bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative and qualitative impairments in GATA2 and myeloid neoplasms
Authors: Shimizu Ritsuko , Yamamoto Masayuki
Published: November 2019

GATA2 is a key transcription factor critical for hematopoietic cell development. During the past decade, it became clear that heterozygous germline mutations in the GATA2 gene cause bone marrow failure and primary immunodeficiency syndrome, conditions that lead to a predisposition toward myeloid neoplasms, such as myelodysplastic syndrome, acute myeloid leukemia, and chronic myelomonocytic leukemia. Somatic mutations of the GATA2 gene are also involved in the pathogenesis of myeloid malignancies. Cases with GATA2 gene mutations are divided into two groups, resulting in either a quantitative deficiency or a qualitative defect in the GATA2 protein depending on the mutation position and type. In the former case, GATA2 mRNA expression from the mutant allele is markedly reduced or completely abrogated, and reduced GATA2 protein expression is involved in the pathogenesis. In the latter case, almost equal amounts of structurally abnormal and wildtype GATA2 proteins are predicted to be present and contribute to the pathogenesis. The development of mouse models of these human GATA2‐related diseases has been undertaken, which naturally develop myeloid neoplasms.
BMP‐Smad Signaling Regulates Postnatal Crown Dentinogenesis in Mouse Molar
Authors: Omi Maiko , Kulkarni Anshul K , Raichur Anagha , Fox Mason , Uptergrove Amber , Zhang Honghao , Mishina Yuji
Published: November 2019

Dentinogenesis, a formation of dentin by odontoblasts, is an essential process during tooth development. Bone morphogenetic proteins (BMPs) are one of the most crucial growth factors that contribute to dentin formation. However, it is still unclear how BMP signaling pathways regulate postnatal crown and root dentinogenesis. BMPs transduce signals through canonical Smad and non‐Smad signaling pathways including p38 and ERK signaling pathways. To investigate the roles of Smad and non‐Smad signaling pathways in dentinogenesis, we conditionally deleted Bmpr1a, which encodes the type 1A receptor for BMPs, to remove both Smad and non‐Smad pathways in Osterix‐expressing cells. We also expressed a constitutively activated form of Bmpr1a (caBmpr1a) to increase Smad1/5/9 signaling activity without altered non‐Smad activity in odontoblasts. To understand the function of BMP signaling during postnatal dentin formation, Cre activity was induced at the day of birth. Our results showed that loss of BmpR1A in odontoblasts resulted in impaired dentin formation and short molar roots at postnatal day 21. Bmpr1a cKO mice displayed a reduction of dentin matrix production compared to controls associated with increased cell proliferation and reduced Osx and Dspp expression. In contrast, caBmpr1a mutant mice that show increased Smad1/5/9 signaling activity resulted in no overt tooth phenotype. To further dissect the functions of each signaling activity, we generated Bmpr1a cKO mice also expressing caBmpr1a to restore only Smad1/5/9 signaling activity. Restoring Smad activity in the compound mutant mice rescued impaired crown dentin formation in the Bmpr1a cKO mice; however, impaired root dentin formation and short roots were not changed. These results suggest that BMP‐Smad signaling in odontoblasts is responsible for crown dentin formation, while non‐Smad signaling may play a major role in root dentin formation and elongation. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Retracted: Long noncoding RNA PCAT‐1 knockdown prevents the development of ovarian cancer cells via microRNA‐124‐3p
Authors: Min Fengying , Chu Guoyan
Published: November 2019

Long noncoding RNA prostate cancer‐associated transcript 1 (PCAT‐1) is overexpressed in human malignancies and its silence abates the exaggeration of cancers. Whereas, the activity of PCAT‐1 silence in ovarian cancer (OC) remains elusive. Here, our study was designed to corroborate the function of PCAT‐1 silence in cellular activities and the molecular mechanisms. PCAT‐1 in human ovarian tumor tissue specimens and cell lines (A2780 and SKOV3) were quantified by real‐time quantitative reverse polymerase chain reaction (qRT‐PCR). Reinforced silence of PCAT‐1 and microRNA (miR)‐124‐3p was established by transfection and identified by qRT‐PCR. The viability, apoptosis as well as migration and invasion were examined. Western blot was exploited for analysis of proteins involved in proliferation, apoptosis, migration and invasion, and signaling transduction. OC tissues showed the accumulation of PCAT‐1. Silencing PCAT‐1 caused the impediment of proliferation, migration, and invasion with the increase in apoptosis. PCAT‐1 knockdown repressed the expression of cyclin D1, CDK6, p53, Bax, cleaved caspase‐3, metallopeptidases, and vimentin with the restoration of miR‐124‐3p. However, the roles of PCAT‐1 silence were weakened in the absence of miR‐124‐3p. PCAT‐1 silence caused decrease in Wnt3a, β‐catenin, and phosphorylation of protein kinase B and mechanistic target of rapamycin was abolished by miR‐124‐3p inhibitor. The tumor‐suppressive role of PCAT‐1 silence was mediated by miR‐124‐3p.
Five genes as a novel signature for predicting the prognosis of patients with laryngeal cancer
Authors: Zhang Guihai , Fan Erxi , Yue Guojun , Zhong Qiuyue , Shuai Yu , Wu Mingna , Feng Guangyong , Chen Qiying , Gou Xiaoxia
Published: November 2019

