bluuebunny/crossref_metadata_2025 huggingface dataset:
Occupational exposures and risk of nasopharyngeal carcinoma in a high‐risk area: A population‐based case‐control study
Authors: Chen Yufeng , Chang Ellen T. , Liu Qing , Cai Yonglin , Zhang Zhe , Chen Guomin , Huang Qi‐Hong , Xie Shang‐Hang , Cao Su‐Mei , Jia Wei‐Hua , Zheng Yuming , Li Yancheng , Lin Longde , Ernberg Ingemar , Wang Dongming , Chen Weihong , Feng Ruimei , Huang Guangwu , Zeng Yi‐Xin , Adami Hans‐Olov , Ye Weimin
Published: April 2021

BACKGROUND

The potential role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high‐incidence areas.

METHODS

The authors conducted a population‐based case‐control study, consisting of 2514 incident NPC cases and 2586 randomly selected population controls, in southern China from 2010 to 2014. Occupational history and other covariates were self‐reported using a questionnaire. Multivariate logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with occupational exposures. Restricted cubic splines were used to evaluate potentially nonlinear duration‐response relations.

RESULTS

Individuals who had exposure to occupational dusts (OR, 1.45; 95% CI, 1.26‐1.68), chemical vapors (OR, 1.37; 95% CI, 1.17‐1.61), exhausts/smokes (OR, 1.42; 95% CI, 1.25‐1.60), or acids/alkalis (OR, 1.56; 95% CI, 1.30‐1.89) in the workplace had an increased NPC risk compared with those who were unexposed. Risk estimates for all 4 categories of occupational exposures appeared to linearly increase with increasing duration. Within these categories, occupational exposure to 14 subtypes of agents conferred significantly higher risks of NPC, with ORs ranging from 1.30 to 2.29, including dust from metals, textiles, cement, or coal; vapor from formaldehyde, organic solvents, or dyes; exhaust or smoke from diesel, firewood, asphalt/tar, vehicles, or welding; and sulfuric acid, hydrochloric acid, nitric acid, and concentrated alkali/ammonia.

CONCLUSIONS

Occupational exposures to dusts, chemical vapors, exhausts/smokes, or acids/alkalis are associated with an excess risk of NPC. If the current results are causal, then the amelioration of workplace conditions might alleviate the burden of NPC in endemic areas.

LAY SUMMARY

The role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high‐incidence areas.

The authors conducted a population‐based study with 2514 incident NPC cases and 2586 population controls in southern China and observed that occupational exposures were associated with an increased risk of NPC.

Duration‐response trends were observed with increasing duration of exposure.

These findings provide new evidence supporting an etiologic role of occupational exposures for NPC in a high‐incidence region.
Textile pattern recommendations with convolutional neural networks and autoencoder
Authors: Mao Kuang , Wu Sai , He Jiajia , Huang Haichao , Yin Yanlong , Ren Zujie
Published: April 2021

Textile pattern design is a time‐consuming and tedious work. Mihui, our ongoing developing system, employs deep‐learning techniques to automatically generate huge volumes of patterns with the help of human guidance. However, trained as a black box, Mihui cannot provide customized service for each individual designer who shows unique aesthetics preferences. In this article, we introduce the recommendation module of Mihui. The module forwards all generated pattern images to a deep encoding network, where images are mapped into 128‐dimension vectors. For each user of Mihui, we create a profile by his/her purchased or downloaded history. A novel encoder network is proposed to learn a personal taste vector for each user, based on which, we recommend new patterns to him/her. Our records in Mihui show that the recommendation module effectively improve users' experience on Mihui.
Self‐training with one‐shot stepwise learning method for person re‐identification
Authors: Xia Daoxun , Liu Haojie , Xu Lili , Li Jiawen , Wang Linna
Published: April 2021

Person re‐identification (Re‐ID) aims at identifying the same person across multiple non‐overlapping camera views. A number of existing methods have been presented for this task in a fully‐supervised manner that requires a large amount of training annotations. However, obtaining high quality labels is extremely time consuming and expensive. In this article, we focus on the semi‐supervised person Re‐ID and propose a one‐shot stepwise learning method to address the above issue. It exploits only one labeled data along with additional unlabeled samples to gradually but steadily improving the discriminative capability of the feature representation. Specifically, we first construct labeled data portion to train Re‐ID model. Then we fine‐tune the overall system by the following two steps iteratively: (1) assigning the estimated labels to the unlabeled portion; (2) updating the network parameters according to the selected data. During the propagation process, different from conventional sampling method, we propose a novel dynamic sampling strategy to enlarge the pseudo‐labeled subset step by step to make the pseudo labels more reliable. On Market‐1501, DukeMTMC‐ReID and MARS datasets, we conducted extensively experiments to demonstrate that our proposed method contributes indispensably and achieves a very competitive Re‐ID performance.
Considering sampling bias in close‐kin mark–recapture abundance estimates of Atlantic salmon
Authors: Wacker Sebastian , Skaug Hans J. , Forseth Torbjørn , Solem Øyvind , Ulvan Eva M. , Fiske Peder , Karlsson Sten
Published: April 2021

