bluuebunny/crossref_metadata_2025 huggingface dataset:
From eyes‐closed to eyes‐open: Role of cholinergic projections in EC‐to‐EO alpha reactivity revealed by combining EEG and MRI
Authors: Wan Lu , Huang Haiqing , Schwab Nadine , Tanner Jared , Rajan Abhijit , Lam Ngoc B. , Zaborszky Laszlo , Li Chiang‐shan R. , Price Catherine C. , Ding Mingzhou
Published: September 2018

Alpha rhythm (8 to 12 Hz) observed in EEG over human posterior cortex is prominent during eyes‐closed (EC) resting and attenuates during eyes‐open (EO) resting. Research shows that the degree of EC‐to‐EO alpha blocking or alpha desynchronization, termed alpha reactivity here, is a neural marker of cognitive health. We tested the role of acetylcholine in EC‐to‐EO alpha reactivity by applying a multimodal neuroimaging approach to a cohort of young adults and a cohort of older adults. In the young cohort, simultaneous EEG‐fMRI was recorded from twenty‐one young adults during both EO and EC resting. In the older cohort, functional MRI was recorded from forty older adults during EO and EC resting, along with FLAIR and diffusion MRI. For a subset of twenty older adults, EEG was recorded during EO and EC resting in a separate session. In both young and older adults, functional connectivity between the basal nucleus of Meynert (BNM), the major source of cortical acetylcholine, and the visual cortex increased from EC to EO, and this connectivity increase was positively associated with alpha reactivity; namely, the stronger the BNM‐visual cortex functional connectivity increase from EC to EO, the larger the EC‐to‐EO alpha desynchronization. In older adults, lesions of the fiber tracts linking BNM and visual cortex quantified by leukoaraiosis volume, associated with reduced alpha reactivity. These findings support a role of acetylcholine and particularly cholinergic pathways in mediating EC‐to‐EO alpha reactivity and suggest that impaired alpha reactivity could serve as a marker of the integrity of the cholinergic system.
CEACAM1 Is Associated With the Suppression of Natural Killer Cell Function in Patients With Chronic Hepatitis C
Authors: Suda Takahiro , Tatsumi Tomohide , Nishio Akira , Kegasawa Tadashi , Yoshioka Teppei , Yamada Ryoko , Furuta Kunimaro , Kodama Takahiro , Shigekawa Minoru , Hikita Hayato , Sakamori Ryotaro , Fukuhara Takasuke , Matsuura Yoshiharu , Takehara Tetsuo
Published: September 2018

Natural killer cells (NK cells) play an essential role in the immunological mechanism underlying chronic hepatitis C (CHC). Impairment of NK cell function facilitates persistent infection with hepatitis C virus (HCV) and hepatocellular carcinogenesis. However, the mechanism by which NK cell activity is suppressed in CHC is not completely understood. In this study, we focused on carcinoembryonic antigen–related cell‐adhesion molecule 1 (CEACAM1). CEACAM1 is thought to suppress NK cell function. We examined the effect of CEACAM1 on NK cell function in CHC. We investigated the function of CEACAM1 in vitro using Huh7.5.1 cells and the HCV‐Japanese fulminant hepatitis (JFH)‐1 strain. We analyzed serum CEACAM1 level, NK cell function, and CEACAM1 messenger RNA (mRNA) level in human liver samples. Levels of CEACAM1 on the cell surface, CEACAM1 mRNA levels, and soluble CEACAM1 levels in supernatants were significantly higher in Huh7.5.1 cells infected with JFH‐1 (Huh7.5.1/JFH‐1 cells) than in Huh7.5.1 cells. Significantly higher NK cell cytotoxicity was observed toward K562 cells after coculture with CEACAM1 knockout Huh7.5.1/JFH‐1 cells than after coculture with Huh7.5.1/JFH‐1 cells. CEACAM1 expression was induced by the HCV E2 glycoprotein in HCV infection. Significantly higher serum CEACAM1 levels were detected in patients with CHC compared with healthy subjects and patients who achieved sustained virological responses. The expression of CD107a on NK cells from patients with CHC was negatively correlated with serum CEACAM1 levels. Significantly higher levels of CEACAM1 mRNA were detected in HCV‐infected livers compared with uninfected livers. Conclusion: CEACAM1 expression was induced in hepatocytes following HCV infection and decreased NK cell cytotoxicity. These results demonstrate a possible role for CEACAM1 in the pathogenesis of CHC and hepatocellular carcinoma progression.
Gamma Glutamyltransferase Reduction Is Associated With Favorable Outcomes in Pediatric Primary Sclerosing Cholangitis
Authors: Deneau Mark R. , Mack Cara , Abdou Reham , Amin Mansi , Amir Achiya , Auth Marcus , Bazerbachi Fateh , Marie Broderick Anne , Chan Albert , DiGuglielmo Matthew , El‐Matary Wael , El‐Youssef Mounif , Ferrari Federica , Furuya Katryn N. , Gottrand Frederic , Gupta Nitika , Homan Matjaž , Jensen M.K. , Kamath Binita M. , Mo Kim Kyung , Kolho Kaija‐Leena , Konidari Anastasia , Koot Bart , Iorio Raffaele , Martinez Mercedes , Mohan Parvathi , Palle Sirish , Papadopoulou Alexandra , Ricciuto Amanda , Saubermann Lawrence , Sathya Pushpa , Shteyer Eyal , Smolka Vratislav , Tanaka Atsushi , Valentino Pamela L. , Varier Raghu , Venkat Veena , Vitola Bernadette , Vos Miriam B. , Woynarowski Marek , Yap Jason , Miloh Tamir
Published: September 2018

