bluuebunny/crossref_metadata_2025 huggingface dataset:
Translational Model‐Informed Approach for Selection of Tuberculosis Drug Combination Regimens in Early Clinical Development
Authors: Susanto Budi O. , Wicha Sebastian G. , Hu Yanmin , Coates Anthony R.M. , Simonsson Ulrika S.H.
Published: February 2020

The development of optimal treatment regimens in tuberculosis (TB) remains challenging due to the need of combination therapy and possibility of pharmacodynamic (PD) interactions. Preclinical information about PD interactions needs to be used more optimally when designing early bactericidal activity (EBA) studies. In this work, we developed a translational approach which can allow for forward translation to predict efficacy of drug combination in EBA studies using the Multistate Tuberculosis Pharmacometric (MTP) and the General Pharmacodynamic Interaction (GPDI) models informed by in vitro static time‐kill data. These models were linked with translational factors to account for differences between the in vitro system and humans. Our translational MTP‐GPDI model approach was able to predict the EBA0–2 days, EBA0–5 days, and EBA0–14 days from different EBA studies of rifampicin and isoniazid in monotherapy and combination. Our translational model approach can contribute to an optimal dose selection of drug combinations in early TB clinical trials.
Analysis of nonidealities of N‐path circuits using impulse response
Authors: Mohammadpour Amin , Nabavi Abdolreza
Published: February 2020

This paper presents a new method to analyze nonidealities of N‐path circuits. This method utilizes Fourier transform of the impulse response of an N‐path circuit in the time domain to calculate the transfer functions. The time domain analysis makes the method simple and intuitive. Instead of conventional sophisticated calculations, this method limits the analysis to some integral calculations. This analysis can take into account two common nonidealities: parallel capacitance and overlapping clocks. The accuracy of the analysis is verified by simulations for both cases. Further, the analysis has been expanded to differential filters.
Hop distance–based bandwidth allocation technique for elastic optical networks
Authors: Mavridopoulos Stathis B. , Beletsioti Georgia , Nicopolitidis Petros , Papadimitriou Georgios I. , Varvarigos Emmanouel
Published: February 2020

Elastic optical networks (EON) have emerged as a solution to the growing needs of the future internet, by allowing for greater flexibility, spectrum efficiency, and scalability, when compared to WDM solutions. EONs achieve those improvements through finer spectrum allocation granularity. However, due to the continuity and contiguity constrains, distant connections that are routed through multiple hops suffer from increased bandwidth blocking probability (BBP), while more direct connections are easier to form. This paper proposes HopWindows, a novel method that strategically allocates bandwidth to connections based on their hop distance. This new algorithm applies masks that control the range of frequency slots (FSs) allocated to each n‐hop connection. Furthermore, a new network metric is introduced, the normalized bandwidth blocking probability (normalized BBP). Utilization of this metric ensures increased fairness to distant connections. Extended simulation results are presented which indicate that the proposed HopWindows method achieves a superior performance over the well‐known FirstFit algorithm. The proposed algorithm may achieve a decrease in bandwidth blocking probability of up to 50%.
Evaluating forest resilience to global threats using functional response traits and network properties
Authors: Aquilué Núria , Filotas Élise , Craven Dylan , Fortin Marie‐Josée , Brotons Lluís , Messier Christian
Published: February 2020

Ecosystem functions provided by forests are threatened by direct and indirect effects of global change drivers such as climate warming land‐use change, biological invasions, and shifting natural disturbance regimes. To develop resilience‐based forest management, new tools and methods are needed to quantitatively estimate forest resilience to management and future natural disturbances. We propose a multidimensional evaluation of ecological resilience based on species functional response traits (e.g., functional response diversity and functional redundancy) and network properties of forested patches (e.g., connectivity, modularity, and centrality). Using a fragmented rural landscape in temperate south‐eastern Canada as a reference landscape, we apply our multidimensional approach to evaluate two alternative management strategies at three levels of intensity: (1) functional enrichment of current forest patches and (2) multi‐species plantations in previously non‐forested patches. Within each management strategy, planted species are selected to maximize functional diversity, drought tolerance, or pest resistance. We further compare how ecological resilience under these alternative management strategies responds to three simulated disturbances: drought, pest outbreak, and timber harvesting. We found that both management strategies enhance resilience at the landscape scale by increasing functional response diversity and connectivity. Specifically, when the less functionally diverse patches are prioritized for management, functional enrichment is more effective than the establishment of new multi‐species plantations in increasing resilience. In addition, randomly allocated multi‐species plantations increased connectivity more than those allocated in riparian areas. Our results show that across various management strategies, planting species to enhance biodiversity led to the highest increase in functional response diversity while planting pest‐resistant species led to the highest increase in landscape connectivity. Planting biodiversity‐enhancing species (i.e., species that maximize functional diversity) mitigated drought effects equally well as planting with drought‐tolerant species. Our multidimensional approach facilitates the characterization at the landscape scale of forest resilience to disturbances using both functional diversity and network properties while accounting for the importance of response traits to future disturbances. The simulation approach we used can be applied to forest landscapes across different biomes for the evaluation and comparison of forest management initiatives to enhance resilience.
Consumer impacts on ecosystem functions in coastal wetlands: The data gap
Authors: Moore Alexandria , Fauset Emma , Asher Frederick
Published: February 2020

