bluuebunny/crossref_metadata_2025 huggingface dataset:
The atypical MAPK ERK3 potently suppresses melanoma cell growth and invasiveness
Authors: Chen Minyi , Myers Amanda K. , Markey Michael P. , Long Weiwen
Published: December 2018

Mitogen‐activated protein kinase 6 (MAPK6) represents an atypical MAPK also known as extracellular signal‐regulated kinase 3 (ERK3), which has been shown to play roles in cell motility and metastasis. ERK3 promotes migration and invasion of lung cancer cells and head and neck cancer cells by regulating the expression and/or activity of proteins involved in cancer progression. For instance, ERK3 upregulates matrix metallopeptidases and thereby promotes cancer cell invasiveness, and it phosphorylates tyrosyl‐DNA phosphodiesterase 2, thereby enhancing chemoresistance in lung cancer. Here we discovered that ERK3 plays a converse role in melanoma. We observed that BRAF, an oncogenic Ser/Thr kinase, upregulates ERK3 expression levels by increasing both ERK3 messenger RNA levels and protein stability. Interestingly, although BRAF's kinase activity was required for upregulating ERK3 gene transcription, BRAF stabilized ERK3 protein in a kinase‐independent fashion. We further demonstrate that ERK3 inhibits the migration, proliferation and colony formation of melanoma cells. In line with this, high level of ERK3 predicted increased survival among patients with melanomas. Taken together, these results indicate that ERK3 acts as a potent suppressor of melanoma cell growth and invasiveness.
Pharmacoinformatics and molecular docking reveal potential drug candidates against Schizophrenia to target TAAR6
Authors: Tahir Rana Adnan , Wu Hao , Javed Naima , Khalique Anila , Khan Seemab Amjad Fateh , Mir Asif , Ahmed Muhammad Saad , Barreto George E. , Qing Hong , Ashraf Ghulam Md , Sehgal Sheikh Arslan
Published: December 2018

Schizophrenia (SZ) is a complex disabling disorder that leads to the mental disability and afflicts 1% of the world's total population and placed in top ten medical disorders. In current work, bioinformatics analyses were carried out on Trace amine (TA)‐associated receptor 6 (TAAR6) to recognize the potential drugs and compounds against SZ. Comparative modeling and threading‐based approaches were utilized for the structure prediction of TAAR6. Fifty‐nine predicted structures were evaluated by various model assessment techniques and final model having only eight amino acids in the outlier region and 98.5% overall quality factor was chosen for further pharmacoinformatics and molecular docking analyses. From an extensive literature review, 11 Food and Drug Administration (FDA) approved drugs were analyzed by computational techniques and Aripiprazole was found as the most effective drug against SZ by targeting TAAR6. Here, we report five novel molecules which exhibited the highest binding affinity, effective drug properties, and interestingly, observed better results than the approved selected drugs against SZ by targeting TAAR6. The docking analyses revealed that Arg‐92, Trp‐98, Gln‐191, Thr‐192, Ala‐290, Cys‐291, Tyr‐293, and Glu‐294 residues were observed as critical interacting residues in receptor‐ligand interactions. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, Lipinski rule of five, highest binding affinity coupled with virtual screening (VS), and pharmacophore modeling approach illustrated that aripiprazole (−8.6 kcal/mol) and TAAR6_0094 (−9.3 kcal/mol) are potential inhibitors for targeting TAAR6. It is suggested that schizophrenic patients have to use Aripiprazole for the medication of SZ by targeting TAAR6 and develop effective therapies by utilizing scrutinized novel compound.
Comprehensive insights into the inorganic coagulants on sludge dewatering: comparing aluminium and iron salts
Authors: Liang Jialin , Zhang Siwei , Huang Jinjia , Huang Shaosong , Zheng Li , Sun Shuiyu , Zhong Zhenyi , Zhang Xinghong , Yu Xiaoyu
Published: December 2018

BACKGROUND

Extracellular polymeric substances (EPS) play an important role in sludge dewatering. Inorganic coagulants treatment has been widely used to remove the EPS and improve sludge dewaterability. This research evaluates whether there are advantages of selecting one of two chemical coagulation pretreatments, conventional aluminium or iron salts, over the other to enhance sludge dewaterability. The study traced variations in EPS characteristics to understand the mechanisms of sludge dewaterability.

RESULTS

The results showed that iron coagulants improved dewatering more than aluminium coagulants, by approximately 28.66%. The improved sludge dewaterability was further confirmed in pilot‐scale experiments. Compared with aluminium salts conditioning, iron salts were better able to neutralize stronger charge, formed smaller and more compact flocs, and had a stronger acidification effect. Sludge dewaterability was significantly related to EPS concentrations (i.e. the protein and polysaccharides), EPS composition (i.e. tyrosine/tryptophan amino acid, tyrosine/tryptophan protein, and polysaccharide), and functional groups (i.e. random coil, β‐sheet, and Npr) in the loosely bound EPS (LB‐EPS). A two‐step mechanism was proposed for the iron conditioning process. Moreover, the economic analysis shows iron treatment was more economical than that of aluminium.

