bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of the BODE index in patients with α1-antitrypsin deficiency-related COPD
Authors: Thabut Gabriel , Mornex Jean-François , Pison Christophe , Cuvelier Antoine , Balduyck Malika , Pujazon Marie-Christine , Fournier Michel , AitIlalne Brahim , Porcher Raphaël 
Published: February 2014

The BODE (body mass index, airflow obstruction, dyspnoea and exercise capacity) index is used to decide on referral and transplantation of patients with chronic obstructive pulmonary disease (COPD). The BODE index has not been validated in patients with α1-antitrypsin deficiency, who account for 15% of COPD patients undergoing lung transplantation. We sought to validate the BODE index in α1-antitrypsin deficiency-related COPD.We assessed the prognostic value of the BODE index in 191 patients followed from 2006 to 2012 in a French prospective cohort of patients with α1-antitrypsin deficiency.20 patients died during follow-up and 22 underwent lung transplantation. Survival (95% CI) was 93.0% (91.7–94.3%) at 3 years and 76.0% (72.9–79.1%) at 5 years. The 3-year survival was 97.4% (96.6–98.2%), 98.0% (96.7–99.3%), 87.7% (84.5–90.9%) and 75.3% (66.0–84.6%) for patients with BODE index 0–2, 3–4, 5–6 and 7–10, respectively. Survival discrimination of the BODE index was better than with both forced expiratory volume in 1 s and Global Initiative for Chronic Obstructive Lung Disease classification. Regarding calibration, expected survival by BODE index was noticeably lower than observed survival.The BODE index showed very good survival discrimination in patients with α1-antitrypsin deficiency-related COPD. Larger studies are needed to support its use to drive patient referral for lung transplantation.
Importance of concomitant local and systemic eosinophilia in uncontrolled asthma
Authors: Schleich Florence Nicole , Chevremont Anne , Paulus Virginie , Henket Monique , Manise Maité , Seidel Laurence , Louis Renaud 
Published: February 2014

Systemic and airway eosinophilia are recognised features of asthma. There are, however, patients who exhibit discordance between local and systemic eosinophilia. In this study, we sought to determine the prevalence and characteristics of patients with concordant and discordant systemic and bronchial eosinophilia.We conducted a retrospective study on 508 asthmatics with successful sputum induction. We assessed the relationship between blood and sputum eosinophils by breaking down the population into four groups according to blood (≥400 cells per mm3) and sputum (≥3%) eosinophils. Then, we prospectively reassessed the link between eosinophils and asthma control (Asthma Control Questionnaire (ACQ)) and exacerbation rate in a new cohort of 250 matched asthmatics.In our retrospective cohort, asthmatics without eosinophilic inflammation were the largest group (49%). The group with isolated sputum eosinophilia (25%) was, compared with noneosinophilic asthma, associated with lower forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity ratio and higher bronchial hyperresponsiveness and exhaled nitric oxide fraction (FeNO). Asthmatics exhibiting isolated systemic eosinophilia (7%) had similar characteristics as noneosinophilic asthmatics. The group with concordant systemic and airway eosinophilia (19%) showed remarkable male predominance, and had the lowest airway calibre, asthma control and quality of life, and the highest bronchial hyperresponsiveness,FeNOand exacerbation rate. The prospective cohort confirmed the different subgroup proportions and the higher ACQ and exacerbation rates in cases of diffuse eosinophilia compared with noneosinophilic asthmatics.Concomitant systemic and bronchial eosinophilic inflammation contribute to poor asthma control.
Multimodal management of malignant pleural mesothelioma: where are we today?
Authors: Van Schil Paul E. , Opitz Isabelle , Weder Walter , De Laet Christophe , Domen Andreas , Lauwers Patrick , Hendriks Jeroen M. , Van Meerbeeck Jan P. 
Published: February 2014

