bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atrial myxomas arise from multipotent cardiac stem cells
Authors: Scalise Mariangela , Torella Michele , Marino Fabiola , Ravo Maria , Giurato Giorgio , Vicinanza Carla , Cianflone Eleonora , Mancuso Teresa , Aquila Iolanda , Salerno Luca , Nassa Giovanni , Agosti Valter , De Angelis Antonella , Urbanek Konrad , Berrino Liberato , Veltri Pierangelo , Paolino Donatella , Mastroroberto Pasquale , De Feo Marisa , Viglietto Giuseppe , Weisz Alessandro , Nadal-Ginard Bernardo , Ellison-Hughes Georgina M , Torella Daniele 
Published: March 2020

Abstract

Aims
Cardiac myxomas usually develop in the atria and consist of an acid-mucopolysaccharide-rich myxoid matrix with polygonal stromal cells scattered throughout. These human benign tumours are a valuable research model because of the rarity of cardiac tumours, their clinical presentation and uncertain origin. Here, we assessed whether multipotent cardiac stem/progenitor cells (CSCs) give rise to atrial myxoma tissue.

Methods and results
Twenty-three myxomas were collected and analysed for the presence of multipotent CSCs. We detected myxoma cells positive for c-kit (c-kitpos) but very rare Isl-1 positive cells. Most of the c-kitpos cells were blood lineage-committed CD45pos/CD31pos cells. However, c-kitpos/CD45neg/CD31neg cardiac myxoma cells expressed stemness and cardiac progenitor cell transcription factors. Approximately ≤10% of the c-kitpos/CD45neg/CD31neg myxoma cells also expressed calretinin, a characteristic of myxoma stromal cells. In vitro, the c-kitpos/CD45neg/CD31neg myxoma cells secrete chondroitin-6-sulfate and hyaluronic acid, which are the main components of gelatinous myxoma matrix in vivo. In vitro, c-kitpos/CD45neg/CD31neg myxoma cells have stem cell properties being clonogenic, self-renewing, and sphere forming while exhibiting an abortive cardiac differentiation potential. Myxoma-derived CSCs possess a mRNA and microRNA transcriptome overall similar to normal myocardium-derived c-kitpos/CD45neg/CD31negCSCs , yet showing a relatively small and relevant fraction of dysregulated mRNA/miRNAs (miR-126-3p and miR-335-5p, in particular). Importantly, myxoma-derived CSCs but not normal myocardium-derived CSCs, seed human myxoma tumours in xenograft’s in immunodeficient NOD/SCID mice.

Conclusion
Myxoma-derived c-kitpos/CD45neg/CD31neg CSCs fulfill the criteria expected of atrial myxoma-initiating stem cells. The transcriptome of these cells indicates that they belong to or are derived from the same lineage as the atrial multipotent c-kitpos/CD45neg/CD31neg CSCs. Taken together the data presented here suggest that human myxomas could be the first-described CSC-related human heart disease.
Using photography to explore people with diabetes’ perspectives on food environments in urban and rural South Africa
Authors: Spires Mark , Delobelle Peter , Sanders David , Puoane Thandi 
Published: March 2020

Abstract
Diabetes, a serious disease resulting in significant morbidity and early mortality, is currently on the rise globally. A major contributor to this observed increase in low- and middle-income countries, such as South Africa, has been the observed change in diet at the population level—a shift from a traditional diet, to one consisting of more energy-dense, processed foods, with more added sugar, salt and fat. Implicated in this degradation of diet are changing local food environments. Participant-generated digital photographs and facilitated focus group discussion-style workshops were utilized to better understand diabetic community members’ perspectives on their food environments in both an urban and rural setting in South Africa, and what (and how) aspects of these physical environments influence their food acquisition behaviours and diet. Qualitative data were analysed using a deductive thematic analysis approach. The resulting predominant themes of accessibility, availability and affordability are outlined and discussed. Findings from this study have implications beyond the self-management of diabetes and extend to the self-management and reduction of all diet-related non-communicable diseases.
Single cell transcriptome profiling of the human alcohol-dependent brain
Authors: Brenner Eric , Tiwari Gayatri R , Kapoor Manav , Liu Yunlong , Brock Amy , Mayfield R Dayne 
Published: March 2020

