bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with age at autism diagnosis in a community sample of Australian adults
Authors: Huang Yunhe , Arnold Samuel R. C. , Foley Kitty‐Rose , Lawson Lauren P. , Richdale Amanda L. , Trollor Julian N.
Published: September 2021

Autism diagnosis in adulthood has become increasingly common due to a range of factors including changes in awareness, diagnostic criteria, and professional practices. Past research identified a range of demographic and autism‐related factors associated with autism diagnosis age in children. However, it is unclear whether these apply to autistic adults. This study aimed to examine predictors of autism diagnosis age in adults while controlling for current age and autistic traits. We used a cross‐sectional sample of 657 adults aged 15–80 from three self and carer‐report studies: the Australian Longitudinal Study of Autism in Adulthood (ALSAA), Study of Australian School‐Leavers with Autism (SASLA) and Pathways, Predictors and Impact of Receiving an Autism Spectrum Diagnosis in Adulthood (Pathways). Using hierarchical multiplicative heteroscedastic regression, we found that older current age and higher self‐reported autistic traits predicted older diagnosis age, and that female gender, lack of intellectual disability, language other than English, family history of autism, lifetime depression, and no obsessive–compulsive disorder predicted older diagnosis age beyond current age and autistic traits. The paradoxical relationship between high autistic traits and older diagnosis age requires further investigation. Based on these findings, we recommended strategies to improve autism recognition in women and people from non‐English‐speaking backgrounds. Future studies could extend the findings by examining the effects of childhood and adulthood socioeconomic status on adult diagnosis age.

Lay Summary

We studied the relationship between age at autism diagnosis and other characteristics in adults. We found that both older current age and higher autistic traits, female gender, language other than English, family history of autism, and history of depression were related to older age at diagnosis, while intellectual disability and history of obsessive–compulsive disorder were related to younger age at diagnosis. Our findings suggest more work is needed to help recognize autism in women and people from non‐English‐speaking backgrounds.
Evaluating the effect of cultivation conditions on palmitoleic acid‐rich lipid production by Scheffersomyces segobiensis DSM 27193
Authors: Zhou Xinhai , Bao Xinhui , Zhou Jie , Xin Fengxue , Zhang Wenming , Qian Xiujuan , Dong Weiliang , Jiang Min , Ochsenreither Katrin
Published: September 2021

Palmitoleic acid (POA) is a valuable monounsaturated fatty acid but it is rarely found in high proportions in microbial lipids. Recently, the newly isolated oleaginous yeast Scheffersomyces segobiensis DSM 27193 has been confirmed to be able to accumulate >10% POA in its intracellular lipids. This study comprehensively investigated the effect of medium composition and cultivation conditions on POA‐rich lipid accumulation by this yeast. The results showed that the lipid content could be improved significantly in shake flask cultivations from 3.6% to 27.3% by using yeast extract as a nitrogen source. Increasing Mg2+ concentration from 0.04 to 0.16 g L−1 resulted in the formation of 15.3 g L−1 of biomass and 4.2 g L−1 of POA‐rich lipids. The initial pH, temperature, and inoculation size also influenced POA‐rich lipid production positively. Under optimal conditions, the highest lipid content of 31.7% with the highest POA content of 12.50% was achieved, corresponding to 5.3 g L−1 of lipids and 0.7 g L−1 of POA. Fermentation conducted in a 2.5 L bioreactor led to 28.1 g L−1 of biomass with 39.4% of lipid content, corresponding to 11.1 g L−1 of total lipids and 1.4 g L−1 of POA. These results suggest that this yeast could be a potentially well‐suited host for POA‐rich lipid production. © 2021 Society of Chemical Industry and John Wiley & Sons, Ltd
Comparison of tissue pharmacokinetics of esflurbiprofen plaster with flurbiprofen tablets in patients with knee osteoarthritis: A multicenter randomized controlled trial
Authors: Amemiya Masaki , Nakagawa Yusuke , Yoshimura Hideya , Takahashi Toru , Inomata Kei , Nagase Tsuyoshi , Ju Young‐Jin , Shimaya Masayuki , Tsukada Sachiyuki , Hirasawa Naoyuki , Koga Hideyuki
Published: September 2021

This open‐label, multicenter, prospective, randomized controlled trial aimed to determine the effectiveness of esflurbiprofen plaster (SFPP) and flurbiprofen tablets (FPTs) on knee osteoarthritis in patients scheduled for total knee arthroplasty by comparing the transfer of esflurbiprofen and flurbiprofen to tissues and fluids. Thirty‐eight patients were randomly assigned in a 1:1 ratio to receive SFPP or FPT. Both groups were then divided into four subgroups, according to whether they received the final dose of SFPP or FPT at 2, 7, 12, or 24 h before planned surgery. The primary endpoints were the esflurbiprofen concentrations in synovium, synovial fluid, and plasma. Areas under concentration–time curves (AUC0–24 h) of esflurbiprofen were calculated for each group. Pain was assessed using a numeric rating scale (NRS) 7 days before and immediately before surgery. The AUC0–24 h in the synovium were 4401.24 and 4862.70 ng·h/g in the SFPP and FPT groups, respectively. Maximum esflurbiprofen concentrations were observed in the synovium, synovial fluids, and plasma after SFPP application for 12 h. The NRS results indicated a long‐lasting effect of SFPP. The AUC of the synovial esflurbiprofen concentration of SFPP indicated that the SFPP is transferred to the synovium and synovial fluid in high concentration. The efficient deep‐tissue transfer of esflurbiprofen suggests that its pharmacokinetic characteristics differ from those of conventional topical NSAIDs. This study was prospectively registered in the Japan Registry of Clinical Trials (registration number: jRCTs031180228).
Preparation of cellulose‐based electrospun fluorescent nanofibres doped with perylene encapsulated in silica nanoparticles for potential flexible electronics
Authors: Hassabo Ahmed G. , Mohamed Amina L. , Khattab Tawfik A.
Published: September 2021

