bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do patient and proxy agree? Long-term changes in multiple sclerosis physical impact and walking ability on patient-reported outcome scales
Authors: Sonder Judith M , Balk Lisanne J , Bosma Libertje VAE , Polman Chris H , Uitdehaag Bernard MJ 
Published: April 2014

Background: Patient-reported outcome scales (PROs) are useful in monitoring changes in multiple sclerosis (MS) over time. Although these scales are reliable and valid measures in longitudinal studies in MS patients, it is unknown what the impact is when obtaining longitudinal data from proxies. Objective: The objective of this paper is to compare longitudinal changes in patient and proxy responses on PROs assessing physical impact of MS and walking ability. Methods: In a prospective observational study, data on the Multiple Sclerosis Impact Scale (MSIS-29 physical) and Multiple Sclerosis Walking Scale (MSWS-12) were obtained from 137 patient-proxy couples at baseline and at two-year follow-up. Demographic and disease-related variables explaining agreement or disagreement between patients and proxies were investigated using linear regression analyses. Results: Full agreement was found in 56% (MSIS) and 62% (MSWS) of the patient-proxy couples. Complete disagreement was very rare for both scales (2% MSIS, 5% MSWS). When patients were more positive than proxies, a higher age, longer disease duration, longer patient-proxy relationship and increased levels of depression, anxiety and caregiver burden in proxies were observed. Conclusion: In the majority of the patient-proxy couples there was agreement. Proxies can serve as a valuable source of information, but caution remains essential when using scores from proxies.
Transition to adult services for young people with mental health needs: A systematic review
Authors: Paul Moli , Street Cathy , Wheeler Nicola , Singh Swaran P 
Published: April 2014

Background: Young people’s transition from child and adolescent (CAMHS) to adult mental health services (AMHS). Objectives: To systematically review evidence on the effectiveness of different models of CAMHS–AMHS transitional care, service user and staff perspectives, and facilitators of/barriers to effective CAMHS–AMHS transition. Data sources: A systematic search in May 2012 of Medline, PsycINFO, CINAHL, EMBASE, AMED, Health Business Elite, HMIC, Cochrane Database, Web of Science and ASSIA; ancestral searches; and consultation with experts in the field. Study selection: Qualitative, quantitative and mixed-methods primary research on the CAMHS–AMHS health-care transition of young people (aged 16–21 years) with mental health problems. Data extraction: Two reviewers independently completed a standardised data extraction form and critically evaluated identified documents using a validated appraisal tool for empirical studies with varied methodologies. Results: A total of 19 studies of variable quality were identified. None were randomised or case-controlled trials. Studies incorporating service user/carer perspectives highlighted the need to tackle stigma and provide accessible, age-appropriate services. Parents/carers wanted more involvement with AMHS. Transitional care provision was considered patchy and often not prioritised within mental health services. There was no clear evidence of superior effectiveness of any particular model. Conclusions: High-quality evidence of transitional care models is lacking. Data broadly support the development of programmes that address the broader transitional care needs of ‘emerging adults’ and their mental health needs but further evaluation is necessary. Developing robust transitional mental health care will require the policy–practice gap to be addressed and development of accessible, acceptable, responsive, age-appropriate provision.
The clinic-pathological characteristics of prostate cancer in an Irish subpopulation with a serum PSA less than 4.0ng/ml
Authors: O’Kelly F , McGuire BB , Flynn RJ , Grainger R , McDermott TED , Thornhill JA 
Published: April 2014

