bluuebunny/crossref_metadata_2025_split huggingface dataset:
Firsthand and Secondhand Exposure Levels of Maltol-Flavored Electronic Nicotine Delivery System Vapors Disrupt Amino Acid Metabolism
Authors: Jarrell Zachery R , Smith Matthew Ryan , He Xiaojia , Orr Michael , Jones Dean P , Go Young-Mi 
Published: April 2021

AbstractElectronic nicotine delivery system (ENDS) use has become a popular, generally regarded as safe, alternative to tobacco use. The e-liquids used for ENDS vapor generation commonly contain flavoring agents, such as maltol, which have been subjected to little investigation of their effects on lung health from ENDS usage. In the present study, we examined the impacts of firsthand (3.9 mM) and secondhand (3.9 µM) exposure levels to maltol-flavored ENDS vapors on lung metabolism. Human lung bronchial epithelial cells were exposed to ENDS vapors using a robotic system for controlled generation and delivery of exposures, and the effects on metabolism were evaluated using high-resolution metabolomics. The results show that maltol in e-liquids impacts lung airway epithelial cell metabolism at both firsthand and secondhand exposure levels. The effects of maltol were most notably seen in amino acid metabolism while oxidative stress was observed with exposure to all ENDS vapors including e-liquids alone and maltol-contained e-liquids. Many effects of firsthand exposure were also observed with secondhand exposure, suggesting need for systematic investigation of both firsthand and secondhand effects of flavored ENDS vapors on lung metabolism and risk of lung disease.
Is mimicry a diversification-driver in ants? Biogeography, ecology, ethology, genetics and morphology define a second West-PalaearcticColobopsisspecies (Hymenoptera: Formicidae)
Authors: Schifani Enrico , Giannetti Daniele , Csősz Sándor , Castellucci Filippo , Luchetti Andrea , Castracani Cristina , Spotti Fiorenza A , Mori Alessandra , Grasso Donato A 
Published: April 2021

AbstractThe West-Palaearctic Colobopsis ant populations have long been considered a single species (Colobopsis truncata). We studied the diversity of this species by employing a multidisciplinary approach and combining data from our surveys, museum and private collections, and citizen science platforms. As a result, we have revealed the existence of a second species, which we describe as Colobopsis imitans sp. nov., distributed allopatrically from Co. truncata and living in the Maghreb, Sicily and southern Iberia. While the pigmentation of Co. truncata is reminiscent of Dolichoderus quadripunctatus, that of Co. imitans is similar to Crematogaster scutellaris, with which Co. imitans lives in close spatial association, and whose foraging trails it habitually follows, similar to Camponotus lateralis and other ant-mimicking ants. The isolation between Co. imitans and Co. truncata seems to have occurred relatively recently because of significant, yet not extreme, morphometric differentiation, and to mtDNA polyphyly. Both Co. imitans and Co. truncata appear to employ mimicry of an unpalatable or aggressive ant species as an important defensive strategy; this ‘choice’ of a different model species is motivated by biogeographic reasons and appears to act as a critical evolutionary driver of their diversification.
PHarmacist Avoidance or Reductions in Medical Costs in Patients Presenting the EMergency Department: PHARM-EM Study
Authors: Rech Megan A. , Adams William , Smetana Keaton S. , Gurnani Payal K. , Van Berkel Patel Megan A. , Peppard William J. , Hammond Drayton A. , Flannery Alexander H. 
Published: April 2021

Objectives:
To comprehensively classify interventions performed by emergency medicine clinical pharmacists and quantify cost avoidance generated through their accepted interventions.

Design:
A multicenter, prospective, observational study was performed between August 2018 and January 2019.

Setting:
Community and academic hospitals in the United States.

Participants:
Emergency medicine clinical pharmacists.

Interventions:
Recommendations classified into one of 38 intervention categories associated with cost avoidance.

Measurements and Main Results:
Eighty-eight emergency medicine pharmacists at 49 centers performed 13,984 interventions during 917 shifts that were accepted on 8,602 patients and generated $7,531,862 of cost avoidance. The quantity of accepted interventions and cost avoidance generated in six established categories were as follows: adverse drug event prevention (1,631 interventions; $2,225,049 cost avoidance), resource utilization (628; $310,582), individualization of patient care (6,122; $1,787,170), prophylaxis (24; $22,804), hands-on care (3,533; $2,836,811), and administrative/supportive tasks (2,046; $342,881). Mean cost avoidance was $538.61 per intervention, $875.60 per patient, and $8,213.59 per emergency medicine pharmacist shift. The annualized cost avoidance from an emergency medicine pharmacist was $1,971,262. The monetary cost avoidance to pharmacist salary ratio was between $1.4:1 and $10.6:1.

