bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced estimations of post‐stroke aphasia severity using stacked multimodal predictions
Authors: Pustina Dorian , Coslett Harry Branch , Ungar Lyle , Faseyitan Olufunsho K. , Medaglia John D. , Avants Brian , Schwartz Myrna F.
Published: August 2017

The severity of post‐stroke aphasia and the potential for recovery are highly variable and difficult to predict. Evidence suggests that optimal estimation of aphasia severity requires the integration of multiple neuroimaging modalities and the adoption of new methods that can detect multivariate brain‐behavior relationships. We created and tested a multimodal framework that relies on three information sources (lesion maps, structural connectivity, and functional connectivity) to create an array of unimodal predictions which are then fed into a final model that creates “stacked multimodal predictions” (STAMP). Crossvalidated predictions of four aphasia scores (picture naming, sentence repetition, sentence comprehension, and overall aphasia severity) were obtained from 53 left hemispheric chronic stroke patients (age: 57.1 ± 12.3 yrs, post‐stroke interval: 20 months, 25 female). Results showed accurate predictions for all four aphasia scores (correlation true vs. predicted: r = 0.79–0.88). The accuracy was slightly smaller but yet significant (r = 0.66) in a full split crossvalidation with each patient considered as new. Critically, multimodal predictions produced more accurate results that any single modality alone. Topological maps of the brain regions involved in the prediction were recovered and compared with traditional voxel‐based lesion‐to‐symptom maps, revealing high spatial congruency. These results suggest that neuroimaging modalities carry complementary information potentially useful for the prediction of aphasia scores. More broadly, this study shows that the translation of neuroimaging findings into clinically useful tools calls for a shift in perspective from unimodal to multimodal neuroimaging, from univariate to multivariate methods, from linear to nonlinear models, and, conceptually, from inferential to predictive brain mapping. Hum Brain Mapp 38:5603–5615, 2017. © 2017 Wiley Periodicals, Inc.
Distinguishing stimulus and response codes in theta oscillations in prefrontal areas during inhibitory control of automated responses
Authors: Mückschel Moritz , Dippel Gabriel , Beste Christian
Published: August 2017

Response inhibition mechanisms are mediated via cortical and subcortical networks. At the cortical level, the superior frontal gyrus, including the supplementary motor area (SMA) and inferior frontal areas, is important. There is an ongoing debate about the functional roles of these structures during response inhibition as it is unclear whether these structures process different codes or contents of information during response inhibition. In the current study, we examined this question with a focus on theta frequency oscillations during response inhibition processes. We used a standard Go/Nogo task in a sample of human participants and combined different EEG signal decomposition methods with EEG beamforming approaches. The results suggest that stimulus coding during inhibitory control is attained by oscillations in the upper theta frequency band (∼7 Hz). In contrast, response selection codes during inhibitory control appear to be attained by the lower theta frequency band (∼4 Hz). Importantly, these different codes seem to be processed in distinct functional neuroanatomical structures. Although the SMA may process stimulus codes and response selection codes, the inferior frontal cortex may selectively process response selection codes during inhibitory control. Taken together, the results suggest that different entities within the functional neuroanatomical network associated with response inhibition mechanisms process different kinds of codes during inhibitory control. These codes seem to be reflected by different oscillations within the theta frequency band. Hum Brain Mapp 38:5681–5690, 2017. © 2017 Wiley‐Liss, Inc.
Audiovisual integration as conflict resolution: The conflict of the McGurk illusion
Authors: Morís Fernández Luis , Macaluso Emiliano , Soto‐Faraco Salvador
Published: August 2017

There are two main behavioral expressions of multisensory integration (MSI) in speech; the perceptual enhancement produced by the sight of the congruent lip movements of the speaker, and the illusory sound perceived when a speech syllable is dubbed with incongruent lip movements, in the McGurk effect. These two models have been used very often to study MSI. Here, we contend that, unlike congruent audiovisually (AV) speech, the McGurk effect involves brain areas related to conflict detection and resolution. To test this hypothesis, we used fMRI to measure blood oxygen level dependent responses to AV speech syllables. We analyzed brain activity as a function of the nature of the stimuli—McGurk or non‐McGurk—and the perceptual outcome regarding MSI—integrated or not integrated response—in a 2 × 2 factorial design. The results showed that, regardless of perceptual outcome, AV mismatch activated general‐purpose conflict areas (e.g., anterior cingulate cortex) as well as specific AV speech conflict areas (e.g., inferior frontal gyrus), compared with AV matching stimuli. Moreover, these conflict areas showed stronger activation on trials where the McGurk illusion was perceived compared with non‐illusory trials, despite the stimuli where physically identical. We conclude that the AV incongruence in McGurk stimuli triggers the activation of conflict processing areas and that the process of resolving the cross‐modal conflict is critical for the McGurk illusion to arise. Hum Brain Mapp 38:5691–5705, 2017. © 2017 Wiley Periodicals, Inc.
Primary treatment for oropharyngeal squamous cell carcinoma in Alberta, Canada: A population‐based study
Authors: Hobbs Amy J. , Brockton Nigel T. , Matthews T. Wayne , Chandarana Shamir P. , Bose Pinaki , Guggisberg Kelly , Fick Gordon H. , Dort Joseph C.
Published: August 2017

Background

The incidence of human papillomavirus (HPV)‐related oropharyngeal squamous cell carcinoma (SCC) is increasing and has better survival than non‐HPV related oropharyngeal SCC. This study compared surgical to nonsurgical treatments and demographic, clinical, and survival differences in patients with oropharyngeal SCC, stratified by p16 status.

