bluuebunny/crossref_metadata_2025 huggingface dataset:
Level of Physical Activity at Lebanese Universities’ Students of Both Genders: A Comparative Study
Authors: Fayyad Fadi , Dopsaj Milivoj
Published: September 2021

Background: Examining students’ levels of physical activity is important because these students will be the future leaders of their communities. Objectives: The aim of this study was to generate primary information and describe the lifestyle behavior patterns considering physical activity prevalence among gender-related Lebanese college students. Methods: The study involved 600 students (346 Men, 254 Women with mean age 23.5 ± 3.96). The participants’ levels of physical activity was examined by utilizing the International Physical Activity Questionnaire (IPAQ). The over-all level of physical activity including the four-lifestyle fields: work, transportation, home and gardening, and leisure-time, was presented as metabolic equivalent-min per week (MET-min/week). Results: Findings indicated 22% of students with high physical activity level, 61% and 17 % with moderate and low levels respectively. Based on activity Intensity, 47% (n= 282) of students were engaged in vigorous activity, while 45.2% (n= 271) were engaged in moderate activity, and 68.3% (n=410) were engaged in walking activities. Average time spent sitting for the whole sample was 6.23 daily hours. The level of weekly total physical activity expressed in metabolic equivalent represented 2970.5 MET/min/week in males and 2719.5 MET/min/week in females. Conclusion: In general, Lebanese universities students were equally active, with trivial supremacy for males. Lebanese university students met the (WHO) recommendations for physical activity (>150 min/week of moderate activity or > 75 min/week of vigorous activity or an equivalent combination of both activities). Physical Activity must be developed by the provision of physical activity classes in the university curriculum and extracurricular activities.
The Effect of Perfectionism on Workflow Experience: The Mediating Role of Proactive Personality and Generalized Anxiety Disorder
Authors: Yesiltas Meryem Derya , Andic Sezin
Published: September 2021

Workflow experience, proactive personality, perfectionism and generalized anxiety disorder, which play an important role in the productivity, performance and happiness of employees, are the focus of this study. The aim of the study is to examine the relationships between these variables, as well as to determine the mediating role of proactive personality and generalized anxiety disorder in the effect of perfectionism on work flow experience. Data were collected from public (58.4%) and private sector (41.6%) employees in order to find an answer to the research question created in line with the purpose of the study and to test the hypotheses. Data collection tools include the Work Related Flow Inventory (WOLF), Proactive Personality Scale, Perfectionism Scale, Generalized Anxiety Disorder Scale, as well as a personal information form. Pearson Correlation analysis and SPSS Process Macro regression analyzes were conducted to examine the relationships between the variables. Research findings show that there are significant relationships between employees' proactive personality traits, generalized anxiety disorder, and workflow experiences. The perfectionism level of employees is significantly related to proactive personality and work flow experience. In addition, it has been revealed that proactive personality trait and generalized anxiety disorder symptoms have serial multiple mediation effects on the relationship between employees' perfectionism levels and workflow experiences. It is thought that the present study will contribute to both the relevant literature and practitioners in terms of determining the antecedents of the workflow experience by examining the variables of perfectionism, proactive personality traits, generalized anxiety disorder and workflow experience together. Keywords: Workflow experience, proactive personality, perfectionism, anxiety, employee
Self‐Driven Droplet Vehicle for Material Patterning
Authors: Li Zheng , Li Huizeng , Li An , Liu Zhaoxin , Zhang Zeying , Li Kaixuan , Qiao Yali , Song Yanlin
Published: September 2021

Anisotropic dewetting is an important physical phenomenon, which manipulates the process of liquid transport and material deposition. However, the anisotropic dewetting process is usually dependent on artificial templates and designed substrates. Herein, a unique anisotropic dewetting system of the self‐driven droplet vehicle is revealed, driven by the Marangoni effect among inter‐droplets, to fabricate patterned materials. The droplet vehicle is made up of two miscible droplets but with different surface tension through the spontaneous assembly process induced by vapors. The motion of the droplet vehicle is controlled by the surface tension coefficient, and it can fabricate parallel lines of materials at the same time. Combining the droplet vehicle with superhydrophilic‐hydrophobic patterned substrates, the millimeter‐scale droplet can produce various micrometer‐scale lines of materials in tens of seconds. The understanding and founding of the self‐driven droplet vehicle may develop a new strategy for liquid transport and functional materials patterning.
The costs of developing treatments for Alzheimer's disease: A retrospective exploration
Authors: Cummings Jeffrey L. , Goldman Dana P. , Simmons‐Stern Nicholas R. , Ponton Eric
Published: September 2021

Introduction

With the exception of the recent accelerated approval of aducanumab, in over 26 years of research and development (R&D) investment in Alzheimer's disease (AD), only five novel drugs—all for symptomatic treatment only—have reached FDA approval. Here, we estimate the costs of AD drug development during this period in the private sector.

Methods

To estimate private R&D funding, we collected information on AD clinical trials (n = 1099; phases 1–4) conducted between January 1, 1995 and June 21, 2021 from various databases. Costs were derived using previously published methodologies and adjusted for inflation.

Results

Since 1995, cumulative private expenditures on clinical stage AD R&D were estimated at $42.5 billion, with the greatest costs (57%; $24,065 million) incurred during phase 3; approximately 184,000 participants were registered or are currently enrolled in clinical trials.

