bluuebunny/crossref_metadata_2025_split huggingface dataset:
A variationally separable splitting for the generalized‐α method for parabolic equations
Authors: Behnoudfar Pouria , Calo Victor M. , Deng Quanling , Minev Peter D. 
Published: October 2019

AbstractWe present a variationally separable splitting technique for the generalized‐α method for solving parabolic partial differential equations. We develop a technique for a tensor‐product mesh which results in a solver with a linear cost with respect to the total number of degrees of freedom in the system for multidimensional problems. We consider finite elements and isogeometric analysis for the spatial discretization. The overall method maintains user‐controlled high‐frequency dissipation while minimizing unwanted low‐frequency dissipation. The method has second‐order accuracy in time and optimal rates (hp+1 in L2 norm of u and hp in L2 norm of ∇u) in space. We present the spectral analysis on the amplification matrix to establish that the method is unconditionally stable. Various numerical examples illustrate the performance of the overall methodology and show the optimal approximation accuracy.
A general and efficient multistart algorithm for the detection of loss of ellipticity in elastoplastic structures
Authors: Al Kotob Moubine , Combescure Christelle , Mazière Matthieu , Rose Tonya , Forest Samuel 
Published: October 2019

SummaryThe present paper proposes a new efficient and robust algorithm for evaluating the loss of ellipticity criterion. While commonly used in two‐dimensional models for thin metal sheet forming processes, it is rarely evaluated in three‐dimensional structures due to the computational cost. The proposed algorithm is based on a Newton‐Raphson scheme and a multisampling optimization method based on a discretization method of the half unit sphere. First the new process is compared to the existing methods in the literature and then it is applied to a structural problem, namely tubes in torsion. The evolution of the loss of ellipticity in these structures is analyzed leading to conclusions about the failure of the structure. Meanwhile, the stability of the discretized problem is analyzed in order to better understand the loss of regularity of the finiteelement method problem. These results are then used to predict the failure of an experimentally tested torsion sample.
Crystal and solution structures of human oncoprotein Musashi‐2 N‐terminal RNA recognition motif 1
Authors: Lan Lan , Xing Minli , Kashipathy Maithri , Douglas Justin , Gao Philip , Battaile Kevin , Hanzlik Robert , Lovell Scott , Xu Liang 
Published: October 2019

AbstractMusashi‐2 (MSI2) belongs to Musashi family of RNA binding proteins (RBP). Like Musashi‐1 (MSI1), it is overexpressed in a variety of cancers and is a promising therapeutic target. Both MSI proteins contain two N‐terminal RNA recognition motifs and play roles in posttranscriptional regulation of target mRNAs. Previously, we have identified several inhibitors of MSI1, all of which bind to MSI2 as well. In order to design MSI2‐specific inhibitors and compare the differences of binding mode of the inhibitors, we set out to solve the structure of MSI2‐RRM1, the key motif that is responsible for the binding. Here, we report the crystal structure and the first NMR solution structure of MSI2‐RRM1, and compare these to the structures of MSI1‐RBD1 and other RBPs. A high degree of structural similarity was observed between the crystal and solution NMR structures. MSI2‐RRM1 shows a highly similar overall folding topology to MSI1‐RBD1 and other RBPs. The structural information of MSI2‐RRM1 will be helpful for understanding MSI2‐RNA interaction and for guiding rational drug design of MSI2‐specific inhibitors.
Revisiting Quantum Feedback Control: Disentangling the Feedback‐Induced Phase from the Corresponding Amplitude
Authors: Barkemeyer Kisa , Finsterhölzl Regina , Knorr Andreas , Carmele Alexander 
Published: October 2019

AbstractCoherent time‐delayed feedback allows the control of a quantum system and its partial stabilization against noise and decoherence. The crucial and externally accessible parameters in such control setups are the round‐trip‐induced delay time τ and the frequencies ω of the involved optical transitions which are typically controllable via global parameters like temperature, bias, or strain. They influence the dynamics via the amplitude and the phase of the feedback signal. These quantities are, however, not independent. Here, the aim is to control the feedback phase via a microwave pump field. Using the example of a Λ‐type three‐level system, it is shown that the Rabi frequency of the pump field induces phase shifts on demand and therefore increases the applicability of coherent quantum feedback control protocols.
Complex Formation between Soy Proteins and Potato Starch: Effect of pH, Biopolymer Ratio, and Biopolymer Concentration
Authors: Dong Die , Qi Zhengliang , Cui Bo 
Published: October 2019