Conclusions:
Pharmacist involvement in the care of patients presenting to the emergency department results in significant avoidance of healthcare costs, particularly in the areas of hands-on care and adverse drug event prevention. The potential monetary benefit-to-cost ratio for emergency medicine pharmacists is between $1.4:1 and $10.6:1.
Midlevel Injectable Practice Patterns in Dermatology and Plastic Surgery Offices
Authors: Nesi Lauren , Belcher Matthew , Decker Ashley , Lawrence Naomi 
Published: April 2021

BACKGROUND
There is limited knowledge on the extent physicians delegate cosmetic procedures to midlevel providers.

OBJECTIVE
To assess dermatology and plastic surgery practice patterns for the injections of neurotoxins and dermal fillers.

MATERIALS AND METHODS
Four hundred ninety-two dermatology and plastic surgery practices were identified from 10 major US metropolitan areas. These practices were contacted, and staff were asked a series of questions to best characterize the practice patterns in regard to who performs the injectables in the office.

RESULTS
Although most dermatology and plastic surgery practices had physicians as the only provider who gives injectables, 18.35% of dermatology and 25.4% of plastic surgery practices had nurse practioners and physician assistants giving injectables both with and without oversight of the supervising physician onsite.

CONCLUSION
In a large majority of both plastic surgery and dermatology practices, physicians exclusively perform injections of neurotoxins and fillers. For practices that allow midlevel providers to perform injectables, the level of physician supervision is variable. In a small percentage of plastic surgery practices, surveyed midlevel providers exclusively performed injectables.
Diagnosis and Therapy of Infectious Encephalitis in Children: A Ten-Years Retrospective Study
Authors: Pata Davide , Buonsenso Danilo , Frasca Giampiero , Lazzareschi Ilaria , Salerno Gilda , Turriziani Colonna Arianna , Mariotti Paolo , Valentini Piero 
Published: April 2021

Background:
Infectious encephalitis represents a rare but potentially severe clinical condition. However, limited international data are available in pediatric age.

Methods:
We conducted a retrospective study to review (a) the clinical presentation; (b) laboratory, radiology, and neurophysiology findings; (c) the correlations between these exams and outcome; and (d) the therapy performed.

Results:
Fifty-six patients were enrolled [22 female (39.6%), mean age 4.7 years, IQR 0.7–8.7 years], 19.6% presented neurologic sequelae. HSV was the single most frequently isolated pathogen (19.6%), although in most cases, the etiology remained undefined. 41.1% children presented prodromal before the development of neurologic signs. Fever was the most frequent constitutional symptom (83.9% of cases). Cerebrospinal fluid was normal in 48.5% of cases and electroencephalograpy in 24.5% cases. Brain computed tomography scans was normal in 33 (91.7%) cases, while cerebral magnetic resonance imaging (MRI) showed pathologic findings in 62.5% of cases. MRI was the only parameter associated with neurologic sequalae [P = 0.01; OR, 8.1 (95% CI: 1.52–42.84)].

Conclusions:
Pediatric encephalitis is a heterogeneous entity with nonspecific clinical and laboratory findings, with undefined etiologies in most times. MRI can play a primary role, both on a diagnostic and prognostic point-of-view, and its role should be implemented and made more accessible. Further studies are needed to define the exact role and timing of steroids.
Current Clinical Practices of Saudi Physiotherapists in Stroke Rehabilitation
Authors: Alatawi Salem F. 
Published: April 2021

Background and Purpose:
Stroke is a major cause of disability and the third leading cause of death worldwide. Clinical practice guidelines for stroke rehabilitation identify stroke physiotherapists as an essential interdisciplinary team member to minimize residual impairments and disability, thereby improving the patient's ability to execute daily tasks. This article uses an existing American survey to compare Saudi physiotherapists' current practice and preferred interventions in stroke rehabilitation with their counterparts in other countries.

