bluuebunny/crossref_metadata_2025 huggingface dataset:
Thyroid‐stimulating hormone within the normal range and risk of major adverse cardiovascular events in nonischemic dilated cardiomyopathy patients with severe left ventricular dysfunction
Authors: Li Xiaofei , Yao Yan , Chen Zhaoran , Fan Siyang , Hua Wei , Zhang Shu , Fan Xiaohan
Published: November 2018

Background

The association between thyroid‐stimulating‐hormone (TSH) and prognosis of nonischemic dilated cardiomyopathy (NIDCM) in patients with normal thyroid function remains unclear.

Hypothesis

Our aim was to investigate the association between TSH and major adverse cardiovascular events in euthyroid NIDCM patients.

Methods

The original cohort consisted of 216 consecutive euthyroid NIDCM patients, with left ventricular ejection fraction (LVEF) ≤35%, who were observed from 2010 to 2013. Patients with persistent ventricular arrhythmia (VA) histories, amiodarone taken for VA prevention, or on heart transplant list within 1 year were excluded. A follow‐up evaluation was performed, and VA events, heart failure (HF) exacerbation/heart transplant, cardiac death, or death from any cause were separately evaluated.

Results

A total of 184 patients were enrolled, and 97.8% (180/184) ultimately received follow‐up evaluations. During the median 4.6‐year follow‐up, 24 VA events, 28 cardiac deaths, 30 all‐cause deaths, 40 HF exacerbations, and 11 heart transplant events occurred. Serum TSH levels showed good predictive efficacies for VA events (area under the curve [AUC] = 0.702, 95% confidence interval [CI]: 0.629‐0.767), and the risk of VA events increased, according to serum TSH quarters, as determined by Kaplan‐Meier analysis (2.2% vs 13.4% vs 21.0% vs 30.0%, Q1‐Q4, P = 0.011). Multivariable Cox analysis showed that patients at the Q4 level of serum TSH (>2.67 mIU/L) suffered an increased risk of VA events, compared with those at the Q1 level of TSH (hazard ratio [HR] = 15.88, 95% CI: 2.01‐65.15) or those at the other three quarters (HR = 3.17, 95% CI: 1.38‐7.26). However, the Q4 TSH level was not associated with other adverse cardiac events.

Conclusion

An association between TSH levels and the risk of VA events may exist in euthyroid NIDCM patients.
Utilization of palliative care in patients hospitalized with heart failure: A contemporary national perspective
Authors: Alqahtani Fahad , Balla Sudarshan , Almustafa Ahmad , Sokos George , Alkhouli Mohamad
Published: November 2018

Background

Despite advances in therapy, heart failure (HF) patients have significant symptom burden and poor quality of life. However, data on palliative care (PC) utilization in this population are scarce. We sought to assess national trends in PC utilization in patients admitted with acute HF.

Methods

Adults hospitalized with HF without acute coronary syndrome were identified in the National inpatient sample. PC was identified using ICD‐9‐CM‐Code V66.7. Trends in PC utilization, its predictors and its association with length‐of‐stay and cost were assessed.

Results

A total of 939 680 HF patients were hospitalized with HF between 2003 and 2014. Of those,1.2% received PC during the hospitalization, with an upward trend in the use of PC over time (0.12% in 2003 to 3.6% in 2014, P < 0.001). Compared with patients who did not receive PC, those who had PC were older (79 ± 12 vs 69 ± 16 years), and had higher prevalence of Caucasian race (73.4% vs 51.8%), coronary disease (45.6% vs 39.3%), chronic renal disease (79.3% vs 42.8%), and pulmonary hypertension (28.3% vs 15.1%) (P < 0.001). In‐hospital mortality (35.2% vs 2.2%), length‐of‐stay (9 ± 13 days vs 6 ± 6, P < 0.001), cost ($19 984 ± 42 922 vs $11 921 ± 18 175), and non‐home discharges (46% vs 19.2%) (P < 0.001) were higher in the PC group. In‐hospital mortality in PC group trended downward over time (69% in 2003 vs 29% in 2014, P < 0.001).

Conclusion

PC is being utilized in an increasing but overall small number of patients hospitalized with HF. Further research is needed to identify the optimal role and timing of PC in HF patients.
Protein Abundance of Clinically Relevant Drug Transporters in the Human Liver and Intestine: A Comparative Analysis in Paired Tissue Specimens
Authors: Drozdzik Marek , Busch Diana , Lapczuk Joanna , Müller Janett , Ostrowski Marek , Kurzawski Mateusz , Oswald Stefan
Published: November 2018

