bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hemodynamic effect of external counterpulsation is a different measure of impaired cerebral autoregulation from vasoreactivity to breath‐holding
Authors: Lin W. , Xiong L. , Han J. , Leung T. , Leung H. , Chen X. , Wong K. S. L. 
Published: December 2013

Background and purposeExternal counterpulsation (ECP) is a novel method to increase cerebral blood flow, which may benefit acute ischaemic stroke patients. Our aim was to identify whether the hemodynamic effect of ECP is associated with cerebral vasoreactivity to breath‐holding.MethodsThirty‐seven recent ischaemic stroke patients with large artery steno‐occlusive disease were recruited together with 20 healthy controls. All underwent ECP treatment and a breath‐holding test combined with transcranial Doppler monitoring on bilateral middle cerebral arteries was performed. The data of the stroke patients were designated as ipsilateral or contralateral based on the side of the infarct, whilst the average of both sides was used in controls. The cerebral augmentation index (CAI) was used to evaluate the augmentation effects of ECP. Cerebral vasoreactivity was assessed by using the breath‐holding index (BHI).ResultsMiddle cerebral artery mean flow velocities significantly increased in the stroke group after ECP but not in controls. BHIs were much smaller in the stroke group than in the controls. The CAI did not correlate with the BHI in either the ipsilateral or contralateral side of the stroke group or in controls. For stroke patients, BHI was significantly lower on the ipsilateral side than the contralateral side, but the CAI showed no difference between the two cerebral hemisphere sides. The CAI of stroke patients was significantly related to mean blood pressure change on the ipsilateral side.ConclusionThe dynamic augmentation effects of ECP as measured by the CAI were different from the well established vasoreactivity to breath‐holding. The CAI is suggested as a measure of how well the brain accommodates blood flow augmentation during ECP.
Genetic assessment of familial and early‐onset Parkinson's disease in a Greek population
Authors: Bozi M. , Papadimitriou D. , Antonellou R. , Moraitou M. , Maniati M. , Vassilatis D. K. , Papageorgiou S. G. , Leonardos A. , Tagaris G. , Malamis G. , Theofilopoulos D. , Kamakari S. , Stamboulis E. , Hadjigeorgiou G. M. , Athanassiadou A. , Michelakakis H. , Papadimitriou A. , Gasser T. , Stefanis L. 
Published: December 2013

Background and purposeAlthough the first mutation associated with Parkinson's disease (PD) was identified several years ago in the alpha‐synuclein (SNCA) gene in families of Greek and Italian ancestry, a more systematic study of this and other known PD mutations has not been performed in the Greek population.MethodsA genetic analysis in 111 familial or sporadic with early‐onset (≤50 years, EO) PD patients was performed for the presence of the A53T SNCA mutation. In separate subgroups of these patients, further mutations in the SNCA, LRRK2, Parkin, PINK1 and DJ‐1 genes were searched for. Additionally, a subgroup of familial cases was analysed for mutations in the glucocerebrosidase (GBA) gene.ResultsIn total, five patients (4.5% of our whole population) were identified with the A53T SNCA mutation, two with a heterozygote dosage mutation and one with a heterozygote point mutation in the Parkin gene, and seven patients (10.3% of our familial cohort) with GBA gene mutations.ConclusionsThe A53T mutation in the SNCA gene, although uncommon, does represent a cause of PD in the Greek population, especially of familial EOPD with autosomal dominant inheritance. GBA mutations in the familial cohort tested here were as common as in a cohort of sporadic cases previously examined from the same centres. For the remainder of the genes, genetic defects that could definitively account for the disease were not identified. These results suggest that further Mendelian traits that lead to PD in the Greek population remain to be identified.
Hepatitis C viral infection and the risk of dementia
Authors: Chiu W.‐C. , Tsan Y.‐T. , Tsai S.‐L. , Chang C.‐J. , Wang J.‐D. , Chen P.‐C. ,   Health Data Analysis in Taiwan (hDATa) Research Group
Published: December 2013

