bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Player at the Flagellar Motor: FliL Controls both Motor Output and Bias
Authors: Partridge Jonathan D. , Nieto Vincent , Harshey Rasika M. 
Published: February 2015

ABSTRACT
The bacterial flagellum is driven by a bidirectional rotary motor, which propels bacteria to swim through liquids or swarm over surfaces. While the functions of the major structural and regulatory components of the flagellum are known, the function of the well-conserved FliL protein is not. In Salmonella and Escherichia coli, the absence of FliL leads to a small defect in swimming but complete elimination of swarming. Here, we tracked single motors of these bacteria and found that absence of FliL decreases their speed as well as switching frequency. We demonstrate that FliL interacts strongly with itself, with the MS ring protein FliF, and with the stator proteins MotA and MotB and weakly with the rotor switch protein FliG. These and other experiments show that FliL increases motor output either by recruiting or stabilizing the stators or by increasing their efficiency and contributes additionally to torque generation at higher motor loads. The increased torque enabled by FliL explains why this protein is essential for swarming on an agar surface expected to offer increased resistance to bacterial movement.

IMPORTANCE
FliL is a well-conserved bacterial flagellar protein whose absence leads to a variety of motility defects, ranging from moderate to complete inhibition of swimming in some bacterial species, inhibition of swarming in others, structural defects that break the flagellar rod during swarming in E. coli and Salmonella, and failure to eject the flagellar filament during the developmental transition of a swimmer to a stalk cell in
Caulobacter crescentus
. Despite these many phenotypes, a specific function for FliL has remained elusive. Here, we established a central role for FliL at the Salmonella and E. coli motors, where it interacts with both rotor and stator proteins, increases motor output, and contributes to the normal rotational bias of the motor.
Transmitted/Founder Hepatitis C Viruses Induce Cell-Type- and Genotype-Specific Differences in Innate Signaling within the Liver
Authors: Mitchell Angela M. , Stone Amy E. L. , Cheng Linling , Ballinger Kimberly , Edwards Michael G. , Stoddard Mark , Li Hui , Golden-Mason Lucy , Shaw George M. , Khetani Salman , Rosen Hugo R. 
Published: February 2015

ABSTRACT
Hepatitis C virus (HCV) infection leads to persistence in the majority of cases despite triggering complex innate immune responses within the liver. Although hepatocytes are the preferred site for HCV replication, nonparenchymal cells (NPCs) can also contribute to antiviral immunity. Recent innovations involving single-genome amplification (SGA), direct amplicon sequencing, and phylogenetic inference have identified full-length transmitted/founder (T/F) viruses. Here, we tested the effect of HCV T/F viral RNA (vRNA) on innate immune signaling within hepatocytes and NPCs, including the HepG2 and Huh 7.5.1 cell lines, a human liver endothelial cell line (TMNK-1), a plasmacytoid dendritic cell line (GEN2.2), and a monocytic cell line (THP-1). Transfection with hepatitis C T/F vRNA induced robust transcriptional upregulation of type I and III interferons (IFNs) within HepG2 and TMNK-1 cells. Both the THP-1 and GEN2.2 lines demonstrated higher type I and III IFN transcription with genotype 3a compared to genotype 1a or 1b. Supernatants from HCV T/F vRNA-transfected TMNK-1 cells demonstrated superior viral control. Primary human hepatocytes (PHH) transfected with genotype 3a induced canonical pathways that included chemokine and IFN genes, as well as overrepresentation of RIG-I (DDX58), STAT1, and a Toll-like receptor 3 (TLR3) network. Full-length molecular clones of HCV induce broad IFN responses within hepatocytes and NPCs, highlighting that signals imparted by the various cell types within the liver may lead to divergent outcomes of infection. In particular, the finding that HCV genotypes differentially induce antiviral responses in NPCs and PHH might account for relevant clinical-epidemiological observations (higher clearance but greater necroinflammation in persistence with genotype 3).

