bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a sensitive MEDLINE search strategy to identify literature relevant to limb prostheses
Authors: Nylander Elisabeth , Ramstrand Nerrolyn , Hjort Margareta , Rusaw David F. 
Published: May 2021

Background:
Researchers and clinicians may find it challenging to identify relevant articles about limb prostheses in online databases. Searches may be improved by using standardized strategies, also known as filters or hedges.

Objectives:
To develop and validate a highly sensitive MEDLINE (EBSCOHost) search strategy for limb prostheses.

Study Design:
Search strategy development/validation.

Methods:
A gold standard (GS) list of peer-reviewed articles on the topic of limb prostheses was created using a relative recall method. This involved identifying and including relevant systematic reviews/meta-analyses and then adding articles that were included in the analysis section of these reviews. Possible terms for the search strategy were identified through brainstorming and exploration of medical subject headings in MEDLINE (MeSH) and standards from the International Organization for Standardization (ISO). Concepts were grouped using relevant Boolean operators (e.g. AND and OR) and database record search fields (i.e. MeSH terms, title, and abstract). Part of the GS was used to refine the search strategy and reduce the number of records retrieved in total. The remaining GS set was used to validate and calculate sensitivity of the search strategy. Performance of the search strategy was compared against searches using only relevant MeSH terms.

Results:
After screening, the final GS totaled 853 records. The developed search strategy was highly sensitive (99.80%) and performed with higher relative recall than searches with relevant MeSH terms.

Conclusions:
This study provides a highly sensitive search strategy that can be used by clinicians and researchers when searching for relevant literature on limb prostheses in MEDLINE (EBSCOHost).
Prehospital tourniquet use: An evaluation of community application and outcome
Authors: Barnard Leslie M. , Guan Sally , Zarmer Lori , Mills Brianna , Blackwood Jennifer , Bulger Eileen , Yang Betty Y. , Johnston Peter , Vavilala Monica S. , Sayre Michael R. , Rea Thomas D. , Murphy David L. 
Published: May 2021

BACKGROUND
There is substantial investment in layperson and first responder training involving tourniquet use for hemorrhage control. Little is known however about prehospital tourniquet application, field conversion, or outcomes in the civilian setting. We describe the experience of a metropolitan region with prehospital tourniquet application.

METHODS
We conducted a retrospective cohort study characterizing prehospital tourniquet use treated by emergency medical services (EMS) in King County, Washington, from January 2018 to June 2019. Emergency medical services and hospital records were abstracted for demographics, injury mechanism, tourniquet details, clinical care, and outcomes. We evaluated the incidence of tourniquet application, who applied the device (EMS, law enforcement, or layperson), and subsequent course.

RESULTS
A total of 168 patients received tourniquet application, an incidence of 5.1 per 100,000 person-years and 3.48 per 1,000 EMS responses for trauma. Tourniquets were applied for penetrating trauma (64%), blunt trauma (30%), and bleeding ateriovenous fistulas (7%). A subset was critically ill: 13% had systolic blood pressures of <90 mm Hg, 8% had Glasgow Coma Scale score of <13, and 3% had cardiac arrest. Among initial applications, 48% were placed by law enforcement, 33% by laypersons, and 18% by EMS. Among tourniquets applied by layperson or law enforcement (n = 137), EMS relied solely on the original tourniquet in 45% (n = 61), placed a second tourniquet in 20% (n = 28), and removed the tourniquet without replacement in 35% (n = 48). Overall, 24% required massive transfusion, 59% underwent urgent surgery, and 21% required vascular surgery. Mortality was 3% (n = 4). At hospital discharge, the tourniquet limb was fully functional in 81%, partially functional in 10%, and nonfunctional in 9%; decreased function was not attributed to tourniquet application.

CONCLUSION
The high rate of application, need for urgent hospital intervention in a subset, and low incidence of apparent complication suggest that efforts to increase access and early tourniquet use can provide public health benefit.