Adverse clinical events in primary sclerosing cholangitis (PSC) happen too slowly to capture during clinical trials. Surrogate endpoints are needed, but no such validated endpoints exist for children with PSC. We evaluated the association between gamma glutamyltransferase (GGT) reduction and long‐term outcomes in pediatric PSC patients. We evaluated GGT normalization (< 50 IU/L) at 1 year among a multicenter cohort of children with PSC who did or did not receive treatment with ursodeoxycholic acid (UDCA). We compared rates of event‐free survival (no portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or liver‐related death) at 5 years. Of the 287 children, mean age of 11.4 years old, UDCA was used in 81% at a mean dose of 17 mg/kg/day. Treated and untreated groups had similar GGT at diagnosis (314 versus 300, P= not significant [NS]). The mean GGT was reduced at 1 year in both groups, with lower values seen in treated (versus untreated) patients (99 versus 175, P= 0.002), but 5‐year event‐free survival was similar (74% versus 77%, P= NS). In patients with GGT normalization (versus no normalization) by 1 year, regardless of UDCA treatment status, 5‐year event‐free survival was better (91% versus 67%, P< 0.001). Similarly, larger reduction in GGT over 1 year (> 75% versus < 25% reduction) was also associated with improved outcome (5‐year event‐free survival 88% versus 61%, P= 0.005). Conclusion:A GGT < 50 and/or GGT reduction of > 75% by 1 year after PSC diagnosis predicts favorable 5‐year outcomes in children. GGT has promise as a potential surrogate endpoint in future clinical trials for pediatric PSC.
A Simple Probe for Super‐Resolution Imaging of the Endoplasmic Reticulum in Living Cells
Authors: Halabi Elias A. , Püntener Salome , Rivera‐Fuentes Pablo
Published: September 2018

Super‐resolution imaging of living cells can reveal nanoscopic details of live biological systems. The development of small‐molecule fluorophores that allow optimal imaging conditions is the key to enable live‐specimen imaging with minimal invasiveness. In this study, we report a simple and non‐toxic rhodamine‐based diazoindanone probe compatible with direct stochastic optical reconstruction microscopy (d‐STORM). Co‐localization studies performed in human cervical cancer (HeLa) cells indicated that this probe targets the endoplasmic reticulum (ER). Photophysical experiments carried out in polyvinyl alcohol films revealed that each molecule yields a high number of photons before photodecomposition (80’000 photons), allowing good localization precision (42±12 nm) in single‐molecule localization experiments. Super‐resolution imaging employing this photoactivatable probe permitted the visualization of nanoscopic pores within the network of tubules and sheets of the endoplasmic reticulum. We further analyzed this structure in three dimensions to distinguish pores from concave surfaces and built 3D reconstructions of these nanometric tubules and cisternae.
Evaluation of the accuracy, reliability, efficiency, and acceptability of fast forwarding to score problem behavior
Authors: Machado Mychal A. , Luczynski Kevin C. , Hood Stephanie A.
Published: September 2018

Technological advances have allowed professionals to obtain extended recordings of caregiver–client interactions in natural settings, but scoring recorded video at normal speed to identify instances of low‐rate problem behavior is impractical in terms of scoring time. Fast forwarding is a continuous measurement system in which all seconds of an observation are viewed at a speed faster than normal. In Study 1, we evaluated whether three groups of five observers could discriminate problem behavior at three fast‐forwarding speeds across 10‐min observations. We analyzed the efficiency of using fast forwarding compared to continuous scoring, and interobserver agreement across the fast‐forwarding speeds. In Study 2, we compared the accuracy, efficiency, and social acceptability of fast forwarding (3.5x) and momentary time sampling (3.5 s) across 90‐min observations. Results support the use of 3.5x fast forwarding as a viable measurement system of improving the practicality of scoring problem behavior from video.
Individual and combined toxicity of T‐2 toxin and deoxynivalenol on human C‐28/I2 and rat primary chondrocytes
Authors: Lin Xialu , Shao Wanzhen , Yu Fangfang , Xing Ke , Liu Huan , Zhang Feng'e , Goldring Mary B. , Lammi Mikko J. , Guo Xiong
Published: September 2018

Deoxynivalenol (DON) and T‐2 toxin are prevalent mycotoxin contaminants in the food and feed stuffs worldwide, with non‐negligible co‐contamination and co‐exposure conditions. Meanwhile, they are considerable risk factors for Kashin‐Beck disease, a chronic endemic osteochondropathy. The aim of this study was to investigate the individual and combined cytotoxicity of DON and T‐2 toxin on proliferating human C‐28/I2 and newborn rat primary costal chondrocytes by MTT assay. Four molar concentration combination ratios of DON and T‐2 toxin were used, 1:1 for R1 mixture, 10:1 for R10, 100:1 for R100 and 1000:1 for R1000. The toxicological interactions were quantified by the MixLow method. DON, T‐2 toxin, and their mixtures all showed a clear dose‐dependent toxicity for chondrocytes. The cytotoxicity of T‐2 toxin was 285‐fold higher than DON was in human chondrocytes, and 22‐fold higher in the rat chondrocytes. The combination of DON and T‐2 toxin was significantly synergistic at middle and high level concentrations of R10 mixtures in rat chondrocytes, but significantly antagonistic at the low concentrations of R100 mixtures in both cells and at the middle concentrations of R1000 mixtures in rat chondrocytes. These results indicated that the combined toxicity was influenced by the cell sensitivity for toxins, the difference between the combination ratio and equitoxic ratio, the concentrations and other factors.
Bone regeneration in rabbit calvarial critical‐sized defects filled with composite in situ formed xenogenic dentin and biphasic tricalcium phosphate/hyroxyapatite mixture
Authors: Kamal Mohammad , Andersson Lars , Al‐Asfour Adel , Bartella Alexander K. , Gremse Felix , Rosenhain Stefanie , Gabato Severino , Hölzle Frank , Kessler Peter , Lethaus Bernd
Published: September 2018

