bluuebunny/crossref_metadata_2025 huggingface dataset:
Denoising of diffusion MRI improves peripheral nerve conspicuity and reproducibility
Authors: Sneag Darryl B. , Zochowski Kelly C. , Tan Ek T. , Queler Sophie C. , Burge Alissa , Endo Yoshimi , Lin Bin , Fung Maggie , Shin Jaemin
Published: October 2019

Background

Quantitative diffusion MRI is a promising technique for evaluating peripheral nerve integrity but low signal‐to‐noise ratio (SNR) can impede measurement accuracy.

Purpose

To evaluate principal component analysis (PCA) and generalized spherical deconvolution (genSD) denoising techniques to improve within‐subject reproducibility and peripheral nerve conspicuity.

Study Type

Prospective.

Subjects

Seven healthy volunteers and three peripheral neuropathy patients.

Field Strength/Sequence

3T/multiband single‐shot echo planar diffusion sequence using multishell 55‐direction scheme.

Assessment

Images were processed using four methods: "original" (no denoising), "average" (10 repetitions), "PCA‐only," and "PCA + genSD." Tibial and common peroneal nerve segmentations and masks were generated from volunteer diffusion data. Quantitative (SNR and contrast‐to‐noise ratio [CNR]) values were calculated. Three radiologists qualitatively evaluated nerve conspicuity for each method. The two denoising methods were also performed in three patients with peripheral neuropathies.

Statistical Tests

For healthy volunteers, calculations included SNR and CNRFA (computed using FA values). Coefficient of variation (CV%) of CNRFA quantified within‐subject reproducibility. Groups were compared with two‐sample t‐tests (significance P < 0.05; two‐tailed, Bonferroni‐corrected). Odds ratios (ORs) quantified the relative rates of each of three radiologists confidently identifying a nerve, per slice, for the four methods.

Results

"PCA + genSD" yielded the highest SNR (meanoverall = 14.83 ± 1.99) and tibial and common peroneal nerve CNRFA (meantibial = 3.45, meanperoneal = 2.34) compared to "original" (P
SNR < 0.001; P
CNR = 0.011) and "PCA‐only" (P
SNR < 0.001, P
CNR < 0.001). "PCA + genSD" had higher within‐subject reproducibility (low CV%) for tibial (6.04 ± 1.98) and common peroneal nerves (8.27 ± 2.75) compared to "original" and "PCA‐only." The mean FA was higher for "original" than "average" (P < 0.001), but did not differ significantly between "average" and "PCA + genSD" (P = 0.14). "PCA + genSD" had higher tibial and common peroneal nerve conspicuity than "PCA‐only" (ORtibial = 2.50, P < 0.001; ORperoneal = 1.86, P < 0.001) and "original" (ORtibial = 2.73, P < 0.001; ORperoneal = 2.43, P < 0.001).

Data Conclusion

PCA + genSD denoising method improved SNR, CNRFA, and within‐subject reproducibility (CV%) without biasing FA and nerve conspicuity. This technique holds promise for facilitating more reliable, unbiased diffusion measurements of peripheral nerves.

Level of Evidence: 2

Technical Efficacy Stage: 1

J. Magn. Reson. Imaging 2020;51:1128–1137.
Valvular imaging in the era of feature‐tracking: A slice‐following cardiac MR sequence to measure mitral flow
Authors: Seemann Felicia , Heiberg Einar , Carlsson Marcus , Gonzales Ricardo A. , Baldassarre Lauren A. , Qiu Maolin , Peters Dana C.
Published: October 2019

Background

In mitral valve dysfunction, noninvasive measurement of transmitral blood flow is an important clinical examination. Flow imaging of the mitral valve, however, is challenging, since it moves in and out of the image plane during the cardiac cycle.

Purpose

To more accurately measure mitral flow, a slice‐following MRI phase contrast sequence is proposed. This study aimed to implement such a sequence, validate its slice‐following functionality in a phantom and healthy subjects, and test its feasibility in patients with mitral valve dysfunction.

Study Type

Prospective.

Phantom and Subjects

The slice‐following functionality was validated in a cone‐shaped phantom by measuring the depicted slice radius. Sixteen healthy subjects and 10 mitral valve dysfunction patients were enrolled at two sites.

Field Strength/Sequence

1.5T and 3T gradient echo cine phase contrast.

Assessment

A single breath‐hold retrospectively gated sequence using offline feature‐tracking of the mitral valve was developed. Valve displacements were measured and imported to the scanner, allowing the slice position to change dynamically based on the cardiac phase. Mitral valve imaging was performed with slice‐following and static imaging planes. Validation was performed by comparing mitral stroke volume with planimetric and aortic stroke volume.

Statistical Tests

Measurements were compared using linear regression, Pearson's R, parametric paired t‐tests, Bland–Altman analysis, and intraclass correlation coefficient (ICC).

Results

Phantom experiments confirmed accurate slice displacements. Slice‐following was feasible in all subjects, yielding physiologically accurate mitral flow patterns. In healthy subjects, mitral and aortic stroke volumes agreed, with ICC = 0.72 and 0.90 for static and slice‐following planes; with bias ±1 SDs 23.2 ± 13.2 mls and 8.4 ± 10.8 mls, respectively. Agreement with planimetry was stronger, with ICC = 0.84 and 0.96; bias ±1 SDs 13.7 ± 13.7 mls and –2.0 ± 8.8 mls for static and slice‐following planes, respectively.