Genetic methods for the estimation of population size can be powerful alternatives to conventional methods. Close‐kin mark–recapture (CKMR) is based on the principles of conventional mark–recapture, but instead of being physically marked, individuals are marked through their close kin. The aim of this study was to evaluate the potential of CKMR for the estimation of spawner abundance in Atlantic salmon and how age, sex, spatial, and temporal sampling bias may affect CKMR estimates. Spawner abundance in a wild population was estimated from genetic samples of adults returning in 2018 and of their potential offspring collected in 2019. Adult samples were obtained in two ways. First, adults were sampled and released alive in the breeding habitat during spawning surveys. Second, genetic samples were collected from out‐migrating smolts PIT‐tagged in 2017 and registered when returning as adults in 2018. CKMR estimates based on adult samples collected during spawning surveys were somewhat higher than conventional counts. Uncertainty was small (CV < 0.15), due to the detection of a high number of parent–offspring pairs. Sampling of adults was age‐ and size‐biased and correction for those biases resulted in moderate changes in the CKMR estimate. Juvenile dispersal was limited, but spatially balanced sampling of adults rendered CKMR estimates robust to spatially biased sampling of juveniles. CKMR estimates based on returning PIT‐tagged adults were approximately twice as high as estimates based on samples collected during spawning surveys. We suggest that estimates based on PIT‐tagged fish reflect the total abundance of adults entering the river, while estimates based on samples collected during spawning surveys reflect the abundance of adults present in the breeding habitat at the time of spawning. Our study showed that CKMR can be used to estimate spawner abundance in Atlantic salmon, with a moderate sampling effort, but a carefully designed sampling regime is required.
A novel data mining application to detect safety signals for newly approved medications in routine care of patients with diabetes
Authors: Fralick Michael , Kulldorff Martin , Redelmeier Donald , Wang Shirley V. , Vine Seanna , Schneeweiss Sebastian , Patorno Elisabetta
Published: April 2021

Background

Clinical trials are often underpowered to detect serious but rare adverse events of a new medication. We applied a novel data mining tool to detect potential adverse events of canagliflozin, the first sodium glucose co‐transporter 2 (SGLT2 inhibitor) in the United States, using real‐world data from shortly after its market entry and before public awareness of its potential safety concerns.

Methods

In a U. S. commercial claims dataset (29 March 2013–30 Sept 2015), two pairwise cohorts of patients over 18 years of age with type 2 diabetes (T2D) who were newly dispensed canagliflozin or an active comparator, that is a dipeptidyl peptidase 4 inhibitor (DPP4) or a glucagon‐like peptide 1 receptor agonist (GLP1), were identified and propensity score‐matched. We used variable ratio matching with up to four people receiving a DPP4 or GLP1 for each person receiving canagliflozin. We identified potential safety signals using a hierarchical tree‐based scan statistic data mining method with the hierarchical outcome tree constructed based on international classification of disease coding. We screened for incident adverse events where there were more outcomes observed among canagliflozin vs. comparator initiators than expected by chance, after adjusting for multiple testing.

Results

We identified two pairwise propensity score variable ratio matched cohorts of 44,733 canagliflozin vs. 99,458 DPP4 initiators, and 55,974 canagliflozin vs. 74,727 GLP1 initiators. When we screened inpatient and emergency room diagnoses, diabetic ketoacidosis was the only severe adverse event associated with canagliflozin initiation with p < .05 in both cohorts. When outpatient diagnoses were also considered, signals for female and male genital infections emerged in both cohorts (p < .05).

Conclusions and relevance

In a large population‐based study, we identified known but no other adverse events associated with canagliflozin, providing reassurance on its safety among adult patients with T2D and suggesting the tree‐based scan statistic method is a useful post‐marketing safety monitoring tool for newly approved medications.
PHANE‐TetraPHOS, the First D2 Symmetric Chiral Tetraphosphane. Synthesis, Metal Complexation, and Application in Homogeneous Stereoselective Hydrogenation
Authors: Vaghi Luca , Cirilli Roberto , Pierini Marco , Rizzo Simona , Terraneo Giancarlo , Benincori Tiziana
Published: April 2021

PHANE‐TetraPHOS, a new D2 symmetric tetraphosphane based on the [2.2]paracyclophane scaffold, has been synthesized and characterized. The peculiarity of this system is the presence of four homotopic diphenylphosphane groups, exchangeable through C2 symmetry operations and consequently indistinguishable. Their spatial arrangement allows the simultaneous complexation of two metal atoms. Enantiomeric purity was attained at tetra‐phosphane oxide level by fractional crystallization of the diastereomeric adducts obtained from the racemate with enantiopure dibenzoyltartaric acids. Alkaline treatment of diastereomerically pure adducts followed by exhaustive P−O groups reduction with HSiCl3 gave both PHANE‐TetraPHOS antipodes in an enantiopure state. They were tested as rhodium ligands in the homogeneous enantioselective hydrogenation of some benchmark unsaturated compounds. Catalytic activity and enantiodiscrimination ability were found comparable to those exhibited by the complexes of the parent bidentate ligand PHANEPHOS, but only half a mole of precious chiral ligand was employed.
The Pseudotransannular Ring Opening of 1‐Aminocyclohept‐4‐ene‐derived Epoxides in the Synthesis of Tropane Alkaloids: Total Synthesis of (±)‐Ferrugine
Authors: Rodriguez Sandra , Uria Uxue , Reyes Efraim , Prieto Liher , Rodríguez‐Rodríguez Marta , Tejero Tomás , Merino Pedro , Vicario Jose L.
Published: April 2021

