bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA-recognition motif in Matrin-3 mediates neurodegeneration through interaction with hnRNPM
Authors: Ramesh Nandini , Kour Sukhleen , Anderson Eric N. , Rajasundaram Dhivyaa , Pandey Udai Bhan 
Published: August 2020

Abstract
Background
Amyotrophic lateral sclerosis (ALS) is an adult-onset, fatal neurodegenerative disease characterized by progressive loss of upper and lower motor neurons. While pathogenic mutations in the DNA/RNA-binding protein Matrin-3 (MATR3) are linked to ALS and distal myopathy, the molecular mechanisms underlying MATR3-mediated neuromuscular degeneration remain unclear.

Methods
We generated Drosophila lines with transgenic insertion of human MATR3 wildtype, disease-associated variants F115C and S85C, and deletion variants in functional domains, ΔRRM1, ΔRRM2, ΔZNF1 and ΔZNF2. We utilized genetic, behavioral and biochemical tools for comprehensive characterization of our models in vivo and in vitro. Additionally, we employed in silico approaches to find transcriptomic targets of MATR3 and hnRNPM from publicly available eCLIP datasets.

Results
We found that targeted expression of MATR3 in Drosophila muscles or motor neurons shorten lifespan and produces progressive motor defects, muscle degeneration and atrophy. Strikingly, deletion of its RNA-recognition motif (RRM2) mitigates MATR3 toxicity. We identified rump, the Drosophila homolog of human RNA-binding protein hnRNPM, as a modifier of mutant MATR3 toxicity in vivo. Interestingly, hnRNPM physically and functionally interacts with MATR3 in an RNA-dependent manner in mammalian cells. Furthermore, common RNA targets of MATR3 and hnRNPM converge in biological processes important for neuronal health and survival.

Conclusions
We propose a model of MATR3-mediated neuromuscular degeneration governed by its RNA-binding domains and modulated by interaction with splicing factor hnRNPM.
BRAF V600E mutation mediates FDG-methionine uptake mismatch in polymorphous low-grade neuroepithelial tumor of the young
Authors: Tateishi Kensuke , Ikegaya Naoki , Udaka Naoko , Sasame Jo , Hayashi Takahiro , Miyake Yohei , Okabe Tetsuhiko , Minamimoto Ryogo , Murata Hidetoshi , Utsunomiya Daisuke , Yamanaka Shoji , Yamamoto Tetsuya 
Published: August 2020

AbstractWe present a case of a 14-year old boy with tumor-associated refractory epilepsy. Positron emission tomography imaging demonstrated a region with heterogeneous high 11C-methionine uptake and a region with homogenous low 18F-fluorodeoxyglucose uptake within the tumor. Histopathological and genomic analyses confirmed the tumor as BRAF V600E-mutated polymorphous low-grade neuroepithelial tumor of the young (PLNTY). Within the high-methionine-uptake region, we observed increased protein levels of L-type amino acid transporter 1 (LAT1), a major transporter of methionine; c-Myc; and constituents of the mitogen-activated protein kinase (MAPK) pathway. We also found that LAT1 expression was linked to the BRAF V600E mutation and subsequent activation of MAPK signaling and c-Myc. Pharmacological and genetic inhibition of the MAPK pathway suppressed c-Myc and LAT1 expression in BRAF V600E-mutated PLNTY and glioblastoma cells. The BRAF inhibitor dabrafenib moderately suppressed cell viability in PLNTY. Collectively, our results indicate that BRAF V600E mutation-activated MAPK signaling and downstream c-Myc induces specific metabolic alterations in PLNTY, and may represent an attractive target in the treatment of the disease.
Development and validation of the role identity surveys in engineering (RIS-E) and STEM (RIS-STEM) for elementary students
Authors: Paul Kelli M. , Maltese Adam V. , Svetina Valdivia Dubravka 
Published: August 2020

