bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hemodynamic Adverse Effects of Dexmedetomidine and Propofol in a Critically Ill Trauma and Surgical Population: A Retrospective Cohort
Authors: Nicholson Carli R. , Mullen Chanda , Frazee Lawrence A. , Cucci Michaelia D. 
Published: May 2021

Background:
Propofol and dexmedetomidine may cause hemodynamic adverse effects (AEs) and more data are needed in a trauma and surgical population.

Objective:
The objective of this study was to evaluate the rate of hemodynamic AEs requiring an intervention between dexmedetomidine and propofol in a critically ill trauma and surgical population.

Methods:
This was a retrospective cohort study at a Level 1 trauma center. Intensive care unit patients admitted from October 1, 2017, through October 31, 2018, were divided into two groups: dexmedetomidine or propofol. The primary end point was the proportion of patients who required a therapeutic intervention for a hemodynamic AE within the first 24 hr of initiation of dexmedetomidine or propofol.

Results:
A total of 800 charts were reviewed and 85 patients (dexmedetomidine [n = 35] and propofol [n = 50]) were included. The study population consisted of Caucasian (86%) males (61%) with a median age of 61 [interquartile range—IQR 48, 72], and 18% and 24% required antihypertensive and vasopressor agents, respectively. No difference in the primary outcome was observed (17 [49%] vs. 27 [54%], p = .624). There was no difference in the overall incidence of hemodynamic AE (18 [51%] vs. 30 [60%], p = .433). Dexmedetomidine patients had a greater decrease in median heart rate (HR) compared with the propofol (23 [IQR 16, 41] vs. 14 [IQR 5, 24] beats/min, p = .002).

Conclusions:
The rate of hemodynamic AEs requiring therapeutic interventions was similar between dexmedetomidine and propofol in a critically ill trauma and surgical population; however, dexmedetomidine may be associated with a larger decrease in HR.
Matter of Balance Classes Through Physical Therapist Fall Risk Assessment
Authors: Geyer Rebecca L. , Thompson Tara 
Published: May 2021

Background:
Falls remain the leading cause of injury-related death for 65 years and older. Matter of Balance is a well-documented community-based program designed to reduce participants' fear of falling. However, Matter of Balance classes' effect on physical measures remains less well studied.

Objective:
The objective of this study was to evaluate the effects of the Matter of Balance program on balance, strength, and fall risk.

Methods:
This is a single-group pretest–posttest evaluation of balance and strength in community participants enrolled in 8-week Matter of Balance classes. Physical therapist assessments of the Functional Reach Test and five times sit-to-stand test at week 1 and week 8 were compared.

Results:
A total of 33 class participants were studied. The average improvement in the Functional Reach Test was M = 1.33 (SD = 1.6) inches and the five times sit-to-stand test was M = −3.24 (SD = 3.42) seconds; p < .05.

Conclusions
Matter of Balance classes resulted in improvement in both balance and strength. This study's findings support Matter of Balance classes' efficacy as a community-based program that can reduce a participant's physical risk for falls.
Natural Disasters Related Traumatic Injuries/Fatalities in the United States and Their Impact on Emergency Preparedness Operations
Authors: Gill Sabrina , Sutherland Mason , Raslan Shahm , McKenney Mark , Elkbuli Adel 
Published: May 2021

Introduction:
From 2015 to 2019, the United States experienced a 17% increase in weather-related disasters.

Objectives:
We aimed to study the patterns of natural disaster-related traumatic injuries and fatalities across the United States from 2014 to 2019 and to provide recommendations that can serve to mitigate the impact these natural disasters have on trauma patient morbidity and mortality.

Methods:
A retrospective analysis of the National Safety Council (2014–2019) of natural disaster-related injuries and fatalities was conducted. Descriptive statistics and independent-samples t tests were performed, with significance defined as p < .05.

