bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of perioperative anaphylaxis: Systematic review
Authors: Admass Biruk Adie , Hassen Alemayehu Eshetu , Agegnehu Abatneh Feleke , Temesgen Mamaru Mollalign , Gebeyehu Natnael Atnafu , Ferede Yonas Admasu , Tegegne Biresaw Ayen
Published: February 2023

Abstract

Background

Perioperative anaphylaxis typically manifests unexpectedly and, in many cases, with severe symptoms requiring prompt recognition and action. This review was conducted in order to establish a clear plan for handling perioperative anaphylaxis.

Methods

A thorough search strategy of electronic sources was carried out after determining the main questions, scope, and criteria for the literatures to be included. Advanced search techniques from databases and websites were used to identify the articles. A proper evaluation was used when screening the literature. The preferred reporting items for systematic reviews and meta-analyses 2020 statement was used when conducting this review.

Results

From databases and websites, 545 articles were identified. After reading at the titles and abstracts of these articles, 195 papers were excluded, and 98 were eliminated for duplication. 87 items were retrieved and checked for eligibility during the screening step. Finally, 50 papers that addressed the management of anaphylaxis during the perioperative period were reviewed.

Conclusion

Antibiotics and neuromuscular blocking agents are the major causes of IgE-mediated anaphylaxis. When the onset is particularly abrupt, the clinical manifestation can differ and the diagnosis may be missed. Clinical presentation guides management. Adrenaline and intravenous fluids are the main components of treatment. Plasma Tryptase level and skin tests are helpful to identify the culprit agent. A thorough assessment provides clarity about the culprit drug and safe substitutes, therefore, guaranteeing patient safety for future anaesthetics.

Highlights
Explainable machine learning for public policy: Use cases, gaps, and research directions
Authors: Amarasinghe Kasun , Rodolfa Kit T. , Lamba Hemank , Ghani Rayid
Published: February 2023

Explainability is highly desired in machine learning (ML) systems supporting high-stakes policy decisions in areas such as health, criminal justice, education, and employment. While the field of explainable ML has expanded in recent years, much of this work has not taken real-world needs into account. A majority of proposed methods are designed with generic explainability goals without well-defined use cases or intended end users and evaluated on simplified tasks, benchmark problems/datasets, or with proxy users (e.g., Amazon Mechanical Turk). We argue that these simplified evaluation settings do not capture the nuances and complexities of real-world applications. As a result, the applicability and effectiveness of this large body of theoretical and methodological work in real-world applications are unclear. In this work, we take steps toward addressing this gap for the domain of public policy. First, we identify the primary use cases of explainable ML within public policy problems. For each use case, we define the end users of explanations and the specific goals the explanations have to fulfill. Finally, we map existing work in explainable ML to these use cases, identify gaps in established capabilities, and propose research directions to fill those gaps to have a practical societal impact through ML. The contribution is (a) a methodology for explainable ML researchers to identify use cases and develop methods targeted at them and (b) using that methodology for the domain of public policy and giving an example for the researchers on developing explainable ML methods that result in real-world impact.
Path dependence or steps for major reforms? Pandemic-related social protection measures in ten OECD countries
Authors: Mäntyneva Päivi , Ketonen Eeva-Leena , Hiilamo Heikki
Published: February 2023

This article examines with empirical evidence the social protection measures implemented in response to the COVID-19 pandemic in ten welfare states in the Global North. We analysed the potential similarities and differences in responses by welfare regimes. The comparative study was conducted with data from 169 measures, collected from domestic sources as well as from COVID-19 response databases and reports. In qualitative terms, we redeveloped Hall’s theory on the distinction between first-, second- and third-order changes. In accordance with the path-dependence thesis, we show systematically that the majority of the studied changes (91%) relied on a pre-pandemic tool demonstrating flexibility within social security systems. The relative share of completely new instruments was notable but modest (9%). Thematically, the social protection measures converged beyond traditional welfare regimes, particularly among the European welfare states. Somewhat surprisingly, the changes to social security systems related not just to emergency aid to mitigate traditional risks but, to a greater extent, also to prevent new risks from being actualised.
What is the role of gender in perceived coercion during psychiatric admission?
Authors: O’Callaghan Aoife K. , Plunkett Róisín , Kelly Brendan D.
Published: February 2023

Objectives:

This paper explores factors linking gender with increased perceived coercion, perceived negative pressures and procedural injustice during psychiatric admission.