CONCLUSION

Iron salts conditioning removed more LB‐EPS than aluminium salts, thus more significantly improving sludge dewaterability. © 2018 Society of Chemical Industry
Role of flow cytometry for the improvement of bioprocessing of oleaginous microorganisms
Authors: Sonowal Shashanka , Chikkaputtaiah Channakeshavaiah , Velmurugan Natarajan
Published: December 2018

Oleaginous microorganisms, such as yeast, fungi, microalgae and bacteria, represent a key segment of second generation feed‐stock materials and are considered to synthesize a wide range of industrially important chemical compounds. Oleaginous microorganisms possess a broad varieties of chemical compounds such as carotenoids, pigments, carbohydrates, chlorophyll, and storage‐material lipids. Oleaginous microorganisms have been recognized as promising sources for the synthesis of unsaturated, especially polyunsaturated fatty acids (PUFA). So far, a variety of high‐throughput screening methodologies (HTMs) have been employed for the development of bioprocessing of oleaginous microorganisms for sustainable production of industrially valuable compounds. Of HTMs, flow cytometry (FC) and sorters (FACS) have received substantial interest as better HTMs because of their ability to screen large numbers of cells within seconds, and interrogate and isolate living cells at single‐cell level. Forward and side scattering signals of FC are used to determine the physiological state of the cell while different channels available in the FC facilitate the detection of signals produced from fluorophores. Simultaneous measurement of physiological characteristics along with specific compound accumulation at single‐cell level enables the possibility of separating a particular phenotype with specific properties from a population. Different microbial strain development strategies in combination with FACS produced improved phenotypes with desired properties. This review first summarizes the FACS methodologies suitable for oleaginous microorganisms and the significant progress that has been achieved in oleaginous microorganisms using FACS, and highlights the important, advanced and future prospects of FACS methodologies that are suitable for the development of bioprocessing in oleaginous microorganisms. © 2018 Society of Chemical Industry
Frequency and value both matter in the suboptimal choice procedure
Authors: Pisklak Jeffrey M. , McDevitt Margaret A. , Dunn Roger M. , Spetch Marcia L.
Published: December 2018

Pigeons chose between two options on a concurrent‐chains task with a single response requirement in the initial link. The suboptimal option ended with food 20% of the time whereas the optimal option ended with food 80% of the time. During a Sig‐Both condition, terminal‐link stimuli on both options signaled whether or not food would occur. During a Sig‐Sub condition, terminal‐link stimuli on the suboptimal option provided differential signals, but stimuli on the optimal option did not differentially signal the food and no food outcomes. Initial‐link choices revealed a clear preference for the optimal option in the Sig‐Both condition, but preference shifted toward suboptimality in the Sig‐Sub condition. These findings show that pigeon suboptimal choice is not singularly driven by signal value, as has been suggested, but also by reinforcer frequency.
Clique‐cutsets beyond chordal graphs
Authors: Boncompagni Valerio , Penev Irena , Vušković Kristina
Published: December 2018

Truemper configurations (thetas, pyramids, prisms, and wheels) have played an important role in the study of complex hereditary graph classes (eg, the class of perfect graphs and the class of even‐hole‐free graphs), appearing both as excluded configurations, and as configurations around which graphs can be decomposed. In this paper, we study the structure of graphs that contain (as induced subgraphs) no Truemper configurations other than (possibly) universal wheels and twin wheels. We also study several subclasses of this class. We use our structural results to analyze the complexity of the recognition, maximum weight clique, maximum weight stable set, and optimal vertex coloring problems for these classes. Furthermore, we obtain polynomial ‐bounding functions for these classes.
Bolus vs Continuous Nasogastric Feeds in Mechanically Ventilated Pediatric Patients: A Pilot Study
Authors: Brown Ann‐Marie , Fisher Elaine , Forbes Michael L.
Published: December 2018

Background

Malnutrition increases the risk of mortality and morbidity in the pediatric intensive care unit (PICU). Barriers to adequate delivery of enteral nutrition (EN) include hemodynamic instability, feeding interruptions and intolerance, and lack of standardized feeding protocols. The most recent guidelines on nutrition support for the critically ill child describe a paucity of evidence around the best method to deliver EN. There is an untested clinical assumption that bolus gastric feeding (B‐GF) in intubated patients is associated with aspiration events, lung injury, and associated morbidity compared with continuous gastric feeding (C‐GF). This study compared the effectiveness and safety of C‐GF vs B‐GF in intubated pediatric patients.

Methods

We enrolled randomized patients aged 1 month–12 years who were intubated within 24 hours and received EN starting within 48 hours of admission to a C‐GF or B‐GF group. Goal‐directed EN volume and caloric density were increased every 3 and 12 hours, respectively, to target. Feeding interruptions and intolerance events were recorded.

Results

Twenty‐five subjects were enrolled (B‐GF = 11; C‐GF = 14). At 24 hours, B‐GF was associated with higher energy and protein delivery (P < 0.007) and was associated with faster time to goal volume (median B‐GF = 15 hours; C‐GF = 29.5 hours). No aspiration events resulting in additional lung injury were noted for either group (P = 0.866).

Conclusions

B‐GF was associated with superior delivery of EN with a comparable safety profile to C‐GF. Further study is needed to compare both EN methods in other PICU populations.
The Effect of Polar Head and Chain Length on the Physicochemical Properties of Micellization and Adsorption of Amino Alcohol‐Based Surfactants
Authors: Hafidi Zakaria , El Achouri Mohammed
Published: December 2018

