bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Affecting the Perception of New Approach Methodologies (NAMs) in the Ecotoxicology Community
Authors: Mondou Matthieu , Hickey Gordon M , Rahman HM Tuihedur , Maguire Steve , Pain Guillaume , Crump Doug , Hecker Markus , Basu Niladri
Published: January 2020

Given current legislative mandates to assess the safety of thousands of chemicals and the slow pace at which conventional testing proceeds, there is a need to accelerate chemical risk assessment. Governments and businesses are increasingly interested in new approach methodologies (NAMs) that promise to reduce costs and delays. We explore 5 sociological factors within the ecotoxicology community that can influence the perception of NAMs: 1) professional profile (educational cohort, employer), 2) internal science communication within professional forums, 3) concern for “error cost,” 4) collaboration across stakeholders, and 5) fundamental beliefs regarding toxicology. We conducted an online survey (n = 171; 2018) asking participants about their experiences and perspectives at events of the Society of Environmental Toxicology and Chemistry (SETAC) to assess 1) how NAMs are discussed compared to conventional testing and 2) how respondents perceive their viability. We developed ordered logistic regression (OLR) models to understand the influence of exploratory variables (cohort, core views on toxicology, frequency of collaboration) on respondents' evaluation of the viability of different NAMs. Our results showed that 1) NAMs were more likely than conventional methods to be challenged in forum discussions, which may be fueled by concerns for error costs in regulatory decision making; 2) perceptions of the viability of NAMs tended to follow a “pattern of familiarity,” whereby respondents that were more knowledgeable about a test method tended to find it more viable; 3) respondents who agreed with the Paracelsus maxim had a greater likelihood of finding conventional testing viable; and 4) the more a respondent reported collaborating with industry on alternative testing strategies, the more likely she or he was to report that NAMs were less viable. These results suggest that there are professional and organizational barriers to greater acceptance of NAMs that can be addressed through a social learning process within the professional community. Integr Environ Assess Manag 2020;16:269–281. © 2020 SETAC
Stabilization of Ni(I)(1,4,8,11‐tetraazacyclotetradecane)+ in a Sol‐Gel Matrix: It's Plausible Use in Catalytic Processes
Authors: Shamir Dror , Wolfer Yaniv , Shames Alexander I. , Albo Yael , Burg Ariela
Published: January 2020

Monovalent nickel is used as a catalyst in a diversity of important chemical systems due to its properties as a strong reducing agent. However, monovalent nickel is unstable in homogeneous systems; its lifetime is very short, and therefore, its efficiency as a catalyst is quite limited. In this article, we demonstrate the catalytic capabilities of Ni(I)(1,4,8,11‐tetraazacyclotetradecane)+ as a reducing and catalytic agent by its entrapment in the silica sol gel matrix. The EPR results indicate that the sol‐gel matrix plays two roles: it inhibits the common mechanism of Ni(I)L+ decomposition in aqueous solutions, and it also facilitates its functionality as a heterogeneous catalyst, by stabilizing it for at least several hours. The activity of Ni(I)L+ which is entrapped within the matrix, was studied by reducing 2,2‐Bis(bromomethyl)‐1,3‐Propanediol and I3−. The results indicate that Ni(I)L+/Ni(III)L−H2+ acts as a good reducing agent. These results have important implications for a variety of essential catalytic reactions by shedding light on a new feature of sol‐gel matrices and their use as active species stabilizers.
Comparative Adsorption of Tungsten and Silicon Oxides by Alumina Matrix
Authors: Holovenko V. O. , Kalinichenko O. O. , Roienko K. V. , Girin O. B. , Snizhko L. O.
Published: January 2020

The incorporation of tungsten oxides on the surface of the oxidized aluminum alloy was investigated. Deposition was carried out in two ways – during the process of plasma‐electrolytic oxidation (PEO) and by impregnation of the oxide in solutions of tungsten salts. The experimental program was performed using a central composite rotatable planning. It is established that the amount of tungsten oxides in coatings obtained by PEO in mixed silicate‐tungstate electrolyte is 50 times higher than in coatings received by PEO in silicate electrolyte with following soaking in WO42− containing solutions.
Future time perspective drives younger and older adults to continue investing in failing activities
Authors: Liu Xueping , Peng Huamao , Cai Xu
Published: January 2020

Inspired by socioemotional selectivity theory, we investigated age differences in further investment in failing situations by considering goal type and future time perspective. In Experiment 1, 32 younger and 30 older adults reported their likelihood of continued investing following an unsuccessful investment. Older adults were more willing to invest with emotional goals as opposed to knowledge and unspecified goals, while younger adults showed a greater willingness to invest with emotional and knowledge goals rather than unspecified goals. In Experiment 2, another sample of 32 younger and 34 older adults completed the same decision tasks as those in Experiment 1. After future time perspective restriction, the younger adults made decisions resembling Experiment 1's older adults, while after future time perspective expansion, the older adults behaved like Experiment 1's younger adults. These results indicate that future time perspective modification could reverse participants' goal prioritisation, manifesting in differential willingness to pursue further investment in decision scenarios with different goals. Our results represent important steps towards understanding the mechanism of older and younger adults' further investment in failing situations and illustrate that forging connections between the lifespan theory of motivation and further investment decision is critical for understanding adults' decision behaviours.
Cyto‐genotoxic and inflammatory effects of commercial Linde Type A (LTA) nanozeolites on human alveolar epithelial cells
Authors: Cavallo Delia , Ursini Cinzia Lucia , Fresegna Anna Maria , Ciervo Aureliano , Maiello Raffaele , Del Frate Valentina , Iavicoli Sergio
Published: January 2020

