bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytosolic sequestration of the vitamin D receptor as a therapeutic option for vitamin D-induced hypercalcemia
Authors: Rovito Daniela , Belorusova Anna Y. , Chalhoub Sandra , Rerra Anna-Isavella , Guiot Elvire , Molin Arnaud , Linglart Agnès , Rochel Natacha , Laverny Gilles , Metzger Daniel 
Published: December 2020

AbstractThe bioactive vitamin D3, 1α,25(OH)2D3, plays a central role in calcium homeostasis by controlling the activity of the vitamin D receptor (VDR) in various tissues. Hypercalcemia secondary to high circulating levels of vitamin D3leads to hypercalciuria, nephrocalcinosis and renal dysfunctions. Current therapeutic strategies aim at limiting calcium intake, absorption and resorption, or 1α,25(OH)2D3synthesis, but are poorly efficient. In this study, we identify WBP4 as a new VDR interactant, and demonstrate that it controls VDR subcellular localization. Moreover, we show that the vitamin D analogue ZK168281 enhances the interaction between VDR and WBP4 in the cytosol, and normalizes the expression of VDR target genes and serum calcium levels in 1α,25(OH)2D3-intoxicated mice. As ZK168281 also blunts 1α,25(OH)2D3-induced VDR signaling in fibroblasts of a patient with impaired vitamin D degradation, this VDR antagonist represents a promising therapeutic option for 1α,25(OH)2D3-induced hypercalcemia.
Improving the informativeness of Mendelian disease-derived pathogenicity scores for common disease
Authors: Kim Samuel S. , Dey Kushal K. , Weissbrod Omer , Márquez-Luna Carla , Gazal Steven , Price Alkes L. 
Published: December 2020

AbstractDespite considerable progress on pathogenicity scores prioritizing variants for Mendelian disease, little is known about the utility of these scores for common disease. Here, we assess the informativeness of Mendelian disease-derived pathogenicity scores for common disease and improve upon existing scores. We first apply stratified linkage disequilibrium (LD) score regression to evaluate published pathogenicity scores across 41 common diseases and complex traits (average N = 320K). Several of the resulting annotations are informative for common disease, even after conditioning on a broad set of functional annotations. We then improve upon published pathogenicity scores by developing AnnotBoost, a machine learning framework to impute and denoise pathogenicity scores using a broad set of functional annotations. AnnotBoost substantially increases the informativeness for common disease of both previously uninformative and previously informative pathogenicity scores, implying that Mendelian and common disease variants share similar properties. The boosted scores also produce improvements in heritability model fit and in classifying disease-associated, fine-mapped SNPs. Our boosted scores may improve fine-mapping and candidate gene discovery for common disease.
Molecular rotors with designed polar rotating groups possess mechanics-controllable wide-range rotational speed
Authors: Shao Jian , Zhu Wenpeng , Zhang Xiaoyue , Zheng Yue 
Published: December 2020

AbstractMolecular rotors with controllable functions are promising for molecular machines and electronic devices. Especially, fast rotation in molecular rotor enables switchable molecular conformations and charge transport states for electronic applications. However, the key to molecular rotor-based electronic devices comes down to a trade-off between fast rotational speed and thermal stability. Fast rotation in molecular rotor requires a small energy barrier height, which disables its controllability under thermal excitation at room temperature. To overcome this trade-off dilemma, we design molecular rotors with co-axial polar rotating groups to achieve wide-range mechanically controllable rotational speed. The interplay between polar rotating groups and directional mechanical load enables a “stop-go” system with a wide-range rotational energy barrier. We show through density functional calculations that directional mechanical load can modulate the rotational speed of designed molecular rotors. At a temperature of 300 K, these molecular rotors operate at low rotational speed in native state and accelerates tremendously (up to 1019) under mechanical load.
Extremely low-frequency electric field suppresses not only induced stress response but also stress-related tissue damage in mice
Authors: Harakawa Shinji , Nedachi Takaki , Suzuki Hiroshi 
Published: December 2020

