bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cefiderocol Activity Against ClinicalPseudomonas aeruginosaIsolates Exhibiting Ceftolozane-Tazobactam Resistance
Authors: Simner Patricia J , Beisken Stephan , Bergman Yehudit , Posch Andreas E , Cosgrove Sara E , Tamma Pranita D 
Published: June 2021

AbstractBackgroundMutations in the AmpC-AmpR region are associated with treatment-emergent ceftolozane-tazobactam (TOL-TAZ) and ceftazidime-avibactam (CAZ-AVI) resistance. We sought to determine if these mutations impact susceptibility to the novel cephalosporin-siderophore compound cefiderocol.MethodsThirty-two paired isolates from 16 patients with index P. aeruginosa isolates susceptible to TOL-TAZ and subsequent P. aeruginosa isolates available after TOL-TAZ exposure from January 2019 to December 2020 were included. TOL-TAZ, CAZ-AVI, imipenem-relebactam (IMI-REL), and cefiderocol minimum inhibitory concentrations (MICs) were determined using broth microdilution. Whole-genome sequencing of paired isolates was used to identify mechanisms of resistance to cefiderocol that emerged, focusing on putative mechanisms of resistance to cefiderocol or earlier siderophore-antibiotic conjugates based on the previously published literature.ResultsAnalyzing the 16 pairs of P. aeruginosa isolates, ≥4-fold increases in cefiderocol MICs occurred in 4 of 16 isolates. Cefiderocol nonsusceptibility criteria were met for only 1 of the 4 isolates, using Clinical and Laboratory Standards Institute criteria. Specific mechanisms identified included the following: AmpC E247K (2 isolates), MexR A66V and L57D (1 isolate each), and AmpD G116D (1 isolate) substitutions. For both isolates with AmpC E247K mutations, ≥4-fold MIC increases occurred for both TOL-TAZ and CAZ-AVI, while a ≥4-fold reduction in IMI-REL MICs was observed.ConclusionsOur findings suggest that alterations in the target binding sites of P. aeruginosa–derived AmpC β-lactamases have the potential to reduce the activity of 3 of 4 novel β-lactams (ie, ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol) and potentially increase susceptibility to imipenem-relebactam. These findings are in need of validation in a larger cohort.
Novel Applications of Spinal Navigation in Deformity and Oncology Surgery—Beyond Screw Placement
Authors: Massaad Elie , Shankar Ganesh M , Shin John H 
Published: June 2021

Abstract
Computer-assisted navigation has made a major impact on spine surgery, providing surgeons with technological tools to safely place instrumentation anywhere in the spinal column. With advances in intraoperative image acquisition, registration, and processing, many surgeons are now using navigation in their practices. The incorporation of navigation into the workflow of surgeons continues to expand with the evolution of minimally invasive techniques and robotic surgery. While numerous investigators have demonstrated the benefit of navigation for improving the accuracy of instrumentation, few have reported applying this technology to other aspects of spine surgery. Surgeries to correct spinal deformities and resect spinal tumors are technically demanding, incorporating a wide range of techniques not only for instrumentation placement but also for osteotomy planning and executing the goals of surgery. Although these subspecialties vary in their objectives, they share similar challenges with potentially high complications, invasiveness, and consequences of failed execution. Herein, we highlight the utility of using spinal navigation for applications beyond screw placement: specifically, for planning and executing osteotomies and guiding the extent of tumor resection. A narrative review of the work that has been done is supplemented with illustrative cases demonstrating these applications.
Present and Future Spinal Robotic and Enabling Technologies
Authors: Khalsa Siri Sahib S , Mummaneni Praveen V , Chou Dean , Park Paul 
Published: June 2021

Abstract
Enabling technologies include surgical planning software, computer-assisted navigation, intraoperative three-dimensional (3D) imaging, and robotic systems. Presently, these technologies are in various stages of refinement. Spinal robots in particular are currently limited to the positioning of an alignment guide for pedicle screw placement. Current generation spinal robots, therefore, play a more limited role in spinal surgery. In contrast to spinal robots, intraoperative imaging technology has been developed further, to a stage that allows accurate 3D spinal image acquisition that can be readily utilized for spinal navigation. The integration of these various technologies has the potential to maximize the safety, consistency, reliability, and efficacy of surgical procedures. To that end, the trend for manufacturers is to incorporate various enabling technologies into the spinal robotic systems. In the near-term, it is expected that integration of more advanced planning software and navigation will result in wider applicability and value. In the long-term, there are a variety of enabling technologies such as augmented reality that may be a component of spinal robots. This article reviews the features of currently available spinal robots and discusses the likely future advancements of robotic platforms in the near- and long-term.
Operationalizing Intersectionality in Social Work Research: Approaches and Limitations
Authors: Matsuzaka Sara , Hudson Kimberly D , Ross Abigail M 
Published: June 2021

