bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Structure‐Photophysics Evaluation of 2‐N‐Amino‐quinazolines: Small Molecule Fluorophores for Solution and Solid State
Authors: Motoyama Miho , Doan Thu‐Hong , Hibner‐Kulicka Paulina , Otake Ryo , Lukarska Malgorzata , Lohier Jean‐Francois , Ozawa Kota , Nanbu Shinkoh , Alayrac Carole , Suzuki Yumiko , Witulski Bernhard
Published: June 2021

2‐N‐aminoquinazolines were prepared by consecutive SNAr functionalization. X‐ray structures display the nitrogen lone pair of the 2‐N‐morpholino group in conjugation with the electron deficient quinazoline core and thus representing electronic push‐pull systems. 2‐N‐aminoquinazolines show a positive solvatochromism and are fluorescent in solution and in solid state with quantum yields up to 0.73. Increase in electron donor strength of the 2‐amino substituent causes a red‐shift of the intramolecular charge transfer (ICT) band (300–400 nm); whereas the photoluminescence emission maxima (350–450 nm) is also red‐shifted significantly along with an enhancement in photoluminescence efficiency. HOMO‐LUMO energies were estimated by a combination of electrochemical and photophysical methods and correlate well to those obtained by computational methods. ICT properties are theoretically attributed to an excitation to Rydberg‐MO in SAC‐CI method, which can be interpreted as n‐π* excitation. 7‐Amino‐2‐N‐morpholino‐4‐methoxyquinazoline responds to acidic conditions with significant increases in photoluminescence intensity revealing a new turn‐on/off fluorescence probe.
Tryptophan in the diet ameliorates motor deficits in a rotenone‐induced rat Parkinson's disease model via activating the aromatic hydrocarbon receptor pathway
Authors: Wang Yilin , Chen Shuangxi , Tan Jian , Gao Yijiang , Yan Hongye , Liu Yao , Yi Shanqing , Xiao Zijian , Wu Heng
Published: June 2021

Background and purpose

Parkinson's disease (PD), a common neurodegenerative disorder with motor and nonmotor symptoms, does not have effective treatments. Dietary tryptophan (Trp) supplementation has potential benefits for the treatment of multiple disorders. However, whether additional Trp in the diet could be beneficial for PD remains to beinvestigated. In the present study, the neuroprotective role of dietary Trp on a rotenone‐induced rat model of PD was determined.

Methods

The rotenone was injected to build the PD model, and then the rats were treated with Trp in the diet. And then, an open field test, western blot analysis, and enzyme linked immunosorbent assay (ELISA) were performed.

Results

We observed that dietary Trp significantly ameliorated impaired motor function, upregulated tyrosine hydroxylase expression, inhibited the nuclear transport of Nuclear factor‐kappa B (NF‐κB) in substantia nigra (SN), and downregulated the protein levels of IL‐1β, IL‐6, and TNF‐α in serum in rotenone‐treated rats. However, these patterns were reversed in response to treatment with ampicillin, an agent that can clean intestinal Trp metabolism flora. Moreover, after using CH223191, an inhibitor of the aromatic hydrocarbon receptor (AhR) pathway, dietary Trp could not exert neuroprotective roles in the rotenone‐induced rat model of PD.

Conclusion

These results suggest that Trp in the diet can protect against rotenone‐induced neurotoxicity to ameliorate motor deficits, which may be mediated through activating AhR pathway.
Informing or obfuscating stakeholders: Integrated reporting and the information environment
Authors: Sinnewe Elisabeth , Yao Troy , Zaman Mahbub
Published: June 2021

The global development of integrated reporting (IR) is underpinned by the recognition of increased complexity of businesses and stakeholder demands for information relating to financial performance, management, corporate governance, and sustainability being provided in a single, coherent document which facilitates stakeholder decision making. This paper examines the lexical properties of IR following the introduction of the International Integrated Reporting Council (IIRC) Framework. Using an international sample, we find that when adopted voluntarily, IR are lengthier, use more complex language, and contain more boilerplate statements. Our findings suggest that without regulation, firms may continue to produce long and difficult to understand reports in fear of being perceived as omitting “bad news.” This fear might be justified as we find loss of analyst following and greater analyst uncertainty when voluntarily adopted IR is concise. In the regulated setting of South Africa, however, we find IR has become more concise, and firms that produce longer and more complex documents suffer from a deterioration of their information environment. Our findings suggest that regulators and practitioners need to be cognizant of the potential for an increased volume in reporting to obfuscate the message rather than inform stakeholders.
Heparin, compression, and radial artery occlusion: Less is more
Authors: Tehrani David M. , Seto Arnold H.
Published: June 2021

Key Points

Radial artery occlusion is a function of anticoagulation, compression time, compression pressure, and vascular injury from sheath size and puncture attempts.

This study showed that increased levels of anticoagulation during transradial cases is associated with a higher incidence of occlusive hemostasis, increasing the risk of radial artery occlusion.

