bluuebunny/crossref_metadata_2025 huggingface dataset:
The Raman spectra of the Na2SO4‐K2SO4 system: Applicability to soluble salts studies in built heritage
Authors: Prieto‐Taboada Nagore , Fdez‐Ortiz de Vallejuelo Silvia , Veneranda Marco , Lama Estibaliz , Castro Kepa , Arana Gorka , Larrañaga Aitor , Madariaga Juan Manuel
Published: December 2018

The Raman spectra of the Na2SO4‐K2SO4‐H2O system are not well‐defined in the literature. Specifically, the proper identification of sodium and potassium sulphate (aphthitalite or glaserite, K3Na(SO4)2) and anhydrous sodium sulphate (thenardite, Na2SO4) is particularly problematic because their vibrational profiles present the same main Raman peak at 993 cm−1 and very similar low frequency bands. As proved in bibliography, the similarity of their spectra can often lead to uncertain or erroneous identifications. Considering that aphthitalite and thenardite can be found as degradation products on built heritage materials and the degree of danger associated to them is not the same, being the second one the most harmful, the resolution of this problem has a critical importance. For this reason, in the present work, the Raman spectra of aphthitalite and thenardite are deeply studied to identify the vibrational fingerprints enabling their correct identification. The results here summarized and provided by two different Raman instruments highlight that the spectrum of aphthitalite displays characteristic bands at 1,084 and 1,202 cm−1. In contrast, the bands at 1,100, 1,129, and 1,152 cm−1 seem to be characteristic of thenardite. Furthermore, when those secondary bands are not observed or mixtures of both compounds are present, the ratio between their most intense bands at 452 and 993 cm−1 is the key for their correct characterization. On the whole, this study fills the gaps observed in literature and gives the solution for the correct identification of aphthitalite and thenardite even when secondary bands are not observed.
Characterizing chemical composition of polyolefin‐based copolymers from spectral features in the C―H stretching region
Authors: Tomba J. Pablo , Silva Leonel I. , García Genga Melisa , Barrera Galland Griselda , Perez C. Javier
Published: December 2018

The comonomer content of a series of commercial ethylene–octene (Engage®, Infuse®), ethylene–butene (Engage), and ethylene–propylene (Versify®, Nordel®) copolymers is investigated using the Raman spectroscopy. The analysis relies upon the different content of methyl, methylene, and methine groups of each copolymer and focuses on the spectral features of the C―H stretching region. Raman spectra of a series of molecules with well‐defined content of methyl, methylene, and methine groups (alkanes and well‐defined polymer chains) are first addressed to rationalize the complex spectral features arising from different stretching modes, their Fermi resonance, and the different molecular conformations. Results are interpreted on the base of recent work on the topic. A curve‐fitting procedure is proposed to resolve contributions arising from CH2 and CH3 groups. The sum of intensity of bands at 2,855 and 2,865 cm−1 (symmetric C―H stretching and Fermi resonance) correlates linearly with CH2 content whereas that at 2,880 cm−1 (symmetric C―H stretching) does with CH3 content. With that base, Raman spectra of ethylene‐based copolymers are analyzed to quantify comonomer content. Results are compared with independent results from 13C nuclear magnetic resonance analysis with good agreement between the methods. Overall, it highlights the importance of Raman spectroscopy as versatile tool for process monitoring, quality control, or sample identification not only at academics but also in industrial environments.
Ankle and Foot Ultrasound: Reliability of Side‐to‐Side Comparison of Small Anatomic Structures
Authors: Rossi Federica , Zaottini Federico , Picasso Riccardo , Martinoli Carlo , Tagliafico Alberto Stefano
Published: December 2018

Objectives

In sonography of clinically relevant small structures of the ankle and foot, the healthy contralateral side can be used as a reference to identify subtle abnormalities. Intrasubject side‐to‐side variability must be minimal. The aim of this study was to assess the reliability of side‐to‐side sonographic evaluation of small structures of the ankle and foot.

Methods

Thirty healthy volunteers were prospectively studied. Small structures of the ankle and foot were evaluated bilaterally by 2 musculoskeletal radiologists in separate sessions. The deep peroneal nerve, superior extensor retinacula, calcaneofibular ligament, superior peroneal retinacula, tibialis posterior tendon, tibial nerve, Achilles tendon, plantaris tendon, plantar fascia, and sural nerve were considered. To assess intra‐ and interreader agreements, 30 (100%) examinations were repeated. A nonparametric statistic was used.

Results

Data were not normally distributed (P > .001). Intrareader agreement was k = 0.67 (95% confidence interval, 0.57–0.78) and interreader agreement was k = 0.73 (95% confidence interval, 0.68–0.77). The mean values and standard deviation for all the structures were 0.36 ± 1.85 mm. The overall coefficient of variation was 18.5%. The intraclass correlation coefficient was 0.93 (95% confidence interval, 0.92–0.94).

Conclusions

In ankle and foot sonography, the healthy contralateral side can be used as a reference during a real‐time musculoskeletal ultrasound evaluation of small structures.
Modiolar rotational cheiloplasty: Addressing the central oval in facial paralysis
Authors: Vincent Aurora G. , Hohman Marc H. , Moe Kris S.
Published: December 2018

Objectives/Hypothesis

Current static reanimation of the midface fails to provide adequate functional and aesthetic improvement; there is a need for more effective static correction of the ptotic midface. Our objective herein was to describe a novel method of static midface suspension that produces improved functional and aesthetic outcomes compared to previous techniques. Specifically, our goal was to describe the technique of alar and oral commissure repositioning via modiolar rotational cheiloplasty with alar base transposition, and gingivobuccal sulcoplasty.