Background: Prostate specific antigen (PSA) has been used as a biomarker for prostate cancer for the last 20 years. Traditionally, a serum PSA <4 ng/ml has been used as a general cut-off between normal and abnormal readings. There is evidence to demonstrate that men with a normal serum PSA can develop prostate cancer. The aim of this study was to investigate the clinico-pathological features of prostate cancer in a non-screened Irish cohort with serum PSA <4 ng/ml. Methods: A retrospective analysis was performed of all patients who underwent radical retropubic prostatectomy (RRP) in a tertiary referral unit over a 10-year period (2000–2010). Clinico-pathological characteristics were collated including those from trans-rectal ultrasound-guided (TRUS) prostate biopsies and radical prostatectomy specimens. Results: Between 2000 and 2010, 651 men underwent an RRP, with 43 (6.6%) having a serum PSA <4 ng/ml. The median PSA was 3.2 ng/ml (range 0.8–4.0). Nineteen (44.2%) had palpable disease on direct rectal examination (DRE). Following prostatectomy, 28 (65.12%) had Gleason 6 disease, 14 (32.56%) had Gleason 7 disease and one (2.32%) had Gleason 8 disease. Five (11.63%) patients were upgraded from TRUS biopsy to final histopathology. Six (13.95%) patients had pathological evidence of extracapsular extension on final pathology. Three (6.98%) patients experienced biochemical recurrence and received salvage radiation therapy after a median time of 24 months. The median follow-up was 106 months (range 36–158). Twenty (46.51%) patients had a first-degree family history of prostate cancer. Conclusions: A PSA cut-off of 4 ng/ml has commonly been used in the detection of prostate cancer. Our study emphasizes that this cut-off is inappropriate and that no specific level of PSA can be used. Management decisions need to be individualized based on index of suspicion with concomitant counselling and rectal examination.
pth moment stability in stochastic neutral Volterra-Levin equation with Lévy noise and variable delays
Authors: Yin Hongwei , Xiao Shuiming , Xiao Xiaoyong , Wen Xiaoqing 
Published: April 2014

Abstract
In this paper, we study a class of stochastic neutral Volterra-Levin equations which are equipped with Lévy noise and variable delay and we obtain p th moment exponential stability. Some well-known results are improved and generalized.
Laboratory assessment of molluscicidal and cercariacidal effects of Glinus lotoides fruits
Authors: Kiros Gebrehiwot , Erko Berhanu , Giday Mirutse , Mekonnen Yalemtsehay 
Published: April 2014

Abstract

Background
The negative impact of synthetic molluscicides on the environment and their high cost necessitated search for an alternative approach of using plant extracts for the control of schistosomiasis. The objective of this study was, therefore, to evaluate aqueous and ethyl acetate crude extracts of Glinus lotoides fruits for their cercariacidal activity and molluscicidal effect against schistosome snail intermediate hosts.

Methods
Assessment of the molluscicidal activity against Biomphalaria pfeifferi was made by immersion method in accordance with WHO guideline. The results of mortality were statistically analyzed using probit analysis. The attenuating effect of the plant on Schistosoma mansoni cercariae was determined using establishment of adult worms as a parasitological parameter post exposure.

Results
The 24 and 48 hour-LC50 values for the aqueous extract of G. lotoides fruits were 47.1 and 44.1 mg/L, respectively, whereas that of ethyl acetate were 66.1 and 59.6 mg/L, respectively. The 24 and 48 hour LC90 values for the aqueous extract of G. lotoides fruits were 56.96 and 51.0 mg/L, respectively, while that of ethyl acetate were 77.2 and 70.0 mg/L, respectively. The in vitro cercariacidal activity was determined after 2 hrs of exposure to the aqueous plant extract. It was found out that the LC50 and LC90 values were 18.7 and 41.7 mg/L, respectively. Besides, infectivity of Schistosoma mansoni cercariae to mice was determined by exposing mice to cercariae pre-treated with the sub-lethal concentrations (3.7, 11.6 and 18.7 mg/L) of the aqueous extract. A significant reduction in worm burden in mice was obtained at 11.6 mg/L (p < 0.05). Moreover, the reduction in number of worms recovered was highly significant at 18.7 mg/L (p < 0.001).

Conclusions
The results showed that G. lotoides has molluscicidal activity against B. pfeifferi snails and cercariacidal activity against S. mansoni. Yet, further comprehensive evaluation is recommended for the possible use of G. lotoides against B. pfeifferi and the schistosome parasite.
Predictors of exacerbation frequency in chronic obstructive pulmonary disease
Authors: Yang Hui , Xiang Pingchao , Zhang Erming , Guo Wei’An , Shi Yanwei , Zhang Shuo , Tong Zhaohui 
Published: April 2014

Abstract

Background
Exacerbations of chronic obstructive pulmonary disease (COPD) are sporadic, acute worsening of symptoms. Identifying predictors of exacerbation frequency may facilitate medical interventions that reduce exacerbation frequency and severity. The objective of this study was to determine predictors of exacerbation frequency and mortality.

