bluuebunny/crossref_metadata_2025_split huggingface dataset:
P05 In vivo efficacy of VRP-034 in lung and thigh infection models
Authors: Vishwakarma Kamlesh Kumar , Payasi Anurag , Kumar Shailesh , Sharma Arun , Chaudhary Saransh , Aggarwal Anmol 
Published: February 2022

Abstract

Background
Polymyxin B-induced kidney injury is an important clinical concern that undermines patient care. This injury occurs in 30%–60% of patients receiving systemic polymyxin B (PMB). VRP-034, a novel PMB formulation, has previously shown a promising safety profile as compared with marketed PMB in animal models (Roy et al.1). The objective of this study was to assess the efficacy of VRP-034 versus marketed PMB in murine lung and thigh infection models.

Materials and methods
26 neutropenic BALB/c mice (n = 12 for lung; n = 14 for thigh) were infected by inoculating Pseudomonas aeruginosa (ATCC 27853, pathogenic, PMB MIC 0.5 μg/mL) either into the lungs (5 × 106 cfu) via intratracheal administration (lung model) or in both thighs (106 cfu/thigh) via intramuscular administration (thigh model). Treatment mice received VRP-034 or marketed PMB subcutaneously at 8 mg/kg every 8 h (HED: 2 mg/kg/day). Mice were humanely euthanized at 0 h (control) and at different timepoints post-treatment (24 h—lung model; 6 h and 12 h—thigh model). Lung or thigh tissues were collected, homogenized, serially diluted, plated on permissive media with cfu counted after 24 h of incubation. Changes in log10 cfu/mL at each timepoint were compared with 0 h control to assess efficacy.

Results
In the lung infection model, the mean (±SEM) log10 cfu/mL increased from 8.01 ± 0.43 (at 0 h) to 12.02 ± 0.85 (at 24 h) in the vehicle control group. Treatment with marketed PMB and VRP-034 resulted in 1.96 ± 0.87 and 2.07 ± 0.42 log-reduction respectively in bacterial burden when compared with 0 h control. In the thigh infection model, the log10 cfu/mL increased from 6.40 ± 0.11 (at 0 h) to 9.85 ± 0.08 (at 6 h) and 11.23 ± 0.07 (at 12 h) in the vehicle control group. Treatment with marketed PMB reduced the bacterial burden by 0.65 ± 0.08 and 2.79 ± 0.14 log at 6 h and 12 h, respectively and treatment with VRP-034 reduced the bacterial burden by 0.85 ± 0.17 and 2.68 ± 0.01 log at 6 h and 12 h, respectively.

Conclusions
The results from the murine lung and thigh infection models suggest that there is no marked difference between the efficacy of VRP-034 and marketed PMB. Further work should explore the clinical utility of these findings in the light of the promising safety profile of VRP-034.
P06 Pharmacokinetics and renal accumulation of VRP-034
Authors: Vishwakarma Kamlesh Kumar , Chilbule Rahul , Chaudhary Manu , Sharma Arun , Chaudhary Saransh , Aggarwal Anmol 
Published: February 2022

Abstract

Background
Nephrotoxicity is a dose-limiting factor for polymyxin B (PMB), a last-line therapy for MDR Gram-negative bacterial infections. The majority of the filtered PMB undergoes extensive tubular reabsorption leading to significant accumulation of the drug in tubular cells, causing renal tubular damage. We have previously reported that VRP-034, a novel PMB formulation, attenuates this damage (Roy et al.1). The objective of this study was to characterize the pharmacokinetics (PK) and renal accumulation of VRP-034 versus marketed PMB.

