bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlational analysis of chemokine and inflammatory cytokine expression in the intervertebral disc and blood in patients with lumbar disc disease
Authors: Hiyama Akihiko , Suyama Kaori , Sakai Daisuke , Tanaka Masahiro , Watanabe Masahiko 
Published: July 2021

AbstractThe involvement of intervertebral disc (IVD) tissues, whole blood (WB) cytokines, and chemokines in pain in patients with lumbar degenerative disc disease (LDD) is unknown. We investigated the relationships between inflammatory cytokines and chemokines in human IVD tissues and WB samples and their association with pain. Expression levels of chemokines and cytokine gene expression were measured in samples from 20 patients with LDD and compared between IVD tissues and WB samples. The associations between WB chemokine and cytokine gene expression levels and pain intensity (numeric rating scale) were also analyzed. The mRNA of C‐C chemokine ligand 20 (CCL20), C‐C chemokine receptor 6 (CCR6), interleukin‐6 (IL‐6), IL‐1β, IL‐17, and tumor necrosis factor‐α (TNF‐α) was expressed in degenerated IVD tissues. Pearson's product–moment correlation analysis produced positive correlations between CCR6 and IL‐6 expression levels in IVD tissues (r = 0.845, p < 0.001) and WB samples (r = 0.963, p < 0.001). WB IL‐6 and CCR6 mRNA expression levels correlated significantly with present pain, maximum pain, and average pain. By contrast, low back pain (LBP) did not correlate with serum chemokine/cytokine expression. This is the first study to report correlations between chemokine and inflammatory cytokine gene expression levels in IVD tissues and WB samples in patients with LDD in relation to pain intensity. WB CCR6 and IL‐6 gene expression levels correlated significantly with present pain, maximum pain, and average pain, but not with LBP. These data provide a new understanding of the role of chemokines and inflammatory cytokines in patients with LDD and may lead to new treatment strategies for pain.
Antenatal corticosteroids affecting enteral feeding and growth of preterm infants: A retrospective cohort study
Authors: Luo Ping , Liu Xudong , Ma Liya , Chen You , Zhang Kun , Zhou Ping , Jiang Yan‐Nan , Jiang Ping‐Ping 
Published: July 2021

AbstractBackgroundTreatment of antenatal corticosteroids (ACSs) to women at risk of preterm labor can decrease neonatal mortality and morbidity. However, effect of ACS exposure on enteral feeding and body growth of preterm infants remains elusive.MethodsThis retrospective study collected information of eligible singleton infants born between 22+0 and 36+6 weeks’ gestation from 2017 to 2019. Logistic regression and multivariate linear regression were adopted to examine the associations of the ACS exposure with various outcomes of enteral feeding and growth considering potential confounders. Stratified analysis was performed based on gestational age (GA) (<34 vs ≥34 weeks).ResultsOf the 1694 preterm infants included, 1222 (72.1%) were exposed to ACSs. Infants with ACS exposure had a higher incidence of feeding intolerance (odds ratio 1.51; 95% CI, 1.05 to 2.20; P = .03), slower advancement of enteral feeding (β coefficient −0.86; 95% CI, −1.48 to −0.25; P = .01), and lower delta body‐weight z‐scores (β coefficient−0.13; 95% CI, −0.18 to −0.08; P < .001). Unlike in infants with GA <34 weeks, ACS exposure was associated with slower advancement of enteral feeding, longer time to regain birth weight, and lower delta body‐weight z‐scores in the ones with GA ≥34 weeks.ConclusionACS exposure is associated with poorer enteral feeding process and body growth in our study population, which is more prominent in late preterm infants. A multicenter prospective study and mechanistic studies using animal models are required.
Methods for population adjustment with limited access to individual patient data: A review and simulation study
Authors: Remiro‐Azócar Antonio , Heath Anna , Baio Gianluca 
Published: July 2021

