bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reflux‐cough syndrome: Assessment of temporal association between reflux episodes and cough bursts
Authors: Herregods T. V. K. , Pauwels A. , Tack J. , Smout A. J. P. M. , Bredenoord A. J. 
Published: June 2017

AbstractBackgroundGastro‐esophageal reflux can be the cause of chronic cough. In the assessment of the temporal association between reflux and cough, previous studies have used a two‐minute time window, based on studies in patients with heartburn. However, it remains unclear whether the optimal time window duration for the evaluation of reflux‐induced cough is two minutes as well. Therefore, we aimed to determine whether a two‐minute time window is optimal to diagnose reflux‐induced cough.MethodsIn this multicenter study, 137 patients with chronic cough were evaluated using 24‐h pH‐impedance‐pressure monitoring. Repetitive symptom association analysis was employed using an array of time windows of various duration. For each time window, the symptom association probability (SAP) and symptom index (SI) were calculated.Key ResultsA total of 4377 cough burst episodes and 5074 reflux episodes were detected. The number of patients with a positive SAP increased with increasing window duration until a plateau was reached around a time window duration of 1.5 min. Similarly, the SI increased steeply until a window duration of about 2 min, after which a linear increase was seen.Conclusions and InferencesA two‐minute time window seems appropriate for evaluation of the relationship between reflux and chronic cough using 24‐h pH‐impedance‐pressure monitoring. A time window duration of 30 s or 1 min is too short to diagnose patients with reflux‐induced cough accurately.
Architecture of the paracellular channels formed by claudins of the blood–brain barrier tight junctions
Authors: Irudayanathan Flaviyan Jerome , Wang Nan , Wang Xiaoyi , Nangia Shikha 
Published: June 2017

AbstractTight junctions (TJs) are key players in determining tissue‐specific paracellular permeability across epithelial and endothelial membranes. Claudin proteins, the primary determinants of TJs structure and functionality, assemble in paracellular spaces to form channels and pores that are charge and size selective. Here, using molecular dynamics (MD) simulations, we elucidate the molecular assembly of claudin‐3 and claudin‐5 proteins of blood–brain barrier TJs. Despite having a high degree of sequence and structural similarity, these two claudins form different types of cis‐interactions. Molecular docking of the observed cis‐interfaces into trans‐forms revealed two putative pore models that were also observed in the self‐assembly simulations. The observed pore structures (pore I and II) have pore‐lining residues that have been previously reported in the literature. The pore I model is consistent with a previously reported claudin‐15 model. The pore II model, also consistent with biochemical results, has not been reported previously. Further analysis using in silico site‐directed mutations provide convincing support for the validity of the pore II model. Using steered MD and umbrella sampling, we computed the transport properties of water and α‐d‐glucose through pore II. The study offers new insight into the selectivity of blood–brain barrier TJs.
A case of classical maple syrup urine disease that was successfully managed by living donor liver transplantation
Authors: Takano Chika , Ishige Mika , Ogawa Erika , Usui Hiromi , Kagawa Reiko , Tajima Go , Fujiki Ryoji , Fukao Toshiyuki , Mizuta Koichi , Fuchigami Tatsuo , Takahashi Shori 
Published: June 2017

AbstractClassical MSUD is often fatal without appropriate medical interventions because of metabolic crisis. There are numerous reports suggesting the therapeutic potential of deceased donor liver transplantation for MSUD. However, the usefulness of LDLT for MSUD is unknown. We report a case of classical MSUD, which was successfully managed by LDLT from the patient's father at 1 year of age. Abnormal brain findings, which were cured with effective treatment, gradually disappeared after LDLT. The patient then developed normally. Findings from this case suggest the importance of LDLT for maintaining low leucine levels and subsequent normal neurological development. Although LDLT involves a modest surgical insult, LDLT with a related donor achieves acceptable leucine levels for life.
Development, characterization and application of genomic SSR markers for the oat stem rust pathogen Puccinia graminis f. sp. avenae
Authors: Gnocato F. S. , Dracatos P. M. , Karaoglu H. , Zhang P. , Berlin A. , Park R. F. 
Published: June 2017

