bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary ensemble feature selection learning for image‐based assessment of lymphedema arm volume
Authors: Yaghoobi Notash Anaram , Bayat Peyman , Haghighat Shahpar , Yaghoobi Notash Ali
Published: August 2021

Arm lymphedema is a side effect of surgery and radiation therapy in patients with breast cancer. There are several methods to measure lymphedema arm volume, such as water displacement (WD) and circumferential measurement (CM). Although these techniques have a satisfactory level of accuracy, they have some limitations for clinical use in practical applications. To overcome these drawbacks, a horizontal‐vertical image scanning (HVIS) tool, is presented as a valid method for arm volume measurement. To predict the arm volume, an evolutionary ensemble feature selection learning (named EEFSL) comprising different base learners (KNN, SVM, ANFIS, Decision Tree, and Naïve Bayes) is presented. In order to improve the performance of the EEFSL model, its hyperparameters are optimized using genetic algorithm (GA). The hyperparameters include the weights of different base learners and the specific features for each base learner. The fitness function of GA is to maximize the correlation between predicted and actual arm volumes. The proposed method was successfully developed for arm measurement of 60 arms from 30 women with arm lymphedema. Obtained results indicate that the proposed HVIS‐EEFSL method is a reliable and valid technique to measure arm volume of patients with lymphedema, suitable for daily clinical use instead of WD and CM.
Models of Depression: Unpredictable Chronic Mild Stress in Mice
Authors: Nollet Mathieu
Published: August 2021

Major depression is a complex psychiatric disorder characterized by affective, cognitive, and physiological impairments that lead to maladaptive behavior. The high lifetime prevalence of this disabling condition, coupled with limitations of existing medications, make necessary the development of improved therapeutics. This requires animal models that allow investigation of key biological correlates of the disorder. Described in this article is the unpredictable chronic mild stress mouse model that can be used to screen for antidepressant drug candidates. Originally designed for rats, this model has been adapted for mice to capitalize on the advantages of this species as an experimental model, including inter‐strain variability, which permits an exploration of the contribution of genetic background; the ability to create transgenic animals; and lower cost. Thus, because it combines genetic features and socio‐environmental chronic stressful events, the unpredictable chronic mild stress model in mice is a relevant and valuable paradigm to gain insight into the etiological and developmental components of major depression, as well as to identify novel treatments for this condition. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Unpredictable Chronic Mild Stress (UCMS) Test in Mice

Basic Protocol 2: Assessment Of Self‐Directed Activity And Anhedonia in Mice
Reference standards for flow cytometric estimation of absolute nuclear DNA content in plants
Authors: Temsch Eva M. , Koutecký Petr , Urfus Tomáš , Šmarda Petr , Doležel Jaroslav
Published: August 2021

The estimation of nuclear DNA content has been by far the most popular application of flow cytometry in plants. Because flow cytometry measures relative fluorescence intensities of nuclei stained by a DNA fluorochrome, ploidy determination, and estimation of the nuclear DNA content in absolute units both require comparison to a reference standard of known DNA content. This implies that the quality of the results obtained depends on the standard selection and use. Internal standardization, when the nuclei of an unknown sample and the reference standard are isolated, stained, and measured simultaneously, is mandatory for precise measurements. As DNA peaks representing G1/G0 nuclei of the sample and standard appear on the same histogram of fluorescence intensity, the quotient of their position on the fluorescence intensity axis provides the quotient of DNA amounts. For the estimation of DNA amounts in absolute units, a number of well‐established standards are now available to cover the range of known plant genome sizes. Since there are different standards in use, the standard and the genome size assigned to it has always to be reported. When none of the established standards fits, the introduction of a new standard species is needed. For this purpose, the regression line approach or simultaneous analysis of the candidate standard with several established standards should be prioritized. Moreover, the newly selected standard organism has to fulfill a number of requirements: it should be easy to identify and maintain, taxonomically unambiguous, globally available, with known genome size stability, lacking problematic metabolites, suitable for isolation of sufficient amounts of nuclei, and enabling measurements with low coefficients of variation of DNA peaks, hence suitable for the preparation of high quality samples.
Influence of Substitution Effect on MMCT in Mixed‐Valence Cyanido‐Bridged FeII−CN−Ru2III,III−NC−FeII System
Authors: Su Shao‐Dong , Zhu Xiao‐Quan , Wen Yue‐Hong , Wu Xin‐Tao , Sheng Tian‐Lu
Published: August 2021

This work reports the designed synthesis and characterization of nine tetranuclear mixed valence cyanido‐bridged complexes [CpMen(dppe)FeIICNRu2III,III(X‐DMBA)4NCFeII(dppe)CpMen][PF6]2 (1–9: CpMen=polymethylcyclopentadienyl, n=0, 4, 5; DMBA=N,N’‐dimethylbenzamidinate, X= H, MeO, CF3). The regular variation of crystallographic data, IR and UV/Vis/NIR spectra for complexes 1–9 demonstrates that the substitution effect of the ligand at the donor or acceptor fragment has explicit influence on the MMCT properties. Moreover, the electrochemical measurement might suggest the existence of long‐range electronic coupling between the two terminal FeII in this FeII−CN−Ru2III,III−NC−FeII array.
Critical Ligand and Salt Effects in Organomagnesiate‐Promoted 3,3‐Disubstituted Phthalides Synthesis from 2‐Iodobenzoate Derivatives
Authors: Touchet Sabrina , Yeardley Callum , O'Hara Charles T. , Gros Philippe C.
Published: August 2021