Over the last 30 yr, our understanding of the factors that control the structure and function of coastal wetlands has shifted from a narrative that focused on bottom‐up control to one that explicitly includes top‐down factors. However, the emphasis of this transition has been on how consumers influence wetland vegetation; comparatively, few studies evaluate how consumers influence broader ecosystem properties and functions such as nutrient cycling and decomposition while fewer still investigate how trophic interactions affect these relationships. Here, we review the literature on consumer impacts on coastal wetland ecosystems and highlight areas where additional studies are sorely needed. It is our hope that identifying the current gaps in our knowledge will provide additional impetus for the study of community and ecosystem ecology within these globally important ecosystems.
Climate warming and heat waves alter harmful cyanobacterial blooms along the benthic–pelagic interface
Authors: Urrutia‐Cordero Pablo , Zhang Huan , Chaguaceda Fernando , Geng Hong , Hansson Lars‐Anders
Published: February 2020

In addition to a rise in mean air and water temperatures, more frequent and intense extreme climate events (such as heat waves) have been recorded around the globe during the past decades. These environmental changes are projected to intensify further in the future, and we still know little about how they will affect ecological processes driving harmful cyanobacterial bloom formation. Therefore, we conducted a long‐term experiment in 400‐L shallow freshwater mesocosms, where we evaluated the effects of a constant +4°C increase in mean water temperatures and compared it with a fluctuating warming scenario ranging from 0 to +8°C (i.e., including heat waves) but with the same +4°C long‐term elevation in mean water temperatures. We focused on investigating not only warming effects on cyanobacterial pelagic dynamics (phenology and biomass levels), but also on their recruitment from sediments—which are a fundamental part of their life history for which the response to warming remains largely unexplored. Our results demonstrate that (1) a warmer environment not only induces a seasonal advancement and boosts biomass levels of specific cyanobacterial species in the pelagic environment, but also increases their recruitment rates from the sediments, and (2) these species‐specific benthic and pelagic processes respond differently depending on whether climate warming is expressed only as an increase in mean water temperatures or, in addition, through an increased warming variability (including heat waves). These results are important because they show, for the first time, that climate warming can affect cyanobacterial dynamics at different life‐history stages, all the way from benthic recruitment up to their establishment in the pelagic community. Furthermore, it also highlights that both cyanobacterial benthic recruitment and pelagic biomass dynamics may be different as a result of changes in the variability of warming conditions. We argue that these findings are a critical first step to further our understanding of the relative importance of increased recruitment rates for harmful cyanobacterial bloom formation under different climate change scenarios.
An empirical investigation of time‐varying cost‐effectiveness across the product life cycle
Authors: Stevens Warren , Incerti Devin , Peneva Desi , Shrestha Anshu , Smith Gregory , Ramaswamy Krishnan
Published: February 2020

Cost‐effectiveness is traditionally treated as a static estimate driven by clinical trial efficacy and drug price at launch. Prior studies suggest that cost‐effectiveness varies over the drug's lifetime. We examined the impact of “learning by doing,” one of the least studied drivers of changes in cost‐effectiveness across the product life cycle. We combined time‐series trends in effectiveness over time by cancer regimen using the Surveillance, Epidemiology, and End Results‐Medicare database. We estimated the time‐varying effects of treatments in colorectal and pancreatic cancer over their life cycle, including FOLFOX (leucovorin, 5‐fluorouracil, and oxaliplatin) and gemcitabine, on survival of patients. Mean prices over time by strength and dosage form were calculated using historical wholesale acquisition costs. We found consistent downward trends in the mortality hazard ratios, which suggest that effectiveness improves over time. In the case of first‐line FOLFOX for colorectal cancer, the implied incremental cost‐effectiveness ratio based on the observational data fell from $610,000 per life year gained in 2004 to $27,000 per life year gained in 2011. Cost‐effectiveness estimated at launch is unlikely to be representative of cost‐effectiveness over the drug's lifetime. In the drugs studied, the impact of time‐varying clinical effectiveness dominated the impact of changing prices overtime.
The efficacy and safety of Epstein‐Barr virus‐specific antigen peptide‐activated cytotoxic T‐cells treatment for refractory or recurrent angioimmunoblastic T‐cell lymphoma: A prospective clinical observational study
Authors: Bingjie Wang , Lihong Wang , Yongjin Shi , Huihui Liu , Jinping Ou , Xi'nan Cen
Published: February 2020