Methods

We assembled a cohort of adult patients with oropharyngeal SCC diagnosed between 2000 and 2008 in Alberta. The tumor p16 biomarker was measured using fluorescent immunohistochemistry.

Results

In this cohort, p16 data were available for 115 of 357 patients; and 66% (n = 76) were p16‐positive. Patients with p16 data had comparable outcomes to those without. Surgically treated p16‐negative patients had improved 5‐year disease‐specific survival (DSS) and overall survival (OS) compared with nonsurgical patients. There were no differences in survival outcomes between surgical and nonsurgical treatment for patients with p16‐positive disease.

Conclusion

Patients with p16‐positive oropharyngeal SCC had similar outcomes regardless of treatment. Patients with p16‐negative tumors may benefit from primary surgery with postoperative adjuvant therapy.
Measuring generalised expectancies for negative mood regulation in China: The Chinese language Negative Mood Regulation scale
Authors: Wang Guofang , Mearns Jack , Yang Xiaohui , Han Peng , Catanzaro Salvatore J.
Published: August 2017

Negative mood regulation expectancies (NMRE) represent people's confidence that they can alleviate their negative affect or induce a positive emotional state through thought or action. NMRE predict coping behaviour and mood outcomes for individuals under stress. Since 1990, much research documents the reliability and validity of the English language Negative Mood Regulation (NMR) scale as a measure of NMRE. The current research reports two studies developing a Chinese language translation of the NMR (NMR‐C) scale that goes beyond literal translation to be a culturally sensitive measure of NMRE in China. In Study 1, 713 college students from both a major city and a rural setting in China were surveyed. Data support the resulting 32‐item NMR‐C's reliability (alpha = .88) and validity. The NMR‐C showed both direct and indirect links to depression and anxiety; coping mediated the indirect effect. In Study 2, 331 prison police officers in three Chinese provinces participated. NMRE buffered the effect of high role pressure, moderating the relationship between prison police role stress and job engagement. Results of the two studies support the reliability and validity of the Chinese language NMR scale and parallel results found with measures of NMRE in the West and in other Asian countries.
The effect of amino plasma‐enhanced chemical vapor deposition‐treated titanium surface on Schwann cells
Authors: Zhao Jinghui , Guo Yu , Lan A , Luo Wenjing , Wang Xiaona , Fu Li , Cai Qing , Zhou Yanmin
Published: August 2017

The surface modification of titanium and its alloys with amino group plasma‐enhanced chemical vapor deposition has been proven to enhance the performance of implants on initial osteoblast bioactivity in vitro. However, scarce information on the effect of this kind of surface modification on nerve regeneration exists. In this study, the surface chemistry of pure Ti disks and surface‐modified disks was examined using X‐ray photoelectron spectroscopy. Cell counting kit 8 assay, 4,6‐diamidino‐2‐phenylindole staining, flow cytometry, and scanning electron microscopy showed that either the p30% or cw + p30% mode‐mediated surface significantly promote Schwann cell adhesion without any cytotoxicity compared with the pure Ti surface, and the cw + p30% group showed the best performance on cell adhesion. However, results of polymerase chain reaction and Western blot analyses showed that the mRNA and protein levels of glial cell‐derived neurotrophic factor and nerve growth factor of the p30% and cw + p30% groups were lower than those of the Ti group at some time points. Generally, the results indicate that amino‐functionalized Ti surfaces can promote Schwann cell adhesion without cytotoxicity, but this modification, in fact, inhibited the expression of the key growth factors GDNF and NGF of Schwann cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 265–271, 2018.
Cytocompatibility testing of hydrogels toward bioprinting of mesenchymal stem cells
Authors: Benning Leo , Gutzweiler Ludwig , Tröndle Kevin , Riba Julian , Zengerle Roland , Koltay Peter , Zimmermann Stefan , Stark G. Björn , Finkenzeller Günter
Published: August 2017

Mesenchymal stem cells (MSCs) represent a very attractive cell source for tissue engineering applications aiming at the generation of artificial bone substitutes. The use of three‐dimensional bioprinting technologies has the potential to improve the classical tissue engineering approach because bioprinting will allow the generation of hydrogel scaffolds with high spatial control of MSC allocation within the bioprinted construct. In this study, we have performed direct comparisons between commercially available hydrogels in the context of their cytocompatibility toward MSCs and their physicochemical parameters with the aim to identify the most suitable hydrogel for drop‐on‐demand (DoD) printing of MSCs. In this context, we examined matrigel, fibrin, collagen, gelatin, and gelatin/alginate at various hydrogel concentrations. Matrigel, fibrin, collagen, and gelatin were able to support cell viability, but the latter showed a limited potential to promote MSC proliferation. We concentrated our study on fibrin and collagen hydrogels and investigated the effect of hydroxyapatite (HA) inclusion. The inclusion of HA enhanced proliferation and osteogenic differentiation of MSCs and prevented degradation of fibrin in vitro. According to viscosity and storage moduli measurements, HA‐blends displayed physicochemical characteristics suitable for DoD printing. In bioprinting experiments, we confirmed that fibrin and collagen and their respective HA‐blends represent excellent hydrogels for DoD‐based printing as evidenced by high survival rates of printed MSCs. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3231–3241, 2017.
AAV delivery of GRP78/BiP promotes adaptation of human RPE cell to ER stress
Authors: Ghaderi Shima , Ahmadian Shahin , Soheili Zahra‐Soheila , Ahmadieh Hamid , Samiei Shahram , Kheitan Samira , Pirmardan Ehsan R.
Published: August 2017