AbstractUnderstanding the factors that induce protein–starch complex formation under acidic conditions is important for the production of acidic beverages. This study investigates the formation of complexes between soy proteins (SP) and potato starch (PS). Measurements of turbidity and ζ potential are used to study complex formation as a function of pH (7.0–2.0), SP/PS ratio (1:8–4:1, w/w), biopolymer concentration (Cp, 0.1–0.8%, w/v), and PS concentration (CPS, 0.05–0.8%, w/v). For 1:4 SP/PS mixtures, the highest turbidity (OD600 = 0.33) is reached at pH 3.2 (defined as the optimal pH [pHopt]), where the ζ potential is 0 mV. Thus, biopolymer interactions reach a maximum at the charge balanced point. With increasing SP/PS ratio (1:8–1:4), the pHopt increases. At SP/PS ratios > 1:2, soy protein aggregates affect the turbidity. The turbidity increases with increasing biopolymer concentration (0.1%–0.5%), indicating more interactions between SP and PS. Sedimentation measurements prove that the addition of PS reduces SP aggregation at its isoelectric point owing to electrostatic repulsion. Soy protein aggregates are confirmed to be involved in SP/PS complex formation, leading to higher and broader turbidity curves. This study will provide necessary theoretical support for the application of starch in acid protein beverage.
Identification of major ADH genes in ethanol metabolism of Pichia pastoris
Authors: Karaoğlan Mert , Erden‐Karaoğlan Fidan , Yılmaz Semiramis , İnan Mehmet 
Published: October 2019

AbstractThe methylotrophic yeast Pichia pastoris (syn. Komagataella phaffii) is a successful host widely used in recombinant protein production. The widespread use of a methanol‐regulated alcohol oxidase 1 (AOX1) promoter for recombinant protein production has directed studies particularly about methanol metabolism in this yeast. Although there is comprehensive knowledge about methanol metabolism, there are other mechanisms in P. pastoris that have not been investigated yet, such as ethanol metabolism. The gene responsible for the consumption of ethanol ADH2 (XM_002491337, known as ADH3) was identified and characterized in our previous study. In this study, the ADH genes (XM_002489969, XM_002491163, XM_002493969) in P. pastoris genome were investigated to determine their roles in ethanol production by gene disruption analysis. We report that the ADH900 (XM_002491163) is the main gene responsible for ethanol production in P. pastoris. The ADH2 gene, previously identified as the only gene responsible for ethanol consumption, also plays a minor role in ethanol production in the absence of the ADH900 gene. The investigation of the carbon source regulation mechanism has also revealed that the ADH2 gene exhibit similar expression behaviours with ADH900 on glucose, glycerol, and methanol, however, it is strongly induced by ethanol.
A comparison of understanding of the amphibian crisis by zoo visitors across three countries
Authors: Dos Santos Marcileida M. , Griffiths Richard A. , Jowett Tim , Rock Jennifer , Bishop Phillip J. 
Published: October 2019

AbstractDespite the global declines in the rate of amphibians, evaluation of public understanding of the crisis has not yet been carried out. We surveyed visitors (n = 1,293) at 15 zoos in Brazil, New Zealand, and the United Kingdom, using a certainty‐based assessment method to compare visitor knowledge of the global amphibian crisis. We further analyzed zoo educational material about amphibians to explore its potential to raise awareness through amphibian‐focused environmental education. Visitors in the three countries had relatively little understanding of amphibians and the global amphibian crisis. When the degree of confidence in answering the questions (high, medium, and low) is accounted for, correct answers varied between 28% and 39%. This compared to scores of between 58% and 73% when the degree of confidence in responding was not accounted for. However, specific areas of knowledge (e.g., biology, conservation, biogeography, and conceptual ideas) varied significantly across the countries. Visitors had a weaker grasp of biogeographical and conservation issues than general amphibian biology. Zoo visitors in Brazil knew less about amphibian conservation than those in New Zealand or the United Kingdom. There was less amphibian‐focused content in educational materials in zoos in Brazil than there was in the United Kingdom. Improving information about the global amphibian crisis may increase support for future conservation actions. Outreach education is one of the most important approaches in any strategic planning for conservation of species. Amphibian‐focused environmental education at institutions such as zoos and aquaria can be a crucial intervention to support amphibian conservation worldwide.
Phosphorylation-dependent regulation of the NOTCH1 intracellular domain by dual-specificity tyrosine-regulated kinase 2
Authors: Morrugares Rosario , Correa-Sáez Alejandro , Moreno Rita , Garrido-Rodríguez Martín , Muñoz Eduardo , de la Vega Laureano , Calzado Marco A. 
Published: October 2019

