bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV Fusion in Dendritic Cells Occurs Mainly at the Surface and Is Limited by Low CD4 Levels
Authors: Chauveau Lise , Donahue Daniel Aaron , Monel Blandine , Porrot Francoise , Bruel Timothée , Richard Lea , Casartelli Nicoletta , Schwartz Olivier 
Published: August 2017

ABSTRACTHIV-1 poorly infects monocyte-derived dendritic cells (MDDCs). This is in large part due to SAMHD1, which restricts viral reverse transcription. Pseudotyping HIV-1 with vesicular stomatitis virus G protein (VSV-G) strongly enhances infection, suggesting that earlier steps of viral replication, including fusion, are also inefficient in MDDCs. The site of HIV-1 fusion remains controversial and may depend on the cell type, with reports indicating that it occurs at the plasma membrane or, conversely, in an endocytic compartment. Here, we examined the pathways of HIV-1 entry in MDDCs. Using a combination of temperature shift and fusion inhibitors, we show that HIV-1 fusion mainly occurs at the cell surface. We then asked whether surface levels or intracellular localization of CD4 modulates HIV-1 entry. Increasing CD4 levels strongly enhanced fusion and infection with various HIV-1 isolates, including reference and transmitted/founder strains, but not with BaL, which uses low CD4 levels for entry. Overexpressing coreceptors did not facilitate viral infection. To further study the localization of fusion events, we generated CD4 mutants carrying heterologous cytoplasmic tails (LAMP1 or Toll-like receptor 7 [TLR7]) to redirect the molecule to intracellular compartments. The intracellular CD4 mutants did not facilitate HIV-1 fusion and replication in MDDCs. Fusion of an HIV-2 isolate with MDDCs was also enhanced by increasing surface CD4 levels. Our results demonstrate that MDDCs are inefficiently infected by various HIV-1 and HIV-2 strains, in part because of low CD4 levels. In these cells, viral fusion occurs mainly at the surface, and probably not after internalization.IMPORTANCEDendritic cells (DCs) are professional antigen-presenting cells inducing innate and adaptive immune responses. DCs express the HIV receptor CD4 and are potential target cells for HIV. There is debate about the sensitivity of DCs to productive HIV-1 and HIV-2 infection. The fusion step of the viral replication cycle is inefficient in DCs, and the underlying mechanisms are poorly characterized. We show that increasing the levels of CD4 at the plasma membrane allows more HIV fusion and productive infection in DCs. We further demonstrate that HIV fusion occurs mainly at the cell surface and not in an intracellular compartment. Our results help us understand why DCs are poorly sensitive to HIV infection.
The volume of peripapillary vessels within the retinal nerve fibre layer: an optical coherence tomography angiography study of normal subjects
Authors: Allegrini Davide , Montesano Giovanni , Fogagnolo Paolo , Pece Alfredo , Riva Roberta , Romano Mario R , Rossetti Luca 
Published: August 2017

Background/aimsTo investigate the contribution of vascular volume calculated by optical coherence tomography angiography (OCTA) to the measurement of peripapillary retinal nerve fibre layer (RNFL) thickness.MethodsWe used OCTA scans to build volumetric maps of the RNFL angiograms by thresholding the decorrelation images and summing the number of white pixels along the z-axis at each location. We used these maps to calculate the contribution of the vascular tissue to the RNFL thickness.ResultsWe analysed 51 eyes from 36 subjects. The mean RNFL volume calculated on the peripapillary region was 0.607±0.045 mm3 and the mean vessel volume was 0.217±0.035 mm3, with a mean vessel/total RNFL ratio of 35.627%±3.942%. When evaluated in the peripapillary circular section, the total contribution of the vascular tissue to the global RNFL thickness was 29.071%±3.945%. The superior and inferior sectors showed the highest percentage of vascular tissue within the RNFL circular profile (31.369% and 34.788% respectively).ConclusionsWe found that the vascular contribution to the RNFL thickness is 29.07±3.945%. This is much higher than what has been reported from calculations made on the structural OCT alone (13% reported by Hood et al and 11.3%±1.6% for the Cirrus OCT and 11.8%±1.4% for the Spectralis OCT reported by Patel et al). We conclude that evaluation of the vascular tissue contribution to the RNFL thickness with OCTA might be useful when performing precise quantification of the neuronal tissue.
Intravitreal bevacizumab monotherapy in myopic choroidal neovascularisation: 5-year outcomes for the PAN-American Collaborative Retina Study Group
Authors: Chhablani Jay , Paulose Remya Mareen , Lasave Andres F , Wu Lihteh , Carpentier Cristian , Maia Mauricio , Lujan Silvio , Rojas Sergio , Serrano Martin , Berrocal Maria H , Arevalo J Fernando 
Published: August 2017

