bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variation in theAvrSr35gene determinesSr35resistance against wheat stem rust race Ug99
Authors: Salcedo Andres , Rutter William , Wang Shichen , Akhunova Alina , Bolus Stephen , Chao Shiaoman , Anderson Nickolas , De Soto Monica Fernandez , Rouse Matthew , Szabo Les , Bowden Robert L. , Dubcovsky Jorge , Akhunov Eduard 
Published: December 2017

Fungal effectors of wheat stem rustThe fungal pathogen Ug99 (named for its identification in Uganda in 1999) threatens wheat crops worldwide. Ug99 can kill entire fields of wheat and is undeterred by many of the disease-resistance genes that otherwise protect wheat crops. Two papers describe two peptides secreted by the fungus as it attacks the wheat (see the Perspective by Moscou and van Esse). Chenet al.show that fungal AvrSr50 binds to the plant's immune receptor Sr50, and Salcedoet al.show that fungal AvrSr35 binds to Sr35. Successful binding activates the plant's immune defenses. Removing or inactivating these Avr effectors leaves the plant defenseless and susceptible to disease.Science, this issue p.1607, p.1604; see also p.1541
Dramatic Increase of Amoxicillin-Induced Crystal Nephropathy Found in a Cohort Study of French Pharmacovigilance Centers
Authors: Vodovar Dominique , Thomas Laure , Mongardon Nicolas , Lepeule Raphaël , Lebrun-Vignes Bénédicte , Biour Michel , Netzer Florence , Haouache Hakim , Le Beller Christine , Dhonneur Gilles 
Published: December 2017

ABSTRACT

An increase in amoxicillin-induced crystal nephropathy (AICN) incidence has been recently suggested. The aims of this study were to investigate the trend of AICN incidence through Paris' regional centers of pharmacovigilance (Paris RCPVs) and better describe this rare adverse drug reaction. Forty-five AICN cases were identified between 1985 and 2016. All cases, except one, were reported since 2010. Amoxicillin (AMX) was administered intravenously (65 [interquartile range {IQR}, 43 to 110] mg/kg of body weight/day) in all patients, either for treating infection (
n
= 15) or as surgical prophylaxis (
n
= 30). Delay between AMX administration and AICN onset was 1 (IQR, 1 to 3) day; 30, 4, and 11 patients developed KDIGO stage 1, 2, and 3 acute kidney injury, respectively. Delay between AICN onset and kidney function recovery was 4 (IQR, 2 to 6) days. Precipitating factors were identified in only one-third of cases. Twelve patients required intensive care unit admission, and 8 needed renal replacement therapy. Neither chronic kidney disease nor death was observed. We confirmed the recent and dramatic increase of AICN in the Paris RCPVs since 2010. The absence of precipitating factors in the majority of cases and the onset of AICN in apparent routine indications, such as surgical prophylaxis, are alarming and justify a high vigilance from all AMX prescribers.
Impact of Real-Time Therapeutic Drug Monitoring on the Prescription of Antibiotics in Burn Patients Requiring Admission to the Intensive Care Unit
Authors: Fournier A. , Eggimann P. , Pantet O. , Pagani J. L. , Dupuis-Lozeron E. , Pannatier A. , Sadeghipour F. , Voirol P. , Que Y.-A. 
Published: December 2017