Methods:

We used validated tools to perform detailed assessments of 107 adult psychiatry inpatients admitted to acute psychiatry admission units at two general hospitals in Dublin, Ireland, between September 2017 and February 2020.

Results:

Among female inpatients (n = 48), perceived coercion on admission was associated with younger age and involuntary status; perceived negative pressures were associated with younger age, involuntary status, seclusion, and positive symptoms of schizophrenia; and procedural injustice was associated with younger age, involuntary status, fewer negative symptoms of schizophrenia, and cognitive impairment. Among females, restraint was not associated with perceived coercion on admission, perceived negative pressures, procedural injustice, or negative affective reactions to hospitalisation; seclusion was associated with negative pressures only. Among male inpatients (n = 59), not being born in Ireland appeared more relevant than age, and neither restraint nor seclusion were associated with perceived coercion on admission, perceived negative pressures, procedural injustice, or negative affective reactions to hospitalisation.

Conclusions:

Factors other than formal coercive practices are primarily linked with perceived coercion. Among female inpatients, these include younger age, involuntary status, and positive symptoms. Among males, not being born in Ireland appears more relevant than age. Further research is needed on these correlations, along with gender-aware interventions to minimise coercive practices and their consequences among all patients.
Inertial focusing of spherical particles in curved microfluidic ducts at moderate Dean numbers
Authors: Harding Brendan , Stokes Yvonne M.
Published: February 2023

We examine the effect of Dean number on the inertial focusing of spherical particles suspended in flow through curved microfluidic ducts. Previous modelling of particle migration in curved ducts assumed the flow rate was small enough that a leading-order approximation of the background flow with respect to the Dean number produces a reasonable model. Herein, we extend our model to situations involving a moderate Dean number (in the microfluidics context) while the particle Reynolds number remains small. Variations in the Dean number cause a change in the axial velocity profile of the background flow which influences the inertial lift force on a particle. Simultaneously, changes in the cross-sectional velocity components of the background flow directly affect the secondary flow induced drag. In keeping the particle Reynolds number small, we continue to approximate the inertial lift force using a regular perturbation while capturing the subtle effects from the modified background flow. This approach pushes the limits at which a regular perturbation is applicable to provide some insights into how variations in the Dean number influence particle focusing. Our results illustrate that, as the extrema in the background flow move towards the outside of edge of the cross-section with increasing Dean number, we observe a similar shift in the stable equilibria of some, but not all, particle sizes. This might be exploited to enhance the lateral separation of particles by size in a number of practical scenarios.
Willingness: Human Rights Crises and State Response in Mexico
Authors: Anaya-Muñoz Alejandro , Gallagher Janice K.
Published: February 2023

States targeted by human rights criticism usually do something—whether ratifying treaties, passing laws, establishing institutions, prosecuting perpetrators, or shifting discourse. But how do we know how coordinated, comprehensive, and effective these actions are? This article proposes five questions to assess how willing a state is to take the steps necessary to meaningfully respond to human rights crises. It applies this approach to two human rights crises in Mexico: femicides and violence against women, and disappearances. This approach effectively differentiates state responses that initially appear similar, demonstrating that the Mexican government has been more willing to address violence against women and femicides than disappearances. An explanation for this difference in outcomes points to a combination of factors related to the underlying preferences of the government involved, the characteristics of victims, and the specific human right being violated.
Infrastructure for Inclusion: Exploring the Evolution of Afro-Colombian Movement and Inclusiveness from the 1991 Constituent Process to the 2016 Peace Agreement
Authors: Rodríguez Iglesias Ana Isabel , Rosen Noah
Published: February 2023

This article explores the experience of the Afro-Colombian movement over the course of two peace processes, investigating the relationship between opportunities for participation and effective inclusion. The 1991 Constituent Assembly that emerged from the peace processes of the late 1980s presented a particularly open opportunity for civil society participation, and yet the Afro-Colombian movement was unable to gain representation in negotiations for a new constitution. In the 2016 peace process with the Fuerzas Armadas Revolucionarias de Colombia, or FARC, despite insistence from the government that its negotiations with FARC were exclusively bilateral, the Afro movement was able to gain a seat at the table along with its Indigenous counterparts and generate a commitment from both parties to protect ethnic rights, known as the Capítulo Étnico (Ethnic Chapter). In contrast to existing literature that focuses on international actors as drivers of inclusion, we argue that effective inclusion reflects in large part the internal capacity, coherence, and unity of the movements themselves.
The Dark Side of Judicialization: Criminalizing Mining Protests in Peru
Authors: Lindt Angela
Published: February 2023

