bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of estimation methods adjusting for selection bias in adaptive enrichment designs with time‐to‐event endpoints
Authors: Di Stefano Fulvio , Pannaux Matthieu , Correges Anne , Galtier Stephanie , Robert Veronique , Saint‐Hilary Gaelle
Published: January 2022

Adaptive enrichment designs in clinical trials have been developed to enhance drug developments. They permit, at interim analyses during the trial, to select the sub‐populations that benefits the most from the treatment. Because of this selection, the naive maximum likelihood estimation of the treatment effect, commonly used in classical randomized controlled trials, is biased. In the literature, several methods have been proposed to obtain a better estimation of the treatments' effects in such contexts. To date, most of the works have focused on normally distributed endpoints, and some estimators have been proposed for time‐to‐event endpoints but they have not all been compared side‐by‐side. In this work, we conduct an extensive simulation study, inspired by a real case‐study in heart failure, to compare the maximum‐likelihood estimator (MLE) with an unbiased estimator, shrinkage estimators, and bias‐adjusted estimators for the estimation of the treatment effect with time‐to‐event data. The performances of the estimators are evaluated in terms of bias, variance, and mean squared error. Based on the results, along with the MLE, we recommend to provide the unbiased estimator and the single‐iteration bias‐adjusted estimator: the former completely eradicates the selection bias, but is highly variable with respect to a naive estimator; the latter is less biased than the MLE estimator and only slightly more variable.
Landmarking 2.0: Bridging the gap between joint models and landmarking
Authors: Putter Hein , van Houwelingen Hans C.
Published: January 2022

The problem of dynamic prediction with time‐dependent covariates, given by biomarkers, repeatedly measured over time, has received much attention over the last decades. Two contrasting approaches have become in widespread use. The first is joint modeling, which attempts to jointly model the longitudinal markers and the event time. The second is landmarking, a more pragmatic approach that avoids modeling the marker process. Landmarking has been shown to be less efficient than correctly specified joint models in simulation studies, when data are generated from the joint model. When the mean model is misspecified, however, simulation has shown that joint models may be inferior to landmarking. The objective of this article is to develop methods that improve the predictive accuracy of landmarking, while retaining its relative simplicity and robustness. We start by fitting a working longitudinal model for the biomarker, including a temporal correlation structure. Based on that model, we derive a predictable time‐dependent process representing the expected value of the biomarker after the landmark time, and we fit a time‐dependent Cox model based on the predictable time‐dependent covariate. Dynamic predictions based on this approach for new patients can be obtained by first deriving the expected values of the biomarker, given the measured values before the landmark time point, and then calculating the predicted probabilities based on the time‐dependent Cox model. We illustrate the approach in predicting overall survival in liver cirrhosis patients based on prothrombin index.
TITE‐BOIN12: A Bayesian phase I/II trial design to find the optimal biological dose with late‐onset toxicity and efficacy
Authors: Zhou Yanhong , Lin Ruitao , Lee J. Jack , Li Daniel , Wang Li , Li Ruobing , Yuan Ying
Published: January 2022

In the era of immunotherapies and targeted therapies, the focus of early phase clinical trials has shifted from finding the maximum tolerated dose to identifying the optimal biological dose (OBD), which maximizes the toxicity‐efficacy trade‐off. One major impediment to using adaptive designs to find OBD is that efficacy or/and toxicity are often late‐onset, hampering the designs' real‐time decision rules for treating new patients. To address this issue, we propose the model‐assisted TITE‐BOIN12 design to find OBD with late‐onset toxicity and efficacy. As an extension of the BOIN12 design, the TITE‐BOIN12 design also uses utility to quantify the toxicity‐efficacy trade‐off. We consider two approaches, Bayesian data augmentation and an approximated likelihood method, to enable real‐time decision making when some patients' toxicity and efficacy outcomes are pending. Extensive simulations show that, compared to some existing designs, TITE‐BOIN12 significantly shortens the trial duration while having comparable or higher accuracy to identify OBD and a lower risk of overdosing patients. To facilitate the use of the TITE‐BOIN12 design, we develop a user‐friendly software freely available at
http://www.trialdesign.org.
Split and combine simulation extrapolation algorithm to correct geocoding coarsening of built environment exposures
Authors: Won Jung Y. , Sanchez‐Vaznaugh Emma V. , Zhai Yuqi , Sánchez Brisa N.
Published: January 2022

A major challenge in studies relating built environment features to health is measurement error in exposure due to geocoding errors. Faulty geocodes in built environment data introduce errors to exposure assessments that may induce bias in the corresponding health effect estimates. In this study, we examine the distribution of the measurement error in measures constructed from point‐referenced exposures, quantify the extent of bias in exposure effect estimates due to geocode coarsening, and extend the simulation extrapolation (SIMEX) method to correct the bias. The motivating example focuses on the association between children's body mass index and exposure to the junk food environment, represented by the number of junk food outlets within a buffer area near their schools. We show, algebraically and through simulation studies, that coarsening of food outlet coordinates results in exposure measurement errors that have heterogeneous variance and nonzero mean, and that the resulting bias in the health effect can be away from the null. The proposed SC‐SIMEX procedure accommodates the nonstandard measurement error distribution, without requiring external data, and provides the best bias correction compared to other SIMEX approaches.
Insights into Antiperovskite Ni3In1‐xCuxN Multi‐Crystalline Nanoplates and Bulk Cubic Particles as Efficient Electrocatalysts on Hydrogen Evolution Reaction
Authors: Su Hang , Tang Yanqun , Shen Haoming , Zhang Hao , Guo Penghui , Gao Lei , Zhao Xin , Xu Xiaoshan , Li Suqin , Zou Ruqiang
Published: January 2022