The prognosis of patients with malignant pleural mesothelioma remains poor and although it is clear that multimodal therapy is necessary to improve long-term results, precise treatment schemes have not yet been unequivocally established. Single-modality therapy does not have a major impact on long-term survival and combined-modality therapies are being further evaluated. However, the relative contributions of chemotherapy, radiotherapy and surgery have not been clearly determined at the present time. Moreover, the extent of resection and precise surgical procedure remain a highly debated topic. To better compare and combine results from different institutions and trials, uniform definitions of surgical procedures including extrapleural pneumonectomy and different forms of pleurectomy have recently been introduced. Due to the relatively higher morbidity and mortality of extrapleural pneumonectomy, there is currently a shift towards pleurectomy/decortication when a macroscopic complete resection of all tumour can be obtained by this procedure. In most recent trials, induction chemotherapy was administered to improve surgical resection rates but pathological complete responses are infrequently observed. The role of post-operative radiotherapy has to be further elucidated.Further treatment options that are currently explored include hyperthermic intrapleural chemotherapy, immunotherapy, gene therapy and photodynamic therapy. However, no randomised comparisons are available yet.
Major aging-associated RNA expressions change at two distinct age-positions
Authors: Gheorghe Marius , Snoeck Marc , Emmerich Michael , Bäck Thomas , Goeman Jelle J , Raz Vered 
Published: February 2014

AbstractBackgroundGenome-wide expression profiles are altered during biological aging and can describe molecular regulation of tissue degeneration. Age-regulated mRNA expression trends from cross-sectional studies could describe how aging progresses. We developed a novel statistical methodology to identify age-regulated expression trends in cross-sectional datasets.ResultsWe studied six cross-sectional RNA expression profiles from different human tissues. Our methodology, capable of overcoming technical and genetic background differences, identified an age-regulation in four of the tissues. For the identification of expression trends, five regression models were compared and the quadratic model was found as the most suitable for this study. Afterk-meansclustering of the age-associated probes, expression trends were found to change at two major age-positions in brain cortex and inVastus lateralismuscles. The first age-position was found to occur during the fifth decade and a later one during the eighth decade. In kidney cortex, however, only one age-position was identified correlating with a late age-position. Functional mapping of genes at each age-position suggests that calcium homeostasis and lipid metabolisms are initially affected and subsequently, in elderly mitochondria, apoptosis and hormonal signaling pathways are affected.ConclusionsOur results suggest that age-associated temporal changes in human tissues progress at distinct age-positions, which differ between tissues and in their molecular composition.
Dynamic comparison between Daan real-time PCR and Cobas TaqMan for quantification of HBV DNA levels in patients with CHB
Authors: Cai Shao-hang , Lv Fang-fang , Zhang Yong-hong , Jiang Ye-gui , Peng Jie 
Published: February 2014

Abstract

Background
Hepatitis B virus (HBV) DNA levels are crucial for managing chronic hepatitis B (CHB). It was unclear whether Daan real-time polymerase chain reaction test (Daan test) or COBAS TaqMan HBV DNA Test (Cobas TaqMan) was superior in measuring different HBV DNA levels in clinical specimens.

Methods
We enrolled 67 treatment-naïve, HBV surface antigen-positive CHB patients (high baseline viral levels) who received either lamivudine/adefovir or entecavir. Serum samples were tested at baseline and treatment week 24 using the Daan test and Cobas TaqMan.

Results
In the 67-baseline samples, the HBV DNA levels with the Cobas TaqMan (7.90 ± 0.73 log10 IU/mL) were significantly greater than those of the Daan test (7.11 ± 0.44 log10 IU/mL; P < 0.001). Of the 67 24-week samples (low viral levels), the Cobas TaqMan detected 59 (88.1%; 8 undetected); the Daan test detected 33 (49.3%; 34 undetected; P < 0.001). The Cobas TaqMan detected HBV DNA in 26 of 34 samples undetectable by the Daan test (range, 1.4–3.7 log10 IU/mL) or 38% of samples (26/67). The reductions in viral load after 24 weeks of oral antiviral treatment in the 33 samples that were positive for both the Daan test and the Cobas TaqMan test were significantly different (3.59 ± 1.11 log10 IU/mL versus 4.87 ± 1.58 log10 IU/mL, respectively; P = 0.001). Spearman correlation analysis showed positive correlation between results from two tests (rp = 0.602,P<0.001). The HBV genotypes and the anti-viral treatment did not affect the measurements of the HBV DNA by the Daan assay and the Cobas Taqman assay.