Discussion

Measures to reduce expenditures while moving toward disease‐modifying therapies that alleviate the rising burden of AD require continued investment from industry, government, and academia.
Current directions in tau research: Highlights from Tau 2020
Authors: Sexton Claire , Snyder Heather , Beher Dirk , Boxer Adam L. , Brannelly Pat , Brion Jean‐Pierre , Buée Luc , Cacace Angela M. , Chételat Gaël , Citron Martin , DeVos Sarah L. , Diaz Kristophe , Feldman Howard H. , Frost Bess , Goate Alison M. , Gold Michael , Hyman Bradley , Johnson Keith , Karch Celeste M. , Kerwin Diana R. , Koroshetz Walter J. , Litvan Irene , Morris Huw R. , Mummery Catherine J. , Mutamba James , Patterson Marc C. , Quiroz Yakeel T. , Rabinovici Gil D. , Rommel Amy , Shulman Melanie B. , Toledo‐Sherman Leticia M. , Weninger Stacie , Wildsmith Kristin R. , Worley Susan L. , Carrillo Maria C.
Published: September 2021

Studies supporting a strong association between tau deposition and neuronal loss, neurodegeneration, and cognitive decline have heightened the allure of tau and tau‐related mechanisms as therapeutic targets. In February 2020, leading tau experts from around the world convened for the first‐ever Tau2020 Global Conference in Washington, DC, co‐organized and cosponsored by the Rainwater Charitable Foundation, the Alzheimer's Association, and CurePSP. Representing academia, industry, government, and the philanthropic sector, presenters and attendees discussed recent advances and current directions in tau research. The meeting provided a unique opportunity to move tau research forward by fostering global partnerships among academia, industry, and other stakeholders and by providing support for new drug discovery programs, groundbreaking research, and emerging tau researchers. The meeting also provided an opportunity for experts to present critical research‐advancing tools and insights that are now rapidly accelerating the pace of tau research.
Copper Pairing in the Mordenite Framework as a Function of the CuI/CuII Speciation
Authors: Deplano Gabriele , Martini Andrea , Signorile Matteo , Borfecchia Elisa , Crocellà Valentina , Svelle Stian , Bordiga Silvia
Published: September 2021

A series of gas‐phase reactants is used to treat a Cu‐exchanged mordenite zeolite with the aim of studying the influence of the reaction environment on the formation of Cu pairs. The rearrangement of Cu ions to form multimeric sites as a function of their oxidation state was probed by X‐ray absorption spectroscopy (XAS) and also by applying advanced analysis through wavelet transform, a method able to specifically locate Cu–Cu interactions also in the presence of overlapping contributions from other scattering paths. The nature of the Cu‐oxo species formed upon oxidation was further crosschecked by DFT‐assisted fitting of the EXAFS data and by resonant Raman spectroscopy. Altogether, the CuI/CuII speciation clearly correlates with Cu proximity, with metal ion pairs quantitatively forming under an oxidative environment.
An Effective Strategy for Designing Nonlinear Optical Crystals by Combining the Structure‐Directing Property of Oxyfluorides with Chemical Substitution
Authors: Hou Ying , Wu Hongping , Yu Hongwei , Hu Zhanggui , Wang Jiyang , Wu Yicheng
Published: September 2021

Rationally designing a high‐performance nonlinear optical (NLO) crystal remains a great ongoing challenge. It involves not only the design of noncentrosymmetric structures but also property optimization. In this communication, a new strategy for effectively designing the NLO crystal has been put forward, that is, using the structure‐directing property of oxyfluoride anions to obtain a noncentrosymmetric and polar structure, and then by substitution of IO3− for isovalent F− anions to further enhance the SHG response. With this strategy, a new iodate fluoride, Ba2[MoO3F(IO3)](MoO3F2) has been successfully designed from the Ba2(MoO3F2)F2 with the cis‐directing [MoO4F2]4− groups. It exhibits a large SHG response (≈8×KDP), a wide transparent region (0.30–10.92 μm), a high laser‐induced damage threshold (LDT) (88.53 MW cm−2), and a large birefringence (≈0.264@532 nm). These indicate Ba2[MoO3F(IO3)](MoO3F2) would be a promising NLO crystal.
Solvation Effect on the Improved Sodium Storage Performance of N‐Heteropentacenequinone for Sodium‐Ion Batteries
Authors: Sun Tao , Feng Xi‐Lan , Sun Qi‐Qi , Yu Yue , Yuan Guo‐Bao , Xiong Qi , Liu Da‐Peng , Zhang Xin‐Bo , Zhang Yu
Published: September 2021

The performance of electrode material is correlated with the choice of electrolyte, however, how the solvation has significant impact on electrochemical behavior is underdeveloped. Herein, N‐heteropentacenequinone (TAPQ) is investigated to reveal the solvation effect on the performance of sodium‐ion batteries in different electrolyte environment. TAPQ cycled in diglyme‐based electrolyte exhibits superior electrochemical performance, but experiences a rapid capacity fading in carbonate‐based electrolyte. The function of solvation effect is mainly embodied in two aspects: one is the stabilization of anion intermediate via the compatibility of electrode and electrolyte, the other is the interfacial electrochemical characteristics influenced by solvation sheath structure. By revealing the failure mechanism, this work presents an avenue for better understanding electrochemical behavior and enhancing performance from the angle of solvation effect.
Property enhancement in flexible poly(vinylidene fluoride)‐based piezoelectric films with large‐area preparation
Authors: Zhang Chao , Yu Honglin , Sun Huajun , Zhu Quanyao
Published: September 2021