AbstractAlthough extremely low-frequency electric fields (ELF-EF) have been utilised for therapeutic purposes, the biological effect and the underlying mechanism of ELF-EF have not been elucidated. Here, we developed a mouse model of immobilisation-induced increase in glucocorticoid (GC) to evaluate the effect of ELF-EF. Mice were exposed to 50-Hz 10 kV/m EF via a parallel plate electrode and immobilised as needed. The ELF-EF suppressed the immobilisation-induced increase in blood GC level. Here, the results of 32 tests using the model were pooled and analysed. The suppressive effect of ELF-EF on immobilisation-induced increase in GC was reproduced, and the GC level was slightly higher in the ELF-EF-treated mice than in the sham-controlled mice, a novel observation. The immobilisation-induced increase in lactate dehydrogenase, glutamic oxaloacetic transaminase, and glutamic pyruvic transaminase, markers of tissue damage, was suppressed by co-treatment with EF in the biochemical tests using the same plasma sample. In the metabolome analysis, the changes in corticosterones, leukotrienes, and hydroxyeicosatetraenoic acids, markers of inflammation, showed a pattern similar to that of the plasma GC level. Thus, ELF-EF suppresses the stress response that causes an increase in the GC level and slightly promotes GC production in the absence of stress. Moreover, the suppressive effect of ELF-EF on induced stress response might be involved in stress-induced tissue damage or inflammation in immobilised mice. Overall, the model and the data help explore the biological effect of ELF-EF and explain the stress-relieving effect of EF. They would be useful in determining the medical applications of EF in humans and animals.
Construction and validation of a nomogram for predicting cancer-specific survival in hepatocellular carcinoma patients
Authors: Liu Kang , Huang Gaobo , Chang Pengkang , Zhang Wei , Li Tao , Dai Zhijun , Lv Yi 
Published: December 2020

AbstractThe prognosis of patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is a research hotspot. This study aimed to incorporate important factors obtained from SEER database to construct and validate a nomogram for predicting the cancer-specific survival (CSS) of patients with HCC and ICC. We obtained patient data from SEER database. The nomogram was constructed base on six prognostic factors for predicting CSS rates in HCC patients. The nomogram was validated by concordance index (C-index), the receiver operating characteristic (ROC) curve and calibration curves. A total of 3227 patients diagnosed with HCC (3038) and ICC (189) between 2010 and 2015 were included in this study. The C-index of the nomogram for HCC patients was 0.790 in the training cohort and 0.806 in the validation cohort. The 3- and 5-year AUCs were 0.811 and 0.793 in the training cohort. The calibration plots indicated that there was good agreement between the actual observations and predictions. In conclusion, we constructed and validated a nomogram for predicting the 3- and 5-year CSS in HCC patients. We have confirmed the precise calibration and excellent discrimination power of our nomogram.
Robust quantum point contact operation of narrow graphene constrictions patterned by AFM cleavage lithography
Authors: Kun Péter , Fülöp Bálint , Dobrik Gergely , Nemes-Incze Péter , Lukács István Endre , Csonka Szabolcs , Hwang Chanyong , Tapasztó Levente 
Published: December 2020

AbstractDetecting conductance quantization in graphene nanostructures turned out more challenging than expected. The observation of well-defined conductance plateaus through graphene nanoconstrictions so far has only been accessible in the highest quality suspended or h-BN encapsulated devices. However, reaching low conductance quanta in zero magnetic field, is a delicate task even with such ultra-high mobility devices. Here, we demonstrate a simple AFM-based nanopatterning technique for defining graphene constrictions with high precision (down to 10 nm width) and reduced edge-roughness (+/−1 nm). The patterning process is based on the in-plane mechanical cleavage of graphene by the AFM tip, along its high symmetry crystallographic directions. As-defined, narrow graphene constrictions with improved edge quality enable an unprecedentedly robust QPC operation, allowing the observation of conductance quantization even on standard SiO2/Si substrates, down to low conductance quanta. Conductance plateaus, were observed at n × e2/h, evenly spaced by 2 × e2/h (corresponding to n = 3, 5, 7, 9, 11) in the absence of an external magnetic field, while spaced by e2/h (n = 1, 2, 3, 4, 5, 6) in 8 T magnetic field.
The link between star formation and gas in nearby galaxies
Authors: Feldmann Robert 
Published: December 2020

AbstractObservations of the interstellar medium are key to deciphering the physical processes regulating star formation in galaxies. However, observational uncertainties and detection limits can bias the interpretation unless carefully modeled. Here I re-analyze star formation rates and gas masses of a representative sample of nearby galaxies with the help of multi-dimensional Bayesian modeling. Typical star forming galaxies are found to lie in a ‘star forming plane’ largely independent of their stellar mass. Their star formation activity is tightly correlated with the molecular and total gas content, while variations of the molecular-gas-to-star conversion efficiency are shown to be significantly smaller than previously reported. These data-driven findings suggest that physical processes that modify the overall galactic gas content, such as gas accretion and outflows, regulate the star formation activity in typical nearby galaxies, while a change in efficiency triggered by, e.g., galaxy mergers or gas instabilities, may boost the activity of starbursts.
Sentence Imitation With Masked Morphemes in Czech: Memory, Morpheme Frequency, and Morphological Richness
Authors: Smolík Filip , Matiasovitsová Klára 
Published: December 2020