AbstractPopulation‐adjusted indirect comparisons estimate treatment effects when access to individual patient data is limited and there are cross‐trial differences in effect modifiers. Popular methods include matching‐adjusted indirect comparison (MAIC) and simulated treatment comparison (STC). There is limited formal evaluation of these methods and whether they can be used to accurately compare treatments. Thus, we undertake a comprehensive simulation study to compare standard unadjusted indirect comparisons, MAIC and STC across 162 scenarios. This simulation study assumes that the trials are investigating survival outcomes and measure continuous covariates, with the log hazard ratio as the measure of effect. MAIC yields unbiased treatment effect estimates under no failures of assumptions. The typical usage of STC produces bias because it targets a conditional treatment effect where the target estimand should be a marginal treatment effect. The incompatibility of estimates in the indirect comparison leads to bias as the measure of effect is non‐collapsible. Standard indirect comparisons are systematically biased, particularly under stronger covariate imbalance and interaction effects. Standard errors and coverage rates are often valid in MAIC but the robust sandwich variance estimator underestimates variability where effective sample sizes are small. Interval estimates for the standard indirect comparison are too narrow and STC suffers from bias‐induced undercoverage. MAIC provides the most accurate estimates and, with lower degrees of covariate overlap, its bias reduction outweighs the loss in precision under no failures of assumptions. An important future objective is the development of an alternative formulation to STC that targets a marginal treatment effect.
Establishing multilayered coating on Mo–12Si–8.5 B alloy by Si pack cementation and its oxidation behavior at 900°C–1300°C
Authors: Wang Juan , Li Bin , Li Rui , Chen Xuan , Zhang Guojun 
Published: July 2021

AbstractA multilayered oxidation protection coating consisting of MoSi2 outer layer, Mo5Si3 internal layer, and Mo5SiB2/MoB inner layer was developed on the surface of Mo–12Si–8.5B 1.0 wt% ZrB2 alloy via Si pack cementation. The multilayered coating significantly enhanced the oxidation resistance of the alloy at 900°C, 1100°C, and 1300°C in the air by exhibiting negligible oxidation recession. MoSi2 outer layer provided admirable oxidation protection for the alloy at high temperatures by forming a thin and protective SiO2‐rich glass scale on its surface. This was supplemented by the Mo5Si3 internal layer and Mo5SiB2/MoB inner layer that reduced the thermal expansion mismatch between the MoSi2 outer layer and substrate, and therefore no obvious cracks were found in the MoSi2 outer layer. More importantly, the Mo5SiB2/MoB layer as an in situ barriers of Si interdiffusion ensured the stable existence of MoSi2 and Mo5Si3 layers without obvious thickness change during oxidation at 900°C and 1100°C. Mechanical property test indicated that the formation of the coating layers could not affect the fracture toughness of the alloy.
Solriamfetol for Excessive Daytime Sleepiness in Parkinson's Disease: Phase 2 Proof‐of‐Concept Trial
Authors: Videnovic Aleksandar , Amara Amy W. , Comella Cynthia , Schweitzer Paula K. , Emsellem Helene , Liu Kris , Sterkel Amanda L. , Gottwald Mildred D. , Steinerman Joshua R. , Jochelson Philip , Zomorodi Katie , Hauser Robert A. 
Published: July 2021

AbstractBackgroundSolriamfetol is approved (US and EU) for excessive daytime sleepiness (EDS) in narcolepsy and obstructive sleep apnea.ObjectivesEvaluate solriamfetol safety/efficacy for EDS in Parkinson's disease (PD).MethodsPhase 2, double‐blind, 4‐week, crossover trial: adults with PD and EDS were randomized to sequence A (placebo, solriamfetol 75, 150, 300 mg/d), B (solriamfetol 75, 150, 300 mg/d, placebo), or C (placebo). Outcomes (safety/tolerability [primary]; Epworth Sleepiness Scale [ESS]; Maintenance of Wakefulness Test [MWT]) were assessed weekly. P values are nominal.ResultsCommon adverse events (n = 66): nausea (10.7%), dizziness (7.1%), dry mouth (7.1%), headache (7.1%), anxiety (5.4%), constipation (5.4%), dyspepsia (5.4%). ESS decreased both placebo (−4.78) and solriamfetol (−4.82 to −5.72; P > 0.05). MWT improved dose‐dependently with solriamfetol, increasing by 5.05 minutes with 300 mg relative to placebo (P = 0.0098).ConclusionsSafety/tolerability was consistent with solriamfetol's known profile. There were no significant improvements on ESS; MWT results suggest possible benefit with solriamfetol in PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Expert recommendations and clinical considerations in the use of onasemnogene abeparvovec gene therapy for spinal muscular atrophy
Authors: Kichula Elizabeth A. , Proud Crystal M. , Farrar Michelle A. , Kwon Jennifer M. , Saito Kayoko , Desguerre Isabelle , McMillan Hugh J. 
Published: July 2021