Study Design

Retrospective case series.

Methods

We retrospectively reviewed the results of a series of adult patients desiring surgical intervention for paralysis of the central oval of the face at a tertiary care referral center. We present our technique of modiolar rotational cheiloplasty first with an example case, including subjective outcomes reported by the patient and objective improvements in facial appearance using Massachusetts Eye and Ear Infirmary Facial Assessment by Computer Evaluation Program (MEEI FACE‐Gram) software, then demonstrate long‐term outcomes from the series.

Results

Clinically, patients noted subjective improvement in drooling, buccal stasis of food, dysarthria, nasal obstruction, and overall appearance. Patients with significant atrophy and lateral displacement of the lower lip underwent concomitant wedge resection, which further improved the symmetry and position of the lips. The MEEI FACE‐Gram software demonstrated objective improvement in symmetry of smile and position of the philtrum and nasal base in an example case.

Conclusions

Modiolar rotational cheiloplasty with alar base transposition is an effective and efficient static procedure for midface palsy that improves both function and appearance.

Level of Evidence

4

Laryngoscope, 129:2262–2268, 2019
Wideband tympanometry and absorbance measurements in otosclerotic ears
Authors: Niemczyk Elżbieta , Lachowska Magdalena , Tataj Emanuel , Kurczak Katarzyna , Niemczyk Kazimierz
Published: December 2018

Objectives

This study aimed to assess absorbance using a thorough analysis of individual points of its plot in ears with intraoperatively confirmed otosclerosis. To the best of our knowledge, until recently no analyses have been performed that concerned the shape of an absorbance plot and a detailed analysis of its individual points. This study is the first to undertake such an issue.

Methods

A total of 77 otosclerotic ears were included in the study. Pure tone audiometry, low frequency tympanometry, and wide band tympanometry including absorbance were performed preoperatively. The average patients’ age in the group was 43.49 years (standard deviation = 10.44). Individual points of absorbance plot were thoroughly analyzed. Parameters were analyzed, such as resonance frequency; number of peaks; maximum absorbance (Height); and plot Width at the following Heights: 1/3, 1/2, and 2/3 (Width1/3, Width1/2, Width2/3, respectively), as well as associated absorbance parameters and frequencies.

Results

Data analysis revealed five different types of absorbance plots. Numerous statistically significant differences regarding the parameters of individual points of the plots were found among the distinguished types.

Conclusions

There are five types of absorbance plots in otosclerotic ears: type I, characterized by two distinct peaks, closely resembling normal ear absorbance plot; type II with a single distinct peak reaching high values of absorbance; type III with reduced absorbance for frequencies <2000 Hz; type IV with reduced absorbance for all frequencies; and type V with reduced absorbance for frequencies >2000 Hz. Absorbance measurements may play an important role in the diagnostics of otosclerosis; however, further research is necessary in this area.

Levels of Evidence

4

Laryngoscope, 129:E365–E376, 2019
Pediatric emergency department visits for uncontrolled pain in postoperative adenotonsillectomy patients
Authors: Billings Kathleen R. , Manworren Renee C.B. , Lavin Jennifer , Stake Christine , Hebal Ferdynand , Leon Astrid H. , Barsness Katherine
Published: December 2018

Objective

Identify demographic variables related to emergency department (ED) returns, and analgesic administration in the ED for postoperative pain after adenotonsillectomy (T&A).

Study Design

Pediatric Health Information System (PHIS) database analysis.

Methods

Forty‐seven children's hospitals included in the PHIS database were queried for all ED visits within 30 days of surgery with a diagnosis of acute postoperative pain (n = 2459) from 2014 to 2015. The subset of postoperative T&A patients (n = 861) was further analyzed for variables associated with return, and for pain management strategies, specifically opioids, employed by the ED.

Results

Of the 2459 pediatric patients returning to the ED for acute postoperative pain, the largest subset included T&A patients (n = 861, 35%). Patients were seen an average of 4 days (SD 2.4) after their surgery. ED administration of opioids was not associated with gender, race, surgical diagnosis, or ethnicity. The rate of opioid administration by the ED increased with advancing age of the children analyzed (P = .01). The incidence was also higher for those with commercial versus Medicaid insurance carriers. A total of 204 (23.7%) patients received opioids while in the ED, 439 (51%) received both opioids and non‐opioids, and only 51 (5.9%) received no pain medication.

Conclusion

T&A patients make up the largest subset of patients returning to the ED for postoperative pain. A total of 74.7% of patients receive opioids, either alone or in combination with non‐opioids, on return to the ED. ED opioid administration was associated with older age of the child and payer, but not with gender, race, surgical diagnosis, or ethnicity.

Level of Evidence

4
Administration of Fenofibrate Markedly Elevates Fabp3 in Rat Liver and Plasma and Confounds Its Use as a Preclinical Biomarker of Cardiac and Muscle Toxicity
Authors: Kochansky Christopher J. , Lyman Michael J. , Fauty Scott E. , Vlasakova Katerina , D'mello Anil P.
Published: December 2018