Data Conclusion

Slice‐following outperformed the conventional sequence and improved the accuracy of transmitral flow, which is important for assessment of diastolic function and mitral regurgitation.

Level of Evidence: 2

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2020;51:1412–1421.
Extracellular matrix alterations in low‐grade lung adenocarcinoma compared with normal lung tissue by imaging mass spectrometry
Authors: Angel Peggi M. , Bruner Evelyn , Bethard Jennifer , Clift Cassandra L. , Ball Lauren , Drake Richard R. , Feghali‐Bostwick Carol
Published: October 2019

Lung adenocarcinoma (LUAD) is the second most common cancer, affecting both men and women. Fibrosis is a hallmark of LUAD occurring throughout progression with excess production of extracellular matrix (ECM) components that lead to metastatic cell processes. Understanding the ECM cues that drive LUAD progression has been limited due to a lack of tools that can access and report on ECM components within the complex tumor microenvironment. Here, we test whether low‐grade LUAD can be distinguished from normal lung tissue using a novel ECM imaging mass spectrometry (ECM IMS) approach. ECM IMS analysis of a tissue microarray with 20 low‐grade LUAD tissues and 20 normal lung samples from 10 patients revealed 25 peptides that could discriminate between normal and low‐grade LUAD using area under the receiver‐operating curve (AUC) ≥0.7, P value ≤.001. Principal component analysis demonstrated that 62.4% of the variance could be explained by sample origin from normal or low‐grade tumor tissue. Additional work performed on a wedge resection with moderately differentiated LUAD demonstrated that the ECM IMS analytical approach could distinguish LUAD spectral features from spectral features of normal adjacent lung tissue. Conventional liquid chromatography with tandem mass spectrometry (LC‐MS/MS) proteomics demonstrated that specific sites of hydroxylation of proline (HYP) were a main collagen post translational modification that was readily detected in LUAD. A distinct peptide from collagen 3A1 modified by HYP was increased 3.5 fold in low‐grade LUAD compared with normal lung tissue (AUC 0.914, P value <.001). This suggests that regulation of collagen proline hydroxylation could be an important process during early LUAD fibrotic deposition. ECM IMS is a useful tool that may be used to define fibrotic deposition in low‐grade LUAD.
Mass spectrometry imaging of endogenous metabolites in response to doxorubicin in a novel 3D osteosarcoma cell culture model
Authors: Palubeckaitė Ieva , Crooks Lucy , Smith David P. , Cole Laura M. , Bram Heijs , Le Maitre Christine , Clench Malcolm R. , Cross Neil A.
Published: October 2019

Three‐dimensional (3D) cell culture is a rapidly emerging field, which mimics some of the physiological conditions of human tissues. In cancer biology, it is considered a useful tool in predicting in vivo chemotherapy responses, compared with conventional two‐dimensional (2D) cell culture. We have developed a novel 3D cell culture model of osteosarcoma composed of aggregated proliferative tumour spheroids, which shows regions of tumour heterogeneity formed by aggregated spheroids of polyclonal tumour cells. Aggregated spheroids show local necrotic and apoptotic regions and have sizes suitable for the study of spatial distribution of metabolites by mass spectrometry imaging (MSI). We have used this model to perform a proof‐of‐principle study showing a heterogeneous distribution of endogenous metabolites that colocalise with the necrotic core and apoptotic regions in this model. Cytotoxic chemotherapy (doxorubicin) responses were significantly attenuated in our 3D cell culture model compared with those of standard cell culture, as determined by resazurin assay, despite sufficient doxorubicin diffusion demonstrated by localisation throughout the 3D constructs. Finally, changes to the distribution of endogenous metabolites in response to doxorubicin were readily detected by MSI. Principal component analysis identified 50 metabolites which differed most in their abundance between treatment groups, and of these, 10 were identified by both in‐software t test and mixed‐effects analysis of variance (ANOVA). Subsequent independent MSIs of identified species were consistent with principle component analysis findings. This proof‐of‐principle study shows for the first time that chemotherapy‐induced changes in metabolite abundance and distribution may be determined in 3D cell culture by MSI, highlighting this method as a potentially useful tool in the elucidation of chemotherapy responses as an alternative to in vivo testing.
Potential contribution of winter dominant atmospheric mode over the mid‐latitude Eurasia to the prediction of subsequent spring Arctic Oscillation
Authors: Han Shuangze , Sun Jianqi
Published: October 2019

Spring Arctic Oscillation (AO) has been revealed to exert a great impact on the Northern Hemispheric climate; however, its seasonal prediction skill has been limited so far. In this paper, we find that the dominant mode of the winter 500‐hPa geopotential height anomalies over the mid‐latitude Eurasia has a close connection with the succeeding spring AO. The analysis on the physical processes indicates that the troposphere–stratosphere interaction plays an important role in the connection between the two. This predominant atmospheric mode in the mid‐latitude Eurasia during winter can change the vertical wave activity and lead to an anomalous stratospheric polar vortex. Thereafter, the signal of the anomalous stratospheric polar vortex propagates downward to troposphere in the subsequent spring, consequently inducing the anomalous AO pattern in the troposphere. The results in this study imply that this previous winter leading atmospheric mode over the mid‐latitude Eurasia may supply a potential source for a spring AO's prediction.
Early Parenteral Nutrition in Critically Ill Children Not Receiving Early Enteral Nutrition Is Associated With Significantly Higher Mortality
Authors: Goday Praveen S. , Kuhn Evelyn M. , Mikhailov Theresa A.
Published: October 2019

Background

To determine whether early parenteral nutrition (PN) (25% of goal energy within 48 hours of PICU admission) is associated with poorer outcomes in children receiving no enteral nutrition (EN).

