bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of PtHMGR enhances drought and salt tolerance of poplar
Authors: Wei Hui , Movahedi Ali , Xu Chen , Sun Weibo , Li Lingling , Wang Pu , Li Dawei , Zhuge Qiang 
Published: September 2019

AbstractBackground and AimsSoil salinization and aridification are swiftly engulfing the limited land resources on which humans depend, restricting agricultural production. Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is important in the biosynthesis of terpenoids, which are involved in plant growth, development and responses to environmental stresses. This study aimed to provide guidance for producing salt- and drought-resistant poplar.MethodsA protein expression system was used to obtain PtHMGR protein, and high-performance liquid chromatography was used to detect the activity of PtHMGR protein in vitro. In addition, a simplified version of the leaf infection method was used for transformation of ‘Nanlin895’ poplar (Populus×euramericana). qRT–PCR was used to identify expression levels of genes.Key ResultsPtHMGR catalysed a reaction involving HMG-CoA and NADPH to form mevalonate. Overexpression of PtHMGR in Populus × euramericana ‘Nanlin895’ improved drought and salinity tolerance. In the presence of NaCl and PEG6000, the rates of rooting and survival of PtHMGR-overexpressing poplars were higher than those of wild-type poplars. The transgenic lines also exhibited higher proline content and peroxidase and superoxide dismutase activities, and a lower malondialdehyde level under osmotic stress. In addition, the expression of genes related to reactive oxygen species (ROS) scavenging and formation was altered by osmotic stress. Moreover, the effect of osmotic stress on transcript levels of stress-related genes differed between the transgenic and wild-type poplars.ConclusionPtHMGR catalysed a reaction involving HMG-CoA and NADPH to form mevalonate in vitro. Overexpression of PtHMGR promoted root development, increased the expression of ROS scavenging-related genes, decreased the expression of ROS formation-related genes, and increased the activity of antioxidant enzymes in transgenic poplars, enhancing their tolerance of osmotic stress. In addition, overexpression of PtHMGR increased expression of the stress-related genes KIN1, COR15 and AAO3 and decreased that of ABI, MYB, MYC2 and RD22, enhancing the stress resistance of poplar.
Social Media’s Influence on Breast Augmentation
Authors: Zahedi Sanam , Hancock Ellen , Hameed Samee , Phillips Linda G , Moliver Clayton L 
Published: September 2019

Abstract

Background
The purpose of this study is to evaluate if and what social media use influences our patients’ decisions to undergo breast augmentation.

Objectives
A single-institution study was designed to evaluate women who underwent elective breast augmentation from 2017 to 2018.

Methods
Patients were contacted via validated, prompted telephone survey. Data regarding their demographic information and social media utilization pertaining to breast augmentation were collected after obtaining verbal consent.

Results
Inclusion criteria were met by 180 patients, of which 69% participated in the survey. Ninety-seven percent of the participants reported utilizing social media in general; the most common platforms were Facebook, Instagram, and the physician’s website. Millennials (97%) and Generation X (92%) utilized social media the most and none of the baby boomers. Sixty-four percent of participants reported utilizing some form of social media to research breast augmentation, with the most common resource being Instagram. When analyzing the impact of the social media resources utilized by the participants, Instagram was reported as the most impactful at 54%. Only 18% of participants were utilizing a physician’s social media account to research breast augmentation. Among the 50% of patients who utilized social media to compare their surgeon’s work with another physician’s, the majority (83%) were utilizing the physician’s website.

Conclusions
Social media influences patients’ education and decisions to undergo breast augmentation, with Instagram being the most impactful. This study evaluated the patient population to stay up to date on their social media utilization and resources of education prior to breast augmentation.
Interindividual spacing affects the finder’s share in ring-tailed coatis (Nasua nasua)
Authors: Hirsch Ben T , Malpass Erica , Di Blanco Yamil E 
Published: September 2019

