bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased cellular senescence in the murine and human stenotic kidney: Effect of mesenchymal stem cells
Authors: Kim Seo Rin , Zou Xiangyu , Tang Hui , Puranik Amrutesh S. , Abumoawad Abdelrhman M. , Zhu Xiang‐Yang , Hickson LaTonya J. , Tchkonia Tamara , Textor Stephen C. , Kirkland James L. , Lerman Lilach O. 
Published: July 2020

AbstractCell stress may give rise to insuperable growth arrest, which is defined as cellular senescence. Stenotic kidney (STK) ischemia and injury induced by renal artery stenosis (RAS) may be associated with cellular senescence. Mesenchymal stem cells (MSCs) decrease some forms of STK injury, but their ability to reverse senescence in RAS remains unknown. We hypothesized that RAS evokes STK senescence, which would be ameliorated by MSCs. Mice were studied after 4 weeks of RAS, RAS treated with adipose tissue‐derived MSCs 2 weeks earlier, or sham. STK senescence‐associated β‐galactosidase (SA‐β‐Gal) activity was measured. Protein and gene expression was used to assess senescence and the senescence‐associated secretory phenotype (SASP), and staining for renal fibrosis, inflammation, and capillary density. In addition, senescence was assessed as p16+ and p21+ urinary exosomes in patients with renovascular hypertension (RVH) without or 3 months after autologous adipose tissue‐derived MSC delivery, and in healthy volunteers (HV). In RAS mice, STK SA‐β‐Gal activity increased, and senescence and SASP marker expression was markedly elevated. MSCs improved renal function, fibrosis, inflammation, and capillary density, and attenuated SA‐β‐Gal activity, but most senescence and SASP levels remained unchanged. Congruently, in human RVH, p21+ urinary exosomes were elevated compared to HV, and only slightly improved by MSC, whereas p16+ exosomes remained unchanged. Therefore, RAS triggers renal senescence in both mice and human subjects. MSCs decrease renal injury, but only partly mitigate renal senescence. These observations support exploration of targeted senolytic therapy in RAS.
Overview on the Amendments of Provisions for Drug Registration in China
Authors: Dai Weijun , Zhong Mingru , Lin Weitong , Su Ling 
Published: July 2020

AbstractThe revised Provisions for Drug Registration was promulgated by the State Administration for Market Regulation of China in March 2020 and came into force on July 1, 2020. This article describes the history of the drug registration management system in China, explains the background of the revision of the Provisions for Drug Registration in 2020, and introduces the main modifications of the Provisions for Drug Registration in 2020 in the aspects of registration classification, application for clinical trial on drug, application for drug marketing authorization, accelerated procedure for drug registration, working timeline, and supervision and administration. This article is intended to give a brief overview for those who wish to submit a drug registration application in China or for those who would like to get more acquainted with drug registration in China.
Mortality in malnourished older adults diagnosed by ESPEN and GLIM criteria in the SarcoPhAge study
Authors: Sanchez‐Rodriguez Dolores , Locquet Médéa , Reginster Jean‐Yves , Cavalier Etienne , Bruyère Olivier , Beaudart Charlotte 
Published: July 2020

