bluuebunny/crossref_metadata_2025 huggingface dataset:
Injectable Immunotherapeutic Thermogel for Enhanced Immunotherapy Post Tumor Radiofrequency Ablation
Authors: Chen Muchao , Tan Yanjun , Hu Jiaying , Jiang Yanping , Wang Zixian , Liu Zhuang , Chen Qian
Published: November 2021

Tumor radiofrequency ablation (RFA) is a local and minimally invasive application using high temperature to induce coagulative necrosis of tumor, which has been commonly used in clinic. Although the tumor fragments generated by RFA can activate the host's immune system, it may be insufficient to inhibit cancer recurrence due to many factors such as the inefficient antigen presentation by dendritic cells (DCs). In this research, a convenient local administration strategy by blocking rho‐associated kinases (ROCK) is applied to amplify the immune responses triggered by RFA via promoting the phagocytosis capacity of DCs. Briefly, ROCK inhibitor, Y27632, is successfully dispersed in the amphiphilic copolymer poly(D,L‐lactide‐co‐glycolide)‐b‐poly(ethyleneglycol)‐b‐poly(D,L‐lactideco‐glycolide) (PLGA‐PEG‐PLGA) solution, which is sol at room temperature and forms hydrogel quickly at body temperature, obviously prolonging the retention of Y27632 after injection. Interestingly, in the melanoma tumor model, the generated tumor fragments after RFA treatment are swallowed by DCs and undergo reinforced antigen presentation process with the help of gradual released Y27632, further effectively activating T cell mediated anti‐tumor immune responses and significantly improving the therapeutic efficiency of RFA. Overall, such strategy remarkably prolongs the survival of mice after RFA treatment, showing great potential for clinical translation as an improvement strategy for RFA.
Properties and heavy metal leaching characteristics of leachate sludge‐derived biochar
Authors: Zhang Huiqin , Wang Zixian , Du Chenyu , Liu Wenlong , Gerson Andrea R. , Pi Kewu
Published: November 2021

Heavy metals and metalloids, in sludge and sediments, are environmental pollutants of concern with long‐term negative effects on human and ecological health. In this study, sludge from biological treatment of municipal waste leachate was pyrolyzed into leachate sludge‐derived biochar (LSDB) at 300°C to 900°C, comprising complex organic and inorganic (particularly heavy metals) species formed from heterogeneous chemical reactions. Based on different advanced material analyses, that is, Thermogravimetric Analysis (TGA), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), and X‐ray diffraction (XRD) analysis, this study revealed that mass loss and microstructural changes of LSDBs occurred primarily due to decomposition of volatiles, aromatic rings, carbonates, and hydroxides. The leaching behaviors of heavy metals from LSDBs were evaluated using the Synthetic Precipitation Leaching Procedure (SPLP). The final pH in SPLP increased from 7.5 to 12.5 with pyrolysis temperature. The pH increase favored the retention of heavy metals in the LSDBs due to the formation of low soluble precipitates at alkaline pH. The heavy metals and metalloids in the LSDBs were present as surface precipitates due to precipitation and cation exchange rather than surface complexation. The leaching contents of metals and metalloids, such as Cr, Cd, Ni, Pb, and As, were all below their respective maximum discharge standards for the first priority pollutants in China.
Innovation and Growth: Theory
Authors: Licandro Omar
Published: November 2021

This survey reviews the literature on firm dynamics, innovation and growth aiming to better understand the main channels through which innovation affects the performance of modern economies. Since innovations fundamentally diffuse through a complex process of firm and product creation and destruction, this survey concentrates on the recent literature on firm dynamics and innovation.
The QUEST III R&D Model
Authors: Roeger Werner , Varga Janos , in’t Veld Jan
Published: November 2021

This chapter provides a description of the QUEST III model, with a special emphasis on its innovation mechanisms, and offers an example of its application to the analysis of the impact of innovation policies in the EU. In particular, the results of the simulations of an ex-ante impact assessment of Horizon Europe Framework Programme 2021–2027 are presented and discussed.
The NEMESIS Macro-Econometric Model
Authors: Boitier Baptiste , Le Mouël Pierre , Ravet Julien , Zagamé Paul
Published: November 2021

This Chapter presents the NEMESIS macro-econometric model. This model has been used for several ex-ante and ex-post evaluations of the macroeconomic impact of EU R&I policies. After a general overview of the model, a thorough description of the representation of innovation in the model is provided. As an example of its workings, an application to the interim evaluation of the Horizon 2020 programme is also provided.
Mediation Analysis
Authors: Hair Joseph F. , Hult G. Tomas M. , Ringle Christian M. , Sarstedt Marko , Danks Nicholas P. , Ray Soumya
Published: November 2021

Mediation occurs when a third variable, referred to as a mediator construct, intervenes between two other directly related constructs. More precisely, a change in the exogenous construct results in a change of the mediator construct, which in turn changes the endogenous construct. The mediator analysis evaluates the factors related to the cause–effect relationship between an exogenous construct and an endogenous construct. In the simplest form, the analysis considers only one mediator construct, but the path model can also include multiple mediating constructs simultaneously, as well as moderated mediation. We illustrate mediation analysis in PLS-SEM by using the SEMinR package and the corporate reputation model as an example.
An Analysis of World Protests 2006–2020
Authors: Ortiz Isabel , Burke Sara , Berrada Mohamed , Saenz Cortés Hernán
Published: November 2021