Results:
Floods produced significantly more mean fatalities per year than tornadoes (118 vs. 33; 95% CI [32.0, 139.0]), wildfires (118 vs. 43, 95% CI [24.8, 155.6]), hurricanes (118 vs. 13, 95% CI [51.5, 159.2]), and tropical storms (118 vs. 15, 95% CI [48.8, 158.2]). Tornadoes produced significantly more mean injuries per year than floods (528 vs. 43, 95% CI [255.9, 715.8]), wildfires (528 vs. 69, 95% CI [227.1, 691.2]), hurricanes (528 vs. 26, 95% CI [270.1, 734.2]), and tropical storms (528 vs. 4, 95% CI [295.9, 753.5]). Southern states experienced greater disaster-related morbidity and mortality over the 6-year study period than other regions with 2,752 injuries and 771 fatalities.

Conclusions:
The incidence of traumatic injuries and fatalities related to certain natural disasters in the United States has significantly increased from 2014 to 2019. Hospital leaders, public health, emergency preparedness personnel, and policy makers must collaborate to implement protocols and guidelines that ensure adequate training, supplies, and personnel to maintain trauma surge capacity, improve emergency preparedness response, and reduce associated morbidity and mortality.
Trauma Prehospital Hypothermia Prevention and Treatment: An Observational Study
Authors: Mota Mauro A. L. , Santos Margarida Reis , Santos Eduardo J. F. , Henriques Carla , Matos Ana , Cunha Madalena 
Published: May 2021

Background:
Hypothermia in trauma patients causes increased morbidity and mortality. Swift recognition and treatment are important to prevent any further heat loss. In addition, patient discomfort from cold decreases satisfaction with care. The administration of active and passive rewarming measures is important in the prevention and treatment of hypothermia, but their use in prehospital trauma patients in Portugal has not been previously reported.

Objective:
To assess the prevalence of hypothermia, the impact of rewarming measures, and the management of the discomfort caused by cold.

Methods:
This is a prospective cohort study conducted in Immediate Life Support Ambulances in Portugal between March 1, 2019, and April 30, 2020.

Results:
This study included records of 586 trauma patients; of whom, 66.2% were men. Cranioencephalic trauma was the most common trauma observed, followed by lower limb and thoracic traumas. Mean body temperature increased 0.12 °C between the first and last assessments (p < .05). Most patients experiencing a level of discomfort of 5 or more on a 0–10 scale reported improvement (from 17.2% to 2.4% after nurses' intervention). Warmed intravenous fluids proved to be effective (p < .05) in increasing body temperature, and passive rewarming measures were effective in preventing hypothermia.

Conclusions:
Hypothermia management has to consider the initial temperature, the season, the available rewarming measures, and the objectives to be achieved. The optimization of resources for the monitoring and treatment of hypothermia should be a priority in prehospital assistance. The implementation of rewarming measures improves patients' outcomes and decreases the discomfort caused by cold in prehospital care.
Preparing for an American College of Surgeons Virtual Trauma Reverification Site Visit: One Center's Experience
Authors: McMahon Maria F. 
Published: May 2021

Background:
The American College of Surgeons (ACS), Committee on Trauma, trauma center verification process is designed to help hospitals improve trauma care. Due to the COVID-19 pandemic social distancing restrictions, performing virtual site visits was piloted.

Objective:
The purpose of this article is to describe the first pilot ACS pediatric trauma center virtual reverification visit performed in the United States.

Methods:
This is a descriptive review of a 2020 pilot virtual Level I pediatric trauma center reverification visit. In-person site visit checklists were altered to adjust to the virtual format. All documents, prereview questionnaire, patient charts, and resource documents were prepared electronically. Collaboration with the departments of information technology, clinical education and informatics, and the general counsel's office prepared the infrastructure to allow reviewers access to protected health information.

Results:
Multiple hospital departments collaborated to facilitate the transition to an electronic format. Organized virtual meeting room scheduling, communications, and coordination between the ACS staff, the reviewers, and the various hospital departments resulted in a successful virtual visit.

