bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards understanding mechanistic subgroups of osteoarthritis: 8‐year cartilage thickness trajectory analysis
Authors: Iriondo Claudia , Liu Felix , Calivà Francesco , Kamat Sarthak , Majumdar Sharmila , Pedoia Valentina
Published: September 2020

Many studies have validated cartilage thickness as a biomarker for knee osteoarthritis (OA); however, few studies investigate beyond cross‐sectional observations or comparisons across two timepoints. By characterizing the trajectory of cartilage thickness changes over 8 years in healthy individuals from the OA initiative data set, this study discovers associations between the dynamics of cartilage changes and OA incidence. A fully automated cartilage segmentation and thickness measurement method were developed and validated against manual measurements: mean absolute error = 0.11–0.14 mm (n = 4129 knees) and automatic reproducibility = 0.04–0.07 mm (n = 316 knees). The mean thickness for the medial and lateral tibia (MT, LT), central weight‐bearing medial and lateral femur (cMF, cLF), and patella (P) cartilage compartments were quantified for 1453 knees at seven timepoints. Trajectory subgroups were defined per cartilage compartment such as stable, thinning to thickening, accelerated thickening, plateaued thickening, thickening to thinning, accelerated thinning, or plateaued thinning. For tibiofemoral compartments, the stable (22%–36%) and plateaued thinning (22%–37%) trajectories were the most common, with an average initial velocity (μm/month), acceleration (μm/month2) for the plateaued thinning trajectories LT: −2.66, 0.0326; MT: −2.49, 0.0365; cMF: −3.51, 0.0509; and cLF: −2.68, 0.041. In the patella compartment, the plateaued thinning (35%) and thickening to thinning (24%) trajectories were the most common, with an average initial velocity, acceleration for each −4.17, 0.0424; 1.95, −0.0835. Knees with nonstable trajectories had higher adjusted odds of OA incidence than stable trajectories: accelerated thickening, accelerated thinning, and plateaued thinning trajectories of the MT had adjusted odds ratio (OR) of 18.9, 5.48, and 1.47, respectively; in the cMF, adjusted OR of 8.55, 10.1, and 2.61, respectively.
An overview of de novo bone generation in animal models
Authors: Taguchi Takashi , Lopez Mandi J.
Published: September 2020

Some of the earliest success in de novo tissue generation was in bone tissue, and advances, facilitated by the use of endogenous and exogenous progenitor cells, continue unabated. The concept of one health promotes shared discoveries among medical disciplines to overcome health challenges that afflict numerous species. Carefully selected animal models are vital to development and translation of targeted therapies that improve the health and well‐being of humans and animals alike. While inherent differences among species limit direct translation of scientific knowledge between them, rapid progress in ex vivo and in vivo de novo tissue generation is propelling revolutionary innovation to reality among all musculoskeletal specialties. This review contains a comparison of bone deposition among species and descriptions of animal models of bone restoration designed to replicate a multitude of bone injuries and pathology, including impaired osteogenic capacity.
A novel engineered purified exosome product patch for tendon healing: An explant in an ex vivo model
Authors: Shi Guidong , Wang Yicun , Wang Zhanwen , Thoreson Andrew R. , Jacobson Daniel S. , Amadio Peter C. , Behfar Atta , Moran Steven L. , Zhao Chunfeng
Published: September 2020

Reducing tendon failure after repair remains a challenge due to its poor intrinsic healing ability. The purpose of this study is to investigate the effect of a novel tissue‐engineered purified exosome product (PEP) patch on tendon healing in a canine ex vivo model. Lacerated flexor digitorum profundus (FDP) tendons from three canines' paws underwent simulated repair with Tisseel patch alone or biopotentiated with PEP. For the ex vivo model, FDP tendons were randomly divided into three groups: FDP tendon repair alone group (Control), Tisseel patch alone group, and the Tisseel plus PEP (TEPEP) patch group. Following 4 weeks of tissue culture, the failure load, stiffness, histology, and gene expression of the healing tendon were evaluated. Transmission electron microscopy revealed that in exosomes of PEP the diameters ranged from 93.70 to 124.65 nm, and the patch release test showed this TEPEP patch could stably release the extracellular vesicle over 2 weeks. The failure strength of the tendon in the TEPEP patch group was significantly higher than that of the Control group and Tisseel alone group. The results of histology showed that the TEPEP patch group had the smallest healing gap and the largest number of fibroblasts on the surface of the injured tendon. Quantitative reverse transcription polymerase chain reaction showed that TEPEP patch increased the expression of collagen type III, matrix metallopeptidase 2 (MMP2), MMP3, MMP14, and reduced the expression of transforming growth factor β1, interleukin 6. This study shows that the TEPEP patch could promote tendon repair by reducing gap formation and inflammatory response, increasing the activity of endogenous cells, and formation of type III collagen.
Treadmill running initiation times and bone‐tendon interface repair in a murine rotator cuff repair model
Authors: Lu Hongbin , Li Shengcan , Zhang Tao , Wang Zhanwen , Chen Can , Chen Huabin , Xiao Han , Wang Linfeng , Chen Yang , Tang Yifu , Xie Shanshan , Wu Bing , Hu Jianzhong
Published: September 2020