Methods

Multicenter retrospective study of patients aged 1 month to 18 years who had a PICU length of stay (PLOS) >96 hours. We obtained weight, sex, pediatric index of mortality 2 score (PIM‐2), PLOS, duration of mechanical ventilation (DMV), mortality data, and nutrition intake data. Logistic and mixed model regression analysis were used to compare data.

Results

2069 patients (53.2% male, median age 6.61 years) received no EN in the first 4 days. Children receiving early PN were more likely to die than those who did not when adjusted for PIM‐2, propensity score, and center (odds ratio = 2.10 [1.41–3.13], median [IQR]; P = 0.0003). The unadjusted PLOS (9.48 [5.94–18.19], and unadjusted DMV (6.73 [3.48–13.98]) for patients receiving early PN were both significantly longer than those who did not (6.75 [4.95–11.65]; P < 0.0001 and 4.9 [1.88–10.19]; P = 0.009, respectively). When adjusted for PIM‐2, center, percentage of energy from protein, and age, the PLOS and DMV for those receiving early PN did not differ from those who did not (P = 0.14 and P = 0.76, respectively).

Conclusion

In children with PLOS >96 hours receiving no EN for 4 days, early PN is strongly associated with higher mortality but not with differences in PLOS or DMV.
Identification and determination of chemical constituents of Citrus reticulata semen through ultra high performance liquid chromatography combined with Q Exactive Orbitrap tandem mass spectrometry
Authors: Zheng GuoDong , Yang XiuJuan , Chen BaiZhong , Chao YingXin , Hu PingJun , Cai Yi , Wu Bo , Wei MinYan
Published: October 2019

Citrus reticulata semen, a traditional Chinese medicinal material, has desirable medicinal and dietary properties. In this study, a method combining ultra high performance liquid chromatography with Q Exactive Orbitrap tandem mass spectrometry was established and validated for the identification and analysis of the chemical components of C. reticulata semen for the first time. The evaluation of different retention times and fragmentation characteristics, as well as comparative analysis with the literature, resulted in the identification of 35 chemical constituents, including 21 flavonoids and 14 other compounds. The 21 flavonoids derived from C. reticulata semen were reported for the first time. Seven of the chemical components of C. reticulata semen were quantitatively analyzed using the developed method under the optimal conditions. The results showed that the content of limonin, hesperidin, nobiletin, synephrine, tangeretin, 3,5,6,7,8,3′,4′‐heptamethoxyflavone and 5‐hydroxide‐6,7,8,3′,4′‐pentamethoxyflavone in C. reticulata semen was 11.1666, 0.0404, 0.0092, 0.0255, 0.0087, 0.0010, and 0.0008 mg/g, respectively. This study demonstrated that the ultra high performance liquid chromatography Q Exactive Orbitrap mass spectrometry based method can be used to rapidly and reliably analyze the chemical constituents of C. reticulata semen. These results provide a scientific basis for further studies of C. reticulata semen.
Microfluidic chip electrophoresis for biochemical analysis
Authors: Ou Xiaowen , Chen Peng , Huang Xizhi , Li Shunji , Liu Bi‐Feng
Published: October 2019

Microfluidic chip electrophoresis has been widely employed for separation of various biochemical species owing to its advantages of low sample consumption, low cost, fast analysis, high throughput, and integration capability. In this article, we reviewed the development of four different modes of microfluidics‐based electrophoresis technologies including capillary electrophoresis, gel electrophoresis, dielectrophoresis, and field (electric) flow fractionation. Coupling detection schemes on microfluidic electrophoresis platform were also reviewed such as optical, electrochemical, and mass spectrometry method. We further discussed the innovative applications of microfluidic electrophoresis for biomacromolecules (nucleic acids and proteins), biochemical small molecules (amino acids, metabolites, ions, etc.), and bioparticles (cells and pathogens) analysis. The future direction of microfluidic chip electrophoresis was predicted.
Primary Laryngectomy Versus Salvage Laryngectomy: A Comparison of Outcomes in the Chemoradiation Era
Authors: Sullivan Christopher Blake , Ostedgaard Katharine L. , Al‐Qurayshi Zaid , Pagedar Nitin A. , Sperry Steven M.
Published: October 2019

Objective

To compare primary total laryngectomy (TL) versus salvage TL and analyze the functional outcomes, complications, recurrence rates, and survival.

Study Design

Case series with chart review.

Setting

Tertiary care center.

Subjects and Methods

Fifteen‐year retrospective analysis of 208 patients with laryngeal squamous cell carcinoma treated by TL was completed. Outcome measures included survival, swallowing rehabilitation, speech rehabilitation, complications, and assessment of comorbidity. Survival estimates were analyzed with Kaplan‐Meier method, and regression analysis utilized the Cox proportional hazards model.

Results

Alaryngeal speech was not significantly different between primary TL and salvage TL, 68% versus 82% (P = 0.14). Comparing primary and salvage TL, the perioperative complication rate was 33% versus 48% (P = 0.036). Thirty‐six percent of primary TL patients had recurrence compared to 26% of salvage patients. Five‐year overall survival rates between primary TL and salvage TL were not significantly different (P = 0.68). Comorbidity was an independent predictor of survival.

Conclusions

Development of a functional voice was not significantly different between salvage and primary TL patients, with a majority achieving alaryngeal speech. Perioperative complications were more prevalent in the salvage TL group. Recurrence and survival are significantly associated with comorbidity status.