Conclusion:
Lessons learned and opportunities for improvement were identified for this first-ever pilot virtual pediatric trauma center reverification site visit. Once the information technology logistic questions were answered, allowing reviewers protected health information access, the general program and document preparation for a virtual trauma reverification site visit was similar to an in-person site visit. Although the review day agenda was similar, execution challenges were identified.
Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19
Authors: Kory Pierre , Meduri Gianfranco Umberto , Varon Joseph , Iglesias Jose , Marik Paul E. 
Published: May 2021

Background:
After COVID-19 emerged on U.S shores, providers began reviewing the emerging basic science, translational, and clinical data to identify potentially effective treatment options. In addition, a multitude of both novel and repurposed therapeutic agents were used empirically and studied within clinical trials.

Areas of Uncertainty:
The majority of trialed agents have failed to provide reproducible, definitive proof of efficacy in reducing the mortality of COVID-19 with the exception of corticosteroids in moderate to severe disease. Recently, evidence has emerged that the oral antiparasitic agent ivermectin exhibits numerous antiviral and anti-inflammatory mechanisms with trial results reporting significant outcome benefits. Given some have not passed peer review, several expert groups including Unitaid/World Health Organization have undertaken a systematic global effort to contact all active trial investigators to rapidly gather the data needed to grade and perform meta-analyses.

Data Sources:
Data were sourced from published peer-reviewed studies, manuscripts posted to preprint servers, expert meta-analyses, and numerous epidemiological analyses of regions with ivermectin distribution campaigns.

Therapeutic Advances:
A large majority of randomized and observational controlled trials of ivermectin are reporting repeated, large magnitude improvements in clinical outcomes. Numerous prophylaxis trials demonstrate that regular ivermectin use leads to large reductions in transmission. Multiple, large “natural experiments” occurred in regions that initiated “ivermectin distribution” campaigns followed by tight, reproducible, temporally associated decreases in case counts and case fatality rates compared with nearby regions without such campaigns.

Conclusions:
Meta-analyses based on 18 randomized controlled treatment trials of ivermectin in COVID-19 have found large, statistically significant reductions in mortality, time to clinical recovery, and time to viral clearance. Furthermore, results from numerous controlled prophylaxis trials report significantly reduced risks of contracting COVID-19 with the regular use of ivermectin. Finally, the many examples of ivermectin distribution campaigns leading to rapid population-wide decreases in morbidity and mortality indicate that an oral agent effective in all phases of COVID-19 has been identified.
Mapping evoked fields in primary motor and sensory areas via magnetoencephalography in tetraplegia
Authors: Foldes Stephen , Chandrasekaran Santosh , Camerone Joseph , Lowe James , Ramdeo Richard , Ebersole John , Bouton Chad E 
Published: May 2021

1AbstractDevices interfacing with the brain through implantation in cortical or subcortical structures have great potential for restoration and rehabilitation in patients with sensory or motor dysfunction. Typical implantation surgeries are planned based on maps of brain activity generated from intact function. However, mapping brain activity for planning implantation surgeries is challenging in the target population due to abnormal residual function and, increasingly often, existing MRI-incompatible implanted hardware. Here, we present methods and results for mapping impaired somatosensory and motor function in an individual with paralysis and an existing brain-computer interface (BCI) device. Magnetoencephalography (MEG) was used to directly map the neural activity evoked during transcutaneous electrical stimulation and attempted movement of the impaired hand. Evoked fields were found to align with the expected anatomy and somatotopic organization. This approach may be valuable for guiding implants in other applications, such as cortical stimulation for pain and to improve implant targeting to help reduce the craniotomy size.
Adaptive radiation and burst speciation of hillstream cyprinid fishGarrain African river
Authors: Levin Boris , Simonov Evgeniy , Franchini Paolo , Mugue Nikolai , Golubtsov Alexander , Meyer Axel 
Published: May 2021