IMPORTANCE
Hepatitis C virus (HCV) has become a major worldwide problem, and it is now the most common viral infection for which there is no vaccine. HCV infection often leads to persistence of the virus and is a leading cause of chronic hepatitis, liver cancer, and cirrhosis. There are multiple genotypes of the virus, and patients infected with different viral genotypes respond to traditional therapy differently. However, the immune response to the virus within the liver has not been fully elucidated. Here, we determined the responses to different genotypes of HCV in cell types of the liver. We found that the immune response varied according to both cell type and HCV genotype, leading to a more pronounced induction of inflammatory pathways after exposure to certain genotypes. Therefore, inflammatory pathways that are being robustly activated by certain HCV genotypes could lead to more severe damage to the liver, inducing diverse outcomes and responses to therapy.
Effects of Acupuncture at St36 on Pharmacokinetics of Schisandra lignans in rats
Authors: Ji De , Ning Ziwan , Mao Chunqin , Sun Yong , Liu Jing , Ji Lin , Yang Huan , Huang Zhi-Jun , Lu Tulin 
Published: February 2015

Objective To investigate the influence of acupuncture at ST36 on the pharmacokinetics of Schisandra lignans including schisandrin, deoxyschisandrin and schisandrin B after intragastric administration of Schisandra chinensis (SC) in rats. Methods Twelve male Sprague-Dawley rats were randomly divided into two study groups: SC and SC+acupuncture. Rats in both groups received intragastric SC extract at 5.0 g/kg. Rats in the SC+acupuncture group additionally received acupuncture stimulation at ST36 for 30 min after SC administration. Acupuncture needles were rotated bilaterally for 1 min, left in situ for 20 min, then electrically stimulated for 10 min at 50 Hz frequency and 1–3 mA intensity. A sensitive and specific high performance liquid chromatography electrospray tandem mass spectrometry procedure was developed and validated for simultaneous analysis of three bioactive lignans (schisandrin, deoxyschisandrin and schisandrin B) in rat plasma. Results There were significant differences (p<0.05) between the two study groups in various pharmacokinetic parameters. Area under the plasma concentration–time curve (AUC0–t), area under the plasma concentration–time curve to time infinity (AUC0–∞) and peak plasma concentration (Cmax) for schisandrin, absorption half-life (T1/2α) and AUC0–t for deoxyschisandrin, and Cmax for schisandrin B were increased in the SC+acupuncture group compared with the SC group. T1/2α for schisandrin B only and time to peak concentration (Tmax) for all three lignans were reduced following acupuncture. Conclusions Acupuncture stimulation at ST36 affects the pharmacokinetics of SC in rats. Acupuncture may have a beneficial role in promoting the absorption of lignans from extracts of SC.
Preparticipation injury complaint is a risk factor for injury: a prospective study of the Moscow 2013 IAAF Championships
Authors: Alonso Juan-Manuel , Jacobsson Jenny , Timpka Toomas , Ronsen Ola , Kajenienne Alma , Dahlström Örjan , Spreco Armin , Edouard Pascal 
Published: February 2015

ObjectivesTo determine the health status of athletes before the start of an international athletics championship and to determine whether preparticipation risk factors predicted in-championship injuries.MethodsAt the beginning of the 2013 International Association of Athletics Federations (IAAF) World Championships, all registered athletes (n=1784) were invited to complete a preparticipation health questionnaire (PHQ) on health status during the month preceding the championships. New injuries that occurred at the championships were prospectively recorded.ResultsThe PHQ was completed by 698 (39%) athletes; 204 (29.2%) reported an injury complaint during the month before the championships. The most common mode of onset of preparticipation injury complaints was gradual (43.6%). Forty-nine athletes in the study reported at least one injury during the championships. Athletes who reported a preparticipation injury complaint were at twofold increased risk for an in-championship injury (OR=2.09; 95% CI 1.16 to 3.77); p=0.014). Those who reported a preparticipation gradual-onset injury complaint were at an almost fourfold increased risk for an in-championship time-loss injury (OR=3.92; 95% CI 1.69 to 9.08); p=0.001). Importantly, the preparticipation injury complaint severity score was associated with the risk of sustaining an in-championship injury (OR=1.14; 95% CI 1.06 to 1.22); p=0.001).Summary and conclusionsAbout one-third of the athletes participating in the study reported an injury complaint during the month before the championships, which represented a risk factor for sustaining an injury during the championship. This study emphasises the importance of the PHQ as a screening tool to identify athletes at risk of injuries before international championships.
Comparison of the China growth charts with the WHO growth standards in assessing malnutrition of children
Authors: Yang Zhenyu , Duan Yifan , Ma Guansheng , Yang Xiaoguang , Yin Shian 
Published: February 2015

