bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of US Food and Drug Administration Expedited Drug Development and Review Programs by Orphan and Nonorphan Novel Drugs Approved From 2008 to 2021
Authors: Monge Andrea N. , Sigelman Daniel W. , Temple Robert J. , Chahal Harinder Singh
Published: November 2022

Importance

The US Food and Drug Administration (FDA) has 4 programs that can be used alone or in combination to expedite drug availability: Accelerated Approval, Breakthrough Therapy, Fast Track, and Priority Review. Drugs using these programs can include novel drugs, which do not contain a previously FDA-approved active moiety, and orphan drugs, intended for diseases or conditions affecting fewer than 200 000 people; to date, no comprehensive evaluation of how these programs have been used in combination has been published.

Objective

To assess how often and in what combinations expedited programs are used in the development and review of approved novel biologics and small-molecule drugs, stratified by orphan drug status and indication.

Design, Setting, and Participants

This cross-sectional study evaluated all novel drugs that were FDA approved between January 1, 2008, and December 31, 2021.

Main Outcomes and Measures

The main outcome was the frequency with which expedited programs were used and in what combinations, stratified by orphan drug status and drug type (small molecule vs therapeutic biologic). The unit of analysis was the novel drug–indication pair because a drug can be approved for multiple indications, each of which may use a different expedited program or differ in orphan drug status.

Results

The study included 581 novel drug–indication pairs approved during the 14-year study period; 252 (43.4%) were orphan drugs, 139 (23.9%) were therapeutic biologics, and 442 (76.1%) were small-molecule drugs. Use of at least 1 expedited program increased from 11 of 26 drug-indication pairs (42.3%) in 2008 to 41 of 55 (74.5%) in 2021. Of the 363 approved drug-indication pairs using at least 1 expedited program, 225 (62.0%) were orphan drugs; at least 1 expedited program was used by 97 of the 139 approved biologic drugs (69.8%) and by 266 of the 442 approved small-molecule drugs (60.2%). Eighty-two of the 581 novel drug–indication pairs (14.1%) used the Accelerated Approval Program; of those, 65 (79.3%) were oncology drugs and 70 (85.4%) had an orphan designation.

Conclusions and Relevance

The study showed that use of the FDA’s expedited programs to bring novel drugs to market in the US increased from 2008 to 2021. The findings suggest that this trend is likely to continue.
Association of Gonadotropin-Releasing Hormone Analogue Use With Subsequent Use of Gender-Affirming Hormones Among Transgender Adolescents
Authors: Nos Andrea L. , Klein David A. , Adirim Terry A. , Schvey Natasha A. , Hisle-Gorman Elizabeth , Susi Apryl , Roberts Christina M.
Published: November 2022

Importance

Gonadotropin-releasing hormone analogue (GnRHa) use during puberty improves mental health among transgender and gender-diverse (TGD) adolescents. In previous studies, most (96.5%-98.1%) TGD adolescents who started GnRHa subsequently started gender-affirming hormones (GAH), raising concerns that GnRHa use promotes later use of GAH.

Objective

To determine whether GnRHa use among TGD adolescents is associated with increased subsequent GAH use.

Design, Setting, and Participants

This is a retrospective cohort study of administrative records collected between 2009 and 2018. The current analysis was completed in August 2022. Participants were enrolled in the US Military Healthcare System (MHS) with an initial TGD-related encounter occurring between ages 10 and 17 years.

Exposures

GnRHa use.

Main Outcomes and Measures

Initiation of GAH.

Results

The 434 patients were a mean (SD) of 15.4 (1.6) years old at the time of their first TGD-related encounter; 312 (71.9%) were assigned female at birth, and 300 (69.1%) had an enlisted insurance sponsor. GnRHa use was more common among patients who were assigned male at birth (28 patients [23.0%]) than those assigned female (42 patients [13.5%]), but GAH use was not. Socioeconomic status was not associated with GnRHa or GAH use. Compared with older patients (aged 14-17 years), those who were younger (aged 10-13 years) at the time of the initial TGD-related encounter had a higher rate of GnRHa use (32 patients [57.1%] vs 38 patients [10.1%]) and a longer median time to starting GAH. The median interval from the date of the initial encounter to starting GAH decreased over time, from 2.3 years (95% CI, 1.7-2.8 years) between October 2009 and December 2014 to 0.6 years (95% CI, 0.5-0.6 years) between September 2016 and April 2018. Patients who were prescribed GnRHa had a longer median time to starting GAH (1.8 years; 95% CI, 1.1-2.4 years) than patients who were not (1.0 years; 95% CI, 0.8-1.2 years) and were less likely to start GAH during the 6 years after their first TGD-related encounter (hazard ratio, 0.52; 95% CI, 0.37-0.71). Among 54 younger (aged 10-13 years) patients who were not eligible to start GAH at their first encounter, GnRHa use was associated with a longer median time to starting GAH, but age at the first TGD-related visit was not.

Conclusions and Relevance

In this cohort study of TGD adolescents, GnRHa use was not associated with increased subsequent GAH use. These findings suggest that clinicians can offer the benefits of GnRHa treatment without concern for increasing rates of future GAH use.
Clinical commissioning of an adaptive radiotherapy platform: Results and recommendations
Authors: Kisling Kelly , Keiper Timothy D. , Branco Daniela , Kim Grace Gwe‐Ya , Moore Kevin L , Ray Xenia
Published: November 2022

Online adaptive radiotherapy platforms present a unique challenge for commissioning as guidance is lacking and specialized adaptive equipment, such as deformable phantoms, are rare. We designed a novel adaptive commissioning process consisting of end‐to‐end tests using standard clinical resources. These tests were designed to simulate anatomical changes regularly observed at patient treatments. The test results will inform users of the magnitude of uncertainty from on‐treatment changes during the adaptive workflow and the limitations of their systems. We implemented these tests for the cone‐beam computed tomography (CT)‐based Varian Ethos online adaptive platform.