We have optimized a synthetic approach to (±)‐Ferrugine in 8 steps starting from 5‐aminocyclohept‐1‐ene and using the Brønsted acid‐catalyzed pseudotransannular ring‐opening of the epoxide derived from this cycloheptene as the key step for the construction of the 8‐azabicyclo[3.2.1]octane central core. While attempting the enantioselective synthesis of this natural product from enantiopure 2‐hydroxy‐8‐azabicyclo[3.2.1]octane we have found that this compound shows a pronounced tendency to racemize via an achiral symmetric aziridinium intermediate. This racemization side process has been studied in detail using both experimental and computational methods.
Methoxy‐methylheptane as a cleaner fuel additive: An energy‐ and cost‐efficient enhancement for separation and purification units
Authors: Hussain Arif , Qyyum Muhammad Abdul , Minh Le Quang , Riaz Amjad , Haider Junaid , Naqvi Muhammad , Naqvi Salman Raza , Lee Moonyong
Published: April 2021

Environmental protection agencies have begun imposing stringent regulations on the existing refineries to control the levels of gasoline additives. In this context, a novel compound, 2‐methoxy‐2‐methylheptane (MMH), had drawn attention as fuel additive for cleaner combustion. The conventional process of MMH production features three distillation columns in a direct sequence. These columns are used to maintain the required product purities and to utilize the unreacted reactants through recycling streams. The distillation system of the existing MMH plant can afford significant energy savings, leading to a reduction in the total annual costs (TAC). The aim of this investigation is to demonstrate that the reported conventional process can be significantly enhanced by modifying the design and operational parameters and by replacing two distillation columns with an intensified dividing wall column (DWC) configuration. The DWC design is further optimized using several algorithms such as the modified coordinate method (MCD), robust particle swarm paradigm (PSP), and firefly (FF) with nonlinear constraints. Compared to conventional process, the optimized DWC resulted in 24% and 11.5% savings in the plant operating and total annual costs, respectively.
Multi‐agent spectrum access with sensing skipping based on reinforcement learning
Authors: Zeng Linghui , Zhang Jianzhao
Published: April 2021

The spectrum sharing among high‐density users in the dynamic spectrum environment of future mobile communication systems is analyzed in this article. First, the channel competitions of multiple users are modeled by multi‐player multi‐armed bandit. Then, a channel selection strategy based on the distributed reinforcement learning is proposed, with which the channel selection could be optimized online in accordance to the real‐time competition condition. Thus the collisions of channel access can be effectively reduced with relatively less cooperation overhead. Furthermore, a Bayesian estimation‐based spectrum sensing skipping scheme is designed, which avoids unnecessary spectrum sensing through predicting the idle time of channels. Simulation results demonstrate that the the spectrum sensing times can be reduced by at least 37% and the system throughput can be improved by 1.5 times compared to existing solutions.
Power control scheme for device‐to‐device communication using uplink channel in 5G mm‐Wave network
Authors: Sarma Subhra Sankha , Khuntia Pratap , Hazra Ranjay
Published: April 2021

Mm‐Wave communication ushers next‐gen communication to new heights guaranteeing higher speed and throughput. Enabling device‐to‐device (D2D) communication in next‐gen wireless communication is a Herculean task. This is due to introduction of pathloss attenuation by various environmental factors which deteriorates the signal. This article aims to minimize the effect of interference for quality reception of signals for D2D communication and increase system throughput. Thus, a power control scheme is proposed in underlay mode for uplink channel in mm‐Wave band. Here, D2D communication takes place through two modes namely, general mode and mm‐Wave mode. In presence of large number of proximity D2D users and increasing pathloss attenuation, it switches to mm‐Wave mode for communication. The formulated problem is converted to semiconvex form by expressing it into exponential form in Laplace domain. Our final objective is to maximize the energy efficiency (EE) of the proposed system under certain constraints. To reduce complexity of the problem, feasible regions of transmission power is introduced, that is, least and upper bounds which will ensure that power is maintained within a limit guaranteeing better throughput for D2D users. Enhanced EE and outage probability values also depict better performance of proposed system. Finally, fairness index (FI) shows that the proposed scheme yields better performance for the D2D users to communicate in the mm‐Wave band. A detailed comparison of FI for the proposed scheme is also done with other existing methods to prove the adequate performance of the proposed method. Simulation results also prove the efficacy of the proposed scheme.
A preliminary study on the effect of gender‐matched odours on the evaluation of emotional, cognitive and aesthetic characteristics of faces
Authors: Risso Paola , Maggioni Emanuela , Gallace Alberto
Published: April 2021

Facial attractiveness plays an important role in everyday social interactions. In the present study, we investigated whether people's evaluation of attractiveness can be modulated by odours. In Experiment 1, twelve participants rated a series of odours on several perceptual and synaesthetic characteristics (gender, pleasantness, cheerfulness, intensity, arousal and association with food), along visual analogue scales. In Experiment 2, the participants judged the attractiveness of female and male faces, while smelling an odour that was rated in Experiment 1 as more feminine (caramel), masculine (licorice) or when odourless water was presented. The results showed that the participants evaluated female faces as more attractive when the caramel odour was concurrently presented. By contrast, the participants evaluated the male faces as more attractive when the licorice odour was presented. These results highlight the importance of the synaesthetic associations between “gender” and odours on people's judgements of facial attractiveness.
Insertion of an SVA element in MSH2 as a novel cause of Lynch syndrome
Authors: Yang Ciyu , Li Yirong , Trottier Magan , Farrell Michael P. , Rai Vikas K. , E. Salo‐Mullen Erin , Gallagher David J. , Stadler Zsofia K. , van der Klift Heleen M. , Zhang Liying
Published: April 2021

