bluuebunny/crossref_metadata_2025_split huggingface dataset:
A registry-based observational study comparing emergency calls assessed by emergency medical dispatchers with and without support by registered nurses
Authors: Torlén Wennlund Klara , Kurland Lisa , Olanders Knut , Castrén Maaret , Bohm Katarina 
Published: January 2022

Abstract
Background
The requirement concerning formal education for emergency medical dispatcher (EMD) is debated and varies, both nationally and internationally. There are few studies on the outcomes of emergency medical dispatching in relation to professional background. This study aimed to compare calls handled by an EMD with and without support by a registered nurse (RN), with respect to priority level, accuracy, and medical condition.

Methods
A retrospective observational study, performed on registry data from specific regions during 2015. The ambulance personnel’s first assessment of the priority level and medical condition was used as the reference standard. Outcomes were: the proportion of calls dispatched with a priority in concordance with the ambulance personnel’s assessment; over- and undertriage; the proportion of most adverse over- and undertriage; sensitivity, specificity and predictive values for each of the ambulance priorities; proportion of calls dispatched with a medical condition in concordance with the ambulance personnel’s assessment. Proportions were reported with 95% confidence intervals. χ2-test was used for comparisons. P-levels < 0.05 were regarded as significant.

Results
A total of 25,025 calls were included (EMD n = 23,723, EMD + RN n = 1302). Analyses relating to priority and medical condition were performed on 23,503 and 21,881 calls, respectively. A dispatched priority in concordance with the ambulance personnel’s assessment were: EMD n = 11,319 (50.7%) and EMD + RN n = 481 (41.5%) (p < 0.01). The proportion of overtriage was equal for both groups: EMD n = 5904, EMD + RN n = 306, (26.4%) p = 0.25). The proportion of undertriage for each group was: EMD n = 5122 (22.9%) and EMD + RN n = 371 (32.0%) (p < 0.01). Sensitivity for the most urgent priority was 54.6% for EMD, compared to 29.6% for EMD + RN (p < 0.01), and specificity was 67.3% and 84.8% (p < 0.01) respectively. A dispatched medical condition in concordance with the ambulance personnel’s assessment were: EMD n = 13,785 (66.4%) and EMD + RN n = 697 (62.2%) (p = 0.01).

Conclusions
A higher precision of emergency medical dispatching was not observed when the EMD was supported by an RN. How patient safety is affected by the observed divergence in dispatched priorities is an area for future research.
Hyperoxemia in postsurgical sepsis/septic shock patients is associated with reduced mortality
Authors: Martín-Fernández Marta , Heredia-Rodríguez María , González-Jiménez Irene , Lorenzo-López Mario , Gómez-Pesquera Estefanía , Poves-Álvarez Rodrigo , Álvarez F. Javier , Jorge-Monjas Pablo , Beltrán-DeHeredia Juan , Gutiérrez-Abejón Eduardo , Herrera-Gómez Francisco , Guzzo Gabriella , Gómez-Sánchez Esther , Tamayo-Velasco Álvaro , Aller Rocío , Pelosi Paolo , Villar Jesús , Tamayo Eduardo 
Published: January 2022

Abstract
Background
Despite growing interest in treatment strategies that limit oxygen exposure in ICU patients, no studies have compared conservative oxygen with standard oxygen in postsurgical patients with sepsis/septic shock, although there are indications that it may improve outcomes. It has been proven that high partial pressure of oxygen in arterial blood (PaO2) reduces the rate of surgical-wound infections and mortality in patients under major surgery. The aim of this study is to examine whether PaO2 is associated with risk of death in adult patients with sepsis/septic shock after major surgery.

Methods
We performed a secondary analysis of a prospective observational study in 454 patients who underwent major surgery admitted into a single ICU. Patients were stratified in two groups whether they had hyperoxemia, defined as PaO2 > 100 mmHg (n = 216), or PaO2 ≤ 100 mmHg (n = 238) at the day of sepsis/septic shock onset according to SEPSIS-3 criteria maintained during 48 h. Primary end-point was 90-day mortality after diagnosis of sepsis. Secondary endpoints were ICU length of stay and time to extubation.