Nanozeolites (NZs) are increasingly used in several sectors, including catalysts, ion exchange materials or thermal isolators, taking advantage of the major property of NZs to absorb residual water and moisture to preserve the insulation of devices and products, but very few data are available on their toxicity. We investigated the potential cyto‐genotoxicity and pro‐inflammatory effects of manufactured Linde Type A (LTA)‐NZs on human alveolar cells (A549) exposed to 10, 25, 50 and 100 μg/mL. LTA NZs were characterized by dynamic light scattering (DLS). Cell viability, mortality and apoptosis were evaluated by cytofluorimetric assay after 24h exposure. Membrane damage was evaluated by lactate dehydrogenase release and direct and oxidative DNA damage induction by formamide‐pyrimidine glycosylase‐Comet assay after 4 and 24 h. The induction of pro‐inflammatory effects was evaluated in terms of interleukin 6 (IL‐6) and IL‐8 cytokine release after 24 h by ELISA. We found a slight increase in apoptotic cell percentage at 50 and 100 μg/mL and dead cell percentage at 100 μg/mL after 24 h; slight, but statistically significant, direct DNA damage starting from 25 μg/mL and slight oxidative DNA damage both at 4 and at 24 h; increased release of IL‐6 only at the lowest concentration after 24 h. The results show lack of cytotoxicity, early moderate genotoxicity and slight inflammatory effects at the lowest used concentration. These findings represent the first data on potential genotoxic, oxidative and inflammatory effects of LTA NZs and highlight the need to perform further studies to confirm such results.
Circular RNA SMARCA5 may serve as a tumor suppressor in non‐small cell lung cancer
Authors: Tong Suiju
Published: January 2020

Background

This study aimed to investigate the correlation of circular RNA SMARCA5 (circ‐SMARCA5) expression with clinicopathological characteristics and survival profiles, furthermore, to explore the function of circ‐SMARCA5 on regulating cell proliferation and chemotherapy sensitivity in non‐small cell lung cancer (NSCLC).

Methods

A total of 460 NSCLC patients were retrospectively reviewed, and circ‐SMARCA5 expressions in tumor tissue and adjacent tissue were detected by RT‐qPCR. Clinical characteristics were collected. Disease‐free survival (DFS) and overall survival (OS) were calculated. In vitro, circ‐SMARCA5 overexpression and control overexpression plasmids were transfected into NCI‐H1437 as well as NCI‐H1299 cells, which were further treated with different concentrations of cisplatin and gemcitabine.

Results

Circ‐SMARCA5 expression was decreased in tumor tissues compared to adjacent tissues. Moreover, circ‐SMARCA5 expression negatively correlated with tumor size, lymph node metastasis, and TNM stage, but positively correlated with DFS and OS. Subsequent analysis displayed that circ‐SMARCA5 high expression independently predicted prolonged DFS and OS. In vitro, circ‐SMARCA5 expression was reduced in NSCLC cell lines (NCI‐H650, NCI‐H1299, NCI‐H1437, and A549) compared to human normal lung bronchus epithelial cell line (BEAS‐2B). In NCI‐H1437 and NCI‐H1299 cells, cell proliferation was decreased by circ‐SMARCA5 overexpression, furthermore, chemosensitivity to cisplatin and gemcitabine were enhanced in circ‐SMARCA5 overexpression treated cells compared to the control cells.

Conclusion

Circ‐SMARCA5 may serve as a tumor suppressor in NSCLC, which provides insight to the exploration of novel strategies in NSCLC management.
The Shc protein Rai enhances T‐cell survival under hypoxia
Authors: Criscuoli Mattia , Ulivieri Cristina , Filippi Irene , Monaci Sara , Guerrini Giuditta , Crifò Bianca , De Tommaso Domiziana , Pelicci Giuliana , Baldari Cosima T. , Taylor Cormac T. , Carraro Fabio , Naldini Antonella
Published: January 2020

Hypoxia occurs in physiological and pathological conditions. T cells experience hypoxia in pathological and physiological conditions as well as in lymphoid organs. Indeed, hypoxia‐inducible factor 1α (HIF‐1α) affects T cell survival and functions. Rai, an Shc family protein member, exerts pro‐survival effects in hypoxic neuroblastoma cells. Since Rai is also expressed in T cells, we here investigated its role in hypoxic T cells. In this work, hypoxia differently affected cell survival, proapoptotic, and metabolic programs in T cells, depending upon Rai expression. By using Jurkat cells stably expressing Rai and splenocytes from Rai−/−mice, we demonstrated that Rai promotes T cell survival and affects cell metabolism under hypoxia. Upon exposure to hypoxia, Jurkat T cells expressing Rai show (a) higher HIF‐1α protein levels; (b) a decreased cell death and increased Akt/extracellular‐signal‐regulated kinase phosphorylation; (c) a decreased expression of proapoptotic markers, including caspase activities and poly(ADP‐ribose) polymerase cleavage; (d) an increased glucose and lactate metabolism; (e) an increased activation of nuclear factor‐kB pathway. The opposite effects were observed in hypoxic splenocytes from Rai−/−mice. Thus, Rai plays an important role in hypoxic signaling and may be relevant in the protection of T cells against hypoxia.
Learning curve for mastery of colorectal endoscopic submucosal dissection: Perspectives from a large Japanese cohort
Authors: Zorron Cheng Tao Pu Leonardo , Yamamura Takeshi , Nakamura Masanao , Esaki Masaya , Kaosombatwattana Uayporn , Rodriguez Miguel R , Edwards Suzanne , Burt Alastair D , Singh Rajvinder , Hirooka Yoshiki , Fujishiro Mitsuhiro
Published: January 2020

Background and Aim

Endoscopic submucosal dissection (ESD) is a challenging procedure. A dissection speed of ≥9 cm2/h has been acknowledged as a mark for expertise, alongside a complication rate of ≤5% and en bloc resection rate of ≥90%. However, there is lack of objective information on whether the three measures correlate with each other. This study aims to evaluate the dissection speed, safety, and efficacy of colorectal ESDs performed by experts and trainees.