Germline mutations in the DNA mismatch repair (MMR) genes cause Lynch syndrome (LS). In this study, we identified and characterized a novel SINE‐VNTR‐Alu (SVA) insertion in exon 12 of MSH2 in an individual with early‐onset colorectal cancer and a very strong LS family history. RT‐PCR analysis indicated a larger aberrant MSH2 transcript in one of the family members. MSK‐IMPACT next‐generation sequencing and long‐range PCR analyses revealed an insertion in MSH2 exon 12 at the c.1972 position in an antisense orientation. The insertion was further characterized as an SVA element approximately 3 kb in length, belonging to the SVA_F1 family of retrotransposons. This variant also segregated with LS related cancers in four affected family members in this family. Based on this evidence, this MSH2 SVA insertion is considered pathogenic.
Hierarchical syntactic processing is beyond mere associating: Functional magnetic resonance imaging evidence from a novel artificial grammar
Authors: Chen Luyao , Goucha Tomás , Männel Claudia , Friederici Angela D. , Zaccarella Emiliano
Published: April 2021

Grammar is central to any natural language. In the past decades, the artificial grammar of the AnBn type in which a pair of associated elements can be nested in the other pair was considered as a desirable model to mimic human language syntax without semantic interference. However, such a grammar relies on mere associating mechanisms, thus insufficient to reflect the hierarchical nature of human syntax. Here, we test how the brain imposes syntactic hierarchies according to the category relations on linearized sequences by designing a novel artificial “Hierarchical syntactic structure‐building Grammar” (HG), and compare this to the AnBn grammar as a “Nested associating Grammar” (NG) based on multilevel associations. Thirty‐six healthy German native speakers were randomly assigned to one of the two grammars. Both groups performed a grammaticality judgment task on auditorily presented word sequences generated by the corresponding grammar in the scanner after a successful explicit behavioral learning session. Compared to the NG group, we found that the HG group showed a (a) significantly higher involvement of Brodmann area (BA) 44 in Broca's area and the posterior superior temporal gyrus (pSTG); and (b) qualitatively distinct connectivity between the two regions. Thus, the present study demonstrates that the build‐up process of syntactic hierarchies on the basis of category relations critically relies on a distinctive left‐hemispheric syntactic network involving BA 44 and pSTG. This indicates that our novel artificial grammar can constitute a suitable experimental tool to investigate syntax‐specific processes in the human brain.
A rare variant in EZH2 is associated with prostate cancer risk
Authors: Raspin Kelsie , FitzGerald Liesel M. , Marthick James R. , Field Matt A. , Malley Roslyn C. , Banks Annette , Donovan Shaun , Thomson Russell J. , Foley Georgea R. , Stanford Janet L. , Dickinson Joanne L.
Published: April 2021

Prostate cancer (PrCa) is highly heritable, and although rare variants contribute significantly to PrCa risk, few have been identified to date. Herein, whole‐genome sequencing was performed in a large PrCa family featuring multiple affected relatives spanning several generations. A rare, predicted splice site EZH2 variant, rs78589034 (G > A), was identified as segregating with disease in all but two individuals in the family, one of whom was affected with lymphoma and bowel cancer and a female relative. This variant was significantly associated with disease risk in combined familial and sporadic PrCa datasets (n = 1551; odds ratio [OR] = 3.55, P = 1.20 × 10−5). Transcriptome analysis was performed on prostate tumour needle biopsies available for two rare variant carriers and two wild‐type cases. Although no allele‐dependent differences were detected in EZH2 transcripts, a distinct differential gene expression signature was observed when comparing prostate tissue from the rare variant carriers with the wild‐type samples. The gene expression signature comprised known downstream targets of EZH2 and included the top‐ranked genes, DUSP1, FOS, JUNB and EGR1, which were subsequently validated by qPCR. These data provide evidence that rs78589034 is associated with increased PrCa risk in Tasmanian men and further, that this variant may be associated with perturbed EZH2 function in prostate tissue. Disrupted EZH2 function is a driver of tumourigenesis in several cancers, including prostate, and is of significant interest as a therapeutic target.
Moderate mechanical stress suppresses the IL‐1β‐induced chondrocyte apoptosis by regulating mitochondrial dynamics
Authors: Zhang Jiaming , Hao Xiaoxia , Chi Ruimin , Qi Jun , Xu Tao
Published: April 2021

Mitochondrial dysfunction contributes to osteoarthritis (OA) onset and progress. Mitochondrial dynamics, coupled with mitophagy, is critical for the maintenance of mitochondrial fitness, involving many cellular processes, such as proliferation and apoptosis. Excessive mechanical stress induces chondrocyte apoptosis; however, the effects of mechanical stress on mitochondrial dynamics remain elusive. In this study, we performed fluorescence staining, flow cytometry, transmission electron microscope, Western blot analysis, and RNA‐sequencing to assess the effects of different strength of mechanical stimulation on mitochondrial functions of chondrocyte treated with interleukin‐1β (IL‐1β). We found that moderate mechanical stress reduced the IL‐1β‐induced apoptosis by maintaining mitochondrial function and scavenging the reactive oxygen species, while excessive mechanical stress induced strong mitochondrial dysfunction and apoptosis. Moreover, RNAsequencing revealed that mitophagy and mitochondrial dynamics were involved in the regulation of mechanical stress on chondrocyte biology. In addition to the elevated mitophagy, moderate mechanical stress also promoted mitochondrial dynamics by enhancing the expression of MFN1/2 and OPA1 and the translocation of dynamin‐related protein 1 from the cytoplasm to the mitochondria. However, an uncoupling of mitochondrial dynamics, characterized by strongly elevated fission, resulted in the unfavorable apoptosis of excessive mechanical stress‐stimulated chondrocytes. This study revealed the effects of mechanical stress upon mitochondrial dynamics in chondrocyte.
Characterization of extracellular vesicles and synthetic nanoparticles with four orthogonal single‐particle analysis platforms
Authors: Arab Tanina , Mallick Emily R. , Huang Yiyao , Dong Liang , Liao Zhaohao , Zhao Zezhou , Gololobova Olesia , Smith Barbara , Haughey Norman J. , Pienta Kenneth J. , Slusher Barbara S. , Tarwater Patrick M. , Tosar Juan Pablo , Zivkovic Angela M. , Vreeland Wyatt N. , Paulaitis Michael E. , Witwer Kenneth W.
Published: April 2021