Intrinsic hydrogen evolution reaction (HER) activity and the mechanism of antiperovskite Ni3In1‐xCuxN bulk cubic particles and multi‐crystalline nanoplates are thoroughly investigated. Stoichiometric Ni3In0.6Cu0.4N reaches the best HER performance, with an overpotential of 102 mV in its multi‐crystalline nanoplates obtained from the LDH‐derived method, and 143 mV in its bulk cubic particles from the citric method. DFT calculation reveals that Ni‐In or Ni‐Cu paired on the (100) plane serve as primary active sites. The Ni‐Cu pair exhibits stronger OH* and H* affinity that correspondingly reduce OH* and H* adsorption free energy. Introducing specific amounts of the Ni‐Cu pair, that is In:Cu = 0.6:0.4 in Ni3In0.6Cu0.4N, can optimize OH* and H* adsorption free energy to facilitate water dissociation in the HER process, while avoiding OH* adsorption getting too strong to block active sites. Besides, Ni3In0.6Cu0.4N turns the water adsorption step spontaneous, which may be attributed to the shifted d‐band center and polarizing effect from surface In‐Cu charge distribution. This work expands the scope for material design in an antiperovskite system by tailoring the chemical components and morphology for optimal reaction free energy and performance.
Cation‐Dependent Hydrogel Template‐Activation Strategy: Constructing 3D Anode and High Specific Surface Cathode for Dual‐Carbon Potassium‐Ion Hybrid Capacitor
Authors: Pan Zhen , Qian Yong , Li Yang , Lin Ning , Qian Yitai
Published: January 2022

Here, a universal template‐activation strategy is proposed to prepare two different types of porous carbonaceous materials for potassium ion hybrid capacitor (PIHC) anode and cathode, which is realized by only changing the type of cation (Na+ and K+) in the polysilicic acid‐organic mixed hydrogel precursor originating from adding organic acid into Na2SiO3 and K2SiO3 solution, respectively. TG‐IR data demonstrate that K+ exhibits a stronger etching ability for activating carbonaceous materials during the annealing process. Accordingly, a 3D carbon anode obtained with the assistance of NaOH (NPC‐500) exhibits abundant edge‐N doping (8.14 at%), displaying a high K‐storage capacity of 314.1 mA h g‐1 at 0.2 A g‐1 and a capacity of 219.3 mA h g‐1 at 10 A g‐1 after 10000 cycles. A porous carbon particles cathode prepared in the presence of KOH (KCP‐800) shows a high specific surface area (1326.8 m2 g‐1), contributing to high PF6‐ (de)adsorb capacity of 103.0 mA h g‐1 at 1 A g‐1. Remarkably, the assembled NPC//KCP PIHC delivers a high energy density of 137.7 W h kg‐1 at a power density of 275.4 W kg‐1 even over 20 000 cycles.
Homologous Nitrogen‐Doped Hierarchical Carbon Architectures Enabling Compatible Anode and Cathode for Potassium‐Ion Hybrid Capacitors
Authors: Yi Yuyang , Zeng Zhihan , Lian Xueyu , Dou Shixue , Sun Jingyu
Published: January 2022

Potassium‐ion hybrid capacitors (PIHCs) have been considered as an emerging device to render grid‐scale energy storage. Nevertheless, the sluggish kinetics at the anode side and limited capacity output at the cathode side remain daunting challenges for the overall performances of PIHCs. Herein, an exquisite “homologous strategy” to devise multi‐dimensional N‐doped carbon nanopolyhedron@nanosheet anode and activated N‐doped hierarchical carbon cathode targeting high‐performance PIHCs is reported. The anode material harnessing a dual‐carbon structure and the cathode candidate affording a high specific surface area (2651 m2 g−1) act in concert with a concentrated ether‐based electrolyte, resulting in an excellent half cell performance. The related storage mechanism is systematically revealed by in situ electrokinetic characterizations. More encouragingly, the thus‐derived PIHC full cell demonstrates a favorable energy output (157 Wh kg−1), showing distinct advantages over the state‐of‐the‐art PIHC counterparts.
Synthesizing secure software development activities for linear and agile lifecycle models
Authors: Alenezi Mamdouh , Basit Hamid Abdul , Beg Maham Anwar , Shaukat Muhammad Saad
Published: January 2022

Application security is an important concern, and security activities to support software development lifecycle processes, such as specification, design, implementation, and testing are increasingly in need. Despite the plethora of knowledge available for secure software development in online and books, software systems are seldom secure as developers lack security knowledge. The primary reason for this paradox is the diversity and overwhelming nature of the available security knowledge. In this article, we propose to synthesize the well‐known secure software development practices for both linear and agile lifecycle models. Using theMediaWikiplatform, we make this knowledge available to software developers and designers from a single source.
Transfer length of corroded wires in prestressed concrete members
Authors: Anaya Pablo , Martín‐Pérez Beatriz , Rodríguez Jesús , Andrade Carmen
Published: January 2022

