bluuebunny/crossref_metadata_2025 huggingface dataset:
Defect Engineering in Metal–Organic Frameworks Towards Advanced Mixed Matrix Membranes for Efficient Propylene/Propane Separation
Authors: Lee Tae Hoon , Jung Jae Gu , Kim Yu Jin , Roh Ji Soo , Yoon Hee Wook , Ghanem Bader S. , Kim Hyo Won , Cho Young Hoon , Pinnau Ingo , Park Ho Bum
Published: March 2021

Highly permselective and durable membrane materials have been sought for energy‐efficient C3H6/C3H8 separation. Mixed‐matrix membranes (MMMs) comprising a polymer matrix and metal–organic frameworks (MOFs) are promising candidates for this application; however, rational matching of filler‐matrix is challenging and their separation performances need to be further improved. Here, we propose a novel strategy of “defect engineering” in MOFs as an additional degree of freedom to design advanced MMMs. MMMs incorporated with defect‐engineered MOFs exhibit exceptionally high C3H6 permeability and maintained C3H6/C3H8 selectivity, especially with enhanced stability under industrial mixed‐gas conditions. The gas transport, sorption, and material characterizations reveal that the defect sites in MOFs provide the resulting MMMs with not only ultrafast diffusion pathways but also favorable C3H6 sorption by forming complexation with unsaturated open metal sites, confirmed by in situ FT‐IR studies. Most importantly, the concept is also valid for different polymer matrices and gas pairs, demonstrating its versatile potential in other fields.
Bedeutung der Frequenz für das Vibrationsrammen von Spundbohlen
Authors: Massarsch Karl Rainer , Wersäll Carl , Fellenius Bengt H. , Ehrmanntraut Editha
Published: March 2021

Bei modernen Vibratoren können die Vibrationsfrequenz und das exzentrische Moment während des Rammens verändert werden. Das dynamische Zusammenwirken der schwingenden Bohle mit dem umgebenden Boden kann durch Feldmessungen untersucht werden. Bisher wurde der Einfluss der Vibrationsfrequenz auf den Eindringvorgang und die Ausstrahlung von Vibrationen in die Umgebung nicht ausreichend beachtet, obwohl die Frequenz für die Rammbarkeit und die Erschütterungsausbreitung von Bedeutung sind. In vorliegendem Beitrag werden die Ergebnisse von drei Proberammungen beschrieben, bei denen Doppelbohlen in einen mitteldichten kiesigen Sandboden einvibriert wurden. Messungen wurden am Vibrator, an der Spundbohle und im Boden durchgeführt, womit u. a. die Frequenz, die Schwingungsamplitude, die Eindringgeschwindigkeit der Bohle und die Bodenerschütterungen registriert wurden. Eine Analyse der Messwerte zeigt, dass die Schwingungsfrequenz ein wichtiger Parameter ist. Wenn die Bohle nahe der Resonanzfrequenz des Vibrator‐Bohle‐Bodensystems erregt wird, schwingt die Bohle in Phase mit dem umgebenden Boden. In diesem Zustand sinkt die Eindringgeschwindigkeit ab, während die Vibrationsausstrahlung in den Boden ansteigt. Die Resonanzfrequenz kann einfach durch Messung der Bodenschwingungen bestimmt werden. Effektives Vibrationsrammen wird erreicht, wenn die Vibrationsfrequenz deutlich höher als die Resonanzfrequenz ist. Vibrationsmessungen zeigen, dass durch das Absenken des exzentrischen Moments stärkere Bodenerschütterungen verursacht werden können.
Clash of the calculators: External validation of prostate cancer risk calculators in men undergoing mpMRI and transperineal biopsy
Authors: Wei G. , Kelly B. D. , Timm B. , Perera M. , Lundon D. J. , Jack G. , Bolton D. M.
Published: March 2021

Objective

To compare the accuracy of the European Randomized Study of Screening for Prostate Cancer (ERSPC) RC, MRI‐ERSPC‐RC, and Prostate Biopsy Collaborative Group (PBCG) RC in patients undergoing transperineal prostate biopsy.

Patients and methods

We identified 392 patients who underwent mpMRI before transperineal prostate biopsy across multiple public and private institutions between January 2017 and August 2019. The estimated probabilities of detecting PCa and significant PCa were calculated using the MRI‐ERSPC‐RC, ERSPC‐RC, and PBCG‐RC. Receiver operating characteristic (ROC) curves for each calculator were generated and the area underneath the curve (AUC) was compared. Calibration and clinical utility were assessed with calibration plots and decision curve analysis, respectively.

Results

PCa was detected in 285 patients (72.7%) with significant PCa found in 200 patients (51.1%). ROC curve analysis found the MRI‐ERSPC‐RC outperformed the ERSPC‐RC and PBCG‐RC. For the prediction of PCa, the AUC was 0.756, 0.696, and 0.675 for the MRI‐ERSPC‐RC, ERSPC‐RC, and PBCG‐RC, respectively. The AUC for the prediction of significant PCa was 0.803, 0.745, and 0.746 for the MRI‐ERSPC‐RC, ERSPC‐RC, and PBCG‐RC, respectively.