Proteins involved in lipid homeostasis are often regulated through the nuclear peroxisome proliferator‐activated receptors (PPAR). PPARα is the target for the fibrate‐class of drugs. Fenofibrate has been approved for its lipid‐lowering effects in patients with hypercholesterolemia and hypertriglyceridemia. We were interested in understanding the expression of the energy transporters in energy‐utilizing tissues like liver, heart, muscle, and adipose tissues in rat with the hypothesis that the change in transporter expression would align with the known lipid‐lowering effects of PPARα agonists like fenofibrate. We found that several fatty‐acid transporter proteins had significantly altered levels following 8 days of fenofibrate dosing. The mRNA levels of the highly abundant Fatp2 and Fatp5 in rat liver increased approximately twofold and decreased fourfold, respectively. Several fatty‐acid‐binding proteins and acyl‐CoA‐binding proteins had a significant increase in mRNA abundance but not the major liver fatty‐acid‐binding protein, Fabp1. Of particular interest was the increased liver expression of Fabp3 also known as heart‐fatty acid binding protein (H‐FABP or FABP3). FABP3 has been proposed as a circulating clinical biomarker for cardiomyopathy and muscle toxicity, as well as a preclinical marker for PPARα‐induced muscle toxicity. Here, we show that fenofibrate induces liver mRNA levels of Fabp3 ~5000‐fold resulting in an approximately 50‐fold increase in FABP3 protein levels in the whole liver. This increased liver expression complicates the interpretation and potential use of FABP3 as a specific biomarker for PPARα‐induced muscle toxicities.
Predicting temperature impacts on aquatic productivity: Questioning the metabolic theory of ecology's “canonical” activation energies
Authors: Wang Qing , Lyu Zhao , Omar Said , Cornell Stephen , Yang Zhou , Montagnes David J. S.
Published: December 2018

Microalgae contribute ~ 50% to global primary production, most of which is consumed by protozoa. Determining the thermal‐sensitivity of this trophic interaction is, therefore, fundamental to predicting impacts of climate change. Here, we question the application of current predictive approaches. Thermal responses are commonly described by the Arrhenius function: , where r is a rate (e.g., growth), A is a scaling factor, Ea is the activation energy, k is the Boltzmann‐constant, and T is absolute temperature. The influential metabolic theory of ecology (MTE) proposes that estimates of Ea for heterotrophs and autotrophs are 0.65 eV and 0.32 eV, respectively; when applied to specific growth rate of algae and protozoa, this difference has significant predictive consequences. Through literature review and statistical evaluation, we show that the MTE predictions do not apply to taxon‐specific responses of protozoa (n = 103) or algae (n = 183), with mean Ea of 0.71 eV (95% confidence interval [CI]: 0.69–0.74) and 0.61 eV (95% CI: 0.58–0.63), respectively. To obtain these, we fitted a series of models where Ea was constant within a defined group (e.g., protozoa), and the amplitude A depended on the individual responses within the group. Then, by applying the MTE and our predictions to a generic protozoan‐algal, predator‐prey model we show that: (1) the “canonical” MTE values lead to misrepresenting productivity by several fold; (2) a general response encompassing both groups (0.69 eV) should suffice for such models; and (3) applying our new responses has substantial effects on algal‐protozoan population dynamics over temperature shifts of ~ 5°C.
MR‐guided laser interstitial thermal therapy in the treatment of recurrent intracranial meningiomas
Authors: Rammo Richard , Scarpace Lisa , Nagaraja Tavarekere , Lee Ian
Published: December 2018

Objective

Recurrent meningiomas can prove problematic for treatment, especially if anaplastic, as options are limited primarily to surgery and radiation therapy. Laser interstitial thermal therapy (LITT) is a minimally invasive technique for achieving immediate cytoreduction. This study seeks to determine the utility of LITT in the setting of recurrent meningiomas.

Materials and Methods

Patients undergoing LITT for tumor treatment at our institution between November 2014 and February 2016 were identified. Those with biopsy‐confirmed meningiomas were reviewed with attention to ablation volume, survival, demographic data, and complications. Data from imaging performed at set intervals post‐operatively were available for all.

Results

Four patients were identified, three of whom had successful treatment with a total of four ablations. The one case that did not result in a successful ablation was due to problems with stereotactic placing of the laser catheter. One patient had a grade 1 meningioma, with the other two being Grade 3. Immediate ablation volumes averaged 75% of preoperative tumor volume and increased to 97% at 2 weeks before dropping to 65% at 3 months. One patient had acute hemiparesis with speech difficulty, which resolved after 6 months. At date of last follow‐up, two of three had progression at an average of nine weeks, and one had no progression at 28 weeks.

Conclusion

LITT appeared to be a potentially viable treatment for recurrent meningiomas. Ablation volumes increased over time, but not beyond the initial meningioma volume. Larger studies are needed to better determine complications and outcomes. Lasers Surg. Med. 51:245–250, 2019. © 2018 Wiley Periodicals, Inc.
Genetic variations in familial hypercholesterolemia and cascade screening in East Asians
Authors: Chan Melody Lok‐Yi , Cheung Ching‐Lung , Lee Alan Chun‐Hong , Yeung Chun‐Yip , Siu Chung‐Wah , Leung Jenny Yin‐Yan , Pang Ho‐Kwong , Tan Kathryn Choon‐Beng
Published: December 2018

Background

Familial hypercholesterolemia (FH) is a monogenic disorder of lipoprotein metabolism leading to an increased risk of premature cardiovascular disease. Genetic testing for FH is not commonly used in Asian countries. We aimed to define the genetic spectrum of FH in Hong Kong and to test the feasibility of cascade genetic screening.

Methods

Ninety‐six Chinese subjects with a clinical diagnosis of FH were recruited, and family‐based cascade screening incorporating genetic testing results was performed.

Results

Forty‐two distinct mutations were identified in 67% of the index FH cases. The majority of causative mutations were in the LDLR gene. The three commonest mutations in the LDLR gene were NM_000527.4(LDLR): c.1241 T>G, NM_000527.4(LDLR): c.1474G>A, and NM_000527.4(LDLR): c. 682G>A, and nine novel variants were identified. The NM_000384.2(APOB): c.10579 C>T variant of the APOB gene was found in 5% of the index subjects. The presence of causative mutation significantly increased the odds of successful family recruitment for screening with an OR of 3.7 (95% CI: 1.53–9.11, p = 0.004).