The efficacy and safety of Epstein‐Barr virus (EBV)‐specific antigen peptide‐activated cytotoxic T lymphocytes (CTLs) in the treatment of refractory or recurrent angioimmunoblastic T‐cell lymphoma (AITL) was determined in this prospective one‐arm clinical study. Seven males and two females were enrolled with a median age of 70 years. The tumor stages were all stage III and IV. All patients had group B symptoms and IPI scores of 3 to 5 points. All patients received chemotherapy before CTLs infusion which the median chemotherapy cycle was three. The diseases states before CTLs included five cases of disease progression (PD), two cases of recurrence (R), and two cases with residual lesions after chemotherapy. Eight patients received HLA‐haploidentical EBV‐specific CTLs, and one patient chose autologous CTLs. The number of transfused cells was 1.67 to 2.38 × 1010 for one course of CTLs therapy. One patient was treated with three courses of CTLs, three patients were treated with two courses of CTLs, and five patients were treated with one course of CTLs. During the infusion, eight patients had fever, one patient had rash, and no graft‐vs‐host diseases were observed. The EBV‐DNA decreased by more than two orders of magnitude in six patients, and the response rate was 66.7%. Two patients of PD status achieved complete remission (CR), one patient of PD status achieved partial remission, two patients with residual lesions after chemotherapy achieved CR, and four patients had no response. The objective remission rate was 55.6%. After the median follow‐up of 14.5 months, five patients died, and three patients were completely relieved while one patient was lost during follow‐up. The 3‐year overall survival was 44.4% and 3‐year progression‐free survival was 33.3%. EBV‐specific antigen peptide‐activated CTLs showed positive effect in certain patients with refractory and recurrent AITL with high clinical safety.
Analysis of a fully wetted moving fin with temperature‐dependent internal heat generation using the finite element method
Authors: Sowmya Ganeshappa , Gireesha Bijjanal Jayanna , Madhu Macha
Published: February 2020

The temperature field of a moving longitudinal porous fin with varying internal heat generation with respect to temperature has been studied under natural radiation and convection effects. The Darcy model was implemented for the analysis and the parameters, whose effect on the thermal process were grouped and nondimensionalized. By using the finite element method, the obtained highly nonlinear second order ordinary differential equations were numerically solved. The relevant parameters were studied by means of graphs and subsequently their importance in the rate of heat transfer was interpreted.
The Evolution of Decarboxylative Allylation: Overcoming pKa Limitations
Authors: Tunge Jon A.
Published: February 2020

Since early focus on development of the allylation of non‐stabilized enolates, decarboxylative allylation has undergone tremendous evolution. This account describes the progression of decarboxylative allylation within the Tunge group with a focus on efforts to identify and overcome pKa requirements that initially limited the carboxylates that would undergo decarboxylative allylation.
Development and validation of autophagy‐related‐gene biomarker and nomogram for predicting the survival of cutaneous melanoma
Authors: Wan Qi , Jin Lin , Su Yaru , liu Ying , Li Chaoyang , Wang Zhichong
Published: February 2020

Autophagy plays a critical role in cutaneous melanoma, but the prognostic research of differentially expressed autophagy‐related genes (DEARGs) in melanoma is lacking. Therefore, autophagy‐related gene expression data of 630 melanoma patients were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas database. The DEARGs were identified by “limma” package in R software. Best survival analysis and the least absolute shrinkage and selection operator method were performed to identify a robust 7‐DEARG signature as well as construct nomogram associated with the clinical characteristics and validation in internal and external sets. This 7‐DEARG signature could be regarded as an independent prognostic signature in clinical setting, and nomogram may supply a more simple and accurate prediction for the prognosis of melanoma. Moreover, 5 cancer hallmarks and 18 potential compounds are commonly enriched in high‐risk expression phenotype. Thus, our finding provides new clinical evidences for the accurate diagnosis and identifies a potential prognostic autophagy‐related marker for the treatment of melanoma.
Toxicological assessments of an ethanol extract complex of Descurainia sophia and Peucedanum praeruptorum: Subacute oral toxicity and genotoxicity studies
Authors: Cho Eun‐Sang , Shin Sarah , Lee You Jin , Kim No Soo , Kim Jinhee , Lee Seok‐Jong , Son Hwa‐Young , Lee Woo‐Joo , Bang Ok‐Sun
Published: February 2020

An ethanol extract complex of Descurainia sophia seeds and Peucedanum praeruptorum roots, called BP10A, has antitumor potential against colorectal cancer. In the present study, we evaluated the 28‐day oral toxicity and the genotoxicity of BP10A. The subacute toxicity test was done through oral administration to mice. ICR mice (n = 10) received daily oral BP10A doses of 0, 500, 1000 and 2000 mg/kg for 28 consecutive days. During administration, general clinical signs, food consumption, organ weights, and hematologic, biochemical and histopathological parameters in male and female mice were assessed. No significant adverse effects up to the highest dose (2000 mg/kg) were found. The genotoxicity was evaluated using a battery of tests, including an in vitro bacterial reverse mutation (Ames) test, an in vivo micronucleus test using bone marrow cells in ICR mice and a chromosomal aberration test using CHL/IU cells. BP10A did not show any genotoxic signs in the Ames (up to 5000 μg/plate), micronucleus (up to 5000 mg/kg) and the chromosomal aberration tests (550‐1750 μg/mL). Therefore, BP10A was considered safe based on the subacute toxicity and genotoxicity results, indicating that it is a useful pharmaceutical material with no adverse toxicity.
Comparison of optical microscopy and optical coherence tomography as quality assurance methods for evaluating lubricious hydrophilic coatings surrounding catheter shafts
Authors: Oliver Alexander A. , Stinson Jonathan S. , Osborne Ashley , Taylor Catherine , Goldman Jeremy , Kirkpatrick Sean J.
Published: February 2020