Results
In patients with PaO2 ≤ 100 mmHg, we found prolonged mechanical ventilation (2 [8] vs. 1 [4] days, p < 0.001), higher ICU stay (8 [13] vs. 5 [9] days, p < 0.001), higher organ dysfunction as assessed by SOFA score (9 [3] vs. 7 [5], p < 0.001), higher prevalence of septic shock (200/238, 84.0% vs 145/216) 67.1%, p < 0.001), and higher 90-day mortality (37.0% [88] vs. 25.5% [55], p = 0.008). Hyperoxemia was associated with higher probability of 90-day survival in a multivariate analysis (OR 0.61, 95%CI: 0.39–0.95, p = 0.029), independent of age, chronic renal failure, procalcitonin levels, and APACHE II score > 19. These findings were confirmed when patients with severe hypoxemia at the time of study inclusion were excluded.

Conclusions
Oxygenation with a PaO2 above 100 mmHg was independently associated with lower 90-day mortality, shorter ICU stay and intubation time in critically ill postsurgical sepsis/septic shock patients. Our findings open a new venue for designing clinical trials to evaluate the boundaries of PaO2 in postsurgical patients with severe infections.
Systematic identification of ACE2 expression modulators reveals cardiomyopathy as a risk factor for mortality in COVID-19 patients
Authors: Kaur Navchetan , Oskotsky Boris , Butte Atul J. , Hu Zicheng 
Published: January 2022

AbstractBackgroundAngiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for SARS-CoV-2. It plays critical roles in both the transmission and the pathogenesis of COVID-19. Comprehensive profiling of ACE2 expression patterns could reveal risk factors of severe COVID-19 illness. While the expression of ACE2 in healthy human tissues has been well characterized, it is not known which diseases and drugs might be associated with ACE2 expression.ResultsWe develop GENEVA (GENe Expression Variance Analysis), a semi-automated framework for exploring massive amounts of RNA-seq datasets. We apply GENEVA to 286,650 publicly available RNA-seq samples to identify any previously studied experimental conditions that could be directly or indirectly associated with ACE2 expression. We identify multiple drugs, genetic perturbations, and diseases that are associated with the expression of ACE2, including cardiomyopathy, HNF1A overexpression, and drug treatments with RAD140 and itraconazole. Our joint analysis of seven datasets confirms ACE2 upregulation in all cardiomyopathy categories. Using electronic health records data from 3936 COVID-19 patients, we demonstrate that patients with pre-existing cardiomyopathy have an increased mortality risk than age-matched patients with other cardiovascular conditions. GENEVA is applicable to any genes of interest and is freely accessible athttp://genevatool.org.ConclusionsThis study identifies multiple diseases and drugs that are associated with the expression of ACE2. The effect of these conditions should be carefully studied in COVID-19 patients. In particular, our analysis identifies cardiomyopathy patients as a high-risk group, with increased ACE2 expression in the heart and increased mortality after SARS-COV-2 infection.
PATHWEIGH, pragmatic weight management in adult patients in primary care in Colorado, USA: study protocol for a stepped wedge cluster randomized trial
Authors: Suresh Krithika , Holtrop Jodi Summers , Dickinson L. Miriam , Willems Emileigh , Smith Peter C. , Gritz R. Mark , Perreault Leigh 
Published: January 2022

Abstract
Background
Despite the overwhelming prevalence and health implications of obesity, it is rarely adequately addressed in a health care setting. PATHWEIGH is a pragmatic approach to weight management that uses tools built into the electronic medical record to overcome barriers and guide care. Implementation strategies are employed to facilitate adoption and use of the PATHWEIGH tools and processes. The current study will compare the effectiveness of PATHWEIGH versus standard of care (SOC) on patient weight loss in primary care and explore factors for its successful implementation.

Methods
A stepped wedge cluster randomized trial design will be used within an effectiveness-implementation hybrid study. Adult patient weight loss and weight loss maintenance will be compared in PATHWEIGH versus SOC in 57 family and internal medicine clinics in a large health system in Colorado, USA. Effectiveness will be evaluated using generalized linear mixed models to determine statistical differences in weight loss and weight loss maintenance at 6, 12, and 18 months. Patient-, provider-, and clinic-level predictors will be identified using mediator and moderator analyses. Conceptually guided by the Practical, Robust, Implementation and Sustainability Model (PRISM), a mixed methods approach including quantitative (practice surveys, use tracking) and qualitative (interviews, observations) data collection will be used to determine factors impeding and facilitating adoption, implementation, and maintenance of PATHWEIGH and evaluate specified implementation strategies. A cost analysis of the practice and system costs and resources required by PATHWEIGH relative to the reimbursement collected will be performed.

