bluuebunny/crossref_metadata_2025_split huggingface dataset:
ATR kinase activity promotes antibody class switch recombination in B cells through cell cycle regulation without suppressing DSB resection and microhomology usage
Authors: Sun Xikui , Liu Meiling , Bai Jingning , Xu Jiejie , Zhu Chengming , Dong Junchao , Chen Chun 
Published: April 2021

AbstractClass switch recombination (CSR) changes the effector functions of antibodies and is carried out by classical and alternative nonhomologous end joining (c-NHEJ and A-EJ) of repetitive switch (S) region double-strand breaks (DSBs). The master DNA damage response (DDR) kinase ataxia-telangiectasia mutated (ATM) is critical for CSR in part by suppressing S region DSB resection. However, whether another related DDR kinase ATM- and Rad3-related (ATR) plays similar role in CSR remains elusive. In this study, we investigated the requirement for ATR kinase activity on CSR in both c-NHEJ competent and deficient B cell lines with high-throughput sequencing of S-S junctions. We found that ATR kinase inhibition efficiently blocked both c-NHEJ- and A-EJ-mediated CSR without affecting germline transcription and activation-induced cytosine deaminase expression. In contrast to ATM, ATR does not suppress S region DSB resection and microhomology usage. In addition, ATR kinase inhibition did not affect Cas9-generated DSB end joining by either c-NHEJ and A-EJ. ATR kinase-inhibited stimulated B cells proliferate much slower than controls and exhibited altered cell cycle profile with increased G1 and G2/M phase cells. In summary, our data revealed a role for ATR in promoting both c-NHEJ- and A-EJ-mediated CSR through regulating cell proliferation upon damage without negatively influencing DSB end-joining features.
The lymphatic drainage system of the CNS plays a role in lymphatic drainage, immunity, and neuroinflammation in stroke
Authors: Chen Jinman , Wang Linmei , Xu Hao , Wang Yongjun , Liang Qianqian 
Published: April 2021

AbstractThe lymphatic drainage system of the central nervous system (CNS) plays an important role in maintaining interstitial fluid balance and regulating immune responses and immune surveillance. The impaired lymphatic drainage system of the CNS might be involved in the onset and progression of various neurodegenerative diseases, neuroinflammation, and cerebrovascular diseases. A significant immune response and brain edema are observed after stroke, resulting from disrupted homeostasis in the brain. Thus, understanding the lymphatic drainage system of the CNS in stroke may lead to the development of new approaches for therapeutic interventions in the future. Here, we review recent evidence implicating the lymphatic drainage system of the CNS in stroke.
Artificial intelligence–based design optimization of nonuniform microstrip line band pass filter
Authors: Mahouti Tarlan , Yıldırım Tülay , Kuşkonmaz Nilgün 
Published: April 2021

AbstractDesign optimization of many electromagnetic and multiphysics problems have multiscale issues that require a fast, efficient, and accurate surrogate‐based model to be used. Recently, in microwave engineering field, artificial intelligence–based models are being used for modeling of complex microwave stages. In all the studies, the main aim is to form models inner structure parameters, by using the given data to predict the linear/nonlinear relationships between given inputs and outputs. Herein, a surrogate‐based model of a nonuniform microstrip transmission line (NTL) with a typical application of design optimization of a band‐pass filter for ISM band application using deep learning (DL) and meta‐heuristic optimization has been presented. In order to have a computationally efficient and accurate optimization process, firstly a 3D EM unit element model of NTL has been designed. The training and test data sets are created based on different sampling methods. A DL regression model modified multilayer perceptron M2LP have been used for prediction of scattering parameters (S) of the NTL, with respect to the variation of geometrical design parameters. The proposed S‐parameters will then be used to calculate the equivalent S‐parameters of the cascading NTL to be used to calculate the NTL‐based microstrip band‐pass filter S‐parameter response. The optimal design parameters of each line used in the filter design have been determined using a fast and powerful optimization algorithm differential evolutionary algorithm.
Improved multi‐model ensemble forecasts of Iran's precipitation and temperature using a hybrid dynamical‐statistical approach during fall and winter seasons
Authors: Najafi Husain , Robertson Andrew W. , Massah Bavani Ali R. , Irannejad Parviz , Wanders Niko , Wood Eric F. 
Published: April 2021