Abstract
Alcoholism remains a prevalent health concern throughout the world. Previous studies have identified transcriptomic patterns in the brain associated with alcohol dependence in both humans and animal models. But none of these studies have systematically investigated expression within the unique cell types present in the brain. We utilized single nucleus RNA sequencing (snRNA-seq) to examine the transcriptomes of over 16 000 nuclei isolated from the prefrontal cortex of alcoholic and control individuals. Each nucleus was assigned to one of seven major cell types by unsupervised clustering. Cell type enrichment patterns varied greatly among neuroinflammatory-related genes, which are known to play roles in alcohol dependence and neurodegeneration. Differential expression analysis identified cell type-specific genes with altered expression in alcoholics. The largest number of differentially expressed genes (DEGs), including both protein-coding and non-coding, were detected in astrocytes, oligodendrocytes and microglia. To our knowledge, this is the first single cell transcriptome analysis of alcohol-associated gene expression in any species and the first such analysis in humans for any addictive substance. These findings greatly advance the understanding of transcriptomic changes in the brain of alcohol-dependent individuals.
International Relations Theory and the Future of European Integration
Authors: Maher Richard 
Published: March 2020

AbstractWhat are the prospects and likely future direction of European integration? Will it be marked by resilience and perhaps even deepening integration among European Union (EU) member states, or will it encounter further instability that could lead to fragmentation and disintegration? The answers to these questions are currently unknown but are important not just for the citizens and countries of the EU but for world politics more broadly. Scholars and other observers have advanced a range of arguments to answer these questions, many of which are derived from the three mainstream theoretical paradigms of contemporary International Relations (IR): realism, liberalism, and constructivism. These arguments reveal disagreement both within and across paradigms over the question of the EU's future. While it is commonly thought that realists are generally pessimistic and liberals and constructivists broadly optimistic regarding the EU's future prospects, it is possible to identify arguments derived from liberal IR theory that the EU faces possibly fatal challenges and realists who see powerful reasons for the EU to stick together, while there are constructivists who think it can go either way. There are thus six basic positions on the future of the EU derived from IR theory. This paper identifies and evaluates a broad range of causal forces that will affect the future of European integration. The paper concludes by discussing the enduring role and value of theory in the study of international relations.
Grazoprevir/elbasvir for the immediate treatment of recently acquired HCV genotype 1 or 4 infection in MSM
Authors: Boyd Anders , Miailhes Patrick , Chas Julie , Valantin Marc-Antoine , Yazdanpanah Yazdan , Rosenthal Eric , Chevaliez Stephane , Piroth Lionel , Rougier Hayette , Peytavin Gilles , Pialoux Gilles , Girard Pierre-Marie , Lacombe Karine 
Published: March 2020

Abstract

Background
In Europe, increases in HCV infection have been observed over the last two decades in MSM, making them a key population for recently acquired HCV. Alternative combinations of direct-acting antiviral agents against early HCV infection need to be assessed.

Patients and methods
In this pilot trial, MSM with recently acquired genotype 1 or 4 HCV infection were prospectively included and received 8 weeks of oral grazoprevir 100 mg and elbasvir 50 mg in a fixed-dose combination administered once daily. The primary endpoint was sustained virological response evaluated 12 weeks after the end of treatment (EOT) (SVR12). Secondary endpoints were the virological characterization of failures, the quality of life before, during and after treatment and the rate of reinfection.

Results
In a 15 month period, 30 patients were enrolled, all of whom were MSM. Of the 29 patients completing follow-up, 28 (96%, 95% CI = 82%–99%) achieved SVR12. One patient interrupted follow-up (suicide) but had undetectable plasma HCV RNA at EOT. One patient with suboptimal adherence confirmed by plasma drug monitoring relapsed and developed NS3, NS5A and NS5B resistance-associated substitutions (V36M, M28V and S556G). The most common adverse events related to study drug were diarrhoea (n = 4, 13%), insomnia (n = 2, 7%) and fatigue (n = 2, 7%), although no patient discontinued treatment. No HIV RNA breakthrough was reported in the 28 patients with HIV coinfection. At Week 48, reinfection was diagnosed in three patients.

