bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term insulin treatment leads to a change in myosin heavy chain fiber distribution in OLETF rat skeletal muscle
Authors: Hong Oak‐Kee , Choi Yoon‐Hee , Kwon Hyuk‐Sang , Jeong Hee‐Kyoung , Son Jang‐Won , Lee Seong‐Su , Kim Sung‐Rae , Yoon Kun‐Ho , Yoo Soon Jib
Published: September 2018

The objective of this study was to investigate molecular and physiological changes in response to long‐term insulin glargine treatment in the skeletal muscle of OLETF rats. Male Otsuka Long‐Evans Tokushima Fatty (OLETF) and Long‐Evans Tokushima Otsuka (LETO) rats aged 24 weeks were randomly allocated to either treatment with insulin for 24 weeks or no treatment, resulting in three groups. Insulin glargine treatment in OLETF rats (OLETF‐G) for 24 weeks resulted in changes in blood glucose levels in intraperitoneal glucose tolerance tests compared with age‐matched, untreated OLETF rats (OLETF‐C), and the area under the curve was significantly decreased for OLETF‐G rats compared with OLETF‐C rats (P < 0.05). The protein levels of MHC isoforms were altered in gastrocnemius muscle of OLETF rats, and the proportions of myosin heavy chain type I and II fibers were lower and higher, respectively, in OLETF‐G compared with OLETF‐C rats. Activation of myokines (IL‐6, IL‐15, FNDC5, and myostatin) in gastrocnemius muscle was significantly inhibited in OLETF‐G compared with OLETF‐C rats (
P < 0.05). MyoD and myogenin levels were decreased, while IGF‐I and GLUT4 levels were increased, in the skeletal muscle of OLETF‐G rats (
P < 0.05). Insulin glargine treatment significantly increased the phosphorylation levels of AMPK, SIRT1, and PGC‐1α. Together, our results suggested that changes in the distribution of fiber types by insulin glargine could result in downregulation of myokines and muscle regulatory proteins. The effects were likely associated with activation of the AMPK/SIRT1/PGC‐1α signaling pathway. Changes in these proteins may at least partly explain the effect of insulin in skeletal muscle of diabetes mellitus.
Interaction of long noncoding RNA MEG3 with miRNAs: A reciprocal regulation
Authors: Moradi Mohammad‐Taher , Fallahi Hossein , Rahimi Zohreh
Published: September 2018

The competitive endogenous RNA (ceRNA) hypothesis suggests that a long noncoding RNA (lncRNA) can function as sinks for pools of microRNAs (miRNAs); thereby, in the presence of ceRNA, messenger RNAs (mRNAs) targeted by specific miRNAs can liberate and translate to protein. Maternally expressed gene 3 (MEG3) is a lncRNA, which its expression has been detected in various normal tissues, while it is lost or downregulated in human tumors. The
MEG3 is an imprinted gene which, is methylated and suppressed by DNA methyltransferases (DNMTs) family. Also, miRNAs are involved in the regulation of
MEG3 gene expression. Interestingly, the lncRNA MEG3 (lnc‐MEG3), as a ceRNA affects various cell processes such as proliferation, apoptosis, and angiogenesis by sponging miRNAs. These miRNAs, in turn, regulate different mRNAs in different pathways. This review focuses on the interaction between lnc‐MEG3 and experimentally validated miRNAs. In addition, the discussion supplemented by some data obtained from mirPath (v.3) and TarBase (v.8) databanks to provide more details about the pathways affected by this ceRNA.
Long noncoding RNAs antisense noncoding RNA in the INK4 locus (ANRIL) correlates with lower acute exacerbation risk, decreased inflammatory cytokines, and mild GOLD stage in patients with chronic obstructive pulmonary disease
Authors: Ge Jianli , Geng Shasha , Jiang Hua
Published: September 2018

Background

We aimed to assess the predictive value of long noncoding RNAs antisense noncoding RNA in the INK4 locus (lncRNAs ANRIL) for acute exacerbation of chronic obstructive pulmonary disease (COPD) and evaluate its correlation with inflammatory cytokines as well as the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage in COPD patients.

Methods

A total of 136 acute exacerbations of COPD (AECOPD) patients, 138 stable COPD patients, and 140 healthy controls (HCs) were consecutively recruited, and plasma samples were collected. Real‐time polymerase chain reaction was used to detect lncRNA ANRIL expression. Enzyme‐linked immunosorbent assay was performed to detect inflammatory cytokines expressions.

Results

LncRNA ANRIL expression was lower in AECOPD patients compared with stable COPD patients and HCs (Both P < 0.001). Receiver operating characteristic curves revealed lncRNA ANRIL could distinguish AECOPD patients from HCs (area under curve (AUC):0.700, 95% CI: 0.638‐0.762) and stable COPD patients (AUC: 0.659, 95% CI: 0.594‐0.724). For inflammatory cytokines, lncRNA ANRIL expression was negatively correlated with TNF‐α (P < 0.001), IL‐1β (P = 0.015), IL‐8 (P = 0.008), IL‐17A (P = 0.002), and LTB‐4 (P = 0.004) in AECOPD patients, while it was negatively correlated with TNF‐α (P = 0.049), IL‐1β (P = 0.005), IL‐17A (P = 0.030), and LTB‐4 (P = 0.011) in stable COPD patients. Furthermore, lncRNA ANRIL expression negatively correlated with GOLD stage in AECOPD patients (P = 0.001), but not in stable COPD patients (P = 0.131).