Conclusions

Our study validated the ERSPC‐RC, MRI‐ERSPC‐RC, and PBCG‐RC in a cohort undergoing transperineal prostate biopsy with the MRI‐ERSPC‐RC performing the best. These RCs may enable improved shared decision making and help to guide patient selection for biopsy.
Experimentelle Untersuchungen zum Materialverhalten von Polymerbeton
Authors: Lambert Thomas , Bender Michél , Becker Wieland
Published: March 2021

Polymerbeton ist ein hochleistungsfähiges Material, welches im Bau‐ und Maschinenbauwesen bereits eine vielfältige Anwendung erfährt. Im Bauwesen kann das Potenzial des Materials allerdings bislang nicht gänzlich genutzt werden. Ursache ist neben fehlenden normativen Grundlagen für das Material und dessen Bemessung auch eine fehlende Klassifizierung des Materials nach den relevanten bautechnischen Normen. Gerade im Anwendungsbereich tragender Bauteile, wie z. B. hochbeanspruchter Knoten‐ und Anschlussgeometrien von Stabtragwerken und Ingenieurkonstruktionen, liegt jedoch das Potenzial des Polymerbetons mit seiner hohen Druck‐ und Biegezugfestigkeit. Um die Anwendungsmöglichkeiten im Bauwesen entsprechend zu erweitern, werden maßgebende Materialparameter eines handelsüblichen Polymerbetons, wie die Druck‐, Biegezug‐, Zugfestigkeit, der E‐Modul sowie die Verbundfestigkeit zum gerippten Betonstahl, nach bautechnischen Normen geprüft und charakteristische Materialkennwerte abgeleitet. Die Untersuchungen variieren nach Probekörpergeometrien, Betonalter und Temperatur. Die Einordnung und Klassifizierung der Materialeigenschaften erfolgt im Vergleich mit normal‐, hoch‐ und ultrahochfesten Betonen.
Biotechnological production of the European corn borer sex pheromone in the yeast Yarrowia lipolytica
Authors: Petkevicius Karolis , Koutsoumpeli Eleni , Betsi Petri Christina , Ding Bao‐Jian , Kildegaard Kanchana Rueksomtawin , Jensen Hilbert , Mezo Nora , Mazziotta Andrea , Gabrielsson Anders , Sinkwitz Christina , Lorantfy Bettina , Holkenbrink Carina , Löfstedt Christer , Raptopoulos Dimitris , Konstantopoulou Maria , Borodina Irina
Published: March 2021

The European corn borer (ECB) Ostrinia nubilalis is a widespread pest of cereals, particularly maize. Mating disruption with the sex pheromone is a potentially attractive method for managing this pest; however, chemical synthesis of pheromones requires expensive starting materials and catalysts and generates hazardous waste. The goal of this study was to develop a biotechnological method for the production of ECB sex pheromone. Our approach was to engineer the oleaginous yeast Yarrowia lipolytica to produce (Z)‐11‐tetradecenol (Z11‐14:OH), which can then be chemically acetylated to (Z)‐11‐tetradecenyl acetate (Z11‐14:OAc), the main pheromone component of the Z‐race of O. nubilalis. First, a C14 platform strain with increased biosynthesis of myristoyl‐CoA was obtained by introducing a point mutation into the α‐subunit of fatty acid synthase, replacing isoleucine 1220 with phenylalanine (Fas2pI1220F). The intracellular accumulation of myristic acid increased 8.4‐fold. Next, fatty acyl‐CoA desaturases (FAD) and fatty acyl‐CoA reductases (FAR) from nine different species of Lepidoptera were screened in the C14 platform strain, individually and in combinations. A titer of 29.2 ± 1.6 mg L‐1 Z11‐14:OH was reached in small‐scale cultivation with an optimal combination of a FAD (Lbo_PPTQ) from Lobesia botrana and FAR (HarFAR) from Helicoverpa armigera. When the second copies of FAD and FAR genes were introduced, the titer improved 2.1‐fold. The native FAS1 gene's overexpression led to a further 1.5‐fold titer increase, reaching 93.9 ± 11.7 mg L‐1 in small‐scale cultivation. When the same engineered strain was cultivated in controlled 1 L bioreactors in fed‐batch mode, 188.1 ± 13.4 mg L‐1 of Z11‐14:OH was obtained. Fatty alcohols were extracted from the biomass and chemically acetylated to obtain Z11‐14:OAc. Electroantennogram experiments showed that males of the Z‐race of O. nubilalis were responsive to biologically‐derived pheromone blend. Behavioral bioassays in a wind tunnel revealed attraction of male O. nubilalis, although full precopulatory behavior was observed less often than for the chemically synthesized pheromone blend. The study paves the way for the production of ECB pheromone by fermentation.
RETRACTED: LINC01224 accelerates malignant transformation via MiR‐193a‐5p/CDK8 axis in gastric cancer
Authors: Sun Hui , Yan Jihong , Tian Guangyu , Chen Xiaojun , Song Wenbo
Published: March 2021

Background

Gastric cancer (GC) is a malignant tumor with a significantly high mortality rate, yet, its pathogenesis is not fully understood. Bioinformatics predicted that LINC01224 is highly expressed in stomach adenocarcinoma (STAD), and showed that LINC01224 adsorbed miR‐193a‐5p to target CDK8. Therefore, this study intended to verify the effect of the LINC01224/miR‐193a‐5p/CDK8 axis on the biological behavior of gastric cancer.

Methods

Expressions of LINC01224, miR‐193a‐5p, CDK8, apoptosis‐, and EMT‐related genes were analyzed using the GEPIA website, RT‐qPCR, in situ hybridization, and Western blot as needed. Bioinformatics and dual luciferase assay were used to evaluate the relationship between LINC01224, miR‐193a‐5p, and CDK8. Functional experiments and rescue experiments (MTT assay, flow cytometry, wound healing assay, and Transwell) were conducted to detect the effects of the above genes on the biological characteristics of GC cells. Tumorigenesis assay was used to verify the results of in vitro experiments.

Results

LINC01224 adsorbed miR‐193a‐5p to target and upregulate CDK8. The expressions of LINC01224 and CDK8 were increased, while the expression of miR‐193a‐5p was decreased in GC. Overexpressed LINC01224 promoted cell viability, migration and invasion, accelerated tumor formation, attenuated apoptosis, inhibited the expressions of apoptosis‐related proteins, and promoted the expressions of EMT‐related proteins, whereas silenced LINC01224 led to the opposite effect. MiR‐193a‐5p inhibitor partially offset the effect of silenced LINC01224; interestingly, siCDK8 significantly reversed the effect of miR‐193a‐5p inhibitor on GC cells.