ObjectivesTo compare the difference between the China growth reference and the WHO growth standards in assessing malnutrition of children under 5 years.SettingsThe households selected from 31 provinces, autonomous regions and municipalities in mainland China (except Taiwan, Hong Kong and Macao).ParticipantsHouseholds were selected by using a stratified, multistage probability cluster sampling. Children under 5 years of age in the selected households were recruited (n=15 886).Primary and secondary outcome measuresUnderweight, stunting, wasting, overweight and obesity.ResultsAccording to the China growth reference, the prevalence of underweight (8.7% vs 4.8%), stunting (17.2% vs 16.1%) and wasting (4.4% vs 3%) was significantly higher than that based on the WHO growth standards, respectively (p<0.001); the prevalence of overweight was lower than that based on the WHO growth standards (9.4% vs 10.2%, p<0.001). In most cases, the prevalence of undernutrition assessed by using the China growth reference was significantly higher. However, the prevalence of overweight was significantly lower by using China charts for boys aged 3–4, 6, 8, 10, 12–18 and 24 months.ConclusionsThe WHO growth standards could be more conservative in undernutrition estimation and more applicable for international comparison for Chinese children. Future researches are warranted for using the WHO growth standards within those countries with local growth charts when there are distinct differences between the two.
Electrophysiological and spinal imaging evidences for sensory dysfunction in amyotrophic lateral sclerosis
Authors: Iglesias Caroline , Sangari Sina , El Mendili Mohamed-Mounir , Benali Habib , Marchand-Pauvert Véronique , Pradat Pierre-François 
Published: February 2015

ObjectivesThe prevalence of sensory impairment at an early stage of amyotrophic lateral sclerosis (ALS) is still debated. The study aim was to investigate the anatomofunctional properties of sensory pathways in patients with ALS, combining spinal diffusion tensor imaging (DTI) and somatosensory evoked potentials (SEPs).DesignCase–control study.SettingsALS referral centre and laboratory of biomedical imaging (Paris, France).ParticipantsWell-characterised group of 21 patients with ALS with moderate disability (mean amyotrophic lateral sclerosis Functional Rating Scale (ALSFRS) score 39.3±1.0) and no clinical sensory signs and control group of 21 gender and age-matched healthy subjects.Outcome measuresFractional anisotropy and diffusivity of the dorsal columns at C5-T1 levels (DTI metrics) and SEPs after median and ulnar nerve stimulations (latency and amplitude of N9 and N20 components).ResultsAbnormal DTI metrics indicated anatomical damages of ascending sensory fibres in ∼60% of patients (p<0.05). Raw SEPs (μV) were smaller in ∼40% of patients but the difference with healthy subjects was not significant (p>0.16). Their normalisation to prestimulus activity strengthened the difference between groups (p<0.05) and allowed identification of ∼60% of patients with abnormal values. According to N9 latency, the peripheral conduction time was normal in patients (p>0.32) but based on N20 latency, the central conduction time (between spinal cord and parietal cortex) was found to be slower (p<0.05). Significant correlation was found between DTI metrics and N9 amplitude (p<0.05). Altered SEPs were also correlated with the disease duration (p<0.05). Taken together, spinal imaging and electrophysiology helped to identify ∼85% of patients with subclinical sensory defect while separated methods revealed abnormal values in ∼60%.ConclusionsSensory impairments have been underestimated at early stages of ALS. These results show for the first time the interest to combine electrophysiology and imaging to assess non-motor system involvement in ALS.Trial registration numberIDRCB2012-A00016-37.
Burden of irritable bowel syndrome in an increasingly cost-aware National Health Service
Authors: Soubieres Anet , Wilson Patrick , Poullis Andrew , Wilkins Julia , Rance Mark 
Published: February 2015