Novel fluorescent nanofibres were developed via the electrospinning of chromophore‐doped cellulose. Two different perylene‐doped cellulose fluorescent fibres were fabricated using cellulose as a host material and perylene dye derivatives as active dopants. Fluorescent cellulose nanofibres were prepared via the electrospinning technique using two different perylene dyes, including perylene diimide and perylene mono‐imide sodium/potassium salts. The generated fluorescent silica nanoparticles exhibited diameters varying in the range 80–180 nm. The generated electrospun fluorescent nanofibrous structures displayed smooth surfaces with average diameters of 200–300 nm for cellulose comprising perylene diimide and sodium/potassium salts of perylene mono‐imide dyes, respectively, dispersed uniformly in the cellulose matrix. The generated fluorescent nanoparticles and nanofibres were characterized by different standard methods, including scanning electron microscopy (SEM), transmission electron microscopy (TEM), fluorescent optical microscope (FOM) and Fourier‐transform infrared spectra (FT‐IR). The fluorescence properties of the fabricated cellulose nanofibres were explored. Those fluorescent nanofibres pave the way for the development of promising textile fluorescence materials, such as flexible displays, photonics, and optical devices.
Spectroscopic investigation of CuxMg0.2−xZn0.8S (x = 0, 0.05, 0.10, 0.15) thin films for deep and dilute blue LED applications
Authors: V S Ganesha Krishna , Chattopadhyay Saikat , Misra Kamakhya Prakash , M G Mahesha
Published: September 2021

The effect of copper (Cu) doping on the luminescent properties of the spray deposited Mg0.2Zn0.8S thin films were investigated for the first time. The Mg0.2Zn0.8S film is an excellent luminescent material with strong blue emissions. In the current investigation, we doped Mg0.2Zn0.8S with Cu by taking (Cu + Mg) as 20 at% by keeping other element ratios constant. Among the different samples in the series, Cu0.05Mg0.15Zn0.8S has shown promising results with dark blue emission. Also, these films showed good structural formation with lower or no other impurities, which is evident from the X‐ray diffraction (XRD). Scanning electron microscopy (SEM), energy‐dispersive X‐ray spectroscopy (EDX) and atomic force microscopy (AFM) confirmed the improved material quality of Cu0.05Mg0.15Zn0.8S as compared to the pristine. Raman and X‐ray photoelectron spectroscopy (XPS) studies have been carried out for the samples. Various defects induced in the films were investigated by recording the photoluminescence (PL) spectra and Cu:(Mg0.2Zn0.8S) films exhibited the capability to produce dilute blue luminescence by absorbing ultraviolet (UV) light. The Cu0.05Mg0.15Zn0.8S film showed promising material property, which is suitable for light‐emitting diode (LED) applications.
A simple fluorescent assay for the detection of peptide nucleic acid‐directed double strand duplex invasion
Authors: Heidari Ali , Hermann Mason , Hudson Robert H. E.
Published: September 2021

Peptide nucleic acid (PNA) is a mimic of nucleic acids that is able to bind complementary oligonucleotides with high affinity and excellent selectivity. As such, the use of PNA has been proposed in numerous applications in biochemistry, medicine, and biotechnology. Sequences of pseudo‐complementary PNAs containing diaminopurine (D)‐2‐thiouracil (SU) base pairs bind to complementary regions within double‐stranded DNA targets. This type of binding is termed “double duplex invasion” and involves unwinding of the duplex accompanied by simultaneous hybridization of both DNA strands by the two pseudo‐complementary PNAs. In this study, a simple method of assaying DNA strand invasion by pseudo‐complementary PNAs was developed. This method is based on the incorporation of a single fluorescent cytidine analog, phenylpyrrolocytidine (PhpC), into the double‐stranded DNA target such that upon invasion by PNA, the PhpC is displaced to a single‐stranded region resulting in the turn‐on of fluorescence emission. This fluorescent assay is applicable to studies both at equilibrium and approach‐to‐equilibrium (time‐dependent) conditions.
Study of the Ribavirin drug adsorption on the surfaces of carbon nanotube and graphene nanosheet using density functional theory calculations
Authors: Sheikhi Masoome , Shahab Siyamak , Balali Ebrahim , Alnajjar Radwan , Kaviani Sadegh , Khancheuski Maksim , Al Saud Sultan
Published: September 2021

Density functional theory (DFT) and time‐dependent density functional theory (TD‐DFT) calculations were performed in the solvent water for the study of the adsorption of the Ribavirin (RIB) on surfaces of the carbon nanotube (CNT) and graphene nanosheet (GNS). After the adsorption, the electronic properties of the CNT and GNS change. The adsorption energies are shown the strong adsorption in GNS/RIB (−0.816 eV) rather than CNT/RIB (0.544 eV). The dipole moment of CNT and GNS changes with the adsorption of the RIB from 0.00 to 4.57 and 7.05 Debye in CNT/RIB and GNS/RIB, respectively. The adsorption of the RIB molecule on CNT and GNS increases the value of λmax. The localized orbital locator and electron location function values for the CC bond confirm the stronger interaction between carbon atoms of GNS and RIB. Based on the results, it is suggested that GNS with a lower energy gap (3.03 eV) is a more suitable structure for adsorption of the RIB in comparison with the CNT (3.021).
Insight into the histidine tautomerism effect on heterodimers of Aβ40
Authors: Li Hao , Salimi Abbas , Burnea Francis Kirby B. , Shi Hu , Lee Jin Yong
Published: September 2021