PurposeTo report the long-term anatomical and visual outcomes of intravitreal bevacizumab (IVB) monotherapy in naive choroidal neovascularisation (CNV) caused by myopia.MethodsRetrospective analysis of naive CNV secondary to myopia that underwent antivascular endothelial growth factor monotherapy was performed. Collected data included demographic details, clinical examination details including visual acuity at presentation and follow-up with imaging and treatment details. Main outcome measures were resolution of CNV activity at the last visit. Secondary outcomes included change in visual acuity, number of injections and adverse events.ResultsThirty-three eyes of 31 subjects with a mean age of 51.48±16.4 years were included. The mean follow-up was 66.47 months. 27 eyes had type 2 CNV and the rest seven eyes had type 1 CNV. The mean number of IVB injections per eye was 4.9. Mean visual acuity at baseline reduced from 0.65±0.33 logMAR units (Snellen equivalent=20/89) to 0.73±0.50 logMAR units (20/107) at final follow-up (p=0.003). The mean central macular thickness decreased from 309.31±86 µm at baseline to 267.5±70.89 µm at the last visit (p=0.03). However, visual acuity was maintained (±1 line of baseline) in 13 eyes (39.4%), ≥2 line improvement in nine (27.3%) eyes and more than two lines worsening in 11 eyes (33.3%). Foveal atrophy was observed at baseline and last visit in 6 (12.5%) and 14 (29.1%), respectively (p=0.007). No systemic adverse events were observed.ConclusionIVB monotherapy is safe and effective for long-term treatment of CNV secondary to myopia in real life.
Identification of imaging features that determine quality and repeatability of retinal capillary plexus density measurements in OCT angiography
Authors: Fenner Beau J , Tan Gavin S W , Tan Anna C S , Yeo Ian Y S , Wong Tien Yin , Cheung Gemmy C M 
Published: August 2017

PurposeOptical coherence tomography angiography (OCT-A) potentially allows for rapid and non-invasive quantification of retinal capillary plexus density in various disease states. This study aims to identify the key features that influenced the repeatability of OCT-A measurements.MethodsWe obtained OCT-A images on two separate visits in 44 healthy eyes from 44 subjects, each imaged with using the Topcon DRI OCT Triton imaging system. The parafoveal vessel density within a 1.5 mm radius centred over the fovea was obtained with the built-in tool for the superficial and deep retinal plexuses. Repeatability of vessel density was determined by intraclass correlation (ICC) and mean variation. We evaluated several image parameters to determine their influence on the repeatability of vessel density measurement in each of the two capillary plexuses.ResultsThe mean age of the subjects was 70.2±9.2 years, with 64% males. Mean parafoveal vessel density measurements for the first and second visits were 53.3±11.1 and 53.3±10.3 for the superficial plexus and 27.3±8.59 and 27.0±8.78 for the deep plexus. ICC analyses demonstrated that high fine vessel visibility, the absence of motion artefact and software-derived image quality score of 60 or above were necessary to obtain a good (ICC>0.6) or excellent (ICC>0.75) repeatability.ConclusionsOur study identified the imaging parameters that determined the repeatability of quantitative retinal vessel density measurements. These findings have implications in determining if OCT-A images can be used to accurately evaluate serial changes in retinal vessel density.
Examining self-reported and biological stress and near misses among Emergency Medicine residents: a single-centre cross-sectional assessment in the USA
Authors: Arnetz Bengt B , Lewalski Philip , Arnetz Judy , Breejen Karen , Przyklenk Karin 
Published: August 2017