Reductions in compression time as made possible by adjunctive hemostatic patches may obviate the need for high doses of heparin.
Hollow‐fibre Membrane Contactors for Nitrogen Recovery from Municipal Wastewater
Authors: Richter Lea , Paulsen Svea , Wichern Marc , Grömping Markus , Robecke Ulrich , Haberkamp Jens
Published: June 2021

Prozesswasser aus der Faulschlammentwässerung von kommunalen Kläranlagen stellt eine zusätzliche stoffliche Belastung der Anlage in Form von Stickstoff dar. Die Hauptkläranlage Münster betreibt zur Stickstoffentfernung und ‐rückgewinnung aus Prozesswasser eine innovative Membrankontaktorenanlage im großtechnischen Maßstab. Im Rahmen dieser Studie werden Auswirkungen auf die Leistung und den Betrieb der Membran sowie die Verwertung des produzierten Düngers untersucht. Erste Ergebnisse zeigen Stickstoffentfernungsleistungen von ca. 85 % und eine regionale Verwertbarkeit des produzierten Düngers.
Effect of electrical cardioversion on 1‐year outcomes in patients with early recurrence after catheter ablation for atrial fibrillation
Authors: Dong Zheng , Du Xin , Hou Xiao‐Xia , He Liu , Dong Jian‐Zeng , Ma Chang‐Sheng
Published: June 2021

Background

Atrial fibrillation (AF) recurrence is common in the 3‐month blanking‐period after catheter ablation, during which electrical cardioversion (ECV) is usually performed to restore sinus rhythm. Whether ECV can affect the clinical outcome of post‐ablation AF patients is inconsistent, however. We aimed to explore the 1‐year effect of ECV on AF recurrence and rehospitalization in patients experienced recurrence within 3‐month after AF catheter ablation.

Methods

Patients who experienced recurrence within 3‐month after AF catheter ablation procedure were enrolled from the China Atrial Fibrillation Registry (China‐AF). A 1:3 Propensity score matching (PSM) method was applying to adjust the confounders between patients who had been treated by ECV or not. Logistic regression models were conducted to evaluate the association of ECV with 1‐year AF recurrence and rehospitalization.

Results

In this study, 2961 patients experienced AF recurrence within 3‐month after the procedure, and 282 of them underwent successful ECV, 2155 patients did not undergo ECV. One‐year AF recurrence rates were 56.4% in ECV group versus 65.4% in non‐ECV group (p = .003), and were 55.9% versus 65.9%, respectively, after PSM (adjusted odds ratio [OR] 0.66; 95% confidence interval (CI): 0.49–0.88, p = .005). However, the difference of 1‐year rehospitalization rates between two groups were not statistically significant before (ECV group: 23.7% vs. non‐ECV group: 22.3%, p = .595) and after PSM (ECV group: 24.4% vs. non‐ECV group: 21.6%, adjusted OR1.14; 95% CI 0.81–1.62, p = .451).

Conclusions

Successful ECV was associated with lower rate of one‐year recurrence in patients with early recurrent AF after catheter ablation.
Effects of Lemborexant on the Pharmacokinetics of Oral Contraceptives: Results From a Phase 1 Drug‐Drug Interaction Study in Healthy Females
Authors: Landry Ishani , Aluri Jagadeesh , Hall Nancy , Filippov Gleb , Dayal Satish , Moline Margaret , Reyderman Larisa
Published: June 2021

Lemborexant is a dual orexin receptor antagonist approved in multiple countries including the United States, Canada, and Japan for the treatment of insomnia in adults. As women of childbearing potential may be prescribed insomnia drugs, a drug‐drug interaction study was conducted. This single‐center, open‐label, fixed‐sequence study examined potential drug‐drug interactions between lemborexant and an oral contraceptive (OC) in healthy females (18–44 years, n = 20). The purpose of this study was to determine the effect of lemborexant 10 mg (at steady state) on the pharmacokinetics of a single dose of OC (0.03 mg ethinyl estradiol and 1.5 mg norethindrone acetate), assess the effect of a single dose of OC on lemborexant pharmacokinetics, and evaluate safety and tolerability of lemborexant and OC coadministration. Ethinyl estradiol maximum plasma drug concentration was not altered by lemborexant coadministration; area under the curve from zero time to the last quantifiable concentration was slightly increased, by 13%. No clinically relevant effects on norethindrone acetate pharmacokinetics were observed. Coadministration of OC with lemborexant had no clinically relevant effect on the steady‐state pharmacokinetics of lemborexant. Adverse events were consistent with the known safety profile. These results support the conclusion that lemborexant and OC can be coadministered without dose adjustment.
Intravaginal Tolterodine Formulation Intended for Overactive Bladder Treatment—Results of a Pharmacokinetic Phase I Pilot Study in Healthy, Postmenopausal Women
Authors: Donath Frank , Hoffmann Larissa , Todorova‐Sanjari Marina , Wedemeyer Ralph‐Steven , Warnke André , Nickisch Klaus
Published: June 2021