Bond is an essential property that guarantees the composite action in prestressed concrete (PC) members. This bond may be degraded due to different reasons, corrosion‐induced damage being one of the most frequent ones. The transfer length is the key indicator that describes the bond properties between prestressing steel and concrete. The analysis and design of PC members with prestressing wires require a realistic assessment of the bond transfer length. This paper presents an analytical study of the influence of the governing geometrical and mechanical variables on bond behavior in PC members undergoing steel corrosion. A model describing the deterioration of the transfer length due to corrosion, calibrated and verified through experimental tests, is proposed along with simplified expressions for the assessment of transfer lengths in PC members with corroded wires.
SLC6A3 gene polymorphisms are associated with striatal dopamine transporter changes after glucose loading
Authors: Pak Kyoungjune , Seo Seongho , Kim Keunyoung , Lee Myung Jun , Kim In Joo
Published: January 2022

We investigated the association between SLC6A3 gene polymorphisms and changes in dopamine transporter (DAT) availability after glucose loading in humans. An intravenous injection of 18F‐FP‐CIT was administered after infusion of glucose or placebo, and the emission data were acquired over 90 min in 38 healthy male participants. DAT availability expressed in terms of binding potential (BPND) was recorded. The 40‐bp variable number of tandem repeats (VNTR) in the 3′ untranslated region and two single nucleotide polymorphisms (SNPs), rs2652511 and rs2937639, in the SLC6A3 gene were genotyped. Among the 38 participants, those with a VNTR other than 10R/10R (n = 7) were excluded. The alleles of the two SNPs (rs2652511 and rs2937639) appeared to be inherited together in two fixed combinations (C–G or T–A) in 29 of 31 individuals. The BPND in the ventral striatum (VST), caudate nucleus, and putamen was not significantly different after glucose or placebo loading according to genotype. However, BPNDs from the caudate nucleus and putamen of all participants with rs2652511 CT/rs2937639 AG (n = 6) were higher after glucose loading. In conclusion, the SLC6A3 gene polymorphism is associated with the changes in DAT availability after glucose loading. DAT availability after glucose or placebo loading in the VST, caudate nucleus, and putamen did not differ according to the SLC6A3 genotype.
2,4‐dichlorophenoxyacetic acid induces ROS activation in NLRP3 inflammatory body‐induced autophagy disorder in microglia and the protective effect of Lycium barbarum polysaccharide
Authors: Zhou Jian , Wang Faxuan , Jia Leina , Chai Ru , Wang Hengquan , Wang Xiaolan , Li Jiangping , Wang Kai , Zhang Pengju , Yang Huifang
Published: January 2022

The pesticide 2,4‐dichlorophenoxyacetic acid (2,4‐D) exerts neurotoxic effects; however, its action mechanism remains unclear. Here, we used BV2 cells as a model and divided them into six groups: control group (serum‐free medium), lipopolysaccharide (LPS) (1 μg/mL), 2,4‐D (1.2 μmol/mL), Lycium barbarum polysaccharide (LBP; 300 μg/mL LBP), LPS (1 μg/mL) + LBP (300 μg/mL), and 2,4‐D (1.2 μmol/mL) + LBP (300 μg/mL) with dimethyl sulfoxide as the solvent. Our results showed that 2,4‐D treatment decreased superoxide dismutase and glutathione peroxidase activities and increased malondialdehyde content. The percentage of microglial activation (co‐expression of ionized calcium‐binding adaptor protein‐1 + CD68) in the LPS and 2,4‐D groups and the levels of tumor necrosis factor alpha, interleukin (IL) 1 beta, IL‐6, and IL‐18 in the cell supernatant were increased. The protein and mRNA levels of Nod‐like receptor protein 3 (NLRP3), apoptosis‐associated speck‐like protein, caspase‐1, IL‐1β, IL‐18, and p62 increased, whereas those of LC3II/I and Beclin‐1 decreased in the 2,4‐D group. The protein expression and mRNA levels of NLRP3, cleaved caspase‐1, IL‐1β, IL‐18, and p62 decreased significantly, whereas the protein expression and mRNA levels of LC3II/I and Beclin‐1 increased in small interfering RNA of NLRP3‐treated BV2 cells stimulated with 2,4‐D and LPS. In conclusion, 2,4‐D enhanced cell migration, promoted oxidative stress, induced excessive release of mitochondrial reactive oxygen species, promoted microglial cell activation, released inflammatory factors, activated NLRP3 inflammasomes, and inhibited autophagy. Meanwhile, LBP reduced inflammation and the release of mitochondrial reactive oxygen species, inhibited NLRP3 inflammasome activation, and regulated autophagy, thereby playing a neuroprotective role.
Norethindrone alters growth, sex differentiation and gene expression in marine medaka (Oryzias melastigma)
Authors: Dong Zhongdian , Chen Yuebi , Li Xueyou , Zhang Ning , Guo Yusong , Liang Yan‐Qiu , Wang Zhongduo
Published: January 2022