Abstract
NOTCH proteins constitute a receptor family with a widely conserved role in cell cycle, growing and development regulation. NOTCH1, the best characterised member of this family, regulates the expression of key genes in cell growth and angiogenesis, playing an essential role in cancer development. These observations provide a relevant rationale to propose the inhibition of the intracellular domain of NOTCH1 (Notch1-IC) as a strategy for treating various types of cancer. Notch1-IC stability is mainly controlled by post-translational modifications. FBXW7 ubiquitin E3 ligase-mediated degradation is considered one of the most relevant, being the previous phosphorylation at Thr-2512 residue required. In the present study, we describe for the first time a new regulation mechanism of the NOTCH1 signalling pathway mediated by DYRK2. We demonstrate that DYRK2 phosphorylates Notch1-IC in response to chemotherapeutic agents and facilitates its proteasomal degradation by FBXW7 ubiquitin ligase through a Thr-2512 phosphorylation-dependent mechanism. We show that DYRK2 regulation by chemotherapeutic agents has a relevant effect on the viability, motility and invasion capacity of cancer cells expressing NOTCH1. In summary, we reveal a novel mechanism of regulation for NOTCH1 which might help us to better understand its role in cancer biology.
Investigating Wilms’ Tumours Worldwide: A Report of the OxPLORE Collaboration—A Cross‐Sectional Observational Study
Authors: Ford K. , Gunawardana S. , Manirambona E. , Philipoh G. S. , Mukama B. , Kanyamuhunga A. , Cartledge P. , Nyoni M. J. , Mwaipaya D. , Mpwaga J. , Bokhary Z. , Scanlan T. , Heinsohn T. , Hathaway H. , Mansfield R. , Wilson S. , Lakhoo K. 
Published: October 2019

AbstractBackgroundChildhood cancer is neglected within global health. Oxford Pediatrics Linking Oncology Research with Electives describes early outcomes following collaboration between low‐ and high‐income paediatric surgery and oncology centres. The aim of this paper is twofold: to describe the development of a medical student‐led research collaboration; and to report on the experience of Wilms’ tumour (WT).MethodsThis cross‐sectional observational study is reported as per STROBE guidelines. Collaborating centres included three tertiary hospitals in Tanzania, Rwanda and the UK. Data were submitted by medical students following retrospective patient note review of 2 years using a standardised data collection tool. Primary outcome was survival (point of discharge/death).ResultsThere were 104 patients with WT reported across all centres over the study period (Tanzania n = 71, Rwanda n = 26, UK n = 7). Survival was higher in the high‐income institution [87% in Tanzania, 92% in Rwanda, 100% in the UK (X2 36.19, p < 0.0001)]. Given the short‐term follow‐up and retrospective study design, this likely underestimates the true discrepancy. Age at presentation was comparable at the two African sites but lower in the UK (one‐way ANOVA, F = 0.2997, p = 0.74). Disease was more advanced in Tanzania at presentation (84% stage III–IV cf. 60% and 57% in Rwanda and UK, respectively, X2 7.57, p = 0.02). All patients had pre‐operative chemotherapy, and a majority had nephrectomy. Post‐operative morbidity was higher in lower resourced settings (X2 33.72, p < 0.0001). Methodology involving medical students and junior doctors proved time‐ and cost‐effective. This collaboration was a valuable learning experience for students about global research networks.ConclusionsThis study demonstrates novel research methodology involving medical students collaborating across the global south and global north. The comparison of outcomes advocates, on an institutional level, for development in access to services and multidisciplinary treatment of WT.
Does the ATA Risk Stratification Apply to Patients with Papillary Thyroid Microcarcinoma?
Authors: Stefanova Dessislava I. , Bose Arpita , Ullmann Timothy M. , Limberg Jessica N. , Finnerty Brendan M. , Zarnegar Rasa , Fahey Thomas J. , Beninato Toni 
Published: October 2019