Many adaptive platforms perform online dose calculation on a synthetic CT (synCT). To assess the impact of the synCT generation and online dose calculation on dosimetric accuracy, we conducted end‐to‐end tests using commonly available equipment: a CIRS IMRT Thorax phantom, PinPoint ionization chamber, Gafchromic film, and bolus. Four clinical scenarios were evaluated: weight gain and weight loss were simulated by adding and removing bolus, internal target shifts were simulated by editing the CTV during the adaptive workflow to displace it, and changes in gas were simulated by removing and reinserting rods in varying phantom locations. The effect of overriding gas pockets during planning was also assessed.

All point dose measurements agreed within 2.7% of the calculated dose, with one exception: a scenario simulating gas present in the planning CT, not overridden during planning, and dissipating at treatment. Relative film measurements passed gamma analysis (3%/3 mm criteria) for all scenarios. Our process validated the Ethos dose calculation for online adapted treatment plans. Based on our results, we made several recommendations for our clinical adaptive workflow. This commissioning process used commonly available equipment and, therefore, can be applied in other clinics for their respective online adaptive platforms.
Potential utility of cone‐beam CT‐guided adaptive radiotherapy under end‐exhalation breath‐hold conditions for pancreatic cancer
Authors: Ogawa Ayaka , Nakamura Mitsuhiro , Iramina Hiraku , Yoshimura Michio , Mizowaki Takashi
Published: November 2022

Purpose

The purpose of this study was to demonstrate the potential utility of cone‐beam computed tomography (CBCT)‐guided online adaptive radiotherapy (ART) under end‐exhalation breath‐hold (EE‐BH) conditions for pancreatic cancer (PC).

Methods

Eleven PC patients who underwent 15‐fraction volumetric‐modulated arc therapy under EE‐BH conditions were included. Planning CT images and daily 165 CBCT images were imported into a dedicated treatment planning system. The prescription dose was set to 48 Gy in 15 fractions. The reference plan was automatically generated along with predefined clinical goals. After segmentation was completed on CBCT images, two different plans were generated: One was an adapted (ADP) plan in which re‐optimization was performed on the anatomy of the day, and the other was a scheduled (SCH) plan, which was the same as the reference plan. The dose distributions calculated using the synthetic CT created from both planning CT and CBCT were compared between the two plans. Independent calculation‐based quality assurance was also performed for the ADP plans, with a gamma passing rate of 3%/3 mm.

Results

All clinical goals were successfully achieved during the reference plan generation. Of the 165 sessions, gross tumor volume D98% and clinical target volume D98% were higher in 100 (60.1%) and 122 (74.0%) ADP fractions. In each fraction, the V3 Gy < 1 cm3 of the stomach and duodenum was violated in 47 (28.5%) and 48 (29.1%), respectively, of the SCH fractions, whereas no violations were observed in the ADP fractions. There were statistically significant differences in the dose–volume indices between the SCH and ADP fractions (p < 0.05). The gamma passing rates were above 95% in all ADP fractions.

Conclusions

The CBCT‐guided online ART under EE‐BH conditions successfully reduced the dose to the stomach and duodenum while maintaining target coverage.
Digital Doubles: The Major Agency of Minor Bits
Authors: Oyarzun Lucía Jalón
Published: November 2022

In a world that seeks to describe, codify and quantify everything, and particularly our viscerality and its interactions with our actual and digital environments, can we find interstitial spaces, currently unseen, unobserved and unlegislated, where we might be able to create minor architectures capable of blooming? Architect and interdisciplinary researcher Lucía Jalón Oyarzun reveals where these spaces might be found.
Earth Versus FIFA: Resisting Globalisation on the Open Pitch
Authors: le Roux Hannah
Published: November 2022

Hannah le Roux is an architect and architectural historian specialising in the modern architecture of Southern Africa. An Associate Professor at the University of the Witwatersrand, here she documents the importance of football to local communities and its binding effect in strengthening societal bonds and providing a sense of self‐determination.
A Space of Problems: The Child‐Cities of Columbus
Authors: Newsom Jennifer , Carruthers Tom
Published: November 2022

Jennifer Newsom and Tom Carruthers are architects, artists and co‐founders of creative studio Dream The Combine. They describe their recent artwork/landscape intervention in Columbus, Indiana, and their attempts to unravel the associations of the town's name, its colonial legacies and rich histories of marginalised communities and their contribution to the culture of the place as a microcosm of American social politics.
Chiral Phosphoric Acid‐Catalyzed Chemo‐ and Enantioselective N‐Alkylation of Indoles with Imines
Authors: Yang Shuyuan , Li Linger , Zhao Junling
Published: November 2022

A chemo‐ and enantioselective protocol for the N‐alkylation of indoles with imines was developed. This process was catalyzed by a BINOL‐derived phosphoric acid catalyst to give the corresponding acyclic aminals of indoles in 46–99% yields with 70–98% ee. The application of this method for the “late‐stage” functionalization of a bioactive compound was performed with high efficency. The products showed good stability and enabled many further transformations.