Phthalides, also called isobenzofuranones, are widespread in many biologically active compounds and natural products. To date, most of their synthetic routes are non‐convergent. Herein we report a convergent route using a metal halogen exchange (MHE) strategy. Indeed MHE of easily available 2‐iodobenzoate derivatives, using the bimetallic organomagnesiate complex (rac)‐(BIPHEN)BuMgLi, where (rac)‐BIPHEN is (rac)‐5,5′,6,6′‐tetramethyl‐3,3′‐di‐t‐butyl‐1,1′‐biphenyl‐2,2′‐diol, followed by addition of a ketone which lead to an intramolecular cyclisation, and the formation of a series of diverse 3,3‐disubstituted isobenzofuranones in good yield. Among the several MHE agents investigated, (rac)‐(BIPHEN)BuMgLi was the only one to make such a process possible with full tolerance of various reactive functional substituents useful for subsequent transformations. The synthetic pathway to access the magnesiate has been found to play a prominent role in its reactivity. Therefore, the bimetallic magnesiate complex has been characterized by solution‐state 1H, 7Li and 1H DOSY NMR experiments.
A survey: Making “Smart Contracts” really smart
Authors: TİMUÇİN Tunahan , BİROĞUL Serdar
Published: August 2021

Blockchain technology is a distributed data recording system developed to monitor and secure all encrypted transactions with the shortest identification. Blockchain technology made a name for itself in 2008. However, the real development of this technology has been realized with use of smart contracts in Blockchain technology. In the cryptocurrency world, a smart contract can be defined as an application or program running on the Blockchain. They operate as digital deals that have to comply with certain rules. These rules are predetermined by computer codes and then copied and implemented by the servers in the entire network. The use of the word “smart” as a term in smart contracts comes from the fact that it is not made manually and is realized digitally. In this study, it is aimed to contribute to future studies in the transformation of smart contracts into real “smart” contract structures by applying artificial intelligence algorithms.
Astrocyte arborization enhances Ca2+ but not cAMP signaling plasticity
Authors: Pirnat Samo , Božić Mićo , Dolanc Dorian , Horvat Anemari , Tavčar Petra , Vardjan Nina , Verkhratsky Alexei , Zorec Robert , Stenovec Matjaž
Published: August 2021

The plasticity of astrocytes is fundamental for their principal function, maintaining homeostasis of the central nervous system throughout life, and is associated with diverse exposomal challenges. Here, we used cultured astrocytes to investigate at subcellular level basic cell processes under controlled environmental conditions. We compared astroglial functional and signaling plasticity in standard serum‐containing growth medium, a condition mimicking pathologic conditions, and in medium without serum, favoring the acquisition of arborized morphology. Using opto−/electrophysiologic techniques, we examined cell viability, expression of astroglial markers, vesicle dynamics, and cytosolic Ca2+ and cAMP signaling. The results revealed altered vesicle dynamics in arborized astrocytes that was associated with increased resting [Ca2+]i and increased subcellular heterogeneity in [Ca2+]i, whereas [cAMP]i subcellular dynamics remained stable in both cultures, indicating that cAMP signaling is less prone to plastic remodeling than Ca2+ signaling, possibly also in in vivo contexts.
Synergistic combination of cytotoxic chemotherapy and cyclin‐dependent kinase 4/6 inhibitors in biliary tract cancers
Authors: Arora Mansi , Bogenberger James M. , Abdelrahman Amro M. , Yonkus Jennifer , Alva‐Ruiz Roberto , Leiting Jennifer L. , Chen Xianfeng , Serrano Uson Junior Pedro Luiz , Dumbauld Chelsae R. , Baker Alexander T. , Gamb Scott I. , Egan Jan B. , Zhou Yumei , Nagalo Bolni Marius , Meurice Nathalie , Eskelinen Eeva‐Liisa , Salomao Marcela A. , Kosiorek Heidi E. , Braggio Esteban , Barrett Michael T. , Buetow Kenneth H. , Sonbol Mohamad B. , Mansfield Aaron S. , Roberts Lewis R. , Bekaii‐Saab Tanios S. , Ahn Daniel H. , Truty Mark J. , Borad Mitesh J.
Published: August 2021

Background and aims

Biliary tract cancers (BTCs) are uncommon, but highly lethal, gastrointestinal malignancies. Gemcitabine/cisplatin is a standard‐of‐care systemic therapy, but has a modest impact on survival and harbors toxicities, including myelosuppression, nephropathy, neuropathy, and ototoxicity. Whereas BTCs are characterized by aberrations activating the cyclinD1/cyclin‐dependent kinase (CDK)4/6/CDK inhibitor 2a/retinoblastoma pathway, clinical use of CDK4/6 inhibitors as monotherapy is limited by lack of validated biomarkers, diffident preclinical efficacy, and development of acquired drug resistance. Emerging studies have explored therapeutic strategies to enhance the antitumor efficacy of CDK4/6 inhibitors by the combination with chemotherapy regimens, but their mechanism of action remains elusive.

Approach and results

Here, we report in vitro and in vivo synergy in BTC models, showing enhanced efficacy, reduced toxicity, and better survival with a combination comprising gemcitabine/cisplatin and CDK4/6 inhibitors. Furthermore, we demonstrated that abemaciclib monotherapy had only modest efficacy attributable to autophagy‐induced resistance. Notably, triplet therapy was able to potentiate efficacy through elimination of the autophagic flux. Correspondingly, abemaciclib potentiated ribonucleotide reductase catalytic subunit M1 reduction, resulting in sensitization to gemcitabine.