Postoperative exercise has been demonstrated to be beneficial for bone‐tendon interface (BTI) healing, yet the debate regarding the optimal time to initiate exercise after tendon enthesis repair is ongoing. This study aimed to evaluate the initiation times for exercise after enthesis repair. A total of 192 C57BL/6 mice underwent acute supraspinatus tendon injury repair. The animals were then randomly assigned to four groups: free cage activity after repair (control group); treadmill running started on postoperative day 2 (2‐day delayed group); treadmill running started on postoperative day 7 (7‐day delayed group), and treadmill running started on postoperative day 14 (14‐day delayed group). Mice were euthanized at 4 and 8 weeks postoperatively, and histological, biomechanical, and bone morphometric tests were performed. Higher failure loads and bone volume fractions were found for the 7‐day delayed group and the 14‐day delayed group at 4 weeks postoperatively. The 7‐day delayed group had better biomechanical properties and higher bone volume fractions than the 2‐day delayed group at 4 weeks postoperatively. Histologically, the 7‐day delayed group exhibited lower modified tendon‐to‐bone maturity scores than the control group and the 2‐day delayed group at 4 and 8 weeks postoperatively. Quantitative reverse‐transcription polymerase chain reaction results showed that the 7‐day delayed group had higher expressions of chondrogenic‐ and osteogenic‐related genes. Statement of clinical significance: Postoperative treadmill running initiated on postoperative day 7 had a more prominent effect on BTI healing than other treatment regimens in this study and could accelerate BTI healing and rotator cuff repair.
Ultrasonographic Diagnosis of Intussusception in Children
Authors: Li Xing‐Zhao , Wang Hui , Song Jun , Liu Yan , Lin Yuan‐Qiang , Sun Zhi‐Xia
Published: September 2020

Ultrasonography offers a unique advantage in the clinical diagnosis of intussusception. We aimed to evaluate the diagnostic accuracy of ultrasonography in pediatric intussusception. The PubMed, Embase, Web of Science, Cochrane Library databases, and African Journals Online database were searched for studies pertaining to ultrasonographic diagnosis of intussusception in children. Finally, 14 studies (combined n = 2367) were found eligible for inclusion. Pooled sensitivity and specificity were 0.94 (95% confidence interval: 0.91–0.96) and 0.96 (95% confidence interval: 0.93–0.98), respectively. In conclusion, ultrasonography has high sensitivity and specificity in the diagnosis of intussusception.
Transvaginal Ultrasound Findings After Laparoscopic Rectosigmoid Segmental Resection for Deep Infiltrating Endometriosis
Authors: Martire Francesco G. , Zupi Errico , Lazzeri Lucia , Morosetti Giulia , Conway Francesca , Centini Gabriele , Solima Eugenio , Pietropolli Adalgisa , Piccione Emilio , Exacoustos Caterina
Published: September 2020

Objectives

To evaluate transvaginal ultrasound (TVUS) findings in patients who underwent segmental rectosigmoid resection for deep infiltrating endometriosis (DIE) and to correlate postsurgical ultrasound findings with symptoms.

Methods

A retrospective study including 50 premenopausal women with bowel endometriosis who underwent segmental rectosigmoid resection was conducted. Within 12 months after surgery, a TVUS examination was conducted in all patients to evaluate the presence of postsurgical endometriosis locations and symptoms, including dysmenorrhea, dyspareunia, dysuria, dyschezia, and chronic pelvic pain. Pelvic pain was assessed in all women by a visual analog scale.

Results

At the follow‐up 32 of 50 patients were receiving medical treatment, whereas 18 women declined postsurgical medical therapy and tried to conceive. A high percentage of adhesions (90%) was found. A negative sliding sign (a simple diagnostic sign that can be performed during a TVUS examination, consisting of gentle pressure applied by both the vaginal transducer and the examiner's hand on the abdomen; if the uterus does not glide freely along with the rectum and posterior fornix, the sign is considered negative, and adhesions can be suspected) was found in 29 (58%) women and was associated with bowel symptoms. Recurrence of posterior DIE was found in 9 cases (18%) and endometriomas in 8 cases (16%). Adenomyosis was observed in 80% of women and was present in all symptomatic patients.

Conclusions

After rectosigmoid segmental resection patients with DIE may continue to be symptomatic, and postoperative TVUS may reveal foci of disease or pelvic adhesions. Moreover, adenomyosis could be linked to symptoms experienced during follow up. Women should be aware that painful symptoms and alterations of pelvic organs could still be present after surgery and be detectable by TVUS.
Findings and Prognostic Value of Lung Ultrasound in COVID‐19 Pneumonia
Authors: Castelao Jorge , Graziani Desirée , Soriano Joan B. , Izquierdo José Luis
Published: September 2020

Objectives

The aim of this study was to systematically describe the findings of lung ultrasound (US) in patients with coronavirus 2019 (COVID‐19) pneumonia and to analyze its prognostic value.

Methods

Lung US examinations were performed in 63 patients with COVID‐19 pneumonia admitted to a university hospital. Lung involvement was evaluated on a 4‐point scale with a 12‐area pulmonary division, obtaining a lung score (LS). Ultrasound findings and clinical characteristics were recorded.

Results

All patients showed US involvement in at least 1 area (mean ± SD, 8 ± 3.5). The total LS was 15.3 ± 8.1, without differences between left and right lungs. Most affected regions were the lower region (95.2%) and the posterior region (73.8%). The total LS showed a strong correlation (r = −0.765) with the oxygen pressure–to–fraction of inspired oxygen ratio; by lung region, those with a higher correlation were the LS of the anterior region (r = −0.823) and the LS of the upper region (r = −0.731). In total, 22.2% of patients required noninvasive respiratory support (NIRS). A multivariate analysis showed that the anterior region LS, adjusted for age and sex, was significant (odds ratio, 2.159; 95% confidence interval, 1.309–3.561) for the risk of requiring NIRS. An anterior region LS of 4 or higher and a total LS of 19 or higher had similar characteristics to predict the need for NIRS.