AbstractSpinal muscular atrophy (SMA) is an autosomal recessive, neurodegenerative disease caused by biallelic mutations in the survival motor neuron 1 (SMN1) gene. SMA is characterized by motor neuron degeneration, resulting in progressive muscle atrophy and weakness. Before the emergence of disease‐modifying therapies, children with the most severe form of SMA would never achieve the ability to sit independently. Only 8% survived beyond 20 months of age without permanent ventilator support. One such therapy, onasemnogene abeparvovec, an adeno‐associated virus–based gene replacement therapy, delivers functional humanSMNthrough a one‐time intravenous infusion. In addition to substantially improving survival, onasemnogene abeparvovec was found to increase motor milestone attainment and reduce the need for respiratory or nutritional support in many patients. This expert opinion provides recommendations and practical considerations on the patient‐centered decisions to use onasemnogene abeparvovec. Recommendations include the need for patient‐centered multidisciplinary care and patient selection to identify those with underlying medical conditions or active infections to reduce risks. We also describe the importance of retesting patients with elevated anti–adeno‐associated virus serotype 9 antibodies. Recommendations for prednisolone tapering and monitoring for potential adverse events, including hepatotoxicity and thrombotic microangiopathy, are described. The need for caregiver education on managing day‐to‐day care at time of treatment and patient‐ and family‐centered discussions on realistic expectations are also recommended. We detail the importance of following standard‐of‐care guidance and long‐term monitoring of all children with SMA who have received one or more disease‐modifying therapy using registries. We also highlight the need for presymptomatic or early symptomatic treatment of this disorder.
Maize genetics through the lens of many disciplines: The career of George Beadle
Authors: Hrabik Grant , Milam Noah , Lambley Madison , Durham Brooks Tessa 
Published: July 2021

Core Ideas
George Beadle was a first‐generation college who eventually won the Nobel Prize.
Beadle had a central interest in the function of genes and the origin of maize.
Driven by big questions, Beadle collaborated across biological disciplines to answer them.
Beadle used three different organisms in his research to see several sides of the same problem.
Beadle showed incredible tenacity in circling back decades later to confirm maize origins.
Characterization and Management of Adverse Reactions in Patients with Advanced Endometrial Carcinoma Treated with Lenvatinib Plus Pembrolizumab
Authors: Makker Vicky , Taylor Matthew H. , Oaknin Ana , Casado Herraez Antonio , Orlowski Robert , Dutta Lea , Ren Min , Zale Melissa , O'Malley David M. 
Published: July 2021

AbstractBackgroundThe combination of lenvatinib plus pembrolizumab has shown efficacy in treatment of advanced endometrial carcinoma (that is not microsatellite instability–high or mismatch repair deficient) following prior systemic therapy in any setting in the open-label, single-arm, phase Ib/II Study 111/KEYNOTE-146. With the exception of hypothyroidism, the safety profile of the combination was comparable to that of each monotherapy. Given the medical complexity and fragility of patients with endometrial carcinoma, further characterization of adverse reactions (ARs) associated with treatment will help health care professionals to optimize treatment with lenvatinib plus pembrolizumab combination therapy.Patients and MethodsIn Study 111/KEYNOTE-146, patients received lenvatinib at a starting dose of 20 mg orally once daily and pembrolizumab 200 mg intravenously every 3 weeks. Selected ARs (hypertension, fatigue, nausea/vomiting, diarrhea, decreased appetite/weight loss, hypothyroidism, palmar-plantar erythrodysesthesia syndrome, musculoskeletal pain, stomatitis, and proteinuria) were chosen for detailed post hoc analyses.ResultsMedian times to first onset of the selected ARs in this analysis all occurred within the first 10 weeks of treatment. Of the selected ARs, grade ≥3 severity of fatigue, hypertension, and nausea occurred in ≥5% of patients. Overall incidence of hypothyroidism was 51%, primarily of grade 2 severity (46%). Most of the ARs assessed were managed with a combination of study drug dose modifications and concomitant medications.ConclusionNo new safety signals were identified and the toxicity profile in this study was manageable with supportive medications, dose interruptions, and/or lenvatinib dose reductions. This analysis provides AR management guidance for patients with endometrial cancer receiving lenvatinib plus pembrolizumab combination therapy.Implications for PracticeLenvatinib plus pembrolizumab has shown efficacy in the treatment of patients with advanced endometrial carcinoma (that is, not microsatellite instability–high or mismatch repair deficient) following at least one prior systemic therapy in any setting. Patients may experience toxicity associated with this combination, including adverse reactions of hypertension, fatigue, nausea/vomiting, diarrhea, decreased appetite/weight loss, hypothyroidism, palmar-plantar erythrodysesthesia syndrome, musculoskeletal pain, stomatitis, and proteinuria. These adverse reactions may be managed with a combination of concomitant supportive care medications and judicious lenvatinib dose modifications. This article provides context and guidance for the recognition and management of adverse reactions in patients receiving lenvatinib plus pembrolizumab.
Microparticles based on alginate/chitosan/casein three‐dimensional system for oral insulin delivery
Authors: Xu Zhenyu , Chen Long , Duan Xiaoya , Li Xueming , Ren Hao 
Published: July 2021

