bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time-Degenerative Factors and the Risk of Hepatocellular Carcinoma after Antiviral Therapy among Hepatitis C Virus Patients: A Model for Prioritization of Treatment
Authors: Yu Ming-Lung , Huang Chung-Feng , Yeh Ming-Lun , Tsai Pei-Chien , Huang Ching-I. , Hsieh Meng-Hsuan , Hsieh Ming-Yen , Lin Zu-Yau , Chen Shinn-Cherng , Huang Jee-Fu , Dai Chia-Yen , Chuang Wan-Long 
Published: October 2016

Abstract
Purpose: Age and hepatic fibrosis are the factors that increase the risk of hepatocellular carcinoma over time. We aimed to explore their impact at the initiation of antiviral therapy on hepatocellular carcinoma among chronic hepatitis C (CHC) patients.
Experimental Design: A total of 1,281 biopsy-proven CHC patients receiving IFN-based therapy were followed for a mean period of 5.5 years.
Results: The 5-year cumulative incidence of hepatocellular carcinoma did not differ between non–sustained virological response (SVR) and SVR patients who were &lt;40 years old (7.7% vs. 0.5%, P = 0.1) but was significantly higher in non-SVR patients between 40 and 55 years old (18.0% vs. 1.3%, P &lt; 0.001) and &gt;55 years old (15.1% vs. 7.9%, P = 0.03). Compared with SVR, non-SVR was independently predictive of hepatocellular carcinoma in patients 40 to 55 years old [HR/95% confidence intervals (CI), 10.92/3.78–31.56; P &lt; 0.001] and &gt;55 years old (HR/CI, 1.96/1.06–3.63; P = 0.03) but not in patients &lt;40 years old (HR/CI, 2.76/0.41–18.84; P = 0.3). The 5-year cumulative incidence of hepatocellular carcinoma did not differ between non-SVR and SVR patients whose fibrosis stage was F0–1 (4.6% vs. 1.9%, P = 0.25) but was higher in non-SVR patients with F2–3 (21.4% vs. 4.3%, P &lt; 0.001) or F4 (33.5% vs. 8.4%, P = 0.002). Compared with SVR, non-SVR was independently predictive of hepatocellular carcinoma in patients with F2–3 (HR/CI, 4.36/2.10–9.03; P &lt; 0.001) and F4 (HR/CI, 3.84/1.59–9.30; P = 0.03) but not in those with F0–1 (HR/CI, 1.53/0.49–4.74; P = 0.47).
Conclusions: Delayed hepatitis C virus clearance for patients with CHC &gt;40 years old or with a fibrosis stage &gt;2 increases the risk of hepatocellular carcinoma over time. Clin Cancer Res; 23(7); 1690–7. ©2016 AACR.
Identifying patients at high risk of heparin-induced thrombocytopenia-associated thrombosis with a platelet activation assay using flow cytometry
Authors: Maeda Takuma , Nakagawa Katsura , Murata Kuniko , Kanaumi Yoshiaki , Seguchi Shu , Kawamura Shiori , Kodama Mayumi , Kawai Takeshi , Kakutani Isami , Ohnishi Yoshihiko , Kokame Koichi , Okazaki Hitoshi , Miyata Shigeki 
Published: October 2016

