bluuebunny/crossref_metadata_2025 huggingface dataset:
Red Snow—When the Climate Bleeds: A Nordic Art and Science Project Aimed at Overcoming Climate Apathy Through Collaboration Between Artists and Scientists
Authors: Endresen Bente Elisabeth
Published: March 2022

This chapter describes the transformative potential of arts and science collaboration. The aim of the Nordic art and science project “Red Snow—When the Climate Bleeds” which was undertaken in 2014–2016 was to increase people's awareness of the accelerating climate changes we are witnessing in the twenty-first century. This chapter shows how people can be encouraged to take action for the care of our planet and to live in a more sustainable way. The project was centred around an exhibition, consisting of artwork and scientific presentations, established collaboration with students at schools and universities and was implemented in four countries. In order to highlight the urgency of the need for change, the project showed some future scenarios presented by climate researchers. With the use of visual art, music and dance, it was possible to reach a larger audience than science alone could: this opened people's hearts and minds to new knowledge. The chapter concludes that the collaboration between the arts and science is increasingly important. Art can successfully go beyond the mental mindset, and speak directly to the emotions of the audience, and once works of art have made an impression, visitors are generally more open to new knowledge.
Setting the Scene: How to Connect with a World as an Interconnected Whole
Authors: Kuenkel Petra
Published: March 2022

This chapter offers a conceptual deep dive into the complex field of mindset shifts as prerequisite for regenerative civilizations and a driver of transformations. The chapter explores why a global shift in mindsets is a necessary condition for accelerating proactive and collective behaviour change, and how this could happen. It suggests that mindsets are both place-based and global. They emerge from culture and traditions and are at the same time heavily influenced by global exchange and communication. The stories about how the world works, how reality emerges and how people can co-create futures give rise to narratives of possibilities—the key leverage points for transformation literacy. The chapter identifies three noticeable trends which have implications for transformation literacy. The first trend is a deeper understanding of co-evolution which refers to the world’s complex relationality in dynamic co-evolutionary patterns. The second trend is the emerging theme of a relational quality of life that refers to the interaction of social, political and natural systems. The third trend is the emerging realization of the need for stewardship referring to a caring role in future-making. The chapter concludes with an overview of the different authors’ chapters and how they relate to the emerging trends.
Memories of Our Collective Future
Authors: Nnoli-Edozien Ndidi
Published: March 2022

This chapter explores the mindset humanity needs to develop in preparation for an emerging future, from an African perspective. The required human consciousness must be holistic and encompassing, bridging the gap between thought and action, linking the past to the present and the future, democratizing access to resources, eliminating waste and fostering regeneration. One opportunity in view is leveraging the power of emerging twenty-first-century technology, specifically blockchain-based decentralized financial (De-Fi) networks, because of their potential to build a global community where trust is once more a currency and where we can rely on humanity to do good for each other and for the planet. We need to design solutions and approaches that enable all persons, especially those marginalized in emerging economies, to find their voices and fulfil their aspirations. The author makes a strong case for combining past wisdom with contemporary know-how to create a new future that is more inclusive and equitable. Drawing on African traditional philosophy and practices, learning from Ubuntu and the Igbo people, she explores the balance between individual rights and communal values. The chapter also offers insights into the SevenPillars® framework that allows business interests, private and public, to thrive whilst safeguarding our natural ecosystem and upholding human dignity and equity.
The Same Tone, but a New Sound—Understanding the Story of the Soul as Pathway to Regenerative Civilizations
Authors: Zettel Christa
Published: March 2022

This chapter takes not only into a historic perspective that looks at human consciousness development over many millennia, but emphasizes the importance of mythology as the most deeply ingrained way of humankind to keep learning for transformations. The author argues, contrary to the modern mind’s needs, that the creative aspect of change or transformation is not order, but disorder or chaos. To avoid the final fragmentation or destruction of our world, the intuitive ‘universal power of self-renewal’ (the life instinct) needs to be reintegrated into rational science, to fill our scientific particularization (the death instinct) with meaning, which is adequate to living in a humane way on our planet. This makes the story of the soul (Greek: psyche), which is passed on by peoples and cultures in a nonlinear-out-of-time-way, not only an important resource to understand the entire civilizational process and subsequently the development of regenerative civilizations. By allowing the forthcoming of an innate integral structure in the human mind, which uses both rationality and intuition, creative mythology is a discipline important for transformation literacy. It can contribute to the so much needed acceleration and speed up the process of collective regeneration, because this is a creative act and unleashes what was previously impossible.
Setting the Scene: Viewing the World as Interconnected Systems
Authors: Ragnarsdottir Kristin Vala
Published: March 2022

This chapter gives a conceptual overview for viewing the world as interconnected systems. Systems have interconnected stock and flows, and change in one part of the system has nonlinear effects on the whole system due to causes and effects that can be mapped. The systems that are outlined are the Earth system, the economic system, the financial system, the education system, and the innovation system. Other systems that are briefly mentioned include the food system, the biological system, the climate system, and community systems. All of these systems (and more) are interconnected in a complex manner, and to achieve a regenerative global system, it is not enough to focus in our education system on environmental and sustainability literacy but on an overarching transformation literacy as outlined in this book. Thus, due to of the interconnectedness of the various systems, holistic education and environmental policy making alone will not achieve the transformations called for.
Everything is Connected—Envisioning How a Regenerative World Looks Like
Authors: Ragnarsdottir Kristin Vala
Published: March 2022

