bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hard signs gone soft: A critical evaluation of presenting signs of extremity vascular injury
Authors: Romagnoli Anna Noel , DuBose Joseph , Dua Anahita , Betzold Richard , Bee Tiffany , Fabian Timothy , Morrison Jonathan , Skarupa David , Podbielski Jeanette , Inaba Kenji , Feliciano David , Kauvar David ,   AAST PROOVIT Study Group
Published: October 2020

BACKGROUND
Despite advances in management of extremity vascular injuries, “hard signs” remain the primary criterion to determine need for imaging and urgency of exploration. We propose that hard signs are outdated and that hemorrhagic and ischemic signs of vascular injury may be of greater clinical utility.

METHODS
Extremity arterial injuries from the American Association for the Surgery of Trauma PROspective Observational Vascular Injury Treatment registry were analyzed to examine the relationships between hard signs, ischemic signs, and hemorrhagic signs of extremity vascular injury with workup, diagnosis, and management.

RESULTS
Of 1,910 cases, 1,108 (58%) had hard signs of vascular injury. Computed tomography angiography (CTA) was more commonly used as the diagnostic modality in patients without hard signs, while operative exploration was primarily used for diagnosis in hard signs. Patients undergoing CTA were more likely to undergo endovascular or hybrid repair (EHR) (10.7%) compared with patients who underwent exploration for diagnosis (1.5%). Of 915 patients presenting with hemorrhagic signs, CTA was performed 14.5% of the time and was associated with a higher rate of EHR and observation. Of the 490 patients presenting with ischemic signs, CTA was performed 31.6% of the time and was associated with higher rates of EHR and observation. Hemorrhagic signs were associated with arterial transection, while ischemic signs were associated with arterial occlusion. Patients with ischemic signs undergoing exploration for diagnosis received more units of packed red blood cells during the first 24 hours. There was no difference in amputation rate, reintervention rate, hospital length of stay, or mortality in comparing groups who underwent CTA versus exploration.

CONCLUSION
Hard signs have limitations in identification and characterization of extremity arterial injuries. A strategy of using hemorrhagic and ischemic signs of vascular injury is of greater clinical utility. Further prospective study is needed to validate this proposed redefinition of categorization of presentations of extremity arterial injury.

LEVEL OF EVIDENCE
Diagnostic, level III.
Does preoperative magnetic resonance imaging alter the surgical plan in patients with acute traumatic cervical spinal cord injury?
Authors: Buchanan Frank R. , Wang Vincent Y. , Amadio Jordan P. , Ortega-Barnett Juan R. , Brown Lawrence H. , Teixeira Pedro G. , Aydelotte Jayson D. , Leede Emily , Ali Sadia , Brown Carlos V.R. 
Published: October 2020

BACKGROUND
Whether magnetic resonance imaging (MRI) adds value to surgical planning for patients with acute traumatic cervical spinal cord injury (ATCSCI) remains controversial. In this study, we compared surgeons' operative planning decisions with and without preoperative MRI. We had two hypotheses: (1) the surgical plan for ATCSCI would not change substantially after the MRI and (2) intersurgeon agreement on the surgical plan would also not change substantially after the MRI.

METHODS
We performed a vignette-based survey study that included a retrospective review of all adult trauma patients who presented to our American College of Surgeons-verified level 1 trauma center from 2010 to 2019 with signs of acute quadriplegia and underwent computed tomography (CT), MRI, and subsequent cervical spine surgery within 48 hours of admission. We abstracted patient demographics, admission physiology, and injury details. Patient clinical scenarios were presented to three spine surgeons, first with only the CT and then, a minimum of 2 weeks later, with both the CT and MRI. At each presentation, the surgeons identified their surgical plan, which included timing (none, <8, <24, >24 hours), approach (anterior, posterior, circumferential), and targeted vertebral levels. The outcomes were change in surgical plan and intersurgeon agreement. We used Fleiss' kappa (κ) to measure intersurgeon agreement.

