bluuebunny/crossref_metadata_2025 huggingface dataset:
Zebrafish: An emerging model system to study liver diseases and related drug discovery
Authors: Katoch Swati , Patial Vikram
Published: July 2020

The zebrafish has emerged as a powerful vertebrate model for studying liver‐associated disorders. Liver damage is a crucial problem in the process of drug development and zebrafish have proven to be an important tool for the high‐throughput screening of drugs for hepatotoxicity. Although the structure of the zebrafish liver differs to that of mammals, the fundamental physiologic processes, genetic mutations and manifestations of pathogenic responses to environmental insults exhibit much similarity. The larval transparency of the zebrafish is a great advantage for real‐time imaging in hepatic studies. The zebrafish has a broad spectrum of cytochrome P450 enzymes, which enable the biotransformation of drugs via similar pathways as mammals, including oxidation, reduction and hydrolysis reactions. In the present review, we appraise the various drugs, chemicals and toxins used to study liver toxicity in zebrafish and their similarities to the rodent models for liver‐related studies. Interestingly, the zebrafish has also been effectively used to study the pathophysiology of nonalcoholic and alcoholic fatty liver disease. The genetic models of liver disorders and their easy manipulation provide great opportunity in the area of drug development. The zebrafish has proven to be an influential model for the hepatic system due to its invertebrate‐like advantages coupled with its vertebrate biology. The present review highlights the pivotal role of zebrafish in bridging the gap between cell‐based and mammalian models.
Chalcogen–mercury bond formation and disruption in model Rabenstein's reactions: A computational analysis
Authors: Madabeni Andrea , Dalla Tiezza Marco , Omage Folorunsho Bright , Nogara Pablo Andrei , Bortoli Marco , Rocha João Batista Teixeira , Orian Laura
Published: July 2020

Methylmercury is a highly toxic compound and human exposure is mainly related to consumption of polluted fish and seafood. The inactivation of thiol‐based enzymes, promoted by the strong affinity binding of electrophilic mercuric ions to thiol and selenol groups of proteins, is likely an important factor explaining its toxicity. A key role is played by the chemistry and reactivity of the mercury–chalcogens bond, particularly HgS and HgSe, which is the focus of this computational work (level of theory: (COSMO)‐ZORA‐BLYP‐D3(BJ)/TZ2P). We analyze nine ligand‐exchange model reactions (the so‐called Rabenstein's reactions) involving an entering ligand (methylchalcogenolate) and a substrate (methylchalcogenolatemethylmercury). Trends in reaction and activation energies are discussed and a change in mechanism is reported for all cases when going from gas phase to water, that is, from a single‐well potential energy surface (PES) to a canonical SN2‐like mechanism. The reasons accounting for the biochemically challenging and desired displacement of methylmercury from a seleno/thiol protein can be found already in these model reactions, as can be seen from the similarities of the ligand exchange reactions in solution in thermodynamics and kinetics.
Laboratory abnormalities and risk factors associated with in‐hospital death in patients with severe COVID‐19
Authors: Chen Xing , Yan Li , Fei Yang , Zhang Chi
Published: July 2020

Background

In the context of the COVID‐19 outbreak of worldwide, we aim to analyze the laboratory risk factors of in‐hospital death in patients with severe COVID‐19.

Methods

All ≥18‐year‐old patients with confirmed severe COVID‐19 admitted to Tongji Hospital (Wuhan, China) from February 3 to February 20, 2020, were retrospectively enrolled and followed up until March 20, 2020. Epidemiological, clinical, laboratory, and treatment data were collected and explored the risk factors associated with in‐hospital death.