Cardiac catheters are a vital tool in medicine due to their widespread use in many minimally invasive procedures. To aid in advancing the catheter within the patient's vasculature, many catheters are coated with a lubricious hydrophilic coating (HPC). Although HPCs benefit patients, their delamination during use is a serious safety concern. Adverse health effects associated with HPC delamination include pulmonary and myocardial embolism, embolic stroke, infarction, and death. In order to improve patient outcomes, more consistent manufacturing methods and improved quality assurance techniques are needed to evaluate HPC medical devices. The present work investigates the efficacy of two novel methods to image and evaluate HPCs post‐manufacturing, relative to industry‐standard scanning electron microscopy (SEM)‐based methods. We have shown that novel evaluation approaches based on optical microscopy (OM) and optical coherence tomography (OCT) are capable of imaging HPC layers and quantifying HPC thickness, saving hours of time relative to SEM sample preparation and imaging. Additionally, the nondestructive nature of OCT avoids damage and alteration to the HPC prior to imaging, leading to more reliable HPC thickness measurements. Overall, the work demonstrated the feasibility and advantages of using OM and OCT to image and measure HPC thickness relative to industry‐standard SEM methods.
A novel signal‐on fluorescent aptasensor for ochratoxin A detection based on RecJf exonuclease‐induced signal amplification
Authors: Wei Min , He Xing , Xie Yanli
Published: February 2020

This article describes a simple and homogeneous fluorescent aptasensor for the detection of ochratoxin A (OTA). With its high specificity and simplicity; RecJf exonuclease is used to cleave DNA strand of the FAM‐aptamer/OTA complex and realize target recycling signal amplification. In order to avoid the loss of reaction system, magnetic beads (MBs) are added only once at the last experimental step. This proposed fluorescent aptasensor showed the higher sensitivity in the range of 0.1–100 ng/mL with LOD of 0.056 ng/mL, and the good selectivity against other interfering toxins. The feasibility of the prepared aptasensor was studied by detecting OTA in spiked liquor and cereal samples. The obtained average recoveries ranged from 92% to 115%. This study provides a promising application with convenience and rapidness in the aptasensor fabrication for food safety analysis.
Early outcomes of robotic extended cholecystectomy for the treatment of gallbladder cancer
Authors: Byun Yoonhyeong , Choi Yoo Jin , Kang Jae Seung , Han Youngmin , Kim Hongbeom , Kwon Wooil , Jang Jin‐Young
Published: February 2020

Background

Simple laparoscopic cholecystectomy is sufficient for patients with early gallbladder cancer (GBC). However, because advanced GBCs of T2 or more advanced stages require more complex procedures such as liver resection and lymph node dissection, minimally invasive surgery (MIS) has not been popularized. To evaluate the applicability of MIS for GBC, we report the early outcomes of robotic extended cholecystectomies (RECs).

Methods

Thirteen patients who radiologically suspected to have T2 or more advanced stages of GBC underwent REC from February 2018 to April 2019. Thirty‐nine patients who underwent open extended cholecystectomy were selected by 1:3 propensity score matching, and the differences of clinicopathologic features according to surgical methods were analyzed.

Results

Compared with open method, operation time, estimated blood loss, postoperative complication rate, and number of retrieved lymph nodes were not significantly different. In REC group, duration of hospital stay was shorter (6.6 vs 8.3 days, P = .002) and postoperative pain was significantly lower in the REC group (P = .024).

Conclusion

The early outcomes of REC were favorable with regard to early recovery and less pain, with similar number of retrieved lymph nodes. REC is a promising option for treatment of GBC, but further long‐term survival studies are needed.
Developments in the treatment of Fabry disease
Authors: van der Veen Sanne J. , Hollak Carla E. M. , van Kuilenburg André B. P. , Langeveld Mirjam
Published: February 2020

Enzyme replacement therapy (ERT) with recombinant α‐galactosidase A (r‐αGAL A) for the treatment of Fabry disease has been available for over 15 years. Long‐term treatment may slow down disease progression, but cardiac, renal, and cerebral complications still develop in most patients. In addition, lifelong intravenous treatment is burdensome. Therefore, several new treatment approaches have been explored over the past decade. Chaperone therapy (Migalastat; 1‐deoxygalactonojirimycin) is the only other currently approved therapy for Fabry disease. This oral small molecule aims to improve enzyme activity of mutated α‐galactosidase A and can only be used in patients with specific mutations. Treatments currently under evaluation in (pre)clinical trials are second generation enzyme replacement therapies (Pegunigalsidase‐alfa, Moss‐aGal), substrate reduction therapies (Venglustat and Lucerastat), mRNA‐ and gene‐based therapy. This review summarises the knowledge on currently available and potential future options for the treatment of Fabry disease.
Nitisinone causes acquired tyrosinosis in alkaptonuria
Authors: Khedr Milad , Cooper Maggie S. , Hughes Andrew T. , Milan Anna M. , Davison Andrew S. , Norman Brendan P. , Sutherland Hazel , Jarvis Jonathan C. , Fitzgerald Richard , Markinson Louise , Psarelli Eftychia‐Eirini , Ghane Parisa , Deutz Nicolaas E. P. , Gallagher James A. , Ranganath Lakshminarayan R.
Published: February 2020

For over two decades, nitisinone (NTBC) has been successfully used to manipulate the tyrosine degradation pathway and save the lives of many children with hereditary tyrosinaemia type 1. More recently, NTBC has been used to halt homogentisic acid accumulation in alkaptonuria (AKU) with evidence suggesting its efficacy as a disease modifying agent. NTBC‐induced hypertyrosinaemia has been associated with cognitive impairment and potentially sight‐threatening keratopathy. In the context of a non‐lethal condition (ie, AKU), these serious risks call for an evaluation of the wider impact of NTBC on the tyrosine pathway. We hypothesised that NTBC increases the tyrosine pool size and concentrations in tissues.