The intrinsic origin of amyloid aggregation has been pursued as a new pathogenesis for Alzheimer's disease (AD). The aggregation mechanisms influenced by histidine tautomerism were previously investigated in Aβ40 and Aβ42 monomers. In the present study, we focus on the structural properties of Aβ40 heterodimer under the influence of histidine. The results of molecular dynamics simulation detected different aggregation trends were detected in different heterodimers formed by the εεε isomer and other isomers. In the (εεε:δδδ) dimer, the highest β‐sheet content was obtained in the δδδ chain, which is in agreement with our previous studies that δδδ monomer is the most easily formed β‐sheet secondary structure in the monomer. Further analysis confirmed that (εεε:δδδ) dimers more easily aggregate into fibrils in comparison with other heterodimers. This research will help in understanding the tautomeric effect on Aβ heterodimers, thereby helping to figure out the pathogenesis of AD.
The Role of Spike Protein Mutations in the Infectious Power of SARS‐COV‐2 Variants: A Molecular Interaction Perspective
Authors: Gómez Santiago A. , Rojas‐Valencia Natalia , Gómez Sara , Cappelli Chiara , Restrepo Albeiro
Published: September 2021

Specific S477N, N501Y, K417N, K417T, E484K mutations in the receptor binding domain (RBD) of the spike protein in the wild type SARS‐COV‐2 virus have resulted, among others, in the following variants: B.1.160 (20A or EU2, first reported in continental Europe), B1.1.7 (α or 20I501Y.V1, first reported in the United Kingdom), B.1.351 (β or 20H/501Y.V2, first reported in South Africa), B.1.1.28.1 (γ or P.1 or 20J/501Y.V3, first reported in Brazil), and B.1.1.28.2 (ζ, or P.2 or 20B/S484K, also first reported in Brazil). From the analysis of a set of bonding descriptors firmly rooted in the formalism of quantum mechanics, including Natural Bond Orbitals (NBO), Quantum Theory of Atoms In Molecules (QTAIM) and highly correlated energies within the Domain Based Local Pair Natural Orbital Coupled Cluster Method (DLPNO‐CCSD(T)), and from a set of computed electronic spectral patterns with environmental effects, we show that the new variants improve their ability to recognize available sites to either hydrogen bond or to form salt bridges with residues in the ACE2 receptor of the host cells. This results in significantly improved initial virus⋅⋅⋅cell molecular recognition and attachment at the microscopic level, which trigger the infectious cycle.
Lagophthalmos of the upper eyelid after rhinoplasty: A case report
Authors: Jahandideh Hesam , Dehghani Firouzabadi Fatemeh , Dehghani Firouzabadi Mohammad , Roomiani Maryam
Published: September 2021

Lagophthalmos is an inability to close the eyelids which can result from many causes. Septorhinoplasty surgery is an uncommon reason for that. This paper reports the lagophthalmos complication, after a septorhinoplasty surgery.
Malignant carcinoma and skin melanoma neoplasms concomitantly in the thyroid
Authors: Al‐Harake Ali , Dandache Israa , Moukadem Hiba , Saliba Marwan , Chahine Jimmy , Yazbeck Hosni , Abdel‐Sater Fadi , Karnib Hussein , Younes Mahmoud H.
Published: September 2021

Malignant melanomas metastatic to the thyroid gland are uncommon. Based on microscopy and DNA methylation profile, we report a rare coexistence of neoplasms in the thyroid, presumably in our case, with relapse‐free condition on adjuvant therapy.
Isolated torsion of the fallopian tube associated with hydrosalpinx in a 17‐year‐old sexually inactive girl: A case report
Authors: Daniilidis Angelos , Charitidou Sonia , Petousis Stamatios , Margioula‐Siarkou Chrysoula , Liberis Anastasios , Dinas Konstantinos
Published: September 2021

Isolated tubal torsion is an unusual cause of acute abdominal pain in young sexually inactive patients. However, it should be still taken into account regarding the differential diagnosis of such conditions.
Stable Pd(0) Complexes with Ferrocene Bisphosphanes Bearing Phosphatrioxaadamantyl Substituents Efficiently Catalyze Selective C‐H Arylation of Benzoxazoles by Aryl Chlorides
Authors: Horký Filip , Císařová Ivana , Štěpnička Petr
Published: September 2021

Versatile applications and unique performance of 1,1’‐bis(diphenylphosphanyl)ferrocene (dppf) in coordination chemistry and catalysis prompted the search for its analogs. This contribution describes the synthesis of the first donor‐unsymmetric dppf congeners bearing bulky and rigid 1,3,5,7‐tetramethyl‐2,4,6‐trioxa‐8‐phosphaadamantyl (CgP) donor groups, viz. Ph2PfcPCg (1) and Ph2PfcCH2PCg (2; fc=ferrocene‐1,1’‐diyl). Bis‐phosphanes 1 and 2 were converted into air‐stable Pd(0) complexes, [Pd(ma)(L^L)] (L^L=1 and 2; ma=maleic anhydride). Together with [Pd(ma)(dppf)], these complexes were applied as catalysts in Pd‐catalyzed C−H arylation of benzoxazoles with aryl chlorides in n‐butanol as an environmentally benign solvent. Among all catalysts tested in this study, complex [Pd(ma)(2)] performed the best, providing a high‐yield and selective synthesis of 2‐arylbenzoxazoles from a range of the generally less reactive chloroarenes at low catalyst loading (typically 1 mol.%). Under similar conditions, the structurally related heterocycles (e. g., 1‐methylbenzimidazole and benzothiazole) did not react.
Standing on the Shoulders of Giants – Your Mentors and Role Models Will Shape Your Career
Authors: García‐Martínez Javier
Published: September 2021