BackgroundThe National Health Service (NHS) is faced with increasing cost pressures that make the efficient use of resources paramount. Irritable bowel syndrome (IBS) places a large burden on the NHS as it has been estimated that at least 12% of the UK population is affected. However, poor clinical coding makes accurate assessment of this burden challenging.ObjectiveTo calculate primary-care prescribing and both hospital outpatient and admission costs associated with the management of IBS in England.Design and main outcome measuresHospital Episode Statistics data for 2012–2013 for all clinical commissioning groups in England were analysed to calculate the tariff cost of IBS. Prescribing analysis and cost tabulation (PACT) data for this period were also analysed.ResultsIn 2012–2013, there were 1 219 961 outpatient attendances in gastroenterology and colorectal surgery specialties. Despite this, only 1982 patients were recorded with IBS-specific codes, with a total estimated tariff cost of £812 336. In addition, 28 849 patients were recorded with IBS-related symptom codes at a cost of £11 002 874. In 2011–2012, there were 658 698 diagnostic lower gastrointestinal endoscopies at a tariff cost of £16 967 670 4. Of these, 323 752 (49%) had no further follow-up in secondary care over the subsequent 12 months. PACT data indicated that £44 977 959 and £25 582 752, respectively, were spent on selected laxatives and antispasmodics commonly used to treat IBS in primary care.ConclusionsBetter diagnosing, through improved clinical coding and standardisation of diagnostic criteria, is required to more accurately assess the true burden and allow optimal management of IBS.
LEF1: a highly specific marker for the diagnosis of chronic lymphocytic B cell leukaemia/small lymphocytic B cell lymphoma
Authors: Menter Thomas , Dirnhofer Stephan , Tzankov Alexandar 
Published: February 2015

AimsChronic lymphocytic B cell leukaemia (CLL)/small lymphocytic B cell lymphoma (SLL) has proven to be not a uniform entity but to consist of various disease subtypes. CLL might also pose diagnostic challenges by demonstrating an uncommon immunohistochemical profile. Recently, the role of lymphocyte enhancer-binding factor 1 (LEF1) in CLL was elucidated being highly expressed and seeming to have a prognostic value. Our aim was to test the applicability of LEF1 as marker for CLL in a diagnostic setting.MethodsWe investigated LEF1 expression in lymphomas by immunohistochemistry on tissue microarrays containing several lymphoma entities (altogether 720 cases, including 61 CLL cases). We also separated CLL cases by zeta-chain-associated protein kinase 70 (ZAP70) and CD38 stainings and fluorescence in situ hybridisation analyses forTP53deletions and trisomy 12 into respective groups and correlated data with LEF1 expression.ResultsThe area under the receiver operating characteristic curve for LEF1 as a diagnostic marker for CLL was 0.815 (95% CI 0.742 to 0.888). The relevant diagnostic cut-off value for LEF1 positivity determined by the Youden's index was 10% (specificity 92%, sensitivity 70%). The majority of CLL cases (70%) expressed LEF1. Eighteen per cent of (transformed) diffuse large B cell lymphoma cases also expressed LEF1. In most other lymphoma entities, LEF1 was negative. There was a positive correlation of LEF1 staining with ZAP70 expression (Spearman's rho: 0.438, p<0.001), but not with CD38 expression,TP53deletions or trisomy 12.ConclusionsLEF1 is a useful marker in the differential diagnosis of CLL in difficult cases. It shows a high specificity (92%) and a reasonable sensitivity (70%) for this entity.
Antiepileptic prophylaxis following severe traumatic brain injury within a military cohort
Authors: Cranley Mark R , Craner M , McGilloway E 
Published: February 2015

IntroductionTraumatic brain injury increases the risk of both early and late seizures. Antiepileptic prophylaxis reduces early seizures, but their use beyond 1 week does not prevent the development of post-traumatic epilepsy. Furthermore, prolonged prophylaxis exposes patients to side effects of the drugs and has occupational implications. The American Academy of Neurology recommends that antiepileptic prophylaxis should be started for patients with severe traumatic brain injury and discontinued after 1 week. An audit is presented here that investigates the use of prophylaxis in a cohort of military patients admitted to the UK Defence Medical Rehabilitation Centre (DMRC).MethodsData were collected and analysed retrospectively from electronic and paper records between February 2009 and August 2012. The timing and duration of antiepileptic drug use and the incidence of seizures were recorded.ResultsDuring the study period, 52 patients with severe traumatic brain injury were admitted to the rehabilitation centre: 25 patients (48%) were commenced on prophylaxis during the first week following injury while 27 (52%) did not receive prophylaxis. Only one patient (2%) received prophylaxis for the recommended period of 1 week, 22 patients (42%) received prophylaxis for longer than 1 week with a mean duration of 6.2 months. Two patients (4%) had post-traumatic epilepsy and started on treatment at DMRC.ConclusionsThe use of antiepileptic prophylaxis varies widely and is generally inconsistent with evidence-based guidance. This exposes some patients to a higher risk of early seizures and others to unnecessary use of antiepileptics. Better implementation of prophylaxis is required.
Depression is a stronger predictor of the risk to consider work disability in early arthritis than disease activity or response to therapy
Authors: Callhoff Johanna , Albrecht Katinka , Schett Georg , Zink Angela , Westhoff Gisela 
Published: February 2015