Method:
An electronic survey was sent between September and October 2020 to physiotherapists (n = 287) treating persons with stroke in Saudi Arabia. The questionnaire consisted of items related to stroke rehabilitation, including treatment approach, the goal of interventions, management of tone, facilitation of movement, function, and improved motor control. Chi-square tests (χ2) were used to test any associations between physiotherapists' responses with respect to their demographic characteristics. Quantitative data analysis was conducted using SPSS.

Results:
A total of 197 participants returned completed questionnaires (68.6%). Participants were asked which methods of stroke treatment they had practiced in their profession and which methods had been taught in school training. The Bobath/neurodevelopmental treatment (NDT) approach was the most commonly known approach in practice (77.66%), followed by the proprioceptive neuromuscular facilitation/Brunnstrom and motor relearning program (63.45%, 25.38%, respectively). The results showed a significant relationship between Saudi physiotherapists' current practice and the aim of treatment and function (P < .05). In general, respondents have agreed on preferred treatment approaches, with the majority referring to the Bobath/NDT method, although variation is observed between participants in some sections of the survey. The preferred treatment was based on the frequency of responses of the participants.

Discussion and Conclusion:
Variation has been observed between therapists regarding treatment applications in stroke rehabilitation. The current findings emphasize the need to investigate how and why practitioners use or do not use evidence in this area (such as national stroke guidelines). Future studies might need to engage Saudi stroke physiotherapists to find suitable ways to close the gap between the evidence for best practice and the use of evidence within day-to-day practices.
Gene-Environment Interactions Between Environmental Response Genes Polymorphisms and Mitochondrial DNA Copy Numbers Among Benzene Workers
Authors: Ji Buqiang , Xiao Long Yan , Ren Jing-Chao , Zhang Guang-Hui , Wang Yongbin , Dong Tingting , Li Jingzhi , Zhang Fengquan , Xia Zhao-Lin 
Published: April 2021

Objective:
To determine the effect of mitochondrial DNA copy number (mtDNAcn) as a biomarker of benzene exposure.

Methods:
A total of 294 benzene-exposed workers and 102 controls were recruited. Biomarkers of mtDNAcn, cytokinesis-block micronucleus (MN) frequency, and peripheral blood white blood cells (WBC) were detected. Eighteen polymorphism sites in DNA damage repair and metabolic genes were analyzed.

Results:
Benzene exposure increased mtDNAcn and indicated a dose–response relationship (P < 0.001). mtDNAcn was negatively correlated with WBC count and DNA methylation and positively correlated with MN frequency. The AG type in rs1695 interacted with benzene exposure to aggravate mtDNAcn (β = 0.006, 95% CI: 0, 0.012, P = 0.050). rs13181, rs1695, rs1800975, and GSTM1 null were associated with benzene-induced mtDNAcn. Rs1695 interacted with benzene to increase mitochondrial damage.

Conclusions:
Benzene exposure increases mtDNAcn levels in benzene-exposed workers.
Low-Level HIV RNA in Cerebrospinal Fluid and Neurocognitive Performance: A Longitudinal Cohort Study
Authors: Anderson Albert M. , Tang Bin , Vaida Florin , Mcclernon Daniel , Deutsch Reena , Cherner Mariana , Cookson Debra , Crescini Melanie , Grant Igor , Ellis Ronald J. , Letendre Scott L. 
Published: April 2021

Background:
Cognitive complications persist in persons with HIV during suppressive antiretroviral therapy (ART). Low levels of HIV during ART could contribute to these complications. In this study, we measured cerebrospinal fluid (CSF) HIV using a single-copy assay (SCA) to investigate a possible relationship between low-level HIV and cognition.

Design/Methods:
SCA data were analyzed from 3 consecutively paired CSF–plasma specimens collected over a mean of 456 days from 96 participants on suppressive ART. Using mixed models, the presence of CSF HIV by SCA as a risk factor for worse neurocognitive performance was examined.

Results:
At baseline on the SCA, 45.8% of participants had detectable plasma HIV RNA (median 8 copies/mL and interquartile range = 3–17 among detectable values) and 17.7% had detectable CSF HIV RNA (median CSF concentration= 3 copies/mL and interquartile range= 2–13 among detectable values). The frequency of CSF HIV RNA detection declined over time in CSF (P = 0.018) with a trend toward decline in plasma (P = 0.064). Detectable CSF HIV RNA during the study was associated with worse performance in the domains of recall (P = 0.014) and motor (P = 0.040) and a trend with worse overall global performance (P = 0.078). Integrase inhibitor use, although very infrequent in this cohort, was associated with better performance in 2 domains.