Abstract
Despite intersectionality’s relevance to social work, scholars have raised concerns that its misguided applications place it “in danger of being co-opted, depoliticized, and diluted.” This scoping review examined the use of intersectionality in empirical social work research, specific to the extent, contexts, and degree of responsibility with which it has been applied. Using the search term convention [“social work” OR “social services”] AND [“intersectional” OR “intersectionality”], 22 databases were searched for peer-reviewed research published between 2009 and 2019, yielding 153 articles. The 33 studies meeting inclusion criteria were examined according to two frameworks: (1) typologies for intersectional conceptual approach and (2) intersectionality responsible use guidelines (RUG). Most studies used an intracategorical approach (n = 24), while fewer used an intercategorical (n = 7) or a mixed intra- and intercategorical approach (n = 2). On average, studies met approximately half of the RUG. Studies most frequently (n = 29) aligned with the guideline “Recommend ways to promote positive social transformation and justice through research, teaching, and practice.” Studies least frequently (n = 3) conformed to the guideline “Credits Black feminist activist roots of intersectionality.” Responsible stewardship is recommended to address power in knowledge production, researcher positionalities, and social justice action.
Phase Resolution of Heterozygous Sites in Diploid Genomes is Important to Phylogenomic Analysis under the Multispecies Coalescent Model
Authors: Huang Jun , Bennett Jeremy , Flouri Tomáš , Leaché Adam D , Yang Ziheng 
Published: June 2021

Abstract
Genome sequencing projects routinely generate haploid consensus sequences from diploid genomes, which are effectively chimeric sequences with the phase at heterozygous sites resolved at random. The impact of phasing errors on phylogenomic analyses under the multispecies coalescent (MSC) model is largely unknown. Here, we conduct a computer simulation to evaluate the performance of four phase-resolution strategies (the true phase resolution, the diploid analytical integration algorithm which averages over all phase resolutions, computational phase resolution using the program PHASE, and random resolution) on estimation of the species tree and evolutionary parameters in analysis of multilocus genomic data under the MSC model. We found that species tree estimation is robust to phasing errors when species divergences were much older than average coalescent times but may be affected by phasing errors when the species tree is shallow. Estimation of parameters under the MSC model with and without introgression is affected by phasing errors. In particular, random phase resolution causes serious overestimation of population sizes for modern species and biased estimation of cross-species introgression probability. In general, the impact of phasing errors is greater when the mutation rate is higher, the data include more samples per species, and the species tree is shallower with recent divergences. Use of phased sequences inferred by the PHASE program produced small biases in parameter estimates. We analyze two real data sets, one of East Asian brown frogs and another of Rocky Mountains chipmunks, to demonstrate that heterozygote phase-resolution strategies have similar impacts on practical data analyses. We suggest that genome sequencing projects should produce unphased diploid genotype sequences if fully phased data are too challenging to generate, and avoid haploid consensus sequences, which have heterozygous sites phased at random. In case the analytical integration algorithm is computationally unfeasible, computational phasing prior to population genomic analyses is an acceptable alternative. [BPP; introgression; multispecies coalescent; phase; species tree.]
A relational theory of fiduciary accountability
Authors: Flannigan Robert 
Published: June 2021

Abstract
Believing that the law of fiduciary accountability lacks coherent definition, various active writers have sought to provide that definition. Their analyses, however, are misinformed or misconceived. The consequence is that the fiduciary literature continues to be a source of obfuscation, rather than illumination. Here I examine the attempt of one writer to frame the law in what he describes as a ‘relational’ theory. I discuss the diverse misconceptions that impair his work.
Beware the ‘gifted’ Trojan horse: analysing the equitable maxim—‘Equity will not perfect an imperfect gift’
Authors: Keat Edwin Teong Ying 
Published: June 2021

Abstract
This article analyses and argues for the continued relevance of the maxim—Equity will not perfect an imperfect gift for three reasons. First, it is principally sound. Centuries of historical development should not be discarded due to its arbitrary application. Second, the deviations from the maxim were justified. The cases which were decided wrongly have subsequently been accounted for. Third, common law jurisdictions including Singapore, Malaysia and the United Kingdom still apply Milroy v Lord, as proven by empirical analysis. Last, this article proposes a new three-step test to prevent further arbitrary application: (i) As a starting point, Equity will not perfect an imperfect gift. (ii) However, it may do so where the settlor has objectively done all he could to transfer legal title. (iii) If step (ii) conflicts with step (i), Equity looks to the substance, not the form, considering the facts of each case.
Necessary lives: reformulating the rule against perpetuities
Authors: Pratt Simon D 
Published: June 2021