Social conflicts stemming from industrial mining projects in Peru have increasingly been fought in court cases in recent years. This article analyzes the dark side of this judicialization of mining conflicts, a process through which state authorities criminalize participation in social protests and attempt to prevent the mobilization of social movements. This use of the law by public authorities is an example of the so-called shrinking space in which the scope of action of civil society actors is increasingly restricted and constrained worldwide. This article presents an in-depth analysis of a specific court case against a group of mining opponents in the Cajamarca region of Peru. Based on ethnographic field research conducted in Peru, the article discusses three different modalities of the law’s domination, exploring the various ways the law rules those who oppose large-scale extractive projects.
Cannabidiol modulates contextual fear memory consolidation in animals with experimentally induced type-1 diabetes mellitus
Authors: Chaves Yane Costa , Raymundi Ana Maria , Waltrick Ana Paula Farias , de Souza Crippa José Alexandre , Stern Cristina Aparecida Jark , da Cunha Joice Maria , Zanoveli Janaína Menezes
Published: February 2023

Objectives:

In view of the neuroprotective characteristic of cannabidiol (CBD) and its beneficial action on aversive memory in non-diabetic animals, we aimed to investigate in animals with experimentally induced type-1 diabetes mellitus (T1DM) whether CBD treatment would be able to impair the contextual fear memory consolidation, its generalisation and whether the effect would be lasting. We also investigated the CBD effect on anxiety-like responses.

Methods:

After T1DM induction, animals received single or more prolonged treatment with CBD and were submitted to the contextual fear conditioning test. As expression of activity-regulated cytoskeletal-associated (Arc) protein is necessary for memory consolidation, we evaluated its expression in the dorsal hippocampus (DH). For evaluating anxiety-related responses, animals were submitted to the elevated plus maze test (EPMT), in which the time and number of entries in the open arms were used as anxiety index.

Results:

A single injection of CBD impaired the contextual fear memory consolidation and its generalisation, which was evaluated by exposing the animal in a neutral context. This single injection was able to reduce the elevated expression of Arc in the DH from these animals. Interestingly, more prolonged treatment with CBD also impaired the persistence of context-conditioned fear memory and induced an anxiolytic-like effect, as the treated group spent more time in the open arms of the EPMT.

Conclusion:

CBD interferes with contextual fear memory and the dosage regimen of treatment seems to be important. Moreover, we cannot rule out the involvement of emotional aspects in these processes related to fear memory.
Convergent evolution of spherical shells in Miocene planktonic foraminifera documents the parallel emergence of a complex character in response to environmental forcing
Authors: Kiss Peter , Hudáčková Natália , Titschack Jürgen , Siccha Michael G. R. , Heřmanová Zuzana , Silye Lóránd , Ruman Andrej , Rybár Samuel , Kučera Michal
Published: February 2023

The spherical encompassing final chamber of the planktonic foraminifera Orbulina universa is a prime example of a complex character whose evolution has been documented by a sequence of intermediate forms. However, the mechanism that induced evolution of the spherical chamber remain unclear. Here we show that shortly after the emergence of Orbulina, documented throughout the oceans, a convergent evolutionary transition occurred in the semi-isolated Paratethys, leading to the emergence of the endemic Velapertina, which occupied a similar niche to Orbulina in the surface waters. Using X-ray computed tomography scanning, we show that the evolution of the encompassing final chamber involved the same sequence of steps in both lineages, combining a progressively spherical shell shape with changes in the position, number, and sizes of apertures. The similarity in the sequence of character acquisitions suggests structural determinism in the way foraminiferal shells are constructed and the presence of natural selection favoring a spherical morphology. Collectively, the emergence of spherical chambers in the two lineages at a similar time suggests that the evolution of this spectacular complex character occurred in response to a singular environmental driver.
Trampling on Indigenous and Treaty Rights afterR v. Stanley: “That's What You Get for Trespassing”
Authors: Zurawski Cheryl
Published: February 2023

