bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elite attitudes and the future of global governance
Authors: Scholte Jan Aart , Verhaegen Soetkin , Tallberg Jonas 
Published: March 2021

Abstract
This article examines what contemporary elites think about global governance and what these attitudes might bode for the future of global institutions. Evidence comes from a unique survey conducted in 2017–19 across six elite sectors (business, civil society, government bureaucracy, media, political parties, research) in six countries (Brazil, Germany, the Philippines, Russia, South Africa, the United States) and a global group. Bearing in mind some notable variation between countries, elite types, issue-areas and institutions, three main interconnected findings emerge. First, in principle, contemporary leaders in politics and society hold considerable readiness to pursue global-scale governance. Today's elites are not generally in a nationalist-protectionist-sovereigntist mood. Second, in practice, these elites on average hold medium-level confidence towards fourteen current global governance institutions. This evidence suggests that, while there is at present no legitimacy crisis of global governance among elites (as might encourage its decline), neither is there a legitimacy boom (as could spur its expansion). Third, if we probe what elites prioritize when they evaluate global governance, the surveyed leaders generally most underline democracy in the procedures of these bodies and effectiveness in their performance. This finding suggests that, to raise elites' future confidence in global governance, the institutions would do well to become more transparent in their operations and more impactful problem-solvers in their outcomes.
The feminist critique of liberalism and the challenge of right-wing populism: A reply to Gila Stopler
Authors: Baehr Amy 
Published: March 2021

Abstract
In this Reply, I argue that the Okin/Rawls debate is a debate within ideal theory; so if ideal theory is the problem, Okin’s feminist critique of liberalism will not help. I argue in addition, however, that Rawlsian ideal theory is more helpful than we might think in addressing the threat of illiberal populism to really-existing constitutional democracies, and that before we despair we should up our liberal game.
A global perspective of Indigenous child health research: a systematic review of longitudinal studies
Authors: Lloyd-Johnsen Catherine , Eades Sandra , McNamara Bridgette , D’Aprano Anita , Goldfeld Sharon 
Published: March 2021

AbstractBackgroundRigorously designed longitudinal studies can inform how best to reduce the widening health gap between Indigenous and non-Indigenous children.MethodsA systematic review was performed to identify and present the breadth and depth of longitudinal studies reporting the health and well-being of Indigenous children (aged 0–18 years) globally. Databases were searched up to 23 June 2020. Study characteristics were mapped according to domains of the life course model of health. Risk of bias was assessed using the National Institutes of Health (NIH) Study Quality Assessment Tools. Reported level of Indigenous involvement was also appraised; PROSPERO registration CRD42018089950.ResultsFrom 5545 citations, 380 eligible papers were included for analysis, representing 210 individual studies. Of these, 41% were located in Australia (n = 88), 22.8% in the USA (n = 42), 11.9% in Canada (n = 25) and 10.9% in New Zealand (n = 23). Research tended to focus on either health outcomes (50.9%) or health-risk exposures (43.8%); 55% of studies were graded as ‘good’ quality; and 89% of studies made at least one reference to the involvement of Indigenous peoples over the course of their research.ConclusionsWe identified gaps in the longitudinal assessment of cultural factors influencing Indigenous child health at the macrosocial level, including connection to culture and country, intergenerational trauma, and racism or discrimination. Future longitudinal research needs to be conducted with strong Indigenous leadership and participation including holistic concepts of health. This is critical if we are to better understand the systematic factors driving health inequities experienced by Indigenous children globally.
SARS-CoV-2 spike protein binding selectively accelerates substrate-specific catalytic activity of ACE2
Authors: Kiseleva Anna A , Troisi Elizabeth M , Hensley Scott E , Kohli Rahul M , Epstein Jonathan A 
Published: March 2021

