bluuebunny/crossref_metadata_2025_split huggingface dataset:
The K-Ras(G12D)-inhibitory peptide KS-58 suppresses growth of murine CT26 colorectal cancer cell-derived tumors
Authors: Sakamoto Kotaro , Lin Bangzhong , Nunomura Kazuto , Izawa Takeshi , Nakagawa Shinsaku 
Published: May 2022

AbstractMutations in the cell proliferation regulator K-Ras are found with a variety of cancer types, so drugs targeting these mutant proteins could hold great clinical potential. Very recently, a drug targeting the K-Ras(G12C) mutant observed in lung cancer gained regulatory approval and several clinical trials are currently underway to examine the efficacy of this agent when combined with other drugs such as a monoclonal antibody inhibitor of programmed cell death 1 receptor (anti-PD-1). Alternatively, there are currently no approved drugs targeting K-Ras(G12D), the most common cancer-associated K-Ras mutant. In 2020, we described the development of the K-Ras(G12D) inhibitory bicyclic peptide KS-58 and presented evidence for anticancer activity against mouse xenografts derived from the human pancreatic cancer cell line PANC-1 stably expressing K-Ras(G12D). Here, we show that KS-58 also possess anticancer activity against mouse tumors derived from the colorectal cancer cell line CT26 stably expressing K-Ras(G12D). Further, KS-58 treatment reduced phosphorylation of ERK, a major downstream signaling factor in the Ras pathway, confirming that KS-58 inhibits K-Ras(G12D) function. Unexpectedly; however, KS-58 did not show additive or synergistic anticancer activity with mouse anti-PD-1. Morphological analysis and immunostaining demonstrated no obvious differences in CD8+ cells infiltration or PD-L1 expression levels in CT26-derived tumors exposed to monotherapy or combination treatment. Nonetheless, KS-58 demonstrated reasonable stability in blood (t1/2 ≈ 30 min) and no obvious systemic adverse effects, suggesting clinical potential as a lead molecule against colorectal cancer.
Machine learning based algorithms to impute PaO2 from SpO2 values and development of an online calculator
Authors: Ren Shuangxia , Zupetic Jill A. , Tabary Mohammadreza , DeSensi Rebecca , Nouraie Mehdi , Lu Xinghua , Boyce Richard D. , Lee Janet S. 
Published: May 2022

AbstractWe created an online calculator using machine learning (ML) algorithms to impute the partial pressure of oxygen (PaO2)/fraction of delivered oxygen (FiO2) ratio using the non-invasive peripheral saturation of oxygen (SpO2) and compared the accuracy of the ML models we developed to published equations. We generated three ML algorithms (neural network, regression, and kernel-based methods) using seven clinical variable features (N = 9900 ICU events) and subsequently three features (N = 20,198 ICU events) as input into the models. Data from mechanically ventilated ICU patients were obtained from the publicly available Medical Information Mart for Intensive Care (MIMIC III) database and used for analysis. Compared to seven features, three features (SpO2, FiO2 and PEEP) were sufficient to impute PaO2 from the SpO2. Any of the ML models enabled imputation of PaO2 from the SpO2 with lower error and showed greater accuracy in predicting PaO2/FiO2 ≤ 150 compared to the previously published log-linear and non-linear equations. To address potential hidden hypoxemia that occurs more frequently in Black patients, we conducted sensitivity analysis and show ML models outperformed published equations in both Black and White patients. Imputation using data from an independent validation cohort of ICU patients (N = 133) showed greater accuracy with ML models.
The redistribution of anthropogenic excess heat is a key driver of warming in the North Atlantic
Authors: Messias Marie-José , Mercier Herlé 
Published: May 2022

AbstractUnderstanding ocean excess heat uptake is crucial for assessing climate warming, yet uncertainties remain about its history and redistribution. Here, we reconstruct ocean heat content change along the 25°N Atlantic hydrographic section and assess its spatiotemporal origin and fate. We show that the delayed response of the ocean below 700 m to sea surface temperature change contribute to 62% of full depth warming at this latitude for 1850–2018, falling to 35% for 1975–2018 when anthropogenic warming in the upper ocean accelerated. The regional climate fluctuations shape ocean heat content variability at 25°N with contributions from the Labrador Sea producing most of the decadal variability and the Nordic Seas bound to become the main contributor to deep ocean warming in the coming decades. Chiefly, the net excess heat transport across 25°N has increased recently, warming the domain north of 25°N at a rate of 0.89 ± 0.19 W m−2 during 2012–2018, revealing that excess heat redistribution is a key driver of North Atlantic heat gain.
3Es: An All-Inclusive Stuttering Therapy Tool
Authors: Gore Katie , Luckman Margulis Courtney 
Published: May 2022