Conclusions

As such, these data provide robust preclinical mechanistic evidence of synergy between gemcitabine/cisplatin and CDK4/6 inhibitors and delineate a path forward for translation of these findings to preliminary clinical studies in advanced BTC patients.
Reorganization in a Simple Database System
Authors: Williams M. H. , Pattison I. M. , Neves J. C.
Published: August 2021

When a database is set up initially its structure is designed to match the expected pattern of usage. With time, changes to the database and to its pattern of usage may cause the structure to be less than ideal for the pattern of usage, and the database may need to be reorganized. A set of tools is described which will assist the database administrator in the tasks associated with reorganization. The tools have been implemented in Prolog and incorporated into a database accessed via the database language Query‐by‐Example.
TBLP—A Simple Preprocessor for Tables
Authors: Dewey Michael E.
Published: August 2021

Although powerful text processing programs have removed much of the tedium from the preparation of documents, some types of text are still difficult to lay out. Specialized preprocessors have been developed to prepare such text for input to general purpose text processors, and this paper discusses a program which lays out tabular material. The program has two main design aims: operation with very simple terminals, printers and text processors, and independence from the devices and other programs in the system. The paper also considers ways in which a variety of other types of text material can be processed as though they were tables: examples include simple diagrams, histograms and mathematical formulae.
Concurrent C
Authors: Gehani N. H. , Roome W. D.
Published: August 2021

Concurrent programming is becoming increasingly important because multicomputers, particularly networks of microprocessors, are rapidly becoming attractive alternatives to traditional maxicomputers. Effective use of such network computers requires that programs be written with components that can be executed in parallel. The C programming language does not have concurrent programming facilities. Our objective is to enhance C so that it can be used to write concurrent programs that can run efficiently on both single computers and multicomputers. Our concurrent programming extensions to C are based on the rendezvous concept. These extensions include mechanisms for the declaration and creation of processes, for process synchronization and interaction, and for process termination and abortion. We give a rationale for our decisions and compare Concurrent C extensions with the concurrent programming facilities in Ada. Concurrent C has been implemented on the UNIX system running on a single processor. A distributed version of Concurrent C is being implemented.
Health Effects of Calcium: Evidence From Mendelian Randomization Studies
Authors: Chen Yiheng , Forgetta Vincenzo , Richards J. Brent , Zhou Sirui
Published: August 2021

Calcium is widely used in conjunction with vitamin D to prevent osteoporosis. The use of calcium supplementation is also promoted for its potential benefits in lowering the risk for metabolic syndromes and cancers. However, the causal link between calcium and various health outcomes remains unclear. This review focuses on the evidence from 24 Mendelian randomization (MR) studies that were designed to minimize bias from confounding and reverse causation. These MR studies evaluated the effect of lifelong genetically higher serum calcium levels on various health outcomes. Overall, available MR studies found no conclusive effects of serum calcium levels on bone mineral density and fracture, ischemic stroke and heart failure, cancers, type 2 diabetes, Parkinson disease, or offspring birth weight. However, a higher serum calcium concentration was reported to have estimated causal effects on increased risks for coronary artery disease (especially myocardial infarction), migraine, renal colic, allergy/adverse effect of penicillin, and reduced risks for osteoarthrosis and osteoarthritis. In conclusion, supplementation of calcium in individuals from the general population is not predicted to influence the risk of most investigated diseases to date. Moreover, long‐term high serum calcium concentrations may result in adverse health outcomes. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
The Use of Oral Amino-Bisphosphonates and Coronavirus Disease 2019 (COVID-19) Outcomes
Authors: Degli Esposti Luca , Perrone Valentina , Sangiorgi Diego , Andretta Margherita , Bartolini Fausto , Cavaliere Arturo , Ciaccia Andrea , Dell'orco Stefania , Grego Stefano , Salzano Sara , Ubertazzo Loredana , Vercellone Adriano , Gatti Davide , Fassio Angelo , Viapiana Ombretta , Rossini Maurizio , Adami Giovanni
Published: August 2021

The determinants of the susceptibility to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and severe coronavirus disease 2019 (COVID-19) manifestations are yet not fully understood. Amino-bisphosphonates (N-BPs) have anti-inflammatory properties and have been shown to reduce the incidence of lower respiratory infections, cardiovascular events, and cancer. We conducted a population-based retrospective observational cohort study with the primary objective of determining if oral N-BPs treatment can play a role in the susceptibility to development of severe COVID-19. Administrative International Classification of Diseases, Ninth Revision, Clinical ModificationI (ICD-9-CM) and anatomical-therapeutic chemical (ATC) code data, representative of Italian population (9% sample of the overall population), were analyzed. Oral N-BPs (mainly alendronate and risedronate) were included in the analysis, zoledronic acid was excluded because of the low number of patients at risk. Incidence of COVID-19 hospitalization was 12.32 (95% confidence interval [CI], 9.61–15.04) and 11.55 (95% CI, 8.91–14.20), of intensive care unit (ICU) utilization because of COVID-19 was 1.25 (95% CI, 0.38–2.11) and 1.42 (95% CI, 0.49–2.36), and of all-cause death was 4.06 (95% CI, 2.50–5.61) and 3.96 (95% CI, 2.41–5.51) for oral N-BPs users and nonusers, respectively. Sensitivity analyses that excluded patients with prevalent vertebral or hip fragility fractures and without concomitant glucocorticoid treatment yielded similar results. In conclusion, we found that the incidence of COVID-19 hospitalization, intensive care unit (ICU) utilization, and COVID-19 potentially related mortality were similar in N-BPs–treated and nontreated subjects. Similar results were found in N-BPs versus other anti-osteoporotic drugs. We provide real-life data on the safety of oral N-BPs in terms of severe COVID-19 risk on a population-based cohort. Our results do not support the hypothesis that oral N-BPs can prevent COVID-19 infection and/or severe COVID-19; however, they do not seem to increase the risk. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
DJMol: An open‐source modeling platform for computational chemistry and materials science with a Python interpreter
Authors: G. Prasanna Krishnamohan , Sunil Rahul , Gupta Kapil , Lee Seung‐Cheol
Published: August 2021