Methods
A total of 227 COPD patients were enrolled in a prospective clinical study between January 2000 and December 2011. Reported exacerbations were recorded for the year preceding enrollment and annually thereafter, and patients were grouped by median annual exacerbation frequency into those experiencing infrequent exacerbations (less than one exacerbation annually) and frequent exacerbations (one or more exacerbation annually). Patients experiencing frequent exacerbations were further divided into those experiencing moderately frequent exacerbations (fewer than two exacerbations per year) and severely frequent exacerbations (two or more exacerbations per year). The rate of clinical relapse and survival was recorded over a 10-year period. The mean of follow-up time was 5.15 years per patient.

Results
For patients experiencing infrequent, moderately frequent, and severely frequent exacerbations, median exacerbations in the year preceding enrollment were 0.0, 0.5, 1.0, respectively, and more frequent exacerbations correlated with lower baseline forced expiratory volume in one second (FEV1) (0.81 L, 0.75 L, and 0.66 L, respectively), higher comorbidity (70.7%, 75.0%, and 89.4%, respectively), and greater NPPV use during hospitalization (16.4%, 35.9% and 51.1%, respectively). FEV1 declined and mortality increased with increasing exacerbation frequency.

Conclusions
Exacerbation frequency can be used to generate discreet patient subpopulations, supporting the hypothesis that multiple COPD phenotypes exist and can be used in patient risk stratification.
Might axial myofascial properties and biomechanical mechanisms be relevant to ankylosing spondylitis and axial spondyloarthritis?
Authors: Masi Alfonse T 
Published: April 2014

AbstractAnkylosing spondylitis and axial spondyloarthropathy have characteristic age- and sex-specific onset patterns, typical entheseal lesions, and marked heritability, but the integrative mechanisms causing the pathophysiological and structural alterations remain largely undefined. Myofascial tissues are integrated in the body into webs and networks which permit transmission of passive and active tensional forces that provide stabilizing support and help to control movements. Axial myofascial hypertonicity was hypothesized as a potential excessive polymorphic trait which could contribute to chronic biomechanical overloading and exaggerated stresses at entheseal sites. Such a mechanism may help to integrate many of the characteristic host, pathological, and structural features of ankylosing spondylitis and axial spondyloarthritis. Biomechanical stress and strain were recently documented to correlate with peripheral entheseal inflammation and new bone formation in a murine model of spondyloarthritis. Ankylosing spondylitis has traditionally been classified by the modified New York criteria, which require the presence of definite radiographic sacroiliac joint lesions. New classification criteria for axial spondyloarthritis now include patients who do not fulfill the modified New York criteria. The male-to-female sex ratios clearly differed between the two patient categories - 2:1 or 3:1 in ankylosing spondylitis and 1:1 in non-radiographic axial spondyloarthritis - and this suggests a spectral concept of disease and, among females, milder structural alterations. Magnetic resonance imaging of active and chronic lesions in ankylosing spondylitis and axial spondyloarthritis reveals complex patterns, usually interpreted as inflammatory reactions, but shows similarities to acute degenerative disc disease, which attributed to edema formation following mechanical stresses and micro-damage. A basic question is whether mechanically induced microinjury and immunologically mediated inflammatory mechanisms operate in both ankylosing spondylitis and degenerative disc disease but differ in relative degrees. The hypothesized biomechanical properties raised in this commentary require documentation of their association with the onset risk and course of ankylosing spondylitis and axial spondyloarthritis. If particular subsets of ankylosing spondylitis and axial spondyloarthritis patients are confirmed to have altered axial myofascial properties, their biological basis and underlying biomechanical mechanisms promise to become clarified. Understanding how biomechanical and physical properties can affect symptomatic and structural manifestations of these disorders could also improve their management.
Ultrasonographic assessment reveals detailed distribution of synovial inflammation in Blau syndrome
Authors: Ikeda Kei , Kambe Naotomo , Takei Syuji , Nakano Taiji , Inoue Yuzaburo , Tomiita Minako , Oyake Natsuko , Satoh Takashi , Yamatou Tsuyoshi , Kubota Tomohiro , Okafuji Ikuo , Kanazawa Nobuo , Nishikomori Ryuta , Shimojo Naoki , Matsue Hiroyuki , Nakajima Hiroshi 
Published: April 2014