Materials and methods
A total of 19 Sprague-Dawley rats were used in the study. For PK evaluation, 10 rats were administered a single subcutaneous dose (6 mg/kg) of either VRP-034 or marketed PMB. Serial plasma samples were collected up to 24 h and assayed for major PMB components (PMB B1, B1-I, B2) using a validated LC-tandem MS method. PK parameters were calculated using noncompartmental analysis. For evaluating renal deposition, nine rats (n = 3 each group) were administered VRP-034 or marketed PMB at a dose of 6 mg/kg/8 h for 48 h or normal saline (control). After 48 h, rats were euthanized and kidneys were excised by making a midline incision, washed with saline, homogenized in 1:9 w/v 0.1 M phosphate buffer (pH 7.4) and the homogenate was used for determining PMB concentration. All values are expressed as mean ± SEM.

Results
The plasma pharmacokinetic parameters for both VRP-034 and marketed PMB were found similar [AUC0–24: 54.3 ± 4.7 μg/mL·h versus 51.5 ± 1.6 μg/mL·h; Cmax: 4.73 ± 0.6 μg/mL versus 5.02 ± 0.5 μg/mL; T½: 5.95 ± 0.5 h versus 5.6 ± 0.3 h]. In the renal deposition study, a 40% reduction (P&lt;0.05) in renal deposition of PMB was found in VRP-034 treated rat kidneys compared with marketed PMB group after 48 h of treatment.

Conclusions
The results highlight that while the plasma PK parameters remained unchanged, a marked reduction in PMB renal deposition was observed in VRP-034 group and likely explains the previous reports of attenuated PMB-induced kidney injury with VRP-034.
P07 Toxicokinetic profile of VRP-034
Authors: Murkunde Yogeshkumar Vishnupant , Chaudhary Saransh , Vishwakarma Kamlesh Kumar , Aggarwal Anmol , Chilbule Rahul 
Published: February 2022

Abstract

Background
Polymyxin B (PMB) can be an effective option for treating resistant Gram-negative pathogens, however, its use is severely compromised by its’ dose-limiting toxicity. VRP-034, a novel formulation of PMB, has previously reported a favourable safety profile compared with marketed PMB (Roy et al.1). This study was conducted to understand the toxicokinetic profile of VRP-034 vis-à-vis marketed PMB.

Materials and methods
30 healthy Sprague-Dawley rats (divided into six groups of n = 5) received one of three doses (3, 9 and 18 mg/kg/day) of either marketed PMB or VRP-034, administered subcutaneously q8 h over 2 days. Blood samples were collected prior to initiation of experiment and at 0.5, 1, 2, 4, 6, 8, 12 and 24 h after the last dose. Plasma concentrations of PMB were quantified by LC-MS. Additionally, renal toxicity was assessed via clinical pathology, kidney injury biomarkers, oxidative stress markers (3-nitrotyrosine and renal tissue lactate), gross and histopathologic observations of kidney. Urine and blood samples were collected at baseline and Day 2 for the assessment of kidney injury (KIM-1, cystatin-C, BUN and serum creatinine) using respective biochemical or ELISA kits. All values are expressed as mean ± SEM.

Results
The plasma levels of PMB were found to increase in dose-dependent manner in both the groups. At 3 and 9 mg/kg/day, the plasma PMB exposure were similar for both VRP-034 and marketed PMB groups (AUC0–24: 6.47 ± 0.41 μg/mL·h versus 5.66 ± 0.24 μg/mL·h, P&gt;0.05 and 22.90 ± 1.96 μg/mL·h versus 26.84 ± 1.43 μg/mL·h, P&gt;0.05). At the highest dose of 18 mg/kg/day, the AUC0–24 was higher in the VRP-034 group (AUC0–24: 97.83 ± 12.95 μg/mL·h versus 70.48 ± 4.22 μg/mL·h), however this increase was not statistically significant (P&gt;0.05). The levels of early kidney injury urinary biomarkers increased with dose in both the groups (Table 1). On Day 2, Kim-1 levels in the marketed PMB group increased from baseline by 3.96-fold (versus 2.31-fold in VRP-034 group), 8.21-fold (versus 5.41-fold) and 23.41-fold (versus 9.51-fold) at 3, 9, 18 mg/kg/day dose levels respectively. Likewise, cystatin-C levels increased by 6.22-fold (versus 3.26-fold in VRP-034 group), 6.25-fold (versus 3.67-fold) and 13.57-fold (versus 4.33-fold), respectively, at the three dose levels tested. Oxidative stress markers, tissue lactate and 3-nitrotyrosine, were significantly lower (P&lt;0.05) for VRP-034 group compared with marketed PMB group at the highest dose. Histopathology revealed EGTI grade 3 kidney damage in the marketed PMB group compared with grade 1 damage in the VRP-034 group.