The rationale for why visioning a regenerative world in the future is presented. Based on the visioning strategy of Donella Meadows, the future is envisioned from 2021 on. In addition to answering the questions of Meadows of how a regenerative world would look like, the importance of building a sustainable economy is outlined, an economy that regenerates the natural world and communities. Several models have been outlined, and in this chapter, the focus is on the wellbeing economy, the regenerative economy in service of life, and the doughnut economy. An action plan of how to direct the economy to be within planetary boundaries based on degrowth for the global North is presented. Other systems are briefly outlined as being important including sustainable natural- and food systems. All of these systems are interconnected in a complex manner and therefore need to be studied together.
Holographic complexity of quantum black holes
Authors: Emparan Roberto , Frassino Antonia Micol , Sasieta Martin , Tomašević Marija
Published: March 2022

Abstract

We analyze different holographic complexity proposals for black holes that include corrections from bulk quantum fields. The specific setup is the quantum BTZ black hole, which encompasses in an exact manner the effects of conformal fields with large central charge in the presence of the black hole, including the backreaction corrections to the BTZ metric. Our results show that Volume Complexity admits a consistent quantum expansion and correctly reproduces known limits. On the other hand, the generalized Action Complexity picks up large contributions from the singularity, which is modified due to quantum backreaction, with the result that Action Complexity does not reproduce the expected classical limit. Furthermore, we show that the doubly-holographic setup allows computing the complexity coming purely from quantum fields — a notion that has proven evasive in usual holographic setups. We find that in holographic induced-gravity scenarios the complexity of quantum fields in a black hole background vanishes to leading order in the gravitational strength of CFT effects.
Spectral functions of heavy quarkonia in a bulk-viscous quark gluon plasma
Authors: Thakur Lata , Hirono Yuji
Published: March 2022

Abstract

We study the properties of quarkonia inside a bulk-viscous quark gluon plasma. The non-equilibrium nature of the medium is encoded in the deformed distribution functions of thermal quarks and gluons, with which we compute the dielectric permittivity within the hard thermal loop approximation at one-loop. The modified dielectric permittivity is used to calculate the in-medium heavy quark potential, and using the potential we compute spectral functions, which reflect the physical properties of heavy quarkonia. We discuss how the bulk viscous effect influences quantities such as binding energies and thermal widths. Based on those properties, we discuss the implications of the bulk viscous effect on the physical observables such as ψ′ to J/ψ ratio and the nuclear modification factor, RAA. In particular, we argue that the nuclear modification factors of excited and ground states show different sensitivities to the bulk viscous nature of a plasma, which is potentially useful for the critical point search.
Thermalization of holographic excited states
Authors: Martínez Pedro Jorge , Silva Guillermo A
Published: March 2022

Abstract

We propose a real time holographic framework to study thermalization processes of a family of QFT excited states. The construction builds on Skenderis-van Rees’s holographic duals to QFT Schwinger-Keldysh complex-time ordered paths. Thermalization is explored choosing a set of observables Fn which essentially isolate the excited state contribution. Focusing on theories defined on compact manifolds and with excited states defined in terms of Euclidean path integrals, we identify boundary conditions that allow to avoid any number of modes in the initial field state. In the large conformal dimensions regime, we give precise prescriptions on how to compute the observables in terms of bulk geodesics.
Wormholes and spectral statistics in the Narain ensemble
Authors: Collier Scott , Maloney Alexander
Published: March 2022

Abstract

We study the spectral statistics of primary operators in the recently formulated ensemble average of Narain’s family of free boson conformal field theories, which provides an explicit (though exotic) example of an averaged holographic duality. In particular we study moments of the partition function by explicit computation of higher-degree Eisenstein series. This describes the analog of wormhole contributions coming from a sum of over geometries in the dual theory of “U(1) gravity” in AdS3. We give an exact formula for the two-point correlation function of the density of primary states. We compute the spectral form factor and show that the wormhole sum reproduces precisely the late time plateau behaviour related to the discreteness of the spectrum. The spectral form factor does not exhibit a linear ramp.
VH + jet production in hadron-hadron collisions up to order $$ {\alpha}_{\mathrm{s}}^3 $$ in perturbative QCD
Authors: Gauld R. , Gehrmann-De Ridder A. , Glover E. W. N. , Huss A. , Majer I.
Published: March 2022

Abstract

We present precise predictions for the hadronic production of an on-shell Higgs boson in association with a leptonically decaying gauge boson and a jet up to order $$ {\alpha}_{\mathrm{s}}^3 $$