We present a modular and extendable software suite, DJMol, for performing molecular simulations and it is demonstrated with DFTB+, Siesta, Atomic Simulation Environment, and OpenMD codes. It supports many of the standard features of an integrated development environment and consists of a structure builder and viewer, which could be connected with these electronic structure codes along with a set of data analyzers. This program comprises Java and Python modules and its libraries to carry out a different set of modeling tasks in materials science and chemistry. By adopting a Python interpreter into the software, a range of scriptable Python codes, such as Pymatgen can be incorporated into this programmable modeling platform. DJMol, through its common application programming interface (API), supports multiple modeling codes in the backend and several post‐processing tools. It benefits an experienced user by increasing efficiency, while a nonexpert user by easy to use API.
Momentum removal to obtain the position‐dependent diffusion constant in constrained molecular dynamics simulation
Authors: Fujimoto Kazushi , Nagai Tetsuro , Yamaguchi Tsuyoshi
Published: August 2021

The position‐dependent diffusion coefficient along with free energy profile are important parameters needed to study mass transport in heterogeneous systems such as biological and polymer membranes, and molecular dynamics (MD) calculation is a popular tool to obtain them. Among many methodologies, the Marrink–Berendsen (MB) method is often employed to calculate the position‐dependent diffusion coefficient, in which the autocorrelation function of the force on a fixed molecule is related to the friction on the molecule. However, the diffusion coefficient is shown to be affected by the period of the removal of the center‐of‐mass velocity, , which is necessary when performing MD calculations using the Ewald method for Coulombic interaction. We have clarified theoretically in this study how this operation affects the diffusion coefficient calculated by the MB method, and the theoretical predictions are proven by MD calculations. Therefore, we succeeded in providing guidance on how to select an appropriate value in estimating the position‐dependent diffusion coefficient by the MB method. This guideline is applicable also to the Woolf–Roux method.
Incidence and predictors of early and late sudden cardiac death in hospitalized Japanese patients with new‐onset systolic heart failure
Authors: Minami Yoshiaki , Kikuchi Noriko , Shiga Tsuyoshi , Suzuki Atsushi , Shoda Morio , Hagiwara Nobuhisa
Published: August 2021

Background

Patients with heart failure (HF) and low left ventricular ejection fraction (LVEF) are at high risk of sudden cardiac death (SCD). Optimal HF treatment can improve LVEF and reduce the risk of SCD. The aim of this study was to evaluate the incidence and predictors of SCD in Japanese patients with new‐onset systolic HF and to investigate factors that affect LVEF improvement.

Methods

We retrospectively studied 174 consecutive hospitalized patients with new‐onset HF and LVEF ≤35% (median age, 66 years; men, 71%). The primary outcome was a composite of SCD, sustained ventricular arrhythmias, and appropriate implantable cardioverter‐defibrillator therapy.

Results

The cumulative rates of meeting of the primary outcome at 3, 12, and 36 months after discharge were 3.9%, 8.1%, and 10.5%, respectively. Atrial fibrillation was a significant predictor of the primary outcome within 12 months after discharge (odds ratio, 5.87; 95% confidence interval [CI], 1.60–21.57). Among 104 patients who completed follow‐up echocardiography within 12 months after discharge, changes in LVEF were inversely associated with SCD (odds ratio/1% increase, 0.78; 95% CI, 0.65–0.93). A QRS duration <130 ms and a B‐type natriuretic peptide level <170 pg/mL were predictors of LVEF improvement to >35% (odds ratio, 3.69; 95% CI, 1.15–11.77; odds ratio, 3.19; 95% CI, 1.33–7.69, respectively).

Conclusions

Our results showed a high incidence of meeting of the primary outcome within 12 months after discharge in hospitalized patients with new‐onset systolic HF. An improved LVEF may reduce the risk of late SCD.
Periodontal disease progression in the second half of life and following a single episode of scaling and root planing: A clinical study in the Sri Lankan tea plantation cohort with documented clinical parameters for more than 40 years
Authors: Duong Ho‐Yan , Schmid Eric , Ramseier Christoph A. , Suvan Jean E. , Lang‐Hua Bich Hue , Burkhardt Rino , Schätzle Marc , Lang Niklaus P.
Published: August 2021

Background

To evaluate periodontal disease progression (PDP) and potentially detectable effects of a single episode of scaling and root planing (se‐SRP) in subjects lacking professional dental care and oral hygiene practices for >40 years.

Methods

In 2013, se‐SRP was offered to all available subjects from the original cohort of 480 males initially established in 1970. From a total of 75 attending the previous examination in 2010 (baseline), 27 consented to receive the intervention while 18 declined and served as controls. Clinical data were recorded again in 2014 (follow‐up) similarly to the previous surveys (1970 to 2010).