AbstractBackgroundThe Global Leadership Initiative on Malnutrition (GLIM) criteria have been recently launched by consensus of the major nutrition societies. GLIM criteria are partly constructed on the previous definition of malnutrition developed by the European Society of Clinical Nutrition and Metabolism (ESPEN). We aimed to assess malnutrition according to the ESPEN and GLIM criteria at baseline and to determine the corresponding risk of mortality during a 4‐year follow‐up in community‐dwelling older adults from the SarcoPhAge (Sarcopenia and Physical Impairment with advancing Age) study. The relationship between malnutrition and incidence of 4‐year adverse health consequences (institutionalization, hospitalization, falls, and fractures) was assessed.MethodsThis prospective population‐based cohort was part of SarcoPhAge, which included 534 older adults in Belgium, followed up from 2013 to 2019. Community‐dwelling healthy volunteers ≥65 years old were recruited. Mortality and adverse health consequences were collected annually by interview or phone call. Baseline malnutrition was defined according to the GLIM and ESPEN criteria. Agreement between the two definitions was reported by Cohen's kappa coefficient. Adjusted Cox regression and Kaplan–Meier survival curves were performed for malnutrition. Logistic regression was used for the other outcomes.ResultsFrom 534 subjects in SarcoPhAge, the records for 411 participants (73.2 ± 6.05 years old; 55.7% women) had all the variables needed to apply the GLIM criteria. Prevalence of baseline malnutrition was 23.4% for GLIM and 7% for ESPEN criteria (k = 0.30, low agreement). The adjusted Cox regression showed a significant increased mortality risk according to malnutrition status as defined by the GLIM [adjusted hazard ratio = 4.41 (95% confidence interval: 2.17–8.97)] and ESPEN [adjusted hazard ratio = 2.76 (95% confidence interval: 1.16–6.58)] criteria. Survival curves differed significantly between malnourished and non‐malnourished groups, regardless of the definition used (log rank P < 0.001 for both). No association was found between baseline malnutrition according to these two criteria and 4‐year risk of institutionalization, hospitalization, falls, or fractures (all P > 0.05).ConclusionsMalnutrition according to the GLIM criteria was associated with a 4.4‐fold higher mortality risk, double that of the ESPEN criteria, during a 4‐year follow‐up. No association was found between malnutrition according to these two criteria and incidence of other health adverse consequences. GLIM criteria anticipate mortality and might guide interventions, with important implications for clinical practice and research.
Abusive according to whom? Manager and subordinate perceptions of abusive supervision and supervisors' performance
Authors: Ambrose Maureen L. , Ganegoda Deshani B. 
Published: July 2020

SummaryRecognizing that supervisor–subordinate dyads exist within a broader organizational hierarchy, we examine how the individual's role within the organizational hierarchy influences perceptions of abusive supervision. Specifically, we examine how supervisors' abusive behaviors are perceived by abusive supervisors' managers as well as abusive supervisors' subordinates. Drawing on role theory, we propose that these perceptions will differ. Further, we suggest that these differences will be reflected in different relationships between manager‐rated abusive supervision and subordinate‐rated abusive supervision and managers' evaluations of supervisor performance. Results from manager–supervisor–subordinate triads indicate differences between managers' and subordinates' view of abusive supervision. Further, managers' perceptions of abuse were related to supervisors' in‐role performance, whereas subordinates' perceptions of abuse were related to workgroup performance. In Study 2, we replicate these findings and expand our investigation to an examination of supervisors' contextual performance. Additionally, we examine another contextual characteristic—aggressive climate—and demonstrate it influences how abusive supervision relates to managerial evaluations of supervisor performance. Future research and managerial implications are discussed.
Evaluation of Upper Airway in Children with Obstructive Sleep Apnea Using Cone‐Beam Computed Tomography
Authors: Hsu Wei‐Chung , Kang Kun‐Tai , Yao Chung‐Chen Jane , Chou Chen‐Han , Weng Wen‐Chin , Lee Pei‐Lin , Chen Yunn‐Jy 
Published: July 2020

ObjectiveCone‐beam computed tomography (CBCT) offers three‐dimensional structures in assessing upper airway of patients. This study aims to compare the cone‐beam computerized tomography scan measurements between children with obstructive sleep apnea (OSA) and primary snoring.Study DesignCase–control study.MethodsThis prospective study was conducted in a tertiary referral center. Thirty‐six children with moderate‐to‐severe OSA (with apnea‐hypopnea index [AHI] > 5 events/hour) and 36 age‐, gender‐, and obesity‐matched children with primary snoring (AHI <1) were enrolled. The measurements in CBCT parameters were compared between children with moderate‐to‐severe OSA and primary snorers by conditional logistic regression model.ResultsA total of 72 children (mean age, 7.9 ± 2.8 years; 64% male) were included. Children with moderate‐to‐severe OSA had a significantly smaller nasopharyngeal (2900 ± 1400 vs. 3800 ± 1800 mm3, P = .017) and oropharyngeal airway volume (5600 ± 2700 vs. 7400 ± 4000 mm3, P = .026) than those with primary snoring. Children with moderate‐to‐severe OSA, as compared to primary snorers, also had a significantly smaller minimal airway area in nasopharynx (77.4 ± 37.7 vs. 107.7 ± 52.0 mm2, P = .006) and oropharynx (66.6 ± 61.9 vs. 101.6 ± 65.8 mm2, P = .023). Moreover, the airway length was not significantly different between children with moderate‐to‐severe OSA and primary snoring.ConclusionsThe three‐dimensional CBCT airway analysis could be used as a useful tool to evaluate upper airway in children with OSA.Level of Evidence3 Laryngoscope, 131:680–685, 2021
Orders on computable rings
Authors: Wu Huishan 
Published: July 2020

