bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonselective β‐blockers do not affect mortality in cirrhosis patients with ascites: Post Hoc analysis of three randomized controlled trials with 1198 patients
Authors: Bossen Lars , Krag Aleksander , Vilstrup Hendrik , Watson Hugh , Jepsen Peter
Published: November 2015

The safety of nonselective β‐blockers (NSBBs) in advanced cirrhosis has been questioned. We used data from three satavaptan trials to examine whether NSBBs increase mortality in cirrhosis patients with ascites. The trials were conducted in 2006‐2008 and included 1198 cirrhosis patients with ascites followed for 1 year. We used Cox regression to compare all‐cause mortality and cirrhosis‐related mortality between patients who did and those who did not use NSBBs at randomization, controlling for age, gender, Model for End‐Stage Liver Disease score, Child‐Pugh score, serum sodium, previous variceal bleeding, cirrhosis etiology, and ascites severity. Moreover, we identified clinical events predicting that a patient would stop NSBB treatment. At randomization, the 559 NSBB users were more likely than the 629 nonusers to have a history of variceal bleeding but less likely to have Child‐Pugh class C cirrhosis, hyponatremia, or refractory ascites. The 52‐week cumulative all‐cause mortality was similar in the NSBB user and nonuser groups (23.2% versus 25.3%, adjusted hazard ratio = 0.92, 95% confidence interval 0.72‐1.18), and NSBBs also did not increase mortality in the subgroup of patients with refractory ascites (588 patients, adjusted hazard ratio = 1.02, 95% confidence interval 0.74‐1.40) or in any other subgroup. Similarly, NSBBs did not increase cirrhosis‐related mortality (adjusted hazard ratio = 1.00, 95% confidence interval 0.76‐1.31). During follow‐up, 29% of initial NSBB users stopped taking NSBBs, and the decision to stop NSBB treatment marked a sharp rise in mortality and coincided with hospitalization, variceal bleeding, bacterial infection, and/or development of hepatorenal syndrome. Conclusion: This large and detailed data set on worldwide nonprotocol use of NSBBs in cirrhosis patients with ascites shows that NSBBs did not increase mortality; the decision to stop NSBB treatment in relation to stressful events may have added to the safety. (Hepatology 2016;63:1968‐1976)
The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota
Authors: Boursier Jérôme , Mueller Olaf , Barret Matthieu , Machado Mariana , Fizanne Lionel , Araujo‐Perez Felix , Guy Cynthia D. , Seed Patrick C. , Rawls John F. , David Lawrence A. , Hunault Gilles , Oberti Frédéric , Calès Paul , Diehl Anna Mae
Published: November 2015

Several animal studies have emphasized the role of gut microbiota in nonalcoholic fatty liver disease (NAFLD). However, data about gut dysbiosis in human NAFLD remain scarce in the literature, especially studies including the whole spectrum of NAFLD lesions. We aimed to evaluate the association between gut dysbiosis and severe NAFLD lesions, that is, nonalcoholic steatohepatitis (NASH) and fibrosis, in a well‐characterized population of adult NAFLD. Fifty‐seven patients with biopsy‐proven NAFLD were enrolled. Taxonomic composition of gut microbiota was determined using 16S ribosomal RNA gene sequencing of stool samples. Thirty patients had F0/F1 fibrosis stage at liver biopsy (10 with NASH), and 27 patients had significant F≥2 fibrosis (25 with NASH). Bacteroides abundance was significantly increased in NASH and F≥2 patients, whereas Prevotella abundance was decreased. Ruminococcus abundance was significantly higher in F≥2 patients. By multivariate analysis, Bacteroides abundance was independently associated with NASH and Ruminococcus with F≥2 fibrosis. Stratification according to the abundance of these two bacteria generated three patient subgroups with increasing severity of NAFLD lesions. Based on imputed metagenomic profiles, Kyoto Encyclopedia of Genes and Genomes pathways significantly related to NASH and fibrosis F≥2 were mostly related to carbohydrate, lipid, and amino acid metabolism. Conclusion: NAFLD severity associates with gut dysbiosis and a shift in metabolic function of the gut microbiota. We identified Bacteroides as independently associated with NASH and Ruminococcus with significant fibrosis. Thus, gut microbiota analysis adds information to classical predictors of NAFLD severity and suggests novel metabolic targets for pre‐/probiotics therapies. (Hepatology 2016;63:764–775)
Esophageal balloon tamponade versus esophageal stent in controlling acute refractory variceal bleeding: A multicenter randomized, controlled trial
Authors: Escorsell Àngels , Pavel Oana , Cárdenas Andrés , Morillas Rosa , Llop Elba , Villanueva Càndid , Garcia‐Pagán Juan C. , Bosch Jaime ,   ; for the Variceal Bleeding Study Group
Published: November 2015

Balloon tamponade is recommended only as a “bridge” to definitive therapy in patients with cirrhosis and massive or refractory esophageal variceal bleeding (EVB), but is frequently associated with rebleeding and severe complications. Preliminary, noncontrolled data suggest that a self‐expandable, esophageal covered metal stent (SX‐ELLA Danis; Ella‐CS, Hradec Kralove, Czech Republic) may be an effective and safer alternative to balloon tamponade. We conducted a randomized, controlled trial aimed at comparing esophageal stent versus balloon tamponade in patients with cirrhosis and EVB refractory to medical and endoscopic treatment. Primary endpoint was success of therapy, defined as survival at day 15 with control of bleeding and without serious adverse events (SAEs). Twenty‐eight patients were randomized to Sengstaken‐Blakemore tube (n = 15) or SX‐ELLA Danis stent (n = 13). Patients were comparable in severity of liver failure, active bleeding at endoscopy, and initial therapy. Success of therapy was more frequent in the esophageal stent than in balloon tamponade group (66% vs. 20%; P = 0.025). Moreover, control of bleeding was higher (85% vs. 47%; P = 0.037) and transfusional requirements (2 vs 6 PRBC; P = 0.08) and SAEs lower (15% vs. 47%; P = 0.077) in the esophageal stent group. TIPS was used more frequently in the tamponade group (4 vs. 10; P = 0.12). There were no significant differences in 6‐week survival (54% vs. 40%; P = 0.46). Conclusion: Esophageal stents have greater efficacy with less SAEs than balloon tamponade in the control of EVB in treatment failures. Our findings favor the use of esophageal stents in patients with EVB uncontrolled with medical and endoscopic treatment. (Hepatology 2016;63:1957‐1967)
Modeling Neuronal Pathology in Yeast: Insights into the Molecular Basis of Parkinson’s Disease
Authors: Amen Triana , Lázaro Diana F. , Outeiro Tiago F. , Kaganovich Daniel
Published: November 2015