The purpose of this study was to evaluate bone healing in calvarial defects using two bone graft substitute materials; biphasic beta‐tricalcium phosphate/hydroxyapatite in hydrogel (ß‐TCP/HA) versus composite non‐demineralized xenogenic dentin with ß‐TCP/HA mixture. Full thickness critical‐sized defects were created bilaterally in 10 New Zealand male rabbits. Seven defects were left empty, six filled with biphasic tricalcium phosphate putty, and seven were filled with composite non‐demineralized xenogenic dentin with biphasic tricalcium phosphate. Animals were sacrificed at eight weeks postoperatively and the healing of the biomaterial‐filled defects was compared radiographically and by histomorphometry. Micro‐computed tomography (μCT) was utilized to analyze the osteogenesis and healing patterns of the defects. Quantitative analysis of volume fraction (%) of the newly formed bone and remaining graft material (FV=filling volume/TV=tissue volume) and mean intensity [HU] in the defects were evaluated. Defects filled with composite dentin with biphasic tri‐calcium phosphate showed volume fraction (FV/TV) in the order of 55.81% ± 17.72%, whereas defects filled with only biphasic tricalcium phosphate showed a fraction of 39.84% ± 16.06%, which represent the ratio of remaining graft material and new bone formation to the tissue volume. The empty negative control defects showed a volume fraction of 19.14% ± 8.787%. Histological analysis showed significant percentage increase in bone formation and residual graft with the composite Dentin/ß‐TCP group after 8 weeks. The findings suggest that composite xenogenic dentin with biphasic tricalcium phosphate showed improved osteogenesis when compared to biphasic tricalcium phosphate without the addition of non‐demineralized dentin. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 773–782, 2019.
Do rim cracks and backside grinding affect the aging kinetics of alumina‐matrix composite acetabular liners?
Authors: Seki Takeshi , Takahashi Yasuhito , Pezzotti Giuseppe , Tateiwa Toshiyuki , Shishido Takaaki , Masaoka Toshinori , Yamamoto Kengo
Published: September 2018

The acetabular liner malalignment and rim impingement have been problematic issues in ceramic‐on‐ceramic (CoC) total hip arthroplasty (THA). Commercial ceramic liners made of alumina‐matrix composite (AMC) have polished articulation and rim, and roughly ground backside with a button‐like apical projection (post) to resist tilting. In this study, we hypothesized that rim cracks and backside grind critically affect the aging kinetics of tetragonal zirconia dispersed in AMC structure. We analyzed phase transformation in the zirconia phase and residual stresses in the alumina matrix during aging by Raman and fluorescence spectroscopy. We demonstrated that the polished surfaces showed environmental stability in vitro, while the roughly‐ground backside showed a significant stability loss and tensile stress accumulation as a consequence of enhancing the inter‐component fixation between the liner and the metallic shell. Rim cracking locally produced a preferential transformation at the tip and the surrounding of the crack. Note that the tensile stress concentration at the crack tip was counteracted by the phase transformation after a few hours of aging. This suggests the presence of a time lag in vivo before further transformation around the crack could provide a crack shielding effect in the material. © 2018 Wiley Periodicals, Inc. J. Biomed. Mater. Res. Part B, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 791–798, 2019.
Structural heteropolysaccharides as air‐tight sealants of the human pleura
Authors: Servais Andrew B. , Kienzle Arne , Ysasi Alexandra B. , Valenzuela Cristian D. , Wagner Willi L. , Tsuda Akira , Ackermann Maximilian , Mentzer Steven J.
Published: September 2018

Pulmonary “air leaks,” typically the result of pleural injury caused by lung surgery or chest trauma, result in the accumulation of air in the pleural space (pneumothorax). Air leaks are a major source of morbidity and prolonged hospitalization after pulmonary surgery. Previous work has demonstrated structural heteropolysaccharide (pectin) binding to the mouse pleural glycocalyx. The similar lectin‐binding characteristics and ultrastructural features of the human and mouse pleural glycocalyx suggested the potential application of these polymers in humans. To investigate the utility of pectin‐based polymers, we developed a simulacrum using freshly obtained human pleura. Pressure‐decay leak testing was performed with an inflation maneuver that involved a 3 s ramp to a 3 s plateau pressure; the inflation was completely abrogated after needle perforation of the pleura. Using nonbiologic materials, pressure‐decay leak testing demonstrated an exponential decay with a plateau phase in materials with a Young's modulus less than 5. In human pleural testing, the simulacrum was used to test the sealant function of four mixtures of pectin‐based polymers. A 50% high‐methoxyl pectin and 50% carboxymethylcellulose mixture demonstrated no sealant failures at transpleural pressures of 60 cmH2O. In contrast, pectin mixtures containing 50% low‐methoxyl pectin, 50% amidated low‐methoxyl pectins, or 100% carboxymethylcellulose demonstrated frequent sealant failures at transpleural pressures of 40–50 cmH2O (p < 0.001). Inhibition of sealant adhesion with enzyme treatment, dessication and 4°C cooling suggested an adhesion mechanism dependent upon polysaccharide interpenetration. We conclude that pectin‐based heteropolysaccharides are a promising air‐tight sealant of human pleural injuries. © 2018 Wiley Periodicals, Inc. J. Biomed. Mater. Res. Part B, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 799–806, 2019.
Studies of two different types of intramolecular C–H···F–C interactions from polyfluorinated diiodometal(II) diimine complexes
Authors: Lu Norman , Zheng Jing‐Hung , Lin Lei‐Chin , Liu Ling‐Kang , Chiang Hsing‐Fang , Li Ting‐You , Wen Yuh‐Sheng , Yang Chung‐Kuang , Chen Shih‐Wen , Thrasher Joseph S.
Published: September 2018