Results

A total of 73 severe patients were enrolled in the study, of whom 20 (27%) patients died in hospital during the average 28 days of follow‐up period. The median age of non‐survivors was significantly older than survivors (69 [64‐76.5] years vs 64 [56‐71.3] years, P = .033) and 15 (75%) patients were males. The laboratory abnormalities of non‐survivors mainly presented in serious inflammation response and multiple organ failure, with high levels of cytokines and deranged coagulation parameters. Multivariable regression showed that neutrophil count greater than 4.47 × 109/L (OR, 58.35; 95%CI: 2.16‐1571.69; P = .016), hypersensitivity C‐reactive protein greater than 86.7 mg/L (OR, 14.90; 95%CI: 1.29‐171.10; P = .030), creatine kinase greater than 101 U/L (OR, 161.62; 95%CI: 6.45‐4045.20; P = .002), and blood urea nitrogen greater than 6.7 mmol/L (OR, 11.18; 95%CI: 1.36‐91.62; P = .024) were risk factors for in‐hospital death.

Conclusion

The risk factors of neutrophil count, hypersensitivity C‐reactive protein, creatine kinase, and blood urea nitrogen could help clinicians to early identify COVID‐19 severe patients with poor outcomes on admission. Virus direct attack and cytokine storm play a major role in the death of COVID‐19.
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

Cell 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

The 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

Background

The 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.

Methods

This 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.

Results

From 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).

Conclusions

Malnutrition 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

Recognizing 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.
Color Doppler Ultrasound in Portal Hypertension
Authors: Cannella Roberto , Giambelluca Dario , Pellegrinelli Alice , Cabassa Paolo
Published: July 2020

Portal hypertension is one of the most important causes of morbidity and mortality in cirrhotic patients. A color Doppler evaluation of the left gastric vein (LGV) has proven utility in the prediction of esophageal varices and variceal bleeding in patients with portal hypertension. The purpose of this review is to discuss the ultrasound evaluation, imaging findings, and clinical application of Doppler ultrasound in the assessment of the LGV. Knowledge of the color Doppler technique and imaging findings of the LGV may help clinicians improve the monitoring of portal hypertension and predict patients with a high risk of esophageal varices.
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

Objective

Cone‐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 Design

Case–control study.

Methods

This 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.

Results

A 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.

Conclusions

The three‐dimensional CBCT airway analysis could be used as a useful tool to evaluate upper airway in children with OSA.

Level of Evidence

3 Laryngoscope, 131:680–685, 2021
Orders on computable rings
Authors: Wu Huishan
Published: July 2020

The 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 .
Pricing goods for retailers: A new approach
Authors: Badra Yassine , Gaumont Damien
Published: July 2020

In the retail sector, pricing goods is usually based on practitioner's experiences. Most of the time, the selling price is obtained by multiplying the buying price by an exogenous multiplier. However, There is no particular scientific procedure to determine such a multiplier except from the Lerner index, which is applicable only if the price elasticity of demand is inferior to −1. This paper generalizes the Lerner index to both elastic and inelastic goods by proposing an original model to determine the optimal markup for both static and intertemporal markets no matter what the price elasticity is. Finally, the paper considers the case of the social planner.
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

Objective

The 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).

Background

Chronic 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.

Methods

This 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.

Results

We 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).

Conclusions

The 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

Following 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.
Entropy functionals for finding requirements in hierarchical reaction‐diffusion models for inflammations
Authors: Reisch Cordula , Langemann Dirk
Published: July 2020

Based on an established model for liver infections, we open the discussion on the used reaction terms in the reaction‐diffusion system. The mechanisms behind the chronification of liver infections are widely unknown, therefore we discuss a variety of reaction functions. By using theorems about existence, uniqueness, and nonnegativity, we identify properties of reaction functions which are indispensable to modelling liver infections. We introduce an entropy functional for reaction‐diffusion models of this type, which allows predictions of the longtime behavior of the solutions. As a result, we find more conditions on the reaction functions to derive a model covering different inflammation courses. Finally, we discuss the models in the frame of a hierarchical model family.
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

Purpose

As 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.

Methods

Lipid‐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.

Results

Image 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).

Conclusions

Results 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.
Vascular bed and nerve vessels in the skin biopsy: Beyond intraepidermal nerve fibers
Authors: Nolano Maria , Provitera Vincenzo
Published: July 2020

See article on pages 492–501 in this issue.
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

Back 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

Aims

The 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).