In the past, oral insulin has been developed to reduce the suffering of diabetic patients. However, the physiological barriers in gastrointestinal (GI) tract are the major challenges in oral delivery of insulin. In this study, a novel oral delivery system of insulin called NiM (NPs in MPs) has been developed to overcome the GI barriers, which based on a three‐dimensional system of biocompatible chitosan/alginate/casein. Alginate/chitosan nanoparticles (AC‐NPs) were firstly prepared by ionic pre‐gel method and complexation with polyelectrolytes. Then, they were subsequently coated with casein as a protective agent to form NiM, which could keep stability and physiological activity of insulin in gastric tract. The characterization of NiM showed stable hydrodynamic parameters, and the entrapment efficiency of insulin reached 51.1%. In vitro, only 13.5% of insulin was released in the simulated gastric fluid for the first 2 h. But about 57.4% of insulin was slowly released in the simulated intestinal fluid for 10 h. These results indicated that the coating of casein could increase stability of insulin in gastric tract and control release of insulin in intestinal tract. Furthermore, NiM provided a sustained and significant reduction of the blood glucose levels of diabetic mice. Overall, the results demonstrated that our formed NiM may be a promising oral delivery system of insulin for diabetic patients.
Synergistic effect of ZnO and TiO2 nanoparticles on the thermal stability and mechanical properties of glass fiber‐reinforced LY556 epoxy composites
Authors: Thipperudrappa Sridhar , Hiremath Anupama , Kurki Nagaraj Bharath 
Published: July 2021

AbstractThe article discusses the fabrication, mechanical characterization, and heat resistance of nano ZnO‐TiO2‐filled glass fiber‐reinforced LY556 epoxy composites, with focus on the synergistic effect of ZnO and TiO2 nanofillers. The fabrication of the composite laminates is achieved by the addition of the nanofillers in different wt% ranging from 1 to 5 wt%. The composites are prepared using simple hand layup technique followed by curing under vacuum. The 3D atomic force microscopy scans indicated even distribution of the nanofillers up to 2 wt% loading. Severe agglomeration of the nanofillers is evident for 3 to 5 wt% loading. The surface roughness, microhardness, flexural strength, tensile strength, and impact strength of the composites indicate a relationship with dispersion, wt% loading, and the wettability of the nanofiller with the LY556. In general, it is found that the incorporation of hard nanofillers favored the improvement of impact strength to a greater extent compared to tensile and flexural strengths. Detailed analysis of the obtained mechanical property values favors an optimum 2 wt% incorporation of the selected nanofillers to obtain improvement in various strength values of the fabricated composites. The thermal stability of the fabricated composites improved through the incorporation of ceramic nanofillers.
The Habitual Tendencies Questionnaire: A tool for psychometric individual differences research
Authors: Ramakrishnan Smriti , Robbins Trevor W. , Zmigrod Leor 
Published: July 2021

AbstractHabits are automatic responses to learned stimuli or contextual cues that are insensitive to goals. Although habits may allow for automated behaviours that increase efficiency in our daily lives, an over‐reliance on habits has been suggested to contribute to disorders such as obsessive–compulsive disorder (OCD). There are currently few established measures of individual differences in habitual tendencies. To fill this gap, the present study generated and validated a novel 11‐item scale, the Habitual Tendencies Questionnaire (HTQ), to measure individual differences in habitual tendencies in the general population. In Study 1, factor analysis revealed three underlying subcomponents of the HTQ: Compulsivity, Preference for Regularity, and Aversion to Novelty, with Compulsivity showing the strongest association with subclinical OCD symptomatology. Study 2 validated the HTQ and replicated the findings of Study 1 in a larger sample, and explored relationships with other personality traits. The results emphasise the importance of measuring individual variation in habitual thinking styles, illustrating that different facets of habitual tendencies may contribute to diverse behavioural and clinical outcomes. The present investigation provides a new, reliable way of measuring habitual tendencies and has important implications for future explorations into the nature of individual differences from a dimensional perspective to psychiatry.
Fractional paradigms in quantum chemistry
Authors: Mostafanejad Mohammad 
Published: July 2021