In this study, we purpose to investigate a novel five‐gene signature for predicting the prognosis of patients with laryngeal cancer. The laryngeal cancer datasets were obtained from The Cancer Genome Atlas (TCGA). Both univariate and multivariate Cox regression analysis was applied to screening for prognostic differential expressed genes (DEGs), and a novel gene signature was obtained. The performance of this Cox regression model was tested by receiver operating characteristic (ROC) curves and area under the curve (AUC). Further survival analysis for each of the five genes was carried out through the Kaplan‐Meier curve and Log‐rank test. Totally, 622 DEGs were screened from the TCGA datasets in this study. We construct a five‐gene signature through Cox survival analysis. Patients were divided into low‐ and high‐risk groups depending on the median risk score, and a significant difference of the 5‐year overall survival was found between these two groups (P < .05). ROC curves verified that this five‐gene signature had good performance to predict the prognosis of laryngeal cancer (AUC = 0.862, P < .05). In conclusion, the five‐gene signature consist of EMP1, HOXB9, DPY19L2P1, MMP1, and KLHDC7B might be applied as an independent prognosis predictor of laryngeal cancer.
Prevalence of Ureaplasma urealyticum, Chlamydia trachomatis, and Neisseria gonorrhoeae in gynecological outpatients, Taizhou, China
Authors: Cai Shasha , Pan Jie , Duan Darong , Yu Changfa , Yang Zaixing , Zou Jinyan
Published: November 2019

Objectives

Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), and Neisseria gonorrhoeae (NG) are highly prevalent worldwide and may lead to some genital diseases. The objective of this large‐scale study was to estimate the prevalence characteristics of UU, CT, and NG among women in Taizhou, Zhejiang Province, China.

Methods

A total of 13 303 women who visited the gynecologic outpatient service of Taizhou First People's Hospital in Taizhou from 2013 to 2018 were analyzed. The testing of UU, CT, and NG was performed on the collected vaginal swabs using real‐time fluorescence quantitative polymerase chain reaction (RT‐PCR) method.

Results

The overall infection rates of UU, CT, and NG were 62.04%, 10.20%, and 4.09% in the Taizhou‐based population, respectively. The age‐specific prevalence showed that younger women (age <25 years) were the preferred period for the positive detection of UU or CT, while elder women (age ≥40 years) had the highest prevalence of NG. In addition, the UU‐CT co‐infection pattern (7.32%) predominated in the study population, and CT was significantly associated with UU and NG.

Conclusions

Our novel data demonstrated that UU, CT, and NG infection are prevalent among women in Taizhou, and comprehensive UU, CT, and NG screening guidelines and treatment policies for this population are warranted.
PEG‐PLA nanoparticles decorated with small‐molecule PSMA ligand for targeted delivery of galbanic acid and docetaxel to prostate cancer cells
Authors: Afsharzadeh Maryam , Hashemi Maryam , Babaei Maryam , Abnous Khalil , Ramezani Mohammad
Published: November 2019

Prostate cancer (PCa) is one of the most prevalent non‐drug delivery system cutaneous malignancies. Undoubtedly, introducing novel treatment options to achieve higher therapeutic index will be worthwhile. In this study, we report for the first time, a novel targeted self‐assembled based on PEG‐PLA nanoparticles (PEG‐PLA NPs) containing galbanic acid (GBA) and docetaxel, which was targeted using ((S)‐2‐(3‐((S)‐5‐amino‐1‐carboxypentyl) ureido) pentanedioic acid (ACUPA), a small molecule inhibitor targeting prostate‐specific membrane antigen (PSMA), in prostate cancer cell line. The prepared NPs were characterized by different analytical methods. The MTT assay was used to compare the anti‐proliferation of drugs‐loaded PEG‐PLA NPs and ACUPA‐PEG‐PLA against LNCaP (PSMA+) and PC3 (PSMA−) cells. PEG‐PLA NPs with an average size of 130–140 nm had an enhanced release of GBA and docetaxel at pH 5.5 compared with pH 7.5. Spectrofluorometric analysis suggested that ACUPA‐modified PEG‐PLA could effectively enhance the drug uptake in PSMA+ prostate cancer cells. Cytotoxicity studies showed that the targeted NPs loaded with different concentrations of GBA and fixed concentration of docetaxel (4 nM) have shown higher toxicity (IC50 30 ± 3 µM) than both free GBA (80 ± 4.5 µM) and nontargeted NPs (IC50 40 ± 4.6 µM) in LNCaP cells. Collectively, these findings suggest that ACUPA‐conjugated PEG‐PLA nanosystem containing GBA and docetaxel is a viable delivery carrier for various cancer‐targeting PSMA that suffer from short circulation half‐life and limited therapeutic efficacy.
Salient Volunteering Behavior Increases Monetary Risk‐taking
Authors: Blekher Maria , Danziger Shai , Grinstein Amir
Published: November 2019

Research finds that engaging in prosocial behavior has many positive psychological outcomes (e.g., enhanced well‐being, optimism, perceived control, and a boost in self‐concept), and research on monetary risk‐taking reveals these psychological outcomes are associated with increased risk‐taking. Merging these findings, we propose that when people's volunteering behavior is made salient in their minds, they take more monetary risks. Making research participants’ volunteering behavior salient by having them recall an act of prior volunteering (studies 1 and 3), choosing whether to volunteer (study 2), or choosing one of two volunteering activities (study 4), four experiments (and a fifth reported in the Appendix S2) reveal increased risk‐taking across several monetary‐risk outcomes (incentive‐compatible gambles, allocation of a windfall gain, and a behavioral risk‐taking measure involving escalating risk). Lastly, when the decision maker attributes a decision to volunteer to an external source, the effect of salient volunteering on monetary risk‐taking attenuates.
Diagnostic Value of Gd‐EOB‐DTPA‐Enhanced MRI for the Expression of Ki67 and Microvascular Density in Hepatocellular Carcinoma
Authors: Chen Yidi , Qin Xiali , Long Liling , Zhang Ling , Huang Zhongkui , Jiang Zijian , Li Chenhui
Published: November 2019

Contract grant sponsor

National Natural Science Foundation of China; Contract grant number: 81260214.