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that has given rise to the devastating global pandemic. In most cases, SARS-CoV-2 infection results in the development of viral pneumonia and acute respiratory distress syndrome, known as ‘coronavirus disease 2019’ or COVID-19. Intriguingly, besides the respiratory tract, COVID-19 affects other organs and systems of the human body. COVID-19 patients with pre-existing cardiovascular disease have a higher risk of death, and SARS-CoV-2 infection itself may cause myocardial inflammation and injury. One possible explanation of such phenomena is the fact that SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as the receptor required for viral entry. ACE2 is expressed in the cells of many organs, including the heart. ACE2 functions as a carboxypeptidase that can cleave several endogenous substrates, including angiotensin II, thus regulating blood pressure and vascular tone. It remains largely unknown if the SARS-CoV-2 infection alters the enzymatic properties of ACE2, thereby contributing to cardiovascular complications in patients with COVID-19. Here, we demonstrate that ACE2 cleavage of des-Arg9-bradykinin substrate analogue is markedly accelerated, while cleavage of angiotensin II analogue is minimally affected by the binding of spike protein. These findings may have implications for a better understanding of COVID-19 pathogenesis.
Chemical Burns from Secondary Exposure to Paraquat Through Mishandling Urine of a Patient with Toxic Exposure
Authors: Denise Holley-Harrison H , Cunningham David , Velamuri Sai R , Hickerson William L , Hill David M 
Published: March 2021

Abstract
Paraquat is used throughout the world as an herbicide due to its efficacy and relative safety with proper handling. Accidents and misuse still occur, leading to countries banning its use or employing extra safeguards and special handling certifications. Severe toxicity is primarily associated with ingestion, but skin exposure leads to corrosive injury to the dermis, occurs rapidly, and progresses for up to 24 h. Prolonged skin exposure or the presence of open wounds can lead to systemic absorption. This is the first known report of burn injury and treatment due to secondary exposure to the urine of a patient who had accidental ingestion of paraquat. A 50-year-old Caucasian male presented to the emergency room after accidental ingestion of eight ounces of Gramoxone extra (Paraquat 30% concentration). During the initial care of the patient, the bedside registered nurse was placing an indwelling foley catheter when her forearms were contaminated with urine while wearing basic personal protective equipment (gloves). The registered nurse noticed bullae to bilateral forearms a short time after exposure to the urine. She presented to the burn center for evaluation and treatment. Poison Control was contacted but was unable to offer advise due to a lack of supportive literature. The risk and effects of primary exposure to Paraquat is described throughout the literature and documented in Material Safety Data Sheets (MSDS), but data regarding risk and treatment of secondary exposure is lacking. This case will aid outreach efforts for the prevention and treatment of burn injuries from secondary exposure to paraquat.
Digital Integrity
Authors: Fiorella Giancarlo , Godart Charlotte , Waters Nick 
Published: March 2021

Abstract
Researchers working with digital evidence must be aware of its vulnerabilities if they hope to maximize its value for justice and accountability. In this paper, we highlight two important vulnerabilities: the impermanent nature of digital evidence, and its susceptibility to attack from online dis/misinformation campaigns. We argue that to overcome the challenge that the impermanent nature of digital evidence presents, researchers can implement rapid response archiving techniques that, while not as rigorous as protocols set out for the collection of evidence in legal cases, could leave them with digital breadcrumbs to aid with the recovery of deleted digital evidence. We further propose that researchers consider implementing a stance of radical transparency in the collection, synthesis, and presentation of digital evidence with the goal of fortifying it against dis/misinformation campaigns.
Two New Alternatives to the Conventional Arm-in-Cage Test for Assessing Topical Repellents
Authors: Moreno-Gómez Mara , Bueno-Marí Rubén , Carr B Thomas , Bowman Gary R , Faherty Genevieve W , Gobbi Carlota , Palm Julie M , Van Sloun Petra , Miranda Miguel Ángel 
Published: March 2021