AbstractThe realization of fractional quantum chemistry is presented. Adopting the integro‐differential operators of the calculus of arbitrary‐order, we develop a general framework for the description of quantum nonlocal effects in the complex electronic environments. After a brief overview of the historical and fundamental aspects of the calculus of arbitrary‐order, various classes of fractional Schrödinger equations are discussed and pertinent controversies and open problems around their applications to model systems are detailed. We provide a unified approach toward fractional generalization of the quantum chemical models such as Hartree–Fock and Kohn–Sham density functional theory and develop fractional variants of the fundamental molecular integrals and correlation energy. Furthermore, we offer various strategies for modeling static‐ and dynamic‐order quantum nonlocal effects through constant‐ and variable‐order fractional operators, respectively. Possible directions for future developments of fractional quantum chemistry are also outlined.
RobustH∞output feedback control for type‐2Takagi‐Sugenofuzzy systems with multiple time‐delays and disturbances: A descriptor redundancy approach
Authors: Zheng Wei , Zhang Zhiming , Sun Fuchun , Wen Shuhuan , Li Xiaolei , Wang Hongbin 
Published: July 2021

AbstractTheH∞stability analysis and interval type‐2 Takagi‐Sugeno (T‐S) fuzzy control is studied for a class of interval type‐2 T‐S fuzzy systems. Firstly, the interval type‐2 T‐S fuzzy model is employed to approximate the system plant. Secondly, the delay‐dependent interval type‐2 T‐S fuzzy dynamic output feedback controller is designed. Thirdly, two classes of stability conditions in terms of linear matrix inequalities (LMIs) are derived, and the closed‐loop system is asymptotically stable and prescribedH∞performance is achieved. The delay‐dependent interval type‐2 T‐S fuzzy dynamic output feedback controller is designed to relax the control design conditions. The descriptor redundancy method is employed for avoiding the crossing vectors between the system gain matrices and controller gain matrices. The delay‐dependent Lyapunov functional with descriptor redundancy matrix is introduced, and the upper and lower membership functions information is considered. Some slack matrices are introduced via the upper and lower membership functions information to solve the obtained LMIs. Finally, simulation examples are performed to show the effectiveness of the proposed methods.
Gap Junction-Mediated Cell-Cell Interaction Between Transplanted Mesenchymal Stem Cells and Vascular Endothelium in Stroke
Authors: Kikuchi-Taura Akie , Okinaka Yuka , Saino Orie , Takeuchi Yukiko , Ogawa Yuko , Kimura Takafumi , Gul Sheraz , Claussen Carsten , Boltze Johannes , Taguchi Akihiko 
Published: July 2021

Abstract
We have shown previously that transplanted bone marrow mononuclear cells (BM-MNC), which are a cell fraction rich in hematopoietic stem cells, can activate cerebral endothelial cells via gap junction-mediated cell-cell interaction. In the present study, we investigated such cell-cell interaction between mesenchymal stem cells (MSC) and cerebral endothelial cells. In contrast to BM-MNC, for MSC we observed suppression of vascular endothelial growth factor uptake into endothelial cells and transfer of glucose from endothelial cells to MSC in vitro. The transfer of such a small molecule from MSC to vascular endothelium was subsequently confirmed in vivo and was followed by suppressed activation of macrophage/microglia in stroke mice. The suppressive effect was absent by blockade of gap junction at MSC. Furthermore, gap junction-mediated cell-cell interaction was observed between circulating white blood cells and MSC. Our findings indicate that gap junction-mediated cell-cell interaction is one of the major pathways for MSC-mediated suppression of inflammation in the brain following stroke and provides a novel strategy to maintain the blood-brain barrier in injured brain. Furthermore, our current results have the potential to provide a novel insight for other ongoing clinical trials that make use of MSC transplantation aiming to suppress excess inflammation, as well as other diseases such as COVID-19 (coronavirus disease 2019).