Background

Recent studies have highlighted the diagnostic value of Gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA)‐enhanced MRI in small hepatocellular carcinoma (HCC). Ki67 and CD34 are histologic markers that reflect the proliferation of tumor cells and the microvascular density (MVD).

Purpose

To explore the diagnostic value of Gd‐EOB‐DTPA‐enhanced MRI for Ki67 expression and MVD in HCC.

Study Type

Retrospective.

Subjects

In all, 180 patients with HCC.

Field Strength/Sequence

3.0T, Gd‐EOB‐DTPA‐enhanced T1WI volumetric interpolated breath‐hold examination (VIBE) axial fat suppression plain, and enhanced scanning.

Assessment

The T1 relaxation time (T1rt) and signal intensity (SI) of the lesion were measured. The Ki67 expressions and MVD were evaluated by immunohistochemistry.

Statistical Test

Receiver operating characteristic (ROC) curves were used to analyze the diagnostic efficacy of T1rt for high Ki67 expression (≥50%) and high MVD (≥100).

Results

The T1rt‐20min, rrT1rt‐20min, and SI‐hepatobiliary phase (SI‐HBP) were strongly correlated with Ki67, the r values were 0.846, –0.765, and –0.760 (P < 0.05), respectively. There were moderate correlations with CD34, with r values –0.444, 0.336, and –0.463 (P < 0.05), respectively. The T1rt‐Pre, T1rt‐20min, SI‐Pre, and SI‐HBP were significantly different both between the high and low ki67 expression groups (P < 0.05) and between the high MVD and low MVD groups (P < 0.05). In the two groups the T1rt‐20min and SI‐HBP was 800.06 ± 128.91 vs. 530.06 ± 139.29 (P < 0.05) and 122.29 ± 39.39 vs. 173.49 ± 46.15 (P < 0.05); T1rt‐20min was found to have high diagnostic efficiency for high ki67 expression (area under the curve [AUC], 0.937; P < 0.05) T1rt‐20min had moderate diagnostic value for high MVD (AUC, 0.716; P < 0.05).

Data Conclusion

The T1rt and SI of Gd‐EOB‐DTPA‐enhanced MRI were correlated with Ki67 expression and MVD. T1rt‐20min has a high diagnostic value for high ki67 expression and high MVD in HCC tissues.

Level of Evidence: 3

Technical Efficacy Stage: 2

J. Magn. Reson. Imaging 2020;51:1755–1763.
MRI‐Based Radiomics: Associations With the Recurrence‐Free Survival of Patients With Hepatocellular Carcinoma Treated With Conventional Transcatheter Arterial Chemoembolization
Authors: Song Wenlong , Yu Xiangling , Guo Dajing , Liu Huan , Tang Zhuoyue , Liu Xinjie , Zhou Jun , Zhang Haiping , Liu Yangyang , Liu Xi
Published: November 2019

Background

Preoperative estimation of hepatocellular carcinoma (HCC) recurrence after conventional transcatheter arterial chemoembolization (c‐TACE) is crucial for subsequent follow‐up and therapy decisions.

Purpose

To evaluate the associations of radiomics models based on pretreatment contrast‐enhanced MRI, a clinical‐radiological model and a combined model with the recurrence‐free survival (RFS) of patients with HCC after c‐TACE, and to develop a radiomics nomogram for individual RFS estimations and risk stratification.

Study Type

Retrospective.

Population

In all, 184 consecutive HCC patients.

Field Strength/Sequence

1.5T or 3.0T, including T2WI, T1WI, and contrast‐enhanced T1WI.

Assessment

All HCC patients were randomly divided into the training (n = 110) and validation datasets (n = 74). Radiomics signatures capturing intratumoral and peritumoral expansion (1, 3, and 5 mm) were constructed, and the radiomics models were set up using least absolute shrinkage and selection operator (LASSO) Cox regression. Clinical‐radiological features were identified by univariate and multivariate Cox regression. The clinical‐radiological model and the combined model fusing the radiomics signature with the clinical‐radiological risk factors were developed by a multivariate Cox proportional hazard model. A radiomics nomogram derived from the combined model was established.

Statistical Tests

LASSO Cox regression, univariate and multivariate Cox regression, Kaplan–Meier analysis were performed. The discrimination performance of each model was quantified by the C‐index.

Results

Among the different peritumoral expansion models, only the 3‐mm peritumoral expansion model (C‐index, 0.714) showed a comparable performance (P = 0.4087) to that of the portal venous phase intratumoral model (C‐index, 0.727). The combined model showed the best performance and the C‐index was 0.802. Kaplan–Meier analysis showed that the cutoff values of the combined model relative to a median value (1.7426) perfectly stratified these patients into high‐risk and low‐risk subgroups.

Data Conclusion

The combined model is more valuable than the clinical‐radiological model or radiomics model alone for evaluating the RFS of HCC patients after c‐TACE, and the radiomics nomogram can be used to preoperatively and individually estimate RFS.