AbstractSocial foraging models are often used to explain how group size can affect an individual’s food intake rate and foraging strategies. The proportion of food eaten before the arrival of conspecifics, the finder’s share, is hypothesized to play a major role in shaping group geometry, foraging strategy, and feeding competition. The variables that affect the finder’s share in ring-tailed coatis were tested using a series of food trials. The number of grapes in the food trials had a strong negative effect on the finder’s share and the probability that the finder was joined. The effect of group size on the finder’s share and foraging success was not straightforward and was mediated by sociospatial factors. The finder’s share increased when the time to arrival of the next individual was longer, the group was more spread out, and the finder was in the back of the group. Similarly, the total amount of food eaten at a trial was higher when more grapes were placed, arrival time was longer, and the number of joiners was smaller. Individuals at the front edge of the group found far more food trials, but foraging success was higher at the back of the group where there were fewer conspecifics to join them. This study highlights the importance of social spacing strategies and group geometry on animal foraging tactics and the costs and benefits of sociality.
bayNorm: Bayesian gene expression recovery, imputation and normalization for single-cell RNA-sequencing data
Authors: Tang Wenhao , Bertaux François , Thomas Philipp , Stefanelli Claire , Saint Malika , Marguerat Samuel , Shahrezaei Vahid 
Published: September 2019

AbstractMotivationNormalization of single-cell RNA-sequencing (scRNA-seq) data is a prerequisite to their interpretation. The marked technical variability, high amounts of missing observations and batch effect typical of scRNA-seq datasets make this task particularly challenging. There is a need for an efficient and unified approach for normalization, imputation and batch effect correction.ResultsHere, we introduce bayNorm, a novel Bayesian approach for scaling and inference of scRNA-seq counts. The method’s likelihood function follows a binomial model of mRNA capture, while priors are estimated from expression values across cells using an empirical Bayes approach. We first validate our assumptions by showing this model can reproduce different statistics observed in real scRNA-seq data. We demonstrate using publicly available scRNA-seq datasets and simulated expression data that bayNorm allows robust imputation of missing values generating realistic transcript distributions that match single molecule fluorescence in situ hybridization measurements. Moreover, by using priors informed by dataset structures, bayNorm improves accuracy and sensitivity of differential expression analysis and reduces batch effect compared with other existing methods. Altogether, bayNorm provides an efficient, integrated solution for global scaling normalization, imputation and true count recovery of gene expression measurements from scRNA-seq data.Availability and implementationThe R package ‘bayNorm’ is publishd on bioconductor at https://bioconductor.org/packages/release/bioc/html/bayNorm.html. The code for analyzing data in this article is available at https://github.com/WT215/bayNorm_papercode.Supplementary informationSupplementary data are available at Bioinformatics online.
Historical allopatry and secondary contact or primary intergradation in the Puerto Rican crested anole, Anolis cristatellus, on Vieques Island in the Caribbean
Authors: Quach Quynh N , Reynolds R Graham , Revell Liam J 
Published: September 2019

AbstractRecent work has revealed surprisingly deep mitochondrial genetic divergence in the lizard Anolis cristatellus among samples obtained from the small Caribbean island of Vieques. Here we sought to determine whether this had resulted from natural or anthropogenic causes, and (if the former) whether divergence occurred in a biogeographical context of allopatry followed by secondary contact, or via isolation-by-distance across the species’ historical range. We first estimated a mitochondrial gene tree for 379 samples and then genotyped 3407 single nucleotide polymorphic sites from 48 individuals using a modified genotyping-by-sequencing approach. We found that A. cristatellus samples from Vieques belong to two highly divergent mitochondrial subclades, but the geographical distribution of these haplogroups indicates that this pattern is probably natural in origin. Analysis of our single nucleotide polymorphic dataset revealed differentiation that is consistent with isolation-by-distance between the western and eastern ends of Vieques, suggesting that the overall pattern of divergence probably reflects primary intergradation with a mitochondrial break on the historical Puerto Rico Bank palaeo-island that happened to coincide with the present-day location of Vieques. Our findings help to underline the growing consensus that results from a single genetic marker can prove highly misleading in studies of historical population genetic structure.
Altered Sex Chromosome Dosage Induces Coordinated Shifts in Cortical Anatomy and Anatomical Covariance
Authors: Xenophontos Anastasia , Seidlitz Jakob , Liu Siyuan , Clasen Liv S , Blumenthal Jonathan D , Giedd Jay N , Alexander-Bloch Aaron , Raznahan Armin 
Published: September 2019