The aim was to assess the pharmacokinetics of tolterodine released from vaginal rings and of its active metabolite 5‐hydroxymethyl tolterodine (5‐HMT) compared to the respective pharmacokinetics resulting from oral administration of extended‐release tolterodine in healthy, postmenopausal women. In this single‐center, open‐label trial, subjects received 4 treatments in a fixed sequence: fasted oral extended‐release tolterodine 2.74 mg/d (reference, 5 days), single vaginal rings; tolterodine releasing rates: 0.95 mg/d (test 1, 13 days), 1.40 mg/d (test 2, 28 days), 1.90 mg/d (test 3, 28 days). Systemic exposure of tolterodine, 5‐HMT, and the molar sum of unbound tolterodine/5‐HMT (active moiety [AM]) in steady state was determined. Sixteen of 18 included women completed the study. For the oral formulation, peak‐trough fluctuations of tolterodine, 5‐HMT, and AM plasma concentrations (AM: mean maximum/minimum concentration, 2580/574 pmol/L = 4.5) were large. Intravaginal application led to steadier plasma concentrations (AM, test 3: mean maximum/minimum concentration, 1880/814 pmol/L = 2.3; fluctuation due to initial peak), which is the result of constant releasing rates after ring insertion over the 28‐day application period. The vaginal rings demonstrated a favorable local tolerability. The most common adverse events with oral and vaginal tolterodine were headache (n = 11) and dry mouth (n = 8). Vaginal rings releasing tolterodine represent a promising new formulation for overactive bladder treatment with little fluctuation of drug plasma levels. This is expected to lead to a more predictable and continuous therapeutic effect and a reduced frequency of side effects compared to oral tolterodine.
Improved multi‐party verification protocol with reduced computational overhead in cloud storage system
Authors: George Anju Susan , Nargunam A. Shajin
Published: June 2021

Although in industry and academia cloud computing provides several services, cloud storage is the most unavoidable one. Cloud storage allows remote data validation of the deployed user's data without keeping a local copy. A third‐party auditor is delegated by the users in order to examine the remote data integrity thereby reducing the burden of the users. Data integrity checking protects the user's data from tinkering and illicit access especially when they store data in public clouds such as AWS. Various schemes were proposed by several scholars which possess computational overhead and communication overhead during the integrity checking. Most of the schemes proposed were possessing computational overhead in the cloud server side which increases the financial overwhelming of the clients. In this article an improved multiparty computation architecture is proposed to minimize the computational overhead in the cloud server side while generating the proof of the data blocks in public clouds. The proposed scheme can be implemented on semi‐trusted cloud environments and allows a set of server nodes called ingestion nodes to compute on private inputs thus preserving the privacy and soundness of the computing data. The improved protocol also uses an indistinguishability obfuscation program with a message authentication code tag to minimize the verification overhead of the third‐party auditor as well as preserves the privacy and security of the stored data.
Two‐Dimensional Organic/Inorganic Hybrid Nanosheet Electrodes for Enhanced Electrical Conductivity toward Stable and High‐Performance Sodium‐Ion Batteries
Authors: Lee Minseop , Kim Min‐Sung , Oh Jae‐Min , Park Jin Kuen , Paek Seung‐Min
Published: June 2021

To investigate the effect of electrical conductivity on the energy‐storage characteristics of anode materials in sodium‐ion batteries, covalent organic nanosheets (CONs) are hybridized with highly conductive graphene nanosheets (GNs) via two different optimized synthesis routes, that is, reflux and solvothermal methods. The reflux‐synthesized hybrid shows a well‐overlapped 2D structure, whereas the solvothermally prepared hybrid forms a segregated phase in which the contact area between the CONs and GNs is reduced. These two hybrids synthesized by facile methods are fully characterized, and the results reveal that their energy‐storage properties can be significantly improved by enhancing the electrical conductivity via the formation of a well‐overlapped structure between CONs and GNs. The discharge capacity and rate capability of the reflux‐synthesized hybrid was considerably larger than that of the bare CONs, highlighting that the improvement in the charge‐carrier transport properties can improve the accessibility of Na ions to the surface of the hybrids. This synthetic methodology can be extended to the fabrication of high‐performance anodes for Na‐ion batteries.
A Cu2O‐derived Polymeric Carbon Nitride Heterostructured Catalyst for the Electrochemical Reduction of Carbon Dioxide to Ethylene
Authors: Lin Wenwen , Chen Hao , Li Zihao , Sasaki Kotaro , Yao Siyu , Zhang Zihao , Li Jing , Fu Jie
Published: June 2021

The electroreduction of carbon dioxide to hydrocarbons has been proposed as a promising way to utilize CO2 and maintain the ecosystem carbon balance. However, the selective reduction of CO2 to C2 hydrocarbons is still challenging. In this study, a highly efficient heterostructured catalyst has been developed, composed of a carbon nitride (CN)‐encapsulated copper oxide hybrid (CuxO/CN). The interaction between the metal and carbon nitride in the heterostructured catalysts improves the intrinsic electrical conductivity and the charge transfer processes at metal–support interfaces. A remarkable enhancement in the selectivity of hydrocarbons is achieved with these modified Cu‐based electrocatalysts, with an onset potential of −0.4 V and high C2H4 faradaic efficiency of 42.2 %, and these catalysts can also effectively suppress H2 evolution during the CO2 reduction reaction. This work provides a simple and cost‐effective method for synthesizing CN‐encapsulated catalysts that provides the possibility of efficiently converting CO2 into C2 hydrocarbons.
Rapid serial naming: Developmental trajectory and relationship with the Bangor Dyslexia Test in Spanish students
Authors: Outón Paula , Ferraces María José
Published: June 2021

This study aimed to analyse the developmental trajectory of the accuracy and speed of naming among dyslexics and developing readers from 1st to 6th grade of primary education. It examined how familiarity with the stimulus influences the performance of different naming tasks in both groups and evaluated the link between naming speed and the Bangor Dyslexia Test. With a descriptive and correlational design, eight naming tasks and the Bangor Dyslexia Test (Miles, 1982; Outón & Suárez, 2010) were administered to a sample of 198 dyslexics and 245 developing readers. The results showed that the dyslexics were slower and more inaccurate in all the naming tasks, compared with the developing readers of the same age. Greater difficulty was observed with the less familiar stimuli. It became evident that naming performance improved with age among both groups of subjects. Finally, a greater number of significant and positive correlations were found between the naming tasks and the Bangor Dyslexia Test in the dyslexic group; the strongest relationship was obtained by naming letters.
Relative importance of deterministic and stochastic processes for beta diversity of bird assemblages in Yunnan, China
Authors: He Xuelian , Brown Calum , Lin Luxiang
Published: June 2021