This section of the book “World Protests: A Study of Key Protest Issues in the 21st Century” analyzes in-depth 2809 protests that occurred between 2006 and 2020 in 101 countries covering over 93% of the world population. This section focuses on: (i) major grievances and demands driving world protests, such as the failure of political representation/systems, anti-austerity, and for civil rights and global justice; (ii) who was demonstrating; (iii) what protest methods they used; (iv) who the protestors opposed; (v) what was achieved; and (vi) violence and repression in terms of arrests, injuries, and deaths.
Diagnostik und Therapie der Riesenzellarteriitis
Authors: Kraemer Markus , Becker Jana , Bley Thorsten Alexander , Steinbrecher Andreas , Minnerup Jens , Hellmich Bernhard
Published: November 2021

Die Riesenzellarteriitis (RZA) ist in der Altersgruppe der über 50-Jährigen die häufigste idiopathische systemische Vaskulitis. Die Erkrankung bedarf einer zeitnahen Diagnostik und Therapie, um schwere Komplikationen wie eine Erblindung oder einen Schlaganfall zu vermeiden. Die Rezidivneigung erfordert eine mehrjährige, zum Teil lebenslange Glukokortikoid(GC)-Therapie, was das Risiko GC-induzierter Langzeitnebenwirkungen erhöht. Daher wird bei der Mehrzahl der Patienten eine additive GC-einsparende Therapie empfohlen. Hierzu steht der Anti-IL-6-Rezeptor-Antikörper Tocilizumab in subkutaner Applikation als zugelassene Substanz zur Verfügung, alternativ kann Methotrexat (MTX) eingesetzt werden (off-label).
The influence of region of interest width in fetal 2D-speckle tracking echocardiography late in pregnancy
Authors: Omdal Tom Roar , Khan Umael , Ebbing Cathrine , Kessler Jörg , Karlsen Henriette Odland , Leirgul Elisabeth , Matre Knut , Greve Gottfried
Published: November 2021

Speckle tracking echocardiography is a promising method for assessment of myocardial function in fetal and neonatal hearts, but further studies are necessary to validate and optimize the settings for use in fetal cardiology. Previous studies have shown that the definition of the region of interest (ROI) affects strain values in adults. The aim of this study was to investigate how different widths of ROI influences measurements of four-chamber longitudinal systolic strain in fetuses late in pregnancy. Thirty-one singleton, healthy fetuses born to healthy mothers underwent an echocardiographic examination during gestational week 37. Speckle tracking was performed with two different settings for ROI width; the narrowest and second most narrow, provided both widths were assessed as suitable for the myocardial wall thickness of the fetus. We found an inverse correlation between the ROI width and the strain values. Four-chamber longitudinal strain changed from − 20.7 ± 3.6% to − 18.0 ± 4.4% (p < 0.001) with increasing ROI width. Further, strain decreased from the endocardium to the epicardium with multilayer measurements. Different widths of ROI influenced the strain measurements significantly in the fetal heart, comparable to what has been reported in adults. A standardization of the ROI setting could improve the interpretation, and reduce variability in fetal strain measurements.
Evaluating the Effect of Parent–Child Interactive Groups in a School-Based Parent Training Program: Parenting Behavior, Parenting Stress and Sense of Competence
Authors: Buchanan-Pascall Sarah , Melvin Glenn A. , Gordon Michael S. , Gray Kylie M.
Published: November 2021

The Exploring Together program is a group-based parent training program that comprises separate parent, child, and teacher components, and a combined parent–child interactive component. A cluster-randomized trial design was used to compare the Exploring Together program with (Exploring Together; ET) and without (Exploring Together-Adapted; ET-Adapted) the parent–child interactive component. One hundred and thirty-six parents and their children (aged 5–10 years) with externalizing and/or internalizing problems participated in the trial, recruited from primary schools. There was a significant reduction in negative parenting behavior across both treatment groups (ET and ET-Adapted) but no significant improvement in positive parenting behaviors. Parenting self-efficacy improved significantly across both treatment groups however there was no significant change in parenting satisfaction or parenting stress. There was no consistent evidence of superiority of one version of the Exploring Together program over the other. Further investigation regarding treatment dosage and mastery of parenting skills associated with the program is warranted.
Entanglement Swapping and Action at a Distance
Authors: Price Huw , Wharton Ken
Published: November 2021

A 2015 experiment by Hanson and Delft colleagues provided further confirmation that the quantum world violates the Bell inequalities, being the first Bell test to close two known experimental loopholes simultaneously. The experiment was also taken to provide new evidence of ‘spooky action at a distance’. Here we argue for caution about the latter claim. The Delft experiment relies on entanglement swapping, and our main claim is that this geometry introduces an additional loophole in the argument from violation of the Bell inequalities to action at a distance: the apparent action at a distance may be an artifact of ‘collider bias’. In the absence of retrocausality, the sensitivity of such experiments to this ‘Collider Loophole’ (CL) depends on the temporal relation between the entanglement swapping measurement C and the two measurements A and B between which we seek to infer a causal connection. CL looms large if the C is in the future of A and B, but not if C is in the past. The Delft experiment itself is the intermediate case, in which the separation is spacelike. We argue that this leaves it vulnerable to CL, unable to establish conclusively that it avoids it.
Lactic acid induces fibroblast growth factor 23 (FGF23) production in UMR106 osteoblast-like cells
Authors: Alber Jana , Föller Michael
Published: November 2021