α
s
3

. We include the complete set of NNLO QCD corrections to both charged- and neutral-current Drell-Yan type contributions, as well as the previously known leading heavy quark loop induced contributions which involve a direct Higgs-quark coupling. As an application, we study a range of differential observables in proton-proton collisions at $$ \sqrt{s} $$

s

= 13 TeV for both the charged- and neutral-current production modes. For each Higgs production process, we assess the improvement in the theoretical uncertainty for both the exclusive (njet = 1) and inclusive (njet ≥ 1) jet categories. We find that the inclusion of the NNLO corrections to the Drell-Yan type contributions is essential in stabilising the predictions and in reducing the theoretical uncertainty for both inclusive and exclusive jet production for all three modes. This is particularly true in the kinematical regimes associated with low to medium values of the transverse momentum of the produced vector boson and where the differential cross sections are the largest. For the neutral-current process, we find that the heavy quark loop induced contributions have their largest phenomenological impact (an increase in the size of the NNLO corrections, a distortion of the distribution shape and an enlargement of the left over remaining uncertainties) in kinematical regions associated to large values of pT,Z (typically above 150 GeV) where the cross sections are smaller.
All-multiplicity amplitudes with four massive quarks and identical-helicity gluons
Authors: Lazopoulos Achilleas , Ochirov Alexander , Shi Canxin
Published: March 2022

Abstract

We explore the on-shell recursion for tree-level scattering amplitudes with massive spinning particles. Based on the factorization structure encoded in the same way by two different recursion relations, we conjecture an all-multiplicity formula for two gauged massive particles of arbitrary spin and any number of identical-helicity gluons. Specializing to quantum chromodynamics (QCD), we solve the on-shell recursion relations in the presence of two pairs of massive quarks and an arbitrary number of identical-helicity gluons. We find closed-form expressions for the two distinct families of color-ordered four-quark amplitudes, in which all gluons comprise a single color-adjacent set. We compare the efficiency of the numerical evaluation of the two resulting analytic formulae against a numerical implementation of the off-shell Berends-Giele recursion. We find the formulae for both amplitude families to be faster for large multiplicities, while the simpler of the two is actually faster for any number of external legs. Our analytic results are provided in a computer-readable format as two files in the supplementary material.
Meprin β knockout reduces brain Aβ levels and rescues learning and memory impairments in the APP/lon mouse model for Alzheimer’s disease
Authors: Marengo Liana , Armbrust Fred , Schoenherr Caroline , Storck Steffen E. , Schmitt Ulrich , Zampar Silvia , Wirths Oliver , Altmeppen Hermann , Glatzel Markus , Kaether Christoph , Weggen Sascha , Becker-Pauly Christoph , Pietrzik Claus U.
Published: March 2022

β-Site amyloid precursor protein (APP) cleaving enzyme-1 (BACE1) is the major described β-secretase to generate Aβ peptides in Alzheimer’s disease (AD). However, all therapeutic attempts to block BACE1 activity and to improve AD symptoms have so far failed. A potential candidate for alternative Aβ peptides generation is the metalloproteinase meprin β, which cleaves APP predominantly at alanine in p2 and in this study we can detect an increased meprin β expression in AD brain. Here, we report the generation of the transgenic APP/lon mouse model of AD lacking the functional Mep1b gene (APP/lon × Mep1b−/−). We examined levels of canonical and truncated Aβ species using urea-SDS-PAGE, ELISA and immunohistochemistry in brains of APP/lon mouse × Mep1b−/−. Additionally, we investigated the cognitive abilities of these mice during the Morris water maze task. Aβ1-40 and 1–42 levels are reduced in APP/lon mice when meprin β is absent. Immunohistochemical staining of mouse brain sections revealed that N-terminally truncated Aβ2–x peptide deposition is decreased in APP/lon × Mep1b−/− mice. Importantly, loss of meprin β improved cognitive abilities and rescued learning behavior impairments in APP/lon mice. These observations indicate an important role of meprin β within the amyloidogenic pathway and Aβ production in vivo.
Positive Jantzen sum formulas for cyclotomic Hecke algebras
Authors: Mathas Andrew
Published: March 2022

This paper proves a “positive” Jantzen sum formula for the Specht modules of the cyclotomic Hecke algebras of type A and uses it to obtain new bounds on decomposition numbers. Quite remarkably, our results are proved entirely inside the cyclotomic Hecke algebras. Our positive sum formula shows that, in the Grothendieck group, the Jantzen sum formula can be written as an explicit non-negative linear combination of modules $$[E^{\varvec{\nu }}_{f,e}]$$

[

E

f
,
e

ν

]

, which are the modular reductions of simple modules of related Hecke algebras in characteristic zero. The coefficient of $$[E^{\varvec{\nu }}_{f,e}]$$

[

E

f
,
e

ν

]

in the sum formula is determined by the graded decomposition numbers in characteristic zero, which are known, and by the characteristic of the field. As a consequence we give an explicit upper bound for the decomposition numbers in characteristic $$p>0$$

p
>
0

in terms of linear combinations of decomposition numbers of a cyclotomic Hecke algebra at $$ep^r$$

e

p
r

th roots of unity in characteristic zero, for $$r\ge 0$$

r
≥
0

. Finally, we prove a new and more elegant “classical” Jantzen sum formula for these algebras.
Multiple phenotypic traits predict male mating success in a critically endangered frog
Authors: Kelleher Shannon R. , Silla Aimee J. , McFadden Michael S. , Stares Mitchell G. , Endler John A. , Byrne Phillip G.
Published: March 2022