Discussion
The effectiveness and implementation of PATHWEIGH, and their interrelatedness, for patient weight loss are collectively the focus of the current trial. Findings from this study are expected to serve as a blueprint for available and effective weight management in primary care medical practice.

Trial registration
ClinicalTrials.govNCT04678752. Registered on December 21, 2020.
Ecological and environmental factors affecting transmission of sylvatic yellow fever in the 2017–2019 outbreak in the Atlantic Forest, Brazil
Authors: Abreu Filipe Vieira Santos de , de Andreazzi Cecilia Siliansky , Neves Maycon Sebastião Alberto Santos , Meneguete Patrícia Soares , Ribeiro Mário Sérgio , Dias Cristina Maria Giordano , de Albuquerque Motta Monique , Barcellos Christovam , Romão Anselmo Rocha , Magalhães Mônica de Avelar Figueiredo Mafra , Lourenço-de-Oliveira Ricardo 
Published: January 2022

Abstract
Background
Yellow fever virus (YFV) is an arbovirus that, despite the existence of a safe and effective vaccine, continues to cause outbreaks of varying dimensions in the Americas and Africa. Between 2017 and 2019, Brazil registered un unprecedented sylvatic YFV outbreak whose severity was the result of its spread into zones of the Atlantic Forest with no signals of viral circulation for nearly 80 years.

Methods
To investigate the influence of climatic, environmental, and ecological factors governing the dispersion and force of infection of YFV in a naïve area such as the landscape mosaic of Rio de Janeiro (RJ), we combined the analyses of a large set of data including entomological sampling performed before and during the 2017–2019 outbreak, with the geolocation of human and nonhuman primates (NHP) and mosquito infections.

Results
A greater abundance of Haemagogus mosquitoes combined with lower richness and diversity of mosquito fauna increased the probability of finding a YFV-infected mosquito. Furthermore, the analysis of functional traits showed that certain functional groups, composed mainly of Aedini mosquitoes which includes Aedes and Haemagogus mosquitoes, are also more representative in areas where infected mosquitoes were found. Human and NHP infections were more common in two types of landscapes: large and continuous forest, capable of harboring many YFV hosts, and patches of small forest fragments, where environmental imbalance can lead to a greater density of the primary vectors and high human exposure. In both, we show that most human infections (~ 62%) occurred within an 11-km radius of the finding of an infected NHP, which is in line with the flight range of the primary vectors.

Conclusions
Together, our data suggest that entomological data and landscape composition analyses may help to predict areas permissive to yellow fever outbreaks, allowing protective measures to be taken to avoid human cases.

Graphical Abstract
The impact of lung ultrasound on clinical-decision making across departments: a systematic review
Authors: Heldeweg Micah L. A. , Vermue Lian , Kant Max , Brouwer Michelle , Girbes Armand R. J. , Haaksma Mark E. , Heunks Leo M. A. , Mousa Amne , Smit Jasper M. , Smits Thomas W. , Paulus Frederique , Ket Johannes C. F. , Schultz Marcus J. , Tuinman Pieter Roel 
Published: January 2022

Abstract
Background
Lung ultrasound has established itself as an accurate diagnostic tool in different clinical settings. However, its effects on clinical-decision making are insufficiently described. This systematic review aims to investigate the impact of lung ultrasound, exclusively or as part of an integrated thoracic ultrasound examination, on clinical-decision making in different departments, especially the emergency department (ED), intensive care unit (ICU), and general ward (GW).

Methods
This systematic review was registered at PROSPERO (CRD42021242977). PubMed, EMBASE, and Web of Science were searched for original studies reporting changes in clinical-decision making (e.g. diagnosis, management, or therapy) after using lung ultrasound. Inclusion criteria were a recorded change of management (in percentage of cases) and with a clinical presentation to the ED, ICU, or GW. Studies were excluded if examinations were beyond the scope of thoracic ultrasound or to guide procedures. Mean changes with range (%) in clinical-decision making were reported. Methodological data on lung ultrasound were also collected. Study quality was scored using the Newcastle–Ottawa scale.