Bioavailability of orally administered drugs is partly determined by function of drug transporters in the liver and intestine. Therefore, we explored adenosine triphosphate–binding cassette (ABC) and solute carriers family transporters expression (quantitative polymerase chain reaction) and protein abundance (liquid chromatography tandem mass spectrometry (LC‐MS/MS)) in human liver and duodenum, jejunum, ileum, and colon in paired tissue specimens from nine organ donors. The transporter proteins were detected in the liver (permeability‐glycoprotein (P‐gp), multidrug resistance protein (MRP)2, MRP3, breast cancer resistance protein (BCRP), organic anion‐transporting polypeptide (OATP)1B1, OATP1B3, OATP2B1, organic cation transporter (OCT)1, OCT3, organic anion transporter 2, Na+‐taurocholate cotransporting polypeptide, monocarboxylate transporter (MCT)1, and multidrug and toxin extrusion 1) and the intestine (P‐gp, multidrug‐resistance protein (MRP)2, MRP3, MRP4, BCRP, OATP2B1, OCT1, apical sodium–bile acid transporter (only ileum), MCT1, and peptide transporter (PEPT1)). Significantly higher hepatic gene expression and protein abundance of ABCC2/MRP2, SLC22A1/OCT1, and SLCO2B1/OATP2B1 were found, as compared to all intestinal segments. No correlations between hepatic and small intestinal protein levels were observed. These observations provide a description of drug transporters distribution without the impact of interindividual variability bias and may help in construction of superior physiologically based pharmacokinetic and humanized animal models.
Dosage Considerations for Canakinumab in Children With Periodic Fever Syndromes
Authors: Zhuang Luning , Chen Jianmeng , Yu Jingyu , Marathe Anshu , Sahajwalla Chandra , Borigini Mark , Maynard Janet , Burckart Gilbert J. , Wang Yaning
Published: November 2018

Periodic fever syndromes are a group of rare diseases with a highly variable onset, yet limited treatment options are available for children at an early age. Canakinumab has been approved to treat patients with cryopyrin‐associated periodic syndrome, a periodic fever syndrome, and systemic juvenile systemic arthritis, with age cutoffs of 4 years and 2 years, respectively. In 2016, the US Food and Drug Administration (FDA) approved canakinumab, without an age restriction, for the treatment of three conditions of periodic fever syndromes, including familial Mediterranean fever, hyperimmunoglobulin D syndrome/mevalonate kinase deficiency, and tumor necrosis factor receptor‐associated periodic syndrome. This review discusses the pharmacokinetic (PK), efficacy, safety, and exposure‐response relationship of canakinumab and provides the rationale for dosage recommendation in children younger than 2 years of age with the three conditions of periodic fever syndromes. The approval of canakinumab for these pediatric patients addresses a critical unmet medical need.
Cortisol secretion moderates the association between mother–infant attachment at 17 months and child behavior at age 5 years
Authors: Nofech‐Mozes Jaclyn , Pereira Jessica , Gonzalez Andrea , Atkinson Leslie
Published: November 2018

This study examined infant cortisol secretion as a moderator of the association between mother–infant attachment security at age 17 months and child behavior at age 5 years. A longitudinal community sample of 96 mother–child dyads participated in the strange situation procedure (SSP) at age 17 months. Cortisol was collected at baseline, and at 20 and 40 min post‐SSP. Maternal reports of child behavior were collected at age 5 years. Results revealed that the associations between nonsecure mother–infant attachment and higher total, internalizing, and externalizing behavior were stronger for infants with high cortisol secretion, relative to infants with low cortisol secretion. The model of interaction differed depending on the outcome, with diathesis‐stress explaining variance in total as well as internalizing behavior, and with differential susceptibility explaining variance in externalizing behavior. These findings augment our understanding of risk and resilience to the impact of the early rearing environment on later psychopathology.
Use it or lose it? Effects of age, experience, and disuse on crawling
Authors: Cole Whitney G. , Vereijken Beatrix , Young Jesse W. , Robinson Scott R. , Adolph Karen E.
Published: November 2018

What happens to early acquired but later abandoned motor skills? To investigate effects of disuse on early‐developing motor skills, we examined crawling in two groups of habitual crawlers (34 6–12‐month‐old infants and five adults with Uner Tan Syndrome) and two groups of rusty crawlers (27 11–12‐year‐old children and 13 college‐aged adults). Habitual crawlers showed striking similarities in gait patterns, limbs supporting the body, and crawling speed, despite dramatic differences in crawling practice, posture, and body size. Habitual crawlers trotted predominantly, whereas rusty crawlers showed a variety of gait patterns. Within sequences, habitual crawlers and children showed more switches in gait patterns than young adults. Children crawled faster and kept fewer limbs on the grounds than the other groups. Old crawling patterns were retained despite disuse, but new ones were also added. Surprisingly, results indicate that nothing was lost with disuse, but some features of crawling were gained or altered.
Understanding the growing epidemic of type 2 diabetes in the Hispanic population living in the United States
Authors: Aguayo‐Mazzucato Cristina , Diaque Paula , Hernandez Sonia , Rosas Silvia , Kostic Aleksandar , Caballero Augusto Enrique
Published: November 2018

The prevalence and incidence of type 2 diabetes (T2D) among the Hispanic population in the United States are higher than the national average. This is partly due to sociocultural factors, such as lower income and decreased access to education and health care, as well as a genetic susceptibility to obesity and higher insulin resistance. This review focuses on understanding the Hispanic population living in the United States from a multidisciplinary approach and underlines the importance of cultural, social, and biological factors in determining the increased risk of T2D in this population. An overview of the acute and chronic complications of T2D upon this population is included, which is of paramount importance to understand the toll that diabetes has upon this population, the health system, and society as a whole. Specific interventions directed to the Hispanic populations are needed to prevent and alleviate some of the burdens of T2D. Different prevention strategies based on medications, lifestyle modifications, and educational programmes are discussed herein. Diabetes self‐management education (DSME) is a critical element of care of all people with diabetes and is considered necessary to improve patient outcomes. To be more effective, programmes should take into consideration cultural factors that influence the development and progression of diabetes. These interventions aim to enhance long‐term effects by reducing the incidence, morbidity, and mortality of T2D in the Hispanic population of the United States.
Theories of the multinational firm: A microfoundational perspective
Authors: Kano Liena , Verbeke Alain
Published: November 2018