ObjectivesTo examine the relationship between perceived and biological stress and near misses among Emergency Medicine residents.DesignSelf-rated stress and stress biomarkers were assessed in residents in Emergency Medicine before and after a day shift. The supervising physicians and residents reported numbers of near misses.SettingThe study took place in the Emergency Department of a large trauma 1 centre, located in Detroit, USA.ParticipantsResidents in Emergency Medicine volunteered to participate. The sample consisted of 32 residents, with complete data on 28 subjects. Residents’ supervising physicians assessed the clinical performance of each resident.Primary and secondary outcome measuresParticipants’ preshift and postshift stress, biological stress (salivary cortisol, plasma interleukin-6, tumour necrosis factor-alpha (TNF-α) and high-sensitivity C-reactive protein), residents’ and supervisors’ reports of near misses, number of critically ill and patients with trauma seen during the shift.ResultsResidents’ self-reported stress increased from an average preshift level of 2.79 of 10 (SD 1.81) to a postshift level of 5.82 (2.13) (p<0.001). Residents cared for an average of 2.32 (1.52) critically ill patients and 0.68 (1.06) patients with trauma. Residents reported a total of 7 near misses, compared with 11 reported by the supervising physicians. After controlling for baseline work-related exhaustion, residents that cared for more patients with trauma and had higher levels of TNF-α reported a higher frequency of near misses (R2=0.72; p=0.001). Residents’ preshift ratings of how stressful they expected the shift to be were related to the supervising physicians’ ratings of residents’ near misses during the shift.ConclusionResidents’ own ratings of near misses were associated with residents’ TNF-α, a biomarker of systemic inflammation and the number of patients with trauma seen during the shift. In contrast, supervisor reports on residents’ near misses were related only to the residents’ preshift expectations of how stressful the shift would be.
Effect of patient weight on first pass success and neuromuscular blocking agent dosing for rapid sequence intubation in the emergency department
Authors: Patanwala Asad E , Sakles John C 
Published: August 2017

ObjectivesThe primary objective of this study was to determine the association between patient weight and first pass success (FPS) during rapid sequence intubation (RSI) in the ED. The secondary objective was to evaluate the association between patient weight and neuromuscular blocking agent (NMBA) dosing.MethodsThis was a retrospective cohort study conducted in a tertiary care academic ED. Consecutive adult patients who underwent RSI in the ED between January 2014 and June 2016 were included. Data were collected on patient, operator and procedural characteristics. The cohort was categorised into the following weight strata: <80 kg, 80 to <100 kg, 100 to <120 kg and ≥120 kg. The primary outcome of interest was FPS. A multivariable logistic regression analysis was conducted to evaluate the relationship between patient weight category and FPS. NMBA dosing was reported descriptively.ResultsThe sample included 891 patients. FPS for each weight category was as follows: <80 kg (91%), 80 to <100 kg (90%), 100 to <120 kg (91%) and ≥120 kg (76%). After adjusting for potential confounders, the heaviest weight category was associated with decreased odds of FPS (OR 0.2, 95% CI 0.1 to 0.5, p<0.001). Median doses for succinylcholine (based on total body weight) decreased as weight increased: <80 kg (1.5 mg/kg), 80 to <100 kg (1.3 mg/kg), 100 to <120 kg (1.2 mg/kg) and ≥120 kg (1.0 mg/kg). Median doses for rocuronium (based on ideal body weight) were similar across weight categories: <80 kg (1.3 mg/kg), 80 to <100 kg (1.4 mg/kg), 100 to <120 kg (1.3 mg/kg) and ≥120 kg (1.4 mg/kg).ConclusionsVery heavy patients (>120 kg) undergoing RSI in the ED had a reduced FPS, and succinylcholine was more commonly underdosed than rocuronium in the heavier weight group.
Plausibility criteria for putative pathophysiological mechanisms in functional gastrointestinal disorders: a consensus of experts
Authors: Tack Jan , Corsetti Maura , Camilleri Michael , Quigley Eamonn MM , Simren Magnus , Suzuki Hidekazu , Talley Nicholas J , Tornblom Hans , Van Oudenhove Lukas 
Published: August 2017