Abstract
Introduction
Arthritis is the most frequent manifestation of Blau syndrome, an autoinflammatory disorder caused by the genetic mutation of NOD2. However, detailed information on arthritis in Blau syndrome on which the therapeutic strategy should be based on is lacking. This multi-center study aimed to accurately characterize the articular manifestation of Blau syndrome and also to demonstrate the utility of musculoskeletal ultrasound in Blau syndrome.

Methods
Patients who had been diagnosed with Blau syndrome by genetic analysis of NOD2 were recruited. A total of 102 synovial sites in 40 joints were assessed semiquantitatively by ultrasound for gray-scale synovitis and synovial power Doppler (PD) signal.

Results
In total, 10 patients whose age ranged from 10 months to 37 years enrolled in this study. Although only 4 joints (0.8%) were tender on physical examination, 81 joints (16.9%) were clinically swollen. Moreover, 240 (50.0%), and 124 (25.8%) joints showed gray-scale (GS) synovitis and synovial PD signal on ultrasound, respectively. Importantly, GS synovitis was present in 168 out of 399 non-swollen joints, in which 61 also exhibited synovial PD signal. Among 40 joint regions, the ankle, the wrist, and the proximal interphalangeal joints were the most frequently and severely affected joints. Comparisons between different synovial tissues demonstrated a significantly higher proportion of the joints with tenosynovitis as compared with that with intra-articular synovitis (41.5% versus 27.9%, P < 0.0001). In respect of age and treatment, synovial PD signals were minimal in the youngest patient and in the oldest two patients, and were relatively mild in patients receiving treatment with methotrexate plus TNF antagonists. In two patients who underwent the second ultrasound examination, total PD scores markedly decreased after initiating the treatment with a tumor necrosis factor (TNF) antagonist.

Conclusions
The detailed information on synovial inflammation obtained by ultrasound confirms the dissociation between pain and inflammation and the frequently involved joint regions and synovial tissue in the arthritis of Blau syndrome. Our data also demonstrate that ultrasonography can be a potent tool in monitoring the activity of synovial inflammation and in investigating the pathophysiology of arthritis in this rare but archetypical autoinflammatory condition.
Mammographic texture resemblance generalizes as an independent risk factor for breast cancer
Authors: Nielsen Mads , Vachon Celine M , Scott Christopher G , Chernoff Konstantin , Karemore Gopal , Karssemeijer Nico , Lillholm Martin , Karsdal Morten A 
Published: April 2014

Abstract
Introduction
Breast density has been established as a major risk factor for breast cancer. We have previously demonstrated that mammographic texture resemblance (MTR), recognizing the local texture patterns of the mammogram, is also a risk factor for breast cancer, independent of percent breast density. We examine if these findings generalize to another population.

Methods
Texture patterns were recorded in digitalized pre-diagnosis (3.7 years) film mammograms of a nested case–control study within the Dutch screening program (S1) comprising of 245 breast cancers and 250 matched controls. The patterns were recognized in the same study using cross-validation to form resemblance scores associated with breast cancer. Texture patterns from S1 were examined in an independent nested case–control study within the Mayo Mammography Health Study cohort (S2) of 226 cases and 442 matched controls: mammograms on average 8.5 years prior to diagnosis, risk factor information and percent mammographic density (PD) estimated using Cumulus were available. MTR scores estimated from S1, S2 and S1 + S2 (the latter two as cross-validations) were evaluated in S2. MTR scores were analyzed as both quartiles and continuously for association with breast cancer using odds ratios (OR) and adjusting for known risk factors including age, body mass index (BMI), and hormone usage.