Adeno associated virus (AAV)‐mediated gene delivery of GRP78 (78 kDa glucose‐regulated protein) attenuates the condition of endoplasmic reticulum (ER) stress and prevents apoptotic loss of photoreceptors in Retinitis pigmentosa (RP) rats. In the current study we overexpressed Grp78 with the help of AAV‐2 in primary human retinal pigmented epithelium (hRPE) cell cultures and examined its effect on cell response to ER stress. The purpose of this work was studying potential stimulating effect of GRP78 on adaptation/pro‐survival of hRPE cells under ER stress, as an in vitro model for RPE degeneration. To investigate the effect of Grp78 overexpression on unfolded protein response (UPR) markers under ER stress, hRPE primary cultures were transduced by recombinant virus rAAV/Grp78, and treated with ER stressor drug, tunicamycin. Expression changes of four UPR markers including GRP78, PERK, ATF6α, and GADD153/CHOP, were assessed by real‐time PCR and western blotting. We found that GRP78 has a great contribution in modulation of UPR markers to favor adaptive response in ER‐stressed hRPE cells. In fact, GRP78 overexpression affected adaptation and apoptotic phases of early UPR, through enhancement of two master regulators/ER stress sensors (PERK and ATF6α) and down‐regulation of a key pro‐apoptotic cascade activator (GADD153/CHOP). Together these findings demonstrate the promoting effect of GRP78 on adaptation/pro‐survival of hRPE cells under ER stress. This protein with anti‐apoptotic actions in the early UPR and important role in cell fate regulation, can be recruited as a useful candidate for future investigations of RPE degenerative diseases.
The participation of fibroblast growth factor 23 (FGF23) in the progression of osteoporosis via JAK/STAT pathway
Authors: Xu Lijun , Zhang Lixia , Zhang Huijuan , Yang Zaigang , Qi Lei , Wang Yurong , Ren Shuxin
Published: August 2017

Osteoporosis (OP) is a major skeletal disorder for the old man. The fibroblast growth factor 23 (FGF23) is a phosphaturic hormone produced by osteoblasts and osteocytes. However, the regulatory mechanisms of FGF23 in the progression of osteoporosis remain poorly understood. This study aims to explore the downstream regulating pathway of FGF23 in postmenopausal osteoporosis. The rat model of osteoporosis was established through ovariectomy (OVX). The investigation demonstrated that the serum levels of FGF23 and the phosphorylation levels of JAK2, STAT1, and STAT3 were up‐regulated in the OVX + NVP‐BGJ398 group while were down‐regulated in the OVX + Anti‐FGF23 group than that in the OVX group. Moreover, the JAK2/STAT1/3 inhibitor, AG490 promoted the OVX‐induced increase in the osteocalcin, ALP, BALP, TRAP, and CTX‐I levels. Besides, AG490 enhanced cartilage lesions and increased TUNEL‐positive chondrocytes in the OVX group. In addition, higher protein expression of MMP‐1 and MMP‐13 and lower expression of COX‐II were observed in the OVX + AG490 group than that in the OVX group. Our findings suggested that FGF23 was involved in the progression of osteoporosis via the JAK/STAT signaling pathway.
Lipid composition of membrane microdomains isolated detergent‐free from PUFA supplemented RAW264.7 macrophages
Authors: Hellwing Christine , Tigistu‐Sahle Feven , Fuhrmann Herbert , Käkelä Reijo , Schumann Julia
Published: August 2017

Profound alterations in the lipid profile of raft and non‐raft plasma membrane microdomains were found when RAW264.7 macrophages were supplemented with polyunsaturated fatty acids (PUFAs) in physiologically relevant concentrations. For the first time lipids in the detergent‐free isolated membrane domains of phagocytic immune cells were characterized by mass spectrometry. The extent of remodeling of the membrane lipids differed with different n3 and n6 PUFA supplements. The mildest effects were detected for α‐linolenic acid (LNA) and linoleic acid (LA), the C18 precursors of the n3 and n6 families, respectively. When the effects of highly unsaturated PUFAs were compared, eicosapentaenoic acid (EPA) caused more extensive restructuring of membrane lipids than docosahexaenoic acid (DHA) or arachidonic acid (AA). The supplements altered the lipid species composition of both the raft and non‐raft membrane fractions. The rafts containing elevated proportions of highly unsaturated lipid species may relocate sterically incompatible lipids and proteins originally belonging to this microdomain. Such effect was evident for sphingomyelin, which favored non‐rafts instead of rafts after EPA supplementation. The current work suggests that the different functional consequences found previously when supplementing macrophages with either EPA or DHA have their origin in the different effects of these PUFAs on membrane architecture.
DHQZ‐17, a potent inhibitor of the transcription factor HNF4A, suppresses tumorigenicity of head and neck squamous cell carcinoma in vivo
Authors: Tentu Shilpa , Nandarapu Kumarswamyreddy , Muthuraj Prakash , Venkitasamy Kesavan , Venkatraman Ganesh , Rayala Suresh K.
Published: August 2017

A series of 2, 3‐dihydroquinazolinone derivatives were synthesized, characterized and their anticancer activity was determined. Among the compounds synthesized and screened, one compound (17) showed potent anticancer activity against human head and neck squamous cell carcinoma cell line, SCC131 and was non‐toxic to normal cells. The compound inhibited the growth of SCC131 cells, with an IC50 of 1.75 μM, triggered apoptotic mode of cell death and caused tumor regression of SCC131 tumor xenografts in athymic mice. To decipher the target for the lead compound, a high throughput qPCR array was performed. Results showed that the compound 17, inhibited the expression of a vital transcription factor HNF4A, involved in regulation of metabolic pathways. Thus, the present work has identified a lead compound 17, with potent anticancer activity, minimal normal cell toxicity and a plausible target and hence definitely holds future prospects as an anticancer agent.
Balanced caterpillars of maximum degree 3 and with hairs of arbitrary length are subgraphs of their optimal hypercube
Authors: Monien Burkhard , Wechsung Gerd
Published: August 2017