In this work, we have synthesized a series of quaternary ammonium from amino alcohols and n‐bromoalkanes. The compounds are referred to as CnEtOH, CnPrOH, and CniPrOH (where n = 12 and 14 carbons, EtOH = ethanol, PrOH = propanol, iPrOH = iso‐propanol). Their structures were checked using the usual spectroscopic methods [1H, 13C nuclear magnetic resonance (NMR) and infrared (IR)]. Their physicochemical properties in aqueous solution were studied using conductivity, surface tension, and ultra violet (UV)–visible absorption spectroscopy measurements. This study was conducted to show the effect of the linear hydrophobic chain and the location of the OH polar group with respect to the N+ quaternary ammonium on the physicochemical properties of the surfactants. The comparison between the physicochemical properties of the surfactants studied shows a distinct effect of the position of the OH group on the critical micelle concentration (CMC), the ionization degree (α), the area occupied at the interface (Amin), the free energy of adsorption (), and the free energy of micellization (). The intermolecular interaction between the synthetic surfactants and the methyl orange (OM) dye is related to the degree of hydration of the micelle, proven by the hypsochromic displacement of OM wavelength (λmax) and ionization (α) of the micelles. The CMC, the degree of ionization, and the degree of hydration of the micelle follow the same trend.
Vitamin and bioactive compound diversity of seven fruit species from south Brazil
Authors: Schmidt Helena de Oliveira , Rockett Fernanda C , Pagno Carlos H , Possa Jucelaine , Assis Renato Q , de Oliveira Viviani R , da Silva Vanuska L , Flôres Simone H , Rios Alessandro de Oliveira
Published: December 2018

BACKGROUND

The consumption of native tropical fruits represents an important source of bioactive food and vitamins for consumers. The aim of this study was to determine the composition of vitamins, bioactive compounds and the antioxidant activity of seven native fruits of the Myrtaceae family from south Brazil.

RESULTS

Sample 1 ofEugenia pyriformispresented the highest value of β‐carotene (0.1021 g kg−1), lutein (0.0511 g kg−1), zeaxanthin (0.0370 g kg−1), and α‐carotene (0.0112 g kg−1), of all analyzed samples. The three samples ofEugenia unifloraL presented the highest lycopene (0.1876, 0.1240 and 0.1615 g kg−1) and vitamin A content (0.106, 0.035 and 0.178 g kg−1RAE) of all seven species analyzed. The cyanidin 3‐glucoside was the most common anthocyanin found in fruits in the present study. Two samples ofPlinia peruvianapresented higher antioxidant capacity by the ABTS radical method (0.80 and 0.67 mol TEs kg−1) among the fruits analyzed. The samples ofCampomanesia xanthocarpaanalyzed stood out owing to the high content of vitamin C present (23.89, 36.83 and 35.05 g kg−1). The values of pantothenic acid inPlinia peruvianaaccount for 20% of daily requirements.

CONCLUSION

In conclusion, the native fruits studied can provide an appreciable amount of vitamins and bioactive compounds. © 2018 Society of Chemical Industry
How should we turn data into decisions in AgriFood?
Authors: Serazetdinova Liliya , Garratt James , Baylis Alan , Stergiadis Sokratis , Collison Martin , Davis Simon
Published: December 2018

BACKGROUND

The AgriFood supply chain is under significant pressures related to food security, climate change, and consumer demands for affordable and higher quality food. Various technologies are already deployed producing a large amount of data, which can be utilised to guide decision‐making to improve productivity, reduce wastage, and increase traceability across the AgriFood supply chain.

RESULTS

Several examples of the use of data are given, including improving efficiency in livestock production, supporting automation and use of robotics in crop production, increasing food safety and evidencing its provenance. The opportunities and ways forward were discussed at a workshop in November 2017, run by the Society of Chemical Industry and the Knowledge Transfer Network in the United Kingdom.

CONCLUSION

This article presents a summary of the key messages from the presentations and focus‐group discussions during this event, as interpreted by the authors. A number of challenges in digitalisation of the AgriFood supply chain are discussed, such as low inter‐operability of different data sets, silo mentality, low willingness to share data and a significant skills gap. Various approaches are presented that could help to unlock the benefits of using data, from practical support to producers and addressing skills gaps, to industrial leadership and the role of government departments and regulatory bodies in leading by example. Looking forward, data are already revolutionising the AgriFood supply chain, however, the benefits will remain piecemeal until the leaders of today are able to bring together the disparate groups into a cohesive whole. © 2018 Society of Chemical Industry
Sterol‐based oleogels' characterization envisioning food applications
Authors: Martins Artur J , Cerqueira Miguel A , Pastrana Lorenzo M , Cunha Rosiane L , Vicente António A
Published: December 2018

BACKGROUND

Phytosterols, in particular a mixture of pure γ‐oryzanol and β‐sitosterol, develop a tubular system that is able to structure oil. In this study, different concentrations of a combination of γ‐oryzanol and a commercial phytosterol mixture, Vitaesterol®, were used for the development of edible oil oleogels.

RESULTS

Small‐angle X‐ray scattering (SAXS) and X‐ray diffraction (XRD) were used to characterize at nano and molecular scale the aforementioned oleogels and confirm the formation of sterols‐based hollow tubule structures. Increased hardness was observed with the increase of gelator content used in oleogel manufacturing. The produced oleogels showed promising features such as tailored mechanical strength and low opacity, which are important features when considering their incorporation into food products.

CONCLUSION

Despite differences in gel strength, oleogels exhibited textural characteristics that make these structures suitable for incorporation in food products. The oil migration profile associated with these oleogels can provide a solution for the controlled release of lipophilic compounds as well as for the retention of oil in cooked food products. © 2018 Society of Chemical Industry
Ultrasound Characteristics of the Hair Follicles and Tracts, Sebaceous Glands, Montgomery Glands, Apocrine Glands, and Arrector Pili Muscles
Authors: Wortsman Ximena , Carreño Laura , Ferreira‐Wortsman Camila , Poniachik Rafael , Pizarro Kharla , Morales Claudia , Calderon Perla , Castro Ariel
Published: December 2018

Objectives

To explore the capability of very high‐frequency ultrasound (US; 50–71 MHz) to detect the normal morphologic characteristics of the hair follicles and tracts, sebaceous glands, Montgomery glands, apocrine glands, and arrector pili muscles.