Poly(vinylidene fluoride) (PVDF)‐based film exhibits high degrees of electromechanical coupling, widely applied as flexible piezoelectric sensors, soft robotics, energy harvesters, and actuators. In this article, five different types of PVDF‐based piezoelectric films were prepared by the extrusion‐casting process. The mechanical, dielectric, ferroelectric, piezoelectric, and electrically induced deformation properties of different films were studied. It is found that the addition of lead zirconate titanate (PZT) can improve the dielectric constant of piezoelectric films. PZT powders modified by titanate coupling reagent (UP‐105) can further improve the mechanical and electrical properties of composite films by improving the combination and dispersion of organic and inorganic phases. The addition of boron nitride nanosheets can effectively inhibit the generation of leak current, especially at high temperatures. The piezoelectric coefficients (d33) of composite films can reach up to 21pC/N, and its strain ratio is about 0.6% under the electric field intensity of 200 kV/mm.
Integrated analysis identifies a novel lncRNA prognostic signature associated with aerobic glycolysis and hub pathways in breast cancer
Authors: Li Zheng , Zheng Juan , Feng Yang , Li Yaming , Liang Yiran , Liu Ying , Wang Xiaolong , Yang Qifeng
Published: September 2021

Long noncoding RNAs (lncRNAs) play a crucial role in cancer aerobic glycolysis. However, glycolysis‐related lncRNAs are still underexplored in breast cancer. In this study, we identified the five most glycolysis‐related lncRNAs in breast cancer to construct a prognostic signature, which could distinguish between patients with unfavorable and favorable prognoses. To investigate the role of signature lncRNAs in breast cancer, we profiled their expression levels in breast cancer progression cell line model. Real‐time PCR revealed that the five lncRNAs could contribute to breast cancer initiation or progression. Furthermore, we observed that the levels of four lncRNAs expression had a significant trend of gradient upregulation with the addition of glycolysis inhibitor in breast cancer cells. Afterward, random forest and logistic regression were conducted to assess the model's performance in stratifying glycolysis status. Finally, a nomogram including the lncRNA signature and clinical features was developed, and its efficacy in predicting the survival time and clinical utility was evaluated using a calibration curve, concordance index, and decision curve analysis. In this study, gene set enrichment analysis showed that the mTOR pathway, a central pathway in tumor initiation and progression, was significantly enriched in the high‐risk group. In addition, gene set variation analysis was performed to validate our findings in two independent datasets. Subsequent weighted gene co‐expression network analysis, followed by enrichment analysis, indicated that downstream cell growth‐related signaling was strikingly activated in the high‐risk group, and may directly promote tumor progression and escalate mortality risk in patients with high‐risk scores. Overall, our findings may provide novel insight into lncRNA‐related metabolic regulation, and help to develop promising prognostic indicators and therapeutic targets for breast cancer patients.
The Diverse Antimicrobial Activities of Human Milk Oligosaccharides against Group B Streptococcus
Authors: Moore Rebecca E. , Townsend Steven D. , Gaddy Jennifer A.
Published: September 2021

Streptococcus agalactiae or Group B Streptococcus (GBS) is a Gram‐positive bacterial pathobiont that is the etiological cause of severe perinatal infections. GBS can colonize the vagina of pregnant patients and invade tissues causing ascending infections of the gravid reproductive tract that lead to adverse outcomes including preterm birth, neonatal sepsis, and maternal or fetal demise. Additionally, transmission of GBS during labor or breastfeeding can also cause invasive infections of neonates and infants. However, human milk has also been shown to have protective effects against infection; a characteristic that is likely derived from antimicrobial and immunomodulatory properties of molecules that comprise human milk. Recent evidence suggests that human milk oligosaccharides (HMOs), short‐chain sugars that comprise 8–20 % of breast milk, have antimicrobial and anti‐biofilm activity against GBS and other bacterial pathogens. Additionally, HMOs have been shown to potentiate the activity of antibiotics against GBS. This review presents the most recent published work that studies the interaction between HMOs and GBS.
Redox‐active BIAN‐based Diimine Ligands in Metal‐Catalyzed Small Molecule Syntheses**
Authors: Bernauer Josef , Pölker Jennifer , Jacobi von Wangelin Axel
Published: September 2021

α‐Diimine ligands have significantly shaped the coordination chemistry of most transition metal complexes. Among them, bis(imino)acenaphthene ligands (BIANs) have recently been matured to great versatility and applicability to catalytic reactions. Besides variations of the ligand periphery, the great versatility of BIAN ligands resides within their ability to undergo facile electronic manipulations. This review highlights key aspects of BIAN ligands in metal complexes and summarizes recent contributions of metal‐BIAN catalysts to syntheses of small and functionalized organic molecules.
Spin‐Phonon Coupling and Slow‐Magnetic Relaxation in Pristine Ferrocenium
Authors: Amoza Martín , Maxwell Lindley , Aliaga‐Alcalde Núria , Gómez‐Coca Silvia , Ruiz Eliseo
Published: September 2021

We report the spin dynamic properties of non‐substituted ferrocenium complexes. Ferrocenium shows a field‐induced single‐molecule magnet behaviour in DMF solution while cobaltocene lacks slow spin relaxation neither in powder nor in solution. Multireference quantum mechanical calculations give a non‐Aufbau orbital occupation for ferrocenium with small first excitation energy that agrees with the relatively large measured magnetic anisotropy for a transition metal S=1/2 system. The analysis of the spin relaxation shows an important participation of quantum tunnelling, Raman, direct and local‐mode mechanisms which depend on temperature and the external field conditions. The calculation of spin‐phonon coupling constants for the vibrational modes shows that the first vibrational mode, despite having a low spin‐phonon constant, is the most efficient process for the spin relaxation at low temperatures. In such conditions, vibrational modes with higher spin‐phonon coupling constants are not populated. Additionally, the vibrational energy of this first mode is in excellent agreement with the experimental fitted value obtained from the local‐mode mechanism.
Tailoring the Properties of Optical Force Probes for Polymer Mechanochemistry
Authors: He Siyang , Stratigaki Maria , Centeno Silvia P. , Dreuw Andreas , Göstl Robert
Published: September 2021