Purpose:
There are many therapy approaches for stuttering, but speech-language pathologists (SLPs) often report that they are uncomfortable treating stuttering. The 3Es model for stuttering therapy (education, ease, and empowerment) is proposed to help SLPs understand stuttering treatment options efficiently and effectively. This model is based on emerging stuttering research trends such as redefining stuttering, anticipation of stuttering, and stigma of stuttering. A primary function of the 3Es model is to serve as a translational research-to-practice funnel for practicing SLPs.

Conclusions:
This tool is conceptualized by identifying three key thematic components of stuttering therapy: education, ease, and empowerment. The Es are the values-based themes of stuttering therapy, and a successful application of the model will create an accessible, robust, and structured “menu” of activities for clinicians to use in treatment planning. These therapy activities can be flexibly combined to provide holistic stuttering therapy and communication outcomes, which include competence, confidence, and change.
A review on short‐term load forecasting models for micro‐grid application
Authors: Kondaiah V. Y. , Saravanan B. , Sanjeevikumar P. , Khan Baseem 
Published: May 2022

AbstractLoad forecasting (LF), particularly short‐term load forecasting (STLF), plays a vital role throughout the operation of the conventional power system. The precise modelling and complex analyses of STLF have become more significant in advanced microgrid (MG) applications. Several models are proposed for STLF and tested successfully in the literature. The selection of a forecasting method is mostly based on data availability and its objectives. This article presents a survey of the latest analytical and approximation techniques reported in the literature to model STLF in an MG environment. This article mainly focusses on the review on important methods applied to forecast renewable energy availability, energy demand, and price and load demand. Different models, their main objectives, methodology, error percentage, and so forth, are critically reviewed and analysed. For quick reference, we have highlighted the important points in the form tables. The researchers can quickly identify and frame their research problem related to the LF area by reading this review paper.
Dancing with the stars: Stirring up extraordinary turbulence in Galactic center clouds
Authors: Tassis Konstantinos , Pavlidou Vasiliki 
Published: May 2022

Context. Molecular clouds in the central molecular zone (CMZ) have been observed to feature turbulent line widths that are significantly higher, and scale with cloud size more steeply, than in the rest of the Milky Way. In the same Galactic region, the stellar density is also much higher than in the rest of the Milky Way, and the vertical stellar velocity dispersion is large, meaning that even young stars are likely to cross the entire vertical extent of the CMZ within their lifetimes.
Aims. We investigate whether interactions of CMZ molecular clouds with crossing stars can account for the extraordinary properties of observed turbulence in this part of the Galaxy.
Methods. We calculated the rate of energy deposition by stars crossing CMZ clouds due to (a) stellar winds and (b) dynamical friction, and compared it to the rate of turbulence decay. We calculated the predicted scaling of turbulence line width with cloud size in each case.
Results. We find that energy deposition by stellar winds of crossing massive stars can account for both the level and the scaling of CMZ cloud turbulence with cloud size. We also find that the mechanism stops being effective at a Galactocentric distance comparable to the CMZ extent. On the other hand, we find that dynamical friction by crossing stars does not constitute a significant driver of turbulence for CMZ clouds.
The Close AGN Reference Survey (CARS)
Authors: Winkel N. , Husemann B. , Davis T. A. , Smirnova-Pinchukova I. , Bennert V. N. , Combes F. , Gaspari M. , Jahnke K. , Neumann J. , O’Dea C. P. , Pérez-Torres M. , Singha M. , Tremblay G. R. , Rix H. W. 
Published: May 2022