A caterpillar is a tree having a path that contains all vertices of of degree at least 3. We show in this article that every balanced caterpillar with maximum degree 3 and 2n vertices is a subgraph of the n‐dimensional hypercube. This solves a long‐standing open problem and generalizes a result of Havel and Liebl (1986), who considered only such caterpillars that have a path containing all vertices of degree at least 2.
Comparative study of the influence of hawthorn (Crataegus monogyna) berry ethanolic extract and butylated hydroxylanisole (BHA) on lipid peroxidation, myoglobin oxidation, consistency and firmness of minced pork during refrigeration
Authors: Papuc Camelia , Predescu Corina Nicoleta , Tudoreanu Liliana , Nicorescu Valentin , Gâjâilă Iuliana
Published: August 2017

BACKGROUND

Following public concern on the use of synthetic food antioxidants, there is an increasing demand for the application of mixed or purified natural antioxidants to maintain quality of meat products quality during storage. The aim of this research was to investigate the effect of ethanolic extract of hawthorn berry, compared to butylated hydroxylanisole (BHA), on lipid peroxidation, myoglobin oxidation, protein electrophoresis pattern, consistency and firmness of minced pork during refrigeration at 4 °C, and to identify the relationship between chemical modifications and consistency variation.

RESULTS

After 6 days of refrigeration it was found that the thiobarbituric acid reactive substances value of minced pork containing 200 mg GAE kg−1 total phenolics in minced meat (200 HP) was significantly lower (0.1543 ± 0.006 mg) compared to BHA‐treated meat. The ratio of oxymyoglobin to metmyoglobin in treated minced pork was respectively 0.845 for 200 HP and 0.473 for BHA‐treated minced meat. Concentrations of 100 HP or 300 HP will generate statistically higher firmness than BHA in minced pork.

CONCLUSION

Hawthorn berry ethanolic extract was more effective than BHA in reducing lipid oxidation and protein degradation, for maintaining firmness and consistency of minced pork during 6 days of refrigeration at 4 °C. © 2017 Society of Chemical Industry
Sulfonated poly(styrene‐divinylbenzene) modified with amines and the application for pipette‐tip solid‐phase extraction of carbendazim in apples
Authors: Ma Yuxin , Liu Lingling , Tang Weiyang , Zhu Tao
Published: August 2017

Sulfonated poly(styrene‐divinylbenzene) modified with five kinds of amine functional groups was applied to the determination of carbendazim in apple samples with a pipette‐tip solid‐phase extraction method. The structures of the polymers were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. Five different modifications of the solid‐phase extraction sorbent based on sulfonated poly(styrene‐divinylbenzene) were tested under static and pipette‐tip solid‐phase extraction conditions. The polymer modified with p‐methoxyaniline showed the best recognition capacity and adsorption amount for carbendazim. Under the optimum conditions, 3.00 mg of the adsorbent, 1.00 mL of ethyl acetate as washing solvent, and 1.00 mL of ammonia/acetonitrile (5:95, v/v) as elution solvent were used in the pretreatment procedure of apple samples. The calibration graphs of carbendazim in methanol were linear over 5.00–200.00 μg/mL, and the limits of detection and quantification were 0.01 and 0.03 μg/mL, respectively. The method recoveries of carbendazim were in the range of 91.31–98.13% with associated intraday relative standard deviations of 0.76–2.13% and interday relative standard deviations of 1.10–1.85%. Sulfonated poly(styrene‐divinylbenzene) modified with p‐methoxyaniline showed satisfactory results (recovery: 97.96%) and potential for the rapid purification of carbendazim in apple samples combined with the pipette‐tip solid‐phase extraction.
Sirolimus as treatment for 19 patients with refractory cervicofacial lymphatic malformation
Authors: Strychowsky Julie E. , Rahbar Reza , O'Hare Meghan J. , Irace Alexandria L. , Padua Horacio , Trenor Cameron C.
Published: August 2017

Objective

Lymphatic malformations (LMs) are challenging to manage, particularly those involving the cervicofacial region and airway. Traditional therapy is sclerotherapy and/or resection. We aim to establish the emerging therapeutic role of sirolimus.

Study Design

Institutional review board‐approved retrospective review.

Methods

All patients treated for cervicofacial LM with sirolimus at Boston Children's Hospital, Massachusetts, from November 2012 to October 2016 were included. Chart review included response to therapy (defined as reduction in LM bulk by clinical photographs and radiologic imaging), type of LM (microcystic, macrocystic, mixed), extent of disease, duration of therapy, patient/parent‐reported quality‐of‐life, airway status (tracheostomy dependence), and complications (opportunistic infection, hemorrhage, other). Follow‐up and clinical outcomes were included up until October 2016.

Results

Nineteen patients were treated with sirolimus for cervicofacial LM from November 2012 to October 2016 at Boston Children's Hospital. Seven patients remain on uninterrupted sirolimus. Of 12 patients who stopped therapy, seven have resumed due to recurrence of symptoms. All patients demonstrated reduction in LM bulk, ranging from modest to significant. All patients with mucosal vesicles (n = 14) resolved or improved on sirolimus. Six patients developed cellulitis, and four had bleeding within the LM during treatment. No patients developed opportunistic or systemic bacterial infection.