Conclusion

LncRNA ANRIL associates with lower acute exacerbation risk, decreased inflammatory cytokines, and mild GOLD stage in COPD patients.
MiR‐499 regulates myoblast proliferation and differentiation by targeting transforming growth factor β receptor 1
Authors: Wu Jiyao , Yue Binglin , Lan Xianyong , Wang Yanhuan , Fang Xingtang , Ma Yun , Bai Yueyu , Qi Xingshan , Zhang Chunlei , Chen Hong
Published: September 2018

MicroRNAs (miRNAs or miRs) are small noncoding RNAs that play critical roles in muscle cell proliferation and differentiation via post‐transcriptional regulation of gene expression. Here, based on our previous high‐throughput sequencing results, we evaluated miRNA‐499 (miR‐499) functions during myoblast proliferation and differentiation. In addition, we analyzed miR‐499 expression profiles and characterized the associated functional roles. MiR‐499 is known to be a skeletal muscle fiber‐type‐associated miRNA. However, its roles in skeletal myoblast proliferation and differentiation are poorly understood. MiR‐499 overexpression promoted C2C12 cell proliferation and significantly attenuated C2C12 cell myogenic differentiation. Furthermore, miR‐499 inhibition enhanced C2C12 cell proliferation and suppressed C2C12 cell differentiation. Using dual‐luciferase reporter assays and western blot analysis, we confirmed that miR‐499 targeted transforming growth factor β receptor 1 (TGFβR1), a known regulator of skeletal myoblast development. Additionally, our RNA interference analysis, in which TGFβR1 was downregulated, showed that TGFβR1 significantly promoted the differentiation of C2C12 cells and inhibited their proliferation.
Retracted: MicroRNA‐363 inhibits angiogenesis, proliferation, invasion, and migration of renal cell carcinoma via inactivation of the Janus tyrosine kinases 2–signal transducers and activators of transcription 3 axis by suppressing growth hormone receptor gene
Authors: Zhu Jie , Zhu Da‐Qing , Zhang Yu , Liu Qi‐Ming , Wang Peng‐Chao , Li Hong‐Zhao , Ma Xin , Zhang Xu
Published: September 2018

Renal cell carcinoma (RCC) is the most common malignancy involving the kidneys and a major cause of cancer mortality. The involvement of microRNA (miRNA) expression in the tumorigenesis and progression of RCC has been previously highlighted. Therefore, we conducted this study to investigate whether microRNA‐363 (miR‐363) affects the development of RCC via the Janus tyrosine kinases (JAK2)–signal transducers and activators of transcription (STAT) axis by targeting the growth hormone receptor (GHR), by observing the changes that occurred in the RCC and the normal adjacent tissues of patients with RCC. RCC cells were transfected with a series of miR‐363 mimic, miR‐363 inhibitor, or small interfering RNA against GHR to determine the influence of miR‐363 on the expression of GHR and JAK2–STAT3 axis‐related genes with the use of reverse transcription quantitative polymerase chain reaction and Western blot analysis. The angiogenesis, viability, invasion, and migration of cells were evaluated by means of in vitro angiogenesis, 3‐(4,5)‐dimethylthiahiazo (‐z‐y1)‐3,5‐di‐phenytetrazoliumromide (MTT), wound‐healing, and Transwell assays. The results revealed reduced miR‐363 expression and elevated GHR expression in RCC. It was also found that miR‐363 altered the activation of the JAK2–STAT3 axis through the inhibition of GHR. Cells treated with the miR‐363 inhibitor presented with increased capillary vessels, cell viability, invasion, and migration, whereas it was on the contrary in the RCC cells with overexpressed miR‐363. These results implicated that the overexpression of miR‐363 could specifically bind to GHR to downregulate the expression of GHR, which, in turn, inactivates the JAK2–STAT3 axis, thereby influencing the angiogenesis, cell invasion, and migration abilities in RCC.
New advances of lncRNAs in liver fibrosis, with specific focus on lncRNA–miRNA interactions
Authors: Bian Er‐Bao , Xiong Zhi‐Gang , Li Jun
Published: September 2018

Noncoding RNAs (ncRNAs) were initially thought to be transcriptional byproducts. However, recent advances of ncRNAs research have increased our understanding of the importance of ncRNA in gene regulation and disease pathogenesis. Consistent with these developments, liver fibrosis research is also experiencing rapid growth in the investigation of links between ncRNAs and the pathology of this disease. The initial focus was on studying the function and regulation mechanisms of microRNAs (miRNAs). However, recently, elucidation of the mechanisms of long noncoding RNAs (lncRNAs) and lncRNA‐mediated liver fibrosis has just commenced. In this review, we emphasize on abnormal expression of lncRNAs in liver fibrosis. Furthermore, we also discuss that the interaction of lncRNAs with miRNAs is involved in the regulation of the expression of protein‐coding genes in liver fibrosis. Recent advances in understanding dysregulated lncRNAs expression and the lncRNAs–miRNAs interaction in liver fibrosis will help for developing new therapeutic targets and biomarkers of liver fibrosis.
The predictive value of intra‐left atrial mechanical delay for 1‐year recurrence of atrial fibrillation after catheter ablation: A clinical follow‐up study using dual Doppler echocardiography
Authors: Zhou Yanxiang , Chen Jinling , Hu Bo , Cao Sheng , Zhou Qing , Guo Ruiqiang
Published: September 2018

Purpose

The availability of dual Doppler echocardiography (DDE), which facilitates the simultaneous recording of Doppler waveforms at two different sites, has enhanced ability to assess single‐beat atrial mechanical delay. We sought to investigate the predictive value of intra‐left atrial mechanical delay for atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA) with DDE.

Methods

Eighty‐six patients with paroxysmal AF scheduled to undergo RFCA were prospectively enrolled. Intra‐atrial and interatrial mechanical delays were evaluated by DDE and traditional tissue Doppler imaging (tTDI), respectively. The time of whole analysis process with each method was recorded. After RFCA, patients were followed for 1 year.