Conclusion

LINC01224 affects the biological behavior of gastric cancer by mediating miR‐193a‐5p to regulate CDK8.
When should retailers increase prices during a crisis? A longitudinal inquiry during the COVID‐19 pandemic
Authors: Jeong Haeyoung , Ye Hongjun , Bhatt Siddharth , Zhang Jintao , Suri Rajneesh
Published: March 2021

The consumer price index in the United States has increased since the COVID‐19 outbreak. Little is known about how consumers perceive price increases during such a crisis. Our research focuses on how consumers' price fairness perceptions change at different time points of the COVID‐19 pandemic. Results from a longitudinal study (April–May, 2020, N = 271) suggest that when the lockdown restrictions were eased, consumers experienced changes in affect and perceived price increases to be less unfair. Our analysis reveals that such an effect was driven by changes in positive affect rather than negative affect. This research advances pricing literature by showing that affect, triggered by external situations such as a crisis, influences price fairness perceptions over and above the negative affect induced by the price increase.
Green Emulsified Liquid Membrane for Hexavalent Chromium Extraction: Formulation and Process Optimization
Authors: Anarakdim Katia , Gutiérrez Gemma , Cambiella Ángel , Senhadji‐Kebiche Ounissa , Matos María
Published: March 2021

The influence of several formulation and operating conditions on hexavalent chromium extraction by green emulsified liquid membranes (GELMs) was studied. An excellent removal efficiency was achieved under optimized conditions. The optimum GELM formulation in terms of stability was obtained with tri‐n‐octylphosphine oxide (TOPO) as extractant, polyglycerol polyricinoleate (PGPR) and polyoxyethylene sorbitan monooleate (Tween 80) as stabilizers in sunflower oil. Optimum GELMs showed a monomodal distribution of sizes around 1.29 µm. Results confimed that the use of a vegetable solvent and PGPR for GELM formulation is a promising alternative to petroleum organic solvents.
Comparison of partial least squares‐discriminant analysis and soft independent modeling of class analogy methods for classification of Saccharomyces cerevisiae cells based on mid‐infrared spectroscopy
Authors: Sampaio Pedro Sousa , Calado Cecília R. C.
Published: March 2021

Saccharomyces cerevisiae is a widely studied and highly utilized eukaryotic organism, ideally suited to high throughput metabolic analysis, being a powerful model for understanding basic cell biology. This study compares the models developed by two supervised methods, such as the partial least squares‐discriminant analysis (PLS‐DA) and soft independent modeling of class analogy (SIMCA), using mid‐infrared (MIR) spectra registered during the growth of S. cerevisiae in bioreactor. The spectra were analyzed using the principal component analysis (PCA), with resolution in five different classes, which were well defined in terms of their biochemical parameters. The SIMCA model showed a significant fitting, 99%, validation, 98%, and prediction parameters, 97%, comparatively with PLS‐DA model. Regarding accuracy, sensitivity, and specificity parameters, a value between 83% and 100% was achieved for both methods, but the SIMCA method showed significant specificity and sensitivity values, 98%–100%, representing a suitable classification tool of yeast cells. According to these results, the MIR spectra associated with chemometric tools can be considered a valued strategy for a classification and detailed analysis for an accurate control, allowing to predict the evolution of the corrected process in advance, avoiding losses of time and costs associated with new fermentations, identifying a significant number of samples in any biotechnological process.
The Simplest Model for Doped Poly(3,4‐ethylenedioxythiophene) (PEDOT): Single‐crystalline EDOT Dimer Radical Cation Salts
Authors: Kameyama Ryohei , Fujino Tomoko , Dekura Shun , Kawamura Mitsuaki , Ozaki Taisuke , Mori Hatsumi
Published: March 2021

Invited for the cover of this issue is the group of Tomoko Fujino and Hatsumi Mori at the University of Tokyo. The image depicts the structural information of doped PEDOT uncovered by the single‐crystalline EDOT dimer model. Read the full text of the article at .10.1002/chem.202005333
A coupled hydrodynamic‐biokinetic simulation of three‐phase flow in an oxidation ditch using CFD
Authors: Norouzi‐Firouz Hossein , Sarrafzadeh Mohammad‐Hossein , Zarghami Reza , Moshiri‐Tabrizi Iman
Published: March 2021

Coupling the hydrodynamic and biokinetic models, was done on a lab‐scale oxidation ditch as the bioreactor of the activated sludge process and validated against the available experimental data. The simulation was carried out in three‐phase, three‐dimensional conditions with k‐є and Eulerian–Eulerian methods. A simplified activated sludge model No.1 (ASM1) has been added to transport terms to account for the biokinetic model. Rotatory speed for surface aerator was initially increased and its corresponding effects on solid volume fraction, dissolved oxygen, and velocity profile and values were observed. A 150 rpm increase in the rotational velocity resulted in 36% higher average liquid phase velocity for the one‐aerator arrangement, which was 3% more than that of the two‐aerator oxidation ditch. The 150% increase in the solid volume fraction led to a 10% reduction in the maximum liquid phase velocity. The effect of aerators number has been considered explicitly on baffle performance and liquid phase velocity profile. Finally, a new design for the aerator has been offered that provides an ordered flow field and optimal conditions for the performance of the baffle and oxidation process.
Origin of the Electron Transport Properties of Aromatic and Antiaromatic Single Molecule Circuits
Authors: Arasu Narendra P. , Vázquez Héctor
Published: March 2021