Context.The host galaxy conditions for rapid supermassive black hole growth are poorly understood. Narrow-line Seyfert 1 (NLS1) galaxies often exhibit high accretion rates and are hypothesized to be prototypes of active galactic nuclei (AGN) at an early stage of their evolution.Aims.We present adaptive optics (AO) assisted VLT MUSE NFM observations of Mrk 1044, the nearest super-Eddington accreting NLS1. Together with archival MUSE WFM data, we aim to understand the host galaxy processes that drive Mrk 1044’s black hole accretion.Methods.We extracted the faint stellar continuum emission from the AGN-deblended host and performed spatially resolved emission line diagnostics with an unprecedented resolution. Combining both MUSE WFM and NFM-AO observations, we used a kinematic model of a thin rotating disk to trace the stellar and ionized gas motion from 10 kpc galaxy scales down to ∼30 pc around the nucleus.Results.Mrk 1044’s stellar kinematics follow circular rotation, whereas the ionized gas shows tenuous spiral features in the center. We resolve a compact star-forming circumnuclear ellipse (CNE) that has a semi-minor axis of 306 pc. Within this CNE, the gas is metal-rich and its line ratios are entirely consistent with excitation by star formation. With an integrated star formation rate of 0.19 ± 0.05 M⊙ yr−1, the CNE contributes 27% of the galaxy-wide star formation.Conclusions.We conclude that Mrk 1044’s nuclear activity has not yet affected the circumnuclear star formation. Thus, Mrk 1044 is consistent with the idea that NLS1s are young AGN. A simple mass budget consideration suggests that the circumnuclear star formation and AGN phase are connected and the patterns in the ionized gas velocity field are a signature of the ongoing AGN feeding.
Implantatversagen nach Instrumentierungen bei Osteoporose: Ursachen und
Behandlungskonzepte
Authors: Schmidt René 
Published: May 2022

ZusammenfassungDie Osteoporose stellt eine der grössten Herausforderungen in der instrumentierten
Wirbelsäulenchirurgie dar. Verschiedene prä-, intra- und postoperative Ansätze können
verfolgt werden um die Komplikationsrate zu verringern. Die verschiedenen Ansätze werden
in diesem Artikel beleuchtet.
Implantatversagen aufgrund von Infekt/Low-grade Infekt – Ursachen und
Behandlungskonzepte
Authors: Ringel Florian , Jägersberg Max 
Published: May 2022

ZusammenfassungImplantatversagen im Sinne von Implantatlockerungen sind eine regelmäßige Komplikation
spinaler Instrumentierungen. Die Ursachen von Implantatlockerungen sind oft aseptisch.
Allerdings zeigen eine Reihe jüngerer Studien, dass Infektionen, insbesondere „low-grade“
Infektionen für einen relevanten Anteil der Implantatlockerungen ursächlich sind. Diese
Infekt-bedingten Implantatlockerungen bedürfen einer angepassten Strategie im Hinblick auf
Diagnostik und Therapie. Zur sicheren Diagnostik Infekt-bedingter Lockerungen sind
Sonikate der Implantate notwendig. Die Implantatentfernung oder ein -tausch bei Lockerung
sollte von einer angepassten Antibiotikatherapie begleitet sein.
Aegroti salus suprema lex
Authors: Bergmann Antje , Schwarz Peter E.H. 
Published: May 2022

Liebe Kollegen,gerade geht der diesjährige Internistenkongress in Wiesbaden zu Ende. Es war sehr erquickend, sich wieder mal persönlich zu treffen, es war fantastisch, durch die Kongresshalle zu laufen und an vielen Ecken Kollegen, Freunde, Bekannte und Mitstreiter zu treffen, miteinander zu sprechen̶ erst dann merkt man, was wir die letzen Jahre vermisst haben. Es war aber auch sehr interessant zu beobachten, dass sehr viele Kollegen online am Kongress teilgenommen haben und sich intensiv eingebracht, mitdiskutiert, Fragen gestellt haben und in den Hallen präsent gewesen sind.
Influence of the Type and Thickness of Cervical Margins on the Strength of Posterior Monolithic Zirconia Crowns: A Review
Authors: Haddad Camille , Azzi Kathy 
Published: May 2022

AbstractThe aim of this research is to review the literature for the influence of the thickness and shape of cervicalmargins on the strength of posterior monolithic zirconia crowns. Studies to assess the fracture resistance of monolithic zirconia crowns with different types of cervical margins, published from 2014 to 2020, were searched using the electronic database PubMed and Google Scholar using the following keywords: “monolithic zirconia,” “translucent,” “shoulderless,” and “margin preparation design.” Analysis of studies has shown that overall the design of the margin would have a significant effect on the strength of these crowns. Monolithic zirconia crowns with a knife-edge margin have shown a breaking load higher than the maximum chewing force of humans. It would be safe to suggest the utilization of posteriormonolithic zirconia crowns with vertical preparation. As the new translucent monolithic zirconia crowns are recent, further studies would be needed to guide the selection of the appropriate minimum thickness of the knife-edge margin to meet the clinical guidelines for their use.
Management of Multisystem Inflammatory Syndrome in Children with Combined Use of Corticosteroids and Intravenous Immunoglobulin—Report from Bursa, Turkey
Authors: Bozdemir Sefika Elmas , Türe Esra , Altin Hakan , Ertek Sümeyye , Aktürk Berna , Kırkas Özlem Gül , Koçkuzu Esra , Yarci Erbu , Sahin Sabit 
Published: May 2022