Oat stem rust, caused by Puccinia graminis f. sp. avenae (Pga), is one of the most severe diseases of oats worldwide. Population studies are scarce for this pathogen, mainly due to the lack of polymorphic molecular markers suitable for genetic analysis. In this study, an Australian Pga isolate was sequenced, the abundance of simple sequence repeats (SSRs) was determined and PCR‐based polymorphic markers suitable for genetic diversity analysis were developed. The amplification of 194 primer pairs was initially assessed using a set of 12 isolates of different cereal rust species and their formae speciales. A high frequency of cross‐species amplification was observed for most markers; however, 36 SSRs were diagnostic for P. graminis only. A subset of 19 genome‐derived SSRs were deemed useful for genetic diversity analysis of Pga and were assessed on 66 Pga isolates from Australia, Brazil and Sweden. Brazilian and Australian isolates were characterized by one and two predominant clonal lineages, respectively. In contrast, the Swedish isolates, previously shown to undergo sexual recombination, were highly diverse (nine distinct genotypes out of 10 isolates) and divided into two subpopulations. The genome‐derived SSR markers developed in this study were well suited to the population studies undertaken, and have diagnostic capabilities that should aid in the identification of unknown rust pathogen species.
Continuous non‐invasive PCO2 monitoring in weaning patients: Transcutaneous is advantageous over end‐tidal PCO2
Authors: Schwarz Sarah B. , Windisch Wolfram , Magnet Friederike S. , Schmoor Claudia , Karagiannidis Christian , Callegari Jens , Huttmann Sophie E. , Storre Jan H. 
Published: June 2017

ABSTRACTBackground and objectiveContinuous partial pressure of carbon dioxide (PCO2) assessment is essential for the success of mechanical ventilation (MV). Non‐invasive end‐tidal PCO2 (PetCO2) and transcutaneous PCO2 (PtcCO2) measurements serve as alternatives to the gold standard arterial PCO2 (PaCO2) method, but their eligibility in critical care is unclear.MethodsThe present study therefore performed methodological comparisons of PaCO2 versus PetCO2 and PtcCO2, respectively, in weaning patients receiving invasive MV via tracheal cannulas. PetCO2 and PtcCO2 were recorded continuously, while PaCO2 was analysed at baseline, and after 30 and 60 min. Using the Bland–Altman analysis, a clinically acceptable range was defined as a mean difference of ±4 mm Hg between PaCO2 and non‐invasive strategies.ResultsA total of 60 patients (COPD (n = 30) and non‐COPD (n = 30)) completed the protocol. Mean PCO2 values were 42.4 ± 8.6 mm Hg (PaCO2), 36.5 ± 7.5 mm Hg (PetCO2) and 41.7 ± 8.7 mm Hg (PtcCO2). Mean differences between PtcCO2 and PaCO2 were −0.7 ± 3.6 mm Hg (95% CI: −1.6/0.3 mm Hg; 95% limits of agreement: −7.8 to 6.4 mm Hg), and between PetCO2 and PaCO2 −5.9 ± 5.3 mm Hg (95% CI: −7.2/−4.5 mm Hg; 95% limits of agreement: −16.2 to 4.5 mm Hg). Underestimation of PaCO2 by PetCO2 was most pronounced in COPD patients.ConclusionOur data therefore support PtcCO2 as a suitable means for monitoring PCO2 in patients undergoing invasive MV. This is in contrast to PetCO2, which clearly underestimated PaCO2, especially in patients with COPD.
The Malaria Parasite Cyclin H Homolog PfCyc1 Is Required for Efficient Cytokinesis in Blood-Stage
Plasmodium falciparum
Authors: Robbins Jonathan A. , Absalon Sabrina , Streva Vincent A. , Dvorin Jeffrey D. 
Published: June 2017

ABSTRACT

All well-studied eukaryotic cell cycles are driven by cyclins, which activate cyclin-dependent kinases (CDKs), and these protein kinase complexes are viable drug targets. The regulatory control of the
Plasmodium falciparum
cell division cycle remains poorly understood, and the roles of the various CDKs and cyclins remain unclear. The
P. falciparum
genome contains multiple CDKs, but surprisingly, it does not contain any sequence-identifiable G
1
-, S-, or M-phase cyclins. We demonstrate that
P. falciparum
Cyc1 (PfCyc1) complements a G
1
cyclin-depleted
Saccharomyces cerevisiae
strain and confirm that other identified malaria parasite cyclins do not complement this strain. PfCyc1, which has the highest sequence similarity to the conserved cyclin H, cannot complement a temperature-sensitive yeast cyclin H mutant. Coimmunoprecipitation of PfCyc1 from
P. falciparum
parasites identifies PfMAT1 and PfMRK as specific interaction partners and does not identify PfPK5 or other CDKs. We then generate an endogenous conditional allele of PfCyc1 in blood-stage
P. falciparum
using a destabilization domain (DD) approach and find that PfCyc1 is essential for blood-stage proliferation. PfCyc1 knockdown does not impede nuclear division, but it prevents proper cytokinesis. Thus, we demonstrate that PfCyc1 has a functional divergence from bioinformatic predictions, suggesting that the malaria parasite cell division cycle has evolved to use evolutionarily conserved proteins in functionally novel ways.