Evaluating the relative importance of deterministic and stochastic processes underlying taxonomic and functional beta diversity is crucial in community ecology, because it can reveal the dominant processes of community assembly. However, studies of bird communities remain rare and of limited spatial extents. In this study, we described the taxonomic and functional beta diversity patterns of 32 passerine bird assemblages of Yunnan Province, China. We constructed null models based on observed species beta diversity and used multiple regressions on distance matrices to evaluate the relative contributions of deterministic and stochastic processes to passerine bird assemblage dissimilarity. Our results showed significant geographic distance decay in taxonomic and functional similarity, with passerine bird assemblages located in the northwest and southwest of the province having higher functional beta diversity values than expected. Environmental distance and geographic distance explained a similar amount taxonomic beta diversity, but environmental distance explained much more functional beta diversity. Our results suggest that both deterministic and stochastic processes drive taxonomic beta diversity, but that deterministic processes, particularly environmental filtering, play a dominant role in driving functional beta diversity of passerine bird assemblages at sub‐national scale.
Stronger predation intensity and impact on prey communities in the tropics
Authors: Freestone Amy L. , Torchin Mark E. , Jurgens Laura J. , Bonfim Mariana , López Diana P. , Repetto Michele F. , Schlöder Carmen , Sewall Brent J. , Ruiz Gregory M.
Published: June 2021

The hypothesis that biotic interactions strengthen toward lower latitudes provides a framework for linking community‐scale processes with the macroecological scales that define our biosphere. Despite the importance of this hypothesis for understanding community assembly and ecosystem functioning, the extent to which interaction strength varies across latitude and the effects of this variation on natural communities remain unresolved. Predation in particular is central to ecological and evolutionary dynamics across the globe, yet very few studies explore both community‐scale causes and outcomes of predation across latitude. Here we expand beyond prior studies to examine two important components of predation strength:intensityof predation (including multiple dimensions of the predator guild) andimpacton prey community biomass and structure, providing one of the most comprehensive examinations of predator–prey interactions across latitude. Using standardized experiments, we tested the hypothesis that predation intensity and impact on prey communities were stronger at lower latitudes. We further assessed prey recruitment to evaluate the potential for this process to mediate predation effects. We used sessile marine invertebrate communities and their fish predators in nearshore environments as a model system, with experiments conducted at 12 sites in four regions spanning the tropics to the subarctic. Our results show clear support for an increase in both predation intensity and impact at lower relative to higher latitudes. The predator guild was more diverse at low latitudes, with higher predation rates, longer interaction durations, and larger predator body sizes, suggesting stronger predation intensity in the tropics. Predation also reduced prey biomass and altered prey composition at low latitudes, with no effects at high latitudes. Although recruitment rates were up to three orders of magnitude higher in the tropics than the subarctic, prey replacement through this process was insufficient to dampen completely the strong impacts of predators in the tropics. Our study provides a novel perspective on the biotic interaction hypothesis, suggesting that multiple components of the predator community likely contribute to predation intensity at low latitudes, with important consequences for the structure of prey communities.
Siloxane Coordination Revisited: Si−O Bond Character, Reactivity and Magnificent Molecular Shapes
Authors: Dankert Fabian , von Hänisch Carsten
Published: June 2021

Siloxanes have evolved into a multi‐million dollar business due to their manifold of commercial and industrial applications. As siloxanes have high hydrophobicity, low basicity, high flexibility and also high chemical inertness in common, their chemistry differs significantly from that of organic ethers. The discovery of organic crown ethers, for instance, is commonly accepted as the birth of synthetic host‐guest chemistry. Regarding the chemical properties of siloxanes, cyclic siloxanes which formally resemble silicon analogues of crown ethers, have received considerably less interest in terms of their host‐guest chemistry. Hence, only little is known about siloxane coordination chemistry in the chemical community and the number of published works in this field has been very low till lately. In the last few years, the field has significantly advanced and elegant methods were established to enable the Si−O−Si unit for coordination. This review therefore summarizes the recent developments in the field, recapitulates the historical aspects of siloxane coordination chemistry and describes the specific Si−O bond character with regard to different siloxane linkages. Implications on Si−O bond activation are included and the limits of siloxane coordination are redefined.
Techno‐economic analysis of a hybrid solar‐geothermal power plant integrated with a desalination system
Authors: Aviles Daniel , Sabri Farhad , Hooman Kamel
Published: June 2021