Level of Evidence

4 Laryngoscope, 130:2179–2185, 2020
The prevalence of cognitive impairment in laryngology treatment–seeking patients
Authors: Leclerc Andrée‐Anne , Gillespie Amanda I. , Tadic Stasa D. , Smith Libby J. , Rosen Clark A.
Published: October 2019

Objectives/Hypothesis

The incidence of cognitive impairment (CI) in the elderly general population is 10% to 20%. The incidence of CI in the elderly laryngology treatment–seeking population is unknown, and CI may impact decision making for elective medical/surgical treatment and negatively impact the outcome of voice/swallowing therapy. We sought to determine the prevalence of CI in elderly patients who are seeking laryngology care and to evaluate the feasibility of administering a cognitive screening instrument.

Study Design

Prospective, Cross‐sectional.

Methods

One hundred fifty patients (≥65 years old) without a previous diagnosis of CI, seeking laryngology evaluation, were administered the Montreal Cognitive Assessment (MoCA) test by a trained physician. Other members of the clinical team were blinded to the MoCA results.

Results

Twenty‐five percent of participants obtained a score diagnostic for at least mild CI. The results showed a correlation between the MoCA scores and 1) the time needed to complete the test, 2) participant age, and 3) participant education level. No differences were observed between gender, alcohol consumption, or use of medications that can affect cognition and MoCA score.

Conclusion

One in four elderly laryngology treatment‐seeking patients were found to have undiagnosed CI. This finding warrants consideration for CI screening for these patients being evaluated for voice therapy and elective surgery. Treatment decision making in this population may benefit from additional family involvement.

Level of Evidence

2c Laryngoscope, 130: 2003–2007, 2020
Direct‐To‐Consumer Advertising of Over‐the‐Counter Sinonasal Remedies: A History of Mixed Messages
Authors: McCoul Edward D.
Published: October 2019

Sinus, cold, and allergy remedies comprise the most widely used sector of the over‐the‐counter (OTC) drug market. Direct‐to‐consumer advertising (DTCA) of pharmaceutical products has increased over the past 30 years, including the promotion of OTC drugs. The influence of DTCA on OTC sinonasal remedies comprises several positive and negative effects. Favorable aspects of this influence include empowerment and promotion of autonomy among patients, avoidance of low‐value clinical encounters, self‐directed education, and decreased healthcare expenditures. This is balanced by potential concerns, including the lack of rigorous regulation of OTC drugs, the burden of self‐diagnosis, the risk of unsupervised use resulting in adverse effects or drug interactions, and redistribution of pharmacy costs to the consumer. Despite the proliferation of product options and consumer‐directed information, healthcare utilization and cost of treating sinonasal disease remains high. Moreover, the availability of OTC sinonasal remedies and exposure to DTCA has had mixed effects without apparent overall benefit to patient and consumer health. Laryngoscope, 130:2114–2119, 2020
Hypermanganesemia with Dystonia 1: A Novel Mutation and Response to Iron Supplementation
Authors: Yapici Zuhal , Tuschl Karin , Eraksoy Mefkure
Published: October 2019

View Supplementary Video 1
HSD10 mitochondrial disease: p.Leu122Val variant, mild clinical phenotype, and founder effect in French‐Canadian patients from Quebec
Authors: Waters Paula J. , Lace Baiba , Buhas Daniela , Gravel Serge , Cyr Denis , Boucher Renée‐Myriam , Bernard Geneviève , Lévesque Sébastien , Maranda Bruno
Published: October 2019

Background

HSD10 mitochondrial disease (HSD10MD), originally described as a deficiency of 2‐methyl‐3‐hydroxybutyryl‐CoA dehydrogenase (MHBD), is a rare X‐linked disorder of a moonlighting protein encoded by the HSD17B10. The diagnosis is usually first suspected on finding elevated isoleucine degradation metabolites in urine, reflecting decreased MHBD activity. However, it is now known that clinical disease pathogenesis reflects other independent functions of the HSD10 protein; particularly its essential role in mitochondrial transcript processing and tRNA maturation. The classical phenotype of HSD10MD in affected males is an infantile‐onset progressive neurodegenerative disorder associated with severe mitochondrial dysfunction.

Patients, Methods, and Results

In four unrelated families, we identified index patients with MHBD deficiency, which implied a diagnosis of HSD10MD. Each index patient was independently investigated because of neurological or developmental concerns. All had persistent elevations of urinary 2‐methyl‐3‐hydroxybutyric acid and tiglylglycine. Analysis of HSD17B10 identified a single missense variant, c.364C>G, p.Leu122Val, in each case. This rare variant (1/183336 alleles in gnomAD) was previously reported in one Dutch patient and was described as pathogenic. The geographic origins of our families and results of haplotype analysis together provide evidence of a founder effect for this variant in Quebec. Notably, we identified an asymptomatic hemizygous adult male in one family, while a second independent genetic disorder contributed substantially to the clinical phenotypes observed in probands from two other families.

