bluuebunny/crossref_metadata_2025 huggingface dataset:
HDAC8 regulates canonical Wnt pathway to promote differentiation in skeletal muscles
Authors: Ferrari Luca , Bragato Cinzia , Brioschi Loredana , Spreafico Marco , Esposito Simona , Pezzotta Alex , Pizzetti Fabrizio , Moreno‐Fortuny Artal , Bellipanni Gianfranco , Giordano Antonio , Riva Paola , Frabetti Flavia , Viani Paola , Cossu Giulio , Mora Marina , Marozzi Anna , Pistocchi Anna
Published: September 2018

Histone deacetylase 8 (HDAC8) is a class 1 histone deacetylase and a member of the cohesin complex. HDAC8 is expressed in smooth muscles, but its expression in skeletal muscle has not been described. We have shown for the first time that HDAC8 is expressed in human and zebrafish skeletal muscles. Using RD/12 and RD/18 rhabdomyosarcoma cells with low and high differentiation potency, respectively, we highlighted a specific correlation with
HDAC8 expression and an advanced stage of muscle differentiation. We inhibited HDAC8 activity through a specific PCI‐34051 inhibitor in murine C2C12 myoblasts and zebrafish embryos, and we observed skeletal muscles differentiation impairment. We also found a positive regulation of the canonical Wnt signaling by HDAC8 that might explain muscle differentiation defects. These findings suggest a novel mechanism through which HDAC8 expression, in a specific time window of skeletal muscle development, positively regulates canonical Wnt pathway that is necessary for muscle differentiation.
Distinct Tie2 tyrosine phosphorylation sites dictate phenotypic switching in endothelial progenitor cells
Authors: Siavashi Vahid , Nassiri Seyed Mahdi , Rahbarghazi Reza , Mohseni Zahra , Sharifi Ali Mohammad
Published: September 2018

Angiogenesis is a regulated process involving the proliferation, migration, and remodeling of different cell types particularly mature endothelial and their progenitor cells, nominated as endothelial progenitor cells (EPCs). Tie2/Tek is a tyrosine kinase receptor expressed by endothelial cells that induces signal transduction pathways involved in endothelial biology. To address the potential importance of the various tyrosine residues of Tie2 in EPC development, we generated a series of Tie2 tyrosine mutated (Y1106F, Y1100F, and Y1111F) EPCs and then assess the biological features of these cells. Clonogenic, tubulogenic, proliferative, migratory, and functional properties of these cells were analyzed. Next, GFP‐positive EPCs containing Tie2 tyrosine mutations were systemically transplanted into sublethaly irradiated mice to analyze the potency of these cells for marrow reconstitution. We found that mutation in the Tie2 tyrosine 1106 residue directed EPCs toward a mature endothelial phenotype, which was associated with augmented tubulogenic and migratory properties, and increased phosphorylation of the active site (tyrosine 992) as well as increased vascular perfusion in the in vivo Matrigel plug assay. Moreover, transplantation of 1106 Tie2 mutant EPCs failed to reconstitute the bone marrow after myeloablation, whereas transplantation of EPCs with the 1100 or 1111 Tie2 tyrosine mutation resulted in bone marrow engraftment, leading to improved survival of recipient mice. Our findings demonstrate that the tyrosine 1106 residue in Tie2 plays a key role to maintain the stemness features of EPCs.
Gene expression of TWIST1 and ZBTB16 is regulated by methylation modifications during the osteoblastic differentiation of mesenchymal stem cells
Authors: Marofi Faroogh , Vahedi Ghasem , Solali Saeed , Alivand Mohammadreza , Salarinasab Sadegh , Zadi Heydarabad Milad , Farshdousti Hagh Majid
Published: September 2018

Background

Osteoblastic differentiation of mesenchymal stem cells (MSCs) is the principal stage during the restoration and regeneration of bone tissue. Epigenetic modifications such as DNA methylation play a key role in the differentiation process of stem cells. In this study, the methylation status of the promoter region of ZBTB16 and Twist1 genes and their role in controlling osteoblastic differentiation in MSCs was investigated during the osteoblastic differentiation of MSCs.

Methods

The MSCs were cultured under standard conditions and differentiated into the osteoblasts. We had three treatment groups including 5‐azacytidine (methylation inhibitor), metformin (Twist‐inhibitor), and procaine (Wnt/β‐catenin inhibitor) and a non‐treated group (control). Methylation level of DNA in the promoter regions was monitored by methylation specific‐quantitative polymerase chain reaction (PCR). Also, the mRNA levels of key genes in osteoblastic differentiation were measured using real‐time PCR.

Results

ZBTB16 gene expression was upregulated, and promoter methylation was decreased. For Twist1 messenger RNA (mRNA) level decreased and promoter methylation increased during osteoblastic differentiation of MSCs. 5‐Azacytidine caused a significant reduction in methylation and increased the mRNA expression of ZBTB16 and Twist1. Metformin repressed the Twist1 expression, and therefore osteoblastic differentiation was increased. On the opposite side, procaine could block the WNT/β‐catenin signaling pathway, as a consequence the gene expression of key genes involved in osteoblastic differentiation was declined.