Level of Evidence: 3

Technical Efficacy Stage: 4

J. Magn. Reson. Imaging 2020;52:461–473.
Poliovirus serotype 2 and coxsackievirus A promote the natural recombination of poliovirus
Authors: Qian Yongjiang , Pu Xufeng , Yu Yu , Yu Xintian , Kong Liang , Liu Lu , Wang Hua , Shen Hongxing
Published: November 2019

Poliovirus (PV) is a member of the species Enterovirus C (EV‐C), which may cause irreversible paralysis and death. So, for the purpose of analyzing the evolution of PV2 to help in eradicating PVs globally, a recombination analysis was performed to verify all viral genomes of EV‐C, and we found 13 putative recombination events that produced PV1, 14 recombination events that can give rise to PV2, and 9 events that can lead to PV3. By analyzing our findings, we found that PV2 was involved in 25 of 36 PV recombination events, whereas coxsackievirus A (CVA) strains were involved in 12 of 36 PV recombination events, indicating that PV2 and CVAs play major roles in the natural recombination of PV. In addition, we found 11 of 36 breakpoint positions located in 2A region, which is the most active region of the recombination events.
Evaluation of cloud base height in the North American Regional Reanalysis using ceilometer observations
Authors: An Ning , Pinker Rachel T. , Wang Kaicun , Rogers Eric , Zuo Zhiyan
Published: November 2019

Future climate change predictions by global climate models or earth system models diverge significantly, most likely due to their different cloud responses to global warming. There is an uncertainty as to how the cloud frequency (or cloud fraction) and height will change, in turn, affecting the sign, and amount of cloud feedbacks. While satellite observations have been very useful in augmenting information on clouds, it is mostly related to cloud tops, and there is a lack of information on cloud base height (CBH). In this study, a unique record of CBH information was collected at 706 Automated Surface Observing System (ASOS) ceilometer stations to evaluate the ability of the North American Regional Reanalysis (NARR) model to correctly simulate similar information. It was found that NARR can capture the geographical distribution and the seasonal variation of CBH and cloud base frequency (CBF). On average, the CBF values of NARR were 7% fewer and the CBH values of NARR were 631 m lower than those from observations that span the distance from the surface to 7,600 m. NARR simulates CBH better in arid area in the west of the contiguous United States (CONUS) than in humid areas, where NARR frequently predicted cloud bases too low compared with observations. In the west coast area of the CONUS, the discontinuity between high cloud bases over arid inland areas and low marine cloud layers from the Pacific Ocean over coastal areas produced especially large deviations between the NARR‐simulated and ASOS‐observed CBHs.
Qualitative study of pharmacists’ perceptions of motivators, institutional supports and challenges towards career planning and advancement in a public tertiary hospital in Malaysia
Authors: Chang Chee‐Tao , HSS Amar-Singh , Hassali Mohamed Azmi
Published: November 2019

Background

Career planning and career advancement is related to more successful careers. Previous studies among pharmacists focused on overall job satisfaction but did not specifically explore their views regarding career planning and career advancement.

Aim

This study explored hospital pharmacists’ views on career planning and advancement.

Methods

This was a qualitative study conducted using a descriptive phenomenology approach. A semistructured interview guide was used to conduct face‐to‐face interviews with 11 hospital‐based pharmacists. All interviews were audio recorded and transcribed verbatim. The interviews took, on average, 20–30 min. A constant comparison method was used during data analysis to identify the saturation point, after which data collection was considered complete.

Results

Five themes were identified after the interviews: career planning, opinions regarding the subject matter expert advancement pathway, motivators for better career performance, barriers to career advancement and suggestions to overcome barriers. The findings revealed a lack of career planning among public pharmacists. Generally, the lack of a well‐established specialisation pathway for pharmacists in the public service was perceived as a major barrier to career advancement. A revamp of human resource management and the pharmacist advancement scheme in the public service was felt to be necessary.

Conclusion

The study findings highlight the current scenario of a lack of career planning among hospital pharmacists. Most pharmacists were motivated by a positive working environment and the nature of their job. Most felt that the current pharmacist employment scheme and lack of management support were major barriers to career advancement. Several recommendations and suggestions were provided to improve pharmacist career advancement in Malaysia.
Determination of lipid mediators in breast cancer cells using lyophilization‒supercritical fluid extraction online coupled with supercritical fluid chromatography‒quadrupole tandem mass spectrometry
Authors: Ye Fengying , Zhong Qisheng , Liang Yanshan , Zhou Ting
Published: November 2019

A lyophilization‒supercritical fluid extraction coupled with supercritical fluid chromatography‒quadrupole tandem mass spectrometry online method was developed for the determination of lipid mediators in breast cancer cells. Supercritical fluid extraction was applied to the cell samples for the first time due to the use of lyophilization. The conditions of supercritical fluid extraction and supercritical fluid chromatography‒quadrupole tandem mass spectrometry were investigated systematically. Under the optimized conditions, all the calibration curves for the lipid mediators showed good linearity (correlation coefficient > 0.99). The limits of detection and the limits of quantification were in the range of 0.190‒5.36 pg and 0.560‒16.2 pg, respectively. The recoveries were in the range of 70.3‒125%. The relative standard deviations of the precision ranged from 1.49‒18.7% and the accuracies were higher than 84%. Compared with liquid‒liquid extraction coupled with liquid chromatography and tandem mass spectrometry method, the present approach reduced the manual labor and obtained higher sensitivity as well as higher extraction recoveries for all 15 lipid mediators. Finally, the online method was applied to the quantification of lipid mediators in breast cancer cells and normal mammary epithelial cells. On the basis of the results, this lyophilization‒supercritical fluid extraction online coupled with supercritical fluid chromatography‒quadrupole tandem mass spectrometry method showed great promise in the analysis of lipid mediators in complex biological samples.
Targeting the NLRP3 Inflammasome in Neuroinflammation: Health Promoting Effects of Dietary Phytochemicals in Neurological Disorders
Authors: Hung Wei‐Lun , Ho Chi‐Tang , Pan Min‐Hsiung
Published: November 2019