Conclusion

Approximately two‐third of the subjects in this clinically ascertained sample of patients with FH had a discrete genetic basis. Genetic identification improves the response rate and efficiency of family screening.
A prospective, multicenter study of a novel, miniaturized rechargeable sacral neuromodulation system: 12‐month results from the RELAX‐OAB study
Authors: Blok Bertil , Van Kerrebroeck Philip , de Wachter Stefan , Ruffion Alain , Van der Aa Frank , Jairam Ranjana , Perrouin‐Verbe Marie Aimée , Elneil Sohier
Published: December 2018

Aims

Historically, providing SNM therapy required use of a non‐rechargeable implantable pulse generator (IPG) with an average device lifespan of 4.4 years. Multiple device replacement surgeries are necessary with this device for long‐term overactive bladder (OAB) management. A longer‐lived device can reduce and potentially eliminate the need for replacement surgeries, thereby improving the long‐term safety and cost‐effectiveness of SNM therapy. The objective of this study was to evaluate the safety and efficacy of a miniaturized, rechargeable SNM system.

Methods

This prospective, multi‐center study implanted 51 subjects with the SNM system in a single stage procedure without an external trial period. Subjects had overactive bladder as demonstrated on a 3‐day voiding diary (≥8 voids/day and/or ≥2 incontinence episodes over 72‐h). Outcome measures at 1‐year follow‐up included quality of life (evaluated by ICIQ‐OABqol questionnaire), therapy responder rates (≥50% reduction in voids and/or leaks or <8 voids per day), subject satisfaction questionnaire, and adverse events (AEs).

Results

At 1‐year, 94% of Test Responders continued to respond to r‐SNM therapy based on bladder diary criteria. Subjects experienced significant improvement of 21.1 points on the ICIQ‐OABqol. 84% of subjects were satisfied with r‐SNM therapy and 98% found their charging experience acceptable. Device‐related AEs occurred in 21% of subjects, with discomfort due to stimulation occurring in 20% of subjects. This AE was resolved with reprogramming in all instances.

Conclusions

The Axonics r‐SNM System provides sustained clinically significant improvements in OAB subjects after 1‐year. Subjects were satisfied with r‐SNM therapy and reported an easy and acceptable recharging experience.
Novel immediate/sustained‐release formulation of acetaminophen‐ibuprofen combination (Paxerol®) for severe nocturia associated with overactive bladder: A multi‐center, randomized, double blinded, placebo‐controlled, 4‐arm trial
Authors: Lee King C. , Rauscher Frank , Kaminesky Jed , Ryndin Igor , Xie Lei , Zhao Yunzhu , Khusid Johnathan A. , Weiss Jeffrey P.
Published: December 2018

Aim

To determine short‐term efficacy and safety of Paxerol®, novel immediate:sustained (50%:50%) release tablets containing 325 mg acetaminophen and 150 mg ibuprofen per tablet.

Methods

One of three dose levels, corresponding to the amounts in 1, 2, and 3 tablets, of Paxerol and placebo were administered for 14 consecutive days to patients with severe nocturia (defined in this study as an average nocturnal voids [NV] ≥2.5) associated with overactive bladder (OAB). Changes in NV, as well as Nocturia Quality of Life (NQOL), duration of first uninterrupted sleep (DFUS), and total hours of nightly sleep (THNS) associated with treatment were assessed. Short‐term safety/tolerability was assessed throughout the study and for at least 30 days post‐treatment.

Results

Paxerol at all three doses reduced NV to a greater degree than placebo (average NV −1.1, −1.4, −1.3 voids for low, mid, and high doses, respectively, vs −0.3 void for placebo). NQOL and THNS were similar between baseline and treatment values in all four groups. There were also no between‐group differences. Paxerol at high dose tended to (although not statistical significantly) increase DFUS to a greater degree than placebo (1.2 vs 0.4 h, P = 0.057). There were no treatment related adverse events in any of the four groups.

Conclusions

This study demonstrates short‐term efficacy and short‐term safety of Paxerol in patients with severe nocturia associated with OAB. The results warrant further investigation of the long‐term efficacy and safety of Paxerol in larger patient populations.
Two‐stage phase separation of cellulose acetate membranes modified with plasma‐treated natural zeolite: Response surface modeling
Authors: Safarpour Mahdie , Barzin Jalal , Khataee Alireza , Kordkatooli Zahra
Published: December 2018

Cellulose acetate (CA) microfiltration membranes were prepared by two‐stage vapor‐induced phase separation (VIPS) and immersion precipitation. To improve the hydrophilicity and permeability of the membranes at low operating pressures, plasma‐treated natural zeolite was incorporated into the membranes. A response surface methodology based on the three‐level central composite design (CCD) was used to model and optimize the casting solution composition of the membranes with the aim of maximizing membranes permeability. Three independent variables for CCD optimization were concentration of CA, polyvinylpyrrolidone (PVP) pore former, and plasma‐treated zeolite additive. The results showed that a second‐order polynomial model could properly predict the response (pure water flux) at any input variable values with a satisfying determination coefficient (R2) of 0.954. Also, analysis of variance (ANOVA) confirmed the adequacy of the obtained model. The permeability of the prepared membranes increased by increasing zeolite loading from 0.10 to 0.50 wt%, which was related to the membranes morphology and porosity and confirmed by scanning electron microscopy (SEM) images. Pure water flux of the membranes decreased by increasing CA concentration while an optimum PVP amount was required to reach the maximum flux. The result of the bubble point analysis well matched with surface SEM images of the membranes and permeability trend predicted by CCD model. Also, the prepared CA membranes with different compositions showed no toxicity for mouse L929 fibroblast, which indicated their nontoxic and biocompatible nature.
Toward Standardization of Mesenchymal Stromal Cell‐Derived Extracellular Vesicles for Therapeutic Use: A Call for Action
Authors: Roura Santiago , Bayes‐Genis Antoni
Published: December 2018

