bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation and Characterization of Patient‐Derived Head and Neck, Oral, and Esophageal Cancer Organoids
Authors: Karakasheva Tatiana A. , Kijima Takashi , Shimonosono Masataka , Maekawa Hisatsugu , Sahu Varun , Gabre Joel T. , Cruz‐Acuña Ricardo , Giroux Veronique , Sangwan Veena , Whelan Kelly A. , Natsugoe Shoji , Yoon Angela J. , Philipone Elizabeth , Klein‐Szanto Andres J. , Ginsberg Gregory G. , Falk Gary W. , Abrams Julian A. , Que Jianwen , Basu Devraj , Ferri Lorenzo , Diehl J. Alan , Bass Adam J. , Wang Timothy C. , Rustgi Anil K. , Nakagawa Hiroshi
Published: April 2020

Esophageal cancers comprise adenocarcinoma and squamous cell carcinoma, two distinct histologic subtypes. Both are difficult to treat and among the deadliest human malignancies. We describe protocols to initiate, grow, passage, and characterize patient‐derived organoids (PDO) of esophageal cancers, as well as squamous cell carcinomas of oral/head‐and‐neck and anal origin. Formed rapidly (<14 days) from a single‐cell suspension embedded in basement membrane matrix, esophageal cancer PDO recapitulate the histology of the original tumors. Additionally, we provide guidelines for morphological analyses and drug testing coupled with functional assessment of cell response to conventional chemotherapeutics and other pharmacological agents in concert with emerging automated imaging platforms. Predicting drug sensitivity and potential therapy resistance mechanisms in a moderate‐to‐high throughput manner, esophageal cancer PDO are highly translatable in personalized medicine for customized esophageal cancer treatments. © 2020 by John Wiley & Sons, Inc.

Basic Protocol 1: Generation of esophageal cancer PDO

Basic Protocol 2: Propagation and cryopreservation of esophageal cancer PDO

Basic Protocol 3: Imaged‐based monitoring of organoid size and growth kinetics

Basic Protocol 4: Harvesting esophageal cancer PDO for histological analyses

Basic Protocol 5: PDO content analysis by flow cytometry

Basic Protocol 6: Evaluation of drug response with determination of the half‐inhibitory concentration (IC50)

Support Protocol: Production of RN in HEK293T cell conditioned medium
Production of Antiviral Substance from Sugarcane Bagasse by Chemical Alteration of its Native Lignin Structure through Microwave Solvolysis
Authors: Kimura Chihiro , Li Ruibo , Ouda Ryota , Nishimura Hiroshi , Fujita Takashi , Watanabe Takashi
Published: April 2020

The production of bioactive agents from lignocelluloses has received limited attention because plant cell walls are essentially non‐bioactive. In this study, a chemical reaction is reported, which produces a lignin‐derived antiviral substance from sugarcane bagasse by microwave heating at 200 °C in aqueous glycerol containing 0.5 % H2SO4. The purified fraction, designated as FR200, strongly inhibited the replication of encephalomyocarditis virus (EMCV) in L929 cells without cytotoxicity. HSQC NMR spectra demonstrated that the principal interunit linkages in the native lignin were cleaved by the reaction. Gel permeation chromatography (GPC) and pyrolysis‐GCMS revealed that FR200 is composed of oligomeric lignin with a weight average molecular weight of approximately 2000. When the bagasse was reacted at lower temperatures, 140 °C and 160 °C, the native lignin substructures were partially retained and the antiviral activity significantly decreased. The results thus indicate that the antiviral activity emerged through severe alteration of the native lignin structure. Furthermore, it was revealed that the antiviral lignin inactivated the EMCV virions through direct contact, as the innate immune system of L929 was not activated by FR200 treatment, and no antiviral activity was found when L929 was pre‐treated with the lignin before viral infection.
Across the Board: Runcang Sun on Lignin Nanoparticles
Authors: Sun Runcang
Published: April 2020

In this series of articles, the board members of ChemSusChem discuss recent research articles that they consider of exceptional quality and importance for sustainability. This entry features Prof. R. C. Sun, who highlights the fabrication of lignin nanoparticles and their application in composites, suggesting that further studies and discoveries of the structures and inherent properties of lignin will contribute to extensive and standardized applications of this new green nanomaterial.
An FPGA comparative study of high‐level and low‐level combined designs for HEVC intra, inverse quantization, and IDCT/IDST 2D modules
Authors: Ben Atitallah Ahmed , Kammoun Manel , Ali Karim M.A. , Ben Atitallah Rabie
Published: April 2020

Two main design methods are currently widely adopted in dealing with complex signal processing algorithms. The first method is based on low‐level synthesis (LLS), which consists in writing the hardware description languages (HDL) code manually. However, the second method, called high‐level synthesis (HLS), generates the register transfer level (RTL) description automatically starting from a high‐level description language. The challenge in this paper was to study the impact of both design methods on such a complex application as the High Efficiency Video Coding (HEVC) decoder. With this end in view, we analyzed the complexity of the HEVC decoder in a software environment using version 10 of the HEVC test model (HM) reference software to determine which portions tended to get optimized. The combined architecture for the intra prediction (IP) and the inverse quantization and transform (IQ/IT) was then implemented in hardware using HLS and LLS. The findings obtained under the Xilinx Zynq 7045‐based field‐programmable gate array (FPGA) proved that the HLS implementation enabled a gain of about 80% in Look Up Table (LUTs) with an increase of 93% in DSP blocks compared with LLS implementation. Yet only the LLS solution could achieve the real‐time decoding of 4K@26fps instead of the 1080p@24fps by the HLS design.
Adrenocortical attunement, reactivity, and potential genetic correlates among parent–daughter dyads from low‐income families
Authors: Byrd‐Craven Jennifer , Criss Michael M. , Calvi Jessica L. , Cui Lixian , Baraldi Amanda , Sheffield Morris Amanda
Published: April 2020