Results

Subjects’ mean age in 2010 was 62.5 (± 3.6, test) and 61.9 (± 3.8, control) years. At follow‐up, both groups presented with elevated tooth loss of 1.2 (from 15.5 ± 9.0, test) and 1.5 (from 17.9 ± 6.6, control) resulting in 1,392 (test) and 1,061 (control) sites available for further analysis. In both groups, clinical attachment level (CAL) loss and probing depths (PD) deteriorated. PD increase of 0.22 mm (± 1.70) in the test group was significantly higher compared with the control group (0.08 mm ± 1.30) (P <0.0001) demonstrating unaffected PDP. Computed estimates of further PDP revealed CAL and PD reductions in subjects aged ≥40 years. Specifically, the latter was positively correlated with tooth loss in subjects aged ≥40 years (P = 0.69, P = 0.0012) and ≥50 years (r = 0.62, P <0.0001).

Conclusion

se‐SRP in previously untreated periodontitis subjects aged ≥50 years may be ineffective in reducing PDP thus demanding advanced preventive measures, treatment in the first half of life, and sustained access to supportive care.
Evaluation of losses and quality maintenance of wheat during storage in a commercial unit in Brazil
Authors: Meneghetti Volnei L , Biduski Bárbara , Tibola Casiane S , Junior Alberto LM , de Miranda Martha Z , Lima Maria IPM , Guarienti Eliana M , Gutkoski Luiz C
Published: August 2021

BACKGROUND

Specific studies of Brazilian wheat storage on a commercial scale on the maintenance of wheat quality are required since the continental extent of Brazil has regions of different weather and because of the diversity of the storage network. This study aimed to evaluate the technological quality (physicochemical and rheological), sanitary quality (insects, fungi and mycotoxins) and dry matter loss of wheat stored in a metal silo in a commercial storage unit. Two dynamic samples, collected during loading and unloading of wheat in silos, and four static samples, collected using a commercial pneumatic grain sampler, were used in this study.

RESULTS

Silo temperature was higher than 20 °C during the summer season. The temperature was approximately 15 °C from June to December and provided excellent conditions for grain aeration, which resulted in the maintenance of wheat quality, with no changes in hectoliter weight and rheological properties of wheat (falling number, wet gluten and stability). The effect of Alternaria spp. (~220) and Aspergillus flavus (~7) infection on wheat did not differ statistically during the storage period, although a slight increase in A. flavus infection was noted in February (summer season). The wheat mycotoxins deoxynivalenol, zearalenone, aflatoxins and ochratoxin A were not detected during the studied storage period. Finally, dry matter reduced by approximately 0.4% after the storage period – approximately 0.013% per month.

CONCLUSION

The management practices and climate conditions in southern Brazil provided excellent conditions for grain aeration at ambient air temperature and led to the maintenance of wheat quality during the post‐harvest period. © 2021 Society of Chemical Industry.
Enhanced production of 2‐phenylethanol by salicylic acid and cyclodextrins in cell suspension cultures of the unexplored filamentous fungus Monochaetinula geoffroeana
Authors: Vázquez María Belén , Matencio Adrián , Bianchinotti María Virginia , García‐Carmona Francisco , López‐Nicolás José Manuel
Published: August 2021

BACKGROUND

2‐Phenylethanol (PEA) is a higher aromatic alcohol with a rose‐like odor, which is used in several industries. Although PEA can be synthesized, consumers are increasingly concerned about the toxicity of chemically synthesized products, and prefer natural aroma compound. PEA occurs naturally in the environment but concentrations are too low to justify extraction.

RESULTS

The present study offers a novel biological source of PEA: the filamentous fungi Monochaetinula geoffroeana. We report the highest recorded yield of PEA of fungal origin to date: 6.52 g L−1. The volatility and low water solubility of PEA can affect its use in many industries, for which reason complexation studies of PEA and cyclodextrins were carried out using the phase solubility technique. PEA formed 1:1 stoichiometric inclusion complexes with natural and modified CDs, the highest encapsulation constant being obtained with MβCD (K1:1 = 299.88 L mol−1). The complexation process significantly increased the water solubility of PEA. A computational study showed a high degree of correlation between computed scores and experimental values. Furthermore, this study reports the role of salicylic acid as an effective elicitor for improved PEA production by the studied fungi. Supplementation with 10 μmol L−1 salicylic acid increased PEA production from 6.52 to 10.54 g L−1.

CONCLUSION

The best treatment to enhance PEA production by M. geoffroeana under laboratory conditions was to use salicylic acid 10 μmol L−1. Due to the commercial importance of PEA, further investigation is needed to improve PEA production by M. geoffroeana and to optimize culture conditions in order to standardize yields. © 2021 Society of Chemical Industry.
Synthesis of cocoa butter alternatives from palm kernel stearin, coconut oil and fully hydrogenated palm stearin blends by chemical interesterification
Authors: Ornla‐ied Pimwalan , Podchong Pawitchaya , Sonwai Sopark
Published: August 2021

BACKGROUND

Chemical interesterification (CIE) is one of the important technological processes for the production of zero‐transfats. The aim of this study was to producetrans‐free cocoa butter alternatives (CBAs) from palm kernel stearin (PKS), coconut oil (CNO) and fully‐hydrogenated palm stearin (FHPS) blends via CIE using sodium methoxide as a catalyst. The physicochemical properties, crystallization and melting behavior, solid fat content (SFC), crystal morphology and polymorphism of the structured lipids (SLs) obtained and the corresponding physical blends (PBs) were characterized and compared with commercial CBAs.