Neurological disorders occur in the central and peripheral nervous system and include Alzheimer's disease, stroke, and spinal cord injury. Activation of the innate immune system inevitably occurs in all forms of neurological disorders. The NOD‐, LRR‐ and pyrin domain‐containing 3 (NLRP3) inflammasome is a multimolecular complex that can sense danger signals associated with neurological disorders. Assembly of the NLRP3 inflammasome promotes caspase‐1‐mediated interleukin‐1β and interleukin‐18 maturation in microglia, where neuroinflammation contributes to neurological disease development and progression. Thus, this review attempts to elucidate the current knowledge regarding NLRP3 inflammasome activation and its crucial role in the pathogenesis of neurological disorders. Recent scientific findings with respect to neuroprotective effects of dietary phytochemicals against NLRP3 inflammasome‐mediated neurological disorders summarized in this review suggest that modulation of the NLRP3 inflammasome assembly by plant‐derived phytochemicals could be a potential strategy for prevention or treatment of neurological disorders.
Interaction of Gut Microbiota and High‐Sodium, Low‐Potassium Diet in Altering Plasma Triglyceride Profiles Revealed by Lipidomics Analysis
Authors: Folz Jacob , Oh Young Taek , Blaženović Ivana , Richey Joyce , Fiehn Oliver , Youn Jang H.
Published: November 2019

Scope

High sodium and low potassium (HNaLK) intake increases the risk of cardiovascular disease (CVD) and metabolic syndrome. The authors investigate if the dietary minerals interact with the gut microbiota to alter circulating lipid profiles, implicated in CVD and metabolic syndrome.

Methods and results

Plasma samples from Wistar rats fed a control or HNaLK diet with or without antibiotic treatment (n = 7 each, a total of 28) are subjected to lipidomics analysis. Lipidomic data are then analyzed using statistical and bioinformatics tools, which detect numerous lipid species altered by the treatments, and consistently demonstrated interactions between the gut microbiota and the HNaLK diet in altering circulating lipids, mainly triglycerides (TGs). Two distinct TG groups differentially regulated by antibiotic treatment are identified. One group (cluster 1), representing the majority of TG species detected, is downregulated, whereas the other group (cluster 2) is upregulated by antibiotic treatment. Interestingly, cluster 2 TGs are also regulated by the diet. Cluster 2 TGs exhibit greater carbon‐chain length and double‐bond content and include TGs composed of very‐long‐chain polyunsaturated fatty acids, associated with reduced diabetes risk.

Conclusion

The HNaLK diet interacts with gut bacteria to alter plasma lipid profiles, which may be related to its health effects.
Simple ultra‐wider‐bandwidth MIMO antenna integrated by double decoupling branches and square‐ring ground structure
Authors: Tang Zhijun , Zhan Jie , Wu Xiaofeng , Xi Zaifang , Wu Shigang
Published: November 2019

A small and simple four‐port ultra‐wideband multiple input multiple output (UWB‐MIMO) antenna is designed in this letter. Each element of the designed antenna is composed of a circular patch, two smaller parasitic U‐shaped patches, a microstrip feed line, and a common square‐ring ground plane. To increase impedance bandwidth and reduce the size, this letter introduces the circular patch, two smaller parasitic U‐shaped patches, and the common square‐ring ground structure with multislits and the truncated corners. On the other hand, all the elements are identical and symmetrical, and neighboring elements are orthogonal to each other for improving the isolation. Furthermore, the double decoupling branches are added on diagonal position of the common square‐ring ground to further enhance the isolation and broaden the bandwidth. Therefore, the proposed UWB‐MIMO antenna is designed by using a novel and effective method of integrating the symmetric layout, orthogonal structure, four‐directional double branches decoupling, parasitic structure, truncated corners, and multislit techniques. Thus, the designed UWB‐MIMO antenna has the small physical size of 40 mm × 40 mm and obtains the ultra‐wider bandwidth of 3.0 to 18.0 GHz, higher isolation (>20 dB), smaller envelope correlation coefficient (
ρe < 0.03), and higher multiplex efficiency (
ηmux > −3.0 dB). Besides, the UWB‐MIMO antenna also achieves the acceptable peak realized gain, and stable radiating characteristics. Consequently, the designed antenna can be used for most UWB‐MIMO applications.
Knowledge‐based automated planning with three‐dimensional generative adversarial networks
Authors: Babier Aaron , Mahmood Rafid , McNiven Andrea L. , Diamant Adam , Chan Timothy C.Y.
Published: November 2019

Purpose

To develop a knowledge‐based automated planning pipeline that generates treatment plans without feature engineering, using deep neural network architectures for predicting three‐dimensional (3D) dose.

Methods

Our knowledge‐based automated planning (KBAP) pipeline consisted of a knowledge‐based planning (KBP) method that predicts dose for a contoured computed tomography (CT) image followed by two optimization models that learn objective function weights and generate fluence‐based plans, respectively. We developed a novel generative adversarial network (GAN)‐based KBP approach, a 3D GAN model, which predicts dose for the full 3D CT image at once and accounts for correlations between adjacent CT slices. Baseline comparisons were made against two state‐of‐the‐art deep learning–based KBP methods from the literature. We also developed an additional benchmark, a two‐dimensional (2D) GAN model which predicts dose to each axial slice independently. For all models, we investigated the impact of multiplicatively scaling the predictions before optimization, such that the predicted dose distributions achieved all target clinical criteria. Each KBP model was trained on 130 previously delivered oropharyngeal treatment plans. Performance was tested on 87 out‐of‐sample previously delivered treatment plans. All KBAP plans were evaluated using clinical planning criteria and compared to their corresponding clinical plans. KBP prediction quality was assessed using dose‐volume histogram (DVH) differences from the corresponding clinical plans.