Research Summary

We analyze the six core international business (IB) strategy frameworks highlighted by Forsgren (2013) to identify the explicit or implicit microfoundations embedded therein. We start from two, broad microfoundations, namely bounded rationality and bounded reliability, covering a total of ten microfoundational facets, recently put forward as supposedly essential to any predictive and managerially relevant theory of the firm (Kano and Verbeke, 2015). We show how these various facets, embedded in the conceptual foundations underlying the various theoretical approaches, can be made actionable by articulating them explicitly and by connecting them to firm‐level IB strategy outcomes. We also describe how reflecting on these microfoundational facets and on the likely actionable implications thereof for managerial decision making, allows enhancing these theories’ conceptual power, predictive capacity, and managerial relevance.

Managerial Summary

We analyze the six main theories of the multinational enterprise (MNE), as described in Mats Forsgren's (2013) classic book,Theories of the Multinational Firm. We assess whether individual‐level assumptions about managerial behavior and decision‐making are present in the logic of the theories. We find that each theory builds upon specific micro‐level assumptions, but these assumptions are typically neither articulated, nor linked to MNE strategy decisions, e.g., in the realm of geographic footprint, operating mode selection, interaction with the external environment, internal organization etc. We show how assumptions about human behavior implied in IB theories can be made actionable by spelling these out and connecting them to international strategic choices by MNEs. We also describe how reflecting on micro‐level assumptions can enhance actionable managerial implications of IB theory.
Versatility of cervicofacial flaps: Cervical‐medial cheek flap for reconstruction in cutaneous substance loss of the inner cheek
Authors: Hufschmidt Katharina , Bozec Alexandre , Camuzard Olivier , Clerico Cyril , Berguiga Riadh , Dassonville Olivier , Santini Joseph , Poissonnet Gilles
Published: November 2018

Background

Preservation of facial harmony is a major challenge in reconstruction after resection of head and neck skin tumors. For large medial cheek‐skin defects, we used a derived posterior‐based cervicofacial flap, or cervical‐medial cheek flap (CMCF).

Methods

We present a retrospective review of cases treated at a university‐based cancer center. Patient characteristics, surgical technique, and complication rates are described.

Results

Eighteen patients were treated between 2014 and 2017 with reconstruction for integumentary cheek defect after skin tumor surgery using CMCF. Mean defect size was 5.7 cm in length and 3.9 cm in width. The main histological subtype was lentigo maligna (33.3%). We report no flap necrosis but 4 minor complications occurred over a mean follow‐up of 14.4 months. At last follow‐up, satisfaction rate was very high (88.9%) with no evidence of recurrence.

Conclusion

The CMCF is a promising yet infrequently used option in medial cheek reconstruction, with excellent cosmetic and functional outcomes.
Prognostic factors and survival in adenoid cystic carcinoma of the sinonasal cavity
Authors: Mays Ashley C. , Hanna Ehab Y. , Ferrarotto Renata , Phan Jack , Bell Diana , Silver Natalie , Mulcahy Collin F. , Roberts Dianna , Abdelmeguid Ahmed Salama Ahmed , Fuller Clifton D. , Frank Steven J. , Raza Shaan M. , Kupferman Michael E. , DeMonte Franco , Su Shirley Y.
Published: November 2018

Background

Optimal treatment and prognostic factors affecting long‐term survival in patients with sinonasal adenoid cystic carcinoma (ACC) have yet to be clearly defined.

Methods

We conducted a retrospective review of patients treated with curative intent from 1980‐2015 at MD Anderson Cancer Center.

Results

One hundred sixty patients met inclusion criteria, including 8 who were treated with radiotherapy alone. Median follow‐up time was 55 months. The 5‐year overall survival (OS) and disease‐free survival (DFS) rates were 67.0% and 49.0%, respectively. The 10‐year OS and DFS rates were 44.8% and 25.4%, respectively. Factors that portended for poor survival on multivariate analysis were recurrent disease, any solid type histology, epicenter in the sinus cavity, the presence of facial symptoms, or the original disease not treated with surgery. There was no association between surgical margin status or nodal status and survival.

Conclusion

In this large cohort of patients with sinonasal ACC with extended follow‐up, long‐term survival is better than reported in prior literature. Future research should target patients with adverse risk factors.
Frequency‐specific noninvasive modulation of memory retrieval and its relationship with hippocampal network connectivity
Authors: Hermiller Molly S. , VanHaerents Stephen , Raij Tommi , Voss Joel L.
Published: November 2018