Methods

We 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.

Results

Four 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).

Conclusions

Due 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

Conventional 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

Objective

Intensive 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.

Methods

Six‐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).

Results

About 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.

Conclusions

Systematically 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.
Reference group influences and campaign exposure effects on rhino horn demand: Qualitative insights from Vietnam
Authors: Dang Vu Hoai Nam , Nielsen Martin Reinhardt , Jacobsen Jette Bredahl
Published: July 2020

While considerable effort is invested in rhino horn demand reduction campaigns, it is unclear to what extent users are exposed to and accept the messages in these ads.

We investigate recall as an indicator of exposure and the influence of different reference groups by conducting 50 semi‐structured interviews with self‐reported rhino horn users in Hanoi using an interpretative thematic analysis.

The decision to buy or use rhino horn was almost exclusively influenced by peers with perceived expertise using rhino horn, whereas commonly used deliverers of such campaigns—traditional medicine practitioners, doctors, government officials, business leaders and celebrities—had very little influence.

Campaign exposure was relatively high, but campaign influence low as consumers considered recent demand reduction campaigns and the reference groups delivering the message as well as the implementing organizations unreliable and driven by profit.

Willingness to sign a pledge to refrain from buying, using or gifting rhino horn encouraged by employers or association was relatively high. However, the majority of respondents stated they would not comply with this pledge.

Case studies of users or their next of kin having experienced negative or no effect of rhino horn were suggested possibly effective in reducing demand by consumers themselves.

To increase the acceptance of demand reduction campaigns, organizations could consider forgoing their own branding to reduce distrust in the target audience.

We highlight the importance of conducting formative research using both quantitative and qualitative methods based on interviews with actual rhino horn users. While qualitative studies of motivations by confirmed users entail the risk that they retrospectively explain motivations in order to appear internally consistent with their usage of the product, it provides valuable insight into their self‐image and thereby options for affecting their behaviour.

A free Plain Language Summary can be found within the Supporting Information of this article.
Metro‐SMHOP 01: Metronomics combination with cyclophosphamide‐etoposide and valproic acid for refractory and relapsing pediatric malignancies
Authors: El kababri Maria , Benmiloud Sarra , Cherkaoui Siham , El houdzi Jamila , Maani Khadija , Ansari Nawal , Khoubila Nissrine , Kili Amina , El khorassani Mohammed , Madani Abdellah , Tazi Mohammed Adnane , Ahid Samir , Hessissen Laila , Quessar Asmaa , Harif Mhamed , Khattab Mohammed , André Nicolas
Published: July 2020

Background

In low‐ and middle‐income countries, therapeutic options for advanced, refractory, or relapsing malignancies are limited due to local constraints such as cost of drugs, distance from oncology centers, and lack of availability of new anticancer drugs. Metronomics, which combines metronomic chemotherapy (MC) and drug repositioning, allows for the provision of new therapeutic options for patients in this setting.

Aim of the study

To evaluate the activity and toxicity of a metronomic regimen in Moroccan pediatric patients with refractory or relapsing malignancies.

Patients and methods

From July 2014 to January 2018, patients with refractory/relapsing solid tumors treated in five pediatric oncology centers were consecutively enrolled. The metronomic regimen consisted of 28‐day cycles with daily oral administration of cyclophosphamide (30 mg/m2) from days 1 to 21, together with oral etoposide (25 mg/m2) from days 1 to 21 followed by break of one week and daily valproic acid (20 mg/kg) from days 1 to 28.

Results

Ninety‐eight children (median age, 8 years) were included. Underlying malignancies were neuroblastoma (24 patients), Ewing sarcoma (18), osteosarcoma (14), rhabdomyosarcoma (14), and miscellaneous tumors (28). A total of 557 cycles were given (median: 6; range, 1‐18 cycles). One‐year progression‐free survival of our patients was 19%, and one‐year overall survival was 22%. Complete response was obtained in three cases (3%), partial response in 11 cases (11%), and tumor stabilization for more than six months in 28 cases (28%).