AbstractBackgroundDespite the increasing number of science, technology, engineering, and mathematics (STEM) jobs available, concern continues to grow over the low number of students who choose to study and enter STEM fields. Research suggests that children begin to identify their interests and career aspirations related to STEM as early as elementary school when they begin to shape their personal identities and start making decisions about who theyareandcould bein the future, their role identities (e.g., scientist, engineer). Existing surveys that assess identity target high school or post-secondary students, with less work on elementary and middle school students. This paper describes the development and validation of survey instruments to assess engineering identity in elementary students and its adaptation to a more general STEM context.ResultsThe role identity survey in engineering (RIS-E) was developed across four phases of pilot testing where it was administered to 634 students in third–sixth grade enrolled in classrooms in the West, Midwest, and Northeastern United States. Exploratory modeling approaches and scale reliability were used to narrow down items, while confirmatory factor analyses (CFA) and item response theory (IRT) approaches were used to examine item performance. The final survey contained four scales that assess aspects of one’s identity (competence, interest, self-recognition, and recognition by others), all of which demonstrated strong psychometric properties. The RIS-E was then adapted to assess STEM identity (RIS-STEM), and it was administered to 678 fourth–fifth grade students enrolled in classrooms in the Southwestern United States. CFA and IRT analyses provided support for use of the RIS-STEM in a more general STEM context.ConclusionsThe RIS-E and RIS-STEM appear to produce reliable scores that measure aspects of identity (engineering and STEM) in elementary students. Suggestions are made for future studies to examine how the RIS-E and RIS-STEM function across diverse student populations and the impact on one’s identity as a result of curricula or programs designed to encourage and support identity development in youth, especially in engineering and STEM.
Oxygen torus and its coincidence with EMIC wave in the deep inner magnetosphere: Van Allen Probe B and Arase observations
Authors: Nosé M. , Matsuoka A. , Kumamoto A. , Kasahara Y. , Teramoto M. , Kurita S. , Goldstein J. , Kistler L. M. , Singh S. , Gololobov A. , Shiokawa K. , Imajo S. , Oimatsu S. , Yamamoto K. , Obana Y. , Shoji M. , Tsuchiya F. , Shinohara I. , Miyoshi Y. , Kurth W. S. , Kletzing C. A. , Smith C. W. , MacDowall R. J. , Spence H. , Reeves G. D. 
Published: August 2020

AbstractWe investigate the longitudinal structure of the oxygen torus in the inner magnetosphere for a specific event found on 12 September 2017, using simultaneous observations from the Van Allen Probe B and Arase satellites. It is found that Probe B observed a clear enhancement in the average plasma mass (M) up to 3–4 amu at L = 3.3–3.6 and magnetic local time (MLT) = 9.0 h. In the afternoon sector at MLT ~ 16.0 h, both Probe B and Arase found no clear enhancements in M. This result suggests that the oxygen torus does not extend over all MLT but is skewed toward the dawn. Since a similar result has been reported for another event of the oxygen torus in a previous study, a crescent-shaped torus or a pinched torus centered around dawn may be a general feature of the O+ density enhancement in the inner magnetosphere. We newly find that an electromagnetic ion cyclotron (EMIC) wave in the H+ band appeared coincidently with the oxygen torus. From the lower cutoff frequency of the EMIC wave, the ion composition of the oxygen torus is estimated to be 80.6% H+, 3.4% He+, and 16.0% O+. According to the linearized dispersion relation for EMIC waves, both He+ and O+ ions inhibit EMIC wave growth and the stabilizing effect is stronger for He+ than O+. Therefore, when the H+ fraction or M is constant, the denser O+ ions are naturally accompanied by the more tenuous He+ ions, resulting in a weaker stabilizing effect (i.e., larger growth rate). From the Probe B observations, we find that the growth rate becomes larger in the oxygen torus than in the adjacent regions in the plasma trough and the plasmasphere.
Self-similar stochastic slip distributions on a non-planar fault for tsunami scenarios for megathrust earthquakes
Authors: Nakano Masaru , Murphy Shane , Agata Ryoichiro , Igarashi Yasuhiko , Okada Masato , Hori Takane 
Published: August 2020

