tumor antigen peptides to detect the frequency of antigen specific CD4+and CD8+T-cells by flow cytometry. Splenocytes were then stimulated and expanded by αCD3 or peptides and adoptive T-cell therapy experiments were performed to identify the antitumor efficacy of T-cells induced by RFA and cryo-thermal therapy. Naïve mice and tumor-bearing mice were used as control groups.ResultsLocal cryo-thermal therapy generated a stronger systematic antitumor immune response than RFA and a long-lasting antitumor immunity that protected against tumor rechallenge. In vitro studies showed that the antigen-specific CD8+T-cell response was induced by both cryo-thermal therapy and RFA, but the strong neoantigen-specific CD4+T-cell response was only induced by cryo-thermal therapy. Cryo-thermal therapy-induced strong antitumor immune response was mainly mediated by CD4+T-cells, particularly neoantigen-specific CD4+T-cells.ConclusionCryo-thermal therapy induced a stronger and broader antigen-specific memory T-cells. Specifically, cryo-thermal therapy, but not RFA, led to a strong neoantigen-specific CD4+T-cell response that mediated the resistance to tumor challenge.
The 'armed concrete' approach: stent-screw-assisted internal fixation (SAIF) reconstructs and internally fixates the most severe osteoporotic vertebral fractures
Authors: Distefano Daniela , Scarone Pietro , Isalberti Maurizio , La Barbera Luigi , Villa Tomaso , Bonaldi Giuseppe , Hirsch Joshua A , Cianfoni Alessandro 
Published: September 2020

BackgroundThe treatment of severe osteoporotic vertebral compression fractures (VCFs) with middle-column (MC) involvement, high fragmentation, large cleft and/or pedicular fracture is challenging. Minimally invasive 'stent-screw-assisted internal fixation' (SAIF) can reduce the fracture, reconstruct the vertebral body (VB) and fix it to the posterior elements.ObjectiveTo assess feasibility, safety, technical and clinical outcome of the SAIF technique in patients with severe osteoporotic VCFs.Methods80 treated vertebrae were analyzed retrospectively. Severe VCFs were characterized by advanced collapse (Genant grade 3), a high degree of osseous fragmentation (McCormack grade 2 and 3), burst morphology with MC injury, pediculo-somatic junction fracture, and/or large osteonecrotic cleft. VB reconstruction was evaluated on postprocedure radiographs and CT scans by two independent raters. Clinical and radiological follow-ups were performed at 1 and 6 months.ResultsSAIF was performed at 28 thoracic and 52 lumbar levels in 73 patients. One transient neurological complication occurred. VB reconstruction was satisfactory in 98.8% of levels (inter-rater reliability 96%, κ=1). Follow-up at 1 month was available for 78/80 levels and at 6 months or later (range 6–24, mean 7.9 months) for 73/80 levels. Significant improvement in the Visual Analog Scale score was noted at 1 and 6 months after treatment (p<0.05). Patients reported global clinical benefit during follow-up (Patient’s
Global Impression of Change Scale 5.6±0.9 at 1 month and 6.1±0.9 at 6 months). Fourteen new painful VCFs occurred at different levels in 11 patients during follow-up, treated with vertebral augmentation or SAIF. Target-level stability was maintained in all cases.ConclusionsSAIF is a minimally invasive, safe, and effective treatment for patients with severe osteoporotic VCFs with MC involvement.
Clinical and epidemiological features of tibial tubercle avulsion fracture in Chinese adolescents
Authors: Mo Yueqiang , Wang Dahui 
Published: September 2020

BackgroundTibial tubercle avulsion fracture is rare in children. Accumulated knowledge on clinical and epidemiological features of this fracture is of practical significance for clinical colleagues to deal effectively with such fractures.MethodsClinical and epidemiological parameters were reviewed retrospectively in 29 patients with tibial tubercle avulsion fracture that was treated in our hospital in the past 7 years.ResultsTotally, 29 children with 30 tibial tubercle fractures were enrolled. They were all boys; the average age was 13.8 (12–15) years, and the average Body Mass Index (BMI) was 26.4 (19.2–34.3). Statistically, 41.4% of injuries occurred during jumping activities, and 1 (3.4%), 12 (41.4%) and 16 (55.2%) patients were injured bilaterally, on the right and left sides, respectively. The patients were classified into type I (4), II (3), III (13) and IV (10) fractures. Two patients (three knees) with fractures of type IV received close reduction and cast immobilization for 6 weeks. One patient with fracture of type IV underwent close reduction and was fixed with two cannulated screws. The remaining 26 patients underwent open reduction and were fixed with two or three cannulated screws. The average follow-up time was 38 (14–98) months; no complication was noted. Twenty-seven patients had an excellent outcome.ConclusionIn Chinese adolescents, the tibial tubercle avulsion fracture predisposes to boys with higher body weight; jumping is the most common cause of injury; treatments show satisfactory outcome regardless of fracture types.
MGD-decoupled black holes, anisotropic fluids and holographic entanglement entropy
Authors: Rocha Roldão da , Tomaz Anderson A. 
Published: September 2020