Conclusion

We found that methylation of DNA in the promoter region of ZBTB16 and Twist1 genes might be one of the main mechanisms that controlling the gene expression during osteoblastic differentiation of MSCs. Also, we could find an association between regulation of Twist1 and ZBTB16 genes and osteoblastic differentiation in MSCs by showing the relation between their expression and some key genes involved in osteoblastic differentiation. In addition, we found a connection between the Twist1 expression level and osteoblastic differentiation by using a Twist‐inhibitor (metformin).
TGF‐β1‐PML SUMOylation‐peptidyl‐prolyl cis–trans isomerase NIMA‐interacting 1 (Pin1) form a positive feedback loop to regulate cardiac fibrosis
Authors: Wu Di , Huang Di , Li Liang‐Liang , Ni Ping , Li Xiu‐Xian , Wang Bing , Han Yan‐Na , Shao Xiao‐Qi , Zhao Dan , Chu Wen‐Feng , Li Bai‐Yan
Published: September 2018

Transforming growth factor‐β (TGF‐β) signaling pathway is involved in fibrosis in most, if not all forms of cardiac diseases. Here, we evaluate a positive feedback signaling the loop of TGF‐β1/promyelocytic leukemia (PML) SUMOylation/Pin1 promoting the cardiac fibrosis. To test this hypothesis, the mice underwent transverse aortic constriction (3 weeks) were developed and the morphological evidence showed obvious interstitial fibrosis with TGF‐β1, Pin1 upregulation, and increase in PML SUMOylation. In neonatal mouse cardiac ﬁbroblasts (NMCFs), we found that exogenous TGF‐β1 induced the upregulation of TGF‐β1 itself in a time‐ and dose‐dependent manner, and also triggered the PML SUMOylation and the formation of PML nuclear bodies (PML‐NBs), and consequently recruited Pin1 into nuclear to colocalize with PML. Pharmacological inhibition of TGF‐β signal or Pin1 with LY364947 (3 μM) or Juglone (3 μM), the TGF‐β1‐induced PML SUMOylation was reduced significantly with downregulation of the messenger RNA and protein for TGF‐β1 and Pin1. To verify the cellular function of PML by means of gain‐ or loss‐of‐function, the positive feedback signaling loop was enhanced or declined, meanwhile, TGF‐β‐Smad signaling pathway was activated or weakened, respectively. In summary, we uncovered a novel reciprocal loop of TGF‐β1/PML SUMOylation/Pin1 leading to myocardial fibrosis.
Curcumin induces concentration‐dependent alterations in mitochondrial function through ROS in C2C12 mouse myoblasts
Authors: Yu Tianzheng , Dohl Jacob , Elenberg Falicia , Chen Yifan , Deuster Patricia
Published: September 2018

Curcumin exhibits antioxidant properties in normal cells where the uptake is low, unlike in tumor cells where uptake is high and curcumin increases reactive oxygen species (ROS) production and cell death. Mitochondria are the main source and primary target of cellular ROS. We hypothesized that curcumin would regulate cellular redox status and mitochondrial function, depending on cell sensitivity and/or curcumin concentration in normal cells. We examined the differences between low and high concentrations of curcumin, with specific attention focused on ROS levels, mitochondrial function, and cell viability in mouse C2C12 myoblast under normal and simulated conditions of diabetes. Cells incubated with high concentrations of curcumin (10–50 μM) resulted in decreased cell viability and sustained robust increases in ROS levels. Mechanistic studies showed that increased ROS levels in cells incubated with 20 μM curcumin induced opening of mitochondrial permeability transition pores and subsequent release of cytochrome c, activation of caspases 9 and 3/7, and apoptotic cell death. Low concentrations of curcumin (1–5 μM) did not affect cell viability, but induced a mild increase in ROS levels, which peaked at 2 hr after the treatment. Incubation with 5 μM curcumin also induced ROS‐dependent increases in mitochondrial mass and membrane potential. Finally, pretreatment with 5 μM curcumin prevented high glucose‐induced oxidative cell injury. Our study suggests that mitochondria respond differentially depending on curcumin concentration‐dependent induction of ROS. The end result is either cell protection or death. Curcumin may be an effective therapeutic target for diabetes and other mitochondrial diseases when used in low concentrations.
Dynamics changes in the transcription factors during early human embryonic development
Authors: Godini Rasoul , Fallahi Hossein
Published: September 2018

Development of an embryo from a single cell, zygote, to multicellular morulae requires activation of hundreds of genes that were mostly inactivated before fertilization. Inevitably, transcription factors (TFs) would be involved in modulating the drastic changes in gene expression pattern observed at all preimplantation stages. Despite many ongoing efforts to uncover the role of TFs at the early stages of embryogenesis, still many unanswered questions remained that need to be explored. This could be done by studying the expression pattern of multiple genes obtained by high‐throughput techniques. In the current study, we have identified a set of TFs that are involved in the progression of the zygote to blastocyst. Global gene expression patterns of consecutive stages were compared and differences documented. Expectedly, at the early stages of development, only a few sets of TFs differentially expressed while at the later stages hundreds of TFs appear to be upregulated. Interestingly, the expression levels of many TFs show an oscillation pattern during development indicating a need for their precise expression. A significant shift in gene expression was observed during the transition from four‐ to eight‐cell stages, an indication of zygote genome activation. Additionally, we have found 11 TFs that were common in all stages including ATF3, EN1, IFI16, IKZF3, KLF3, NPAS3, NR2F2, RUNX1, SOX2, ZBTB20, and ZSCAN4. However, their expression patterns did not follow similar trends in the steps studied. Besides, our findings showed that both upregulation and active downregulation of the TFs expression is required for successful embryogenesis. Furthermore, our detailed network analysis identified the hub TFs for each transition. We found that HNF4A, FOXA2, and EP300 are the three most important elements for the first division of zygote.
Prognostic value of aberrantly expressed methylation gene profiles in lung squamous cell carcinoma: A study based on The Cancer Genome Atlas
Authors: Gao Chundi , Zhuang Jing , Zhou Chao , Ma Ke , Zhao Minzhang , Liu Cun , Liu Lijuan , Li Huayao , Feng Fubin , Sun Changgang
Published: September 2018