The budding yeastSaccharomyces cerevisiaehas been extensively studied as a model organism for biochemical and genetic research for almost a century. In recent years, yeast has been successfully used to model many aspects of human diseases. These “humanized” yeast models have had a profound influence on our understanding of the molecular events underlying neurodegenerative disorders. Yeast models can recapitulate important molecular events that occur in neurodegeneration, and provide clues about the underpinnings of toxicity in animal models of disease. Moreover, yeast models have also served as a powerful tool for drug discovery. In this mini‐review, we describe yeast models that have been used to study the molecular aspects of Parkinson’s disease pathology and recent advances in the field based on these models.
Meis1 promotes poly (rC)‐binding protein 2 expression and inhibits angiotensin II‐induced cardiomyocyte hypertrophy
Authors: Zhang Yunjiao , Si Yi , Ma Nan
Published: November 2015

The poly(rC)‐binding protein 2 (PCBP2) is currently reported to inhibit cardiac hypertrophy. However, how PCBP2 is regulated at transcriptional level remains unknown. Here, we show that Meis1, a PBX1‐related homeobox gene, binds to PCBP2 promoter and promotes its transcription. In human failing heart tissues and murine hypertrophic heart tissues, the mRNA and protein levels of Meis1 are markedly downregulated, and the level of Meis1 significantly correlates with levels of Nppa, Myh7, and PCBP2. In neonatal rat cardiomyocytes, angiotensin II (Ang II) treatment induces hypertrophic growth of the cells (increase in cell size, enhanced protein synthesis, and hyperexpression of hypertrophic fetal genes), which are significantly inhibited by Meis1 overexpression or promoted by Meis1 knockdown. Meis1 also reduces Ang II‐induced activation of Akt‐mTOR pathway. Finally, we show that PCBP2 overexpression rescues the Meis1 effects of Akt‐mTOR pathway and hypertrophy of cardiomyocytes. © 2015 IUBMB Life, 68(1):13–22, 2016
100 years running: The need to understand why employee physical activity benefits organizations
Authors: Calderwood Charles , Gabriel Allison S. , Rosen Christopher C. , Simon Lauren S. , Koopman Joel
Published: November 2015

Employee physical activity initiatives are commonplace, but management scholarship has not kept pace with theoretical and empirical work to validate such initiatives. In this Incubator, we clarify the employee physical activity construct, present mechanisms linking physical activity to organizationally valued outcomes, and consider the dark side of employee physical activity initiatives. Copyright © 2015 John Wiley & Sons, Ltd.
Hypopharyngeal squamous cell carcinoma: Three‐dimensional or Intensity‐modulated radiotherapy? A single institution's experience
Authors: Katsoulakis Evangelia , Riaz Nadeem , Hu Man , Morris Luc , Sherman Eric , McBride Sean , Lee Nancy
Published: November 2015

Objectives/Hypothesis

Compare outcomes of hypopharyngeal carcinoma that received conventional radiotherapy versus intensity‐modulated radiotherapy (IMRT).

Study Design

Retrospective single‐institution trial.

Methods

Between April 1990 and May 2011, 100 patients with hypopharyngeal cancer underwent curative radiotherapy (RT) at our institution: 50 with IMRT and 50 with conventional RT. The median age was 63 years. There were 12 T1, 22 T2, 37 T3, and 28 T4 patients. The majority of patients (82%) had nodal disease: 54% N2 and 8% N3. The majority of patients (83%) received chemotherapy. Of the patients who received chemotherapy, 84% received a platinum‐based regimen. The median RT dose was 7,000 cGy. The majority of patients (62%) had prophylactic percutaneous endoscopic gastrostomy tube placement. Toxicities were reviewed. Local control (LC), locoregional control (LRC), freedom from distant metastasis (FFM) rates, functional larynx preservation (LP), laryngectomy‐free survival (LFS), and overall‐survival (OS) curves were generated using the Kaplan‐Meier method. The log‐rank test was used to test prognostic variables.

Results

With a median follow up of 48.4 months, the 3/5‐year LC, LRC, FFM, LP, LFS and OS rates were 74%/69%, 77%/74%, 70%/66%, 51%/29%, 49.6%/31.8%, and 49%/34%, respectively. The median OS was 2.9 years. The 3‐year LC rate for IMRT was 77% versus 81% for conventional RT (P = .91); 3‐year LRC for IMRT was 85% versus 76% for conventional RT (P = .32). There was no increased local failure with IMRT. There was no difference in the rate of stricture with IMRT (32%) versus conventional RT (25.3%) (P = .86).

Conclusions

IMRT achieved comparable LC and LRC rates to conventional RT.