The correlation of mechanical properties of polymer materials with those of their molecular constituents is the foundation for their holistic comprehension and eventually for improved material designs and syntheses. Over the last decade, optical force probes (OFPs) were developed, shedding light on various unique mechanical behaviors of materials. The properties of polymers are diverse, ranging from soft hydrogels to ultra‐tough composites, from purely elastic rubbers to viscous colloidal solutions, and from transparent glasses to super black dyed coatings. Only very recently, researchers started to develop tailored OFP solutions that account for such material requirements in energy (both light and force), in time, and in their spatially detectable resolution. We here highlight notable recent examples and identify future challenges in this emergent field.
Triptycene derivatives as chiral probes for studying the molecular enantiorecognition on sub‐2‐μm particle cellulose tris(3,5‐dimethylphenylcarbamate) chiral stationary phase
Authors: Rosetti Alessia , Preda Giovanni , Villani Claudio , Pierini Marco , Pasini Dario , Cirilli Roberto
Published: September 2021

Two chiral triptycene derivatives were analyzed on the Chiralpak IB‐U column packed with cellulose tris(3,5‐dimethylphenylcarbamate)‐based sub‐2‐μm diameter particles. Under normal‐phase conditions, sub‐minute baseline enantioseparations were obtained. Differences in structural elements and chromatographic behavior of the investigated compounds were evaluated to identify the interactions that drive the chiral discrimination process. From the evaluation of the experimental chromatographic data, it was found that hydrogen bond formation is essential for the separation of enantiomers.
Metallacycle Expansion and Annulation: Access to Tetrazolo‐Fused Osmacycles by Reaction of Cyclic Osmium Carbyne with Sodium Azide
Authors: Wang Hongjian , Lin Yu‐Mei , Chen Siyuan , Ruan Yonghong , Xia Haiping
Published: September 2021

Main observation and conclusion

The reaction of a cyclic osmacarbyne complex with sodium azide led to the formation of a ring expansion‐annulation product, a unique tetrazole annulated polycyclic metallacycle. The reaction proceeds by insertion of a nitrogen atom into the metal carbon triple bond and the second azide participating in the [2+3] cycloaddition. The successful isolation and characterization of metalla‐azirine complex and metallapyridinium derivative strongly validated the mechanism for the formation of the title complex. The work demonstrates a new strategy to enrich the varieties of aza‐metallacyclic species.
Development of a blended learning course for teacher training with digital and analogue content as part of Experimento|10+
Authors: Knie Lisa , Schwarzer Stefan
Published: September 2021

Mit der Weiterentwicklung der Lehrkräftefortbildung Experimento | 10+ der Siemens Stiftung wird ein neuartiges Bildungsprogramm vorgestellt, das sowohl in der Lernform als auch inhaltlich die Chancen der Digitalität nutzt: Es wechseln sich in einem Blended‐Learning‐Format digitale und analoge Experimentierphasen ab, wobei die digitalen Phasen über Online‐Selbstlern‐Module realisiert werden. Die Themenmodule Wertebildung, Inklusion und sprachsensibler Fachunterricht sowie Computational Thinking sind für die Lehrkräfte während der zweitägigen Fortbildung fakultativ. Während der Präsenzveranstaltungen liegt ein besonderer Fokus auf der Erprobung von Experimenten zu den Themenbereichen Energie, Umwelt und Gesundheit, welche sich im Besonderen für den Einsatz im Chemieunterricht eignen. Im vorliegenden Beitrag wird vor allem die Gestaltung der Online‐Module näher vorgestellt, welche über das Medienportal der Siemens Stiftung verfügbar sind.
On Ill‐ and Well‐Posedness of Dissipative Martingale Solutions to Stochastic 3D Euler Equations
Authors: Hofmanová Martina , Zhu Rongchan , Zhu Xiangchan
Published: September 2021

We are concerned with the question of well‐posedness of stochastic, three‐dimensional, incompressible Euler equations. In particular, we introduce a novel class of dissipative solutions and show that (i) existence; (ii) weak–strong uniqueness; (iii) nonuniqueness in law; (iv) existence of a strong Markov solution; (v) nonuniqueness of strong Markov solutions: all hold true within this class. Moreover, as a by‐product of (iii) we obtain existence and nonuniqueness of probabilistically strong and analytically weak solutions defined up to a stopping time and satisfying an energy inequality. © 2021 Wiley Periodicals LLC.
Mobility speed prediction using ARIMA and RNN for random walk mobility model in mobile ad hoc networks
Authors: Theerthagiri Prasannavenkatesan , Thangavelu Menakadevi
Published: September 2021