Extracellular vesicles (EVs), which include a variety of nano‐sized membrane‐encapsulated particles, are released to the extracellular microenvironment by the vast majority of cells and carry lipids, proteins, mRNA, and miRNA or non‐coding RNA. Increasing evidence suggests the great versatility and potential of EV‐based applications in humans. In this issue, van Balkom et al. explore and compare the reported proteomic signature of mesenchymal stromal cell (MSC)‐derived small EVs. In particular, their paper offers a valuable approach and point of view on MSC‐EV manufacturing and therapeutic potential. Briefly, van Balkom et al. aimed to identify a common protein signature that may be useful in ensuring the homogeneity of therapeutic MSC‐EVs. In addition to excessive variability in EV‐producing cell sources and culture conditions, the harvesting time for the EV‐containing conditioned medium, and EV isolation procedure, the authors found a specific protein signature from the publicly available MSC‐EVs proteome. In light of their findings and those from the plentiful studies published in this continuously growing area of research, potential focus areas and issues are outlined for the more rational design and optimization of MSC‐EV production and potency for therapeutics.
Intramolecular and intermolecular bifurcated hydrogen bonds in 2‐pyrrolyl‐7‐hydroxy‐2‐methylidene‐2,3‐dihydro‐1H‐inden‐1‐one
Authors: Chipanina Nina N. , Oznobikhina Larisa P. , Sigalov Mark V. , Shainyan Bagrat A.
Published: December 2018

Cyclic and linear dimers as well as the solvate H‐bonded complexes of the Z and E isomers of 2‐pyrrolyl‐7‐hydroxy‐2‐methylidene‐2,3‐dihydro‐1H‐inden‐1‐one 1 were investigated by theoretical calculations, and their formation was proved by FT‐IR and UV spectroscopy. In dimers, both strengthening and weakening of the intramolecular component of the bifurcated hydrogen bond are observed depending on the type of the formed intermolecular hydrogen bond. The effect of proton donors MeOH, HCN, and proton acceptor DMSO on the intramolecular components in solvent H‐bonded complexes is discussed. A larger energy gap in the 1‐E than in 1‐Z isomer allows to predict photoinduced isomeric transition 1‐Е → 1‐Z in nonpolar aprotic solvents.
Theoretical elaboration about the excited state dynamical behaviors for a novel fluorescent sensor
Authors: Zhang Tianjie , Zhang Qiaoli , Lu Xuemei , Jia Min , Song Xiaoyan , Yang Dapeng
Published: December 2018

Using the density functional theory (DFT) and time‐dependent density functional theory (TDDFT) methods, we theoretically explore a novel fluorescent sensor molecule (abbreviated as “2”) (Sensors Actuat B‐Chem. 2018, 263, 585). Because of its symmetry, three stable structures can be located, ie, 2‐enol, 2‐SPT, and 2‐DPT forms in both S0 and S1 states. Via comparing the bond lengths and bond angles involved in the hydrogen bonding moieties, we find the dual intramolecular hydrogen bonds should be strengthened in the S1 state. And based on infrared (IR) vibrational simulations, we further confirm the strengthening dual hydrogen bonds. Upon the photo‐excitation process, the charge redistribution via frontier molecular orbitals (MOs) reveals the tendency of excited state intramolecular proton transfer (ESIPT) reaction. In addition, the constructed S0‐state and S1‐state potential energy curves demonstrate that the excited state single proton transfer (ESSPT) should be the most supported one from 2‐enol to 2‐SPT form. In view of the S1‐state stable 2‐SPT and 2‐DPT structures as well as the fluorescence peaks of them, we can further confirm the ESSPT mechanism for 2 chemosensor. This work not only clarifies the excited state behaviors of 2 system but also successfully explain the previous experimental phenomenon.
Increases in Tumor N‐Glycan Polylactosamines Associated with Advanced HER2‐Positive and Triple‐Negative Breast Cancer Tissues
Authors: Scott Danielle A. , Casadonte Rita , Cardinali Barbara , Spruill Laura , Mehta Anand S. , Carli Franca , Simone Nicole , Kriegsmann Mark , Del Mastro Lucia , Kriegsmann Joerg , Drake Richard R.
Published: December 2018

Purpose

Using a recently developed matrix‐assisted laser desorption/ionization imaging mass spectrometry (MALDI‐IMS) method, human breast cancer formalin‐fixed paraffin‐embedded (FFPE) tissue sections and tissue microarrays (TMA) are evaluated for N‐linked glycan distribution in the tumor microenvironment.

Experimental design

Tissue sections representing multiple human epidermal growth factor receptor 2 (HER2) receptor–positive and triple‐negative breast cancers (TNBC) in both TMA and FFPE slide format are processed for high resolution N‐glycan MALDI‐IMS. An additional FFPE tissue cohort of primary and metastatic breast tumors from the same donors are also evaluated.