Episodic memory is thought to rely on interactions of the hippocampus with other regions of the distributed hippocampal‐cortical network (HCN) via interregional activity synchrony in the theta frequency band. We sought to causally test this hypothesis using network‐targeted transcranial magnetic stimulation. Healthy human participants completed four experimental sessions, each involving a different stimulation pattern delivered to the same individualized parietal cortex location of the HCN for all sessions. There were three active stimulation conditions, including continuous theta‐burst stimulation, intermittent theta‐burst stimulation, and beta‐frequency (20‐Hz) repetitive stimulation, and one sham condition. Resting‐state fMRI and episodic memory testing were used to assess the impact of stimulation on hippocampal fMRI connectivity related to retrieval success. We hypothesized that theta‐burst stimulation conditions would most strongly influence hippocampal‐HCN fMRI connectivity and retrieval, given the hypothesized relevance of theta‐band activity for HCN memory function. Continuous theta‐burst stimulation improved item retrieval success relative to sham and relative to beta‐frequency stimulation, whereas intermittent theta‐burst stimulation led to numerical but nonsignificant item retrieval improvement. Mean hippocampal fMRI connectivity did not vary for any stimulation conditions, whereas individual differences in retrieval improvements due to continuous theta‐burst stimulation were associated with corresponding increases in fMRI connectivity between the hippocampus and other HCN locations. No such memory‐related connectivity effects were identified for the other stimulation conditions, indicating that only continuous theta‐burst stimulation affected memory‐related hippocampal‐HCN connectivity. Furthermore, these effects were specific to the targeted HCN, with no significant memory‐related fMRI connectivity effects for two distinct control brain networks. These findings support a causal role for fMRI connectivity of the hippocampus with the HCN in episodic memory retrieval and indicate that contributions of this network to retrieval are particularly sensitive to continuous theta‐burst noninvasive stimulation.
How in silico and QSAR approaches can increase confidence in environmental hazard and risk assessment
Authors: Thomas Paul C , Bicherel Pascal , Bauer Franklin J
Published: November 2018

In silico methods are typically underrated in the current risk assessment paradigm, as evidenced by the recent document from the European Chemicals Agency (ECHA) on animal alternatives, in which quantitative structure–activity relationships (QSARs) were practically used only as a last resort. Their primary use is still to provide supporting evidence for read-across strategies or to add credence to experimental results of unknown or limited validity (old studies, studies without good laboratory practices [GLPs], limited information reported, etc.) in hazard assessment, but under the pressure of increasing burdens of testing, industry and regulators alike are at last warming to them. Nevertheless, their true potential for data-gap filling and for resolving sticking points in risk assessment methodology and beyond has yet to be recognized. We postulate that it is possible to go beyond the level of simply increasing confidence to the point of using in silico approaches to accurately predict results that cannot be resolved analytically. For example, under certain conditions it is possible to obtain meaningful results by in silico extrapolation for tests that would be technically impossible to conduct in the laboratory or at least extremely challenging to obtain reliable results. The following and other concepts are explored in this article: the mechanism of action (MechoA) of the substance should be determined, as an aid verifying that the QSAR model is applicable to the substance under review; accurate QSARs should be built with high-quality data that were not only curated but also validated with expert judgment; although a rule of thumb for acute to chronic ratios appears applicable for nonpolar narcotics, it seems unlikely that a “one-value-fits-all” answer exists for other MechoAs; a holistic approach to QSARs can be employed (via reverse engineering) to help validate or invalidate an experimental endpoint value on the basis of multiple experimental studies. Integr Environ Assess Manag 2019;15:40–50. © 2018 SETAC
Long noncoding RNA MIR31HG is a bona fide prognostic marker with colorectal cancer cell‐intrinsic properties
Authors: Eide Peter W. , Eilertsen Ina A. , Sveen Anita , Lothe Ragnhild A.
Published: November 2018

Elevated miR‐31 expression is associated with poor outcome in colorectal cancer (CRC). Whether the prognostic information is independent of known molecular subgroups and gene expression‐based consensus molecular subtypes (CMS) is currently unknown. To investigate this, we analyzed nearly 2000 CRC biopsies and preclinical models. The expression of miR‐31‐5p and its host transcript, long noncoding RNA MIR31HG, was strongly correlated (Spearman's ρ > 0.80). MIR31HG outlier expression was observed in 158/1265 (12%) of pCRCs and was associated with depletion of CMS2‐canonical subgroup (odds ratio = 0.21 [0.11–0.35]) and shorter relapse‐free survival (RFS) in multivariable analysis (adjusted hazard ratio = 2.2 [1.6–3.0]). For stage II disease, 5‐year RFS for patients with MIR31HG outlier status was 49% compared to 77% for those with normal‐like expression. MIR31HG outlier status was associated with inferior outcome also within clinical high risk groups and within the poor prognostic CMS4‐mesenchymal gene expression subtype specifically. Preclinical models with MIR31HG outlier expression were characterized by reduced expression of MYC targets as well as elevated epithelial‐mesenchymal transition, TNF‐α/NFκB, TGF‐β, and IFN‐α/γ gene expression signatures, indicating cancer cell‐intrinsic properties resembling the CMS4 subgroup—associations which were recapitulated in patient biopsies. Moreover, the prognostic value of MIR31HG outlier status was independent of cytotoxic T lymphocyte and fibroblast infiltration. We here present evidence that MIR31HG expression provides clinical stratification beyond major gene expression phenotypes and tumor immune and stromal cell infiltration and propose a model where increased expression is an indicator of a cellular state conferring intrinsic invasive and/or immuno‐evasive capabilities.
Pharmacist‐led medication education groups on an inpatient psychiatric unit—Impact on readmissions and emergency department visits
Authors: Werremeyer Amy , Orr Megan
Published: November 2018

Introduction

The optimal mechanism for delivery of medication education by pharmacists in the inpatient setting is unclear.

Objectives

To evaluate the impact of pharmacist‐led patient medication education groups (PMEGs) conducted in an inpatient psychiatry unit and to further delineate factors associated with psychiatric rehospitalization.