Choosing the right mentors and role models has a profound impact in both our lives and professional careers; however, most often, not enough time or thought is given to this important decision. Because of that, we may miss some great opportunities and limit the potential benefits. In this invited contribution, I share my personal experience on nurturing the relationship with mentors and on choosing role models with my same values and a strong sense of service.
An Isolable Three‐Coordinate Germanone and Its Reactivity
Authors: Zhao Xuan‐Xuan , Szilvási Tibor , Hanusch Franziska , Inoue Shigeyoshi
Published: September 2021

A rare three‐coordinate germanone [IPrN]2Ge=O (IPrN=bis(2,6‐diisopropylphenyl)imidazolin‐2‐imino) was successfully isolated. The germanone has a rather high thermal stability in arene solvent, and no detectable change was observed at 80 °C for at least one week. However, high thermal stability of [IPrN]2Ge=O does not prevent its reactivity toward small molecules. Structural analysis and initial reactivity studies revealed the highly polarized nature of the terminal Ge=O bond. Besides, the addition of phenylacetylene, as well as O‐atom transfer with 2,6‐dimethylphenyl isocyanide make it a mimic of nucleophilic transition‐metal oxides. Mechanism for O‐atom transfer reaction was investigated via DFT calculations, which revealed that the reaction proceeds via a [2+2] cycloaddition intermediate.
A Water Molecule Triggers Guest Exchange at a Mono‐Zinc Centre Confined in a Biomimetic Calixarene Pocket: A Model for Understanding Ligand Stability in Zn Proteins
Authors: Brunetti Emilio , Marcelis Lionel , Zhurkin Fedor E. , Luhmer Michel , Jabin Ivan , Reinaud Olivia , Bartik Kristin
Published: September 2021

Invited for the cover of this issue are Kristin Bartik, Olivia Reinaud and co‐workers at the Université libre de Bruxelles and Université Paris Descartes. The image depicts a Zn protein and highlights the role that a single water molecule can play in catalysing ligand exchange. Read the full text of the article at 10.1002/chem.202102184.
Altered Peptide Self‐Assembly and Co‐Assembly with DNA by Modification of Aromatic Residues
Authors: Feng Ruilu , Ni Rong , Chau Ying
Published: September 2021

Aromatic residues are widely used as building blocks for driving self‐assemblies in natural and designer biomaterials. The noncovalent interactions involving aromatic rings determine proteins’ structure and biofunction. Here, we studied the effects of changes in the proximity of the aromatic rings in a self‐assembling peptide for modulating interactions involving the aromatic residues. By changing the distance between the aromatic ring and peptide backbone and replacing the side chain with a sulfur atom, we altered the nanostructures and gene transfection efficiency of peptide‐DNA co‐assemblies. This study demonstrates the significance of subtle alterations in aromatic interactions and facilitates deeper understanding of the aromatic‐involving interactions.
Alarming recent rises in early‐onset colorectal cancer
Authors: Thompson Caroline A. , Begi Talia , Parada Humberto
Published: September 2021

Because of recent increases in early‐onset diagnoses, nearly 10% of colorectal cancers are now diagnosed in individuals younger than 50 years. In this issue of Cancer, Shah et al report a comprehensive analysis of trends in early‐onset colorectal cancer across all 50 states through 2017.
Clinical and cytopathological features of suspected thyroglossal duct cysts and neoplasms arising from them: A large series from a referral cancer center
Authors: Hou Tieying , Liu Zhonghua , Gan Qiong , Debnam J. Matthew , Krishnamurthy Savitri
Published: September 2021

Background

Thyroglossal duct cysts (TGDCs) are the most common congenital midline cystic lesions in the neck, and they are often evaluated by fine‐needle aspiration. Recognizing the cytomorphologic features of TGDCs and their mimics is important for clinical management.

Methods

This study examined the clinical, radiological, and cytopathological features of 86 ultrasonography‐guided fine‐needle aspiration (US‐FNA) specimens from clinically suspected TGDCs or malignancies arising from TGDCs and correlated the findings with surgical follow‐up and/or imaging studies.

Results

According to ultrasound examinations of 66 lesions, 17 (25.8%) were cystic, 8 (12.1%) were cystic with septations, 21 (31.8%) were cystic with solid nodules, and 20 (30.3%) were solid or cystic with internal debris. Cytopathologically, 81 lesions (94%) were categorized as benign, 2 (2%) were categorized as atypical, and 3 (3%) were categorized as malignant. In benign lesions, proteinaceous material (63%), histiocytes (63%), colloid (37%), squamous cells (35%), columnar cells (32%), follicular cells (15%), inflammatory cells (9%), and multinucleated giant cells (9%) were noted. Diagnoses in the benign category included TGDC in 64 patients (75%), TGDC or mimics (colloid nodule/epidermoid cyst) in 14 patients (17%), a colloid nodule in 1 patient, and thyroiditis in 1 patient. Surgical resection, performed in 23 patients, confirmed TGDCs in 12, benign mimics in 7, and carcinoma in 4.