Conclusion

The use of sirolimus in the management of cervicofacial LM often is efficacious, with limited adverse events. Long‐term follow‐up, durability of response, and coordination of sirolimus prior to procedural therapies need further study.

Level of Evidence

4. Laryngoscope, 128:269–276, 2018
Epidermal growth factor receptor detection in serum and saliva as a diagnostic and prognostic tool in oral cancer
Authors: Zanotti Laura , Paderno Alberto , Piazza Cesare , Pagan Eleonora , Bignotti Eliana , Romani Chiara , Bandiera Elisabetta , Calza Stefano , Del Bon Francesca , Nicolai Piero , Ravaggi Antonella
Published: August 2017

Objectives/Hypothesis

Epidermal growth factor receptor (EGFR) is a type I transmembrane glycoprotein that is overexpressed in a wide variety of malignancies, including oral squamous cell carcinoma (OSCC). Our objective was to assess the EGFR diagnostic and prognostic value in OSCC by investigating its expression in serum and saliva of patients in comparison with healthy subjects.

Study Design

Prospective case‐control study.

Methods

Serum and saliva samples were collected from a cohort of 63 treatment‐naïve OSCC patients before surgery and a matched group of 60 healthy subjects. EGFR concentrations in serum and saliva were quantified by an enzyme‐linked immunosorbent assay.

Results

OSCC patients showed lower values of serum EGFR compared with controls (P = .0002). Conversely, saliva EGFR concentrations were higher in OSCC patients than in controls (P = .0014). Saliva EGFR levels were also increased in patients with higher T category (pT4 vs. pT <4, median 6.0 vs. 3.8 ng/mL, P = .02). Considering 9.2 ng/mL (fourth quartile) as the cutoff value, patients with higher levels of saliva EGFR had worse prognosis in terms of overall survival (P = .04). Conversely, no association was found between serum EGFR and clinical outcomes in OSCC patients.

Conclusions

Saliva EGFR can be considered as a potential tumor marker for OSCC with both diagnostic and prognostic values. Serum EGFR levels, on the other hand, were lower in OSCC patients, but did not show any prognostic impact. Saliva EGFR levels are worthy of further investigation as a potential diagnostic and prognostic biomarker for OSCC.

Level of Evidence

3b. Laryngoscope, 127:E408–E414, 2017
Selective patient experience with the Blom‐Singer Dual Valve voice prosthesis
Authors: Brownlee Ben , Ahmad Saniya , Grammer Tracy , Krempl Greg
Published: August 2017

Objectives/Hypothesis

This study compares the overall durability, phonation effort, and speech quality achieved by the Blom‐Singer Dual Valve prosthesis to the same characteristics achieved by the single‐valve prosthesis used in a select population of total laryngectomy patients who have demonstrated single‐valve prosthesis failure within 3 months of placement.

Study Design

Prospective phase IV study.

Methods

Fourteen patients who had previously experienced early valve failure using a single‐valve prosthesis had a Dual Valve placed by a speech language pathologist. A total of seventeen Dual Valves were inserted during routine clinical visits for valve replacement. Time intervals from insertion to replacement of the Dual Valve, as well as the average lifespan of patients’ three previous single valves were collected. Subjective, categorical responses to speech quality and phonation effort for the Dual Valve compared to the single valve were collected on a questionnaire upon failure of the device.

Results

The mean duration of the single valve was 60 days, with a median of 51 days, whereas the mean duration of the Dual Valve was 164 days, with a median duration of 84 days. Both sets of data were statistically significant, with a P value of .0131. Valve life was increased in 86% of patients, with 43% experiencing greater than 150 days improvement in valve duration when using the Dual Valve. Phonation effort was increased in 14% of patients, and speech quality was not significantly affected in any patients.

Conclusions

In this select population, the Dual Valve offers improved durability over the single valve without sacrificing speech quality, making it a preferred prosthesis option for patients experiencing single‐valve failure in less than 3 months.

Level of Evidence

4. Laryngoscope, 128:422–426, 2018
Optical coherence tomography image‐guided smart laser knife for surgery
Authors: Katta Nitesh , McElroy Austin B. , Estrada Arnold D. , Milner Thomas E.
Published: August 2017

Background and Objective

Surgical oncology can benefit from specialized tools that enhance imaging and enable precise cutting and removal of tissue without damage to adjacent structures. The combination of high‐resolution, fast optical coherence tomography (OCT) co‐aligned with a nanosecond pulsed thulium (Tm) laser offers advantages over conventional surgical laser systems. Tm lasers provide superior beam quality, high volumetric tissue removal rates with minimal residual thermal footprint in tissue, enabling a reduction in unwanted damage to delicate adjacent sub‐surface structures such as nerves or micro‐vessels. We investigated such a combined Tm/OCT system with co‐aligned imaging and cutting beams—a configuration we call a “smart laser knife.”

Methods

A blow‐off model that considers absorption coefficients and beam delivery systems was utilized to predict Tm cut depth, tissue removal rate and spatial distribution of residual thermal injury. Experiments were performed to verify the volumetric removal rate predicted by the model as a function of average power. A bench‐top, combined Tm/OCT system was constructed using a 15W 1940 nm nanosecond pulsed Tm fiber laser (500 μJ pulse energy, 100 ns pulse duration, 30 kHz repetition rate) for removing tissue and a swept source laser (1310 ± 70 nm, 100 kHz sweep rate) for OCT imaging. Tissue phantoms were used to demonstrate precise surgery with blood vessel avoidance. Depth imaging informed cutting/removal of targeted tissue structures by the Tm laser was performed.