The X‐ray crystal structures of the polyfluorinated complexes [5,5′‐bis(HCF2CF2CF2CF2CH2OCH2)‐2,2′‐bpy]MI2 (55‐8F‐PtI2 and 55‐8F‐PdI2 where M = Pt and Pd, respectively) were obtained. These two structures are found to show not only two different types of intramolecular, six‐membered cyclic C–H···F–C interactions (F2C–H···F–C and HC–H···F–C) as important structural features but also alternating fluorinated and non‐fluorinated layers. The F2C–H···F–C interactions, which are close to the metal core, are much better structurally characterized in this type of complexes with fluorous ponytails at the 5,5′ positions than those previously reported at the 4,4′ positions. The molecular planes of (bpy)MI2 are extended by self‐matching, using two C–H···I hydrogen bonds and one C–H···F–C blue‐shifting hydrogen bond. The F2C–H···F–C hydrogen bonds interact at the supramolecular level such that one polyfluorinated ponytail of the title compounds is transoid without an intramolecular C–H···F–C interaction, while the other polyfluorinated ponytail is cisoid with an intramolecular C–H···F–C interaction. Why one ponytail is cisoidal while the other is transoidal will be explained. Furthermore, the second type of C–H···F–C interactions involving the methylene H atom has been identified for the first time. In addition, these two metal structures are studied by density functional theory (DFT).
Impact of the site of necrosis on outcome of acute pancreatitis
Authors: Dhaka Narendra , Sinha Saroj K , Samanta Jayanta , Gupta Vikas , Yadav Thakur Deen , Gulati Ajay , Kochhar Rakesh
Published: September 2018

Objecives

To compare the clinical outcome of patients with extrapancreatic necrosis (EXPN) alone with that of acute interstitial pancreatitis (AIP), pancreatic parenchymal necrosis (PPN) alone, and combined PPN and EXPN.

Background

There are only a few studies in the literature in which EXPN has been recently recognized as a subtype of acute necrotizing pancreatitis (ANP), with a better prognosis.

Methods

We analyzed clinical data and outcome variables of 411 consecutive acute pancreatitis (AP) patients between January 2012 and December 2014. Contrast‐enhanced computed tomography (CECT) images of each patient were reviewed and characterized as AIP or ANP. Patients with ANP were divided into EXPN alone, PPN alone, and combined PPN and EXPN. Outcome variables were then compared between these groups.

Results

Of the 411 patients, 74 (18%) had AIP, and 337 (82%) had ANP. Patients with EXPN alone (n = 40; 11.8%) had similar outcomes as patients with PPN alone (n = 12; 3.5%); however, their outcome was worse than that of patients with AIP, with a higher frequency of persistent organ failure (POF), need for percutaneous catheter drainage (PCD), and longer length of hospitalization (LOH). Patients with combined PPN and EXPN (n = 285; 84.7%) had the worst clinical course, with higher frequency of POF, infected necrosis, intervention requirement, and longer LOH.

Conclusion

Patients with combined PPN and EXPN have a severe disease course with the worst clinical outcomes; patients with AIP patients have the most benign course, while patients with EXPN alone stand between the two extremes of disease course with an intermediate grade of severity.
REPAIRit: Improving Myocardial Nulling and Ghosting Artifacts of 3D Navigator‐Gated Late Gadolinium Enhancement Imaging During Arrhythmia
Authors: Hu Chenxi , Huber Steffen , Latif Syed R. , Santacana‐Laffitte Guido , Mojibian Hamid R. , Baldassarre Lauren A. , Peters Dana C.
Published: September 2018

Background

Cardiac 3D navigator‐gated late gadolinium enhancement (LGE) imaging is important for assessment of left atrial fibrosis, but the image quality is often degraded due to arrhythmia.

Purpose

To investigate a novel 3D LGE sequence with improved myocardial nulling and reduced ghosting artifacts during arrhythmia.

Study Type

Prospective.

Population

Arrhythmia patients (n = 14).

Sequence

The proposed technique, REPAIRit (Regrowth Equalization Pulse for Arrhythmias in Inversion Recovery with automatic inversion time calculation), inserts a saturation pulse with a dynamic flip angle into the 3D LGE sequence to minimize arrhythmia‐induced signal fluctuations. Using ShMOLLI (shortened modified Look–Locker imaging) to estimate myocardial T1, REPAIRit automatically calculates the optimal inversion time (TI) based on Bloch equations.

Assessment

REPAIRit LGE and the standard LGE were compared with simulations, phantom imaging, and patient studies. Patient images were assessed quantitatively, based on ghost‐to‐noise ratio (GNR), blood signal‐to‐noise ratio (SNRb), myocardial signal‐to‐noise ratio (SNRm), and blood‐to‐myocardium contrast‐to‐noise ratio (CNR), and qualitatively on a 4‐point scale. Patients were subgrouped based on the presence of arrhythmia to assess the image quality difference.

Statistical Tests

The two LGE sequences were compared by Student's t‐test and Wilcoxon signed‐rank test. The two patient‐subgroups were compared using Welch's t‐test and Wilcoxon rank‐sum test.

Results

In 14 analyzed patients, REPAIRit LGE significantly lowered GNR (1.25 ± 0.41 vs. 1.42 ± 0.42, P = 0.04), reduced SNRm (1.90 ± 0.60 vs. 3.16 ± 1.66, P = 0.01), improved ghosting artifact scores (2.5 ± 0.6 vs. 2.2 ± 0.9, P = 0.03), myocardial nulling scores (2.7 ± 0.5 vs. 2.3 ± 0.7, P = 0.02), and atrial quality scores (2.8 ± 0.3 vs. 2.4 ± 0.8, P = 0.03) compared with the standard LGE. Comparing patients with arrhythmia (n = 6) to those without (n = 8) during the scan, the former had lower left ventricular (LV) myocardial T1s (430 ± 26 msec vs. 469 ± 39 msec, P = 0.06) but similar blood T1s (318 ± 55 msec vs. 316 ± 27 msec, P = 0.96), and significantly lower blood SNR (5.2 ± 1.8 vs. 9.2 ± 3.0, P = 0.01) and significantly worse image quality (P = 0.01 for REPAIRit and P = 0.03 for standard).