Conclusions

Ultrasound involvement in COVID‐19 pneumonia is bilateral and heterogeneous. Most affected regions are the posterior and the lower regions. The anterior region has prognostic value because its involvement strongly correlates with the risk of requiring NIRS, and an anterior region LS of 4 or higher has high sensitivity and specificity for predicting the need for NIRS.
Tolerance of Continuous Positive Airway Pressure After Sinonasal Surgery
Authors: Reilly Erin K. , Boon Maurits S. , Vimawala Swar , Chitguppi Chandala , Patel Jena , Murphy Kira , Doghramji Karl , Nyquist Gurston G. , Rosen Marc R. , Rabinowitz Mindy R. , Huntley Colin T.
Published: September 2020

Objectives/Hypothesis

For patients with obstructive sleep apnea (OSA) undergoing sinonasal surgery, there is a lack of consensus on the risk and appropriate postoperative use of continuous positive airway pressure (CPAP). The aim of this study was to assess the tolerability of restarting CPAP on postoperative day one.

Study Design

Prospective cohort study.

Methods

A prospective study on patients with OSA on CPAP who required a septoplasty/turbinectomy and/or functional endoscopic sinus surgery (FESS) was performed. Data from the memory card of a patient's CPAP machine and subjective information were obtained on the day of surgery and at scheduled follow‐up visits. All subjects were instructed to restart CPAP on the first postoperative night.

Results

A total of 14 patients were analyzed; nine underwent FESS and five had a septoplasty/turbinectomy. There were no postoperative complications encountered. The only significant change in the first postoperative week was a reduction in the percentage of nights used over 4 hours (P < .05). By the third postoperative visit, average 22‐item Sino‐Nasal Outcome Test, Nasal Obstruction Symptom Evaluation, and CPAP tolerance scores improved from preoperative values. CPAP pressures, residual apnea–hypopnea index, and number of hours and mean percentage of nights used remained stable throughout the study period.

Conclusions

Both quality‐of‐life and CPAP outcomes improved or remained the same when restarting CPAP immediately postoperatively. Combined with a lack of significant complications, this study suggests that CPAP is well‐tolerated when restarted the day after a septoplasty/turbinectomy or FESS.

Level of Evidence

4 Laryngoscope, 131:E1013–E1018, 2021
Secondary enrichment of soil by alkaline emissions: The specific form of anthropo‐geogenic soil degradation near magnesite processing factories and possibilities of land management
Authors: Polláková Nora , Hamar Ján , Šimanský Vladimír , Bartkowiak Agata , Lemanowicz Joanna
Published: September 2020

Over the past 90 years, anthropogenic degradation of soil caused by alkaline, magnesium‐rich dust deposition has presented a serious problem near magnesite processing factories in Jelšava and in Lubeník (Slovakia). The objective of this study was to investigate the chemical and biological soil properties in 14 sampling sites at different distances from factories, and based on the results, to propose further use of affected land. Results revealed that the available Mg was 3‐ to 68‐fold that of medium‐textured soils at all grassland sampling sites, and areas close to the factories contained up to 14,366–17,394 mg kg−1. Higher amounts of available Mg caused significant increase of soil pH (up to 9.39) and worsened the conditions for the growth of vegetation. As a result, a lower stock of labile soil organic carbon (501–961 mg kg−1) with consequently weaker enzymatic activity occurred. Enrichment by organic matter provides a means to support the biological activity of soil. The content of monitored heavy metals (Zn, Cu, Pb, and Ni) was not related to Mg and did not influence the enzymatic activity of soil. Because alkaline emissions have decreased by 99.8% since 1970, the application of established measures (mechanical removal of the Mg‐rich crust, incorporation of gypsum and manure into the soil), or newer methods (growing of Mg hyper‐accumulating plants) can offer more lasting positive effects than could be achieved 50 years ago. This study concluded alkaline dust was the main factor affecting soil degradation. Nevertheless, the natural origin of Mg from Mg‐parent rocks should be allowed for.
Tight coupling of fungal community composition with soil quality in a Chinese fir plantation chronosequence
Authors: Chen Liang , Xiang Wenhua , Ouyang Shuai , Wu Huili , Xia Qi , Ma Jiani , Zeng Yelin , Lei Pifeng , Xiao Wenfa , Li Shenggong , Kuzyakov Yakov
Published: September 2020

Predicting changes in carbon and nutrient cycles in plantations requires a mechanistic understanding of the effects of stand age on soil quality and microbial communities. Here, we evaluated soil quality by using an integrated soil quality index (SQI) and traced the parallel shifts in fungal community composition using high‐throughput sequencing in a chronosequence of Chinese fir (Cunninghamia lanceolata) plantations (stand age of 3, 16, 25, 32, >80 years). Soil properties showed pronounced changes with stand age in the topsoil. Soil organic carbon (SOC), total nitrogen (TN) and available phosphorus (AP) were 2.1, 1.9 and 2.2 times higher, respectively, in the oldest stands than in the youngest stands. SQI of the top 5 cm increased logarithmically with stand age. Mycorrhizal fungi initially increased in younger stands, but then they were gradually replaced by saprotrophs in older stands due to larger litterfall. Strong positive correlations between saprotrophic fungi and key soil quality indicators, such as TN, AP and NH4+, confirmed that abundance of decomposers is tightly linked with higher soil quality. Mycorrhizal orders Thelephorales, Sebacinales and Russulales increased in abundance and raised the activity of acid phosphatase to mobilise limiting phosphorus from organic matter. Consequently, mycorrhizal fungi are especially relevant in younger stands to acquire nutrients to sustain tree productivity. In developed stands, however, saprotrophic fungi are crucial in recycling nutrients from the litter. Collectively, the increase of topsoil quality during the life cycle of Chinese fir plantations is closely linked with the observed transition of fungal communities from mycorrhizae to saprotrophs.
Simultaneously Improving Dielectric and Mechanical Properties of Crown Ether/Fluorinated Polyimide Films with Necklace‐Like Supramolecular Structure
Authors: Liu Shumei , Feng Qi , Li Yang , Chen Zhigeng , Zhao Jianqing
Published: September 2020