AbstractSex chromosome dosage (SCD) variation increases risk for neuropsychiatric impairment, which may reflect direct SCD effects on brain organization. Here, we 1) map cumulative X- and Y-chromosome dosage effects on regional cortical thickness (CT) and investigate potential functional implications of these effects using Neurosynth, 2) test if this map is organized by patterns of CT covariance that are evident in health, and 3) characterize SCD effects on CT covariance itself. We modeled SCD effects on CT and CT covariance for 308 equally sized regions of the cortical sheet using structural neuroimaging data from 301 individuals with varying numbers of sex chromosomes (169 euploid, 132 aneuploid). Mounting SCD increased CT in the rostral frontal cortex and decreased CT in the lateral temporal cortex, bilaterally. Regions targeted by SCD were associated with social functioning, language processing, and comprehension. Cortical regions with a similar degree of SCD-sensitivity showed heightened CT covariance in health. Finally, greater SCD also increased covariance among regions similarly affected by SCD. Our study both 1) develops novel methods for comparing typical and disease-related structural covariance networks in the brain and 2) uses these techniques to resolve and identify organizing principles for SCD effects on regional cortical anatomy and anatomical covariance.
Cefiderocol: Discovery, Chemistry, and In Vivo Profiles of a Novel Siderophore Cephalosporin
Authors: Sato Takafumi , Yamawaki Kenji 
Published: September 2019

AbstractThe emergence of antimicrobial resistance is a significant public health issue worldwide, particularly for healthcare-associated infections caused by carbapenem-resistant gram-negative pathogens. Cefiderocol is a novel siderophore cephalosporin targeting gram-negative bacteria, including strains with carbapenem resistance. The structural characteristics of cefiderocol show similarity to both ceftazidime and cefepime, which enable cefiderocol to withstand hydrolysis by β-lactamases. The unique chemical component is the addition of a catechol moiety on the C-3 side chain, which chelates iron and mimics naturally occurring siderophore molecules. Following the chelation of iron, cefiderocol is actively transported across the outer membrane of the bacterial cell to the periplasmic space via specialized iron transporter channels. Furthermore, cefiderocol has demonstrated structural stability against hydrolysis by both serine- and metallo-β-lactamases, including clinically relevant carbapenemases such as Klebsiella pneumoniae carbapenemase, oxacillin carbapenemase-48, and New Delhi metallo-β-lactamase. Cefiderocol has demonstrated promising in vitro antibacterial and bactericidal activity, which correlates with its in vivo efficacy in several animal models. This article reviews the discovery and chemistry of cefiderocol, as well as some of the key microbiological and in vivo findings on cefiderocol from recently conducted investigations.
Pharmacokinetic and Pharmacodynamic Profiles of Cefiderocol, a Novel Siderophore Cephalosporin
Authors: Katsube Takayuki , Echols Roger , Wajima Toshihiro 
Published: September 2019

AbstractCefiderocol, a novel parenteral siderophore cephalosporin, exhibits potent in vitro activity and in vivo efficacy against most gram-negative bacteria, including carbapenem-resistant strains of Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. In phase 1 studies, cefiderocol demonstrated linear pharmacokinetics, primarily urinary excretion, an elimination half-life of 2–3 hours, and a protein binding of 58% in human plasma. Cefiderocol is a time-dependent cephalosporin; the probability of a target attainment at ≥75% of the dosing interval during which the free drug concentration exceeds the minimum inhibitory concentration (ƒT/MIC) for bacterial strains with an MIC of ≤4 μg/mL is likely to be achieved at the therapeutic dose of 2 g over 3-hour infusion every 8 hours in most patients. As expected, renal function markers were the most influential covariates for the pharmacokinetics of cefiderocol for patients with renal impairment or augmented renal clearance (ARC). Dose adjustment is recommended for patients with impaired renal function, and additionally, in ARC patients with creatinine clearance >120 mL/minute, a more frequent dosing regimen (ie, 2 g every 6 hours) was predicted to achieve the target fT > MIC. The single and multiple doses of cefiderocol tested were well tolerated in both healthy subjects and those with renal impairment. Furthermore, neither QT interval prolongation nor drug–drug interaction via organic anion transporters was demonstrated in healthy subjects. Cefiderocol is being investigated in phase 3 clinical studies for the treatment of infections caused by carbapenem-resistant bacteria.
Pathogen-focused Clinical Development to Address Unmet Medical Need: Cefiderocol Targeting Carbapenem Resistance
Authors: Echols Roger , Ariyasu Mari , Nagata Tsutae Den 
Published: September 2019