Abstract
The discussions in two preceding articles are now consolidated to help reformulate the Rule Against Perpetuities and to explain its search for a so-called measuring life in being. Here, it is argued that unsolved problems regarding the Effective Lives and Causal Connection hypotheses are overcome by applying Aristotelian and Avicennian ideas of necessary and proximate causation to Bractonian notions that valid conditions must be annexed to the limitation.
Decreased aconitase and cytochrome c oxidase activity in skeletal muscle of ATM‐deficient mice
Authors: McDonald Todd M. , Patel Akshar Y. , Fisher Jonathan S. 
Published: June 2021

Cells that lack ataxia telangiectasia mutated (ATM) reportedly have high levels of reactive oxygen species (ROS) and impaired mitochondrial function. We hypothesized that activities of mitochondrial enzymes that are susceptible to modification by ROS, such as aconitase and cytochrome c oxidase (COX), would be decreased by ATM deficiency. In tibialis anterior muscles, aconitase activity was ~50% lower for ATM‐deficient (ATM −/−) mice than for wild‐type (ATM +/+) animals (P<0.05, n=7/group). However, aconitase activity from ATM −/− muscle was completely rescued by preincubation of muscle homogenates under reducing conditions. COX activity was ~40% lower in tibialis anterior from ATM −/− animals than for wild‐type mice (P<0.005, n=9/group). Inhibition of COX activity by ATP was greater for ATM +/+ muscles than for ATM −/− muscles (38±7% vs. 15±5%, P<0.05, n=7/group), suggesting that COX tends to be in its inefficient, ROS‐producing state in ATM −/− muscle. Incubation of wild‐type soleus muscles for 1 h with the ATM inhibitor KU55933 tended to cause a 22% reduction (P=0.17, n=4/group) in COX activity compared to muscles incubated with vehicle alone. Overall, the findings suggest that activities of ROS‐susceptible mitochondrial enzymes are decreased by ATM deficiency.This work was supported by NIH R15DK080437 and ARRA funding. Todd McDonald was an APS Frontiers in Physiology Fellow.
Psychological Stress and Changes in the Intestinal Microflora Impact Memory in Mice
Authors: Gareau Melanie G , Wine Eytan , Rodrigues David M , Whary Mark T , MacQueen Glenda , Sherman Philip M 
Published: June 2021

The brain‐gut axis is a regulator of intestinal physiology and psychological stress is linked to altered gut barrier function, food allergies, and altered behavior.AIMTo determine the effects of Citrobacter rodentium infection, probiotics, or the absence of a gut microflora on anxiety and memory.METHODSThe impact of psychological stress (1h water avoidance stress; WAS) was assessed following acute bacterial infection and in germ‐free mice. Mice were infected and anxiety and memory assessed during acute infection (10d) and post‐infection (30d). Whether daily treatment with probiotics could normalize behavior was then determined. Immunohistochemistry for brain‐derived neurotropic factor (BDNF) and c‐Fos was performed.RESULTSAnxiety and memory were normal at 10d and 30d in C. rodentium‐infected mice. However, exposure of infected mice to WAS caused memory dysfunction at 10d and 30d post enteric infection. This defect was associated with reduced levels of BDNF and c‐Fos in the CA1 region of the hippocampus. Memory defects were prevented by probiotics, together with normalization of hippocampal c‐Fos. Memory was absent in germ‐free mice, irrespective of stress, in contrast to gut colonized controls.CONCLUSIONSAlterations in the intestinal microbiota exert a measurable impact on memory. These findings are relevant to post‐infectious irritable bowel syndrome in humans.Funding provided by CIHR.
The provision of the fermentable fibers soy polysaccharides and fructooligosaccharides increases short‐chain fatty acid transporter abundance in healthy piglets
Authors: Woodard Jennifer , Correa‐Matos Nancy J , Tappenden Kelly A 
Published: June 2021