Results

The best performing KBAP plans were generated using predictions from the 3D GAN model that were multiplicatively scaled. These plans satisfied 77% of all clinical criteria, compared to the clinical plans, which satisfied 67% of all criteria. In general, multiplicatively scaling predictions prior to optimization increased the fraction of clinical criteria satisfaction by 11% relative to the plans generated with nonscaled predictions. Additionally, these KBAP plans satisfied the same criteria as the clinical plans 84% and 8% more frequently as compared to the two benchmark methods, respectively.

Conclusions

We developed the first knowledge‐based automated planning framework using a 3D generative adversarial network for prediction. Our results, based on 217 oropharyngeal cancer treatment plans, demonstrated superior performance in satisfying clinical criteria and generated more realistic plans as compared to the previous state‐of‐the‐art approaches.
Consensus Recommendations for Optimizing Electronic Health Records for Nutrition Care
Authors: Kight Cassandra E. , Bouche Jean M. , Curry Angie , Frankenfield David , Good Katy , Guenter Peggi , Murphy Brian , Papoutsakis Constantina , Brown Richards Emily , Vanek Vincent W. , Wilk Deanne , Wootton Amy ,   Academy of Nutrition and Dietetics,   American Society for Parenteral and Enteral Nutrition,   the Association of Clinical Documentation Improvement Specialists
Published: November 2019

Provision of nutrition care is vital to the health and well‐being of any patient who enters the health care system, whether in the ambulatory, inpatient, or long‐term care setting. Interdisciplinary professionals—nurses, physicians, advanced practice providers, pharmacists, and dietitians—identify and treat nutrition problems or clinical conditions in each of these health care settings. The documentation of nutrition care in a structured format from screening and assessment to discharge allows communication of the nutrition treatment plans. The goal of this document is to provide recommendations to clinicians for working with an organization's Information Systems department to create tools for documentation of nutrition care in the electronic health record. These recommendations can also serve as guidance for health care organizations choosing and implementing health care software.
The implementation of the nursing process in lower‐income countries: An integrative review
Authors: Lotfi Mojgan , Zamanzadeh Vahid , Valizadeh Leila , Khajehgoodari Mohammad , Ebrahimpour Rezaei Mehdi , Khalilzad Mohammad Amin
Published: November 2019

Aims

This review study aimed to investigate the strategies for implementing the nursing process in the clinical practice and the assessment of the implementation rate of this process in clinical settings of lower‐income countries.

Design

An integrative review.

Method

The search was conducted of EMBASE, MEDLINE, CINAHL, Scopus and ISI databases from 1975–July 2018. Following the formation of the research team, two researchers independently selected the eligible studies; finally, 39 articles were approved by the research team for this study.

Results

The researchers identified three themes: Effects of implementing the NP in clinical settings, Development and application of electronic software in the NP and Factors affecting the implementation of the NP. This review revealed that nurses and nursing managers in hospitals are interested in implementing the nursing process in the form of widely and continuously. But the necessary infrastructure, such as manpower, electronically or manually tools, has not yet been provided, and the implementation of the nursing process is done either imperfectly or not done.
The spectrum of acute central nervous system symptoms during the treatment of childhood acute lymphoblastic leukaemia
Authors: Banerjee Joanna , Niinimäki Riitta , Lähteenmäki Päivi , Hed Myrberg Ida , Arola Mikko , Riikonen Pekka , Lönnqvist Tuula , Palomäki Maarit , Ranta Susanna , Harila‐Saari Arja , Taskinen Mervi
Published: November 2019

Background

Children with central nervous system (CNS) toxicity during therapy for acute lymphoblastic leukaemia (ALL) are at risk for treatment modifications, long‐term sequelae and even higher mortality. A better understanding of CNS symptoms and their complications improves the potential to prevent and treat them.

Methods

Patient files from 649 children treated with Nordic Society of Pediatric Hematology and Oncology ALL92 and ALL2000 protocols in Finland were reviewed retrospectively for any acute CNS symptom. Detailed data on symptoms, examinations and treatment of the underlying CNS complications were collected from the medical records. Disease‐related and outcome data were retrieved from the Nordic leukaemia registry.

Results

Altogether, 13% (86) of patients with ALL had acute CNS symptoms. Most symptoms (64%) occurred during the first 2 months of therapy. Posterior reversible encephalopathy syndrome was the most frequent complication (4.5%). Cerebrovascular events were diagnosed in 10 cases (1.6%), while methotrexate‐related stroke‐like syndrome (SLS) was observed in only one patient (0.2%). CNS symptoms due to systemic or unclear conditions, especially sepsis, were important for differential diagnosis. CNS leukaemia was associated with CNS symptoms (hazard ratio [HR] = 4.03; P = .003), and epilepsy was a common sequel of CNS complications (19%).