ABSTRACT

As pharmacokinetics after burn trauma are difficult to predict, we conducted a 3-year prospective, monocentric, randomized, controlled trial to determine the extent of under- and overdosing of antibiotics and further evaluate the impact of systematic therapeutic drug monitoring (TDM) with same-day real-time dose adaptation to reach and maintain antibiotic concentrations within the therapeutic range. Forty-five consecutive burn patients treated with antibiotics were prospectively screened. Forty fulfilled the inclusion criteria; after one patient refused to participate and one withdrew consent, 19 were randomly assigned to an intervention group (patients with real-time antibiotic concentration determination and subsequent adaptations) and 19 were randomly assigned to a standard-of-care group (patients with antibiotic administration at the physician's discretion without real-time TDM). Seventy-three infection episodes were analyzed. Before the intervention, only 46/82 (56%) initial trough concentrations fell within the range. There was no difference between groups in the initial trough concentrations (adjusted hazard ratio = 1.39 [95% confidence interval {CI}, 0.81 to 2.39],
P
= 0.227) or the time to reach the target. However, thanks to real-time dose adjustments, the trough concentrations of the intervention group remained more within the predefined range (57/77 [74.0%] versus 48/85 [56.5%]; adjusted odd ratio [OR] = 2.34 [95% CI, 1.17 to 4.81],
P
= 0.018), more days were spent within the target range (193 days/297 days on antibiotics [65.0%] versus 171 days/311 days in antibiotics [55.0%]; adjusted OR = 1.64 [95% CI, 1.16 to 2.32],
P
= 0.005), and fewer results were below the target trough concentrations (25/118 [21.2%] versus 44/126 [34.9%]; adjusted OR = 0.47 [95% CI, 0.26 to 0.87],
P
= 0.015). No difference in infection outcomes was observed between the study groups. Systematic TDM with same-day real-time dose adaptation was effective in reaching and maintaining therapeutic antibiotic concentrations in infected burn patients, which prevented both over- and underdosing. A larger multicentric study is needed to further evaluate the impact of this strategy on infection outcomes and the emergence of antibiotic resistance during long-term burn treatment. (This study was registered with the ClinicalTrials.gov platform under registration no. NCT01965340 on 27 September 2013.)
Relation between Skin Pharmacokinetics and Efficacy in AmBisome Treatment of Murine Cutaneous Leishmaniasis
Authors: Wijnant Gert-Jan , Van Bocxlaer Katrien , Yardley Vanessa , Harris Andy , Murdan Sudaxshina , Croft Simon L. 
Published: December 2017

ABSTRACT

AmBisome (LAmB), a liposomal formulation of amphotericin B (AmB), is a second-line treatment for the parasitic skin disease cutaneous leishmaniasis (CL). Little is known about its tissue distribution and pharmacodynamics to inform clinical use in CL. Here, we compared the skin pharmacokinetics of LAmB with those of the deoxycholate form of AmB (DAmB; trade name Fungizone) in murine models of
Leishmania major
CL. Drug levels at the target site (the localized lesion) 48 h after single intravenous (i.v.) dosing of the individual AmB formulations (1 mg/kg of body weight) were similar but were 3-fold higher for LAmB than for DAmB on day 10 after multiple administrations (1 mg/kg on days 0, 2, 4, 6, and 8). After single and multiple dosing, intralesional concentrations were 5- and 20-fold, respectively, higher than those in the healthy control skin of the same infected mice. We then evaluated how drug levels in the lesion after LAmB treatment relate to therapeutic outcomes. After five administrations of the drug at 0, 6.25, or 12.5 mg/kg (i.v.), there was a clear correlation between dose level, intralesional AmB concentration, and relative reduction in parasite load and lesion size (
R
2
values of >0.9). This study confirms the improved efficacy of the liposomal over the deoxycholate AmB formulation in experimental CL, which is related to higher intralesional drug accumulation.
Transcriptional Response to Lactic Acid Stress in the Hybrid Yeast Zygosaccharomyces parabailii
Authors: Ortiz-Merino Raúl A. , Kuanyshev Nurzhan , Byrne Kevin P. , Varela Javier A. , Morrissey John P. , Porro Danilo , Wolfe Kenneth H. , Branduardi Paola 
Published: December 2017

ABSTRACT

Lactic acid has a wide range of applications starting from its undissociated form, and its production using cell factories requires stress-tolerant microbial hosts. The interspecies hybrid yeast
Zygosaccharomyces parabailii
has great potential to be exploited as a novel host for lactic acid production, due to high organic acid tolerance at low pH and a fermentative metabolism with a high growth rate. Here we used mRNA sequencing (RNA-seq) to analyze
Z. parabailii
's transcriptional response to lactic acid added exogenously, and we explore the biological mechanisms involved in tolerance.
Z. parabailii
contains two homeologous copies of most genes. Under lactic acid stress, the two genes in each homeolog pair tend to diverge in expression to a significantly greater extent than under control conditions, indicating that stress tolerance is facilitated by interactions between the two gene sets in the hybrid. Lactic acid induces downregulation of genes related to cell wall and plasma membrane functions, possibly altering the rate of diffusion of lactic acid into cells. Genes related to iron transport and redox processes were upregulated, suggesting an important role for respiratory functions and oxidative stress defense. We found differences in the expression profiles of genes putatively regulated by Haa1 and Aft1/Aft2, previously described as lactic acid responsive in
Saccharomyces cerevisiae
. Furthermore, formate dehydrogenase (
FDH
) genes form a lactic acid-responsive gene family that has been specifically amplified in
Z. parabailii
in comparison to other closely related species. Our study provides a useful starting point for the engineering of
Z. parabailii
as a host for lactic acid production.