Results

The cumulative N‐glycan MALDI‐IMS analysis of breast cancer FFPE tissues and TMAs indicate the distribution of specific glycan structural classes to stromal, necrotic, and tumor regions. A series of high‐mannose, branched and fucosylated glycans are detected predominantly within tumor regions. Additionally, a series of polylactosamine glycans are detected in advanced HER2+, TNBC, and metastatic breast cancer tissues. Comparison of tumor N‐glycan species detected in paired primary and metastatic tissues indicate minimal changes between the two conditions.

Conclusions and clinical relevance

The prevalence of tumor‐associated polylactosamine glycans in primary and metastatic breast cancer tissues indicates new mechanistic insights into the development and progression of breast cancers. The presence of these glycans could be targeted for therapeutic strategies and further evaluation as potential prognostic biomarkers.
Imperfect repeats in the functional amyloid protein FapC reduce the tendency to fragment during fibrillation
Authors: Rasmussen Casper B. , Christiansen Gunna , Vad Brian S. , Lynggaard Carina , Enghild Jan J. , Andreasen Maria , Otzen Daniel
Published: December 2018

Functional amyloid (FA) is widespread in bacteria and serves multiple purposes such as strengthening of biofilm and contact with eukaryotic hosts. Unlike pathological amyloid, FA has been subjected to evolutionary optimization which is likely to be reflected in the aggregation mechanism. FA from different bacteria, including Escherichia coli (CsgA) and Pseudomonas (FapC), contains a number of imperfect repeats which may be key to efficient aggregation. Here we report on the aggregative behavior of FapC constructs which represent all single, double, and triple deletions of the protein's three imperfect repeats. Analysis of the fibrillation kinetics by the program Amylofit reveals that the removal of these repeats increases the tendency of the growing fibrils to fragment and also generally increases aggregation half‐times. Remarkably, even the mutant lacking all three repeats was able to fibrillate, although fibrillation was much more irregular and led to significantly altered and destabilized fibrils. We conclude that imperfect repeats can promote fibrillation efficiency thanks to their modular design, though the context of the imperfect repeats also plays a significant role.
Reducing proteolytic liability of a MMP‐14 inhibitory antibody by site‐saturation mutagenesis
Authors: Lee Ki Baek , Dunn Zachary , Ge Xin
Published: December 2018

Playing pivotal roles in tumor growth and metastasis, matrix metalloproteinase‐14 (MMP‐14) is an important cancer target. Potent inhibitory Fab 3A2 with therapy‐desired high selectivity has been isolated from a synthetic antibody library carrying long CDR‐H3s. However, like many standard mechanism protease inhibitors, Fab 3A2 can be cleaved by high concentrations of MMP‐14 after extended incubation at acidic pH. Edman sequencing of generated 3A2 fragments indicated that cleavage occurred within its CDR‐H3 between residues N100h (P1) and L100i (P1’). To improve proteolytic stability of 3A2, three positions adjacent to its cleavage site (P1, P1’, and P3’) were subjected to site‐saturation mutagenesis (SSM). Mutations at P1’ (L100i) resulted in loss of inhibition function, while screening of 3A2 Fab mutants at P1 (N100h) or P3’ (A100k) positions identified four clones exhibiting improvements in both stability and inhibition potency. The majority of these mutants with improved stability were substitutions to either hydrophobic (Lue, Trp) or basic residues (Arg, Lys, His). Combinations of these beneficial mutations resulted in a double mutant N100hR/A100kR, which prolonged half‐life twofold with an inhibition potency KI of 6.6 nM. Enzyme kinetics and competitive ELISA suggested that N100hR/A100kR was a competitive inhibitor overlapping its binding epitope with that of nTIMP‐2. This study demonstrated that site‐directed mutagenesis at or near the cleavage position reduced proteolytic liability of standard mechanism protease inhibitors especially inhibitory antibodies.
Crystallographic identification of spontaneous oxidation intermediates and products of protein sulfhydryl groups
Authors: Wang Jimin
Published: December 2018

In the absence of protective reducing agents, Cys residues in purified proteins can be oxidized spontaneously by oxygen in the air, as frequently observed in protein crystal structures. However, the formation of an O‐bridge via dehydration mechanism between a peroxidized Cys side chain and a primary amine of Lys side chain in proteins has not yet been reported. When an electron density feature was observed for an extra group or an extra atom between side chains of Cys‐245 and Lys‐158 in the crystal structure of histidinol phosphate phosphatase, mass spectrometric analysis was carried out for its chemical identification. That analysis led to a conclusion that this extra density corresponded to a methylene group. It was then proposed that these two residues were able to absorb CO2 and reduced it to CH2 spontaneously. Further examination of other protein structures in the PDB showed that the formation of this cross‐linking species was a widespread phenomenon. This claim is examined in this study using methods recently developed for quantification of electrons around nucleus as the means for direct chemical identification. It is found that an O‐bridge is actually formed between Cys and Lys side chains, instead of a CH2‐bridge.
Fabrication and Characterization of Epitaxial Gd‐Doped SBN Thin Films
Authors: Lam Ka Kin , Chan Ka Ho , Ng Sheung Mei , Wong Hon Fai , Liu Yu Kuai , Leung Chi Wah , Mak Chee Leung
Published: December 2018

Gd‐doped Sr0.5Ba0.5Nb2O6 (SBN50) thin films with Gd‐doping concentration ranging from 1 to 4% are grown on Pt‐coated MgO (100) substrates using pulsed laser deposition technique. X‐ray diffraction studies show that the films are highly (001)‐oriented and epitaxially grown on the substrates. Electrical measurements show that the Gd‐SBN films possess good ferroelectric properties. Ramanent polarization of +Pr = 1.36 μC cm−2 and −Pr = −5.73 μC cm−2 and coercive field of +Ec = 158.0 kV and −Ec = −30.8 kV are obtained.
Study of Tunable Plasmonic, Photoluminscence, and Nonlinear Optical Behavior of Ag Nanoclusters Embedded in a Glass Matrix for Multifunctional Applications
Authors: Kumar Promod , Mathpal Mohan C. , Prakash Jai , Hamad Syed , Rao Soma Venugopal , Viljoen Bennie C. , Duvenhage Mart‐Mari , Njoroge Eric G. , Roos Wiets D. , Swart Hendrik C.
Published: December 2018