LEVEL OF EVIDENCE
Therapeutic, level IV.
Extrathoracic multiple trauma dysregulates neutrophil function and exacerbates pneumonia-induced lung injury
Authors: Leonard Jennifer M. , Zhang Christina X. , Lu Liang , Hoofnagle Mark H. , Fuchs Anja , Clemens Regina A. , Ghosh Sarbani , Hughes Shin-Wen , Bochicchio Grant V. , Hotchkiss Richard , Turnbull Isaiah R. 
Published: May 2021

BACKGROUND
Forty percent of critically ill trauma patients will develop an infectious complication. Pneumonia is the most common cause of death of trauma patients surviving their initial insult. We previously demonstrated that polytrauma (PT), defined as two or more severe injuries in at least two areas of the body, induces emergency hematopoiesis characterized by accelerated myelopoiesis in the bone marrow and increased myeloid cell frequency in the peripheral tissues. We hypothesized that PT alone induces priming of neutrophils, resulting in hyperactivation upon secondary exposure to bacteria and causing acute lung injury and increased susceptibility to secondary exposure to Pseudomonas aeruginosa pneumonia.

METHODS
C57BL/6 mice were subjected to PT consisting of a lower extremity pseudofracture, liver crush injury, and 15% blood-volume hemorrhage. Pneumonia was induced by intratracheal injection of 5 × 106 CFU live P. aeruginosa or 1 × 107 of heat-killed P. aeruginosa (HKPA). For reactive oxygen species (ROS), studies polymorphonuclear neutrophils (PMNs) were isolated by immunomagnetic bead negative selection and stimulated ex-vivo with HKPA. Reactive oxygen species production was measured by immunofluorescence. For histology, lung sections were stained by hematoxylin-eosin and analyzed by a blinded grader.

RESULTS
Polytrauma induced persistent changes in immune function at baseline and to secondary infection. Pneumonia after injury resulted in increased mortality (60% vs. 5% p < 0.01). Blood neutrophils from PT mice had higher resting (unstimulated) ROS production than in naive animals (p < 0.02) demonstrating priming of the neutrophils following PT. After intratracheal HKPA injection, bronchoalveolar lavage PMNs from injured mice had higher ROS production compared with naive mice (p < 0.01), demonstrating an overexuberant immunopathologic response of neutrophils following PT.

CONCLUSION
Polytrauma primes neutrophils and causes immunopathologic PMN ROS production, increased lung injury and susceptibility to secondary bacterial pneumonia. These results suggest that trauma-induced immune dysfunction can cause immunopathologic response to secondary infection and suggests neutrophil-mediated pulmonary damage as a therapeutic target for posttrauma pneumonia.
The impact of delayed management of fall-related hip fracture management on health outcomes for African American older adults
Authors: Jarman Molly P. , Sokas Claire , Dalton Michael K. , Castillo-Angeles Manuel , Uribe-Leitz Tarsicio , Heng Marilyn , von Keudell Arvind , Cooper Zara , Salim Ali 
Published: May 2021

BACKGROUND
Black hip fracture patients experience worse health outcomes than otherwise similar White patients, but causes of these disparities are not known. We sought to determine if delays in hip fracture surgery and/or hospital structures contribute to racial disparities in hip fracture outcomes.

METHODS
Using 2006 to 2016 Trauma Quality Program Public Use Files, we identified hip fracture patients with primary mechanisms of fall from standing and determined surgical treatment category (no surgery, surgery within 24 hours after arrival, surgery 24–48 hours after arrival, surgery more than 48 hours after arrival) as well as hospital structure characteristics (trauma center designation, teaching status, profit status, bed size). We used generalized structural equation models to conduct path analyses and determine if hip fracture treatment and hospital characteristics mediated the relationship between race (non-Hispanic Black/non-Hispanic White) and outcomes (complications, length of stay, disposition).

RESULTS
Non-Hispanic Black patients were more likely than non-Hispanic White patients to receive treatment at an academic medical center (49.1% vs. 28.0%), at a hospital with >600 inpatient beds (39.5% vs. 25.3%), and at a level I or II trauma center (86.8% vs. 77.7%); were more likely to go without hip fracture repair surgery (22.8% vs. 21.4%); and were more likely to have delayed surgery >48 hours after hospital arrival (15.5% vs. 10.6%). Path analysis suggests hip fracture treatment group and hospital characteristics mediate the relationship with complications, length of stay, and disposition.