Conclusion

The phenotype associated with p.Leu122Val in HSD17B10 currently appears to be attenuated and nonprogressive. This report widens the spectrum of phenotypic severity of HSD10MD and contributes to genotype–phenotype correlation. At present, we consider p.Leu122Val a “variant of uncertain significance.” Nonetheless, careful follow‐up of our patients remains advisable, to assess long‐term clinical course and ensure appropriate management. It will also be important to identify other potential patients in our population and to characterize their phenotype.
Unconditionally maximum principle preserving finite element schemes for the surface Allen–Cahn type equations
Authors: Xiao Xufeng , He Ruijian , Feng Xinlong
Published: October 2019

In this paper, we present two types of unconditionally maximum principle preserving finite element schemes to the standard and conservative surface Allen–Cahn equations. The surface finite element method is applied to the spatial discretization. For the temporal discretization of the standard Allen–Cahn equation, the stabilized semi‐implicit and the convex splitting schemes are modified as lumped mass forms which enable schemes to preserve the discrete maximum principle. Based on the above schemes, an operator splitting approach is utilized to solve the conservative Allen–Cahn equation. The proofs of the unconditionally discrete maximum principle preservations of the proposed schemes are provided both for semi‐ (in time) and fully discrete cases. Numerical examples including simulations of the phase separations and mean curvature flows on various surfaces are presented to illustrate the validity of the proposed schemes.
Oral stress and paleodiet changes among hunter‐gatherers from Negro River (northern Patagonia, Argentina) during the late Holocene
Authors: Flensborg Gustavo , Serna Alejandro , Prates Luciano
Published: October 2019

The objective of this work is to evaluate temporal variation of dento‐alveolar lesions in hunter‐gatherer groups who inhabited the middle course of the Negro River during the late Holocene (ca. 3000‐750 years BP) in order to discuss cultural practices and changes in the paleodiet. Caries, dental calculus, periodontal disease, periapical lesions, antemortem tooth loss, tooth wear, dislocation, and osteoarthrosic lesions in the temporomandibular joint were analysed. The sample is represented by 567 teeth and 547 alveoli, corresponding to 32 adult and subadult individuals, who were divided into two periods for comparative purposes: pre‐1000 and post‐1000 BP. The results indicate a low prevalence of oral lesions without differences between sex and age. In the pre‐1000 BP period, there is a larger frequency of antemortem tooth loss, parafunctional wear of the anterior teeth, dental dislocations, and osteoarthrosis in the mandibular condyles compared with the post‐1000 period. This tendency indicates that the individuals would have been exposed to greater stress in chewing. However, the variations were not significant, so there is no clear evidence of changes in the diet and particularly in carbohydrate and plant intake through the late Holocene. Severe tooth wear is the main factor that caused some pathologies (e.g., antemortem tooth loss), and limited the development of others (e.g., caries). The results obtained here agree with other microregions from northeastern Patagonia and differ from Humid Pampas, eastern Pampa‐Patagonian transition, and lower course of the Negro River due to differences in carbohydrate consumption in the last ca. 1000 years BP.
A Brief Neuropsychological Battery for Measuring Cognitive Functions Associated with Obesity
Authors: Hovens Iris B. , Dalenberg Jelle R. , Small Dana M.
Published: October 2019

Objective

Although ample evidence links obesity to cognitive dysfunction, the trajectory of cognitive change, the underlying mechanisms, and the involvement of related factors, such as metabolic disease and diet, remain unclear. To support further investigations of BMI and cognition, this study aimed to create a concise test battery to be used in future trials.

Methods

Twenty neurocognitive measures were regressed on BMI in the Human Connectome Project Healthy Young Adult S1200 data release by using linear mixed models and by adjusting for major confounders. Measures were then identified by using least absolute shrinkage and selection operator regression analysis to select tests most strongly associated with BMI. To guide further test selection, the explained variance for each variable was visualized in the final model.

Results

BMI was negatively associated with seven neurocognitive measures. Variable selection yielded a model that included years of education and, in order of model weight, delay discounting, the relational task, the Penn Progressive Matrices test, the oral reading recognition test, the Variable Short Penn Line Orientation test, and the Penn Word Memory test.

Conclusions

This research resulted in an approximate 40‐minute test battery for the BMI‐cognition relationship in young adults that can be used in trials investigating the interrelationship between obesity and cognitive performance.
Iron deficiency in children at the time of initial neuroblastoma diagnosis
Authors: Fan Hongjun , Su Yan , Duan Chao , Zhao Qian , Wang Xisi , Zhu Shuai , Zhao Wen , Jin Mei , Ma Xiaoli
Published: October 2019

Importance

There is a high incidence of iron deficiency in children worldwide. Notably, however, while iron deficiency is the most common cause of anemia, little is known about the prevalence and different types of iron deficiency in neuroblastoma patients.

Objective

The aim of the present study was to investigate the prevalence of iron deficiency in patients newly diagnosed with neuroblastoma.

Methods

A total of 195 newly diagnosed neuroblastoma patients from November 2015 to January 2018 were analyzed retrospectively. The survival analysis was estimated by the Kaplan‐Meier method.

Results

Of the 195 neuroblastoma patients included in the study, 121 (62.1%) had iron deficiency, 55 (28.2%) had absolute iron deficiency, and 66 (33.9%) had functional iron deficiency. Being aged ≥ 18 months, tumor originating in the abdomen, International Neuroblastoma Risk Group Staging System M, high‐risk neuroblastoma, lactate dehydrogenase ≥ 1500 U/L, neuron‐specific enolase ≥ 100 U/L, unfavorable histologic category, MYCN amplification, chromosome 1p loss, and bone marrow metastasis were associated with significantly higher rates of functional iron deficiency (P < 0.05).