Data Conclusion

REPAIRit improves myocardial nulling and reduces ghosting artifacts of 3D LGE under arrhythmia.

Level of Evidence: 2

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2019;49:688–699.
Quantitative Assessment of Regional Dynamic Airway Collapse in Neonates via Retrospectively Respiratory‐Gated 1H Ultrashort Echo Time MRI
Authors: Bates Alister J. , Higano Nara S. , Hysinger Erik B. , Fleck Robert J. , Hahn Andrew D. , Fain Sean B. , Kingma Paul S. , Woods Jason C.
Published: September 2018

Background

Neonatal dynamic tracheal collapse (tracheomalacia, TM) is a common and serious comorbidity in infants, particularly those with chronic lung disease of prematurity (bronchopulmonary dysplasia, BPD) or congenital airway or lung‐related conditions such as congenital diaphragmatic hernia (CDH), but the underlying pathology, impact on clinical outcomes, and response to therapy are not well understood. There is a pressing clinical need for an accurate, objective, and safe assessment of neonatal TM.

Purpose

To use retrospectively respiratory‐gated ultrashort echo‐time (UTE) MRI to noninvasively analyze moving tracheal anatomy for regional, quantitative evaluation of dynamic airway collapse in quiet‐breathing, nonsedated neonates.

Study Type

Prospective.

Population/Subjects

Twenty‐seven neonatal subjects with varying respiratory morbidities (control, BPD, CDH, abnormal polysomnogram).

Field Strength/Sequence

High‐resolution 3D radial UTE MRI (0.7 mm isotropic) on 1.5T scanner sited in the neonatal intensive care unit.

Assessment

Images were retrospectively respiratory‐gated using the motion‐modulated time‐course of the k‐space center. Tracheal surfaces were generated from segmentations of end‐expiration/inspiration images and analyzed geometrically along the tracheal length to calculate percent‐change in luminal cross‐sectional area (A
%) and ratio of minor‐to‐major diameters at end‐expiration (r
D,exp). Geometric results were compared to clinically available bronchoscopic findings (n = 14).

Statistical Tests

Two‐sample t‐test.

Results

Maximum A
% significantly identified subjects with/without a bronchoscopic TM diagnosis (with: 46.9 ± 10.0%; without: 27.0 ± 5.8%; P < 0.001), as did minimum r
D,exp (with: 0.346 ± 0.146; without: 0.671 ± 0.218; P = 0.008). Subjects with severe BPD exhibited a far larger range of minimum r
D,exp than subjects with mild/moderate BPD or controls (0.631 ± 0.222, 0.782 ± 0.075, and 0.776 ± 0.030, respectively), while minimum r
D,exp was reduced in CDH subjects (0.331 ± 0.171) compared with controls (P < 0.001).

Data Conclusion

Respiratory‐gated UTE MRI can quantitatively and safely evaluate neonatal dynamic tracheal collapse, as validated with the clinical standard of bronchoscopy, without requiring invasive procedures, anesthesia, or ionizing radiation.

Level of Evidence: 2

Technical Efficacy: Stage 3

J. Magn. Reson. Imaging 2019;49:659–667.
Radiomics Analysis of DTI Data to Assess Vision Outcome After Intravenous Methylprednisolone Therapy in Neuromyelitis Optic Neuritis
Authors: Tian Yuan , Liu Zhenyu , Tang Zhenchao , Li Mingge , Lou Xin , Dong Enqing , Liu Gang , Wang Yulin , Wang Yan , Bian Xiangbin , Wei Shihui , Tian Jie , Ma Lin
Published: September 2018

Background

Neuromyelitis optica‐optic neuritis (NMO‐ON) patients are routinely treated with intravenous methylprednisolone (IVMP). For the patients nonresponsive to IVMP, more effective but aggressive therapy of plasma exchange (PE) should be employed instead of IVMP in the first line.

Purpose

To assess the visual outcomes of NMO‐ON patients after IVMP by radiomics analysis of whole brain diffusion tensor imaging (DTI) data.

Study Type

Retrospective.

Population

In all, 57 NMO‐ON patients receiving IVMP therapy for 3 days.

Field Strength/Sequence

3.0T; DTI images acquired by a single‐shot echo planar image sequence; T1 images acquired by 3D fast spoiled gradient echo (3D‐FSPGR) MRI.

Assessment

In all, 200 DTI measures were extracted from the DTI data and employed as features to construct a radiomics assessment model for visual outcomes of NMO‐ON patients after IVMP. The assessment performance was evaluated by area under the receiver operating characteristic curve (AUC), classification accuracy (ACC), sensitivity, specificity, and positive and negative predicted values (PPV and NPV). The selected DTI measures would reveal the white matter impairments related to visual recovery of NMO‐ON patients.

Statistical Tests

The relationship between the selected DTI measures and the clinical visual characteristics were investigated by Pearson correlation, Spearman's rank correlation, and one‐way analysis of variance analysis.

Results

The radiomics model obtained an ACC of 73.68% (P = 0.002), AUC of 0.7931, sensitivity of 0.6207, specificity of 0.8571, PPV of 0.8182, and NPV of 0.6857 in assessing visual outcomes of the NMO‐ON patients after IVMP treatment. The selected DTI measures revealed white matter impairments related to the visual outcomes in the white matter tracts of vision‐relevant regions, motor‐related regions, and corpus callosum. The white matter impairments were found significantly correlated with the disease duration and the length of lesions in the optic nerve.

