bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diffusion-weighted MR imaging of salivary glands with gustatory stimulation: comparison before and after radiotherapy
Authors: Zhang Yunyan , Ou Dan , Gu Yajia , He Xiayun , Peng Weijun , Mao Jian , Yue Lei , Shen Xigang 
Published: July 2013

Background Xerostomia is the most prominent complication in patients with head and neck carcinoma after radiotherapy (RT). Diffusion-weighted magnetic resonance imaging (DWI) with gustatory stimulation may contribute to the evaluation of salivary gland function. Purpose To investigate the value of DWI for quantifying physiological changes of the parotid gland during gustatory stimulation in patients before and after RT. Material and Methods Magnetic resonance imaging (MRI) was performed in 28 consecutive patients with nasopharyngeal carcinoma before and after RT and clinical xerostomia was also assessed. A DWI sequence was performed once at rest and continually repeated seven times during stimulation with ascorbic acid. Apparent diffusion coefficient (ADC) maps for parotid glands at different time points and the range of increase with stimulation were calculated. Paired two-tailed Student t tests were used to compare the ADC values before and after stimulation, and before and after RT. Results Before RT, the ADC showed an initial increase ( P < 0.001) and then fluctuated during stimulation. After RT, as the clinical xerostomia changed from Grade 0 to Grade 2, the mean ADC at rest increased compared with the pre-RT value ( P < 0.001). A similar response to stimulation was observed, but the range of increase between the maximum ADC during stimulation and the baseline value at rest was higher post-RT than pre-RT ( P = 0.022). The minimum ADC during stimulation was higher than the baseline value post-RT ( P = 0.028), but there was no difference pre-RT ( P = 0.603). Conclusion DWI combined with gustatory stimulation seems to display the physiological changes of the parotid gland following RT and may be a potential tool for non-invasively assessing salivary gland function.
Prospective Study of the Effect on Gait of a Two-Component Total Ankle Replacement
Authors: Choi Jae Hyuck , Coleman Scott C. , Tenenbaum Shay , Polo Fabian E. , Brodsky James W. 
Published: July 2013

Background: The purpose of this study was to evaluate the functional outcome as measured by prospective gait analysis of patients undergoing total ankle arthroplasty using a 2-component Salto Talaris total ankle prostheses with a fixed polyethylene bearing. Methods: Twenty-one patients with severe ankle arthritis who underwent unilateral total ankle arthroplasty using a 2-component Salto Talaris device with a fixed polyethylene bearing were studied prospectively. Mean age was 69 years in 16 female and 5 male patients, and mean follow-up was 37.2 (range, 24-50) months. Three-dimensional gait analysis was performed using a 12-camera digital-motion capture system preoperatively and repeated at a minimum of 2 years postoperatively. Temporospatial measurements included velocity, cadence, step length, and support times. Measured kinematic parameters included sagittal plane range of motion of the ankle, knee, and hip. Kinetic parameters included sagittal plane ankle power and ankle plantarflexion moment. Results: There was significant improvement in temporospatial parameters, including step length ( P = .014) and walking velocity, which increased from 0.9 to 1 m/s ( P = .01). Kinematic results showed sagittal plane range of motion of the ankle increased significantly from a mean of 15.8 degrees preoperatively to 20.6 degrees ( P = .00005) postoperatively with the increase occurring primarily in dorsiflexion. Kinetic results showed ankle peak power increased from a mean of 0.7 Nm/kg to 1.1 Nm/kg ( P = .004). Conclusions: A prospective study of gait in patients undergoing total ankle arthroplasty using a 2-component Salto Talaris device with a fixed polyethylene bearing showed, at midterm follow-up, significant improvements in multiple parameters of gait when compared to the patients’ own preoperative function. Level of Evidence: Level IV, prospective case series.
Modeling of experts’ divergent prior beliefs for a sequential phase III clinical trial
Authors: Moatti Marion , Zohar Sarah , Facon Thierry , Moreau Philippe , Mary Jean-Yves , Chevret Sylvie 
Published: July 2013