A necklace‐like supramolecular structure is constructed from 18‐crown ether‐6 (18CE6) as the host molecule and fluorinated polyimide (FPI) as the guest molecule to enhance the mechanical properties as well as to further lower the dielectric constant of FPI. The introduction of 18CE6 simultaneously enhances the stiffness and toughness of FPI films. In particular, the elongation at break is increased by over 200%. Furthermore, the dielectric constant of FPI films with 40 mol% 18CE6 is decreased to 2.74 from 3.15 of pure FPI, which is attributed to the enlarged free volume by the necklace‐like supramolecular structure of 18CE6/FPI. Accordingly, the glass transition temperature of 18CE6/FPI films is slightly reduced to 305 °C, which is still high enough during the soldering process for the preparation of flexible copper clad laminate. In addition, the water absorption of FPI films is gradually decreased to 0.52% as the loading of 18CE6 raises to 40 mol%, representing the excellent moisture resistance of 18CE6/FPI films.
Glass Transition Temperature Regulates Mechanical Performance in Nacre‐Mimetic Nanocomposites
Authors: Lossada Francisco , Abbasoglu Tansu , Jiao Dejin , Hoenders Daniel , Walther Andreas
Published: September 2020

Although research in bioinspired nanocomposites is delivering mechanically superior nanocomposite materials, there remain gaps in understanding some fundamental design principles. This article discusses how the mechanical properties of nacre‐mimetic polymer/nanoclay nanocomposites with nanoconfined polymer layers are controlled by the thermo‐mechanical polymer properties, that is, glass transition temperature, Tg, using a series of poly(ethylene glycol methyl ether methacrylate‐co‐N,N‐dimethylacrylamide) copolymers with tunable Tg from 130 to −55 °C. It is elucidated that both the type of copolymer and the nanoconfined polymer layer thickness control energy dissipation and inelastic deformation at high fractions of reinforcements in such bioinspired nanocomposites.
Cylindrical Zwitterionic Particles via Interpolyelectrolyte Complexation on Molecular Polymer Brushes
Authors: Pelras Théophile , Nonappa  , Mahon Clare S. , Müllner Markus
Published: September 2020

The fabrication of macromolecular architectures with high aspect ratio and well‐defined internal and external morphologies remains a challenge. The combination of template chemistry and self‐assembly concepts to construct peculiar polymer architectures via a bottom‐up approach is an emerging approach. In this study, a cylindrical template—namely a core–shell molecular polymer brush—and linear diblock copolymers (DBCP) associate to produce high aspect ratio polymer particles via interpolyelectrolyte complexation. Induced, morphological changes are studied using cryogenic transmission electron and atomic force microscopy, while the complexation is further followed by isothermal titration calorimetry and ξ‐potential measurements. Depending on the nature of the complexing DBCP, distinct morphological differences can be achieved. While polymers with a non‐ionic block lead to internal compartmentalization, polymers featuring zwitterionic domains lead to a wrapping of the brush template.
The Application of Covalent Organic Frameworks for Chiral Chemistry
Authors: Zhuo Siqi , Zhang Xiaoyue , Luo Huan , Wang Xuehua , Ji Yibing
Published: September 2020

Covalent organic frameworks (COFs) made their debut in 2005 and caused enthusiastic attention because of their ordered, crystalline structure. They are constructed with pure organic building blocks that are linked together by robust covalent linkages. COFs are applied in numerous fields due to their large surface area, architecture and chemistry stabilities, functional pore walls, and tunable frameworks. Incorporating COFs with chiral compounds can build chiral COFs (CCOFs), which have exhibited significant advantages in the chiral chemistry field. This review focuses on the applications of COFs for chiral catalysis, chiral separation, and chiral sensoring up to now. Furthermore, the synthesis and design strategies of CCOFs are also discussed in this article, since the COFs used in chiral chemistry are generally CCOFs. There also sums up the benefits and defects of COFs used in the chiral field and outlines future opportunities. The studies described in this review demonstrate not only the advantages of COFs in practical use but also novel solutions for the problems in the chirality area.
Seasonal Presence of Atlantic Sturgeon and Sharks at Cape Hatteras, a Large Continental Shelf Constriction to Coastal Migration
Authors: Rulifson Roger A. , Bangley Charles W. , Cudney Jennifer L. , Dell'Apa Andrea , Dunton Keith J. , Frisk Michael G. , Loeffler Michael S. , Balazik Matthew T. , Hager Christian , Savoy Tom , Brundage Harold M. , Post William C.
Published: September 2020

