bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Poxvirus Vector Priming, Protein Coadministration, and Vaccine Intervals on HIV gp120 Vaccine-Elicited Antibody Magnitude and Function in Infant Macaques
Authors: Phillips Bonnie , Fouda Genevieve G. , Eudailey Josh , Pollara Justin , Curtis Alan D. , Kunz Erika , Dennis Maria , Shen Xiaoying , Bay Camden , Hudgens Michael , Pickup David , Alam S. Munir , Ardeshir Amir , Kozlowski Pamela A. , Van Rompay Koen K. A. , Ferrari Guido , Moody M. Anthony , Permar Sallie , De Paris Kristina 
Published: August 2017

ABSTRACTDespite success in reducing vertical HIV transmission by maternal antiretroviral therapy, several obstacles limit its efficacy during breastfeeding, and breast-milk transmission is now the dominant mode of mother-to-child transmission (MTCT) of HIV in infants. Thus, a pediatric vaccine is needed to eradicate oral HIV infections in newborns and infants. Utilizing the infant rhesus macaque model, we compared 3 different vaccine regimens: (i) HIV envelope (Env) protein only, (ii) poxvirus vector (modified vaccinia virus Ankara [MVA])-HIV Env prime and HIV Env boost, and (iii) coadministration of HIV Env and MVA-HIV Env at all time points. The vaccines were administered with an accelerated, 3-week-interval regimen starting at birth for early induction of highly functional HIV Env-specific antibodies. We also tested whether an extended, 6-week immunization interval using the same vaccine regimen as in the coadministration group would enhance the quality of antibody responses. We found that pediatric HIV vaccines administered at birth are effective in inducing HIV Env-specific plasma IgG. The vaccine regimen consisting of only HIV Env protein induced the highest levels of variable region 1 and 2 (V1V2)-specific antibodies and tier 1 neutralizing antibodies, whereas the extended-interval regimen induced both persistent Env-specific systemic IgG and mucosal IgA responses. Antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies in plasma were elicited by all vaccine regimens. These data suggest that infant immunizations beginning at birth are effective for the induction of functional HIV Env-specific antibodies that could potentially protect against breast milk transmission of HIV and set the stage for immunity prior to sexual debut.
Molecular Diagnosis of Invasive Aspergillosis and Detection of Azole Resistance by a Newly Commercialized PCR Kit
Authors: Dannaoui Eric , Gabriel Frédéric , Gaboyard Manuel , Lagardere Gaëlle , Audebert Lucile , Quesne Gilles , Godichaud Sandrine , Verweij Paul E. , Accoceberry Isabelle , Bougnoux Marie-Elisabeth 
Published: August 2017

ABSTRACT

Aspergillus fumigatus
is the main species responsible for aspergillosis in humans. The diagnosis of aspergillosis remains difficult, and the rapid emergence of azole resistance in
A. fumigatus
is worrisome. The aim of this study was to validate the new MycoGENIE
A. fumigatus
real-time PCR kit and to evaluate its performance on clinical samples for the detection of
A. fumigatus
and its azole resistance. This multiplex assay detects DNA from the
A. fumigatus
species complex by targeting the multicopy 28S rRNA gene and specific TR
34
and L98H mutations in the single-copy-number
cyp51A
gene of
A. fumigatus
. The specificity of
cyp51A
mutation detection was assessed by testing DNA samples from 25 wild-type or mutated clinical
A. fumigatus
isolates. Clinical validation was performed on 88 respiratory samples obtained from 62 patients and on 69 serum samples obtained from 16 patients with proven or probable aspergillosis and 13 patients without aspergillosis. The limit of detection was <1 copy for the
Aspergillus
28S rRNA gene and 6 copies for the
cyp51A
gene harboring the TR
34
and L98H alterations. No cross-reactivity was detected with various fungi and bacteria. All isolates harboring the TR
34
and L98H mutations were accurately detected by quantitative PCR (qPCR) analysis. With respiratory samples, qPCR results showed a sensitivity and specificity of 92.9% and 90.1%, respectively, while with serum samples, the sensitivity and specificity were 100% and 84.6%, respectively. Our study demonstrated that this new real-time PCR kit enables sensitive and rapid detection of
A. fumigatus
DNA and azole resistance due to TR
34
and L98H mutations in clinical samples.
The impact of urban speed reduction programmes on health system cost and utilities
Authors: Mohit Babak , Rosen Zohn , Muennig Peter A 
Published: August 2017