Data Conclusion

Radiomics analysis of DTI data has great potential in assessing visual outcomes of NMO‐ON patients after IVMP therapy.

Level of Evidence: 2

Technical Efficacy: Stage 4

J. Magn. Reson. Imaging 2019;49:1365–1373.
Medial and Lateral Patellofemoral Joint Retinaculum Thickness in People With Patellofemoral Pain: A Case‐Control Study
Authors: Lack Simon , Anthony Luke , Noake James , Brennan Kay , Zhang Bairu , Morrissey Dylan
Published: September 2018

Objectives

To measure the medial and lateral retinaculum thickness in individuals with and without patellofemoral pain using ultrasound and to assess associations with the symptom duration and function.

Methods

Medial and lateral patellofemoral joint retinaculum thicknesses of 32 knees (16 with patellofemoral pain and 16 asymptomatic) were measured with B‐mode ultrasound at 0.5, 1, and 1.5 cm from the patella border. Participants with patellofemoral pain completed a Kujala questionnaire, and both groups underwent a single‐leg squat performance assessment. Two‐way analyses of variance (site × group) determined the overall effect, and Cohen d values were calculated to describe the magnitude of the difference for each measurement.

Results

The groups were matched for age, height, and weight. Compared to controls, participants with patellofemoral pain had thicker lateral (overall effect, P = .03) and medial (overall effect, P < 0.01) retinacula. No correlations between retinaculum thickness and Kujala scores (lateral retinaculum, r = 0.106 [0.5 cm], –0.093 [1 cm], and –0.207 [1.5 cm]; and medial retinaculum, r = 0.059, 0.109, and –0.219), symptom duration (lateral retinaculum, r = 0.001, –0.041, and 0.302; and medial retinaculum, r = –0.027, –0.358, and –0.346), or single‐leg squat performance scores (lateral retinaculum, r = 0.051, 0.114, and 0.046; and medial retinaculum, r = –0.119, –0.292, and 0.011) were observed.

Conclusions

Increased lateral and medial retinaculum thickness in individuals with patellofemoral pain compared to controls identifies structural changes that may be associated with the pathogenesis of patellofemoral pain. The absence of a significant correlation between retinaculum thickness and the symptom duration or function further shows a lack of an association between structure and function in individuals with patellofemoral pain.
Vegetation restoration changes topsoil biophysical regulations of carbon fluxes in an eroding soil landscape
Authors: Li Jianye , Fu Bojie , Liu Shuguang , Dargush Paul , Gao Guangyao , Liu Jianbo , Wei Fangli
Published: September 2018

The dynamics of biophysical regulations of carbon fluxes can have a major effect on an ecosystems' carbon budget. Only a handful of comprehensive assessments of such dynamics exist. To better understand the carbon cycle, we measured all major carbon flux by biophysical regulations including rainfall, runoff, infiltration, and sediment yield at eight runoff plots in an eroding soil landscape on the Chinese Loess Plateau, a typical vegetation restoration area for the region. Results show that topsoil carbon flux by infiltration into deep soil layers was the largest efflux from topsoil in plots with vegetation, followed by runoff and sediment carbon effluxes. On the contrary, the carbon flux by sediment was the largest efflux from topsoil in plot without vegetation, followed by infiltration and runoff carbon effluxes. Total topsoil carbon flux by biophysical regulations to the deep layer is about 71 ± 10% of the typical carbon sequestration rate in the region. Topsoil carbon sequestration capacity might be underestimated by up to 43 ± 3% if the infiltrated carbon was not factored into estimates. The results of this study improve understanding of soil carbon dynamics and expand the dynamic carbon replacement hypothesis; photosynthesis replaces not only lateral carbon lost by erosion but also vertical carbon lost by infiltration.
The Marriage of Aggregation‐Induced Emission with Polymer Science
Authors: Qiu Zijie , Liu Xiaolin , Lam Jacky W. Y. , Tang Ben Zhong
Published: September 2018

Aggregation‐induced emission (AIE) is a novel photophysical phenomenon coined in 2001 by our group and describes the enhanced light emission of some luminogens in the aggregate or solid state. The combination of AIE research and polymer science is a smart approach to produce functional luminescent materials with mechanical strength and excellent processability for real‐world applications. In this feature article, recent progress in AIE polymeric systems, including chemical synthesis and physical blending strategies, is summarized. Through chemical synthesis, various AIE‐active polymers, such as covalently bonded polymers, supramolecular polymers, and nonconjugated luminescent polymers, can be obtained. Serving as environmentally sensitive probes, AIE luminogens can also be physically doped into polymers to generate interesting systems. Finally, outlooks and perspectives on the future direction of AIE polymeric systems are discussed.
Mechanistic/mammalian target of rapamycin: Recent pathological aspects and inhibitors
Authors: Abdel‐Maksoud Mohammed S. , El‐Gamal Mohammed I. , Benhalilou Dalia Reyane , Ashraf Sandy , Mohammed Shatha Abdulghaffar , Oh Chang‐Hyun
Published: September 2018

The mechanistic/mammalian target of rapamycin (mTOR), also known as the mechanistic target of rapamycin, regulates many normal cell processes such as transcription, cell growth, and autophagy. Overstimulation of mTOR by its ligands, amino acids, sugars, and/or growth factors leads to physiological disorders, including cancer and neurodegenerative diseases. In this study, we reviewed the recent advances regarding the mechanism that involves mTOR in cancer, aging, and neurodegenerative diseases. The chemical and biological properties of recently reported small molecules that function as mTOR kinase inhibitors, including adenosine triphosphate‐competitive inhibitors and dual mTOR/PI3K inhibitors, have also been reviewed. We focused on the reports published in the literature from 2012 to 2017.
Field weighs in on passage of legislation to combat opioid crisis
Authors: Canady Valerie A.
Published: September 2018