Conclusions
Our data support the use of grazoprevir/elbasvir for immediate treatment against HCV in order to reduce HCV transmission in MSM.
8 The Adoption of Rescue Colloid During Resuscitation Decreases Fluid Administered and Returns End Organ Perfusion
Authors: Comish Paul , Castillo-Angeles Manuel , Carlson Deborah , Phelan Herb , Arnoldo Brett , Kubasiak John 
Published: March 2020

Abstract

Introduction
Traditionally lactated ringers (LR) has been utilized for the resuscitation of thermally injured patients. Both the Parkland and Brooke formula’s include the addition of albumin as part of their ongoing resuscitation after the initial 24 hours. Over the last five years, the addition of albumin to current protocols has been reported to decrease fluid creep. Our institution has adopted these practices and here we present our findings during the adoption phase of rescue albumin during resuscitation.

Methods
A prospectively collected burn registry was queried for patients greater than 18 years, between July 2017 and December 2018, who sustained a thermal injury and required a formal resuscitation. Patients were included in the rescue albumin group if the treating team administered 25% albumin for a sustained urine output less than 0.5ml/kg over 2–3 hours. Our primary outcome was a total volume of resuscitation ml LR/%TBSA/kg. Our secondary outcomes were the change in resuscitation rate and the change in urine output three hours before and three hours after the administration of albumin normalized to %TBSA/kgs. Finally, we compared clinical outcomes of ICU days and length of stay (LOS) between the rescue albumin and no rescue albumin group.

Results
A total of 92 patients with thermal injuries were included: median age was 40 (IQR 31–57), 73% were male, and 30 patients received rescue albumin. The TBSA was increased in those who received rescue albumin (47% vs 38% p=0.02). Despite a higher TBSA in the albumin group the total LR given during resuscitation normalized to TBSA and KG was not significantly different (ml LR/%TBSA/kg: 3.66 vs. 4.31, p=0.149). Similarly, the total urine output (UOP) and the adjusted UOP showed no significant difference, total UOP 1,781 ml no albumin vs 1,483ml rescue albumin (p=0.149) and UOP/kg 21.7ml no albumin vs 18.9 ml rescue albumin (p=0.341). But our secondary outcomes did demonstrate there was a decrease in the LR rate by -0.06 ml/%TBSA/kg/hr (SD 0.13) and an increase in the UOP by 1.61 ml/kg/hr (SD 3.25), see Figure 1.

Conclusions
Rescue albumin administration decreases the amount of fluid administered during resuscitation, and increases end organ function as evidenced by increase UOP. This was observed in patients who sustained larger burns and were failing traditional increases in resuscitation LR. These findings are the basis for a modification to our current protocol and a prospective study of the clinical outcomes.

Applicability of Research to Practice
We believe these findings support the limited use of albumin in patients who fail a conventional LR based resuscitation.
17 The Impact of Modifiable Comorbid Conditions on Long-term Patient Reported Outcomes in Burn Survivors
Authors: Sheckter Clifford C , Li Kevin , Carrougher Gretchen J , Pham Tam N , Gibran Nicole S , Stewart Barclay T 
Published: March 2020

Abstract

Introduction
Pre-existing comorbidities in burn survivors increase the risk of death and negatively impact quality of life. Investigations to date have only evaluated comorbidities as cumulative indices, which prevents identification of specific conditions for risk reduction after injury. Therefore, we aimed to evaluate the differential effects of specific conditions on patient reported outcomes.

Methods
A prospectively maintained trauma registry was merged with a longitudinal burn database using unique patient identifiers for burn survivors from 2007–2018. Admission comorbidities included: chronic liver disease, diabetes, hypertension, chronic pulmonary disease, chronic gastrointestinal disease, malignancy, cerebrovascular accident, congestive heart failure, bleeding disorder, coagulopathy, congenital condition, psychiatric illness, major depressive disorder, smoking status, alcohol use disorder, substance use disorder, trauma history, and steroid use. Demographic and burn related variables included age, gender, race, surface area burned, and number of operations during admission. Health related quality of life was assessed using the Short Form-12/Veterans RAND 12(SF/VR-12©) health survey component scores at 6, 12, & 24 months post injury. SF/VR-12 outcomes were evaluated with generalized linear models.