SummaryTo diagnose heparin-induced thrombocytopenia (HIT), detection of platelet-activating antibodies (HIT antibodies) is crucial. However, serum platelet activation profiles vary across patients and depend on test conditions. We evaluated the association between clinical outcomes and platelet-activating profiles assessed by a platelet microparticle assay (PMA), which detects activation of washed platelets induced by HIT antibodies, in 401 consecutive patients clinically suspected of having HIT. We made modifications to the assay, such as donor selection for washed platelets that increased sensitivity. Serum that activated platelets at a therapeutic (but not high) heparin concentration was defined as positive. Of these, serum that activated platelets within 30 minutes or in the absence of heparin was defined as strongly positive. The remaining samples were considered weakly positive. As a result, 97 % and 93 % of patients who tested strongly and weakly positive had clinical profiles consistent with HIT, respectively. The incidence of thromboembolic events (TEEs) after heparin exposure in patients who tested strongly positive, weakly positive, and negative was 61 %, 40 %, and 29 %, respectively. Among patients who did not experience a TEE on the day HIT was suspected, there was no significant difference in the cumulative incidence of subsequent TEEs between patients who tested strongly and weakly positive when argatroban was initiated on the same day (19.0 % vs 7.1 %, p=0.313), but there was a significant difference when argatroban therapy was delayed by one or more days (61.1 % vs 17.6 %, p=0.007). The modified PMA is effective in diagnosing HIT and identifying patients at high risk for HIT-associated TEEs.Supplementary Material to this article is available online at www.thrombosis-online.com.
A Magnetic Resonance Imaging–Conditional External Cardiac Defibrillator for Resuscitation Within the Magnetic Resonance Imaging Scanner Bore
Authors: Schmidt Ehud J. , Watkins Ronald D. , Zviman Menekhem M. , Guttman Michael A. , Wang Wei , Halperin Henry A. 
Published: October 2016

Background—
Subjects undergoing cardiac arrest within a magnetic resonance imaging (MRI) scanner are currently removed from the bore and then from the MRI suite, before the delivery of cardiopulmonary resuscitation and defibrillation, potentially increasing the risk of mortality. This precludes many higher-risk (acute ischemic and acute stroke) patients from undergoing MRI and MRI-guided intervention. An MRI-conditional cardiac defibrillator should enable scanning with defibrillation pads attached and the generator ON, enabling application of defibrillation within the seconds of MRI after a cardiac event. An MRI-conditional external defibrillator may improve patient acceptance for MRI procedures.

Methods and Results—
A commercial external defibrillator was rendered 1.5 Tesla MRI-conditional by the addition of novel radiofrequency filters between the generator and commercial disposable surface pads. The radiofrequency filters reduced emission into the MRI scanner and prevented cable/surface pad heating during imaging, while preserving all the defibrillator monitoring and delivery functions. Human volunteers were imaged using high specific absorption rate sequences to validate MRI image quality and lack of heating. Swine were electrically fibrillated (n=4) and thereafter defibrillated both outside and inside the MRI bore. MRI image quality was reduced by 0.8 or 1.6 dB, with the generator in monitoring mode and operating on battery or AC power, respectively. Commercial surface pads did not create artifacts deeper than 6 mm below the skin surface. Radiofrequency heating was within US Food and Drug Administration guidelines. Defibrillation was completely successful inside and outside the MRI bore.

Conclusions—
A prototype MRI-conditional defibrillation system successfully defibrillated in the MRI without degrading the image quality or increasing the time needed for defibrillation. It can increase patient acceptance for MRI procedures.
On the Life Cycle of Individual Contrails and Contrail Cirrus
Authors: Schumann Ulrich , Heymsfield Andrew J. 
Published: October 2016

Abstract
The life cycle of individual (initially line shaped) contrails behind aircraft and of contrail cirrus (aged contrails mixed with other ice clouds) is described. The full contrail life cycle is covered, from ice formation for given water, heat, and particulate emissions; to changes in the jet, wake, and dispersion phases; through final sublimation or sedimentation. Contrail properties are deduced from various in situ, remote sensing, and model studies. Aerodynamically induced contrails and distrails are explained briefly. Contrails form both in clear air and inside cirrus. Young contrails consume most of the ambient ice supersaturation. Optical properties of contrails are age and humidity dependent. Contrail occurrence and radiative forcing depends on the ambient Earth–atmosphere conditions. Contrail cirrus seems to be optically thicker than assessed previously and may not only increase cirrus coverage but also thicken existing cirrus. Some observational constraints for contrail cirrus occurrence and radiative forcing are derived. Key parameters controlling contrail properties—besides aircraft and fuel properties, ambient pressure, temperature, and humidity—are the number of ice particles per flight distance surviving the wake vortex phase, the contrail depth, and particle sedimentation, wind shear, turbulence, and vertical motions controlling contrail dispersion. The climate impact of contrails depends among other things on the ratio of shortwave to longwave radiative forcing (RF) and on the efficacy with which contrail RF contributes to surface warming. Several open issues are identified, including renucleation from residuals of sublimated contrail ice particles.
Elevated serum DAND5 is associated with metastasis and predicts poor prognosis in colorectal cancer
Authors: Miao Xiaofei , Zhang Ye , Sun Jialin , Cui Songkui , Meng Qingyang , Zhu Kuiyu , Hu Xingqian , Wang Tong 
Published: October 2016