AbstractEuropean guidelines for testing attractant and repellent efficacy (i.e., Product type 19 [PT19]) have been in revision since 2017. A key topic of discussion is the current approach to evaluating topical repellents. The European Chemical Agency has stated field testing should be avoided because of mosquito-borne disease risks. However, the most common laboratory method, the arm-in-cage (AIC) test, may limit the reliable extrapolation of lab results to field conditions. This study’s main goal was to assess alternative laboratory methods for evaluating topical mosquito repellents that use mosquito landing rates more representative of those in the field. The study took place at three European testing labs using 30 study participants per test and the mosquito, Aedes albopictus (Skuse, 1894, Diptera: Culicidae). In phase 1, a conventional AIC test and a sleeved AIC test were performed. Respectively, the arm area exposed was 600 and 100 cm2, and cage volume was 0.040 and 0.064 m3. Mosquito density was the same for both: 1 female/840 cm3. In phase 2, room-based testing (40 ± 5 mosquitoes in 25–30 m3) was used as a proxy for field testing. The mosquito repellent employed was 15% N,N-diethyl-m-toluamide in ethanol at two doses: 1 and 0.5 g/600 cm2. The protection times measured at each laboratory were analyzed both separately and together using nonparametric (Kruskal–Wallis) test. The two alternatives methods showed to be potential alternatives to the current AIC method recreated field mosquito landing rates and achieved reproducible protection times across laboratories.
Preexisting Somatic Mutations of Estrogen Receptor Alpha (ESR1) in Early-Stage Primary Breast Cancer
Authors: Dahlgren Malin , George Anthony M , Brueffer Christian , Gladchuk Sergii , Chen Yilun , Vallon-Christersson Johan , Hegardt Cecilia , Häkkinen Jari , Rydén Lisa , Malmberg Martin , Larsson Christer , Gruvberger-Saal Sofia K , Ehinger Anna , Loman Niklas , Borg Åke , Saal Lao H 
Published: March 2021

Abstract

Background
More than three-quarters of primary breast cancers are positive for estrogen receptor alpha (ER; encoded by the gene ESR1), the most important factor for directing anti-estrogenic endocrine therapy (ET). Recently, mutations in ESR1 were identified as acquired mechanisms of resistance to ET, found in 12% to 55% of metastatic breast cancers treated previously with ET.

Methods
We analyzed 3217 population-based invasive primary (nonmetastatic) breast cancers (within the SCAN-B study, ClinicalTrials.gov NCT02306096), sampled from initial diagnosis prior to any treatment, for the presence of ESR1 mutations using RNA sequencing. Mutations were verified by droplet digital polymerase chain reaction on tumor and normal DNA. Patient outcomes were analyzed using Kaplan-Meier estimation and a series of 2-factor Cox regression multivariable analyses.

Results
We identified ESR1 resistance mutations in 30 tumors (0.9%), of which 29 were ER positive (1.1%). In ET-treated disease, presence of ESR1 mutation was associated with poor relapse-free survival and overall survival (2-sided log-rank test P &lt; .001 and P = .008, respectively), with hazard ratios of 3.00 (95% confidence interval = 1.56 to 5.88) and 2.51 (95% confidence interval = 1.24 to 5.07), respectively, which remained statistically significant when adjusted for other prognostic factors.

Conclusions
These population-based results indicate that ESR1 mutations at diagnosis of primary breast cancer occur in about 1% of women and identify for the first time in the adjuvant setting that such preexisting mutations are associated to eventual resistance to standard hormone therapy. If replicated, tumor ESR1 screening should be considered in ER-positive primary breast cancer, and for patients with mutated disease, ER degraders such as fulvestrant or other therapeutic options may be considered as more appropriate.
#28: Serum Posaconazole Concentrations Among Children, Adolescents, and Young Adults Receiving Delayed-Release Tablet And Intravenous Posaconazole
Authors: Bernardo Valeria , Liverman Rochelle , Tippett Ashley , Yildirimb Inci 
Published: March 2021

Abstract

Background
Posaconazole is a broad-spectrum antifungal used for prophylaxis and treatment of invasive fungal infections. There are limited data on the optimal dosing, safety, and effectiveness of the delayed-released tablets (DRT) and intravenous (IV) formulations in immunocompromised pediatric and adolescent patients.

Methods
A retrospective chart review was performed to study all immunocompromised patients who received DRT or IV formulations of posaconazole at our institution from January 1, 2014, to July 31, 2019, and had at least one plasma trough concentration. Plasma concentrations ≥0.7 µg /mL were considered therapeutic for prophylaxis, and ≥1.0 µg/mL for treatment. We describe our experience including dosing, plasma trough concentrations, safety, and tolerability.