We compared four orthogonal technologies for sizing, counting, and phenotyping of extracellular vesicles (EVs) and synthetic particles. The platforms were: single‐particle interferometric reflectance imaging sensing (SP‐IRIS) with fluorescence, nanoparticle tracking analysis (NTA) with fluorescence, microfluidic resistive pulse sensing (MRPS), and nanoflow cytometry measurement (NFCM). EVs from the human T lymphocyte line H9 (high CD81, low CD63) and the promonocytic line U937 (low CD81, high CD63) were separated from culture conditioned medium (CCM) by differential ultracentrifugation (dUC) or a combination of ultrafiltration (UF) and size exclusion chromatography (SEC) and characterized by transmission electron microscopy (TEM) and Western blot (WB). Mixtures of synthetic particles (silica and polystyrene spheres) with known sizes and/or concentrations were also tested. MRPS and NFCM returned similar particle counts, while NTA detected counts approximately one order of magnitude lower for EVs, but not for synthetic particles. SP‐IRIS events could not be used to estimate particle concentrations. For sizing, SP‐IRIS, MRPS, and NFCM returned similar size profiles, with smaller sizes predominating (per power law distribution), but with sensitivity typically dropping off below diameters of 60 nm. NTA detected a population of particles with a mode diameter greater than 100 nm. Additionally, SP‐IRIS, MRPS, and NFCM were able to identify at least three of four distinct size populations in a mixture of silica or polystyrene nanoparticles. Finally, for tetraspanin phenotyping, the SP‐IRIS platform in fluorescence mode was able to detect at least two markers on the same particle, while NFCM detected either CD81 or CD63. Based on the results of this study, we can draw conclusions about existing single‐particle analysis capabilities that may be useful for EV biomarker development and mechanistic studies.
hsa_circ_0001610 knockdown modulates miR‐646‐STAT3 axis to suppress endometrial carcinoma progression
Authors: Wang Bo , Lu Ye , Feng Eryan
Published: April 2021

Background

Endometrial carcinoma (EC) development is associated with dysregulated circular RNA profiles. The purpose of the current research is to study the role and mechanism of hsa_circ_0001610 (circ_0001610) in EC progression.

Methods

circ_0001610, microRNA (miR)‐646, and signal transducer and activator of transcription 3 (STAT3) expression levels were measured in EC. Functional analyses were performed using Cell Counting Kit‐8, colony formation, transwell, wound healing, flow cytometry, glycolysis, and xenograft analyses. Binding association was evaluated with dual‐luciferase reporter assay.

Results

circ_0001610 levels were upregulated in EC samples (n = 30) and cells. circ_0001610 interference restrained cell proliferation, migration, and invasion, and promoted apoptosis. circ_0001610 downregulation constrained glycolysis through reducing glucose consumption, lactate production, and levels of adenosine triphosphate, extracellular acidification, hexokinase 2, and lactate dehydrogenase A, and increasing oxygen consumption rate. miR‐646 is targeted by circ_0001610, and miR‐646 inhibition attenuated interference of circ_0001610‐mediated suppression of EC development. STAT3 was modulated by miR‐646, and miR‐646 upregulation restrained EC progression by decreasing STAT3. circ_0001610 silencing reduced STAT3 levels by sponging miR‐646 and reduced the growth of xenograft tumor established by EC cells.

Conclusion

circ_0001610 knockdown represses EC progression through modulating the miR‐646‐STAT3 axis.
The low excretor phenotype of glutaric acidemia type I is a source of false negative newborn screening results and challenging diagnoses
Authors: Guenzel Adam J. , Hall Patricia L. , Scott Anna I. , Lam Christina , Chang Irene J. , Thies Jenny , Ferreira Carlos R. , Pichurin Pavel , Laxen William , Raymond Kimiyo , Gavrilov Dimitar K. , Oglesbee Devin , Rinaldo Piero , Matern Dietrich , Tortorelli Silvia
Published: April 2021

Background

Glutaric acidemia type I (GA1) is an organic acidemia that is often unrecognized in the newborn period until patients suffer an acute encephalopathic crisis, which can be mistaken for nonaccidental trauma. Presymptomatic identification of GA1 patients is possible by newborn screening (NBS). However, the biochemical “low‐excretor” (LE) phenotype with nearly normal levels of disease metabolites can be overlooked, which may result in untreated disease and irreversible neurological sequelae. The LE phenotype is also a potential source of false negative (FN) NBS results that merits further investigation.

Methods

Samples from six LE GA1 patients were analyzed by biochemical and molecular methods and newborn screen outcomes were retrospectively investigated.

Results

Five LE GA1 patients were identified that had normal NBS results and three of these presented clinically with GA1 symptoms. One additional symptomatic patient was identified who did not undergo screening. Semiquantitative urine organic acid analysis was consistent with a GA1 diagnosis in two (33%) of the six patients, while plasma glutarylcarnitine was elevated in four (67%) of the six and urine glutarylcarnitine was elevated in four (80%) of five patients. Five GCDH variants were identified in these patients; three of which have not been previously linked to the biochemical LE phenotype.