Background and purposeHepatitis C virus (HCV) infection may cause cognitive impairment, but no studies have focused specifically on cognitive impairment stemming from HCV. The purpose of this study was to investigate the potential increased risk for dementia in HCV‐infected patients.MethodsA population‐based cohort study based on the Taiwan National Health Insurance Research Database was conducted. From all potential participants aged 50 years or more, a total of 58 570 matched (1:1) pairs of HCV‐infected patients and non‐HCV‐infected patients were included. Each subject was individually tracked from 1997 to 2009 to identify incident cases of dementia (onset in 1999 or later). Cox proportional hazards regressions were employed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HCV infection and dementia.ResultsThere were 2989 dementia cases from the HCV‐infected cohort during the follow‐up period of 533 861.1 person‐years; the overall incidence rates of dementia differed from the non‐HCV cohort (56.0 vs. 47.7 cases per 10 000 person‐years, P < 0.05). The adjusted HR for dementia was 1.36 (95% CI 1.27–1.42) for HCV‐infected patients after adjusting for alcohol‐related disease, liver cirrhosis, hepatic encephalopathy and hepatocellular carcinoma.ConclusionsHCV infection may increase the risk for dementia. Further mechanistic research is needed.
Compliant treatment with anti‐copper agents prevents clinically overt Wilson's disease in pre‐symptomatic patients
Authors: Dzieżyc K. , Karliński M. , Litwin T. , Członkowska A. 
Published: December 2013

Background and purposeWilson's disease (WD) is an inherited copper metabolism disorder that leads to dysfunction of affected tissues, mostly in the liver and brain. Anti‐copper treatment should prevent clinically overt WD in pre‐symptomatic patients but this has not been supported by strong evidence. Our aim was to evaluate the long‐term effectiveness of treatment in clinically pre‐symptomatic patients, with particular emphasis on patient compliance with treatment.MethodsData were analyzed for 87 consecutive patients with no clinical symptoms of WD who were identified between 1957 and 2009 by family screening. All of them since diagnosis were treated with either zinc sulphate (Zn) (66.7%) or D‐penicillamine (DPA) (33.3%).ResultsDuring a median follow‐up of 12 years (range 3–52), 55 (63%) patients remained without clinical symptoms, 13 (15%) developed neuropsychiatric symptoms and 21 (24%) developed hepatic dysfunction, including five deaths from hepatic failure. Non‐compliance for at least three consecutive months was observed in 39 patients, and in 29 cases this extended for more than 12 months. Multivariate analysis showed that the odds of developing symptomatic WD were independently increased by non‐compliance (odds ratio 24.0, 95% confidence interval 6.0–99.0). According to Kaplan–Meier analysis patients who were compliant to treatment had a significantly higher likelihood of remaining symptom‐free, and their overall survival was similar to the survival rate observed in the general population.ConclusionThe use of anti‐copper agents in clinically pre‐symptomatic patients diagnosed with WD allows clinically overt disease to be effectively prevented. However, compliance with therapy is extremely important.
Greater occipital nerve blocks in chronic cluster headache: a prospective open‐label study
Authors: Lambru G. , Abu Bakar N. , Stahlhut L. , McCulloch S. , Miller S. , Shanahan P. , Matharu M. S. 
Published: December 2013

Background and purposeGreater occipital nerve blockade (GONB) has been shown to be effective in episodic cluster headache. However, its use in chronic cluster headache (CCH) is less certain. The study aims to prospectively assess the efficacy and consistency of response to GONB in a large series of CCH patients.MethodsCCH patients who had a unilateral GONB and were referred to the National Hospital for Neurology and Neurosurgery were studied prospectively. Headache characteristics were collected using headache diaries. Responders were considered to be patients with a complete or partial response lasting at least 7 days. In a subgroup of responders the outcomes of serial GONB performed at 3‐monthly intervals were also analysed.ResultsEighty‐three CCH patients were studied. After the first GONB, a positive response was observed in 47 (57%) patients: 35 (42%) were rendered pain free, 12 (15%) had a partial benefit and one patient obtained <50% improvement. The duration of a positive response lasted a median of 21 days (range 7–504 days). There was a transient worsening of condition in 6% of patients. The overall rate and average duration of response remained consistent after the second [n = 37; 31 responders (84%); median duration 21 days], third [n = 28; 20 responders (71%); median duration 25 days] and fourth [n = 14; 10 responders (71%); median duration 23 days] injections.ConclusionGONB seems to be an efficacious treatment with reproducible effects in CCH patients. Performed three monthly, GONB may have a useful role in the management of CCH.
Temporal lobe surgery in Germany from 1988 to 2008: diverse trends in etiological subgroups
Authors: Helmstaedter C. , May T. W. , von Lehe M. , Pfaefflin M. , Ebner A. , Pannek H. W. , Elger C. E. , Stefan H. , Schramm J. 
Published: December 2013