Results
We identified 54 patients (28 males/26 females) who received DRT or IV formulations of posaconazole. The median age was 14 years (range 2–21 years). Thirty-one (57%) patients received posaconazole for treatment and 23 (43%) for prophylaxis. The most common underlying condition was hematological malignancies (66%) and 19 patients (35%) had received an allogeneic HSCT and were receiving immunosuppressive therapy. Overall, 36 (67%) patients achieved targeted initial plasma trough concentrations (median 1.3 µg/mL, IQR 0.758–1.760 µg/mL) (Figure). The median daily dose among patients &lt;13 years of age who achieved the targeted initial plasma trough concentrations was 7.3 mg/kg/day (IQR 6.8–11.0) for the DRT formulation and 9.8 mg/kg/day (IQR 7.4–11.7) for the IV formulation. The median daily dose among patients ≥ 13 years of age who achieved the targeted initial plasma trough concentrations was 4.9 mg/kg/day (IQR 4.1–6.5) for the DRT formulation and 5.6 mg/kg/day (IQR 3.9–5.8) for the IV formulation. Concomitant use of H2-receptor blockers (H2RA) and/or proton pump inhibitors (PPI) medications were not associated with failure to achieve target trough levels (P = 0.96). Thirty-six patients (67%) developed transaminitis, mostly grade 1.

Conclusions
Our results show that DRT and IV formulations are safe and effective in immunocompromised children, adolescents, and young adults. Higher dosing per body weight of DRT and IV posaconazole may be required in patients &lt;13 years of age compared with patients 13 years of age and older to achieve therapeutic plasma concentrations. It appears that neither a PPI nor an H2RA has an effect on the plasma exposure of the DRT.
#62: Safety of Live Attenuated Vaccines Administered after Pediatric Liver Transplantation
Authors: Tao-Kidoguchi Chiaki , Funaki Takanori , Shoji Kensuke , Akinari Fukuda , Seisuke Sakamoto , Mureo Kasahara , Miyairi Isao 
Published: March 2021

Abstract

Background
Live attenuated vaccines (LAVs) are currently contraindicated in immunocompromised patients such as solid-organ transplant (SOT) recipients. The guideline published by the Infectious Disease Society of America also cautions that LAVs after SOT are contraindicated. However, several articles have demonstrated that these patients may receive LAVs safely by adhering to a protocol consisting of an evaluation of many immunological parameters. The aim of this study was to evaluate the safety of LAVs, including measles, mumps, rubella, and varicella to liver transplant (LT) recipients under our clinically based immunization protocol for LT recipients.

Methods
We conducted a retrospective cohort study on the safety of live attenuated vaccines (LAVs) for measles, rubella, varicella, and mumps to LT recipients at the National Center for Child Health and Development from July 2010 to July 2019. Patients who underwent LT at age under 20 years, who visited our outpatient clinic for vaccination were included. Our institutional protocol for vaccination is shown in Table. Patients’ demographics, underlying diseases, administered vaccines, number and date of vaccination, and adverse events were extracted from their medical records. Adverse events occurring within 4 weeks after vaccination were collected and classified into 4 stages based on severity.

Results
During the study period, there were 1,904 outpatient clinic visits by 361 patients. Of these, multiple vaccines (median: 2, range: 1–7) including inactivated vaccines and LAVs were simultaneously administered during the 1,213 visits (64%). LAVs were administered to 422 times (209 patients) who met the criteria and included 225 doses of measles and rubella combination vaccine, 224 doses of varicella vaccine, and 215 doses of mumps vaccine. Underlying diseases included cholestatic liver disease (n = 125), followed by metabolic disease (n = 33), acute liver failure (n = 19). Eleven mild adverse events (2.6%) possibly associated with LAVs were reported, but there were no serious adverse events, including vaccine-strain infection, hospitalization, and death.

Conclusion
LAVs administration for LT recipients were safe without any serious adverse events under our relatively simplistic institutional protocol. However, further research is needed to closely monitor the efficacy and safety of LAVs to LT recipients.
#78: Use of Isavuconazonium for Treatment Of Invasive Fungal Infection in Immunocompromised Pediatric Patients
Authors: Mohandas Sindhu , Mongkolrattanothai Kanokporn , Stach Leslie , Orbach Regina , Neely Michael 
Published: March 2021

Abstract

Background
Isavuconazole (ISZ), dosed as the pre-drug isavuconazonium (ISM), is active against a wide variety of clinically important fungal pathogens. ISM is approved for the treatment of invasive aspergillosis and mucormycosis in adults ≥18 years of age. We present our experience with ISM to treat proven or probable fungal infection in immunocompromised pediatric patients.