Conclusions

Cytopathological features, in conjunction with imaging, allowed a definite diagnosis of TGDC in most patients (75%). The presence of mature squamous cells, thyroid follicular cells, with or without colloid and/or lymphocytes alone allowed a differential diagnosis of TGDC and its mimics in 17%. US‐FNA findings could not distinguish primary carcinomas arising from TGDCs from metastatic tumors.
USVs‐Sim: A general simulation platform for unmanned surface vessels autonomous learning
Authors: Wang Wei , Zhang Han , Li Yang , Zhang Zhenyu , Luo Xiangfeng , Xie Shaorong
Published: September 2021

Unmanned surface vessels (USVs) have been fully used in the civilian and military fields in recent years, which dramatically expands protective capability and detection range. However, the marine environment's complexity and variability make that verification of various advanced USVs control algorithms face high costs and high risks. In this article, we present USVs‐Sim, a novel high‐fidelity general simulation platform for USVs autonomous navigation data generation and control strategy testing. USVs‐Sim is a collection of high‐level extensible modules that allows the rapid development and testing of USVs configurations and facilitates the construction of complex ocean scenarios. USVs‐Sim supports the steering or thrusting limits of USVs, as well as unique dynamics profiles. The platform can specify specific USVs sensor systems and change the time of day and weather conditions to generate robust data. USVs‐Sim facilitates training of deep‐learning algorithms by enabling data export from USVs sensors, including vision data, lidar, relative positions of ocean targets. Therefore, USVs‐Sim allows for the rapid prototyping, development, and testing of USVs autonomous control algorithms in a complex marine environment. In this article, we detail the general simulation platform and testing several representative USVs intelligent control algorithms on the platform.
Ultrafast Excited State Relaxation Dynamics of New Fuchsine‐ a Triphenylmethane Derivative Dye
Authors: Biswas Chinmoy , Rao Soma Venugopal , Chetti Prabhakar , Santosh Kumar Raavi Sai
Published: September 2021

An all‐inclusive investigation of the ultrafast excited state relaxation dynamics of a triphenylmethane derivative molecule, New Fuchsine (NF), using a combined approach of density functional theory (DFT), femtosecond transient absorption spectroscopy (fs‐TAS), and photoluminescence spectroscopy is presented in this work. The DFT calculations confirmed the formation of twisted molecular structure in the excited state of NF in ethanol solution with bond rotation of ≈86°. TAS measurements of NF solution exhibited ultrafast ground state‐recovery pathway via a conical intersection confirming an ultrafast structural reorientation. On the contrary, TAS measurements of NF thin‐film exhibited a longer excited‐state lifetime suggesting a hindered molecular twisted state formed as an intermediate step. Photophysical kinetic models are proposed to globally fit the fs‐TAS data establishing the twisted intramolecular charge transfer (TICT) state mediated ground state recovery for NF in solution and thin film, respectively. Temperature‐dependent photoluminescence study of NF film provided a clear insight into the effect of rotational motion of phenyl rings in NF molecules over the TICT mediated emission.
Evolving Acceptance and Use of RWE for Regulatory Decision Making on the Benefit/Risk Assessment of a Drug in Japan
Authors: Nishioka Kinue , Makimura Tomomi , Ishiguro Akihiro , Nonaka Takahiro , Yamaguchi Mitsune , Uyama Yoshiaki
Published: September 2021

There is growing interest in the utilization of real‐world data (RWD) and real‐world evidence (RWE) for regulatory purposes. However, there are challenges in the practical utilization of RWD to provide RWE as a basis for regulatory decision making. This article presents the regulatory initiatives in Japan and efforts taken to promote the utilization of RWD/RWE for regulatory decision making at the pre‐ and postapproval stages of a drug. There has been a rapid increase in the number of RWD cases evaluated for drug safety assessment in Japan. Nevertheless, more regulatory experiences and considerations are necessary for the utilization of RWD in the efficacy evaluation of a drug. Based on past experiences, data reliability and appropriateness of the methodology for analysis are the major discussion points in utilizing RWD and RWE for regulatory decision making. International harmonization of regulatory requirements is another important area in utilizing RWD and sharing the RWE globally. We describe our perspective on providing RWE, which is useful for regulatory decision making throughout a drug’s life cycle.
Applying Machine Learning to Stem Cell Culture and Differentiation
Authors: Ashraf Mishal , Khalilitousi Mohammadali , Laksman Zachary
Published: September 2021

Machine learning techniques are increasingly becoming incorporated into biological research workflows in a variety of disciplines, most notably cancer research and drug discovery. Efforts in stem cell research comparatively lag behind. We detail key paradigms in machine learning, with a focus on equipping stem cell biologists with the understanding necessary to begin conceptualizing and designing machine learning workflows within their own domain of expertise. Supervised approaches in both regression and classification as well as unsupervised clustering techniques are all covered, with examples from across the biological sciences. High‐throughput, high‐content, multiplex assays for data acquisition are also discussed in the form of single‐cell RNA sequencing and image‐based approaches. Lastly, potential applications in stem cell biology, including the development of novel cell types, and improving model maturation are also discussed. Machine learning approaches applied in stem cell biology show promise in accelerating progress in developmental biology, drug screening, disease modeling, and personalized medicine. © 2021 Wiley Periodicals LLC.
Interspecies interaction intensity influences water consumption in wheat–maize intercropping by regulating root length density
Authors: Wang Yifan , Yin Wen , Hu Falong , Fan Zhilong , Zhao Cai , Yu Aizhong , Chai Qiang
Published: September 2021

