bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association study of varicose veins identifies a protective missense variant in GJD3 enriched in the Finnish population
Authors: Helkkula Pyry , Hassan Shabbeer , Saarentaus Elmo , Vartiainen Emilia , Ruotsalainen Sanni , Leinonen Jaakko T. ,   FinnGen, Palotie Aarno , Karjalainen Juha , Kurki Mitja , Ripatti Samuli , Tukiainen Taru 
Published: January 2023

AbstractVaricose veins is the most common manifestation of chronic venous disease that displays female-biased incidence. To identify protein-inactivating variants that could guide identification of drug target genes for varicose veins and genetic evidence for the disease prevalence difference between the sexes, we conducted a genome-wide association study of varicose veins in Finns using the FinnGen dataset with 17,027 cases and 190,028 controls. We identified 50 associated genetic loci (P < 5.0 × 10−8) of which 29 were novel including one near ERG with female-specificity (rs2836405-G, OR[95% CI] = 1.09[1.05–1.13], P = 3.1 × 10−8). These also include two X-chromosomal (ARHGAP6 and SRPX) and two autosomal novel loci (TGFB2 and GJD3) with protein-coding lead variants enriched above 56-fold in Finns over non-Finnish non-Estonian Europeans. A low-frequency missense variant in GJD3 (p.Pro59Thr) is exclusively associated with a lower risk for varicose veins (OR = 0.62 [0.55–0.70], P = 1.0 × 10−14) in a phenome-wide scan of the FinnGen data. The absence of observed pleiotropy and its membership of the connexin gene family underlines GJD3 as a potential connexin-modulating therapeutic strategy for varicose veins. Our results provide insights into varicose veins etiopathology and highlight the power of isolated populations, including Finns, to discover genetic variants that inform therapeutic development.
Transcriptomic survey of key reproductive and metabolic tissues in mouse models of polycystic ovary syndrome
Authors: Pei Yu , Risal Sanjiv , Jiang Hong , Lu Haojiang , Lindgren Eva , Stener-Victorin Elisabet , Deng Qiaolin 
Published: January 2023

AbstractExcessive androgen production and obesity are key to polycystic ovary syndrome (PCOS) pathogenesis. Prenatal androgenized (PNA), peripubertal androgenized, and overexpression of nerve growth factor in theca cells (17NF) are commonly used PCOS-like mouse models and diet-induced maternal obesity model is often included for comparsion. To reveal the molecular features of these models, we have performed transcriptome survey of the hypothalamus, adipose tissue, ovary and metaphase II (MII) oocytes. The largest number of differentially expressed genes (DEGs) is found in the ovaries of 17NF and in the adipose tissues of peripubertal androgenized models. In contrast, hypothalamus is most affected in PNA and maternal obesity models suggesting fetal programming effects. The Ms4a6e gene, membrane-spanning 4-domains subfamily A member 6E, a DEG identified in the adipose tissue in all mouse models is also differently expressed in adipose tissue of women with PCOS, highlighting a conserved disease function. Our comprehensive transcriptomic profiling of key target tissues involved in PCOS pathology highlights the effects of developmental windows for androgen exposure and maternal obesity, and provides unique resource to investigate molecular mechanisms underlying PCOS pathogenesis.
A streamlined tandem tip-based workflow for sensitive nanoscale phosphoproteomics
Authors: Tsai Chia-Feng , Wang Yi-Ting , Hsu Chuan-Chih , Kitata Reta Birhanu , Chu Rosalie K. , Velickovic Marija , Zhao Rui , Williams Sarah M. , Chrisler William B. , Jorgensen Marda L. , Moore Ronald J. , Zhu Ying , Rodland Karin D. , Smith Richard D. , Wasserfall Clive H. , Shi Tujin , Liu Tao 
Published: January 2023