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Nebulized mRNA‐Encoded Antibodies Protect Hamsters from SARS‐CoV‐2 Infection
Authors: Vanover Daryll , Zurla Chiara , Peck Hannah E. , Orr‐Burks Nichole , Joo Jae Yeon , Murray Jackelyn , Holladay Nathan , Hobbs Ryan A. , Jung Younghun , Chaves Lorena C. S. , Rotolo Laura , Lifland Aaron W. , Olivier Alicia K. , Li Dapeng , Saunders Kevin O. , Sempowski Gregory D. , Crowe James E. , Haynes Barton F. , Lafontaine Eric R. , Hogan Robert J. , Santangelo Philip J.
Published: November 2022

Despite the success of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) vaccines, there remains a clear need for new classes of preventatives for respiratory viral infections due to vaccine hesitancy, lack of sterilizing immunity, and for at‐risk patient populations, including the immunocompromised. While many neutralizing antibodies have been identified, and several approved, to treat COVID‐19, systemic delivery, large doses, and high costs have the potential to limit their widespread use, especially in low‐ and middle‐income countries. To use these antibodies more efficiently, an inhalable formulation is developed that allows for the expression of mRNA‐encoded, membrane‐anchored neutralizing antibodies in the lung to mitigate SARS‐CoV‐2 infections. First, the ability of mRNA‐encoded, membrane‐anchored, anti‐SARS‐CoV‐2 antibodies to prevent infections in vitro is demonstrated. Next, it is demonstrated that nebulizer‐based delivery of these mRNA‐expressed neutralizing antibodies potently abrogates disease in the hamster model. Overall, these results support the use of nebulizer‐based mRNA expression of neutralizing antibodies as a new paradigm for mitigating respiratory virus infections.
Multi‐Modal Locomotion of Caenorhabditis elegans by Magnetic Reconfiguration of 3D Microtopography
Authors: Park Jeong Eun , Yoon Sunhee , Jeon Jisoo , Kim Chae Ryean , Jhang Saebohm , Jeon Tae‐Joon , Lee Seung Goo , Kim Sun Min , Wie Jeong Jae
Published: November 2022

Miniaturized untethered soft robots are recently exploited to imitate multi‐modal curvilinear locomotion of living creatures that perceive change of surrounding environments. Herein, the use of Caenorhabditis elegans (C. elegans) is proposed as a microscale model capable of curvilinear locomotion with mechanosensing, controlled by magnetically reconfigured 3D microtopography. Static entropic microbarriers prevent C. elegans from randomly swimming with the omega turns and provide linear translational locomotion with velocity of ≈0.14 BL s−1. This velocity varies from ≈0.09 (for circumventing movement) to ≈0.46 (for climbing) BL s−1, depending on magnetic bending and twisting actuation coupled with assembly of microbarriers. Furthermore, different types of neuronal mutants prevent C. elegans from implementing certain locomotion modes, indicating the potential for investigating the correlation between neurons and mechanosensing functions. This strategy promotes a platform for the contactless manipulation of miniaturized biobots and initiates interdisciplinary research for investigating sensory neurons and human diseases.
Estimation of the net photosynthetic rate for waterlogged winter wheat based on digital image technology
Authors: Li Yanli , Gao Xiaomei , Li Tao , Jin Huifang , Zhu Hai , Wu Qixia , Lu Bilin , Xiong Qinxue
Published: November 2022

The net photosynthetic rate (Pn) is one of the important indicators to measure photosynthetic capacity of crops. Therefore, it is critically important to find real‐time methods for accurately estimating Pn of winter wheat (Triticum aestivum L.). This information could provide guidance on the management of waterlogging stress. To explore the optimal monitoring method for Pn of winter wheat under waterlogging stress, the correlations between Pn and 16 characteristic image indices were analyzed in irrigated and drained microplot experiments. Then, based on the indices values, Pn was estimated using the multiple linear regression (MLR), support vector machine (SVM), backpropagation neural network (BP), and random forest (RF) models, which were constructed based on the optimal monitoring image indices. Water logging when compared to no waterlogged wheat had similar Pn values <6 days. After 12 days, waterlogged wheat plants had a lower Pn value than in no waterlogged plants. All indices were correlated with the Pn (p < 0.05), and Pn estimation accuracy was lower at the winter wheat flowering and complete ripeness periods than at the milky and waxy ripe maturity periods. Based on the results of the models tested, the RF model had higher R2 (0.904) values than the other models. These findings suggest that machine learning models could be used to accurately predict Pn, and the random forest algorithm was the best.
Distinguishing the Quantum Yield and Lifetime of Carbazole‐Based Room‐Temperature Phosphorescence Materials: QM/MM Study
Authors: Yang Yonggang , Guan Tiantian , Liu Yang , Zhang Qi , Jiang Zhinan , Jiang Kai , Liu Yufang
Published: November 2022