In this article, an auto‐regressive integrated moving average (ARIMA) modeling has been proposed to predict the mobility speed of the nodes in the mobile ad hoc networks (MANETs). The mobility speed prediction supports effective route discovery to enhance efficient and reliable routing. The random walk mobility model had been used to forecast the mobility of the nodes. Subsequently, various the recurrent neural network (RNN) model has been developed with different number hidden neurons, and the prediction results are compared with proposed ARIMA based results. The Akaike information criterion, auto‐correlation function metrics are evaluated to assess the dataset's quality. Several network scenarios are evaluated with various speeds and the number of nodes. The results of the proposed ARIMA model are compared with the RNN results. It demonstrates that the proposed model has higher prediction rates with reduced error rates of 0.1%–1.4% than RNN values. Such that the proposed methods facilitate the higher prediction rate of 10%–26% as compared with the RNN. Therefore, the proposed mobility speed prediction techniques support the effective routing in the MANETs.
TPMT and NUDT15 Variants Predict Discontinuation of Azathioprine for Myelotoxicity in Patients with Inflammatory Disease: Real‐World Clinical Results
Authors: Dickson Alyson L. , Daniel Laura L. , Zanussi Jacy , Dale Plummer W. , Wei Wei‐Qi , Liu Ge , Reese Tyler , Anandi Prathima , Birdwell Kelly A. , Kawai Vivian , Cox Nancy J. , Dupont William D. , Hung Adriana M. , Feng QiPing , Stein C. Michael , Chung Cecilia P.
Published: September 2021

Azathioprine is used frequently to treat several inflammatory conditions. However, treatment is limited by adverse events—in particular, myelotoxicity. Thiopurine‐S‐methyltransferase (TPMT) and nudix hydrolase‐15 (NUDT15) are enzymes involved in azathioprine metabolism; variants in the genes encoding these enzymes increase the risk for azathioprine myelotoxicity. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has recommended dose adjustments based on the results of TPMT and NUDT15 genotyping. However, little is known about the importance of this genetic information in routine clinical care. We hypothesized that in patients with inflammatory diseases, TPMT and NUDT15 genotype data predict the risk of discontinuing azathioprine due to myelotoxicity. This was a retrospective cohort study in 1,403 new adult azathioprine users for the management of inflammatory conditions for whom we had genetic information and clinical data. Among patients who discontinued azathioprine, we adjudicated the reason(s). Genotyping was performed using the Illumina Infinium Expanded Multi‐Ethnic Genotyping Array plus custom content. We used CPIC guidelines to determine TPMT and NUDT15 metabolizer status; patients were grouped as either: (i) poor/intermediate, or (ii) normal/indeterminate metabolizers. We classified 110 patients as poor/intermediate, and 1,293 patients as normal/indeterminate metabolizers. Poor/intermediate status was associated with a higher risk for azathioprine discontinuation due to myelotoxicity compared to normal/indeterminate metabolizers (hazard ratio (HR) = 2.90, 95% confidence interval (CI): 1.58–5.31, P = 0.001). This association remained significant after adjustment for race, age at initiation, sex, primary indication, and initial daily dose of azathioprine (adjusted HR (aHR) = 2.67, 95% CI: 1.44–4.94, P = 0.002). In conclusion, TPMT and NUDT15 metabolizer status predicts discontinuation due to myelotoxicity for patients taking azathioprine for inflammatory conditions.
Evaluating patient acceptability and bowel preparation efficacy of sodium picosulfate‐magnesium citrate for colonoscopy
Authors: Shimada Masaaki , Hirashima Noboru , Iwase Hiroaki , Saito Masashi , Kondo Hisashi , Urata Noboru , Unita Satoshi , Kondo Takashi , Tanaka Daiki , Tsunekawa Takuya , Nakamura Sumie , Nishikura Miho , Miyazawa Kaori , Fukuhara Kiyoko , Fujishiro Mitsuhiro
Published: September 2021

Objective

To evaluate patient acceptability and bowel preparation efficacy of sodium picosulfate‐magnesium citrate (PICOPREP) for colonoscopy.

Methods

A questionnaire survey regarding the patient acceptability of bowel preparation agent PICOPREP was administered to 54 patients, and its efficacy was evaluated using the Ottawa Bowel Preparation Scale (OBPS).

Results

Eighteen (33.3%) participants reported that PICOPREP is very easy to drink, 30 (55.5%) easy, four (7.4%) acceptable, one (1.9%) difficult, and one (1.9%) very difficult. The flavor was very good as reported by eight (14.8%) participants, good by 25 (46.3%), neutral by 20 (37.0%), bad by one (1.9%), and very bad by none. The number of patients who requested PICOPREP was 42 (77.7%), indicating its high acceptability. Evaluation of the OBPS score showed that the rectosigmoid colon had significantly better polyethylene glycol (PEG) scores than PICOPREP, but the entire colon did not show a significant difference between PICOPREP and PEG scores (1.09 ± 0.65 vs. 1.17 ± 0.76, p = 0.632 in the right colon; 0.48 ± 0.52 vs. 0.72 ± 0.66, p = 0.079 in the mid colon, 0.93 ± 0.49 vs. 0.63 ± 0.52, p = 0.012 in the rectosigmoid colon, and 3.28 ± 1.70 vs. 3.20 ± 1.90, p = 0.836 in the entire colon).