Norethindrone (NET) is a widely used synthetic progestin, which appears in water environments and threatens aquatic organisms. In this study, marine medaka (Oryzias melastigma) larvae were exposed to 7.6 and 80.1 ng/L NET for 190 days. The effects of NET on growth, sex differentiation, gonad histology and transcriptional expression profiles of hypothalamic‐pituitary‐gonadal (HPG) axis‐related genes were determined. The results showed that exposure to 80.1 ng/L NET caused an all‐male marine medaka population and significantly decreased the growth of males. Exposure to 7.6 ng/L NET increased the ratio of males/females in the marine medaka population, decreased the growth of males and delayed the ovary maturation in females. However, the sperm maturation was accelerated by 7.6 or 80.1 ng/L NET. In females, the transcription levels of cytochrome P450 aromatase (cyp19a1a) and progesterone receptor (pgr) in ovaries, glucocorticoid receptor (gr) and vitellogenin (vtg) in livers were suppressed after exposure to 7.6 ng/L NET, which may cause delayed ovary maturation. In males, NET significantly decreased the transcription levels of follicle stimulating hormone β (fshβ) and Luteinizing hormone β (lhβ)in the brain, Estrogen receptor β (erβ)，gr and pgr in the liver, and vitellogenin receptor (vtgr) in the testes, while NET of 80.1 ng/L led to a significant up‐regulation of steroidogenic acute regulatory protein (star) in the testes of males. These results showed that NET could influence growth, sex differentiation and gonadal maturation and significantly alter the transcriptional expression levels of HPG axis‐related genes.
Advances in nanoparticle‐based lateral flow immunoassay for point‐of‐care testing
Authors: Lou Doudou , Fan Lin , Jiang Tao , Zhang Yu
Published: January 2022

As a representative technology for point‐of‐care testing (POCT), lateral flow immunoassay (LFIA) has been broadly used to detect analytes in many fields. However, its clinical application is severely limited by the unsatisfactory sensitivity, which makes it difficult to obtain accurate results when detecting biomarkers of trace levels, especially in complex matrices. Nanoparticles have been introduced into LFIA for years and become an indispensable part, acting not only as carriers that load and enrich biomolecules, such as antibodies and dyes, but also a miniature platform applied for creative design and construction of nanoprobes. Due to the unique properties at the nanoscale, including the mimetic enzyme activity, the characteristic plasma resonance spectrum and so on, nanomaterials exhibit great potential in the development of novel LFIA and high‐sensitivity detection.
Modulating the blood–brain tumor barrier for improving drug delivery efficiency and efficacy
Authors: Song Yujun , Hu Chuan , Fu Yao , Gao Huile
Published: January 2022

The blood–brain barrier (BBB) is a highly regulated and efficient barrier that controls the mass transfer between blood and brain, severely limits brain penetration of systemically administered therapeutics. During the onset and progression of brain tumors, BBB alters, and the blood–brain tumor barrier (BBTB) forms. Though BBTB differs from BBB in certain aspects, such as neuronal connections and aberrant pericyte distribution, it retains critical aspects of BBB. Hence, one major challenge in the development of therapeutics for brain tumor is to achieve sufficient BBTB penetration thus improving the efficiency of drug delivery to the tumor site. In this review, we summarize the strategies that can overcome BBTB and improve BBTB penetration efficiency from the perspectives of regulating BBTB structure and transport processes.
Novel gas‐based nanomedicines for cancer therapy
Authors: Yao Xianxian , Yang Binru , Xu Jian , He Qianjun , Yang Wuli
Published: January 2022

Gas therapy, an emerging cancer treatment method of inflammation‐related diseases, has recently received substantial attention. The rapid advances in nanomedicine and nanotechnology have made gas precision treatment possible through tumor targeted delivery and controlled release of therapeutic agents. Single therapeutic is often inevitably accompanied with limited therapy efficacy. Gas therapy combined with other treatment methods can sensitize different therapy modes to augment cancer therapy. Understanding the mechanism through which gas enhances other therapeutic modalities will enable the design of reasonable strategies for clinical cancer therapy. In this review, we summarize novel gas‐based nanomedicines, focusing on gas‐based nanomedicine carriers, along with the release of gas molecules and the mechanisms of gas enhanced therapy. We describe the design of novel gas‐releasing nanoplatforms and the underlying synergistic mechanisms against cancer. Moreover, we describe the current challenges and outlook for future prospects in novel gas‐based nanomedicines for gas therapy in cancer.
Advanced techniques for gene heterogeneity research: Single‐cell sequencing and on‐chip gene analysis systems
Authors: Dong Zaizai , Wang Yu , Yin Dedong , Hang Xinxin , Pu Lei , Zhang Jianfu , Geng Jia , Chang Lingqian
Published: January 2022

Gene heterogeneity leads to the differences in cellular behaviors in a wide range, such as tumor drug‐resistant mutation, epithelial‐mesenchymal transition, and migration, posing significant challenges to the development of biomedicine. Traditional gene analysis methods, such as polymerase chain reaction, employ a mass of cells as the gene source, resulting in that the gene properties from a specific single cell are hidden in massive gene information. Recent decades have seen the emerging single‐cell gene analysis techniques with their unprecedented opportunities to study gene heterogeneity with high precision and high throughput. In this review, we summarized the state‐of‐the‐art techniques for single‐cell sequencing and on‐chip gene analysis systems. The principles of each technique are introduced in detail, with the focus on the application scenarios in gene heterogeneity research. Looking forward, we also introduced the challenges in current technologies and point out the future direction for facilitating the technical improvement and clinical applications of single‐cell gene analysis techniques.
A case of leukaemia cutis in a dog with T‐cell chronic lymphocytic leukaemia
Authors: Bae Hyeona , Yoon Ji‐Seon , Choi Eulsoo , Kim Sang‐Hyun , Jung Dong‐In , Park Jinho , Kim Sang‐Ki , Kim Dae Young , Yu DoHyeon
Published: January 2022