Endocrine and paracrine fibroblast growth factor 23 (FGF23) is a protein predominantly produced by bone cells with strong impact on phosphate and vitamin D metabolism by targeting the kidney. Plasma FGF23 concentration early rises in kidney and cardiovascular diseases correlating with progression and outcome. Lactic acid is generated in anaerobic glycolysis. Lactic acidosis is the consequence of various physiological and pathological conditions and may be fatal. Since FGF23 production is stimulated by inflammation and lactic acid induces pro-inflammatory signaling, we investigated whether and how lactic acid influences FGF23. Experiments were performed in UMR106 osteoblast-like cells, Fgf23 mRNA levels estimated from quantitative real-time polymerase chain reaction, and FGF23 protein determined by enzyme-linked immunosorbent assay. Lactic acid dose-dependently induced Fgf23 gene expression and up-regulated FGF23 synthesis. Also, Na+-lactate as well as formic acid and acetic acid up-regulated Fgf23. The lactic acid effect was significantly attenuated by nuclear factor kappa-light-chain enhancer of activated B-cells (NFκB) inhibitors wogonin and withaferin A. Lactic acid induces FGF23 production, an effect at least in part mediated by NFκB. Lactic acidosis may, therefore, be paralleled by a surge in plasma FGF23.
Business as usual? Assessing the impact of the COVID-19 pandemic to research, development and innovation (RDI) activities of universities of applied sciences
Authors: Salomaa Maria , Caputo Andrea
Published: November 2021

Universities of applied sciences (UAS) have a strong mandate to carry out research, development and innovation (RDI) activities in collaboration with local stakeholders. Geographical proximity is one of the key factors for the creation and success of RDI activities because of the positive balance between costs and benefits of local knowledge transfer, but they also depend on the networks of individual staff members. This paper aims to explore how maintaining and developing purpose-built and individual RDI partnerships during the COVID-19 pandemic has been managed. An enhanced conceptual framework for assessing contextual dimensions of the RDI activities beyond academic entrepreneurship as business ventures has been developed. The paper focuses on a single case study drawing on semi-structured research interviews investigating how the swap to remote working have affected RDI activities at Tampere University of Applied Sciences, one of the biggest UAS in Finland with intense regional linkages. The contribution of the study is twofold; firstly, the paper introduces an expanded theoretical approach for assessing the external and internal factors having an impact on the RDI activities beyond academic entrepreneurship. Secondly, by testing the proposed framework, it shares insights and good practices derived from empirical evidence, namely binary data and semi-structured interviews revealing experiences of RDI personnel and project managers involved with different phases of RDI process, for optimising high-quality innovation support, knowledge transfer activities and co-creation of new knowledge in exceptional circumstances.
The Permian–Triassic boundary section at Baghuk Mountain, Central Iran: carbonate microfacies and depositional environment
Authors: Heuer Franziska , Leda Lucyna , Moradi-Salimi Hemen , Gliwa Jana , Hairapetian Vachik , Korn Dieter
Published: November 2021

Sections at Baghuk Mountain, 45 km NNW of Abadeh (Central Iran), have excellent exposures of fossiliferous marine Late Permian to Early Triassic sedimentary successions. Detailed bed-by-bed sampling enables the analysis of microfacies changes of three successive rock units across the Permian–Triassic boundary. The Late Permian Hambast Formation is mainly the result of biogenic carbonate production. Its carbonate microfacies is dominated by biogen-rich and bioturbated nodular limestones, indicating a well-oxygenated aphotic to dysphotic environment. The biogen-dominated carbonate factory in the Permian ceased simultaneously with the main mass extinction pulse, which is marked by a sharp contact between the Hambast-Formation and the overlaying Baghuk Member (= ‘Boundary Clay’). The clay and silt deposits of the Baghuk Member with some carbonate beds show only a few signs of bioturbation or relics of benthic communities. The Early Triassic Claraia Beds are characterised by a partly microbially induced carbonate production, which is indicated by frequent microbialite structures. The depositional environment does not provide evidence of large amplitude changes of sea level or subaerial exposure during the Permian–Triassic boundary interval. The deposition of the Baghuk Mountain sediments took place in a deep shelf environment, most of the time below the storm wave base.
Using nanotechnology to deliver biomolecules from nose to brain — peptides, proteins, monoclonal antibodies and RNA
Authors: Borrajo Mireya L. , Alonso María José
Published: November 2021

There is a growing number of biomolecules, including peptides, proteins, monoclonal antibodies and RNA, that could be potentially used for the treatment of central nervous system (CNS) diseases. However, the realization of their potential is being hampered by the extraordinary difficulties these complex biomolecules have to reach the brain in therapeutically meaningful amounts. Nose-to-brain (N-to-B) delivery is now being investigated as a potential option for the direct transport of biomolecules from the nasal cavity to different brain areas. Here, we discuss how different technological approaches enhance this N-to-B transport, with emphasis on those that have shown a potential for clinical translation. We also analyse how the physicochemical properties of nanocarriers and their modification with cell-penetrating peptides (CPPs) and targeting ligands affect their efficacy as N-to-B carriers for biomolecules.