AbstractMegathrust earthquakes that occur repeatedly along the plate interface of subduction zones can cause severe damage due to strong ground motion and the destructive tsunamis they can generate. We developed a set of scenario earthquakes to evaluate tsunami hazards and tsunami early warning systems for such devastating earthquakes. Although it is known that the slip distribution on a fault strongly affects the tsunami height distribution in near-field coastal areas, the slip distribution of future earthquakes cannot be exactly predicted. One way to resolve this difficulty is to create a set of scenario earthquakes in which a set of heterogeneous slip distributions on the source fault is stochastically generated based on a given slip probability density function (SPDF). The slip distributions generated in this manner differ from event to event, but their average over a large ensemble of models converges to a predefined SPDF resembling the long-term average of ruptures on the target fault zone. We created a set of SPDF-based scenario earthquakes for an expected future Mw8.2 Tonankai earthquake in the eastern half of the Nankai trough, off southwest Japan, and computed the ensuing tsunamis. We found that the estimated peak coastal amplitudes among the ensemble of tsunamis along the near-field coast differed by factors of 3 to 9, and the earliest and latest arrivals at each observation site differed by 400 to 700 s. The variations in both peak tsunami amplitude and arrival time at each site were well approximated by a Gaussian distribution. For cases in which the slip distribution is unknown, the average and standard deviation of these scenario datasets can provide first approximations of forecast tsunami height and arrival time and their uncertainties, respectively. At most coastal observation sites, tsunamis modeled similarly but using a uniform slip distribution underpredicted tsunami amplitudes but gave earlier arrival times than those modeled with a heterogeneous slip distribution. Use of these earlier arrival times may be useful for providing conservative early warnings of tsunami arrivals. Therefore, tsunami computations for both heterogeneous and uniform slip distributions are important for tsunami disaster mitigation.Graphical abstract
Association of the ward pharmacy service with active implementation of therapeutic drug monitoring for vancomycin and teicoplanin—an epidemiological surveillance study using Japanese large health insurance claims database
Authors: Imai Shungo , Momo Kenji , Kashiwagi Hitoshi , Miyai Takayuki , Sugawara Mitsuru , Takekuma Yoh 
Published: August 2020

Abstract
Background
Ward pharmacists are required for the active implementation of therapeutic drug monitoring (TDM). This epidemiological study verified whether Japanese ward pharmacists contribute to improving the TDM implementation proportions of anti-methicillin-resistant Staphylococcus aureus (MRSA) agents using the large health insurance claims database.

Methods
The patients who received intravenous anti-MRSA agents from April 2012 to March 2017 were enrolled. We defined ward pharmacy service as the “drug management and guidance fee” and/or “inpatient pharmaceutical services premium”. In addition, implementation of TDM was identified by “the specific drug treatment management fee”. We compared the proportions of TDM implementation for vancomycin (VCM), teicoplanin (TEIC), and arbekacin (ABK) in the ward and non-ward pharmacy service groups. To avoid confounding, the propensity score method was employed. Moreover, the clinical variables affecting TDM implementation in each anti-MRSA agent were analyzed by using a multiple logistic regression model.

Results
The following number of patients were included in the study: VCM (n = 2138), TEIC (n = 596), and ABK (n = 142). After propensity score matching, the proportions of TDM implementation for VCM and TEIC were higher in the ward pharmacy service group than in the non-ward pharmacy service group (VCM: 69.2% vs 60.3%, TEIC: 51.4% vs 34.7%), while no significant difference was observed for ABK (21.2% vs 23.1%). As independent clinical variables affecting TDM implementation for VCM and TEIC, several clinical variables, including ward pharmacy services, were extracted. In contrast, no clinical variables were extracted for ABK.

Conclusions
We found that the ward pharmacy service is associated with the active implementation of TDM for anti-MRSA agents, such as VCM and TEIC.
Rapidly progressed neuroendocrine carcinoma in the extrahepatic bile duct: a case report and review of the literature
Authors: Kamiya Mariko , Yamamoto Naoto , Kamioka Yuto , Inoue Hirohide , Yotsumoto Hirokazu , Murakawa Masaaki , Aoyama Toru , Washimi Kota , Kawachi Kae , Oshima Takashi , Ueno Makoto , Yukawa Norio , Rino Yasushi , Masuda Munetaka , Morinaga Soichiro 
Published: August 2020

Abstract
Background
Neuroendocrine carcinoma (NEC) originating from the extrahepatic bile duct (EHBD) is very rare but is known for its aggressiveness and poor prognosis. We herein report a case of rapidly progressed NEC in the extrahepatic bile duct.