Level of Evidence

4 Laryngoscope, 126:620–626, 2016
Human papillomavirus infection on initiating synchronous esophageal neoplasia in patients with head and neck cancer
Authors: Wang Wen‐Lun , Wang Yu‐Chi , Chang Chi‐Yang , Lo Jo‐Lin , Kuo Yao‐Hung , Hwang Tzer‐Zen , Wang Chih‐Chun , Mo Lein‐Ray , Lin Jaw‐Town , Lee Ching‐Tai
Published: November 2015

Objectives/Hypothesis

Human papillomavirus (HPV) is a risk factor for head and neck squamous cell carcinoma (HNSCC) as well as esophageal squamous cell carcinoma (ESCC). We aimed to investigate whether HPV infection underlies the field cancerization phenomenon over upper aerodigestive tract to develop synchronous multiple cancers.

Study Design

A case control study.

Methods

The presence and subtype of HPV‐DNA sequence in cancers were examined by polymerase chain reaction and sequencing in a prospective cohort with 100 HNSCCs, 50 of which had synchronous ESCCs. The clinicopathologic characteristics were further analyzed according to the presence of HPV.

Results

Twelve patients were HPV‐positive, of which 11 were positive for HPV‐16. The prevalence of HPV infection were not different between the synchronous and HNSCC alone groups (P = 0.357). Testing for HPV in paired HNSCC and ESCC tissues from the same patient revealed that none were concomitantly HPV‐positive. Multivariate logistic regression showed drinking alcohol (odds ratio [OR], 18.75; P = 0.030), alcohol flushing (OR, 2.53; P = 0.041), and body mass index (OR, 0.77; P = 0.001) but not HPV infection were independent risk factors for synchronous phenotype. The patients with synchronous ESCCs had significantly poorer survival than those with HNSCC alone (5‐year overall survival: 30% vs. 70%; log‐rank P < 0.001). However, patients with HPV‐positive HNSCC tend to have favorable outcome than those with HPV‐negative HNSCC.

Conclusions

HPV infection plays little role in field cancerization phenomenon to initiate synchronous SCC. The synchronous HNSCC and ESCC from the same patients had no clonal relationship. Routine endoscopic examination of the esophagus should be recommended for patients with risk factors identified.

Levels of Evidence

NA. Laryngoscope, 126:1097–1102, 2016
Combination of mTOR and EGFR targeting in an orthotopic xenograft model of head and neck cancer
Authors: Bozec Alexandre , Ebran Nathalie , Radosevic‐Robin Nina , Sudaka Anne , Monteverde Martino , Toussan Nicolas , Etienne‐Grimaldi Marie‐Christine , Nigro Cristiana Lo , Merlano Marco , Penault‐Llorca Frédérique , Milano Gérard
Published: November 2015

Objectives/Hypothesis

Recent preclinical and clinical studies on head and neck squamous cell carcinoma (HNSCC) revealed synergistic effects when combining anti‐EGFR agents with conventional chemotherapeutic drugs. Activation of the PI3‐kinase/AKT/mTOR signaling pathway has been identified as an important mechanism implicated in tumor progression and resistance to EGFR inhibitors. The aim of this study was to investigate the effects of combining the mTOR inhibitor temsirolimus (Tem) with the anti‐EGFR agent cetuximab (Cet) and conventional chemotherapeutic drugs (cisplatin and fluorouracil (C/F)) on an orthotopic model of HNSCC.

Study Design

Preclinical in vivo study.

Methods

We evaluated the anti‐tumor efficacy (measured tumor volume) of Tem, Cet, and C/F, administered alone or in combination. Investigations were performed using a human HNSCC cell line, CAL33, injected into the mouth floor of nude mice.

Results

As compared with the control, the combination of Tem and Cet led to the highest tumor inhibition and induced almost complete tumor growth arrest (P = 0.001). Tem significantly enhanced the impact of the Cet‐C/F combination on tumor growth (P < 0.001). The highest inhibitory effects of treatments on cell proliferation (Ki67 labeling), MAPK (pP42/44 labeling), and PI3K/AKT/mTOR (pS6R labeling) signaling pathways were found with the Tem‐Cet association.

Conclusion

In this orthotopic HNSCC model, the combination of Tem with Cet produced synergistic effects on tumor growth. These results were corroborated by a strong inhibition of both MAPK and PI3K‐mTOR signaling pathways.

Level of Evidence

N/A. Laryngoscope, 126:E156–E163, 2016
Early glottic cancer involving the anterior commissure treated by transoral laser cordectomy
Authors: Hoffmann Caroline , Cornu Nicolas , Hans Stéphane , Sadoughi Babak , Badoual Cécile , Brasnu Daniel
Published: November 2015

Objectives/Hypothesis

Anterior commissure involvement is considered to be a risk factor for poorer outcomes after transoral laser cordectomy (TLC) for early glottic cancer. The objective of this study was to determine the outcomes and relevance of the tumor‐node‐metastasis (TNM) classification in a large series of patients with early glottic cancer involving the anterior commissure treated by TLC.

Methods

The clinical and surgical parameters, as well as follow‐up results, of the patients treated consecutively for early‐stage glottic squamous cell carcinoma involving the anterior commissure (Tis, T1a, T1b, and T2) by transoral CO2 laser cordectomy in an urban academic medical center from January 2001 to March 2013 were analyzed retrospectively.

The main outcomes measures were: 5‐year disease free survival (DFS), ultimate local control with laser alone, laryngeal preservation, overall‐survival (OS) rates, and disease‐specific survival (DSS) rates (Kaplan‐Meier).

Results

Ninety‐six patients treated from January 2001 to March 2013 were included. The 5‐year DFS and ultimate local control with laser alone rates were 61.7% and 74.4%, respectively. The laryngeal preservation rate was 93.4%; and the OS and DSS rates were 79.2% and 91.5%, respectively. Postoperative T classification (pT) status was not found to be a significant predictor of recurrences, but was predictive of more severe recurrences requiring other treatments than laser.

Conclusion

TLC is an effective treatment for early stage glottic cancer involving the anterior commissure. The TNM classification is a relevant prognosis factor for severe recurrences.