Antiaromatic molecules have been predicted to exhibit increased electron transport properties when placed between two nanoelectrodes compared to their aromatic analogues. While some studies have demonstrated this relationship, others have found no substantial increase. We use atomistic simulations to establish a general relationship between the electronic spectra of aromatic, antiaromatic, and quinoidal molecules and illustrate its implications for electron transport. We compare the electronic properties of a series of aromatic‐antiaromatic counterparts and show that antiaromaticity effectively p‐dopes the aromatic electronic spectra. As a consequence, the conducting properties of aromatic‐antiaromatic analogues are closely related. For similar attachment points to the electrodes, an interference feature is expected in the HOMO‐LUMO gap of one whenever it is absent in the other one. We demonstrate how the relative conductance of aromatic‐antiaromatic pairs can be tuned and even reversed through the choice of chemical linker groups. Our work provides a general picture relating connectivity, (anti)aromaticity, and quantum interference and establishes new design rules for single molecule circuits.
Mechanistic insights into the heterogeneous response to anti‐VEGF treatment in tumors
Authors: Li Ding , Finley Stacey D.
Published: March 2021

Vascular endothelial growth factor (VEGF) is a strong promoter of angiogenesis in tumors, and anti‐VEGF treatment, such as a humanized antibody to VEGF, is clinically used as a monotherapy or in combination with chemotherapy to treat cancer patients. However, this approach is not effective in all patients or cancer types. To better understand the heterogeneous responses to anti‐VEGF and the synergy between anti‐VEGF and other anticancer therapies, we constructed a computational model characterizing angiogenesis‐mediated growth of in vivo mouse tumor xenografts. The model captures VEGF‐mediated cross‐talk between tumor cells and endothelial cells and is able to predict the details of molecular‐ and cellular‐level dynamics. The model predictions of tumor growth in response to anti‐VEGF closely match the quantitative measurements from multiple preclinical mouse studies. We applied the model to investigate the effects of VEGF‐targeted treatment on tumor cells and endothelial cells. We identified that tumors with lower tumor cell growth rate and higher carrying capacity have a stronger response to anti‐VEGF treatment. The predictions indicate that the variation of tumor cell growth rate can be a main reason for the experimentally observed heterogeneous response to anti‐VEGF. In addition, our simulation results suggest a new synergy mechanism where anticancer therapy can enhance anti‐VEGF simply through reducing the tumor cell growth rate. Overall, this work generates novel insights into the heterogeneous response to anti‐VEGF treatment and the synergy of anti‐VEGF with other therapies, providing a tool that be further used to test and optimize anticancer therapy.
The efficacy and safety of the combination of axitinib and pembrolizumab‐activated autologous DC‐CIK cell immunotherapy for patients with advanced renal cell carcinoma: a phase 2 study
Authors: Song Meng‐Jia , Pan Qiu‐Zhong , Ding Ya , Zeng Jianxiong , Dong Pei , Zhao Jing‐Jing , Tang Yan , Li Jingjing , Zhang Zhiling , He Junyi , Yang Jieying , Huang Yue , Peng Ruiqing , Wang Qi‐Jing , Gu Jia‐Mei , He Jia , Li Yong‐Qiang , Chen Shi‐Ping , Huang Rongxing , Zhou Zi‐Qi , Yang Chaopin , Han Yulong , Chen Hao , Liu Heping , Xia Shangzhou , Wan Yang , Weng De‐Sheng , Xia Liming , Zhou Fang‐Jian , Xia Jian‐Chuan
Published: March 2021

Objectives

Although axitinib has achieved a preferable response rate for advanced renal cell carcinoma (RCC), patient survival remains unsatisfactory. In this study, we evaluated the efficacy and safety of a combination treatment of axitinib and a low dose of pembrolizumab‐activated autologous dendritic cells–co‐cultured cytokine‐induced killer cells in patients with advanced RCC.

Methods

All adult patients, including treatment‐naive or pretreated with VEGF‐targeted agents, were enrolled from May 2016 to March 2019. Patients received axitinib 5 mg twice daily and pembrolizumab‐activated dendritic cells–co‐cultured cytokine‐induced killer cells intravenously weekly for the first four cycles, every 2 weeks for the next four cycles, and every month thereafter.

Results

The 43 patients (22 untreated and 21 previously treated) showed a median progression‐free survival (mPFS) of 14.7 months (95% CI, 11.16–18.30). mPFS in treatment‐naive patients was 18.2 months, as compared with 14.4 months in pretreated patients (log‐rank P‐value = 0.07). Overall response rates were 25.6% (95% CI, 13.5–41.2%). Grade 3 or higher adverse events occurred in 5% of patients included hypertension (11.6%) and palmar‐plantar erythrodysesthesia (7.0%). Peripheral blood lymphocyte immunophenotype and serum cytokine profile analyses demonstrated increased antitumor immunity after combination treatment particularly in patients with a long‐term survival benefit, while those with a minimal survival benefit demonstrated an elevated proportion of peripheral CD8+TIM3+ T cells and lower serum‐level immunostimulatory cytokine profile.