Interpretation

Functional iron deficiency at the time of initial neuroblastoma diagnosis predicted lower event‐free survival. Long‐term effects of iron supplementation in neuroblastoma patients with different types of iron deficiency need to be further studied.
Design of a novel co‐electrospinning system with flat spinneret for producing helical nanofibers
Authors: Zhao Tienan , Zheng Yuansheng , Zeng Yongchun
Published: October 2019

A kind of biomimetic fibers of helical structures at nanoscale has attracted increasing interest. In this study, a novel co‐electrospinning setup with a designed flat spinneret, used for the fabrication of helical nanofibers, is reported in this study. Poly(m‐phenylene isophthalamide) (Nomex) and Thermoplastic polyurethane (TPU) are chosen as the two components in co‐electrospinning. To display the efficiency for producing helical fibers, a generally used core–shell needle spinneret is used for comparison. The effect of the uniformity of electric field distribution created by these two types of spinnerets on the jet motion and the resultant helical fibers is developed, with systematical simulation and experimental research. The results showed that the co‐electrospinning system with the newly designed flat spinneret can produce helical nanofibers efficiently. Compared with the needle spinneret, the flat spinneret created more uniform electric field, leading to better morphology and structure of the resultant helical fibers. In addition, an approach to achieve the scale‐up of this co‐electrospinning system is developed. This novel design is expected to provide a promising method to fabricate nanofiber materials with helical structures. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019, 57, 1496–1505
Competition Between Interfacial Interaction and Microphase Separation in Crystallization of Filled Block Copolymers
Authors: Liu Rongjuan , Zhou Zhiping , Liu Yong , Liang Zhaopeng , Ming Yongqiang , Nie Yijing , Hao Tongfan
Published: October 2019

Understanding the effect of repulsive interaction between blocks on crystallization in block copolymers is beneficial for the design and development of sophisticated nanostructures. Dynamic Monte Carlo simulations were performed to reveal the crystallization mechanism of block copolymers containing one‐dimensional nanofiller under different repulsive interaction strengths between crystallizable and noncrystallizable blocks. During crystallization, crystalline morphology is determined by the competition between segmental orientation perpendicular to microphase interfaces dominated by microphase separation and that along the direction of the long axis of the nanofiller controlled by interfacial interaction. As the repulsive interaction between different blocks is strengthened, the competition between microphase separation and interfacial interaction is intensified, eventually leading to an increase in crystallization rate and a degradation in crystalline morphology. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys.2019,57, 1516–1526
Stigma and its correlates in people living with lung cancer: A cross‐sectional study from China
Authors: Liu Xiao Hang , Zhong Jiu Di , Zhang Jun E. , Cheng Yu , Bu Xiu Qing
Published: October 2019

Objectives

This study aimed to examine the level of stigma and identify the correlates of stigma among lung cancer patients in China.

Methods

In total, 283 lung cancer patients were recruited from a tertiary cancer center in China by the convenience sampling method and completed a demographic, disease‐related information and situational characteristics questionnaire and self‐reported measures assessing stigma, state self‐esteem, and coping self‐efficacy.

Results

The mean stigma score was moderate (2.38 ± 0.45). Stigma was significantly and negatively associated with state self‐esteem (r = –0.607, P < .001) and coping self‐efficacy (r = –0.424, P < .001). Multivariable linear regression showed that age, cancer stage, negative changes (ie, in financial burden, body image, and family relationship), cancer disclosure, perceived blame, state self‐esteem, and coping self‐efficacy accounted for 49.9% of the variance in stigma.

Conclusions

Stigma is a widespread psychosocial phenomenon among patients with lung cancer in China. Health care policy‐makers and professionals should pay more attention to this issue and take effective measures to address stigma among lung cancer patients by improving their state self‐esteem and coping self‐efficacy, encouraging cancer disclosure and providing support for adjusting to negative changes after diagnosis.
Sexual function, menopausal symptoms, depression and cancer worry in women with BRCA mutations
Authors: Powell C. Bethan , Alabaster Amy , Le Amy , Stoller Nicole , Armstrong Mary Anne , Raine‐Bennett Tina
Published: October 2019

Objectives

Assess sexual function, menopausal symptoms, and depression in women with BRCA mutations associated with oophorectomy and menopause status.

Methods

Women age 40 and older with BRCA mutations completed a questionnaire with validated measures of sexual activity, menopausal symptoms, depression, and cancer worry. These measures were compared between those with intact ovaries and those who had undergone pre‐ or post‐menopausal risk‐reducing salpingo‐oophorectomy (RRSO).

Results

Of the 244 women, 21 had intact ovaries and 223 had undergone RRSO. Women with intact ovaries had less menopausal symptoms (Menopausal Symptom Checklist (MSCL) score 14 versus 23, P = .01) but more cancer worry than women who had undergone RRSO (median Cancer Worry Scale (CWS) score 5 versus 4, P < .0001) with no significant difference in sexual activity or function. Compared with women with postmenopausal RRSO, women with premenopausal RRSO were more likely to be sexually active (56.3% versus 42.0%, P =.04) but had similar sexual functioning, including frequency, pleasure and discomfort. Women with premenopausal RRSO were also more likely to report menopausal symptoms (MSCL score 26 versus 19, P = .04) and depression (PHQ‐8 score 4 versus 2, P < .001). Factors associated with sexual activity included younger age, lower BMI, living with a partner, and lower depression scores. Higher current depression score was associated with history of depression and more menopausal symptoms.