This article reports on institutional ethnographic research into how texts and talk were mobilized in social relations leading to the Government of Saskatchewan's enactment of the Trespass to Property Amendment Act, 2019. The act, proclaimed January 1, 2022, requires First Nations people to get advance permission from rural landowners before exercising their Indigenous and treaty rights to hunt and fish on land deemed private property. Findings (1) connect the 2018 acquittal of Gerald Stanley for the 2016 killing of Colten Boushie to political developments that paved the way for the new legislation and (2) trace how the advance permission requirement at the heart of the new legislation tramples on Indigenous and treaty rights, making it even more difficult for First Nations people to access their traditional territories for purposes such as hunting and fishing.
The Impact of Uncertainty on Investment: Empirical Challenges and a New Estimator
Authors: Li Delong , Sun Yiguo
Published: February 2023

This article proposes a new method for examining the impact on a firm’s investment of uncertainty reflected in its stock-return volatility. We simultaneously address the endogeneity of uncertainty and mismeasurement in Tobin’sQ, but earlier empirical work often neglects one of the two issues. Our nonparametric estimates further suggest that the relation between investment and uncertainty is significantly decreasing and strongly concave. This result contrasts with the existing literature that widely adopts linear regressions. Ignoring nonlinearity or measurement error inQcan lead to a substantial estimation bias. However, the bias due to the endogeneity of uncertainty is small.
Corporate Patenting, Customer Capital, and Financial Market Outcomes
Authors: Ertugrul Mine , Krishnan Karthik , Xu Bo , Yu Qianqian
Published: February 2023

We study how patenting enhances customer capital and creates financial value in a product market characterized by information asymmetry between firm insiders and customers. We find that firms with more and higher quality patents develop greater customer capital, as measured by more positive customer perceptions of product novelty and quality. To establish causality, we exploit the exogenous variation in the random assignment of patent examiners to review applications and use the average examiner leniency as an instrument for patent grants. Our mediation analysis documents a positive impact of patenting on firm performance and financial market valuation through enhanced customer capital.
Multiomic prioritisation of risk genes for anorexia nervosa
Authors: Adams Danielle M. , Reay William R. , Cairns Murray J.
Published: February 2023

Background

Anorexia nervosa (AN) is a psychiatric disorder associated with marked morbidity. Whilst AN genetic studies could identify novel treatment targets, integration of functional genomics data, including transcriptomics and proteomics, would assist to disentangle correlated signals and reveal causally associated genes.

Methods

We used models of genetically imputed expression and splicing from 14 tissues, leveraging mRNA, protein, and mRNA alternative splicing weights to identify genes, proteins, and transcripts, respectively, associated with AN risk. This was accomplished through transcriptome, proteome, and spliceosome-wide association studies, followed by conditional analysis and finemapping to prioritise candidate causal genes.

Results

We uncovered 134 genes for which genetically predicted mRNA expression was associated with AN after multiple-testing correction, as well as four proteins and 16 alternatively spliced transcripts. Conditional analysis of these significantly associated genes on other proximal association signals resulted in 97 genes independently associated with AN. Moreover, probabilistic finemapping further refined these associations and prioritised putative causal genes. The gene WDR6, for which increased genetically predicted mRNA expression was correlated with AN, was strongly supported by both conditional analyses and finemapping. Pathway analysis of genes revealed by finemapping identified the pathway regulation of immune system process (overlapping genes = MST1, TREX1, PRKAR2A, PROS1) as statistically overrepresented.

Conclusions

We leveraged multiomic datasets to genetically prioritise novel risk genes for AN. Multiple-lines of evidence support that WDR6 is associated with AN, whilst other prioritised genes were enriched within immune related pathways, further supporting the role of the immune system in AN.
Policing Sati: Law, Order, and Spectacle in Postcolonial India
Authors: Saxena Saumya
Published: February 2023