Commercial carbazole derivatives are widely used as typical electron donors in room‐temperature phosphorescence materials. The high phosphorescence quantum yield (Φp) and short lifetime (τp) of the carbazole‐based (9H‐carbazol‐9‐yl)isonicotinonitrile (P‐34N) crystal are distinguished by quantum mechanics and molecular mechanics method. Two inducements are accounted for the high Φp of P‐34N: i) large spin–orbit coupling (0.63 cm−1) induces fast intersystem crossing (ISC) of the lowest singlet excited state (S1) to the lowest triplet excited state (T1), ii) the intermolecular π–π interactions stabilize triplet excitons. Meanwhile, the 3(n, π*) →1(π, π*) of P‐34N favors the nonradiative decay of T1to the ground state (S0), and thus, causes short τp. In contrast to P‐34N, the low Φp of 6‐(9H‐carbazol‐9‐yl)nicotinonitrile (P‐24N) crystal results from the effective reverse ISC process induced by small ΔEST (0.3 eV) between S1 state and the higher triplet state (T2), and the long τp is due to the unfavorable orbital reversals of T1 (π, π*)→S0 (π, π*) transition and the internal conversion process of T2 → T1. This work presents a reasonable interpretation of the Φp and τp of two carbazole‐based crystals.
Third‐Order Nonlinear Effect and Polarization‐Dependent Modulation Using Spherical‐Like MoS2 Nanoparticles
Authors: Li Tianlun , Hao Rui , Hou Yaping , Gao Duorui , Xu Yunfan , Zhang Yanpeng , Fang Jixiang , Zhang Lei
Published: November 2022

A type of MoS2 nanoparticle with a spherical‐like shape is chemically synthesized with favorable third‐order and suppressed second‐order nonlinear optical response, which results from the isotropy induced by the geometrical uniformity of nanoparticles and an artificial symmetry center. It is found that the linewidth of third harmonic signal is broadened due to the self‐phase modulation effect, another third‐order nonlinearity. Moreover, the intensity of harmonic signal can be conveniently adjusted by controlling the polarization state of applied optical field. The artificially designed material morphology may provide a reference for designing all‐optical modulation devices.
Dual‐drug delivery of sodium ceftriaxone and metronidazole by applying salt‐assisted chitosan nanoparticles: Stability, drug release, and time‐kill assay study against Bacteroides fragilis
Authors: Binesh Nafiseh , Farhadian Nafiseh , Mohammadzadeh Alireza , Karimi Mohammad
Published: November 2022

The purpose of this study was to develop a polymeric biomaterial with regulated dual drug release and increased bactericidal strength of the antibiotics sodium ceftriaxone (CTX) and metronidazole (MTZ) for the treatment of intra‐abdominal infections. Chitosan nanoparticles (CS NPs) were produced by ionic crosslinking process in the presence of NaCl monovalence salt. The antibacterial activity and drug release behavior of CS NPs were investigated against anaerobic Bacteroides fragilis. The optimum initial drug ratio for designing dual drug carriers containing CTX and MTZ in a 4:3 ratio was 1:1. After 6 months, the salt‐assisted CTX‐MTZ‐loaded CS NPs were 300 nm in size and had a polydispersity index of 0.09 with high stability. It has been demonstrated that drug release from NPs is more tightly controlled than drug release from free drugs. Furthermore, the data show that the minimum inhibitory concentration and minimum bactericidal concentration for nanostructure carriers are one‐quarter of those of free medicines. Free drugs could completely kill the bacterium after 24 h, but the dual drug carrier could kill the bacteria in 10 h. Finally, salt‐assisted CTX‐MTZ‐loaded CS NPs were proposed as a feasible alternative to standard intra‐abdominal infection treatment.
Mindfulness or expectancy? The label of mindfulness leads to expectancy effects
Authors: Ghanbari Noshari Mona , Kempton Heather Mary , Kreplin Ute
Published: November 2022

The increasing popularity of mindfulness practices has seen an accompanying growth in research that includes the development of several self‐report mindfulness measures. However, while caution has been recommended in the use of these self‐reports, there has been little direct assessment of their susceptibility to expectancy effects. This research aimed at understanding whether expectancy effects exist for self‐reported mindfulness measures (Study 1; n = 60), and how expectancy effects might manifest in relation to positive and negative expectancy (Study 2; n = 60). The first study manipulated whether (i) the task (jigsaws) was labelled as “mindfulness,” and (ii) whether “authentic” mindfulness instructions were given. Given any increases in self‐reported mindfulness might potentially occur due to engaging in the mindful and attentionally demanding task, the second study manipulated whether the introduction placed mindfulness in a positive or negative context. A pre‐/post‐test design was employed using the Five Facet Mindfulness Questionnaire and Applied Mindfulness Process Scale self‐report measures for mindfulness and the Perceived Stress Scale for well‐being. The findings revealed expectancy effects for simply using the term mindfulness and that the direction of effects could be manipulated. This research suggests that researchers need to be cautious in evaluating self‐reports of mindfulness practice due to expectancy effects, especially in the context of brief interventions without objective measures.
Confused‐Prism[5]arene: a Conformationally Adaptive Host by Stereoselective Opening of the 1,4‐Bridged Naphthalene Flap
Authors: Della Sala Paolo , del Regno Rocco , Capobianco Amedeo , Iuliano Veronica , Talotta Carmen , Geremia Silvano , Hickey Neal , Neri Placido , Gaeta Carmine
Published: November 2022

The confused‐prism[5]arene macrocycle (c‐PrS[5]Me) shows conformational adaptive behavior in the presence of ammonium guests. Upon guest inclusion, the 1,4‐bridged naphthalene flap reverses its planar chirality from pSto pR(with reference to the pS(pR)4enantiomer). Stereoselective directional threading is also observed in the presence of directional axles, in whichup/downstereoisomers of homochiral (pR)5‐c‐PrS[5]Mepseudorotaxanes are formed.
Modulating the G‐Quadruplex and Duplex DNA Binding by Controlling the Charge of Fluorescent Molecules
Authors: Gil‐Martínez Ariadna , López‐Molina Sònia , Galiana‐Roselló Cristina , Lázaro‐Gómez Andrea , Schlüter Friederike , Rizzo Fabio , González‐García Jorge
Published: November 2022