Conclusion

This three‐drug metronomic combination was well tolerated and associated with tumor response and disease stabilization in 42 patients even for a long period.
Structure design and multiobjective optimization of CFRP/aluminum hybrid crash box
Authors: Ma Qihua , Zha Yibin , Dong Boyan , Gan Xuehui
Published: July 2020

To improve the crashworthiness and reduce vehicle weight, a crash box made of carbon fiber reinforced plastics (CFRP)/aluminum (Al) hybrid materials was introduced in the paper. Quasistatic axial compression tests and numerical simulations were conducted for pure Al tubes and CFRP/Al hybrid tubes. The simulation models were validated and were further employed to investigate the effects of geometry, aluminum tube thickness, fiber wrapping angle and CFRP layers on the crashworthiness of the hybrid crash box under axial loading and 30° oblique collision. The multiobjectives were taken to obtain the optimal geometrical dimensions, aluminum tube thickness, wrapping angle, and the number of layers. The crashworthiness of the optimal CFRP/Al hybrid crash box was compared with that of original aluminum crash box. It was found that the mass of the crash box was reduced by 35.21%, while the specific energy absorption (SEA) and mean crushing force (Fmean) were increased by more than 18% and 46%, respectively. The paper was aimed to provide some references for the design and optimization of composite crash box.
Synthesis and fundamental properties of methacrylate polymer containing five‐membered cyclic trithiocarbonate group
Authors: Nishi Masayuki , Komeda Masahiro , Aoyagi Naoto , Yoshida Yoshiaki , Endo Takeshi
Published: July 2020

4‐(1,3‐Dithia‐2‐thioxocyclopenthyl)methacrylate (TCMA), containing the five‐membered trithiocarbonate moiety, was prepared from glycidyl methacrylate (GMA) through 2,3‐epithiopropyl methacrylate (ETMA). At first step, GMA was converted to ETMA by the reaction using thiourea. At second step, ETMA was reacted efficiently with carbon disulfide in the presence of a catalytic amount of 1,2‐dimethyltetrahydropyrimidine to give TCMA. The polymerization of TCMA proceeded under standard radical conditions to give the polymeric TCMA in 94% yield. The copolymerizations of TCMA with ethyl acrylate (EA) or acrylonitrile (AN) were conducted by changing the feed molar ratios of the monomers, in which the corresponding copolymers were obtained in over 83% yields. In addition, the obtained polymers showed the high values of refractive index over ca. 1.6 due to the presence of the cyclic trithiocarbonate structure.
Synthesis of a conjugated polymer for sensing ferric/ferrous cations based on dual responses
Authors: Zhang Yichen , Zhan Hao , Chen Jiajun , Sun Lijuan , Fan Li‐Juan
Published: July 2020

A conjugated polymer (PPETE‐RB) with poly[p‐(phenylene ethynylene)‐alt‐(thienylene‐ethynylene)] (PPETE) as the backbone with pendant rhodamine B (RB) groups in the close‐ring spirolactam form was synthesized. With long spacer between backbone and pedant groups as well as long solubilizing side chains, the polymer possesses good solubility in most organic solvents and relatively large molecular weight. The fluorescence of the conjugated polymer in THF exhibited selective dual responses upon adding Fe3+/Fe2+ but negligible response upon other cations. The emission around 481 nm (excited at 360 nm) decreased and that around 571 nm (excited at 520 nm) emerged and increased when increasing the concentration of iron ions. The responses to Fe3+ and Fe2+ are very similar. The limits of detection were found to fall in between 6 μM and 8 μM. The mechanism study showed that the quenching around 481 nm was due to the inner filter effect (IFE) between the Fe3+/Fe2+ and PPETE‐RB; while that enhancement around 571 nm could be attributed to the formation of fluorescent ring‐open structure from nonfluorescent spirolactam of pedant RB group upon Fe3+/Fe2+. Such dual and opposite responses provided more reliable information than single response for sensing applications.
CXCL12γ induces human prostate and mammary gland development
Authors: Jung Younghun , Kim Jin Koo , Lee Eunsohl , Cackowski Frank C. , Decker Ann M. , Krebsbach Paul H. , Taichman Russell S.
Published: July 2020