IMPORTANCE
Human infection by the eukaryotic parasite
Plasmodium falciparum
causes malaria. Most well-studied eukaryotic cell cycles are driven by cyclins, which activate cyclin-dependent kinases (CDKs) to promote essential cell division processes. Remarkably, there are no identifiable cyclins that are predicted to control the cell cycle in the malaria parasite genome. Thus, our knowledge regarding the basic mechanisms of the malaria parasite cell cycle remains unsatisfactory. We demonstrate that
P. falciparum
Cyc1 (PfCyc1), a transcriptional cyclin homolog, complements a cell cycle cyclin-deficient yeast strain but not a transcriptional cyclin-deficient strain. We show that PfCyc1 forms a complex in the parasite with PfMRK and the
P. falciparum
MAT1 homolog. PfCyc1 is essential and nonredundant in blood-stage
P. falciparum
. PfCyc1 knockdown causes a stage-specific arrest after nuclear division, demonstrating morphologically aberrant cytokinesis. This work demonstrates a conserved PfCyc1/PfMAT1/PfMRK complex in malaria and suggests that it functions as a schizont stage-specific regulator of the
P. falciparum
life cycle.
A Herpesviral Immediate Early Protein Promotes Transcription Elongation of Viral Transcripts
Authors: Fox Hannah L. , Dembowski Jill A. , DeLuca Neal A. 
Published: June 2017

ABSTRACT
Herpes simplex virus 1 (HSV-1) genes are transcribed by cellular RNA polymerase II (RNA Pol II). While four viral immediate early proteins (ICP4, ICP0, ICP27, and ICP22) function in some capacity in viral transcription, the mechanism by which ICP22 functions remains unclear. We observed that the FACT complex (comprised of SSRP1 and Spt16) was relocalized in infected cells as a function of ICP22. ICP22 was also required for the association of FACT and the transcription elongation factors SPT5 and SPT6 with viral genomes. We further demonstrated that the FACT complex interacts with ICP22 throughout infection. We therefore hypothesized that ICP22 recruits cellular transcription elongation factors to viral genomes for efficient transcription elongation of viral genes. We reevaluated the phenotype of an ICP22 mutant virus by determining the abundance of all viral mRNAs throughout infection by transcriptome sequencing (RNA-seq). The accumulation of almost all viral mRNAs late in infection was reduced compared to the wild type, regardless of kinetic class. Using chromatin immunoprecipitation sequencing (ChIP-seq), we mapped the location of RNA Pol II on viral genes and found that RNA Pol II levels on the bodies of viral genes were reduced in the ICP22 mutant compared to wild-type virus. In contrast, the association of RNA Pol II with transcription start sites in the mutant was not reduced. Taken together, our results indicate that ICP22 plays a role in recruiting elongation factors like the FACT complex to the HSV-1 genome to allow for efficient viral transcription elongation late in viral infection and ultimately infectious virion production.

IMPORTANCE
HSV-1 interacts with many cellular proteins throughout productive infection. Here, we demonstrate the interaction of a viral protein, ICP22, with a subset of cellular proteins known to be involved in transcription elongation. We determined that ICP22 is required to recruit the FACT complex and other transcription elongation factors to viral genomes and that in the absence of ICP22 viral transcription is globally reduced late in productive infection, due to an elongation defect. This insight defines a fundamental role of ICP22 in HSV-1 infection and elucidates the involvement of cellular factors in HSV-1 transcription.
The Primary Enveloped Virion of Herpes Simplex Virus 1: Its Role in Nuclear Egress
Authors: Newcomb William W. , Fontana Juan , Winkler Dennis C. , Cheng Naiqian , Heymann J. Bernard , Steven Alasdair C. 
Published: June 2017