Background and purposeIn the epilepsy community, there is talk that the number of classical patients with early onset temporal lobe epilepsy (TLE) and Ammon's horn sclerosis (AHS) is decreasing. This is counterintuitive, considering the success story of epilepsy surgery, improved diagnostic methods and the current recommendation of early admission to surgery. In order to recognize trends, the development of temporal lobe surgery over 20 years in three major German epilepsy centers was reviewed.MethodsAge at surgery and duration of epilepsy, which was differentiated according to histopathology (AHS, developmental, tumor, vascular), year of surgery and center, were evaluated in a cohort of 2812 patients from three German epilepsy centers who underwent temporal lobe surgery between 1988 and 2008. The analysis was carried out for the pooled cohort as well as for each center separately.ResultsOf all patients, 52% showed AHS. Compared with other pathologies, the AHS group had the earliest epilepsy onset and the longest duration of epilepsy. Across five time epochs, the diagnosis of AHS increased in the first epoch, remaining constant thereafter. Contrary to the trends in other pathologies, in the AHS group the mean age of patients at surgery increased by 7 years and the duration of epilepsy until surgery increased by 5 years. This trend could be replicated in all three centers. As initially hypothesized for all groups, age and duration of epilepsy in other pathology groups remained constant or indicated earlier submission to surgery.ConclusionsDuring the first few years studied, most probably due to progress in brain imaging, the proportion of patients with AHS increased. However, despite stable numbers over time, and contrary to the trends in other pathology groups, age and duration of epilepsy in mesial TLE with AHS (mTLE + AHS) increased over time. This supports the hypothesis of a decreasing incidence of AHS. This trend is discussed with respect to disease‐modifying factors which have changed the incidence of classical mTLE + AHS or, alternatively, to recent developments in antiepileptic drug treatment, the appraisal of surgery and economic incentives for treatment options other than surgery.
Dysarthria plus dysphagia is associated with severe sleep‐disordered breathing in patients with acute intracerebral hemorrhage
Authors: Shibazaki K. , Kimura K. , Aoki J. , Uemura J. , Fujii S. , Sakai K. 
Published: December 2013

Background and purposeSleep‐disordered breathing (SDB) is a risk factor for stroke. The frequency of SDB in Japanese patients with acute intracerebral hemorrhage (ICH) was investigated, as well as factors associated with SDB severity.MethodsBetween April 2010 and April 2013, patients with ICH within 24 h of onset were prospectively enrolled to participate in a sleep study within 7 days of admission. SDB was defined as a respiratory disturbance index (RDI: apnea or hypopnea events per hour) of ≥5. Patients were assigned to groups based on RDI values of ≥30 (severe SDB) and <30 (absent or not severe SDB). The frequency of SDB and factors associated with its severity were investigated using multivariate logistic regression analysis.ResultsOf 97 patients (55 males; mean age 68.1 years) enrolled in the study, 91 (94%) had SDB. Severe SDB was evident in 29 (30%) patients. Compared with the RDI< 30 group, the RDI≥ 30 group had a higher frequency of dysarthria plus dysphagia (76% vs. 47%, P = 0.008), larger waist circumference [86 (84–92) vs. 84 (78–88) cm, P = 0.019] and a greater body mass index [23.8 (21.1–26.8) vs. 21.5 (19.4–25.0) kg/m2, P = 0.046]. Multivariate logistic regression analysis showed that dysarthria plus dysphagia was independently associated with severe SDB (odds ratio 3.4; 95% confidence interval 1.250–9.252, P = 0.017).ConclusionMost Japanese patients with acute ICH had SDB, and dysarthria plus dysphagia was associated with severe SDB.
Dynamic interplay between autophagic flux and Akt during melanoma progression in vitro
Authors: Maes Hannelore , Martin Shaun , Verfaillie Tom , Agostinis Patrizia 
Published: December 2013