This paper proposes the use of a hybrid 5 MW power generation system combining concentrated solar thermal and solar photovoltaic technology where the efficiency of the power block is increased by taking advantage of hot water from a low‐temperature geothermal source. Aiming at a case study for Winton in Queensland the pertinent meteorological data are used for our simulations. In addition, the paper analyzes the feasibility of including a thermal desalination technology that uses the waste heat from the power block for producing clean water from wastewater. Our design replaces the traditional dry cooling system with a water‐cooled heat exchanger to remove the waste heat from the power block. Finally, this work explores the ratio of concentrated solar thermal and photovoltaic electricity production that optimizes the levelized cost of electricity and water production. the results indicate that the incorporation of the desalination system does not produce a significant increase in this value, and the optimal ratio of electricity production is obtained when the photovoltaic system contributes to 27.5% of the total electricity generation. Our water production cost can be as low as 40 ₵/m3 while for the combined system our minimum levelized cost of electricity figures out at 12.4 ₵/kWh to generate the base load with thermal storage.
Microencapsulation of nattokinase from fermentation by spray drying: Optimization, comprehensive score, and stability
Authors: Li Ganlu , Li Tao , He Feng , Chen Cheng , Xu Xu , Tian Weilong , Yang Yue , He Xun , Li Hui , Chen Kequan , Hao Ning , Ouyang Pingkai
Published: June 2021

Nattokinase from fermentation has recently gained more attention due to its beneficial effects on cardiovascular system. However, the instability of free nattokinase limits its application. The aim of the study was to develop a spray‐drying microencapsulation process to obtain the nattokinase powder with high activity, high quality, and strong storage stability. Hence, the microencapsulation process of nattokinase from fermentation by spray drying was optimized. Experiments of single‐factor and response surface methodology were used to assess the comprehensive scores and nattokinase activities. According to single‐factor and response surface methodology results, optimum parameters of microencapsulation process of the nattokinase power by spray drying were 30% of mass ratio of wall materials, 139°C of air inlet temperature, 8 L/h of feed rate, and 80°C of outlet temperature. The final optimized result encompassed a comprehensive score of 96, nattokinase activity of 1,340 IU/ml, and moisture content of 4.1 ± 0.1%. In addition, the microencapsulated nattokinase power showed strong storage stability in the conditions of different temperatures and pH. After 30 days of storage, the nattokinase powder was still white or light yellow, with a special smell, no peculiar smell and paste taste, and no impurity. These results build the basis of further industrialization of the nattokinase powder from fermentation broth by spray drying.
Structured learning of rigid‐body dynamics: A survey and unified view from a robotics perspective
Authors: Geist A. René , Trimpe Sebastian
Published: June 2021

Accurate models of mechanical system dynamics are often critical for model‐based control and reinforcement learning. Fully data‐driven dynamics models promise to ease the process of modeling and analysis, but require considerable amounts of data for training and often do not generalize well to unseen parts of the state space. Combining data‐driven modeling with prior analytical knowledge is an attractive alternative as the inclusion of structural knowledge into a regression model improves the model's data efficiency and physical integrity. In this article, we survey supervised regression models that combine rigid‐body mechanics with data‐driven modeling techniques. We analyze the different latent functions (such as kinetic energy or dissipative forces) and operators (such as differential operators and projection matrices) underlying common descriptions of rigid‐body mechanics. Based on this analysis, we provide a unified view on the combination of data‐driven regression models, such as neural networks and Gaussian processes, with analytical model priors. Furthermore, we review and discuss key techniques for designing structured models such as automatic differentiation.
YAP/TAZ Suppress Drug Penetration Into Hepatocellular Carcinoma Through Stromal Activation
Authors: Cho Kyungjoo , Ro Simon Weonsang , Lee Hye Won , Moon Hyuk , Han Sojung , Kim Hye Rim , Ahn Sang Hoon , Park Jun Yong , Kim Do Young
Published: June 2021

Background and Aims

HCC is the most predominant type of liver cancer affecting 800,000 people globally each year. Various small‐molecule compounds targeting diverse oncogenic signaling pathways have been tested for patients with HCC, and clinical outcomes were not satisfactory. In this study, we investigated molecular signaling that determines the efficiency of drug delivery into HCC.

Approach and Results

Hydrodynamics‐based transfection (HT) was performed to develop mouse models for HCC induced by various oncogenes. Mice bearing liver cancer were treated with verteporfin at 5 weeks after HT. Multicellular HCC organoid (MCHO) models were established that contained various types of stromal cells, such as hepatic stellate cells, fibroblasts, and endothelial cells together with HCC cells. Tumor organoids were treated with verteporfin, and distributions of the drug in the organoids were assessed using fluorescence microscopy. Murine HCC models developed by HT methods showed that a high Yes‐associated protein/Transcriptional co‐activator with PDZ‐binding motif (YAP/TAZ) activity in HCC cells impaired verteporfin penetration into the cancer. Activation of tumor stroma was observed in HCC with a high YAP/TAZ activity. Consistent with the findings in the in vivo models of HCC, MCHOs with activated YAP/TAZ signaling showed stromal activation and impaired penetration of verteporfin into the tumor organoids. Inhibition of YAP/TAZ transcriptional activity in HCC cells significantly increased drug penetration into the MCHO.

Conclusions

Drug delivery into liver cancer is impaired by YAP/TAZ signaling in tumor cells and subsequent activation of stroma by the signaling. Disrupting or targeting activated tumor stroma might improve drug delivery into HCC with an elevated YAP/TAZ activity.
Evaluating the Prevention Benefit of HCV Treatment: Modeling the SToP‐C Treatment as Prevention Study in Prisons
Authors: Lim Aaron G. , Stone Jack , Hajarizadeh Behzad , Byrne Marianne , Chambers Georgina M. , Martin Natasha K. , Grebely Jason , Dore Gregory J. , Lloyd Andrew R. , Vickerman Peter
Published: June 2021

Background and Aims

Between 2014 and 2019, the SToP‐C trial observed a halving in HCV incidence in four Australian prisons following scale‐up of direct‐acting antiviral (DAA) therapy. However, the contribution of HCV treatment to this decline is unclear because the study did not have a control group. We used modeling to consider this question.