Conclusions

The data presented here raise awareness of potential FN NBS results for LE GA1 patients. The LE phenotype is not protective against adverse clinical outcomes, and the possibility of FN NBS results calls for high vigilance amongst clinicians, even in the setting of a normal NBS result.
Chemical binding of pyrrolidinyl peptide nucleic acid (acpcPNA‐T9) probe with AuNPs toward label‐free monitoring of miRNA‐21: A novel biosensing platform for biomedical analysis and POC diagnostics
Authors: Fathi Nazanin , Saadati Arezoo , Hasanzadeh Mohammad , Samiei Mohammad
Published: April 2021

miRNAs are attractive factors in cancer research studies due to their important roles for regulating of gene expression. Because of miRNA‐21 expression surplus in many types of cancers, so accurate identification is important. Increasing efforts have caused different methods to improve the sensitivity and specificity of detection. Present study is an attempt to report a new electrochemical label‐free PNA‐based bioassay for detection of miRNA‐21. In this study, gold electrode was modified by gold nanoparticles to improve a functional PNA‐based biosensor. The EDS and field emission scanning electron microscope (FE‐SEM) were used to detect fabrication of biosensor. The electrochemical behavior of sensor was evaluated after inserting of acpcPNA probes and miRNA‐21 on the stucture of electrode and analyzed essential parameters such as various concentration of target miRNA, hybridization time, reproducibility, stability, and applicability. The results of study demonstrated that engineered biosensor was successfully fabricated. The findings showed the highest amount of current in 5 minutes hybridization time, with suitable reproducibility and stability. This innovative miRNA‐based biosensor presents a sensitive and specific method in fast and may be lab‐on chip assay in future.
Diagnostic Accuracy of Spiral Whole‐Heart Quantitative Adenosine Stress Cardiovascular Magnetic Resonance With Motion Compensated L1‐SPIRIT
Authors: Pan Jonathan A. , Robinson Austin A. , Yang Yang , Lozano Patricia Rodriguez , McHugh Stephen , Holland Eric M. , Meyer Craig H. , Taylor Angela M. , Kramer Christopher M. , Salerno Michael
Published: April 2021

Background

Variable density spiral (VDS) pulse sequences with motion compensated compressed sensing (MCCS) reconstruction allow for whole‐heart quantitative assessment of myocardial perfusion but are not clinically validated.

Purpose

Assess performance of whole‐heart VDS quantitative stress perfusion with MCCS to detect obstructive coronary artery disease (CAD).

Study Type

Prospective cross sectional.

Population

Twenty‐five patients with chest pain and known or suspected CAD and nine normal subjects.

Field strength/Sequence

Segmented steady‐state free precession (SSFP) sequence, segmented phase sensitive inversion recovery sequence for late gadolinium enhancement (LGE) imaging and VDS sequence at 1.5 T for rest and stress quantitative perfusion at eight short‐axis locations.

Assessment

Stenosis was defined as ≥50% by quantitative coronary angiography (QCA). Visual and quantitative analysis of MRI data was compared to QCA. Quantitative analysis assessed average myocardial perfusion reserve (MPR), average stress myocardial blood flow (MBF), and lowest stress MBF of two contiguous myocardial segments. Ischemic burden was measured visually and quantitatively.

Statistical Tests

Student's t‐test, McNemar's test, chi‐square statistic, linear mixed‐effects model, and area under receiver‐operating characteristic curve (ROC).

Results

Per‐patient visual analysis demonstrated a sensitivity of 84% (95% confidence interval [CI], 60%–97%) and specificity of 83% [95% CI, 36%–100%]. There was no significant difference between per‐vessel visual and quantitative analysis for sensitivity (69% [95% CI, 51%–84%] vs. 77% [95% CI, 60%–90%], P = 0.39) and specificity (88% [95% CI, 73%–96%] vs. 80% [95% CI, 64%–91%], P = 0.75). Per‐vessel quantitative analysis ROC showed no significant difference (P = 0.06) between average MPR (0.68 [95% CI, 0.56–0.81]), average stress MBF (0.74 [95% CI, 0.63–0.86]), and lowest stress MBF (0.79 [95% CI, 0.69–0.90]). Visual and quantitative ischemic burden measurements were comparable (P = 0.85).

Data Conclusion

Whole‐heart VDS stress perfusion demonstrated good diagnostic accuracy and ischemic burden evaluation. No significant difference was seen between visual and quantitative diagnostic performance and ischemic burden measurements.

Evidence Level

2

Technical Efficacy

Stage 2
Self‐Assembled Cathode Patterning in AMOLEDs
Authors: Wang Zhibin , Chang Yi‐lu , Wang Qi , Zhang Yingjie , Qiu Jacky , Helander Michael G.
Published: April 2021

A new approach based on self‐assembled patterning forms a metal cathode with micrometer‐ to millimeter‐scale features for active‐matrix organic light‐emitting diodes. Here, the authors focus on five applications made possible through this approach.
Future direction of addiction research—An expert questionnaire survey in Japan
Authors: Takahashi‐Omoe Hiromi , Ide Soichiro , Miyata Hisatsugu , Ikeda Kazutaka
Published: April 2021