CONCLUSION
Non-Hispanic Black patients with fall-related hip fracture are more likely to experience delays in care, complications, and longer inpatient stays. Hospital characteristics contribute to increased risk of complications and longer length of stay, both as independent determinants of outcomes and as determinants of delays in hip fracture surgery.

LEVEL OF EVIDENCE
Prognostic and epidemiologic, level III.
A systematic review of neuropsychological and psychiatric sequalae of COVID-19: implications for treatment
Authors: Vanderlind William Michael , Rabinovitz Beth B. , Miao Iris Yi , Oberlin Lauren E. , Bueno-Castellano Christina , Fridman Chaya , Jaywant Abhishek , Kanellopoulos Dora 
Published: May 2021

Purpose of review
COVID-19 impacts multiple organ systems and is associated with high rates of morbidity and mortality. Pathogenesis of viral infection, co-morbidities, medical treatments, and psychosocial factors may contribute to COVID-19 related neuropsychological and psychiatric sequelae. This systematic review aims to synthesize available literature on psychiatric and cognitive characteristics of community-dwelling survivors of COVID-19 infection.

Recent findings
Thirty-three studies met inclusion/exclusion criteria for review. Emerging findings link COVID-19 to cognitive deficits, particularly attention, executive function, and memory. Psychiatric symptoms occur at high rates in COVID-19 survivors, including anxiety, depression, fatigue, sleep disruption, and to a lesser extent posttraumatic stress. Symptoms appear to endure, and severity of acute illness is not directly predictive of severity of cognitive or mental health issues. The course of cognitive and psychiatric sequelae is limited by lack of longitudinal data at this time. Although heterogeneity of study design and sociocultural differences limit definitive conclusions, emerging risk factors for psychiatric symptoms include female sex, perceived stigma related to COVID-19, infection of a family member, social isolation, and prior psychiatry history.

Summary
The extant literature elucidates treatment targets for cognitive and psychosocial interventions. Research using longitudinal, prospective study designs is needed to characterize cognitive and psychiatric functioning of COVID-19 survivors over the course of illness and across illness severity. Emphasis on delineating the unique contributions of premorbid functioning, viral infection, co-morbidities, treatments, and psychosocial factors to cognitive and psychiatric sequelae of COVID-19 is warranted.
Effects of the COVID-19 pandemic and lockdown on alcohol use disorders and complications
Authors: Murthy Pratima , Narasimha Venkata Lakshmi 
Published: May 2021

Purpose of review
To understand the effect of COVID-19 pandemic and lockdown on persons with alcohol use disorders.

Recent findings
From a total of 455 titles on COVID-19 and alcohol, 227 abstracts were screened, and 95 articles were reviewed (on November 25th, 2020). The immediate effect was an increase in alcohol related emergencies including alcohol withdrawal, related suicides, and methanol toxicity. Although there are mixed findings with respect to changes in the quantity of drinking, there are reports of binge/heavy drinking during the lockdown as well as relapse postlockdown. Psychological, social, biological, economic and policy-related factors appear to influence the changes in drinking. Although preliminary data suggest no change in alcohol use among persons with comorbid mental illness, findings in this population are presently limited. Among patients with alcohol related liver disease, outcomes appear worse and caution is warranted with the use of medications. Alcohol also appears to increases the risk of COVID-19 infection and complicates its course.
Although some nations banned alcohol sales completely during lockdown, others declared it as an essential commodity, resulting in different problems across countries. Alcohol use has added to the burden of the problem particularly among vulnerable groups like the adolescents, elderly, patients with cancer, as well as health professionals. Services for patients with alcohol use disorders have been affected.