AbstractBackgroundThe incidence of papillary thyroid microcarcinoma (PTMC) has increased over the past decade. The American Thyroid Association (ATA) suggests that these patients may undergo either thyroid lobectomy or active surveillance. It remains unclear whether there exists a subgroup of PTMC patients who may benefit from more aggressive treatment due to increased risk of recurrence.MethodsWe retrospectively reviewed 357 patients with PTMC who underwent surgery at a single institution from 2004 to 2016. Patients were classified according to 2015 ATA risk stratification for structural disease recurrence. Demographic, oncologic, and clinicopathologic data were compared between groups.ResultsOut of 357 patients, 246 were classified as low‐risk PTMC, 93 were intermediate‐risk, and 18 were high‐risk. There were more male patients in the high‐risk group (38.9%) than the intermediate‐ (31.2%) or low‐risk groups (15.4%) (p < 0.001). Patients with low‐risk microcarcinomas were more likely to have an incidental PTMC when compared to intermediate‐ or high‐risk groups (98[39.8%], 15[16.1%], 1[5.6%], respectively, p < 0.001). Patients with high‐risk PTMCs, compared to those with intermediate‐ and low‐risk PTMCs, were more likely to have rising postoperative thyroglobulin levels after total thyroidectomy (6[40.0%], 4[5.1%], 9[5.7%], respectively, p = 0.001) and structural recurrence after lobectomy or total thyroidectomy (3[16.7%], 0[0%], 0[0%], respectively, p < 0.001). The median follow‐up time was 17.5 (IQR 3–55) months.ConclusionsPatients with high‐risk PTMC have an increased risk of recurrence when compared to low‐ and intermediate‐risk microcarcinomas, whereas intermediate‐risk PTMC may behave similarly to low‐risk tumors. ATA risk stratification may inform clinical decision making for patients with PTMC.
Epidemiological Data and Treatment of Gastroenteropancreatic Neuroendocrine Neoplasms: Insights From Tertiary Referral Hospitals in Latvia
Authors: Ptasnuka Margarita , Ozolins Arturs , Narbuts Zenons , Truskovs Arturs , Sperga Maris , Plaudis Haralds 
Published: October 2019

AbstractBackgroundGastroenteropancreatic neuroendocrine neoplasms (GEP‐NEN) are rare, heterogeneous group which tend to rise in incidence. Epidemiological profile and outcomes of GEP‐NEN may vary among countries. The aim of study was to provide baseline clinical and histopathological features of patients with GEP‐NEN from tertiary referral hospitals in Latvia.MethodsA retrospective study of patients with histologically confirmed diagnosis of GEP‐NEN treated between 2006 and 2018. Joinpoint regression modeling was used to estimate annual percentage change (APC) for incidence trends. Overall survival (OS) rate was obtained by Kaplan–Meier method.ResultsIn total, 205 patients were included. The median age at diagnosis was 61.0 (IQR 52.0–70.5) years, 69.3% were females. The age‐adjusted incidence per 100 000 inhabitants increased from 0.03 in 2006 to 0.67 in 2018 with APC of 24.1%,p < 0.005. The most common primary tumor site was pancreas (30.7%), followed by stomach (24.9%) and small intestine (20.5%). Non‐functional tumors are present in 83.4%, while carcinoid syndrome in 7.8%. Stage IV metastatic disease was present in 27.8% tumors. The majority of patients (82%) received an operation with radical or palliative intent. The 1‐ and 3‐year OS rate were 88.0% (95% CI 83.3–92.7) and 77.1% (95% CI 70.4–83.8), respectively. Increasing tumor grade, stage and the presence of distant metastases were associated with significantly worse OS.ConclusionOur study highlights increasing incidence of GEP‐NEN in Latvia. The most common primary site was pancreas and surgery considered as main modality of treatment. Registry and long‐term data collection are necessary to develop GEP‐NEN management concept in Latvia.
Prognostic Assessment of Non‐functioning Neuroendocrine Pancreatic Neoplasms as a Basis for Risk‐Adapted Resection Strategies
Authors: Watzka F. M. , Meyer F. , Staubitz J. I. , Fottner C. , Schad A. , Lang H. , Musholt T. J. 
Published: October 2019