Addiction has become a major worldwide medical, public health, and social problem. Because the prevalence of addiction varies widely geographically, due to differences in ethnicity, culture, education, social environment, and regulation, each country or region needs to understand its current state of addiction and to take appropriate measures, in multidisciplinary collaboration. In order to understand the direction of addiction research in Japan, we analyzed 50 research and development topics and their characteristics, based on an expert questionnaire survey. The topics were placed in five categories, as follows. Category 1: Basic science; all 10 topics were of the Long‐term project and International cooperation types. Category 2: Translational and clinical research; 6 out of 10 topics were of the Long‐term project. Category 3: Fact‐finding surveys; 8 out of 10 topics were of the Japan‐specific type. Category 4: Health system and service; 8 out of 10 topics were of the Japan‐specific type and Short‐term project. Category 5: Study on society, culture, environment, education, and regulation; 7 out of 10 topics were of the Short‐term project (similar to Category 4). As far as we know, this is the first systematic questionnaire survey on the direction of addiction research. The results of this study might support developing a strategy for addiction research, not only in Japan, but also in other countries.
Design of experiments‐based strategy for development and optimization of polylactide membranes preparation by wet inversion phase method
Authors: Gadomska‐Gajadhur Agnieszka , Kruk Aleksandra , Wierzchowski Kamil , Ruśkowski Paweł , Pilarek Maciej
Published: April 2021

Cells‐containing scaffolds made of biomaterial are modern hybrid constructs which allow regeneration or reconstruction of damaged connective tissue, e.g. cartilage or bone. The basic aim of the study was to recognize the impact of the scaffold production parameters (i.e. type of applied pore precursor, its concentration) on morphology and mechanical properties of polylactide (PLLA) membrane‐based constructs, as well as their biocompatibility exhibited as cellular response. Design of experiments (DoE) strategy has been applied to quantitatively recognize the effects of synthesis parameters on PLLA‐membrane properties. Two independent correlations have been introduced to provide the influence of the synthesis parameters on the pore size, as well as the Young's modulus identifying the surface properties of scaffolds. PLLA membrane‐based scaffolds characterized by average pore diameter exceeded 100 microns and average Young's modulus exceeded 10 MPa have been obtained. The evaluation of scaffolds biocompatibility has been performed due to comprehensive analysis of proliferation effects and metabolic activity of mouse L929 fibroblasts maintained on the surface of developed PLLA‐membranes. The Application of PVP as the pore precursor positively impacted on the surface properties of the constructs. The lack of cytotoxicity of the developed PLLA membranes has been detected.
A computational study of the Hofmann elimination pathway for Morita–Baylis–Hillman reaction under DABCO catalysis: Participation of a bridge‐head ylide
Authors: Yadav Veejendra K.
Published: April 2021

In comparison to the popular pathway involving proton transfer via a four‐membered transition state (TS) structure, the recently proposed overall lower energy pathway involving proton transfer via a seven‐centered TS structure followed by yet another proton transfer through a five‐membered TS structure in Hofmann elimination fashion for the Me3N‐catalyzed Morita–Baylis–Hillman reaction is equally applicable to the DABCO‐catalyzed reaction as well. This finding establishes that the bridge‐head ylide formed from the DABCO‐derived ammonium ion is surprisingly well tolerated. The activation energy of the rate‐limiting aldol step under DABCO catalysis is lower than Me3N catalysis, which suggests that DABCO is a likely better catalyst than Me3N to achieve faster conversion.
Effect of hepatic impairment on pharmacokinetics, safety, and tolerability of lemborexant
Authors: Dayal Satish , Aluri Jagadeesh , Hall Nancy , Filippov Gleb , Moline Margaret , Reyderman Larisa , Landry Ishani
Published: April 2021

Lemborexant, a dual orexin receptor antagonist, is approved in the United States, Japan, and Canada for the treatment of insomnia in adults. This phase I, multicenter, open‐label, parallel‐group study assessed the impact of mild or moderate hepatic impairment (HI) on lemborexant pharmacokinetics and metabolism. The pharmacokinetics, tolerability, and safety of lemborexant were evaluated in subjects with mild (Child–Pugh class A) or moderate (Child–Pugh class B) HI and healthy age‐, sex‐, and body mass index (BMI)‐matched control subjects (n = 8 subjects/group). Subjects received a single oral dose of lemborexant 10 mg (LEM10). Blood samples were collected up to 312 hours post dosing for lemborexant pharmacokinetics assessments. Median time to maximum plasma concentration was similar across all groups. Compared with healthy subjects, exposure measures (maximum plasma concentration [Cmax] and area under the curve extrapolated to infinity [AUC0‐inf]) increased by ~58% (Cmax) and ~25% (AUC0‐inf) in subjects with mild HI and ~22% (Cmax) and ~54% (AUC0‐inf) in subjects with moderate HI. Clearance decreased by 20% and 35% in subjects with mild and moderate HI, respectively, versus healthy subjects. Lemborexant unbound fraction was similar in all groups (range: 0.060–0.065). All treatment‐emergent adverse events (TEAEs) were mild in severity; no serious TEAEs occurred. In conclusion, following a single LEM10 dose, lemborexant exposure was similar in subjects with mild HI and increased in subjects with moderate HI versus healthy subjects. No dose adjustment is required in subjects with mild HI. Dosing in subjects with moderate HI should be restricted to 5 mg. Lemborexant was well tolerated in all groups.
East meets west: regional impact on agrochemical discovery and innovation
Authors: Sparks Thomas C , Bryant Robert J
Published: April 2021