Results
The mean ages of S1 and S2 were 58.0 ± 5.7 years and 55.2 ± 10.5 years, respectively. The MTR scores on S1 showed significant capability to discriminate cancers from controls (area under the operator characteristics curve (AUC) = 0.63 ± 0.02, P <0.001), which persisted after adjustment for PD. S2 showed an AUC of 0.63, 0.61, and 0.60 based on PD, MTR scores trained on S2, and MTR scores trained on S1, respectively. When adjusted for PD, MTR scores of S2 trained on S1 showed an association with breast cancer for the highest quartile alone: OR in quartiles of controls as reference; 1.04 (0.59 to 1.81); 0.95 (0.52 to 1.74); 1.84 (1.10 to 3.07) respectively. The combined continuous model with both PD and MTR scores based on S1 had an AUC of 0.66 ± 0.03.

Conclusions
The local texture patterns associated with breast cancer risk in S1 were also an independent risk factor in S2. Additional textures identified in S2 did not significantly improve risk segregation. Hence, the textural patterns that indicated elevated risk persisted under differences in X-ray technology, population demographics, follow-up time and geography.
Multilevel competing risk models to evaluate the risk of nosocomial infection
Authors: Wolkewitz Martin , Cooper Ben S , Palomar-Martinez Mercedes , Alvarez-Lerma Francisco , Olaechea-Astigarraga Pedro , Barnett Adrian G , Harbarth Stephan , Schumacher Martin 
Published: April 2014

Abstract
Introduction
Risk factor analyses for nosocomial infections (NIs) are complex. First, due to competing events for NI, the association between risk factors of NI as measured using hazard rates may not coincide with the association using cumulative probability (risk). Second, patients from the same intensive care unit (ICU) who share the same environmental exposure are likely to be more similar with regard to risk factors predisposing to a NI than patients from different ICUs. We aimed to develop an analytical approach to account for both features and to use it to evaluate associations between patient- and ICU-level characteristics with both rates of NI and competing risks and with the cumulative probability of infection.

Methods
We considered a multicenter database of 159 intensive care units containing 109,216 admissions (813,739 admission-days) from the Spanish HELICS-ENVIN ICU network. We analyzed the data using two models: an etiologic model (rate based) and a predictive model (risk based). In both models, random effects (shared frailties) were introduced to assess heterogeneity. Death and discharge without NI are treated as competing events for NI.

Results
There was a large heterogeneity across ICUs in NI hazard rates, which remained after accounting for multilevel risk factors, meaning that there are remaining unobserved ICU-specific factors that influence NI occurrence. Heterogeneity across ICUs in terms of cumulative probability of NI was even more pronounced. Several risk factors had markedly different associations in the rate-based and risk-based models. For some, the associations differed in magnitude. For example, high Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were associated with modest increases in the rate of nosocomial bacteremia, but large increases in the risk. Others differed in sign, for example respiratory vs cardiovascular diagnostic categories were associated with a reduced rate of nosocomial bacteremia, but an increased risk.

Conclusions
A combination of competing risks and multilevel models is required to understand direct and indirect risk factors for NI and distinguish patient-level from ICU-level factors.
Excision of viral reprogramming cassettes by Cre protein transduction enables rapid, robust and efficient derivation of transgene-free human induced pluripotent stem cells
Authors: Kadari Asifiqbal , Lu Min , Li Ming , Sekaran Thileepan , Thummer Rajkumar P , Guyette Naomi , Chu Vi , Edenhofer Frank 
Published: April 2014

AbstractIntegrating viruses represent robust tools for cellular reprogramming; however, the presence of viral transgenes in induced pluripotent stem cells (iPSCs) is deleterious because it holds the risk of insertional mutagenesis leading to malignant transformation. Here, we combine the robustness of lentiviral reprogramming with the efficacy of Cre recombinase protein transduction to derive iPSCs devoid of transgenes. By genome-wide analysis and targeted differentiation towards the cardiomyocyte lineage, we show that transgene-free iPSCs are superior to iPSCs before Cre transduction. Our study provides a simple, rapid and robust protocol for the generation of clinical-grade iPSCs suitable for disease modeling, tissue engineering and cell replacement therapies.