Summary
The COVID-19 pandemic has had considerable impact on alcohol use, with an increase in alcohol related emergencies, changes in alcohol use patterns, increased risk of contracting COVID-19, effect on alcohol policies and sales, and an effect on vulnerable groups. It is essential to understand and respond to the current situation, intervene early, and prevent further repercussions of the pandemic.
Video abstract link: https://drive.google.com/file/d/1IJWtIs6e554PryKWhdma4VB--mjSZq1C/view?usp=sharing.
SARS-CoV-2 infection of BNT162b2(mRNA)-vaccinated individuals is not restricted to variants of concern or high-risk exposure environments
Authors: Magalis Brittany Rife , Mavian Carla , Tagliamonte Massimiliano , Rich Shannan N. , Cash Melanie , Riva Alberto , Loeb Julia C. , Norris Michael , Amador David Moraga , Zhang Yanping , Shapiro Jerne , Starostik Petr , Marini Simone , Myers Paul , Ostrov David , Lednicky John A. , Glenn Morris J. John , Lauzardo Michael , Salemi Marco 
Published: May 2021

AbstractThe emergence of SARS-CoV-2 variants of concern (VOC) has raised questions regarding the extent of protection of currently implemented vaccines. Ten “vaccination breakthrough” infections were identified in Alachua County, Florida, among individuals fully vaccinated with the BNT162b2 mRNA vaccine as a result of social or household transmission. Eight individuals presented mild symptoms in the absence of infection with other common respiratory viruses, confirmed using viral genetic sequencing. SARS-CoV-2 genomes were successfully generated for five of the vaccine breakthroughs and 399 individuals in the surrounding area and were included for reference-based phylogenetic investigation. These five individuals were characterized by infection with both VOCs and low-frequency variants present within the surrounding population. Mutations, in the Spike glycoprotein, were consistent with their respective circulating lineages. However, we detected an additional mutation in Spike’s N-terminal domain of a B.1.1.7 strain, present at low-frequency (∼1%) in the unvaccinated population, potentially affecting protein’s stability and functionality. The findings highlight the critical need for continued testing and monitoring of infection among individuals regardless of vaccination status.
Dysbiosis and structural disruption of the respiratory microbiota in COVID-19 patients with severe and fatal outcomes
Authors: Hernández-Terán Alejandra , Mejía-Nepomuceno Fidencio , Herrera María Teresa , Barreto Omar , García Emma , Castillejos Manuel , Boukadida Celia , Matias-Florentino Margarita , Rincón-Rubio Alma , Avila-Rios Santiago , Mújica-Sánchez Mario , Serna-Muñoz Ricardo , Becerril-Vargas Eduardo , Guadarrama-Pérez Cristobal , Ahumada-Topete Víctor Hugo , Rodríguez Sebastián , Martínez-Orozco José Arturo , Salas-Hernández Jorge , Pérez-Padilla Rogelio , Vázquez-Pérez Joel Armando 
Published: May 2021

AbstractCOVID-19 outbreak has caused over 3 million deaths worldwide. Understanding disease pathology and the factors that drive severe and fatal clinical outcomes is of special relevance. Studying the role of the respiratory microbiota in COVID-19 is particularly important since it’s known that the respiratory microbiota interacts with the host immune system, contributing to clinical outcomes in chronic and acute respiratory diseases. Here, we characterized the microbiota in the respiratory tract of patients with mild, severe, or fatal COVID-19, and compared with healthy controls and patients with non-COVID-19-pneumonia. We comparatively studied the microbial composition, diversity, and microbiota structure across study groups and correlated the results with clinical data. We found differences in diversity and abundance of bacteria between groups, higher levels of dysbiosis in the respiratory microbiota of COVID-19 patients (regardless of severity level), differences in diversity structure among mild, severe, and fatal COVID-19, and the presence of specific bacteria that correlated with clinical variables associated with increased mortality risk. Our data suggest that host-related and environmental factors could be affecting the respiratory microbiota before SARS-CoV-2 infection, potentially compromising the immunological response of the host against disease and promoting secondary bacterial infections. For instance, the high levels of dysbiosis coupled with low microbial structural complexity in the respiratory microbiota of COVID-19 patients, possibly resulted from antibiotic uptake and comorbidities, could have consequences for the host and microbial community level. Altogether, our findings identify the respiratory microbiota as a potential factor associated with COVID-19 severity.
Modelling the relative benefits of using the measles vaccine outside cold chain for outbreak response
Authors: Azam James M. , Saitta Barbara , Bonner Kimberly , Ferrari Matthew J. , Pulliam Juliet R.C. 
Published: May 2021