Conclusions

The combination therapy was active and well tolerated for treatment of advanced RCC, either as first‐ or second‐line treatment following other targeted agents. Changes in immunophenotype and serum cytokine profile may be used as prognostic biomarkers.
A story from the Miocene: Clock‐dated phylogeny of Sisymbrium L. (Sisymbrieae, Brassicaceae)
Authors: Žerdoner Čalasan Anže , German Dmitry A. , Hurka Herbert , Neuffer Barbara
Published: March 2021

Morphological variability and imprecise generic boundaries have hindered systematic, taxonomical, and nomenclatural studies of Sisymbrium L. (Brassicaceae, Sisymbrieae DC.). The members of this almost exclusively Old‐World genus grow mostly on highly porous substrates across open steppe, semidesert, or ruderal habitats in the temperate zone of the Northern Hemisphere and African subtropics. The present study placed the biological history of Sisymbrium L. into time and space and rendered the tribus Sisymbrieae as monotypic. Five nuclear‐encoded and three chloroplast‐encoded loci of approximately 85% of all currently accepted species were investigated. Several accessions per species covering their whole distribution range allowed for a more representative assessment of intraspecific genetic diversity. In the light of fossil absence, the impact of different secondary calibration methods and taxon sets on time spans was tested, and we showed that such a combinatorial nested dating approach is beneficial. Multigene phylogeny accompanied with a time divergence estimation analysis placed the onset and development of this tribus into the western Irano‐Turanian floristic region during the Miocene. Continuous increase in continentality and decrease in temperatures promoted the diversity of the Sisymbrieae, which invaded the open grasslands habitats in Eurasia, Mediterranean, and South Africa throughout the Pliocene and Pleistocene. Our results support the assumption of the Irano‐Turanian region as a biodiversity reservoir for adjacent regions.
Influence of limited replacement of NaCl with KCl and yeast extract on microbiological, chemical, sensory, and textural properties of emulsion‐type chicken sausages
Authors: Mohammadzadeh Majid , Berizi Enayat , Shekarforoush Seyed Shahram
Published: March 2021

‏In this study, the production of emulsion‐type sausage by replacement of 20% to 40% KCl plus 1% or 2% yeast extract instead of NaCl was studied. The physical, chemical, microbiological, and sensory properties of the samples were analyzed up to 28 days of storage. The sample sausages were approved by the panelists. The physical, chemical, and microbiological properties of emulsion‐type sausages were not considerably influenced by these changes. The 40% replaced salt by KCl showed a similar property rather than the regular sausages. The aroma and taste of the sausages improved by using yeast extract. In addition, the adverse flavors resulted from adding KCl were excluded by adding the yeast extract. As a result, production of healthy emulsion‐type sausages (having 40% lower NaCl) with acceptable sensory qualities was introduced.
The Precise Relationship Between Model for End‐Stage Liver Disease and Survival Without a Liver Transplant
Authors: VanDerwerken Douglas N. , Wood Nicholas L. , Segev Dorry L. , Gentry Sommer E.
Published: March 2021

Background and Aims

Scores from the Model for End‐Stage Liver Disease (MELD), which are used to prioritize candidates for deceased donor livers, are widely acknowledged to be negatively correlated with the 90‐day survival rate without a liver transplant. However, inconsistent and outdated estimates of survival probabilities by MELD preclude useful applications of the MELD score.

Approach and Results

Using data from all prevalent liver waitlist candidates from 2016 to 2019, we estimated 3‐day, 7‐day, 14‐day, 30‐day, and 90‐day without‐transplant survival probabilities (with confidence intervals) for each MELD score and status 1A. We used an adjusted Kaplan‐Meier model to avoid unrealistic assumptions and multiple observations per person instead of just the observation at listing. We found that 90‐day without‐transplant survival has improved over the last decade, with survival rates increasing >10% (in absolute terms) for some MELD scores. We demonstrated that MELD correctly prioritizes candidates in terms of without‐transplant survival probability but that status 1A candidates’ short‐term without‐transplant survival is higher than that of MELD 40 candidates and lower than that of MELD 39 candidates. Our primary result is the updated survival functions themselves.

Conclusions

We calculated without‐transplant survival probabilities for each MELD score (and status 1A). The survival function is an invaluable tool for many applications in liver transplantation: awarding of exception points, calculating the relative demand for deceased donor livers in different geographic areas, calibrating the pediatric end‐stage liver disease score, and deciding whether to accept an offered liver.
An Updated Assessment of Chronic Hepatitis B Prevalence Among Foreign‐Born Persons Living in the United States
Authors: Wong Robert J. , Brosgart Carol L. , Welch Sue , Block Tim , Chen Mark , Cohen Chari , Kim W. Ray , Kowdley Kris V. , Lok Anna S. , Tsai Naoky , Ward John , Wong Steven S. , Gish Robert G.
Published: March 2021

Background and Aims

Although prevalence of chronic hepatitis B (CHB) in the USA includes 0.42 million (range, 0.28‐0.67) U.S.‐born persons, foreign‐born (FB) persons contribute a substantially larger number to the burden of CHB in the USA. Over the past decade, patterns of U.S. immigration have changed and many countries have implemented HBV prevention programs. This study aims to estimate the number of FB persons with CHB in the USA by country of origin, updating our 2011 study.

Approach and Results

We performed systematic searches for articles published in 2009–2019 reporting HBsAg seroprevalence in emigrants and in‐country populations of 117 countries. Data meeting inclusion criteria were combined with data from our 2011 study to calculate pooled prevalence estimates for 99 countries using meta‐analyses (total 2,800 surveys involving 112 million subjects). Combining country‐specific CHB rate estimates with the number of FB in the USA in 2018, by country of origin from the U.S. Census Bureau, we estimate that the number of FB with CHB in the USA in 2018 was 1.47 million (95% CI, 1.21‐1.73), substantially higher than previously reported. The weighted average CHB prevalence for all FB in the USA in 2018 was 3.07%. Approximately 59% of FB with CHB in the USA in 2018 emigrated from Asia, 19% from the Americas, and 15% from Africa. Subgroup analyses found that for many countries, CHB rates are higher in males than females and have declined over the past three decades, but no consistent pattern is observed between emigrant and in‐country rates.

Conclusions

Including FB and U.S.‐born persons, the total prevalence of CHB in the USA may be as high as 2.4 million.
Front Cover
Authors: Memeo Roberto , Paiè Petra , Sala Federico , Castriotta Michele , Guercio Chiara , Vaccari Thomas , Osellame Roberto , Bassi Andrea , Bragheri Francesca
Published: March 2021

In our work we present an optofluidic‐based microscope on chip for 3D imaging of Drosophila embryos with dual color capabilities. The cover image shows the device during experimental validation along with the acquired images of two different embryos which are automatically optically sectioned while flowing in the microfluidic channel. The frames reveal internal volumetric features of the specimens.