AbstractEffective phosphoproteome of nanoscale sample analysis remains a daunting task, primarily due to significant sample loss associated with non-specific surface adsorption during enrichment of low stoichiometric phosphopeptide. We develop a tandem tip phosphoproteomics sample preparation method that is capable of sample cleanup and enrichment without additional sample transfer, and its integration with our recently developed SOP (Surfactant-assisted One-Pot sample preparation) and iBASIL (improved Boosting to Amplify Signal with Isobaric Labeling) approaches provides a streamlined workflow enabling sensitive, high-throughput nanoscale phosphoproteome measurements. This approach significantly reduces both sample loss and processing time, allowing the identification of >3000 (>9500) phosphopeptides from 1 (10) µg of cell lysate using the label-free method without a spectral library. It also enables precise quantification of ~600 phosphopeptides from 100 sorted cells (single-cell level input for the enriched phosphopeptides) and ~700 phosphopeptides from human spleen tissue voxels with a spatial resolution of 200 µm (equivalent to ~100 cells) in a high-throughput manner. The new workflow opens avenues for phosphoproteome profiling of mass-limited samples at the low nanogram level.
Zyxin regulates embryonic stem cell fate by modulating mechanical and biochemical signaling interface
Authors: Zhang Songjing , Chong Lor Huai , Woon Jessie Yong Xing , Chua Theng Xuan , Cheruba Elsie , Yip Ai Kia , Li Hoi-Yeung , Chiam Keng-Hwee , Koh Cheng-Gee 
Published: January 2023

AbstractBiochemical signaling and mechano-transduction are both critical in regulating stem cell fate. How crosstalk between mechanical and biochemical cues influences embryonic development, however, is not extensively investigated. Using a comparative study of focal adhesion constituents between mouse embryonic stem cell (mESC) and their differentiated counterparts, we find while zyxin is lowly expressed in mESCs, its levels increase dramatically during early differentiation. Interestingly, overexpression of zyxin in mESCs suppresses Oct4 and Nanog. Using an integrative biochemical and biophysical approach, we demonstrate involvement of zyxin in regulating pluripotency through actin stress fibres and focal adhesions which are known to modulate cellular traction stress and facilitate substrate rigidity-sensing. YAP signaling is identified as an important biochemical effector of zyxin-induced mechanotransduction. These results provide insights into the role of zyxin in the integration of mechanical and biochemical cues for the regulation of embryonic stem cell fate.
The germline factor DDX4 contributes to the chemoresistance of small cell lung cancer cells
Authors: Noyes Christopher , Kitajima Shunsuke , Li Fengkai , Suita Yusuke , Miriyala Saradha , Isaac Shakson , Ahsan Nagib , Knelson Erik , Vajdi Amir , Tani Tetsuo , Thai Tran C. , Xu Derek , Murai Junko , Tapinos Nikos , Takahashi Chiaki , Barbie David A. , Yajima Mamiko 
Published: January 2023

AbstractHuman cancers often re-express germline factors, yet their mechanistic role in oncogenesis and cancer progression remains unknown. Here we demonstrate that DEAD-box helicase 4 (DDX4), a germline factor and RNA helicase conserved in all multicellular organisms, contributes to increased cell motility and cisplatin-mediated drug resistance in small cell lung cancer (SCLC) cells. Proteomic analysis suggests that DDX4 expression upregulates proteins related to DNA repair and immune/inflammatory response. Consistent with these trends in cell lines, DDX4 depletion compromised in vivo tumor development while its overexpression enhanced tumor growth even after cisplatin treatment in nude mice. Further, the relatively higher DDX4 expression in SCLC patients correlates with decreased survival and shows increased expression of immune/inflammatory response markers. Taken together, we propose that DDX4 increases SCLC cell survival, by increasing the DNA damage and immune response pathways, especially under challenging conditions such as cisplatin treatment.
Short‐time wind speed prediction based on Legendre multi‐wavelet neural network
Authors: Zheng Xiaoyang , Jia Dongqing , Lv Zhihan , Luo Chengyou , Zhao Junli , Ye Zeyu 
Published: January 2023

AbstractAs one of the most widespread renewable energy sources, wind energy is now an important part of the power system. Accurate and appropriate wind speed forecasting has an essential impact on wind energy utilisation. However, due to the stochastic and uncertain nature of wind energy, more accurate forecasting is necessary for its more stable and safer utilisation. This paper proposes a Legendre multiwavelet‐based neural network model for non‐linear wind speed prediction. It combines the excellent properties of Legendre multi‐wavelets with the self‐learning capability of neural networks, which has rigorous mathematical theory support. It learns input‐output data pairs and shares weights within divided subintervals, which can greatly reduce computing costs. We explore the effectiveness of Legendre multi‐wavelets as an activation function. Meanwhile, it is successfully being applied to wind speed prediction. In addition, the application of Legendre multi‐wavelet neural networks in a hybrid model in decomposition‐reconstruction mode to wind speed prediction problems is also discussed. Numerical results on real data sets show that the proposed model is able to achieve optimal performance and high prediction accuracy. In particular, the model shows a more stable performance in multi‐step prediction, illustrating its superiority.
The bubble formation characteristics of oil‐paper insulation and its influence on insulation performance
Authors: Zhang Yiyi , Du Qianlun , Wei Wenchang , Wang Wenqiang , Wang Gang , Liu Yansong , Xie Qing 
Published: January 2023