Two fluorescent and non‐toxic spirobifluorene molecules bearing either positive (Spiro‐NMe3) or negative (Spiro‐SO3) charged moieties attached to the same aromatic structure have been investigated as binders for DNA. The novel Spiro‐NMe3 containing four alkylammonium substituents interacts with G‐quadruplex (G4) DNA structures and shows preference for G4s over duplex by means of FRET melting and fluorescence experiments. The interaction is governed by the charged substituents of the ligands as deduced from the lower binding of the sulfonate analogue (Spiro‐SO3). On the contrary, Spiro‐SO3 exhibits higher binding affinity to duplex DNA structure than to G4. Both molecules show a moderate quenching of the fluorescence upon DNA binding. The confocal microscopy evaluation shows the internalization of both molecules in HeLa cells and their lysosomal accumulation.
A Randomized, Single‐dose, Phase I Clinical Comparison of a Trastuzumab Biosimilar With a Reference Trastuzumab Formulation in Healthy Chinese Male Volunteers
Authors: Pu Huahua , Jia Jingying , Zhao Chunyang , Hou Sheng , Guo Huaizu , Li Jing , Qian Weizhu , Wang Hao , Sun Chan , Zou Yang
Published: November 2022

The test drug, a recombinant humanized monoclonal antibody, is a biosimilar candidate for the reference drug. The purpose of this study was to evaluate the bioequivalence of these two drugs. The study was divided into two parts, a pre‐study and a formal trial. The pre‐study included two subjects who were each given a single intravenous infusion of 6 mg/kg test drug. The formal trial was designed to be a randomized, double‐blind, parallel controlled trial in which 70 subjects were randomly assigned 1:1 to receive either test or reference drug as a single 6 mg/kg intravenous infusion. In the pre‐study, the immunogenicity was negative in both subjects and the safety of the test drug was considered to be good. The two groups in the formal trial had similar demographic characteristics. The 90% confidence interval of geometric mean ratios of area under the serum concentration‐time curve from the time 0 to the time of last quantifiable concentration, area under the serum concentration‐curve from time 0 to infinity, and maximum observed serum concentration between the test group and the reference group fell between 80% and 125% and the bioequivalence was recognized. There was no significant difference in the positive rate of antidrug antibodies. The treatment‐emergent adverse events in the test group were similar to those in the reference group. This study showed that the test drug has similar pharmacokinetics, immunogenicity, and safety to the reference drug in healthy male subjects.
Bipolar Verdazyl Radicals for Symmetrical Batteries: Properties and Stability in All States of Charge
Authors: Steen Jelte S. , de Vries Folkert , Hjelm Johan , Otten Edwin
Published: November 2022

Redox flow batteries based on organic electrolytes are promising energy storage devices, but stable long‐term cycling is often difficult to achieve. Bipolar organic charge‐storage materials allow the construction of symmetrical flow batteries (i. e., with identical electrolyte composition on both sides), which is a strategy to mitigate crossover‐induced degradation. One such class of bipolar compounds are verdazyl radicals, but little is known on their stability/reactivity either as the neutral radical, or in the charged states. Here, we study the chemical properties of a Kuhn‐type verdazyl radical (1) and the oxidized/reduced form (1+/−). Chemical synthesis of the three redox‐states provides spectroscopic characterization data, which are used as reference for evaluating the composition of the electrolyte solutions of an H‐cell battery during/after cycling. Our data suggest that, rather than the charged states, the decomposition of the parent verdazyl radical is responsible for capacity fade. Kinetic experiments and DFT calculations provide insight in the decomposition mechanism, which is shown to occur by bimolecular disproportionation to form two closed‐shell products (leuco‐verdazyl 1H and triazole derivative 2).
Green entrepreneurial orientation and financial performance in Chinese firms: The role of stakeholder engagement and green absorptive capacity
Authors: Zhang Xiue , Le Yuan , Meng Qiao , Teng Xinyu
Published: November 2022

Based on the natural‐resource‐based view and capability theory, this study explores the impact of green entrepreneurial orientation (GEO) on financial performance, the separate and joint moderating effects of stakeholder engagement and green absorptive capacity (GAC). Using data obtained from 230 Chinese manufacturing firms, it was found that GEO has positive influence on financial performance, supplier engagement and GAC strengthen the positive effect of GEO on financial performance while customer engagement has not. In addition, our empirical findings show that when a high level of supplier engagement combined with a high level of GAC, the positive effect of GEO on financial performance is increased. These findings provide important theoretical and practical implications for Chinese manufacturing firms to achieve sustainable development.
(Epi)genomic adaptation driven by fine geographical scale environmental heterogeneity after recent biological invasions
Authors: Chen Yiyong , Ni Ping , Fu Ruiying , Murphy Kieran J. , Wyeth Russell C. , Bishop Cory D. , Huang Xuena , Li Shiguo , Zhan Aibin
Published: November 2022