AbstractDespite advances in cancer diagnosis and therapy, metastatic melanoma remains untreatable, due to its notorious resistance to apoptosis, deeming traditional therapies obsolete. Deregulated PI3K/Akt signalling is a common oncogenic event enabling melanocyte transformation and represents a significant and ‘druggable’ pathway in melanoma. Emerging data show that the ability of cancer cells to survive is also facilitated by alteration of vital homoeostatic mechanisms, such as autophagy. Although the role of autophagy in melanoma is still controversial, recent studies suggest that basal autophagy is down‐modulated in primary melanomas. However, the dynamic connection between pro‐tumorigenic PI3K/Akt and autophagy during melanoma progression has not been systematically studied. By using human primary melanocytes, incipient melanoma and metastatic melanoma cell lines, we show that early in melanomagenesis, increased Akt activity is associated with a low baseline autophagic flux. However, during melanoma progression, metastatic melanoma cells regain the ability to stimulate autophagic flux, supporting survival. Heightened autophagy is associated with an attenuated Akt activation status and can be suppressed by overexpressing a constitutive active mutant of Akt. On the other hand, blocking the higher Akt activity of primary melanoma is sufficient to incite autophagy. Interestingly, we found that although Akt supports survival of melanocytes and all melanoma cell lines, autophagy inhibition specifically targeted the metastatic melanoma cells, thus indicating a stage‐specific requirement for Akt and autophagic flux, throughout melanoma progression. Therefore, this study highlights a dynamic interplay between Akt signalling and autophagic rescue in melanoma, which should be considered in the design of therapeutic strategies targeting these pathways.
Lack of expression of an alternative CD20 transcript variant in circulating B cells from patients with pemphigus
Authors: Gamonet Clémentine , Ferrand Christophe , Colliou Natacha , Musette Philippe , Joly Pascal , Girardin Marie , Humbert Philippe , Aubin François 
Published: December 2013

AbstractWe have identified a spliced mRNA transcript of CD20 (named D393‐CD20) which was associated with resistance to RTX in primary B cell from patients with lymphoma and leukaemia. In the present work, we wished to investigate whether D393‐CD20 variant was expressed by B cells from patients with pemphigus. Ten patients with bullous pemphigoid and twenty‐five patients with pemphigus were included. All patients were responder to conventional immunosuppressive agents or rituximab (n = 11). Efficacy of B‐cell activation by pokeweed mitogen was assessed by CD86 expression using a FACS Canto II flow cytometer. mRNA CD20 expression study was then performed using RT‐PCR assay allowing first to discriminate wild‐type (wt)‐CD20 and D393‐CD20 transcript. Although wt‐CD20 expression was always detected, we were unable to detect D393‐CD20, even after B‐cell activation or RTX treatment. Our results suggest that D393‐CD20 transcript may be a molecular marker of B‐cell malignancies rather than autoimmune disease like pemphigus. Further study of RTX non‐responders or non‐escaping PV patients is thus still required to appreciate whether D393‐CD20 expression may be detected under the pressure of RTX therapy.
Origin of Langerhans cells in normal skin and chronic GVHD after hematopoietic stem‐cell transplantation
Authors: Andani Rafiq , Robertson Ivan , MacDonald Kelli P. A. , Durrant Simon , Hill Geoffrey R. , Khosrotehrani Kiarash 
Published: December 2013

AbstractChronic graft‐versus‐host disease (cGVHD) is a common complication following allogeneic stem‐cell transplantation (SCT). Past studies have implicated the persistence of host antigen‐presenting cells (APCs) in GVHD. Our objective was to determine the frequency of host Langerhans cells (LCs) in normal skin post‐SCT and ask if their persistence could predict cGVHD. Biopsies of normal skin from 124 sex‐mismatched T‐cell‐replete allogenic SCT recipients were taken 100 days post‐transplant. Patients with acute GVHD and those with <9 months of follow‐up were excluded and prospective follow‐up information was collected from remaining 22 patients. CD1a staining and X and Y chromosome in‐situ hybridization were performed to label LCs and to identify their host or donor origin. At 3 months, 59 ± 5% of LCs were host derived. The density of LCs and the proportion of host‐derived LCs were similar between patients that did or did not develop cGVHD. Most LCs in the skin remained of host origin 3 months after SCT regardless of cGVHD status. This finding is in line with the redundant role of LCs in acute GVHD initiation uncovered in recent experimental models.
AML1–ETO triggers epigenetic activation of early growth response gene l, inducing apoptosis in t(8;21) acute myeloid leukemia
Authors: Fu Lin , Huang Wenrong , Jing Yu , Jiang Mengmeng , Zhao Yu , Shi Jinglong , Huang Sai , Xue Xue , Zhang Qingyi , Tang Juying , Dou Liping , Wang Lili , Nervi Clara , Li Yonghui , Yu Li 
Published: December 2013