BackgroundThe biologic and clinical significance of DAND5 remains unknown in colorectal cancer (CRC).ObjectiveHerein, we investigated the function of DAND5 and evaluated its clinical significance in both serum and matched primary tumors in patients with CRC.MethodsThe role of DAND5 was explored in CRC cells and clinical significance of DAND5 was investigated in CRC patients (n  = 217) and healthy controls (n  = 63).ResultsKnockdown of DAND5 significantly decreased CRC cell proliferation, migration and invasion partly associated with epithelial–mesenchymal transition phenotype. Serum DAND5 levels in CRC were significantly higher than in normal controls and accurately distinguished CRC from healthy subjects. High serum DAND5 levels were significantly correlated with tumor differentiation, large tumor size, advanced Tumor Node Metastasis (TNM) stage, lymph node and liver metastasis, high carcinoembryonic antigen level, recurrence, poor overall and disease‐free survival. Serum DAND5 level, together with lymph node metastasis, were independent prognostic factors for CRC patients. High DAND5 protein expression in CRC tissues was increased according to TNM stage. A significant positive correlation existed between serum DAND5 levels and matched DAND5 expression in CRC tissues.ConclusionOur data provide novel evidence for the clinical significance of DAND5 as a potential biomarker for CRC prognosis.
Establishing human leukemia xenograft mouse models by implanting human bone marrow–like scaffold-based niches
Authors: Antonelli Antonella , Noort Willy A. , Jaques Jenny , de Boer Bauke , de Jong-Korlaar Regina , Brouwers-Vos Annet Z. , Lubbers-Aalders Linda , van Velzen Jeroen F. , Bloem Andries C. , Yuan Huipin , de Bruijn Joost D. , Ossenkoppele Gert J. , Martens Anton C. M. , Vellenga Edo , Groen Richard W. J. , Schuringa Jan Jacob 
Published: October 2016

Key Points
Humanized niche xenograft mouse models were generated that enabled engraftment of patients’ leukemia cells covering all risk groups. Self-renewal was better maintained in the humanized niches as determined by serial transplantation and genome-wide transcriptome studies.
The prognostic value of multiparametric flow cytometry in AL amyloidosis at diagnosis and at the end of first-line treatment
Authors: Muchtar Eli , Jevremovic Dragan , Dispenzieri Angela , Dingli David , Buadi Francis K. , Lacy Martha Q. , Gonsalves Wilson , Hayman Suzanne R. , Kapoor Prashant , Leung Nelson , Russell Stephen , Lust John A. , Lin Yi , Go Ronald S. , Chakraborty Rajshekhar , Zeldenrust Steven , Kumar Shaji K. , Kyle Robert A. , Rajkumar S. Vincent , Gertz Morie A. 
Published: October 2016

Key PointsThe monotypic and polytypic PC compartments assessed by MFC are prognostic in AL amyloidosis. MFC may play a role in the definition of hematologic response to treatment.
Extending digital PCR analysis by modelling quantification cycle data
Authors: Wilson Philip J. , Ellison Stephen L. R. 
Published: October 2016

Abstract
Background
Digital PCR (dPCR) is a technique for estimating the concentration of a target nucleic acid by loading a sample into a large number of partitions, amplifying the target and using a fluorescent marker to identify which partitions contain the target. The standard analysis uses only the proportion of partitions containing target to estimate the concentration and depends on the assumption that the initial distribution of molecules in partitions is Poisson. In this paper we describe a way to extend such analysis using the quantification cycle (Cq) data that may also be available, but rather than assuming the Poisson distribution the more general Conway-Maxwell-Poisson distribution is used instead.