Methods

A retrospective cohort study of 593 individual admissions in which PMEG attenders (n = 298) participated in one or more medication education sessions. The pharmacist leader served as moderator and utilized a motivational interviewing approach. PMEG nonattenders (n = 285) received usual care. Binomial logistic analyses and multiple linear regression analysis were used to identify factors associated with 90‐day and 12‐month psychiatric readmission, 12‐month medical hospitalization, 12‐month emergency department (ED) visits for psychiatric reasons, and time to psychiatric readmission.

Results

After controlling for multiple factors, attendance at a single PMEG session was not associated with a reduction in any of the above outcomes. Attendance at two or more PMEG sessions was associated with a reduction in ED visits for psychiatric reasons (P = 0.0433). For each additional diagnosis, odds of a 90‐day psychiatric readmission rose by a factor of 1.4. Patients prescribed antipsychotic or hypnotic medications were 2.4 and 2.5 times, respectively, more likely to experience 90‐day psychiatric readmission. PMEG attendance did not lower the readmission risk for these high risk patients.

Conclusion

A single PMEG intervention for psychiatric inpatients was not effective in reducing psychiatric readmission, but patients who participated in two or more PMEGs had fewer ED visits than those who attended only one PMEG. Additional research is needed regarding PMEG impacts on medication knowledge and attitude, as well as other potential reasons for psychiatric health care utilization.
Unrolr: Structural analysis of protein conformations using stochastic proximity embedding
Authors: Eberhardt Jérôme , Stote Roland H. , Dejaegere Annick
Published: November 2018

Molecular dynamics (MD) simulations are widely used to explore the conformational space of biological macromolecules. Advances in hardware, as well as in methods, make the generation of large and complex MD datasets much more common. Although different clustering and dimensionality reduction methods have been applied to MD simulations, there remains a need for improved strategies that handle nonlinear data and/or can be applied to very large datasets. We present an original implementation of the pivot‐based version of the stochastic proximity embedding method aimed at large MD datasets using the dihedral distance as a metric. The advantages of the algorithm in terms of data storage and computational efficiency are presented, as well as the implementation realized. Application and testing through the analysis of a 200 ns accelerated MD simulation of a 35‐residue villin headpiece is discussed. Analysis of the simulation shows the promise of this method to organize large conformational ensembles. © 2018 Wiley Periodicals, Inc.
Evaluation of non‐monoexponential diffusion models for hepatocellular carcinoma using b values up to 2000 s/mm2: A short‐term repeatability study
Authors: Kuai Zi‐Xiang , Sang Xi‐Qiao , Yao Yuan‐Fei , Chu Chun‐Yu , Zhu Yue‐Min
Published: November 2018

Background

Non‐monoexponential diffusion models are being used increasingly for the characterization and curative effect evaluation of hepatocellular carcinoma (HCC). But the fitting quality of the models and the repeatability of their parameters have not been assessed for HCC.

Purpose

To evaluate kurtosis, stretched exponential, and statistical models for diffusion‐weighted imaging (DWI) of HCC, using b‐values up to 2000 s/mm2, in terms of fitting quality and repeatability.

Study Type

Prospective.

Population

Eighteen patients with HCC.

Field Strength/Sequence

Conventional and DW images (b = 0, 200, 500, 1000, 1500, 2000 s/mm2) were acquired at 3.0T.

Assessment

The parameters of the kurtosis, stretched exponential, and statistical models were calculated on regions of interest (ROIs) of each lesion.

Statistical Tests

The fitting quality was evaluated through comparing the fitting residuals produced on the average data of ROI between different models using a paired t‐test or Wilcoxon rank‐sum test. Repeatability of the fitted parameters at the median values on the voxelwise data of ROI was assessed using the within coefficient of variation (WCV), the intraclass correlation coefficient (ICC), and the 95% Bland–Altman limits of agreements (BA‐LA). The repeatability was divided into four levels: excellent, good, acceptable, and poor, referring to the values of ICC and WCV.

Results

Among three models, the stretched exponential model provided the best fit to HCC (P < 0.05), whereas the statistical model produced the largest fitting residuals (P < 0.05). The repeatability of K from the kurtosis model was excellent (ICC 0.915; WCV 8.79%), while the distributed diffusion coefficient (DDC) from the stretched model was just acceptable (ICC 0.477; WCV 27.83%). The repeatability was good for other diffusion‐related parameters.

Data Conclusion

Considering the model fit and repeatability, the kurtosis and stretched exponential models are the preferred models for the description of the DW signals of HCC with respect to the statistical model.

Level of Evidence: 2

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;50:297–304.
Intravenous contrast‐free standardized exercise perfusion imaging in diabetic feet with ulcers
Authors: Edalati Masoud , Hastings Mary K. , Muccigrosso David , Sorensen Christopher J. , Hildebolt Charles , Zayed Mohamed A. , Mueller Michael J. , Zheng Jie
Published: November 2018

Background

Impaired foot perfusion is a primary contributor to foot ulcer formation. There is no existing device nor method that can be used to measure local foot perfusion during standardized foot muscle exercise in an MRI environment.

Purpose

To develop a new MRI‐compatible foot dynamometer and MRI methods to characterize local perfusion in diabetic feet with ulcers.

Study Type

Prospective.