AbstractBackgroundIn contrast to exocrine pancreatic carcinomas, prognosis and treatment of pancreatic neuroendocrine neoplasms (PNEN) are significantly different. The variable growth pattern and associated clinical situation of functioning and non‐functioning PNEN demand an individualized surgical approach. However, due to the scarce evidence associated with the rare disease, guidelines lack detailed recommendations for indication and for the required extent of surgical resection.MethodsIn a retrospective single‐center study from 1990 to 2018, 239 patients with PNEN were identified. Clinical data were collected in the MaDoc database of the University Medical Center Mainz. A total of 155 non‐functional PNEN were selected for further analysis.ResultsAccording to the classification of NET by the WHO in 2017, 28.8% (n = 40) of the tumors were G1, 61.9% (n = 86) G2, and 9.4% (n = 13) G3. In 73 patients, hepatic metastases were present. Sixty patients had lymph node metastasis. An R0 resection was achieved in 98 cases, an R1 situation in 10 cases. Five times, a tumor debulking was carried out (R2) and 5 times the operation was aborted without any resection because of the advanced tumor stage. A relapse occurred in 29 patients. Different prognostic factors (grade, tumor size, age) were analyzed. Grade‐dependent 10‐year overall survival rates were 79.5% (grade 1) and 60.1% (grade 2), respectively. The survival rate of grade 3 patients was limited to 66.7% after 13 months.ConclusionIn our study, patients with non‐functioning PNEN had a longer overall survival after successful R0 resection. The risk analysis confirmed a Ki‐67 cutoff value of 5%, which divided a high‐ and low‐risk group. Patients with a PNEC G3 (Ki‐67 index > 50%) had a very poor prognosis.
Liver Resection Versus Embolization for Recurrent Hepatocellular Carcinoma
Authors: Midorikawa Yutaka , Takayama Tadatoshi , Moriguchi Masamichi , Yagi Rempei , Yamagishi Shunsuke , Nakayama Hisashi , Aramaki Osamu , Yamazaki Shintaro , Tsuji Shingo , Higaki Tokio 
Published: October 2019

AbstractBackgroundDespite curative resection, hepatocellular carcinoma (HCC) has a high probability of recurrence. We validated the potential role of liver resection (LR) for recurrent HCC.MethodsPatients with intrahepatic recurrence with up to three lesions were included. We compared survival times of patients undergoing their first LR to those of patients undergoing repeated LR. Then, survival times of the patients who had undergone LR and transcatheter chemoembolization (TACE) for recurrent HCC after propensity score matching were compared.ResultsAfter a median follow‐up period of 3.1 years (range, 0.2–16.3), median overall survival times were 6.5 years (95% CI 6.0–7.0), 5.7 years (5.2–6.2), and 5.1 years (4.9–7.3) for the first LR (n = 1234), second LR (n = 273), and third LR (n = 90) groups, respectively. Severe complications frequently occurred in the first LR group (p = 0.059). Operative times were significantly longer for the third LR group (p = 0.012). After the first recurrence, median survival times after one‐to‐one pair matching were 5.7 years (95% CI 4.5–6.5) and 3.1 years (2.1–3.8) for the second LR group (n = 146) and TACE group (n = 146), respectively (p < 0.001). The median survival time of the third LR group (n = 41) (6.2 years; 95% CI 3.7–NA) was also longer than that of TACE group (n = 41) (3.4 years; 1.8–4.5; p = 0.010) after the second recurrence.ConclusionsRepeated LR for recurrent HCC is the procedure of choice if there are three or fewer tumors.
Ineffective Esophageal Motility in Patients with GERD is no Contraindication for Nissen Fundoplication
Authors: Nikolic Milena , Schwameis Katrin , Kristo Ivan , Paireder Matthias , Matic Aleksa , Semmler Georg , Semmler Lorenz , Schoppmann Sebastian F. 
Published: October 2019

AbstractBackgroundPatients with preoperative ineffective esophageal motility (IEM) are thought to be at increased risk for postoperative dysphagia leading to the recommendations for tailoring or avoiding anti‐reflux surgery in these patients. The aim of this study was to evaluate if IEM has an influence on postoperative outcome after laparoscopic Nissen fundoplication (LNF).MethodsSeventy‐two consecutive patients with IEM underwent LNF and were case‐matched with 72 patients without IEM based on sex, age, BMI, HH size, total pH percentage time, total number of reflux episodes and the presence of BE. Standardized interview assessing postoperative gastrointestinal symptoms, proton pump inhibitor intake, GERD‐health‐related‐quality‐of‐life (GERD‐HRQL), alimentary satisfaction and patients’ overall satisfaction was evaluated.ResultsAlthough a higher rate of preoperative dysphagia was observed in patients with IEM (29% IEM vs. 11% no IEM, p = 0.007), there was no significant difference in rates of dysphagia postoperatively (2 IEM vs. 1 no IEM, p = 0.559). Furthermore, no distinction was found in the postoperative outcome regarding symptom relief, quality of life, gas bloating syndrome, ability to belch and/or vomit or revision surgery between the two groups.ConclusionAlthough preoperative IEM has an influence on GERD presentation, it has no effect on postoperative outcome after LNF. IEM should not be a cause for avoiding LNF, as is has been shown as the most effective and safe anti‐reflux treatment.