Examining the multitude of influences on the development of adolescent stress responses, especially among low‐income families, is a critical and understudied topic in the field. The current study examined cortisol attunement between adolescent girls and parents (mostly mothers) from predominantly low‐income, single parent, ethnic minority families before and after an in‐laboratory disagreement discussion task. The sample consisted of 118 adolescents (Mage = 13.79 years, 76.3% ethnic minorities, 23.7% European Americans) and primary caregivers (Mage = 40.62 years; Mdn yearly income = $24,000; 43.2% single parents; 50% living below poverty line). We investigated oxytocin receptor (OXTR rs53576) gene variations as a potential contributor to attunement within the dyad. Results showed that parents and adolescents showed stress system attunement across the disagreement task, but that parent and adolescent oxytocin receptor genotype did not impact attunement. Future studies should detail biological factors that contribute to the calibration of stress response systems of adolescents across a variety of samples, particularly those experiencing a combination of stressors.
Optimal fasting plasma glucose and haemoglobin A1c levels for screening of prediabetes and diabetes according to 2‐hour plasma glucose in a high‐risk population: The Korean Diabetes Prevention Study
Authors: Cha Seon‐Ah , Chon Suk , Yun Jae‐Seung , Rhee Sang Youl , Lim Sun‐Young , Yoon Kun‐Ho , Ahn Yu‐Bae , Ko Seung‐Hyun , Woo Jeong‐Taek , Lee Jin‐Hee
Published: April 2020

Background

The primary aim of this study was to assess the utility of fasting plasma glucose (FPG) and HbA1c to identify diabetes by the 2‐hour plasma glucose (PG) criterion in the Korean population at high risk for diabetes.

Methods

A total of 1646 participants with a body mass index of ≥23 kg/m2 without having a history of diabetes were recruited in this study. The cut‐off values of FPG and HbA1c for detecting diabetes were identified using the Youden index using receiver operating characteristic (ROC) analysis. The gold standard for diabetes prediction was defined by the 2‐hour PG level of ≥200 mg/dL.

Results

The participants comprised 54.0% women, and the mean age of all participants was 55.0 ± 8.1 years. At baseline, FPG was 104.1 ± 14.2 mg/dL, the 2‐hour PG value was 162.9 ± 55.3 mg/dL, and HbA1c was 5.9% ± 0.5%. Four hundred and forty‐six subjects (27.1%) were diagnosed with diabetes and 976 subjects (59.3%) were determined to be at prediabetes. The area under the ROC curve (AUC) of FPG and HbA1c for diabetes were 0.776 and 0.802, while the AUC of FPG and HbA1c for prediabetes were 0.515 and 0.477. The optimal cut‐off value for diagnosing diabetes of FPG and HbA1c were 104.5 mg/dL (sensitivity 75.8%, specificity 67.5%) and 5.9% (sensitivity 80.6%, specificity 63.8%), respectively.

Conclusions

FPG of 104.5 mg/dL and HbA1c value of 5.9% (41 mmol/mol) can be used as an optimal screening value for diabetes by 2‐hour PG criterion in the Korean population at high risk for diabetes.
Generation of B6‐Ddx4em1(CreERT2)Utr, a novel CreERT2 knock‐in line, for germ cell lineage by CRISPR/Cas9
Authors: Le Hoai Thu , Hasegawa Yoshikazu , Daitoku Yoko , Kato Kanako , Miznuo‐Iijima Saori , Dinh Tra Thi Huong , Kuba Yumeno , Osawa Yuki , Mikami Natsuki , Morimoto Kento , Ayabe Shinya , Tanimoto Yoko , Murata Kazuya , Yagami Ken‐ichi , Takahashi Satoru , Mizuno Seiya , Sugiyama Fumihiro
Published: April 2020

Germ cell development is essential for maintaining reproduction in animals. In postpubertal females, oogenesis is a highly complicated event for producing fertilizable oocytes. It starts when dormant primordial oocytes undergo activation to become growing oocytes. In postpubertal males, spermatogenesis is a differentiation process for producing sperm from spermatogonial stem cells. To obtain full understanding of the molecular mechanisms underlying germ cell development, the Cre/loxP system has been widely applied for conditional knock‐out mouse studies. In this study, we established a novel knock‐in mouse line, B6‐Ddx4
em1(CreERT2)Utr, which expresses CreERT2 recombinase under the control of the endogenous DEAD‐box helicase 4 (Ddx4) gene promoter. Ddx4 was specifically expressed in both female and male germ cell lineages. We mated the CreERT2 mice with R26GRR mice, expressing enhanced green fluorescent protein (EGFP) and tDsRed before and after Cre recombination. We found tDsRed signals in the testes and ovaries of tamoxifen‐treated B6‐Ddx4
em1(CreERT2)Utr::R26GRR mice, but not in untreated mice. Immunostaining of their ovaries clearly showed that Cre recombination occurred in all oocytes at every follicle stage. We also found 100% Cre recombination efficiency in male germ cells via the progeny test. In summary, our results indicate that B6‐Ddx4
em1(CreERT2)Utr is beneficial for studying female and male germ cell development.
Iridium Carbene and Carbamoyl Complexes Supported by a Tetradentate Pyridine‐Carboxamide Ligand
Authors: Wong Kai‐Hong , Cheung Wai‐Man , Sung Herman H. ‐Y. , Williams Ian D. , Leung Wa‐Hung
Published: April 2020