Case presentation
An 84-year-old man was referred to our facility with obstructive jaundice and abdominal pain. Imaging studies revealed an irregular filling defect in the middle bile duct by endoscopic retrograde cholangiopancreatography and an enhanced wall thickening from the middle to distal portion by enhanced computed tomography. The patient was initially diagnosed with extrahepatic cholangiocarcinoma by a bile duct biopsy and underwent pancreatoduodenectomy with lymph node dissection. The pathological findings showed an NEC with an adenosquamous carcinoma component in the extrahepatic bile duct with lymph node metastases. The patient experienced multiple liver metastases 1 month after surgery and died 3 months after surgery. Due to the rapid progression of his disease, his general condition deteriorated, and he was unable to receive any additional treatments, such as chemotherapy.

Conclusion
As shown in our case, NEC of the EHBD has an extremely poor prognosis and can sometimes progress rapidly. Multimodality treatment should be considered, even in cases of locoregional disease.
Magnetic compression anastomosis is effective in treating stenosis after esophageal cancer surgery: a case report
Authors: Isozaki Tetsuro , Murakami Kentaro , Yamanouchi Eigoro , Uesato Masaya , Toyozumi Takeshi , Koide Yoshio , Tsukamoto Soichiro , Sakata Haruhito , Hayano Koichi , Kano Masayuki , Hayashi Hideki , Matsubara Hisahiro 
Published: August 2020

Abstract
Background
Esophagostomy is important in the treatment of esophageal cancer. However, esophagectomy has a higher risk of postoperative complications. Treatment for complications is often difficult, and in some cases, oral intake is no longer possible. Recently, magnetic compression anastomosis (MCA) was developed; it is a relatively safe method of anastomosis that does not require surgery in patients with stricture, obstruction, or dehiscence of the anastomosis after surgery.

Case presentation
The patient was a 76-year-old Japanese man. He underwent esophagectomy with a three-field dissection for esophageal cancer. A cervical esophagostomy and chest drainage were performed for necrosis of the gastric tube. Following infection control, colon interposition was performed. However, after the operation, the colon necrotized and formed an abscess. Drainage controlled the infection, but the colon was completely obstructed. The patient was referred to our hospital to restore oral ingestion. Contrast studies showed that the length of the occlusion was 10 mm. The reconstruction was examined; reanastomosis by surgery was judged to be a high risk, so the strategy of anastomosis by MCA was adopted. In the operation, the anterior chest was opened to expose the colon, and a magnet was inserted directly into the blind end of the colon. The magnet was guided to the blind end of the esophagus using an oral endoscope. Two weeks after MCA, a contrast study confirmed the passage of the contrast agent from the esophagus to the colon. The patient eventually took 18 bougies after the MCA. However, since then, he has not needed a bougie. As of 1 year and 8 months after the MCA, the patient is living at home with oral intake restored.

Conclusions
MCA is an effective and safe treatment for complete stenosis after esophageal cancer surgery.
Unicompartmental vs. segmental bicompartmental vs. total knee replacement: comparison of clinical outcomes
Authors: Al-Dadah Oday , Hawes Georgina , Chapman-Sheath Philip J. , Tice John William , Barrett David S. 
Published: August 2020

AbstractPurposeCombined medial tibiofemoral and symptomatic patellofemoral osteoarthritis is not amenable to unicompartmental knee replacement (UKR). Total knee replacement (TKR) is an invasive option in younger adults with high functional demands. The aim of this study was to compare the clinical outcome of patients who have undergone UKR, bicompartmental knee replacement (BKR) and TKR up to 2 years post-operatively.Materials and methodsThis prospective study comprised 133 subjects including 30 patients in the medial UKR group, 53 patients in the BKR group (combined medial UKR with patellofemoral joint replacement) and 50 patients in the TKR group. All subjects were evaluated using the Oxford Knee Score (OKS) and the Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC). Patients in each group were assessed using both scoring systems pre-operatively and 6 months, 1 year and 2 years post-operatively.ResultsSignificant improvement of OKS was found at 6 months compared to baseline for UKR (22.7 to 38.1,p = 0.046), BKR (22.6 to 36.8,p < 0.001) and TKR (16.6 to 34.5,p < 0.001). Significant improvement was also found for the WOMAC sub-scores for all three groups during this time period. After 6 months, there was no further statistically significant improvement in either outcome score in any of the groups up to the 2-year follow-up results. There was no significant difference in either outcome score post-operatively between the three groups.ConclusionThe magnitude of clinical improvement following knee replacement is greatest at 6 months; thereafter, only modest improvements continue to occur. This study also found no significant differences of outcomes at 2 years after surgery among UKR, BKR and TKR. BKR is a good alternative option for combined symptomatic medial and patellofemoral arthritis of the knee.
Prevalence of Opioid-Induced Adrenal Insufficiency in Patients Taking Chronic Opioids
Authors: Li Taoran , Cunningham Julie L , Gilliam Wesley P , Loukianova Larissa , Donegan Diane M , Bancos Irina 
Published: August 2020