In intercropping systems, interspecies interaction intensity has an important effect on water consumption. However, how interspecies interaction intensity reduces water consumption in intercropping is still unclear. The effects of interspecies interaction intensity in wheat (Triticum aestivum)–maize (Zea mays) intercropping system on water consumption characteristics, root length density, and grain yield were examined. A 3‐yr field experiment was conducted to evaluate three root interaction intensities: complete belowground interaction (W/M, without root barrier), partial belowground interaction (NW/M, nylon mesh barrier), and without belowground interaction (PW/M, plastic sheet barrier), with two plant densities of maize (45,000 plants ha−1, M1, and 52,500 plants ha−1, M2) in wheat–maize intercropping system. During co‐growth period of wheat and maize and independent growth of maize, evaporation was reduced by W/M and with increased maize plant density. Root length density of maize was inhibited by intercropped wheat during the co‐growth period. Root length density of maize in the W/M treatment was increased by 14% in 2014 and 45% in 2015, compared with the NW/M treatment, and increased by 26% in 2014 and 119% in 2015, compared with the PW/M treatment, expect for 2016, during maize independent growth. Moreover, there was a negative correlation between evaporation and root length density of maize. Grain yield was increased by W/M2 treatment. Increasing interspecies interaction intensity can decrease evaporation by increasing the root length density of intercropping crops.
Interactions of the barley SD1 and SD2 seed dormancy loci influence preharvest sprouting, seed dormancy, and malting quality
Authors: Sweeney Daniel W. , Rooney Travis E. , Walling Jason G. , Sorrells Mark E.
Published: September 2021

Preharvest sprouting (PHS) can severely damage barley (Hordeum vulgare L.) malting quality and is of particular concern in locations with a high frequency of precipitation around harvest. Malting quality and PHS resistance are often negatively correlated, and the SD2 locus on chromosome 5H has been associated with both traits. Using three spring barley populations, PHS, seed dormancy, and germination rate were mapped over six time points to identify changes in genetic control of these traits during the after‐ripening period. HvAlaAT1 at the SD1 locus was associated with long‐term dormancy and reduced germination rate. Ninety lines were Sanger sequenced for HvGA20ox1, but variants were not associated with PHS or germination traits. The allelic state of HvMKK3 was strongly associated with genetic PHS susceptibility in North American spring two‐row barley germplasm and interactions between HvAlaAT1 and HvMKK3 were associated with changes in seed dormancy and germination rate over time. Several malting quality traits were associated with HvMKK3 alleles. Kompetitive allele‐specific polymerase chain reaction (KASP) markers were developed for the causal mutations in HvAlaAT1 and HvMKK3 and a diagnostic mutation in HvGA20ox1. Haplotypes with PHS resistance, short primary dormancy, and a high germination rate were identified that could be useful for breeding for PHS resistance and malting quality.
Prevalence of high‐risk human papillomavirus DNA and mRNA and its association with abnormal anal cytology in the Czech male anal cancer screening cohort
Authors: Nemcova Jana , Cerna Katerina , Rob Filip , Smahelova Jana , Tresnak Hercogova Jana , Marx Josef , Traxmandlova Iva , Ondic Ondrej
Published: September 2021

Background

Anal cancer (AC) screening is justified in high‐risk populations, particularly HIV‐positive men having sex with men (MSM). HR‐HPV testing could improve the efficiency of cytologically based screening of AC, as in the screening of biologically analogical cervical cancer. The specificity of HR‐HPV testing is influenced by the prevalence of HR‐HPV infection in the screened population. Reported anal HR‐HPV DNA prevalence in MSM is high, but HR‐HPV mRNA reflects rather long‐term infections and is more specific for high‐grade lesions. However, no data were published about HR‐HPV DNA and mRNA prevalence in the Czech AC screening population.

Method

Results of liquid‐based anal cytology of 203 predominantly HIV‐positive MSM from the Czech AC screening cohort were correlated with results of DNA and E6/E7 mRNA testing of 14 HR‐HPV types, and HPV16 genotyping. Eighty‐one MSM underwent a standard anoscopy.

Results

A total of 109 (53.7%) samples had abnormal cytology, with 12 (5.9%) ASC‐H/HSIL, 67 (33.0%) samples cytologically negative, and 27 (13.3%) unsatisfactory. HR‐HPV DNA was detected in 134 (66.0%) and HR‐HPV RNA in 72 (35.5%) anal smears. HR‐HPV mRNA and HPV16 mRNA positivity were associated with abnormal cytology (p = .0037, p = .0021). No significant association was found between HR‐HPV DNA or HPV16 DNA positivity and abnormal cytology. No high‐grade lesions were revealed by anoscopy.

Conclusion

Prevalence of anal HR‐HPV DNA among Czech MSM is high, however, the prevalence of HR‐HPV mRNA is half and associated with abnormal cytology. Our results indicate an increased efficiency of cytological screening when combined with HR‐HPV mRNA testing.
Finding Liebig’s law of the minimum
Authors: Tang Jinyun , Riley William J.
Published: September 2021

Liebig’s law of the minimum (LLM) is often used to interpret empirical biological growth data and model multiple substrates co‐limited growth. However, its mechanistic foundation is rarely discussed, even though its validity has been questioned since its introduction in the 1820s. Here we first show that LLM is a crude approximation of the law of mass action, the state of art theory of biochemical reactions, and the LLM model is less accurate than two other approximations of the law of mass action: the synthesizing unit model and the additive model. We corroborate this conclusion using empirical data sets of algae and plants grown under two co‐limiting substrates. Based on our analysis, we show that when growth is modeled directly as a function of substrate uptake, the LLM model improperly restricts the organism to be of fixed elemental stoichiometry, making it incapable of consistently resolving biological adaptation, ecological evolution, and community assembly. When growth is modeled as a function of the cellular nutrient quota, the LLM model may obtain good results at the risk of incorrect model parameters as compared to those inferred from the more accurate synthesizing unit model. However, biogeochemical models that implement these three formulations are needed to evaluate which formulation is acceptably accurate and their impacts on predicted long‐term ecosystem dynamics. In particular, studies are needed that explore the extent to which parameter calibration can rescue model performance when the mechanistic representation of a biogeochemical process is known to be deficient.
Polar O–Co–P Surface for Bimolecular Activation in Catalytic Hydrogen Generation
Authors: Zhang Huanhuan , Zhang Ke , Ashraf Saima , Fan Yanping , Guan Shuyan , Wu Xianli , Liu Yushan , Liu Baozhong , Li Baojun
Published: September 2021