The efficient production of the food needed to nourish an expanding global population continues to fuel the demand for new crop protection compounds. This task is made all the more difficult by the need to meet increasingly demanding grower, consumer and regulatory constraints. The discovery and development of new synthetic organic crop protection compounds has been largely the responsibility of the agrochemical industry in Europe, Japan and the USA, with government‐funded academic research often playing a crucial role in the early stages of the invention and testing of novel activity. The way in which this process takes place has undergone a dramatic evolution over the past 75 years. Drastic consolidation and globalization among the research and development (R&D)‐based companies in these regions have characterized these changes. This evolution in the agrochemical industry has, in turn, shaped the rate of introduction and geographic origin of new crop protection compounds. In spite of these changes, the rate of invention of new classes of crop protection compounds has remained relatively constant. During the past 30 years, the forefront of new compound introductions has moved towards Asia, and Japan in particular. Although there are now more agrochemical companies in Japan involved in the discovery and development of new crop protection compounds than in Europe and the USA combined, on a compound‐per‐company basis, US companies currently generate the highest output. However, it is expected that there will continue to be changes in the numbers and origins of new crop protection compounds, with contributions continuing from Europe, Japan and the USA, and increasingly from China. © 2021 Society of Chemical Industry.
Silibinin as potential tool against SARS‐Cov‐2: In silico spike receptor‐binding domain and main protease molecular docking analysis, and in vitro endothelial protective effects
Authors: Speciale Antonio , Muscarà Claudia , Molonia Maria Sofia , Cimino Francesco , Saija Antonella , Giofrè Salvatore Vincenzo
Published: April 2021

The spread of SARS‐CoV‐2, along with the lack of targeted medicaments, encouraged research of existing drugs for repurposing. The rapid response to SARS‐CoV‐2 infection comprises a complex interaction of cytokine storm, endothelial dysfunction, inflammation, and pathologic coagulation. Thus, active molecules targeting multiple steps in SARS‐CoV‐2 lifecycle are highly wanted. Herein we explored the in silico capability of silibinin from Silybum marianum to interact with the SARS‐CoV‐2 main target proteins, and the in vitro effects against cytokine‐induced‐inflammation and dysfunction in human umbilical vein endothelial cells (HUVECs). Computational analysis revealed that silibinin forms a stable complex with SARS‐CoV‐2 spike protein RBD, has good negative binding affinity with Mpro, and interacts with many residues on the active site of Mpro, thus supporting its potentiality in inhibiting viral entry and replication. Moreover, HUVECs pretreatment with silibinin reduced TNF‐α‐induced gene expression of the proinflammatory genes IL‐6 and MCP‐1, as well as of PAI‐1, a critical factor in coagulopathy and thrombosis, and of ET‐1, a peptide involved in hemostatic vasoconstriction. Then, due to endothelium antiinflammatory and anticoagulant properties of silibinin and its capability to interact with SARS‐CoV‐2 main target proteins demonstrated herein, silibinin could be a strong candidate for COVID‐19 management from a multitarget perspective.
Active cellulose acetate‐carvacrol films: Antibacterial, physical and thermal properties
Authors: Laroque Denise Adamoli , de Aragão Glaucia Maria Falcão , de Araújo Pedro Henrique Hermes , Carciofi Bruno Augusto Mattar
Published: April 2021

Cellulose acetate (CA) is a low cost, biodegradable polymer obtained from renewable resources. The development of CA active films to reduce or inhibit microbial growth in food could increase food products' shelf‐life while decreasing the use of petroleum‐based non‐biodegradable polymers on food packaging. In this work, CA films containing carvacrol, a major antimicrobial compound in oregano essential oil, were obtained by solvent‐casting and extensively characterised. Results showed that carvacrol in concentrations up to 10 wt.% was homogeneously distributed on transparent and continuous films. Carvacrol had little effect on water barrier properties, elongation, and stiffness while decreasing the melting and glass transition temperatures of the CA films. The sustained release of carvacrol to the vapour phase was observed over 10 weeks. Films with 10 wt.% of carvacrol were bactericidal against Weissella viridescens and Pseudomonas fluorescens and extended in 2.8 times the shelf‐life for the vacuum‐packaged ham. The physical and antibacterial properties demonstrated the feasibility of CA films containing carvacrol for active packaging and food shelf life extension.
Sensitivity of some African heavy rainfall events to microphysics and planetary boundary layer schemes: Impacts on localised storms
Authors: Meroni Agostino N. , Oundo Kizito A. , Muita Richard , Bopape Mary‐Jane , Maisha Thizwilondi R. , Lagasio Martina , Parodi Antonio , Venuti Giovanna
Published: April 2021

High‐resolution numerical weather prediction (NWP) simulations of heavy rainfall events are known to be strongly sensitive to the choice of the sub‐grid scale parameterisation schemes. In the African continent, studies on such a choice at the convective‐resolving scales are not numerous. By exploiting a state‐of‐the‐art NWP model, the Weather Research and Forecasting (WRF) model, the sensitivity of the simulation of three heavy rainfall events in Sub‐Saharan Africa to the microphysical (MP) and planetary boundary layer (PBL) schemes is studied. Validating the numerical outputs against rainfall satellite estimates, ground‐based weather stations, radiosonde profiles and satellite‐derived cloud‐top temperature maps with an object‐based tool, the best‐performing setup is identified. In terms of heavy rainfall forecast location, it is found that the PBL scheme has a greater impact than the MP, which is shown to control the cloud‐top temperature simulation. Among the schemes considered, the best performances are achieved with a six‐class single‐moment microphysical scheme and a non‐local planetary boundary layer scheme which properly includes the vertical mixing by the large eddies in the atmosphere.