Cape Hatteras is a major topographic feature on the continental shelf of the U.S. eastern seaboard that changes the dynamics of nearshore large ocean currents, including the Labrador Current and Gulf Stream. Cape Hatteras constricts shelf habitat and restricts the migratory corridors of highly migratory species through this area. Our objective was to describe the seasonal patterns of presence for three species—the Spiny Dogfish Squalus acanthias, Atlantic Sturgeon Acipenser oxyrinchus oxyrinchus, and Sandbar Shark Carcharhinus plumbeus—and analyze environmental conditions associated with fish presence near this feature. These species are managed under the Magnuson–Stevens Act, and two of them are also listed as species of concern under the Endangered Species Act. Transmitter detections from tagged fish recorded by the Cape Hatteras acoustic array, which was deployed just south of the cape, indicated that these species are present year-round. The greatest number of detections occurred from November through April. This simple baseline of seasonal presence can provide insights for regional offshore development activities, which have the potential to affect movement patterns of migratory species through the Cape Hatteras constriction. Our results show the value of strategically placed acoustic arrays for observing fish habitat use and provide presence/absence data to enhance our understanding of species ecology and distribution.
Assessing the Relative Selectivity of Multiple Sampling Gears for Managed Reef Fishes in the Eastern Gulf of Mexico
Authors: Christiansen Heather M. , Switzer Theodore S. , Keenan Sean F. , Tyler-Jedlund Amanda J. , Winner Brent L.
Published: September 2020

Fishery-independent data are important for the effective management of reef fishes in the eastern Gulf of Mexico. Proper characterization of selectivity, or the effectiveness of each type of sampling gear in capturing a species or a size-class, is essential to ensure that assessment models treat various sources of data appropriately. In this study, we analyzed fishery-independent data that was collected using stereo-baited remote underwater video (S-BRUV) arrays, chevron traps (TRAP), and two types of hooked gear (repetitive timed-drop [RTD] and vertical longline [VLL]) to assess gear-related differences of species composition and size selectivity of managed reef fishes in the eastern Gulf of Mexico. Significant differences were detected in the assemblage structures of reef fishes in relation to region, gear type, and depth. Overall, eight managed species were identified as contributing to the top 70% of the assemblage structure for each gear type. Stereo-baited remote underwater video had the highest abundances for most of the species and the highest number of species captured, while VLL had the lowest. Two economically and ecologically important species (Red Grouper Epinephelus morio and Red Snapper Lutjanus campechanus) were common to all four gear types, and the size selectivity of these two species generally overlapped. However, significant differences among gear types were detected. Unimodal selection curves for hooked gears indicated that size of Red Snapper and Red Grouper increased as hook size increased. These data provide insight on species and size selectivity of multiple gears, which will contribute to future survey design and aid in the management of reef-fish populations.
GDNF/RET Signaling Pathway Activation Eliminates Lewy Body Pathology in Midbrain Dopamine Neurons
Authors: Chmielarz Piotr , Er Şafak , Konovalova Julia , Bandres Laura , Hlushchuk Irena , Albert Katrina , Panhelainen Anne , Luk Kelvin , Airavaara Mikko , Domanskyi Andrii
Published: September 2020

Background

Parkinson's disease (PD) is associated with proteostasis disturbances and accumulation of misfolded α‐synuclein (α‐syn), a cytosolic protein present in high concentrations at pre‐synaptic neuronal terminals. It is a primary constituent of intracellular protein aggregates known as Lewy neurites or Lewy bodies. Progression of Lewy pathology caused by the prion‐like self‐templating properties of misfolded α‐syn is a characteristic feature in the brains of PD patients. Glial cell line‐derived neurotrophic factor (GDNF) promotes survival of mature dopamine (DA) neurons in vitro and in vivo. However, the data on its effect on Lewy pathology is controversial.

Objectives

We studied the effects of GDNF on misfolded α‐syn accumulation in DA neurons.

Methods

Lewy pathology progression was modeled by the application of α‐syn preformed fibrils in cultured DA neurons and in the adult mice.

Results

We discovered that GDNF prevented accumulation of misfolded α‐syn in DA neurons in culture and in vivo. These effects were abolished by deletion of receptor tyrosine kinase rearranged during transfection (RET) or by inhibitors of corresponding signaling pathway. Expression of constitutively active RET protected DA neurons from fibril‐induced α‐syn accumulation.

Conclusions

For the first time, we have shown the neurotrophic factor‐mediated protection against the misfolded α‐syn propagation in DA neurons, uncovered underlying receptors, and investigated the involved signaling pathways. These results demonstrate that activation of GDNF/RET signaling can be an effective therapeutic approach to prevent Lewy pathology spread at early stages of PD. © 2020 International Parkinson and Movement Disorder Society
On a nonlocal Sturm–Liouville problem with composite fractional derivatives
Authors: Li Jing , Qi Jiangang
Published: September 2020

In this paper, we obtain the existence of solutions for a nonlocal Sturm–Liouville problem with composite fractional derivatives under some initial value conditions. Furthermore, applying above results and operator theory, we specifically research the geometric multiplicity of eigenvalues for the nonlocal Sturm–Liouville eigenvalue problem.
Segmented K‐space blipped‐controlled aliasing in parallel imaging for high spatiotemporal resolution EPI
Authors: Stirnberg Rüdiger , Stöcker Tony
Published: September 2020

Purpose

A segmented k‐space blipped‐controlled aliasing in parallel imaging (skipped‐CAIPI) sampling strategy for EPI is proposed, which allows for a flexible choice of EPI factor and phase encode bandwidth independent of the controlled aliasing in parallel imaging (CAIPI) sampling pattern.

Theory and Methods

With previously proposed approaches, exactly two EPI trajectories were possible given a specific CAIPI pattern, either with slice gradient blips (blipped‐CAIPI) or following a shot‐selective CAIPI approach (higher resolution). Recently, interleaved multi‐shot segmentation along shot‐selective CAIPI trajectories has been applied for high‐resolution anatomical imaging. For more flexibility and a broader range of applications, we propose segmentation along any blipped‐CAIPI trajectory. Thus, all EPI factors and phase encode bandwidths available with traditional segmented EPI can be combined with controlled aliasing.