Results

Thirty (34.88%) patients had AF recurrence, and 56 (65.12%) patients maintained sinus rhythm. Cut‐off values of 39.38 ms for intra‐left atrial mechanical delay obtained by DDE and 32.70 ms by tTDI predicted AF recurrence. Areas under curves were comparable in receiver operator characteristic analysis (P > .05). The whole analysis time of DDE was less than tTDI. Parameters obtained by DDE had better reproducibility.

Conclusion

Intra‐left atrial mechanical delay best predicted 1‐year AF recurrence after RFCA. Compared with tTDI, DDE can noninvasively assess single‐beat atrial mechanical delay with high predictive power, less analysis time, and better reproducibility.
Radiomics Analysis of Multiparametric MRI Evaluates the Pathological Features of Cervical Squamous Cell Carcinoma
Authors: Wu Qingxia , Shi Dapeng , Dou Shewei , Shi Ligang , Liu Mingbo , Dong Li , Chang Xiaowan , Wang Meiyun
Published: September 2018

Background

Robust parameters to evaluate pathological aggressiveness are needed to provide individualized therapy for cervical cancer patients.

Purpose

To investigate the radiomics analysis of multiparametric MRI to evaluate tumor grade, lymphovascular space invasion (LVSI), and lymph node (LN) metastasis of cervical squamous cell carcinoma (CSCC).

Study Type

Retrospective.

Subjects

Fifty‐six patients with histopathologically confirmed CSCC.

Field Strength/Sequence

3T, axial T2 and T2 with fat suppression (FS), diffusion‐weighted imaging (DWI) (multi‐b values), axial dynamic contrast enhanced (DCE) MRI (8 sec temporal resolution).

Assessment

Regions of interest were drawn around the tumor on each axial slice and fused to generate the whole tumor volume. Sixty‐six radiomics features were derived from each image sequence, including axial T2 and T2 FS, ADC maps, and Ktrans, Ve, and Vp maps from DCE MRI.

Statistical Tests

A univariate analysis was performed to assess each parameter's association with tumor grade and the presence of lymphovascular space invasion (LVSI) and lymph node (LN) metastasis. A principal component analysis was employed for dimension reduction and to generate new discriminative valuables. Using logistic regression, a discriminative model of each parameter was built and a receiver operating characteristic curve (ROC) was generated.

Results

The area under the ROC curve (AUC) of anatomical, diffusion, and permeability parameters in discriminating the presence of LVSI ranged from 0.659 to 0.814, with Ve showing the best discriminative value. The AUC in discriminating the presence of LN metastasis and distinguishing tumor grade ranged from 0.747 to 0.850, 0.668 to 0.757, with ADC and Ve showing the best discriminative value, respectively.

Data Conclusion

Functional maps exhibit better discriminative values than anatomical images for discriminating the pathological features of CSCC, with ADC maps showing the best discrimination performance for LN metastasis and Ve maps showing the best discriminative value for LVSI and tumor grade.

Level of Evidence: 3

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;49:1141–1148.
Detection and genotyping of enteric viruses in hospitalized children with acute gastroenteritis in Belém, Brazil: Occurrence of adenovirus viremia by species F, types 40/41
Authors: Portal Thayara Morais , Reymão Tammy Kathlyn Amaral , Quinderé Neto Germano Alves , Fiuza Mercedes Kamila Da C , Teixeira Dielle Monteiro , Lima Ian Carlos Gomes , Sousa Júnior Edivaldo Costa , Bandeira Renato Da Silva , De Deus Danielle Rodrigues , Justino Maria Cleonice A , Linhares Alexandre Da Costa , Silva Luciana Damascena Da , Resque Hugo Reis , Gabbay Yvone Benchimol
Published: September 2018

Enteric adenovirus (AdV), sapovirus (SaV), and human astrovirus (HAstV) are important pathogens involved in the gastroenteritis etiology. In this study, a total of 219 fecal samples and sera were collected from children hospitalized for acute gastroenteritis (AGE) in two large pediatric hospitals in Belém, from March 2012 to April 2015. The samples were analyzed by polymerase chain reaction (PCR) for AdV and HAstV (astrovirus) detection, and Nested‐PCR and qPCR for SaV detection. AdV was detected in 50.2% (110/219) of the cases, with 42.7% (47/110) being sequenced and classified as: species F (63.9% – 30/47), A (4.2% – 2/47), B (6.4% – 3/47), C (17.1% – 8/47), D (4.2% – 2/47), and E (4.2% – 2/47). Of the 110 AdV‐positive feces samples, 80 paired sera presented sufficient amounts and were also tested for this virus, of which 51 (63.7%) showed positive results and 26 (70.3%) pairs (feces plus sera) presented concordant results after sequencing being classified as: species F (21/26; 80.8%), A (1/26; 3.8%), B (1/26; 3.8%), and C (3/26; 11.5%). Overall, HAstV rate in the feces samples was 1.8% (4/219), including both HAstV‐1a (2/4; 50%) and HAstV‐2c (2/4; 50%). SaV was detected in 4.6% (10/219) of the fecal samples, out of which 50% (5/10) of the positive samples were characterized into the genogroups GI.1 (1), GI.2 (2), and GII.4 (2). These findings highlighted the important contributions of AdV, HAstV, and SaV in the enteric virus spectrum in our region and showed the high genetic diversity of AdV. In addition, it demonstrated for the first time in Brazil, the circulation of AdV in the serum of hospitalized children with AGE.
Role of full‐thickness cartilage defects in knee osteoarthritis (OA) incidence and progression: Data from the OA Initiative
Authors: Everhart Joshua S. , Abouljoud Moneer M. , Flanigan David C.
Published: September 2018