RESULTS
Twenty-nine patients met the criteria and were included. Ninety-three percent of the surgical plans were changed after the MRI. Intersurgeon agreement was “slight” to “fair” both before the MRI (timing, κ = 0.22; approach, κ = 0.35; levels, κ = 0.13) and after the MRI (timing, κ = 0.06; approach, κ = 0.27; levels, κ = 0.10).

CONCLUSION
Surgical plans for ATCSCI changed substantially when the MRI was presented in addition to the CT; however, intersurgeon agreement regarding the surgical plan was low and not improved by the addition of the MRI.

LEVEL OF EVIDENCE
Diagnostic, level II.
Prognostic value of CT perfusion and permeability imaging in traumatic brain injury
Authors: Avsenik Jernej , Bajrović Fajko F. , Gradišek Primož , Kejžar Nataša , Šurlan Popović Katarina 
Published: October 2020

BACKGROUND
Currently established prognostic models in traumatic brain injury (TBI) include noncontrast computed tomography (CT) which is insensitive to early perfusion alterations associated with secondary brain injury. Perfusion CT (PCT) on the other hand offers insight into early perfusion abnormalities. We hypothesized that adding CT perfusion and permeability data to the established outcome predictors improves the performance of the prognostic model.

METHODS
A prospective cohort study of consecutive 50 adult patients with head injury and Glasgow Coma Scale score of 12 or less was performed at a single Level 1 Trauma Centre. Perfusion CT was added to routine control CT 12 hours to 24 hours after admission. Region of interest analysis was performed in six major vascular territories on perfusion and permeability parametric maps. Glasgow Outcome Scale (GOS) was used 6 months later to categorize patients’ functional outcomes to favorable (GOS score > 3) or unfavorable (GOS score ≤ 3). We defined core prognostic model, consisting of age, motor Glasgow Coma Scale score, pupillary reactivity, and CT Rotterdam Score. Next, we added perfusion and permeability data as predictors and compared updated models to the core model using cross-validated areas under the receiver operator curves (cv-AUC).

RESULTS
Significant advantage over core model was shown by the model, containing both mean cerebral extravascular-extracellular volume per unit of tissue volume and cerebral blood volume of the least perfused arterial territory in addition to core predictors (cv-AUC, 0.75; 95% confidence interval, 0.51–0.84 vs. 0.6; 95% confidence interval, 0.37–0.74).

CONCLUSION
The development of cerebral ischemia and traumatic cerebral edema constitutes the secondary brain injury and represents the target for therapeutic interventions. Our results suggest that adding CT perfusion and permeability data to the established outcome predictors improves the performance of the prognostic model in the setting of moderate and severe TBI.

LEVEL OF EVIDENCE
Prognostic study, level III.
Dementia Incidence in the Elderly Population of Greece
Authors: Vlachos George S. , Kosmidis Mary H. , Yannakoulia Mary , Dardiotis Efthimios , Hadjigeorgiou Georgios , Tzoulaki Ioanna , Georgiou Andrea N. , Sakka Paraskevi , Anastasiou Costas A. , Stefanis Leonidas , Scarmeas Nikolaos 
Published: October 2020

Objectives:
Recently a declining trend in dementia incidence rates has been reported in high-income countries. We investigated dementia incidence in a representative sample of the Greek population in the age group of 65 years and above.

Methods:
This research is part of the Hellenic Epidemiological Longitudinal Investigation of Aging and Diet (HELIAD). The incidence cohort consisted of 1072 participants who were reevaluated after a mean period of 3.09 years.

Results:
The incidence rate of dementia was 19.0 cases per 1000 person-years (age-standardized and sex-standardized incidence: 25.4/1000 person-years), of which 16.3 per 1000 person-years were attributable to Alzheimer disease. Each additional year of age increased dementia risk by 19.3% and each additional year of education decreased dementia risk by 12.1%. Apolipoprotein E (APOE)-ε4 homozygous participants were 18 times more likely to be diagnosed with dementia. A baseline diagnosis of mild cognitive decline (MCI) resulted in a risk for dementia increased by 3.7 times compared with the cognitively normal; in participants with MCI at baseline, APOE-ε4 carriage increased dementia risk by 4.5 times.