Results
A software package for the open source language R has been created for performing the analysis. This was used to validate the method by analysing Cq data from dPCR experiments involving 3 types of DNA (attenuated, virulent and plasmid) at 3 concentrations. Results indicate some deviation from the Poisson distribution, which is strongest for the virulent DNA sample. Theoretical calculations indicate that the deviation from the Poisson distribution results in a bias of around 5 % for the analysed data if the standard analysis is used, but that it could be larger for higher concentrations. Compared to the estimates of subsequent efficiency, the estimates of 1st cycle efficiency are much lower for the virulent DNA, moderately lower for the attenuated DNA and close for the plasmid DNA. Further method validation using simulated data gave results closer to the true values and with lower standard deviations than the standard method, for concentrations up to approximately 2.5 copies/partition.

Conclusions
The Cq-based method is effective at estimating DNA concentration and is not seriously affected by data issues such as outliers and moderately non-linear trends. The data analysis suggests that the Poisson assumption of the standard approach does lead to a bias that is fairly small, though more research is needed. Estimates of the 1st cycle efficiency being lower than estimates of the subsequent efficiency may indicate samples that are mixtures of single-stranded and double-stranded DNA. The model can reduce or eliminate the resulting bias.
Essential role for the histone acetyltransferase KAT7 in T cell development, fitness, and survival
Authors: Newman Dane M , Voss Anne K , Thomas Tim , Allan Rhys S 
Published: October 2016

Abstract
Histone acetylation has an important role in gene regulation, DNA replication, and repair. Because these processes are central to the development of the immune system, we investigated the role of a previously unstudied histone acetyltransferase named KAT7 (also known as Myst2 or HBO1) in the regulation of thymopoiesis and observed a critical role in the regulation of conventional and innate-like T cell development. We found that KAT7-deficient thymocytes displayed normal, positive selection and development into mature single-positive αβ thymocytes; however, we observed few peripheral CD4+ or CD8+ T cells. The observed effects did not appear to arise from alterations to DNA replication, the TCR repertoire, or a block in thymocyte maturation and, more likely, was linked to survival defects related to gene deregulation because KAT7 deficiency led to an almost complete and specific loss of global histone-H3 lysine 14 acetylation (H3K14ac). Overall, we demonstrated a nonredundant role for KAT7 in the maintenance of H3K14ac, which is intimately linked with the ability to develop a normal immune system.
Galectin-3–null mice display defective neutrophil clearance during acute inflammation
Authors: Wright Rachael D , Souza Patricia R , Flak Magdalena B , Thedchanamoorthy Prasheetha , Norling Lucy V , Cooper Dianne 
Published: October 2016

Abstract
Galectin-3 has been associated with a plethora of proinflammatory functions because of its ability, among others, to promote neutrophil activation and because of the reduction in neutrophil recruitment in models of infection in Gal-3-null mice. Conversely, it has also been linked to resolution of inflammation through its actions as an opsonin and its ability to promote efferocytosis of apoptotic neutrophils. Using a self-resolving model of peritonitis, we have addressed the modulation and role of Gal-3 in acute inflammation. We have shown that Gal-3 expression is increased in neutrophils that travel to the inflamed peritoneum and that cellular localization of this lectin is modulated during the course of the inflammatory response. Furthermore, neutrophil recruitment to the inflamed peritoneum is increased in Gal-3–null mice during the course of the response, and that correlates with reduced numbers of monocytes/macrophages in the cavities of those mice, as well as reduced apoptosis and efferocytosis of Gal-3–null neutrophils. These data indicate a role for endogenous Gal-3 in neutrophil clearance during acute inflammation.
A Comparison Between the Conventional and the Laryngoscope-Assisted Lightwand Intubation Techniques in Patients With Cervical Immobilization: A Prospective Randomized Study
Authors: Kim Eugene , Kim Byung-Gun , Lim Young-Jin , Jeon Young-Tae , Hwang Jung-Won , Lee Seo-Yun , Park Hee-Pyoung 
Published: October 2016

BACKGROUND:
Positioning of a lightwand in the midline of the oral cavity can be challenging in patients with cervical immobilization. Direct laryngoscopy may permit the lightwand tip to more easily access the glottic opening. We tested our hypothesis that a laryngoscope-assisted lightwand technique allows more successful endotracheal intubation than does a conventional lightwand approach.