The purpose of this study is to determine whether full‐thickness tibiofemoral cartilage defects are predictive of incident radiographic OA, progression of radiographic OA, and progression to severe radiographic OA. Participants in the OA Initiative (n = 1317, 38.1% male, mean age 60.9 years SD 9.2) with baseline MRIs and Kellgren–Lawrence (KL) OA grade 0–3 (none to moderate OA) were included. All participants had follow‐up radiographs at mean 4.9 years (max 8.0). The effect of full‐thickness defect presence, size, and location on risk of incident OA (KL grade 2+), overall progression of OA (increase in KL grade 1+ points), or compartment‐specific OA progression was assessed with Cox proportional hazards modeling with adjustment for demographic factors, weight, and knee alignment. The yearly incidence of tibiofemoral OA was 0.3% (CI 0.2–0.4%); defect presence, size, and location were not associated with incident OA risk. The yearly rate of OA progression was 3.8% in participants without tibiofemoral full‐thickness defects, 6.7% with medial defects, and 6.3% with lateral defects. Medial bipolar (kissing) lesions were an independent risk factor for OA progression as well as medial compartment progression. Lateral tibial‐sided full‐thickness defects increased risk of lateral progression (increase in lateral OARSI grade). In older adults, isolated full‐thickness cartilage defects do not increase short‐term risk of incident OA. However, in the setting of preexisting mild or moderate OA, medial bipolar (kissing) defects increase risk of overall OA progression (KL grade) as well as progression of medial compartment OA. Lateral tibial defects increase risk of lateral compartment OA progression. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
High muscle co‐contraction does not result in high joint forces during gait in anterior cruciate ligament deficient knees
Authors: Khandha Ashutosh , Manal Kurt , Capin Jacob , Wellsandt Elizabeth , Marmon Adam , Snyder‐Mackler Lynn , Buchanan Thomas S.
Published: September 2018

The mechanism of knee osteoarthritis development after anterior cruciate ligament injuries is poorly understood. The objective of this study was to evaluate knee gait variables, muscle co‐contraction indices and knee joint loading in young subjects with anterior cruciate ligament deficiency (ACLD, n = 36), versus control subjects (n = 12). A validated, electromyography‐informed model was used to estimate joint loading. For the involved limb of ACLD subjects versus control, muscle co‐contraction indices were higher for the medial (p = 0.018, effect size = 0.93) and lateral (p = 0.028, effect size = 0.83) agonist–antagonist muscle pairs. Despite higher muscle co‐contraction, medial compartment contact force was lower for the involved limb, compared to both the uninvolved limb (mean difference = 0.39 body weight, p = 0.009, effect size = 0.70) as well as the control limb (mean difference = 0.57 body weight, p = 0.007, effect size = 1.14). Similar observations were made for total contact force. For involved versus uninvolved limb, the ACLD group demonstrated lower vertical ground reaction force (mean difference = 0.08 body weight, p = 0.010, effect size = 0.70) and knee flexion moment (mean difference = 1.32% body weight * height, p = 0.003, effect size = 0.76), during weight acceptance. These results indicate that high muscle co‐contraction does not always result in high knee joint loading, which is thought to be associated with knee osteoarthritis. Long‐term follow‐up is required to evaluate how gait alterations progress in non‐osteoarthritic versus osteoarthritic subjects. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Intranasal Corticosteroids Do Not Lead to Ocular Changes: A Systematic Review and Meta‐analysis
Authors: Valenzuela Carla V. , Liu James C. , Vila Peter M. , Simon Laura , Doering Michelle , Lieu Judith E. C.
Published: September 2018

Objectives

The safety and efficacy of intranasal corticosteroids (INCS) are well established, but there remains apprehension that INCS could lead to systemic side effects, as with oral steroids. The objective of this systematic review was to assess whether the use of INCS lead to increased intraocular pressure (IOP) above 20 mm Hg, glaucoma, or formation of posterior subcapsular cataracts in adult patients with rhinitis.

Methods

Two medical librarians searched the published literature for records discussing the use of “nasal steroids” in “rhinitis” and their effect on “intraocular pressure,” “cataracts,” or “glaucoma.”

Results

A total of 484 studies were identified, and 10 randomized controlled trials met our inclusion criteria. Meta‐analysis of 2,226 patients revealed that the relative risk of elevated IOP in those who received INCS was 2.24 (95% confidence interval [CI]: 0.68 to 7.34) compared to placebo. The absolute increased incidence of elevated IOP in patients using INCS compared to placebo was 0.8% (95% CI: 0% to 1.6%). There were zero cases of glaucoma in both placebo and INCS groups at 12 months. The absolute increased incidence of developing a posterior subcapsular cataract was 0.02% (95% CI: −0.3% to 0.4%).

Conclusions

Use of INCS is not associated with a significant risk of elevating IOP or developing a posterior subcapsular cataract in patients with allergic rhinitis. Presence of glaucoma, however, is the real clinical adverse event of concern. There were zero reported cases of glaucoma at 12 months. Future studies should formally evaluate for glaucoma rather than use IOP measures as a surrogate. Laryngoscope, 129:6–12, 2019
Long‐term outcomes of cartilage‐buttressed T‐tube tympanoplasty for prolonged middle ear ventilation
Authors: Zuniga Steven A. , Larner Sean , Souza David M. , Khan Andleeb , Hillman Todd A. , Chen Douglas A.
Published: September 2018

Objectives/Hypothesis

To report on the safety and efficacy of cartilage‐buttressed T‐tube tympanoplasty for long‐term middle ear ventilation, specifically by examining duration of tube survival, as well as adverse events associated with prolonged middle ear intubation, including persistent tympanic membrane perforation.

Study Design

Retrospective case series of patients undergoing cartilage‐buttressed T‐tube tympanoplasty between January 2005 and December 2016 in a tertiary‐care neurotology private practice.