BackgroundVehicle speed changes impact the probability of injuring a pedestrian in ways that differ from the way that it impacts the probability of a collision or of death. Therefore, return on investment in speed reduction programmes has complex and unpredictable manifests. The objective of this study is to analyse the impact of motor vehicle speed reduction on the collision-related morbidity and mortality rates of urban pedestrians.Methods and FindingsWe created a simple way to estimate the public health impacts of traffic speed changes using a Markov model. Our outcome measures include the cost of injury, quality-adjusted life years (QALYs) gained and probability of death and injury due to a road traffic collision. Our two-way sensitivity analysis of speed, both before the implementation of a speed reduction programme and after, shows that, due to key differences in the probability of injury compared with the probability of death, speed reduction programmes may decrease the probability of death while leaving the probability of injury unchanged. The net result of this difference may lead to an increase in injury costs due to the implementation of a speed reduction programme. We find that even small investments in speed reductions have the potential to produce gains in QALYs.ConclusionsOur reported costs, effects and incremental cost-effectiveness ratios may assist urban governments and stakeholders to rethink the value of local traffic calming programmes and to implement speed limits that would shift the trade-off to become between minor injuries and no injuries, rather than severe injuries and fatalities.
Physician training protocol within the WEB Intrasaccular Therapy (WEB-IT) study
Authors: Arthur Adam , Hoit Daniel , Coon Alexander , Delgado Almandoz Josser E , Elijovich Lucas , Cekirge Saruhan , Fiorella David 
Published: August 2017

IntroductionThe WEB Intra-saccular Therapy (WEB-IT) trial is an investigational device exemption study to demonstrate the safety and effectiveness of the WEB device for the treatment of wide-neck bifurcation aneurysms. The neurovascular replicator (Vascular Simulations, Stony Brook, New York, USA) creates a physical environment that replicates patient-specific neurovascular anatomy and hemodynamic physiology, and allows devices to be implanted under fluoroscopic guidance.ObjectiveTo report the results of a unique neurovascular replicator-based training program, which was incorporated into the WEB-IT study to optimize technical performance and patient safety.MethodsUS investigators participated in a new training program that incorporated full surgical rehearsals on a neurovascular replicator. No roll-in cases were permitted within the trial. Custom replicas of patient-specific neurovascular anatomy were created for the initial cases treated at each center, as well as for cases expected to be challenging. On-site surgical rehearsals were performed before these procedures.ResultsA total of 48 participating investigators at 25 US centers trained using the replicator. Sessions included centralized introductory training, on-site training, and patient-specific full surgical rehearsal. Fluoroscopy and procedure times in the WEB-IT study were not significantly different from those seen in two European trials where participating physicians had significant WEB procedure experience before study initiation.ConclusionsA new program of neurovascular-replicator-based physician training was employed within the WEB-IT study. This represents a new methodology for education and training that may be an effective means to optimize technical success and patient safety during the introduction of a new technology.
Air pollution as a catalyst for supporting tobacco control policies? Evidence from a nationwide study on Chinese medical students
Authors: Yang Xiaozhao Yousef , Yang Tingzhong , Nie Fanhao 
Published: August 2017

PurposeFew studies have discussed how the increasing ambient air pollution may affect policy-related attitudes. Medical professionals constitute an important interest group who analyse and solve public issues within a medicalised framework. The current study investigates whether ambient air pollution is associated with a greater likelihood of supporting tobacco control measures among medical students.MethodsWe conducted multistage sampling among the medical students from 42 cities in China. We employed propensity-score matching to eliminate the selection bias and used multilevel logistic regressions for the main analysis (n1=9458, n2=42).Resultswe found that city-level air particulate matter is consistently associated with the support for tobacco control among medical students, net of other individual-level and city-level covariates. For one standard increase in air particulate matter, people are 1.21 times more likely to fully support tobacco control measures (p<0.05). This association is significantly stronger among medical students who are financially worse-off and are ethnic majority.ConclusionsEnvironmental pollution has a significant correlation with people’s attitudes towards health policies, even when such policies are not directly concerned with the natural environment. Policy makers may use this opportunity to implement tobacco control measures against the backdrop of China’s pollution crisis.
Prominent deep medullary veins: a predictive biomarker for stroke risk from transient ischemic attack?
Authors: Duan Yang , Xu Zhihua , Li Hongyi , Cai Xiaonan , Chang Cancan , Yang Benqiang 
Published: August 2017