RESULTS

After CIE, randomization of fatty acid distribution within and among triacylglycerol (TAG) molecules of PKS, CNO and FHPS resulted in a modification in TAG compositions of the PKS/CNO/FHPS blends and improved the properties and crystallization behavior of the blends. SFC and slip melting points of all SLs decreased from those of their respective PBs. In particular, SLs obtained from CIE of blends with 60–70% wt. PKS (blend ratios 60:10:30 and 70:10:20) exhibited the melting characteristic, SFC curves, crystal morphology and polymorphic form most similar to the commercial CBAs. In addition, these blends melted almost completely at body temperature, an improvement from that of the commercial CBAs.

CONCLUSION

SLs obtained from CIE of blends with 60–70% wt. PKS has high potential to be used commercially astrans‐free CBAs for the confectionery industry. © 2021 Society of Chemical Industry.
Photophysical/Photochemical, Kinetic, and Migration Stability Studies of One‐Component Polymerizable Thioxanthone‐Based Photoinitiators
Authors: Wu Qingqing , Mo Yongfei , Zhang Yachao , Li Fushao , Deng Mingsen
Published: August 2021

Herein, N‐benzyl‐N‐(9‐oxo‐9H‐thioxanthen‐2‐yl)acrylamide (TXNBA) is designed and synthesized as one‐component polymerizable photoinitiator (PI). It is investigated in terms of its photophysical/photochemical, kinetic, and migration stability properties by ultraviolet‐visible spectrophotometer, Fourier transform infrared spectrometer, and EPR spin trapping experiments. In conjunction with the experimental studies, series of density functional theory calculations are performed and various photophysical and photochemical properties are computationally calculated and visualized. The photolysis and photoinitiation mechanism of TXNBA is clarified. Comparison of the results of 2‐isopropylthioxanthone (ITX) system has shown that TXNBA is an efficient one‐component polymerizable PI with excellent migration stability. The photoinitiator's migration ratio of TXNBA system to ITX system is 8.52%.
Role of the Aryl Hydrocarbon Receptor (AhR) in Mediating the Effects of Coffee in the Colon
Authors: Chapkin Robert S. , Davidson Laurie A. , Park Hyejin , Jin Un‐Ho , Fan Yang‐Yi , Cheng Yating , Hensel Martha E. , Landrock Kerstin K. , Allred Clinton , Menon Rani , Klemashevich Cory , Jayaraman Arul , Safe Stephen
Published: August 2021

Scope

This study investigates the mechanism of action and functional effects of coffee extracts in colonic cells, on intestinal stem cell growth, and inhibition of dextran sodium sulfate (DSS)‐induced intestinal barrier damage in mice.

Methods and Results

Aqueous coffee extracts induced Ah receptor (AhR) ‐responsive CYP1A1, CYP1B1, and UGT1A1 gene expression in colon‐derived Caco2 and YAMC cells. Tissue‐specific AhR knockout (AhRf/f x Lgr5‐GFP‐CreERT2 x Villin‐Cre), wild‐type (Lgr5‐CreERT2 x Villin‐Cre) mice are sources of stem cell enriched organoids and both coffee extracts and norharman, an AhR‐active component of these extracts inhibited stem cell growth. Coffee extracts also inhibit DSS‐induced damage to intestinal barrier function and DSS‐induced mucosal inflammatory genes such as IL‐6 and TGF‐β1 in wild‐type (AhR+/+) but not AhR–/– mice. In contrast, coffee does not exhibit protective effects in intestinal‐specific AhR knockout mice. Coffee extracts also enhanced overall formation of AhR‐active microbial metabolites.

Conclusions

In colon‐derived cells and in the mouse intestine, coffee induced several AhR‐dependent responses including gene expression, inhibition of intestinal stem cell‐enriched organoid growth, and inhibition of DSS‐induced intestinal barrier damage. We conclude that the anti‐inflammatory effects of coffee in the intestine are due, in part, to activation of AhR signaling.
Adjoint image warping using multivariate splines with application to four‐dimensional computed tomography
Authors: Renders Jens , Sijbers Jan , De Beenhouwer Jan
Published: August 2021

Purpose

Adjoint image warping is an important tool to solve image reconstruction problems that warp the unknown image in the forward model. This includes four‐dimensional computed tomography (4D‐CT) models in which images are compared against recorded projection images of various time frames using image warping as a model of the motion. The inversion of these models requires the adjoint of image warping, which up to now has been substituted by approximations. We introduce an efficient implementation of the exact adjoints of multivariate spline based image warping, and compare it against previously used alternatives.

Methods

Using symbolic computer algebra, we computed a list of 64 polynomials that allow us to compute a matrix representation of trivariate cubic image warping. By combining an on‐the‐fly computation of this matrix with a parallelized implementation of columnwise matrix multiplication, we obtained an efficient, low memory implementation of the adjoint action of 3D cubic image warping. We used this operator in the solution of a previously proposed 4D‐CT reconstruction model in which the image of a single subscan was compared against projection data of multiple subscans by warping and then projecting the image. We compared the properties of our exact adjoint with those of approximate adjoints by warping along inverted motion.

Results

Our method requires halve the memory to store motion between subscans, compared to methods that need to compute and store an approximate inverse of the motion. It also avoids the computation time to invert the motion and the tunable parameter of the number of iterations used to perform this inversion. Yet, a similar and often better reconstruction quality was obtained in comparison with these more expensive methods, especially when the motion is large. When compared against a simpler method that is similar to ours in computational demands, our method achieves a higher reconstruction quality in general.