Methods

Patients who underwent cartilage T‐tube tympanoplasty with complete pre‐ and postoperative audiometric data and a minimum follow‐up duration of 12 months were analyzed. T‐tube survival and adverse events including persistent tympanic membrane perforation were recorded and compared to published data for other long‐term middle ear ventilation techniques.

Results

The study cohort included 72 cartilage‐buttressed T‐tube tympanoplasties in 68 patients. Median tube survival was 34 months (range, 2–131 months). Incidence of persistent tympanic membrane perforation (n = 1) was 1.4%

Conclusions

Cartilage‐buttressed T‐tube tympanoplasty is a safe and effective means of accomplishing long‐term middle ear ventilation with a considerably lower rate of persistent tympanic membrane perforation as compared to alternative methods of prolonged middle ear ventilation.

Level of Evidence

4 Laryngoscope, 129:203–208, 2019
Role of Skin Layers on Mechanical Properties and Supercontraction of Spider Dragline Silk Fiber
Authors: Yazawa Kenjiro , Malay Ali D. , Masunaga Hiroyasu , Numata Keiji
Published: September 2018

Spider dragline silk is a composite biopolymer that harbors extraordinary mechanical characteristics, and consists of a hierarchically arranged protein core surrounded by outer “skin” layers. However, the contribution of the successive fiber layers on material properties has not been well defined. Here, the influence of the different components on the physicochemical and mechanical properties of dragline is investigated. The crystal structure and the mechanical properties are not changed significantly after the removal of skin constituents, indicating that the core region of dragline silk fibers determines the structural and mechanical properties. Furthermore, the outer layers have little influence on supercontraction, suggesting they do not function as protection against the penetration of water molecules. On the other hand, the outer layers offer some protection against protease digestion. The present study provides insight into how the function and structure of silk fibers are modulated and facilitates the design of silk‐inspired functional materials.
Placebo and nocebo responses in other movement disorders besides Parkinson's disease: How much do we know?
Authors: Ferreira Joaquim J. , Trenkwalder Claudia , Mestre Tiago A.
Published: September 2018

Among movement disorders and medicine in general, PD is one of the conditions for which there is a greater knowledge of the placebo and nocebo responses. In other movement disorders, the knowledge of placebo and nocebo responses is less. An advance in this field is expected to contribute to a better understanding of the nature of a therapeutic benefit in clinical research and clinical practice, and mechanisms of placebo and nocebo. We conducted a review on placebo and nocebo responses in other movement disorders besides PD by primarily examining meta‐analyses of clinical trials assessing specifically the placebo and/or nocebo responses. Second, we examined both efficacy and safety results of a placebo arm in pivotal placebo‐controlled trials for the different movement disorders. RLS is the movement disorder for which the most data exist, followed by tic disorders and Huntington's disease. Data available in other conditions document a placebo response in a varied phenomenology. We found different placebo responses according to clinical domains assessed, type of outcomes used for the same clinical domain, and modes of treatment administration, including rehabilitation and surgical interventions. Data on the nocebo response were very scarce. Although the data available are limited, RLS has the better documentation of placebo and nocebo responses. In contrast, atypical parkinsonisms are the group of movement disorders with the least knowledge. The clinical entities with a more robust placebo response are those that have the most beneficial available symptomatic treatments. © 2018 International Parkinson and Movement Disorder Society
Symplectomorphic registration with phase space regularization by entropy spectrum pathways
Authors: Galinsky Vitaly L. , Frank Lawrence R.
Published: September 2018

Purpose

The ability to register image data to a common coordinate system is a critical feature of virtually all imaging studies. However, in spite of the abundance of literature on the subject and the existence of several variants of registration algorithms, their practical utility remains problematic, as commonly acknowledged even by developers of these methods.

Methods

A new registration method is presented that utilizes a Hamiltonian formalism and constructs registration as a sequence of symplectomorphic maps in conjunction with a novel phase space regularization. For validation of the framework a panel of deformations expressed in analytical form is developed that includes deformations based on known physical processes in MRI and reproduces various distortions and artifacts typically present in images collected using these different MRI modalities.

Results

The method is demonstrated on the three different magnetic resonance imaging (MRI) modalities by mapping between high resolution anatomical (HRA) volumes, medium resolution diffusion weighted MRI (DW‐MRI) and HRA volumes, and low resolution functional MRI (fMRI) and HRA volumes.

Conclusions

The method has shown an excellent performance and the panel of deformations was instrumental to quantify its repeatability and reproducibility in comparison to several available alternative approaches.
Compressed sensing acceleration of biexponential 3D‐T1ρrelaxation mapping of knee cartilage
Authors: Zibetti Marcelo V. W. , Sharafi Azadeh , Otazo Ricardo , Regatte Ravinder R
Published: September 2018

Purpose

Use compressed sensing (CS) for 3D biexponential spin‐lattice relaxation time in the rotating frame (T1ρ) mapping of knee cartilage, reducing the total scan time and maintaining the quality of estimated biexponential T1ρparameters (short and long relaxation times and corresponding fractions) comparable to fully sampled scans.

Methods

Fully sampled 3D‐T1ρ‐weighted data sets were retrospectively undersampled by factors 2–10. CS reconstruction using 12 different sparsifying transforms were compared for biexponential T1ρ‐mapping of knee cartilage, including temporal and spatial wavelets and finite differences, dictionary from principal component analysis (PCA), k‐means singular value decomposition (K‐SVD), exponential decay models, and also low rank and low rank plus sparse models. Synthetic phantom (N = 6) and in vivo human knee cartilage data sets (N = 7) were included in the experiments. Spatial filtering before biexponential T1ρparameter estimation was also tested.