Currently, research on genome‐scale epigenetic modifications for studying the pathogenesis of lung cancer is lacking. Aberrant DNA methylation, as the most common and important modification in epigenetics, is an important means of regulating genomic function and can be used as a biomarker for the diagnosis and prognosis of lung squamous cell carcinoma (LUSC). In this paper, methylation information and gene expression data from patients with LUSC were extracted from the TCGA database. Univariate and multivariate COX analyses were used to screen abnormally methylated genes related to the prognosis of LUSC. The relationship between key DNA methylation sites and the transcriptional expression of LUSC‐related genes was explored. A prognostic risk model constructed by four abnormally methylated genes (VAX1, CH25H, AdCyAP1, and Irx1) was used to predict the prognosis of LUSC patients. Also, the methylation levels of the key gene IRX1 are significantly correlated with the prognosis and correlated with the methylation of the site cg09232937 and cg10530883. This study is based on high‐throughput data mining and provides an effective bioinformatics basis for further understanding the pathogenesis and prognosis of LUSC, which has important theoretical significance for follow‐up studies on LUSC.
Raloxifene attenuates oxidative stress and preserves mitochondrial function in astrocytic cells upon glucose deprivation
Authors: Vesga‐Jiménez Diego J. , Hidalgo‐Lanussa Oscar , Baez‐Jurado Eliana , Echeverria Valentina , Ashraf Ghulam Md , Sahebkar Amirhossein , Barreto George E.
Published: September 2018

Oxidative stress and mitochondrial dysfunction induced by metabolic insults are both hallmarks of various neurological disorders, whereby neuronal cells are severely affected by decreased glucose supply to the brain. Likely injured, astrocytes are important for neuronal homeostasis and therapeutic strategies should be directed towards improving astrocytic functions to improve brain's outcome. In the present study, we aimed to assess the actions of raloxifene, a selective estrogen receptor modulator in astrocytic cells under glucose deprivation. Our findings indicated that pretreatment with 1 µM raloxifene results in an increase in cell viability and attenuated nuclei fragmentation. Raloxifene's actions also rely on the reduction of oxidative stress and preservation of mitochondrial function in glucose‐deprived astrocytic cells, suggesting the possible direct effects of this compound on mitochondria. In conclusion, our results demonstrate that raloxifene's protective actions might be mediated in part by astrocytes in the setting of a metabolic insult.
The Path to Perfect Pediatric Posology — Drug Development in Pediatrics
Authors: Korth‐Bradley Joan M.
Published: September 2018

Reluctance to enroll pediatric subjects in clinical trials has left gaps in information about dosing, safety, and efficacy of medications. Pharmacotherapeutic information for pediatric patients may be available for only a small range of ages and may be deficient, as children respond differently as they grow and mature from prematurity to adolescence. Current regulations, however, require early planning for the participation of children in drug development, as pediatric plans must be submitted at the end of phase 1 (European Union) or the end of phase 2 (United States). These plans are extensive, outlining planned studies, subjects to be enrolled, dose and dosage form justification, planned observations, and statistical analysis as well as planned modeling, simulation, and extrapolation analyses. The extent to which efficacy information in adults can be extrapolated to children depends on how similar the disease is in adults and each of the 5 pediatric age groups. Extrapolation may not be possible for conditions that do not occur in adults, requiring a complete development plan in adults, or extrapolation may be complete because of similar pathology and response to treatment. Pharmacokinetic and safety information cannot be extrapolated and must be collected in children of all ages, unless a waiver is granted. Physiologically based pharmacokinetic modeling, optimal design, population pharmacokinetics, and scavenged samples are all examples of new methodologies being used to study pediatric therapeutics. Clinicaltrials.gov and EU Clinical Trials registry are good sources of results of pediatric trials, although sponsors are also working toward prompt publication of study results in peer‐reviewed journals.
Potassium recovery from centrate: taking advantage of autotrophic nitrogen removal for multi‐nutrient recovery
Authors: Johansson Sara , Ruscalleda Maël , Saerens Bart , Colprim Jesús
Published: September 2018

BACKGROUND

Potassium is a key macronutrient, but little attention has been paid to its recovery from waste streams. This study investigates simultaneous recovery of phosphorus and potassium in the form of potassium struvite (MgKPO4·6H2O) from centrate after nitrogen removal by partial nitritation–anammox (PNA). Lab‐scale batch experiments to assess the influence of pH, Mg:P ratio and temperature on nutrient removal were conducted on effluent from two PNA reactors fed with centrate from municipal wastewater treatment plants.

RESULTS

pH had a strong impact on potassium removal, which increased up to pH 11. At this pH, a product containing 11.4% P, 3.51% N and 4.34% K was obtained. X‐ray diffraction confirmed the presence of potassium struvite together with ammonium struvite (MgNH4PO4.6H2O). PNA reduced the alkalinity by 90%, which surpasses the performance of conventional CO2 stripping by aeration.