Conclusions
VRP-034 exhibited a more promising toxicokinetic profile as compared with marketed PMB at all dose levels. Our future work will explore the clinical translation of these findings in humans.
P32 Occurrence of bla
KPC, bla
NDM and bla
OXA-48 genes among carbapenemase-producing Enterobacteriaceae (CRE) in National Cancer Institute, Sri Lanka
Authors: Suranadee Y. W. S. , Jyalathacrachchi H. R. , Gamage S. , Gunasekara S. P. 
Published: February 2022

Abstract

Background
Carbapenemase-producing Enterobacteriaceae (CRE) are a global problem and prevalence of CR genes differs across geographical regions. The current Sri Lankan situation is unknown; hence, this study aimed to identify three commonly occurring CR genes in the region.

Methods
Enterobacteriaceae isolates resistant to carbapenems were collected from clinical samples submitted for routine testing to the microbiology laboratory of National Cancer Institute. Species identification was done using conventional biochemicals and CLSI disc diffusion method was used for ABST of CRE isolates. Identification of CR genes was done by in-house conventional multiplex PCR, using previously described primers (Table 1). Ten microlitres of total DNA from each sample, extracted by heat shock method, was subjected to multiplex PCR in a 50 μL of PCR mixture which contained 5× PCR buffer (10 mmol/L Tris–HCl, 50 mmol/L KCl), 2.5 mmol/L of MgCl2, 10 mmol/L of deoxynucleotide triphosphate, 5 U/mL of Taq Polymerase and 20 μmol/L of each primer. The PCR program was run at 94°C for 3 min, followed by 30 cycles of 95°C for 1 min, 55°C for 30 s and 73°C for 1 min, with a final extension at 72°C for 5 min. Products were visualized by electrophoresis in 2% agarose gel (Figure 1).

Results
A total of 123 isolates were tested. Klebsiella pneumoniae was the predominant carbapenemase producer (58.5%). Sixty-six (53.6%) isolates harboured blaOXA-48 and 47 (38.2%) had blaNDM. Only one isolate was positive for blaKPC. Thirteen (10.5%) had both blaOXA-48 and blaNDM and 9 (7%) tested negative for all three genes.

Conclusions
bla OXA-48 and blaNDM being common and blaKPC being very rare is expected with the geographical location of the country. Noted high prevalence and co-occurrence of CR genes among CRE isolates is alarming and pose a threat to patient management and infection control of the institution.
P49 Determinants of trends in reported antibiotic use for sick children from LMICs (2005–17): analysis of 132 national surveys from 73 countries
Authors: Allwell-Brown Gbemisola , Hussain-Alkhateeb Laith , Sewe Maquins Odhiambo , Kitutu Freddy , Strömdahl Susanne , Mårtensson Andreas , Johansson Emily White 
Published: February 2022

Abstract

Objectives
To analyse trends in reported antibiotic use for children aged &lt;5 years with fever, diarrhoea or cough with fast or difficult breathing (outcome) from low- and middle-income countries (LMICs) during 2005–17, disaggregated by the following user characteristics: rural/urban residence, maternal education, household wealth and healthcare source visited.

Methods
Based on 132 Demographic and Health Surveys and Multiple Indicator Cluster Surveys from 73 LMICs, the outcome, disaggregated by user characteristics for all country-years was estimated using a hierarchical Bayesian linear regression model.