AbstractHistorically, the regulatory requirements of the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for developing new antibiotics have not addressed pathogen-focused indications for drug approval. The design of the necessary randomized controlled trials traditionally involves the enrollment of patients with site-specific infections caused by susceptible as well as resistant pathogens. Cefiderocol has undergone a streamlined clinical development program to address serious carbapenem-resistant infections. The regulatory approach, and the pivotal clinical trials, differed between the FDA and EMA. In the United States, the APEKS-cUTI (Acinetobacter, Pseudomonas, Escherichia coli, Klebsiella, Stenotrophomonas–complicated urinary tract infection) study was conducted to provide the basis for FDA approval of a site-specific cUTI indication. The EMA, however, preferred the CREDIBLE-CR (A MultiCenter, RandomizED, Open-label ClInical Study of S-649266 or Best AvailabLE Therapy for the Treatment of Severe Infections Caused by Carbapenem-Resistant Gram-negative Pathogens) study, in which patients with nosocomial pneumonia, bloodstream infections, or cUTIs were enrolled if they had a carbapenem-resistant pathogen. The resulting European label will be pathogen focused rather than infection site specific (ie, treatment of gram-negative infection in patients with limited treatment options). The implications and limitations of these different regulatory processes are discussed.
Consensus Report on Shigella Controlled Human Infection Model: Clinical Endpoints
Authors: MacLennan Calman A , Riddle Mark S , Chen Wilbur H , Talaat Kawsar R , Jain Varsha , Bourgeois A Louis , Frenck Robert , Kotloff Karen , Porter Chad K 
Published: September 2019

AbstractThe Shigella controlled human infection model (CHIM) is valuable for assessing candidate Shigella vaccine efficacy and potentially accelerating regulatory approval. The Shigella CHIM is currently being conducted at 3 sites in the United States using Shigella flexneri 2a strain 2457T and Shigella sonnei strain 53G. Shigellosis can present variably as watery diarrhea alone or with dysentery, and can be accompanied by manifestations including fever, abdominal cramps, tenesmus, and malaise. For comparability, it is important to harmonize the primary clinical endpoint. An expert working group was convened on 2 February 2018 to review clinical data from Shigella CHIM studies performed to date and to develop a consensus primary endpoint. The consensus endpoint enabled “shigellosis” to present as severe diarrhea or moderate diarrhea or dysentery. The latter 2 criteria are met when concurrent with fever of 38.0°C and/or vomiting, and/or a constitutional/enteric symptom graded at least as “moderate” severity. The use of a blinded independent committee to adjudicate the primary endpoint by subject was also regarded as important. As safety of volunteers in challenge studies is of paramount importance and treatment timing can affect primary outcomes, a standard for early antibiotic administration was established as follows: (1) when the primary endpoint is met; (2) if a fever of ≥39.0°C develops; or (3) if the study physician deems it appropriate. Otherwise, antibiotics are given at 120 hours postinfectious challenge. The working group agreed on objective and subjective symptoms to be solicited, and standardized methods for assessing subject-reported severity of symptoms.
Trial design and baseline characteristics of CaLIPSO: a randomized, double-blind placebo-controlled trial of SNF472 in patients receiving haemodialysis with cardiovascular calcification
Authors: Bellasi Antonio , Raggi Paolo , Bover Jordi , Bushinsky David A , Chertow Glenn M , Ketteler Markus , Rodriguez Mariano , Sinha Smeeta , Salcedo Carolina , Garg Rekha , Gold Alex , Perelló Joan 
Published: September 2019

Abstract

Background
The objective of CaLIPSO, a Phase 2b, randomized, double-blind, placebo-controlled clinical trial, is to test the hypothesis that myo-inositol hexaphosphate (SNF472) attenuates the progression of cardiovascular calcification in patients receiving maintenance haemodialysis. Here we report the trial design and baseline characteristics of trial participants.