Boron hydrides release an abundant amount of hydrogen in the presence of a suitable catalyst. Accelerating bimolecular activation kinetics is the key to designing cost‐effective catalysts for borohydride hydrolysis. In this study, the bimolecular activation of a polar O–Co–P site demonstrated superior hydrogen‐generation kinetics (turnover frequency, TOF = 37 min−1, 298 K) and low activation energy (41.0 kJ mol−1) close to that of noble‐metal‐based catalysts. Through a combination of experiments and theoretical calculations, it was revealed that the activated dangling oxygen atom in the Co–O precursor effectively replaced via surface‐phosphorization because of strong electronic interactions between the dangling oxygen and P atoms. This substitution modulated the local coordination environment and electronegativity around the surface Co sites and formed a new polar O–Co–P active site for optimizing the activation kinetics of ammonia borane and water. This strategy based on bimolecular activation may create new avenues in the field of catalysis.
Boosting Capacitive Deionization Performance of Commercial Carbon Fibers Cloth via Structural Regulation Based on Catalytic‐Etching Effect
Authors: Zhang Chunjie , Wang Dong , Wang Zhen , Zhang Guangshuai , Liu Zhichao , Wu Jie , Hu Jin , Wen Guangwu
Published: September 2021

Monolithic carbon electrodes with robust mechanical integrity and porous architecture are highly desired for capacitive deionization but remain challenging. Owing to the excellent mechanical strength and electroconductivity, commercial carbon fibers cloth demonstrates great potential as high‐performance electrodes for ions storage. Despite this, its direct application on capacitive deionization is rarely reported in terms of limited pore structure and natural hydrophobicity. Herein, a powerful metal‐organic framework‐engaged structural regulation strategy is developed to boost the desalination properties of carbon fibers. The obtained porous carbon fibers features hierarchical porous structure and hydrophilic surface providing abundant ions‐accessible sites, and continuous graphitized carbon core ensuring rapid electrons transport. The catalytic‐etching mechanism involving oxidation of Co and subsequent carbonthermal reduction is proposed and highly relies on annealing temperature and holding time. When directly evaluated as a current collector‐free capacitive deionization electrode, the porous carbon fibers demonstrates much superior desalination capability than pristine carbon fibers, and remarkable cyclic stability up to 20 h with negligible degeneration. Particularly, the PCF‐1000 showcases the highest areal salt adsorption capacity of 0.037 mg cm−2 among carbon microfibers. Moreover, monolithic porous carbon fibers‐carbon nanotubes with increased active sites and good structural integrity by in‐situ growth of carbon nanotubes are further fabricated to enhance the desalination performance (0.051 mg cm−2). This work demonstrates the great potential of carbon fibers in constructing high‐efficient and robust monolithic electrode for capacitive deionization.
Unveiling the Underlying Mechanism of Transition Metal Atoms Anchored Square Tetracyanoquinodimethane Monolayers as Electrocatalysts for N2 Fixation
Authors: Lv Shengyao , Huang Chunxiang , Li Guoliang , Yang Liming
Published: September 2021

We for the first time systematically studied the structures and electrochemical nitrogen reduction reaction properties of two‐dimensional single transition‐metal anchored square tetracyanoquinodimethane monolayers (labeled as: TM‐sTCNQ, TM = 3d, 4d, 5d series transition metals) by employing density functional theory method. Through high‐throughput screenings and full reaction path researches, two promising electrochemical nitrogen reduction reaction catalysts Nb‐sTCNQ and Mo‐sTCNQ have been obtained. The nitrogen reduction reaction onset potential on Nb‐sTCNQ is as low as −0.48 V. Furthermore, the Nb‐sTCNQ catalyst can quickly desorb NH3 produced with a free energy of 0.65 eV, giving Nb‐sTCNQ excellent catalytic cycle performance. The high catalytic activity of the two materials might be attributed to the effective charge transfer between the active center and adsorbed N2, which enables the active center to adsorb and activate inert N2 molecules well, and the reduction processes require small energy input (i.e., the maximum free energy changes are small). This work provides insights for finding highly efficient, stable, and low‐cost nitrogen reduction reaction electrocatalysts. We hope our results can promote further experimental and theoretical research of this field.
Structure and Reactivity of NO/NO+/NO−Pincer and Porphyrin Complexes
Authors: Gallego Cecilia Mariel , Mazzeo Agostina , Gaviglio Carina , Pellegrino Juan , Doctorovich Fabio
Published: September 2021

This review covers recent progress in the field of nitrosyl pincer and porphyrinate complexes, and how their reactivity depends on the redox state of the NO ligand. Synthetic methods, and the most significant structural information, spectroelectrochemical studies, and different reactivities of nitrosyl pincer complexes are presented. These include selective activation and functionalization of carbon‐halogen bonds, catalysis for a variety of specific organic reactions, mediation of NO disproportionation and reversible coordination of solvents and weakly‐coordinating anions. Regarding the porphyrinate complexes, the focus is on biorelevant nitroxyl (NO−/HNO) complexes, discussing pioneering studies along with preparation and common characterization methods. Their relative stability in different conditions is compared, and possible decomposition mechanisms are discussed in terms of their ability to act as biomimetic models for enzymatic systems.
Some Surprising Transformations of Colchicone and Other Colchicine‐Derived Tropolones
Authors: Stein Andreas , Hilken née Thomopoulou Persefoni , Schulte Tim , Neudörfl Jörg , Breugst Martin , Schmalz Hans‐Günther
Published: September 2021