AbstractThe Artin‐Schreier theorem says that every formally real field has orders. Friedman, Simpson and Smith showed in [6] that the Artin‐Schreier theorem is equivalent to over . We first prove that the generalization of the Artin‐Schreier theorem to noncommutative rings is equivalent to over . In the theory of orderings on rings, following an idea of Serre, we often show the existence of orders on formally real rings by extending pre‐orders to orders, where Zorn's lemma is used. We then prove that “pre‐orders on rings not necessarily commutative extend to orders” is equivalent to .
Glycopyrrolate Improves Disability From Sialorrhea in Parkinson's Disease: A 12‐Week Controlled Trial
Authors: Mestre Tiago A. , Freitas Eliza , Basndwah Ahmed , Lopez Marta Ruiz , de Oliveira Lais Machado , Al‐Shorafat Duha Mohammed , Zhang Tinghua , Lui Jane P. , Grimes David , Fox Susan H. 
Published: July 2020

AbstractObjectiveThe objective of this study was to assess the 12‐week efficacy and safety of oral glycopyrrolate for moderate‐to‐severe sialorrhea in Parkinson's disease (PD).BackgroundChronic moderate‐to‐severe sialorrhea has a negative impact on quality of life in PD. There is no robust evidence for oral treatments for sialorrhea longer than 1 week.MethodsThis was a 12‐week, double‐blinded, placebo‐controlled, parallel phase II study in patients with PD and Movement Disorder Society–Unified Parkinson's Disease Rating Scale item 2.2 > 2. The intervention was glycopyrrolate up to 4.5 mg/d; the primary outcome was sialorrhea related–disability (Radboud Oral Motor Inventory for Parkinson's Disease–Saliva). We used an intention‐to‐treat analysis. A P < 0.05 was deemed significant.ResultsWe recruited 28 patients (age, 71.1 ± 6.9 years; PD duration, 11.4 ± 7.2 years; Radboud Oral Motor Inventory for Parkinson's Disease–Saliva, 22.4 ± 5.7). Glycopyrrolate was superior to placebo at 12 weeks in the Radboud Oral Motor Inventory for Parkinson's Disease–Saliva (between‐group difference, 5.3; 95% confidence interval, 1.0–9.6). Dry mouth was the most common adverse event (glycopyrrolate, n = 6; placebo, n = 2).ConclusionsThe results support the efficacy of glycopyrrolate to treat sialorrhea‐related disability up to 12 weeks and contribute to addressing unmet nonmotor care needs in PD. © 2020 International Parkinson and Movement Disorder Society
Harnessing endophenotypes and network medicine for Alzheimer's drug repurposing
Authors: Fang Jiansong , Pieper Andrew A. , Nussinov Ruth , Lee Garam , Bekris Lynn , Leverenz James B. , Cummings Jeffrey , Cheng Feixiong 
Published: July 2020

AbstractFollowing two decades of more than 400 clinical trials centered on the “one drug, one target, one disease” paradigm, there is still no effective disease‐modifying therapy for Alzheimer's disease (AD). The inherent complexity of AD may challenge this reductionist strategy. Recent observations and advances in network medicine further indicate that AD likely shares common underlying mechanisms and intermediate pathophenotypes, or endophenotypes, with other diseases. In this review, we consider AD pathobiology, disease comorbidity, pleiotropy, and therapeutic development, and construct relevant endophenotype networks to guide future therapeutic development. Specifically, we discuss six main endophenotype hypotheses in AD: amyloidosis, tauopathy, neuroinflammation, mitochondrial dysfunction, vascular dysfunction, and lysosomal dysfunction. We further consider how this endophenotype network framework can provide advances in computational and experimental strategies for drug‐repurposing and identification of new candidate therapeutic strategies for patients suffering from or at risk for AD. We highlight new opportunities for endophenotype‐informed, drug discovery in AD, by exploiting multi‐omics data. Integration of genomics, transcriptomics, radiomics, pharmacogenomics, and interactomics (protein–protein interactions) are essential for successful drug discovery. We describe experimental technologies for AD drug discovery including human induced pluripotent stem cells, transgenic mouse/rat models, and population‐based retrospective case–control studies that may be integrated with multi‐omics in a network medicine methodology. In summary, endophenotype‐based network medicine methodologies will promote AD therapeutic development that will optimize the usefulness of available data and support deep phenotyping of the patient heterogeneity for personalized medicine in AD.
Transcranial activation and imaging of low boiling point phase‐change contrast agents through the temporal bone using an ultrafast interframe activation ultrasound sequence
Authors: Jing Bowen , Kashyap Esha P. , Lindsey Brooks D. 
Published: July 2020