AbstractEngineering experience shows that for transformers with long service life and serious moisture exposure, the inter‐turn paper insulation inside the winding will precipitate bubbles under the condition of electric field and conductor heating, which will endanger the equipment insulation. In order to explore the influence factors of bubbles formation in the moist insulating paper of transformers, based on the existing research on the influence of moisture content and gas dissolution in transformer oil, this study further considers the influence of air pressure (AP) and electric field and establishes an experimental platform to change the air pressure and electric field, thereby studying the formation characteristics of bubbles in oil‐paper insulation. The results show that air pressure and electric field can affect the initial temperature, volume, and shape of bubble formation. From 0 to −0.05 MPa for air pressure, the initial temperature of bubble generation decreased by 41°C, its maximum two‐dimensional projected area increased by 418.4% with more severe distortion, and the breakdown voltage decreased. When the AC voltage applied on the needle plate electrode increased from 0 to 10 kV, the initial temperature of bubble formation increased by 29°C, and the maximum two‐dimensional projection area increased by 336.6%.
Parallel diode‐clamped linear converter for withstand test and partial discharge measurement of electric equipment
Authors: Zhou Yuxiong , Chen Baichao , Tian Cuihua , Yuan Jiaxin , Chen Yaojun 
Published: January 2023

AbstractHigh‐voltage withstand tests are essential for electric equipment like power transformers, electric cable lines, gas insulated switchgears etc. The partial discharge (PD) measurement for such equipment under applied high voltage is also required at the same time. Pulse Width Modulation (PWM)‐based variable frequency power supply (VFPS) finds wide applications in the series resonance high‐voltage testing circuits. However, the steep rising and falling voltage edges in the PWM process will produce large amount of partial discharge interference in a wide spectrum range, which will confuse the real partial discharge signal of the device and lead to the wrong estimation of the insulation status. This paper proposes a new VFPS based on the high‐efficiency linear power amplifier without PD interference. The topology and principle of the VFPS are given and discussed. A prototype rated at 232 V/35 A was designed and constructed to verify the feasibility of the proposed VFPS. Physical experiments were carried out on the prototype.
Asgard/NOTT: L-band nulling interferometry at the VLTI
Authors: Laugier Romain , Defrère Denis , Woillez Julien , Courtney-Barrer Benjamin , Dannert Felix A. , Matter Alexis , Dandumont Colin , Gross Simon , Absil Olivier , Bigioli Azzurra , Garreau Germain , Labadie Lucas , Loicq Jérôme , Martinod Marc-Antoine , Mazzoli Alexandra , Raskin Gert , Sanny Ahmed 
Published: January 2023

Context. NOTT (formerly Hi-5) is a new high-contrast L′ band (3.5–4.0 µm) beam combiner for the VLTI designed with an ambitious aim to be sensitive to young giant exoplanets down to 5 mas separation around nearby stars. The performance of nulling interferometers in these wavelengths is affected both by fundamental noise from the background and contributions of instrumental noise. This motivates the development of end-to-end simulations to optimize these instruments.
Aims. The aim of this study is to enable a performance evaluation of NOTT and inform the design of such instruments with current and future infrastructures in mind, taking into account the different sources of noise and their correlation.
Methods. SCIFYsim is an end-to-end simulator for single-mode-filtered beam combiners, with an emphasis on nulling interferometers. We use it to compute a covariance matrix of the errors. We then use statistical detection tests based on likelihood ratios to compute compound detection limits for the instrument.
Results. With the current assumptions as to the performance of the wavefront correction systems, the errors are dominated by correlated instrumental errors down to stars of magnitude 6–7 in the L band, beyond which thermal background from the telescopes and relay system becomes dominant.
Conclusions. SCIFYsim is suited to anticipating some of the challenges of design, tuning, operation, and signal processing for integrated-optics beam combiners. The detection limits found for this early version of NOTT simulation with the unit telescopes are compatible with detections at contrasts up to 105 in the L band at separations of 5–80 mas around bright stars.
Disk Evolution Study Through Imaging of Nearby Young Stars (DESTINYS): Characterization of the young star T CrA and its circumstellar environment
Authors: Rigliaco E. , Gratton R. , Ceppi S. , Ginski C. , Hogerheijde M. , Benisty M. , Birnstiel T. , Dima M. , Facchini S. , Garufi A. , Bae J. , Langlois M. , Lodato G. , Mamajek E. , Manara C. F. , Ménard F. , Ribas A. , Zurlo A. 
Published: January 2023