This article explores the response of the postcolonial state to the question of widow immolation – sati. It demonstrates that the conversation on the practice of sati at the high point of Hindu law reform in the 1950s reflected the simultaneous pressures on the new democracy to establish rule of law while also accommodating the renewed reverence for tradition and religious custom in an independent nation state. Distinct from the colonial response to sati that treated women as either “helpless and pathetic” or “brave and valiant,” post-independence police records describe women committing sati mostly as “insane” or “not in their senses,” and yet chiefly responsible for their actions. The article contrasts administrative and parliamentary narratives of the crime. Local belief in miracles surrounding the performance of sati not only obscured the experience of the woman's suffering but also made collection of evidence in such a case particularly difficult. This rendered convictions of the abettors of such “painless suicide by insane women” weaker. Legal interventions in sati eventually prompted administrative responses to shift from emphasizing the “uncontrollability” of the spectacle to deeming the spectacle a necessary precondition in distinguishing a sati from suicide.
Visions of public and private mobility: the Kowloon railway terminus in Hong Kong
Authors: Li Adonis M.Y.
Published: February 2023

This article explores and complicates notions of public and private urban mobility through the exploration of one site of transport, the Kowloon railway terminus in Hung Hom, Hong Kong. It considers the question: how did the conflicts and tensions between public and private forms of mobility affect policies for the urban environment in colonial Hong Kong? This article explores the Hung Hom railway terminus and its tensions and interactions with automobility and other forms of transport, most pertinently the bus network. Hong Kong's imperial and colonial context further throws into question seemingly straightforward divisions of public and private mobility.
ON THE NUMBER OF QUADRATIC ORTHOMORPHISMS THAT PRODUCE MAXIMALLY NONASSOCIATIVE QUASIGROUPS
Authors: DRÁPAL ALEŠ , WANLESS IAN M.
Published: February 2023

Let q be an odd prime power and suppose that
$a,b\in \mathbb {F}_q$
are such that
$ab$
and
$(1{-}a)(1{-}b)$
are nonzero squares. Let
$Q_{a,b} = (\mathbb {F}_q,*)$
be the quasigroup in which the operation is defined by
$u*v=u+a(v{-}u)$
if
$v-u$
is a square, and
$u*v=u+b(v{-}u)$
if
$v-u$
is a nonsquare. This quasigroup is called maximally nonassociative if it satisfies
$x*(y*z) = (x*y)*z \Leftrightarrow x=y=z$
. Denote by
$\sigma (q)$
the number of
$(a,b)$
for which
$Q_{a,b}$
is maximally nonassociative. We show that there exist constants
$\alpha \approx 0.029\,08$
and
$\beta \approx 0.012\,59$
such that if
$q\equiv 1 \bmod 4$
, then
$\lim \sigma (q)/q^2 = \alpha $
, and if
$q \equiv 3 \bmod 4$
, then
$\lim \sigma (q)/q^2 = \beta $
.
Contextual realities and poverty traps: why South Asian smallholder farmers negatively evaluate conservation agriculture
Authors: Chaudhary A. , Timsina P. , Karki E. , Sharma A. , Suri B. , Sharma R. , Brown B.
Published: February 2023

Conservation agriculture-based sustainable intensification (CASI) is gaining prominence as an agricultural pathway to poverty reduction and enhancement of sustainable food systems among government and development actors in the Eastern Gangetic Plains (EGP) of South Asia. Despite substantial investment in research and extension programs and a growing understanding of the agronomic, economic and labor-saving benefits of CASI, uptake remains limited. This study explores farmer experiences and perspectives to establish why farmers choose not to implement CASI systems despite a strong body of recent scientific evidence establishing the benefits of them doing so. Through thematic coding of semi-structured interviews, key constraints are identified, which establishes a narrative that current households' resources are insufficient to enable practice change, alongside limited supporting structures for resource supplementation. Such issues create a dependency on subsidies and outside support, a situation that is likely to impact any farming system change given the low-risk profiles of farmers and their limited resource base. This paper hence sets out broad implications for creating change in smallholder farming systems in order to promote the adoption of sustainable agricultural technologies in resource-poor smallholder contexts, especially with regard to breaking the profound poverty cycles that smallholder farmers find themselves in and which are unlikely to be broken by the current set of technologies promoted to them.
Environmental factors influencing the growth and pathogenicity of microgreens bound for the market: a review
Authors: Abaajeh Asomiba Rita , Kingston Caroline Elliott , Harty Mary
Published: February 2023