Graphical abstract
Tolerability, course and follow-up of specific immunotherapy using a modified ultra-rush procedure in children and adolescents with insect venom allergy
Authors: Steiß Jens-Oliver , Weber Conrad , Becker Max
Published: November 2021

Background

Specific immunotherapy with insect venom (hymenoptera venom (HG)-AIT) is an effective and the only causal treatment for patients with systemic reactions due to IgE-mediated insect venom allergy. The present study investigated the quality of care after bee and wasp venom allergy, the tolerability of modified ultra-rush immunotherapy and the course after the conclusion of maintenance therapy in children and adolescents. Studies on the quality of life of children with insect venom allergy are scarce.

Methods

The efficacy, safety and tolerability of an ultra-rush protocol was analysed in 114 patients aged 4–17 years with insect venom allergy. After the end of HG-AIT, patients were contacted by questionnaire and asked to report on the quality of care as well as the course of insect venom allergy, including accidental stinging events. Quality of life was validated using the established questionnaire VQLQ‑d (Vespid Quality of Life Questionnaire), which is also used for bee venom allergy patients.

Results

Discontinuation of the initial therapy was not necessary in any patient. Side effects were mostly mild and did not require treatment. In 16 patients, a new sting reaction occurred during maintenance therapy, in another 15 patients a sting event was documented after cessation of HG-AIT. The intensity of the reaction to the accidental insect bite according to the severity classification after Ring and Messmer decreased from an average of 2.3 to 0.9 in these patients. This corresponds to a decrease of 61%. An emergency kit was carried by 70% of the patients, the expiry date of which, however, had already passed in almost 40% of the respondents. After the end of the therapy, most patients were not under any medical care or had never been to a check-up (92%). The evaluation of the VQLQ‑d showed a medium to low level of stress during or after therapy.

Discussion

Ultra-rush AIT in childhood and adolescence is safe, tolerable and effective. HG-AIT has a lasting positive effect on the health-related quality of life of patients. However, after the end of HG-AIT, there are deficits in the follow-up and care of the patients.
What role for regional organizations in goal-setting global governance? An analysis of the role of the European Union and ASEAN in the Sustainable Development Goals
Authors: Marx Axel , Pertiwi Sukmawani Bela , Depoorter Charline , Hoornick Michiel , Mursitama Tirta Nugraha , Otteburn Kari , Arnakim Lili Yulyadi
Published: November 2021

This paper analyzes the current role of regional organizations in the implementation of the 2030 Agenda for Sustainable Development and its 17 Sustainable Development Goals (SDGs). We construct a conceptual model and distinguish four potential roles that regional organizations can play in the implementation of the SDGs: the translating role, supporting role, coordinating role and monitoring role. We apply this framework to the European Union and ASEAN. The case studies are analyzed on the basis of document analysis from primary and secondary sources, voluntary national reviews and interviews. We show that regional organizations play different roles in the implementation of the SDGs.
Beyond dueling: roles of the type VI secretion system in microbiome modulation, pathogenesis and stress resistance
Authors: Lin Jinshui , Xu Lei , Yang Jianshe , Wang Zhuo , Shen Xihui
Published: November 2021

Bacteria inhabit diverse and dynamic environments, where nutrients may be limited and toxic chemicals can be prevalent. To adapt to these stressful conditions, bacteria have evolved specialized protein secretion systems, such as the type VI secretion system (T6SS) to facilitate their survival. As a molecular syringe, the T6SS expels various effectors into neighboring bacterial cells, eukaryotic cells, or the extracellular environment. These effectors improve the competitive fitness and environmental adaption of bacterial cells. Although primarily recognized as antibacterial weapons, recent studies have demonstrated that T6SSs have functions beyond interspecies competition. Here, we summarize recent research on the role of T6SSs in microbiome modulation, pathogenesis, and stress resistance.
‘Stretched But Not Snapped’: A Response to Russell and Serban on Retiring the ‘Westminster Model’
Authors: Flinders Matthew , Judge David , Rhodes R.A.W. , Vatter Adrian
Published: November 2021

This article engages with Meg Russell and Ruxandra Serban's (2021) argument that the Westminster model is ‘a concept stretched beyond repair’ that deserves ‘to be retired’. We examine the logic, theory and methods that led to such a powerful, potent and provocative argument. We suggest their approach may have inadvertently ‘muddied’ an already muddled concept. We assess the implications of ‘muddying’ for their conclusion that the Westminster model is, in essence, a dead concept in need of a decent funeral. We suggest the concept is ‘stretched but not snapped’ by developing a simple four-perspective broadening of the analytical lens. This approach aids understanding about what the concept covers, how it is operationalized and why it remains useful in comparative research.
Why it Is Indeed Time for the Westminster Model to Be Retired from Comparative Politics
Authors: Russell Meg , Serban Ruxandra
Published: November 2021

The term ‘Westminster model’ is frequently used by political scientists and practitioners. But our recent examination (Russell and Serban 2021), published in this journal, uncovered wide variation in how it is defined – demonstrating that it is more ‘muddle’ than ‘model’. This sparked a response article from Flinders et al. (2021), which we in turn respond to in this piece. We briefly revisit our initial research questions, methodology and findings, before reflecting on their analysis. We emphasize that, notwithstanding the critics’ negative tone, we and they agree on certain fundamentals. In particular on our original central point, that the ‘Westminster model’ is an ill-defined term with a long history, which mostly makes it unsuited to positivist comparative political science research. While the ‘Westminster model’ may have some valid vestigial uses, within the UK political system, or as an object of study for interpretivist political science, it does not provide a rigorous basis for case selection and comparative political science analysis.
Stratified Taylor–Couette flow: nonlinear dynamics
Authors: Lopez Juan M. , Marques Francisco
Published: November 2021