Results
A total of 13 studies were included: five studies on the ED (546 patients), five studies on the ICU (504 patients), two studies on the GW (1150 patients), and one study across all three wards (41 patients). Lung ultrasound changed the diagnosis in mean 33% (15–44%) and 44% (34–58%) of patients in the ED and ICU, respectively. Lung ultrasound changed the management in mean 48% (20–80%), 42% (30–68%) and 48% (48–48%) of patients in the ED, in the ICU and in the GW, respectively. Changes in management were non-invasive in 92% and 51% of patients in the ED and ICU, respectively. Lung ultrasound methodology was heterogeneous across studies. Risk of bias was moderate to high in all studies.

Conclusions
Lung ultrasound, exclusively or as a part of thoracic ultrasound, has substantial impact on clinical-decision making by changing diagnosis and management in the EDs, ICUs, and GWs. The current evidence level and methodological heterogeneity underline the necessity for well-designed trials and standardization of methodology.
Attitude and communication skills of German medical students
Authors: Groene Oana R. , Ehrhardt Maren , Bergelt Corinna 
Published: January 2022

Abstract
Objective
While the development of communication competencies in medical schools plays a pivotal role in the curriculum, studies show that students’ communication skills and patient-centred attitudes may vary based on gender and ethnicity. The goal of this study was to investigate the socio-demographic factors that influence medical students’ communication abilities and, more specifically, to what extent their attitude toward communication skills learning and patient orientation associate with communication abilities. Our population included medical students admitted in 2017. Used tools included a communication score, the patient-provider orientation and communication skills attitudes scales.

Results
Three hundred and sixty-five students participated in the study (56.4% female, 85.2% German native speakers, mean age 24.2 ± 3.5 years). Female and German native speaking students had a better communication skills OSCE performance, were more patient-oriented and had more positive attitudes toward communication skills learning than male and non-native speaking students. There was a significant association between gender, native tongue, attitudes towards communication skills learning and communication skills OSCE performance. In conclusion, to support medical students to improve their communication proficiency and attitudes towards the importance of clear communication and patient-oriented care, medical educators should consider teaching and assessment strategies that address socio-cultural aspects of communication.
Functional tissue-engineered microtissue formed by self-aggregation of cells for peripheral nerve regeneration
Authors: Zhang Jian , Li Chaochao , Meng Fanqi , Guan Yanjun , Zhang Tieyuan , Yang Boyao , Ren Zhiqi , Liu Xiuzhi , Li Dongdong , Zhao Jinjuan , Zhao Jie , Wang Yu , Peng Jiang 
Published: January 2022

Abstract
Background
Peripheral nerve injury (PNI) is one of the essential causes of physical disability with a high incidence rate. The traditional tissue engineering strategy, Top-Down strategy, has some limitations. A new tissue-engineered strategy, Bottom-Up strategy (tissue-engineered microtissue strategy), has emerged and made significant research progress in recent years. However, to the best of our knowledge, microtissues are rarely used in neural tissue engineering; thus, we intended to use microtissues to repair PNI.

Methods
We used a low-adhesion cell culture plate to construct adipose-derived mesenchymal stem cells (ASCs) into microtissues in vitro, explored the physicochemical properties and microtissues components, compared the expression of cytokines related to nerve regeneration between microtissues and the same amount of two-dimension (2D)-cultured cells, co-cultured directly microtissues with dorsal root ganglion (DRG) or Schwann cells (SCs) to observe the interaction between them using immunocytochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA). We used grafts constructed by microtissues and polycaprolactone (PCL) nerve conduit to repair sciatic nerve defects in rats.

Results
The present study results indicated that compared with the same number of 2D-cultured cells, microtissue could secrete more nerve regeneration related cytokines to promote SCs proliferation and axons growth. Moreover, in the direct co-culture system of microtissue and DRG or SCs, axons of DRG grown in the direction of microtissue, and there seems to be a cytoplasmic exchange between SCs and ASCs around microtissue. Furthermore, microtissues could repair sciatic nerve defects in rat models more effectively than traditional 2D-cultured ASCs.