Results
Across LMICs during 2005–17, the greatest relative increases in the outcome occurred in rural areas, poorest quintiles and least educated populations, particularly in low-income countries and South-East Asia. In low-income countries, rural areas had a 72% relative increase from 17.8% [uncertainty interval (UI): 5.2%–44.9%] in 2005 to 30.6% (11.7%–62.1%) in 2017, compared with a 29% relative increase in urban areas from 27.1% (8.7%–58.2%) in 2005 to 34.9% (13.3%–67.3%) in 2017. Despite these increases, the outcome was consistently highest in urban areas, wealthiest quintiles, and populations with the highest maternal education.

Conclusions
These estimates suggest that the increasing reported antibiotic use for sick children aged &lt;5 years in LMICs during 2005–17 was driven by gains among groups often underserved by formal health services.
Potential abuses of dominance by big tech through their use of Big Data and AI
Authors: Hutchinson Christophe Samuel 
Published: February 2022

Abstract
While companies are targeting online shoppers with increased precision thanks to their combined use of Big Data and Artificial Intelligence, concerns have been expressed among competition law scholars that giant tech companies may use their enhanced market power resulting from their access and control of Big Data and AI to foreclose the market from potential competitors and subsequently charge higher prices to consumers. If proven, such practices amount to abuses of dominance in the meaning of Article 102 of the Treaty of the Functioning of the European Union. The recent adoption by the European Commission of its proposal for a Regulation on the Digital Markets Act aiming at setting up rules to ensure that markets characterized by large platforms acting as gatekeepers, remain fair and contestable and the launch of a new string of investigations by the European Commission into possible anti-competitive conducts of Google Amazon, Apple, and Facebook have shown that these concerns are not purely hypothetical.
Pharmacokinetic Profile of ∆9-Tetrahydrocannabinol, Cannabidiol and Metabolites in Blood following Vaporization and Oral Ingestion of Cannabidiol Products
Authors: Bergeria Cecilia L , Spindle Tory R , Cone Edward J , Sholler Dennis , Goffi Elia , Mitchell John M , Winecker Ruth E , Bigelow George E , Flegel Ronald , Vandrey Ryan 
Published: February 2022

Abstract
There is limited data on the comparative pharmacokinetics of cannabidiol (CBD) across oral and vaporized formulations. This within-subject, double-blind, double-dummy, placebo-controlled laboratory study analyzed the pharmacokinetic profile of CBD, ∆9-tetrahydrocannabinol (∆9-THC) and related metabolites in blood and oral fluid (OF) after participants (n = 18) administered 100 mg of CBD in each of the following formulations: (1) oral CBD, (2) vaporized CBD and (3) vaporized CBD-dominant cannabis containing 10.5% CBD and 0.39% ∆9-THC (3.7 mg); all participants also completed a placebo condition. Oral CBD was administered in three formulations: (1) encapsulated CBD, (2) CBD suspended in pharmacy-grade syrup and (3) Epidiolex, allowing for pharmacokinetic comparisons across oral formulations (n = 6 per condition). An optional fifth experimental condition was completed for six participants in which they fasted from all food for 12 h prior to oral ingestion of 100 mg of CBD. Blood and OF samples were collected immediately before and for 57–58 h after each drug administration. Immunoassay screening and LC–MS-MS confirmatory tests were performed, the limit of quantitation was 0.5 ng/mL for ∆9-THC and 1 ng/mL for CBD. The mean Cmax and range of CBD blood concentrations for each product were as follows: vaporized CBD-dominant cannabis, 171.1 ng/mL, 40.0–665.0 ng/mL, vaporized CBD 104.6 ng/mL, 19.0–312.0 ng/mL and oral CBD, 13.7 ng/mL, 0.0–50.0 ng/mL. Of the three oral formulations, Epidiolex produced the greatest peak concentration of CBD (20.5 ng/mL, 8.0–37.0 ng/mL) relative to the capsule (17.8 ng/mL, 2.0–50.0 ng/mL) and syrup (2.8 ng/mL, 0–7.0 ng/mL). ∆9-THC was detected in the blood of 12/18 participants after vaporized CBD-dominant cannabis use, but neither ∆9-THC nor its metabolite THC-COOH were detected in the blood of any participants after vaporized or oral CBD-only administration. These data demonstrate that different oral and vaporized formulations produce substantial variability in the pharmacokinetics of CBD and that CBD alone is unlikely to convert to ∆9-THC or produce positive drug tests for ∆9-THC or its metabolite.
The Gender Divide in Wikipedia: Quantifying and Assessing the Impact of Two Feminist Interventions
Authors: Langrock Isabelle , González-Bailón Sandra 
Published: February 2022