Results

Most CS methods performed satisfactorily for an acceleration factor (AF) of 2, with relative median normalized absolute deviation (MNAD) around 10%. Some sparsifying transforms, such as low rank with spatial finite difference (L + S SFD), spatiotemporal finite difference (STFD), and exponential dictionaries (EXP) significantly improved this performance, reaching MNAD below 15% with AF up to 10, when spatial filtering was used.

Conclusion

Accelerating biexponential 3D‐T1ρmapping of knee cartilage with CS is feasible. The best results were obtained by STFD, EXP, and L + S SFD regularizers combined with spatial prefiltering. These 3 CS methods performed satisfactorily on synthetic phantom as well as in vivo knee cartilage for AFs up to 10, with median error below 15%.
Non‐contrast enhanced simultaneous 3D whole‐heart bright‐blood pulmonary veins visualization and black‐blood quantification of atrial wall thickness
Authors: Ginami Giulia , Lòpez Karina , Mukherjee Rahul K. , Neji Radhouene , Munoz Camila , Roujol Sébastien , Mountney Peter , Razavi Reza , Botnar René M. , Prieto Claudia
Published: September 2018

Purpose

Pre‐interventional assessment of atrial wall thickness (AWT) and of subject‐specific variations in the anatomy of the pulmonary veins may affect the success rate of RF ablation procedures for the treatment of atrial fibrillation (AF). This study introduces a novel non‐contrast enhanced 3D whole‐heart sequence providing simultaneous information on the cardiac anatomy—including both the arterial and the venous system—(bright‐blood volume) and AWT (black‐blood volume).

Methods

The proposed MT‐prepared bright‐blood and black‐blood phase sensitive inversion recovery (PSIR) BOOST framework acquires 2 differently weighted bright‐blood volumes in an interleaved fashion. The 2 data sets are then combined in a PSIR‐like reconstruction to obtain a complementary black‐blood volume for atrial wall visualization. Image‐based navigation and non‐rigid respiratory motion correction are exploited for 100% scan efficiency and predictable acquisition time. The proposed approach was evaluated in 11 healthy subjects and 4 patients with AF scheduled for RF ablation.

Results

Improved depiction of the cardiac venous system was obtained in comparison to a T2‐prepared BOOST implementation, and quantified AWT was shown to be in good agreement with previously reported measurements obtained in healthy subjects (right atrium AWT: 2.54 ± 0.87 mm, left atrium AWT: 2.51 ± 0.61 mm). Feasibility for MT‐prepared BOOST acquisitions in patients with AF was demonstrated.

Conclusion

The proposed motion‐corrected MT‐prepared BOOST sequence provides simultaneous non‐contrast pulmonary vein depiction as well as black‐blood visualization of atrial walls. The proposed sequence has a large spectrum of potential clinical applications and further validation in patients is warranted.
Segmentation of left ventricle in late gadolinium enhanced MRI through 2D‐4D registration for infarct localization in 3D patient‐specific left ventricular model
Authors: Leong Chen Onn , Lim Einly , Tan Li Kuo , Abdul Aziz Yang Faridah , Sridhar Ganiga Srinivasaiah , Socrates Dokos , Chee Kok Han , Lee Zhen‐Vin , Liew Yih Miin
Published: September 2018

Purpose

To evaluate a 2D‐4D registration‐cum‐segmentation framework for the delineation of left ventricle (LV) in late gadolinium enhanced (LGE) MRI and for the localization of infarcts in patient‐specific 3D LV models.

Methods

A 3‐step framework was proposed, consisting of: (1) 3D LV model reconstruction from motion‐corrected 4D cine‐MRI; (2) Registration of 2D LGE‐MRI with 4D cine‐MRI; (3) LV contour extraction from the intersection of LGE slices with the LV model. The framework was evaluated against cardiac MRI data from 27 patients scanned within 6 months after acute myocardial infarction. We compared the use of local Pearson's correlation (LPC) and normalized mutual information (NMI) as similarity measures for the registration. The use of 2 and 6 long‐axis (LA) cine‐MRI scans was also compared. The accuracy of the framework was evaluated using manual segmentation, and the interobserver variability of the scar volume derived from the segmented LV was determined using Bland‐Altman analysis.

Results

LPC outperformed NMI as a similarity measure for the proposed framework using 6 LA scans, with Hausdorrf distance (HD) of 1.19 ± 0.53 mm versus 1.51 ± 2.01 mm (endocardial) and 1.21 ± 0.48 mm versus 1.46 ± 1.78 mm (epicardial), respectively. Segmentation using 2 LA scans was comparable to 6 LA scans with a HD of 1.23 ± 0.70 mm (endocardial) and 1.25 ± 0.74 mm (epicardial). The framework yielded a lower interobserver variability in scar volumes compared with manual segmentation.

Conclusion

The framework showed high accuracy and robustness in delineating LV in LGE‐MRI and allowed for bidirectional mapping of information between LGE‐ and cine‐MRI scans, crucial in personalized model studies for treatment planning.
Effects of Strength Training in Amyotrophic Lateral Sclerosis: How Much Do We Know?
Authors: Shefner Jeremy M.
Published: September 2018

See article on pages 40–46 in this issue.
Investigation of analysis methods for hyperpolarized 13C‐pyruvate metabolic MRI in prostate cancer patients
Authors: Larson Peder E. Z. , Chen Hsin‐Yu , Gordon Jeremy W. , Korn Natalie , Maidens John , Arcak Murat , Tang Shuyu , Criekinge Mark , Carvajal Lucas , Mammoli Daniele , Bok Robert , Aggarwal Rahul , Ferrone Marcus , Slater James B. , Nelson Sarah J. , Kurhanewicz John , Vigneron Daniel B.
Published: September 2018

MRI using hyperpolarized (HP) carbon‐13 pyruvate is being investigated in clinical trials to provide non‐invasive measurements of metabolism for cancer and cardiac imaging. In this project, we applied HP [1‐13C]pyruvate dynamic MRI in prostate cancer to measure the conversion from pyruvate to lactate, which is expected to increase in aggressive cancers. The goal of this work was to develop and test analysis methods for improved quantification of this metabolic conversion.