Leukaemia cutis (LC) is the infiltration of neoplastic leukocytes into the skin, characterised by haemorrhagic papules, nodules, and plaques. LC has been reported in human leukaemia patients, but it is extremely rare in dogs. A 13‐year‐old spayed female Golden Retriever that was previously diagnosed with chronic lymphocytic leukaemia was managed with chlorambucil (20 mg/m2 orally, every 2 weeks) and prednisolone (2 mg/kg orally, every other day) for 8 months; however, immunosuppression was temporarily discontinued because of a bacterial urinary tract infection. Cutaneous signs, including multifocal ecchymosis and white plaques, appeared 1 month after cessation of chemotherapy. Histopathological examination revealed small‐ to intermediate‐sized lymphocytes with mild atypia in a perivascular to interstitial pattern within the superficial dermis. The bands of atypical cells within the superficial dermis were strongly and extensively positive for CD3 on immunohistochemistry. Polymerase chain reaction analysis of the biopsied skin revealed clonal rearrangement of the T‐cell receptor gamma locus gene. Given the evidence of clinical signs, peripheral immunophenotyping, histopathology, immunohistochemistry, and clonal gene arrangement, LC was diagnosed. The lesions disappeared when chemotherapy was restarted but were occasionally observed when chemotherapy was stopped. To the authors’ best knowledge, this is the first case report of LC in a dog.
Synergistic effect of avidin/biotin system with biofunctionalized graphene oxide based nanocarrier in targeted co‐delivery of hydrophobic anticancer drug SN‐38
Authors: Karki Neha , Tiwari Himani , Matiyani Monika , Bal Rajaram , Pal Mintu , Sahoo Nanda Gopal
Published: January 2022

Co‐delivery of chemotherapeutic drugs with protein (avidin) within a solitary nanocarrier system has emerged as a promising combination therapy approach for treating cancers owing to their synergistic effect. In this study, we developed a potential nanocarrier by using graphene oxide (GO), activated folic acid (FA), polyethylene glycol (PEG), and TiO2 nanoparticles. PEG was introduced to enhance the nanocarrier's water solubility and biocompatibility. Further the synthesized primary nanocarrier that is, GO–FA–PEG–TiO2 employed with avidin‐biotin (Avi/Bio) system and synthesized more efficient nanocarrier that is, GO–FA–PEG–TiO2–Avi/Bio to enhance potential anti‐tumor activity and targeted co‐delivery of anticancer drug, SN‐38. The morphological analysis of nanocarrier GO–FA–PEG–TiO2–Avi/Bio was confirmed by basic characterization techniques including RAMAN, Fourier transforms infrared, Thermo gravimetric Analyzer, and Field Emission Scanning Electron Microscopy. The loading capacity of SN‐38 revealed that the nanocarrier integrated with Avi/Bio complex possessed higher adsorption capability than nanocarrier without Avi/Bio system. Furthermore, GO–FA–PEG–TiO2–Avi/Bio showed pH‐responsive behavior of releasing SN‐38. In‐vitro experiments confirmed sustained release of the drug, with a better performance at physiological pH (7.4) than at acidic pH (5.0). The developed nanocarrier with Avi/Bio complex showed higher cytotoxic effects than the GO–FA–PEG–TiO2 system. The cytotoxicity screening of GO–FA–PEG–TiO2–SN‐38 and GO–FA–PEG–TiO2–Avi/Bio–SN‐38 was conducted with MDA‐MB‐231 cells. Thus, GO–FA–PEG–TiO2–Avi/Bio system, when used as nanocarriers, showed high payload capacity to target cancer cells with increased cytotoxicity.
Carboxylated gums as additives in the production of interpenetrating hydrogel beads and slow release of glimepiride
Authors: Dhua Manabendra , Sen Kalyan Kumar , Maiti Sabyasachi
Published: January 2022

The properties of polysaccharide‐based hydrogels can be effectively modified by developing an interpenetrating polymer network (IPN) for the purpose of controlled drug delivery. This study aims to unearth the potential of a more viscous, highly carboxylated xanthan (CX) gum as an additive in the design of IPN hydrogel beads with carboxylated guar (CG) gum and control of glimepiride release in simulated gastrointestinal milieu. The carboxylated gums were characterized by infrared spectroscopy, degree of substitution, and viscosity. The incorporation of CX up to 75% into CG matrix did not alter the spherical morphology of the beads after drug loading and ensured ~69% drug entrapment efficiency. The CX as additive provided compatible environment for drug entrapment. Thermal and x‐ray analyses suggested amorphous dispersion of drug in the IPNs. Depending on the concentration of CX, IPN hydrogels demonstrated variable swelling and drug release rate in simulated gastrointestinal pH. It was noticed that at least 25% CX as an additive could be beneficial in controlling drug release rate from the IPNs. The weight percent of CX influenced the drug release mechanism. Hence, the inclusion of CX as an additive in CG matrix seemed to be a promising approach for controlled drug release and further evaluations in vivo.
Adaptation to transboundary climate risks in trade: Investigating actors and strategies for an emerging challenge
Authors: Bednar‐Friedl Birgit , Knittel Nina , Raich Joachim , Adams Kevin M.
Published: January 2022