The alkaloid colchicine represents a prominent lead structure for the development of tubulin‐binding chemotherapeutics. In the course of explorative research into semi‐synthetic colchicinoids we stumbled upon a number of unexpected and mechanistically surprising transformations which reflect the very particular reactivity of the tropolone ether unit and its interplay with adjacent functional groups. Examples are the selective C‐8‐methylation of colchicone upon reaction with the Wittig reagent triphenylphosphonium methylide, the AlMe3‐mediated isomerization of colchicone to a tetracyclic lactone, and the cyanide‐induced reaction of the colchicol‐derived mesylate to a rearranged and ring B‐defunctionalized cyano‐allo‐colchicinoid. Finally, the fragmenting rearrangement of a tetracyclic colchicinoid with BF3⋅OEt2 in the presence of vinyl‐MgBr afforded a tropolonyl difluoroborate under concomitant transfer of an O‐methyl group from ring C to ring A.
Auditory change‐related cortical response is associated with hypervigilance to pain in healthy volunteers
Authors: Otsuru Naofumi , Ogawa Mayu , Yokota Hirotake , Miyaguchi Shota , Kojima Sho , Saito Kei , Inukai Yasuto , Onishi Hideaki
Published: September 2021

Background

Patients with chronic pain exhibit hypervigilance (heightened responsiveness to stimuli) to innocuous auditory stimuli as well as noxious stimuli. “Generalized hypervigilance” suggests that individuals who show heightened responsiveness to one sensory system also show hypervigilance to other modalities. However, research exploring the existence of generalized hypervigilance in healthy subjects is limited.

Methods

We investigated whether hypervigilance to pain is associated with auditory stimuli in healthy subjects using the pain vigilance and awareness questionnaire (PVAQ) and auditory change‐related cortical responses (ACRs). ACRs are thought to reflect a change detection system, based on preceding sensory memory. We recorded ACRs under conditions that varied in terms of the accumulation of sensory memory as follows: short‐ACR, with short preceding continuous stimuli and long‐ACR, with long preceding continuous stimuli. In addition, the attention to pain (PVAQ‐AP) and attention to changes in pain (PVAQ‐ACP) subscales were evaluated.

Results

Amplitudes of long‐ACR showed significant positive correlations with PVAQ‐ACP, whereas those of short‐ACR did not show any significant correlations.

Conclusions

Generalized hypervigilance may be observed even in healthy subjects. ACR may be a useful index to evaluate the hypervigilance state in the human brain.
Contemporary electrochemical sensing and affinity biosensing to assist traces metal ions determination in clinical samples
Authors: Campuzano Susana , Pedrero María , Yáñez‐Sedeño Paloma , Pingarrón José M.
Published: September 2021

The determination of metals in clinical samples is an important challenge since their levels are relevant to ensure personal exposure to safe environments, as well as to assist in the prevention and treatment of disease. The low concentrations of metal ions in clinical samples and their coexistence with other metals and/or molecules of diverse nature implies the need for sensitive and selective analytical methodologies, which can be provided by conventional techniques. However, most of these techniques do not satisfy other highly demanded requirements such as high sampling frequency, multiplexed ability, and in‐field analysis. In this context, the simplicity, speed of response, and compatibility with single or multiplexed point‐of‐care determinations have led to the successful incursion of electrochemical (bio)sensing into the clinical field for the determination of these analytes. Electrochemical (bio)devices have come on strong by exploiting and combining the unique attributes provided by electrochemical techniques (primarily voltammetry but also giving way to impedimetry in electrochemical affinity biosensing), electrode materials (Hg, Bi, Sb, Au, GCE, CPE, ITO, FTO), and substrates (conventional, screen‐printed, flexible, paper, wearable or tattoo‐type), suitable modifiers (nanomaterials, polymers, mesoporous films), bioreceptors (aptamers, peptides, biomolecular switches, DNAzymes, and DNA molecules), and nucleic acid amplification strategies (rolling circle and exonucleases‐assisted target recycling). Therefore, the purpose of this review is to provide a bird's eye view of the state of the art, discussing the remarkable opportunities and potentialities demonstrated in the last decade by electrochemical sensors and electrochemical affinity biosensors for the analysis of metal ions in challenging clinical samples and forecasting future directions in this exciting field.
A Feasibility Study of an on‐Grid PV/Wind/Battery/Diesel for Residential Buildings Under Various Climates in Cameroon
Authors: Hermann Djeudjo Temene , Donatien Njomo , Armel Talla Konchou Franck , René Tchinda
Published: September 2021

Hybrid renewable energy system (HRES) appears to be a very good solution to solve the problem energy deficit encountered in developing countries such as Cameroon. This article presents an optimal design and selection made on four grid‐connected hybrid renewable energy systems or configurations with criteria loss of power supply probability (LPSP), cost of energy (COE), net present cost (NPC), total emission (TE), and the grid contribution factor (GCF) using Sine–Cosine Algorithm (SCA) and a proposed hybrid Sine–Cosine Algorithm–Particle Swarm Optimization (SCAPSO); for three residential building types in four climatic zones of Cameroon. The five cities that are chosen from the four climatic zones of the country include Maroua, Garoua, Bamenda, Kribi, and Abong‐Mbang. The selection of the energy configurations is done using hybrid Multi‐Criteria Decision‐Making known as Analytic Hierarchy Process‐Evaluation Based on Distance from Average Solution methods (AHP‐EDAS). Configuration 1 (photovoltaic/wind/battery/diesel generator/grid) appears to be the best configuration in the cities of Maroua, Garoua, Bamenda, and Kribi. Configuration 4 (photovoltaic/battery/grid) is the best for the city of Abong‐Mbang. All the best configurations appear to have lesser values of COE compared with what is usually paid to the main grid; the GCF values are also very low.