Plasmonic based hybrid noble metal nanoclusters (NCs) have gained much interest in various technological applications such as optoelectronics, photonic devices and nonlinear media including biomedical applications due to their tunable optical properties. Here, Ag NCs are grown as embedded in glass using simple ion‐exchange process and effect of various parameter including post thermal treatment is studied on tunability of their optical behavior (plasmonic, optical nonlinearity, and photoluminescence properties) in view of their potential applications in nanophotonics devices and as nonlinear media. The tunable optical, structural and thermodynamic properties associated with the rapid growth and agglomeration of Ag NCs in the glass is also studied under the post thermal treatment process. The various techniques such as XRD, RBS, Z‐scan and UV‐vis, XPS, PL and TEM are used for characterizing ion exchanged samples. A blue shift of 15 nm is observed significantly in optical absorbance as a function of post thermal treatment. Open and closed aperture Z‐scan experiments show strong nonlinear absorption coefficients for the Ag NCs. The thermodynamic parameters such as enthalpy (ΔH), entropy (ΔS) and Gibbs energy (ΔG) for the nucleation and growth of the Ag NCs in the glass matrix are calculated at different temperatures with an activation energy of 59 kJ mol−1 obtained by the Arrhenius linear equation and a model is suggested. In addition, these Ag NCs embedded glasses exhibit good antimicrobial activities (against E. coli bacteria) with a change in antibacterial behavior at higher annealing temperature indicating their multifunctional applications.
Subgroup analysis and interpretation for phase 3 confirmatory trials: White paper of the EFSPI/PSI working group on subgroup analysis
Authors: Dane Aaron , Spencer Amy , Rosenkranz Gerd , Lipkovich Ilya , Parke Tom ,   on behalf of the PSI/EFSPI Working Group on Subgroup Analysis
Published: December 2018

Subgroup by treatment interaction assessments are routinely performed when analysing clinical trials and are particularly important for phase 3 trials where the results may affect regulatory labelling. Interpretation of such interactions is particularly difficult, as on one hand the subgroup finding can be due to chance, but equally such analyses are known to have a low chance of detecting differential treatment effects across subgroup levels, so may overlook important differences in therapeutic efficacy. EMA have therefore issued draft guidance on the use of subgroup analyses in this setting. Although this guidance provided clear proposals on the importance of pre‐specification of likely subgroup effects and how to use this when interpreting trial results, it is less clear which analysis methods would be reasonable, and how to interpret apparent subgroup effects in terms of whether further evaluation or action is necessary.

A PSI/EFSPI Working Group has therefore been investigating a focused set of analysis approaches to assess treatment effect heterogeneity across subgroups in confirmatory clinical trials that take account of the number of subgroups explored and also investigating the ability of each method to detect such subgroup heterogeneity. This evaluation has shown that the plotting of standardised effects, bias‐adjusted bootstrapping method and SIDES method all perform more favourably than traditional approaches such as investigating all subgroup‐by‐treatment interactions individually or applying a global test of interaction. Therefore, these approaches should be considered to aid interpretation and provide context for observed results from subgroup analyses conducted for phase 3 clinical trials.
Calculations of electron inelastic mean free paths. XII. Data for 42 inorganic compounds over the 50 eV to 200 keV range with the full Penn algorithm
Authors: Shinotsuka Hiroshi , Tanuma Shigeo , Powell Cedric J. , Penn Dave R.
Published: December 2018

We have calculated inelastic mean free paths (IMFPs) for 42 inorganic compounds (AgBr, AgCl, AgI, Al2O3, AlAs, AlN, AlSb, cubic BN, hexagonal BN, CdS, CdSe, CdTe, GaAs, GaN, GaP, GaSb, GaSe, InAs, InP, InSb, KBr, KCl, MgF2, MgO, NaCl, NbC0.712, NbC0.844, NbC0.93, PbS, PbSe, PbTe, SiC, SiO2, SnTe, TiC0.7, TiC0.95, VC0.76, VC0.86, Y3Al5O12, ZnS, ZnSe, and ZnTe) for electron energies from 50 eV to 200 keV. These calculations were made with energy‐loss functions (ELFs) obtained from measured optical constants for 15 compounds while calculated ELFs were utilized for the other 27 compounds. Checks based on ELF sum rules showed that the calculated ELFs were superior to the measured ELFs that we had used previously. Our calculated IMFPs could be fitted to a modified form of the relativistic Bethe equation for inelastic scattering of electrons in matter for energies from 50 eV to 200 keV. The average root‐mean‐square (RMS) deviation in these fits was 0.60%. The IMFPs were also compared with a relativistic version of our predictive Tanuma‐Powell‐Penn (TPP‐2M) equation. The average RMS deviation in these comparisons was 10.7% for energies between 50 eV and 200 keV. This average RMS deviation is almost the same as that found in a similar comparison for a group of 41 elemental solids (11.9%) although relatively large deviations were found for cubic BN (65.6%) and hexagonal BN (34.3%). If these two compounds are excluded in the comparisons, the average RMS deviation becomes 8.7%. We found generally satisfactory agreement between our calculated IMFPs and values from other calculations and from experiments.
Punching shear behavior of reinforced concrete footings with a varying amount of shear reinforcement
Authors: Kueres Dominik , Schmidt Philipp , Hegger Josef
Published: December 2018