In AKU mice tyrosine concentrations of tissue homogenates were measured before and after treatment with NTBC. In humans, pulse injection with l‐[13C9]tyrosine and l‐[d8]phenylalanine was used along with compartmental modelling to estimate the size of tyrosine pools before and after treatment with NTBC. We found that NTBC increased tyrosine concentrations in murine tissues by five to nine folds. It also significantly increased the tyrosine pool size in humans (P < .001), suggesting that NTBC increases tyrosine not just in serum but also in tissues (ie, acquired tyrosinosis).

This study provides, for the first time, the experimental proof for the magnitude of NTBC‐related acquired tyrosinosis which should be overcome to ensure the safe use of NTBC in AKU.
Recently increased cold air outbreaks over Mongolia and their specific synoptic pattern
Authors: Munkhjargal Erdenebadrakh , Shinoda Masato , Iijima Yoshihiro , Nandintseteseg Banzragch
Published: February 2020

In recent years, extreme cold air outbreak events (COEs) in winter have tended to occur more frequently over the mid‐latitudes of Eurasia, including Mongolia, despite marked warming across the continent. In the 2000s, an increase in COEs contributed to huge losses of livestock throughout Mongolia, causing socioeconomic stagnation. This study diagnosed the interdecadal variability of the frequency of COEs during cold season (November–March) using observations from 70 meteorological stations in Mongolia by contrasting a past period (PP:1981–1999) and a recent period (RP:2000–2016). Then, this analysis was extended to characterize the synoptic pattern of each period using ERA‐Interim reanalysis data in terms of the ridge and trough system and cold advection. We defined a COE as an event having at least five continuous days with a daily average air temperature lower than minus one standard deviation from the daily climatology during cold season in 1981–2016. The results revealed that totally 112 COEs could be identified over Mongolia during 1981–2016 with a higher number of events (59) during the RP. Regionally, a slight increase in COEs was observed in the north, whereas no clear change was evident in the south. Composite analyses for each period demonstrated that a trough in the central Eurasian mid‐troposphere was deepened and southwestward advection of cold air enhanced during the RP, in comparison with the PP, which changed the wind direction over northern Mongolia from westerly to northwesterly. In addition, the number of snow cover days have increased slightly in the RP in northern Mongolia, likely acting as a favourable condition for low air temperatures with intensifying surface cooling. These findings suggest that a deepened trough over central Eurasia, strengthened northerly cold advection into Mongolia, and cooling from the snow‐covered surface are most likely to have resulted in the increased frequency of COEs overnorthern Mongolia in the RP.
The Geriatric Nutritional Risk Index as a Prognostic Factor in Patients with Advanced Head and Neck Cancer
Authors: Nakayama Masahiro , Gosho Masahiko , Adachi Masahiro , Ii Rieko , Matsumoto Shin , Miyamoto Hidetaka , Hirose Yuki , Nishimura Bungo , Tanaka Shuho , Wada Tetsuro , Tabuchi Keiji
Published: February 2020

Objective

The Geriatric Nutritional Risk Index (GNRI) is a simple and well‐established nutritional assessment tool and is a significant prognostic factor in various cancers. However, the role of the GNRI in predicting clinical outcomes in patients with advanced head and neck cancer (AHNC) has not been investigated. The aim of the present study was to examine the association between the GNRI and prognosis in patients with AHNC.

Study Design

Retrospective cohort study.

Methods

Data collected between 2002 and 2013 from Tsukuba University Hospital were reviewed. The GNRI was calculated according to the equation, 1.489 × serum albumin (g/l) + 41.7 × (body weight/ideal body weight). Characteristics and prognosis were compared among three risk groups: high (GNRI <82); intermediate (GNRI 82–98); and normal (GNRI >98). The primary endpoint was overall survival.

Results

A total of 248 AHNC patients were enrolled, among whom 134 (54%) exhibited no nutritional risk, 53 (21%) had an intermediate risk for malnutrition, and 61 (25%) exhibited a high risk for malnutrition. Three‐year survival rates according to the three‐group GNRI scores for normal, intermediate, and high risk were 76.6%, 56.3%, and 19.5%, respectively. As the three‐group GNRI score increased, the risk for mortality significantly increased (adjusted hazard ratio [HR] for intermediate to normal, 1.73 [95% CI, 1.02–2.92]; adjusted HR for high to normal, 4.31 [95% CI, 2.71–6.84]).

Conclusions

The GNRI could be considered a useful prognostic factor in patients with AHNC.