Conclusions

Acute CNS symptoms are common during ALL therapy, occurring mainly during the first 2 months of treatment. Patients with CNS leukaemia at diagnosis are at a higher risk for CNS toxicity. Despite intensive CNS‐directed methotrexate treatment, SLS was diagnosed extremely rarely in our series.
Buprenorphine pharmacotherapy for the management of neonatal abstinence syndrome in methadone‐exposed neonates
Authors: Taleghani Afshin A. , Isemann Barbara T. , Rice Ward R. , Ward Laura P. , Wedig Kathy E. , Akinbi Henry T.
Published: November 2019

We aimed to compare the outcomes of pharmacotherapy with either buprenorphine or methadone in infants treated for neonatal abstinence syndrome (NAS) secondary to intrauterine exposure to methadone. This is a multi‐center, retrospective cohort study to assess length of treatment (LOT), hospital length of stay (LOS), and cumulative opioid exposure between infants treated with either methadone or buprenorphine for NAS secondary to in utero exposure to methadone. Infants delivered at a gestational age ≥35 weeks and a maternal history of opioid‐use disorder and/or urine drug screen positive for methadone, and postnatal pharmacotherapy for NAS with either buprenorphine or methadone as first‐line opioid replacement therapy, were eligible. Median LOT, LOS, and cumulative opioid exposure were compared between buprenorphine‐ and methadone‐treated infants. A total of 156 infants (48 treated with buprenorphine and 108 with methadone) were identified. The median LOT and LOS for buprenorphine‐treated infants was 8 and 13 days compared with 15 and 20 days for methadone‐treated infants, respectively, P < .001 for both outcomes. Median cumulative opioid dose in morphine equivalents was 0.6 mg/kg for buprenorphine‐treated infants vs 1.05 mg/kg for methadone‐treated infants, P < .001. No adverse effects were noted among either group. Of infants treated with buprenorphine, 34 (71%) required the addition of adjunctive pharmacotherapy during the NICU stay, compared with 31 (32%) in the methadone‐treated group, P = .0008. However, significantly fewer infants treated with buprenorphine required continuation of therapy beyond discharge as compared with those treated with methadone. The difference is most likely a reflection of the protocols used by the sites. In infants that required pharmacotherapy for NAS secondary to intrauterine exposure to methadone, treatment with buprenorphine, compared with methadone therapy, was associated with better outcomes. If confirmed with prospective data, buprenorphine could be considered first‐line therapy for the two medication‐assisted treatment regimens recommended by the American College of Obstetricians and Gynecologists.
Quantitative Systems Pharmacology for Neuroscience Drug Discovery and Development: Current Status, Opportunities, and Challenges
Authors: Geerts Hugo , Wikswo John , van der Graaf Piet H. , Bai Jane P.F. , Gaiteri Chris , Bennett David , Swalley Susanne E. , Schuck Edgar , Kaddurah‐Daouk Rima , Tsaioun Katya , Pelleymounter Mary
Published: November 2019

The substantial progress made in the basic sciences of the brain has yet to be adequately translated to successful clinical therapeutics to treat central nervous system (CNS) diseases. Possible explanations include the lack of quantitative and validated biomarkers, the subjective nature of many clinical endpoints, and complex pharmacokinetic/pharmacodynamic relationships, but also the possibility that highly selective drugs in the CNS do not reflect the complex interactions of different brain circuits. Although computational systems pharmacology modeling designed to capture essential components of complex biological systems has been increasingly accepted in pharmaceutical research and development for oncology, inflammation, and metabolic disorders, the uptake in the CNS field has been very modest. In this article, a cross‐disciplinary group with representatives from academia, pharma, regulatory, and funding agencies make the case that the identification and exploitation of CNS therapeutic targets for drug discovery and development can benefit greatly from a system and network approach that can span the gap between molecular pathways and the neuronal circuits that ultimately regulate brain activity and behavior. The National Institute of Neurological Disorders and Stroke (NINDS), in collaboration with the National Institute on Aging (NIA), National Institute of Mental Health (NIMH), National Institute on Drug Abuse (NIDA), and National Center for Advancing Translational Sciences (NCATS), convened a workshop to explore and evaluate the potential of a quantitative systems pharmacology (QSP) approach to CNS drug discovery and development. The objective of the workshop was to identify the challenges and opportunities of QSP as an approach to accelerate drug discovery and development in the field of CNS disorders. In particular, the workshop examined the potential for computational neuroscience to perform QSP‐based interrogation of the mechanism of action for CNS diseases, along with a more accurate and comprehensive method for evaluating drug effects and optimizing the design of clinical trials. Following up on an earlier white paper on the use of QSP in general disease mechanism of action and drug discovery, this report focuses on new applications, opportunities, and the accompanying limitations of QSP as an approach to drug development in the CNS therapeutic area based on the discussions in the workshop with various stakeholders.
Aggregative Characteristics of Nanocarbon and of a Stabilizing Surfactant in the Aqueous‐Polymer Matrix versus Optical Power Limiting Performance
Authors: Vlasov Andrey Yu. , Venediktova Anastasia V. , Ivanov Pavel V. , Nikolaeva Alexandra L. , Anufrikov Yuri A. , Venediktov Vladimir Yu.
Published: November 2019

By the example of single‐walled carbon nanotubes (SWCNT) stabilized by sodium deoxycholate in “water + polyvinyl alcohol” medium, the impact of aggregative peculiarities of a stabilizer on the efficacy of dispersing the photoactive agent is investigated. This feature is collated with respect to alternative common anionic surfactants in SWCNT suspensions. The temporal stability of dispersions of the nanocarbon (SWCNT vs carbon black) stabilized by sodium deoxycholate in a medium with controlled viscosity is juxtaposed. The optical power limiting characteristics of these dispersions versus concentration of a polymer dopant (0–3 wt%) is also monitored. In particular, the resistibility of such materials regarding bleaching phenomena in a pulse‐periodic regime (pulse repetition rate 10 Hz) of nanosecond laser irradiation (wavelength 532 nm) is addressed. It is demonstrated that optimal concentration of a polymer dopant (≈1.0 wt%) ensures elimination of bleaching with respect to the irradiation conditions studied.
Methane dehydrogenation on Cu and Ni surfaces with low and moderate oxygen coverage
Authors: Rahmani Didar Behnaz , Balbuena Perla B.
Published: November 2019