Conclusions:
The incidence rate of dementia in people 65 years and above in Greece is generally consistent with recently published rates in Europe and North America. Advancing age, baseline MCI, and APOE-ε4 homozygosity are risk factors, while higher educational attainment seems protective.
Biomarker Use for Dementia With Lewy Body Diagnosis
Authors: Armstrong Melissa J. , Irwin David J. , Leverenz James B. , Gamez Noheli , Taylor Angela , Galvin James E. 
Published: October 2020

Background:
Dementia with Lewy body (DLB) diagnostic criteria define “indicative” and “supportive” biomarkers, but clinical practice patterns are unknown.

Methods:
An anonymous survey querying clinical use of diagnostic tests/biomarkers was sent to 38 center of excellence investigators. The survey included “indicative” biomarkers (dopamine transporter scan, myocardial scintigraphy, polysomnography), “supportive” biomarkers [magnetic resonance imaging (MRI)], positron emission tomography, or single-photon emission computed tomography perfusion/metabolism scans, quantitative electroencephalography), and other diagnostic tests (neuropsychological testing, cerebrospinal fluid analysis, genetics). Responses were analyzed descriptively.

Results:
Of the 22 respondents (58%), all reported the capability to perform neuropsychological testing, MRI, polysomnography, dopamine transporter scans, positron emission tomography/single-photon emission computed tomography scans, and cerebrospinal fluid analysis; 96% could order genetic testing. Neuropsychological testing and MRI were the most commonly ordered tests. Diagnostic testing beyond MRI and neuropsychological testing was most helpful in the context of “possible” DLB and mild cognitive impairment and to assist with differential diagnosis. Myocardial scintigraphy and electroencephalograpy use were rare.

Conclusions and Relevance:
Neuropsychological testing and MRI remain the most widely used diagnostic tests by DLB specialists. Other tests—particularly indicative biomarkers—are used only selectively. Research is needed to validate existing potential DLB biomarkers, develop new biomarkers, and investigate mechanisms to improve DLB diagnosis.
Value of Electroconvulsive Therapy in the General Public
Authors: Ulbrich Laura , Kröger Christoph 
Published: October 2020

Objective
The aims of this study were to estimate the value a population-representative sample places on electroconvulsive therapy (ECT) through willingness to pay (WTP) and to assess the effects of individual characteristics on WTP for ECT.

Methods
A German population-representative sample of 518 was presented with a hypothetical health loss scenario of depression and was asked to indicate WTP for ECT. Probit and quantile regression were used to estimate the effects of individual characteristics on the probability of stating a positive WTP and on the amount of money respondents were willing to pay.

Results
Two thirds of respondents stated that they had no knowledge about ECT. Most (56.5%) respondents indicated zero WTP for health gains through ECT treatment. Mean WTP was €5201 ($5612); median WTP was €1000 ($1079). Respondents' monthly household income had a significant effect on the probability of stating a positive WTP. Assessing WTP above zero, income showed a significant positive effect, whereas a higher score of depressive complaints showed a significant negative effect on the amount respondents were willing to pay.

Conclusion
Knowledge about ECT treatment is particularly low in the German public.
Transcranial Direct Current Stimulation for Prader-Willi Syndrome
Authors: Azevedo Caroline C. , Trevizol Alisson Paulino , Gomes July S. , Akiba Henrique , Franco Ruth R. , Simurro Paula B. , Ianni Renata M. , Grigolon Ruth B. , Blumberger Daniel M. , Dias Alvaro M. 
Published: October 2020

Background
Given the limited therapeutic options for Prader-Willi syndrome (PWS), we conducted an open-label clinical trial to evaluate the effects of transcranial direct current stimulation (tDCS) for hyperphagia, food craving, and aberrant behaviors on this population.

Methods
Twelve subjects with PWS (11–35 years old) were included. The subjects underwent 10 daily 20-minute sessions of tDCS in 2 weeks. The anode was positioned over the left dorsolateral prefrontal cortex, and the cathode over the contralateral region.