Further details can be found in the article by Roberto Memeo, Petra Paiè, Federico Sala, Michele Castriotta, Chiara Guercio, Thomas Vaccari, Roberto Osellame, Andrea Bassi, and Francesca Bragheri (e202000396).

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Inside Cover
Authors: Chandra Roy Abhijit , Bangalore Subramanya Shreyas , Manohar Rudresh Shoorashetty , Venkataraman Venkatakrishnan
Published: March 2021

The work demonstrates an on chip optofluidic surface deformable liquid Dove prism (LDP) based low‐fluid flow pressure monitoring device. The smart design of the device in combination with the property of liquid and soft solid enabled by the TIR makes the sensor highly sensitive. The applicability of the sensor is validated by capturing and analyzing respiratory pressure signals of some human subjects at numerous conditions.

Further details can be found in the article by Abhijit Chandra Roy, Shreyas Bangalore Subramanya, Shoorashetty Manohar Rudresh, and Venkatakrishnan Venkataraman (e202000381).

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Beyond the rule of transition state: Identification of roaming routes in some cases of carbonyl compounds
Authors: Lin King‐Chuen , Tso Cheng‐Jui , Kasai Toshio
Published: March 2021

This account focuses on photodissociation of carbonyl compounds to verify a so‐called roaming route, alternative to those passing through a transition state (TS) invoked in the realm of the kinetics of elementary chemical processes. Such a roaming route bypasses the minimum energy path but produces the same molecular products. The photodissociation of the carbonyl compounds of study includes methyl formate (HCOOCH3), formic acid (HCOOH), and aliphatic aldehydes (RCOH, RH, CH3, and large alkyl group). Methyl formate and formic acid were promoted to the excited state, followed by internal conversion via a conical intersection. Then, the energetic precursor dissociated to fragments, which proceeded along either TS or roaming path. As the excitation energy increases, the roaming fraction in methyl formate is significantly interfered with by an open channel of triple fragmentation (H + CO + CH3O), whereas such a channel may not occur in formic acid even at an excitation wavelength of 193 nm. As a distinct roaming type, aliphatic aldehydes are found to possess the structure of the roaming saddle point comprising two moieties weakly bound at a distance. The energy difference between the TS barrier and the roaming saddle point is indicative of the extent for the roaming contribution. The roaming route becomes increasingly dominant when the aliphatic aldehyde is larger. Experimentally, ion imaging was employed to visualize the rotational‐level dependence of the roaming route, while time‐resolved Fourier‐transform infrared emission spectroscopy was applied to determine the vibrational‐state dependence. The roaming signature was verified theoretically by quasi‐classical trajectory calculations. As an alternative, a multi‐center impulsive model was developed to simulate the roaming scalar and vector properties without involving the global energy surface.
Broadening the perspective on youth's systems of support: An ecological examination of supportive peer and adult relationships during adolescence
Authors: Melton Theresa N. , Brehm Margaret V. , Deutsch Nancy L.
Published: March 2021

This study applies the theory of positive youth development (Lerner et al., 2010) and the youth systems framework (Varga & Zaff, 2018) to the examination of supportive peer and adult relationships across multiple contexts in which youth develop. Results of egocentric social network analysis indicated that high school‐aged youth nominated significantly more adults than middle school‐aged youth. Peers and adults both acted as important sources of support, although often the types of support they offer differ. Outdegree centrality of peers was a significant predictor of character. The size of a participant's youth system, measured as the number of contexts accessed, along with average closeness in adult relationships, was a significant predictor of contribution. Thematic analysis of interview data identified four themes, aligned with the five actions of developmental relationships, as contributing factors to youth–adult closeness and youth perceptions of support (Pekel et al., 2018). Implications for youth–adult relationships are discussed.
RFX1‐mediated CCN3 induction that may support chondrocyte survival under starved conditions
Authors: Mizukawa Tomomi , Nishida Takashi , Akashi Sho , Kawata Kazumi , Kikuchi Sumire , Kawaki Harumi , Takigawa Masaharu , Kamioka Hiroshi , Kubota Satoshi
Published: March 2021

Cellular communication network factor (CCN) family members are multifunctional matricellular proteins that manipulate and integrate extracellular signals. In our previous studies investigating the role of CCN family members in cellular metabolism, we found three members that might be under the regulation of energy metabolism. In this study, we confirmed that CCN2 and CCN3 are the only members that are tightly regulated by glycolysis in human chondrocytic cells. Interestingly, CCN3 was induced under a variety of impaired glycolytic conditions. This CCN3 induction was also observed in two breast cancer cell lines with a distinct phenotype, suggesting a basic role of CCN3 in cellular metabolism. Reporter gene assays indicated a transcriptional regulation mediated by an enhancer in the proximal promoter region. As a result of analyses in silico, we specified regulatory factor binding to the X‐box 1 (RFX1) as a candidate that mediated the transcriptional activation by impaired glycolysis. Indeed, the inhibition of glycolysis induced the expression of RFX1, and RFX1 silencing nullified the CCN3 induction by impaired glycolysis. Subsequent experiments with an anti‐CCN3 antibody indicated that CCN3 supported the survival of chondrocytes under impaired glycolysis. Consistent with these findings in vitro, abundant CCN3 production by chondrocytes in the deep zones of developing epiphysial cartilage, which are located far away from the synovial fluid, was confirmed in vivo. Our present study uncovered that RFX1 is the mediator that enables CCN3 induction upon cellular starvation, which may eventually assist chondrocytes in retaining their viability, even when there is an energy supply shortage.
CDH1 variants leading to gastric cancer risk management decision‐making experiences in emerging adults: ‘I am not ready yet’
Authors: Liu Yi , Calzone Kathleen , Fasaye Grace‐Ann , Quillin John
Published: March 2021