Conclusion
The Cobas Taqman was more sensitive at low viral loads than the Daan test and the change from complete to partial virological response could affect clinical decisions. The Cobas Taqman may be more appropriate for detection of HBV DNA levels.
The innervation of the human acetabular labrum and hip joint: an anatomic study
Authors: Alzaharani Abdullah , Bali Kamal , Gudena Ravi , Railton Pamela , Ponjevic Dragana , Matyas John R , Powell James N 
Published: February 2014

Abstract

Background
The aim of the current study was to evaluate the innervation of the acetabular labrum in the various zones and to understand its potential role in nociception and proprioception in hips with labral pathology.

Methods
A total of twenty hip labrums were tagged and excised intraoperatively from patients undergoing a total hip replacement. After preparation, the specimens were cut to a thickness of 10 μm and divided into four quadrants (zones) using a clock face pattern. Neurosensory structure distribution was then evaluated using Hematoxylin and Eosin (H and E), and immunoreactivity to S-100.

Results
All specimens had abundant free nerve endings (FNEs). These were seen predominantly superficially and on the chondral side of the labrum. In addition, predominantly three different types of nerve end organs (NEOs) were identified in all twenty specimens. FNEs and NEOs were more frequently seen in the antero-superior and postero-superior zones. Four specimens had abundant vascularity and disorganised architecture of FNEs in the deeper zones of the antero-superior quadrant suggestive of a healed tear. Myofibroblasts were present in abundance in all the labral specimens and were distributed uniformly throughout all labral zones and depth.

Conclusions
The current study shows that the human acetabular labrum has abundant FNEs and NEOs. These are more abundant in the antero-superior and postero-superior zones. The labrum, by virtue of its neural innervation, can potentially mediate pain as well as proprioception of the hip joint, and be involved in neurosecretion that can influence connective tissue repair.
Notch signaling during development requires the function of awd, the Drosophila homolog of human metastasis suppressor gene Nm23
Authors: Ignesti Marilena , Barraco Marilena , Nallamothu Gouthami , Woolworth Julie A , Duchi Serena , Gargiulo Giuseppe , Cavaliere Valeria , Hsu Tien 
Published: February 2014

Abstract

Background
The Drosophila abnormal wing discs (awd) belongs to a highly conserved family of genes implicated in metastasis suppression, metabolic homeostasis and epithelial morphogenesis. The cellular function of the mammalian members of this family, the Nm23 proteins, has not yet been clearly defined. Previous awd genetic analyses unraveled its endocytic role that is required for proper internalization of receptors controlling different signaling pathways. In this study, we analyzed the role of Awd in controlling Notch signaling during development.

Results
To study the awd gene function we used genetic mosaic approaches to obtain cells homozygous for a loss of function allele. In awd mutant follicle cells and wing disc cells, Notch accumulates in enlarged early endosomes, resulting in defective Notch signaling. Our results demonstrate that awd function is required before γ-secretase mediated cleavage since over-expression of the constitutively active form of the Notch receptor in awd mutant follicle cells allows rescue of the signaling. By using markers of different endosomal compartments we show that Notch receptor accumulates in early endosomes in awd mutant follicle cells. A trafficking assay in living wing discs also shows that Notch accumulates in early endosomes. Importantly, constitutively active Rab5 cannot rescue the awd phenotype, suggesting that awd is required for Rab5 function in early endosome maturation.

Conclusions
In this report we demonstrate that awd is essential for Notch signaling via its endocytic role. In addition, we identify the endocytic step at which Awd function is required for Notch signaling and we obtain evidence indicating that Awd is necessary for Rab5 function. These findings provide new insights into the developmental and pathophysiological function of this important gene family.
HPTN 071 (PopART): Rationale and design of a cluster-randomised trial of the population impact of an HIV combination prevention intervention including universal testing and treatment – a study protocol for a cluster randomised trial
Authors: Hayes Richard , Ayles Helen , Beyers Nulda , Sabapathy Kalpana , Floyd Sian , Shanaube Kwame , Bock Peter , Griffith Sam , Moore Ayana , Watson-Jones Deborah , Fraser Christophe , Vermund Sten H , Fidler Sarah ,   The HPTN 071 (PopART) Study Team
Published: February 2014

Abstract

Background
Effective interventions to reduce HIV incidence in sub-Saharan Africa are urgently needed. Mathematical modelling and the HIV Prevention Trials Network (HPTN) 052 trial results suggest that universal HIV testing combined with immediate antiretroviral treatment (ART) should substantially reduce incidence and may eliminate HIV as a public health problem. We describe the rationale and design of a trial to evaluate this hypothesis.

