bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Tools for the Detection and Deduction of Azole Antifungal Drug Resistance Phenotypes in Aspergillus Species
Authors: Dudakova Anna , Spiess Birgit , Tangwattanachuleeporn Marut , Sasse Christoph , Buchheidt Dieter , Weig Michael , Groß Uwe , Bader Oliver 
Published: September 2017

SUMMARY

The incidence of azole resistance in
Aspergillus
species has increased over the past years, most importantly for
Aspergillus fumigatus
. This is partially attributable to the global spread of only a few resistance alleles through the environment. Secondary resistance is a significant clinical concern, as invasive aspergillosis with drug-susceptible strains is already difficult to treat, and exclusion of azole-based antifungals from prophylaxis or first-line treatment of invasive aspergillosis in high-risk patients would dramatically limit drug choices, thus increasing mortality rates for immunocompromised patients. Management options for invasive aspergillosis caused by azole-resistant
A. fumigatus
strains were recently reevaluated by an international expert panel, which concluded that drug resistance testing of cultured isolates is highly indicated when antifungal therapy is intended. In geographical regions with a high environmental prevalence of azole-resistant strains, initial therapy should be guided by such analyses. More environmental and clinical screening studies are therefore needed to generate the local epidemiologic data if such measures are to be implemented on a sound basis. Here we propose a first workflow for evaluating isolates from screening studies, and we compile the MIC values correlating with individual amino acid substitutions in the products of
cyp51
genes for interpretation of DNA sequencing data, especially in the absence of cultured isolates.
Discrete Dynamical Modeling of Influenza Virus Infection Suggests Age-Dependent Differences in Immunity
Authors: Keef Ericka , Zhang Li Ang , Swigon David , Urbano Alisa , Ermentrout G. Bard , Matuszewski Michael , Toapanta Franklin R. , Ross Ted M. , Parker Robert S. , Clermont Gilles 
Published: September 2017

ABSTRACTImmunosenescence, an age-related decline in immune function, is a major contributor to morbidity and mortality in the elderly. Older hosts exhibit a delayed onset of immunity and prolonged inflammation after an infection, leading to excess damage and a greater likelihood of death. Our study applies a rule-based model to infer which components of the immune response are most changed in an aged host. Two groups of BALB/c mice (aged 12 to 16 weeks and 72 to 76 weeks) were infected with 2 inocula: a survivable dose of 50 PFU and a lethal dose of 500 PFU. Data were measured at 10 points over 19 days in the sublethal case and at 6 points over 7 days in the lethal case, after which all mice had died. Data varied primarily in the onset of immunity, particularly the inflammatory response, which led to a 2-day delay in the clearance of the virus from older hosts in the sublethal cohort. We developed a Boolean model to describe the interactions between the virus and 21 immune components, including cells, chemokines, and cytokines, of innate and adaptive immunity. The model identifies distinct sets of rules for each age group by using Boolean operators to describe the complex series of interactions that activate and deactivate immune components. Our model accurately simulates the immune responses of mice of both ages and with both inocula included in the data (95% accurate for younger mice and 94% accurate for older mice) and shows distinct rule choices for the innate immunity arm of the model between younger and aging mice in response to influenza A virus infection.IMPORTANCEInfluenza virus infection causes high morbidity and mortality rates every year, especially in the elderly. The elderly tend to have a delayed onset of many immune responses as well as prolonged inflammatory responses, leading to an overall weakened response to infection. Many of the details of immune mechanisms that change with age are currently not well understood. We present a rule-based model of the intrahost immune response to influenza virus infection. The model is fit to experimental data for young and old mice infected with influenza virus. We generated distinct sets of rules for each age group to capture the temporal differences seen in the immune responses of these mice. These rules describe a network of interactions leading to either clearance of the virus or death of the host, depending on the initial dosage of the virus. Our models clearly demonstrate differences in these two age groups, particularly in the innate immune responses.
Distinct Mechanism for the Formation of the Ribonucleoprotein Complex of Tomato Spotted Wilt Virus
Authors: Guo Yu , Liu Baocheng , Ding Zhenzhen , Li Guobang , Liu Meizi , Zhu Dantong , Sun Yuna , Dong Shishang , Lou Zhiyong 
Published: September 2017