Conclusions

Risk‐reducing surgery decreases cancer risk and worry in women with BRCA mutations. Among women undergoing oophorectomy, factors such as age and history of depression were related to reduced sexual activity and increased depression, but menopausal status was not related.
Using theory and user‐centered design in digital health: The development of the mychoice communication tool to prepare patients and improve informed decision making regarding clinical trial participation
Authors: Fleisher Linda , Bass Sarah Bauerle , Shwarz Michelle , Washington Armenta , Nicholson Andrea , Alhajji Mohammed , Geynisman Daniel M. , Maurer Laurie , Greener Judith , Kenny Cassidy
Published: October 2019

Objective

Designing salient digital health interventions requires theoretically‐based formative research and user‐center design with stakeholder input throughout impacting content and technology design. mychoice is a theory‐based, stakeholder‐guided digital health tool to improve clinical trial informed decision making, particularly among African American patients.

Methods

mychoice was developed by (1) mixed‐methods formative research, including in‐depth interviews (n=16) and surveys (N=41) with African American cancer patients who had and had not participated in a clinical trial; (2) e‐tool design process including perceptual mapping analysis to prioritize messages, multi‐disciplinary team and stakeholder input; and (3) iterative production and user testing.

Results

Interview findings showed that clinical trial participants expressed more positive attributes about and an openness to consider clinical trials, even though they expressed common concerns such as “fear of being a guinea pig”. Survey results indicated that clinical trial participants expressed they had been given information to make the decision (P = .001), while those who had not more frequently reported (P > .001) that no one had talked to them about trials. Perceptual mapping indicated that values such as “helping find a cure” or “value to society” had little resonance to those who had not participated, providing message strategy for prototype development. User testing of the tool resulted in modifications; the most significant was the adaptation to a multi‐cultural version.

Conclusions

With the promise of digital health interventions, theory‐guided, user‐centered and best practice development is critical and mychoice serves as an example of the application of these principles.
Using smart‐messaging to enhance mindfulness‐based cognitive therapy for cancer patients: A mixed methods proof of concept evaluation
Authors: Wells Chloe , Malins Sam , Clarke Simon , Skorodzien Iwona , Biswas Sanchia , Sweeney Tim , Moghaddam Nima , Levene Jo
Published: October 2019

Objective

Depression and anxiety lead to reduced treatment adherence, poorer quality of life, and increased care costs amongst cancer patients. Mindfulness‐based cognitive therapy (MBCT) is an effective treatment, but dropout reduces potential benefits. Smart‐message reminders can prevent dropout and improve effectiveness. However, smart‐messaging is untested for MBCT in cancer. This study evaluates smart‐messaging to reduce dropout and improve effectiveness in MBCT for cancer patients with depression or anxiety.

Methods

Fifty‐one cancer patients attending MBCT in a psycho‐oncology service were offered a smart‐messaging intervention, which reminded them of prescribed between‐session activities. Thirty patients accepted smart‐messaging and 21 did not. Assessments of depression and anxiety were taken at baseline, session‐by‐session, and one‐month follow‐up. Logistic regression and multilevel modelling compared the groups on treatment completion and clinical effectiveness. Fifteen post‐treatment patient interviews explored smart‐messaging use.

Results

The odds of programme completion were eight times greater for patients using smart‐messaging compared with non‐users, controlling for age, gender, baseline depression, and baseline anxiety (OR = 7.79, 95% CI 1.75 to 34.58, p = .007). Smart‐messaging users also reported greater improvement in depression over the programme (B = ‐2.33, SEB = .78, p = .004) when controlling for baseline severity, change over time, age, and number of sessions attended. There was no difference between groups in anxiety improvement (B = ‐1.46, SEB = .86, p = .097). In interviews, smart‐messaging was described as a motivating reminder and source of personal connection.

Conclusions

Smart‐messaging may be an easily integrated telehealth intervention to improve MBCT for cancer patients.
Impact of fear of cancer recurrence on survival among lymphoma patients
Authors: Kim Seok Jin , Kang Danbee , Kim Im Ryung , Yoon Sang Eun , Kim Won Seog , Butow Phyllis N. , Guallar Eliseo , Cho Juhee
Published: October 2019

Objective

This study aimed to evaluate fear of cancer recurrence (FCR) among lymphoma patients who completed treatment and its impact on survival and quality of life (QOL).

Methods

In this prospective cohort study, 467 lymphoma patients were included who completed treatment with curative intent between February 2012 and March 2017. FCR was measured using a question from the Korean version of the QOL in Cancer Survivors Questionnaire. QOL and general health and functioning were measured using the European Organization for Research and Treatment of Cancer (EORTC) QLQ‐C30. Participants were actively followed up for all‐cause and disease‐specific mortality.

Results

In total, 16.3% of the patients had severe FCR. The adjusted hazard ratio (HR) for all‐cause mortality comparing participants with and without severe FCR was 2.52 (95% CI = 1.15‐5.54), and the association was stronger in indolent non‐Hodgkin lymphoma (NHL) (HR = 6.77; 95% CI = 1.04‐43.92). Participants with severe FCR were also at higher risk of lymphoma‐specific mortality (HR = 2.62; 95% CI = 1.13‐6.05) than patients without severe FCR. Patients with severe FCR had significantly worse general health status (64.3 vs 71.0, P = .03) and physical (82.4 vs 76.7, P < .01), emotional (68.5 vs 84.8, P < .001), and social functioning (67.8 vs 84.2, P < .001) than patients without severe FCR.