Background Deep medullary veins (DMVs) are a biomarker of severity and prognosis in patients with acute cerebral infarction. However, their clinical significance remains unclear in patients with transient ischemic attack (TIA). Purpose To determine whether prominent deep medullary veins (PDMVs) are a predictive biomarker for stroke risk after TIA. Material and Methods Clinical and imaging data of 49 patients with TIA and 49 sex- and age-matched controls were studied. PDMVs were defined as DMVs with a score of 3 (TDMVs) or asymmetric DMVs (ADMVs), and the relationship between PDMVs and clinical features was analyzed. The DMV score based on susceptibility weighted imaging (SWI) ranged from 0 (not visible) to 3 (very prominent) and was calculated for both hemispheres separately. A different score in each hemisphere was defined as ADMVs and an equal score was defined as symmetric DMVs. The asymmetry and score of DMVs were compared between the two groups and with respect to the time from TIA onset to imaging analysis. Results Agreement between neuroradiologists for the DMV asymmetry/score on SWI was excellent. The frequency of ADMVs and TDMVs was significantly higher in patients with TIA than controls ( P < 0.05). The patients showed no correlation between the time from TIA onset to imaging and the DMV asymmetry/score ( P > 0.05); PDMVs were not correlated with age, blood pressure, or diabetes. However, PDMVs were associated with the ABCD2 score (≥4), clinical symptoms, and duration of TIA (≥10 min). Conclusion Prominent deep medullary veins is a predictive biomarker for the risk of stroke in many patients having suffered from TIA.
Effects of telemonitoring on glycaemic control and healthcare costs in type 2 diabetes: A randomised controlled trial
Authors: Warren Robin , Carlisle Karen , Mihala Gabor , Scuffham Paul A 
Published: August 2017

Introduction This study examined the effect of a telehealth intervention on the control of type 2 diabetes and subsequent potential cost-savings to the health system. Methods This prospective randomised controlled trial randomised adults with type 2 diabetes to the intervention (diabetes program) or control (usual care) arm. Key eligibility criteria included an HbA1c level of at least 58 mmol/mol (7.5%) without severe or unstable comorbidities. All participants continued their usual healthcare, but participants in the intervention arm received additional diabetes care from a diabetes care coordinator via a home monitor that captured clinical measures. Data collected included biomedical, quality of life measures and healthcare (GP, outpatient and inpatient) costs. The primary outcome was HbA1c collected at baseline and 6 months. Analysis was conducted on a complete case intention-to-treat basis. The healthcare system perspective was taken to calculate the incremental cost per percentage-point reduction in HbA1c. Results Results from 63 participants from each study arm were analysed. HbA1c in the intervention group decreased from a median 68 mmol/mol (8.4%) to 58 mmol/mol (7.5%), and remained unchanged in the control group at median 65 mmol/mol (8.1%) at the 6-month endpoint. The intervention effect on HbA1c change was statistically significant ( p = .004). Total healthcare costs in the intervention group, including the intervention costs, were lower (mean $3781 vs. $4662; p < .001) compared with usual care. Discussion There was a clinically meaningful and statistically significant benefit from the telehealth intervention at a lower cost; thus, telehealth was cost-saving and produced greater health benefits compared with usual care.
Management of distal radius fractures – A new concept of closed reduction and standardised percutaneous 5-pin fixation
Authors: Vasudevan PN , Lohith BM 
Published: August 2017