Conclusion

PICOPREP is considered as one of the important options due to its good patient acceptability and high efficacy similar to PEG.
Demographic risk assessment for a harvested species threatened by climate change: polar bears in the Chukchi Sea
Authors: Regehr Eric V. , Runge Michael C. , Von Duyke Andrew , Wilson Ryan R. , Polasek Lori , Rode Karyn D. , Hostetter Nathan J. , Converse Sarah J.
Published: September 2021

Climate change threatens global biodiversity. Many species vulnerable to climate change are important to humans for nutritional, cultural, and economic reasons. Polar bearsUrsus maritimusare threatened by sea‐ice loss and represent a subsistence resource for Indigenous people. We applied a novel population modeling‐management framework that is based on species life history and accounts for habitat loss to evaluate subsistence harvest for the Chukchi Sea (CS) polar bear subpopulation. Harvest strategies followed a state‐dependent approach under which new data were used to update the harvest on a predetermined management interval. We found that a harvest strategy with a starting total harvest rate of 2.7% (˜85 bears/yr at current abundance), a 2:1 male‐to‐female ratio, and a 10‐yr management interval would likely maintain subpopulation abundance above maximum net productivity level for the next 35 yr (approximately three polar bear generations), our primary criterion for sustainability. Plausible bounds on starting total harvest rate were 1.7–3.9%, where the range reflects uncertainty due to sampling variation, environmental variation, model selection, and differing levels of risk tolerance. The risk of undesired demographic outcomes (e.g., overharvest) was positively related to harvest rate, management interval, and projected declines in environmental carrying capacity; and negatively related to precision in population data. Results reflect several lines of evidence that the CS subpopulation has been productive in recent years, although it is uncertain how long this will last as sea‐ice loss continues. Our methods provide a template for balancing trade‐offs among protection, use, research investment, and other factors. Demographic risk assessment and state‐dependent management will become increasingly important for harvested species, like polar bears, that exhibit spatiotemporal variation in their response to climate change.
Advances in the synthesis and applications of raspberry ketone: A review
Authors: Guo Hui , Chang Sha , Jia Lili , Wang Zuoyao , Zhang Qian , Zhang Guobao
Published: September 2021

Recent advances in the synthesis and applications of raspberry ketone are reviewed in this paper. Different routes to this material including chemical and biotechnological synthetic methods and extraction from natural sources are compared, and the applications of the ketone in flavour and fragrance, pharmaceuticals and in food and tobacco processing are discussed. Synthesis from petrochemical raw materials has the advantages of ready availability of ingredients and well‐understood synthetic steps, but direct synthesis from petrochemicals will eventually be replaced because of low yields and hazardous results to environment. The ketone can be made from natural raw materials, and the methods are promising if their disadvantages such as limited availability and complex, multi‐step reactions and harsh reaction conditions can be overcome. Biotechnological preparation methods have the advantages of reaction specificity, mild reaction conditions, but are limited in applicability because of complications associated with their synthetic and purification procedures at present. With the development of biotechnology, biotechnological preparation methods of the ketone may be the most important route in the future. Direct extraction of the ketone from natural raw materials is possible, but the cost is very high. From the view of syntheses and applications, the research perspectives of raspberry ketone are outlined in the end of this paper, which are the development of green and effective synthetic methods for raspberry ketone from natural raw materials and the preparation and application of raspberry ketone by biotechnological preparation methods.
The zinc finger and BTB domain containing protein ZBTB20 regulates plasma triglyceride metabolism by repressing lipoprotein lipase gene transcription in hepatocytes
Authors: Li Hao , Liu Gan , Wan Xiaoqing , Zhou Luting , Qin Zhen‐Bang , Ma Xian‐Hua , Su Kai , Liu Ya‐Jin , Yuan Jinghao , Wei Chun‐Chun , Ren An‐Jing , Chen Yu‐Xia , Young Stephen G. , Zhang Hai , Xie Zhifang , Zhang Weiping J.
Published: September 2021

Background and Aims

Lipoprotein lipase (LPL) is responsible for the lipolytic processing of triglyceride‐rich lipoproteins, the deficiency of which causes severe hypertriglyceridemia. Liver LPL expression is high in suckling rodents but relatively low at adulthood. However, the regulatory mechanism and functional significance of liver LPL expression are incompletely understood. We have established the zinc finger protein ZBTB20 as a critical factor for hepatic lipogenesis. Here, we evaluated the role of ZBTB20 in regulating liver Lpl gene transcription and plasma triglyceride metabolism.

Approach and Results

Hepatocyte‐specific inactivation of ZBTB20 in mice led to a remarkable increase in LPL expression at the mRNA and protein levels in adult liver, in which LPL protein was mainly localized onto sinusoidal epithelial cells and Kupffer cells. As a result, the LPL activity in postheparin plasma was substantially increased, and postprandial plasma triglyceride clearance was significantly enhanced, whereas plasma triglyceride levels were decreased. The dysregulated liver LPL expression and low plasma triglyceride levels in ZBTB20‐deficient mice were normalized by inactivating hepatic LPL expression. ZBTB20 deficiency protected the mice against high‐fat diet–induced hyperlipidemia without causing excessive triglyceride accumulation in the liver. Chromatin immunoprecipitation and gel‐shift assay studies revealed that ZBTB20 binds to the LPL promoter in the liver. A luciferase reporter assay revealed that ZBTB20 inhibits the transcriptional activity of LPL promoter. The regulation of LPL expression by ZBTB20 is liver‐specific under physiological conditions.

Conclusions

Liver ZBTB20 serves as a key regulator of LPL expression and plasma triglyceride metabolism and could be a therapeutic target for hypertriglyceridemia.
Integration of glucose and cardiolipin anabolism confers radiation resistance of HCC
Authors: Fang Yuan , Zhan Yizhi , Xie Yuwen , Du Shisuo , Chen Yuhan , Zeng Zhaochong , Zhang Yaowei , Chen Keli , Wang Yongjia , Liang Li , Ding Yi , Wu Dehua
Published: September 2021

Background and Aims

Poor response to ionizing radiation (IR) due to resistance remains a clinical challenge. Altered metabolism represents a defining characteristic of nearly all types of cancers. However, how radioresistance is linked to metabolic reprogramming remains elusive in hepatocellular carcinoma (HCC).