Elucidating processes and mechanisms involved in rapid local adaptation to varied environments is a poorly understood but crucial component in management of invasive species. Recent studies have proposed that genetic and epigenetic variation could both contribute to ecological adaptation, yet it remains unclear on the interplay between these two components underpinning rapid adaptation in wild animal populations. To assess their respective contributions to local adaptation, we explored epigenomic and genomic responses to environmental heterogeneity in eight recently colonized ascidian (Ciona intestinalis) populations at a relatively fine geographical scale. Based on MethylRADseq data, we detected strong patterns of local environment‐driven DNA methylation divergence among populations, significant epigenetic isolation by environment (IBE), and a large number of local environment‐associated epigenetic loci. Meanwhile, multiple genetic analyses based on single nucleotide polymorphisms (SNPs) showed genomic footprints of divergent selection. In addition, for five genetically similar populations, we detected significant methylation divergence and local environment‐driven methylation patterns, indicating the strong effects of local environments on epigenetic variation. From a functional perspective, a majority of functional genes, Gene Ontology (GO) terms, and biological pathways were largely specific to one of these two types of variation, suggesting partial independence between epigenetic and genetic adaptation. The methylation quantitative trait loci (mQTL) analysis showed that the genetic variation explained only 18.67% of methylation variation, further confirming the autonomous relationship between these two types of variation. Altogether, we highlight the complementary interplay of genetic and epigenetic variation involved in local adaptation, which may jointly promote populations' rapid adaptive capacity and successful invasions in different environments. The findings here provide valuable insights into interactions between invaders and local environments to allow invasive species to rapidly spread, thus contributing to better prediction of invasion success and development of management strategies.
Fast and Simple Preparation of a Sensor Based on Electrochemically Reduced Graphene Oxide (rGO) for the Determination of Zopiclone in Pharmaceutical Dosage by Square Wave Adsorptive Stripping Voltammetry (SWAdSV)
Authors: Navarro Freddy , Segura Rodrigo , Godoy Fernando , Martí Angel A. , Mascayano Carolina , Aguirre Maria J. , Flores Erick , Pizarro Jaime
Published: November 2022

The interactions of zopiclone with electrochemically reduced graphene oxide (rGO) modified electrode were examined. A comparison of GC/rGO and glassy carbon electrode (GC) by electrochemical impedance spectroscopy and scanning electrochemical microscopy (SECM) shows that the modified surface is much less conductive than GC. The role of rGO is to act as a site of specific adsorption of the analyte. Molecular dynamics showed that the monoanionic form of zopiclone presents more interactions with defects of rGO. The analytical methodology allowed obtaining a linearity of 10–130 μg L−1, with a limit of detection of 2.14 μg L−1using SWAdSV at pH 10.0.
Design of Quadruple‐Layer Antireflection Coating for AlGaInP/AlGaAs/GaAs Three‐Junction Solar Cell
Authors: Zhang Shujie , Li Xinyi , Li Ge , Lu Hongbo , Wang Xunchun
Published: November 2022

A combination of AlGaInP/AlGaAs/GaAs is commonly used in world‐record five‐ and six‐junction solar cells for their easily tunable bandgap and nearly matched lattice constants. Wide‐range low reflectivity is of significant importance in this three‐junction solar cell (3JSC), but also difficult to achieve particularly in 300–400 nm due to the optical properties of III–V alloys. Therefore, quadruple‐layer antireflection coatings (QLAR) composed of ZnS and MgF2films are studied in this article for both performance and practicability. Optical constants of ZnS and MgF2films are extracted by variable angle spectroscopic ellipsometry. 150 °C is determined as the best deposition temperature to decrease parasitic absorption in ZnS films. The antireflection coating is designed by the transfer‐matrix method considering both low reflectivity in a wide range of 300–900 nm and balanced subcell current density. Fabricated 3JSC with optimized MgF2/ZnS/MgF2/ZnS QLAR is demonstrated to possess low reflection losses in a broadband spectral range, with an average of only 1.59% in 300–900 nm. This boosts the integral current density to 11.58, 11.35, and 11.25 mA cm−2for AlGaInP, AlGaAs, and GaAs subcells, respectively.
Evaluating the reliability, validity, and utility of overlapping networks: Implications for network theories of cognition
Authors: Cookson Savannah L. , D'Esposito Mark
Published: November 2022

Brain network definitions typically assume nonoverlap or minimal overlap, ignoring regions' connections to multiple networks. However, new methods are emerging that emphasize network overlap. Here, we investigated the reliability and validity of one assignment method, the mixed membership algorithm, and explored its potential utility for identifying gaps in existing network models of cognition. We first assessed between‐sample reliability of overlapping assignments with a split‐half design; a bootstrapped Dice similarity analysis demonstrated good agreement between the networks from the two subgroups. Next, we assessed whether overlapping networks captured expected nonoverlapping topographies; overlapping networks captured portions of one to three nonoverlapping topographies, which aligned with canonical network definitions. Following this, a relative entropy analysis showed that a majority of regions participated in more than one network, as is seen biologically, and many regions did not show preferential connection to any one network. Finally, we explored overlapping network membership in regions of the dual‐networks model of cognitive control, showing that almost every region was a member of multiple networks. Thus, the mixed membership algorithm produces consistent and biologically plausible networks, which presumably will allow for the development of more complete network models of cognition.
A case of pseudoprogression in avelumab maintenance therapy for metastatic bladder cancer
Authors: Hayakawa Nozomi , Kikuchi Eiji
Published: November 2022

Introduction

A unique phenomenon of immune therapy is pseudoprogression; however, a definite mechanism and predictive factors remain unclear. We herein report a case of pseudoprogression with avelumab maintenance therapy.

Case presentation

A 67‐year‐old male diagnosed with muscle‐invasive bladder cancer with lung metastasis was treated with four cycles of gemcitabine and cisplatin chemotherapy immediately after cystectomy and ileal conduit urinary diversion. The response to cisplatin‐based chemotherapy was a stable disease. Avelumab maintenance therapy was started after first‐line chemotherapy but was interrupted due to his general fatigue after the third administration of avelumab. At that time, computed tomography (CT) revealed an increased size of lung metastases. Two months after the interruption, avelumab maintenance therapy was restarted. At the end of the seventh dose of avelumab administration, CT showed a dramatic reduction of lung metastatic tumors.