The world is experiencing a global push toward smart agriculture to help feed the burgeoning population by increasing food security while reducing the carbon footprint of food production. The guidelines for healthy eating have increased globally from five to seven servings of vegetables a day and this had led to the quest for a sustainable form of vegetable production that will reduce the carbon footprint and still provide consumers with the required nutrients. Microgreens contain more nutrients than some mature vegetables and can be cultivated on vertical farms, offering a different approach with the potential to resolve environmental and health challenges. Microgreens are young plantlets grown from the seeds of edible leafy vegetables and are usually eaten raw. They contain high levels of bioactive compounds and can be processed into oils to create valuable cosmetic products. Microgreens have become well-known to chefs and are gaining popularity in upmarket grocery outlets. Consequently, growing microgreens are presenting huge market opportunities worldwide. Their nutritional benefits, easy production methods and short production cycle are some of the reasons they are attractive to growers. The most important factors affecting the growth of microgreens are micro and macro-climates. One challenge to producing microgreens is that the growing environment is ideal for microbial organisms to thrive. As such, microgreens are prone to foodborne pathogens such as E. coli, Listeria and Salmonella. Consequently, the microgreens industry is facing various setbacks including product recalls from Salmonella and Listeria food poisoning outbreaks. In addition, the short shelf-life of microgreens is a serious challenge for getting microgreens to market, this is driving studies in several post-harvest treatments. This review examines the nutrient content and health benefits of microgreens and factors affecting microgreens' growth: temperature, humidity, photoperiod, fertilization, etc. and post-harvest treatments, all of which can potentially impact microbial growth, the phytochemical content and the physical appearance of microgreens bound for the market.
Berufliche Teilhabe und Wiedereingliederung in der Neurorehabilitation
Authors: Claros-Salinas Dolores
Published: February 2023

Berufliche Teilhabe und Wiedereingliederung ist eine komplexe therapeutische Aufgabenstellung und durch Leistungsträger-Anforderungen wie MBOR (medizinisch-beruflich orientierte Rehabilitation) von besonderer Relevanz. Ausgehend von einer Übersicht über wesentliche Faktoren, die den Verlauf einer beruflichen Wiedereingliederung nach neurologischen Erkrankungen beeinflussen können, stellt dieser Band unterschiedliche Ansätze berufsorientierter Neurorehabilitation vor. Zunächst wird detailliert auf die notwendige diagnostische Abklärung eingegangen. Die Therapie-Kapitel beschreiben praxisorientiert, wie Erprobungen beruflicher Ressourcen und Trainings beeinträchtigter Leistungen gestaltet werden können. Außerdem wird thematisiert, wie die häufig schwierige Übergangsphase von längerer klinisch-therapeutischer Versorgung zu ersten Wiedereinarbeitungsschritten im realen Berufsleben begleitet werden kann. Erörtert werden zudem Möglichkeiten der berufsorientierten Nachsorge und langfristigen therapeutischen Unterstützung.
Psychotherapie chronischer Depression
Authors: Klein Jan Philipp , Belz Martina
Published: February 2023

Das Cognitive Behavioral Analysis System of Psychotherapy (CBASP) wurde von James McCullough speziell für die Behandlung der chronischen Depression entwick-elt. Patientinnen und Patienten mit einer chronischen Depression haben häufig bei der Bewältigung von interpersonellen Situationen Schwierigkeiten. Beim Vorgehen nach dem CBASP-Ansatz lassen sich Therapeut:innen persönlich und ganz individuell auf ihre Patient:innen ein, um mit ihnen zusammen interpersonelle Fertigkeiten zu trainieren. Das evidenzbasierte Buch vermittelt praxisnah und anhand zahlreicher Beispiele das therapeutische Vorgehen.
Die 2., vollständig überarbeitete Auflage liefert zunächst eine Beschreibung des Störungsbildes und fasst den aktuellen Forschungsstand zu CBASP zusammen. Anschließend vermittelt das Buch Schritt für Schritt alle Techniken des CBASP und die therapeutische Haltung im Umgang mit chronisch depressiven Patient:innen. Der Ablauf der Therapie, beginnend mit der Vermittlung des Krankheitsmodells, der Fallkonzeptualisierung und dem Training interpersoneller Fertigkeiten bis hin zur Rückfallprohylaxe, wird praxisorientiert erläutert. Vorgestellt werden zudem neue Entwicklungen des Ansatzes, wie z. B. der Umgang mit komorbiden psychischen Störungen und die Anwendung des CBASP in der Gruppe oder im stationären Setting. Anhand zahlreicher Fallbeispiele wird außerdem der Umgang mit schwierigen Therapiesituationen aufgezeigt. Die zahlreichen im Buch enthaltenen Arbeitsmaterialien für die Diagnostik, zur Psychoedukation und für die Arbeit mit den Patient:innen können nach erfolgter Registrierung von der Hogrefe Website heruntergeladen werden.
Penetrative Superplumes in the Mantle of Large Super‐Earth Planets: A Possible Mechanism for Active Tectonics in the Massive Super‐Earths
Authors: Shahnas M. H. , Pysklywec R. N.
Published: February 2023