Complex sexual signals spanning multiple sensory modalities may be common in nature, yet few studies have explored how combinations of phenotypic traits influence male attractiveness and mating success. Here, we investigate whether combinations of multiple male phenotypic traits (both within and across sensory modalities) predict male mating and fertilization success in the critically endangered southern corroboree frog,Pseudophryne corroboree. We conducted breeding trials in a standardized captive environment where females were given the opportunity to choose between multiple males over the duration of the breeding season. For each male, we measured multiple call traits, aspects of coloration, body size, and age. We found that complex interactions between multiple traits best predicted male mating and fertilization success. In general, males with lower call frequency, lower call rate, and shorter call duration had the highest mating and fertilization success. Fertilization success was additionally linked to male body size and age. These findings suggest that femaleP. corroboreeselect mates based on a suite of acoustic traits, adding to a growing body of evidence that females use multiple traits to assess male quality. Our results also suggest that females may combine information from multiple signals non-additively. Moreover, our results imply that females gain direct fertility benefits from their mate choice decisions. We argue that understanding female mate choice based on various signals across multiple sensory modalities has important implications for the integration of mate choice into conservation breeding programs and needs to be considered when developing behavior-based captive breeding strategies.

Significance statement

Sexual signals are often highly complex, yet we know little about how multiple signal components both within and across various sensory modalities predict male mating success. We investigated whether combinations of multiple phenotypic traits (within and across sensory modalities) predicted male breeding success in threatened corroboree frogs. We conducted captive breeding trials in a homogeneous environment, where females could choose between multiple males over the duration of a single breeding season. We found that interactions between multiple male traits predicted mating and fertilization success. Males with lower call frequency, call rate, and duration had higher mating success. Fertilization success was also linked to acoustic signals, body size, and age. Understanding mate choice for multiple traits further elucidates the complexity of female mate choice. This study is one of the first to consider the conservation implications of multimodal signaling in mate choice.
The role of computed tomography in the assessment of tumour extent and the risk of residual disease after upfront surgery in advanced ovarian cancer (AOC)
Authors: Asp Mihaela , Malander Susanne , Wallengren Nils-Olof , Pudaric Sonja , Bengtsson Johan , Sartor Hanna , Kannisto Päivi
Published: March 2022

Purpose

Epithelial ovarian cancer is usually diagnosed in the advanced stages. To choose the best therapeutic approach, an accurate preoperative assessment of the tumour extent is crucial. This study aimed to determine whether the peritoneal cancer index (PCI), the amount of ascites, and the presence of cardiophrenic nodes (CPLNs) visualized by computed tomography (CT) can assess the tumour extent (S-PCI) and residual disease (RD) for advanced ovarian cancer (AOC) patients treated with upfront surgery.

Methods

In total, 118 AOC cases were included between January 2016 and December 2018 at Skåne University Hospital, Lund, Sweden. Linear regression and interclass correlation (ICC) analyses were used to determine the relationship between CT-PCI and S-PCI. The patients were stratified in complete cytoreductive surgery (CCS) with no RD or to non-CCS with RD of any size. The amount of ascites on CT (CT-ascites), CA-125 and the presence of radiological enlarged CPLNs (CT-CPLN) were analysed to evaluate their impact on estimating RD.

Results

CT-PCI correlated well with S-PCI (0.397; 95% CI 0.252–0.541; p < 0.001). The risk of RD was also related to CT-PCI (OR 1.069 (1.009–1.131), p < 0.023) with a cut-off of 21 for CT-PCI (0.715, p = 0.000). The sensitivity, specificity, positive predictive value and negative predictive value were 58.5, 70.3, 52.2 and 75.4%, respectively. CT-ascites above 1000 ml predicted RD (OR 3.510 (1.298–9.491) p < 0.013).

Conclusion

CT is a reliable tool to assess the extent of the disease in advanced ovarian cancer. Higher CT-PCI scores and large volumes of ascites estimated on CT predicted RD of any size.
Complex hereditary peripheral neuropathies caused by novel variants in mitochondrial-related nuclear genes
Authors: Hiramatsu Yu , Okamoto Yuji , Yoshimura Akiko , Yuan Jun-Hui , Ando Masahiro , Higuchi Yujiro , Hashiguchi Akihiro , Matsuura Eiji , Nozaki Fumihito , Kumada Tomohiro , Murayama Kei , Suzuki Mikiya , Yamamoto Yuki , Matsui Naoko , Miyazaki Yoshimichi , Yamaguchi Masamitsu , Suzuki Youji , Mitsui Jun , Ishiura Hiroyuki , Tanaka Masaki , Morishita Shinichi , Nishino Ichizo , Tsuji Shoji , Takashima Hiroshi
Published: March 2022