Level of Evidence

4. Laryngoscope, 126:1817–1822, 2016
A comparison of Locacorten‐Vioform and clotrimazole in otomycosis: A systematic review and one‐way meta‐analysis
Authors: Herasym Khrystyna , Bonaparte James P. , Kilty Shaun
Published: November 2015

Objectives/Hypothesis

The goal of this systematic review was to compare the efficacy and ototoxicity of Locacorten‐Vioform (Paladin Labs Inc., Montreal, Quebec, Canada) and clotrimazole in the treatment of patients with otomycosis.

Data Sources

Embase, Cumulative Index to Nursing and Allied Health Literature, MEDLINE, World Health Organization International Clinical Trials Registry Platform, European Union Clinical Trials Register, Cochrane Library databases of clinical trials, and ClinicalTrials.gov.

Methods

We included any randomized controlled trials or nonrandomized studies (case‐control, cohort, and case series) assessing the topical use of Locacorten‐Vioform (Paladin Labs Inc.) and/or clotrimazole in adult and/or pediatric immunocompetent patient population with otomycosis. DerSimonian and Laird's random effects approach was used for meta‐analysis, followed by an assessment of heterogeneity and subgroup analysis.

Results

Of 226 reviewed articles, 14 were retained. Clotrimazole efficacy rate was 85% (95% confidence interval [CI]: 79.7–89.0%), whereas Locacorten‐Vioform (Paladin Labs Inc.) was 73% (95% CI: 56.0–84.5%). Overall, study quality was low. There was high heterogeneity in both groups (I2 of 47 and 49). There were only three studies assessing Locacorten‐Vioform (Paladin Labs Inc.); therefore, comparative assessment was not possible. A one‐way meta‐analysis involving 13 clotrimazole studies was performed. Heterogeneity across studies was high; however, studies using objective analysis assessing treatment efficacy, randomized controlled trials, studies using drops, studies performed in Asia, and studies where Candida was the major fungus at diagnosis demonstrated low heterogeneity.

Conclusion

Although both are safe and effective, there is insufficient evidence supporting increased efficacy of either clotrimazole or Locacorten‐Vioform (Paladin Labs Inc.) for the treatment of otomycosis. High‐quality comparative studies are required.

Level of Evidence

N/A. Laryngoscope, 126:1411–1419, 2016
Variation in costs among surgeons and hospitals in Pediatric tympanostomy tube placement
Authors: Sjogren Phayvanh P. , Gale Craig , Henrichsen Jacob , Olsen Griffin , Ott Mark J. , Peters Matthew , Srivastava Rajendu , Meier Jeremy D.
Published: November 2015

Objectives/Hypothesis

1) Identify the major expenses for outpatient pediatric tympanostomy tube placement in a multihospital network. 2) Compare differences for variations in costs among hospitals and surgeons.

Methods

An observational cohort study in a multihospital network using a standardized activity‐based accounting system to determine hospital costs for tympanostomy tube placement from February 2011 to January 2015. Children aged 6 months to less than 3 years old who underwent same‐day surgery (SDS) for tympanostomy tubes at 15 hospital facilities were included. Subjects with additional procedures were excluded. Hospital costs were subdivided into categories including operating room (OR), SDS preoperative, SDS postoperative, postanesthesia care unit, anesthesia, pharmacy, and OR supplies.

Results

The study cohort included 5,623 patients undergoing tympanostomy tube placement by 67 surgeons. Mean cost per surgery was $769 ± $3. Significant variations (P < 0.001) in mean cost per procedure were identified by hospital (range $1212 ± $38 to $509 ± $11) and by surgeon (range $1330 ± $75 to $660 ± $11). Operating room and SDS preoperative were the greatest expenditures; each category accounted for over 30% of overall costs. Pharmacy costs and OR costs were some of the major drivers of cost variation among surgeons.

Conclusion

This study demonstrates that OR and SDS preoperative costs accounted for the greatest expenditure in tympanostomy tube placement, and significant variation exists among surgeons and hospitals within a multihospital network. Further research is needed to elucidate factors accounting for such variation in cost and the overall impact on patient outcomes.

Level of Evidence

4. Laryngoscope, 126:1935–1939, 2016
Imaging of the internal nasal valve using long‐range Fourier domain optical coherence tomography
Authors: Englhard Anna S. , Wiedmann Maximilian , Ledderose Georg J. , Lemieux Bryan , Badran Alan , Chen Zhongping , Betz Christian S. , Wong Brian J.
Published: November 2015

Objectives/Hypothesis

To evaluate for the first time the feasibility and methodology of long‐range Fourier domain optical coherence tomography (LR‐OCT) imaging of the internal nasal valve (INV) area in healthy individuals.

Study Design

Prospective individual cohort study.

Methods

For 16 individuals, OCT was performed in each nare. The angle and the cross‐sectional area of the INV were measured. OCT images were compared to corresponding digital pictures recorded with a flexible endoscope.

Results

INV angle measured by OCT was found to be 18.3° ± 3.1° (mean ± standard deviation). The cross‐sectional area was 0.65 ± 0.23 cm2. The INV angle measured by endoscopy was 18.8° ± 6.9°. There was no statistically significant difference between endoscopy and OCT concerning the mean INV angle (P = .778), but there was a significant difference in test precision (coefficient of variance 50% vs. 15%; P < .001).

Conclusions

LR‐OCT proved to be a fast and easily performed method. OCT could accurately quantify the INV area. The values of the angle and the cross‐sectional area of the INV were reproducible and correlated well with the data seen with other methods. Changes in size could be reliably delineated. Endoscopy showed similar values but was significantly less precise.

Level of Evidence

2b. Laryngoscope, 126:E97–E102, 2016
Computational analysis of swallowing mechanics underlying impaired epiglottic inversion
Authors: Pearson William G. , Taylor Brandon K. , Blair Julie , Martin‐Harris Bonnie
Published: November 2015

Objectives/Hypothesis

Determine swallowing mechanics associated with the first and second epiglottic movements, that is, movement to horizontal and full inversion, respectively, to provide a clinical interpretation of impaired epiglottic function.