ABSTRACT
Many viruses migrate between different cellular compartments for successive stages of assembly. The HSV-1 capsid assembles in the nucleus and then transfers into the cytoplasm. First, the capsid buds through the inner nuclear membrane, becoming coated with nuclear egress complex (NEC) protein. This yields a primary enveloped virion (PEV) whose envelope fuses with the outer nuclear membrane, releasing the capsid into the cytoplasm. We investigated the associated molecular mechanisms by isolating PEVs from US3-null-infected cells and imaging them by cryo-electron microscopy and tomography. (pUS3 is a viral protein kinase in whose absence PEVs accumulate in the perinuclear space.) Unlike mature extracellular virions, PEVs have very few glycoprotein spikes. PEVs are ~20% smaller than mature virions, and the little space available between the capsid and the NEC layer suggests that most tegument proteins are acquired later in the egress pathway. Previous studies have proposed that NEC is organized as hexamers in honeycomb arrays in PEVs, but we find arrays of heptameric rings in extracts from US3-null-infected cells. In a PEV, NEC contacts the capsid predominantly via the pUL17/pUL25 complexes which are located close to the capsid vertices. Finally, the NEC layer dissociates from the capsid as it leaves the nucleus, possibly in response to pUS3-mediated phosphorylation. Overall, nuclear egress emerges as a process driven by a program of multiple weak interactions.

IMPORTANCE
On its maturation pathway, the newly formed HSV-1 nucleocapsid must traverse the nuclear envelope, while respecting the integrity of that barrier. Nucleocapsids (125 nm in diameter) are too large to pass through the nuclear pore complexes that conduct most nucleocytoplasmic traffic. It is now widely accepted that the process involves envelopment/de-envelopment of a key intermediate—the primary enveloped virion. In wild-type infections, PEVs are short-lived, which has impeded study. Using a mutant that accumulates PEVs in the perinuclear space, we were able to isolate PEVs in sufficient quantity for structural analysis by cryo-electron microscopy and tomography. The findings not only elucidate the maturation pathway of an important human pathogen but also have implications for cellular processes that involve the trafficking of large macromolecular complexes.
The addition of a tension night splint to a structured home rehabilitation programme in patients with chronic plantar fasciitis does not lead to significant additional benefits in either pain, function or flexibility: a single-blinded randomised controlled trial
Authors: Wheeler Patrick C 
Published: June 2017

ObjectiveTo identify any improvements in pain or function in patients with chronic plantar fasciitis following the use of a tension night splint (TNS).MethodsSingle-blinded randomised controlled trial, with participants split evenly between intervention group (TNS + home exercise programme/HEP) and control group (HEP only). Follow-up at 3 months, with interim data at 6 weeks.Results40 patients recruited. Mean age 52.1 years, 33% male, mean body mass index 30.8 kg/m2, mean duration of symptoms of 25 months. Improvement in self-reported ‘average pain' in the intervention group from 6.8/10 at baseline to 5.6/10 at 6 weeks, and 5.3/10 at 3 months (both clinically and statistically significant at both time points), compared with control group of 7.1/10 at baseline to 6.2/10 at 6 weeks and 5.6/10 at 3 months (significant only at 3 months). Improvements in self-reported ‘worst pain', ‘pain walking' and ‘pain first thing in the morning' in both groups at all time periods. Improvements were seen in revised Foot Function Index at all time points in both groups, but limited changes seen in flexibility and no significant changes in anxiety or depression Hospital Anxiety and Depression Scale domains or sleep quality in either group. However, no differences were seen between the outcomes seen in the two groups for the majority of the measures studied.ConclusionsImprovements in pain and some functional measures seen in both groups, with few, if any, differences seen in outcomes between the intervention group compared with the control group. However, ongoing pain symptoms were reported in both groups, suggesting that ‘help' rather than ‘cure' was obtained for the majority. There is a possibility of earlier benefit seen in the intervention group compared with the control group, but data are unclear and further work may be needed.Trial registration numberClinicalTrials.gov:NCT02546115; results.
Phase stability, mechanical and optoelectronic properties of two novel phases of AlN
Authors: Yang Ruike , Zhu Chuanshuai , Wei Qun , Du Zheng 
Published: June 2017