AbstractSkillful seasonal climate forecasts can support decision making in water resources management and agricultural planning. In arid and semi‐arid regions, tailoring reliable forecasts has the potential to improve water management by using key hydroclimate variables months in advance. This article analyses and compares the performance of two common approaches (empirical and hybrid dynamical‐statistical) in seasonal climate forecasting over a drought‐prone area located in Southwest Asia including Iran. Empirical models are framed as a baseline skill that hybrid models need to outperform. Both approaches provide probabilistic forecasts of precipitation and temperature using canonical correlation analysis to provide forecasts at 0.25° resolution. Empirical models are developed based on the large‐scale observed atmosphere–ocean patterns for forecasting using antecedent climate anomalies as predictors, while the hybrid approach makes use of model output statistics to correct systematic errors in dynamical climate model forecast outputs. Eight state‐of‐the‐art dynamical models from the North American Multi‐Model Ensemble project are analysed. Individual models with the highest goodness index are weighted to develop seven different hybrid dynamical‐statistical Multi‐model Ensembles. In this study, (October–December) and (January–February) are considered as target seasons which are the most important periods within the water year for water resource allocation to the agriculture sector. The results show that the hybrid approach has improved performance compared to the raw general circulation models and purely empirical models, and that the performance of the hybrid models is season‐dependent. Seasonal forecasts of precipitation (temperature) have a higher skill in OND (JFM). In addition, in most cases, Multi‐model Ensemble (MME) is more skillful than the empirical models and outperforms individual dynamical models. However, the best individual model might be as skillful as the MME given the target season and region of interest.
The first case with FBXL4 mutation successfully treated with a parenteral ketogenic diet for lactic acidosis
Authors: İnci Aslı , Aktaş Emine , Cengiz Ergin Filiz Başak , Okur İlyas , Biberoğlu Gürsel , Ezgü Fatih Süheyl , Tümer Leyla 
Published: April 2021

AbstractBackgroundThe ketogenic diet (KD) is a low‐carbohydrate, high‐fat diet that has been used as an effective nonpharmacological treatment in many neurological and metabolic disorders for a long time. The effectiveness of the KD is revealed in mitochondrial disorders, mainly in pyruvate dehydrogenase deficiency.Case report: A 4‐year‐old girl who was diagnosed with an F‐box and leucine‐rich repeat protein 4 (FBXL4) gene mutation was hospitalized with sepsis. She was first given standard parenteral nutrition (PN) because of gastrointestinal problems. During the disease course, lactic acidosis became prominent and did not respond to pharmacological treatment; standard PN was gradually switched to parenteral KD, and lactate levels decreased after parenteral KD. The patient was discharged with an enteral KD.ConclusionThis is the first case of mitochondrial depletion syndrome effectively treated with parenteral KD for lactic acidosis.
Paper Patching Versus Watchful Waiting of Traumatic Tympanic Membrane Perforations: A Meta‐Analysis
Authors: Simani Liam , Oron Yahav , Handzel Ophir , Eta Rani Abu , Warshavsky Anton , Horowitz Gilad , Muhanna Nidal , Ungar Omer J. 
Published: April 2021

Objectives/HypothesisThe aim of the study was to investigate the healing rates, the restoration of hearing, and the time for complete healing of paper patching versus watchful waiting for traumatic tympanic membrane perforations (TTMPs).Study DesignSystematic review with meta analysis.MethodsPublications were selected by a search on “PubMed,” “Embase,” and “Web of Science.” A meta‐analysis of risk ratios for paper patching (intervention arm) and watchful waiting (control arm) was performed.ResultsFive studies describing 393 TTMPs were included in the quantitative meta‐analysis. TTMP healing rates ranged between 84.2% and 95.2% in the intervention arm and between 76.7% and 84.8% in the control arm. The pooled risk ratio of healed TTMPs was significantly higher in the intervention arm than in the control arm (risk ratio: 1.12, 95% confidence interval: 1.04–1.21).ConclusionsTTMPs have high healing potential with and without intervention. The healing rate of paper patching was superior to that of watchful waiting alone.Level of EvidenceNA Laryngoscope, 131:2091–2097, 2021
The Prevalence of Incidental Mastoid Opacification and the Need for Intervention: A Meta‐Analysis
Authors: Mughal Zahir , Charlton Alexander Rowan , Clark Matthew 
Published: April 2021