Results

Laser cutting was accomplished around and above phantom blood vessels while avoiding damage to vessel walls. A tissue removal rate of 5.5 mm3/sec was achieved experimentally, in comparison to the model prediction of approximately 6 mm3/sec.

Conclusion

We describe a system that combines OCT and laser tissue modification with a Tm laser. Simulation results of the tissue removal rate using a simple model, as a function of average power, are in good agreement with experimental results using tissue phantoms. Lasers Surg. Med. 50:202–212, 2018. © 2017 Wiley Periodicals, Inc.
Altered behavioral responses to gamma‐aminobutyric acid pharmacological agents in a mouse model of Huntington's disease
Authors: Hsu Yi‐Ting , Chang Ya‐Gin , Chang Ching‐Pang , Siew Jian‐Jing , Chen Hui‐Mei , Tsai Chon‐Haw , Chern Yijuang
Published: August 2017

Background: Disruptions in gamma‐aminobutyric (GABA) acid signaling are believed to be involved in Huntington's disease pathogenesis, but the regulation of GABAergic signaling remains elusive. Here we evaluated GABAergic signaling by examining the function of GABAergic drugs in Huntington's disease and the expression of GABAergic molecules using mouse models and human brain tissues from Huntington's disease.

Methods: We treated wild‐type and R6/2 mice (a transgenic Huntington's disease mouse model) acutely with vehicle, diazepam, or gaboxadol (drugs that selectively target synaptic or extrasynaptic GABAA receptors) and monitored their locomotor activity. The expression levels of GABAA receptors and a major neuron‐specific chloride extruder (potassium‐chloride cotransporter‐2) were analyzed by real‐time quantitative polymerase chain reaction, Western blot, and immunocytochemistry.

Results: The R6/2 mice were less sensitive to the sedative effects of both drugs, suggesting reduced function of GABAA receptors. Consistently, the expression levels of α1/α2 and δ subunits were lower in the cortex and striatum of R6/2 mice. Similar results were also found in 2 other mouse models of Huntington's disease and in Huntington's disease patients. Moreover, the interaction and expression levels of potassium‐chloride cotransporter‐2 and its activator (brain‐type creatine kinase) were decreased in Huntington's disease neurons. These findings collectively suggest impaired chloride homeostasis, which further dampens GABAA receptor‐mediated inhibitory signaling in Huntington's disease brains.

Conclusions: The dysregulated GABAergic responses and altered expression levels of GABAA receptors and potassium‐chloride cotransporter‐2 in Huntington's disease mice appear to be authentic and may contribute to the clinical manifestations of Huntington's disease patients. © 2017 International Parkinson and Movement Disorder Society
Effect of supplementation of recombinant Regucalcin in extender on cryopreservation of spermatozoa of water buffalo (Bubalus bubalis)
Authors: Pillai Harikrishna , Parmar Mehtab S. , Shende Ashish M. , Thomas Jobin , Sharma Harikumar S. , Sharma G Taru , Ghosh Subrata K. , Kumaresan Arumugam , Bhure Sanjeev K.
Published: August 2017

Elevated intracellular calcium concentration and oxidative damage are two major factors contributing to the poor fertility of cryopreserved spermatozoa. Regucalcin (RGN), also known as Senescence marker protein‐30 (SMP‐30), is a calcium‐binding protein with multiple roles that include calcium homeostasis, anti‐oxidative, anti‐apoptosis, and anti‐proliferation. In Drosophila, RGN is reportedly a putative cold‐tolerance gene and a cytoprotective role for RGN against intracellular calcium elevation and oxidative stress was reported in P19 cell lines. Given that RGN has anticapacitatory effect and abundant in the male reproductive tract, we hypothesized that it may play a cryoprotective role for spermatozoa. We investigated this by including RGN, at three different concentrations (20, 40, and 60 μg/ml), as a supplement for Tris‐egg yolk‐based semen extender. Post‐thaw metrics of progressive motility, acrosome integrity, and zona pellucida binding of spermatozoa were evaluated for three ejaculates of three clinically normal, breeding Murrah buffaloes. A concentration of 40 μg/ml of recombinant RGN supplemented during sperm freezing resulted in significant increases in the post‐thaw progressive motility of spermatozoa (50.6 ± 3.5% vs 40.6 ± 2.6%; p < 0.01), acrosome integrity (53.3 ± 7.4 vs 75.6 ± 6.8; p < 0.05), and zona pellucida binding (31.6 ± 14.0 vs 191.9 ± 12.3 bound spermatozoa; p < 0.01) compared to control conditions without RGN. Thus, ∼1 μM recombinant RGN, which retains the ability to bind calcium, has a cryoprotective effect for buffalo spermatozoa in extender.
MRI assessment of coronary microvascular endothelial nitric oxide synthase function using myocardial T1 mapping
Authors: Cui Sophia X. , Epstein Frederick H.
Published: August 2017

Purpose

Endothelial nitric oxide synthase (eNOS) plays a central role in regulating vascular tone, blood flow, and microvascular permeability. Endothelial dysfunction, including eNOS dysfunction, is an early biomarker of vascular disease. This study aimed to show that myocardial T1 mapping during nitric oxide synthase (NOS) inhibition could assess coronary microvascular eNOS function.

Methods

Wild‐type mice, eNOS−/− mice, and wild‐type mice fed a high‐fat diet underwent T1 mapping at baseline and for 20 min after injection of NG‐nitro‐L‐arginine methyl ester (LNAME), a NOS inhibitor. First‐pass perfusion MRI was performed in wild‐type mice at baseline and 5 min after LNAME injection.