Mitochondrial disorders are a group of clinically and genetically heterogeneous multisystem disorders and peripheral neuropathy is frequently described in the context of mutations in mitochondrial-related nuclear genes. This study aimed to identify the causative mutations in mitochondrial-related nuclear genes in suspected hereditary peripheral neuropathy patients. We enrolled a large Japanese cohort of clinically suspected hereditary peripheral neuropathy patients who were mutation negative in the prescreening of the known Charcot–Marie–Tooth disease-causing genes. We performed whole-exome sequencing on 247 patients with autosomal recessive or sporadic inheritance for further analysis of 167 mitochondrial-related nuclear genes. We detected novel bi-allelic likely pathogenic/pathogenic variants in four patients, from four mitochondrial-related nuclear genes: pyruvate dehydrogenase beta-polypeptide (PDHB), mitochondrial poly(A) polymerase (MTPAP), hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, beta subunit (HADHB), and succinate-CoA ligase ADP-forming beta subunit (SUCLA2). All these patients showed sensory and motor axonal polyneuropathy, combined with central nervous system or multisystem involvements. The pathological analysis of skeletal muscles revealed mild neurogenic changes without significant mitochondrial abnormalities. Targeted screening of mitochondria-related nuclear genes should be considered for patients with complex hereditary axonal polyneuropathy, accompanied by central nervous system dysfunctions, or with unexplainable multisystem disorders.
Comprehensive transcriptomic analysis shows disturbed calcium homeostasis and deregulation of T lymphocyte apoptosis in inclusion body myositis
Authors: Johari Mridul , Vihola Anna , Palmio Johanna , Jokela Manu , Jonson Per Harald , Sarparanta Jaakko , Huovinen Sanna , Savarese Marco , Hackman Peter , Udd Bjarne
Published: March 2022

Objective

Inclusion body myositis (IBM) has an unclear molecular etiology exhibiting both characteristic inflammatory T-cell activity and rimmed-vacuolar degeneration of muscle fibers. Using in-depth gene expression and splicing studies, we aimed at understanding the different components of the molecular pathomechanisms in IBM.

Methods

We performed RNA-seq on RNA extracted from skeletal muscle biopsies of clinically and histopathologically defined IBM (n = 24), tibial muscular dystrophy (n = 6), and histopathologically normal group (n = 9). In a comprehensive transcriptomics analysis, we analyzed the differential gene expression, differential splicing and exon usage, downstream pathway analysis, and the interplay between coding and non-coding RNAs (micro RNAs and long non-coding RNAs).

Results

We observe dysregulation of genes involved in calcium homeostasis, particularly affecting the T-cell activity and regulation, causing disturbed Ca2+-induced apoptotic pathways of T cells in IBM muscles. Additionally, LCK/p56, which is an essential gene in regulating the fate of T-cell apoptosis, shows increased expression and altered splicing usage in IBM muscles.

Interpretation

Our analysis provides a novel understanding of the molecular mechanisms in IBM by showing a detailed dysregulation of genes involved in calcium homeostasis and its effect on T-cell functioning in IBM muscles. Loss of T-cell regulation is hypothesized to be involved in the consistent observation of no response to immune therapies in IBM patients. Our results show that loss of apoptotic control of cytotoxic T cells could indeed be one component of their abnormal cytolytic activity in IBM muscles.
Use of Pharyngeal High-Resolution Manometry to Evaluate Dysphagia in Adults with Motor Neurone Disease: A Scoping Review
Authors: Diver Eva Mary , Regan Julie
Published: March 2022

There has been a recent shift towards proactive dysphagia intervention in motor neurone disease (MND) to maintain physiological reserve. Pharyngeal high-resolution manometry (PHRM) can quantify swallowing pathophysiology to inform and evaluate proactive dysphagia intervention. This study aims to explore the current use of PHRM as a dysphagia evaluation in adults with MND. A scoping review based on the Joanna Briggs Framework was completed. Four electronic databases (PubMed, EMBASE, CINAHL and Web of Science core) were searched (inception to March 2021) by two independent researchers. Data were analysed according to (i) PHRM protocol and analysis methods and the feasibility of same, (ii) swallow biomechanics data and (iii) dysphagia intervention effects as measured by PHRM. Six studies with 78 people with MND (PwMND) were included. There was considerable variation in PHRM protocol and analysis methods. Five studies reported a 100% completion rate and three studies reported no adverse events. Swallow biomechanics data were reported across all studies. The effects of sensory stimulation, increased bolus consistency, effortful swallow and cricopharyngeal myotomy were evaluated using PHRM with 20 PwMND across four studies with varying effects. Literature on the use of PHRM in PwMND is limited. Variability in PHRM methods restricts comparison of metrics. PHRM appears to be a feasible tool for PwMND. PHRM can provide novel swallow physiology data in PwMND and quantify discrete effects of compensatory and surgical dysphagia interventions not detectable by videofluoroscopy or FEES. Further research on the effects of proactive dysphagia intervention as measured by PHRM is required.
A review of ferric citrate clinical studies, and the rationale and design of the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) trial
Authors: Hanudel Mark R. , Laster Marciana L. , Portale Anthony A. , Dokras Aditi , Quigley Raymond P. , Guzman German A. Lozano , Zaritsky Joshua J. , Hayde Nicole A. , Kaskel Frederick J. , Mitsnefes Mark M. , Ramirez Jorge A. , Imani Peace D. , Srivaths Poyyapakkam R. , Kogon Amy J. , Denburg Michelle R. , Blydt-Hansen Tom D. , Reyes Loretta Z. , Greenbaum Larry A. , Weidemann Darcy K. , Warady Bradley A. , Elashoff David A. , Mendley Susan R. , Isakova Tamara , Salusky Isidro B.
Published: March 2022