Objectives/HypothesisThe increasing use of cross‐sectional imaging has led to the predicament of incidental mastoid opacification (IMO). We investigated the prevalence of IMO and the clinical need for ENT assessment or intervention when identified.Study DesignSystematic review and meta‐analysis.MethodsThe PRISMA statement standards were used to search electronic databases including Medline, Embase, PubMed, and Web of Science. The selection criteria were mastoid opacification found on computed tomography (CT) or magnetic resonance imaging (MRI) as incidental findings.ResultsA total of 16 studies were identified for qualitative analysis and 15 for quantitative analysis, mainly retrospective. The pooled prevalence of IMO in 246,288 patients was 8.4% (95% CI 5.5–12.0). The prevalence of IMO was significantly higher in studies with children (17.2%, 95% CI 10.9–24.6) than those with adults (6.1%, 95% CI 3.3–9.6); smaller sample size studies (12.4%, 95% CI 8.1–17.3) compared to larger sample size studies (4.1%, 95% CI 1.5–7.8); and when IMO was detected by viewing images (14.5%, 95% CI 9.9–19.8) compared to reading reports (3.5%, 95% CI 1.3–6.6). Imaging modality was not a significant moderator due to similar IMO rate on CT (8.6%, 95% CI 1.8–19.7) and MRI (10.4%, 95% CI 4.9–17.6). Nine studies reported on clinical outcomes of patients with IMO, and none reliably reported any cases of clinical mastoiditis.ConclusionsThe term “mastoiditis” on radiology reports based on IMO does not indicate a clinical diagnosis of mastoiditis, although the current body of evidence is limited. Otolaryngology review is suggested if clinical correlation detects otological signs or symptoms.Level of EvidenceNA Laryngoscope, 132:422–432, 2022
Modified Cyclodextrin Microparticles to Improve PMMA Drug Delivery Without Mechanical Loss
Authors: Lu Chao‐Yi , Church Derek C. , Learn Greg D. , Pokorski Jonathan K. , von Recum Horst A. 
Published: April 2021

AbstractAntibiotic‐loaded poly(methyl methacrylate) (PMMA) cement is commonly used as a local delivery system to treat and prevent orthopedic infections associated with arthroplasties in load‐bearing applications. However, these delivery systems are inefficient as release rate sharply declines to subinhibitory levels. Prior studies have shown that by adding in drug‐filled cyclodextrin (CD) microparticles into PMMA cement, a more consistent release is observed, and antibiotic refilling through simulated implantation can be achieved. However, the mechanical strengths of PMMA is reduced. In order to decrease the mechanical loss, modified CD microparticles (PMMA‐CD) are synthesized that contain covalently appended PMMA chains. The compressive strengths, handling characteristics, and refilling ability of PMMA cement with PMMA‐CD are evaluated. Specifically, up to a 13.7% increase in compressive strength is observed when unmodified CD is substituted with PMMA‐CD in PMMA samples with 10 wt% CD microparticles. Additionally, a 13.3% increase in working time, a 7.5% decrease in maximum polymerization temperature, and up to a 32.1% increase in amount of drug refilled are observed with the addition of 10 wt% CD PMMA‐CD into PMMA in comparison to plain PMMA without CD microparticles.
Assessment of clinical factors affecting outcome of myasthenia gravis
Authors: Yoshimoto Yukiyo , Ishida Shimon , Hosokawa Takafumi , Arawaka Shigeki 
Published: April 2021