Population/Subjects

Seven participants without diabetes and 10 participants with diabetic foot ulcers.

Field Strength/Sequence

3.0T, arterial spin labeling (ASL).

Assessments

Using a new MRI‐compatible foot dynamometer, all participants underwent MRI ASL perfusion assessment at rest and during a standardized toe‐flexion exercise. The participants without diabetes were scanned twice to assess the reproducibility of perfusion measurements. The absolute perfusion and perfusion reserve values were compared between two groups and between regions near ulcers (peri‐ulcer) and away from ulcers (away‐ulcer).

Statistical Tests

Bland–Altman methods for the calculation of coefficient of repeatability (CR) and two‐sided and unpaired Student's t‐test to compare multiple differences.

Results

The perfusion reserves measured had the best reproducibility (CR in medial region: 1.6, lateral region: 0.9). The foot perfusion reserve was significantly lower in the participants with diabetes compared with the participants without diabetes (1.34 ± 0.32, 95% confidence interval [CI]: 1.1, 1.58 vs. 1.76 ± 0.31, 95% CI: 1.53, 1.98, P = 0.02). Both peri‐ulcer exercise perfusion (8.7 ± 3.9 ml/min/100g) and perfusion reserve (1.07 ± 0.39, 95% CI: 0.78, 1.35) were significantly lower than away‐ulcer exercise perfusion (12.7 ± 3.8 ml/min/100g, P = 0.02) and perfusion reserve (1.39 ± 0.37, 95% CI: 1.11, 1.66, P = 0.03), respectively.

Data Conclusion

This study demonstrates intravenous contrast‐free methods for local perfusion in feet with ulcers by standardized exercise‐based MRI. Ischemia regions around foot ulcers can be quantitatively distinguished from normal perfused muscle regions.

Level of Evidence: 2

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;50:474–480.
Orthogonal array design for optimization of phenyllactic acid–sodium alginate blend coating and its effect on the browning and quality of minimally processed lily bulbs
Authors: Fan Wenguang , Ren Haiwei , Wang Yonggang , Peng Cheng , Lian Xiaofeng , Cao Yingying
Published: November 2018

BACKGROUND

In order to develop active packaging of lily products, we for the first time investigated the effects of phenyllactic acid (PLA) incorporated into a sodium alginate (SA)‐based coating on the quality of minimally processed lily bulbs stored at 4 °C for 15 days.

RESULTS

L9 (34) orthogonal array design showed that the optimal concentrations of PLA, SA and glycerinum were 0.03, 0.03 and 0.05 mol L−1, respectively, to prepare a blend coating. It was noticed that a PLA–SA blend coating treatment could inhibit browning and maintain the firmness and ascorbic acid of minimally processed lily bulbs. Compared with the control, polyphenol oxidase (PPO), peroxidase (POD) and phenylalanine ammonia‐lyase (PAL) activities of PLA–SA blend coating treated minimally processed lily bulbs reduced by about 31%, 21% and 29% on the 15th day, respectively. Total phenolic and quinone contents decreased, respectively, by 16% and 55% at the same time. Moreover, PLA–SA blend coating treatment eliminated the accumulation of malonaldehyde (MDA) while inhibiting microbial growth of minimally processed lily bulbs.

CONCLUSIONS

These results showed PLA–SA blend coating could effectively maintain quality of minimally processed lily bulbs stored at 4 °C, and it might be a prospective technology. © 2018 Society of Chemical Industry
Humics‐based interpolyelectrolyte complexes for antierosion protection of soil: Model investigation
Authors: Panova Irina , Drobyazko Alexander , Spiridonov Vasily , Sybachin Andrey , Kydralieva Kamila , Jorobekova Sharipa , Yaroslavov Alexander
Published: November 2018

The aim of this article is to demonstrate a novel polymer‐based technique for stabilization of soil against wind and water erosion. Conventional approaches deal with individual water‐soluble polymers, which, being deposited on the soil, are removed from the soil surface after rewatering. Here, we describe an elegant way for soil stabilization via deposition of interpolyelectrolyte complexes formed by two oppositely charged water‐soluble polymers. Electrostatic complexation in an aqueous solution of a cationic poly(diallyldimethylammonium chloride) with an excess of water‐soluble anionic biopolymers, humic acids, results in formation of a negative non‐stoichiometric interpolyelectrolyte complex (NIPEC). Upon deposition of a NIPEC aqueous solution over soil and drying out, a protective layer (crust) forms on the surface, composed of NIPEC and soil particles, resistant to wind and water erosion. After destruction, the crust is completely restored by rewatering. The high stability of the NIPEC‐soil crust is due to a NIPEC block structure with hydrophilic free anionic units and hydrophobic mutually neutralized anionic/cationic units, which ensures optimum adsorption on the surface of soil particles and binds them to bigger aggregates. The NIPEC treatment retains the porous structure of soil that favors seed germination and plant development. Being effective absorbent of heavy metals, the NIPEC formulation ensures a normal seed germination in the presence of toxic Cu2+ ions. Thus, the humics‐based NIPECs ensures antierosion protection and detoxification of soil. Additionally to ecological and agricultural applications, the NIPEC formulations have potential for immobilization of moving sands, conservation of mining dumps, treatment of road slopes, and so forth.
Con: The Unclear Benefit of Albumin
Authors: O’Brien Alastair
Published: November 2018