METHODS:
A total of 162 patients requiring cervical immobilization during intubation for cervical spine surgery were allocated randomly to 2 groups. The conventional lightwand technique (group C, n = 80) or the laryngoscope-assisted lightwand technique (group L, n = 82) was used for endotracheal intubation. In the group L, a Macintosh laryngoscope was inserted into the oral cavity, advanced until the epiglottis tip was visible, but not used to lift the epiglottis tip. The lightwand tip was placed below the epiglottis under direct view of the epiglottis tip. The primary outcome (the initial intubation success rate) and secondary outcomes (intubation time, hemodynamic changes, and postoperative airway complications) were evaluated.

RESULTS:
The initial intubation success rate was significantly lower (75% vs 89%; relative risk [95% confidence interval]: 1.2 [1.0–1.4]; P = .034) in group C than group L. The intubation time (22 ± 13 vs 24 ± 12 seconds; mean difference [98.33% confidence interval]: 2.4 [−2.3 to 7.2]; P = .217) did not differ between groups. Postoperative sore throat score, incidences of hypertension and tachycardia, postoperative oral mucosal bleeding, and hoarseness also did not differ between groups.

CONCLUSIONS:
Laryngoscope-assisted lightwand intubation did not increase intubation time, and it increased first attempt intubation rates compared with traditional lightwand intubation in patients requiring cervical immobilization for cervical spine surgery.
Cost analysis of cetuximab (Erbitux) plus radiotherapy (ERT) versus concomitant cisplatin plus radiotherapy (CRT) within an NHS oncology unit (single institution): a pilot study
Authors: Caroline Brammer , Sundus Yahya , Dawn Dawson , Carol Glaister , Susan Merrick 
Published: October 2016

Objective:
The aim of this feasibility study is to define the resource effectiveness of cetuximab vs cisplatin given concomitantly with radiotherapy for squamous cell carcinoma within a National Health Service clinical oncology unit.

Methods:
20 patients with Stage 3 or 4 head and neck squamous cell cancers were randomized to receive either cetuximab with radiotherapy (ERT) or cisplatin with radiotherapy concurrent with external beam radiotherapy 70 Gy in 35 fractions on a 1 : 1 basis over a 12-month duration. The study compared the resource utilization of ERT vs cisplatin with radiotherapy taking into account drug costs, clinical management and the costs of managing treatment-related toxicity from first fraction of radiotherapy to 6 months after the completion of therapy. Outcome measures were quality of life (recorded at the entry, end of radiotherapy, 6 weeks post treatment and 6 months post treatment), admissions to hospital, delays to radiotherapy, locoregional control and survival.

Results:
Total drug costs including cost of nutritional supplements for patients treated with cetuximab were £7407.45 compared with £3959.07 for patients treated with cisplatin. Unscheduled admissions for toxicity management were significantly more common in the ERT arm. Healthcare personnel spent significantly more time delivering unscheduled outpatient care for patients receiving cisplatin than for those receiving cetuximab (p = 0.01). No significant difference in the quality of life was suggested at baseline, 6 weeks and 6 months. The mean time to removal of percutaneous gastrostomy (PEG) after completion of radiotherapy was 49.7 weeks in the cisplatin arm and 18.5 weeks in the cetuximab arm (p = 0.04). There was a statistically significant difference in patient-reported use of PEG between the cisplatin and cetuximab arms at 6 months following completion of treatment (p = 0.04). At 21 months, overall survival was 80% in the cisplatin arm vs 50% in the cetuximab (p = 0.332), with disease-free survival being 80% in the cisplatin arm vs 40% in the cetuximab (p = 0.097).

Conclusion:
Cetuximab is still more expensive in simple drug cost terms than cisplatin when delivered with radiotherapy taking into account costs of drugs for toxicity management and nutritional supplements but other resource implications such as inpatient admission, time spent delivering unscheduled care and cost of additional investigations to manage toxicity for patients treated with cisplatin significantly reduce differential. The study suggested significant differences in patient-reported PEG use at 6 months and in time to PEG removal in favour of the cetuximab arm.

Advances in knowledge:
There is paucity of randomized data on cost analysis for cisplatin vs cetuximab radiotherapy; this trial informs on the cost analysis between the two approaches.