Approach and Results

Baseline radiation responsiveness of different HCC cells were identified and cells with acquired radio‐resistance were generated. By performing proteomics, metabolomics, metabolic flux, and other functional studies, we depicted a metabolic phenotype that mediates radiation resistance in HCC, whereby increased glucose flux leads to glucose addiction in radioresistant HCC cells and a corresponding increase in glycerophospholipids biosynthesis to enhance the levels of cardiolipin. Accumulation of cardiolipin dampens the effectiveness of IR by inhibiting cytochrome c release to initiate apoptosis. Mechanistically, mammalian target of rapamycin complex 1 (mTORC1) signaling‐mediated translational control of hypoxia inducible factor‐1α (HIF‐1α) and sterol regulatory element‐binding protein‐1 (SREBP1) remodels such metabolic cascade. Targeting mTORC1 or glucose to cardiolipin synthesis, in combination with IR, strongly diminishes tumor burden. Finally, activation of glucose metabolism predicts poor response to radiotherapy in cancer patients.

Conclusions

We demonstrate a link between radiation resistance and metabolic integration and suggest that metabolically dismantling the radioresistant features of tumors may provide potential combination approaches for radiotherapy in HCC.
MSI2 expression in adrenocortical carcinoma: Association with unfavorable prognosis and correlation with steroid and immune‐related pathways
Authors: Veronez Luciana C. , das Chagas Pablo F. , Corrêa Carolina A. P. , Baroni Mirella , da Silva Keteryne R. , Nagano Luis F. , Borges Kleiton S. , Queiroz Rosane G. P. , Tone Luiz G. , Scrideli Carlos A.
Published: September 2021

Adrenocortical carcinoma (ACC) is a rare, but highly aggressive cancer of the adrenal cortex with a generally poor prognosis. Despite being rare, completely resected ACCs present a high risk of recurrence. Musashi‐2 (MSI2) has recently been recognized as a potential prognostic biomarker and therapeutic target in many cancers. However, no studies have evaluated the clinical significance of MSI2 expression in ACC. Here, we addressed MSI2 expression and its association with ACC prognosis and clinicopathological parameters. MSI2 expression was analyzed in TCGA, GSE12368, GSE33371, and GSE49278 ACC datasets; and its correlation with other genes and immune cell infiltration were investigated by using the R2: Genomics Analysis and Visualization Platform and TIMER databases, respectively. Enrichment analysis was performed with the DAVID Functional Annotation Tool. Kaplan–Meier curves, log‐rank tests, and Cox regression analyses were used to explore the prognostic role of MSI2 in ACC. Our findings demonstrated the potential value of MSI2 overexpression as an independent predictor of poor prognosis in patients with completely resected ACC (hazard ratio 6.715, 95% confidence interval 1.266 – 35.620, p =.025). In addition, MSI2 overexpression was associated with characteristics of unfavorable prognosis, such as cortisol excess (p = .002), recurrence (p =.003), and death (p =.015); positively correlated with genes related to steroid biosynthesis (p < .05); and negatively correlated with immune‐related pathways (p < .05). Our findings demonstrate that MSI2 has value as a prognostic marker for completely resected ACC and reinforce the investigation of its role as a possible therapeutic target for patients with ACC.
Theories, laws, and models in evo‐devo
Authors: Richardson Michael K.
Published: September 2021

Evolutionary developmental biology (evo‐devo) is the study of the evolution of developmental mechanisms. Here, I review some of the theories, models, and laws in evo‐devo, past and present. Nineteenth‐century evo‐devo was dominated by recapitulation theory and archetypes. It also gave us germ layer theory, the vertebral theory of the skull, floral organs as modified leaves, and the “inverted invertebrate” theory, among others. Newer theories and models include the frameshift theory, the genetic toolkit for development, the ABC model of flower development, the developmental hourglass, the zootype, Urbilateria, and the hox code. Some of these new theories show the influence of archetypes and recapitulation. Interestingly, recent studies support the old “primordial leaf,” “inverted invertebrate,” and “segmented head” theories. Furthermore, von Baer's first three laws may now need to be rehabilitated, and the hourglass model modified, in view of what Abzhanov has pointed out about the maternal‐zygotic transition. There are many supposed “laws” of evo‐devo but I argue that these are merely generalizations about trends in particular lineages. I argue that the “body plan” is an archetype, and is often used in such a way that it lacks any scientific meaning. Looking to the future, one challenge for evo‐devo will be to develop new theories and models to accommodate the wealth of new data from high‐throughput sequencing, including single‐cell sequencing. One step in this direction is the use of sophisticated in silico analyses, as in the “transcriptomic hourglass” models.
Post‐treatment clinical course following botulinum toxin injection therapy for adductor spasmodic dysphonia: Analysis of data from a placebo‐controlled, randomized, double‐blinded clinical trial in Japan
Authors: Hirose Kahori , Asano Kento , Sakaguchi Masahiko , Nagao Asuka , Nakahira Maya , Doi Nao , Kobayashi Taisuke , Hyodo Masamitsu
Published: September 2021

Objective

Botulinum toxin (BT) therapy is a first‐line treatment for spasmodic dysphonia (SD). However, a detailed chronological course and clinical factors that affect the therapeutic effect have been vague. In this study, we analyzed the data from our placebo‐controlled, randomized, double‐blinded parallel‐group comparison/open‐label clinical trial of BT (Botox) to clarify these.