Many studies have shown that 20% human albumin solution infusions improve circulatory function in patients with advanced liver disease, and this treatment is widely recommended and used by all hepatologists. However, it is more expensive than other crystalloids or colloids, and several countries suffer shortages of supply. This article examines whether other fluids might be considered for these patients.
Mutations in STAG2 cause an X‐linked cohesinopathy associated with undergrowth, developmental delay, and dysmorphia: Expanding the phenotype in males
Authors: Mullegama Sureni V. , Klein Steven D. , Signer Rebecca H. ,   UCLA Clinical Genomics Center, Vilain Eric , Martinez‐Agosto Julian A.
Published: November 2018

Background

The cohesin complex is a multi‐subunit protein complex which regulates sister chromatid cohesion and separation during cellular division. In addition, this evolutionarily conserved protein complex plays an integral role in DNA replication, DNA repair, and the regulation of transcription. The core complex is composed of four subunits: RAD21, SMC1A, SMC3, and STAG1/2. Mutations in these proteins have been implicated in human developmental disorders collectively termed “cohesinopathies.”

Methods

Using clinical exome sequencing, we have previously identified three female cases with heterozygous STAG2 mutations and overlapping syndromic phenotypes. Subsequently, a familial missense variant was identified in five male family members.

Results

We now present the case of a 4‐year‐old male with developmental delay, failure to thrive, short stature, and polydactyly with a likely pathogenic STAG2 de novo missense hemizygous variant, c.3027A>T, p.Lys1009Asn. Furthermore, we compare the phenotypes of the four previously reported STAG2 variants with our case.

Conclusion

We conclude that mutations in STAG2 cause a novel constellation of sex‐specific cohesinopathy‐related phenotypes and are furthermore, essential for neurodevelopment, human growth, and behavioral development.
Optimal needle placement for extensor hallucis longus muscle using ultrasound verification
Authors: Kwak Jin Myoung , Kim Dong Hyun , Lee Yang Gyun , Choi Yoon‐Hee
Published: November 2018

Introduction: The extensor hallucis longus (EHL) muscle is important for diagnosis of neurologic lesions. It is also a target muscle for treatment. We investigated EHL with ultrasonography to determine optimal needle placement for safety and accuracy. Methods: A total of 96 legs of 48 healthy volunteers were examined through ultrasonography. Four published electromyographic methods for finding the EHL were assessed. We identified the midpoint of EHL (MD) using landmarks to determine optimal needle placement. Results: Mean values of bimalleolar line‐MD on skin (MD‐S) and tibial crest‐MD‐S were 10.5 ± 1.2 cm and 3.6 ± 0.4 cm, respectively. The depth of MD was 1.6 ± 0.2 cm. According to 4 EMG methods, the probability of needle penetrating EHL was 13% to 79% and that of needle penetrating the neurovascular bundle was 50% to 89%. Conclusions: Using ultrasonography, we could determine optimal needle placement in the EHL. Muscle Nerve 59:331–336, 2019
Transported snapshot model order reduction approach for parametric, steady‐state fluid flows containing parameter‐dependent shocks
Authors: Nair Nirmal J. , Balajewicz Maciej
Published: November 2018

A new model order reduction approach is proposed for parametric steady‐state nonlinear fluid flows characterized by shocks and discontinuities whose spatial locations and orientations are strongly parameter dependent. In this method, solutions in the predictive regime are approximated using a linear superposition of parameter‐dependent basis. The sought‐after parametric reduced bases are obtained by transporting the snapshots in a spatially and parametrically dependent transport field. Key to the proposed approach is the observation that the transport fields are typically smooth and continuous, despite the solution themselves not being so. As a result, the transport fields can be accurately expressed using a low‐order polynomial expansion. Similar to traditional projection‐based model order reduction approaches, the proposed method is formulated mathematically as a residual minimization problem for the generalized coordinates. The proposed approach is also integrated with well‐known hyper‐reduction strategies to obtain significant computational speedups. The method is successfully applied to the reduction of a parametric one‐dimensional flow in a converging‐diverging nozzle, a parametric two‐dimensional supersonic flow over a forward‐facing step, and a parametric two‐dimensional jet diffusion flame in a combustor.
Effects of cone combinations on accurate and precise Mg‐isotopic determination using multi‐collector inductively coupled plasma mass spectrometry
Authors: Gou Long‐Fei , Jin Zhangdong , Galy Albert , Sun He , Deng Li , Xu Yang
Published: November 2018

Rationale

High‐precision determination of magnesium (Mg) isotopes can now be routinely achieved by multi‐collector inductively coupled plasma mass spectrometry (MC‐ICP‐MS). The analytical sensitivity and instrumental mass discrimination behavior of this method are, however, sensitive to the types of sample and skimmer cones used in these measurements, so it is important that these parameters should be investigated.

Methods

Using the sample‐standard‐bracketing method in the wet‐plasma mode, four available combinations of sample and skimmer cones [Jet sample cone + H skimmer cone (Jet + H), standard sample cone + H skimmer cone (Standard + H), standard sample cone + X skimmer cone (Standard + X), and Jet sample cone + X skimmer cone (Jet + X)] were systematically investigated for peak shape, sensitivity, mass discrimination, accuracy, and precision in Mg‐isotopic ratio determination using a Neptune plus MC‐ICP mass spectrometer.