Approach and Results

We parameterized and calibrated a dynamic model of HCV transmission in prisons to data from each SToP‐C prison on incarceration dynamics, injecting drug use, HCV prevalence trends among prison entrants, baseline HCV incidence before treatment scale‐up, and subsequent HCV treatment scale‐up. The model projected the decrease in HCV incidence resulting from increases in HCV treatment and other effects. We assessed whether the model agreed better with observed reductions in HCV incidence overall and by prison if we included HCV treatment scale‐up, and its prevention benefits, or did not. The model estimated how much of the observed decrease in HCV incidence was attributable to HCV treatment in prison. The model projected a decrease in HCV incidence of 48.5% (95% uncertainty interval [UI], 41.9‐54.1) following treatment scale‐up across the four prisons, agreeing with the observed HCV incidence decrease (47.6%; 95% CI, 23.4‐64.2) from the SToP‐C trial. Without any in‐prison HCV treatment, the model indicated that incidence would have decreased by 7.2% (95% UI, −0.3 to 13.6). This suggests that 85.1% (95% UI, 72.6‐100.6) of the observed halving in incidence was from HCV treatment scale‐up, with the remainder from observed decreases in HCV prevalence among prison entrants (14.9%; 95% UI, −0.6 to 27.4).

Conclusions

Our results demonstrate the prevention benefits of scaling up HCV treatment in prison settings. Prison‐based DAA scale‐up should be an important component of HCV elimination strategies.
Bispecific antibodies for the treatment of lymphomas: Promises and challenges
Authors: Schuster Stephen J.
Published: June 2021

The potential of bispecific antibodies to direct antigen‐specific T cell‐mediated cytotoxicity toward malignant cells bearing a target antigen was recognized over 35 years ago. Generally, this is accomplished by combining a T‐cell receptor‐specific monoclonal antibody or monoclonal antibody‐derived fragment that is capable of activating and expanding resting T cells with a second monoclonal antibody or monoclonal antibody fragment directed against a tumor target antigen. Bispecific antibodies induce effector T cells that bind to tumor cells independently of their T‐cell receptor specificity and without the requirement of MHC‐mediated antigen presentation, focusing effector T‐cell cytotoxicity on tumor cells bearing the target antigen. The therapeutic efficacy of this approach for treatment of relapsed or refractory B‐cell lymphomas was first demonstrated with blinatumomab, a single molecule comprised of two linked single‐chain variable fragments with binding specificities for CD19 and CD3. The recent demonstration that chimeric antigen receptor (CAR) modified T cells can achieve very durable remissions in some patients with relapsed or refractory B‐cell lymphomas, as well as the potential efficacy of bispecific antibodies in CAR T cell failures, has rekindled interested in bispecific antibodies as a T cell‐mediated therapeutic approach. We review the early results of phase 1 clinical trials of bispecific antibodies targeting CD20 on B cells and engaging T cells via CD3 in 1:1 or 2:1 CD20:CD3 Fab formats for treatment of relapsed or refractory B‐cell lymphomas.
U.S. and Chinese preschoolers' compliance and regulatory behaviours in two challenging contexts
Authors: Wang Jun , Barrett Karen Caplovitz
Published: June 2021

Children are expected to self‐regulate their behaviour, even in emotionally charged situations. Yet, such expectations for self‐regulation, the degree to which compliance is expected, and the specific regulatory behaviours deemed desirable, vary by culture, age of child, and specific situation. In this study, 34 Chinese (17 females) and 39 U.S. (19 females) preschoolers were observed and compared in two socioemotionally challenging situations. Children's compliance to explicit and implicit rules, their regulatory behaviours, and the associations between regulatory behaviours and rule compliance were analysed across the two samples. U.S. children showed greater resistance to temptation and similar levels of repair of mishap as compared to Chinese children. In addition, Chinese children used more avoidance and self‐soothing strategies and fewer distractive strategies than U.S. children. The effectiveness of regulatory behaviours in predicting rule compliance varied by both task condition and cultural group. Object and self distractions were associated with lower rule compliance in the mishap task. Social distraction was positively predictive of U.S. children's rule compliance in the mishap task, but negatively associated with their compliance in the temptation task. Social distraction was unhelpful for Chinese children's compliance in both tasks. The complexities of cultural variations and dynamics in their relations to children's rule compliance and regulatory behaviours are discussed.
Two cases of pelvic schwannomas simultaneously resected with the prostate by robot‐assisted surgery
Authors: Nishikimi Toshinori , Yoshino Yasushi , Yamada Hiroshi , Mizuno Hideki , Yamauchi Yushi , Ohashi Tomoyoshi , Isiguro Shigeki , Morikami Hiroko , Okamura Kikuo
Published: June 2021

Introduction

Schwannoma is a rare benign tumor of peripheral nerves arising from Schwann cells of the ubiquitous nerve sheath. The operative steps and technical aspects of robotic resection of pelvic schwannoma are described herein.