AbstractIntroduction/AimsIn myasthenia gravis (MG) therapy, achieving Myasthenia Gravis Foundation of America minimal manifestation (MM) or better status is proposed as a desirable target. However, this level of control is often not achieved and clinical factors affecting prognosis remain unclear.MethodsParticipants were 104 consecutive patients with MG who visited Osaka Medical College Hospital. We retrospectively assessed the association of clinical and laboratory features at baseline with prognosis. Eighty patients who achieved MM or better status were classified as the good outcome group and the remaining 24 patients were classified as the poor outcome group.ResultsThe rate of dysphagia at baseline was significantly higher in the poor outcome group than in the good outcome group (P = .002). The levels of serum total protein and albumin at baseline were both significantly lower in the poor outcome group than in the good outcome group (P = .036 and P = .014, respectively). In addition, Controlling Nutritional Status scores at baseline were significantly higher in the poor outcome group than in the good outcome group (P = .043). Multivariate analysis using a Cox proportional hazards model showed that dysphagia (hazard ratio [HR], 6.92; 95% confidence interval [CI], 1.49‐40.31) and hypoalbuminemia (HR, 2.57; 95% CI, 1.04‐6.57) at baseline were risk factors that predicted prognosis.DiscussionThese findings suggest that dysphagia and hypoalbuminemia at baseline are associated with outcomes and are predictive risk factors for poorer outcomes in patients with MG.
Soil‐structure interface modeling with the nonlinear incremental approach
Authors: Yang Jie , Yin Zhen‐Yu 
Published: April 2021

AbstractThis paper aims to develop the nonlinear incremental modeling approach for describing both monotonic and cyclic behaviors of the soil‐structure interface. An exponential function is adopted as an example to reproduce the asymptotic relationship between the interface shear stress ratio and the shear displacement. A stress‐dilatancy relation is developed for the shear‐induced change of interface thickness. A shear stress reversal technique is incorporated for cyclic loading effect. Then, three numerical schemes for simulating constant thickness, constant normal load, and constant normal stiffness tests are established respectively. Next, three modifications are made to enhance the model by introducing a nonlinear shear modulus, the critical state concept, and the grain breakage effect. The enhanced model is evaluated with satisfactory performance in simulating interface tests under various loading conditions. Furthermore, the extensions to other nonlinear incremental interface model and clay‐structure interface modeling with rate effect relating to drainage conditions are successfully demonstrated and discussed.
Low‐velocity impact resistance and acoustic emission evaluation on mechanical failure of carbon fiber weft‐knitting‐reinforced composites
Authors: Tian Qin , Qin Zhigang , Shi Bao , Jia Lixia , Lu Suling , Yan Ruosi 
Published: April 2021

AbstractIn this study, the carbon fiber weft‐knitting (CFWK)‐reinforced composites were prepared and the deformation mechanism during acoustic emission (AE) and low‐velocity impact resistance. To fabricate CFWK composites, single‐sided 1 × 1 variable plain stitch, double‐sided interlock structure, and two inter‐ply and intra‐ply hybrid structures of the former two stitches were applied for reinforcements in epoxy films via hot‐pressing. Moreover, we evaluated the tensile and bending properties during AE and investigated the low‐velocity impact properties of CFWK‐reinforced composites to evaluate the failure mechanism of composites. Finally, we analyzed the effects of laminating numbers, ply angle, and fabric structure on the properties of CFWK‐reinforced composites. Results showed that the composites with 1 × 1 variable plain stitch reinforcement exhibited the highest tensile strength and bending strength (206.22 and 213.43 MPa, respectively) among the composites with a two‐layer structure. The tensile fracture strength of [0/90] laying was 35%–50% lower than that of [0/0] laying. In addition, the cluster analysis on AE signal frequency showed that fiber debonding was the main failure mode, accounting for 68% of the total debonding when stretching along the longitudinal direction of the two‐ply composite loop. Under the impact energy of 4 J, the maximum load of CFWK‐reinforced composites with three‐ply interlock increased by 275% compared to that of single‐ply composites. Furthermore, the three‐ply interlock CFWK‐reinforced composites were perforated under impact energy of 10 J.
Organoids in cancer research: a review for pathologist‐scientists
Authors: Wood Laura D , Ewald Andrew J 
Published: April 2021