Pediatric chronic kidney disease (CKD) is characterized by many co-morbidities, including impaired growth and development, CKD-mineral and bone disorder, anemia, dysregulated iron metabolism, and cardiovascular disease. In pediatric CKD cohorts, higher circulating concentrations of fibroblast growth factor 23 (FGF23) are associated with some of these adverse clinical outcomes, including CKD progression and left ventricular hypertrophy. It is hypothesized that lowering FGF23 levels will reduce the risk of these events and improve clinical outcomes. Reducing FGF23 levels in CKD may be accomplished by targeting two key stimuli of FGF23 production—dietary phosphate absorption and iron deficiency. Ferric citrate is approved for use as an enteral phosphate binder and iron replacement product in adults with CKD. Clinical trials in adult CKD cohorts have also demonstrated that ferric citrate decreases circulating FGF23 concentrations. This review outlines the possible deleterious effects of excess FGF23 in CKD, summarizes data from the adult CKD clinical trials of ferric citrate, and presents the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) study, a randomized, placebo-controlled trial to evaluate the effects of ferric citrate on FGF23 in pediatric patients with CKD stages 3–4 (ClinicalTrials.gov Identifier NCT04741646).
A review on the current status and definitions of activity indices in inflammatory bowel disease: how to use indices for precise evaluation
Authors: Kishi Masahiro , Hirai Fumihito , Takatsu Noritaka , Hisabe Takashi , Takada Yasumichi , Beppu Tsuyoshi , Takeuchi Ken , Naganuma Makoto , Ohtsuka Kazuo , Watanabe Kenji , Matsumoto Takayuki , Esaki Motohiro , Koganei Kazutaka , Sugita Akira , Hata Keisuke , Futami Kitarou , Ajioka Yoichi , Tanabe Hiroshi , Iwashita Akinori , Shimizu Hirotaka , Arai Katsuhiro , Suzuki Yasuo , Hisamatsu Tadakazu
Published: March 2022

Many clinical trials have been conducted for inflammatory bowel disease (IBD), so various clinical indices (CIs) and endoscopic indices (EIs) have also been evaluated. However, recently, with the progress of IBD management, review of established indices from previous studies, and establishment of new indices, the landscape of the use of indices in clinical trials have changed. We investigated the number and frequency of the indices adapted in recent clinical trials for ulcerative colitis (CI and EI) and Crohn’s disease (CI, EI, index related to magnetic resonance imaging, index for evaluating patient-reported outcomes, and health-related quality of life). Based on the results, we selected representative indices and further reviewed their content and characteristics. Moreover, various definitions, including clinical and endoscopic response or remission, have been described by means of representative indices in clinical trials.
Studies on the binding of nitrogenous bases to protoporphyrin IX iron(II) in aqueous solution at high pH values
Authors: Silver Jack , Al-Jaff Golzar , Wilson Michael T. , den Engelsen Daniel , Fern George R. , Ireland Terry G.
Published: March 2022

Studies are reported on the formation of low-spin six-coordinate [Fe(PPIX)L2] complexes from iron(II) protoporphyrin where L is one of a series of nitrogenous ligands (aliphatic, aromatic or heterocyclic). The bonding constants have been determined by titration of the metal complex with these ligands and are compared in relation to previous studies. The adduct formation was monitored utilising optical spectroscopy. In addition, Mӧssbauer spectroscopic experiments were conducted to monitor the electronic environment around the central iron atom in these complexes. The two complementary spectroscopic methods indicated that all nitrogen ligands formed low-spin octahedral complexes. The magnitude of the overall binding constants (β2 values) are discussed and related to (a) the pKa values of the free ligands and (b) the Mössbauer parameter ΔEQ, which represents the quadrupole splitting of the haem iron. The β2 and ΔEQ values are also discussed in terms of the structure of the ligand. Cooperative binding was observed for nearly all the ligands with Hill coefficients close to 2 for iron(II) protoporphyrin; one of these ligands displayed a much greater affinity than any we previously studied, and this was a direct consequence of the structure of the ligand. Overall conclusions on these and previous studies are drawn in terms of aliphatic ligands versus aromatic ring structures and the absence or presence of sterically hindered nitrogen atoms. The implications of the work for the greater understanding of haem proteins in general and in particular how the nitrogenous ligand binding results are relevant to and aid the understanding of the binding of inhibitor molecules to the cytochrome P450 mono-oxygenases (for therapeutic purposes) are also discussed.

Graphical abstract

Changes in the electronic absorption spectra of five-coordinate [Fe(II)(PPIX)(2-MeIm)] that occurred as the temperature was lowered from room temperature to 78° K
The altered multiscale dynamics of spontaneous brain activity in depression with Parkinson’s disease
Authors: Liu Zhu , Su Dongning , Ma Lingyan , Chen Huimin , Fang Jinping , Ma Huizi , Zhou Junhong , Feng Tao
Published: March 2022

Background

Depression is one typical mood disorder in Parkinson’s disease (DPD). The alterations in the resting-state brain activities are believed to be associated with DPD. These resting-state activities are regulated by neurophysiological components over multiple temporal scales. The multiscale dynamics of these spontaneous fluctuations are thus complex, but not well-characterized.

Objective

To characterize the complexity of the spontaneous blood-oxygen-level-dependent (BOLD) of fMRI in DPD. We hypothesized that (1) compared to non-depression PD (NDPD), the complexity in DPD would be lower; and (2) the diminished complexity would be associated with lower connections/communications between brain regions.