ABSTRACT

The
Tomato spotted wilt virus
(TSWV) belongs to the
Tospovirus
genus of the
Bunyaviridae
family and represents the sole plant-infecting group within bunyavirus. TSWV encodes a nucleocapsid protein (N) which encapsidates the RNA genome to form a ribonucleoprotein complex (RNP). In addition, the N has multiple roles during the infection of plant cells. Here, we report the crystal structure of the full-length TSWV N. The N features a body domain consisting of an N-lobe and a C-lobe. These lobes clamp a positively charged groove which may constitute the RNA binding site. Furthermore, the body domains are flanked by N- and C-terminal arms which mediate homotypic interactions to the neighboring subunits, resulting in a ring-shaped N trimer. Interestingly, the C terminus of one protomer forms an additional interaction with the protomer of an adjacent trimer in the crystal, which may constitute a higher-order oligomerization contact. In this way, this study provides insights into the structure and trimeric assembly of TSWV N, which help to explain previous functional findings, but also suggests distinct N interactions within a higher-order RNP.

IMPORTANCE
TSWV is one of the most devastating plant pathogens that cause severe diseases in numerous agronomic and ornamental crops worldwide. TSWV is also the prototypic member of the
Tospovirus
genus, which is the sole group of plant-infecting viruses in the bunyavirus family. This study determined the structure of full-length TSWV N in an oligomeric state. The structural observations explain previously identified biological properties of TSWV N. Most importantly, the additional homotypic interaction between the C terminus of one protomer with another protomer indicates that there is a distinct mechanism of RNP formation in the bunyavirus family, thereby enhancing the current knowledge of negative-sense single-stranded RNA virus-encoded N. TSWV N is the last remaining representative N with an unknown structure in the bunyavirus family. Combined with previous studies, the structure of TSWV N helps to build a complete picture of the bunyavirus-encoded N family and reveals a close evolutionary relationship between orthobunyavirus, phlebovirus, hantavirus, and tospovirus.
Polyamines and Their Role in Virus Infection
Authors: Mounce Bryan C. , Olsen Michelle E. , Vignuzzi Marco , Connor John H. 
Published: September 2017

SUMMARY
Polyamines are small, abundant, aliphatic molecules present in all mammalian cells. Within the context of the cell, they play a myriad of roles, from modulating nucleic acid conformation to promoting cellular proliferation and signaling. In addition, polyamines have emerged as important molecules in virus-host interactions. Many viruses have been shown to require polyamines for one or more aspects of their replication cycle, including DNA and RNA polymerization, nucleic acid packaging, and protein synthesis. Understanding the role of polyamines has become easier with the application of small-molecule inhibitors of polyamine synthesis and the use of interferon-induced regulators of polyamines. Here we review the diverse mechanisms in which viruses require polyamines and investigate blocking polyamine synthesis as a potential broad-spectrum antiviral approach.
An evaluation of intracameral mydriasis for routine cataract surgery
Authors: Schulz Christopher B , Goverdhan Srini V , Humphry Roger C 
Published: September 2017

BackgroundIntracameral Mydrane might facilitate a more streamlined cataract service and improve the patient experience. There is limited ‘real-world’ evidence of its use in a UK setting.MethodsAs part of a local evaluation of cataract surgery using intracameral Mydrane (group 2; n=60), data were collected on intraoperative pupil size and postoperative visual acuity (VA), as well as the rate of mechanical pupil dilation, intraoperative floppy iris syndrome (IFIS) and complications. Preoperative and theatre turnaround time was recorded and patients completed a validated measure of satisfaction postoperatively. Data were compared with a previous cohort subjected to the existing standard regime of preoperative topical mydriatics (group 1; n=60).ResultsPostoperative VA was comparable between groups (0.09±0.16 vs 0.08±0.15; p=0.59). Pupil size in group 2 was 7.0±1.0 mm prior to capsulorhexis and 6.5±0.29 mm after cortical aspiration, with a smaller pupil in patients on alpha-antagonists (4.7±1.1 mm; p=0.004) at this later time point. Comparing group 2 with group 1, preoperative waiting was less (87 vs 146 min; p<0.0001) and satisfaction was higher (76.0±11.2 vs 66.3±8.6; p<0.0001), although theatre turnaround time was longer (25 min vs 22 min).ConclusionIntracameral mydriasis was clinically effective in most patients undergoing cataract surgery and might be associated with an improved patient experience and a more streamlined preoperative flow. Mydrane represents a licensed alternative to the off-label use of other intracameral mydriatic agents, but was not judged to be a cost-effective intervention for routine use in this particular setting.
Circulating microRNAs as potential biomarkers to detect transformation of Barrett’s oesophagus to oesophageal adenocarcinoma
Authors: Matsuzaki Juntaro , Suzuki Hidekazu 
Published: September 2017