A series of experiments on stratified Taylor–Couette flow in short aspect ratio wide-gap annuli found an intriguing and not-well-understood dynamics: nonlinear coherent structures appearing and disappearing periodically, along with density layering reminiscent of staircase profiles. A detailed numerical study is presented of the nonlinear dynamics near onset of instability in this setting, which explains most of the characteristics found in the experiments. The simulations show that centrifugal instability of the boundary layer on the inner rotating cylinder produces jets of angular momentum forming Taylor cells that are compressed axially due to the strong stratification. These cells are not axisymmetric from the onset, but are in fact two sets of Taylor cells displaced axially that meet in localized azimuthal defect regions where the cells are patched together; the whole structure is a rotating wave with azimuthal wavenumber

$m=1$

. The presence of endwalls in this short aspect ratio annulus is critical for the understanding of the dynamics. Their impact cannot be accounted for in idealized axially periodic models. Another key ingredient is the role played by the symmetries of the system. Although the axial reflection symmetry is weakly broken by centrifugal buoyancy effects, following instability there are various branches of solutions corresponding to the different ways the system's symmetries may be broken.
A modified Meditation: exploring a grounding modal ontological argument
Authors: Kearns Stephen
Published: November 2021

I present an argument for God's existence based on the idea that the possibility of God requires the existence of God as a ground. After setting this argument out, I compare it to other arguments for God, concentrating on an argument from Descartes's Third Meditation. I then address various objections and conclude by setting out a non-theistic version of the argument.
Neurobiology of subtypes of trichotillomania and skin picking disorder
Authors: Grant Jon E. , Bethlehem Richard A. I. , Chamberlain Samuel R. , Peris Tara S. , Ricketts Emily J. , O’Neill Joseph , Dougherty Darin D. , Stein Dan , Lochner Christine , Woods Douglas W. , Piacentini John , Keuthen Nancy J.
Published: November 2021

Background

Trichotillomania (TTM) and skin picking disorder (SPD) are common and often debilitating mental health conditions, grouped under the umbrella term of body-focused repetitive behaviors (BFRBs). Recent clinical subtyping found that there were three distinct subtypes of TTM and two of SPD. Whether these clinical subtypes map on to any unique neurobiological underpinnings, however, remains unknown.

Methods

Two hundred and fifty one adults [193 with a BFRB (85.5% [n = 165] female) and 58 healthy controls (77.6% [n = 45] female)] were recruited from the community for a multicenter between-group comparison using structural neuroimaging. Differences in whole brain structure were compared across the subtypes of BFRBs, controlling for age, sex, scanning site, and intracranial volume.

Results

When the subtypes of TTM were compared, low awareness hair pullers demonstrated increased cortical volume in the lateral occipital lobe relative to controls and sensory sensitive pullers. In addition, impulsive/perfectionist hair pullers showed relative decreased volume near the lingual gyrus of the inferior occipital–parietal lobe compared with controls.

Conclusions

These data indicate that the anatomical substrates of particular forms of BFRBs are dissociable, which may have implications for understanding clinical presentations and treatment response.
Trevurr: A dialogic composition on dementia, auraldiversity and companion listening
Authors: Cook Chris J. H.
Published: November 2021

This article details the rationale and creative process behind a collaborative – or more accurately in this case, dialogic – sound composition undertaken as part of research into the acoustic ecologies of people in the early stages of a dementia. Changes in abilities around hearing and listening are among the first symptoms of many types of dementia, making such auditory phenotypes an increasingly common part of lived experiences of sound. Following acoustic ecology practice in doing and presenting research in sound, and more specifically Steven Feld in doing so in dialogic or polyvocal ways, co-composition can be a way of exploring the particularities of others’ hearing, listening and sound practices, which is less reliant on the discursive frames of interlocutors and researchers. The process of making sound art together draws attention to particular sounds and experiences, creating dialogic situations of companion listening, discussion and mutual learning. It also provides a framework for engaging interlocutors in soundscape and ethnographic fieldwork methods. The composition discussed here, Trevurr, documents my time working with Trevor, a keen amateur musician in Cornwall who has mild cognitive impairment, and gradually comes to simulate his experience of hyperacusis in a piece of dialogic, auraldiversity-oriented composition.
Sounds of Aliyah: A journey towards a sonic methodology for diaspora studies
Authors: Weleminsky Carter
Published: November 2021

This qualitative inquiry into contemporary experiences of human migration, focusing on Angloolim(English-speaking Jewish diaspora immigrants to Israel) uses interdisciplinary soundscape composition as its primary method. This project is opportune, given the lack of scholarship utilising sound to explore diaspora and Jewish identity. The compositional process was led by the experiences of the interviewees, blending sounds from places familiar to them, melodies and sonic symbolism that mark the seasons of the Jewish year and their own voices telling the story of their journeys. The composition is multilayered, allowing for a rich insight into the in between that diaspora communities inhabit, both in the place they live and in the place they left behind. This article discusses methodological decisions throughout the different stages of the project, with the aim to encourage readers to develop their own work utilising sound to investigate diaspora communities. This investigation sits at the crossroads between the aesthetic concerns connected to the ‘art’ of soundscape composition and the ethical considerations of the ‘science’ of social inquiry. The article concludes that sound studies, and soundscapes in particular, is an especially apt and rich avenue for study of diaspora identities and the oral traditions that underpin them.
Fasting promotes acute hypoxic adaptation by suppressing mTOR-mediated pathways
Authors: Zhao Ruzhou , Zhao Xingcheng , Wang Xiaobo , Liu Yanqi , Yang Jie , Jiang Shuai , Zhou Xiang , Jiao Bo , Zhang Lin , Liu Yong , Yu Zhibin
Published: November 2021