Level of Evidence

4 Laryngoscope, 131:E151–E156, 2021
PEG‐assisted solvothermal synthesis of MoS2 nanosheets with enhanced tribological property
Authors: Chen Jianfeng , Xu Zuxin , Hu Yun , Yi Meirong
Published: February 2020

Molybdenum disulfide (MoS2) nanoparticles are widely used as oil additives for obtaining low friction and wear. In this article, MoS2 nanosheets with ultrathin shape and structure defects were prepared by a facile solvothermal method with the aid of polyethylene glycol (PEG 200). The products were analysed by X‐ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), X‐ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FTIR). Results indicated that PEG 200 played a crucial role as the shape controller in the formation of different MoS2 structures. Interestingly, the prepared MoS2 perform excellent in improving the friction‐reducing and antiwear properties of oils. More importantly, the lubricating behaviour of the obtained MoS2 nanosheets as oil additives was still effective in the harsh condition of heavy load and high temperature. Further, the excellent lubrication performance of the prepared MoS2 was discussed based on the exfoliation into individually ultrathin nanosheets and nanosized debris, and the formation of MoS2‐based tribofilm inside the wear tracks.
Design of master oscillator for frequency locking of a complex of megawatt level microwave sources
Authors: Denisov Grigory G. , Kuftin Andrey N. , Manuilov Vladimir N. , Zavolsky Nikolai A. , Chirkov Alexey V. , Soluyanova Elena A. , Tai Evgeniy M. , Bakulin Mikhail I. , Tsvetkov Alexander I. , Fokin Andrey P. , Novozhilova Yulia V. , Movshevich Boris Z. , Glyavin Mikhail Yu.
Published: February 2020

We present the results of the development of a highly stable gyrotron (with long‐term stability of an operating frequency of 170 GHz being equal to 10−9) for experiments on frequency locking and control of megawatt power sources. The electron‐optical and electrodynamic systems of the gyrotron are calculated and optimized, including the magnetron‐injection gun, interaction space, collector, and quasioptical converter of radiation into a Gaussian wave beam. Main requirements for such systems are described along with their specific features, which allow one to develop a relatively simple, low cost, and reliable master generator for synchronization of a large number of continuous‐wave megawatt gyrotrons. This reveals new possibilities for creation of gyrotron complexes capable of generation coherent radiation of nearly unlimited power levels.
Compact, broadband, and high gain directional endfire antenna
Authors: Chopra Rinkee , Kumar Girish
Published: February 2020

A broadband directional endfire printed antenna is proposed with a simple unbalanced feed, compact size, stable gain, and high front to back ratio (F/B). The antenna consists of a microstrip driven with U‐shaped ground and reflector elements to reduce the antenna size. The reflector increases the directivity and F/B in the lower frequency band. The parasitic element, which is located close to the driven element and also acts like director, enhances the bandwidth (BW) and gain in the upper frequency band. Prototype of the proposed antenna is fabricated with antenna size of 0.48λo × 0.35λo. Experiment results demonstrate that the proposed antenna provides 62.6% (1.606‐3.07 GHz) BW with stable gain (5‐6.8 dBi) and min F/B of 15 dB. The proposed endfire antenna is a good candidate for wireless applications in 2G, 3G, 4G, Wi‐Fi, and lower WiMAX bands.
Demonstration of magnetization transfer and relaxation normalized pH‐specific pulse‐amide proton transfer imaging in an animal model of acute stroke
Authors: Sun Phillip Zhe
Published: February 2020

Purpose

pH‐weighted amide proton transfer (APT) MRI is promising to serve as a new surrogate metabolic imaging biomarker for refined ischemic tissue demarcation. APT MRI with pulse‐RF irradiation (pulse‐APT) is an alternative to the routine continuous wave (CW‐) APT MRI that overcomes the RF duty cycle limit. Our study aimed to generalize the recently developed pH‐specific magnetization transfer and relaxation‐normalized APT (MRAPT) analysis to pulse‐APT MRI in acute stroke imaging.

Methods

Multiparametric MRI, including CW‐ and pulse‐APT MRI scans, were performed following middle cerebral artery occlusion in rats. We calculated pH‐sensitive MTRasym and pH‐specific MRAPT contrast between the ipsilateral diffusion lesion and contralateral normal area.

Results

An inversion pulse of 10 to 15 ms maximizes the pH‐sensitive MRI contrast for pulse‐APT MRI. The contrast‐to‐noise ratio of pH‐specific MRAPT effect between the contralateral normal area and ischemic lesion from both methods are comparable (3.25 ± 0.65 vs. 3.59 ± 0.40, P > .05). pH determined from both methods were in good agreement, with their difference within 0.1.

Conclusions

Pulse‐APT MRI provides highly pH‐specific mapping for acute stroke imaging.
Plasma‐assisted gas‐phase synthesis and in‐line coating of silicon nanoparticles
Authors: Dasgupta Malini , Fortugno Paolo , Wiggers Hartmut
Published: February 2020

This study investigates the feasibility of plasma‐supported in‐line functionalization of silicon nanoparticles (NPs) in an atmospheric pressure gas‐phase reactor. The approach utilizes the synthesis of core silicon NPs and their subsequent coating downstream of the particle formation zone. In‐line coating is accomplished with a cylindrical coating nozzle to achieve homogenous mixing of coating precursor vapors with in‐coming NPs. Multiple siloxanes were tested for their coating suitability and their ability towards coating homogeneity. It was found that tetraethyl orthosilicate is favored for thin layers consisting of almost pure silica while hexamethyldisiloxane and octamethylcyclotetrasiloxane (OMCTS) coatings contained reasonable amounts of hydrocarbons. Moreover, OMCTS showed a pronounced tendency towards homogeneous nucleation, thus leading to the additional formation of silica NPs due to homogeneous nucleation.
Permafrost aggradation along the emerging eastern coast of Hudson Bay, Nunavik (northern Québec, Canada)
Authors: Boisson Antoine , Allard Michel , Sarrazin Denis
Published: February 2020