Purpose
This study examined two markers of language impairment (LI) in a single experiment, testing sentence imitation and grammatical morphology production using an imitation task with masked morphemes. One goal was to test predictions of the morphological richness account of LI in Czech. We also tested the independent contributions of language and memory skills to sentence imitation performance.

Method
Seventeen children with LI (5;1–7;6 [years;months]) and 17 vocabulary-matched typically developing (TD) children (3;8–4;11) were administered a sentence imitation task where each sentence had one noun or verb ending replaced by a coughing sound. In addition, a receptive vocabulary and the digit span (backward and forward) tasks were administered.

Results
Children with LI were significantly less accurate than TD children in sentence imitation task. Both vocabulary and digit span had unique effects on sentence imitation scores. Children with LI were less successful in imitating the target words, especially verbs. However, if they succeeded, their completions of the masked morphemes were no less accurate than in TD children. The accuracy of completions was affected by the morpheme frequency and homophony, but these effects were similar in TD and affected children.

Conclusions
Sentence imitation is a measure of language skills and verbal memory. Results on morpheme completions are consistent with processing models of LI, but some predictions of the morphological richness model were not confirmed. The results suggest that children with LI might have a deficit in organizing morphosyntactic relations in sentences, rather than in morphological processing proper.
A new search for star forming regions in the southern outer Galaxy
Authors: König C. , Urquhart J. S. , Wyrowski F. , Colombo D. , Menten K. M. 
Published: December 2020

Context. Star formation in the outer Galaxy is thought to be different from that in the inner Galaxy, as it is subject to different environmental parameters such as metallicity, interstellar radiation field, or mass surface density, which all change with galactocentric radius. Extending our star formation knowledge, from the inner to the outer Galaxy, helps us to understand the influences of the change of the environment on star formation throughout the Milky Way.
Aims. We aim to obtain a more detailed view on the structure of the outer Galaxy, determining physical properties for a large number of star forming clumps and understanding star formation outside the solar circle. As one of the largest expanding Galactic super-shells is present in the observed region, a unique opportunity is taken here to investigate the influence of such an expanding structure on star formation as well.
Methods. We used pointed 12CO(2–1) observations conducted with the APEX telescope to determine the velocity components towards 830 dust clumps identified from 250 μm Herschel/Hi-GAL SPIRE emission maps in the outer Galaxy between 225° < ℓ < 260°. We determined kinematic distances from the velocity components, in order to analyze the structure of the outer Galaxy and to estimate physical properties such as dust temperatures, bolometric luminosities, clump masses, and H2 column densities for 611 clumps. For this, we determined the dust spectral energy density distributions from archival mid-infrared to submillimeter (submm) emission maps.
Results. We find the identified CO clouds to be strongly correlated with the highest column density parts of the H I emission distribution, spanning a web of bridges, spurs, and blobs of star forming regions between the larger complexes, unveiling the complex three-dimensional structure of the outer Galaxy in unprecedented detail. Using the physical properties of the clumps, we find an upper limit of 6% (40 sources) capable of forming high-mass stars. This is supported by the fact that only two methanol Class II masers, or 34 known or candidate H II regions, are found in the whole survey area, indicating an even lower fraction that are able to form high-mass stars in the outer Galaxy. We fail to find any correlation of the physical parameters of the identified (potential) star forming regions with the expanding supershell, indicating that although the shell organizes the interstellar material into clumps, the properties of the latter are unaffected.
Conclusions. Using the APEX telescope in combination with publicly available Hi-GAL, MSX, and Wise continuum emission maps, we were able to investigate the structure and properties of a region of the Milky Way in unprecedented detail.
Related Research on News Sentiment Tendency and Stock Price Fluctuation
Authors: Li Hongye 
Published: December 2020