Results

Temporal SNR maps of moderate‐to‐high‐resolution time series acquisitions at varying undersampling factors demonstrate beneficial sampling alternatives to blipped‐CAIPI or shot‐selective CAIPI. Rapid high‐resolution scans furthermore demonstrate SNR‐efficient and motion‐robust structural imaging with almost arbitrary EPI factor and minimal noise penalty.

Conclusion

Skipped‐CAIPI sampling increases protocol flexibility for high spatiotemporal resolution EPI. In terms of SNR and efficiency, high‐resolution functional or structural scans benefit vastly from a free choice of the CAIPI pattern. Even at moderate resolutions, the independence of sampling pattern, TE, and image matrix size is valuable for optimized functional protocol design. Although demonstrated with 3D‐EPI, skipped‐CAIPI is also applicable with simultaneous multislice EPI.
Assessment of hepatic pyruvate carboxylase activity using hyperpolarized [1‐13C]‐l‐lactate
Authors: Chen Jun , Hackett Edward P. , Kovacs Zoltan , Malloy Craig R. , Park Jae Mo
Published: September 2020

Purpose

To evaluate the utility of hyperpolarized [1‐13C]‐l‐lactate to detect hepatic pyruvate carboxylase activity in vivo under fed and fasted conditions.

Methods

[1‐13C]‐labeled sodium L‐lactate was polarized using a dynamic nuclear polarizer. Polarization level and the T1 were measured in vitro in a 3 Telsa MR scanner. Two groups of healthy rats (fasted vs. fed) were prepared for in vivo studies. Each rat was anesthetized and intravenously injected with 60‐mM hyperpolarized [1‐13C]‐l‐lactate, immediately followed by dynamic acquisition of 13C (carbon‐13) MR spectra from the liver at 3 Tesla. The dosage‐dependence of the 13C‐products was also investigated by performing another injection of an equal volume of 30‐mM hyperpolarized [1‐13C]‐l‐lactate.

Results

T1 and liquid polarization level of [1‐13C]‐l‐lactate were estimated as 67.8 s and 40.0%, respectively. [1‐13C]pyruvate and [1‐13C]alanine, [13C]bicarbonate () and [1‐13C]aspartate were produced from hyperpolarized [1‐13C]‐l‐lactate in rat liver. Smaller and larger aspartate were measured in the fed group compared to the fasted group. Pyruvate and alanine production were increased in proportion to the lactate concentration, whereas the amount of and aspartate production was consistent between 30‐mM and 60‐mM lactate injections.

Conclusion

This study demonstrates that a unique biomarker of pyruvate carboxylase flux, the appearance of [1‐13C]aspartate from [1‐13C]‐l‐lactate, is sensitive to nutritional state and may be monitored in vivo at 3 Tesla. Because [13C] is largely produced by pyruvate dehydrogenase flux, these results suggest that the ratio of [1‐13C]aspartate and [13C] (aspartate/) reflects the saturable pyruvate carboxylase/pyruvate dehydrogenase enzyme activities.
“Push‐button” noncontrast MR angiography using balanced T1 relaxation‐enhanced steady‐state (bT1RESS)
Authors: Edelman Robert R. , Koktzoglou Ioannis
Published: September 2020

Purpose

We introduce a MR imaging technique, balanced T1 relaxation‐enhanced steady‐state (bT1RESS), that provides the unique capability to efficiently impart a flexible amount of T1 weighting to a balanced steady‐state free precession acquisition using periodically applied contrast‐modifying RF pulses. Leveraging this capability to suppress the signal intensity of background tissues, we implemented a 3D noncontrast MR angiography technique that continuously acquires thin overlapping 3D volumes and tested it for evaluation of the peripheral arteries.

Methods

bT1RESS used a fast interrupted steady‐state readout with a 45° cslab‐selective ontrast‐modifying RF pulse applied at 262 msec intervals. A series of 16.4‐mm thick overlapping 3D volumes was acquired using a radial stack‐of‐stars k‐space trajectory. The combination of slice oversampling, slab overlap, and averaging of edge slices was helpful to reduce venetian blind artifact. Spatial resolution was near isotropic with reconstructed slice thickness = 0.7 mm and in‐plane resolution = 0.5 mm.

Results

Pilot studies in the peripheral arteries demonstrated improved vessel sharpness compared with cardiac‐gated quiescent interval slice‐selective noncontrast MR angiography. bT1RESS noncontrast MR angiography reliably identified stenotic and occlusive arterial disease in a small cohort of patients with peripheral artery disease.

Conclusions

bT1RESS provides the basis for a simplified, completely “push button” approach for noncontrast MR angiography that obviates the need for contrast agents, electrocardiographic gating, scout imaging, breath holding, or tailoring of imaging parameters for the individual patient. Further work is needed for technical optimization and clinical validation.
Compressed sensing MRI using an interpolation‐free nonlinear diffusion model
Authors: Joy Ajin , Jacob Mathews , Paul Joseph Suresh
Published: September 2020

Purpose

Constraints in extended neighborhood system demand the use of a large number of interpolations in directionality‐guided compressed‐sensing nonlinear diffusion MR image reconstruction technique. This limits its practical application in terms of computational complexity. The proposed method aims at multifold improvement in its runtime without compromising the image quality.