In this work, we compared specialized kinetic modeling methods to estimate the pyruvate‐to‐lactate conversion rate, kPL, as well as the lactate‐to‐pyruvate area‐under‐curve (AUC) ratio. The kinetic modeling included an “inputless” method requiring no assumptions regarding the input function, as well as a method incorporating bolus characteristics in the fitting. These were first evaluated with simulated data designed to match human prostate data, where we examined the expected sensitivity of metabolism quantification to variations in kPL, signal‐to‐noise ratio (SNR), bolus characteristics, relaxation rates, and B1 variability. They were then applied to 17 prostate cancer patient datasets.

The simulations indicated that the inputless method with fixed relaxation rates provided high expected accuracy with no sensitivity to bolus characteristics. The AUC ratio showed an undesired strong sensitivity to bolus variations. Fitting the input function as well did not improve accuracy over the inputless method. In vivo results showed qualitatively accurate kPL maps with inputless fitting. The AUC ratio was sensitive to bolus delivery variations. Fitting with the input function showed high variability in parameter maps.

Overall, we found the inputless kPL fitting method to be a simple, robust approach for quantification of metabolic conversion following HP [1‐13C]pyruvate injection in human prostate cancer studies. This study also provided initial ranges of HP [1‐13C]pyruvate parameters (SNR, kPL, bolus characteristics) in the human prostate.
Temperature effect on fatigue behavior of basalt fiber‐reinforced polymer composites
Authors: Zhao Xing , Wang Xin , Wu Zhishen , Keller Thomas , Vassilopoulos Anastasios P.
Published: September 2018

In this study, the temperature effect on the static and tension–tension fatigue behavior of basalt fiber‐reinforced epoxy polymer (BFRP) composites is investigated. The S–N curves, energy dissipation, stiffness degradation, and displacement increment with lifetime under temperatures of −20, 0, 20, 40, and 60°C were derived to evaluate the BFRP fatigue performance under different environmental temperatures. The results showed that the static strength and fatigue life at a certain maximum stress increased with decreasing temperatures. This effect of temperature on the fatigue life was more pronounced at the low cycle fatigue regime. Life differences between the various temperatures became smaller with higher life. While energy dissipation was small for all specimens, the stiffness degradation and permanent displacement increment were sensitive to different temperatures, showing a greater lifetime stiffness loss and permanent displacement increment before failure at lower temperatures. POLYM. COMPOS., 40:2273–2283, 2019. © 2018 Society of Plastics Engineers
ABA‐mediated regulation of stomatal density is OST1‐independent
Authors: Jalakas Pirko , Merilo Ebe , Kollist Hannes , Brosché Mikael
Published: September 2018

Stomata, small pores on the surfaces of leaves formed by a pair of guard cells, adapt rapidly to changes in the environment by adjusting the aperture width. As a long‐term response, the number of stomata is regulated during stomatal development. The hormone abscisic acid (ABA) regulates both processes. In ABA mediated guard cell signaling the protein kinase OPEN STOMATA1 (OST1) has a central role, as stomatal closure in the ost1 mutant is impaired in response to ABA and to different environmental stimuli. We aimed to dissect the contribution of different ABA‐related regulatory mechanisms in determining stomatal conductance, a combination of stomatal density and aperture width, and crossed the ost1 mutant with mutants that either decreased (aba3) or increased (cyp707a1/a3) the concentration of ABA in plants. The double mutant ost1 aba3 had higher stomatal conductance than either parent due to a combination of increased stomatal aperture width and higher stomatal density. In the triple mutant ost1 cyp707a1/a3, stomatal conductance was significantly lower compared to ost1‐3 due to lower stomatal density. Further characterization of the single, double and triple mutants showed that responses to treatments that lead to stomatal closure were impaired in ost1 as well as ost1 aba3 and ost1 cyp707a1/a3 mutants, supporting a critical role for OST1 in stomatal aperture regulation. On the basis of our results, we suggest that two signaling pathways regulate water flux from leaves, that is, stomatal conductance: an ABA‐dependent pathway that determines stomatal density independent of OST1; and an OST1‐dependent pathway that regulates rapid changes in stomatal aperture.
Static and dynamic scaling behavior of a polymer melt model with triple‐well bending potential
Authors: Jabbari‐Farouji Sara
Published: September 2018

We perform molecular‐dynamics simulations for polymer melts of the coarse‐grained poly(vinyl alcohol) model that crystallizes upon slow cooling. To establish the properties of its high temperature, liquid state as a reference point, we characterize in detail the structural features of equilibrated polymer melts with chain lengths5 ≤N≤ 1000at a temperature slightly above their crystallization temperature. We find that the conformations of sufficiently long polymers withN> 50 obey essentially the Flory's ideality hypothesis. The chain length dependence of the end‐to‐end distance and the gyration radius follow the scaling predictions of ideal chains and the probability distributions of the end‐to‐end distance, and form factors are in good agreement with those of ideal chains. The intrachain correlations reveal evidences for incomplete screening of self‐interactions. However, the observed deviations are small. Our results rule out any preordering or mesophase structure formation that are proposed as precursors of polymer crystallization in the melt. Moreover, we characterize in detail primitive paths of long entangled polymer melts and we examine scaling predictions of Rouse and the reptation theory for the mean squared displacement of monomers and polymers center of mass. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys.2018,56, 1376–1392
Proteomics Analysis for Verification of Rheumatoid Arthritis Biomarker Candidates Using Multiple Reaction Monitoring
Authors: Lee Jiyeong , Mun Sora , Kim Doojin , Lee You‐Rim , Sheen Dong‐Hyuk , Ihm Chunhwa , Lee Seung Hoon , Kang Hee‐Gyoo
Published: September 2018

Purpose

Rheumatoid arthritis (RA) is an autoimmune disease in which autoantibodies attack the synovial membrane, causing joint inflammation. Blood tests would offer a powerful, minimally invasive method for early diagnosis of RA. However, no reliable biomarkers for RA are presently available. The aim is to develop biomarkers for RA by multiple reaction monitoring (MRM)‐based quantification of candidate biomarkers.