ObjectiveCirculating microRNAs (miRNAs) are promising biomarkers for the early detection of cancers. This study aimed to address potential circulating miRNAs to monitor the progression from Barrett’s oesophagus (BO) to oesophageal adenocarcinoma (OAC).DesignWe comprehensively analysed tissue and serum miRNA expression profiles of BO mice model (L2-interleukin-1β (IL-1β) mice) using microarray analysis. To validate the data from mice, a published dataset of human plasma miRNAs, consisting of eight patients with OAC, eight with BO and six healthy controls, was used (GSE51410).ResultsWe identified 20 upregulated miRNAs and 44 downregulated miRNAs both in tissues and in sera of 46-week-old mice compared with 28-week-old mice. Two of the 20 miRNAs (miR-128-3 p and miR-328-3 p) were upregulated, and five of the 44 miRNAs (miR-143-3 p, miR-144-3 p, miR-15a-5p, miR-1-3 p and miR-133b) were downregulated in plasma of patients with OAC compared with plasma of patients with BO. Receiver operating characteristic curve analysis revealed that a prediction index calculated by the above-mentioned seven miRNAs could discriminate between patients with OAC and those without OAC with the area under the curve of 0.91, sensitivity of 1 and specificity of 0.75.ConclusionsLevels of the seven circulating miRNAs may represent the tissue miRNA levels and could be promising non-invasive biomarkers to evaluate the carcinogenic process of BO.
Healing journey: a qualitative analysis of the healing experiences of Americans suffering from trauma and illness
Authors: Scott John Glenn , Warber Sara L , Dieppe Paul , Jones David , Stange Kurt C 
Published: September 2017

ObjectivesTo elucidate pathways to healing for people having suffered injury to the integrity of their function as a human being.MethodsA team of physician-analysts conducted thematic analyses of in-depth interviews of 23 patients who experienced healing, as identified by six primary care physicians purposefully selected as exemplary healers.ResultsPeople in the sample experienced healing journeys that spanned a spectrum from overcoming unspeakable trauma and then becoming healers themselves to everyday heroes functioning well despite ongoing serious health challenges.The degree and quality of suffering experienced by each individual is framed by contextual factors that include personal characteristics, timing of their initial or ongoing wounding in the developmental life cycle and prior and current relationships.In the healing journey, bridges from suffering are developed to healing resources/skills and connections to helpers outside themselves. These bridges often evolve in fits and starts and involve persistence and developing a sense of safety and trust.From the iteration between suffering and developing resources and connections, a new state emerges that involves hope, self-acceptance and helping others. Over time, this leads to healing that includes a sense of integrity and flourishing in the pursuit of meaningful goals and purpose.ConclusionMoving from being wounded, through suffering to healing, is possible. It is facilitated by developing safe, trusting relationships and by positive reframing that moves through the weight of responsibility to the ability to respond.
Concordance of opinions between patients and physicians and their relationship with symptomatic control and future risk in patients with moderate–severe asthma
Authors: Crespo-Lessmann Astrid , Plaza Vicente , González-Barcala Francisco-Javier , Fernández-Sánchez Toni , Sastre Joaquín 
Published: September 2017