Methods

A total of 22 patients with abductor SD (ADSD) were enrolled. The female‐to‐male ratio was 20:2 with a mean age of 40.0 ± 10.3 years and a median duration of symptoms of 7.5 years. The therapeutic effect was evaluated based on the change in the number of aberrant morae (phonemes), GRBAS scale, Voice Handicap Index (VHI), and Visual Analogue Scale (VAS).

Results

The change in the number of aberrant morae peaked at 2 weeks and lasted for 12 weeks in the BT group with significance (P < .01) compared to the placebo group. Objective improvement (number of aberrant morae and [S] element in GRBAS) preceded subjective improvement (VHI and VAS). The change in number of aberrant morae and VHI showed a significant correlation (P < .01). The changes in the number of aberrant morae, VHI, and VAS in younger subjects were greater than in older subjects. Patients who presented with post‐treatment breathy hoarseness or dysphagia showed better therapeutic effects.

Conclusions

BT therapy was effective for ADSD based on both objective and subjective assessments. Improvements in subjective parameters were delayed compared to objective measures due to post‐treatment breathy hoarseness. However, this adverse event was believed to reflect the treatment effect.

Level of Evidence

1b.
Metal transporter Slc30a1 controls pharyngeal neural crest differentiation via the zinc‐Snai2‐Jag1 cascade
Authors: Xia Zhidan , Bi Xinying , Yang Sisi , Yang Xiu , Song Zijun , Wei Jiayu , Xu Pengfei , Rink Lothar , Min Junxia , Wang Fudi
Published: September 2021

The pharyngeal arch (PA) is a neural crest (NC)‐derived organ that is transiently developed during embryogenesis and is required for the subsequent development of various tissues. However, the role of zinc during PA differentiation from NC progenitor cells is unknown. Here, we found that the metal transporters Slc30a1a and Slc30a1b mediate zinc homeostasis during PA differentiation. Slc30a1‐deficient zebrafish develop zinc accumulation in NC cells, with increased expression of stemness markers and PA dorsal genes, and SMART‐seq analyses revealed that the genes snai2 and jag1b may serve as downstream targets. Furthermore, functional studies showed that knocking down either snai2 or jag1b rescues PA development in Slc30a1‐deficient zebrafish. Notably, we identified the double zinc‐finger domain in the transcription factor Snai2 as a zinc‐responsive element that regulates jag1b expression. Our findings indicate that the Slc30a1/zinc‐snai2‐jag1b axis is an essential regulatory network controlling PA differentiation, shedding new light on the function of zinc homeostasis in maintaining NC cell stemness and multipotency in vertebrates.
The relationship between multisite peripheral joint pain and physical activity levels in older adults: A cross‐sectional survey
Authors: Smith Robert D. , McHugh Gretl A. , Quicke Jonathan G. , Finney Andrew , Lewis Martyn , Dziedzic Krysia S. , Healey Emma L.
Published: September 2021

Introduction

Research on levels of physical activity (PA) in those with peripheral joint pain have only focused on single sites, in the knee or hips. This study investigated the levels of PA in adults with single‐site and multisite peripheral joint pain compared to adults with no joint pain.

Methods

Analysis of a cross‐sectional population survey mailed to adults aged ≥45 years (n = 28,443) was conducted. Respondents reported any peripheral joint pain in the last 12 months in either the hands, hips, knees or feet; PA levels were self‐reported using the short telephone activity rating scale. The association between PA levels, peripheral joint pain and outcomes of health status (physical and mental component scores, using SF‐12) pain intensity (10‐point scale) and health‐related quality of life (HRQoL) (EQ‐5D) were investigated using analysis of variance and ordinal regressions.

Results

Compared to those with no joint pain, all pain groups reported lower levels of PA: joint pain in one site (odds ratio = 0.91, 95% CI: 0.83–0.99); two sites (0.74, 0.67–0.81), three sites (0.65, 0.59–0.72) and four sites (0.47, 0.42–0.53). Across all joint pain groups, levels of PA were associated with pain intensity, physical health status, mental health status and HRQoL.

Discussion

Adults with more sites of peripheral joint pain were more likely to report lower levels of PA. Those with more sites of pain and lower levels of PA reported poorer outcomes. Health care providers should be aware that those with multisite joint pain are most likely to have low levels of PA.
Indicators of motherhood? Sacral preauricular extensions and notches in identified skeletal collections
Authors: Pany‐Kucera Doris , Spannagl‐Steiner Michaela , Desideri Jocelyne , Rebay‐Salisbury Katharina
Published: September 2021

The sacral preauricular extension (SPE) and sacral preauricular notch (SPN) are morphological changes at the ventral apex of the sacrum. We recently specified their shapes and appearances and suggested a scoring system based on prehistoric Austrian skeletal assemblages. We hypothesized that these specific pelvic changes relate to past pregnancies and parturitions, a hypothesis that we now tested on a subsample of individuals from the Simon Identified Skeletal collection in Geneva (n = 62) and the Christ Church, Spitalfields collection in London (n = 27) linked to historical information on deliveries. We found SPE and SPN in low frequencies and only in female individuals with at least two children in both collections, and a significant association between the emergence of SPE and first births by 25 years. SPN was found only in two females in the Simon collection, but both with a very high number of recorded parturitions including twin births. Based on these results, we are confident in our assumption that at least SPE, and possibly also SPN, result from increased compression forces at the sacroiliac joint, and especially at the ventrosuperior margin, in recurring (complicated) birth events, the interaction of enhanced pelvic joint mobility that is highest up to age 25, and postural changes related to weight gain during pregnancy. Pelvic shape, dimensions, body proportions, biomechanical issues and hormonal levels may also play a role in their emergence.