Rapid adaptation to a hypoxic environment is an unanswered question that we are committed to exploring. At present, there is no suitable strategy to achieve rapid hypoxic adaptation. Here, we demonstrate that fasting preconditioning for 72 h reduces tissue injuries and maintains cardiac function, consequently significantly improving the survival rates of rats under extreme hypoxia, and this strategy can be used for rapid hypoxic adaptation. Mechanistically, fasting reduces blood glucose and further suppresses tissue mTOR activity. On the one hand, fasting-induced mTOR inhibition reduces unnecessary ATP consumption and increases ATP reserves under acute hypoxia as a result of decreased protein synthesis and lipogenesis; on the other hand, fasting-induced mTOR inhibition improves mitochondrial oxygen utilization efficiency to ensure ATP production under acute hypoxia, which is due to the significant decrease in ROS generation induced by enhanced mitophagy. Our findings highlight the important role of mTOR in acute hypoxic adaptation, and targeted regulation of mTOR could be a new strategy to improve acute hypoxic tolerance in the body.
Change of gait after unilateral vestibular neuritis: a prospective longitudinal observation study
Authors: Chae Sung-won , Song Jae-Jun , Kim Woo-Sub
Published: November 2021

Although symptoms of unilateral vestibular neuritis (uVN) resolve spontaneously within several weeks, recovery of gait function has unclearness in gait parameter changes and mediolateral stability improvements. In addition, prospective longitudinal studies on gait parameters after uVN are lacking. This study was conducted to reveal longitudinal change of gait function after acute uVN and to help the precise rehabilitation planning. Twenty three participants with uVN and 20 controls were included. 3D gait analyses were conducted three times after uVN onset at monthly intervals. From the gait analysis data, spatio-temporal parameters, inclination angle (IA) representing the relationship between center of mass (CoM) and center of pressure (CoP) in the frontal plane, and IA variability were obtained. Time effects on gait metrics were tested. Walking speed of participants with uVN improved significantly between the 1st and 3rd tests, but they were not significantly different to that of control, even in the 1st test. The step width of participants with uVN was significantly larger than that of control in the 1st test and improved significantly in the 2nd test. Variability of IA in affected side was significantly larger than that in controls in the 1st test and improved significantly in the 3rd test compared to the 1st test. Improvement of overall gait function and mediolateral stability during gait continued after acute stage of uVN (two months from onset in this study). Rehabilitation intervention should be continued after the acute stage of uVN to enhance appropriate adaptation in gait.
Predicting spring migration of two European amphibian species with plant phenology using citizen science data
Authors: Peer Maria , Dörler Daniel , Zaller Johann G. , Scheifinger Helfried , Schweiger Silke , Laaha Gregor , Neuwirth Gernot , Hübner Thomas , Heigl Florian
Published: November 2021

Habitat fragmentation is one of the drivers for amphibian population declines globally. Especially in industrialized countries roads disrupt the seasonal migration of amphibians between hibernation and reproduction sites, often ending in roadkills. Thus, a timely installing of temporary mitigation measures is important for amphibian conservation. We wanted to find out if plant phenology can be a proxy in advance to determine the start of amphibian migration, since both phenomena are triggered by temperature. We analysed data of 3751 amphibian and 7818 plant phenology observations from citizen science projects in Austria between 2000 and 2018. Using robust regression modelling we compared the migration of common toads (Bufo bufo) and common frogs (Rana temporaria) with the phenology of five tree, one shrub, and one herb species. Results showed close associations between the migration of common frogs and phenological phases of European larch, goat willow and apricot. Models based on goat willow predict migration of common frog to occur 21 days after flowering, when flowering was observed on 60th day of year; apricot based models predict migration to occur 1 day after flowering, observed on the 75th day of year. Common toads showed weaker associations with plant phenology than common frogs. Our findings suggest that plant phenology can be used to determine the onset of temporary mitigation measures for certain amphibian species to prevent roadkills.
RNASeq analysis of drought-stressed guayule reveals the role of gene transcription for modulating rubber, resin, and carbohydrate synthesis
Authors: Dong Chen , Ponciano Grisel , Huo Naxin , Gu Yong , Ilut Daniel , McMahan Colleen
Published: November 2021

The drought-adapted shrub guayule (Parthenium argentatum) produces rubber, a natural product of major commercial importance, and two co-products with potential industrial use: terpene resin and the carbohydrate fructan. The rubber content of guayule plants subjected to water stress is higher compared to that of well-irrigated plants, a fact consistently reported in guayule field evaluations. To better understand how drought influences rubber biosynthesis at the molecular level, a comprehensive transcriptome database was built from drought-stressed guayule stem tissues using de novo RNA-seq and genome-guided assembly, followed by annotation and expression analysis. Despite having higher rubber content, most rubber biosynthesis related genes were down-regulated in drought-stressed guayule, compared to well-irrigated plants, suggesting post-transcriptional effects may regulate drought-induced rubber accumulation. On the other hand, terpene resin biosynthesis genes were unevenly affected by water stress, implying unique environmental influences over transcriptional control of different terpene compounds or classes. Finally, drought induced expression of fructan catabolism genes in guayule and significantly suppressed these fructan biosynthesis genes. It appears then, that in guayule cultivation, irrigation levels might be calibrated in such a regime to enable tunable accumulation of rubber, resin and fructan.
Direct association between rainfall and non-typhoidal Salmonella bloodstream infections in hospital-admitted children in the Democratic Republic of Congo
Authors: Tack Bieke , Vita Daniel , Phoba Marie-France , Mbuyi-Kalonji Lisette , Hardy Liselotte , Barbé Barbara , Jacobs Jan , Lunguya Octavie , Jacobs Liesbet
Published: November 2021