Results
We observed amelioration of hyperphagic and food craving symptoms (P < 0.05), as well as amelioration of behavioral symptoms measured with the Aberrant Behavior Checklist (P < 0.05).

Discussion
To our knowledge, this is the first proof-of-concept trial to report the positive effects of increasing excitability of the left dorsolateral prefrontal cortex, using tDCS, for the behavioral, hyperphagia, and food craving symptoms in PWS, which is a low-cost, well-studied, safe alternative for brain stimulation.
Vagus Nerve Stimulation in Patients Receiving Maintenance Therapy With Electroconvulsive Therapy
Authors: Aaronson Scott T. , Goldwaser Eric L. , Kutzer Dennis J. , McAllister-Williams R. Hamish , Sackeim Harold A. , Rush A. John 
Published: October 2020

Objectives
Electroconvulsive therapy (ECT) is a mainstay in both acute and long-term management of difficult-to-treat depression. However, frequent acute courses of ECT or prolonged maintenance ECT treatment may increase adverse-effect burden and/or reduce patient acceptability. Therefore, we investigated the effectiveness of adjunctive vagus nerve stimulation (VNS) therapy as an alternative strategy for long-term maintenance treatment in ECT-responsive patients.

Methods
This retrospective chart review identified maintenance ECT patients with unipolar (n = 5) and bipolar depression (n = 5) from 2 large hospital systems who had a history of ECT response, but the patients had significant residual incapacitating symptoms or increasing concerns regarding the burden associated with ECT and opted to receive adjunctive VNS therapy. The patients were followed for 2 years after VNS implantation. Response and remission were defined as Clinical Global Impression—Severity scale scores of ≤2 and 1, respectively, obtained at 1- and 2-year postimplantation compared with just before VNS implantation.

Results
One-year postimplantation, 6 of 10 had responded of which 5 met remission criteria. All 10 patients benefited from adjunctive VNS therapy with either fewer hospitalizations and/or ECT sessions. Seven of 10 stopped maintenance ECT by the end of year 1; an additional patient stopped maintenance ECT by year 2. No patients required an acute course of ECT during the 2-year follow-up. There was a statistically significant reduction (P < 0.0001) in mean (SD) Clinical Global Impression—Severity scale scores between baseline (5.4 [0.51]) and the 1-year postimplantation (2.1 [1.37]) time points, and between baseline and the 2-year postimplantation (2.3 [1.16]) time points, whereas no difference existed between the 1- and 2-year postimplantation time points.

Conclusions
Vagus nerve stimulation therapy may be a useful maintenance strategy in patients with difficult-to-treat depression receiving maintenance ECT.
Malaria parasites differentially sense environmental elasticity during transmission
Authors: Ripp Johanna , Kehrer Jessica , Smyrnakou Xanthoula , Tisch Nathalie , de Almodovar Carmen Ruiz , Frischknecht Friedrich 
Published: October 2020

AbstractTransmission of malaria-causing parasites to and by the mosquito rely on active parasite migration and constitute bottlenecks in thePlasmodiumlife cycle. Parasite adaption to the biochemically and physically different environments must hence be a key evolutionary driver for transmission efficiency. To probe how subtle but physiologically relevant changes in environmental elasticity impact parasite migration, we introduce 2D and 3D polyacrylamide gels to study ookinetes, the parasite forms emigrating from the mosquito blood meal and sporozoites, the forms transmitted to the vertebrate host. We show that ookinetes adapt their migratory path but not their speed to environmental elasticity and are motile for over 24 hours on soft substrates. In contrast, sporozoites evolved more short-lived rapid gliding motility for rapidly crossing the skin. Strikingly, sporozoites are highly sensitive to substrate elasticity possibly to avoid adhesion on soft endothelial cells on their long way to the liver. Hence the two migratory stages ofPlasmodiumevolved different strategies to overcome the physical challenges posed by the respective environments and barriers they encounter.HighlightsPlasmodiumookinetes can move for over 24 hours on very soft substrates mimicking the blood mealPlasmodiumookinetes change their migration path according to substrate stiffnessPlasmodiumsporozoites are highly sensitive to subtle changes in substrate elasticitySporozoite may have evolved to not attach to the soft endothelium to help reach the liver
In Vivo Mitochondrial ATP Production Is Improved in Older Adult Skeletal Muscle After a Single Dose of Elamipretide in a Randomized Trial
Authors: Roshanravan Baback , Liu Sophia Z. , Shankland Eric G. , Amory John K. , Robertson H. Thomas , Marcinek David J. , Conley Kevin E. 
Published: October 2020