Abstract
Wikipedia has a well-known gender divide affecting its biographical content. This bias not only shapes social perceptions of knowledge, but it can also propagate beyond the platform as its contents are leveraged to correct misinformation, train machine-learning tools, and enhance search engine results. What happens when feminist movements intervene to try to close existing gaps? Through a quantitative analysis of over 11,000 Wikipedia articles, we provide an evaluation of two popular feminist interventions designed to counteract gender inequality within digital information projects. We find that the interventions are successful at adding content about women that would otherwise be missing, but they are less successful at addressing structural biases that limit the visibility of that content. This leads us to argue for a more granular and cumulative analysis of gender gaps in collaborative environments. We also discuss the implications for future scholarship on digital inequalities.
Laparoscopic transabdominal preperitoneal repair for inguinal hernia in a patient with an adult Still’s disease receiving anti-interleukin-6 receptor monoclonal antibody therapy
Authors: Mimatsu Kenji , Kamitaki Yusuke , Fukino Nobutada 
Published: February 2022

Abstract
Tocilizumab, a monoclonal antibody drug against interleukin-6 receptor, has been reported to cause wound infection and delayed wound healing. Therefore, surgeries using artificial materials in patients receiving tocilizumab require careful observation. A 75-year-old man who had been receiving tocilizumab and steroids for the treatment of adult Still’s disease was diagnosed with an inguinal hernia and underwent laparoscopic transabdominal preperitoneal repair. Tocilizumab administration was discontinued for 3 weeks before surgery and was restarted 2 weeks after the surgery. Postoperatively, there was no fever, and the C-reactive protein level was marginally elevated. The patient was discharged from the hospital on the fourth day without any postoperative complications, and no delayed infection or delayed wound healing 1 year after the surgery. A few weeks withdrawal of tocilizumab administration before and after surgery permitted safe laparoscopic hernia surgery using a surgical mesh without infection or delayed wound healing.
Hybrid cooling of the Cassiopeia A neutron star
Authors: Leinson Lev B 
Published: February 2022

ABSTRACT
The observed rapid cooling of the neutron star Cassiopeia A is usually interpreted as being caused by transitions of neutrons and protons in the star’s core from the normal state to the superfluid and superconducting state. However, this so-called ‘minimal’ cooling paradigm faces the problem of numerically simulating the observed anomalously fast drop in the neutron star surface temperature using theoretical neutrino energy losses from superfluid neutrons. As a solution to this problem, I propose a somewhat more complex cooling model, in which, in addition to superfluid neutrons, direct Urca processes from a very small central part of the neutron star core are also involved. Numerical simulations of the cooling trajectory in this scenario show excellent agreement with observations of the Cassiopeia A neutron star. The proposed cooling scenario unambiguously relates the used equation of state and the mass of the neutron star. For a neutron star constructed according to BSk25 equation of state, the most appropriate are the mass $M=1.62\, {\rm M}_{\odot }$ and the radius R = 12.36 km. If BSk24 equation of state is used, then the most suitable solution is $M=1.60\, {\rm M}_{\odot }$ and R = 12.55 km.
Highly specialized recreationists contribute the most to the citizen science project eBird
Authors: Rosenblatt Connor J , Dayer Ashley A , Duberstein Jennifer N , Phillips Tina B , Harshaw Howard W , Fulton David C , Cole Nicholas W , Raedeke Andrew H , Rutter Jonathan D , Wood Christopher L 
Published: February 2022