Background and aimsThe functional gastrointestinal disorders (FGIDs) are extremely common conditions associated with a considerable personal, social and health economic burden. Managing FGIDs in clinical practice is challenging because of the uncertainty of symptom-based diagnosis, the high frequency of overlap between these conditions and the limited efficacy of available therapies. It has often been argued that successful drug development and management of FGIDs requires knowledge of the underlying pathophysiology. Numerous and highly variable candidate pathophysiological mechanisms have been implicated in the generation of FGID symptoms, but there is no current consensus on how to best define the relevance of these disturbances.MethodsA group of international experts on FGIDs developed plausibility criteria that should be fulfilled by relevant pathophysiological mechanisms in FGIDs.ResultsFive criteria are proposed: (1) the presence of the abnormality in a subset of patients, (2) temporal association between proposed mechanism and symptom(s), (3) correlation between the level of impairment of the mechanism and symptom(s), (4) induction of the symptom(s) by provoking the pathophysiological abnormality in healthy subjects and (5) treatment response by a therapy specifically correcting the underlying disorder or congruent natural history of symptoms and dysfunction in the absence of specific therapy. Based on strength of evidence for these five criteria according to the Grading of Recommendations Assessment, Development and Evaluation system, a plausibility score can be calculated for each mechanism.ConclusionEvaluation of the strength of evidence for candidate pathophysiological abnormalities fulfilling these five plausibility criteria will help to identify the most relevant mechanisms to target for novel diagnostic approaches and for the development of new therapies.
Efficacy of embedded nurse-led versus conventional physician-led follow-up in rheumatoid arthritis: a systematic review and meta-analysis
Authors: de Thurah Annette , Esbensen Bente Appel , Roelsgaard Ida Kristiane , Frandsen Tove Faber , Primdahl Jette 
Published: August 2017

ObjectiveTo compare the efficacy of embedded nurse-led versus conventional physician-led follow-up on disease activity in patients with rheumatoid arthritis (RA).MethodsIn a systematic literature search, we identified randomised controlled trials (RCTs) reporting on the efficacy of nurse-led follow-up on disease control in patients with RA compared with physician-led follow-up. Primary outcome was disease activity indicated by Disease Activity Score (DAS)-28. Secondary outcomes were: patient satisfaction, physical disability, fatigue, self-efficacy and quality of life. Outcomes were assessed after 1-year and 2 year follow-ups.ResultsSeven studies representing five RCTs, including a total of 723 participants, were included. All but one study included stable patients in low disease activity or remission at baseline. No difference in DAS-28 was found after 1 year (mean difference (MD) −0.07 (95% CI −0.23 to 0.09)). After 2 years, a statistically significant difference was seen in favour of nurse-led follow-up (MD −0.28 (95% CI −0.53 to −0.04)). However, the difference did not reach a clinically relevant level.No difference was found in patient satisfaction after 1 year (standard mean difference (SMD) −0.17 (95 % CI −1.0 to 0.67), whereas a statistical significant difference in favour of nurse-led follow-up was seen after 2 years (SMD: 0.6 (95% CI –0.00 to 1.20)).ConclusionAfter 1 year no difference in disease activity, indicated by DAS-28, were found between embedded nurse-led follow-up compared with conventional physician-led follow-up, in RA patients with low disease activity or remission.
Achilles enthesitis defined by ultrasound is not associated with clinical enthesitis in patients with psoriatic arthritis
Authors: Michelsen Brigitte , Diamantopoulos Andreas P , Soldal Dag Magnar , Hammer Hilde Berner , Kavanaugh Arthur , Haugeberg Glenn 
Published: August 2017