Case presentation

We describe two patients with pelvic tumors simultaneously resected with the prostate by robot‐assisted surgery: a 69‐year‐old man with schwannoma of the right side of the pelvic floor and a 68‐year‐old man with schwannoma in the left pelvis. As metastasis of prostate cancer could not be ruled out, tumorectomy was performed using robotic‐associated prostatectomy. Malignancy was absent in the two pelvic tumors, and the patients were diagnosed with schwannoma.

Conclusion

For surgery in a narrow deep pelvis, robot‐assisted surgery is minimally invasive, offers excellent mobility of robotic instruments and visibility of three‐dimensional view, and is a useful approach.
Binary glioma grading framework employing locality preserving projections and Gaussian radial basis function support vector machine
Authors: Singh Rahul , Goel Aditya , Raghuvanshi Deepak Kumar
Published: June 2021

Gliomas are one of the most dangerous brain tumours, which are life‐threatening in their highest grade. Manual diagnosis and detection of brain tumours are time‐consuming. Thus, early and accurate detection of such tumours becomes essential for its prognosis. In this work, we aim to develop a fully automated glioma grade classification framework. The proposed method aims to learn relevant and non‐redundant features from magnetic resonance brain tumour images. Gabor filter banks extract discriminant features from the brain images, and locality preserving projections are utilized for feature reduction to achieve non‐redundant features. We train Gaussian radial basis function–support vector machine classifiers using these features for classifying gliomas into low grade glioma (LGG) or high‐grade glioma. We apply Synthetic Minority Over‐Sampling Technique on the minority class (LGG) to mitigate the class imbalance problem. The performance of the proposed method is validated by conducting fivefold cross‐validation. We evaluate the performance of our proposed framework on different BRATS datasets: BRATS 2013, BRATS 2015, and BRATS 2017. We perform extensive experiments on each dataset separately, and experimental findings demonstrate that our proposed approach provides significantly superior performance compared to state‐of‐the‐art techniques.
Psychometric Synthesis of the Parent‐Child Relationship Inventory
Authors: Nagy Michelle , Kleppin Alison , Erford Bradley T. , Anderson Billie M. , Smith Heather L.
Published: June 2021

Assessment in counseling is strengthened when research exists to demonstrate the psychometric strength of scores from a particular instrument across samples. This study presents a psychometric synthesis of data across 52 publications that met criteria and reported use of the Parent‐Child Relationship Inventory (PCRI; Gerard, 1994) across disciplines and in numerous contexts. Results revealed low score reliability, with aggregated alphas of .63 to .83 and test‐retest coefficients of .62 to .79 over a 1‐year retest period across subscales and total score. There was little evidence of score validity, including no exploratory or confirmatory factor analytic studies, or evidence of diagnostic validity. Cautions for use of the PCRI and implications for professional counselors and researchers are discussed.
Alcohol and Substance Use Symptom Differences Between Classes of Perfectionists
Authors: Moate Randall M. , Gnilka Philip B. , Holm Jessica M.
Published: June 2021

We examined how multidimensional perfectionism is associated with the Substance Abuse Subtle Screening Inventory–3 (SASSI‐3; Miller & Lazowski, 1999) among a sample of 428 undergraduate students. Latent profile analysis based on measures of perfectionism and perceived stress supported a four‐class model (i.e., adaptive perfectionists, mixed perfectionists, nonperfectionists, and maladaptive perfectionists). Overall, adaptive perfectionists reported fewer alcohol and substance use–related symptoms, whereas maladaptive perfectionists reported higher alcohol and substance use–related symptoms. In addition, according to the SASSI‐3 overall classification rule screening for low or high risk of an alcohol or substance use disorder, adaptive perfectionists were the least likely to be classified in the high‐risk category, whereas maladaptive perfectionists were the most likely to be classified in the high‐risk category.
A Clinical Decision Support Tool to Find the Best Initial Intravenous Cyclosporine Regimen in Pediatric Hematopoietic Stem Cell Transplantation
Authors: Leclerc Vincent , Ducher Michel , Ceraulo Antony , Bertrand Yves , Bleyzac Nathalie
Published: June 2021

To optimize cyclosporine A (CsA) dosing regimen in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT), we aimed to provide clinicians with a validated decision support tool for determining the most suitable first dose of intravenous CsA. We used a 10‐year monocentric data set of pediatric patients undergoing HSCT. Discretization of all variables was performed according to literature or thanks to algorithms using Shannon entropy (from information theory) or equal width intervals. The first 8 years were used to build the Bayesian network model. This model underwent a 10‐fold cross‐validation, and then a prospective validation with data of the last 2 years. There were 3.3% and 4.1% of missing values in the training and the validation data set, respectively. After prospective validation, the Tree‐Augmented Naïve Bayesian network shows interesting prediction performances with an average area under the receiver operating characteristic curve of 0.804, 32.8% of misclassified patients, a true‐positive rate of 0.672, and a false‐positive rate of 0.285. This validated model allows good predictions to propose an optimized and personalized initial CsA dose for pediatric patients undergoing HSCT. The clinical impact of its use should be further evaluated.
Anorexia in a hemodialysis patient due to pneumatosis intestinalis: A case report
Authors: Son Daisuke , Inoue Kazuoki , Lee Young , Kamimoto Minako , Imaoka Shintaro , Yamamoto Shiori , Hamada Toshihiro , Taniguchi Shin‐ichi , Koda Masahiko
Published: June 2021