AbstractContributory citizen science projects (hereafter “contributory projects”) are a powerful tool for avian conservation science. Large-scale projects such as eBird have produced data that have advanced science and contributed to many conservation applications. These projects also provide a means to engage the public in scientific data collection. A common challenge across contributory projects like eBird is to maintain participation, as some volunteers contribute just a few times before disengaging. To maximize contributions and manage an effective program that has broad appeal, it is useful to better understand factors that influence contribution rates. For projects capitalizing on recreation activities (e.g., birding), differences in contribution levels might be explained by the recreation specialization framework, which describes how recreationists vary in skill, behavior, and motives. We paired data from a survey of birders across the United States and Canada with data on their eBird contributions (n = 28,926) to test whether those who contributed most are more specialized birders. We assigned participants to 4 contribution groups based on eBird checklist submissions and compared groups’ specialization levels and motivations. More active contribution groups had higher specialization, yet some specialized birders were not active participants. The most distinguishing feature among groups was the behavioral dimension of specialization, with active eBird participants owning specialized equipment and taking frequent trips away from home to bird. Active participants had the strongest achievement motivations for birding (e.g., keeping a life list), whereas all groups had strong appreciation motivations (e.g., enjoying the sights and sounds of birding). Using recreation specialization to characterize eBird participants can help explain why some do not regularly contribute data. Project managers may be able to promote participation, particularly by those who are specialized but not contributing, by appealing to a broader suite of motivations that includes both appreciation and achievement motivations, and thereby increase data for conservation.
1905
Authors: Weinberg Robert 
Published: February 2022

Abstract
In October 1905 the port city of Odessa, located on the Black Sea and the Russian Empire’s fourth largest city, experienced a four-day pogrom against the city’s Jews, who comprised one-third of its population. The outbreak of wanton violence and bloodletting marked the culmination of social and political unrest that had enveloped Odessa since January and drew upon long-standing prejudices and attitudes toward Jews. But it was the erosion of autocratic authority and widespread labor and student unrest that transformed antisemitism into anti-Jewish violence, which resulted in the deaths of hundreds, injuries to thousands, and significant property damage. Government authorities did not organize the pogrom, which resulted from a spontaneous breakdown of law and order and reflected the heightened social, political, and economic tensions that pitted the forces of revolution against the forces of reaction, between those demanding the end of autocratic rule and those who mobilized in defense of the Romanov dynasty.
Anti-Jewish Violence in the Russian Civil War
Authors: Veidlinger Jeffrey 
Published: February 2022

Abstract
On Saturday, February 15, 1919, Ukrainian soldiers murdered over a thousand Jewish civilians in the town of Proskuriv (now Khmelnytsky) in what was at the time possibly the single deadliest episode of violence to befall the Jewish people in their long history of oppression. The massacre in Proskuriv, though, was not an isolated event. Between 1917 and 1921, during the civil war that followed the Russian revolutions, over 1000 separate incidents were documented in about 500 different locales throughout the regions that had been the southwestern provinces of the Russian Empire and the eastern half of the Austrian province of Galicia, predominantly in areas that are now parts of Ukraine. The largest of the anti-Jewish massacres resulted in the deaths of 1,500 to 3,000 people apiece, but the vast majority left at most a few dozen dead in their wake. These casualties were part of a larger civil war that resulted in the deaths of about one million people in Ukraine. It profoundly reshaped the demography of European Jewry and traumatized the affected communities for a generation.