Methods

A retrospective study, approved by the Institutional Review Board, evaluated the normal US morphologic characteristics of the hair and adnexal structures in a database of very high‐frequency US images extracted from the perilesional or contralateral healthy skin of 1117 consecutive patients who underwent US examinations for localized lesions of the skin and 10 healthy individuals from December 2017 to June 2018. These images were matched with their counterparts from the database of normal histologic images according to the corporal region. The Cohen concordance test and regional mean diameters of the hair follicles and adnexal structures were analyzed.

Results

The normal hair follicles and tracts, sebaceous glands, Montgomery glands, apocrine glands, and arrector pili muscles were observed on US images and matched their histological counterparts in all the corporal regions. There was significant US concordance (κ = 0.82; P = .0001) among observers. Regional mean diameters (millimeters) of the hair follicles, sebaceous glands, and apocrine glands are provided.

Conclusions

The hair follicles and tracts, sebaceous glands, Montgomery glands, apocrine glands, and arrector pili muscles are detectable with very high‐frequency US, including some regional and anatomic variants. Knowledge of their normal US appearances is a requisite for detecting subclinical changes, understanding the physiopathologic characteristics, and supporting the early diagnosis and management of common dermatologic diseases.
Body Mass Index and Segmental Mass Correlation With Elastographic Strain Ratios of the Quadriceps Tendon
Authors: Al‐Qahtani Mahdi , Al‐Tayyar Saleh , Mirza Eraj Humayun , Al‐Musallam Abdulrhman , Al‐Suwayyid Ahmed , Javed Ravish
Published: December 2018

Objectives

The aim of this study was to establish a relationship between quadriceps tendon stiffness and its properties and variations in the body mass index (BMI) and segmental mass.

Methods

This study was conducted in 3 groups according to their BMI (A, low [<18.5 kg/m2]; B, normal [18.5–25.0 kg/m2]; and C, high [>25.0 kg/m2]). All of the participants included had a sedentary lifestyle and did not do any weightlifting or any kind of sports activity in the previous 6 months. Ultrasound measurements were performed on the participants’ lower right extremities, since it was the dominant side for all of the participants.

Results

A total of 40 healthy untrained men participated in the study. The mean age of the participants ± SD was 22.1 ± 1.3 years; the age ranges for groups A (n = 6), B (n = 18), and C (n = 16) were 19–23, 19–25, and 20–25 years, respectively; 28 of the participants were nonsmokers, and 12 of were smokers. A strong statistical difference (all P < .05) was witnessed for most of the parameters (BMI, body fat mass, dominant leg body fat content, fat‐free mass index, tendon thickness, and strain ratio) among the groups.

Conclusions

The length of the tendon did not show a significant increase with an increase in the BMI, body fat mass, dominant leg body fat content, and fat‐free mass index. However, a greater intensification was observed for the thickness of the tendon with a significant increase in tendon stiffness (with the use of external reference material).
Incidental mastoid effusion diagnosed on imaging: Are we doing right by our patients?
Authors: Sayal Navdeep R. , Boyd Sara , Zach White G. , Farrugia Matthew
Published: December 2018

Objectives/Hypothesis

To investigate whether radiologist‐produced imaging reports containing the terms mastoiditis or mastoid opacification clinically correlate with physical examination findings of mastoiditis. Additionally, to investigate whether and how often otolaryngology was unnecessarily consulted and inappropriate antibiotic therapy was initiated.

Study Design

Retrospective chart review within a large community hospital setting.

Methods

A retrospective review of 160 patients who had imaging tests performed for nonotolaryngology indications from January 2011 to March 2017 at our facility. Indications, patient demographics, otolaryngology consultations, and new antibiotics started were recorded. Physical examinations were documented.

Results

Physical examination revealed that only 14 of 160 patients (8.8%) had clinical evidence of otologic disease. However, of the 160 patients meeting the inclusion criteria, 18 (11.3%) received an otolaryngology consultation, and 18 (11.3%) had antibiotics started. Eleven of the 18 patients in each group (61.1%) had a normal physical examination, two (11.1%) had serous otitis media, one (5.6%) had chronic otitis media, and four (22.2%) had acute otitis media. No patients were found to have clinical mastoiditis. χ2 analysis revealed no significance in the radiologic diagnosis of mastoiditis versus mastoid opacification in relation to physicians requesting otolaryngology consultations (P = .241) or starting patients on antibiotics (P = .951).

Conclusions

This study highlights the prevalence of incidental but clinically insignificant opacification of the mastoid cavity. We believe that nonotolaryngology physicians are, overall, competent to correlate such radiologic findings clinically and to prevent unnecessary consultations and inappropriate treatment, which add significant costs to our overstretched healthcare system.

Level of Evidence

4 Laryngoscope, 129:852–857, 2019
Predictors of intratonsillar versus peritonsillar abscess: A case‐control series
Authors: Ali S. Ahmed , Kovatch Kevin J. , Smith Josh , Bellile Emily L. , Hanks John E. , Truesdale Carl M. , Hoff Paul T.
Published: December 2018

Objectives/Hypothesis

An uncommon phenomenon in relation to the peritonsillar abscess (PTA) is the intratonsillar abscess (ITA) or formation of an abscess within tonsillar parenchyma. This study sought to characterize our experience with diagnosis and management of ITAs in the context of the PTA patient population.