CONCLUSION

Coupling PNA with struvite precipitation allows for the recovery of N, P and K in a multi‐nutrient product and may drastically reduce the need for alkali dosing for pH control. © 2018 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Cell therapy products: focus on issues with manufacturing and quality control of chimeric antigen receptor T‐cell therapies
Authors: Eyles Jim E , Vessillier Sandrine , Jones Anika , Stacey Glyn , Schneider Christian K , Price Jack
Published: September 2018

Recent accelerated approvals of Chimeric Antigen Receptor T‐cell (CAR‐T) therapies targeting refractory haematological malignancies underscore the potential for this novel technology platform to provide new therapeutic options for oncology areas with high unmet medical needs. However, these powerful ‘living drugs’ are markedly different to conventional small molecule and biologic therapies on several levels. The highly complex nature and varied composition of CAR‐T based products still requires considerable investigation to resolve the best approaches to ensure reproducible and cost‐effective manufacture, clinical development, and application. This review will focus on key issues for manufacturing and quality control of these exciting new therapeutic modalities, preceded by a brief description of CAR principals and clinical development considerations. © 2018 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Polynomial relations between matrices of graphs
Authors: Spiro Sam
Published: September 2018

We derive a correspondence between the eigenvalues of the adjacency matrix and the signless Laplacian matrix of a graph when is ‐biregular by using the relation . This motivates asking when it is possible to have for a polynomial, , and matrices associated to a graph . It turns out that, essentially, this can only happen if is either regular or biregular.
Triangle‐free planar graphs with the smallest independence number
Authors: Dvořák Zdeněk , Masařík Tomáš , Musílek Jan , Pangrác Ondřej
Published: September 2018

Steinberg and Tovey proved that every ‐vertex planar triangle‐free graph has an independent set of size at least , and described an infinite class of tight examples. We show that all ‐vertex planar triangle‐free graphs except for this one infinite class have independent sets of size at least .
Efficient Green Synthesis and Computational Chemical Study of Some Interesting Heterocyclic Derivatives as Insecticidal Agents
Authors: Fahmy A. F. M. , Rizk S. A. , Hemdan M. M. , El‐Sayed A. A. , Hassaballah A. I.
Published: September 2018

A series of 5,5‐diarylhydantoin (Dilantin) 3, 4, and 7, imidazole 1, 2, 5, 6, 8, and 9, thiazole 10–12, triazinthione 13, 15, 16, and 17, and thiadiazine 14 derivatives, containing diverse hydrophobic groups, were green synthesized through one‐pot stepwise reaction of aromatic aldehydes, vitamin B1, and nitrogen nucleophiles, for example, urea, thiourea, and thiosemicarbazide using grinding technique as well as conventional thermal methods. Such synthesized compounds have potent insecticidal activities; for example, compounds 4, 6, and 17 exhibited the highest insecticidal activity against both Plutella xylostella and Helicoverpa armigera with minimum inhibitory concentration values at 500 μg/mL and LD50 activities at 50 μg/mL. The density functional theory was then applied to explore the structural and electronic characteristics of these compounds. All the synthesized compounds have been characterized based on their elemental analyses and spectral data.
The combined effects of questioning technique and interviewer manner on false confessions
Authors: Paton Wendy , Bain Stella A. , Gozna Lynsey , Gilchrist Elizabeth , Heim Derek , Gardner Euan , Cairns David , McGranaghan Paul , Fischer Rico
Published: September 2018

Although it is known that interrogation tactics can elicit false confessions and interviewer manner may determine the outcome of an interview, the combined effects of questioning technique and interviewer manner on false confessions have not been examined empirically. Following a false accusation of theft, participants were interviewed in one of four questioning conditions (minimisation, repetitive questioning, leading questions, and nonleading questions) in which interviewers adopted a stern or friendly manner. Perceptions of pressure to confess and interviewer behaviours were measured. Significantly more false confessions were elicited using nonleading questions rather than repetitive questioning. More false confessions were elicited in the friendly interviewer condition than in the stern interviewer condition. Neither interviewer manner nor questioning technique had a significant effect on subjective ratings of pressure to confess. The finding that false confessions may be elicited in the absence of coercive tactics may have implications for informing best practices in investigative interviewing.
Prediction of Postoperative Vocal Fold Function After Intraoperative Recovery of Loss of Signal
Authors: Schneider Rick , Randolph Gregory , Dionigi Gianlorenzo , Barczynski Marcin , Chiang Feng‐Yu , Wu Che‐Wei , Musholt Thomas , Uludag Mehmet , Makay Özer , Sezer Atakan , Teksöz Serkan , Weber Theresia , Sekulla Carsten , Lorenz Kerstin , Özdemir Murat , Machens Andreas , Dralle Henning
Published: September 2018

Objectives/Hypothesis

This multicenter study aimed to 1) evaluate early postoperative vocal fold function in relation to intraoperative amplitude recovery, and 2) determine optimal absolute and relative thresholds of intraoperative amplitude recovery heralding normal early postoperative vocal fold function, both after segmental type 1 and after global type 2 loss of signal (LOS).

Study Design

Prospective outcome study.

Methods

This study, encompassing nine surgical centers from four countries, correlated intraoperative amplitude recovery with early postoperative vocal fold function using receiver operating characteristic analysis.

Results

Included in this study were 68 patients, 48 women and 20 men, who sustained transient recurrent laryngeal nerve injury during thyroid surgery under continuous intraoperative nerve monitoring. Early transient vocal fold palsy was seen in 18 (64%) of 28 patients with ipsilateral segmental LOS type 1, and in 10 (25%) of 40 patients with ipsilateral global LOS type 2. On receiver operating characteristic analysis, relative amplitude thresholds were superior to absolute amplitude thresholds in predicting vocal fold function after LOS type 2 (area under the curve [AUC]: 0.83 vs. 0.65; P = .01 vs. P = .15; Youden index 44% and 253 µV) and LOS type 1 (AUC: 0.96 vs. 0.97; P < .001 each; Youden index 49% and 455 µV). Amplitude recovery ≥50% of baseline after LOS always indicated intact vocal fold function.