IMPORTANCE
Hybrid yeasts are important in biotechnology because of their tolerance to harsh industrial conditions. The molecular mechanisms of tolerance can be studied by analyzing differential gene expression under conditions of interest and relating gene expression patterns to protein functions. However, hybrid organisms present a challenge to the standard use of mRNA sequencing (RNA-seq) to study transcriptional responses to stress, because their genomes contain two similar copies of almost every gene. Here we used stringent mapping methods and a high-quality genome sequence to study the transcriptional response to lactic acid stress in
Zygosaccharomyces parabailii
ATCC 60483, a natural interspecies hybrid yeast that contains two complete subgenomes that are approximately 7% divergent in sequence. Beyond the insights we gained into lactic acid tolerance in this study, the methods we developed will be broadly applicable to other yeast hybrid strains.
Multicenter Clinical Evaluation of the Alere i Respiratory Syncytial Virus Isothermal Nucleic Acid Amplification Assay
Authors: Hassan Ferdaus , Hays Lindsay M. , Bonner Aleta , Bradford Bradley J. , Franklin Ruffin , Hendry Phyllis , Kaminetsky Jed , Vaughn Michael , Cieslak Kristin , Moffatt Mary E. , Selvarangan Rangaraj 
Published: December 2017

ABSTRACT
The Alere i respiratory syncytial virus (RSV) assay is an isothermal nucleic acid amplification test capable of detecting RSV directly from respiratory specimens, with results being available in ≤13 min after test initiation. The objective of this study was to evaluate the performance characteristics of the Alere i RSV assay in a point-of-care setting by using direct nasopharyngeal (NP) swab specimens (direct NP) and nasopharyngeal swab specimens eluted and transported in viral transport medium (VTM NP). The study was a prospective, multicenter, clinical trial conducted at 9 sites across the United States to evaluate the clinical performance of the Alere i RSV assay with respiratory specimens obtained from both children (age, <18 years) and older adults (age, >60 years). The performance of the Alere i RSV assay was compared with that of the reference method, the Prodesse ProFlu+ real-time reverse transcriptase PCR (RT-PCR) assay. All specimens with discrepant test results were tested further by a second FDA-cleared PCR assay (the Verigene respiratory virus plus nucleic acid test; Luminex Inc., TX). A total of 554 subjects with signs and symptoms of respiratory infections were enrolled, and respiratory samples were collected in this study. In comparison with the ProFlu+ real-time RT-PCR, the overall sensitivity and specificity of Alere i RSV assay for the detection of RSV were 98.6% (95% confidence interval [CI], 94.4 to 99.7%) and 98.0% (95% CI, 95.8 to 99.1%), respectively, for direct NP and 98.6% (95% CI, 94.4 to 99.7%) and 97.8% (95% CI, 95.5 to 98.9%), respectively, for VTM NP. The Alere i RSV is a highly sensitive and specific molecular assay ideal for rapid RSV detection in patients in the point-of-care setting due to its minimal hands-on time and rapid result availability.
RSAD2 and AIM2 Modulate Coxsackievirus A16 and Enterovirus A71 Replication in Neuronal Cells in Different Ways That May Be Associated with Their 5′ Nontranslated Regions
Authors: Yogarajah Thinesshwary , Ong Kien Chai , Perera David , Wong Kum Thong 
Published: December 2017

ABSTRACT

Coxsackievirus A16 (CV-A16) and enterovirus A71 (EV-A71) are closely related enteroviruses that cause the same hand, foot, and mouth disease (HFMD), but neurological complications occur only very rarely in CV-A16 compared to EV-A71 infections. To elucidate host responses that may be able to explain these differences, we performed transcriptomic analysis and real-time quantitative PCR (RT-qPCR) in CV-A16-infected neuroblastoma cells (SK-N-SH), and the results showed that the radical
S
-adenosylmethionine domain containing 2 (RSAD2) was the highest upregulated gene in the antimicrobial pathway. Increased RSAD2 expression was correlated with reduced viral replication, while RSAD2 knockdown cells were correlated with increased replication. EV-A71 replication showed no apparent correlation to RSAD2 expressions. Absent in melanoma 2 (AIM2), which is associated with pyroptotic cell death, was upregulated in EV-A71-infected neurons but not in CV-A16 infection, suggesting that the AIM2 inflammasome played a significant role in suppressing EV-A71 replication. Chimeric viruses derived from CV-A16 and EV-A71 but containing swapped 5′ nontranslated regions (5′ NTRs) showed that RSAD2 expression/viral replication and AIM2 expression/viral replication patterns may be linked to the 5′ NTRs of parental viruses. Differences in secondary structure of internal ribosomal entry sites within the 5′ NTR may be responsible for these findings. Overall, our results suggest that CV-A16 and EV-A71 elicit different host responses to infection, which may help explain the apparent lower incidence of CV-A16-associated neurovirulence in HFMD outbreaks compared to EV-A71 infection.