Methods
Retrospective review of patients who received ISM at our institution between April 2016 and April 2019, we abstracted demographic information, primary diagnosis, indication for ISM therapy, ISZ serum concentrations if available, and outcomes.

Results
Of 14 patients who received ISM, 11 were ≤18 years of age (range 6–18 years). Underlying conditions included leukemia (n = 7), lymphoma (n = 1), post BMT (n = 1), diabetes (n = 1), and cardiac transplant (n = 1). Nine (82%) had proven invasive fungal infection (IFI) with aspergillosis (n = 2), zygomycosis (n = 3), mixed aspergillosis and zygomycosis (n = 2), mixed Rhizopus and Scedosporium (n = 1), and pathology only (n = 1) and 2 had probable IFI. Five of these 11 patients received combination ISM and liposomal amphotericin initially and the other 6 received liposomal amphotericin with or without other azoles prior to changing to ISM monotherapy. This was followed by monotherapy with ISM in 10 patients after a mean of 26 days (range 6–63) and continued dual therapy in the one. ISM dosing was 10 mg/kg q8h on days 1 and 2, followed by q24 thereafter, up to a maximum of 372 mg/dose. There were 19 measured ISZ serum concentrations obtained from 8 patients after &gt;1 week of verified inpatient dosing, ranging from 1.0 to 7.5 mg/L, above the MIC in all cases when known. Three (27%) patients died of underlying non-mycological causes, 1 (9%) died of progressive scedosporiosis, and 7 (64%) improved. ISM was well tolerated with no dose-limiting, drug-related toxicities noted.

Conclusions
ISM is a well-tolerated therapeutic option in pediatric patients at risk for or with invasive mycosis. Only 1 of our 11 patients died from progressive fungal disease.
#77: Impact of Targeted Tacrolimus Levels on BK Polyomavirus DNAemia Among Pediatric Kidney Transplant Recipients
Authors: Yildirim I , Liverman R , Serluco S , George R , Garro R , Winterberg P 
Published: March 2021

Abstract

Background
Uncontrolled BK Polyomavirus (BK) DNAemia in kidney transplant recipients is a significant cause of allograft dysfunction that can lead to BK Polyomavirus-associated nephropathy with permanent damage and graft loss. BK virus DNAemia can occur early (within the first year) or late (after the first year) following a kidney transplant in children. Prospective monitoring for BK viremia with pre-emptive lowering of immunosuppression has been suggested as an effective approach to prevent BK nephropathy. We evaluated the impact of changes in targeted tacrolimus levels on the incidence of BK DNAemia early post-transplant.

Methods
In response to a cluster of early-onset BK virus DNAemia cases in the first quarter of 2015, we pursued a quality improvement study to determine whether changes to tacrolimus trough targets for the first 100 days post-transplant would reduce the incidence and severity of BK DNAemia. Targeted tacrolimus levels were decreased by approximately 25% (see Table) and patients receiving transplant from March 20, 2015, and December 31, 2018, were prospectively monitored. The incidence rates of BK DNAemia detected on monthly surveillance testing in the first-year post-transplant were compared for patients transplanted between January 1, 2013, and March 14, 2015 (pre-intervention) and March 15, 2015, to December 31, 2018 (post-intervention).

Results
Of 148 children who received kidney transplants during the study period, 52 (35%) were transplanted in the pre-intervention era and 96(65%) were transplanted during the post-intervention era. The median age at transplant was 13.9 years [interquartile range (IQR) 8.0–16.7 years]. Age at transplant, gender (overall 55% male), and race (overall 54% White, 35% Black) was not significantly different between the cohorts. The risk of early-onset BK DNAemia within the first 100 days post-transplant was 19 per 100 patients in the pre-intervention cohort and 13 per 100 patients in the post-intervention cohort, corresponding to a 35% reduction after lowering targeted tacrolimus levels. The median time to first detected BK DNAemia increased from 77 days (IQR 45–90 days) in pre-intervention to 104 days (IQR 47–174 days) in the post-intervention cohort.

Conclusions
BK DNAemia heralds a serious complication of kidney transplantation and may represent over immunosuppression and increased risk for other infectious complications. We were able to reduce the rate of early-onset BK DNAemia by reducing tacrolimus target levels in the first 12 weeks post-transplant. Preventing early uncontrolled viremia may decrease the need for immunosuppression reduction which increases the risk for rejection.