Non-typhoidal Salmonella (NTS) ranks first among causes of bloodstream infection in children under five years old in the Democratic Republic of Congo and has a case fatality rate of 15%. Main host-associated risk factors are Plasmodium falciparum malaria, anemia and malnutrition. NTS transmission in sub-Saharan Africa is poorly understood. NTS bloodstream infections mostly occur during the rainy season, which may reflect seasonal variation in either environmental transmission or host susceptibility. We hypothesized that environment- and host-associated factors contribute independently to the seasonal variation in NTS bloodstream infections in children under five years old admitted to Kisantu referral hospital in 2013–2019. We used remotely sensed rainfall and temperature data as proxies for environmental factors and hospital data for host-associated factors. We used principal component analysis to disentangle the interrelated environment- and host-associated factors. With timeseries regression, we demonstrated a direct association between rainfall and NTS variation, independent of host-associated factors. While the latter explained 17.5% of NTS variation, rainfall explained an additional 9%. The direct association with rainfall points to environmental NTS transmission, which should be explored by environmental sampling studies. Environmental and climate change may increase NTS transmission directly or via host susceptibility, which highlights the importance of preventive public health interventions.
Lead optimization of novel quinolone chalcone compounds by a structure–activity relationship (SAR) study to increase efficacy and metabolic stability
Authors: Knockleby James , Djigo Aïcha Dede , Lindamulage Indeewari Kalhari , Karthikeyan Chandrabose , Trivedi Piyush , Lee Hoyun
Published: November 2021

Many agents targeting the colchicine binding site in tubulin have been developed as potential anticancer agents. However, none has successfully made it to the clinic, due mainly to dose limiting toxicities and the emergence of multi-drug resistance. Chalcones targeting tubulin have been proposed as a safe and effective alternative. We have shown previously that quinolone chalcones target tubulin and maintain potent anti-proliferative activity vis-à-vis colchicine, while also having high tolerability and low toxicity in mouse models of cancer and refractivity to multi-drug resistance mechanisms. To identify the most effective anticancer chalcone compound, we synthesized 17 quinolone–chalcone derivatives based on our previously published CTR-17 and CTR-20, and then carried out a structure–activity relationship study. We identified two compounds, CTR-21 [((E)-8-Methoxy-3-(3-(2-methoxyphenyl)-3-oxoprop-1-enyl) quinolin-2(1H)-one)] and CTR-32 [((E)-3-(3-(2-ethoxyphenyl)-3-oxoprop-1-enyl) quinolin-2(1H)-one)] as potential leads, which contain independent moieties that play a significant role in their enhanced activities. At the nM range, CTR-21 and CTR-32 effectively kill a panel of different cancer cells originated from a variety of different tissues including breast and skin. Both compounds also effectively kill multi-drug resistant cancer cells. Most importantly, CTR-21 and CTR-32 show a high degree of selectivity against cancer cells. In silico, both of them dock near the colchicine-binding site with similar energies. Whereas both CTR-21 and CTR-32 effectively prevents tubulin polymerization, leading to the cell cycle arrest at G2/M, CTR-21 has more favorable metabolic properties. Perhaps not surprisingly, the combination of CTR-21 and ABT-737, a Bcl-2 inhibitor, showed synergistic effect in killing cancer cells, since we previously found the “parental” CTR-20 also exhibited synergism. Taken together, CTR-21 can potentially be a highly effective and relatively safe anticancer drug.
Hypoglycemic mechanism of intestinal bypass surgery in type 2 diabetic rats
Authors: Xie Siqi , Wang MingChang , Zhang Bin , Weng ShanGeng
Published: November 2021

To investigate the effect of duodenal-jejunal bypass (DJB) surgery on postoperative blood glucose in type 2 diabetic rats, and further explore possible mechanisms for the effect of surgical treatment of type 2 diabetes. Forty rats with type 2 diabetes were randomly assigned to 4 groups (n = 10 rats per group), which subsequently underwent DJB, new biliopancreatic diversion (NBPD) or duodenal-jejunal exclusion (DJE) surgery or a sham operation (SHAM). Fasting glucose, 2-h postprandial glucose and blood lipids were measured, and the mRNA in liver and intestinal tissue for bile acid receptor (FXR), as well as the FXR protein expression in the liver tissues were determined. Postprandial blood glucose and fasting TG and FFA in the DJB and NBPD groups were significantly lower than those in the SHAM group and preoperative (p < 0.05) at 8 weeks postoperation. Liver FXR protein was expressed at significantly higher in the DJB and NBPD groups than in the other two (p < 0.05), and the intestinal FXR mRNA in the DJE group were highest. DJB up-regulates the expression of bile acid receptors in the liver and down-regulates those receptors in the intestinal tract via biliopancreatic diversion. This process reduces TG levels, and subsequently any lipotoxicity to islet cells to produce a hypoglycemic effect.
n-Butanol production by Rhodopseudomonas palustris TIE-1
Authors: Bai Wei , Ranaivoarisoa Tahina Onina , Singh Rajesh , Rengasamy Karthikeyan , Bose Arpita
Published: November 2021