Context. In recent years, a new hot topic has emerged in the star and planet formation field, namely, the interaction between the circumstellar disk and its birth cloud. The birth environments of young stars leave strong imprints on the star itself and their surroundings. In this context, we present a detailed analysis of the rich circumstellar environment around the young Herbig Ae/Be star T CrA.
Aims. Our aim is to understand the nature of the stellar system and the extended circumstellar structures, as seen in scattered light images.
Methods. We conducted our analysis on the basis of a set of combined archival data and new adaptive optics images at a high contrast and high resolution.
Results. The scattered light images reveal the presence of a complex environment around T CrA, composed of a bright, forward-scattering rim of the disk's surface that is seen at very high inclinations, along with a dark lane of the disk midplane, bipolar outflows, and streamer features that are likely tracing infalling material from the surrounding birth cloud onto the disk. The analysis of the light curve suggests that the star is a binary with a period of 29.6 yr, confirming previous assertions based on spectro-astrometry. The comparison of the scattered light images with the ALMA continuum and 12CO (2–1) line emission shows that the disk is in Keplerian rotation and the northern side of the outflowing material is receding, while the southern side is approaching the observer. The overall system lies on different geometrical planes. The orbit of the binary star is perpendicular to the outflows and is seen edge on. The disk is itself seen edge-on, with a position angle of ~7°. The direction of the outflows seen in scattered light is in agreement with the direction of the more distant molecular hydrogen emission-line objects (MHOs) associated with the star. Modeling of the spectral energy distribution using a radiative transfer scheme is in good agreement with the proposed configuration, as well as the hydrodynamical simulation performed using a smoothed particle hydrodynamics code.
Conclusions. We find evidence of streamers of accreting material around T CrA. These streamers connect the filament, along which T CrA is forming along with the outer parts of the disk, suggesting that the strong misalignment between the inner and outer disk is due to a change in the direction of the angular momentum of the material accreting on the disk during the late phase of star formation. This impacts the accretion taking place in the components of the binary, favoring the growth of the primary with respect the secondary, in contrast to the case of aligned disks.
„Dass man mal sieht, wie es eigentlich sein sollte.“
Konzeption, Pilotierung und Evaluation eines interprofessionellen
rehabilitationsbezogenen Moduls für die Medizin, Pflege und
Physiotherapie
Authors: Retznik Laura , Haucke Elisa , Schmidt Elisabeth , Mau Wilfried 
Published: January 2023