AbstractIntroductionRapid outbreak response vaccination is a strategy for measles control and elimination. Measles vaccines must be stored and transported within a specified temperature range, but this can present significant challenges when targeting remote populations. Measles vaccine licensure for delivery outside cold chain (OCC) could provide more vaccine transport/storage space without ice packs, and a solution to shorten response times. However, due to vaccine safety and wastage considerations, the OCC strategy will require other operational changes, potentially including the use of 1-dose (monodose) instead of 10-dose vials, requiring larger transport/storage equipment currently achieved with 10-dose vials. These trade-offs require quantitative comparisons of vaccine delivery options to evaluate their relative benefits.MethodsWe developed a modelling framework combining elements of the vaccine supply chain - cold chain, vial, team, and transport equipment types - with a measles transmission dynamics model to compare vaccine delivery options. We compared 10 strategies resulting from combinations of the vaccine supply elements and grouped into three main classes: OCC, partial cold chain (PCC), and full cold chain (FCC). For each strategy, we explored a campaign with 20 teams sequentially targeting 5 locations with 100,000 individuals each. We characterised the time needed to freeze ice packs and complete the campaign (campaign duration), vaccination coverage, and cases averted, assuming a fixed pre-deployment delay before campaign commencement. We performed sensitivity analyses of the pre-deployment delay, population sizes, and two team allocation schemes.ResultsThe OCC, PCC, and FCC strategies achieve campaign durations of 50, 51, and 52 days, respectively. Nine of the ten strategies can achieve a vaccination coverage of 80%, and OCC averts the most cases.DiscussionThe OCC strategy, therefore, presents improved operational and epidemiological outcomes relative to current practice and the other options considered.
Implementation of a TMS-fMRI system: A primer
Authors: Alamian Golnoush , Ge Ruiyang , Humaira Afifa , Gregory Elizabeth , MacMillan Erin L. , Barlow Laura , Vila-Rodriguez Fidel 
Published: May 2021

ABSTRACTTranscranial magnetic stimulation (TMS) is a non-invasive and non-pharmacological intervention, approved for the treatment of individuals diagnosed with treatment-resistant depression. This well-tolerated approach uses magnetic pulses to stimulate specific brain regions and induce changes in brain networks at multiple levels of human functioning. Combining TMS with other neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), offers new insights into brain functioning, and allows to map out the causal alterations brought on by TMS interventions on neural network connectivity and behaviour. However, the implemention of concurrent TMS-fMRI brings on a number of technical challenges that must be overcome to ensure good quality of functional images. The goal of this study was thus to investigate the impact of TMS pulses in an MR-environment on the quality of BRAINO phantom images, in terms of the signal of the images, the temporal fluctuation noise, the spatial noise and the signal to fluctuation noise ratio, at the University of British Columbia (UBC) Neuroimaging facility. The results of our analyses replicated those of previous sites, and showed that the present set-up for concurrent TMS-fMRI ensures minimal noise artefact on functional images obtained through this multimodal approach. This step was a key stepping stone for future clinical trials at UBC.
Mutational signatures are markers of drug sensitivity of cancer cells
Authors: Levatić Jurica , Salvadores Marina , Fuster-Tormo Francisco , Supek Fran 
Published: May 2021

AbstractGenomic analyses have revealed mutational signatures that are associated with DNA maintenance gone awry, a common occurrence in tumors. Because cancer therapeutics often target synthesis of DNA building blocks, DNA replication or DNA repair, we hypothesized that mutational signatures would make useful markers of drug sensitivity. We rigorously tested this hypothesis by a global analysis of various drug screening and genetic screening data sets, derived from cancer cell line panels. We introduce a novel computational method that detects mutational signatures in cell lines by stringently adjusting for the confounding germline mutational processes, which are difficult to remove when healthy samples from the same individuals are not available. This revealed many associations between diverse mutational signatures and drug activity in cancer cell lines, which are comparably or more numerous than associations with classical genetic features such as cancer driver mutations or copy number alterations. Validation across independent drug screening data and across genetic screens involving drug target genes revealed hundreds of robustly supported associations, which are provided as a resource for drug repurposing guided by mutational signature markers. We suggest that cancer cells bearing genomic signatures of deficiencies in certain DNA repair pathways may be vulnerable to particular types of therapeutics, such as epigenetic drugs.