ABSTRACTBackgroundLoss of mitochondrial function contributes to fatigue, exercise intolerance and muscle weakness, and is a key factor in the disability that develops with age and a wide variety of chronic disorders. Here, we describe the impact of a first-in-class cardiolipin-binding compound that is targeted to mitochondria and improves oxidative phosphorylation capacity (Elamipretide, ELAM) in a randomized, double-blind, placebo-controlled clinical trial.MethodsNon-invasive magnetic resonance and optical spectroscopy provided measures of mitochondrial capacity (ATPmax) with exercise and mitochondrial coupling (ATP supply per O2 uptake; P/O) at rest. The first dorsal interosseous (FDI) muscle was studied in 39 healthy older adult subjects (60 to 85 yrs of age; 46% female) who were enrolled based on the presence of poorly functioning mitochondria. We measured volitional fatigue resistance by force-time integral over repetitive muscle contractions.ResultsA single ELAM dose elevated mitochondrial energetic capacity in vivo relative to placebo (ΔATPmax; P=0.055, %ΔATPmax; P=0.045) immediately after a 2-hour infusion. No difference was found on day 7 after treatment, which is consistent with the half-life of ELAM in human blood. No significant changes were found in resting muscle mitochondrial coupling. Despite the increase in ATPmax there was no significant effect of treatment on fatigue resistance in the FDI.ConclusionsThese results highlight that ELAM rapidly and reversibly elevates mitochondrial capacity after a single dose. This response represents the first demonstration of a pharmacological intervention that can reverse mitochondrial dysfunction in vivo immediately after treatment in aging human muscle.
A One-Minute Blood Test to Monitor Immune Responses in COVID-19 Patients and Predict Clinical Risks of Developing Moderate to Severe Symptoms
Authors: Deb Chirajyoti , Salinas Allan N. , Middleton Aurea , Kern Katelyn , Penoyer Daleen , Borsadia Rahul , Hunley Charles , Mehta Vijay , Irastorza Laura , Mehta Devendra I. , Zheng Tianyu , Huo Qun 
Published: October 2020

AbstractCoronavirus disease 2019 (COVID-19) has brought enormous loss and interruption to human life and the global economy since the first outbreak reported in China between late 2019 to early 2020, and will likely remain a public health threat in the months and years to come. Upon infection with SARS-CoV-2, the virus that causes COVID-19, most people will develop no or mild symptoms, however, a small percentage of the population will become severely ill, require hospitalization, intensive care, and some succumb to death. The current knowledge of COVID-19 disease progression with worsening symptom complex implicates the critical importance of identifying patients with high clinical risk compared to those who would be at lower risk for disease control and patient management with better therapeutic output. Currently no clinical test is available that can predict risk factors and immune status change at different severity scales. The immune system plays a critical role in the defense against infectious diseases. Extensive research has found that COVID-19 patients with poor clinical outcomes differ significantly in their immune responses to the virus from those who exhibit milder symptoms. We previously developed a nanoparticle-enabled blood test that can detect the humoral immune status change in animals. In this study, we applied this new test to analyze the immune response in relation to disease severity in COVID-19 patients. From the testing of 153 COVID-19 patient samples and 142 negative controls, we detected statistically significant differences between COVID-19 patients with no or mild symptoms from those who developed moderate to severe symptoms. Mechanistic study suggests that these differences are associated with type 1 versus type 2 immune responses. We conclude that this new rapid test could potentially become a valuable clinical tool for COVID-19 patient risk stratification and management.