Zusammenfassung
Hintergrund Vor dem Hintergrund wachsender rehabilitativer
Versorgungsanforderungen ist eine gute interprofessionelle Zusammenarbeit der
Gesundheitsberufe von zentraler Bedeutung und wird verstärkt gefordert.
Obwohl interprofessionelle Zusammenarbeit als wichtiges Erfolgselement einer
ergebnis- und patientenorientierten Gesundheitsversorgung gilt und ein hoher
Bedarf nach ihrer stärkeren Vermittlung in den Ausbildungskontexten der
Gesundheitsberufe besteht, spielt sie diesbezüglich noch keine
bedeutende Rolle. Für die Rehabilitation fehlen bislang lernzielbasierte
interprofessionelle Lehrkonzepte und -materialien.
Methoden Das didaktische und inhaltliche Konzept für das Modul
wurde von einem interprofessionellen Dozent*innen-Team entwickelt. Der
Fokus des Moduls liegt auf dem Rehabilitations- und Entlassmanagement. Die
Lernziele wurden auf Basis des Nationalen Kompetenzbasierten Lernzielkatalogs
Medizin entwickelt. Das Modul vermittelt am ersten Tag fachwissenschaftliche
Inhalte durch Impulsreferate. Anschließend wird in Kleingruppen die
Aufgabenstellung zum Patient*innenbeispiel bearbeitet. Am zweiten Tag
findet das Patient*innengespräch mit anschließendem
strukturiertem Feedbackgespräch statt. Die formative Evaluation erfolgte
auf Basis eines Feedbackbogens der Lernenden und eines Bewertungsbogens der
Lernbegleitung.
Ergebnisse Insgesamt nahmen 47 Lernende an drei Durchläufen teil.
Die Ergebnisse zeigen, dass das Modul insgesamt gut angenommen wurde. Die
Auszubildenden bewerteten das Modul positiver als die Medizinstudierenden,
insbesondere bei der Vertiefung ihrer Kompetenzen zum Rehabilitations- und
Entlassmanagement. Die Teilnehmenden betonten die gute praktische Zusammenarbeit
auf Augenhöhe und das ehrliche Feedbackgespräch, während
sie gleichzeitig auf den erlebten Kontrast zu ihrem Praxisalltag hinwiesen.
Weiterhin wünschten sie sich einen höheren Zeitumfang
für den mündlichen interprofessionellen Austausch. Die
Medizinstudierenden äußerten Kritik darüber, dass
interprofessionelle Module erst am Ende ihrer Ausbildung stattfinden.
Schlussfolgerung Nach Kenntnis der Autor*innen wurde erstmals ein
rehabilitationsbezogenes interprofessionelles Modul zum Rehabilitations- und
Entlassmanagement für die drei Berufsgruppen Medizin, Pflege und
Physiotherapie entwickelt, durchgeführt und positiv evaluiert.
Verbesserungsvorschläge der Lernenden führten zu
nachträglichen Modifizierungen des Moduls und werden bei der
nächsten Durchführung umgesetzt. Mit der Lehrveranstaltung
werden wichtige Impulse für die Weiterentwicklung der
interprofessionellen Zusammenarbeit und der Vermittlung rehabilitationsbezogener
Kompetenzen gesetzt. Das modular einsetzbare Kompaktangebot steht anderen
Dozierenden im Reha-Wiki, einer kostenfreien Online-Plattform für
rehabilitationsbezogene Lehrmaterialien, zur Verfügung.
Is the Level of Pentraxin-3 a Valid Biomarker in Axial
Spondyloarthritis?
Authors: Orucoglu Nurdan , Balci-Fidanci Senay , Tamer Lulufer 
Published: January 2023

Abstract
Background Pentraxin-3 (PTX-3) is essential in inflammation, remodelling
and regulation of inflammation in various rheumatic diseases. This study aimed
to determine whether serum PTX-3 levels indicate increased inflammation and
disease activity in patients with axial spondyloarthritis (AxSpA).
Material and Methods The study comprised 50 AxSpA patients and 20 healthy
controls (HC). Serum PTX-3, interleukin (IL)-17 and IL-23 levels were compared
between AxSpA patients and the control group. The relationship between PTX-3
levels and acute-phase reactants and disease activity was examined. Disease
activity was scored using the Bath Ankylosing Spondylitis Disease Activity Index
(BASDAI) and the Ankylosing Spondylitis Disease Activity Score-CRP (ASDAS-CRP).
Patients with AxSpA were also separated into two subgroups –
non-radiographic AxSpA (nr-AxSpA) and radiographic AxSpA (r-AxSpA) – and
compared based on their PTX-3 levels. PTX-3, IL-17 and IL-23 levels were
measured using the enzyme-linked immunosorbent assay method.
Results PTX-3 levels were higher in patients with AxSpA compared with the
HC (2.69±2.03 vs 1.84±1.03 ng/mL,
p=0.025). When patients were divided into nr-AxSpA and r-AxSpA
subgroups, this difference was found to be only due to patients with r-AxSpA.
The r-AxSpA group had significantly higher PTX-3 levels than the nr-AxSpA and HC
groups (p=0.020 and p=0.016, respectively). There was no
statistically significant difference in PTX-3 levels between the nr-AxSpA and HC
groups (p=0.961). There was no correlation between PTX-3 levels and
acute-phase reactants, IL-17, IL-23 and disease activity scores (BASDAI and
ASDAS-CRP).
Conclusion These findings support the hypothesis that PTX-3 levels are
higher in patients with r-AxSpA, where chronic inflammation and structural
progression are more pronounced and can be used as an inflammation marker.
However, they demonstrate that this relationship does not exist in nr-AxSpA and
that there is no correlation between disease activity and PTX-3 levels. Thus,
PTX-3 levels may be associated with structural changes.