Background There have been few Bayesian analyses of phase III sequential clinical trials that model divergent expert opinions in a single distribution. Purpose We used modeling of experts’ opinions to perform additional Bayesian analyses of a randomized clinical trial (designed as a sequential trial), particularly when a bimodal shape is observed. We provide an illustrative example based on a randomized trial conducted in patients aged between 65 and 75 years with multiple myeloma as the case study. Methods The main endpoint of the trial was overall survival (OS). Prior distribution of the log hazard ratio of death in the experimental versus the control arm ([Formula: see text]) was constructed based on elicitation of experts using a mixture of normal distributions estimated by the Expectation–Maximisation (EM) algorithm. At each interim and terminal analysis, the posterior probability of [Formula: see text] and the resulting increases in median OS in the experimental arm compared to the control were computed. The results were compared to results obtained using either skeptical, enthusiastic, or a mixture of those priors. Finally, we discuss our results in light of the frequentist approach originally designed for the trial. Results A total of 39 experts reported their opinion on the median OS in the experimental arm compared to the median control survival of 30 months. The resulting pooled distribution of the log hazard ratios exhibited a bimodal profile. When the prior mixture of the normal distribution was fitted to the data sets from the experts, 44% of the experts’ opinions were optimistic and 56% were doubtful. At the final analysis, the percentage of doubting experts dropped to 18%. This corresponded to a posterior probability of an improved OS in the experimental arm compared to the control arm of at least 0.98, regardless of the prior. These findings are in agreement with the original conclusion of the trial regarding the beneficial effect of the experimental treatment in this population. Limitations Only 39 experts among the 120 questioned physicians responded to the inquiry. Our approach was hybrid because the prior mixture was estimated using the EM algorithm, and a full Bayesian approach may have been used. Conclusions Bayesian inference allows the quantification of increased survival in terms of probability distributions and provides investigators with an additional tool in the analysis of a randomized phase III clinical trial. Using a mixture of densities appears to be a promising strategy for incorporating the bimodal profile of prior opinion, with actualization of the two components along the trial as an illustration of the evolution of opinions as data are accumulated.
Prognostic value of miR-155 in individuals with monoclonal B-cell lymphocytosis and patients with B chronic lymphocytic leukemia
Authors: Ferrajoli Alessandra , Shanafelt Tait D. , Ivan Cristina , Shimizu Masayoshi , Rabe Kari G. , Nouraee Nazila , Ikuo Mariko , Ghosh Asish K. , Lerner Susan , Rassenti Laura Z. , Xiao Lianchun , Hu Jianhua , Reuben James M. , Calin Steliana , You M. James , Manning John T. , Wierda William G. , Estrov Zeev , O’Brien Susan , Kipps Thomas J. , Keating Michael J. , Kay Neil E. , Calin George A. 
Published: July 2013

Key Points
miR-155 levels are significantly and increasingly overexpressed as normal B cells progress to MBL and to CLL. Plasma levels of miR-155 before treatment were significantly lower in patients with CLL who experienced complete response than in all others.
NOTCH1, SF3B1, and TP53 mutations in fludarabine-refractory CLL patients treated with alemtuzumab: results from the CLL2H trial of the GCLLSG
Authors: Schnaiter Andrea , Paschka Peter , Rossi Marianna , Zenz Thorsten , Bühler Andreas , Winkler Dirk , Cazzola Mario , Döhner Konstanze , Edelmann Jennifer , Mertens Daniel , Kless Sabrina , Mack Silja , Busch Raymonde , Hallek Michael , Döhner Hartmut , Stilgenbauer Stephan 
Published: July 2013

Key Points
In the refractory cohort of the CLL2H trial PFS was significantly longer in patients with NOTCH1 mutation. SF3B1 mutation had no impact on response rates or survival times in fludarabine-refractory patients.
Chromosomal diversification and karyotype evolution of diploids in the cytologically diverse genus Prospero(Hyacinthaceae)
Authors: Jang Tae-Soo , Emadzade Khatere , Parker John , Temsch Eva M , Leitch Andrew R , Speta Franz , Weiss-Schneeweiss Hanna 
Published: July 2013