Pathogenic/likely pathogenic variants (PLPV) in CDH1 are associated with a significantly increased lifetime risk for diffuse gastric cancer, with an average age of onset of 47 years. CDH1 PLPV carriers are recommended to have prophylactic total gastrectomy (PTG) or routine endoscopy surveillance. Emerging adults (EAs) may have unique circumstances that affect their medical management decision‐making about PTG versus endoscopy. The study aim was to use qualitative interpretative phenomenological analysis method to understand the lived experience and medical management decision‐making process for EAs carrying a CDH1 PLPV. Eligible participants were unaffected CDH1 PLPV carriers, ages 18 to 29, who had not undergone PTG and had discussed CDH1 medical management with a health provider. Semi‐structured telephone interviews were transcribed verbatim and analyzed for major themes. Results show EAs wanted to avoid developing diffuse gastric cancer, but most do not feel they are ready for PTG. They had worries about PTG related to their identity exploration, financial stability, and careers. Most did not want to pass the PLPV to their children; however, the cost of preimplantation genetic testing with in vitro fertilization was a concern. Family medical history and self‐understanding of endoscopy and PTG highly influenced medical management decision‐making. Understanding of diffuse gastric cancer detection rate using endoscopy was inconsistent among participants. Body image was not a concern for most, but they worry about dietary restrictions after PTG. Lastly, connection to peers having the same experience was important. These findings increase our understanding of the medical management decision‐making challenges for EA CDH1 carriers. EAs may take an extended time to decide what option is right for them. Thus, genetic counseling for CDH1 PLPV EA carriers requires long‐term support and education.
Impact of cytoreductive surgery on survival of patients with low‐grade serous ovarian carcinoma: A multicentric study of Turkish Society of Gynecologic Oncology (TRSGO‐OvCa‐001)
Authors: Vatansever Dogan , Taskiran Cagatay , Mutlu Meydanli Mehmet , Gungorduk Kemal , Akbayir Ozgur , Yalcin Ibrahim , Demirkiran Fuat , Sozen Hamdullah , Ozgul Nejat , Celik Husnu , Onan Mehmet Anil , Taskin Salih , Oge Tufan , Simsek Tayyup , Abboud Sara , Yuksel Ilkbal Temel , Ayhan Ali
Published: March 2021

Background and Objectives

The aim of this study was to analyze the factors affecting recurrence‐free (RFS) and overall survival (OS) rates of women diagnosed with low‐grade serous ovarian cancer (LGSOC).

Methods

Databases from 13 participating centers in Turkey were searched retrospectively for women who had been treated for stage I–IV LGSOC between 1997 and 2018.

Results

Overall 191 eligible women were included. The median age at diagnosis was 49 years (range, 21–84 years). One hundred seventy‐five (92%) patients underwent primary cytoreductive surgery. Complete and optimal cytoreduction was achieved in 148 (77.5%) and 33 (17.3%) patients, respectively. The median follow‐up period was 44 months (range, 2–208 months). Multivariate analysis showed the presence of endometriosis (p = .012), lymphovascular space invasion (LVSI) (p = .022), any residual disease (p = .023), and the International Federation of Gynecology and Obstetrics (FIGO) stage II–IV disease (p = .045) were negatively correlated with RFS while the only presence of residual disease (p = .002) and FIGO stage II–IV disease (p = .003) significantly decreased OS.

Conclusions

The maximal surgical effort is warranted for complete cytoreduction as achieving no residual disease is the single most important variable affecting the survival of patients with LGSOC. The prognostic role of LVSI and endometriosis should be evaluated by further studies as both of these parameters significantly affected RFS.
Potential of novel colchicine dosage schedule for the palliative treatment of advanced hepatocellular carcinoma
Authors: Lin Zu‐Yau , Yeh Ming‐Lun , Huang Ching‐I , Chen Shinn‐Cherng , Huang Chung‐Feng , Huang Jee‐Fu , Dai Chia‐Yen , Yu Ming‐Lung , Chuang Wan‐Long
Published: March 2021

Previous in vitro and in vivo experiments had demonstrated dose‐dependent anti‐cancer effects of clinical plasma colchicine concentrations on hepatocellular carcinoma (HCC) cells. This phase IIa trial was to evaluate the potential efficiency and safety of our novel colchicine dosage schedule for the palliative treatment of advanced HCC. The dosage schedule started from oral intake of 1 mg colchicine three times per day for 4 days and discontinuation in the following 3 days (one cycle). The treatment cycle was repeated and the dosage was adjusted ranging from 3 to 1.5 mg/day according to the condition of the participant. The control group was originated from chart review of 86 HCC patients treated by sorafenib for more than 2 months. Fifteen participants signed the inform consent. Two participants were excluded due to screening failure in one and less than four treatment cycles in another. For severe adverse events, the colchicine group demonstrated higher incidence of biliary tract obstruction (p = 0.0184) than the sorafenib group. Comparison grade 1 or 2 adverse events between two groups, the colchicine group had higher incidence of diarrhea (p = 0) and the sorafenib group had higher incidence of palmar‐plantar erythrodysesthesia syndrome (p = 0.0045). There was no significant difference in mortality, median survival, and overall survival between two groups (all p > 0.2). In conclusion, our novel colchicine dosage schedule is clinically feasible and has the potential to be applied in the palliative treatment of advanced HCC especially based on the cost‐effectiveness consideration.
Control of Burn Wound Infection by Methylene Blue‐Mediated Photodynamic Treatment With Light‐Emitting Diode Array Illumination in Rats
Authors: Ishiwata Naoto , Tsunoi Yasuyuki , Sarker Roma Rani , Haruyama Yasue , Kawauchi Satoko , Sekine Yasumasa , Onuma Chinami , Tsuda Hitoshi , Saitoh Daizoh , Nishidate Izumi , Sato Shunichi
Published: March 2021

Background and Objectives

Control of burn wound infection is difficult due to the increase in drug‐resistant bacteria and deteriorated immune responses. In this study, we examined the usefulness of methylene blue (MB)‐mediated antimicrobial photodynamic therapy (aPDT) with illumination by a light‐emitting diode (LED) array for controlling invasive infections from the wound to inside the body for rats with an extended deep burn infected with Pseudomonas aeruginosa.