Conclusions

When the nerve amplitude recovers ≥50% of baseline after segmental LOS type 1 or global LOS type 2, it is appropriate to extend completion thyroidectomy to the other side during the same session.

Level of Evidence

2b Laryngoscope, 129:525–531, 2019
Gene Expression Subtype Predicts Nodal Metastasis and Survival in Human Papillomavirus–Negative Head and Neck Cancer
Authors: Zevallos Jose P. , Mazul Angela L. , Walter Vonn , Hayes David Neil
Published: September 2018

Objectives/Hypothesis

Gene expression analyses of head and neck cancer have revealed four molecular subtypes: basal (BA), mesenchymal (MS), atypical (AT), and classical (CL). We evaluate whether gene expression subtypes in oral cavity squamous cell carcinoma (OCSCC) and laryngeal squamous cell carcinoma (LSCC) can be used to predict nodal metastasis and prognosticate survival.

Study Design

Retrospective cohort study and genomic analysis.

Methods

OCSCC and LSCC cases were identified from the The Cancer Genome Atlas (TCGA) head and neck cancer cohort. RNA‐seq by expected maximization (RSEM) was used to quantify gene expression levels from TCGA RNA‐seq data and to assign each case to one of four subtypes. Descriptive statistics were used to describe patient, disease, and treatment characteristics in each subtype. Cox regression and Kaplan‐Meier analyses were used to determine associations with survival.

Results

OCSCC cases were comprised primarily of the MS and BA subtypes, whereas LSCC was comprised primarily of CL and AT subtypes. In OCSCC, the MS subtype was significantly associated with higher risk of nodal metastasis. In a subset analysis of clinically T1‐2N0M0 OCSCC, we demonstrate that the MS subtype was predictive of occult nodal metastasis (relative risk = 3.38, 95% confidence interval [CI]: 1.08‐10.69). In LSCC, the CL subtype was associated with significantly worse overall survival (hazard ratio = 4.32, 95% CI: 1.77‐10.54, P = .001).

Conclusions

Gene expression analysis reveals potential novel markers of nodal metastasis and survival in human papillomavirus–negative head and neck cancer. Future studies will continue to refine and validate these markers, with the goal of providing molecular risk assessments that guide therapy and improve patient outcomes.

Level of Evidence

2b Laryngoscope, 129:154–161, 2019
Upper‐Airway Stimulation Before, After, or Without Uvulopalatopharyngoplasty: A Two‐Year Perspective
Authors: Steffen Armin , Abrams Nils , Suurna Maria V. , Wollenberg Barbara , Hasselbacher Katrin
Published: September 2018

Objective

Upper airway stimulation (UAS) is an effective second‐line treatment for obstructive sleep apnea (OSA). In certain patients, there is a considerable need for advanced programming, notably with inadequate palatal response to therapy. The aim of the study was to investigate the impact of uvulopalatopharyngoplasty and tonsillectomy (UPPP‐TE) on UAS therapy outcomes from a 2‐year perspective after implantation.

Methods

This study included all consecutive patients implanted with UAS in which a full set of 1‐ and 2‐year follow‐up assessments (M12 and M24) were obtained. Cases were analyzed in three groups: patients with UPPP‐TE after (group 1) and before (group 2) UAS, and those without UPPP‐TE (group 3).

Results

Therapy success could be achieved in about 80% of the entire cohort. Groups 2 and 3 did not differ significantly with regard to obesity, Apnea‐Hypopnea Index, or Oxygen Desaturation Index. With regard to initial sleep endoscopy, there were fewer patients without any obstruction at the palatal and oropharyngeal levels and higher prevalence of lateral obstruction patterns at oropharynx in group 1 in contrast to groups 2 and 3. Groups 2 and 3 showed similar results, although group 2 patients underwent UPPP‐TE before UAS implantation.

Conclusion

UPPP‐TE should be considered in patients with persistent OSA after UAS implantation if the obstruction is identified at the level of velum and oropharynx. Although this approach has higher response rates and better outcomes can be achieved in patients with UAS, there is no indication for patients to routinely undergo UPPP‐TE prior to UAS implantation.

Level of Evidence

4 Laryngoscope, 129:514–518, 2019
Analysis of pharyngeal edema post‐chemoradiation for head and neck cancer: Impact on swallow function
Authors: Turcotte Maria C. , Herzberg Erica G. , Balou Matina , Molfenter Sonja M.
Published: September 2018

Objectives

Edema is a frequent clinical observation following chemoradiation treatment (CRT) of oral/oropharyngeal cancer and is thought to contribute to post‐CRT swallowing impairment. Our aims were to reliably quantify pharyngeal edema pre‐ and post‐CRT from videofluoroscopic (VF) swallowing studies and to explore the relationship between edema and swallowing impairment. Swallowing impairment was captured using patient‐reported swallowing outcomes (EAT‐10) and with VF confirmation of impairment (DIGEST).

Methods

40 patients (24 M, age 38–76) with oral/oropharyngeal cancer received radiotherapy (70 Gy, 7 weeks) and 3 weekly doses of cisplatin. VF and EAT‐10 were completed pre‐ and 1‐month post‐CRT. Edema was captured by measuring posterior pharyngeal wall (PPW) thickness, vallecular space, and pharyngeal area (PA) on a single post‐swallow rest frame. Wilcoxon sign rank tests and paired t‐tests evaluated within‐subject changes in impairment and edema respectively. A linear mixed effect regression model explored the influence of time, patient‐reported outcomes, and functional impairment on measures of edema.