PurposeAs a cavitation enhancer, low boiling point phase‐change contrast agents (PCCA) offer potential for ultrasound‐mediated drug delivery in applications including intracerebral hemorrhage or brain tumors. In addition to introducing cavitation, ultrasound imaging also has the ability to provide guidance and monitoring of the therapeutic process by localizing delivery events. However, the highly attenuating skull poses a challenge for achieving an image with useful contrast. In this study, the feasibility of transcranial activation and imaging of low boiling point PCCAs through the human temporal bone was investigated by using a low frequency ultrafast interframe activation ultrasound (UIAU) imaging sequence with singular value decomposition‐based denoising.MethodsLipid‐shelled PCCAs filled with decafluorobutane were activated and imaged at 37°C in tissue‐mimicking phantoms both without and with an ex vivo human skull using the new UIAU sequence and a low frequency diagnostic transducer array at frequencies from 1.5 to 3.5 MHz. A singular value decomposition‐based denoising filter was developed and used to further enhance transcranial image contrast. The contrast‐to‐tissue ratio (CTR) and contrast enhancement (CE) of UIAU was quantitatively evaluated and compared with the amplitude modulation pulse inversion (AMPI) and vaporization detection imaging (VDI) approaches.ResultsImage results demonstrate enhanced contrast in the phantom channel with suppressed background when the low boiling point PCCA was activated both without and with an ex vivo human skull using the UIAU sequence. Quantitative results show that without the skull, low frequency UIAU imaging provided significantly higher image contrast (CTR ≥ 18.56 dB and CE ≥ 18.66 dB) than that of AMPI and VDI (P < 0.05). Transcranial imaging results indicated that the CE of UIAU (≥18.80 dB) was significantly higher than AMPI for free‐field activation pressures of 5 and 6 MPa. The CE of UIAU is also significantly higher than that of VDI when PCCAs were activated at 2.5 MHz and 3 MHz (P < 0.05). The CTR (23.30 [20.07–25.56] dB) of denoised UIAU increased by 12.58 dB relative to the non‐denoised case and was significantly higher than that of AMPI at an activation pressure of 4 MPa (P < 0.05).ConclusionsResults indicate that low boiling point PCCAs can be activated and imaged at low frequencies including imaging through the temporal bone using the UIAU sequence. The UIAU imaging approach provides higher contrast than AMPI and VDI, especially at lower activation pressures with additional removal of electronic noise.
Comparative study of the effects of three data‐interpretation methodologies on the performance of geotechnical back analysis
Authors: Wang Ze‐Zhou , Goh Siang Huat , Koh Chan Ghee , Smith Ian F.C. 
Published: July 2020

SummaryBack analysis can provide engineers with important information for better decision‐making. Over the years, research on back analysis has focused mainly on optimisation techniques, while comparative studies of data‐interpretation methodologies have seldom been reported. This paper examines the use of three data‐interpretation methodologies on the performance of geotechnical back analysis. In general, there are two types of approaches for interpreting model predictions using field measurements, deterministic versus population‐based, both of which are considered in this study. The methodologies that are compared are (a) error‐domain model falsification (EDMF), (b) Bayesian model updating and (c) residual minimisation. Back analyses of an excavation case history in Singapore using the three methodologies indicate that each has strengths and limitations. Residual minimisation, though easy to implement, shows limited capabilities of interpreting measurement data with large uncertainty errors. EDMF provides robustness against incomplete information of the correlation structure. This is achieved at the expense of precision, as EDMF yields wider confidence intervals of the identified parameter values and predicted quantities compared with Bayesian model updating. In this regard, a modified EDMF implementation is proposed, which can improve upon the limitations of the traditional EDMF method, thus enhancing the quality of the identification outcomes.
Is absorbable suture superior to permanent suture for uterosacral ligament suspension?
Authors: Peng Liao , Liu Yu‐hao , He Shi‐xin , Di Xing‐peng , Shen Hong , Luo De‐yi 
Published: July 2020