Theory and Methods

Conventional approach to extended neighborhood computation requires 108 linear interpolations per pixel for 10 sets of neighborhoods. We propose a neighborhood stretching technique that systematically extends the location of neighboring pixels such that 66% to 100% fewer interpolations are required to compute the gradients along multiple directions. A spatial frequency–based deviation measure is then used to choose the most reliable edges from the set of images generated by diffusion along different directions.

Results

The semi‐interpolated and interpolation‐free diffusion techniques proposed in this paper are compared with the fully interpolated diffusion‐based reconstruction by reconstruing multiple multichannel in vivo datasets, undersampled using different sampling patterns at various sampling rates. Results indicate a two‐ to fivefold increase in reconstruction speed with a potential to generate 1 to 2 dB improvement in peak SNR measure.

Conclusion

The proposed method outperforms the state‐of‐the‐art fully interpolated diffusion model and generates high‐quality reconstructions for different sampling patterns and acceleration factors with a two‐ to fivefold increment in reconstruction speed. This makes it the most suitable candidate for edge‐preserving penalties used in the compressed sensing MRI reconstruction methods.
Drug utilization study on immediate release Fentanyl in Spain. Prevalence, incidence, and indication
Authors: González‐Bermejo Diana , Rayón‐Iglesias Pilar , Rodríguez‐Pascual Alfonso , Álvarez‐Gutiérrez Arturo , Fernández‐Dueñas Ana , Montero‐Corominas Dolores , Huerta‐Álvarez Consuelo
Published: September 2020

Purpose

We aimed to characterize the trends of immediate release fentanyl (IRF) use in Spain between 2012 and 2017 and indication for its use. IRF drugs are rapid‐acting opioids approved to treat breakthrough cancer pain (BTCP) in patients already receiving maintenance opioid therapy for chronic cancer pain. A substantial increase in consumption of IRF has been observed with emerging cases of abuse and dependence, most of them in noncancer patients.

Methods

An ecological descriptive consumption study with aggregated data from drug dispensed by community pharmacies and reimbursed by the National Health System in which Defined Daily Doses per 10 000 inhabitants (DID) were calculated and a retrospective cohort study using data from the Spanish Database for Pharmacoepidemiological Research in Primary Care in which participants entered the cohort study after 1 year with the Primary Care Practitioners were performed. Annual prevalence and incidence rate of IRF use were estimated by sex and calendar year. Potential indication was also assessed.

Results

IRF use in Spain increased from 2.1 DID in 2012 to 3.8 DID in 2017. The incidence rate and prevalence increased in 53% and 74%, respectively. Patients without previous cancer or BCTP diagnosis represented 27% of incident users, predominantly women. Half of patients with noncancer‐related diagnosis had a musculoskeletal disorder linked to the first IRF prescription.

Conclusions

National consumption and new IRF users in Spain increased over the study period and one quarter of patients did not have a BTCP or cancer diagnosis registered in their clinical record.
Direct observation of the formation of a cyclic poly(alkyl sorbate) via chain‐growth polymerization by an N‐heterocyclic carbene initiator and ring‐closing without extreme dilution
Authors: Muramatsu Yuki , Takasu Akinori , Higuchi Masahiro , Hayashi Mikihiro
Published: September 2020

1,3‐Di‐tert‐butylimidazol‐2‐ylidene (NHCtBu), which is one of the typical N‐heterocyclic carbene (NHC), was found to initiate the anionic chain‐growth polymerization of methyl sorbate (MS) in toluene at −20°C. The polymerization was accelerated by an aluminum Lewis acid, that is, methylaluminum bis(2,6‐di‐tert‐butyl‐4‐methylphenoxide) (MAD), to afford cyclic poly(MS)s. Subsequently, thiol‐ene click reactions of poly(MS)s with two different alkanethiols were performed using a photoradical initiator to obtain graft‐like polymers, which was for the microscopic observation of the chains directly by transmittance electron microscope (TEM). The contamination of linear polymers was hardly observed. This means that the polymers synthesized by our synthetic strategy were indeed cyclic polymers. We also compared the theoretical and experimental chain diameter and width for the graft‐like cyclic polymers, where these values were dependent on the molecular weight of the cyclic polymers regulated by the feed monomer/initiator ratio and length of the alkanethiols, respectively.
Consistency and variation of protein subcellular location annotations
Authors: Xu Ying‐Ying , Zhou Hang , Murphy Robert F. , Shen Hong‐Bin
Published: September 2020

A major challenge for protein databases is reconciling information from diverse sources. This is especially difficult when some information consists of secondary, human‐interpreted rather than primary data. For example, the Swiss‐Prot database contains curated annotations of subcellular location that are based on predictions from protein sequence, statements in scientific articles, and published experimental evidence. The Human Protein Atlas (HPA) consists of millions of high‐resolution microscopic images that show protein spatial distribution on a cellular and subcellular level. These images are manually annotated with protein subcellular locations by trained experts. The image annotations in HPA can capture the variation of subcellular location across different cell lines, tissues, or tissue states. Systematic investigation of the consistency between HPA and Swiss‐Prot assignments of subcellular location, which is important for understanding and utilizing protein location data from the two databases, has not been described previously. In this paper, we quantitatively evaluate the consistency of subcellular location annotations between HPA and Swiss‐Prot at multiple levels, as well as variation of protein locations across cell lines and tissues. Our results show that annotations of these two databases differ significantly in many cases, leading to proposed procedures for deriving and integrating the protein subcellular location data. We also find that proteins having highly variable locations are more likely to be biomarkers of diseases, providing support for incorporating analysis of subcellular location in protein biomarker identification and screening.
Light‐Assisted and Gate‐Tunable Oxygen Gas Sensor Based on Rhenium Disulfide Field‐Effect Transistors
Authors: Zulkefli Amir , Mukherjee Bablu , Hayakawa Ryoma , Iwasaki Takuya , Nakaharai Shu , Wakayama Yutaka
Published: September 2020