Results

Swallowing function (EAT‐10 and DIGEST) was significantly worse post‐CRT. PPW thickness (but not vallecular space and pharyngeal area) was significantly worse post‐CRT. PPW thickness was only significantly influenced by time (pre‐ vs. post‐CRT) but not by measures of swallow function.

Conclusion

Our findings establish the use of PPW thickness as a reliable measure of acute edema in post‐CRT treatment. In this small, retrospective sample, edema was not significantly correlated with either patient‐reported or measured swallow function. Prospective longitudinal work, examining the relationship between objective measures of edema, patient perception of impairment, and swallow function and biomechanics is warranted.

Level of Evidence

4.
Elongated EABR wave latencies observed in patients with auditory neuropathy caused by OTOF mutation
Authors: Hosoya Makoto , Minami Shujiro B. , Enomoto Chieko , Matsunaga Tatsuo , Kaga Kimitaka
Published: September 2018

Objectives

We sought to determine how the pathology altered electrically evoked auditory brainstem responses (EABRs) in patients with hearing loss by evaluating EABRs in auditory neuropathy patients with OTOF mutations comparing with various types of congenital deafness.

Methods

We included 15 patients with congenital hearing loss, grouped according to pathology: OTOF mutations (n = 4), GJB2 mutations (n = 4), SLC26A4 mutations (n = 4), or cytomegalovirus infections (n = 3). EABRs were recorded when patients underwent cochlear implantation surgery. We evaluated the latencies and amplitudes of the recorded EABRs and compared them statistically between four groups.

Results

The EABR latencies of Wave III and Wave V, and of the interval between them, were significantly longer in the OTOF mutation group than in the GJB2 and SLC26A4 mutation groups (Wave III) and in all three other groups (Wave V and Wave III‐V latency); amplitudes were not significantly different between groups.

Conclusions

Our results suggest OTOF mutations cause delayed (or slowed) postsynaptic neurotransmission, although the presumed mechanism involved reduced presynaptic transmission between hair cells and spiral ganglion neurons.

Level of Evidence

Mainly a case report
A Highly Stretchable, Tough, Self‐Healing, and Thermoprocessable Polyacrylamide–Chitosan Supramolecular Hydrogel
Authors: Dutta Agniva , Maity Supriya , Das Rajat K.
Published: September 2018

Polymerization of acrylamide in concentrated aqueous solution in the presence of chitosan and in the absence of covalent cross‐linker leads to the formation of stiff and tough supramolecular polymer hydrogels that are self‐healing, can be stretched up to ≈30 times their original length, and demonstrate rapid self‐recovery, due to the inter‐chain hydrogen bonds between polyacrylamide and chitosan acting as sacrificial bonds to dissipate energy. These gels show thermoplastic behavior and can be molded into different shapes after a heating–cooling cycle, maintaining reasonable mechanical strength. The gels can withstand repeated compressive loading–unloading cycles, exhibiting reliable load‐bearing capacity.
Enhancing the Fracture Resistance and Impact Toughness of Mechanically Frothed Epoxy Foams with Hollow Elastomeric Microspheres
Authors: Song Wenzhe , Tagarielli Vito L. , Lee Koon‐Yang
Published: September 2018

Nonporous elastomeric particles are often employed to improve the toughness of brittle epoxy foams but this also decreases their compressive strength and stiffness. Herein, a novel strategy utilizing hollow elastomeric microspheres as toughening agent for epoxy foams is presented. The addition of 0.5 wt.% hollow elastomeric microspheres into epoxy foam leads to a 15% increase in critical stress intensity factor (K
1c) to 0.38 MPa m0.5 and 33% increase in Charpy impact strength (acU
) to 1.05 kJ m−2, respectively, compared to unfilled epoxy foam (K
1c = 0.33 MPa m0.5 and acU
 = 0.79 kJ m−2). However, a further increase in the hollow elastomeric microsphere concentration to 1.0 wt.% leads to microsphere agglomeration, which reduces both K
1c and acU
to 0.35 MPa m0.5 and 0.93 kJ m−2, respectively. Nevertheless, the added hollow elastomeric microspheres do not lead to a reduction in the quasi‐static compressive properties of the epoxy foams.
A Self‐Healing Dielectric Supramolecular Elastomer Functionalized with Aniline Tetramer
Authors: Liu Ling , Yan Shu , Zhang Liqun
Published: September 2018

A new design strategy to produce a supramolecular elastomer with self‐healing and dielectric properties by synthesizing an aniline tetramer (AT)‐functionalized supramolecular elastomer (SE‐AT) is demonstrated. The termination of AT in the supramolecular system not only shortens linear amide molecular chain to decrease glass transition temperature but also destroys the crystallization to achieve amorphous structure. The SE‐AT provides two kinds of noncovalent bonding including π–π stacking and the hydrogen bond, which makes the material more easily healed. The SE‐AT20% can heal mechanical properties within 24 h at room temperature without any external stimulus. The dielectric constant shows a continuous increase overall with increasing AT content. The material exhibits good electro‐mechanical properties, which is attributed to a simultaneous increase in dielectric constant and decrease in modulus. The maximum actuated strain significantly increases with the increasing AT content and the SE‐AT20% reaches 10% at 1 V µm−1. Moreover, SE‐AT exhibits the ability to regain actuated strain on the location of the mechanical damage after self‐healing.
“Finger‐Flapping” Hand Stereotypy as a Presenting Feature of Wilson's Disease
Authors: Bhatti Amit , Jain Neeraj , Desai Karan , Ravat Sangeeta H. , Agarwal Pankaj A.
Published: September 2018

View Supplementary Video 1
22q11.2 Deletion Syndrome–Associated Parkinson's Disease
Authors: Boot Erik , Bassett Anne S. , Marras Connie
Published: September 2018

Background

22q11.2 deletion syndrome (22q11.2DS) is a multisystem condition associated with an increased risk of early‐onset Parkinson's disease (PD).