The nucleophilic attack of an IrIII isocyanide complex bearing a tetradentate pyridine‐carboxamide ligand with amines to give carbene and carbamoyl complexes has been studied. The treatment of Na[Ir(bpb)Cl2] {bpb2– = dianion of 1,2‐bis(2‐pyridinecarboxamido)benzene} with PR3 (R = p‐tolyl) in refluxing glycol gave [Ir(bpb)(PR3)Cl] (1). Chloride abstraction of 1 with silver tosylate (AgOTs) led to isolation of a mixture of [Ir(bpb)(PR3)(OTs)] (2a) and [Ir(bpb)(PR3)(H2O)](OTs) (2b) that reacted with 2,6‐dimethylphenyl isocyanide (CNxyl) and 4‐tert‐butylaniline to give [Ir(bpb)(PR3)(CNxyl)](OTs) (3) and [Ir(bpb)(PR3)(4‐tBuC6H4NH2)](OTs) (4), respectively. The reaction of 4 with AgOTf (OTf– = triflate) yielded an Ir–Ag dimeric complex, [Ir(bpb)(PR3)(4‐tBuC6H4NH2){Ag(H2O)(µ‐OTf)}]2(OTf)2 (5). Whereas nucleophilic attack of 3 with benzylamine (BnNH2) afforded the carbene complex [Ir(bpb)(PR3){C(NHBn)(NHxyl)}](OTs) (6), that with tBuNH2 yielded the carbamoyl complex [Ir(bpb)(PR3){C(O)NHxyl}] (7). The IrIV–IrIII redox potentials for Ir(bpb) complexes have been determined using cyclic voltammetry. The crystal structures of 2a, 2b, and 5–7 have been determined.
Enantioselective Organocatalyzed Michael Additions of Nitroalkanes to 4‐Arylidenedihydrofuran‐2,3‐diones and 4‐Arylidenepyrrolidine‐2,3‐diones
Authors: Fofana Mouhamadou , Dudognon Yohan , Bertrand Laura , Constantieux Thierry , Rodriguez Jean , Ndiaye Ibrahima , Bonne Damien , Bugaut Xavier
Published: April 2020

Tremendous efforts have been devoted to the development of organocatalytic enantioselective Michael additions of nitroalkanes to α,β‐unsaturated carbonyl compounds. However, using highly substituted electrophiles remain challenging, since the additional substituents decrease the electrophilicity. β‐Arylidene‐α‐ketolactones and α‐ketolactams are used as highly electrophilic Michael acceptors that afford the corresponding products in moderate to good yields, with high enantioselectivities. This success relies on their rigid structure that prevents deconjugation and the efficient recognition of the α‐dicarbonyl motif by the hydrogen‐bond donor catalyst.
Prediction of Chinese energy structure based on Convolutional Neural Network‐Long Short‐Term Memory (CNN‐LSTM)
Authors: Li Yan , He Yaoyu , Zhang Meizhen
Published: April 2020

With the improvement of environmental protection awareness and transformation of industrial structure, China's energy consumption structure has changed constantly. Although the proportion of coal consumption is gradually decreasing, the consumption has not seen a significant decline; it even increased in 2018. Many researchers have focused on changes in one specific type of energy such as coal or solar. However, the overall energy structure was ignored. In this study, an integrated convolutional neural network (CNN) with Long Short‐term Memory (LSTM) was used to predict the energy structure of China. Historical data were considered as pixels for convolution by layers of the CNN and then encoded by LSTM layers. To verify the effectiveness of the method, CNN‐LSTM was compared with six previous methods using data from 1965 to 2018. The results showed that CNN‐LSTM was superior in predicting energy structure. Finally, the energy structure of China in the next decade was predicted. The prediction results demonstrated that although the share of clean energy consumption will continue to increase, coal consumption will not decline.
An efficient SDN‐based LTE‐WiFi spectrum aggregation system for heterogeneous 5G networks
Authors: Abbas Khizar , Afaq Muhammad , Ahmed Khan Talha , Rafiq Adeel , Iqbal Javed , Ul Islam Ihtesham , Song Wang‐Cheol
Published: April 2020

Nowadays, the continuously increasing demand for high data traffic and providing different quality of services (QoS) to the customer are very challenging tasks for all network operators. In the last few years, mobile data traffic is increased to a significant extent and half of the traffic is provided through WiFi technology which is known as WiFi offloading. To overcome the increasing traffic demand, WiFi offloading is the best option to reduce the burden of cellular networks. So, by aggregating existing indoor WiFi technology to the cellular network increases the network capacity and provides better QoS to customers. In this article, we propose and implement the LTE‐WiFi aggregation system where eNodeB is responsible for the aggregation of the WiFi access point without modifying the core network. Furthermore, the proposed system is integrated with the mobile‐CORD (M‐CORD) platform which leverages software defined networking (SDN), network function virtualization (NFV), and cloud technologies for providing a 5G environment. M‐CORD platform has three main modules: service orchestrator (XOS), SDN controller ONOS, and OpenStack. One of the important features of M‐CORD is to provide virtualized core network functions that enable the users to automatically customize, monitor, and control the resources of the network. Due to ONOS controller support, we can easily scale up the network instances by giving the configurations to service orchestrator XOS of the M‐CORD. The implementation of the proposed system is based on the OpenAirInterface (OAI) platform which provides open sources implementation of core and access networks. The aggregation of both LTE and WiFi technologies is done at the PDCP layer in a very tight coupling way. Moreover, we test our proposed system with three kinds of policies for UDP and TCP traffic: LTE only, WiFi only, and LTE‐WiFi aggregated. The experimental results show that our proposed LTE‐WiFi aggregated system gives better performance and provides high bandwidth as compared to the LTE network.
Decreased copy‐neutral loss of heterozygosity in African American colorectal cancers
Authors: Augustus Gaius J. , Xicola Rosa M. , Llor Xavier , Ellis Nathan A.
Published: April 2020