Results
The dataset included 493 adult participants of which 354 were male (71.8%). Median burn size was 14% TBSA (IQR 5%, 28%), and mean age was 45.0±16.3 years. 343 participants (69.6%) had ≥1 comorbidity, with a mean of 1.32±1.30 comorbidities/participant. SF/VR-12 mental component scores at 6 and 12 months post injury were negatively associated with history of psychiatric illness (p&lt; 0.001, p=0.013); there were no significant predictors at 24 month follow up. SF/VR-12 physical component scores were negatively associated with smoking (p=0.019), diabetes (p=0.001), alcohol use disorder (p=0.001), and history of CVA (p=0.005) at 6 month follow up. 12 month SF/VR-12 physical component scores were negatively associated with trauma history (p=0.001), diabetes (p=0.042), and CHF (p=0.016). 24-month SF/VR-12 physical component scores were negatively associated with psychiatric illness (p=0.003).

Conclusions
Smoking, alcohol use disorder, and diabetes were associated with lower physical component scores 6-months after injury; diabetes persisted a negative covariate at 12 months. Psychiatric illness was negatively associated with mental component scores at 6 and 12 months after injury. Burn survivors may benefit from integrated diabetes management and mental health treatment during their rehabilitation.

Applicability of Research to Practice
Specific comorbid conditions differentially affect quality of life in burn survivors. Targeting management of specific conditions during recovery may improve quality of life.
54 Validation of Infrared Thermography for Prediction of 21-day Burn Wound Healing
Authors: Peterson Michael P , Firpo Matthew A , Fleming Irma D , Vachet Clement , Huston Zachary T , Graham Emily M , Lewis Giavonni 
Published: March 2020

Abstract

Introduction
Although trained specialists easily identify most full and superficial partial thickness burn injuries, deep partial-thickness injuries present a true challenge to the clinician. Various imaging modalities to assess perfusion and determine healing potential include skin biopsy with histology, laser doppler imaging, active dynamic and static infrared thermography, vital dyes, indocyanine green video angiography and others. Prior studies indicate, with small clinical and animal studies, forward looking infrared is a valid tool to assess healing potential and 21-day healing within the first 48 hrs after presentation. The aim of our study is to determine if an absolute increase or decrease in temperature (°C) measurements across a burn wound in a large clinical cohort correlates with 21-day healing after 48 hrs from time of injury.

Methods
After informed photo consent was obtained, thermographic images were captured at presentation, 24hrs, and 48hrs from patients admitted to our center between October 2018 and August 2019. Thermographic images were reviewed and temp measurements obtained using a linear vector through the wound. Next we determined if patients healed within 21 days. Data collected includes demographic data, burn characteristics, injury site (based on Lund Browder segmentation) and wound temp (average, minimum, maximum). Data was analyzed using Wilcoxon rank sum test with continuity correction.

Results
We reviewed images for 159 burn sites from 29 patients, the largest image set to be reviewed to date. The cases were 84% male, the mean and range was 33.1 years (1.7 – 70) for age and 25% (2 – 54.5) for TBSA. We found an average temp difference between 24 hrs – 48 hrs (p-value= 0.007) was significant, and no significant difference in average temp change when evaluating admit – 24 hrs (p-value=0.053) and admit – 48 hrs (p-value=0.316), consistent with predictions of prior studies. Average temp from admit – 24 hrs decreased by 0.86°C in healed (n=48) vs non-healed (n=91); increased on average by 1.25°C in healed (n=39) vs non-healed (n=74) from 24 hrs – 48 hrs; and showed a modest decrease by 0.3°C in healed (n=50) vs non-healed (n=82) when comparing admit 48 hr temp.

Conclusions
These data demonstrate that burn wound temperature difference between 24 and 48 hours after admittance as measured by infrared thermography correlates with clinical outcomes and 21 day healing.

Applicability of Research to Practice
Infrared thermography is a validated tool to assess burn depth after 48 hrs. In the future, this modality may impact triage in the military, rural, accidental and non-accidental disasters.
56 Reduced Length of Stay with Autologous Skin Cell Suspension Reduces Burn Injuries
Authors: Carter Jeffrey E , Platt Blake , Tuggle Charles T 
Published: March 2020

Abstract

Introduction
Burn injuries remain a surgical challenge with few recent innovations. Grafting with split-thickness skin grafts (STSGs) has been the standard of care for decades. Although shown to have mortality benefits, STSGs are associated with significant morbidity in the form of pain and additional open wounds. For years, surgeons have looked for ways to decrease this associated morbidity. To that end, autologous skin cell suspension (ASCS) is a recently FDA-approved point of care regenerative medicine technology that reduces donor skin requirements without compromising clinical outcomes. Our study evaluated the cost and length of stay comparing STSG alone versus ASCS.