Glucagon‐like peptide 2 (GLP‐2) is an intestinotrophic hormone released from the distal ileum and colon shown to be stimulated by short‐chain fatty acids (SCFAs). Previous in vitro work has shown SCFA receptors and transporters play a role in mediating GLP‐2 production. Therefore, the aim of this study was to examine SLC5A8, MCT‐1, GPR43, and T2R38 abundance in vivo following SCFA production. Piglets were randomized to a control formula, formula supplemented with 7.5 g/L soy polysaccharides (SPS), or formula supplemented with 7.5 g/L fructooligosaccharides (FOS) for 14 days. Expression of GPR43 and T2R38 was not significantly different between the treatment groups. Colonic, but not ileal, MCT‐1 abundance was significantly elevated with SPS (1.35 vs. 2.67 MCT‐1/18S; p = 0.0163); expression in the FOS treated animals was intermediate, but not significantly different from either the control or SPS groups. The abundance of SLC5A8 was significantly elevated in the ileum, but not the colon, with FOS fermentation (0.388 vs. 0.880 SLC5A8/18S; p = 0.0578), while SPS was not significantly different than the control animals. Together, these results indicate that SCFAs increase transporter mRNA abundance, particularly in the intestinal segment in which the fiber was fermented, and thus may have implications for the types of fermentable substrates best suited for stimulating GLP‐2.Grant Funding Source: NIH T32 DK59802
Sex‐dependent molecular alterations during development of alcoholic cardiomyopathy in rat
Authors: Fogle Rachel LaDean , Vary Thomas C 
Published: June 2021

Excessive, chronic alcohol consumption can result in alcoholic heart muscle disease (AHMD) and, ultimately, heart failure. Functional and structural damage to the myocardium is consistent with a shift in myocardial protein expression and activity that occurs as the disease progresses. The current study aims to link alcohol‐induced alterations in expression of specific proteins with the differences between male and female using a chronic rat model. This study uses isobaric tags for relative and absolute quantitation (iTRAQ) followed by mass spectrometry to delineate shifts in protein expression in rat myocardium as a consequence of chronic (18 week) alcohol intake. Echocardiography allowed the early detection of changes to the heart. Consuming alcohol for 16 weeks lowered stroke volume and left ventricular diastolic volume in both sexes. Males showed additional significant declines in left ventricular mass and end‐diastolic dimension. At the end of the alcohol‐feeding regimen, hearts were fractionated into myofibrillar, sarcoplasmic, mitochondrial, and nuclear fractions. Early interpretation of the proteomic data obtained from mitochondrial fractions identified variations in structural proteins as well as proteins involved in oxidative phosphorylation and electron transport.NIAAA R01 AA012814 (TCV) and PA Dept of Health Tobacco Settlement Award (RLF)
Reduction of Na/H exchanger‐1 expression limits cardiac injury in mice with chronic intermittent hypoxia
Authors: Chen Ling , Zhang Jin , Prasad Vikram , Scharf Steven M 
Published: June 2021

Obstructive sleep apnea causes chronic intermittent hypoxia (CIH) that contributes to the developments of cardiovascular complications via mechanisms yet to be defined. We hypothesized that Na/H exchanger‐1 (NHE1), the primary intracellular pH regulator, mediates cardiac injury induced by CIH. Heterozygous NHE1 knockout mice (KO) and their wild type siblings (WT) were exposed to either CIH (5% nadir O2 for 1 min, following by 21% O2 for 1 min; 10 daytime hours per day for 8 weeks) or sham control (21% O2 constantly). At 8 weeks and compared to WT/sham, WT/CIH showed a 10% increases in mean blood pressure (MBP), a 2‐fold increases in cardiac NHE1 mRNA expression, and evidence of cardiac injury as suggested by elevated left ventricular (LV) cardiomyocyte size and apoptotic cardiomyocytes, as well as increased LV posterior wall thickness and decreased LV fractional shortening measured by echocardiography. Compared to WT/CIH, KO/CIH had similar increases in MBP, 40% NHE1 expression (but a 30% higher than that in KO/sham), and reduced cardiac injury. In conclusion, CIH increases MAP and NHE1 expression, and leads to cardiac injury. Reduction of NHE1 expression limits CIH‐induced cardiac injury, but not MAP elevation.Supported by AHA.
Effect of Digoxin on Hypoxic Pulmonary Hypertension (HPH)
Authors: Abud Edsel , Undem Clark , Sylvester J T , Semenza Gregg L , Shimoda Larissa A 
Published: June 2021