Methods

Twenty-nine participants (10 in DPD and 19 in NDPD) who were naïve to medications completed a resting-sate functional MRI scan. The BOLD complexity within each voxel was calculated by using multiscale entropy (MSE). The complexity of the whole brain and each of the 90 regions parcellated following automated-anatomical-labeling template was then obtained by averaging voxel-wised complexity across all brain regions or within each region. The level of connections of regions with diminished complexity was measured by their own global functional connectivity (FC).

Results

As compared to NDPD patients, the whole-brain complexity and complexity in 18 regions were significantly lower in DPD (F > 16.3, p < 0.0005). Particularly, in eight of the 18 regions, lower complexity was associated with lower global FC (Beta = 0.333 ~ 0.611, p = 0.000 ~ 0.030).

Conclusion

The results from this pilot study suggest that the resting-state BOLD complexity may provide critical knowledge into the pathology of DPD. Future studies are thus warranted to confirm the findings of this study.
Grassland contribution to soil organic carbon stock under climate change scenarios in Basque Country (Spain)
Authors: Doblas-Rodrigo Álvaro , Gallejones Patricia , Artetxe Ainara , Rosa Eduardo , del Hierro Óscar , Merino Pilar
Published: March 2022

In this study, we estimated the contribution of managed grasslands to the “4 per 1000” initiative in Basque Country under two climate scenarios (RCP4.5 and RCP8.5) adopted by the IPCC in its Fifth Assessment Report. For this purpose, the RothC model was calibrated and validated with a historic database of grassland soil organic carbon (SOC) (1983 to 2019). The results at field-scale show a rate of increase of 1.26 t C ha−1 year−1 at a depth of 0–30 cm over a 36-year simulation. The model was run at the regional scale in short- (2020–2040), medium- (2041–2070), and long-term (2071–2090) future climate scenarios. For all the simulations, agricultural practices and available data for grassland systems were considered. RothC model projections showed how SOC stock responses varied depending on initial SOC and climate subregions, with higher values for a lower initial SOC stock under the highest precipitation regime subregion. A 4 per 1000 storage rate could be achieved in grassland soils with an initial SOC < 80 t C ha−1. The overall trends showed that future climate change will lead to a decrease in the SOC stock in grasslands with a higher initial SOC if appropriate practices are not implemented to maintain the SOC stock.
Internet use and cognitive frailty in older adults: a large-scale multidimensional approach
Authors: Dequanter Samantha , Gorus Ellen , Van Laere Sven , De Witte Nico , Verté Dominique , Steenhout Iris , Fobelets Maaike , Buyl Ronald
Published: March 2022

Although research on sociodemographic correlates of internet use in older adults without and with pronounced cognitive impairment is already quite extensive, much less is known about the relationship between cognitive frailty (CF) and this behaviour. As CF is associated to multidimensional frailty aspects, this study explored the relationship between internet use and CF, operationalised as Subjective Cognitive Impairment, in older adults by means of a comprehensive explanatory model including sociodemographic factors and multiple frailty measures. The dataset included a sample of community-dwelling 60 + older adults that were included in the Belgian Ageing Studies (BAS) and that completed survey questions on (i) internet use frequency and (ii) internet activities. Multidimensional frailty was measured with the CFAI-Plus. The analysis comprised a structural equation modelling (SEM) procedure. Internet use was frequent; however, it became less frequent with higher CF. Moreover, the latter used less tablets as compared to the no-low CF group. Navigating the web, sharing email and online banking were the most frequently reported activities. Tele-communicating with Skype, online shopping and using e-government services were the least frequent. Age, female gender, lower income and living with a partner were also negatively associated with internet use. To conclude, CF, along with other frailty and sociodemographic factors, was negatively related to internet use in older adults. Future research should focus, amongst others, on the dynamic processes underlying internet use in the population of older adults affected by CF.
Infrared Thermography with High Accuracy in a Neonatal Incubator
Authors: Hamada Keisuke , Hirakawa Eiji , Asano Hidetsugu , Hayashi Hayato , Mine Takashi , Ichikawa Tatsuki , Nagata Yasuhiro
Published: March 2022

As the accuracy of body temperature measurement is especially critical in premature infants on admission to the neonatal intensive care unit (NICU), noninvasive measurement using infrared thermography (IRT) has not been widely adopted in the NICU due to a lack of evidence regarding its accuracy. We have established a new calibration method for IRT in an incubator, and evaluated its accuracy and reliability at different incubator settings using a variable-temperature blackbody furnace. This method improved the accuracy and reliability of IRT with an increase in percentage of data with mean absolute error (MAE) < 0.3 °C to 93.1% compared to 4.2% using the standard method. Two of three IRTs had MAE < 0.1 °C under all conditions examined. This method provided high accuracy not only for measurements at specific times but also for continuous monitoring. It will also contribute to avoiding the risk of neonates' skin trouble caused by attaching a thermistor. This study will facilitate the development of novel means of administering neonatal body temperature.
Lipotoxicity-induced mtDNA release promotes diabetic cardiomyopathy by activating the cGAS-STING pathway in obesity-related diabetes
Authors: Ma Xiu Mei , Geng Kang , Law Betty Yuen-Kwan , Wang Peng , Pu Yue Li , Chen Qing , Xu Hui Wen , Tan Xiao Zhen , Jiang Zong Zhe , Xu Yong
Published: March 2022