Anthropogenic carbon dioxide (CO2) release in the atmosphere from fossil fuel combustion has inspired scientists to study CO2 to biofuel conversion. Oxygenic phototrophs such as cyanobacteria have been used to produce biofuels using CO2. However, oxygen generation during oxygenic photosynthesis adversely affects biofuel production efficiency. To produce n-butanol (biofuel) from CO2, here we introduce an n-butanol biosynthesis pathway into an anoxygenic (non-oxygen evolving) photoautotroph, Rhodopseudomonas palustris TIE-1 (TIE-1). Using different carbon, nitrogen, and electron sources, we achieve n-butanol production in wild-type TIE-1 and mutants lacking electron-consuming (nitrogen-fixing) or acetyl-CoA-consuming (polyhydroxybutyrate and glycogen synthesis) pathways. The mutant lacking the nitrogen-fixing pathway produce the highest n-butanol. Coupled with novel hybrid bioelectrochemical platforms, this mutant produces n-butanol using CO2, solar panel-generated electricity, and light with high electrical energy conversion efficiency. Overall, this approach showcases TIE-1 as an attractive microbial chassis for carbon-neutral n-butanol bioproduction using sustainable, renewable, and abundant resources.
The chromatin remodelling factor Chd7 protects auditory neurons and sensory hair cells from stress-induced degeneration
Authors: Ahmed Mohi , Moon Ruth , Prajapati Ravindra Singh , James Elysia , Basson M. Albert , Streit Andrea
Published: November 2021

Neurons and sensory cells are particularly vulnerable to oxidative stress due to their high oxygen demand during stimulus perception and transmission. The mechanisms that protect them from stress-induced death and degeneration remain elusive. Here we show that embryonic deletion of the chromodomain helicase DNA-binding protein 7 (CHD7) in auditory neurons or hair cells leads to sensorineural hearing loss due to postnatal degeneration of both cell types. Mechanistically, we demonstrate thatCHD7controls the expression of major stress pathway components. In its absence, hair cells are hypersensitive, dying rapidly after brief exposure to stress inducers, suggesting that sound at the onset of hearing triggers their degeneration. In humans,CHD7haploinsufficiency causes CHARGE syndrome, a disorder affecting multiple organs including the ear. Our findings suggest thatCHD7mutations cause developmentally silent phenotypes that predispose cells to postnatal degeneration due to a failure of protective mechanisms.
Zfhx4 regulates endochondral ossification as the transcriptional platform of Osterix in mice
Authors: Nakamura Eriko , Hata Kenji , Takahata Yoshifumi , Kurosaka Hiroshi , Abe Makoto , Abe Takaya , Kihara Miho , Komori Toshihisa , Kobayashi Sachi , Murakami Tomohiko , Inubushi Toshihiro , Yamashiro Takashi , Yamamoto Shiori , Akiyama Haruhiko , Kawaguchi Makoto , Sakata Nobuo , Nishimura Riko
Published: November 2021

Endochondral ossification is regulated by transcription factors that include SRY-box transcription factor 9, runt-related protein 2 (Runx2), and Osterix. However, the sequential and harmonious regulation of the multiple steps of endochondral ossification is unclear. This study identified zinc finger homeodomain 4 (Zfhx4) as a crucial transcriptional partner of Osterix. We found that Zfhx4 was highly expressed in cartilage and that Zfhx4 deficient mice had reduced expression of matrix metallopeptidase 13 and inhibited calcification of cartilage matrices. These phenotypes were very similar to impaired chondrogenesis in Osterix deficient mice. Coimmunoprecipitation and immunofluorescence indicated a physical interaction between Zfhx4 and Osterix. Notably, Zfhx4 and Osterix double mutant mice showed more severe phenotype than Zfhx4 deficient mice. Additionally, Zfhx4 interacted with Runx2 that functions upstream of Osterix. Our findings suggest that Zfhx4 coordinates the transcriptional network of Osterix and, consequently, endochondral ossification.
Two Co(ii) complexes containing pyridylbenzimidazole ligands as chemosensors for the sensing of levofloxacin, acetylacetone, and Ni2+with high selectivity and sensitivity
Authors: Wen Ming-Yue , Ren Li , Cui Guang-Hua
Published: November 2021

Based on the organic ligand 1,1′-(1,6-hexanediyl)bis[2-(2-pyridyl)benzimidazole], two new Co(ii)-based complexes were successfully synthesized hydrothermally, and they are promising sensors for detecting acac, LEV, and Ni2+ions.
Structural determinants of a permeation barrier of the SecYEG translocon in the active state
Authors: Sobakinskaya Ekaterina , Krobath Heinrich , Renger Thomas , Müh Frank
Published: November 2021

The hydrophobic interactions between helix TM7, the plug and the pore ring of the translocon determine the barrier to water and ion permission.
Thermodynamic properties of a molecular dipolar liquid using the two-phase thermodynamic approach
Authors: Palomar Ricardo , Sesé Gemma
Published: November 2021

A revised 2PT methodology leads to better predictability of the entropy, heat capacity and energy of the inherent structures of a system composed of dipolar molecules. Analyses of translation and rotation spectra reinforce the validity of the approach.