Senate lawmakers last week voted 99–0 to pass legislation to combat the opioid epidemic. The bill is aimed at establishing or expanding programs that address prevention, treatment and recovery. While the field is elated, some feel that the legislation did not go far enough, particularly in areas of funding, and expanding a demonstration program based on the Excellence in Mental Health Act to expand access to mental health and addiction care in community‐based settings.
Uniform superconvergence analysis of Ciarlet‐Raviart scheme for Bi‐wave singular perturbation problem
Authors: Shi Dongyang , Wu Yanmi
Published: September 2018

Uniform superconvergence analysis of the Ciarlet‐Raviart mixed finite element scheme is discussed for solving the fourth‐order Bi‐wave singular perturbation problem (SPP) by the bilinear element. Firstly, the existence and uniqueness of the approximation solution are proved. Secondly, with the help of the special characters of this element, uniform superclose result of order O(h2) for the original variable in H1 norm and uniform optimal order estimate of order O(h2) for the intermediate variable in L2 norm are deduced with respect to the real perturbation parameter δ appearing in the considered problem. Furthermore, the global uniform superconvergent estimate is obtained through the interpolated postprocessing approach. Finally, some numerical results are provided to verify the theoretical analysis. Here, h denotes the mesh size.
Blood‐borne biomarkers of osteosarcoma: A systematic review
Authors: Tan Gerald J.S. , Gerrand C.H. , Rankin K.S.
Published: September 2018

Osteosarcoma is the most common type of primary malignant bone tumor in children and young adults. Development of clinically useful biomarkers has the potential to improve treatments. The aim of this review was to investigate the recent literature assessing the utility of biomarkers for osteosarcoma. A detailed literature search was performed, with hand searches for related research publications. The search was limited to publications in English between January 2007 and February 2017. Of 286 studies identified, 24 met the inclusion criteria. There is a wide range of osteosarcoma biomarkers identified which act as clinical prognostic factors in patient outcome.
How I approach: Previously untreated patients with severe congenital hemophilia A
Authors: Thornburg Courtney D.
Published: September 2018

Previously untreated patients with severe hemophilia A are a vulnerable population at risk for severe bleeding which is currently managed with exogenous clotting factor replacement. The primary burden of current treatment is high‐titer inhibitor development. Evolving data on current treatment products as well as emerging therapeutics may inform treatment decisions to prevent bleeding and inhibitor formation. Considerations for diagnosis, education, and shared decision‐making related to product choice and treatment regimen are discussed.
Antihypertensives prescribed for pregnant women in Japan: Prevalence and timing determined from a database of health insurance claims
Authors: Ishikawa Tomofumi , Obara Taku , Nishigori Hidekazu , Miyakoda Keiko , Ishikuro Mami , Metoki Hirohito , Ohkubo Takayoshi , Sugawara Junichi , Yaegashi Nobuo , Akazawa Manabu , Kuriyama Shinichi , Mano Nariyasu
Published: September 2018

Purpose

The purpose of the study is to evaluate the status of prescribed antihypertensives primarily during pregnancy, but also before pregnancy and after delivery, using a large claims database in Japan.

Methods

The dates of pregnancy onset and delivery were identified using reported algorithms and the birth months of infants. The prevalence and timing of prescribed antihypertensives during pregnancy were descriptively evaluated. Time trends in prescriptions were evaluated using multivariate logistic regression analyses. We also evaluated the prevalence of antihypertensives prescribed within 180 days before pregnancy and 180 days after delivery among women who were covered by health insurers during the entire period.

Results

At least one antihypertensive agent was prescribed for 1144 (2.74%) of 41 693 pregnant women. The most frequently prescribed oral antihypertensive during pregnancy was nifedipine, followed by methyldopa, hydralazine, and furosemide. Drugs targeting the renin‐angiotensin system were prescribed for 21 pregnant women (0.05%), including angiotensin II receptor blockers that were prescribed for 19 (0.05%) of them. Nicardipine was the most frequently prescribed injectable antihypertensive during pregnancy, followed by furosemide, hydralazine, and nitroglycerin. Annual prescription trends remained similar except for a significant decrease in those for oral and injectable furosemide and an annual increase in those for organic nitrate. Based on an evaluation of 33 941 pregnant women, the number of prescriptions for antihypertensives increased particularly during the third trimester, then decreased from 91 to 180 days after delivery.

Conclusions

Various types of antihypertensives are prescribed for Japanese pregnant women. The effects of exposing pregnant Japanese women to these agents should be evaluated.
Feasibility of lung ultrasound to assess pulmonary overflow in congenital heart disease children
Authors: Wu Lei , Hou Qiaoru , Lu Yingying , Bai Jie , Sun Liping , Huang Yue , Zhang Mazhong , Zheng Jijian
Published: September 2018

Background

Pulmonary overflow (PO) is one of the most common complications in congenital heart disease (CHD) children with an incidence of 48‐60% approximately. This study explored the feasibility of using lung ultrasound (LUS) to assess pulmonary overcirculation in CHD children and compare the diagnostic performance of LUS and chest radiography (CXR) for the detection of pulmonary overcirculation.

Method

The upper anterior area, lower anterior area, upper lateral area, and lower posterior area, in each hemithorax were scanned in 59 children in the supine position. A‐lines, B‐lines in each scanned region were recorded, and the worst LUS abnormality in the video clip was considered to characterize the examined region. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of LUS and CXR were compared using computed tomography (CT) as a standard criterion.

Results

PO was diagnosed in 53% (31/59), 63% (37/59), and 51% (30/59) children with CT, CXR, and LUS, respectively. The sensitivity, specificity, and diagnostic accuracy of PO were 96%, 94%, and 95% for LUS and 74%, 50%, and 63% for CXR. The percentage of mild, moderate, and severe PO diagnosed via LUS were 31% (18/59), 19% (11/59), and 2% (1/59), respectively. Furthermore, the PO incidence diagnosed by LUS in CHD children less than 1 year old were significantly higher than those beyond 1 year old.