AbstractAdaptive radiation of fishes was long thought to be possible only in lacustrine environments. Recently, several studies have shown that also riverine and stream environments provide the ecological opportunity for adaptive radiation. In this study, we report on a riverine adaptive radiation of six ecomorphs of cyprinid hillstream fishes of the genusGarrain a river located in the Ethiopian Highlands in East Africa.Garraare predominantly highly specialized algae-scrapers with a wide distribution ranging from Southeastern Asia to Western Africa. However, adaptive phenotypic diversification in mouth type, sucking disc morphology, gut length and body shape have been found among these new species in a single Ethiopian river. Moreover, we found two novel phenotypes ofGarra(‘thick-lipped’ and ‘predatory’) that were not described before in this species-rich genus (>160 species). Mitochondrial and genome-wide data suggest monophyletic, intra-basin evolution ofGarraphenotypic diversity with signatures of gene flow from other local populations. Although sympatric ecomorphs are genetically distinct and can be considered to being young species as suggested by genome-wide SNP data, mtDNA was unable to identify any genetic structure suggesting a recent and rapid speciation event. Furthermore, we found evidence for a hybrid origin of the novel ‘thick-lipped’ phenotype, as being the result of the hybridization of two other sympatrically occurring species. Here we highlight how, driven by ecological opportunity, an ancestral trophically highly specialized lineage is likely to have rapidly adaptively radiated in a riverine environment, and that this radiation was promoted by the evolution of novel feeding strategies.
Modeling the Pancreatic Cancer Microenvironment in Search of Control Targets
Authors: Plaugher Daniel , Murrugarra David 
Published: May 2021

AbstractPancreatic Ductal Adenocarcinoma is among the leading causes of cancer related deaths globally due to its extreme difficulty to detect and treat. Recently, research focus has shifted to analyzing the microenvironment of pancreatic cancer to better understand its key molecular mechanisms. This microenvironment can be represented with a multi-scale model consisting of pancreatic cancer cells (PCCs), pancreatic stellate cells (PSCs), as well as cytokines and growth factors which are responsible for intercellular communication between the PCCs and PSCs. We have built a stochastic Boolean network (BN) model, validated by literature and clinical data, in which we probed for intervention strategies that force this gene regulatory network (GRN) from a diseased state to a healthy state. To do so, we implemented methods from phenotype control theory to determine a procedure for regulating specific genes within the microenvironment. We identify target genes and molecules such that the application of their control drives the GRN to the desired state by suppression (or expression) and disruption of specific signaling pathways that will eventually lead to the eradication of the cancer cells. After applying well studied control methods such as stable motifs, feedback vertex set, and computational algebra, we discovered that each produces a different set of control targets that are not necessarily minimal nor unique. Yet, we were able to gain more insight about the performance of each process and the overlap of targets discovered. Nearly every control set contains cytokines, KRas, and HER2/neu which suggests they are key players in the system’s dynamics. To that end, this model can be used to produce further insight into the complex biological system of pancreatic cancer with hopes of finding new potential targets.
Inactivation of the Hippo Tumor Suppressor Pathway Promotes Melanoma
Authors: Vittoria Marc A. , Kingston Nathan , Xia Eric , Hong Rui , Huang Lee , McDonald Shayna , Tilston-Lunel Andrew , Darp Revati , Campbell Joshua , Lang Deborah , Xu Xiaowei , Ceol Craig , Varelas Xaralabos , Ganem Neil J. 
Published: May 2021