Methods

We review the clinical, neuroimaging, and neuropathological observations, as well as diagnostic challenges, of PD in 22q11.2DS. We conducted a search of PubMed up until June 1, 2018 and personal files to identify relevant publications.

Results

22q11.2DS‐associated PD is responsible for approximately 0.5% of early‐onset PD. The hallmark motor symptoms and neuropathology of PD, and typical findings of reduced striatal dopamine transporter binding with molecular imaging, are present in 22q11.2DS‐associated PD. Mean age at PD onset in 22q11.2DS is relatively young (∼40 years). Patients with 22q11.2DS‐associated PD show a good response to levodopa.

Conclusions

Further recognition of 22q11.2DS and study of PD in people with 22q11.2DS could provide insights into the mechanisms that cause PD in the general population. 22q11.2DS may serve as an identifiable PD model to study prodromal PD and disease‐modifying treatments.
Dosimetry of small static fields used in external photon beam radiotherapy: Summary of TRS‐483, the IAEA–AAPM international Code of Practice for reference and relative dose determination
Authors: Palmans Hugo , Andreo Pedro , Huq M. Saiful , Seuntjens Jan , Christaki Karen E. , Meghzifene Ahmed
Published: September 2018

Purpose

A joint IAEA/AAPM international working group has developed a Code of Practice (CoP) for the dosimetry of small static fields used in external megavoltage photon beam radiotherapy, published by the IAEA as TRS‐483. This summary paper introduces and outlines the main aspects of the CoP.

Methods

IAEA TRS‐483 is a condensation of the wide range of different approaches that have been described in the literature for the reference dosimetry of radiotherapy machines with nominal accelerating potential up to 10 MV that cannot establish the conventional 10 cm × 10 cm reference field, and for the determination of field output factors for relative dosimetry in small static photon fields. The formalism used is based on that developed by Alfonso et al. [Med Phys. 2008;35:5179–5186] for this modality.

Results

Three introductory sections describe the rationale and context of the CoP, the clinical use of small photon fields, and the physics of small‐field dosimetry. In the fourth section, definitions of terms that are specific to the CoP (as compared to previous CoPs for broad‐beam reference dosimetry, such as IAEA TRS‐398 and AAPM TG‐51) are given; this section includes a list of the symbols and equivalences between IAEA and AAPM nomenclature to facilitate the practical implementation of the CoP by end users of IAEA TRS‐398 and AAPM TG‐51. The fifth section summarizes the equations and procedures that are recommended in the CoP and the sixth section provides an overview of the methods used to derive the data provided in IAEA TRS‐483.

Conclusions

This is the first time an international Code of Practice for the dosimetry of small photon fields based on comprehensive data and correction factors has been published. This joint IAEA/AAPM CoP will ensure consistent reference dosimetry traceable to the international System of Units and enable common and internationally harmonized procedures to be followed by radiotherapy centers worldwide for the dosimetry of small static megavoltage photon fields.
The new architects: Brazil, China, and innovation in multilateral development lending
Authors: Serrano Oswald Omar Ramon
Published: September 2018

Recent academic works have shed light upon the motives and negotiation dynamics leading to the creation of the New Development Bank (NDB) and Asian Infrastructure Investment Bank (AIIB). We know less about their day‐to‐day activities and if (and if so why) they are being innovative in the field of multilateral development lending. This article evaluates novelty in the two banks. It uncovers and suggests an explanation to the puzzle of why the NDB appears more innovative (in terms of institutional design, staffing, and lending policy guidelines) than the AIIB by exploring the cases of China and Brazil. The two countries played central roles in the set‐up of each the AIIB and NDB. Drawing on extensive field research, the article proposes that their preferences and capability to engage in institutional innovation depend on interests, status, economic power, and regulatory capacity.
A cost‐effectiveness analysis of Erwinia asparaginase therapy in children with acute lymphoblastic leukemia
Authors: Kloos Robin Q. H. , van Litsenburg Raphaële R. L. , Wolf Sarah , Wismans Leonoor , Kaspers Gertjan J. L. , Uyl‐de Groot Carin A. , Pieters Rob , van der Sluis Inge M.
Published: September 2018

Objectives

Erwinia asparaginase is used as a second‐line formulation after a neutralizing hypersensitivity reaction to the first‐line formulation of asparaginase. Here, we have performed a cost‐effectiveness analysis of Erwinia asparaginase treatment.

Methods

Children with acute lymphoblastic leukemia treated according to the Dutch Childhood Oncology ALL‐10 or ALL‐11 protocol were included and initially treated with PEGasparaginase in the intensification phase. The total treatment costs of this treatment phase, quality of life (QoL), and life years saved (LYS) were studied for two scenarios: (a) patients were switched to Erwinia asparaginase treatment after a hypersensitivity reaction, or (b) asparaginase would have been permanently stopped.