AbstractThe use of three‐dimensional (3D) culture models for cancer research has expanded greatly in recent years, with studies in almost every tumor type addressing a wide variety of research questions. Multiple distinct 3D culture approaches are now available, each with its own advantages and disadvantages, as well as most effective applications. In this review, we focus on one of these 3D culture models, organoids, in which multicellular units are isolated from primary or metastatic tumors and cultured in extracellular matrix gels. Organoids can be studied in acute cultures for short times after isolation, or passaged and biobanked for long‐term use. We define this model system and describe some key studies in which organoid culture models were used to investigate cellular strategies and molecular mechanisms driving cancer initiation and progression, highlighting research questions for which this model is particularly well suited. In addition, as interest in implementing organoid systems continues to expand, we discuss key considerations in developing a new organoid research program. Our goal is to demonstrate the power and utility of organoid models and provide guidance for investigators who are considering implementation of these models in their own research programs. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Two‐point blood sampling is sufficient and necessary to estimate the area under the concentration‐time curve for intravenous busulfan in infants and young children
Authors: Utano Tomoyuki , Kato Motohiro , Sakamoto Kenichi , Osumi Tomoo , Matsumoto Kana , Tomizawa Daisuke , Matsumoto Kimikazu , Yamatani Akimasa 
Published: April 2021

AbstractBackgroundTherapeutic drug monitoring for busulfan is important to prevent adverse events and improve outcomes in stem cell transplantation. We investigated intravenous busulfan pharmacokinetics and evaluated the utility of limited sampling strategy (LSS) as a simple method to estimate the area under the concentration‐time curve (AUC).ProcedureThe study comprised 87 busulfan measurements in 54 children who received intravenous busulfan between August 2015 and May 2020. AUCs were calculated from three to five blood sampling points in each patient, and the correlation between AUC and plasma concentrations (ng/mL) at 1, 2, 3, 4, and 6 h after initiating busulfan infusion (C1, C2, C3, C4, and C6, respectively).ResultsBy one‐point sampling strategy, the most relevant predicted AUC was based on C6 (r2 = 0.789; precision, 11.0%) in all patients. The predicted AUC based on C6 was acceptable (r2 = 0.937; precision, 5.9%) for adolescent patients weighing >23 kg, but the correlation was poor in infants and young children weighing ≤ 23 kg (r2 = 0.782; precision, 11.4%). By two‐point sampling strategy, the predicted AUC based on C3 and C6 showed the most relevant concentrations (r2 = 0.943; precision, 6.4%), even in infants and young children, whereas the predicted AUC based on C3 and C6 was acceptable (r2 = 0.963; precision, 5.7%).ConclusionsThe AUC of busulfan can be predicted based on C6 in adolescent patients. However, there was substantial interindividual variation in busulfan pharmacokinetics in infants and young children, in whom two‐point LSS was necessary for accurate AUC prediction.
Simultaneous separation and determination of four active ingredients in Picria fel‐terrae Lour. and its preparations by micellar electrokinetic chromatography
Authors: Wang Hua , Yang Yuhang , Guo Jing , Wang Mengli , Zhang Hongfen , Zhang Guangbin , Chang Ruimiao , Chen Anjia 
Published: April 2021

AbstractIntroductionPicfeltarraenins IA, IB and IV and acteoside are the four bioactive ingredients of Picria fel‐terrae Lour. Their pharmacological effects include central inhibitory, cardiovascular, anti‐inflammatory, anti‐pyretic, analgesic, anti‐bacterial, antioxidative and anti‐tumor effects.ObjectiveWe aimed to develop an efficient micellar electrokinetic chromatography (MEKC) method modified with mixed organic solvents for the simultaneous separation and determination of the four components in Picriae Herba and its formulations.MethodsMethod optimization was carried out by investigating influences of significant factors on the separation, and this method was successfully applied for the determination of the four components in Picriae Herba and its formulations.ResultsThe optimal running buffer was composed of 20 mM sodium tetraborate, 40 mM sodium cholate, 10% (v/v) methanol and 10% (v/v) isopropanol (pH 9.76). The separation voltage was 18 kV, the temperature was 25°C and the detection wavelength was 266 nm. Under the optimal separation conditions, the baseline separation of four components was achieved in less than 14 min. The correlation coefficients of the calibration curves were 0.9984–0.9995 for the analytes. The intraday and interday precision ranged from 1.5% to 2.5% and from 1.4% to 5.0%, respectively. Recoveries of analytes varied from 96.6% to 104.1%.ConclusionThe method was proved suitable for the determination of four components in Picriae Herba and its formulations. Good performance was obtained under optimal conditions, and the method provides an effective tool for the quality control of Picriae Herba and its formulations.