Methods

Consecutive patients undergoing colorectal ESD at a Japanese hospital (2006–2017) were included in a prospectively collected database. Information on patient demographics, proceduralist, and intra‐/postprocedure data was retrieved. The primary outcome was the comparison in dissection speed. The secondary outcomes included differences in safety and efficacy. Log‐linear regression models adjusted for confounders (e.g. R0 resection) were used to assess the differences in dissection speed.

Results

Five hundred ninety procedures (514 patients) performed by 26 endoscopists were analyzed. Experts performed a higher number of difficult lesions (e.g. F2 fibrosis) but achieved higher dissection speed (10.3 vs 6.7 cm2/h). The difference was statistically significant for both unadjusted and adjusted models (P < 0.0001). The en bloc resection rates were similar for both groups (experts = 95.6%; trainees = 94.7%, P = 0.61). Although nonexperts damaged more of the muscularis propria (18.6 vs 12.5%, P = 0.04), this did not translate into a significant difference in perforation (experts = 3.7%; trainees = 6.9%, P = 0.09) or delayed bleeding (experts = 2.9%; trainees = 4.4%, P = 0.34). The dissection speed steadily increased with expertise.

Conclusion

Although dissection speed for colorectal ESD was significantly higher for experts, ESDs could be safely and efficaciously performed by ESD trainees.
A sensitive fluorescent sensor based on the photoinduced electron transfer mechanism for cefixime and ctDNA
Authors: Yang Cheng‐Zhang , Liu Yong‐Chang , Xu Cheng , Bai Ai‐Min , Hu Yan‐Jun
Published: January 2020

Cefixime is a third generation orally administered cephalosporin that is frequently used as a broad spectrum antibiotic against various gram‐negative and gram‐positive bacteria. In this study, a simple and sensitive fluorescent sensor for the determination of the cefixime and ctDNA was established based on the CdTe:Zn2+ quantum dots (QDs). The fluorescence of CdTe:Zn2+ QDs can be effectively quenched by cefixime in virtue of the surface binding of cefixime on CdTe:Zn2+ QDs and the subsequent photoinduced electron transfer process from CdTe:Zn2+ QDs to cefixime, in particular, the high sensitivity of QDs fluorescence emission to cefixime at the micromole per liter level, which render the cefixime‐CdTe:Zn2+ QDs system into fluorescence “OFF” status, then turn on in the presence of ctDNA. Furthermore, the Fourier transform infrared (FTIR) spectra of characteristic bands of C–N and N–H groups of cefixime endow evidence for the interaction of cefixime with CdTe:Zn2+ QDs. The relative electrochemical behavior of the affinity of CdTe:Zn2+ QDs for cefixime and ctDNA reveals the potential molecular binding mechanism.
Characterization of volatile metabolites formed by molds on barley by mass and ion mobility spectrometry
Authors: Erler Alexander , Riebe Daniel , Beitz Toralf , Löhmannsröben Hans‐Gerd , Grothusheitkamp Daniela , Kunz Thomas , Methner Frank‐Jürgen
Published: January 2020

The contamination of barley by molds on the field or in storage leads to the spoilage of grain and the production of mycotoxins, which causes major economic losses in malting facilities and breweries. Therefore, on‐site detection of hidden fungus contaminations in grain storages based on the detection of volatile marker compounds is of high interest. In this work, the volatile metabolites of 10 different fungus species are identified by gas chromatography (GC) combined with two complementary mass spectrometric methods, namely, electron impact (EI) and chemical ionization at atmospheric pressure (APCI)‐mass spectrometry (MS). The APCI source utilizes soft X‐radiation, which enables the selective protonation of the volatile metabolites largely without side reactions. Nearly 80 volatile or semivolatile compounds from different substance classes, namely, alcohols, aldehydes, ketones, carboxylic acids, esters, substituted aromatic compounds, alkenes, terpenes, oxidized terpenes, sesquiterpenes, and oxidized sesquiterpenes, could be identified. The profiles of volatile and semivolatile metabolites of the different fungus species are characteristic of them and allow their safe differentiation. The application of the same GC parameters and APCI source allows a simple method transfer from MS to ion mobility spectrometry (IMS), which permits on‐site analyses of grain stores. Characterization of IMS yields limits of detection very similar to those of APCI‐MS. Accordingly, more than 90% of the volatile metabolites found by APCI‐MS were also detected in IMS. In addition to different fungus genera, different species of one fungus genus could also be differentiated by GC‐IMS.
Human cytomegalovirus infection in Iranian glioma patients correlates with aging and tumor aggressiveness
Authors: Maleki Faezeh , Sadigh Zohreh‐Azita , Sadeghi Farzin , Muhammadnejad Ahad , Farahmand Mohammad , Parvin Mahmoud , Shirkoohi Reza
Published: January 2020