Methods/Design
A rigorously-designed trial of universal testing and treatment (UTT) interventions is needed because: i) it is unknown whether these interventions can be delivered to scale with adequate uptake; ii) there are many uncertainties in the models such that the population-level impact of these interventions is unknown; and ii) there are potential adverse effects including sexual risk disinhibition, HIV-related stigma, over-burdening of health systems, poor adherence, toxicity, and drug resistance.
In the HPTN 071 (PopART) trial, 21 communities in Zambia and South Africa (total population 1.2 m) will be randomly allocated to three arms. Arm A will receive the full PopART combination HIV prevention package including annual home-based HIV testing, promotion of medical male circumcision for HIV-negative men, and offer of immediate ART for those testing HIV-positive; Arm B will receive the full package except that ART initiation will follow current national guidelines; Arm C will receive standard of care. A Population Cohort of 2,500 adults will be randomly selected in each community and followed for 3 years to measure the primary outcome of HIV incidence. Based on model projections, the trial will be well-powered to detect predicted effects on HIV incidence and secondary outcomes.

Discussion
Trial results, combined with modelling and cost data, will provide short-term and long-term estimates of cost-effectiveness of UTT interventions. Importantly, the three-arm design will enable assessment of how much could be achieved by optimal delivery of current policies and the costs and benefits of extending this to UTT.

Trial registration
ClinicalTrials.gov NCT01900977.
Lignans from the bark of Eucommia ulmoides inhibited Ang II-stimulated extracellular matrix biosynthesis in mesangial cells
Authors: Li Zhen-yu , Deng Xiao-lan , Huang Wei-hua , Li Ling , Li Hui , Jing Xian , Tian Ying-ying , Lv Pei-yu , Yang Tian-lun , Zhou Hong-hao , Ouyang Dong-sheng 
Published: February 2014

Abstract

Background
Tree bark of Eucommia ulmoides Oliv., (commonly well-known as “Du-zhong” in China), has been used to treat hypertension, hypercholesterolemia, hyperglycemia, hepatic fibrosis and renal injury. This study aims to investigate the effects of lignans extracted from the bark of Eucommia ulmoides Oliv. on Ang II-induced proliferation and extracellular matrix biosynthesis in rat mesangial cells.

Methods
Rat mesangial cells (RMCs) were cultured in vitro and divided into six groups (control, Ang II, losartan, and low, middle and high concentration lignans groups). RMC proliferation was measured by MTT assay. RT-qPCR and western blotting were used to detect mRNA and protein expression of collagen type I (Col I), collagen type III (Col III), collagen type IV (Col IV), fibronectin and aldose reductase (AR).

Results
Cellular proliferation induced by Ang II was significantly suppressed by Eucommia lignans of different concentrations (P = 0.034, P < 0.001, and P < 0.001). Treatment of cells with Ang II increased Col I, Col III, Col IV, and fibronectin mRNA expression, which was observed at the protein level (P < 0.001, P < 0.001, P = 0.004, and P = 0.004, respectively). The increased mRNA expression and protein levels of Col I, Col III, Col IV, and fibronectin were diminished remarkably with by treatment Eucommia lignans, and elevated AR expression stimulated by Ang II was significantly inhibited by Eucommia lignans.

Conclusions

Eucommia lignans (Du-zhong) inhibited Ang II-stimulated extracellular matrix biosynthesis in mesangial cells.
Association of anti-RNA polymerase III autoantibodies and cancer in scleroderma
Authors: Moinzadeh Pia , Fonseca Carmen , Hellmich Martin , Shah Ami A , Chighizola Cecilia , Denton Christopher P , Ong Voon H 
Published: February 2014

Abstract
Introduction
We assessed the profile and frequency of malignancy subtypes in a large single-centre UK cohort for patients with scleroderma (systemic sclerosis; SSc). We evaluated the cancer risk among SSc patients with different antibody reactivities and explored the temporal association of cancer with the duration between SSc onset and cancer diagnosis.

Methods
We conducted a retrospective study of a well-characterised cohort of SSc patients attending a large tertiary referral centre, with clinical data collected from our clinical database and by review of patient records. We evaluated development of all cancers in this cohort, and comparison was assessed with the SSc cohort without cancer. The effect of demographics and clinical details, including antibody reactivities, were explored to find associations relevant to the risk for development of cancer in SSc patients.