Results

The results showed that different cone combinations do not affect peak shapes but would significantly change the sensitivities for Mg‐isotopic determinations. Compared with using the Standard + H, the sensitivities of Mg‐isotopic determinations were enhanced by approximately a factor of 1.3, 1.4, and 1.9 by using the Standard + X, the Jet + H, and the Jet + X combinations, with the most stable mass discrimination behaviors obtained by the Jet + H. The instrumental mass fractionation slope for any combination of a modified cone geometry (i.e. Standard + X, Jet + X, and Jet + H) is 0.500, while it is 0.510 for the Standard + H. In addition, the mass discrimination behavior is related to Mg concentrations once the combination is set, indicating the necessity of concentration match during Mg‐isotopic determination.

Conclusions

The precision and accuracy of the Jet + H combination are better than those of the other combinations, and this is further supported by the validation of the Mg‐isotope data for four international reference materials: Cambridge‐1, NASS‐6, AGV‐2, and BHVO‐2. As the Jet + H combination also provides a high signal, this combination gives the most robust strategy for the highly precise and accurate determination of Mg isotopes.
The plasma membrane H+‐ATPase, a simple polypeptide with a long history
Authors: Palmgren Michael , Morsomme Pierre
Published: November 2018

The plasma membrane H+‐ATPase of fungi and plants is a single polypeptide of fewer than 1,000 residues that extrudes protons from the cell against a large electric and concentration gradient. The minimalist structure of this nanomachine is in stark contrast to that of the large multi‐subunit FOF1 ATPase of mitochondria, which is also a proton pump, but under physiological conditions runs in the reverse direction to act as an ATP synthase. The plasma membrane H+‐ATPase is a P‐type ATPase, defined by having an obligatory phosphorylated reaction cycle intermediate, like cation pumps of animal membranes, and thus, this pump has a completely different mechanism to that of FOF1 ATPases, which operates by rotary catalysis. The work that led to these insights in plasma membrane H+‐ATPases of fungi and plants has a long history, which is briefly summarized in this review.
Anomalous dimensions from crossing kernels
Authors: Sleight Charlotte , Taronna Massimo
Published: November 2018

Abstract

In this note we consider the problem of extracting the corrections to CFT data induced by the exchange of a primary operator and its descendents in the crossed channel. We show how those corrections which are analytic in spin can be systematically extracted from crossing kernels. To this end, we underline a connection between: Wilson polynomials (which naturally appear when considering the crossing kernels given recently in arXiv:1804.09334), the spectral integral in the conformal partial wave expansion, and Wilson functions. Using this connection, we determine closed form expressions for the OPE data when the external operators in 4pt correlation functions have spins J
1-J
2-0-0, in particular the anomalous dimensions of double-twist operators of the type

$$ {\left[{\mathcal{O}}_{J_1}{\mathcal{O}}_{J_2}\right]}_{n,\ell } $$

O

J
1

O

J
2

n
,
ℓ

in d dimensions and for both leading (n = 0) and sub-leading (n ≠ 0) twist. The OPE data are expressed in terms of Wilson functions, which naturally appear as a spectral integral of a Wilson polynomial. As a consequence, our expressions are manifestly analytic in spin and are valid up to finite spin. We present some applications to CFTs with slightly broken higher-spin symmetry. The Mellin Barnes integral representation for 6j symbols of the conformal group in general d and its relation with the crossing kernels are also discussed.
Statistical Inference and the Replication Crisis
Authors: Colling Lincoln J. , Szűcs Dénes
Published: November 2018

The replication crisis has prompted many to call for statistical reform within the psychological sciences. Here we examine issues within Frequentist statistics that may have led to the replication crisis, and we examine the alternative—Bayesian statistics—that many have suggested as a replacement. The Frequentist approach and the Bayesian approach offer radically different perspectives on evidence and inference with the Frequentist approach prioritising error control and the Bayesian approach offering a formal method for quantifying the relative strength of evidence for hypotheses. We suggest that rather than mere statistical reform, what is needed is a better understanding of the different modes of statistical inference and a better understanding of how statistical inference relates to scientific inference.
Sporocadaceae, a family of coelomycetous fungi with appendage-bearing conidia
Authors: Liu F. , Bonthond G. , Groenewald J.Z. , Cai L. , Crous P.W.
Published: November 2018

Species of Sporocadaceae are endophytic, plant pathogenic or saprobic, and associated with a wide range of host plants. Recent molecular studies that have attempted to address familial and generic boundaries of fungi belonging to Sporocadaceae were based on a limited number
of samples and DNA loci. The taxonomy of this group of fungi is therefore still not fully resolved. The aim of the present study is to provide a natural classification for the Sporocadaceae based on multi-locus phylogenetic analyses, using LSU, ITS, tef-1α, tub2
and rpb2 loci, in combination with morphological data. A total of 30 well-supported monophyletic clades in Sporocadaceae are recognised, representing 23 known and seven new genera. Typifications are proposed for the type species of five genera (Diploceras, Discosia,
Monochaetia, Sporocadus and Truncatella) to stabilise the application of these names. Furthermore, Neotruncatella and Dyrithiopsis are synonymised under Hymenopleella, and the generic circumscriptions of Diploceras, Disaeta, Hymenopleella,
Monochaetia, Morinia, Pseudopestalotiopsis, Sarcostroma, Seimatosporium, Synnemapestaloides and Truncatella are emended. A total of 51 new species, one nomina nova and 15 combinations are introduced.