Human cytomegalovirus (HCMV), as a ubiquitous and opportunistic virus, is a matter for consideration in broad‐spectrum diseases, specifically in immunocompromised individuals. In recent decades, many studies that have evaluated the role of HCMV in inflammation and malignancies, especially in high‐grade gliomas, have reported inconsistent results. Thus, this study was conducted to analyze 97 primary gliomas for human CMV UL83 gene and protein through TaqMan real‐time polymerase chain reaction and immunohistochemistry, respectively. The results were positive for the UL83 gene and pp65 protein in 71% and 24% of samples, respectively. The frequency of HCMV was significantly higher in glioblastomas than other glioma grades (P < .01 and P < .05 for the UL83 gene and protein, respectively). In addition, the association between the prevalence of HCMV and aging strengthened the virus reactivation hypothesis in gliomas. In conclusion, a high frequency of HCMV infection was found in gliomas that correlated with tumor aggressiveness and age. This study recommends a thorough investigation to determine HCMV infection in gliomas to improve the existing knowledge of its role in glial tumors, its prognostic value, and possible efficient antiviral target therapy.
Consequences of HLA‐associated mutations in HIV‐1 subtype C Nef on HLA‐I downregulation ability
Authors: Mann Jaclyn K. , Rajkoomar Erasha , Jin Steven W. , Mkhize Qiniso , Baiyegunhi Omolara , Mbona Pholisiwe , Brockman Mark A. , Ndung'u Thumbi
Published: January 2020

Identification of CD8+ T lymphocyte (CTL) escape mutations that compromise the pathogenic functions of the Nef protein may be relevant for an HIV‐1 attenuation‐based vaccine. Previously, HLA‐associated mutations 102H, 105R, 108D, and 199Y were individually statistically associated with decreased Nef‐mediated HLA‐I downregulation ability in a cohort of 298 HIV‐1 subtype C infected individuals. In the present study, these mutations were introduced by site‐directed mutagenesis into different patient‐derived Nef sequence backgrounds of high similarity to the consensus C Nef sequence, and their ability to downregulate HLA‐I was measured by flow cytometry in a CEM‐derived T cell line. A substantial negative effect of 199Y on HLA‐I downregulation and Nef expression was observed, while 102H and 105R displayed negative effects on HLA‐I downregulation ability and Nef expression to a lesser extent. The total magnitude of CTL responses in individuals harboring the 199Y mutation was lower than those without the mutation, although this was not statistically significant. Overall, a modest positive relationship between Nef‐mediated HLA‐I downregulation ability and total magnitude of CTL responses was observed, suggesting that there is a higher requirement for HLA‐I downregulation with increased CTL pressure. These results highlight a region of Nef that could be targeted by vaccine‐induced CTL to reduce HLA‐I downregulation and maximize CTL efficacy.
Chimeric oncolytic Ad5/3 virus replicates and lyses ovarian cancer cells through desmoglein‐2 cell entry receptor
Authors: Kuryk Lukasz , Møller Anne‐Sophie W.
Published: January 2020

Despite new therapies, the estimated 229 875 women living with ovarian cancer have a 5‐year survival rate of 47.6%. This cavity‐localized cancer lends itself to local administration of modalities, such as the oncolytic adenovirus (Ad) Ad5/3‐D24‐granulocyte‐macrophage colony‐stimulating factor virus (ONCOS‐102). Its repeated administration to a patient with chemotherapy‐refractory ovarian cancer induced CD8+ antitumor immune responses with the overall survival reaching 40 months. Here we probe the dominant receptor used by ONCOS‐102 in four established epithelial ovarian cancer cell lines. Ad3 can use the desmoglein‐2 (DSG2) and CD46 receptors on susceptible cells. DSG2 was nearly absent in A2780 cells but was expressed in more than 90% of OAW42, OVCAR3, and OV‐90 cells. After 96 hours, ONCOS‐102 treatment showed significant oncolytic activity (≧50%) in OAW42, OVCAR3, and OV‐90 cells, but minimal activity in A2780 cells, suggesting DSG2 as the dominant receptor for ONCOS‐102. Furthermore, retrospective analyses of phase I clinical trial of ONCOS‐102 treatment of 12 patients with varied tumors indicated a correlation between viral genomes in blood and DSG2 RNA expression. These data support the role of DSG2 expression on cancer cells in virus infectivity and the continued development of ONCOS‐102 for ovarian cancer treatment.
Of discovery and dread: The importance of work challenges for international business travelers' thriving and global role turnover intentions
Authors: Dimitrova Mihaela
Published: January 2020

As frequent travel across international borders has become common for an ever‐increasing number of workers, it is essential to understand what helps these international business travelers (IBTs) thrive and embrace their global work responsibilities. This study's purpose is to examine the role of developmental opportunities (i.e., work role challenges) in helping IBTs see frequent travel as a predominantly beneficial experience. By integrating two theories of motivation—conservation of resources theory and the challenge‐hindrance demands framework—I build a moderated mediation model of IBTs' intent to cease their global work responsibilities (i.e., global role turnover intentions). Using latent moderated structural equation modeling, I test the model on a sample of 204 IBTs collected at two time points. Results show that, through the psychological state of thriving at work, travel frequency has a negative indirect association with IBTs' global role turnover intentions when IBTs' work roles are challenging and a positive association when their work lacks challenge. This is primarily the case regarding the challenge of being responsible for others at work. The novelty of IBTs' work tasks is also a salient challenge but to a lesser extent. This study contributes to literatures on global work, work role design, and thriving.
Transcriptome analysis reveals delaying of the ripening and cell‐wall degradation of kiwifruit by hydrogen sulfide
Authors: Lin Xiaocui , Yang Rui , Dou Yuan , Zhang Wei , Du Huaying , Zhu Liqin , Chen Jinyin
Published: January 2020