Introduction Management of distal radial fractures is a controversial topic, with poor reported outcomes in up to 30% of cases and a wide variety of treatment options such as closed reduction and POP cast, internal fixation, external fixation and percutaneous pin fixation in many configurations. Over the last 13 years, we have used a novel standardised 5-pin configuration of percutaneous K-wire fixation, which can be used in most types of distal radial fractures, where closed reduction is possible, and the ulna is intact or re-constructible. This study reports the outcomes of this technique. Methods All patients presenting to our unit with distal radial fracture in a 126-month period from June 2005 to December 2015 managed by closed reduction and 5-pin fixation were evaluated for complications including wire loosening and infection, tendon or nerve injury, reflex sympathetic dystrophy and functional outcome. Results A total of 490 consecutive patients with 496 distal radial fractures were treated in the study period with a mean age of 49.4 years; 57% were female and 57% were due to domestic falls. After death from unrelated causes and loss to follow-up, 418 patients were reviewed in clinic, and a further 40 were patients contacted by telephone at one year, and clinical outcome was evaluated using Cooney’s modification of Green and O’Brien’s score. All fractures healed and 95.7% had an ‘excellent’ outcome and 3.9% were ‘good’; only two patients achieved a ‘fair’ outcome, both of whom had comminuted intra-articular fractures with metaphyseal comminution. Complications were minimal and temporary with no cases of deep infection, tendon or nerve injury or reflex sympathetic dystrophy. Conclusions This study proved that our novel customised 5-pin percutaneous fixation was sufficiently stable and controlled all fragments of distal radial fractures effectively to allow early mobilisations to prevent stiffness and reflex sympathetic dystrophy with excellent functional outcomes.
Clinical predictors of specialist treatment requirements in pelvic fracture: A retrospective cohort study
Authors: Caulfield Alexandra , Hamilton William L , Trent Louise , Ellington Matt 
Published: August 2017

Objectives and background To describe the pelvic fracture population presenting to a district hospital in New Zealand and investigate whether clinical measurements can predict subsequent transfer to specialist tertiary care units. Early transfer to tertiary care is associated with improved surgical outcomes and cost-effectiveness, but there has as yet been little research into predictive markers for referral. Methods Retrospective cohort study of all patients admitted with pelvic fracture to the intensive care unit of Hastings Memorial Hospital, New Zealand from 2005 to 2014. The primary outcome was transfer to specialist tertiary care. Secondary outcomes were total duration of hospitalisation and conservative vs. surgical management. Clinical variables including age, sex, observations and comorbidities were analysed against these outcomes using logistic regression. Results Data from 40 patients were collected (24 male, 16 female; median age: 44 years). Median distance from the hospital was 22.6 km, with 27 (67.5%) patients transported by land and 13 (32.5%) arriving by helicopter. Median time from receipt of emergency call to arrival at hospital was 60 min. Three patients died and 14/40 (35%) required transfer to tertiary centres. Damage to intra-abdominal structures such as spleen, liver and bladder lacerations were associated with transfer to tertiary care, unadjusted relative risk 3.34 (95% confidence intervals: 1.39–8.05). Conclusion Despite a 10-year recruitment window, only 40 patients were included in this study, limiting its statistical power. Nonetheless, our data suggest that pelvic fracture patients with injuries to intra-abdominal viscera are more likely to require tertiary care transfer.
Could an endoneurial endothelial crosstalk between Wnt/β-catenin and Sonic Hedgehog pathways underlie the early disruption of the infraorbital blood–nerve barrier following chronic constriction injury?
Authors: Moreau Nathan , Mauborgne Annie , Couraud Pierre-Olivier , Romero Ignacio A , Weksler Babette B , Villanueva Luis , Pohl Michel , Boucher Yves 
Published: August 2017

Background Blood–nerve barrier disruption is pivotal in the development of neuroinflammation, peripheral sensitization, and neuropathic pain after peripheral nerve injury. Activation of toll-like receptor 4 and inactivation of Sonic Hedgehog signaling pathways within the endoneurial endothelial cells are key events, resulting in the infiltration of harmful molecules and immunocytes within the nerve parenchyma. However, we showed in a previous study that preemptive inactivation of toll-like receptor 4 signaling or sustained activation of Sonic Hedgehog signaling did not prevent the local alterations observed following peripheral nerve injury, suggesting the implication of another signaling pathway. Methods Using a classical neuropathic pain model, the infraorbital nerve chronic constriction injury (IoN-CCI), we investigated the role of the Wnt/β-catenin pathway in chronic constriction injury-mediated blood–nerve barrier disruption and in its interactions with the toll-like receptor 4 and Sonic Hedgehog pathways. In the IoN-CCI model versus control, mRNA expression levels and/or immunochemical detection of major Wnt/Sonic Hedgehog pathway (Frizzled-7, vascular endothelial-cadherin, Patched-1 and Gli-1) and/or tight junction proteins (Claudin-1, Claudin-5, and Occludin) readouts were assessed. Vascular permeability was assessed by sodium fluorescein extravasation. Results IoN-CCI induced early alterations in the vascular endothelial-cadherin/β-catenin/Frizzled-7 complex, shown to participate in local blood–nerve barrier disruption via a β-catenin-dependent tight junction protein downregulation. Wnt pathway also mediated a crosstalk between toll-like receptor 4 and Sonic Hedgehog signaling within endoneurial endothelial cells. Nevertheless, preemptive inhibition of Wnt/β-catenin signaling before IoN-CCI could not prevent the downregulation of key Sonic Hedgehog pathway readouts or the disruption of the infraorbital blood–nerve barrier, suggesting that Sonic Hedgehog pathway inhibition observed following IoN-CCI is an independent event responsible for blood–nerve barrier disruption. Conclusion A crosstalk between Wnt/β-catenin- and Sonic Hedgehog-mediated signaling pathways within endoneurial endothelial cells could mediate the chronic disruption of the blood–nerve barrier following IoN-CCI, resulting in increased irreversible endoneurial vascular permeability and neuropathic pain development.
Intrathecal administration of AYX2 DNA decoy produces a long-term pain treatment in rat models of chronic pain by inhibiting the KLF6, KLF9, and KLF15 transcription factors
Authors: Mamet Julien , Klukinov Michael , Harris Scott , Manning Donald C , Xie Simon , Pascual Conrado , Taylor Bradley K , Donahue Renee R , Yeomans David C 
Published: August 2017