Despite improvements over the past 20 years, African Americans continue to have the highest incidence and mortality rates of colorectal cancer (CRC) in the United States. While previous studies have found that copy number variations (CNVs) occur at similar frequency in African American and White CRCs, copy‐neutral loss of heterozygosity (cnLOH) has not been investigated. In the present study, we used publicly available data from The Cancer Genome Atlas (TCGA) as well as data from an African American CRC cohort, the Chicago Colorectal Cancer Consortium (CCCC), to compare frequencies of CNVs and cnLOH events in CRCs in the two racial groups. Using genotype microarray data, we analyzed large‐scale CNV and cnLOH events from 166 microsatellite stable CRCs—31 and 39 African American CRCs from TCGA and the CCCC, respectively, and 96 White CRCs from TCGA. As reported previously, the frequencies of CNVs were similar between African American and White CRCs; however, there was a significantly lower frequency of cnLOH events in African American CRCs compared to White CRCs, even after adjusting for demographic and clinical covariates. Although larger differences for chromosome 18 were observed, a lower frequency of cnLOH events in African American CRCs was observed for nearly all chromosomes. These results suggest that mechanistic differences, including differences in the frequency of cnLOH, could contribute to clinicopathological disparities between African Americans and Whites. Additionally, we observed a previously uncharacterized phenomenon we refer to as small interstitial cnLOH, in which segments of chromosomes from 1 to 5 Mb long were affected by cnLOH.
The perceptions, barriers and enablers to physical activity and minimising sedentary behaviour among Arab‐Australian adults aged 35‐64 years
Authors: El Masri Aymen , Kolt Gregory S. , George Emma S.
Published: April 2020

Issues addressed

The objective of this study was to explore the perceptions, barriers and enablers to physical activity (PA) and minimising sedentary behaviour among Arab‐Australians, a group who have lower levels of PA and higher rates of certain chronic diseases when compared with the general Australian population.

Methods

A total of 28 Arab‐Australians aged 35‐64 years participated in one of five focus groups conducted in Western Sydney during 2017‐2018, a culturally diverse region in New South Wales, Australia. Focus group duration ranged from 35‐90 minutes with 4‐7 participants in each group. Focus group data were recorded and transcribed verbatim and analysed using inductive thematic analysis.

Results

Participants had a general understanding of PA and the associated health benefits. Fewer participants were aware of the independent health effects associated with prolonged sitting. A lack of time and motivation due to work, familial duties, domestic roles and lack of effort reportedly influenced PA participation. Health was perceived to be both a barrier and an enabler to PA. Barriers related to health included pain and existing conditions and enablers included preventive and reactive measures. Social support and accessibility, such as a lack of support networks, the availability of services and costs were also discussed. Cultural and religious influences, such as traditional gender roles and the importance of gender‐exclusive settings, were also important factors influencing the PA behaviours of participants.

Conclusions

This study highlighted the factors that influence the PA levels and sedentary behaviour of Arab‐Australian adults aged 35‐64 years.

So what?

The findings of this study could help inform the design and development of culturally tailored PA interventions for Arab‐Australian adults.
Study on oil fouling in a double pipe heat exchanger with mitigation by a surfactant
Authors: Hasan Basim O. , Majdi Hasan Sh , Hathal Mustafa M.
Published: April 2020

Fouling of oils on heat exchanger surfaces and pipelines is a common problem in a variety of industrial applications. This is because the oil deposits on the heat transfer surface causes an increase in pressure drop and a decrease in heat exchanger efficiency. In the current work, oil fouling in double pipe heat exchanger was investigated and mitigated using a surface‐active agent for the flow of a dispersion fluid containing different dispersed oil fractions in water. The effect of the dispersed oil fraction (5%vol and 10%vol) and temperature (35°C‐55°C) on the oil fouling rate was studied and discussed under turbulent flow conditions for both hot and cold fluids. Different amounts of alkylbenzene sulfonate as a surfactant were added to reduce the fouling rate under turbulent flow. It was found that the fouling thermal resistance (Rf) increases when the fluid temperature decreases. The higher the dispersed oil fraction, the higher the Rf for all temperatures due to higher oil deposition. Addition of 0.2%vol to 0.5%vol of alkylbenzene sulfonate caused an appreciable reduction in Rf depending on oil fraction and Reynolds number. The mitigation percent was higher for a lower Reynolds number, reaching up to 96%.
Thermal performance enhancement studies using graphite nanofluid for heat transfer applications
Authors: Jyothi Sankar P.R. , Venkatachalapathy S. , Asirvatham Lazarus G.
Published: April 2020