Conclusion

Pseudoprogression may also occur with avelumab maintenance therapy in metastatic bladder cancer.
Time‐course analysis of pulmonary inflammation induced by intratracheal instillation of nanosized crystalline silica particles in F344 rats
Authors: Kobayashi Toshio , Tsubokura Yasuhiro , Oshima Yutaka , Sasaki Takeshi , Kawaguchi Kenji , Koga Kenji , Uchida Kunio , Shinohara Naohide , Ajimi Shozo , Kayashima Takakazu , Nakai Makoto , Imatanaka Nobuya
Published: November 2022

Crystalline silica is an important cause of serious pulmonary diseases, and its toxic potential is known to be associated with its surface electrical properties. However, in vivo data clarifying the relevance of silica's toxic potential, especially its long‐term effects, remain insufficient. To investigate the contribution of physico‐chemical property including surface potential on the hazard of nanocrystalline silica, we performed single intratracheal instillation testing using five different crystalline silicas in a rat model and assessed time‐course changes in pulmonary inflammation, lung burden, and thoracic lymph node loads. Silica‐nanoparticles were prepared from two commercial products (Min‐U‐Sil5 [MS5] and SIO07PB [SPB]) using three different pretreatments: centrifugation (C), grinding (G), and surface dissolving (D). The five types of silica particles—MS5, MS5_C, SPB_C, SPB_G, and SPB_D—were intratracheally instilled into male F344 rats at doses of 0 mg/kg (purified water), 0.22 mg/kg (SPB), and 0.67, 2, or 6 mg/kg (MS5). Bronchoalveolar lavage, a lung burden analysis, and histopathological examination were performed at 3, 28, and 91 days after instillation. Granuloma formation was present in MS5 group at 91 days after instillation, although granuloma formation was suppressed in MS5_C group, which had a smaller particle size. SPB_C induced severe and progressive inflammation and kinetic lung overload, whereas SPB_G and SPB_D induced only slight and transient acute inflammation. Our results support that in vivo toxic potential of nanosilica by intratracheal instillation may involve with surface electrical properties leading to prolonged effect and may not be dependent not only on surface properties but also on other physico‐chemical properties.
The voluntary sustainability standards and their contribution towards the achievement of the Sustainable Development Goals: A systematic review on the coffee sector
Authors: Rubio‐Jovel Karla
Published: November 2022

In 2015, the United Nations adopted the Sustainable Development Goals (SDGs). Voluntary sustainability standards (VSSs) precede the SDGs and are a major governance tool for sustainability. Consequently, it is important to understand the role of VSS towards the achievement of the SDGs. This article contributes to answer this question through a systematic review of literature. Results revealed research gaps for key SDGs, such as SDG 5 (Gender Equality) and SDG 10 (Reduced Inequalities). Another relevant finding is that more than half of the studied variables showed no significant difference between intervention or control group, or no significant change over time. This article encourages VSSs and policymakers to work collaboratively towards the use of common indicators and increased data transparency.
既往のない妊娠初期の妊婦が水中毒による意識障害を呈した1例(Impaired consciousness caused by water intoxication in a previously healthy woman in the first trimester of pregnancy: a case report)
Authors: 功祐 三宅 , 成人 石川 , 恒平 蓑田 , 彩華 眞田 , 学 成澤 , 俊一 二瓶 , 俊彦 真弓
Published: November 2022

水中毒は精神科疾患に合併することが多い。今回，精神疾患などの既往がなく，妊娠初期に水中毒を発症した稀な症例を経験したため報告する。症例は31歳の妊娠6週・初産婦。来院日の1週間前から嘔気，気分不良，食思不振を認め，近医産婦人科でつわりと診断された。その後も食事の匂いを嗅ぐだけで気分が悪くなり，来院4日前からは毎日水のみを5L程度摂取していた。来院日まで著変はなかったが，突然倒れ，呼びかけに反応しなくなり当院救急搬送された。来院時，意識レベルはGlasgow coma scale（GCS）E1V1M3，明らかな神経学的所見は認めなかった。頭部CTで異常所見を認めず，血清Na値 112mmol/L，血清浸透圧 250mOsm/kg/H2O，尿中Na値 8mmol/Lと低値であったため，水中毒による低Na血症と診断し，輸液管理・電解質補正を行った。第4病日に血清Na 130mmol/Lまで軽快し意識清明となり，第8病日に自宅退院となった。妊娠40週4日目に経膣分娩で出産し，母児ともに問題なく経過した。本症例ではとくに既往のない妊娠初期の妊婦がつわりのため，水のみを多量に摂取し，水中毒を発症し意識障害を呈したと推察される。食事摂取不良の妊娠初期の意識障害症例では早期から電解質異常を鑑別することが重要である。
Individual local human thermal climates in the Hungarian lowland: Estimations by a simple clothing resistance‐operative temperature model
Authors: Ács Ferenc , Kristóf Erzsébet , Zsákai Annamária
Published: November 2022