AbstractThe holographic entanglement entropy (HEE) is investigated for a black hole under the minimal geometric deformation (MGD) procedure, created by gravitational decoupling via an anisotropic fluid, in an AdS/CFT on the brane setup. The respective HEE corrections are computed and confronted to the corresponding corrections for both the standard MGD black holes and the Schwarzschild ones.
Reflections on the article “Moving contact lines and dynamic contact angles: a ‘litmus test’ for mathematical models and some new challenges” by Yulii D. Shikhmurzaev
Authors: Bothe Dieter 
Published: September 2020

AbstractWe carefully consider the ‘litmus test’ proposed by Yulii D. Shikhmurzaev [Y.D. Shikhmurzaev, Eur. Phys. J. Special Topics 229, 1945 (2020)] in the context of the sharp-interface/sharp-contact line model.
Cancers from Novel Pole-Mutant Mouse Models Provide Insights into Polymerase-Mediated Hypermutagenesis and Immune Checkpoint Blockade
Authors: Galati Melissa A. , Hodel Karl P. , Gams Miki S. , Sudhaman Sumedha , Bridge Taylor , Zahurancik Walter J. , Ungerleider Nathan A. , Park Vivian S. , Ercan Ayse B. , Joksimovic Lazar , Siddiqui Iram , Siddaway Robert , Edwards Melissa , de Borja Richard , Elshaer Dana , Chung Jiil , Forster Victoria J. , Nunes Nuno M. , Aronson Melyssa , Wang Xia , Ramdas Jagadeesh , Seeley Andrea , Sarosiek Tomasz , Dunn Gavin P. , Byrd Jonathan N. , Mordechai Oz , Durno Carol , Martin Alberto , Shlien Adam , Bouffet Eric , Suo Zucai , Jackson James G. , Hawkins Cynthia E. , Guidos Cynthia J. , Pursell Zachary F. , Tabori Uri 
Published: September 2020

Abstract

POLE mutations are a major cause of hypermutant cancers, yet questions remain regarding mechanisms of tumorigenesis, genotype–phenotype correlation, and therapeutic considerations. In this study, we establish mouse models harboring cancer-associated POLE mutations P286R and S459F, which cause rapid albeit distinct time to cancer initiation in vivo, independent of their exonuclease activity. Mouse and human correlates enabled novel stratification of POLE mutations into three groups based on clinical phenotype and mutagenicity. Cancers driven by these mutations displayed striking resemblance to the human ultrahypermutation and specific signatures. Furthermore, Pole-driven cancers exhibited a continuous and stochastic mutagenesis mechanism, resulting in intertumoral and intratumoral heterogeneity. Checkpoint blockade did not prevent Pole lymphomas, but rather likely promoted lymphomagenesis as observed in humans. These observations provide insights into the carcinogenesis of POLE-driven tumors and valuable information for genetic counseling, surveillance, and immunotherapy for patients.

Significance:
Two mouse models of polymerase exonuclease deficiency shed light on mechanisms of mutation accumulation and considerations for immunotherapy.
See related commentary by Wisdom and Kirsch p. 5459
Integrating Mathematical Modeling with High-Throughput Imaging Explains How Polyploid Populations Behave in Nutrient-Sparse Environments
Authors: Kimmel Gregory J. , Dane Mark , Heiser Laura M. , Altrock Philipp M. , Andor Noemi 
Published: September 2020

Abstract

Breast cancer progresses in a multistep process from primary tumor growth and stroma invasion to metastasis. Nutrient-limiting environments promote chemotaxis with aggressive morphologies characteristic of invasion. It is unknown how coexisting cells differ in their response to nutrient limitations and how this impacts invasion of the metapopulation as a whole. In this study, we integrate mathematical modeling with microenvironmental perturbation data to investigate invasion in nutrient-limiting environments inhabited by one or two cancer cell subpopulations. Subpopulations were defined by their energy efficiency and chemotactic ability. Invasion distance traveled by a homogeneous population was estimated. For heterogeneous populations, results suggest that an imbalance between nutrient efficacy and chemotactic superiority accelerates invasion. Such imbalance will spatially segregate the two populations and only one type will dominate at the invasion front. Only if these two phenotypes are balanced, the two subpopulations compete for the same space, which decelerates invasion. We investigate ploidy as a candidate biomarker of this phenotypic heterogeneity and discuss its potential to inform the dose of mTOR inhibitors (mTOR-I) that can inhibit chemotaxis just enough to facilitate such competition.