Enhanced boiling heat transfer using nanofluids is highly relevant due to its potential applications in thermal management of systems producing large heat fluxes. However, the sedimentation of nanoparticles limits their application in heat transfer systems. So, the preparation of a stable nanofluid remains a big research challenge. The stability issues arise due to the large difference in the density of nanoparticle and the base fluid. Graphite nanoparticle is selected in this study, as it has 4.5 times lower density than copper and comparable thermal conductivity. An experimental study is conducted to evaluate the suitability of graphite nanofluid in mesh wick heat pipes, which are devices that utilize boiling and condensation principles to transfer high heat fluxes. Thermal transport properties and boiling heat transfer characteristics showed enhancement and the effect of nanofluid on the device level thermal performance is thoroughly assessed. Experimental results are compared with the published literature. A reduction in thermal resistance by 32.5% and an improvement in the heat transfer coefficient by 48.02% in comparison with base fluid clearly indicate the superiority of the graphite nanofluid for heat transfer applications.
Two‐phase natural convection analysis and hybrid nanoparticle migration around micromixer blades
Authors: Hatami Mohammad , Uddin Md. Jashim , Hu Meibing , Jing Dengwei , Javed Maryiam
Published: April 2020

In this paper, numerical investigations are presented for hybrid nanoparticle migration and free convection heat transfer of two kinds of nanofluids in a micromixer at the fixed propeller condition. The inner blades and outer crust of the micromixer are kept at constant hot and cold temperatures, respectively. Two kinds of hybrid nanofluids, TiO2‐CuO water and ethylene glycol‐(MoS2‐SiO2), are considered. The governing equations including velocity, pressure, temperature formulation, and nanoparticle concentrations are solved by a partial differential equation solver based on the Galerkin finite element method. The results are discussed based on the governing parameters, such as nanoparticle volume fraction, thermal and solutal Rayleigh numbers. The average Nusselt number was found to increase with the increasing nanoparticle volume fractions. Also, increasing the thermal Rayleigh number enhanced heat transfer while the solutal Rayleigh number has an insignificant effect on it. More importantly, increasing the thermal Rayleigh number assisted avoiding the agglomeration of nanoparticles around the blades and ensured more uniform nanoparticle distribution.
A Systems Engineering Approach for Artificial Intelligence: Inspired by the VLSI Revolution of Mead & Conway
Authors: Wade Jon , Buenfil Jorge , Collopy Paul
Published: April 2020

Artificial intelligence is at a tipping point where the technical capabilities it enables are outstripping systems engineers’ ability to employ it in viable systems. This paper reviews the very large scale integration (VLSI) revolution enabled by Mead and Conway in the late 1970's and the lessons learned from this experience. It applies these principles to engineering artificial intelligence (AI) centric systems and formulates approaches to systems engineering and education to successfully meet this critical challenge.
Validation Testing of Autonomous Learning Systems
Authors: Collopy Paul , Sitterle Valerie , Petrillo Jennifer
Published: April 2020

Validating artificial intelligence systems is challenging. Systems continuing to learn new behaviors in the field are particularly difficult, because the designer does not know what the functions need proving. This article reports on a research project using the Toulmin augmentation method to structure validation test plans and validation testing for very difficult systems like field‐learning AI.
Mutational landscape of receptor guanylyl cyclase C: Functional analysis and disease‐related mutations
Authors: Bose Avipsa , Banerjee Sanghita , Visweswariah Sandhya S.
Published: April 2020

Guanylyl cyclase C (GC‐C) is the receptor for the heat‐stable enterotoxin, which causes diarrhea, and the endogenous ligands, guanylin and uroguanylin. GC‐C is predominantly expressed in the intestinal epithelium and regulates fluid and ion secretion in the gut. The receptor has a complex domain organization, and in the absence of structural information, mutational analysis provides clues to mechanisms of regulation of this protein. Here, we review the mutational landscape of this receptor that reveals regulatory features critical for its activity. We also summarize the available information on mutations in GC‐C that have been reported in humans and contribute to severe gastrointestinal abnormalities. Since GC‐C is also expressed in extra‐intestinal tissues, it is likely that mutations thus far reported in humans may also affect other organ systems, warranting a close observation of these patients in future.
Habits of courage: Reconceptualizing risk in social movement organizing
Authors: Oyakawa Michelle , McKenna Elizabeth , Han Hahrie
Published: April 2020

We examine the types of risk that organizers seeking to build people‐based political power take and describe how organizers cultivate habits of courage in themselves and others to regularly confront these risks. While prior literature emphasizes the degree of risk (high vs. low), we identify and elaborate two qualitatively different types of risk: internal and external. Drawing on in‐depth interviews with 88 movement organizers in six states, we found that organizers operating in different issue domains and geographies all cultivated three practices to confront risk: (a) confronting painful experiences to overcome feelings of powerlessness, (b) mastering their own stories and vulnerabilities as a necessary precondition to recruiting others, and (c) holding themselves and others accountable to public commitments.
Reused poultry litter microbiome with competitive exclusion potential against Salmonella Heidelberg
Authors: Bucher Maite Ghazaleh , Zwirzitz Benjamin , Oladeinde Adelumola , Cook Kimberly , Plymel Caroline , Zock Gregory , Lakin Steven , Aggrey Samuel. E. , Ritz Casey , Looft Torey , Lipp Erin , Agga Getahun E. , Abdo Zaid , Sistani Karamat R.
Published: April 2020