AbstractBackgroundProspero(Hyacinthaceae) provides a unique system to assess the impact of genome rearrangements on plant diversification and evolution. The genus exhibits remarkable chromosomal variation but very little morphological differentiation. Basic numbers ofx = 4, 5, 6 and 7, extensive polyploidy, and numerous polymorphic chromosome variants were described, but only three species are commonly recognized:P. obtusifolium,P. hanburyi, andP. autumnales.l., the latter comprising four diploid cytotypes. The relationship between evolutionary patterns and chromosomal variation in diploids, the basic modules of the extensive cytological diversity, is presented.ResultsEvolutionary inferences were derived from fluorescencein situhybridization (FISH) with 5S and 35S rDNA, genome size estimations, and phylogenetic analyses of internal transcribed spacer (ITS) of 35S rDNA of 49 diploids in the three species and all cytotypes ofP. autumnales.l. All species and cytotypes possess a single 35S rDNA locus, interstitial except inP. hanburyiwhere it is sub-terminal, and one or two 5S rDNA loci (occasionally a third inP. obtusifolium) at fixed locations. The localization of the two rDNA types is unique for each species and cytotype. Phylogenetic data in theP. autumnalecomplex enable tracing of the evolution of rDNA loci, genome size, and direction of chromosomal fusions: mixed descending dysploidy ofx = 7 tox = 6 and independently tox = 5, rather than successive descending dysploidy, is proposed.ConclusionsAll diploid cytotypes are recovered as well-defined evolutionary lineages. The cytogenetic and phylogenetic approaches have provided excellent phylogenetic markers to infer the direction of chromosomal change inProspero. Evolution inProspero, especially in theP. autumnalecomplex, has been driven by differentiation of an ancestral karyotype largely unaccompanied by morphological change. These new results provide a framework for detailed analyses of various types of chromosomal rearrangements and karyotypic variation in polyploids.
Adaptation of maize source leaf metabolism to stress related disturbances in carbon, nitrogen and phosphorus balance
Authors: Schlüter Urte , Colmsee Christian , Scholz Uwe , Bräutigam Andrea , Weber Andreas PM , Zellerhoff Nina , Bucher Marcel , Fahnenstich Holger , Sonnewald Uwe 
Published: July 2013

AbstractBackgroundAbiotic stress causes disturbances in the cellular homeostasis. Re-adjustment of balance in carbon, nitrogen and phosphorus metabolism therefore plays a central role in stress adaptation. However, it is currently unknown which parts of the primary cell metabolism follow common patterns under different stress conditions and which represent specific responses.ResultsTo address these questions, changes in transcriptome, metabolome and ionome were analyzed in maize source leaves from plants suffering low temperature, low nitrogen (N) and low phosphorus (P) stress. The selection of maize as study object provided data directly from an important crop species and the so far underexplored C4metabolism. Growth retardation was comparable under all tested stress conditions. The only primary metabolic pathway responding similar to all stresses was nitrate assimilation, which was down-regulated. The largest group of commonly regulated transcripts followed the expression pattern: down under low temperature and low N, but up under low P. Several members of this transcript cluster could be connected to P metabolism and correlated negatively to different phosphate concentration in the leaf tissue. Accumulation of starch under low temperature and low N stress, but decrease in starch levels under low P conditions indicated that only low P treated leaves suffered carbon starvation.ConclusionsMaize employs very different strategies to manage N and P metabolism under stress. While nitrate assimilation was regulated depending on demand by growth processes, phosphate concentrations changed depending on availability, thus building up reserves under excess conditions. Carbon and energy metabolism of the C4maize leaves were particularly sensitive to P starvation.
May early intervention with high dose intravenous immunoglobulin pose a potentially successful treatment for severe cases of tick-borne encephalitis?
Authors: Růžek Daniel , Dobler Gerhard , Niller Hans Helmut 
Published: July 2013

AbstractBackgroundArthropod-borne viral encephalitis of diverse origins shows similar clinical symptoms, histopathology and magnetic resonance imaging, indicating that the patho mechanisms may be similar. There is no specific therapy to date. However, vaccination remains the best prophylaxis against a selected few. Regardless of these shortcomings, there are an increasing number of case reports that successfully treat arboviral encephalitis with high doses of intravenous immunoglobulins.DiscussionTo our knowledge, high dose intravenous immunoglobulin has not been tested systematically for treating severe cases of tick-borne encephalitis. Antibody-dependent enhancement has been suspected, but not proven, in several juvenile cases of tick-borne encephalitis. Although antibody-dependent enhancement during secondary infection with dengue virus has been documented, no adverse effects were noticed in a controlled study of high dose intravenous immunoglobulin therapy for dengue-associated thrombocytopenia. The inflammation-dampening therapeutic effects of generic high dose intravenous immunoglobulins may override the antibody-dependent enhancement effects that are potentially induced by cross-reactive antibodies or by virus-specific antibodies at sub-neutralizing levels.SummaryAnalogous to the increasing number of case reports on the successful treatment of other arboviral encephalitides with high dose intravenous immunoglobulins, we postulate whether it may be possible to also treat severe cases of tick-borne encephalitis with high dose intravenous immunoglobulins as early in the course of the disease as possible.
Activation of AMPK inhibits cervical cancer cell growth through AKT/FOXO3a/FOXM1 signaling cascade
Authors: Yung Mingo Ming Ho , Chan David Wai , Liu Vincent Wing Sun , Yao Kwok-Ming , Ngan Hextan Yuen-Sheung 
Published: July 2013