Conclusions

Our implementation of the exact adjoint of cubic image warping improves efficiency and provides accurate reconstructions.
Tomography of dark‐field scatter including single‐exposure Moiré fringe analysis with X‐ray biprism interferometry—A simulation study
Authors: Tao Weijie , Sung Yongjin , Kim Sally Ji Who , Huang Qiu , Gullberg Grant T. , Seo Youngho , Fuller Michael
Published: August 2021

Purpose

In this work, we present tomographic simulations of a new hardware concept for X‐ray phase‐contrast interferometry wherein the phase gratings are replaced with an array of Fresnel biprisms, and Moiré fringe analysis is used instead of “phase stepping” popular with grating‐based setups.

Methods

Projections of a phantom consisting of four layers of parallel carbon microfibers is simulated using wave optics representation of X‐ray electromagnetic waves. Simulated projections of a phantom with preferential scatter perpendicular to the direction of the fibers are performed to analyze the extraction of small‐angle scatter from dark‐field projections for the following: (1) biprism interferometry using Moiré fringe analysis; (2) grating interferometry using phase stepping with eight grating steps; and (3) grating interferometry using Moiré fringe analysis. Dark‐field projections are modeled as projections of voxel intensities represented by a fixed finite vector basis set of scattering directions. An iterative MLEM algorithm is used to reconstruct, from simulated projection data, the coefficients of a fixed set of seven basis vectors at each voxel representing the small‐angle scatter distribution.

Results

Results of reconstructed vector coefficients are shown comparing the three simulated imaging configurations. The single‐exposure Moiré fringe analysis shows not only an increase in noise because of one‐eighth the number of projection samples but also is obtained with less dose and faster acquisition times. Furthermore, replacing grating interferometry with biprism interferometry provides better contrast‐to‐noise.

Conclusion

The simulations demonstrate the feasibility of the reconstruction of dark‐field data acquired with a biprism interferometry system. With the potential of higher fringe visibility, biprism interferometry with Moiré fringe analysis might provide equal or better image quality to that of phase stepping methods with less imaging time and lower dose.
SABRE‐enhanced real‐time pure shift NMR spectroscopy
Authors: Taylor Daniel A. , Natrajan Louise S. , Nilsson Mathias , Adams Ralph W.
Published: August 2021

Pure shift nuclear magnetic resonance (NMR) methods suppress the effect of homonuclear scalar couplings to produce NMR spectra consisting solely of a single signal for each chemically distinct site. They are increasingly relied upon for analysis of complex molecules and mixtures as they overcome the extensive signal overlap that complicates proton NMR spectra of all but the simplest species. Current broadband pure shift methodologies for 1D proton spectra suffer from reduced sensitivity compared with their conventional counterparts and typically require a large amount of instrument time for low concentration samples. In this study, we demonstrate how the sensitivity limitation may be overcome by transiently increasing the bulk polarization using signal amplification by reversible exchange (SABRE) hyperpolarization. We utilize para‐enriched dihydrogen to enhance the pure shift NMR resonances of pyridine by up to a factor of 60 in a single‐scan experiment and extend this to propose a method to unambiguously determine mixture components based on the enhancement of their pure shift NMR signals.
Deuterium MRS of early treatment‐induced changes in tumour lactate in vitro
Authors: Tan Josephine L. , Djayakarsana Daniel , Wang Hanzhi , Chan Rachel W. , Bailey Colleen , Lau Angus Z.
Published: August 2021

Elevated production of lactate is a key characteristic of aberrant tumour cell metabolism and can be non‐invasively measured as an early marker of tumour response using deuterium (2H) MRS. Following treatment, changes in the 2H‐labelled lactate signal could identify tumour cell death or impaired metabolic function, which precede morphological changes conventionally used to assess tumour response. In this work, the association between apoptotic cell death, extracellular lactate concentration, and early treatment‐induced changes in the 2H‐labelled lactate signal was established in an in vitro tumour model. Experiments were conducted at 7 T on acute myeloid leukaemia (AML) cells, which had been treated with 10 μg/mL of the chemotherapeutic agent cisplatin. At 24 and 48 h after cisplatin treatment the cells were supplied with 20 mM of [6,6′‐2H2]glucose and scanned over 2 h using a two‐dimensional 2H MR spectroscopic imaging sequence. The resulting signals from 2H‐labelled glucose, lactate, and water were quantified using a spectral fitting algorithm implemented on the Oxford Spectroscopy Analysis MATLAB toolbox. After scanning, the cells were processed for histological stains (terminal deoxynucleotidyl transferase UTP nick end labelling and haematoxylin and eosin) to assess apoptotic area fraction and cell morphology respectively, while a colorimetric assay was used to measure extracellular lactate concentrations in the supernatant. Significantly lower levels of 2H‐labelled lactate were observed in the 48 h treated cells compared with the untreated and 24 h treated cells, and these changes were significantly correlated with an increase in apoptotic fraction and a decrease in extracellular lactate. By establishing the biological processes associated with treatment‐induced changes in the 2H‐labelled lactate signal, these findings suggest that 2H MRS of lactate may be valuable in evaluating early tumour response.
Impact of adverse events on patient outcomes in a Japanese intensive care unit: a retrospective observational study
Authors: Aikawa Gen , Ouchi Akira , Sakuramoto Hideaki , Ono Chiemi , Hatozaki Chie , Okamoto Mayu , Hoshino Tetsuya , Shimojo Nobutake , Inoue Yoshiaki
Published: August 2021

Aim

We investigated adverse events (AEs) in a Japanese intensive care unit (ICU) and evaluated the impact of cause‐specific AEs on mortality and length of stay.