IMPORTANCE
Although coxsackievirus A16 (CV-A16) and enterovirus A17 (EV-A71) both cause hand, foot, and mouth disease, EV-A71 has emerged as a leading cause of nonpolio, enteroviral fatal encephalomyelitis among young children. The significance of our research is in the identification of the possible differing and novel mechanisms of CV-A16 and EV-A71 inhibition in neuronal cells that may impact viral neuropathogenesis. We further showed that viral 5′ NTRs may play significant roles in eliciting different host response mechanisms.
Epidemiology and return to play following isolated syndesmotic injuries of the ankle: a prospective cohort study of 3677 male professional footballers in the UEFA Elite Club Injury Study
Authors: Lubberts Bart , D’Hooghe Pieter , Bengtsson Håkan , DiGiovanni Christopher W , Calder James , Ekstrand Jan 
Published: December 2017

AimTo determine the epidemiology of isolated syndesmotic injuries in professional football players.MethodsData from 15 consecutive seasons of European professional football between 2001 and 2016 contributed to the dataset of this study. Match play and training data from a total of 3677 players from 61 teams across 17 countries have been included. Team medical staff recorded player exposure and time loss injuries. Injury incidence was defined as the number of injuries per 1000 player-hours. Injury burden was defined as number of days absence per 1000 player-hours. Seasonal trends for isolated syndesmotic injury incidence, isolated syndesmotic injury proportion of ankle ligament injuries and isolated syndesmotic injury burden were analysed via linear regression.ResultsThe isolated syndesmotic injury incidence was 0.05 injuries per 1000 hours of exposure (95% CI 0.04 to 0.06) or one injury per team every three seasons. The injury incidence during match play was 13 times higher compared with during training, 0.21 (95% CI 0.16 to 0.26) and 0.02 (95% CI 0.01 to 0.02), respectively. Out of the 1320 ankle ligament injuries registered during the 15 seasons, 94 (7%) were diagnosed as isolated syndesmotic injuries. An annual increase in injury incidence was observed (R2=0.495, b=0.003, 95% CI 0.001 to 0.004, P=0.003). However, no significant annual change of injury burden was observed (R2=0.033, b=0.032, 95% CI −0.073 to 0.138, P=0.520). Seventy-four per cent of the injuries were contact related, and the mean (±SD) absence following an isolated syndesmotic injury was 39 (±28) days.ConclusionsThe incidence of isolated syndesmotic injuries in elite professional European football annually increased between 2001 and 2016.
Functional lesional neurosurgery for tremor: back to the future?
Authors: Schreglmann Sebastian R , Krauss Joachim K , Chang Jin Woo , Martin Ernst , Werner Beat , Bauer Ronald , Hägele-Link Stefan , Bhatia Kailash P , Kägi Georg 
Published: December 2017

For nearly a century, functional neurosurgery has been applied in the treatment of tremor. While deep brain stimulation has been in the focus of academic interest in recent years, the establishment of incisionless technology, such as MRI-guided high-intensity focused ultrasound, has again stirred interest in lesional approaches.In this article, we will discuss the historical development of surgical technique and targets, as well as the technological state-of-the-art of conventional and incisionless interventions for tremor due to Parkinson’s disease, essential and dystonic tremor and tremor related to multiple sclerosis (MS) and midbrain lesions. We will also summarise technique-inherent advantages of each technology and compare their lesion characteristics. From this, we identify gaps in the current literature and derive future directions for functional lesional neurosurgery, in particularly potential trial designs, alternative targets and the unsolved problem of bilateral lesional treatment. The results of a systematic review and meta-analysis of the consistency, efficacy and side effect rate of lesional treatments for tremor are presented separately alongside this article.
Hypothalamic control of body temperature: insights from the past
Authors: Mack Gary W. 
Published: December 2017