Significance:
This study identifies the double-edged sword of high ploidy as a prerequisite to personalize combination therapies with cytotoxic drugs and inhibitors of signal transduction pathways such as mTOR-Is.
Spliced Peptides and Cytokine-Driven Changes in the Immunopeptidome of Melanoma
Authors: Faridi Pouya , Woods Katherine , Ostrouska Simone , Deceneux Cyril , Aranha Ritchlynn , Duscharla Divya , Wong Stephen Q. , Chen Weisan , Ramarathinam Sri H. , Lim Kam Sian Terry C.C. , Croft Nathan P. , Li Chen , Ayala Rochelle , Cebon Jonathan S. , Purcell Anthony W. , Schittenhelm Ralf B. , Behren Andreas 
Published: September 2020

Abstract
Antigen recognition by CD8+ T cells is governed by the pool of peptide antigens presented on the cell surface in the context of HLA class I complexes. Studies have shown not only a high degree of plasticity in the immunopeptidome, but also that a considerable fraction of all presented peptides is generated through proteasome-mediated splicing of noncontiguous regions of proteins to form novel peptide antigens. Here, we used high-resolution mass spectrometry combined with new bioinformatic approaches to characterize the immunopeptidome of melanoma cells in the presence or absence of IFNγ. In total, we identified more than 60,000 peptides from a single patient-derived cell line (LM-MEL-44) and demonstrated that IFNγ induced changes in the peptidome, with an overlap of only approximately 50% between basal and treated cells. Around 6% to 8% of the peptides were identified as cis-spliced peptides, and 2,213 peptides (1,827 linear and 386 cis-spliced peptides) were derived from known melanoma-associated antigens. These peptide antigens were equally distributed between the constitutive- and IFNγ-induced peptidome. We next examined additional HLA-matched patient-derived cell lines to investigate how frequently these peptides were identified and found that a high proportion of both linear and spliced peptides was conserved between individual patient tumors, drawing on data amassing to more than 100,000 peptide sequences. Several of these peptides showed in vitro immunogenicity across multiple patients with melanoma. These observations highlight the breadth and complexity of the repertoire of immunogenic peptides that can be exploited therapeutically and suggest that spliced peptides are a major class of tumor antigens.
Signalosome-Regulated Serum Response Factor Phosphorylation Determining Myocyte Growth in Width Versus Length as a Therapeutic Target for Heart Failure
Authors: Li Jinliang , Tan Yuliang , Passariello Catherine L. , Martinez Eliana C. , Kritzer Michael D. , Li Xueyi , Li Xiaofeng , Li Yang , Yu Qian , Ohgi Kenneth , Thakur Hrishikesh , MacArthur John W. , Ivey Jan R. , Woo Y. Joseph , Emter Craig A. , Dodge-Kafka Kimberly , Rosenfeld Michael G. , Kapiloff Michael S. 
Published: September 2020

Background:
Concentric and eccentric cardiac hypertrophy are associated with pressure and volume overload, respectively, in cardiovascular disease both conferring an increased risk of heart failure. These contrasting forms of hypertrophy are characterized by asymmetrical growth of the cardiac myocyte in mainly width or length, respectively. The molecular mechanisms determining myocyte preferential growth in width versus length remain poorly understood. Identification of the mechanisms governing asymmetrical myocyte growth could provide new therapeutic targets for the prevention or treatment of heart failure.

Methods:
Primary adult rat ventricular myocytes, adeno-associated virus (AAV)–mediated gene delivery in mice, and human tissue samples were used to define a regulatory pathway controlling pathological myocyte hypertrophy. Chromatin immunoprecipitation assays with sequencing and precision nuclear run-on sequencing were used to define a transcriptional mechanism.

Results:

We report that asymmetrical cardiac myocyte hypertrophy is modulated by SRF (serum response factor) phosphorylation, constituting an epigenomic switch balancing the growth in width versus length of adult ventricular myocytes in vitro and in vivo. SRF Ser
103
phosphorylation is bidirectionally regulated by RSK3 (p90 ribosomal S6 kinase type 3) and PP2A (protein phosphatase 2A) at signalosomes organized by the scaffold protein mAKAPβ (muscle A-kinase anchoring protein β), such that increased SRF phosphorylation activates AP-1 (activator protein-1)-dependent enhancers that direct myocyte growth in width. AAV are used to express in vivo mAKAPβ-derived RSK3 and PP2A anchoring disruptor peptides that block the association of the enzymes with the mAKAPβ scaffold. Inhibition of RSK3 signaling prevents concentric cardiac remodeling induced by pressure overload, while inhibition of PP2A signaling prevents eccentric cardiac remodeling induced by myocardial infarction, in each case improving cardiac function. SRF Ser
103
phosphorylation is significantly decreased in dilated human hearts, supporting the notion that modulation of the mAKAPβ-SRF signalosome could be a new therapeutic approach for human heart failure.