Emerging polar coasts have different geothermal regimes than those in submergence. While the scientific community is mainly concerned with rapidly eroding permafrost coastlines in sedimentary formations where relative sea level is rising, much less research has been dedicated to permafrost dynamics in emergent coastal regions where post‐glacial uplift is ongoing. The eastern Hudson Bay coast of Nunavik (northern Québec, Canada) is undergoing glacio‐isostatic uplift at a current emergence rate of about 13 mm/yr, outpacing the current global sea‐level rise (~3 mm/yr) and progressively exposing new land to climate conditions favorable for permafrost formation. To observe incipient permafrost in the shore zone over time, in 2005 we strategically installed a thermistor cable down to a depth of 23 m at a high‐tide level site. We detected the formation and the continuing deepening of permafrost near the surface. Freezing of the ground was also favored by a succession of several cold years in Nunavik since 2010. The near 0°C temperature profile at greater depths also reveals the cooling influence of deep Hudson Bay waters on the shore zone ground temperature regime and the probable presence of subsea permafrost offshore of the measurement site.
Quality of Life, Mental Health, Personality and Patterns of Use in Self‐Medicated Cannabis Users with Chronic Diseases: A 12‐Month Longitudinal Study
Authors: Bouso José C. , Jiménez‐Garrido Daniel , Ona Genís , Woźnica Damian , dos Santos Rafael G. , Hallak Jaime E.C. , Paranhos Beatriz A. P. B. , de Almeida Mendes Felipe , Yonamine Mauricio , Alcázar‐Córcoles Miguel Á. , Farré Magí
Published: February 2020

The number of patients using cannabis for therapeutic purposes is growing worldwide. While research regarding the treatment of certain diseases/disorders with cannabis and cannabinoids is also expanding, only a few longitudinal studies have assessed the mid‐term impacts of medical cannabis use on psychological variables and quality of life (QoL). The aim of the study was to assess the psychological safety and QoL of patients with chronic diseases who self‐medicate with cannabis over time. We recruited patients with various chronic diseases who use cannabis and collected data regarding patterns of cannabis use as well as mental health, personality and QoL. Participants were followed‐up at baseline, 4, 8 and 12 months. Hair analysis was conducted to confirm the presence of cannabinoids. Personality assessment showed a consistent decrease in self‐transcendence and self‐directedness scores. Neither cognitive nor psychopathological deterioration was found. There were also no variations in QoL. Mid‐term use of medical cannabis seems to show adequate tolerability regarding cognitive and psychopathological abilities, and it may help patients with chronic diseases to maintain an acceptable QoL.
Wealth in people and the value of historic Oberlin Cemetery, Raleigh, North Carolina
Authors: McGill Dru , Millhauser John K. , McGill Alicia , Melomo Vincent , Bohnenstiehl Del , Wall John
Published: February 2020

In its origins as a concept, wealth in people depended on the circulation and accumulation of rights and obligations among and over the living. But if a person is a source of wealth, what happens when the person dies? Would the person be excised from the relationships upon which wealth in people depends, or might his or her wealth remain accessible to the living? To address this question, we present the case of Oberlin Cemetery in Raleigh, North Carolina. The cemetery was the core of Oberlin Village, a freedperson's African American community founded in the mid‐nineteenth century. Today, development threatens historic resources surrounding the cemetery, but a community organization founded by descendants and neighbors has emerged to preserve and promote their heritage. We are a group of anthropologists, geologists, and historians who live and work near Oberlin Village and who collaborate to help this organization achieve its goals. Here we report how our efforts to document the cemetery's history have bolstered their advocacy and validated their claims to wealth in the people buried there. Thus we show how wealth in people extends to the dead when graves and the people within them are potent sources of value for the living.
Acceleration of an Enzymatic Reaction in Liquid Phase Separated Compartments Based on Intrinsically Disordered Protein Domains
Authors: Küffner Andreas M. , Prodan Marc , Zuccarini Remo , Capasso Palmiero Umberto , Faltova Lenka , Arosio Paolo
Published: February 2020

Spontaneous liquid demixing of biomolecules appears to be an efficient strategy developed by cells to organize reactions in space and time. This process allows cells to modulate biochemical reactions by locally changing the concentration and the environment of specific components. Here, we develop a strategy to couple the formation of biomolecular liquid compartments with reactions occuring within them. In particular, we conjugate a kinase enzyme with biologically derived low complexity domains and develop synthetic micro‐reactors that locally increase the enzyme concentration up to 140‐fold. We show that these micro‐reactors are characterized by a polarity comparable to methanol which promotes recruitment of small molecules. Despite exhibiting higher viscosity with respect to the surrounding solution, the reactors are liquid‐like and allow molecular diffusion within their interior. We demonstrate that the local increase in enzyme concentration accelerates the corresponding enzymatic rate up to 5‐fold. This flexible strategy enables the generation of biomolecular micro‐reactors with enhanced reactivity, with potential applications in heterogeneous biocatalysis.
Signaling in the primary cilium through the lens of the Hedgehog pathway
Authors: Gigante Eduardo D. , Caspary Tamara
Published: February 2020

Cilia are microtubule‐based, cell‐surface projections whose machinery is evolutionarily conserved. In vertebrates, cilia are observed on almost every cell type and are either motile or immotile. Immotile sensory, or primary cilia, are responsive to extracellular ligands and signals. Cilia can be thought of as compartments, functionally distinct from the cell that provides an environment for signaling cascades. Hedgehog is a critical developmental signaling pathway which is functionally linked to primary cilia in vertebrates. The major components of the vertebrate Hedgehog signaling pathway dynamically localize to the ciliary compartment and ciliary membrane. Critically, G‐protein coupled receptor (GPCR) Smoothened, the obligate transducer of the pathway, is enriched and activated in the cilium. While Smoothened is the most intensely studied ciliary receptor, many GPCRs localize within cilia. Understanding the link between Smoothened and cilia defines common features, and distinctions, of GPCR signaling within the primary cilium.