AbstractAimsThe aims of this study were to compare surgical results and suture‐related complications after uterosacral ligament suspension (USLS) with absorbable suture (AS) vs permanent suture (PS).MethodsWe systematically searched PubMed, Embase, clinicalTrial.gov, and Cochrane Library Central Register of Controlled Trials for articles that compared AS with PS for USLS. The primary outcomes were surgical success rate and suture‐related complications (suture exposure/erosion and suture removal). Review Manager 5.3 (Cochrane Collaboration, Oxford, UK) was applied to conduct all analyses.ResultsFour articles involving 647 patients were eventually included. Our findings demonstrated that AS had a similar surgical success rates in comparison with PS (RR = 1.00; 95% CI, 0.94‐1.06) and that no significant differences in anatomic failure rates were noted between two groups (RR = 1.10; 95% CI, 0.65‐1.86). Subgroup analyses in anatomic failure revealed no statistical differences in apical prolapse ≥1/2 TVL (RR = 0.92; 95% CI, 0.48‐1.75), recurrent prolapse beyond the hymen (RR = 1.18; 95% CI, 0.68‐2.04), as well as in recurrent anterior, posterior or apical prolapse (P = .14, P = .08, P = .09, respectively). However, AS group indicated a lower risk in suture exposure/erosion (RR = 0.31; 95% CI, 0.15‐0.63) and lower suture removal rate (RR = 0.35; 95% CI, 0.18‐0.67).ConclusionsDue to similar surgical results, less suture exposure/erosion and less suture removal, the current data supported that AS is as effective as PS, but with a better safety profile.
In situ adaptive reduction of nonlinear multiscale structural dynamics models
Authors: He Wanli , Avery Philip , Farhat Charbel 
Published: July 2020

SummaryConventional offline training of reduced‐order bases in a predetermined region of a parameter space leads to parametric reduced‐order models that are vulnerable to extrapolation. This vulnerability manifests itself whenever a queried parameter point lies in an unexplored region of the parameter space. This article addresses this issue by presenting an in situ, adaptive framework for nonlinear model reduction where computations are performed by default online and shifted offline as needed. The framework is based on the concept of a database of local reduced‐order bases (ROBs), where locality is defined in the parameter space of interest. It achieves accuracy by updating on‐the‐fly a precomputed ROB and approximating the solution of a dynamical system along its trajectory using a sequence of most appropriate local ROBs. It achieves efficiency by managing the dimension of a local ROB and incorporating hyperreduction in the process. While sufficiently comprehensive, the framework is described in the context of dynamic multiscale computations in solid mechanics. In this context, even in a nonparametric setting of the macroscale problem and when all offline, online, and adaptation overhead costs are accounted for, the proposed computational framework can accelerate a single three‐dimensional, nonlinear, multiscale computation by an order of magnitude, without compromising accuracy.
A Factorial Experiment to Optimize Remotely Delivered Behavioral Treatment for Obesity: Results of the Opt‐IN Study
Authors: Spring Bonnie , Pfammatter Angela F. , Marchese Sara H. , Stump Tammy , Pellegrini Christine , McFadden H. Gene , Hedeker Donald , Siddique Juned , Jordan Neil , Collins Linda M. 
Published: July 2020

ObjectiveIntensive behavioral obesity treatments face scalability challenges, but evidence is lacking about which treatment components could be cut back without reducing weight loss. The Optimization of Remotely Delivered Intensive Lifestyle Treatment for Obesity (Opt‐IN) study applied the Multiphase Optimization Strategy to develop an entirely remotely delivered, technology‐supported weight‐loss package to maximize the amount of weight loss attainable for ≤$500.MethodsSix‐month weight loss was examined among adults (N = 562) with BMI ≥ 25 who were randomly assigned to conditions in a factorial experiment crossing five dichotomous treatment components set to either low/high (12 vs. 24 coaching calls) or off/on (primary care provider reports, text messaging, meal replacements, and buddy training).ResultsAbout 84.3% of participants completed the final assessment. The treatment package yielding maximum weight loss for ≤$500 included 12 coaching calls, buddy training, and primary care provider progress reports; produced average weight loss of 6.1 kg, with 57.1% losing ≥5% and 51.8% losing ≥7%; and cost $427 per person. The most expensive candidate‐treatment component (24 vs. 12 coaching calls) was screened out of the optimized treatment package because it did not increase weight loss.ConclusionsSystematically testing each treatment component’s effect on weight loss made it possible to eliminate more expensive but less impactful components, yielding an optimized, resource‐efficient obesity treatment for evaluation in a randomized controlled trial.