Conclusion
Tissue-engineered microtissue is an effective strategy for stem cell culture and therapy in nerve tissue engineering.
Nonwoven-based gelatin/polycaprolactone membrane loaded with ERK inhibitor U0126 for treatment of tendon defects
Authors: Hou Yonghui , Zhou Bingyu , Ni Ming , Wang Min , Ding Lingli , Li Ying , Liu Yamei , Zhang Wencai , Li Gang , Wang Jiali , Xu Liangliang 
Published: January 2022

AbstractBackgroundTendon is a major component of musculoskeletal system connecting the muscles to the bone. Tendon injuries are very common orthopedics problems leading to impeded motion. Up to now, there still lacks effective treatments for tendon diseases.MethodsTendon stem/progenitor cells (TSPCs) were isolated from the patellar tendons of SD rats. The expression levels of genes were evaluated by quantitative RT-PCR. Immunohistochemistry staining was performed to confirm the presence of tendon markers in tendon tissues. Bioinformatics analysis of data acquired by RNA-seq was used to find out the differentially expressed genes. Rat patellar tendon injury model was used to evaluate the effect of U0126 on tendon injury healing. Biomechanical testing was applied to evaluate the mechanical properties of newly formed tendon tissues.ResultsIn this study, we have shown that ERK inhibitor U0126 rather PD98059 could effectively increase the expression of tendon-related genes and promote the tenogenesis of TSPCs in vitro. To explore the underlying mechanisms, RNA sequencing was performed to identify the molecular difference between U0126-treated and control TSPCs. The result showed that GDF6 was significantly increased by U0126, which is an important factor of the TGFβ superfamily regulating tendon development and tenogenesis. In addition, NBM (nonwoven-based gelatin/polycaprolactone membrane) which mimics the native microenvironment of the tendon tissue was used as an acellular scaffold to carry U0126. The results demonstrated that when NBM was used in combination with U0126, tendon healing was significantly promoted with better histological staining outcomes and mechanical properties.ConclusionTaken together, we have found U0126 promoted tenogenesis in TSPCs through activating GDF6, and NBM loaded with U0126 significantly promoted tendon defect healing, which provides a new treatment for tendon injury.
Applications of the amniotic membrane in tissue engineering and regeneration: the hundred-year challenge
Authors: Elkhenany Hoda , El-Derby Azza , Abd Elkodous Mohamed , Salah Radwa A. , Lotfy Ahmed , El-Badri Nagwa 
Published: January 2022

AbstractThe amniotic membrane (Amnio-M) has various applications in regenerative medicine. It acts as a highly biocompatible natural scaffold and as a source of several types of stem cells and potent growth factors. It also serves as an effective nano-reservoir for drug delivery, thanks to its high entrapment properties. Over the past century, the use of the Amnio-M in the clinic has evolved from a simple sheet for topical applications for skin and corneal repair into more advanced forms, such as micronized dehydrated membrane, amniotic cytokine extract, and solubilized powder injections to regenerate muscles, cartilage, and tendons. This review highlights the development of the Amnio-M over the years and the implication of new and emerging nanotechnology to support expanding its use for tissue engineering and clinical applications.
Graphical Abstract
Mesenchymal stromal cell-based therapy for cartilage regeneration in knee osteoarthritis
Authors: Xiang Xiao-Na , Zhu Si-Yi , He Hong-Chen , Yu Xi , Xu Yang , He Cheng-Qi 
Published: January 2022

AbstractOsteoarthritis, as a degenerative disease, is a common problem and results in high socioeconomic costs and rates of disability. The most commonly affected joint is the knee and characterized by progressive destruction of articular cartilage, loss of extracellular matrix, and progressive inflammation. Mesenchymal stromal cell (MSC)-based therapy has been explored as a new regenerative treatment for knee osteoarthritis in recent years. However, the detailed functions of MSC-based therapy and related mechanism, especially of cartilage regeneration, have not been explained. Hence, this review summarized how to choose, authenticate, and culture different origins of MSCs and derived exosomes. Moreover, clinical application and the latest mechanistical findings of MSC-based therapy in cartilage regeneration were also demonstrated.