Study Design

Retrospective cohort study.

Methods

A heterogeneous cohort of patients with swallowing difficulties was identified (n = 92). Two speech‐language pathologists reviewed 5‐mL thin and 5‐mL pudding videofluoroscopic swallow studies per subject, and assigned epiglottic component scores of 0 = complete inversion, 1 = partial inversion, and 2 = no inversion, forming three groups of videos for comparison. Coordinates mapping minimum and maximum excursion of the hyoid, pharynx, larynx, and tongue base during pharyngeal swallowing were recorded using ImageJ software. A canonical variate analysis with post hoc discriminant function analysis of coordinates was performed using MorphoJ software to evaluate mechanical differences between groups. Eigenvectors characterizing swallowing mechanics underlying impaired epiglottic movements were visualized.

Results

Nineteen of 184 video swallows were rejected for poor quality (n = 165). A Goodman‐Kruskal index of predictive association showed no correlation between epiglottic component scores and etiologies of dysphagia (λ = .04). A two‐way analysis of variance by epiglottic component scores showed no significant interaction effects between sex and age (f = 1.4, P = .25). Discriminant function analysis demonstrated statistically significant mechanical differences between epiglottic component scores: 1 and 2, representing the first epiglottic movement (Mahalanobis distance = 1.13, P = .0007); and 0 and 1, representing the second epiglottic movement (Mahalanobis distance = 0.83, P = .003). Eigenvectors indicate that laryngeal elevation and tongue base retraction underlie both epiglottic movements.

Conclusions

Results suggest that reduced tongue base retraction and laryngeal elevation underlie impaired first and second epiglottic movements. The styloglossus, hyoglossus, and long pharyngeal muscles are implicated as targets for rehabilitation in dysphagic patients with impaired epiglottic inversion.

Level of Evidence

2b Laryngoscope, 126:1854–1858, 2016
Microcavity‐Stabilized Quantum Cascade Laser
Authors: Siciliani de Cumis Mario , Borri Simone , Insero Giacomo , Galli Iacopo , Savchenkov Anatoliy , Eliyahu Danny , Ilchenko Vladimir , Akikusa Naota , Matsko Andrey , Maleki Lute , De Natale Paolo
Published: November 2015

Narrow‐linewidth lasers are key elements in optical metrology and spectroscopy. Spectral purity of these lasers determines accuracy of the measurements and quality of collected data. Solid state and fiber lasers are stabilized to relatively large and complex external optical cavities or narrow atomic and molecular transitions to improve their spectral purity. While this stabilization technique is rather generic, its complexity increases tremendously moving to longer wavelenghts, to the infrared (IR) range. Inherent increase of losses of optical materials at longer wavelengths hinders realization of compact, room temperature, high finesse IR cavities suitable for laser stabilization. In this paper, we report on demonstration of quantum cascade lasers stabilized to high‐Q crystalline mid‐IR microcavities. The lasers operating at room temperature in the 4.3‐4.6 μm region have a linewidth approaching 10 kHz and are promising for on‐chip mid‐IR and IR spectrometers.

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Effect of Ti:Sapphire‐femtosecond laser on the surface roughness of ceramics
Authors: Erdur Emire Aybuke , Basciftci Faruk Ayhan
Published: November 2015

Background and Objectives

Some of these adult patients have ceramic crowns, to which orthodontists have concerns about bonding brackets. The aim of the present study was to evaluate the effect of a Ti:Sapphire femtosecond (fs) laser (Integra‐C‐3.5, Quantronix, NY) on the surface roughness of two ceramic surfaces (feldspathic and IPS Empress e‐Max) and to compare results with those of two other lasers (Er:YAG and Nd:YAG) and conventional techniques, i.e., sandblasting (50 µm) and hydrofluoric (HF) acid.

Materials and Methods

Ceramic discs were fabricated (n = 150) and divided into two groups, each of which was then divided into five subgroups prepared with Ti:Sapphire fs, Nd:YAG, or Er:YAG lasers, sandblasting, or HF acid (n = 15). The surface roughness of the ceramic discs was evaluated using a profilometer (Mitotoyo Surf Test SJ 201 P/M; Mitutoyo Corp, Japan) before and after each surface treatment. Three traces were recorded for each specimen at three different locations in each direction, providing nine measurements per sample, which were then averaged to obtain the surface roughness value. Data were analyzed using the Wilcoxon signed‐rank test (P < <0.05), two‐way ANOVA, and Tukey's HSD test (P < 0.05). Additional samples were prepared for each group and evaluated using atomic force microscopy (AFM; NTEGRA Solaris, NTMDT, Russia).

Results

No significant difference was found between the feldspathic and IPS Empress e‐Max ceramics. The Ti:Sapphire fs laser was associated with the highest mean roughness value. AFM images of the ceramic surfaces treated confirmed that the fs‐laser‐treated surfaces had the highest degree of irregularity.