Diabetic cardiomyopathy (DCM) is characterized by lipid accumulation, mitochondrial dysfunction, and aseptic inflammatory activation. Mitochondria-derived cytosolic DNA has been reported to induce inflammation by activating cyclic GMP-AMP synthase (cGAS)/the stimulator of interferon genes (STING) pathway in the adipose, liver, and kidney tissues. However, the role of cytosolic mtDNA in the progression of DCM is unclear. In this study, with an obesity-related DCM mouse model established by feeding db/db mice with a high-fat diet (HFD), we observed increased mtDNA in the cytosol and activated cGAS-STING signaling pathway during DCM, as well as the downstream targets, IRF3, NF-κB, IL-18, and IL-1β. In a further study with a palmitic acid (PA)-induced lipotoxic cell model established in H9C2 cells, we revealed that the cytosolic mtDNA was the result of PA-induced overproduction of mitochondrial ROS, which also led to the activation of the cGAS/STING system and its downstream targets. Notably, treatment of extracted mtDNA alone was sufficient to activate the cGAS-STING signaling pathway in cultured H9C2 cells. Besides, both knockdown of STING in PA-induced H9C2 cells and inhibition of STING by C-176 injection in the DCM mouse model could remarkably block the inflammation and apoptosis of cardiomyocytes. In conclusion, our study elucidated the critical role of cytosolic mtDNA-induced cGAS-STING activation in the pathogenesis of obesity-related DCM and provided preclinical validation for using a STING inhibitor as a new potential therapeutic strategy for the treatment of DCM.

Graphical abstract
Nowcasting and monitoring SDG 8
Authors: Bilek-Steindl Sandra , Url Thomas
Published: March 2022

We propose a nowcasting approach for indicators assigned to the Sustainable Development Goal (SDG) 8, calling for decent work and economic growth. The nowcasts of SDG indicators are based on dynamic factor models. In this mixed frequency framework, we exploit information from a comprehensive set of quarterly data to nowcast annually observed SDG indicators. For the model selection and specification search we evaluate the nowcast properties of the models based on a pseudo real-time data set. More recent information on SDGs can disclose a possible deviation from the desired path at an early stage. As an example, we present nowcasts for SDG objectives in Austria for the year 2020. The design of our assessment follows the method and quantitative rules suggested by Eurostat. SDG 8 indicators are highly related to the underlying economic situation and the effects of the COVID-19 pandemic are clearly visible in the results for 2020.
Deliberation and the Problems of Exclusion and Uptake: The Virtues of Actively Facilitating Equitable Deliberation and Testimonial Sensibility
Authors: Sorial Sarah
Published: March 2022

In this paper, I suggest that one of the ways in which problems of exclusionfromdeliberation and uptakewithindeliberation can be ameliorated is to develop a more robust account of the deliberative virtues that socially privileged speakers/hearers ought to cultivate. Specifically, privileged speakers/hearers ought to cultivate the virtue ofactively facilitatingequitable and inclusive deliberative exchanges (which includes a cluster of virtues, including the practice of silence and of listening) and the deliberative virtue of training their ‘testimonial sensibility’ to correct for prejudicial judgments about other speakers.
Design Principles for User Interfaces in AI-Based Decision Support Systems: The Case of Explainable Hate Speech Detection
Authors: Meske Christian , Bunde Enrico
Published: March 2022

Hate speech in social media is an increasing problem that can negatively affect individuals and society as a whole. Moderators on social media platforms need to be technologically supported to detect problematic content and react accordingly. In this article, we develop and discuss the design principles that are best suited for creating efficient user interfaces for decision support systems that use artificial intelligence (AI) to assist human moderators. We qualitatively and quantitatively evaluated various design options over three design cycles with a total of 641 participants. Besides measuring perceived ease of use, perceived usefulness, and intention to use, we also conducted an experiment to prove the significant influence of AI explainability on end users’ perceived cognitive efforts, perceived informativeness, mental model, and trustworthiness in AI. Finally, we tested the acquired design knowledge with software developers, who rated the reusability of the proposed design principles as high.
Designing Personality-Adaptive Conversational Agents for Mental Health Care
Authors: Ahmad Rangina , Siemon Dominik , Gnewuch Ulrich , Robra-Bissantz Susanne
Published: March 2022

Millions of people experience mental health issues each year, increasing the necessity for health-related services. One emerging technology with the potential to help address the resulting shortage in health care providers and other barriers to treatment access are conversational agents (CAs). CAs are software-based systems designed to interact with humans through natural language. However, CAs do not live up to their full potential yet because they are unable to capture dynamic human behavior to an adequate extent to provide responses tailored to users’ personalities. To address this problem, we conducted a design science research (DSR) project to design personality-adaptive conversational agents (PACAs). Following an iterative and multi-step approach, we derive and formulate six design principles for PACAs for the domain of mental health care. The results of our evaluation with psychologists and psychiatrists suggest that PACAs can be a promising source of mental health support. With our design principles, we contribute to the body of design knowledge for CAs and provide guidance for practitioners who intend to design PACAs. Instantiating the principles may improve interaction with users who seek support for mental health issues.