Conclusions:
We have identified a new molecular switch, namely mAKAPβ signalosome–regulated SRF phosphorylation, that controls a transcriptional program responsible for modulating changes in cardiac myocyte morphology that occur secondary to pathological stressors. Complementary AAV-based gene therapies constitute rationally-designed strategies for a new translational modality for heart failure.
Effect of Pre- and In-Hospital Delay on Reperfusion in Acute Ischemic Stroke Mechanical Thrombectomy
Authors: Kaesmacher Johannes , Maamari Basel , Meinel Thomas R. , Piechowiak Eike I. , Mosimann Pascal J. , Mordasini Pasquale , Goeldlin Martina , Arnold Marcel , Dobrocky Tomas , Boeckh-Behrens Tobias , Berndt Maria , Michel Patrik , Requena Manuel , Benali Amel , Pierot Laurent , Mendes Pereira Vitor , Boulouis Grégoire , Brehm Alex , Sporns Peter B. , Ospel Johanna M. , Gralla Jan , Fischer Urs ,   on behalf of the BEYOND-SWIFT Investigators
Published: September 2020

Background and Purpose:
Post hoc analyses of randomized controlled clinical trials evaluating mechanical thrombectomy have suggested that admission-to-groin-puncture (ATG) delays are associated with reduced reperfusion rates. Purpose of this analysis was to validate this association in a real-world cohort and to find associated factors and confounders for prolonged ATG intervals.

Methods:

Patients included into the BEYOND-SWIFT cohort (Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the Solitaire FR With the Intention for Thrombectomy;
https://www.clinicaltrials.gov
; Unique identifier: NCT03496064) were analyzed (n=2386). Association between baseline characteristics and ATG was evaluated using mixed linear regression analysis. The effect of increasing symptom-onset-to-admission and ATG intervals on successful reperfusion (defined as Thrombolysis in Cerebral Infarction [TICI] 2b-3) was evaluated using logistic regression analysis adjusting for potential confounders.

Results:
Median ATG was 73 minutes. Prolonged ATG intervals were associated with the use of magnetic resonance imaging (+19.1 [95% CI, +9.1 to +29.1] minutes), general anesthesia (+12.1 [95% CI, +3.7 to +20.4] minutes), and borderline indication criteria, such as lower National Institutes of Health Stroke Scale, late presentations, or not meeting top-tier early time window eligibility criteria (+13.8 [95% CI, +6.1 to +21.6] minutes). There was a 13% relative odds reduction for TICI 2b-3 (adjusted odds ratio [aOR], 0.87 [95% CI, 0.79–0.96]) and TICI 2c/3 (aOR, 0.87 [95% CI, 0.79–0.95]) per hour ATG delay, while the reduction of TICI 2b-3 per hour increase symptom-onset-to-admission was minor (aOR, 0.97 [95% CI, 0.94–0.99]) and inconsistent regarding TICI 2c/3 (aOR, 0.99 [95% CI, 0.97–1.02]). After adjusting for identified factors associated with prolonged ATG intervals, the association of ATG delay and lower rates of TICI 2b-3 remained tangible (aOR, 0.87 [95% CI, 0.76–0.99]).

Conclusions:
There is a great potential to reduce ATG, and potential targets for improvement can be deduced from observational data. The association between in-hospital delay and reduced reperfusion rates is evident in real-world clinical data, underscoring the need to optimize in-hospital workflows. Given the only minor association between symptom-onset-to-admission intervals and reperfusion rates, the causal relationship of this association warrants further research.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT03496064.
Re-Mixing Making: examining the Intersections of Hip Hop Culture, Maker Spaces, and Social Justice Education
Authors: Dando Michael 
Published: September 2020

Abstract
Despite the potential to promote critical literacy formation, academic engagement and social justice education, maker activities and maker spaces do not always support or engage historically marginalized communities. This paper chronicles a response to this problem by examining a study created to support equitable engagement with youth in an after-school workshop series over 8-weeks that focused on Hip Hop cultural practices and the simultaneous development of critical literacy and social justice perspectives. The series, open to community youth was located in the makerspace of the local public library. Within this study, project designers drew from Gutierrez and Rogoff’s concept of “repertoires of practice” and focused particularly on questions of what counts as making, and who has agency to make these decisions and how engagement with hip hop culture mediates these understandings.
I consider two instances where students engaged in Hip Hop- centered generative practices (particularly beat making and graffiti writing) and analyze moments of student resistance and agency as opportunities to expand understandings of development of critical media literacy and social justice orientation. This paper foregrounds the importance of iterative analysis and design as participants develop artistic, social, and political identities over the course of the workshop. Finally, this paper explores implications for classroom learning that emerged from the work, including expression, exploration, and collaboration.