Methods
We obtained IRB-approval for single institution, retrospective chart review of patients age &gt;14 years admitted with burn injuries from March 2018 – September 2018. Primary outcome was length of stay/%TBSA for patients undergoing STSG alone as compared to patients undergoing ASCS. The 2016 American Burn Association National Burn Repository (NBR) was used to benchmark LOS/%TBSA. Age, percentage burn injury (TBSA), LOS, mortality, and number of surgeries were reviewed. Student’s t-test was used to assess statistical significance of intragroup analysis.

Results
36 patients were treated with ASCS in combination with meshed autografts for full-thickness acute burn injuries. 37 patients were treated with STSGs at our center. Mean age and %TBSA was 45.2 years and 6.6% for the STSG group and 46.0 years and 18.6% for the ASCS group. The LOS/%TBSA for the STSG was 1.72 versus 1.19 for the ASCS patients (p-value=0.02). The NBR predicts a LOS/%TBSA of 3.38 and 3.42 for the STSG and ASCS groups. Patients in the STSG group and ASCS group had statistically similar surgeries and mortalities.

Conclusions
Burn injured patients treated with ASCS had a decreased LOS/%TBSA when compared to both the STSGs and NBR predictions. ASCS is a novel technology allowing for point-of-care treatment that may decrease LOS for burn injured patients and should be considered as an adjunct to traditional techniques for burn patients.

Applicability of Research to Practice
Reduced length of stay compared to traditional burn care.
75 Burn Survivors Can Exercise for 30 Min, Even in the Heat, Without a Risk of Excessive Hyperthermia
Authors: Crandall Craig G , Cramer Matthew N , Huang Mu , Moralez Gilberto , Belval Luke , Watso Joseph C , Fischer Mads 
Published: March 2020

Abstract

Introduction
Excision of burned skin and subsequent grafting removes sweat glands and thereby impairs thermoregulation. Consequently, rehabilitation and associated exercise may be accompanied by a greater risk of hyperthermia, depending on exercise duration, intensity and environmental temperature. Current physical activity guidelines recommend adults perform at least 150 min of moderate-intensity exercise per week, which is often divided into 30-min daily sessions. This project tested the hypothesis that burn survivors could exercise for 30 min without excessive elevations in core body temperature, regardless of the total body surface area (%TBSA) burned or environmental temperature.

Methods
Ten subjects cycled for 60 min at 1) a moderate intensity (97±8 watts) in a thermoneutral environment (24°C, MOD_NEU), 2) a moderate intensity (100±17 watts) in a hot environment (39°C, MOD_HOT), and 3) a low intensity (65±10 watts) in a hot environment (39°C, LOW_HOT). Burn injuries were simulated by covering 0%, 20%, 40%, or 60% of the individual’s TBSA with an absorbent material that prevented sweat evaporation. Changes in gastrointestinal temperature (ΔTcore) were analyzed at 15-min increments throughout exercise.

Results
For the MOD_NEU trial, there were no differences in ΔTcore between the %TBSA coverage bouts at any time point during exercise. For the MOD_HOT trial, there were no differences in ΔTcore at 15 and 30 min of exercise regardless of the %TBSA coverage, while ΔTcore was appreciably elevated (P&lt; 0.05) at 45 and 60 min of exercise for 20%+ TBSA bouts. For the MILD_HOT trial, there were no differences in ΔTcore at any time point between %TBSA bouts, with the sole exception of 60% simulated burn having a slightly greater ΔTcore (0.3±0.34°C; P&lt; 0.05) at 60 min of exercise relative to the 0% TBSA bout.

Conclusions
These data indicate that individuals with up to 60% of their TBSA burned could exercise at a moderate intensity for 30 min, even in hot environmental conditions, without excessive elevations in body core temperature.

Applicability of Research to Practice
Individuals with significant burn injuries can benefit from exercise, without the risk of excessive hyperthermia, for up to 30 min in the heat or at least 60 min in an air conditioned space. Funding: DOD W81XWH-15-1-0647