BACKGROUND

Hydrogen sulfide (H2S) is a known signaling molecule in plants, which has the ability to delay fruit ripening. Our previous studies have shown that H2S treatment could delay the maturation of kiwifruits by inhibiting ethylene production, improving protective enzyme activities, and decreasing the accumulation of reactive oxygen species to protect the cell membrane during storage. The mechanism related to the way in which H2S affected kiwifruit maturation was still unclear. We performed transcriptome sequencing to explore the influences of H2S on the softening of kiwifruit.

RESULTS

The firmness and the soluble solids content (SSC) of the kiwifruit were significantly better maintained with H2S treatment compared to the control during the storage period (P < 0.05). Transmission electron microscopy (TEM) showed that degradation of the cell wall was inhibited after H2S treatment. Based on transcriptome data analysis and quantitative real‐time polymerase chain reaction (qRT‐PCR), expression levels of endo‐1,4‐β‐glucanase (β‐glu), β‐galactosidase (β‐gal) and pectinesterase (PME) decreased whereas pectinesterase inhibitor (PMEI) significantly increased in response to H2S. The members of the signal transduction pathway involved in ethylene were also identified. Hydrogen sulfide inhibited the expression of ethylene receptor 2 (ETR2), ERF003, ERF5, and ERF016, and increased the expression of ethylene‐responsive transcription factor 4 (ERF4) and ERF113.

CONCLUSION

Hydrogen sulfide could delay the ripening and senescence of kiwifruit by regulating the cell‐wall degrading enzyme genes and affecting ethylene signal transduction pathway genes. Our results revealed the effect of H2S treatment on the softening of kiwifruit at the transcription level, laying a foundation for further research. © 2020 Society of Chemical Industry
A Bibliometric Analysis of Citation Classics in the Journal of Ultrasound in Medicine
Authors: Balica Adrian , Kohut Adrian , Tsai Te‐Jung , Groszmann Yvette S. , Brandt Justin S.
Published: January 2020

Objectives

A bibliometric analysis of articles in the Journal of Ultrasound in Medicine (JUM) identified the journals’ most impactful articles.

Methods

A bibliometric analysis of citation classics that were published in the JUM from its inception in 1982 to 2019 was performed. All citation classics, defined as articles cited 100 or more times, were evaluated for the number of citations, citations per year, publication year, subspecialty, design, and country of origin. Characteristics were compared before and after 1998 by the Mann‐Whitney test for unpaired data and 2‐sample z tests of sample proportions. The Kruskal‐Wallis test for nonparametric continuous data was used to compare the median number of citations per year by decade of publication.

Results

A total of 7868 articles were published in the JUM between 1982 and 2019; 54 (0.7%) were citation classics. The median citation classics year of publication was 1998 (interquartile range [IQR], 1991–2003). Most citation classics originated from the United States (36 of 54 [66.7%]), were observational (47 of 54 [87%]), and were related to obstetric and gynecologic topics (16 of 54 [29.6%]). Citation classics after 1998 received significantly more citations per year (9.3 versus 4.7; P < .001), with no other differences noted. The median number of citations per year increased for each decade, with medians of 4 citations (IQR, 3.6–4.7) in 1982 to 1991 and 11.2 citations (IQR, 9–13.9) in 2002 to 2012 (P < .001).

Conclusions

This list provides insight into the most influential articles that were published in the JUM. Most citation classics were observational, were from the United States, and covered obstetric and gynecologic topics. Citation classics received more citations per year after 1998.
Brainstem Ventilatory Dysfunction: A Plausible Mechanism for Dyspnea in Parkinson's Disease?
Authors: Vijayan Srimathy , Singh Bhajan , Ghosh Soumya , Stell Rick , Mastaglia Frank L
Published: January 2020

Dyspnea is an under‐recognized and debilitating symptom that is reported in up to 40% of patients with Parkinson's disease and may have multiple origins. Despite its frequency, it is poorly researched, and there is a general lack of understanding of the pathophysiology of dyspnea and respiratory dysfunction in PD. Consequently, a number of PD patients are labelled as having “unexplained dyspnea.” Studies to date have focused mainly on evaluating ventilatory capacity and lung volumes, and little is known about the effects of the disease on the medullary and pontine ventilatory control centers within the brainstem. This is of particular relevance in view of neuropathological studies demonstrating early involvement of the dorsal medulla and other brainstem structures by the disease process. The possibility that impaired brainstem ventilatory control is a contributory mechanism for dyspnea and could be a premotor manifestation in some PD patients therefore warrants further attention. This review focuses on clinical, pathological, and experimental evidence for the involvement of brainstem respiratory centers in PD. We highlight the need for further research, particularly in PD patients with unexplained dyspnea. © 2020 International Parkinson and Movement Disorder Society
Genetic and clinical analysis in Chinese patients with retinitis pigmentosa caused by EYS mutations
Authors: Sun Yan , Li Jian‐kang , He Wei , Wang Zhuo‐shi , Bai Jin‐yue , Xu Ling , Xing Bo , Zhang Jian‐guo , Wang Lusheng , Li Wei , Chen Fang
Published: January 2020

Background

Panel‐based targeted exome sequencing was applied to identify the pathogenic variants and genetic characteristics of retinitis pigmentosa (RP) in two Chinese families, and to gain a deeper understanding of the relationship between clinical manifestations and genotypes.