The success of poultry litter reuse in U.S. poultry production can be attributed to the efficient treatment methods used by producers during downtimes (the time lapse between consecutive flocks, during which the broiler house is empty). During this period, reused litter may be decaked, tilled/windrowed, or treated with acid‐based amendments to reduce ammonia and bacteria levels. Competitive exclusion, pH, and temperature are proposed factors that influence the level of pathogens and the overall litter microbiome during downtimes. We previously reported on the bacterial genetic factors associated with the fitness of two strains of Salmonella enterica serovar Heidelberg (SH) incubated for 14 d in reused litter. Here, we investigated the physicochemical parameters and the microbiome of the litter correlating with SH abundance during this period. We used 16S ribosomal RNA gene sequencing to determine the litter microbiome and whole genome sequencing to characterize bacteria with competitive exclusion potential against SH. The β diversity of the litter microbiome was significantly affected by the duration of incubation, microcosm, and microcosm plus Heidelberg strain combinations. In addition, β diversity was significantly affected by litter parameters, including NH4, pH, moisture, water activity, and aluminum. The major phyla observed in the reused litter throughout the 14‐d incubation experiment were Firmicutes and Actinobacteria, although their abundance differed by microcosm and time. Amplicon‐specific variants homologous to the members of the genera Nocardiopsis and Lentibacillus and the family Bacillaceae_2 were found to significantly correlate with the abundance of Salmonella. A consortium of Bacillus subtilis strains isolated from the litter microcosms reduced the growth of SH in vitro.
Appointment reminders to increase uptake of HIV retesting by at‐risk individuals: a randomized controlled study in Thailand
Authors: Salvadori Nicolas , Adam Pierrick , Mary Jean‐Yves , Decker Luc , Sabin Lucie , Chevret Sylvie , Arunothong Surachet , Khamduang Woottichai , Luangsook Prapan , Suksa‐ardphasu Visitsak , Achalapong Jullapong , Rouzioux Christine , Sirirungsi Wasna , Ngo‐Giang‐Huong Nicole , Jourdain Gonzague
Published: April 2020

Introduction

Frequent HIV testing of at‐risk individuals is crucial to detect and treat infections early and prevent transmissions. We assessed the effect of reminders on HIV retesting uptake.

Methods

The study was conducted within a programme involving four facilities providing free‐of‐charge HIV, syphilis and hepatitis B and C testing and counselling in northern Thailand. Individuals found HIV negative and identified at risk by counsellors were invited to participate in a three‐arm, open‐label, randomized, controlled trial comparing: (a) “No Appointment & No Reminder” (control arm); (b) “No Appointment but Reminder”: short message service (SMS) sent 24 weeks after the enrolment visit to remind booking an appointment, and sent again one week later if no appointment was booked; and (c) “Appointment & Reminder”: appointment scheduled during the enrolment visit and SMS sent one week before appointment to ask for confirmation; if no response: single call made within one business day. The primary endpoint was a HIV retest within seven months after the enrolment visit. The cost of each reminder strategy was calculated as the sum of the following costs in United States dollars (USD): time spent by participants, counsellors and hotline staff; phone calls made; and SMS sent. The target sample size was 217 participants per arm (651 overall).

Results

Between April and November 2017, 651 participants were randomized. The proportion presenting for HIV retesting within seven months was 11.2% (24/215) in the control arm, versus 19.3% (42/218) in “No Appointment but Reminder” (p = 0.023) and 36.7% (80/218) in “Appointment & Reminder” (p < 0.001). Differences in proportions compared to the control arm were respectively +8.1% (95% CI: +1.4% to +14.8%) and +25.5% (+17.9% to +33.2%). The incremental cost‐effectiveness ratios of “No Appointment but Reminder” and “Appointment & Reminder” compared to the control arm were respectively USD 0.05 and USD 0.14 per participant for each 5% increase in HIV retesting uptake within seven months.

Conclusions

Scheduling an appointment and sending a reminder one week before was a simple, easy‐to‐implement and affordable intervention that significantly increased HIV retesting uptake in these at‐risk individuals. The personal phone call to clients probably contributed, and also improved service efficiency.
Scrib and Dlg1 polarity proteins regulate Ag presentation in human dendritic cells
Authors: Barreda Dante , Ramón-Luing Lucero A , Duran-Luis Olivia , Bobadilla Karen , Chacón-Salinas Rommel , Santos-Mendoza Teresa
Published: April 2020

We recently reported, for the first time, the expression and regulation of the PDZ polarity proteins Scrib and Dlg1 in human APCs, and also described the viral targeting of these proteins by NS1 of influenza A virus in human dendritic cells (DCs). Scrib plays an important role in reactive oxygen species (ROS) production in Mϕs and uropod formation and migration in T cells, while Dlg1 is important for T cell downstream activation after Ag recognition. Nevertheless, the functions of these proteins in human DCs remain unknown. Here, we knocked-down the expression of both Scrib and Dlg1 in human DCs and then evaluated the expression of co-stimulatory molecules and cytokine production during maturation. We demonstrated that Scrib is necessary for adequate CD86 expression, while Dlg1 is important for CD83 up-regulation and IL-6 production upon maturation, suggesting that Scrib and Dlg1 participate in separate pathways in DCs. Additionally, both proteins are required for adequate IL-12 production after maturation. Furthermore, we showed that the inefficient maturation of DCs induced by Scrib or Dlg1 depletion leads to impaired T cell activation. Our results revealed the previously unknown contribution of Scrib and Dlg1 in human DCs pivotal functions, which may be able to impact innate and adaptive immune response.
Computer‐Aided Detection AI Reduces Interreader Variability in Grading Hip Abnormalities With MRI
Authors: Tibrewala Radhika , Ozhinsky Eugene , Shah Rutwik , Flament Io , Crossley Kay , Srinivasan Ramya , Souza Richard , Link Thomas M. , Pedoia Valentina , Majumdar Sharmila
Published: April 2020

Background

Accurate interpretation of hip MRI is time‐intensive and difficult, prone to inter‐ and intrareviewer variability, and lacks a universally accepted grading scale to evaluate morphological abnormalities.