Gas sensors based on transition metal dichalcogenides (TMDCs) have attracted much attention from a new perspective involving light‐assisted or gate‐voltage operation. However, their combined roles as regards the gas sensing performance and mechanism are not yet understood due to the lack of controlled studies. This study systematically investigates the oxygen sensor performance and mechanism of few‐layer‐thick rhenium disulfide (ReS2) field‐effect transistors (FETs) under light illumination and gate biasing. As a result, a combination of light illumination and positive gate voltage enhances the device response over 100% at a 1% oxygen concentration; that is, the approach achieves a practical sensitivity of 0.01% ppm−1, which outperforms most of the reports available in the literature. Furthermore, the fabricated devices exhibit long‐term stability and stable operation even under humid conditions, indicating the ability of the sensor device to operate in a real‐time application. These results contribute to the development of versatile tunable oxygen sensors based on TMDC FETs.
In‐plane Epitaxy of Bi2S3 Nanowire Arrays for Ultrasensitive NIR Photodetectors
Authors: Xu Xing , Fan Chao , Wang Yanguo , Qi Zhuodong , Dai Beibei , Jiang Haotian , Wang Shaowei , Zhang Qinglin
Published: September 2020

The direct growth of semiconductor nanowire (NW) arrays horizontally aligned on a substrate is critically important for the applications of NWs in electronic or optoelectronic devices at the circuit level. The strict requirement of lattice matching between a substrate and a material in the covalent epitaxy of crystals makes the wire arrays be grown on the substrates only with similar lattice parameters. Herein, a van der Waals epitaxy route is developed to realize the in‐plane growth of large‐scale Bi2S3 NW arrays on mica with a large lattice mismatch. The orthorhombic Bi2S3 NWs grow epitaxially with the axial direction of along the six symmetric directions of the mica. Transmission electron microscope measurements show that the epitaxial relationships are and along the length and width directions of the wires, respectively. More importantly, photodetectors based on Bi2S3 NWs show a wide photoresponse spectrum range from 500 to 980 nm. A high responsivity (5233 A W−1) and a specific detectivity (1.8 × 1012 Jones) are achieved under 830 nm light irradiation with ultralow intensity (64 nW cm−2). In addition, the photodetectors exhibit high stability with at least 48 day storage in ambient atmosphere or with 1000 times bending.
2D Linear Trap Array for Quantum Information Processing
Authors: Holz Philip C. , Auchter Silke , Stocker Gerald , Valentini Marco , Lakhmanskiy Kirill , Rössler Clemens , Stampfer Paul , Sgouridis Sokratis , Aschauer Elmar , Colombe Yves , Blatt Rainer
Published: September 2020

An ion‐lattice quantum processor based on a two‐dimensional arrangement of linear surface traps is presented. The design features a tunable coupling between ions in adjacent lattice sites and a configurable ion‐lattice connectivity, allowing one, for example, to realize rectangular and triangular lattices with the same trap chip. Detailed trap simulations of a simplest‐instance ion array with 2 × 9 trapping sites are presented and the fabrication of a prototype device in an industrial facility is reported on. The design and the employed fabrication processes are scalable to larger array sizes. Trapping of ions in rectangular and triangular lattices and transport of a 2 × 2 ion‐lattice over one lattice period are demonstrated.
Coherent Ising Machines with Error Correction Feedback
Authors: Kako Satoshi , Leleu Timothée , Inui Yoshitaka , Khoyratee Farad , Reifenstein Sam , Yamamoto Yoshihisa
Published: September 2020

A nonequilibrium open‐dissipative neural network, such as a coherent Ising machine based on mutually coupled optical parametric oscillators, has been proposed and demonstrated as a novel computing machine for hard combinatorial optimization problems. However, there is a challenge in the previously proposed approach: The machine can be trapped by local minima which increases exponentially with a problem size. This leads to erroneous solutions rather than correct answers. In this paper, it is shown that it is possible to overcome this problem partially by introducing error detection and correction feedback mechanism. The proposed machine achieves efficient sampling of degenerate ground states and low‐energy excited states via its inherent exploration property during a solution search process.
Explicit multiobjective model predictive control for nonlinear systems under uncertainty
Authors: Hernández Castellanos Carlos I. , Ober‐Blöbaum Sina , Peitz Sebastian
Published: September 2020

In real‐world problems, uncertainties (eg, errors in the measurement, precision errors, among others) often lead to poor performance of numerical algorithms when not explicitly taken into account. This is also the case for control problems, where in the case of uncertainties, optimal solutions can degrade in quality or they can even become unfeasible. Thus, there is the need to design methods that can handle uncertainty. In this work, we consider nonlinear multiobjective optimal control problems with uncertainty on the initial conditions, and in particular their incorporation into a feedback loop via model predictive control. For such problems, not much has been reported in terms of uncertainties. To address this problem class, we design an offline/online framework to compute an approximation of efficient control strategies. In order to reduce the numerical cost of the offline phase—which grows exponentially with the parameter dimension—we exploit symmetries in the control problems. Furthermore, in order to ensure optimality of the solutions, we include an additional online optimization step, which is considerably cheaper than the original multiobjective optimization problem. We test our framework on a car maneuvering problem where safety and speed are the objectives. The multiobjective framework allows for online adaptations of the desired objective. Our results show that the method is capable of designing driving strategies that deal better with uncertainties in the initial conditions, which translates into potentially safer and faster driving strategies.