Many lung diseases induce HPH, leading to increased mortality. HPH, caused by vascular contraction and remodeling, is associated with increased intracellular pH (pHi) and calcium concentration ([Ca2+]i) in pulmonary arterial smooth muscle cells (PASMCs). Hypoxia‐inducible factor 1 (HIF‐1), a transcription factor, plays a critical role in the development of HPH. Recently, digoxin (Dig) was found to inhibit HIF‐1. We hypothesized that Dig could attenuate the development of HPH. Mice were weighed and injected daily with saline or Dig (low = 0.2 mg/kg or high = 1.0 mg/kg; i.p.) and kept in hypoxia (10% O2) or room air. After 21 days, right ventricular (RV) pressures were measured via closed‐chest puncture. Hypoxia increased RV pressures in mice receiving saline. Low Dig reduced, and high Dig normalized, RV pressure in hypoxic mice. RV hypertrophy (RVH) increased in hypoxic mice treated with saline or low Dig, but was reduced in hypoxic mice receiving high Dig. Hypoxia increased hematocrit in mice treated with saline or low Dig, whereas high Dig reduced the hypoxia‐induced increase in hematocrit. Both pHi and [Ca2+]i increased in PASMCs from saline‐treated hypoxic mice, and treatment with low or high Dig prevented these changes in ion homeostasis. From these results, we conclude that digoxin attenuates pulmonary vascular responses to chronic hypoxia and may be a possible candidate for treatment of HPH.HL67191, GM008074
Urinary excretion of angiotensinogen in male and female Sprague Dawley rats during angiotensin II infusion and high salt diet
Authors: Rands Vicky F. , Byrd Charlene , Seth Dale , Kobori Hiroyuki , Prieto Minolfa C 
Published: June 2021

We have found that urinary angiotensinogen (AGT) excretion (uAGT) differs between male(♂)and female(♀) Sprague Dawley (SD) rats on a normal salt diet (♂: 60±26 vs ♀: 4.5 ±0.2ng/day, p<0.05). In this study, we examined if the effects of a high salt (HS) diet on uAGT exhibits sexual dimorphism during Angiotensin (ANG) II dependent hypertension. Four groups of age‐matched (8 weeks) male (n= 20) and female (n=17) SD rats were studied: 1) high salt diet (HS; 8%NaCl); 2) ANG II (80ng/min, sc; for 14 days); 3) ANG II + HS; 4) ANG II + HS + Candesartan. (CAND, 25 mg/L in drinking water). uAGT levels were measured by enzyme immunoassay. HS diet alone did not raise uAGT levels (♂: 107±23 vs. ♀: 5±2ng/day) from baseline; however, AGT increased significantly during ANG II infusion (♂: 1107±1061 vs ♀: 206±74ng/day, p<0.01) and was augmented even further in ANG II + HS (♂: 4363±1673 vs. ♀: 8022±1300ng/day, p=ns). Candesartan ameliorated this effect with a better response in female than in male rats.(♂: 240±28 vs. ♀: 10±4 ng/day, p< 0.01). The results demonstrate a sexual dimorphism in the uAGT excretion rate during baseline conditions and HS diet characterized by higher levels in the males. The augmentation of uAGT with HS + ANG II is ameliorated more effectively by ARB treatment in female ANG II hypertensive rats than in males.NIH (P20 RR 017659), Tulane‐BIRCWH (K12HD043451)
Central mineralocorticoid receptor blockade reduces sodium appetite in rats: new evidence for an old effect
Authors: Formenti Silmara , Schoorlemmer Guus , Menani José V. , Colombari Eduardo 
Published: June 2021

In a previous study we showed that chronic infusion of the mineralocorticoid hormone aldosterone into the fourth ventricle (4V) induces robust dose‐dependent daily sodium intake. In the present study we investigated the effects of the mineralocorticoid receptor (MR) antagonist, RU 28318, injected into the 4V or lateral ventricle (LV) on sodium intake induced by 24 h of sodium depletion (treatment with furosemide, 20 mg/kg b.w., s.c., followed by 24 h of sodium deficient diet), 9 days of sodium deficient diet (0.005% Na+) or chronic treatment with deoxycorticosterone acetate (DOCA, 2 mg/day, s.c. for 7 days). Male Wistar Hannover rats (280–350 g, n=4–7/group) with stainless steel guide cannulas implanted into the 4V or into the LV were used. RU 28318 (100 ng) into the 4V reduced 0.3 M NaCl intake induced by 24 h of sodium depletion (6±1 vs. vehicle: 12±2 mL/2 h) or by sodium deficient diet (1±1 vs. vehicle: 9.5±3 mL/2 h). However, injection of RU 28318 (100 ng) into the LV did not affect sodium intake induced by 24 h of sodium depletion (15±3 vs. vehicle: 15±3 mL/2h). RU 28318 (500 ng) into the 4V also produced no effect on sodium intake induced by DOCA (14±3 vs. vehicle: 11±2 mL/2 h). These data reinforce findings suggesting that hindbrain MRs are involved on aldosterone‐induced sodium appetite. However, it seems they are not involved on DOCA‐induced sodium intake.Supported by: FAPESP, CNPq, CAPES.