Abstract
Objective In this article, we aimed to evaluate the clinical, laboratory, and radiological findings and outcomes of patients treated with corticosteroids and intravenous immunoglobulin (IVIG) with the multisystem inflammatory syndrome in children (MIS-C) in two centers in Bursa, Turkey.
Methods We retrospectively collected the clinical characteristics, laboratory results, and treatment outcomes of MIS-C cases treated in two centers from April 2020 to February 2021. Patients were compared both according to their clinical categorization and the place they were hospitalized in, as well as with studies published in the literature.
Results Fifty-six patients were included. Thirty-six (64.3%) were male with a mean age of 67.95 ± 50.87 months. Thirty patients (53.5%) were categorized as Kawasaki-like disease, 17 (30.3%) sepsis-like disease, and 9 (16%) were toxic shock syndrome (TSS). Admission symptoms were fever (100%), rash (71.4%), myalgia (69.6%), and abdominal pain (62.5%). Seventeen (30.3%) patients were hospitalized in pediatric intensive care unit. Elevated C-reactive protein levels, procalcitonin, erythrocyte sedimentation rate, D-dimer, and troponin were found in 100, 77, 84, 84, and 23.2% of the patients, respectively. Of all, 55 (98.2%) received IVIG, 54 (96.4%) corticosteroids, 56 (100%) antibiotic therapy, 22 (40%) albumin infusion, and 13 (23.2%) inotropic support. Fifty patients (89.3%) received low-molecular-weight heparin: enoxaparin, followed by acetylsalicylic acid treatment. Only one patient who was resistant to both IVIG and steroid treatment received Anakinra. One patient (1.7%) with TSS died within 1 hour of hospitalization.
Conclusion Combined use of IVIG and corticosteroids is an effective way of treatment in MIS-C patients resulting in low mortality.
Cervical Length Ultrasound for the Evaluation of Preterm Labor: A Survey of National Use and Review of Evidence
Authors: Boelig Rupsa C. , Mcintosh Jennifer , Feltovich Helen , House Michael 
Published: May 2022

Objective The objective of this study was to survey national utilization of cervical length (CL) ultrasound on labor and delivery (L&D) for the evaluation of preterm labor (PTL) and identify provider attitudes and barriers to utilization.
Study Design Survey was emailed to Obstetrics and Gynecology Residency and Maternal-Fetal Medicine Fellowship program and advertised via links on obstetric-related Facebook interest groups. The survey was open from August 4, 2020 to January 4, 2021. Characteristics between respondents who did and did not report the use of CL ultrasound for PTL evaluation were compared with chi-square analysis.
Results There were 214 respondents across 42 states. One hundred and thirty-four respondents (63%) reported any use of CL in the evaluation of PTL and eighty (37%) denied it. There was a significant difference in practice location, practice type, delivery volume, and region between those who did and did not utilize CL ultrasound on L&D. Those who did use CL ultrasound were more likely to report no barriers to use (40 vs. 4%, p < 0.001). The most common barriers involved the availability of transvaginal ultrasound (31%), sterilization of transvaginal ultrasound probe (32%), limited availability of persons able to perform/interpret CL imaging (38%). Nineteen percent believed CL ultrasound had little/no utility in clinical practice. Those who did not use CL ultrasound in the evaluation of PTL were significantly more likely to report the feeling that there was little/no utility of CL ultrasound in clinical practice (37 vs. 7%, p < 0.001) and to report transvaginal ultrasound availability as barriers to use (63 vs. 12%, p < 0.001).
Conclusion CL ultrasound is used nationally in PTL evaluation. However, significant barriers limit widespread adoption. These barriers can be addressed through the dissemination of information and practice guidelines, addition of CL ultrasound education in residency training and through CME opportunities after training, and providing support/resources/access for those looking to add this tool to their practice environment.
Key Points
Comparison of Two Stifle Exploratory Methods Using Mini-Arthrotomy for Diagnosis of Canine Medial Meniscal Pathology: An Ex Vivo Study
Authors: Kmieciak Lauren A. , Aulakh Karanvir S. , Harper Tisha A.M. , Mitchell Mark A. , Butler Ryan J. , Liu Chin-Chi , Aulakh Harmeet K. 
Published: May 2022