Human thermal climate in the Hungarian lowland is investigated by using a clothing resistance‐operative temperature model performing individual, local, and long‐term concurrent observations of weather and human thermal perception. Human thermal load is characterized in terms of clothing resistance rcl and operative temperature To. The model is also used as a tool to analyse the relationship between rcl and the structural parameters of the body (relative fat mass index (fatBMI) and relative muscle mass index (muscleBMI)). This analysis works with data collected on more than 1,000 occasions of weather and thermal perception observation and uses body structure data of more than 3,000 adults and children. By analysing the data, the following human thermal climate characteristics have been established. (a) To of about 80°C can be considered as the upper limit of heat stress in the Hungarian lowland, similarly, To of about −35 to −37°C can be taken as the lower limit of cold stress. (b) Interpersonal thermal load variations increase with increasing of cold stress; these variations are the smallest within the “thermoneutral” zone. (c) In cold stress situations, there is a significant sexual dimorphism in the relationship between rcl and fatBMI. (d) In night time period of the day, To can vary between 25°C and the lower limit of cold stress. In this range of To, thermal perception types “neutral,” “cool,” “cold,” and “very cold” occurred. Based on the results, it can be seen that interpersonal thermal load variations cannot be neglected in extreme cold weather conditions, and that interpersonal variations of fatBMI index are determinant in the formation of individual clothing resistance.
Divergent and Convergent Thinking across the Schoolyears: A Dynamic Perspective on Creativity Development
Authors: Eon Duval Philippe , Frick Aurélien , Denervaud Solange
Published: November 2022

Creative thinking is critical to overcome many daily life situations. As such, there has been a growing interest on how creative thinking develops during childhood. However, little is known about the underlying mechanisms driving its development. Indeed, almost all research has focused on divergent thinking, leaving aside convergent thinking, and did not thoroughly investigate how internal and/or external factors influence their development. Here, 222 children aged from 4 to 12 years old attending either a Montessori or a traditional school performed drawing‐based convergent and divergent standardized tasks. In addition, a subset of 41 children were tested using similar tasks for a second session 3 years apart. The results revealed dynamic developmental stages of convergent and divergent thinking. More specifically, a loss of divergent thinking was counterbalanced by a gain of convergent thinking, especially during the fourth‐grade slump (8–10 years old). Although Montessori‐schooled children showed overall higher creative abilities than traditionally schooled children, no differences were observed in the developmental trajectories of convergent and divergent thinking between the two pedagogies. This suggests that progress and decrease in creative thinking may be mostly due to internal factors such as brain maturation factors than external factors such as peer pressure.
Kinematic function of knee implant designs across a range of daily activities
Authors: Kour R. Y. Nigel , Guan Shanyuanye , Dowsey Michelle M. , Choong Peter F. , Pandy Marcus G.
Published: November 2022

The aim of this randomized controlled trial was to measure and compare six‐degree‐of‐freedom (6‐DOF) knee joint motion of three total knee arthroplasty (TKA) implant designs across a range of daily activities. Seventy‐five TKA patients were recruited to this study and randomly assigned a posterior‐stabilized (PS), cruciate‐retaining (CR), or medial‐stabilized (MS) implant. Six months after surgery, patients performed five activities of daily living: level walking, step‐up, step‐down, sit‐to‐stand, and stand‐to‐sit. Mobile biplane X‐ray imaging was used to measure 6‐DOF knee kinematics and the center of rotation of the knee in the transverse plane for each activity. Mean 6‐DOF knee kinematics were consistently similar for PS and CR, whereas MS was more externally rotated and abducted, and lateral shift was lower across all activities. Peak‐to‐peak anterior drawer for MS was also significantly lower during walking, step‐up, and step‐down (p < 0.017). The center of rotation of the knee in the transverse plane was located on the medial side for MS, whereas PS and CR rotated about the lateral compartment or close to the tibial origin. The kinematic function of MS was more similar to that of the healthy knee than PS and CR based on reduced paradoxical anterior translation at low flexion angles and a transverse center of rotation located in the medial compartment. Overall, 6‐DOF knee joint motion for PS and CR were similar across all daily activities, whereas that measured for MS was appreciably different. The kinematic patterns observed for MS reflects a highly conforming medial articulation in the MS design.
Errors in the radiographic measurement of pelvic incidence
Authors: Iwasa Makoto , Hamada Hidetoshi , Uemura Keisuke , Ando Wataru , Takao Masaki , Sugano Nobuhiko
Published: November 2022

Pelvic incidence (PI) is often quantified in patients undergoing total hip arthroplasty. Errors in radiographic PI measurements can affect clinical outcomes. The purposes of this study were (1) to evaluate the error in radiographic PI measurement in patients with hip osteoarthritis (OA) and (2) to analyze the factors related to the error. Radiographs and computer tomography (CT) images of 100 patients (24 men and 76 women; mean age 63.7 years) with unilateral OA were reviewed. The error in radiographic PI measurement was defined as the difference between the radiographic measurement of the PI (rPI) and the accurate value of PI measured using CT images (cPI). Factors related to the error in the rPI were analyzed, including the coronal and axial rotation of the pelvis on lateral radiographs. The degree of coronal and axial rotation was expressed as the angle of rotation around the anteroposterior and craniocaudal axes. The mean rPI was significantly larger than the cPI (57.8° and 54.1°, p < 0.01). The error in the rPI was 3.6° on average and 15.8° at maximum. The mean coronal and axial rotation of the pelvis was 9.6° and 4.4°, respectively. The error in the rPI positively correlated with coronal pelvic rotation and rPI, and negatively correlated with axial pelvic rotation (p < 0.01, r = 0.35, 0.43, and −0.45, respectively). The rPI was 3.6° larger on average than the cPI in patients with hip OA. Coronal and axial rotation of the pelvis and a large PI were related to the error in the rPI.