Experimental design

Proteomics approaches are commonly used to identify and verify disease biomarkers. For discovery of biomarkers for RA, SWATH acquisition is performed and selected candidate biomarkers are validated by MRM. Target serum proteins are compared between patients with RA and healthy controls divided into three groups based on rheumatoid factor level.

Results

A total of 45 differentially expressed proteins are identified, as determined by SWATH acquisition. Of these, 13 proteins are selected as novel candidate biomarkers. A total of five proteins (transthyretin, gelsolin, angiotensinogen, lipopolysaccharide‐binding protein, and protein S100‐A9) are shown to have the potential to distinguish patients with RA from healthy controls.

Conclusions and clinical relevance

These five proteins may improve the efficiency of diagnosis of RA. MRM can be used to easily diagnose RA by detecting five proteins simultaneously in a single sample with high sensitivity.
Predicting X‐ray solution scattering from flexible macromolecules
Authors: Zhou Hao , Guterres Hugo , Mattos Carla , Makowski Lee
Published: September 2018

Wide‐angle X‐ray solution scattering (WAXS) patterns contain substantial information about the structure and dynamics of a protein. Solution scattering from a rigid protein can be predicted from atomic coordinate sets to within experimental error. However, structural fluctuations of proteins in solution can lead to significant changes in the observed intensities. The magnitude and form of these changes contain information about the nature and spatial extent of structural fluctuations in the protein. Molecular dynamics (MD) simulations based on a crystal structure and selected force field generate models for protein internal motions, and here we demonstrate that they can be used to predict the impact of structural fluctuations on solution scattering data. In cases where the observed and calculated intensities correspond, we can conclude that the X‐ray scattering provides direct experimental validation of the structural and MD results. In cases where calculated and observed intensities are at odds, the inconsistencies can be used to determine the origins of these discrepancies. They may be because of overestimates or underestimates of structural fluctuations in MD simulations, under‐sampling of the structural ensemble in the simulations, errors in the structural model, or a mismatch between the experimental conditions and the parameters used in carrying out the MD simulation.
Memory‐type multivariate control charts with auxiliary information for process mean
Authors: Haq Abdul , Khoo Michael B. C.
Published: September 2018

In statistical process control, it is a common practice to increase the sensitivity of a control chart with the help of an efficient estimator of the underlying process parameter. In this paper, we consider an efficient estimator that requires information on several study variables along with one or more auxiliary variables when estimating the mean of a multivariate normally distributed process. Using this auxiliary‐information‐based (AIB) process mean estimator, we propose new multivariate EWMA (MEWMA), double MEWMA (DMEWMA), and multivariate CUSUM (MCUSUM) charts for monitoring the process mean, denoted by the AIB‐MEWMA, AIB‐DMEWMA, and AIB‐MCUSUM charts, respectively. The run length characteristics of the proposed multivariate charts are computed using Monte Carlo simulations. The proposed charts are compared with their existing counterparts in terms of the run length characteristics. It turns out that the AIB‐MEWMA, AIB‐DMEWMA, and AIB‐MCUSUM charts are uniformly and substantially better than the MEWMA, DMEWMA, and MCUSUM charts, respectively, when detecting different shifts in the process mean. A real dataset is considered to explain the implementation of the proposed and existing multivariate control charts.
The matrix‐assisted laser desorption/ionisation in‐source decay of peptides using ion mobility enabled quadrupole‐time‐of‐flight mass spectrometry
Authors: Vrkoslav Vladimír , Muck Alexander , Brown Jeffery M. , Hubálek Martin , Cvačka Josef
Published: September 2018

Rationale

In‐source decay (ISD) matrix‐assisted laser desorption/ionisation (MALDI) mass spectrometry with a 1,5‐diaminonaphthalene (1,5‐DAN) matrix is used for the structural characterisation of peptides. However, MALDI spectra are intrinsically complicated by the presence of matrix ions, which interfere with the peptide fragments. This may cause false‐positive results or reduced sequence coverage. This paper reports investigations of ISD processes in an intermediate pressure MALDI ion source and a protocol for the removal of interfering ions using ion mobility separation (IMS).

Methods

An intermediate pressure MALDI source of a Q‐IMS‐Q‐TOF instrument (Synapt G2) has been employed for the ISD of selected peptides using a 1,5‐DAN matrix.

Results

Successful coupling of the MALDI source tuned for ISD experiments using IMS is demonstrated. The IMS made it possible to remove interfering matrix ions effectively from the spectra and thus to increase the confidence of spectral interpretation. Extensive fragment series corresponding to N–Cα bond cleavages were observed under optimised conditions; on the other hand, weaker series of ions caused by peptide bond cleavages were prevalent for default conditions and/or the α‐hydroxycinnamic acid matrix.

Conclusions

Ion mobility has been used for the elimination of matrix ions. The technique has been applied to top‐down sequencing of non‐tryptic peptides, such as the human palmitoylated analogue of prolactin‐releasing peptide used in recent obesity studies, and human and insect antimicrobial peptides.