Conclusions

A substantial number of participants with lymphoma experience FCR after treatment completion, even in the case of indolent lymphomas. Given the negative impact of severe FCR on survival and general health and functional status, active monitoring and appropriate management of FCR should be considered in clinical settings.
NAGbinder: An approach for identifying N‐acetylglucosamine interacting residues of a protein from its primary sequence
Authors: Patiyal Sumeet , Agrawal Piyush , Kumar Vinod , Dhall Anjali , Kumar Rajesh , Mishra Gaurav , Raghava Gajendra P.S.
Published: October 2019

N‐acetylglucosamine (NAG) belongs to the eight essential saccharides that are required to maintain the optimal health and precise functioning of systems ranging from bacteria to human. In the present study, we have developed a method, NAGbinder, which predicts the NAG‐interacting residues in a protein from its primary sequence information. We extracted 231 NAG‐interacting nonredundant protein chains from Protein Data Bank, where no two sequences share more than 40% sequence identity. All prediction models were trained, validated, and evaluated on these 231 protein chains. At first, prediction models were developed on balanced data consisting of 1,335 NAG‐interacting and noninteracting residues, using various window size. The model developed by implementing Random Forest using binary profiles as the main principle for identifying NAG‐interacting residue with window size 9, performed best among other models. It achieved highest Matthews Correlation Coefficient (MCC) of 0.31 and 0.25, and Area Under Receiver Operating Curve (AUROC) of 0.73 and 0.70 on training and validation data set, respectively. We also developed prediction models on realistic data set (1,335 NAG‐interacting and 47,198 noninteracting residues) using the same principle, where the model achieved MCC of 0.26 and 0.27, and AUROC of 0.70 and 0.71, on training and validation data set, respectively. The success of our method can be appraised by the fact that, if a sequence of 1,000 amino acids is analyzed with our approach, 10 residues will be predicted as NAG‐interacting, out of which five are correct. Best models were incorporated in the standalone version and in the webserver available at https://webs.iiitd.edu.in/raghava/nagbinder/
Building better enzymes: Molecular basis of improved non‐natural nucleobase incorporation by an evolved DNA polymerase
Authors: Ouaray Zahra , Singh Isha , Georgiadis Millie M. , Richards Nigel G. J.
Published: October 2019

Obtaining semisynthetic microorganisms that exploit the information density of “hachimoji” DNA requires access to engineered DNA polymerases. A KlenTaq variant has been reported that incorporates the “hachimoji” P:Z nucleobase pair with a similar efficiency to that seen for Watson–Crick nucleobase incorporation by the wild type (WT) KlenTaq DNA polymerase. The variant polymerase differs from WT KlenTaq by only four amino acid substitutions, none of which are located within the active site. We now report molecular dynamics (MD) simulations on a series of binary complexes aimed at elucidating the contributions of the four amino acid substitutions to altered catalytic activity. These simulations suggest that WT KlenTaq is insufficiently flexible to be able to bind AEGIS DNA correctly, leading to the loss of key protein/DNA interactions needed to position the binary complex for efficient incorporation of the “hachimoji” Z nucleobase. In addition, we test literature hypotheses about the functional roles of each amino acid substitution and provide a molecular description of how individual residue changes contribute to the improved activity of the KlenTaq variant. We demonstrate that MD simulations have a clear role to play in systematically screening DNA polymerase variants capable of incorporating different types of nonnatural nucleobases thereby limiting the number that need to be characterized by experiment. It is now possible to build DNA molecules containing nonnatural nucleobase pairs in addition to A:T and G:C. Exploiting this development in synthetic biology requires engineered DNA polymerases that can replicate nonnatural nucleobase pairs. Computational studies on a DNA polymerase variant reveal how amino acid substitutions outside of the active site yield an enzyme that replicates nonnatural nucleobase pairs with high efficiency. This work will facilitate efforts to obtain bacteria possessing an expanded genetic alphabet.
Performance of the SAEM and FOCEI Algorithms in the Open‐Source, Nonlinear Mixed Effect Modeling Tool nlmixr
Authors: Schoemaker Rik , Fidler Matthew , Laveille Christian , Wilkins Justin J. , Hooijmaijers Richard , Post Teun M. , Trame Mirjam N. , Xiong Yuan , Wang Wenping
Published: October 2019

The free and open‐source package nlmixr implements pharmacometric nonlinear mixed effects model parameter estimation in R. It provides a uniform language to define pharmacometric models using ordinary differential equations. Performances of the stochastic approximation expectation‐maximization (SAEM) and first order‐conditional estimation with interaction (FOCEI) algorithms in nlmixr were compared with those found in the industry standards, Monolix and NONMEM, using the following two scenarios: a simple model fit to 500 sparsely sampled data sets and a range of more complex compartmental models with linear and nonlinear clearance fit to data sets with rich sampling. Estimation results obtained from nlmixr for FOCEI and SAEM matched the corresponding output from NONMEM/FOCEI and Monolix/SAEM closely both in terms of parameter estimates and associated standard errors. These results indicate that nlmixr may provide a viable alternative to existing tools for pharmacometric parameter estimation.
Symmetry Analysis of Some Basic Structural Properties of Incommensurately Modulated Crystals by Projective Representations of Unimodular Groups
Authors: Mészáros Csaba , Nikolényi István R. , Bálint Ágnes
Published: October 2019

Projective representations of the unimodular groups are applied in the general symmetry theory of incommensurately modulated crystals. It is demonstrated that the algebraic condition relevant for the existence of line groups can be directly connected to those related to linear projective groups. As a concrete application example, the formalisms of the thermodynamic modelling of the structural phase transitions and the Fourier‐analysis formulae of the scattering processes in kinematic approximation are discussed by use of this group‐theoretical technique, introduced newly in this study for symmetry analyses of the general structural features of incommensurate systems.