In recent years, with further development of the Internet and artificial intelligence, the research on using news sentiments, and then predicting investor behavior has become more feasible. Based on the news information obtained from the Internet, this article analyzes the investor ‘s emotions about the news, further predicts the behavior of investors, and then the rise and fall of investment asset prices. We use news sentiment tendency and stock price of listed companies to analyze whether the news sentiment really affects the stock price and the degree of its influence.The research results of the thesis are divided into two parts: (1) A CNN neural network capable of analyzing news that may have an impact on stock prices in the near future is designed and trained to obtain a timely response and form a simulated investment decision for investors to adjust the investment strategy timely; (2) Combined with the economic indicators, this article uses the LSTM neural network to comprehensively investigate whether the emotional tendency of the news has a significant impact on the stock price. This article draws four kinds of images, which can test the accuracy of the model from different angles and guide consumers’ investment.
Notfallmedizinische Versorgung adipöser Menschen
Authors: Faisst Maik , Stuhr Markus , Savinsky Godo , Kerner Thoralf 
Published: December 2020

ZusammenfassungMit steigender Prävalenz der Adipositas werden auch alle in der Notfallmedizin Tätigen mit einer steigenden Zahl herausfordernder Einsätze in dieser Patientengruppe konfrontiert. Pathophysiologische Veränderungen bei den adipösen Patienten sowie technische und logistische Herausforderungen prägen diese besonderen Einsätze. Dieser Beitrag gibt einen Überblick zu den wesentlichen Aspekten auf diesem Gebiet, veranschaulicht an einem Einsatzbeispiel aus dem Hamburger Rettungsdienst.
Gesundheit und Lebenszufriedenheit bei Erwerbsminderungsrentnern und
-rentnerinnen: Die Bedeutung von finanziellen Ressourcen und
Einsamkeit
Authors: Lippke Sonia , Ricken Lea , Zschucke Elisabeth , Hessel Aike , Schüz Natalie 
Published: December 2020

Zusammenfassung
Ziel der Studie Erwerbsminderungsrentner1
sind durch geringe finanzielle Ressourcen und einen schlechten
Gesundheitszustand dem Risiko von weiteren gravierenden
Einschränkungen ausgesetzt: Es drohen reduzierte Teilhabe,
Einsamkeit und verminderte Lebenszufriedenheit. In der vorliegenden Arbeit
wurden daher Zusammenhänge zwischen der Anzahl der Erkrankungen,
selbstberichtetem Haushaltseinkommen (zur Verfügung stehende
finanzielle Ressourcen) und Haushaltsauskommen (Auskommen mit dem Einkommen,
d. h. kognitive und emotionale Bewertung der finanziellen
Ressourcen), Einsamkeit und Lebenszufriedenheit untersucht.
Methodik 199 befristete Erwerbsminderungsberentete wurden mittels
strukturierter telefonischer Interviews zu 2 Messzeitpunkten (T1;
T2=T1+ ca. 8 Monate) befragt.
Ergebnisse Die wahrgenommene Einsamkeit und die Lebenszufriedenheit
von Erwerbsminderungsrentnern stehen nicht im Zusammenhang mit der
finanziellen Situation (Haushaltseinkommen). Hingegen hängt eine
stärker wahrgenommene Einsamkeit mit niedrigeren wahrgenommenen
finanziellen Ressourcen (Haushaltsauskommen) zusammen. Diese gehen wiederum
mit einer geringeren Lebenszufriedenheit einher. Einsamkeit spielt eine
vermittelnde Rolle dabei. Je schlechter der Gesundheitszustand, desto
höher war auch die Einsamkeit und desto geringer die
Lebenszufriedenheit.
Schlussfolgerung Spezifische Rehabilitationsmaßnahmen
für Erwerbsminderungsrentner sollten in besonderer Weise auf
negative Wahrnehmungs- und Bewertungsprozesse bezüglich der
subjektiven finanziellen Situation, des Erlebens von Einsamkeit und der
Lebenszufriedenheit ausgerichtet werden. Angebote, die das Auskommen mit dem
zur Verfügung stehenden Geld unterstützen und darauf
abzielen, Einsamkeit zu überwinden und die Teilhabe zu verbessern,
könnten helfen, die Lebenszufriedenheit von
Erwerbsminderungsrentnern zu verbessern. Dies ist zentral, da andere Studien
einen Zusammenhang zwischen Lebenszufriedenheit und der Rückkehr ins
Arbeitsleben sowie sozialer Teilhabe gezeigt haben.
Real Life Data on Efficacy and Safety of Topical NGF Eye Drops (Cenegermin)
Authors: Zwingelberg Sarah Barbara , Bachmann Björn O. , Cursiefen Claus 
Published: December 2020