Conclusion

Within the limitations of this in vitro study, the Ti:Sapphire fs laser yielded the highest surface roughness and could be an alternative ceramic surface treatment to increase bond strength. Lasers Surg. Med. 47:833–838, 2015. © 2015 Wiley Periodicals, Inc.
Recipient aging accelerates acquired transthyretin amyloidosis after domino liver transplantation
Authors: Misumi Yohei , Narita Yasuko , Oshima Toshinori , Ueda Mitsuharu , Yamashita Taro , Tasaki Masayoshi , Obayashi Konen , Isono Kaori , Inomata Yukihiro , Ando Yukio
Published: November 2015

Domino liver transplantation (DLT) with liver grafts from patients with hereditary transthyretin (TTR) amyloidosis has been performed throughout the world because of a severe liver graft shortage. Reports of acquired systemic TTR amyloidosis in domino liver recipients have been increasing; however, the precise pathogenesis and clinical course of acquired TTR amyloidosis remains unclear. We analyzed the relationship between the occurrence of acquired amyloidosis and clinical features in 22 consecutive domino liver donors with hereditary TTR amyloidosis (10 males and 12 females; mean age at DLT: 37.2 years; TTR mutations: V30M [n = 19], Y114C [n = 1], L55P [n = 1], and S50I [n = 1]) and 22 liver recipients (16 males and 6 females; mean age at DLT, 46.2 years). The mean times from DLT to amyloid first appearance and transplant recipient symptom onset were 8.2 years and 9.9 years, respectively. Kaplan‐Meier analysis and quantification of the amyloid deposition revealed aging of recipients correlated with early de novo amyloid deposition. The sex of donors and recipients and the age, disease duration, and disease severity of donors had no significant effect on the latency of de novo amyloid deposition. In conclusion, our results demonstrate that recipient aging is associated with the early onset de novo amyloidosis. Because acquired amyloidosis will likely increase, careful follow‐up for early amyloidosis detection and new treatments, including TTR stabilizers and gene‐silencing therapies, are required. Liver Transplantation 22 656‐664 2016 AASLD.
De novo hepatitis b prophylaxis with hepatitis B virus vaccine and hepatitis B immunoglobulin in pediatric recipients of core antibody–positive livers
Authors: Lee Sanghoon , Kim Jong Man , Choi Gyu Seong , Park Jae Berm , Kwon Choon Hyuck David , Choe Yon‐Ho , Joh Jae‐Won , Lee Suk‐Koo
Published: November 2015

The use of hepatitis B core antibody–positive (HBcAb+) grafts for liver transplantation (LT) has the potential to safely expand the donor pool, as long as proper prophylaxis against de novo hepatitis B (DNHB) is employed. The aim of this study was to characterize the longterm outcome of pediatric LT recipients of HBcAb+ liver grafts under a prophylaxis regimen against DNHB using hepatitis B virus (HBV) vaccine and hepatitis B immunoglobulin (HBIG). From June 1996 to February 2013, 49 patients receiving pediatric LT at our center were from HBcAb+ donors. Forty‐one patients who received DNHB prophylaxis according to our protocol were included in this analysis. Our DNHB prophylaxis protocol consists of HBV vaccine intramuscular injections given intermittently to maintain anti–hepatitis B surface antibody (HBsAb) titers above 100 IU/L. HBIG was also used during the first posttransplant year with a target anti‐HBsAb titer level above 200 IU/L. There were 19 boys and 22 girls. Median age was 1.0 year (range, 4 months to 16 years). Median follow‐up time was 66 months after transplant. Median annual number of HBV vaccine injections was 0.8 per year (range, 0‐1.8 per year). Four patients did not require any HBV vaccine injections during follow‐up. One patient with DNHB was encountered during the follow‐up period (1/41, 2.4%). DNHB was diagnosed at 3.5 years after transplant, when hepatitis B surface antigen was positive upon routine follow‐up serologic testing. Anti‐HBsAb titer was 101.5 IU/L at the time. No grafts were lost because of DNHB‐related events. Overall survival of the 41 recipients of HBcAb+ grafts who received DNHB prophylaxis was 92.3% at 10 years after transplant. In conclusion, longterm prophylaxis against DNHB with HBV vaccine in pediatric LT recipients of HBcAb+ grafts was safe and effective in terms of DNHB incidence as well as graft and patient survival. Liver Transpl 22:247–251, 2016. © 2015 AASLD.
Determination of Homopolymerization Kinetics of 10‐(N‐Methylacrylamido)‐decylphosphonic acid, Its Diethyl ester, and 10‐(Methacryloyloxy)‐decylphosphonic acid, and Their Copolymerization with Methyl methacrylate
Authors: Chmela Štefan , Pavlinec Juraj , Fiedlerová Agnesa , Catel Yohann , Moszner Norbert
Published: November 2015

Two polymerizable phosphonic acids destined to be constituents of self‐etch adhesives as well as a diethyl phosphonate bearing an N‐methylacrylamide group are examined for their polymerization and copolymerization activity in methanol between 45 and 65 °C. Polymerization proceeds readily through a thermal free radical initiator. The intensity exponents for the monomer and initiator are only slightly over 1 and ≈0.5, respectively, in accordance with the results typically observed for an ideal free radical polymerization with bimolecular termination. The specific feature of this process is the absence of auto‐acceleration during the phosphonic acid monomer polymerization and polymer network formation in case of the phosphonate monomer. The kinetics of copolymerization with methyl methacrylate (MMA) are monitored by online 1H NMR spectroscopy. Two copolymerization reactions for each pair of comonomers are sufficient to evaluate the kinetic data using the Jaacks method, the Fineman–Ross method, and the nonlinear least squares method. All three methods give similar results for particular monomer/MMA couples.

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miR‐211 and MITF modulation by Bcl‐2 protein in melanoma cells
Authors: De Luca Teresa , Pelosi Andrea , Trisciuoglio Daniela , D'Aguanno Simona , Desideri Marianna , Farini Valentina , Di Martile Marta , Bellei Barbara , Tupone Maria Grazia , Candiloro Antonio , Regazzo Giulia , Rizzo Maria Giulia , Del Bufalo Donatella
Published: November 2015