Abstract
Objective The main aim of this study was to compare the accuracy of stifle exploratory using either a stifle distractor (SD method) or a combination of Hohmann and Senn retractors (HS method) for diagnosing canine medial meniscal tears in cranial cruciate ligament-deficient stifles.
Study Design Fifteen pairs of canine cadaveric pelvic limbs were used and cranial cruciate ligament were transected in all stifles. Paired limbs were then randomly assigned to one of five groups based on the tears created in the caudal pole of the medial meniscus: no tear, peripheral detachment, or a variation in three vertical longitudinal tears. A craniomedial mini-arthrotomy was performed by two observers and diagnosis of the medial meniscal status was made utilizing the HS and SD methods. Correct diagnosis of the meniscal tear was compared for both methods and observers.
Results Correct diagnoses were made using the HS and SD methods in 24/30 and 24/30 cases for observer 1 respectively; and in 17/30 and 19/30 cases for observer 2 respectively. There was no significant difference in the correct diagnosis of meniscal tears within each observer between the two methods.
Conclusion Both HS and SD methods have equal accuracy for the diagnosis of canine medial meniscal pathology for a board-certified surgeon. Unassisted surgeons using the SD method for the evaluation of the medial meniscus are at no diagnostic disadvantage compared with assisted surgeons utilizing the HS method.
Effect of initial temperature on impact-induced spalling behavior in single-crystal aluminum studied by molecular dynamics simulations
Authors: Luo Guoqiang , Huang Shanglin , Hu Jianian , Zhu Youlin , Wang Junjie , Yang Gang , Zhang Ruizhi , Sun Yi , Zhang Jian , Shen Qiang 
Published: May 2022

Spallation is a typical dynamic fracture mode under shock loading and has attracted the attention of most researchers. However, due to the difficulty in measuring temperature in dynamic experiments, the effect of initial temperature on spalling response has been rarely investigated. Molecular dynamics simulation perfectly corresponds to the short duration and high strain rate of the spalling process. Therefore, in this work, molecular dynamics simulations are used to study the spalling reaction of single-crystal aluminum at different initial temperatures. The research has shown that the evolution of spallation is related to dislocation and hole nucleation. First, the spall strength of the material decreases as initial temperature increases, while the dislocation density gradually increases. However, when the initial temperature increases to 750 K, the dislocation density decreases. Then, the number of holes and the degree of damage change as initial temperature increases. However, at the low impact strength (v &lt; 2.0 km/s), the changes in the number of holes and the degree of damage are highly dependent on the initial temperature. In the case of high impact strength, the opposite is true. Finally, the thermodynamic path of the material during impact compression is studied. It is found that melting may occur during compression, release or tension, and damage stages, depending on the initial temperature and impact strength. The discovery and research of these systems have laid a solid foundation for subsequent studies.
Histology, ultrastructure, and differential gene expression in relation to seasonal sperm storage in the oviduct of the Chinese alligator,
Authors: Nie Haitao , Wen Yue , Zhang Ruidong , Wu Mengjuan , Zhang Yuqian , Xu Yunlu , Zhan Jixiang , Wu Xiaobing 
Published: May 2022

Although oviductal sperm storage are essential steps in reproduction for female animals with internal fertilisation, no systematic study on the identification of genes involving sperm storage has been performed in crocodilian species. In the present research, the relationship between morphological variation related to sperm storage in the oviduct and gene expression patterns derived from RNA sequencing analyses between active period (AP), breeding period (BP), and hibernation period (HP) were investigated. The corresponding results indicated that sperm were observed not only in the ciliated cells within infundibulum and mucosal layer of uterus during BP, but also been detected in the spermatosperm storage tube (SST) in the anterior uterus at HP stage. The further transmission electron microscopy analysis indicated that the differences in the number and activity of the secretory cells likely to attributed to the seasonal variation of microenvironment related to the sperm storage. Based on the RNA-sequecing, 13 147 DEGs related to the Peroxisome proliferator-activated receptors (PPARs) and FOXO signalling were identified, including these, the down-regulated ATG12 and BCL2L11 in the HP group may thus constitute an important point of convergence between autophagy and apoptosis involving the FOXO1 pathway. The genes involved in the PPARs pathway might modulate the immune response and thereby contribute to prolong the life span of stored spermatozoa in Alligator sinensis. The outcomes of this study provide fundamental insights into the mechanism of sperm storage in A. sinensis.