Methods

A total of 17 subjects, comprising two probands (total patients: four subjects) and their family member, were recruited in this study. All subjects underwent comprehensive ophthalmic examinations and clinical evaluations, and the complete history and medical records were collected according to the standard procedures. All participants were screened using the multigene panel test (Target_Eye_792_V2 chip), and Sanger sequencing was used to confirm the candidate variants.

Results

Among these two families, a total of three novel mutations in the EYS gene were identified in patients, including a homozygous frameshift mutation c.9252_9253insT detected in two patients in one family, and the compound heterozygous splicesite mutation c.5644+2T>C and frameshift mutation c.1920_1923delTGAG detected in two patients in the another family. All patients in both families had early onset of night blindness and poor visual acuity, and with typical posterior capsule opacification. The mutation co‐segregated within all recruited individuals. In addition, one patient with compound heterozygous mutations was found to have typical blue‐blindness symptoms and detected a previously reported disease‐causing mutation c.235G>A in OPN1SW gene, which caused blue blindness manifestations and was first discovered in patient combined with RP causative genes.

Conclusions

Panel‐based targeted exome sequencing was used to identify three novel variants of RP causative gene, and we also detected a known pathogenic variants of blue‐blindness causative genes in two patients. Our finding will provide a powerful basis for genetic counseling and enhance our current understanding of the genetics factors for RP families.
Whole‐exome sequencing identified a novel variant in an Iranian patient affected by pycnodysostosis
Authors: Razmara Ehsan , Azimi Homeyra , Bitaraf Amirreza , Daneshmand Mohammad Ali , Galehdari Mohammad , Dokhanchi Maryam , Esmaeilzadeh‐Gharehdaghi Elika , Garshasbi Masoud
Published: January 2020

Background

Whole‐exome sequencing (WES) has emerged as a successful diagnostic tool in molecular genetics laboratories worldwide. In this study, we aimed to find the potential genetic cause of skeletal disease, a heterogeneous disease, revealing the obvious short stature phenotype. In an Iranian family, we used solo‐WES in a suspected patient to decipher the potential genetic cause(s).

Methods

A comprehensive clinical and genotyping examination was applied to suspect the disease of the patient. The solo clinical WES was exploited, and the derived data were filtered according to the standard pipelines. In order to validate the WES finding, the region harboring the candidate variant in the CTSK gene was amplified from genomic DNA and sequenced directly by Sanger sequencing.

Results

Sequence analysis revealed a rare novel nonsense variant, p.(Trp320*); c.905G>A, in the CTSK gene (NM_000396.3). In silico analysis shed light on the contribution of the variant to the pathogenicity of pycnodysostosis. This variant was confirmed by Sanger sequencing and further clinical examinations of the patient confirmed the disease.

Conclusion

The present study shows a rare variant of the CTSK gene, which inherited as autosomal recessive, in an Iranian male patient with pycnodysostosis. Taken together, the novel nonsense CTSK variant meets the criteria of being likely pathogenic according to the American College of Medical Genetics and Genomics‐the Association for Molecular Pathology (ACMG‐AMP) variant interpretation guidelines.
Mouse strain‐dependent egg factors regulate calcium signals at fertilization
Authors: McDonough Caitlin E. , Bernhardt Miranda L. , Williams Carmen J.
Published: January 2020

Calcium (Ca2+) signals triggered at fertilization initiate resumption of the cell cycle and initial steps of embryonic development. In mammals, the sperm factor phospholipase Cζ triggers the release of Ca2+ from the endoplasmic reticulum (ER), initiating an oscillatory pattern of Ca2+ transients that is modulated by egg factors including Ca2+ influx channels, Ca2+ transporters, and phosphoinositide‐regulating enzymes. Here we compared characteristics of Ca2+ oscillations following in vitro fertilization (IVF) and ER Ca2+ stores among nine common laboratory mouse strains: CF1, C57BL6, SJL, CD1, DBA, FVB, 129X1, BALBc, 129S1, and the F1 hybrid B6129SF1. Sperm from B6SJLF1/J males was used for all IVF experiments. There were significant differences among the strains with respect to duration and maximum amplitude of the first Ca2+ transient, frequency of oscillations, and ER Ca2+ stores. With male strain held constant, the differences in Ca2+ oscillation patterns observed result from variation in egg factors across different mouse strains. Our results support the importance of egg‐intrinsic properties in determining Ca2+ oscillation patterns and have important implications for the interpretation and comparison of studies on Ca2+ dynamics at fertilization.
Ability of the Bristol Impact of Hypermobility questionnaire to discriminate between people with and without Joint Hypermobility Syndrome: a known‐group validity study
Authors: Palmer Shea , Macconnell Samuel , Willmore Alison
Published: January 2020

Introduction

A number of psychometric properties of the Bristol Impact of Hypermobility (BIoH) questionnaire have previously been demonstrated, including strong concurrent validity and test–retest reliability. This study aimed to identify whether it can discriminate between those with and without Joint Hypermobility Syndrome (JHS).

Methods

The wording of a small number of BIoH questionnaire items was adapted to create a generic version that asked about ‘general health' rather than ‘hypermobility'. The generic questionnaire was distributed online to university students and staff. A sampling frame was used to create age and sex‐matched samples from the non‐JHS respondents in the current study and a pre‐existing JHS cohort. Questionnaire scores were then compared between samples.