Results

T1 mapping detected an increase in myocardial T1 5 min after an injection of 4 mg/kg LNAME compared with baseline in control mice (T1 = 1515 ± 30 ms with LNAME versus T1 = 1402 ± 30 ms at baseline, P < 0.05). No change in myocardial T1 after LNAME injection was observed in eNOS−/− mice. The change in T1 after LNAME injection was less in high‐fat‐diet mice (ΔT1 = 31 ± 14 ms at 12 weeks of diet and ΔT1 = 16 ± 17 ms at 18 weeks of diet) compared with mice fed a standard diet (ΔT1 = 113 ± 15 ms), with P < 0.05. First‐pass MRI measured similar perfusion at baseline and 5 min after LNAME injection.

Conclusions

NOS inhibition causes an increase in myocardial T1 in healthy mice, and this effect is mediated through eNOS. T1 mapping during NOS inhibition detects coronary microvascular eNOS dysfunction in high‐fat‐diet mice. T1 mapping during NOS inhibition may be useful in preclinical studies aiming to investigate mechanisms underlying and therapies for coronary microvascular eNOS dysfunction. Magn Reson Med 79:2246–2253, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Improvements in Cardiovascular Risk Factors in Young Adults in a Randomized Trial of Approaches to Weight Gain Prevention
Authors: Wing Rena R. , Tate Deborah F. , Garcia Katelyn R. , Bahnson Judy , Lewis Cora E. , Espeland Mark A. ,   for the Study of Novel Approaches to Weight Gain Prevention (SNAP) Research Group
Published: August 2017

Objective

Weight gain occurs commonly in young adults and increases the risk of cardiovascular disease (CVD). Following on a previous report that two self‐regulation interventions reduced weight gain relative to control, this study examines whether these interventions also benefit CVD risk factors.

Methods

The Study of Novel Approaches to Weight Gain Prevention was a randomized trial in two academic settings (N = 599; 18‐35 years; BMI 21‐30 kg/m2) comparing two interventions (Self‐Regulation with Small Changes; Self‐Regulation with Large Changes) and a control group. Small Changes taught participants to make daily small changes in calorie intake (approximately 100 calories) and activity. Large Changes taught participants to initially lose 5 to 10 pounds to buffer anticipated weight gains. CVD risk factors were assessed at baseline and at 2 years in 471 participants.

Results

Although Large Changes was associated with more beneficial changes in glucose, insulin, and homeostatic model assessment of insulin resistance than Control, these differences were not significant after adjusting for multiple comparisons or 2‐year weight change. Comparison of participants grouped by percent weight change from baseline to 2 years showed significant differences for several CVD risk factors, with no interaction with treatment condition.

Conclusions

Magnitude of weight change, rather than specific weight gain prevention interventions, was related to changes in CVD risk factors in young adults.
Specific Binding of Liposomal Nanoparticles through Inverse Electron‐Demand Diels–Alder Click Chemistry
Authors: Brand Christian , Iacono Pasquale , Pérez‐Medina Carlos , Mulder Willem J. M. , Kircher Moritz F. , Reiner Thomas
Published: August 2017

Here, we report a method to specifically bind liposomal radiopharmaceuticals to a CoCrMo alloy, which can be used in arterial stents, via an irreversible inverse electron‐demand Diels–Alder reaction. Inspired by recent accomplishments in pre‐targeted imaging using tetrazine‐trans‐cyclooctene click chemistry, we synthesized 89Zr‐labeled trans‐cyclooctene‐functionalized liposomal nanoparticles, which were validated on a tetrazine‐appended polydopamine‐coated CoCrMo surface. In efforts to ultimately translate this new material to biomedical applications, we compared the ability of 89Zr‐TCO–liposomal nanoparticles (89Zr‐TCO‐LNP) to be immobilized on the tetrazine surface to the control suspensions of non‐TCO functionalized 89Zr‐liposomal nanoparticles. Ultimately, this platform technology could result in a systemic decrease of the radiotherapeutic dose deposited in non‐targeted tissues by specific removal of long‐circulating liposomal radiopharmaceuticals from the blood pool.
Detonation Performance Characterization of a Novel CL‐20 Cocrystal Using Microwave Interferometry
Authors: Vuppuluri Vasant S. , Samuels Philip J. , Caflin Kelley C. , Gunduz I. Emre , Son Steven F.
Published: August 2017

Development of novel energetic materials is a significant challenge. Cocrystallization has been explored as another route to development of novel materials. However, very little characterization of detonation performance has been performed for these energetic cocrystals. A major challenge for performing detonation velocity measurements with cocrystals is that typical measurement techniques require hundreds of grams to kilograms of material, an amount that exceeds the entire supply of many cocrystals. In this work, small‐scale detonation velocity measurements using about 1.2 g of material per test employing microwave interferometry are presented and discussed for a novel cocrystal of 1‐methyl‐3,5‐dinitro‐1,2,4‐triazole (MDNT) and hexanitrohexaazaisowurtzitane (CL‐20) in a 1 : 1 molar ratio and compared to a physical mixture of MDNT and CL‐20 in the same molar ratio. The results are compared with detonation velocity measurements with cyclotetramethylene tetranitramine (HMX), which provide validation of the technique and further comparison of the results. With this technique, detonation velocity differences as low as 100 m/s are resolvable. The MDNT/CL‐20 cocrystal is observed to detonate over 500 m/s faster than the physical mix and over 600 m/s faster than HMX at the same charge density which is held constant in this work. The enthalpy of formation of the MDNT/CL‐20 cocrystal was also measured. Using this, the detonation velocity of the cocrystal was calculated using thermochemistry to be 230 m/s faster than that of the physical mixture of MDNT and CL‐20 in the same molar ratio as is contained within the cocrystal at a charge density of 1.4 g/cm3. The higher detonation velocity of the cocrystal (both measured and predicted) compared to the physical mixture is likely attributable to bonding energy contained within the cocrystal and the arrangement of the coformers within the cocrystal.
Integration of Genome Scale Metabolic Networks and Gene Regulation of Metabolic Enzymes With Physiologically Based Pharmacokinetics
Authors: Maldonado Elaina M. , Leoncikas Vytautas , Fisher Ciarán P. , Moore J. Bernadette , Plant Nick J. , Kierzek Andrzej M.
Published: August 2017