Two novel aluminum nitride (which is bct-AlN at ambient pressure, and h-AlN at higher pressure) were predicted using first-principles calculations. The mechanical and phonon dispersion results indicate that bct-AlN is mechanically and dynamically stable at zero pressure, h-AlN phase can be stabilized by increasing pressure and it is mechanically and dynamically stable at 10 GPa. bct-AlN is more favorable than rs-AlN in thermodynamics at ambient pressure. Our calculated band gap of bct-AlN is 5.85 eV. It can be used as semiconductor device and optoelectronic device due to its inherent wide direct band gap. For bct-AlN, the shortest Al–N bond length is 1.8476 Å and its bond order index is 1.28, which shows that strong covalent bonds are formed between Al atoms and N atoms. Moreover, the anisotropy of Young’s modulus and optical properties can be noticed obviously for bct-AlN.
New insights into the unexploited reservoir potential of the Mid North Sea High (UKCS quadrants 35–38 and 41–43): a newly described intra-Zechstein sulphate–carbonate platform complex
Authors: Patruno Stefano , Reid William , Jackson Christopher A-L. , Davies Chris 
Published: June 2017

Abstract

The Mid North Sea High (MNSH) is located on the UKCS in quadrants 35–38 and 41–43. It is a large structural high that is flanked by the mature hydrocarbon provinces of the Central North Sea (CNS) to the NE and the Southern North Sea (SNS) to the SE. In the MNSH region, the source and reservoir intervals that characterize the SNS (Westphalian, Lower Permian) are absent and therefore the area is relatively underexplored compared to the SNS Basin (
c
. one well per 1000 km
2
). Nevertheless, two discoveries in Dinantian reservoirs (Breagh and Crosgan) prove that a working petroleum system is present, potentially charged either via lateral migration from the SNS or from within the lower Carboniferous itself. Additionally, gas was found in the Z2 carbonate (lower Zechstein Group) in Crosgan, with numerous other wells in the area reporting hydrocarbon shows in this unit. The results of the interpretation of recently acquired 2D and 3D seismic reflection datasets over parts of UKCS quadrants 36, 37 and 42 are presented and provide insight into both the geology and prospectivity of this frontier area.

This study suggests that intra-Zechstein clinoform foresets represent an attractive, hitherto overlooked, exploration target. The Zechstein Group sits on a major unconformity, probably reflecting Variscan-related inversion and structural uplift. Below it, fault blocks and faulted folds occur, containing pre-Westphalian Carboniferous and Devonian sediments, both of which contain potential reservoirs. In the lower Zechstein, a large build-up is observed, covering a total area of 2284 km
2
. This is bounded on its margins by seismically defined clinoforms, with maximum thicknesses of 0.12 s two-way time (
c.
240–330 m). This rigid, near-tabular unit is clearly distinguished from the overlying deformed upper Zechstein evaporites. In map-view, a series of embayments and promontories are observed at the build-up margins. Borehole data and comparisons with nearby discoveries (e.g. Crosgan) suggest this build-up to represent a Z1–Z2 sulphate–carbonate platform, capped by a minor Z3 carbonate platform. Interpreted smaller pinnacle build-ups are observed away from the main bank. The seismic character, geometry, size and inferred composition of this newly described Zechstein platform are similar to those of platforms hosting notable hydrocarbon discoveries in other parts of the Southern Permian Basin. The closest of these discoveries to the study area is Crosgan, which is characterized by the Z2 carbonate clinothem (Hauptdolomit Formation) as a proven reservoir.
Comparative numerical modelling of a debris-flow fan in the Eastern Italian Alps
Authors: Deganutti Andrea M. , Tecca Pia R. , Nigro Giuseppe 
Published: June 2017

Abstract
Knowledge of rheology can reduce damage caused by debris flows, providing a means to delineate hazard-prone areas and to estimate the dangerous effects of these phenomena. The application of numerical models of debris-flow propagation and deposition for hazard prediction requires detailed topographical, hydrological and rheological data, which are not always available. The large Rivoli Bianchi Fan on the Eastern Italian Alps is mainly built from sediment transported by debris flows along the Citate Torrent and its tributaries. We compared the results of numerical simulations performed with two different single-phase, non-Newtonian, two-dimensional models, FLO-2D and IDRA2D-DF, to test their reliability in simulating the behaviour of debris flows on alluvial fans. Data from field topographic surveys and from rain gauges were used as input for the boundary conditions, referring to the Rivoli Bianchi Fan as an example location. The commercial FLO-2D model creates a more accurate representation of the hazard-prone zone in terms of flooded area, but the results in terms of runout distances and deposit thickness are similar to those obtained through the open-source IDRA2D-DF. Parameters obtained through back analysis with both models can be cautiously applied to predict hazard in areas of similar geology, morphology and climate.