IntroductionDifferences between the opinions of patients and physicians on the impact of asthma are common. We hypothesised that patient–physician discordance may negatively affect asthma outcome.MethodsA total of 2902 patients (61% women, mean age 47 years) with moderate–severe asthma and 231 physicians participated in a prospective study. At the baseline visit, data on demographics, clinical variables, degree of asthma control according to the Asthma Control Test (ACT), basic spirometry and the Hospital Anxiety and Depression Scale (HADS) were collected and an ad hoc questionnaire was completed that allowed the degree of concordance between doctors and patients to be assessed. A scheduled telephone call after 3 months was used to elicit the ACT score and the future risk of asthma. At the final visit at 6 months, the following data were recorded: ACT score, spirometry, HADS score and an ad hoc questionnaire to assess the agreement between the doctor and the patient. Changes in study variables according to patient–physician concordance or discordance were analysed.ResultsThe rate of patient–physician discordance was 27.2%, with overestimation of disease impact by the physician in 12.3% and underestimation in 14.9%. Patient–physician opinion discordance, particularly in the case of physicians underestimating the impact of asthma, showed worse results with statistically significant differences in ACT score, a higher percentage of patients with poor asthma control and lower HADS scores. The need for hospital and emergency department admissions was also higher.ConclusionPatient–physician opinion discordance may be contributing to lower symptomatic control and increased future risk, with a higher impact when physicians underestimate the impact of asthma on their patients.
Quantitative MR spectroscopic imaging in metachromatic leukodystrophy: value for prognosis and treatment
Authors: van Rappard Diane F , Klauser Antoine , Steenweg Marjan E , Boelens Jaap Jan , Bugiani Marianna , van der Knaap Marjo S , Wolf Nicole I , Pouwels Petra J W 
Published: September 2017

ObjectiveTo determine whether proton magnetic resonance spectroscopic imaging is useful in predicting clinical course of patients with metachromatic leukodystrophy (MLD), an inherited white matter disorder treatable with haematopoietic cell transplantation (HCT).Methods21 patients with juvenile or adult MLD (12 HCT-treated) were compared with 16 controls in the same age range. Clinical outcome was determined as good, moderate or poor. Metabolites were quantified in white matter, and significance of metabolite concentrations at baseline for outcome prediction was assessed using logistic regression analysis. Evolution of metabolic changes was assessed for patients with follow-up examinations.ResultsIn this retrospective study, 16 patients with baseline scans were included, 5 with good, 3 with moderate and 8 with poor outcome, and 16 controls. We observed significant group differences for all metabolite concentrations in white matter (p<0.001). Compared with controls, patients had decreased N-acetylaspartate and glutamate, and increased myo-inositol and lactate, most pronounced in patients with poor outcome (post hoc, all p<0.05). Logistic regression showed complete separation of data. Creatine could distinguish poor from moderate and good outcome, the sum of glutamate and glutamine could distinguish good from moderate and poor outcome, and N-acetylaspartate could distinguish all outcome groups. For 13 patients (8 with baseline scans), one or more follow-up examinations were evaluated, revealing stabilisation or even partial normalisation of metabolites in patients with moderate and good outcome, clearly visible in the ratio of choline/N-acetylaspartate.ConclusionIn MLD, quantitative spectroscopic imaging at baseline is predictive for outcome and aids in determining eligibility for HCT.
MRI in sarcoglycanopathies: a large international cohort study
Authors: Tasca Giorgio , Monforte Mauro , Díaz-Manera Jordi , Brisca Giacomo , Semplicini Claudio , D’Amico Adele , Fattori Fabiana , Pichiecchio Anna , Berardinelli Angela , Maggi Lorenzo , Maccagnano Elio , Løkken Nicoline , Marini-Bettolo Chiara , Munell Francina , Sanchez Angel , Alshaikh Nahla , Voermans Nicol C , Dastgir Jahannaz , Vlodavets Dmitry , Haberlová Jana , Magnano Gianmichele , Walter Maggie C , Quijano-Roy Susana , Carlier Robert-Yves , van Engelen Baziel G M , Vissing John , Straub Volker , Bönnemann Carsten G , Mercuri Eugenio , Muntoni Francesco , Pegoraro Elena , Bertini Enrico , Udd Bjarne , Ricci Enzo , Bruno Claudio 
Published: September 2017