Study Design

Case‐control series.

Methods

This is a single‐institution retrospective review of patients treated at the University of Michigan between 2000 and 2017.

Results

Six hundred fifty‐five adult patients were identified. The incidence of ITA within the PTA population was 7% (n = 43). Patients with ITA had lower mean white blood cell count (P = .03), lower proportion of trismus (P < .0001), otalgia (P = .007), vocal changes (P < .0001), and fewer incidences of acute progression of symptoms (P = .0007). On multivariable analysis, ITA patients were noted to be older, present with a longer duration of symptoms, and have greater incidence of neck pain and lymphadenopathy. Drainage was attempted in fewer ITA patients and was rarely successful (15%) in comparison to successful drainage for PTA patients (69%) (P < .0001).

Conclusions

Symptomatology differs for ITA, as fewer present with the classic PTA symptoms of otalgia, trismus, and voice alterations. The lack of classic symptoms likely leads to delayed presentation. A greater number of ITA patients presented with neck pain and lymphadenopathy. In the ITA population, aspiration attempts were more infrequent and less successful in yielding purulence. Given infrequent yield of pus and low overall recurrence rate, the diagnosing clinician should consider medical management in this distinct patient population.

Level of Evidence

4

Laryngoscope, 129:1354–1359, 2019
Quality of life after extended versus transsellar endoscopic skull base surgery from 767 patients
Authors: Seo Min Young , Nam Do‐Hyun , Kong Doo‐Sik , Lee Jung Joo , Ryu Gwanghui , Kim Hyo Yeol , Dhong Hun‐Jong , Chung Seung‐Kyu , Lee Kyung Eun , Hong Sang Duk
Published: December 2018

Objectives/Hypothesis

The aim of this study was to compare sinonasal‐related quality of life (QOL) in patients treated by extended or transsellar endoscopic skull base surgery.

Study Design

Prospective data analysis.

Methods

Prospectively collected data from patients who underwent endoscopic skull base surgery between 2012 and 2017 were analyzed. Primary outcomes were preoperative Sino‐Nasal Outcome Test‐20 (SNOT‐20) scores and then 1‐month, 3‐month, and 6‐month follow‐up. Comparative analysis was performed between the endoscopic transsellar approach (ETA) group (n = 647) and an extended endoscopic endonasal approach (EEEA) group (n = 120). In ETA group, the SNOT‐20 score was compared between patients with a nasoseptal flap (NSF) (ETA‐NSF) and without an NSF (ETA‐no NSF).

Results

The mean total SNOT‐20 score was significantly worse in the EEEA than ETA group at 1, 3, and 6 months postoperatively (P < .05). Although there was no significant difference in total SNOT‐20 score between the ETA‐NSF and ETA‐no NSF group at 3 and 6 months after surgery, the percentage of patients with significant change (≥0.8) in the SNOT‐20 score was higher in the NSF used group at 1, 3, and 6 months postoperatively (22.92% vs. 13.51%, P = .029; 20.59% vs. 5.59%, P = .039; and 24.00% vs. 4.03%, P = .003, respectively). According to multivariate analysis conducted regarding factors that deteriorate sinonasal QOL at 6 months following surgery, only NSF usage is significantly associated with poor outcome (odds ratio: 4.371, P = .011)

Conclusions

Sinonasal‐related QOL was significantly worse in patients treated by the EEEA versus ETA. Use of an NSF is the only poor prognostic factor in sinonasal QOL after endoscopic skull base surgery.

Level of Evidence

2b

Laryngoscope, 129:1318–1324, 2019
Long‐term sinonasal outcomes after endoscopic skull base surgery with nasoseptal flap reconstruction
Authors: Riley Charles A. , Tabaee Abtin , Conley Lindsey , Amine Muhamad , Soneru Christian P. , Anand Vijay K. , Schwartz Theodore H.
Published: December 2018

Objectives

The utilization of the nasoseptal flap (NSF) in endoscopic anterior skull base surgery (EASB) has resulted in reduced rates of postoperative cerebrospinal fluid leak (CSF). The long‐term impact on sinonasal function after surgery remains incompletely defined.

Methods

A consecutive series of patients undergoing EASB with NSF and with at least 3 years follow‐up was prospectively evaluated. Patient demographics, pre‐ and postoperative Sino‐nasal Outcome Test‐22 (SNOT‐22) scores, Lund‐Mackay scores (LMS), CSF leak, and sinonasal complications were analyzed.

Results

A total of 46 patients undergoing EASB with NSF met inclusion criteria. The mean follow‐up was 67.4 months (range 39–90, standard deviation [SD] 14.2 months). No statistically significant differences were noted between the mean overall pre‐ (16) and postoperative SNOT‐22 scores (18). SNOT‐22 scores improved in 27 patients (58.7%), deteriorated in 17 patients (37.0%) and stayed the same in two patients (4.3%). Deterioration in SNOT‐22 scores was greater in younger (mean change + 7.2 [SD17.4] vs. older patients −3.4 [SD 7.5], P = 0.010). A statistically significant increase in LMS was noted (mean preoperative LMS0.9 vs. mean postoperative LMS 2.2, P = 0.001). The LMS decreased in nine patients (19.6%), increased in 22 patients (47.8%), and remained the same in 15 patients (32.6%). One patient (2.2%) developed a postoperative CSF leak following resection of metastatic skull base lesion and was successfully treated with placement of a lumbar drain, Foley catheter balloon, and strict bed rest. One patient (2.2%) developed a postoperative mucocele requiring decompression 3 years after initial surgery.