This essay looks at the historical significance of three APS classic papers that are freely available online: Hammel HT, Hardy JD, and Fusco MM. Thermoregulatory responses to hypothalamic cooling in unanesthetized dogs. Am J Physiol 198: 481-486, 1960 ( http://ajplegacy.physiology.org/cgi/reprint/198/3/481 ). Hammel HT, Jackson DC, Stolwijk JAJ, Hardy JD, and Strømme SB. Temperature regulation by hypothalamic proportional control with an adjustable set point. J Appl Physiol 18: 1146-1154, 1963 ( http://jap.physiology.org/cgi/reprint/18/6/1146 ). Hellstrøm B and Hammel HT. Some characteristics of temperature regulation in the unanesthetized dog. Am J Physiol 213: 547-556, 1967 ( http://ajplegacy.physiology.org/cgi/reprint/213/2/547 ).
Long-Term Deprivation of Substance P in PPT-A Mutant Mice Alters the Anoxic Response of the Isolated Respiratory Network
Authors: Telgkamp Petra , Cao Yuqing Q. , Basbaum Allan I. , Ramirez Jan-Marino 
Published: December 2017

The aim of this study was to elucidate the role of the neuromodulator substance P and its related tachykinin neurokinin A (NKA) in the homeostasis of respiratory activity. Respiratory activities, in form of fictive eupneic and sigh activities, were recorded extracellularly from the preBötzinger complex (PBC) in normoxic and anoxic conditions using medullary slice preparations. The effect of a blockade of endogenous substance P was assessed by an acute pharmacological blockade of the receptors with spantide in wild-type animals and by the use of preprotachykinin-A (PPT-A) mutants. These mutants lack from birth the PPT-A gene, which codes for the precursor of substance P and NKA. Spantide treatment reduced frequency (−37%, n = 9) and regularity (twofold) of eupneic-like respiratory activity under normoxic conditions, whereas in PPT-A mutants, eupneic-like activity was under normoxic conditions not significantly different from the wild-type mice (WT). The response to short anoxic episodes (5 min) was characterized in the WT by an increase in respiratory frequencies at the onset of anoxia (ratio anoxic/control frequency = 1.9 ± 0.2, n = 18). This anoxic ratio was unaltered in the presence of spantide (ratio = 2.3 ± 0.4, n = 8) but increased in the mutant (ratio = 4.1, n = 15).We conclude that endogenously released substance P is important for the maintenance of regular respiratory activity. Short-term blockade of substance P receptors decreases the frequency and regularity of rhythmic activity. Long-term deficiency in substance P leads to compensatory mechanisms that result in an apparently normal respiratory activity under normoxic conditions but a significantly altered response of the respiratory network during anoxia.
Retinol and Betacarotene Status in Mother-Infant Dyads and Associations between Them
Authors: Lira Larissa Q. , de Souza Aline F. , Amâncio Amanda de M. , Bezerra Caroline G. , Pimentel Jéssica B. , Moia Melissa N. , Dimenstein Roberto 
Published: December 2017

<b><i>Background/Aims:</i></b> Assessing the diet and biochemical indicators of vitamin A deficiency (VAD) in high-risk populations is crucial in cases where this deficiency is mainly caused by chronically inadequate intake. This study aimed to determine the retinol and betacarotene status in mother-infant dyads, and to evaluate the associations between them. <b><i>Methods:</i></b> Umbilical cord serum, maternal serum, and colostrum were collected from 134 healthy mothers living in a risk region for VAD. Vitamin A and betacarotene were quantified by liquid chromatography, and dietary information was collected using a food frequency questionnaire. <b><i>Results:</i></b> Although the overall mean intakes of vitamin A and betacarotene were considered adequate, 16% of the women had insufficient intake. Mean retinol levels were also adequate, yet low levels were diagnosed in about 8% of the mothers, based on maternal serum and colostrum, and in 16% of the cord serum samples. Retinol and betacarotene were positively associated in cord serum (<i>p</i> = 0.004), maternal serum (<i>p</i> = 0.041), and colostrum (<i>p</i> &#x3c; 0.001) but was not associated with dietary intake. <b><i>Conclusions:</i></b> A diagnosis of adequacy based on mean biochemical and dietary data of this population in fact masks the marginal vitamin A status presented by mothers and children.