There is growing recognition that international trade can transmit climate risks across borders, requiring new forms of and approaches to adaptation. This advanced review synthesizes knowledge on how, by whom and where adaptation actions can be taken in the agriculture and industrial sectors to reduce these transboundary climate risks (TCRs). We find a material difference in the literature on TCRs in agriculture as compared with industrial sectors. Operational and market risks, in particular reductions in food availability, dominate in agriculture, while supply chain and trade‐related risks are highlighted for industry. While the origin of the risk (source) is the primary target of adaptation to agricultural TCRs, the general governance structure, such as UNFCCC and WTO deliberations, are important targets in both sectors. Adaptation at the country of destination and along the trade network is of minor importance in both sectors. Regarding the type of adaptation option, agriculture heavily relies on trade policy, agricultural adaptation, and adaptation planning and coordination, while in industry knowledge creation, research and development, and risk management are seen as essential. Governments and the international community are identified as key actors, complemented by businesses and research as critical players in industry. Some measures, such as protectionist trade policies and irrigation, are controversial as they shift risks across countries and sectors, rather than reduce them. While more research is needed, this review shows that a critical mass of evidence on adaptation to TCRs is beginning to emerge, particularly underscoring the importance of international coordination mechanisms.

This article is categorized under:

Vulnerability and Adaptation to Climate Change > Institutions for Adaptation

Vulnerability and Adaptation to Climate Change > Multilevel and Transnational Climate Change Governance
Deep structural insights into RNA‐binding disordered protein regions
Authors: Zeke András , Schád Éva , Horváth Tamás , Abukhairan Rawan , Szabó Beáta , Tantos Agnes
Published: January 2022

Recent efforts to identify RNA binding proteins in various organisms and cellular contexts have yielded a large collection of proteins that are capable of RNA binding in the absence of conventional RNA recognition domains. Many of the recently identified RNA interaction motifs fall into intrinsically disordered protein regions (IDRs). While the recognition mode and specificity of globular RNA binding elements have been thoroughly investigated and described, much less is known about the way IDRs can recognize their RNA partners. Our aim was to summarize the current state of structural knowledge on the RNA binding modes of disordered protein regions and to propose a classification system based on their sequential and structural properties. Through a detailed structural analysis of the complexes that contain disordered protein regions binding to RNA, we found two major binding modes that represent different recognition strategies and, most likely, functions. We compared these examples with DNA binding disordered proteins and found key differences stemming from the nucleic acids as well as similar binding strategies, implying a broader substrate acceptance by these proteins. Due to the very limited number of known structures, we integrated molecular dynamics simulations in our study, whose results support the proposed structural preferences of specific RNA‐binding IDRs. To broaden the scope of our review, we included a brief analysis of RNA‐binding small molecules and compared their structural characteristics and RNA recognition strategies to the RNA‐binding IDRs.

This article is categorized under:

RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry

RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition

RNA Interactions with Proteins and Other Molecules > Small Molecule–RNA Interactions
Artificial incubation and hand‐rearing of Superb Bird‐of‐paradise(Lophorina superba)
Authors: Theule Jessica , Rimlinger David
Published: January 2022

Since first brought into zoos in 1964, the captive population of Superb Bird‐of‐paradise (Lophorina superba) has remained relatively small. Several decades of artificial incubation and hand‐rearing of this species at the Avian Propagation Center (APC) at the San Diego Zoo has allowed the population to increase and maintain some stability. Successful artificial incubation techniques lead to healthy neonates and allow females to reproductively recycle and produce more offspring in a season. Additionally, hand‐rearing methods have been refined over the years at APC and are shown here as a method that could be employed to help sustain other small populations of birds maintained in zoological institutions.
Introduction
Authors: Timmermans Arco , Brans Marleen
Published: January 2022

Scholars employed by universities not only do their basic academic work but also have a professional environment that may call for their knowledge or be targeted explicitly by scholars themselves. In this book the focus is entirely on such engagement by academic political scientists. What advisory activities and roles do they take? How do they see any work at the intersection of their university home basis and the social and political environment? How do they operate in the spheres where choices must be made about facts, evidence, and normative direction? What are driving factors for such engagement, or conversely for abstention? And how do background variables such as gender, age, and status of employment affect the views and activities of political scientists? These are the central questions in this book. They are contained in a large scale cross-national project on the Professionalization and Social Impact of European Political Science (ProSEPS), with scholars from 39 countries involved and organized under auspices of the European COST Association in the period 2017–2020.
Changing Policy Advisory Dynamics in the 2000s: The Advisory Roles of Political Scientists in Turkey
Authors: Bakir Caner , Bolukbasi H. Tolga
Published: January 2022

This chapter maps the changing features of the policy advisory system in Turkey and explores the policy advisory roles of Turkish political scientists in the 2000s. It situates Turkey’s statist policy advisory system in an environment of increasing centralization of executive power in a hybrid regime. In this system, government actors dictate the terms of engagement for key policy actors. They do so against the background of externalization, politicization, privatization, Europeanization and societalization of advice. In addition to case study material, the chapter relies on the ProSEPS survey. According to the survey findings, the typical political scientist in Turkey is a male opinionator, who gives generally informal face-to-face advice to mostly civil society organizations, think tanks and civil servants. This opinionator is an expert in international relations, comparative politics and political theory. Political scientists in Turkey’s advisory system do not differ markedly from their European colleagues in terms of their demographic characteristics, educational attainment, employment status, specialization subfields, channels they use and levels of governance they provide advice at. The chapter concludes by calling for further research on the advisory roles of political scientists in this hybrid regime.
Strategy of Data Collection and Analysis for Comparing Policy Advisory Roles
Authors: Brans Marleen , Timmermans Arco , Real-Dato José
Published: January 2022