Conclusions:
Low-level CSF HIV RNA declines with time but is associated with worse cognitive performance in 2 domains. Additional research is needed to better understand the relationship between HIV RNA persistence during long-term ART and central nervous system complications in persons with HIV.
The Risk of Infections Associated With JAK Inhibitors in Rheumatoid Arthritis
Authors: Alves Carlos , Penedones Ana , Mendes Diogo , Marques Francisco Batel 
Published: April 2021

Background/Objective
The Janus kinases (JAKs) are cytoplasmic tyrosine kinases associated with membrane cytokine receptors that mediate signaling of multiple cytokines and growth factors, contributing to the pathogenesis of multiple autoimmune disorders. The JAK inhibitors are a new class of targeted therapies with proven efficacy in treating rheumatoid arthritis but are associated with an increased risk of infections. This study is aimed at comparing the relative safety of the different JAK inhibitors with regard to the risk of serious infections in patients with rheumatoid arthritis.

Methods
PubMed, EMBASE, Cochrane Library, and clinicaltrials.gov were searched to identify randomized controlled trials evaluating the efficacy and safety of JAK inhibitors in patients with rheumatoid arthritis. The outcomes assessed were the risk of total and serious infections, tuberculosis, and herpes zoster. Sensitivity analysis disaggregated the results according to background therapy and licensed doses of JAK inhibitors.

Results
Thirty-seven randomized controlled trials that were included met the inclusion criteria. Compared with filgotinib, adalimumab (4.81; 95% confidence interval [CI], 1.39–16.66), etanercept (6.04; 95% CI, 1.79–20.37), peficitinib (7.56; 95% CI, 1.63–35.12), tofacitinib (4.29; 95% CI, 1.43–12.88), and upadacitinib (4.35; 95% CI, 1.46–13.00) have an increased risk of herpes zoster infection. Risk differences between the drugs became statistically nonsignificant when the sensitivity analysis was conducted.

Conclusions
The risk of infections seems to be similar among the currently approved JAK inhibitor drugs. Although the initial results suggested that filgotinib could have a reduced risk of herpes zoster, the sensitivity analyses did not support those findings.
Intersectionality and heart failure: what clinicians and researchers should know and do
Authors: Allana Saleema , Ski Chantal F. , Thompson David R. , Clark Alexander M. 
Published: April 2021

Purpose of review
To review the application of intersectionality to heart failure. Intersectionality refers to the complex ways in which disenfranchisement and privilege intersect to reproduce and influence health and social outcomes.

Recent findings
Intersectionality challenges approaches that focus on a single or small number of socio-demographic characteristics, such as sex or age. Instead, approaches should take account of the nature and effects of a full range of socio-demographic factors linked to privilege, including: race and ethnicity, social class, income, age, gender identity, disability, geography, and immigration status. Although credible and well established across many fields – there is limited recognition of the effects of intersectionality in research into heart disease, including heart failure. This deficiency is important because heart failure remains a common and burdensome syndrome that requires complex pharmacological and nonpharmacological care and collaboration between health professionals, patients and caregivers during and at the end-of-life.

Summary
Approaches to heart failure clinical care should recognize more fully the nature and impact of patients’ intersectionality- and how multiple factors interact and compound to influence patients and their caregivers’ behaviours and health outcomes. Future research should explicate the ways in which multiple factors interact to influence health outcomes.
Update on pain in arthritis
Authors: Bharde Sabah , Caxaria Sara , Dell’Accio Francesco , Sikandar Shafaq 
Published: April 2021

Purpose of review
Osteoarthritis is a degenerative joint disease that features pain as a hallmark symptom. This review summarises progress and obstacles in our understanding of pain mechanisms in arthritis.

Recent findings
Pain phenotypes in osteoarthritis are poorly characterized in clinical studies and animal studies are largely carti-centric. Different animal models incur variable disease progression patterns and activation of distinct pain pathways, but studies reporting both structural and pain outcomes permit better translational insights. In patients, classification of osteoarthritis disease severity is only based on structural integrity of the joint, but pain outcomes do not consistently correlate with joint damage. The complexity of this relationship underlines the need for pain detection in criteria for osteoarthritis classification and patient-reported outcome measures.