Background

Epithelial stem cells (ESCs) demonstrate a capacity to maintain normal tissues homeostasis and ESCs with a deregulated behavior can contribute to cancer development. The ability to reprogram normal tissue epithelial cells into prostate or mammary stem‐like cells holds great promise to help understand cell of origin and lineage plasticity in prostate and breast cancers in addition to understanding normal gland development. We previously showed that an intracellular chemokine, CXCL12γ induced cancer stem cells and neuroendocrine characteristics in both prostate and breast adenocarcinoma cell lines. However, its role in normal prostate or mammary epithelial cell fate and development remains unknown. Therefore, we sought to elucidate the functional role of CXCL12γ in the regulation of ESCs and tissue development.

Methods

Prostate epithelial cells (PNT2) or mammary epithelial cells (MCF10A) with overexpressed CXCL12γ was characterized by quantitative real‐time polymerase chain reaction, Western blots, and immunofluorescence for lineage marker expression, and fluorescence activated cell sorting analyses and sphere formation assays to examine stem cell surface phenotype and function. Xenotransplantation animal models were used to evaluate gland or acini formation in vivo.

Results

Overexpression of CXCL12γ promotes the reprogramming of cells with a differentiated luminal phenotype to a nonluminal phenotype in both prostate (PNT2) and mammary (MCF10A) epithelial cells. The CXCL12γ‐mediated nonluminal type cells results in an increase of epithelial stem‐like phenotype including the subpopulation of EPCAMLo/CD49fHi/CD24Lo/CD44Hi cells capable of sphere formation. Critically, overexpression of CXCL12γ promotes the generation of robust gland‐like structures from both prostate and mammary epithelial cells in in vivo xenograft animal models.

Conclusions

CXCL12γ supports the reprogramming of epithelial cells into nonluminal cell‐derived stem cells, which facilitates gland development.
Composting susceptible fruit wastes reduces Drosophila suzukii (Diptera: Drosophilidae) reproductive habitat
Authors: Hooper Holly , Grieshop Matthew J
Published: July 2020

BACKGROUND

Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) is an invasive, polyphagous vinegar fly pest that is primarily controlled by calendar‐based broad‐spectrum insecticide programs. Nonchemical management tactics are urgently needed to reestablish IPM within affected berry and cherry cropping systems. Composting is a post‐harvest crop sanitation strategy that could potentially be used to manage D. suzukii infestation of fruit wastes.

RESULTS

This study found that D. suzukii emergence decreased exponentially with an increasing proportion of chicken manure, with emergence reduced by 95% in compost treatments containing 25% chicken manure. Furthermore, Drosophila melanogaster (Meigen) (Diptera: Drosophilidae) demonstrated a response similar to D. suzukii in the field.

CONCLUSION

Integrating this control tactic into existing D. suzukii management programs may help to reduce the need for insecticide applications for D. suzukii as well as provide improved management of other Drosophila spp. in post‐harvest systems.
Median control charts for monitoring asymmetric quality characteristics double bounded
Authors: Lima‐Filho Luiz M. A. , Bourguignon Marcelo , Ho Linda L. , Fernandes Fidel Henrique
Published: July 2020