Results

790 responses were received. 414 were excluded, mainly due to self‐reported generalized joint hypermobility or a JHS diagnosis. The sampling frame was applied to the remaining non‐JHS responders (n = 376) and the pre‐existing JHS cohort (n = 448), resulting in 206 age and sex‐matched participants in each sample. The median (IQR) BIoH scores (out of a maximum 360) were 81 (57.25) and 231.5 (74.25) in the non‐JHS and JHS samples respectively (p < 0.001). There was a very strong correlation between BIoH score and the number of painful areas (r = 0.867, p < 0.001).

Conclusions

The BIoH questionnaire discriminates between those with and without JHS. The median difference (151.5 points) far exceeds the smallest detectable change of 42 points previously identified. The results provide further evidence of the psychometric properties of the BIoH questionnaire and its potential to support research and clinical practice.
Trapped or twisted? Teasing out anterior interosseous neuropathy
Authors: van Alfen Nens
Published: January 2020

See article on pages 301–310 in this issue.
Evaluating the safety and potential activity of URO‐902 (hMaxi‐K) gene transfer by intravesical instillation or direct injection into the bladder wall in female participants with idiopathic (non‐neurogenic) overactive bladder syndrome and detrusor overactivity from two double‐blind, imbalanced, placebo‐controlled randomized phase 1 trials
Authors: Rovner Eric , Chai Toby C. , Jacobs Sharon , Christ George , Andersson Karl‐Erik , Efros Mitchell , Nitti Victor , Davies Kelvin , McCullough Andrew R. , Melman Arnold
Published: January 2020

Aims

Two phase 1 trials were performed in healthy women with the overactive bladder (OAB) syndrome and urodynamically demonstrated detrusor overactivity (DO), with the aim to demonstrate the safety and potential efficacy of URO‐902, which comprises a gene therapy plasmid vector expressing the human big potassium channel α subunit.

Methods

ION‐02 (intravesical instillation) and ION‐03 (direct injection) were double‐blind, placebo‐controlled, multicenter studies without overlap in enrollment between studies. Active doses were administered and evaluated sequentially (lowest dose first) for safety. ION‐02 participants received either 5000 µg or 10 000 µg URO‐902, or placebo. ION‐03 participants received either 16 000 or 24 000 µg URO‐902, or placebo, injected directly into the bladder wall using cystoscopy. Primary outcome variables were safety parameters occurring subsequent to URO‐902 administration; secondary efficacy variables also were evaluated.

Results

Among the safety outcomes, there were no dose‐limiting toxicities or significant adverse events (AEs) preventing dose escalation during either trial, and no participants withdrew due to AEs. For efficacy, in ION‐02 (N = 21), involuntary detrusor contractions on urodynamics at 24 weeks in patients receiving URO‐902 (P < .0508 vs placebo) and mean urgency incontinence episodes in the 5000 µg group (P = .0812 vs placebo) each showed a downward trend. In ION‐03 (N = 13), significant reduction versus placebo in urgency episodes (16 000 µg, P = .036; 24 000 µg, P = .046) and number of voids (16 000 µg, −2.16, P = .044; 24 000 µg, −2.73, P = .047) were observed 1 week after injection.

Conclusion

Promising safety and efficacy results in these preliminary phase 1 studies suggest gene transfer may be a promising therapy for OAB/DO, warranting further investigation.
Do overactive bladder symptoms and their treatment‐associated changes exhibit a normal distribution? Implications for analysis and reporting
Authors: Amiri Marjan , Murgas Sandra , Stang Andreas , Michel Martin C.
Published: January 2020

Aims

To explore the use of means vs medians (assuming or not the presence of normal distribution) in studies reporting overactive bladder syndrome symptoms and to test for normal distribution of basal values and treatment‐associated changes thereof in two large noninterventional studies.

Methods

Systematic review of all original studies reporting on at least one overactive bladder syndrome symptom published in four leading urology journals in 2016 to 2017. Testing of the normal distribution of urgency, incontinence, frequency, and nocturia in two large noninterventional studies (n = 1335 and 745).

Results

Among 48 eligible articles, 86% reported means (assuming a normal distribution), 6% medians (not making this assumption), and 8% a combination thereof. Baseline values for all four symptoms and treatment‐associated alterations thereof deviated from a normal distribution (P < .0001 in all cases). Means overestimated basal value and absolute changes thereof as compared with medians, for example, basal number of incontinence episodes in study 1 5.1 vs 4. Differences between means and medians for percentage changes of symptoms were small and did not consistently favor means over medians.

Conclusions

Dominant reporting of means implies the assumption of a normal distribution of overactive bladder syndrome symptoms but our data from two noninterventional studies do not support this assumption. We recommend that basal values and absolute symptom changes should be reported as medians and subjected to nonparametric analysis; means may be appropriate for the reporting of percentage changes of symptoms.
Schedule design for liner services under vessel speed reduction incentive programs
Authors: Zhuge Dan , Wang Shuaian , Zhen Lu , Laporte Gilbert
Published: January 2020

Gas and particulate emissions from ship transportation have been increasing in recent years. In order to mitigate ship emissions near coastal areas, voluntary vessel speed reduction incentive programs (VSRIPs) were put in place by a number of ports. This paper studies a schedule design problem faced by liner shipping companies under VSRIPs. It proposes a mixed‐integer nonlinear mathematical model for the minimization of the total cost, consisting of fuel cost, as well as operating cost, minus dockage refunds. The model balances three determinants, that is, the compliance of VSRIPs, the speed limit (the maximum physical speed of ships and the upper speed limit imposed by VSRIPs), and the limited number of ships. An enumerative algorithm and a piecewise‐linear approximation algorithm are developed, based on some properties of the nonlinear model. The efficiency of the proposed algorithms is validated through extensive computational experiments.
Physical Activity and Adiposity in a Racially Diverse Cohort of US Infants
Authors: Benjamin‐Neelon Sara E. , Bai Jiawei , Østbye Truls , Neelon Brian , Pate Russell R. , Crainiceanu Ciprian
Published: January 2020

Objective

Early life physical activity may help prevent obesity, but objective quantification in infants is challenging.