We report a case of pneumatosis intestinalis (PI) in a hemodialysis patient who presented with anorexia and nausea. Anorexia with postprandial nausea can be caused by gastrointestinal diseases, with one of the rare causes being PI. PI may occur in hemodialysis patients, but it is rarely reported. We experienced a case of benign PI in a hemodialysis patient, for whom the conservative treatment with antibiotics improved the patient's clinical symptoms. In patients with PI, it is important to rule out potentially life‐threatening complications, such as the presence of hepatic intraportal gas on CT scan.
Organic Brønsted acid‐catalyzed cycloadditions of o‐quinone methides with 1, 3‐dicarbonlys: Facile access to xanthenones and chromanones
Authors: Thoppe Sivakumar Priyadarshini , Puthiyaparambath Sharathna , Suresh Varma Sanjay , Parameswaran Sasikumar , Kokkuvayil Vasu Radhakrishnan
Published: June 2021

The in‐situ generation of o‐quinone methides and their inverse‐electron‐demand Diels–Alder reaction in the presence of pentacarboxycyclopentadiene—an organic Brønsted acid—has been reported. The synthesis of xanthenones and chromanones in good to excellent yields from the [4 + 2] cycloaddition of quinone methides with 1, 3‐dicarbonyls and Meldrum's acid has been accomplished. The development of this method helps in generating a number of biologically potent heterocycles with medicinal applications.
Significant increases of the amygdala between immediate and late postpartum: Pronounced effects within the superficial subregion
Authors: Luders Eileen , Gaser Christian , Gingnell Malin , Engman Jonas , Sundström Poromaa Inger , Kurth Florian
Published: June 2021

Research exploring the underlying neuroanatomical correlates of early motherhood seems to suggest that the period after giving birth is marked by tissue increases in the mother's brain. While some studies point to the amygdala as one of the areas undergoing postpartum changes, existing analyses did not discriminate between the different subregions of this functionally heterogeneous structure. Thus, to further extend this understudied field of research and to better understand the potential role of the amygdala when transitioning to motherhood, we applied an advanced region‐of‐interest technique that enabled us to analyze the amygdala as a whole as well as its different subareas, specifically the left and right centromedian (CM), laterobasal (LB), and superficial (SF) regions. Comparing the brains of 14 healthy women between immediate postpartum (within 1–2 days of childbirth) and late postpartum (at 4–6 weeks after childbirth), we revealed increases of the amygdala. However, effects manifested differentially across subareas, with particularly strong effects for the SF region, moderate effects for the CM region, and no effects for the LB region. These findings might reflect region‐specific adaptations of the mother's brain tuning into the distinct and ever‐changing needs of a newborn, either as a cause for it or as a consequence thereof.
Construction of the PG‐deficient mutant of Fusarium equiseti by CRISPR/Cas9 and its pathogenicity of pitaya
Authors: Ge Chunhui , You Wenjing , Li Rui , Li Wen , Shao Yuanzhi
Published: June 2021

Fusarium is an important plant pathogen and many cell wall‐degrading enzymes (CWDEs) are produced in Fusarium‐infected plant tissues. To investigate the role of CWDEs in the pathogenicity of pitaya pathogen, we isolated a Fusarium equiseti strain from the diseased pitaya fruit and the activities of CWDEs were determined. The higher polygalacturonase (PG) activity was confirmed both in vitro and vivo. Aiming at the PG gene, the CRISPR/Cas9 system of F. equiseti was constructed and optimized for the first time. Through the process of microhomology‐mediated end joining, the flanking region containing 30 bp was used to mediate the homologous recombination of Cas9 double‐strand breaks, and the PG gene knockout mutants were obtained by protoplast transformation. Through the phenotypic and pathogenicity experiments of the wild‐type strain and mutant strain, the results showed that the colony growth rate and spore production of the strain without the PG gene decreased to some extent, and the lesion diameter and the degree of pericarp cell damage decreased, which showed that the CRISPR/Cas9 system could be used in F. equiseti and PG enzyme and can play a significant role in the interaction between F. equiseti and pitaya fruit.
ΔO2/N2′ as a tracer of mixed layer net community production: Theoretical considerations and proof‐of‐concept
Authors: Izett Robert W. , Tortell Philippe D.
Published: June 2021

We present a method to estimate net community production (NCP) from underway ΔO2/N2 observations. This approach, based on high‐resolution measurements using relatively low‐cost O2‐optode and gas tension device instrumentation, provides an alternative to NCP derivation from mass spectrometric analysis of ΔO2/Ar. To fully exploit ΔΟ2/Ν2 as an NCP tracer, it is necessary to account for differences in surface water argon (Ar) and nitrogen (Ν2) saturation states. Using a one‐dimensional mixed layer model, evaluated against field observations, we examined the divergence between ΔO2/Ar and ΔΟ2/Ν2 resulting from various physical processes. Results show that changes in sea surface temperature, bubble injection and vertical mixing can decouple mixed layer ΔO2/Ar and ΔΟ2/Ν2, while biological N2‐fixation has a negligible effect. Based on readily available environmental data, we developed a framework to correct for Ar and N2 solubility differences, yielding a new tracer, ΔΟ2/Ν2′, that is a near‐analog of ΔO2/Ar. Through model simulations and field measurements, we show that ΔΟ2/Ν2′ provides an excellent approximation to ΔO2/Ar, and that uncertainty and biases in ΔO2/N2′ are small relative to other errors in NCP calculations. This work demonstrates the potential for ΔO2/N2′ measurements to significantly expand NCP estimates from a variety of sampling platforms.