Methods
Adult patients on maintenance haemodialysis (≥6 months) with an Agatston coronary artery calcium score, as measured by a multidetector computed tomography scanner, of 100–3500 U were enrolled. Patients were stratified by Agatston score (100–&lt;400, 400–1000 or &gt;1000 U) and randomized in a 1:1:1 ratio to receive placebo, SNF472 300 mg or SNF472 600 mg administered intravenously three times weekly during each haemodialysis session.

Results
Overall, 274 patients were randomized. The mean age of trial participants was 63.6 (standard deviation 8.9) years and 39% were women. The coronary artery, aorta and aortic valve median (25th-75th percentile) Agatston scores at baseline were 730 U (315–1435), 1728 U (625–4978) and 103 U (31–262), respectively, and the median (25th–75th percentile) calcium volume scores at baseline were 666 (310–1234), 1418 (536–4052) and 107 (38–278), respectively. Older age and diabetes mellitus were associated with higher calcium scores at baseline.

Conclusions
The CaLIPSO trial enrolled patients on haemodialysis with pre-existent cardiovascular calcification to test the hypothesis that SNF472 attenuates its progression in the coronary arteries, aorta and aortic valve.
An unyielding valve leading to venous spasm during pacemaker implantation: a case report
Authors: Krishnappa Darshan , Sakaguchi Scott , Kasinadhuni Ganesh , Tholakanahalli Venkatakrishna N 
Published: September 2019

Abstract

Background
Subclavian venous spasm is an uncommon complication during permanent pacemaker implantation. The exact aetiology of subclavian venous spasm is not clear but has been suggested to be due to either mechanical irritation of the vein during needle puncture or due to chemical irritation from contrast injection. Here, we report a case of an unyielding subclavian vein valve that impeded guidewire advancement and the repeated guidewire manipulation led to venous spasm.

Case summary
A 45-year-old woman with a history of surgical repair of Tetrology of Fallot in childhood presented with symptomatic bifascicular block and underwent a permanent pacemaker implantation. A subclavian venogram done prior to the procedure showed a prominent valve in the distal portion of the vein. Following venous puncture, guidewire advancement was impeded by the prominent valve. The resulting guidewire manipulation led to subclavian venous spasm necessitating a medial subclavian venous puncture and access.

Discussion
Prolonged mechanical irritation of the vein during pacemaker implantation may lead to venous spasm impeding pacemaker implantation. Early identification of an impeding valve and obtaining access medial to the valve may help prevent this uncommon complication.
Loperamide overdose causing torsades de pointes and requiring Impella temporary mechanical support: a case report
Authors: Cicci Jonathan D , Jagielski Sarah M , Clarke Megan M , Rayson Robert A , Cavender Matthew A 
Published: September 2019

AbstractBackgroundLoperamide is a widely available oral μ-opioid receptor agonist, and loperamide abuse is increasing by those seeking intoxication. Loperamide has potent QTc-prolonging properties, placing patients at risk for ventricular arrhythmias and sudden cardiac death.Case summaryA 23-year-old woman was found to be in pulseless ventricular fibrillation with a QTc of 554 ms and received multiple defibrillations and IV lidocaine. Her toxicology studies were negative. She subsequently experienced multiple episodes of torsades de pointes and was found to be in cardiogenic shock with a left ventricular ejection fraction of 5%. Following multiple defibrillations, an Impella® mechanical circulatory support device was placed, and she was given IV magnesium and IV lidocaine. After mechanical circulatory support was withdrawn, she experienced major bleeding and was found to have a deep vein thrombosis, bilateral radial artery thrombosis, and multiple pulmonary embolisms in the setting of heparin-induced thrombocytopenia. After stabilizing, she admitted to taking 80 tablets of loperamide 2 mg in pursuit of euphoria.DiscussionLoperamide is an increasingly popular agent of abuse. Loperamide-associated ventricular arrhythmias are rare with normal doses but more common with high doses, chronic ingestion, or interacting medications. Loperamide cardiotoxicity may be prolonged due to a long half-life and accumulation. Loperamide abuse may be under-recognized, leading to delays in treatment. Intravenous fluids, magnesium supplementation, chronotropes, transcutaneous or transvenous pacing, and defibrillation may be helpful in mitigating loperamide-associated polymorphic ventricular tachycardia. Clinicians should monitor for drug interactions in patients taking loperamide and screen for electrocardiographic abnormalities in those taking chronic or high-dose loperamide.