Abstract

Background
Although advanced-stage cervical cancer can benefit from current treatments, approximately 30% patients may fail after definitive treatment eventually. Therefore, exploring alternative molecular therapeutic approaches is imperatively needed for this disease. We have recently shown that activation of AMP-activated protein kinase (AMPK), a metabolic sensor, hampers cervical cancer cell growth through blocking the Wnt/β-catenin signaling activity. Here, we report that activated AMPK (p-AMPK) also inhibits cervical cancer cell growth by counteracting FOXM1 function.

Methods
Effect of the activation of AMPK on FOXM1 expression was examined by hypoxia and glucose deprivation, as well as pharmacological AMPK activators such as A23187, AICAR and metformin. RT Q-PCR and Western blot analysis were employed to investigate the activities of AMPK, FOXM1 and AKT/FOXO3a signaling.

Results
Consistent with our previous findings, the activation of AMPK by either AMPK activators such as AICAR, A23187, metformin, glucose deprivation or hypoxia significantly inhibited the cervical cancer cell growth. Importantly, we found that activated AMPK activity was concomitantly associated with the reduction of both the mRNA and protein levels of FOXM1. Mechanistically, we showed that activated AMPK was able to reduce AKT mediated phosphorylation of p-FOXO3a (Ser253). Interestingly, activated AMPK could not cause any significant changes in FOXM1 in cervical cancer cells in which endogenous FOXO3a levels were knocked down using siRNAs, suggesting that FOXO3a is involved in the suppression of FOXM1.

Conclusion
Taken together, our results suggest the activated AMPK impedes cervical cancer cell growth through reducing the expression of FOXM1.
The utility of fat mass index vs. body mass index and percentage of body fat in the screening of metabolic syndrome
Authors: Liu Pengju , Ma Fang , Lou Huiping , Liu Yanping 
Published: July 2013

Abstract

Background
It has been well documented that obesity is closely associated with metabolic syndrome (MetS). Although body mass index (BMI) is the most frequently used method to assess overweightness and obesity, this method has been criticized because BMI does not always reflect true body fatness, which may be better evaluated by assessment of body fat and fat-free mass. The objective of this study was to investigate the best indicator to predict the presence of MetS among fat mass index, BMI and percentage of body fat (BF %) and determine its optimal cut-off value in the screening of MetS in practice.

Methods
A cross-sectional study of 1698 subjects (aged 20–79 years) who participated in the annual health check-ups was employed. Body composition was measured by bioelectrical impedance analysis (BIA). Fat mass index (FMI) was calculated. Sex-specific FMI quartiles were defined as follows: Q1: <4.39, Q2:4.39- < 5.65, Q3:5.65- < 7.03, Q4:≥7.03,in men; and Q1:<5.25, Q2:5.25- < 6.33, Q3:6.33- < 7.93,Q4:≥7.93, in women. MetS was defined by National Cholesterol Education Program/Adult Treatment Panel III criteria. The association between FMI quartiles and MetS was assessed using Binary logistic regression. Receiver operating curve(ROC) analysis was used to determine optimal cutoff points for BMI,BF% and FMI in relation to the area under the curve(AUC),sensitivity and specificity in men and women.

Results
The adjusted odds ratios (95% CI) for the presence of MetS in the highest FMI quartile versus lowest quartile were 79.143(21.243-294.852) for men( P < 0.01) and 52.039(4.144-653.436) for women( P < 0.01) after adjusting age, BMI, BF%, TC, LDL, CRP, smoking status and exercise status, and the odds ratios were 9.166(2.157-38.952) for men( P < 0.01) and 25.574(1.945-336.228) for women( P < 0.05) when WC was also added into the adjustment. It was determined that BMI values of 27.45 and 23.85 kg/m2, BF% of 23.95% and 31.35% and FMI of 7.00 and 7.90 kg/m2 were the optimal cutoff values to predict the presence of MetS among men and women according to the ROC curve analysis. Among the indicators used to predict MetS, FMI was the index that showed the greatest area under the ROC curve in both sexes.