Abstract
Background Topical NGF eye drops (Cenegermin) were approved in 2015 as an orphan drug for the treatment of neurotrophic keratopathy (NK). The active substance Cenegermin is a recombinant form of human NGF (nerve growth factor).
Objectives Presentation of efficacy and safety of Cenegermin for use in patients in an university real-life setting.
Material and Methods Retrospective study at the Köln University Eye Hospital from 2017 to 2019 with n = 11 eyes. Average follow-up was 13.5 ± 7.1 months. Reasons for treatment were neurotrophic keratopathy stage II and III, clinically mostly in combination with corneal neovascularization.
Results Seven eyes with a NK II and 4 eyes with a NK III with a median observation period of 13.6 months (range 1.2 – 20.3 months) from a total of 11 patients were included. The median patient age was 42.8 ± 23.6 years (range 18 – 75 years). Before the start of therapy, the median erosion area measured 3.1 ± 1.4 × 1.9 ± 1.1 mm and the median ulcer area had a size of 2.3 ± 1.1 × 2.1 ± 0.8 mm. After the start of therapy with Cenegermin (application 6×/day), the epithelial defect closed in all 11 study eyes (100%) within 4 – 12 weeks (mean: 49 d ± 9 d). In 9 out of 10 patients (90%) pre-existing corneal neovascularization regressed significantly (p < 0.001). Before the start of therapy, a value in the Luneau test of 2.9 ± 1.9 (minimum 1/6, maximum 4/6) was found and rose to a median value of 4.2 ± 1.7 (minimum 2/6, maximum 6/6) after 18 months (p = 0.015). Therapy with Cenegermin had no long-term effect on intraocular pressure: the pressure ranged between
13.2 ± 4.1 mmHg (minimum 8 mmHg, maximum 21 mmHg). Under therapy with NGF eye drops, 67% of the patients, after an initial decrease, showed a long-term improvement in visual acuity (BSCVA) from 0.72 ± 0.31 to 0.46 ± 0.29 logMAR after 18 months (p = 0.005). Relapses in form of a corneal erosion in the long-term follow-up were observed in only one eye. One patient had to stop therapy because of local pain, no other local and systemic side effects were observed.
Conclusion This real-life series on the use of Cenegermin in a university context shows a good effectiveness of the substance for epithelial closure in various underlying diseases (100% within 12 weeks). There is a long-term improvement in vision and corneal sensitivity. Larger real-life cohorts with various underlying diseases should follow.
Early Troponin I Levels in Newborns Undergoing Therapeutic Hypothermia for Hypoxic Ischemic Encephalopathy and Residual Encephalopathy at Discharge
Authors: Munshi Upender K. , Brown Meredith Monaco , Tauber Kate A. , Horgan Michael J. 
Published: December 2020

Objective Elevation of serum troponin I has been reported in newborns with hypoxic ischemic encephalopathy (HIE), but it is diagnostic and prognostic utility for newborn under 6 hours is not clear. Study the predictive value of early serum troponin I levels in newborns with HIE undergoing therapeutic hypothermia (TH) for persistent residual encephalopathy (RE) at discharge.
Study Design Retrospective chart review of newborns admitted with diagnosis of HIE to neonatal intensive care unit (NICU) for TH over a period of 3 years. Troponin levels were drawn with the initial set of admission laboratories while initiating TH. Newborns were followed up during hospital course and stratified into three groups based on predischarge examination and their electrical encephalography and cranial MRI findings: Group 1: no RE, Group 2: mild-to-moderate RE, and Group 3: severe RE or needing assisted medical technology or death. Demographic and clinical characteristics including troponin I levels were compared in each group.
Results Out of 104 newborns who underwent TH, 65 infants were in Group 1, 26 infants in Group 2, and 13 newborns in Group 3. All groups were comparable in demographic characteristics. There was a significant elevation of serum troponin in group 2 (mild-to-moderate RE) and group 3 (severe RE) as compared with group 1 (no RE). Receiver operator curve analysis for any RE (groups 2 and 3) compared with group 1 (no RE as control) had 0.88 (0.81–0.95) area under curve, p < 0.001. A cut-off level of troponin I ≥0.12 µg/L had a sensitivity of 77% and specificity of 78% for diagnosis of any RE, positive predictive value of 68%, and a negative predictive value of 84%.
Conclusion In newborns undergoing TH for HIE, the elevation of troponin within 6 hours of age predicts high risk of having RE at discharge.
Key Points