ObjectivesTo characterise the pattern and spectrum of involvement on muscle MRI in a large cohort of patients with sarcoglycanopathies, which are limb-girdle muscular dystrophies (LGMD2C–2F) caused by mutations in one of the four genes coding for muscle sarcoglycans.MethodsLower limb MRI scans of patients with LGMD2C–2F, ranging from severe childhood variants to milder adult-onset forms, were collected in 17 neuromuscular referral centres in Europe and USA. Muscle involvement was evaluated semiquantitatively on T1-weighted images according to a visual score, and the global pattern was assessed as well.ResultsScans from 69 patients were examined (38 LGMD2D, 18 LGMD2C, 12 LGMD2E and 1 LGMD2F). A common pattern of involvement was found in all the analysed scans irrespective of the mutated gene. The most and earliest affected muscles were the thigh adductors, glutei and posterior thigh groups, while lower leg muscles were relatively spared even in advanced disease. A proximodistal gradient of involvement of vasti muscles was a consistent finding in these patients, including the most severe ones.ConclusionsMuscle involvement on MRI is consistent in patients with LGMD2C–F and can be helpful in distinguishing sarcoglycanopathies from other LGMDs or dystrophinopathies, which represent the most common differential diagnoses. Our data provide evidence about selective susceptibility or resistance to degeneration of specific muscles when one of the sarcoglycans is deficient, as well as preliminary information about progressive involvement of the different muscles over time.
Improved Approximation for Fréchet Distance on c-Packed Curves Matching Conditional Lower Bounds
Authors: Bringmann Karl , Künnemann Marvin 
Published: September 2017

The Fréchet distance is a well studied and very popular measure of similarity of two curves. The best known algorithms have quadratic time complexity, which has recently been shown to be optimal assuming the Strong Exponential Time Hypothesis (SETH) [Bringmann, FOCS'14]. To overcome the worst-case quadratic time barrier, restricted classes of curves have been studied that attempt to capture realistic input curves. The most popular such class are [Formula: see text]-packed curves, for which the Fréchet distance has a [Formula: see text]-approximation in time [Formula: see text] [Driemel et al., DCG'12]. In dimension [Formula: see text] this cannot be improved to [Formula: see text] for any [Formula: see text] unless SETH fails [Bringmann, FOCS'14]. In this paper, exploiting properties that prevent stronger lower bounds, we present an improved algorithm with time complexity [Formula: see text]. This improves upon the algorithm by Driemel et al. for any [Formula: see text]. Moreover, our algorithm's dependence on [Formula: see text], [Formula: see text] and [Formula: see text] is optimal in high dimensions apart from lower order factors, unless SETH fails. Our main new ingredients are as follows: For filling the classical free-space diagram we project short subcurves onto a line, which yields one-dimensional separated curves with roughly the same pairwise distances between vertices. Then we tackle this special case in near-linear time by carefully extending a greedy algorithm for the Fréchet distance of one-dimensional separated curves.
Partitioning Graph Drawings and Triangulated Simple Polygons into Greedily Routable Regions
Authors: Nöllenburg Martin , Prutkin Roman , Rutter Ignaz 
Published: September 2017

A greedily routable region (GRR) is a closed subset of [Formula: see text], in which any destination point can be reached from any starting point by always moving in the direction with maximum reduction of the distance to the destination in each point of the path. Recently, Tan and Kermarrec proposed a geographic routing protocol for dense wireless sensor networks based on decomposing the network area into a small number of interior-disjoint GRRs. They showed that minimum decomposition is NP-hard for polygonal regions with holes. We consider minimum GRR decomposition for plane straight-line drawings of graphs. Here, GRRs coincide with self-approaching drawings of trees, a drawing style which has become a popular research topic in graph drawing. We show that minimum decomposition is still NP-hard for graphs with cycles and even for trees, but can be solved optimally for trees in polynomial time, if we allow only certain types of GRR contacts. Additionally, we give a 2-approximation for simple polygons, if a given triangulation has to be respected.