Study Design/Materials and Methods

An MB solution with the addition of ethanol, ethylene‐diamine‐tetra‐acetic acid disodium salt, and dimethyl sulfoxide was used as a photosensitizer (PS). An extended deep burn was made on the dorsal skin in rats and the wounds were infected with P. aeruginosa. The rats were divided into three groups: control (no treatment; n = 14), PS mixture application alone (PS alone group; n = 10), and aPDT group (n = 14). For aPDT, after the PS mixture was applied onto the surface of infected wounds, the wounds were illuminated with a 665‐nm LED array at an intensity of 45 mW/cm2 three times per treatment, with an illumination duration of 20 minutes and an interval of 10 minutes. The treatment was repeated each day for 7 consecutive days (day 0–day 6). Bacterial numbers on the wound surface and the weights and survival rates of the animals were evaluated daily. At the endpoints, bacterial numbers in the liver and blood were counted. Since the PS mixture showed high dark toxicity against P. aeruginosa in vitro, the influence of the PS mixture application onto healthy skin was also examined in vivo.

Results

Even in the aPDT group, rapid bacterial regrowth was observed on the wound surface after each day's treatment, but the geometric mean values of the bacterial numbers before and after each aPDT were considerably lower than those in the control group. Application of the PS mixture alone showed a clear bactericidal effect only at day 0, which is attributable to the formation of biofilms after day 1. Rats in the aPDT group showed a smaller weight loss, a higher ratio of no bacterial migration at the endpoints, and significantly higher survival rates than those in the other two groups. Effects of repeated application of the PS mixture onto healthy skin were not evident.

Conclusions

Application of MB‐mediated aPDT with illumination by a high‐intensity LED array daily for seven consecutive days was effective for suppressing invasive infection from the wound to inside the body in rats with an extensive deep burn infected with P. aeruginosa, resulting in significant improvement of their survival. Lasers Surg. Med. © 2021 Wiley Periodicals LLC
Well dispersion of poly(acrylonitrile‐butadiene‐styrene) in isotactic polypropylene mediated by incorporation of graphene and the elevated toughness
Authors: Liu Jingru , Zhang Lingchen , Fang Zhou
Published: March 2021

Polymers with benzene rings in structures including polystyrene (PS) and poly(acrylonitrile‐butadiene‐styrene) (ABS) could function as rigid organic particles and macromolecular β nucleating agents to toughen isotactic polypropylene (iPP), and the toughening effect mainly depends on their dispersibility in iPP matrix. In this work, a third component of graphene (G) was introduced into the iPP/PS and iPP/ABS blends, respectively, to mediate the dispersibility of these polymers in the iPP via melt blending. Selective dispersion of graphene in these immiscible blends has been investigated with SEM, DSC, and a rheometer. It was interesting to obtain a more favorable dispersion of ABS in the iPP/ABS/G blend compared with the iPP/ABS blend, and the corresponding toughness showed a prominent improvement accompanied with an elevation in rigidity. The underlying mechanism for the improved dispersion of ABS in the iPP/ABS/G blends has been discussed in detail. However, because of a better affinity of the graphene to the PS than the iPP matrix, graphene could only locate in the PS phase, resulting in poor compatibilization for the iPP/PS blend followed by the deterioration of mechanical properties.
Comparative neurological safety of fluoroquinolones versus therapeutic alternatives
Authors: Ellis Darcy E. , Hubbard Rebecca A. , Willis Allison W. , Zuppa Athena F. , Zaoutis Theoklis E. , Hennessy Sean
Published: March 2021

Background

Fluoroquinolones, one of the most commonly prescribed antibiotic classes, have been implicated in cases of central nervous system (CNS) and peripheral nervous system (PNS) adverse events, which highlights the need for epidemiologic studies of the neurological safety of fluoroquinolones.

Purpose

To evaluate the safety of fluoroquinolones with regard to risk of diagnosed neurological dysfunction.

Methods

We conducted a propensity score‐matched inception cohort study using claims data from a commercially insured population. Our study included adults prescribed an oral fluoroquinolone or comparator antibiotic between January 2000 and September 2015 for acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, uncomplicated urinary tract infection, or acute bronchitis. Our outcomes were CNS dysfunction, and four separate but complementary PNS dysfunction outcomes. Cox proportional hazards models were estimated after matching on propensity scores fitted using the variables age, sex, epilepsy, hereditary peripheral neuropathy, renal dysfunction, diabetes, gabapentinoid use, statin use, isoniazid use, and chemotherapy use.

Results

Our cohort contained 976 568 individuals exposed to a fluoroquinolone antibiotic matched 1:1 with a comparator. Matching produced balance (standardized mean difference <0.1) on all variables included in the propensity score. The hazard ratio associated with fluoroquinolone exposure was 1.08 (95% confidence interval 1.05–1.11) for CNS dysfunction, and 1.09 (95% CI 1.07–1.11) for the most commonly occurring PNS dysfunction outcome.

Conclusions

Fluoroquinolone antibiotic use was associated with the development of neurological dysfunction versus comparator antibiotic use in the adult population.