In many practical situations, the quality characteristics of interest assume values in the range (0,1), like rates and proportions (but they are not results from Bernoulli experiments). Most control charts built for these quality characteristics rely on monitoring parameters of their probability distribution functions or on their averages after some reparameterization of their density probability function. However, for highly asymmetric distributions, the median is a more appropriate location parameter than the average. In this paper, we propose Shewhart‐type control charts for monitoring the median of observations taken from quality characteristics double bounded after reparameterization of two probability density functions: Kumaraswamy and unit Weibull. The performance of the control charts is evaluated and compared in terms of run length (RL) analysis considering three estimators for the median. Finally, we also carry out two applications to demonstrate the applicability of these control charts.
A method for stable carbon isotope measurement of underivatized individual amino acids by multi‐dimensional high‐performance liquid chromatography and elemental analyzer/isotope ratio mass spectrometry
Authors: Sun Yuchen , Ishikawa Naoto F. , Ogawa Nanako O. , Kawahata Hodaka , Takano Yoshinori , Ohkouchi Naohiko
Published: July 2020

Rationale

To achieve better precision and accuracy for δ13C analysis of individual amino acids (AAs), we have developed a new analytical method based on multi‐dimensional high‐performance liquid chromatography (HPLC) and elemental analyzer/isotope ratio mass spectrometry (EA/IRMS). Unlike conventional methods using gas chromatography, this approach omits pre‐column chemical derivatization, thus reducing systematic errors associated with the isotopic measurement.

Methods

The separation and isolation of individual AAs in a standard mixture containing 15 AAs and a biological sample, spear squid (Heterololigo bleekeri) were performed. AAs were isolated using an HPLC system equipped with a reversed‐phase column and a mixed‐mode column and collected using a fraction collector. After the chromatographic separation and further post‐HPLC purification, the δ13C values of AAs were measured by EA/IRMS.

Results

The complete isolation of all 15 AAs in the standard mixture was achieved. The δ13C values of these AAs before and after the experiment were in good agreement. Also, 15 AAs in the biological sample, H. bleekeri, were successfully measured. The δ13C values of AAs in H. bleekeri varied by as much as 30‰ with glycine being most enriched in13C.

Conclusions

The consistency between the δ13C values of reference and processed AAs demonstrates that the experimental procedure generates accurate δ13C values unaffected by fractionation effects and contamination. This method is therefore suitable for δ13C analysis of biological samples with higher precision than conventional approaches. We propose this new method as a tool to measure δ13C values of AAs in biological, ecological and biogeochemical studies.
Lessons from dermatology about inflammatory responses in Covid‐19
Authors: Criado Paulo Ricardo , Pagliari Carla , Carneiro Francisca Regina Oliveira , Quaresma Juarez Antonio Simões
Published: July 2020

The SARS‐Cov‐2 is a single‐stranded RNA virus composed of 16 non‐structural proteins (NSP 1‐16) with specific roles in the replication of coronaviruses. NSP3 has the property to block host innate immune response and to promote cytokine expression. NSP5 can inhibit interferon (IFN) signalling and NSP16 prevents MAD5 recognition, depressing the innate immunity. Dendritic cells, monocytes, and macrophages are the first cell lineage against viruses' infections. The IFN type I is the danger signal for the human body during this clinical setting. Protective immune responses to viral infection are initiated by innate immune sensors that survey extracellular and intracellular space for foreign nucleic acids. In Covid‐19 the pathogenesis is not yet fully understood, but viral and host factors seem to play a key role. Important points in severe Covid‐19 are characterized by an upregulated innate immune response, hypercoagulopathy state, pulmonary tissue damage, neurological and/or gastrointestinal tract involvement, and fatal outcome in severe cases of macrophage activation syndrome, which produce a ‘cytokine storm’. These systemic conditions share polymorphous cutaneous lesions where innate immune system is involved in the histopathological findings with acute respiratory distress syndrome, hypercoagulability, hyperferritinemia, increased serum levels of D‐dimer, lactic dehydrogenase, reactive‐C‐protein and serum A amyloid. It is described that several polymorphous cutaneous lesions similar to erythema pernio, urticarial rashes, diffuse or disseminated erythema, livedo racemosa, blue toe syndrome, retiform purpura, vesicles lesions, and purpuric exanthema or exanthema with clinical aspects of symmetrical drug‐related intertriginous and flexural exanthema. This review describes the complexity of Covid‐19, its pathophysiological and clinical aspects.