Results

Sixty‐eight patients were included. There was no difference in QoL between patients with and without a hypersensitivity reaction. The mean costs of the intensification phase per patient were $40,925 if PEGasparaginase could be continued, $175,632 if patients had to switch to Erwinia asparaginase, and $21,190 if asparaginase would have been permanently stopped. An extrapolation of the literature suggests that the 5‐year event‐free survival would be 10.3% lower without intensive asparaginase treatment if asparaginase is stopped after a reaction. Thus, the costs per LYS were $1892 for scenario 1 and $872 for scenario 2.

Conclusions

Switching to Erwinia asparaginase increases the costs per LYS by $1020, which is modest in view of the total costs. Moreover, when asparaginase treatment can be completed by switching to Erwinia asparaginase, relapses—and consequential costs—will be avoided. Therefore, from a cost perspective, we recommend a switch to Erwinia asparaginase to complete asparaginase treatment.
Polymorphism and properties of biodegradable poly(1,4‐butylene adipate) tailored using an aliphatic diamide derivative
Authors: Kong Rui , Jia Yuqing , Yang Jinjun , Wang Xiaomin , Sun Yuebing , Lian Jiangru , Chen Jiarui , Kuang Yunqi , Li Yuqin , Huang Minghui
Published: September 2018

N,N′‐Ethylenebis(12‐hydroxystearamide) (EBH), an aliphatic diamide organic compound with environmental friendliness, was selected as an effective nucleating agent to be incorporated into poly(1,4‐butylene adipate) (PBA) polyester. EBH increased the crystallization temperature, crystallinity, crystal density and thermal stability, and shortened the crystallization time of PBA. EBH slowed down the critical temperature of the PBAα‐crystal, accelerated theβ‐to‐αphase transition rate and tailored the polymorphic crystalline structure of the PBA probably via the interfacial interaction and/or crystal lattice matching between PBA and EBH. In the presence of EBH, the degradation rate of PBA decreased. The mechanisms of the nucleation, manipulation of the crystal type, acceleratedβ‐to‐αphase transition, enhanced thermal stability and decreased enzymatic degradation rate of PBA are proposed and discussed in detail. © 2018 Society of Chemical Industry
α‐Fe2O3/Attapulgite‐mediated reaction of benzyl chloride: Synthesis of poly(phenylene methylene)
Authors: Teng Dao‐Guang , Wei Xian‐Yong , Yang Zheng , Zong Zhi‐Min
Published: September 2018

Thermostable and fluorescent poly(phenylene methylene) (PPM) was synthesized via α‐Fe2O3/attapulgite (α‐Fe2O3/A)‐mediated polymerization of benzyl chloride (BC) in CCl4 in good yields. A carbocationic mechanism was proposed based on the controlling experiment. The structure and properties of PPM were characterized by Fourier transform infrared spectrometry, 1H and 13C nuclear magnetic resonance spectrometry, thermogravimetric analysis, elemental analysis, gel permeation chromatography, and UV–vis and fluorescence spectrometry. The results show that PPM possesses outstanding homoconjugation fluorescence and excellent thermal stability with onset decomposition temperature of ca. 420 °C. Recycled α‐Fe2O3/A proved to be still highly active for BC polymerization. Moreover, the strategy features low‐cost and readily accessible starting materials, simple one‐pot operation, and recyclable catalyst, facilitating future applications. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 2280–2285
Polymer‐supported palladium (II) containing N2O2: An efficient and robust heterogeneous catalyst for C–C coupling reactions
Authors: Bi Jiajun , Chen Jian , Dong Yahao , Guo Wen , Zhu Dajian , Li Tao
Published: September 2018

A new polymer was prepared from 1,3,5‐triformylphloroglucinol (noted as TDTB) and o‐phenylenediamine through Schiff base condensation reaction, and palladium (II) was immobilized on the polymer (noted as TbPo‐Pd(II)). This process was easy to work‐up and cost‐effective. The structure and composition of TbPo‐Pd(II) were fully characterized by FTIR, TGA, XPS, AAS, SEM, and TEM analyses. Meanwhile, this catalyst showed desired thermal stability and excellent performance in water/methanol system for Suzuki and Sonogashira coupling reactions. In addition, this heterogeneous catalyst can be readily recovered by simple filtration with no appreciable Pd leaching in the reaction. This work provides a powerful protocol for rapid access to asymmetrical biphenyls and aryl alkynes. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 2344–2353
A structural interpretation of the two components governing the kinetic fragility from the example of interpenetrated polymer networks
Authors: Araujo Steven , Batteux Florian , Li Wenlong , Butterfield Lena , Delpouve Nicolas , Esposito Antonella , Tan Li , Saiter Jean‐Marc , Negahban Mehrdad
Published: September 2018

Kinetic fragility and cooperativity length, two major characteristics of the relaxation dynamics at the glass transition, are, respectively, investigated by dynamic mechanical analysis and modulated temperature differential scanning calorimetry in a series of interpenetrated polymer networks based on acrylate and epoxy systems. The relaxation dynamics are impacted by two variables: the rigidity of the network, and the structural heterogeneity resulting from blending. However, the fragility and the cooperativity do not vary similarly. The glass transition progressively broadens as the mass fractions of acrylate and epoxy become equivalent, leading to a strong decrease in cooperativity. On the other hand, under the same conditions, the fragility transitions between the lower value of pure acrylate and the higher value of pure epoxy. This divergence helps concluding that the variations in the temperature dependence of the relaxation time are not purely related to the more or less cooperative nature of the glass transition. By splitting the fragility index in a volume contribution and an energetic contribution, it is shown that the contribution of cooperativity to the variations of the relaxation time with temperature is increased under two structural conditions: low backbone rigidity and high intermolecular interactions. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018, 56, 1393–1403