This chapter presents the research design of the ProSEPS comparative project on advisory roles of political scientists. In order to operationalize the theoretical concepts on policy advice and policy advisory roles as introduced in Chap. 2, the project uses the questions included in a large scale comparative survey to European political scientists conducted under the ProSEPS COST Action in 2018 to assess whether and how they engage in advisory activities. Chap. 3 first presents details about the content, scope, and implementation of this survey. Second, it describes how survey questions are used to operationalize the four basic types of advisory roles analyzed in the book (pure academic, expert, opinionating scholar, and public intellectual). Finally, the chapter also presents some details about the sample of 12 countries analyzed in the book, including on gender, job status, sub-disciplinary orientation, and external positions of political scientists.
A Small Discipline, Scarce Publicity, and Compromised Outward Reach: The Advisory Roles of Political Scientists in France
Authors: Squevin Pierre , Aubin David
Published: January 2022

Although it has been developing and come through processes of institutionalization since WWII, French political science remains a small and rather marginalized discipline in search for visibility. Several tendencies work against the performance of a decisive advisory role from its part, especially the presence of an already solid and wide-ranging internal, in-house (state) expertise, which is still considered by many as a strong national asset. Consequently, it makes it hard for political scientists, as external academic actors, to exist in the eyes of decision-makers and achieve relevance. Nonetheless, driven by favourable attitudes towards an advisory and public engagement and the presence of facilitating conditions, we show that French political science infrequently manages to move in the policy advisory system. This chapter notably finds that political scientists might individually or collectively benefit from a participatory turn shaping the operation of advisory systems, that some level of boundary work takes place in relation with public administration, and that think tanks and sub-national actors’ reinforcement has opened opportunities for advice-giving and advice circulation. A case study about an important project of reform of the parliament illustrates how involvements from French political scientists in public debates and advisory activities might unfold and translate into practice.
Deepfake Detection Using Multiple Data Modalities
Authors: Hao Hanxiang , Bartusiak Emily R. , Güera David , Mas Montserrat Daniel , Baireddy Sriram , Xiang Ziyue , Yarlagadda Sri Kalyan , Shao Ruiting , Horváth János , Yang Justin , Zhu Fengqing , Delp Edward J.
Published: January 2022

Falsified media threatens key areas of our society, ranging from politics to journalism to economics. Simple and inexpensive tools available today enable easy, credible manipulations of multimedia assets. Some even utilize advanced artificial intelligence concepts to manipulate media, resulting in videos known as deepfakes. Social media platforms and their “echo chamber” effect propagate fabricated digital content at scale, sometimes with dire consequences in real-world situations. However, ensuring semantic consistency across falsified media assets of different modalities is still very challenging for current deepfake tools. Therefore, cross-modal analysis (e.g.,  video-based and audio-based analysis) provides forensic analysts an opportunity to identify inconsistencies with higher accuracy. In this chapter, we introduce several approaches to detect deepfakes. These approaches leverage different data modalities, including video and audio. We show that the presented methods achieve accurate detection for various large-scale datasets.
Detecting Soft-Biometric Privacy Enhancement
Authors: Rot Peter , Peer Peter , Štruc Vitomir
Published: January 2022

With the proliferation of facial analytics and automatic recognition technology that can automatically extract a broad range of attributes from facial images, so-calledsoft-biometric privacy-enhancing techniques have seen increased interest from the computer vision community recently. Such techniques aim to suppress information on certain soft-biometric attributes (e.g., age, gender, ethnicity) in facial images and make unsolicited processing of the facial data infeasible. However, because the level of privacy protection ensured by these methods depends to a significant extent on the fact that privacy-enhanced images are processed in the same way as non-tampered images (and not treated differently), it is critical to understand whether privacy-enhancing manipulations can be detected automatically. To explore this issue, we design a novel approach for the detection of privacy-enhanced images in this chapter and study its performance with facial images processed by three recent privacy models. The proposed detection approach is based on a dedicated attribute recovery procedure that first tries to restore suppressed soft-biometric information and based on the result of the restoration procedure then infers whether a given probe image is privacy enhanced or not. It exploits the fact that a selected attribute classifier generates different attribute predictions when applied to the privacy-enhanced and attribute-recovered facial images. Thispredictionmismatch (PREM) is, therefore, used as a measure of privacy enhancement. In extensive experiments with three popular face datasets we show that the proposed PREM model is able to accurately detect privacy enhancement in facial images despite the fact that the technique requires no supervision, i.e., no examples of privacy-enhanced images are needed for training.
Towards Mapping of Noise Impact
Authors: Marki Ferenc , Rucz Peter , van Oosten Nico , Ganić Emir , Legriffon Ingrid
Published: January 2022