Conclusion

Whereas long‐term sinonasal quality of life is overall improved in the majority of patients following NSF use for EASB, younger patients show higher incidence of deterioration. Increased sinus opacification on imaging is generally noted and may require continued follow‐up and management. The incidence of reoperation for symptomatic mucocele formation is low.

Level of Evidence

4 Laryngoscope, 129:1035–1040, 2019
Head and Neck Squamous Cell Carcinoma Detection and Surveillance: Advances of Liquid Biomarkers
Authors: Swiecicki Paul L. , Brennan Julia R. , Mierzwa Michelle , Spector Matthew E. , Brenner J. Chad
Published: December 2018

Head and neck squamous cell carcinomas are aggressive tumors that often present at advanced stage in difficult‐to‐biopsy regions of the head and neck. With the rapid move to analyze circulating tumor DNA (ctDNA) to either detect cancer or monitor disease progression and response to therapy, we have designed this article as a primer to understand the recent studies that support a transition to use these circulating biomarkers as a part of routine clinical care. Whereas some technical challenges still need to be overcome, the utility of ctDNA in cancer care is already evident from these early studies. Therefore, it is critical to understand recent advances in this area as well as emerging questions that need to be addressed as these biomarkers move closer to enhancing routine clinical care paradigms.

Laryngoscope, 129:1836–1843, 2019
Thermistor‐controlled subdermal skin tightening for the aging face: Clinical outcomes and efficacy
Authors: Sanan Akshay , Hjelm Nikolaus , Tassone Patrick , Krein Howard , Heffelfinger Ryan N.
Published: December 2018

Objective

Patients are increasingly seeking nonsurgical treatment for the aging face. The purpose of this study was to evaluate the clinical efficacy and outcomes of a thermistor‐controlled subdermal skin tightening device (ThermiTight) as a treatment modality for the aging face.

Methods

A retrospective analysis of 12 patients was completed on patients having undergone ThermiTight for midface and neck skin tightening. Only five patients had a greater than 1 year follow‐up and were included in the study. Two blinded reviewers assessed photographs taken pre‐procedure and 1 year post‐procedure using a standardized skin laxity scale. Patient charts were reviewed to assess for complications up to 12 months post‐treatment.

Results

The mean age of included patients was 57 years, and all five patients were female. One (20%) patient treated with ThermiTight was also treated with injectables (Botox, Juvéderm) simultaneously. One (20%) patient developed a wound complication. One (20%) patient complained of incisional site pain at her first postoperative visit that subsequently self‐resolved. On a five‐point scale to assess facial skin laxity, there was an average improved score of 0.85 per patient (P < .001) at one year post‐procedure. Two blinded reviewers correctly categorized photographs as either being “baseline” or “post‐procedure” 100% of the time. There was no significant difference between the skin laxity scores by the blinded reviewers (P = .05).

Conclusion

ThermiTight is a new technology used for nonsurgical treatment of the aging face. Long‐term outcomes demonstrate the safety and efficacy of the procedure. Complications are rare, but possible, in the use of ThermiTight.

Level of Evidence: 3
Hybrid Janus Microparticles Achieving Selective Encapsulation for Theranostic Applications via a Facile Solvent Emulsion Method
Authors: Lim Yi Guang Jerome , Poh Kwok Choon Wilson , Loo Say Chye Joachim
Published: December 2018

Anisotropic Janus particles composed of biocompatible polymers have been gaining considerable interest for biomedical applications. Here, the fabrication of hybrid Janus particles via a single‐step solvent emulsion technique, potentially for theranostic purposes, is shown. Through this technique, the selective encapsulation of therapeutic and diagnostic agents is streamlined into different “faces” of the Janus structure. This facile technique is used to seamlessly fabricate polymeric‐based hybrid Janus particles for theranostic applications with little complexity.
A magic drug target: Androgen receptor
Authors: Li Dan , Zhou Wenfang , Pang Jinping , Tang Qin , Zhong Bingling , Shen Chao , Xiao Li , Hou Tingjun
Published: December 2018

Androgen receptor (AR) is closely associated with a group of hormone‐related diseases including the cancers of prostate, breast, ovary, pancreas, etc and anabolic deficiencies such as muscle atrophy and osteoporosis. Depending on the specific type and stage of the diseases, AR ligands including not only antagonists but also agonists and modulators are considered as potential therapeutics, which makes AR an extremely interesting drug target. Here, we at first review the current understandings on the structural characteristics of AR, and then address why and how AR is investigated as a drug target for the relevant diseases and summarize the representative antagonists and agonists targeting five prospective small molecule binding sites at AR, including ligand‐binding pocket, activation function‐2 site, binding function‐3 site, DNA‐binding domain, and N‐terminal domain, providing recent insights from a target and drug development view. Further comprehensive studies on AR and AR ligands would bring fruitful information and push the therapy of AR relevant diseases forward.
Endothelial Cells Deconjugate Resveratrol Metabolites to Free Resveratrol: A Possible Role in Tissue Factor Modulation
Authors: Fernández‐Castillejo Sara , Macià Alba , Motilva Maria‐José , Catalán Úrsula , Solà Rosa
Published: December 2018

Scope

The antithrombotic effects of resveratrol (RV) and its derivatives remain unknown. The objective is to evaluate the modulatory effects of RV, its glucoside form, piceid, and its biological metabolites (RV‐3‐O‐β‐d‐glucuronide, RV‐4’‐O‐d‐glucuronide, and RV‐3‐O‐sulfate) on tissue factor (TF). Moreover, the endothelial metabolism of RV is assessed.