Conclusions
Higher FMI levels appear to be independently and positively associated with the presence of MetS regardless of BMI and BF%. FMI seems to be a better screening tool in prediction of the presence of metabolic syndrome than BMI and percentage of body fat in men and women.
In vitro chloroquine resistance for Plasmodium vivax isolates from the Western Brazilian Amazon
Authors: Chehuan Yonne F , Costa Monica RF , Costa Jacqueline S , Alecrim Maria GC , Nogueira Fátima , Silveira Henrique , Brasil Larissa W , Melo Gisely C , Monteiro Wuelton M , Lacerda Marcus VG 
Published: July 2013

Abstract

Background
Chloroquine (CQ) and primaquine (PQ) are still the drugs of choice to treat Plasmodium vivax malaria in many endemic areas, Brazil included. There is in vivo evidence for the P. vivax resistance to CQ in the Brazilian Amazon, where the increase in the proportion of P. vivax malaria parallels the increase of unusual clinical complications related to this species. In this study, in vitro CQ and mefloquine (MQ)-susceptibility of P. vivax isolates from the Western Brazilian Amazon was tested using the double-site enzyme-linked lactate dehydrogenase immunodetection (DELI) assay.

Methods
A total of 112 P. vivax isolates were tested in vitro for CQ-susceptibility and out of these 47 were also tested for MQ-susceptibility. The DELI assay was used to detect P. vivax growth at 48-hour short-term culture in isolates with ring stages ranging from 50 to %. Each isolate was tested in triplicate and geometric means of IC50’s was obtained. Nineteen isolates were genetically characterized for pvdhfr, pvmrp1, pvmdr1 and pvdhps candidate genes likely related to CQ resistance (10 with IC50<40 nM and 9 with IC50 >100 nM).

Results
Twelve out of 112 isolates were considered resistant to CQ, resulting in 10.7% (IC95% 5.0-16.4), while 3 out of 47 (6.4%; IC95% 0.0-12.8) were resistant to MQ. A discrete correlation was observed between IC50’s of CQ and MQ (Spearman=0.294; p=0.045). For pvdhps gene, a non-synonymous mutation was found at codon 382 (S→C) in 5/8 CQ-sensitive samples and 1/9 CQ-resistant samples (p=0.027). The other molecular markers were not associated to CQ-susceptibility.

Conclusions

In vitro CQ-resistance estimated in this study, estimated by the DELI test, was very similar to that observed in clinical trials, suggesting that in vitro procedures developed by capable local laboratories are useful in the surveillance of CQ-resistance in the Amazon; concurrent Amazon P. vivax strains with both CQ and MQ resistance may be common; and a non-synonymous mutation at pvdhps codon 382 (S→C) was associated to in vitro susceptibility to CQ, needing further studies to be confirmed.
Age-associated alterations in γδ T-cells are present predominantly in individuals infected with Cytomegalovirus
Authors: Wistuba-Hamprecht Kilian , Frasca Daniela , Blomberg Bonnie , Pawelec Graham , Derhovanessian Evelyna 
Published: July 2013

AbstractBackgroundDespite the common perception that latent Cytomegalovirus (CMV) infection is usually symptom-free, emerging epidemiological evidence suggests that it may in fact be associated with higher mortality over extended follow-up. Mechanisms responsible for this potentially important effect are unclear. CMV infection is known to have a large impact on the distribution of T cell phenotypes, especially the accumulation of late-stage differentiated CD8+, as well as Vδ2-γδ T-cells, which are the main subset of γδ T-cells involved in anti-CMV immunity. Its impact on γδ T-cells in the aging context is less well-defined.ResultsHere, we investigated a group of healthy individuals aged between 21 and 89 years, in order to correlate the frequency and differentiation status of γδ T-cells with age. We found that these parameters were only marginally influenced by age, but were marked in people with a latent CMV infection. Thus, we observed a significant age-associated accumulation of late-differentiated T-cells within the Vδ2-population, but only in CMV-seropositive donors. There was also a strong trend towards reduced frequency of early-differentiated cells within the Vδ2-phenotype. Older people had significantly higher anti-CMV IgG titers, which in turn correlated significantly with a lower Vδ2+/Vδ2-ratio and a shift from early- to a late-differentiated Vδ2-T-cell phenotype.ConclusionsOur findings demonstrate a strong influence of CMV on γδ T-cells during human ageing, similar to that observed for αβ T-cells. Differences between donors of different ages are more marked in CMV-infected individuals. The biological implications of this potent age-associated CMV-mediated immune-modulation require clarification.