Noise impact management goes hand in hand with the capability to predict the noise impact on exposed communities. Three tools to that purpose are presented in this chapter: the Noise Management Toolset (NMT), the Demo Virtual Community Tool (VCT) and Dynamic Noise Mapping. The NMT is a web-based tool giving stakeholders the opportunity to evaluate scenarios through not only noise exposure, but also noise impact, by introducing annoyance related metrics like the awakening index, with an easy-to-use interface. The VCT is the underlying research tool exploring and testing new indicators and options that might be of relevance to target audiences, such as land use planning information about location dependent activities or window insulation. The third approach, Dynamic Noise Mapping, adds the important aspect of population movement to classical noise mapping approaches where temporal changes of noise maps are tracked and included in noise exposure evaluation.
Balanced Approach to Aircraft Noise Management
Authors: Zaporozhets Oleksandr
Published: January 2022

ICAO Balanced Approach (BA) to aircraft noise management in airports is reviewed in accordance with historical and technological challenges. All four basic elements of the BA are subject to noise exposure control with dominant emphasis on reduction of noise at source and compatible land usage inside the noise zoning around the airports. Noise abatement procedures and flight restrictions are used at any airport due to its specific issues and should be implemented on a basis of cost–benefit analysis. Noise exposure reduction is an intermediate goal, a final goal—to reduce noise impact, which is mostly represented by population annoyance as a reaction to noise exposure, is discussed also.
Acetabular labral tear is associated with high pelvic incidence with or without femoroacetabular impingement morphology
Authors: Kwon Hyuck Min , Cho Byung-Woo , Kim Sungjun , Yang Ick-Hwan , Park Kwan Kyu , Son Nak-Hoon , Lee Woo-Suk
Published: January 2022

Purpose

The aim of this study was to investigate the association between pelvic sagittal parameters and acetabular labral tears.

Methods

Three-hundred and sixty-five patients (449 hips) who underwent magnetic resonance imaging (MRI) or magnetic resonance arthrogram (MRA) for hip pain were enrolled in this study. Pelvic sagittal parameters, including the pelvic incidence, pelvic tilt, and sacral slope, were measured with a standing lumbosacral lateral radiograph. All subjects were divided into two groups according to the presence or absence of radiologic acetabular labral tears and compared. Furthermore, the two groups were divided into subgroups according to whether femoroacetabular impingement (FAI) morphology was present or not and compared.

Results

Pelvic incidence was greater in the labral tear group than in the non-labral tear group (52.3° ± 8.2° versus 47.1° ± 6.8°, p < 0.001). After accounting for potentially confounding variables, we found that higher age (odds ratio 1.04, 95% confidence interval [CI] 1.02 to 1.06, p = 0.001), FAI (odds ratio 15.11, 95% CI 7.43 to 30.75, p < 0.001), and high pelvic incidence (odds ratio 1.13, 95% CI 1.09 to 1.17, p < 0.001) were independently associated with acetabular labral tear. When only the patients without FAI (308 hips) were divided into groups with and without acetabular labral tear, we found that higher age (odds ratio 1.03, 95% CI 1.01 to 1.06, p = 0.008) and high pelvic incidence (odds ratio 1.15, 95% CI 1.11 to 1.19, p < 0.001) were independently associated with acetabular labral tear.

Conclusion

Acetabular labral tear is associated with high pelvic incidence with or without FAI morphology.

Level of evidence

III.
Does direct farm marketing fulfill its promises? analyzing job satisfaction among direct-market farmers in Canada
Authors: Azima Stevens , Mundler Patrick
Published: January 2022

Short food supply chains have become the focus of considerable research in the last two decades. However, studies so far remain highly localized, and claims about the economic and social advantages of such channels for farmers are not backed by large-scale empirical evidence. Using a web survey of 613 direct-market farmers across Canada, this article explores the potential economic and social benefits that farmers derive from participating in short food supply chains. We used multivariate analysis to test whether a farmer’s degree of involvement in direct food channels is positively correlated with levels of work enjoyment, social satisfaction, and economic satisfaction. The results indicate that, overall, direct-market farmers report high levels of occupational satisfaction, although work-related challenges persist, such as stress, excessive workloads, and competition. Farmer participation in short food chains was also a positive predictor of work enjoyment and economic satisfaction, but not of social satisfaction, as measured by the share of total farm sales attributable to direct selling. Net annual farm revenue, the share of direct food sales involving a middleman, age, and gender also correlated with one or more dimensions of occupational satisfaction.
Relational Factors and HIV Testing Practices: Qualitative Insights from Urban Refugee Youth in Kampala, Uganda
Authors: Logie Carmen H. , Okumu Moses , Latif Maya , Parker Samantha , Hakiza Robert , Kibuuka Musoke Daniel , Mwima Simon , Batte Shamilah , Kyambadde Peter
Published: January 2022

Despite the global phenomenon of refugee urbanization, little is known of relational contexts that shape HIV testing among urban refugee youth. We explored perspectives, experiences, and preferences for social support in HIV testing among refugee youth aged 16–24 in Kampala, Uganda. We conducted five focus groups with refugee youth (n = 44) and five in-depth key informant interviews. Participant narratives signaled relational contexts shaping HIV testing included informal sources (intimate partners and family members) and formal sources (peer educators and professionals). There was heterogeneity in perspectives based on relationship dynamics. While some felt empowered to test with partners, others feared negative relationship consequences. Participant narratives reflected kinship ties that could facilitate testing with family, while others feared coercion and judgment. Peer support was widely accepted. Professional support was key for HIV testing as well as conflict-related trauma. Findings emphasize bonding and bridging social capital as salient components of enabling HIV testing environments.