Purpose

To 1) develop and evaluate a deep‐learning‐based model for binary classification of hip osteoarthritis (OA) morphological abnormalities on MR images, and 2) develop an artificial intelligence (AI)‐based assist tool to find if using the model predictions improves interreader agreement in hip grading.

Study Type

Retrospective study aimed to evaluate a technical development.

Population

A total of 764 MRI volumes (364 patients) obtained from two studies (242 patients from LASEM [FORCe] and 122 patients from UCSF), split into a 65–25–10% train, validation, test set for network training.

Field Strength/Sequence

3T MRI, 2D T2 FSE, PD SPAIR.

Assessment

Automatic binary classification of cartilage lesions, bone marrow edema‐like lesions, and subchondral cyst‐like lesions using the MRNet, interreader agreement before and after using network predictions.

Statistical Tests

Receiver operating characteristic (ROC) curve, area under curve (AUC), specificity and sensitivity, and balanced accuracy.

Results

For cartilage lesions, bone marrow edema‐like lesions and subchondral cyst‐like lesions the AUCs were: 0.80 (95% confidence interval [CI] 0.65, 0.95), 0.84 (95% CI 0.67, 1.00), and 0.77 (95% CI 0.66, 0.85), respectively. The sensitivity and specificity of the radiologist for binary classification were: 0.79 (95% CI 0.65, 0.93) and 0.80 (95% CI 0.59, 1.02), 0.40 (95% CI –0.02, 0.83) and 0.72 (95% CI 0.59, 0.86), 0.75 (95% CI 0.45, 1.05) and 0.88 (95% CI 0.77, 0.98). The interreader balanced accuracy increased from 53%, 71% and 56% to 60%, 73% and 68% after using the network predictions and saliency maps.

Data Conclusion

We have shown that a deep‐learning approach achieved high performance in clinical classification tasks on hip MR images, and that using the predictions from the deep‐learning model improved the interreader agreement in all pathologies.

Level of Evidence

3

Technical Efficacy Stage

1 J. Magn. Reson. Imaging 2020;52:1163–1172.
Hyperglycemia, hydroxychloroquine, and the COVID‐19 pandemic
Authors: Brufsky Adam
Published: April 2020

Coronavirus disease‐2019 (COVID‐19) infection and its severity can be explained by the concentration of glycosylated severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) viral particles in the lung epithelium, the concentration of glycosylated angiotensin‐converting enzyme receptor 2 (ACE2) in the lung epithelium, and the degree and control of the pulmonary immune response to the SARS‐CoV‐2 spike protein at approximately day 8 to 10 after symptom onset, which may be related to both. Binding of ACE2 by SARS‐CoV‐2 in COVID‐19 also suggests that prolonged uncontrolled hyperglycemia, and not just a history of diabetes mellitus, may be important in the pathogenesis of the disease. It is tempting to consider that the same mechanism acts in COVID‐19 as in SARS, where an overactive macrophage M1 inflammatory response, as neutralizing antibodies to the SARS‐CoV‐2 spike protein form at day 7 to 10, results in acute respiratory distress syndrome (ARDS) in susceptible patients. It also allows consideration of agents, such as hydroxychloroquine, which may interfere with this overly brisk macrophage inflammatory response and perhaps influence the course of the disease, in particular, those that blunt but do not completely abrogate the M1 to M2 balance in macrophage polarization, as well as viral load, which in SARS appears to be temporally related to the onset of ARDS.
Clinical factors related to successful or unsuccessful cardioversion in the EdoxabaN versus warfarin in subjectS UndeRgoing cardiovErsion of Atrial Fibrillation (ENSURE‐AF) randomized trial
Authors: Lip Gregory Y. H. , Merino Jose L. , Banach Maciej , Al‐Saady Naab , Jin James , Melino Michael , Winters Shannon M. , Kozieł Monika , Goette Andreas
Published: April 2020

Background

EdoxabaN versus warfarin in subjectS UndeRgoing cardiovErsion of Atrial Fibrillation evaluated use of nonvitamin K antagonist oral anticoagulant edoxaban vs enoxaparin‐warfarin in patients with nonvalvular atrial fibrillation undergoing electrical cardioversion.

Hypothesis

To assess clinical factors related to successful or unsuccessful cardioversion. To evaluate whether differences in adverse events based on anticoagulation strategy may exist.

Methods

In this multicenter prospective randomized open‐label blinded end‐point evaluation trial, 2199 patients were randomized to edoxaban 60 mg once daily (30 mg for creatinine clearance 15‐50 mL/min, weight ≤ 60 kg, and/or concomitant use of P‐glycoprotein inhibitor) or enoxaparin‐warfarin. Successful cardioversion was confirmed by 12‐lead electrocardiography‐documented sinus rhythm.

Results

Cardioversion was successful in 1578 patients; in 355 patients, cardioversion was unsuccessful. Male, high body weight, high body mass index (BMI), coronary artery disease, concomitant aspirin, or prior statins use were more common in patients with unsuccessful cardioversion; international normalized ratio control did not differ by cardioversion success. On multivariate analysis, gender (P < .05), body weight (P = .0196) and BMI (P = .0377) emerged as independent predictors of successful cardioversion. There were no significant differences in primary efficacy (a composite of stroke, systemic embolic event, myocardial infarction, and cardiovascular death during overall study period) regardless of cardioversion success. There were no significant differences in bleeding rates, regardless of cardioversion outcome; notwithstanding low numbers, edoxaban and enoxaparin‐warfarin did not differ.