Abstract

Context
Chronic opioid use may lead to adrenal insufficiency because of central suppression of the hypothalamic-pituitary-adrenal axis. However, the prevalence of opioid-induced adrenal insufficiency (OIAI) is unclear.

Objective
To determine the prevalence of OIAI and to identify predictors for the development of OIAI in patients taking opioids for chronic pain.

Design
Cross-sectional study, 2016-2018.

Setting
Referral center.

Patients
Adult patients taking chronic opioids admitted to the Pain Rehabilitation Center.

Main outcome measure
Diagnosis of OIAI was considered if positive case detection (cortisol &lt; 10 mcg/dL, ACTH &lt; 15 pg/mL, and dehydroepiandrosterone sulfate &lt; 25 mcg/dL), and confirmed after endocrine evaluation. Daily morphine milligram equivalent (MME) was calculated.

Results
In 102 patients (median age, 53 years [range, 22-83], 67% women), median daily MME was 60 mg (3-840), and median opioid therapy duration was 60 months (3-360). Abnormal case detection testing was found in 11 (10.8%) patients, and diagnosis of OIAI was made in 9 (9%). Patients with OIAI were on a higher daily MME (median, 140 [20-392] mg vs 57 [3-840] mg, P = 0.1), and demonstrated a 4 times higher cumulative opioid exposure (median of 13,440 vs 3120 mg*months, P = 0.03). No patient taking &lt;MME of 20 mg/day developed OIAI (sensitivity of 100% for MME &gt; 20 mg); however, specificity of MME cutoff &gt;20 mg was only 19%. After opioid discontinuation, 6/7 patients recovered adrenal function.

Conclusion
The prevalence of OIAI was 9%, with MME cumulative exposure being the only predictor for OIAI development. Patients on MME of 20 mg/day and above should be monitored for OIAI.
Premature Adrenarche in Girls Characterized By Enhanced 17,20-Lyase and 17β-Hydroxysteroid Dehydrogenase Activities
Authors: Janner Marco , Sommer Grit , Groessl Michael , Flück Christa E 
Published: August 2020

Abstract

Context
Girls with premature adrenarche (PA) may have a higher risk of developing polycystic ovary syndrome (PCOS) and metabolic syndrome. The biological purpose of adrenarche is unknown and the role of novel biosynthetic pathways remains unclear.

Objective
To compare the urinary steroid metabolome and enzyme activities of girls with PA to age-matched control girls and to published steroid values of girls with normal adrenarche and of women with PCOS and their newborn daughters.

Design
Prospective observational study from 2009 to 2014.

Setting
Academic pediatric endocrinology referral center.

Participants
Twenty-three girls with PA and 22 healthy, age-matched girls.

Main Outcome Measures
Steroid metabolites in 24-hour urine samples, including 4 progesterones, 5 corticosterones, aldosterone, 13 androgens, 2 estrogens, 14 glucocorticoids, and enzyme activities represented by metabolite ratios.

Results
Girls with PA had a higher body mass index (mean standard deviation scores 0.9 vs -0.3, P = 0.013). Androgen excretion was higher in PA girls than in control girls (median 3257 nmol/24 hours vs 1627 nmol/24 hours, P &lt; 0.001), in particular metabolites from alternate androgen pathways. The amount of progesterone, corticosterone, aldosterone, estrogen, and cortisol metabolites were similar between groups. Activities of 17β-hydroxysteroid-dehydrogenase and of 17,20-lyase were higher in girls with PA. Activities of 3β-hydroxysteroid-dehydrogenase, 21-hydroxylase, and 5α-reductase activity were not different between groups, in contrast to published results on girls with normal adrenarche or PCOS females.

Conclusions
Metabolites and enzymes involved in alternate androgen pathways appear to be markers of PA. Prospective studies should assess whether steroid production in PA also differs from adrenarche at normal timing and persists into adulthood.