This article is categorized under:

Signaling Pathways > Global Signaling Mechanisms

Signaling Pathways > Cell Fate Signaling
Monitoring a New England Cottontail Reintroduction with Noninvasive Genetic Sampling
Authors: Bauer Melissa L. , Ferry Brett , Holman Heidi , Kovach Adrienne I.
Published: February 2020

Careful monitoring of reintroduced threatened species is essential for informing conservation strategies and evaluating reintroduction efforts in an adaptive management context. We used noninvasive genetic sampling to monitor a reintroduction of a threatened shrubland specialist, the New England cottontail (Sylvilagus transitionalis), in southeastern New Hampshire, USA. We monitored the apparent survival and breeding success of founder individuals and tracked changes in population size and genetic diversity for 5 years following an initial reintroduction in 2013. We released 42 rabbits, documented 29 unique offspring in years following releases through noninvasive surveys, and identified 6 founder individuals and 9 recruited offspring that bred. Apparent survival of founders was variable and greatest in the first year of the reintroduction. Predation was the primary cause of mortality and greatest in the first month after release and after heavy snowfall. Population size remained small but relatively stable until a stochastic decline in the fourth year following reintroduction, followed by a slight rebound after population augmentation and offspring production by wild‐born rabbits. Genetic diversity increased after the initial founders with diverse genetic backgrounds were released and then they and their subsequent offspring bred. We documented successful dispersal 700 m from the release site to a high‐quality patch of habitat, which remained occupied throughout the study. For New England cottontail reintroductions to be successful in the long term, releases will be needed at multiple patches within dispersal distance, and habitat corridors need to be restored among patches to create a functioning metapopulation. For small or isolated reintroduced populations, continued intensive monitoring is needed to detect stochastic declines in population size or changes in sex ratios and guide subsequent management reactions via additional reintroductions or population augmentations. Noninvasive genetic sampling is a valuable tool to monitor reintroductions of the New England cottontail and other threatened species to provide managers with detailed information to inform decision‐making in an adaptive management framework. © 2020 The Wildlife Society.
Relativistic and spectator effects in leptogenesis with heavy sterile neutrinos
Authors: Garbrecht Björn , Klose Philipp , Tamarit Carlos
Published: February 2020

Abstract

For leptogenesis with heavy sterile neutrinos above the electroweak scale, asymmetries produced at early times (in the relativistic regime) are relevant, if they are protected from washout. This can occur for weak washout or when the asymmetry is partly protected by being transferred to spectator fields. We thus study the relevance of relativistic effects for leptogenesis in a minimal seesaw model with two sterile neutrinos in the strongly hierarchical limit. Starting from first principles, we derive a set of momentum-averaged fluid equations to calculate the final B − L asymmetry as a function of the washout strength and for different initial conditions at order one accuracy. For this, we take the leading fluid approximation for the relativistic CP-even and odd rates. Assuming that spectator fields remain in chemical equilibrium, we find that for weak washout, relativistic corrections lead to a sign flip and an enhancement of the asymmetry for a vanishing initial abundance of sterile neutrinos. As an example for the effect of partially equilibrated spectators, we consider bottom-Yukawa and weak-sphaleron interactions in leptogenesis driven by sterile neutrinos with masses ≳ 5 × 1012 GeV. For a vanishing initial abundance of sterile neutrinos, this can give rise to another flip and an absolute enhancement of the final asymmetry in the strong washout regime by up to two orders of magnitude relative to the cases either without spectators or with fully equilibrated ones. These effects are less pronounced for thermal initial conditions for the sterile neutrinos. The CP-violating source in the relativistic regime at early times is important as it is proportional to the product of lepton-number violating and lepton-number conserving rates, and therefore less suppressed than an extrapolation of the nonrelativistic approximations may suggest.
Two loop QCD amplitudes for di-pseudo scalar production in gluon fusion
Authors: Bhattacharya Arunima , Mahakhud Maguni , Mathews Prakash , Ravindran V.
Published: February 2020

Abstract

We compute the radiative corrections to the four-point amplitude g+g → A+A in massless Quantum Chromodynamics (QCD) up to order $$ {\alpha}_s^4 $$

α
s
4

in perturbation theory. We used the effective field theory that describes the coupling of pseudo-scalars to gluons and quarks directly, in the large top quark mass limit. Due to the CP odd nature of the pseudo-scalar Higgs boson, the computation involves careful treatment of chiral quantities in dimensional regularisation. The ultraviolet finite results are shown to be consistent with the universal infrared structure of QCD amplitudes. The infrared finite part of these amplitudes constitutes the important component of any next to next to leading order corrections to observables involving pair of pseudo-scalars at the Large Hadron Collider.