Conclusions

Male gender, higher mean weight and higher mean BMI were associated with unsuccessful cardioversion. Efficacy and safety outcomes were low and did not differ by cardioversion success.
Self‐Compassion, Trait Resilience, and Trauma Exposure in Undergraduate Students
Authors: Shebuski Karen , Bowie Jhodi‐Ann , Ashby Jeffrey S.
Published: April 2020

The authors investigated the relationship between self‐compassion and trait resilience and tested the potential moderating roles of these variables in the relationship between trauma exposure and general psychological distress in a sample of undergraduate students (N = 296). Results revealed a significant relationship between self‐compassion and trait resilience. Self‐compassion emerged as a significant moderator in this relationship, whereas trait resilience did not. Given high rates of trauma exposure in college student populations, implications for counseling are discussed.
College Counselors' Perceptions of Working With First‐Year Students With Chronic Illnesses
Authors: Davis Eric S. , Paro Carly
Published: April 2020

Despite increased interest in college students' success, there has been little research regarding students entering college with chronic illnesses such as asthma, diabetes, and cancer. This qualitative study examined 15 college counselors' perceptions of working with first‐year students with chronic illnesses. Four themes emerged from the findings: counseling preparation, interactions, counseling interventions, and needs of students. The authors discuss implications for college counseling training and practice and directions for future research.
Compositional magnetic resonance imaging in the evaluation of the intervertebral disc: Axial vs sagittal T2 mapping
Authors: Raudner Marcus , Schreiner Markus M. , Weber Michael , Juras Vladimir , Stelzeneder David , Windhager Reinhard , Trattnig Siegfried
Published: April 2020

The aim of this study was to assess T2 values of the lumbar intervertebral discs in the axial and sagittal plane views and assess their respective interobserver reliability. The lumbar intervertebral discs of 23 symptomatic patients (11 female; 12 male; mean age, 44.1 ± 10.6; range, 24‐64 years) were examined at 3T. Region‐of‐interest (ROI) analysis was performed on axial and sagittal T2 maps by two independent observers. Intraclass correlation coefficient (ICC) was assessed for every ROI. The interobserver agreement was excellent for the nucleus pulposus (NP) in the sagittal (0.951; 95% confidence interval [CI], 0.926‐0.968) and axial (0.921; 95% CI, 0.845‐0.955) planes. The posterior 20% region showed a higher ICC in the axial vs the sagittal assessment (0.845; 95% CI, 0.704‐0.911 vs 0.819; 95% CI, 0.744‐0.873). The same was true for the posterior 10%, with the axial ROI showing a higher ICC (0.923; 95% CI, 0.865‐0.953 vs 0.628; 95% CI, 0.495‐0.732). The intraobserver agreement was excellent for every ROI except the sagittal 10% region, which showed good performance (0.869; 95% CI, 0.813‐0.909). The sagittal nucleus pulposus was the best‐performing ROI with regard to intra‐ and interobserver agreement in the T2 assessment of the lumbar intervertebral disc. However, the axial NP showed more stable agreements overall and across the value range. In addition, the annular analysis showed better inter‐ and intraobserver agreement in the axial plane view. Clinical significance: Based on the presented analysis, we highly recommend that further studies use axial T2 mapping due to the higher intra‐ and interreader agreement.
Comparison of Ultrasound‐Derived Muscle Thickness With Computed Tomography Muscle Cross‐Sectional Area on Admission to the Intensive Care Unit: A Pilot Cross‐Sectional Study
Authors: Lambell Kate J. , Tierney Audrey C. , Wang Jessica C. , Nanjayya Vinodh , Forsyth Adrienne , Goh Gerard S. , Vicendese Don , Ridley Emma J. , Parry Selina M. , Mourtzakis Marina , King Susannah J.
Published: April 2020

Introduction

The development of bedside methods to assess muscularity is an essential critical care nutrition research priority. We aimed to compare ultrasound‐derived muscle thickness at 5 landmarks with computed tomography (CT) muscle area at intensive care unit (ICU) admission. Secondary aims were to (1) combine muscle thicknesses and baseline covariates to evaluate correlation with CT muscle area and (2) assess the ability of the best‐performing ultrasound model to identify patients with low CT muscle area.

Methods

Adult patients who underwent CT scanning at the third lumbar area <72 hours after ICU admission were prospectively recruited. Muscle thickness was measured at mid‐upper arm, forearm, abdomen, and thighs. Low CT muscle area was determined using published cutoffs. Pearson correlation compared ultrasound‐derived muscle thickness and CT muscle area. Linear regression was used to develop ultrasound prediction models. Bland‐Altman analyses compared ultrasound‐predicted and CT‐measured muscle area.

Results

Fifty ICU patients were enrolled, aged 52 ± 20 years. Ultrasound‐derived muscle thickness at each landmark correlated with CT muscle area (P < .001). The sum of muscle thickness at mid‐upper arm and bilateral thighs, including age, sex, and the Charlson Comorbidity Index, improved the correlation with CT muscle area (r = 0.85; P < .001). Mean difference between ultrasound‐predicted and CT‐measured muscle area was −2 cm2 (95% limits of agreement, −40 cm2 to +36 cm2). The best‐performing ultrasound model demonstrated good ability to identify 14 patients with low CT muscle area (area under curve = 0.79).

Conclusion

Ultrasound shows potential for assessing muscularity at ICU admission (Clinicaltrials.gov NCT03019913).