First‐principles density functional theory calculations are carried out to evaluate energy barriers and mechanisms for the dehydrogenation reactions of CH4 on clean and oxygen‐covered surfaces of Cu (111) and Ni (111) with low and moderate oxygen coverage. In the presence of oxygen, two possible pathways have been evaluated. The more likely pathway, which is further analyzed, is that CH4 loses an H to the surface O. Results from this pathway agree with previous findings showing that oxygen promotes CH4 dissociation on Cu (111) and hinders that on Ni (111). In addition, our results show lower energy barriers on Cu with higher oxygen coverages up to 0.38 monolayer. However, such an increase in oxygen coverage did not show any favorable effect for CH4 dissociation on Ni (111). The findings are analyzed through electronic factors revealed by charge analysis and density of states.
Lesion positioning method of a CT‐guided surgical robotic system for minimally invasive percutaneous lung
Authors: Zhang Tie‐Feng , Fu Zhuang , Wang Yao , Shi Wei‐Yi , Chen Guang‐Biao , Fei Jian
Published: November 2019

Background

Robot‐assisted puncture has gradually attracted more attention and practical clinical application. The lesion positioning and the needle positioning are the basis to ensure the accuracy of puncture and the key techniques in insertion operation.

Methods

A lesion positioning method is established which is realized only by the robot‐CT system without using external positioning system, and an omnidirectional needle positioning method is also developed and realized by using VRCM, in order to make the puncture needle always keep pointing to the lesion point. A CT‐guided surgical robotic system used for minimally invasive percutaneous lung is designed and the physical prototype is manufactured, to perform in‐vitro experiments, thereby to validate the effectiveness of the lesion positioning method and the feasibility of omnidirectional needle positioning method.

Results

The accuracy of established lesion positioning method based on three non‐collinear markers is within 3 mm, which is similar to that of the least squares method based on the five non‐coplanar markers, but the positioning efficiency can be improved by about 40%, and the non‐collinearity of markers is easier to be satisfied than non‐coplanarity in practical applications. The average calculation error of the established positioning method is 0.997 mm. Moreover, the omnidirectional positioning of the puncture needle under the designed surgical robot is feasible.

Conclusions

The designed surgical robot has good control accuracy and it can satisfy the requirements for use. The established lesion positioning method can provide a good precision basis for robot‐assisted puncture surgery. The suitable insertion point and insertion posture can be determined by the developed omnidirectional needle positioning method. This study can provide theoretical reference for further study of path planning or autonomous positioning.
Integrative and perturbation-based analysis of the transcriptional dynamics of TGFβ/BMP system components in transition from embryonic stem cells to neural progenitors
Authors: Dries Ruben , Stryjewska Agata , Coddens Kathleen , Okawa Satoshi , Notelaers Tineke , Birkhoff Judith , Dekker Mike , Verfaillie Catherine M. , Sol Antonio , Mulugeta Eskeatnaf , Conidi Andrea , Grosveld Frank G. , Huylebroeck Danny
Published: November 2019

Cooperative actions of extrinsic signals and cell-intrinsic transcription factors alter gene regulatory networks enabling cells to respond appropriately to environmental cues. Signaling by transforming growth factor type β (TGFβ) family ligands (eg, bone morphogenetic proteins [BMPs] and Activin/Nodal) exerts cell-type specific and context-dependent transcriptional changes, thereby steering cellular transitions throughout embryogenesis. Little is known about coordinated regulation and transcriptional interplay of the TGFβ system. To understand intrafamily transcriptional regulation as part of this system's actions during development, we selected 95 of its components and investigated their mRNA-expression dynamics, gene-gene interactions, and single-cell expression heterogeneity in mouse embryonic stem cells transiting to neural progenitors. Interrogation at 24 hour intervals identified four types of temporal gene transcription profiles that capture all stages, that is, pluripotency, epiblast formation, and neural commitment. Then, between each stage we performed esiRNA-based perturbation of each individual component and documented the effect on steady-state mRNA levels of the remaining 94 components. This exposed an intricate system of multilevel regulation whereby the majority of gene-gene interactions display a marked cell-stage specific behavior. Furthermore, single-cell RNA-profiling at individual stages demonstrated the presence of detailed co-expression modules and subpopulations showing stable co-expression modules such as that of the core pluripotency genes at all stages. Our combinatorial experimental approach demonstrates how intrinsically complex transcriptional regulation within a given pathway is during cell fate/state transitions.
Cows in Contested Fields
Authors: Valpey Kenneth R.
Published: November 2019

Increasing social and political conflict in the late nineteenth century leads to the rise of the Cow Protection movement, continuing in various forms to the present day. Chapter 2 introduces four prominent figures variously related to this movement (Swami Dayananda Saraswati, M. K. Gandhi, B. R. Ambedkar, and Swami Prabhupada) to locate important features of the modern intellectual terrain on which a controversy has unfolded over textual interpretation: Was animal sacrifice actually performed in ancient Vedic rites, and if so, what relation did those practices have with scriptural admonitions to practice nonviolence (ahimsa)? Differing narratives impact current politics and treatment of cows in particular in India, with rhetoric often clouding balanced ethical thinking.