Design

A retrospective observational study in the ICU of an academic hospital.

Methods

We reviewed medical records with the Global Trigger Tool.

Results

Of the 246 patients, 126 (51%) experienced one or more AEs with an incidence of 201 per 1000 patient‐days and 115 per 100 admissions. A total of 294 AEs were detected with 119 (42%) adverse drug events, 67 (24%) procedural complications, 63 (22%) surgical complications, 26 (9%) nosocomial infections, 5 (2%) therapeutic errors and 4 (1%) diagnostic errors. Adverse event (AE) presence was associated with length of ICU stay (β = 2.85, 95% confidence interval [CI]: 1.09–4.61). Adverse drug events, procedural complications and nosocomial infections were strongly associated with length of ICU stay (β = 2.38, 95% CI: 0.77–3.98; β = 3.75, 95% CI: 2.03–5.48; β = 6.52, 95% CI: 4.07–8.97 respectively).
Trifluridine/Tipiracil and Regorafenib in Patients with Metastatic Colorectal Cancer: A Retrospective Study at a Tertiary Oncology Center
Authors: Patel Anuj K. , Abhyankar Ritika , Brais Lauren K. , Duh Mei Sheng , Barghout Victoria E. , Huynh Lynn , Yenikomshian Mihran A. , Ng Kimmie , Fuchs Charles S.
Published: August 2021

Background

Trifluridine/tipiracil (FTD/TPI) and regorafenib prolong survival for patients with refractory metastatic colorectal cancer (mCRC); limited comparative effectiveness data exist.

Materials and Methods

A retrospective, longitudinal cohort study of patients with mCRC who initiated FTD/TPI or regorafenib (index therapy) between 2012 and 2017 at a U.S. tertiary oncology center, Dana-Farber Cancer Institute, was conducted. Using best tumor response assessments, real-world overall response rates (rwORR) and disease control rates (rwDCR) were described and analyzed using logistic regression. Survival rate was examined for each month after index therapy using Kaplan-Meier. Overall survival (OS) was assessed using Cox proportional hazards models. Subgroup analyses among patients with index therapy as second- or third-line were performed.

Results

One hundred twenty-six and 95 patients were treated with FTD/TPI or regorafenib as index therapy, respectively. Patients treated with FTD/TPI versus regorafenib had a better response (rwORR 52.5% vs. 34.2%; adjusted odds ratio [OR] = 2.6; all p value <.05; rwDCR 64.2% vs. 46.1%; adjusted OR = 2.5; all p value <.05). Similar findings were observed for FTD/TPI versus regorafenib as second- or third-line therapy (rwORR 54.8% vs. 25.9%; adjusted OR = 4.1; all p value <.05; rwDCR 69.0% vs. 37.0%; adjusted OR = 4.9; all p value <.05). A greater proportion of patients treated with FTD/TPI versus regorafenib survived at 3 months (86.2% vs. 73.4%; p value = .016) and 4 months (79.6% vs. 65.8%; p value = .017). Adjusted OS hazard ratio for FTD/TPI versus regorafenib was 0.80, p value = .157.

Conclusion

Patients treated with FTD/TPI had better tumor response and disease control than patients treated with regorafenib. Subgroup analysis in second- or third-line suggests that early use of FTD/TPI may have clinical benefits.

Implications for Practice

In this retrospective cohort study, patients with refractory metastatic colorectal cancer treated with trifluridine/tipiracil (FTD/TPI) were significantly less likely than those treated with regorafenib to have dose modifications and more likely to have higher real-world objective response rate (rwORR) and real-world disease control rate (rwDCR) while treated. Patients treated with FTD/TPI versus regorafenib had significantly higher odds of having rwORR or rwDCR in adjusted analyses. Monthly survival rates were higher overall in patients treated with FTD/TPI versus regorafenib in the first 6 months of follow-up, particularly at months 3 and 4. This study offers insight into patients' treatment experience in real-world clinical settings.
Using psycho‐behavioral phenotyping for overweight and obesity: Confirmation of the 6 factor questionnaire
Authors: Kushner Robert F. , Hammond Michael M.
Published: August 2021

Objective

Questionnaires that assess dietary habits, eating behaviors, and relevant psychosocial constructs are routinely used in obesity research and clinical practice. The 6 factor questionnaire (6FQ) was previously developed as an assessment tool for psycho‐behavioral phenotyping. The primary purpose of this study was to confirm and validate the original findings in a large diverse adult population.

Methods

A total of 5399 self‐selected participants (mean age of 48 ± 13 years and body mass index of 32 ± 8 kg/m2) completed the 6FQ online. The association between self‐reported demographic data and 6FQ responses was assessed using linear regression models.

Results

Mean factor score and odds ratio analyses consistently demonstrated a statistically significant relationship between factors and body weight even after adjusting for age, sex, and race/ethnicity.

Conclusions

Although the study was correlational in design, the results demonstrate that the 6FQ, an instrument that represents multidimensional unhealthful lifestyle patterns associated with diet, physical activity, cognition, and self‐perception worsen with increasing body weight. Psycho‐behavioral phenotyping may be a useful approach when assessing and treating patients with obesity.