ObjectiveTo compare clinical and ultrasonographic (US) evaluation of Achilles enthesitis in patients with psoriatic arthritis (PsA).MethodsThe Achilles insertion of outpatients with PsA was examined by clinical assessment of tenderness and US evaluation of (1) inflammatory activity (defined as the presence of power Doppler signal, tendon thickening and/or hypoechogenicity) and (2) structural damage (defined as the presence of erosions, calcifications and/or enthesophytes). Univariate and multivariate logistic regression analyses were performed0.4 to explore the associations between clinical characteristics and US scores.Results282 Achilles tendons in 141 patients with PsA were assessed. Mean (SD) age was 52.4 (10.2) years, disease duration 9.5 (6.6) years and 50.4% were females. Palpatory tenderness was found in 88 (31.2%), US-verified inflammatory activity in 46 (16.3%) and structural damage in 148 (52.5%) of the Achilles. Total US scores, as well as their components, were similar for patients with and without palpatory tenderness. None of the clinical characteristics were associated with inflammatory activity. Age, body mass index (BMI), regular physical exercise and current use of biological disease-modifying antirheumatic drugs (bDMARDs) were associated with structural damage.ConclusionThere appears to be a lack of association between clinical and US signs of Achilles enthesitis in PsA. Age, BMI, regular physical exercise and current use of bDMARDs were associated with structural damage on US.
Working in cold environment and risk of developing rheumatoid arthritis: results from the Swedish EIRA case–control study
Authors: Zeng Pingling , Bengtsson Camilla , Klareskog Lars , Alfredsson Lars 
Published: August 2017

ObjectivesTo investigate (1) whether working in cold environment (WCE) is associated with an increased risk of developing rheumatoid arthritis (RA) (overall), anticitrullinated protein antibody (ACPA)-positive RA and ACPA-negative RA and (2) whether WCE interacts with occupational physical workload in conferring RA risk.MethodsData from the Swedish population-based case-control study Epidemiological Investigation of Rheumatoid Arthritis involving 3659 incident cases and 5925 controls were analysed. Study participants were asked whether they had ever worked in cold/outdoor environment along with their exposure duration and frequency. Occurrence of RA among exposed and unexposed subjects were compared by calculating ORs with 95% CI using logistic regression. Additive interactions between WCE and six types of physical workload were assessed using the principle of departure from additivity by calculating attributable proportion due to interaction (AP).ResultsThe OR associated with having ever worked in cold environment was 1.5 (95% CI 1.4 to 1.7) for RA (overall), 1.6 (95% CI 1.4 to 1.8) for ACPA-positive RA and 1.4 (95% CI 1.2 to 1.6) for ACPA-negative RA. The risk of developing RA increased with increasing cumulative dose of working in cold indoor environment (p value <0.001), but not working in cold outdoor environment. Positive additive interaction was observed between WCE and repetitive hand/finger movements (AP 0.3 (95% CI 0.1 to 0.5)).ConclusionsWCE is associated with increased risk of developing both ACPA-positive and ACPA-negative RA. A dose–response relationship was found between working in cold indoor environment and risk of developing RA. Moderate additive interaction was observed between exposure to cold environment and exposure to repetitive hand/finger movements.
Simulation study of the effect of strain rate on the mechanical properties and tensile deformation of gold nanowire
Authors: Shi Guo-Jie , Wang Jin-Guo , Hou Zhao-Yang , Wang Zhen , Liu Rang-Su 
Published: August 2017

The mechanical properties and deformation mechanisms of Au nanowire during the tensile processes at different strain rates are revealed by the molecular dynamics method. It is found that the Au nanowire displays three distinct types of mechanical behaviors when tensioning at low, medium and high strain rates, respectively. At the low strain rate, the stress–strain curve displays a periodic zigzag increase–decrease feature, and the plastic deformation is resulted from the slide of dislocation. The dislocations nucleate, propagate, and finally annihilate in every decreasing stages of stress, and the nanowire always can recover to FCC-ordered structure. At the medium strain rate, the stress–strain curve gently decreases during the plastic process, and the deformation is contributed from sliding and twinning. The dislocations formed in the yield stage do not fully propagate and further escape from the nanowire. At the high strain rate, the stress-strain curve wave-like oscillates during the plastic process, and the deformation is resulted from amorphization. The FCC atoms quickly transform into disordered amorphous structure in the yield stage. The relative magnitude between the loading velocity of strain and the propagation velocity of phonons determines the different deformation mechanisms. The mechanical behavior of Au nanowire is similar to Ni, Cu and Pt nanowires, but their deformation mechanisms are not completely identical with each other.