Summary
Variable inflammatory and neuropathic components and spatiotemporal evolution underlie the heterogeneity of osteoarthritis pain phenotypes, which must be considered to adequately stratify patients. Revised classification of osteoarthritis at different stages encompassing both structural and pain outcomes would significantly improve detection and diagnosis at both early and late stages of disease. These are necessary advancements in the field that would also improve trial design and provide better understanding of basic mechanisms of disease progression and pain in osteoarthritis.
Staying on target: Maintaining a balanced resuscitation during damage-control resuscitation improves survival
Authors: Hynes Allyson M. , Geng Zhi , Schmulevich Daniela , Fox Erin E. , Meador Christopher L. , Scantling Dane R. , Holena Daniel N. , Abella Benjamin S. , Young Andrew J. , Holland Sara , Cacchione Pamela Z. , Wade Charles E. , Cannon Jeremy W. ,   PROMMTT Study Group
Published: April 2021

BACKGROUND
Damage-control resuscitation (DCR) improves survival in severely bleeding patients. However, deviating from balanced transfusion ratios during a resuscitation may limit this benefit. We hypothesized that maintaining a balanced resuscitation during DCR is independently associated with improved survival.

METHODS
This was a secondary analysis of the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study. Patients receiving >3 U of packed red blood cells (PRBCs) during any 1-hour period over the first 6 hours and surviving beyond 30 minutes were included. Linear regression assessed the effect of percent time in a high-ratio range on 24-hour survival. We identified an optimal ratio and percent of time above the target ratio threshold by Youden’s index. We compared patients with a 6-hour ratio above the target and above the percent time threshold (on-target) with all others (off-target). Kaplan-Meier analysis assessed the combined effect of blood product ratio and percent time over the target ratio on 24-hour and 30-day survival. Multivariable logistic regression identified factors independently associated with 24-hour and 30-day survival.

RESULTS
Of 1,245 PROMMTT patients, 524 met the inclusion criteria. Optimal targets were plasma/PRBC and platelet/PRBC of 0.75 (3:4) and ≥40% time spent over this threshold. For plasma/PRBC, on-target (n = 213) versus off-target (n = 311) patients were younger (median, 31 years; interquartile range, [22–50] vs. 40 [25–54]; p = 0.002) with similar injury burdens and presenting physiology. Similar patterns were observed for platelet/PRBC on-target (n = 116) and off-target (n = 408) patients. After adjusting for differences, on-target plasma/PRBC patients had significantly improved 24-hour (odds ratio, 2.25; 95% confidence interval, 1.20–4.23) and 30-day (odds ratio, 1.97; 95% confidence interval, 1.14–3.41) survival, while on-target platelet/PRBC patients did not.

CONCLUSION
Maintaining a high ratio of plasma/PRBC during DCR is independently associated with improved survival. Performance improvement efforts and prospective studies should capture time spent in a high-ratio range.

LEVEL OF EVIDENCE
Epidemiologic/prognostic study, level II; Therapeutic, level IV.
The Measurement of Everyday Cognition (ECog)
Authors: Farias Sarah T. , Weakley Alyssa , Harvey Danielle , Chandler Julie , Huss Olivia , Mungas Dan 
Published: April 2021

Introduction:
The Everyday Cognition scale (ECog), a measure of everyday functioning developed in 2008, is sensitive to early detection and progression of neurodegenerative disease. The goal was to update ECog item content to ensure relevancy to contemporary older adults from diverse backgrounds.

Methods:
Participants included 44 culturally diverse older adults (18 with normal cognition, 11 with mild cognitive impairment) and their study partners. Item understandability and relevance was evaluated using iterative interviewing methods that were analyzed using standard qualitative methods. On the basis of this information, items were modified, deleted, or developed as needed.

Results:
Of the 39 original items, 19 were revised, 3 new items were added (primarily to cover contemporary activities such as the use of technology), and 1 was deleted. The revised version (ECog-II) includes 41 items.

Discussion:
To ensure strong psychometric properties, and to facilitate harmonization of previously collected data, we preserved well over half of the items. Future work will validate the revised ECog by measuring associations with neuropsychological performance, external measures of disease, and other functional measures. Overall, the revised ECog will continue to be a useful tool for measuring cognitively relevant everyday abilities in clinical settings and intervention clinical trials.