ObjectivesTo evaluate the factors that influence patients with early inflammatory arthritis to consider a disability pension.MethodsA total of 528 patients aged 63 or younger from an early arthritis cohort with a mean symptom duration of 3 months at inclusion were asked at 12 and 24 months whether they were considering applying for, had applied for or were receiving a disability pension because of arthritis. Possible predictors were analysed with univariate and multivariate logistic regression.Results69 patients (13%) were considering, had applied for or were receiving a disability pension. Univariate predictors were older age, disease activity, several patient-reported outcomes and depression. In a multivariate analysis, age, days on sick leave, impairment of physical function and depression were predictive for considering a disability pension (OR for severe vs no depression: 3.85, 95% CI 1.43 to 10.4).ConclusionsIn patients with early arthritis, depression appears to be a stronger predictor of the risk to consider applying for work disability pension than the features of disease activity. Patients at risk could be identified with one single depression statement. This finding should prompt physicians to react early to signs and symptoms of depression to help patients to maintain their ability to work.
When can an "Expanding Universe" look "Static" and vice versa: A comprehensive study
Authors: Mitra Abhas 
Published: February 2015

The Friedmann–Robertson–Walker (FRW) metric expressed, in terms of comoving coordinates (r, t), always looks nonstatic. But by employing the recently derived curvature/Schwarzschild form, (R, T), of FRW metric (A. Mitra, Gravit. Cosmol. 19 (2013) 134), we show here that FRW metric can assume static forms when the net energy density (ρe) is solely due to the vacuum contribution. Earlier this question was explored by Florides (Gen. Relativ. Gravit. 12 (1980) 563) whose approach was complex and of purely mathematical nature. Also, unlike Florides, we do not assume any a priori separability of T(r, t) = F(r)G(t) and thus our treatment is truly general and yet simpler. More interestingly, even if the net energy density involved in a certain FRW model may appear to be nonzero from its algebric appearance, it may still be possible that tacitly ρe = 0 and the model actually corresponds to a vacuum Minkowski metric. For instance, it has been found that FRW universes which appear to be expanding with a fixed speed in comoving coordinates are intrinsically static universes. While such a linearly expanding universe having k = -1 is well-known as the Milne universe, the corresponding k = 0 case has recently been shown to be vacuum in disguise (A. Mitra, Mon. Not. Roy. Astron. Soc. 442 (2014) 382). In addition, here we show that even the k = +1 linearly "expanding" universe (in comoving coordinates) tacitly corresponds to Einstein's static universe.
Structural geology and well planning in the Clair Field
Authors: Ogilvie Steven , Barr David , Roylance Paul , Dorling Matthew 
Published: February 2015

Abstract
The Clair Field is a giant oilfield located approximately 70 km west of the Shetland Isles, UK. It was discovered in 1977 and brought on stream some 28 years later. Key to unlocking its economic potential was a series of appraisal wells drilled in the early 1990s that identified fractures as the primary production mechanism. Structural geology contributed in several ways to the detailed planning of the development and appraisal wells. In the sandy (Tertiary) tophole section, outcrop analogues and offset wells were used to establish an appropriate standoff from major faults. This was to mitigate the risk of wellbore instability in what is otherwise a relatively benign sequence to drill. The mid-section, Upper Cretaceous mudstone is prone to wellbore instability, believed to be caused by strength anisotropy with respect to bedding. Here, polygonal faulting may contribute directly to wellbore instability. The associated bed rotation also influences anisotropic failure, which depends in part on the wellbore-to-bedding intersection angle. An example is given of how an understanding of the structural evolution of the overburden section impacts well casing placement. Finally, judgement on the nature of the faulted contact between two fault blocks was required for the pressure prognosis of a planned well.