Methods and results

Human aortic endothelial cells (HAECs) are incubated with trans‐piceid, trans‐RV, or their biological metabolites and stimulated with tumor necrosis factor‐α (TNF‐α). TF activity, protein levels, and mRNA expression are determined in cell lysates. Moreover, RV conjugation (phase‐II‐metabolism) to its sulfated or glucuronidated metabolites and their deconjugation to their parent compound (free RV) are also assessed in cell lysates and culture media. RV decreased TF activity, protein levels, and mRNA expression, whereas piceid and RV metabolites (RVmet) had no effects. RV‐3‐O‐sulfate was the main metabolite generated in the endothelium, while RVmet are deconjugated to free RV. Isomerization of trans‐RV and its trans‐metabolites to their cis‐forms is observed.

Conclusions

RV exerts antithrombotic effects by modulating TF. RVmet and piceid does not exert this effect. However, the capacity of endothelial cells to deconjugate RVmet to free RV indicates that RVmet function as an endothelial reservoir for RV regeneration, thus, contributing to the antithrombotic effects of RV.
Short‐Term Isocaloric Intake of a Fructose‐ but not Glucose‐Rich Diet Affects Bacterial Endotoxin Concentrations and Markers of Metabolic Health in Normal Weight Healthy Subjects
Authors: Nier Anika , Brandt Annette , Rajcic Dragana , Bruns Tony , Bergheim Ina
Published: December 2018

Scope

Dietary pattern and impairments of intestinal barrier function are discussed to be critical in the development of metabolic impairments. Here, it is determined if an isocaloric exchange of complex carbohydrates with monosaccharides affects markers of intestinal permeability and metabolic health in healthy subjects.

Methods and Results

After a dietary standardization for 4 days, all 12 subjects aged 21–33 years receive an isocaloric fructose‐ and glucose‐enriched diet for 3 days separated by a wash‐out phase. Anthropometry, blood pressure, markers of intestinal permeability and metabolic as well as inflammatory parameters are determined in blood samples or isolated peripheral blood mononuclear cells collected at baseline, after standardizations and the monosaccharide interventions, respectively. While anthropometric and inflammatory parameters are not changed, the intake of an isocaloric fructose‐ but not glucose‐enriched diet is associated with a significant increase of bacterial endotoxin plasma levels and alanine aminotransferase activity in serum, while total plasma nitrate/nitrite concentrations are significantly decreased. In peripheral blood mononuclear cells, Toll like receptors 4, 2, and MYD88 mRNA expressions are significantly induced after the fructose‐rich but not the glucose‐rich diet.

Conclusion

In metabolically healthy subjects, even a short‐term intake of a fructose‐rich diet can elevate bacterial endotoxin levels and change markers of liver health and vascular endothelial function.
Multislice motion modeling forMRI‐guided radiotherapy gating
Authors: Ginn John S. , Ruan Dan , Low Daniel A. , Lamb James M.
Published: December 2018

Purpose

On‐board magnetic resonance imaging (MRI) greatly enhances real‐time target tracking capability during radiotherapy treatments. However, multislice and volumetricMRItechniques are frame rate limited and introduce unacceptable latency between the target moving out of position and the beam being turned off. We present a technique to estimate continuous volumetric tissue motion using motion models built from a repeated acquisition of a stack ofMRslices. Applications including multislice target visualization and out‐of‐slice motion estimation duringMRI‐guided radiotherapy are demonstrated.

Methods

Eight healthy volunteer studies were performed using a 0.35 TMRI‐guided radiotherapy system. Images were acquired at three frames per second in an interleaved fashion across ten adjacent sagittal slice positions covering 4.5 cm using a balanced steady‐state–free precession sequence. A previously published five‐dimensional (5D) linear motion model used forMRI‐guided radiotherapy gating was extended to include multiple slices. This model utilizes an external respiratory bellows signal recorded during imaging to simultaneously estimate motion across all imaged slices. For comparison to an image‐based approach, the manifold learning technique local linear embedding (LLE) was used to derive a respiratory surrogate for motion modeling. Manifolds for every slice were aligned duringLLEin a group‐wise fashion, enabling motion estimation outside the current imaged slice using a motion model, a process which we denote asmSGA. Additionally, a method is developed to evaluate out‐of‐slice motion estimates. The multislice motion model was evaluated in a single slice with each newly acquired image using a leave‐one‐out approach. Model‐generated gating decision accuracy and beam‐on positive predictive value (PPV) are reported along with the median and 95th percentile distance between model and ground truth target centroids.

Results

The average model gating decision accuracy and PPV across all volunteer studies was 93.7% and 92.8% using the 5D model, and 96.8% and 96.1% using themSGAmodel, respectively. The median and 95th percentile distance between model and ground truth target centroids was 0.91 and 2.90 mm, respectively, using the 5D model and 0.58 and 1.49 mm using themSGAmodel, averaged over all eight subjects. ThemSGAmotion model provided a statistically significant improvement across all evaluation metrics compared to the external surrogate‐based 5D model.