Melanoma, the most lethal form of skin cancer, is frequently associated with alterations in several genes, among which the Bcl‐2 oncogene plays an important role in progression, chemosensitivity and angiogenesis. Also microRNA (miRNA) are emerging as modulators of melanoma development and progression, and among them, miR‐211, located within the melastatin‐1/TRPM1 (transient receptor potential cation channel, subfamily M, member 1 protein) gene, is prevalently expressed in the melanocyte lineage and acts as oncosuppressor. Using several human melanoma cell lines and their Bcl‐2 stably overexpressing derivatives, we evaluated whether there was a correlation between expression of Bcl‐2 and miR‐211. Western blot analysis and quantitative real‐time polymerase chain reaction demonstrated reduced expression of pri‐miR‐211, miR‐211, TRPM1, and MLANA levels, after Bcl‐2 overexpression, associated with increased expression of well‐known miR‐211 target genes. Overexpression of mature miR‐211 in Bcl‐2 overexpressing cells rescued Bcl‐2 ability to increase cell migration. A decreased nuclear localization of microphthalmia‐associated transcription factor (MITF), a co‐regulator of both miR‐211 and TRPM1, and a reduced MITF recruitment at the TRPM1 and MLANA promoters were also evidenced in Bcl‐2 overexpressing cells by immunofluorescence and chromatin immunoprecipitation experiments, respectively. Reduction of Bcl‐2 expression by small interference RNA confirmed the ability of Bcl‐2 to modulate miR‐211 and TRPM1 expression. © 2015 Wiley Periodicals, Inc.
Machine Learning Estimation of Atom Condensed Fukui Functions
Authors: Zhang Qingyou , Zheng Fangfang , Zhao Tanfeng , Qu Xiaohui , Aires‐de‐Sousa João
Published: November 2015

To enable the fast estimation of atom condensed Fukui functions, machine learning algorithms were trained with databases of DFT pre‐calculated values for ca. 23,000 atoms in organic molecules. The problem was approached as the ranking of atom types with the Bradley‐Terry (BT) model, and as the regression of the Fukui function. Random Forests (RF) were trained to predict the condensed Fukui function, to rank atoms in a molecule, and to classify atoms as high/low Fukui function. Atomic descriptors were based on counts of atom types in spheres around the kernel atom. The BT coefficients assigned to atom types enabled the identification (93–94 % accuracy) of the atom with the highest Fukui function in pairs of atoms in the same molecule with differences ≥0.1. In whole molecules, the atom with the top Fukui function could be recognized in ca. 50 % of the cases and, on the average, about 3 of the top 4 atoms could be recognized in a shortlist of 4. Regression RF yielded predictions for test sets with R2=0.68–0.69, improving the ability of BT coefficients to rank atoms in a molecule. Atom classification (as high/low Fukui function) was obtained with RF with sensitivity of 55–61 % and specificity of 94–95 %.
Signal‐domain optimization metrics for MPRAGE RF pulse design in parallel transmission at 7 tesla
Authors: Gras V. , Vignaud A. , Mauconduit F. , Luong M. , Amadon A. , Le Bihan D. , Boulant N.
Published: November 2015

Purpose

Standard radiofrequency pulse design strategies focus on minimizing the deviation of the flip angle from a target value, which is sufficient but not necessary for signal homogeneity. An alternative approach, based directly on the signal, here is proposed for the MPRAGE sequence, and is developed in the parallel transmission framework with the use of the kT‐points parametrization.

Methods

The flip angle‐homogenizing and the proposed methods were investigated numerically under explicit power and specific absorption rate constraints and tested experimentally in vivo on a 7 T parallel transmission system enabling real time local specific absorption rate monitoring. Radiofrequency pulse performance was assessed by a careful analysis of the signal and contrast between white and gray matter.

Results

Despite a slight reduction of the flip angle uniformity, an improved signal and contrast homogeneity with a significant reduction of the specific absorption rate was achieved with the proposed metric in comparison with standard pulse designs.

Conclusion

The proposed joint optimization of the inversion and excitation pulses enables significant reduction of the specific absorption rate in the MPRAGE sequence while preserving image quality. The work reported thus unveils a possible direction to increase the potential of ultra‐high field MRI and parallel transmission. Magn Reson Med 76:1431–1442, 2016. © 2015 International Society for Magnetic Resonance in Medicine
1H‐13C independently tuned radiofrequency surface coil applied for in vivo hyperpolarized MRI
Authors: Cao Peng , Zhang Xiaoliang , Park Ilwoo , Najac Chloe , Nelson Sarah J. , Ronen Sabrina , Larson Peder E.Z.
Published: November 2015

Purpose

To develop a lump‐element double‐tuned common‐mode‐differential‐mode (CMDM) radiofrequency (RF) surface coil with independent frequency tuning capacity for MRS and MRI applications.

Methods

The presented design has two modes that can operate with different current paths, allowing independent frequency adjustment. The coil prototype was tested on the bench and then examined in phantom and in vivo experiments.

Results

Standard deviations of frequency and impedance fluctuations measured in one resonator, while changing the tuning capacitor of another resonator, were less than 13 kHz and 0.55 Ω. The unloaded S21 was −36 dB and −41 dB, while the unloaded Q factor was 260 and 287, for 13C and 1H, respectively. In vivo hyperpolarized 13C MR spectroscopy data demonstrated the feasibility of using the CMDM coil to measure the dynamics of lactate, alanine, pyruvate and bicarbonate signal in a normal rat head along with acquiring 1H anatomical reference images.

Conclusion

Independent frequency tuning capacity was demonstrated in the presented lump‐element double‐tuned CMDM coil. This CMDM coil maintained intrinsically decoupled magnetic fields, which provided sufficient isolation between the two resonators. The results from in vivo experiments demonstrated high sensitivity of both the 1H and 13C resonators. Magn Reson Med 76:1612–1620, 2016. © 2015 International Society for Magnetic Resonance in Medicine
Reproducibility of fractional ventilation derived by Fourier decomposition after adjusting for tidal volume with and without an MRI compatible spirometer
Authors: Voskrebenzev Andreas , Gutberlet Marcel , Becker Lena , Wacker Frank , Vogel‐Claussen Jens
Published: November 2015

Purpose

To reduce the influence of tidal volume on fractional ventilation (FV) derived by Fourier decomposition (FD).