Methods

A total of 506 infants were examined from 2013 to 2016. Infants wore accelerometers for 4 days at ages 3, 6, 9, and 12 months. Daily log‐transformed physical activity counts were computed, averaged, and standardized across assessments. A linear mixed model was used to examine trends in standardized physical activity counts as well as associations between physical activity and BMI z score, sum of subscapular and triceps skinfold thickness for overall adiposity (SS+TR), and their ratio for central adiposity (SS:TR).

Results

Among infants, 66% were black and 50% were female. For each additional visit, standardized physical activity counts increased by 0.23 (CI: 0.18 to 0.27; P < 0.0001). This translates to 126.3 unadjusted physical activity counts or a 4% increase for each visit beyond 3 months. In addition, a 1‐SD increase in standardized physical activity counts (550 unadjusted physical activity counts) was associated with a 0.01‐mm lower SS:TR (95% CI: −0.02 to −0.001; P = 0.03). However, standardized physical activity counts were not associated with BMI z score or SS+TR.

Conclusions

Physical activity increased over infancy and was associated with central adiposity. Despite limitations, researchers should consider objective measurement in infants.
Electrical insulation performance of cross‐linked polyethylene/MgO nanocomposite material for ±320 kV high‐voltage direct‐current cables
Authors: Paramane Ashish , Chen Xiangrong , Dai Chao , Guan Honglu , Yu Linwei , Tanaka Yasuhiro
Published: January 2020

Polymeric nanocomposite insulations are receiving the widespread attention of the electrical cable industry. This paper presents the electrical insulation performance of as‐received commercial 320 kV high‐voltage direct‐current (HVDC) cross‐linked polyethylene (XLPE)/MgO nanocomposite material with reference to the pure XLPE. The results of this commercial‐grade electrical insulation material are not reported hitherto. The scanning electron microscopy confirms the well‐dispersed nanofiller inside the polymer matrix. The DC electrical insulation performance is investigated by DC breakdown strength, space charge, DC electrical conductivity, and surface potential decay measurements. The test samples are subjected to the thermal aging at 135°C for 30 days. The un‐aged nanocomposite exhibits 20% higher DC breakdown strength, negligible hetero space charge accumulation, and the lower DC conductivity by one order than the un‐aged pure XLPE. Moreover, thermally aged nanocomposite shows more restraint to the deterioration of its properties. After the thermal aging, the DC breakdown strength decreased by 38% and 20% in the pure XLPE and its nanocomposite, respectively. Thermally aged nanocomposite shows negligible hetero charges and an increase in the DC conductivity by one order. However, the pure XLPE shows higher hetero charge accumulation and the increased DC conductivity by one order. In un‐aged XLPE nanocomposite higher crystallinity, higher deep trap density, and the lower carbonyl index are found to be the primary attributes of its improved performance. It is postulated that these significantly unchanged attributes can be the reason for the better anti‐thermal aging properties of the XLPE nanocomposite.
Monitoring and mitigation of toxic heavy metals and arsenic accumulation in food crops: A case study of an urban community garden
Authors: Cooper Andrew M. , Felix Didra , Alcantara Fatima , Zaslavsky Ilya , Work Amy , Watson Paul L. , Pezzoli Keith , Yu Qi , Zhu Dan , Scavo Alexander J. , Zarabi Yasman , Schroeder Julian I.
Published: January 2020

Urban community gardens have increased in prevalence as a means to generate fresh fruits and vegetables, including in areas lacking access to healthy food options. However, urban soils may have high levels of toxic heavy metals, including lead and cadmium and the metalloid arsenic, which can lead to severe health risks. In this study, fruit and vegetable samples grown at an urban community garden in southeastern San Diego, the Ocean View Growing Grounds, were sampled repeatedly over a four‐year time period in order to measure potential contamination of toxic heavy metals and metalloids and to develop solutions for this problem. Metal nutrient, heavy metal, and metalloid concentrations were monitored in the leaf and fruit tissues of fruit trees over the sampling period. Several of the fruit trees showed uptake of lead in the leaf samples, with Black Mission fig measuring 0.843–1.531 mg/kg dry weight and Mexican Lime measuring 1.103–1.522 mg/kg dry weight over the sampling period. Vegetables that were grown directly in the ground at this community garden and surrounding areas showed arsenic, 0.80 + 0.073 mg/kg dry weight for Swiss chard, and lead, 0.84 ± 0.404 mg/kg dry weight for strawberries, in their edible tissues. The subsequent introduction of raised beds with uncontaminated soil is described, which eliminated any detectable heavy metal or metalloid contamination in these crops during the monitoring period. Recommendations for facilitating the monitoring of edible tissues and for reducing risk are discussed, including introduction of raised beds and collaborations with local universities and research groups.