Conclusion

The proposed techniques for out‐of‐slice target motion estimation demonstrated accuracy likely sufficient for clinical use. Results indicate themSGAmodel may provide higher accuracy, however, the external surrogate‐based model allows for unbiased in vivo accuracy evaluation.
Modeling soil desiccation cracking by analytical and numerical approaches
Authors: Pouya Amade , Vo Thi Dong , Hemmati Sahar , Tang Anh Minh
Published: December 2018

An energy approach is proposed as a complement to the stress approach commonly considered for investigating soil desiccation cracking. The elastic strain energies before and after crack initiation are estimated by both numerical and analytical solutions. The energy released by cracking is then compared with the fracture energy to discuss crack initiation conditions. This leads to combined energy and stress conditions for crack initiation following Leguillon's theory. An approximate analytical solution is derived from a variational formulation of the porous elastic body equations. A cohesive zone model and finite element code are used to simulate crack propagation in an unsaturated porous body. This analysis shows that the energy criterion is reached before the stress criterion, and this can explain unstable crack propagation at the beginning. The approximate analytical solution allows predicting correctly the crack depth and opening in its initiation stage.
Modification of Nutrition Therapy During Continuous Renal Replacement Therapy in Critically Ill Pediatric Patients: A Narrative Review and Recommendations
Authors: Jonckheer Joop , Vergaelen Klaar , Spapen Herbert , Malbrain Manu L. N. G. , De Waele Elisabeth
Published: December 2018

Introduction

Nutrition is an important part of treatment in critically ill children. Clinical guidelines for nutrition adaptations during continuous renal replacement therapy (CRRT) are lacking. We collected and evaluated current knowledge on this topic and provide recommendations.

Methods

Questions were produced to guide the literature search in the PubMed database.

Results

Evidence is scarce and extrapolation from adult data was often required. CRRT has a direct and substantial impact on metabolism. Indirect calorimetry is the preferred method to assess resting energy expenditure (REE). Moderate underestimation of REE is common but not clinically relevant. Formula‐based calculation of REE is inaccurate and not validated in critically ill children on CRRT. The nutrition impact of nonintentional calories delivered as citrate, lactate, and glucose during CRRT must be considered. Quantifying nitrogen balance is not feasible during CRRT. Protein delivery should be increased by 25% to compensate for losses in the effluent. Fats are not removed by CRRT and should not be adapted during CRRT. Electrolyte disturbances are frequently present and should be treated accordingly. Vitamins B1, B6, B9, and C are lost in the effluent and should be adapted to the effluent dose. Trace elements, with the exception of selenium, are not cleared in relevant quantities. Manganese accumulation is of concern because of potential neurotoxicity.

Conclusion

Current recommendations regarding nutrition support in pediatric CRRT must be extrapolated from adult studies. Recommendations are provided, based on the weak level of evidence. Additional research on this topic is warranted.
Transcriptional Control of Brown and Beige Fat Development and Function
Authors: Shapira Suzanne N. , Seale Patrick
Published: December 2018

Adipose tissue, once viewed as an inert organ of energy storage, is now appreciated to be a central node for the dynamic regulation of systemic metabolism. There are three general types of adipose tissue: white, brown, and brown‐in‐white or “beige” fat. All three types of adipose tissue communicate extensively with other organs in the body, including skin, liver, pancreas, muscle, and brain, to maintain energy homeostasis. When energy intake chronically exceeds energy expenditure, obesity and its comorbidities can develop. Thus, understanding the molecular mechanisms by which different types of adipose tissues develop and function could uncover new therapies for combating disorders of energy imbalance. In this review, the recent findings on the transcriptional and chromatin‐mediated regulation of brown and beige adipose tissue activity are highlighted.
Effects of Intermittent Versus Continuous Energy Intakes on Insulin Sensitivity and Metabolic Risk in Women with Overweight
Authors: Hutchison Amy T. , Liu Bo , Wood Rachel E. , Vincent Andrew D. , Thompson Campbell H. , O’Callaghan Nathan J. , Wittert Gary A. , Heilbronn Leonie K.
Published: December 2018

Objective

This study aimed to compare intermittent fasting (IF) versus continuous energy intakes at 100% or 70% of calculated energy requirements on insulin sensitivity, cardiometabolic risk, body weight, and composition.

Methods

Women with overweight (n = 88; 50 ± 1 years, BMI 32.3 ± 0.5 kg/m2) were randomized to one of four diets (IF70, IF100, dietary restriction [DR70], or control) in a 2:2:2:1 ratio for 8 weeks. IF groups fasted for 24 hours after breakfast on three nonconsecutive days per week. All foods were provided and diets matched for macronutrient composition (35% fat, 15% protein, 50% carbohydrate). Insulin sensitivity by hyperinsulinemic‐euglycemic clamp, weight, body composition, and plasma markers were assessed following a “fed” day (12‐hour fast) and a 24‐hour fast (IF only).

Results

IF70 displayed greater reductions in weight, fat mass, total‐ and low‐density lipoprotein cholesterol, and nonesterified fatty acids compared with DR70 and IF100 (all P ≤ 0.05). IF100 lost more weight and fat than control. However, fasting insulin was increased. There were no group differences in insulin sensitivity by clamp; however, a 24‐hour fast transiently reduced insulin sensitivity.

Conclusions

When prescribed at matched energy restriction, IF reduced weight and fat mass and improved total and low‐density lipoprotein cholesterol more than DR. IF prescribed in energy balance did not improve health compared with other groups, despite modest weight loss.
Obesity as a Disease: The Obesity Society 2018 Position Statement
Authors: Jastreboff Ania M. , Kotz Catherine M. , Kahan Scott , Kelly Aaron S. , Heymsfield Steven B.
Published: December 2018

The emerging obesity epidemic and accompanying health consequences led The Obesity Society (TOS) in 2008 to publish a position paper defining obesity as a disease. Since then, new information has emerged on the underlying mechanisms leading to excess adiposity and the associated structural, cardiometabolic, and functional disturbances. This report presents the updated TOS 2018 position statement on obesity as a noncommunicable chronic disease.