Conclusion

LUS is a noninvasive and useful tool for the detection and assessment of PO in CHD children at the operating room, and is better than CXR in sensitivity and specificity, comparable to CT.
Extracellular Matrix Imaging of Breast Tissue Pathologies by MALDI–Imaging Mass Spectrometry
Authors: Angel Peggi M. , Schwamborn Kristina , Comte‐Walters Susana , Clift Cassandra L. , Ball Lauren E. , Mehta Anand S. , Drake Richard R.
Published: September 2018

Purpose

A new method accessing proteins from extracellular matrix by imaging mass spectrometry (ECM IMS) has been recently reported. ECM IMS is evaluated for use in exploring breast tissue pathologies.

Experimental Design

A tissue microarray (TMA) is analyzed that has 176 cores of biopsies and lumpectomies spanning breast pathologies of inflammation, hyperplasia, fibroadenoma, invasive ductal carcinoma, and invasive lobular carcinoma and normal adjacent to tumor (NAT). NAT is compared to subtypes by area under the receiver operating curve (ROC) >0.7. A lumpectomy is also characterized for collagen organization by microscopy and stromal protein distribution by IMS. LC‐based high‐resolution accurate mass (HRAM) proteomics is used to identify proteins from the lumpectomy.

Results

TMA analysis shows distinct spectral signatures reflecting a heterogeneous tissue microenvironment. Ninety‐four peaks show an ROC > 0.7 compared to NAT; NAT has overall higher intensities. Lumpectomy analysis by IMS visualizes a complex central tumor region with distal tumor regions. A total of 39 stromal proteins are identified by HRAM LC‐based proteomics. Accurate mass matches between image data and LC‐based proteomics demonstrate a heterogeneous collagen type environment in the central tumor.

Conclusions

Data portray the heterogeneous stromal microenvironment of breast pathologies, including alteration of multiple collagen‐type patterns. ECM IMS is a promising new tool for investigating the stromal microenvironment of breast tissue including cancer.
The budding‐yeast RWD protein Csm1 scaffolds diverse protein complexes through a conserved structural mechanism
Authors: Singh Namit , Corbett Kevin D.
Published: September 2018

RWD domains mediate protein–protein interactions in a variety of pathways in eukaryotes. In budding yeast, the RWD domain protein Csm1 is particularly versatile, assembling key complexes in the nucleolus and at meiotic kinetochores through multiple protein interaction surfaces. Here, we reveal a third functional context for Csm1 by identifying a new Csm1‐interacting protein, Dse3. We show that Dse3 interacts with Csm1 in a structurally equivalent manner to its known binding partners Mam1 and Ulp2, despite these three proteins’ lack of overall sequence homology. We theorize that the unique “clamp” structure of Csm1 and the loose sequence requirements for Csm1 binding have led to its incorporation into at least three different structural/signaling pathways in budding yeast.
Local and non‐local topological information in the denatured state ensemble of a β‐barrel protein
Authors: Thakur Abhay K. , Meng Wenli , Gierasch Lila M.
Published: September 2018

The folding of predominantly β‐sheet proteins is complicated by the presence of a large number of non‐local interactions in their native states, which increase the ruggedness of their folding energy landscapes. However, forming non‐local contacts early in folding or even in the unfolded state can smooth the energy landscape and facilitate productive folding. We report that several sequence regions of a β‐barrel protein, cellular retinoic acid‐binding protein 1 (CRABP1), populate native‐like secondary structure to a significant extent in the denatured state in 8 M urea. In addition, we provide evidence for both local and non‐local interactions in the denatured state of CRABP1. NMR chemical shift perturbations (CSPs) under denaturing conditions upon substitution of single residues by mutation support the presence of several non‐local interactions in topologically key sites, arguing that the denatured state is conformationally restricted and contains topological information for the native fold. Among the most striking non‐local interactions are those between the N‐ and C‐terminal regions, which are involved in closure of the native β‐barrel. In addition, CSPs support the presence of two features in the denatured state: a major hydrophobic cluster involving residues from various parts of the sequence and a native‐like interaction similar to one identified in previous studies as forming early in folding (Budyak et al., Structure 21, 476 [2013]). Taken together, our data support a model in which transient structures involving nonlocal interactions prime early folding interactions in CRABP1, determine its barrel topology, and may protect this predominantly β‐sheet protein against aggregation.
Lagrangian transport across the upper Arctic waters in the Canada Basin
Authors: Balibrea‐Iniesta Francisco , Xie Jiping , García‐Garrido Víctor J. , Bertino Laurent , Mancho Ana M. , Wiggins Stephen
Published: September 2018

The goal of this paper is to study transport, from a Lagrangian perspective, across selected circulation patterns in the upper Arctic Ocean waters. To this end, we apply the methodology of Lagrangian descriptors, using the function M, to the velocity field dataset provided by the Copernicus Marine Environment Monitoring Service. We focus our analysis on the Arctic region in the halocline (top 30 m depth), which is based on particular events occurring over the 2012–2016 time period. The advantage of the Lagrangian descriptor is that it highlights large‐scale persistent dynamical structures relating to mathematical objects known as invariant manifolds, which determine fluid transport and mixing processes. These geometric flow structures play a crucial role in the evolution of the salinity content observed over the Arctic Basin. In this work, we identify these dynamical structures in the Beaufort Sea and show how they mediate transport processes according to a clockwise circulating pattern related to the Beaufort Gyre. Additionally, this approach highlights the importance of the Transpolar Drift Stream (TDS) as a transport barrier which maintains the salinity gradient between the Canada Basin and the Atlantic waters. Our approach also illustrates the variability of the intensity of the TDS during the analysed period and identifies secondary currents that feed it.