AbstractHuman melanomas are commonly driven by activating mutations inBRAF, which promote melanocyte proliferation through constitutive stimulation of the MAPK pathway. However, oncogenicBRAFalone is insufficient to promote melanoma; instead, its expression merely induces a transient burst of proliferation that ultimately ceases with the development of benign nevi (i.e. moles) comprised of growth-arrested melanocytes. The tumor suppressive mechanisms that induce this melanocytic growth arrest remain poorly understood. Recent modeling studies have suggested that the growth arrest of nevus melanocytes is not solely due to oncogene activation in individual cells, but rather due to cells sensing and responding to their collective overgrowth, similar to what occurs in normal tissues. This cell growth arrest is reminiscent of the arrest induced by activation of the Hippo tumor suppressor pathway, which is an evolutionarily conserved pathway known to regulate organ size. Herein, we demonstrate that oncogenic BRAF signaling activates the Hippo pathwayin vitro, which leads to inhibition of the pro-growth transcriptional co-activators YAP and TAZ, ultimately promoting the growth arrest of melanocytes. We also provide evidence that the Hippo tumor suppressor pathway is activated in growth-arrested nevus melanocytesin vivo, both from single-cell sequencing of mouse models of nevogenesis and human tissue samples. Mechanistically, we observe that oncogenic BRAF promotes both ERK-dependent alterations in the actin cytoskeleton and whole-genome-doubling events, and that these two effects independently promote Hippo pathway activation. Lastly, we demonstrate that abrogation of the Hippo pathway, via melanocyte-specific deletion of the Hippo kinasesLats1/2, enables oncogenicBRAF-expressing melanocytes to bypass nevus formation, thus leading to the rapid onset of melanoma with 100% penetrance. This model is clinically relevant, as co-heterozygous loss ofLATS1/2is observed in ∼15% of human melanomas. Collectively, our data reveal that the Hippo pathway enforces the stable growth arrest of nevus melanocytes and therefore represents a critical and previously unappreciated barrier to melanoma development.
Single-virus fusion measurements reveal multiple mechanistically equivalent pathways for SARS-CoV-2 entry
Authors: Sengar Anjali , Cervantes Marcos , Bondalapati Sai T. , Hess Tobin , Kasson Peter M. 
Published: May 2021

AbstractSARS-CoV-2 binds to cell-surface receptors and is activated for membrane fusion and cell entry via proteolytic cleavage. Phenomenological data have shown that SARS-CoV-2 can be activated for entry at either the cell surface or in endosomes, but the relative roles in different cell types and mechanisms of entry have been debated. Here we use single-virus fusion experiments and exogenously controlled proteases to probe activation directly. We find that plasma membrane and an appropriate protease are sufficient to support SARS-CoV-2 pseudovirus fusion. Furthermore, fusion kinetics of SARS-CoV-2 pseudoviruses are indistinguishable no matter which of a broad range of proteases was used to activate the virus. This suggests that fusion mechanism is insensitive to protease identity or even whether activation occurs before or after receptor binding. These data support a model for opportunistic fusion by SARS-CoV-2, where subcellular location of entry likely depends on the differential activity of airway, cell-surface, and endosomal proteases, but all support infection. Inhibiting any single host protease may thus reduce infection in some cells but may be less clinically robust.ImportanceSARS-CoV-2 can use multiple pathways to infect cells, as demonstrated recently when new viral variants switched dominant infection pathways. Here, we use single-virus fusion experiments together with biochemical reconstitution to show that these multiple pathways coexist simultaneously and specifically that the virus can be activated by different proteases in different cellular compartments with mechanistically identical effect. The consequences of this are that the virus is evolutionarily plastic and that therapies targeting viral entry should address multiple pathways at once to achieve optimal clinical effects.
Genetic network regulating visual acuity makes limited contribution to visually guided eye emmetropization
Authors: Tkatchenko Tatiana V. , Tkatchenko Andrei V. 
Published: May 2021

AbstractDuring postnatal development, the eye undergoes a refinement process whereby optical defocus guides eye growth towards sharp vision in a process of emmetropization. Optical defocus activates a signaling cascade originating in the retina and propagating across the back of the eye to the sclera. Several observations suggest that visual acuity might be important for optical defocus detection and processing in the retina; however, direct experimental evidence supporting or refuting the role of visual acuity in refractive eye development is lacking. Here, we used genome-wide transcriptomics to determine the relative contribution of the retinal genetic network regulating visual acuity to the signaling cascade underlying visually guided eye emmetropization.Our results provide evidence that visual acuity is regulated at the level of molecular signaling in the retina by an extensive genetic network. The genetic network regulating visual acuity makes relatively small contribution to the signaling cascade underlying refractive eye development. This genetic network primarily affects baseline refractive eye development and this influence is primarily facilitated by the biological processes related to melatonin signaling, nitric oxide signaling, phototransduction, synaptic transmission, and dopamine signaling. We also observed that the visual-acuity-related genes associated with the development of human myopia are chiefly involved in light perception and phototransduction. Our results suggest that the visual-acuity-related genetic network primarily contributes to the signaling underlying baseline refractive eye development, whereas its impact on visually guided eye emmetropization is modest.