The scope of physiologically based pharmacokinetic (PBPK) modeling can be expanded by assimilation of the mechanistic models of intracellular processes from systems biology field. The genome scale metabolic networks (GSMNs) represent a whole set of metabolic enzymes expressed in human tissues. Dynamic models of the gene regulation of key drug metabolism enzymes are available. Here, we introduce GSMNs and review ongoing work on integration of PBPK, GSMNs, and metabolic gene regulation. We demonstrate example models.
Microstructural Effects on the Poisson's Ratio of Star‐Shaped Two‐Dimensional Systems
Authors: Wang Yun‐Che , Shen Meng‐Wei , Liao Si‐Min
Published: August 2017

Microstructured plates, consisting of various conventional and re‐entrant cells, are numerically constructed and analyzed for their effective elastic properties under in‐plane deformation. The finite element numerical method is adopted. The calculated effective Poisson's ratios of the plates are found to be in the range between −1 and 1, in consistency with the theory of two‐dimensional elasticity. Auxetic angles need to be greater than about 20° in order to obtain negative Poisson's ratio. Increasing the auxetic angles reduces the effective pure shear modulus. Elastically anisotropic characteristics of the homogenized plate are analyzed with the calculated effective Young's modulus, Poisson's ratio, and pure shear modulus.
Separation of Nickelocene‐Filled Single‐Walled Carbon Nanotubes by Conductivity Type and Diameter
Authors: Kharlamova Marianna V. , Kramberger Christian , Yanagi Kazuhiro , Sauer Markus , Saito Takeshi , Pichler Thomas
Published: August 2017

We have performed the separation of nickelocene‐filled single‐walled carbon nanotubes (SWCNTs) with a mean diameter of 1.7 nm by conductivity type and diameter using density gradient ultracentrifugation. The separated nanotube fractions were characterized by optical absorption spectroscopy (OAS), X‐ray photoelectron spectroscopy (XPS), and Raman spectroscopy. The OAS investigation of the separated samples showed the absence of optical absorption bands of semiconducting tubes in metallic sample and vice versa, which proved a high purity of the nanotube fractions. The XPS investigation of the separated samples showed different positions, spectral widths and asymmetry of the C 1s core level spectra. The multifrequency Raman spectroscopy investigation of the separated samples allowed performing an analysis of the diameter range of nanotubes. The demonstrated successful separation of the filled SWCNTs by conductivity type and diameter enables demanding applications of ultra pure SWCNTs with tailored properties.
Raman Spectroscopy of Suspended MoS2
Authors: O'Brien Maria , Scheuschner Nils , Maultzsch Janina , Duesberg Georg S. , McEvoy Niall
Published: August 2017

This report details the Raman spectroscopic characterization of suspended MoS2. MoS2 was grown by chemical vapor deposition (CVD) and then transferred onto holey substrates using a polymer‐assisted technique, allowing measurement of suspended MoS2. Significant differences in the spectral characteristics of suspended and supported MoS2 were observed which are attributed to strain in the MoS2 suspended over the holey regions of the substrate. In particular, we investigate the low‐frequency Raman spectrum of free‐standing CVD‐grown MoS2, and estimate the strain caused in the layers by suspension over holes.
Low Doses of Curcuma longa Modulates Cell Migration and Cell–Cell Adhesion
Authors: de Campos Paloma Santos , Matte Bibiana Franzen , Diel Leonardo Francisco , Jesus Luciano Henrique , Bernardi Lisiane , Alves Alessandro Menna , Rados Pantelis Varvaki , Lamers Marcelo Lazzaron
Published: August 2017

Cell invasion and metastasis are involved in clinical failures in cancer treatment, and both events require the acquisition of a migratory behavior by tumor cells. Curcumin is a promising natural product with anti‐proliferative activity, but its effects on cell migration are still unclear. We evaluated the effects of curcumin on the proliferation, apoptosis, migration, and cell–cell adhesion of keratinocyte, oral squamous cell carcinoma (OSCC), and fibroblast cell lines, as well as in a xenograft model of OSCC. Curcumin (2 μM) decreased cell proliferation in cell lines with mesenchymal characteristics, while cell death was detected only at 50 μM. We observed that highly migratory cells showed a decrease on migration speed and directionality when treated with 2 or 5 μM of curcumin (50% and 40%, respectively, p < 0.05). Using spheroids, we observed that curcumin dose dependently decreased cell–cell adhesion, especially on tumor‐derived spheroids. Also, in a xenograft model with patient‐derived OSCC cells, the administration of curcumin decreased tumor growth and aggressiveness when compared with untreated tumors, indicating the potential antitumor effect in oral cancer. These results suggest that lower doses of curcumin can influence several steps involved in tumorigenesis, including migration properties, suggesting a possible use in cancer therapy. Copyright © 2017 John Wiley & Sons, Ltd.