The existing punching shear design provisions according to current codes have either a semi‐empirical (e.g., Eurocode 2) or a more physical (e.g., Model Code 2010) background. Although the design procedures are very similar, the predicted punching shear capacities may differ significantly, depending on the background of the design provisions and the considered influences. Recent test series on reinforced concrete footings without shear reinforcement and with high amounts of shear reinforcement are available and can be used for the evaluation and improvement of the current provisions. Nevertheless, the evaluation of the code equations for the design of the shear reinforcement (failure inside the shear‐reinforced zone) is still not possible since systematic test series on footings with a varying amount of shear reinforcement have not yet been conducted. To investigate the punching shear behavior of reinforced concrete footings with low and medium amounts of shear reinforcement, three systematic test series (11 specimens) with stirrups as shear reinforcement were conducted. In the tests, the amount of shear reinforcement was varied by changing the stirrup diameter only. Further investigated influences were the shear span‐depth ratio and the effective depth. In this paper, the results of the test series are discussed and compared to the predictions according to Eurocode 2, Model Code 2010, and the draft of the second generation of Eurocode 2.
Current concepts in cochlear ribbon synapse formation
Authors: Coate Thomas M. , Scott M. Katie , Gurjar Mansa
Published: December 2018

In mammals, hair cells and spiral ganglion neurons (SGNs) in the cochlea together are sophisticated “sensorineural” structures that transduce auditory information from the outside world into the brain. Hair cells and SGNs are joined by glutamatergic ribbon‐type synapses composed of a molecular machinery rivaling in complexity the mechanoelectric transduction components found at the apical side of the hair cell. The cochlear hair cell ribbon synapse has received much attention lately because of recent and important findings related to its damage (sometimes termed “synaptopathy”) as a result of noise overexposure. During development, ribbon synapses between type I SGNs and inner hair cells form in the time window between birth and hearing onset and is a process coordinated with type I SGN myelination, spontaneous activity, synaptic pruning, and innervation by efferents. In this review, we highlight new findings regarding the diversity of type I SGNs and inner hair cell synapses, and the molecular mechanisms of selective hair cell targeting. Also discussed are cell adhesion molecules and protein constituents of the ribbon synapse, and how these factors participate in ribbon synapse formation. We also note interesting new insights into the morphological development of type II SGNs, and the potential for cochlear macrophages as important players in protecting SGNs. We also address recent studies demonstrating that the structural and physiological profiles of the type I SGNs do not reach full maturity until weeks after hearing onset, suggesting a protracted development that is likely modulated by activity.
Linking reading and writing with picture books: A literacy buddy approach in rural Taiwan
Authors: Wang Hung‐chun , Lin Ming‐Fang
Published: December 2018

This study investigated how a literacy buddy approach may influence the English learning and creative writing of adolescent learners in a rural Taiwanese school. A group of seventh‐grade and eighth‐grade students took part in a winter camp, wherein they read and wrote picture books collaboratively. Based on the students’ feedback, this approach stimulated their English reading skills, motivation to read picture books, and creative thinking. Analysis of their creative stories further shows that this approach led them to produce coherent texts and obtain a concept of narrative writing. Moreover, the students integrated the plot structure and key phrases they had learned from the picture books into their own stories, which suggests that reading the picture books might have facilitated their creative writing. Overall, this study shows that using picture books facilitated the integration of reading and writing instruction in the target rural English classroom.
Triclocarban at environmentally relevant concentrations induces the endoplasmic reticulum stress in zebrafish
Authors: Zhou Ting , Wei Jiajing , Su Yufang , Hu Zhiyong , Li Ying , Yuan Hongfang , Zhao Kai , Liu Chunyan , Zhang Huiping
Published: December 2018

Triclocarban (TCC) is an antibacterial agent commonly found in environmental, wildlife, and human samples. However, with in‐depth study of TCC, its negative effects are increasingly presented. Toxicological studies of TCC at environmentally relevant concentrations have been conducted in zebrafish embryos and indicated that TCC leads to deformity of development causes developmental deformities. However, the molecular mechanisms underlying the toxicity of TCC in zebrafish embryos have not been entirely elucidated. We investigated whether exposure to TCC at environmentally relevant concentrations induces endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in zebrafish. Zebrafish embryos were grown to 32 hours post fertilization and exposed to 2.5, 5, and 10 μg/L TCC and used in whole‐mount in situ hybridization to visualize the expression of ER chaperone hspa5 and ER stress‐related apoptosis factor chop. Zebrafish livers were exposed to different concentrations of TCC to elaborate the relationships between fatty degeneration and ER stress. Then, a human hepatic cell line (HL‐7702) was used to test whether TCC induced ER stress in human livers similar to those of zebrafish. In zebrafish embryos, TCC induced high hspa5 expression, which could defend against external stimulations. Furthermore, hapa5, hsp90b1, and chop exhibited ectopic expressions in the neuromast, intestinal tract, and tail tip of zebrafish embryos. On the one hand, significant differences were observed in the mRNA and protein expressions of the ER stress molecular chaperone pPERK‐pEIF2a‐ATF4 and ATF6 pathways in HL‐7702 cells exposed to TCC. On the other hand, lipid droplet accumulation slightly increased in zebrafish livers exposed to 10 μg/L TCC in vitro. These results demonstrate that TCC not only damages the development of zebrafish embryos and structure of zebrafish liver but also influences human hepatic cells by activating ER stress and the UPR signaling pathway.