The t(8;21)(q22;q22) translocation is the most common chromosomal translocation in acute myeloid leukemia (AML), and it gives rise to acute myeloid gene 1 (AML1)–myeloid transforming gene 8 (ETO)‐positive AML, which has a relatively favorable prognosis. However, the molecular mechanism related to a favorable prognosis in AML1–ETO‐positive AML is still not fully understood. Our results show that the AML1–ETO fusion protein triggered activation of early growth response gene l (EGR1) by binding at AML1‐binding sites on the EGR1 promoter and, subsequently, recruiting acetyltransferase P300, which is known to acetylate histones. However, AML1–ETO could not recruit DNA methyltransferases and histone deacetylases; therefore, EGR1 expression was affected by histone acetylation but not by DNA methylation. Both transcription and translation of EGR1 were higher in AML1–ETO‐positive AML cell lines than in AML1–ETO‐negative AML cell lines, owing to acetylation. Furthermore, when AML1–ETO‐positive AML cell lines were treated with C646 (P300 inhibitor) and trichostatin A (histone deacetylase inhibitor), EGR1 expression was significantly decreased and increased, respectively. In addition, treatment with 5‐azacytidine (methyltransferase inhibitor) did not cause any significant change in EGR1 expression. Overexpression of EGR1 inhibited cell proliferation and promoted apoptosis, and EGR1 knockout promoted cell proliferation. Thus, EGR1 could be a novel prognostic factor for a favorable outcome in AML1–ETO‐positive AML. The results of our study may explain the molecular mechanisms underlying the favorable prognosis in AML1–ETO‐positive AML.
Near‐threshold behaviour of shear‐mode fatigue cracks in metallic materials
Authors: Pokluda J. , Pippan R. , Vojtek T. , Hohenwarter A. 
Published: December 2013

ABSTRACTThis review paper presents a brief state‐of‐the art of the research on long fatigue shear‐mode cracks and describes some recent results on effective crack growth thresholds and mode I branching conditions achieved by the authors for ARMCO iron, titanium with two different microstructures, nickel and stainless steel. A special technique for preparation of fatigue precracks enabled us to substantially suppress the crack closure (friction) effects at the beginning of the experiment, and the measured threshold values could be considered to be very close to the effective ones. In all investigated materials, the effective thresholds under the remote mode II loading were found to be about 1.7 times lower than those under the remote mode III loading. Effective thresholds under mode II loading of investigated materials were found to follow a simple formula assembled by the shear modulus G, the magnitude of Burgers vector b and a goniometrical function nα of the mean deflection angle that depends on the number of available crystallographic slip systems. These quantities determine the intrinsic material resistance to mode II crack propagation at the threshold. A simple criterion for mode I branching in terms of effective threshold values well reflects a transition from the shear‐mode to the opening‐mode controlled crack propagation at the threshold. The associated transition deflection angle of 40° is a material independent constant.
Dynamic fracture behaviour of Fe78Si9B13 metallic glass ribbon under laser shock loading
Authors: Zheng C. , Sun S. , Ji Z. , Song L. , Zhang G. , Zhang J. 
Published: December 2013

ABSTRACTThe fracture behaviour of Fe78Si9B13 metallic glass under laser shock loading was investigated. Morphologies of the fracture surface and laser irradiated surface were characterized using scanning electron microscope. The results show that the fracture surface consists of sliding region and final fracture region with crack propagation. Liquid droplets and melted belts are scattered on the fracture surface as the notable features compared with fracture surface morphology under quasistatic loading, indicating the significant temperature increase in shear bands during dynamic loading. The primary and secondary shear bands are distributed on the specimen surface resulting from the simultaneous operation of multiple shear bands at high strain rates. Ripples with the characteristic spacing of about 1 µm are generated on the laser irradiated surface because of the interaction of laser pulse with solid surface.