Background Nociception is maintained by genome-wide regulation of transcription in the dorsal root ganglia—spinal cord network. Hence, transcription factors constitute a promising class of targets for breakthrough pharmacological interventions to treat chronic pain. DNA decoys are oligonucleotides and specific inhibitors of transcription factor activities. A methodological series of in vivo–in vitro screening cycles was performed with decoy/transcription factor couples to identify targets capable of producing a robust and long-lasting inhibition of established chronic pain. Decoys were injected intrathecally and their efficacy was tested in the spared nerve injury and chronic constriction injury models of chronic pain in rats using repetitive von Frey testing. Results Results demonstrated that a one-time administration of decoys binding to the Kruppel-like transcription factors (KLFs) 6, 9, and 15 produces a significant and weeks–month long reduction in mechanical hypersensitivity compared to controls. In the spared nerve injury model, decoy efficacy was correlated to its capacity to bind KLF15 and KLF9 at a specific ratio, while in the chronic constriction injury model, efficacy was correlated to the combined binding capacity to KLF6 and KLF9. AYX2, an 18-bp DNA decoy binding KLF6, KLF9, and KLF15, was optimized for clinical development, and it demonstrated significant efficacy in these models. Conclusions These data highlight KLF6, KLF9, and KLF15 as transcription factors required for the maintenance of chronic pain and illustrate the potential therapeutic benefits of AYX2 for the treatment of chronic pain.
In-stent hypodense area at two weeks following carotid artery stenting predicts neointimal hyperplasia after two years
Authors: Yamashita Kentaro , Kokuzawa Jouji , Kuroda Tatsuya , Murase Satoru , Kumagai Morio , Kaku Yasuhiko 
Published: August 2017

Introduction It has not been reported how long the follow-up study after carotid artery stenting (CAS) should be continued. The purpose of the present study is to clarify the dynamic change of the in-stent neointimal layer and residual arterial lumen by two years following CAS using three-dimensional computed tomography angiography (3D CTA) with volume rendering. Methods Thirty-six stented carotid arteries in 34 consecutive patients were examined by 3D CTA with volume rendering at two weeks and 3, 6, 12, 24 months of follow-up. Results An in-stent hypodense area could be detected in 10 of 36 (27.8%) carotid arteries at two weeks after CAS. In-stent hypodense areas gradually declined thereafter by three months. In the course of longer follow-up, the layer of the in-stent hypodense area (neointimal hyperplasia) continued to grow in size for up to 24 months. Patients with an in-stent hypodense area at two weeks have a thicker layer of neointimal hyperplasia at 24 months than patients without in-stent hypodense area at two weeks’ follow-up. The predictive factors for growing neointimal hyperplasia at 24 months in multiple regression analysis are ulcer formation in pretreatment stenosis and the thickness of in-stent hypodense area at two weeks following CAS. Conclusion Our results suggest that follow-up study should be continued for a longer period even if in-stent restenosis could not be detected at one year following CAS. Especially in cases with ulcer formation in pretreatment stenosis and with a subacute in-stent hypodense area after CAS, longer follow-up is strongly recommended.