Methods

Twelve volunteers were examined on a 1.5 Tesla scanner. Spoiled gradient echo imaging of coronal and sagittal slices of the lung were performed. The tidal volume variations between different acquisitions were studied by reproducibility and repeatability measurements. To adjust the FV derived by FD for tidal volume differences between the measurements, during all acquisitions, the lung volume changes were measured by a spirometer and used to calculate a global FV parameter. As an alternative, using the FD data, the lung area changes were calculated and used for the adjustment.

Results

Reproducibility analysis of unadjusted coronal FV showed a determination coefficient of
and an intraclass correlation coefficient of
. Differences in the measurements could be ascribed to different tidal volumes. Area adjusted values exhibited an increased
of 84% and a higher ICC of 97%. For the coronal middle slice/sagittal slices in free breathing, the inter‐volunteer coefficient of variation was reduced from 0.23/0.28 (unadjusted) to 0.16/0.20 (spirometer) or 0.12/0.13 (area).

Conclusion

The calculation of lung area changes is sufficient to increase the reproducibility of FV in a volunteer cohort avoiding the need for an MRI compatible spirometer. Magn Reson Med 76:1542–1550, 2016. © 2015 International Society for Magnetic Resonance in Medicine
Functional imaging of the nonhuman primate Placenta with endogenous blood oxygen level–dependent contrast
Authors: Schabel Matthias C. , Roberts Victoria H. J. , Lo Jamie O. , Platt Sarah , Grant Kathleen A. , Frias Antonio E. , Kroenke Christopher D.
Published: November 2015

Purpose

To characterize spatial patterns of
in the placenta of the rhesus macaque (Macaca mulatta), to correlate these patterns with placental perfusion determined using dynamic contrast‐enhanced MRI (DCE‐MRI), and to evaluate the potential for using the blood oxygen level–dependent effect to quantify placental perfusion without the use of exogenous contrast reagent.

Methods

MRI was performed on three pregnant rhesus macaques at gestational day 110. Multiecho spoiled gradient echo measurements were used to compute maps of
. Spatial maxima in these maps were compared with foci of early enhancement determined by DCE‐MRI.

Results

Local maxima in
maps were strongly correlated with spiral arteries identified by DCE‐MRI, with mean spatial separations ranging from 2.34 to 6.11 mm in the three animals studied. Spatial patterns of
( = 1/
) within individual placental lobules can be quantitatively analyzed using a simple model to estimate fetal arterial oxyhemoglobin concentration
and a parameter
, reflecting oxygen transport to the fetus. Estimated mean values of
ranged from 4.25 mM to 4.46 mM, whereas
ranged from 2.80 × 105 cm−3 to 1.61 × 106 cm−3.

Conclusions

Maternal spiral arteries show strong spatial correlation with foci of extended
observed in the primate placenta. A simple model of oxygen transport accurately describes the spatial dependence of
within placental lobules and enables assessment of placental function and oxygenation without requiring administration of an exogenous contrast reagent. Magn Reson Med 76:1551–1562, 2016. © 2015 International Society for Magnetic Resonance in Medicine
Selective channel combination of MRI signal phase
Authors: Vegh Viktor , O'Brien Kieran , Barth Markus , Reutens David C.
Published: November 2015

Purpose

Signal magnitude can robustly be combined using the sum‐of‐squares approach. Methods have been developed to combine complex images. However, techniques based only on signal phase have not been developed and evaluated.

Theory and Methods

We performed simulations to demonstrate the effect of noise on coil combination. 32‐channel 7 Tesla human gradient echo MRI brain data were collected. We combined phase images based on phase noise leading to spatially selective and coil selective combination of phase images. We compared our selective combination approach to optimal noise distribution and adaptive combination methods.

Results

We found that selective combination of signal phases leads to improved phase signal‐to‐noise ratio. Furthermore, a phase shift can be present in combined phase images introduced by the method used to combine multiple channel phases.

Conclusion

Mapping of signal phase from ultra‐high field MRI data undoubtedly provides a wealth of information about the ageing brain and the effects of neurodegenerative disorders. Measurement of signal phase is essential in frequency shift mapping and in quantitative susceptibility mapping. The method used to combine signal phase should be informed by an understanding of the noise distribution in signal phase at the individual channel level. Magn Reson Med 76:1469–1477, 2016. © 2015 International Society for Magnetic Resonance in Medicine
MR‐based detection of individual histotripsy bubble clouds formed in tissues and phantoms
Authors: Allen Steven P. , Hernandez‐Garcia Luis , Cain Charles A. , Hall Timothy L.
Published: November 2015

Purpose

To demonstrate that MR sequences can detect individual histotripsy bubble clouds formed inside intact tissues.

Methods

A line‐scan and an EPI sequence were sensitized to histotripsy by inserting a bipolar gradient whose lobes bracketed the lifespan of a histotripsy bubble cloud. Using a 7 Tesla, small‐bore scanner, these sequences monitored histotripsy clouds formed in an agar phantom and in vitro porcine liver and brain. The bipolar gradients were adjusted to apply phase with k‐space frequencies of 10, 300 or 400 cm−1. Acoustic pressure amplitude was also varied. Cavitation was simultaneously monitored using a passive cavitation detection system.

Results

Each image captured local signal loss specific to an individual bubble cloud. In the agar phantom, this signal loss appeared only when the transducer output exceeded the cavitation threshold pressure. In tissues, bubble clouds were immediately detected when the gradients created phase with k‐space frequencies of 300 and 400 cm−1. When the gradients created phase with a k‐space frequency of 10 cm−1, individual bubble clouds were not detectable until many acoustic pulses had been applied to the tissue.

Conclusion

Cavitation‐sensitive MR‐sequences can detect single histotripsy bubble clouds formed in biologic tissue. Detection is influenced by the sensitizing gradients and treatment history. Magn Reson Med 76:1486–1493, 2016. © 2015 International Society for Magnetic Resonance in Medicine