Results
Among 2,177 patients with SSc, 7.1% had a history of cancer, 26% were positive for anticentromere antibodies (ACAs), 18.2% were positive for anti-Scl-70 antibodies and 26.6% were positive for anti-RNA polymerase III (anti-RNAP) antibody. The major malignancy cancer subtypes were breast (42.2%), haematological (12.3%), gastrointestinal (11.0%) and gynaecological (11.0%). The frequency of cancers among patients with RNAP (14.2%) was significantly increased compared with those with anti-Scl-70 antibodies (6.3%) and ACAs (6.8%) (P < 0.0001 and P < 0.001, respectively). Among the patients, who were diagnosed with cancer within 36 months of the clinical onset of SSc, there were more patients with RNAP (55.3%) than those with other autoantibody specificities (ACA = 23.5%, P < 0.008; and anti-Scl-70 antibodies = 13.6%, P < 0.002, respectively). Breast cancers were temporally associated with onset of SSc among patients with anti-RNAP, and SSc patients with anti-RNAP had a twofold increased hazard ratio for cancers compared to patients with ACAs (P < 0.0001).

Conclusions
Our study independently confirms, in what is to the best of our knowledge the largest population examined to date, that there is an association with cancer among SSc patients with anti-RNAP antibodies in close temporal relationship to onset of SSc, which supports the paraneoplastic phenomenon in this subset of SSc cases. An index of cautious suspicion should be maintained in these cases, and investigations for underlying malignancy should be considered when clinically appropriate.
Anxiety symptoms, cerebral amyloid burden and memory decline in healthy older adults without dementia: 3-year prospective cohort study
Authors: Pietrzak Robert H. , Scott J. Cobb , Neumeister Alexander , Lim Yen Ying , Ames David , Ellis Kathryn A. , Harrington Karra , Lautenschlager Nicola T. , Szoeke Cassandra , Martins Ralph N. , Masters Colin L. , Villemagne Victor L. , Rowe Christopher C. , Maruff Paul 
Published: February 2014

SummaryAlthough beta-amyloid, anxiety and depression have been linked cross-sectionally to reduced memory function in healthy older adults without dementia, prospective data evaluating these associations are lacking. Using data from an observational cohort study of 178 healthy older adults without dementia followed for 3 years, we found that anxiety symptoms significantly moderated the relationship between beta-amyloid level and decline in verbal (Cohen's d = 0.65) and episodic (Cohen's d = 0.38) memory. Anxiety symptoms were additionally linked to greater decline in executive function, irrespective of beta-amyloid and other risk factors. These findings suggest that interventions to mitigate anxiety symptoms may help delay memory decline in otherwise healthy older adults with elevated beta-amyloid.
Socioeconomic status and survival among older adults with dementia and depression
Authors: Chen Ruoling , Hu Zhi , Wei Li , Wilson Kenneth 
Published: February 2014

BackgroundPeople from lower socioeconomic groups have a higher risk of mortality. The impact of low socioeconomic status on survival among older adults with dementia and depression remains unclear.AimsTo investigate the association between socioeconomic status and mortality in people with dementia and late-life depression in China.MethodUsing Geriatric Mental Status – Automated Geriatric Examination for Computer Assisted Taxonomy (GMS-AGECAT) we interviewed 2978 people aged ⩾60 years in Anhui, China. We characterised baseline socioeconomic status and risk factors and diagnosed 223 people with dementia and 128 with depression. All-cause mortality was followed up over 5.6 years.ResultsIndividuals with dementia living in rural areas had a three times greater risk of mortality (multivariate adjusted hazard ratio (HR) = 2.96, 95% CI 1.45–6.04) than those in urban areas, and for those with depression the HR was 4.15 (95% CI 1.59–10.83). There were similar mortality rates when comparing people with dementia with lowv.high levels of education, occupation and income, but individuals with depression with lowv.high levels had non-significant increases in mortality of 11%, 50% and 55% respectively.ConclusionsOlder adults with dementia and depression living in rural China had a significantly higher risk of mortality than urban counterparts. Interventions should be implemented in rural areas to tackle survival inequality in dementia and depression.