Recent theoretical studies suggest that the physical and rheological mantle properties in massive rocky planets fall outside conventional behaviors inferred for mantle properties at the Earth's mantle pressures. The vacancy diffusion occurring at low pressures is assumed to be followed by interstitial diffusion above ∼0.1 TPa resulting in viscosity reduction at higher pressures. In addition, the dissociation transition of MgSiO3 post‐perovskite (pPv) into new phases of minerals at 0.9 and 2.1 TPa, both with large negative Clapeyron slopes, has further impact(s) on the style of circulation in the mantle of super‐Earth planets. Further, the electronic contribution of conductivity increases exponentially with temperature at temperatures ∼5000 K and higher. We employ 3D‐controlled volume spherical convection models to explore the style of mantle circulation in large rocky super‐Earth planets with different core temperatures. Our numerical models resembling a GJ 876 d size super‐Earth reveal that due to the buffering influence of the pPv‐dissociation transition at ∼0.9 TPa, for deep mantle viscosities lower than ∼1022 Pa.s a small‐scale convective layer may develop at the top of the core‐mantle boundary (CMB). Penetrative superplumes originating from deep mantle‐layered regions can maintain the heat flux from the CMB required for the planet's geodynamo, and can survive for billions of years reaching shallow depths of the mantle without significant lateral migration. The strength of the focused penetrative superplumes that can potentially sustain surface volcanism and plate tectonics is enhanced with increasing CMB temperature, but diminished by higher rates of internal heating.
Turbulent Drag at the Ice‐Ocean Interface of Europa in Simulations of Rotating Convection: Implications for Nonsynchronous Rotation of the Ice Shell
Authors: Hay H. C. F. C. , Fenty I. , Pappalardo R. T. , Nakayama Y.
Published: February 2023

Europa's geologically scarred surface shows significant evidence that the ice shell may have rotated nonsynchronously in the past. The long‐term spin state of the ice shell is controlled by the time‐mean torques acting upon it. A torque that has not been previously considered is exerted due to drag from oceanic currents beneath the ice. We estimate this torque for the first time by performing global, nonhydrostatic, three‐dimensional simulations of Europa's ocean, including nonlinear turbulent boundary layer drag at the seafloor and ice‐ocean interface. Our simulations show that ocean dynamics, which manifest in alternating east‐west jets, result in a net torque on the ice shell. The torque can act to either spin up or spin down the ice shell depending on the strength of convection, suggesting that a torque reversal can occur as Europa's interior thermally evolves. Scaling analysis indicates that an average jet speed of at least ∼1 cm s−1 is required for the ice‐ocean torque to be comparable to the tidal torque acting to spin up the ice shell. Our results suggest that ocean currents may contribute to any nonsynchronous rotation of the ice shell. Consequently, Europa's present‐day spin state may hold information about the dynamics of its subsurface ocean.
Light People: Prof. Sir John Pendry, father of metamaterials, spoke about the future of meta
Authors: Guo Chenzi , Luo Yu
Published: February 2023

Editorial

When consulting with the Marconi company in 1995, Prof. Sir John Pendry uncovered exotic structures that gave negative permittivity and negative permeability, respectively. In 1999, Prof. Pendry introduced split ring resonators (SRRs), and later in 2000, Prof. David Smith and Prof. Sheldon Schultz experimentally showed that periodic array of SRRs and continuous wires previously proposed by Prof. Pendry could exhibit simultaneously negative values of effective permeability and permittivity at the same frequency. Shortly after, Prof. Pendry revealed that a slab of material with simultaneous negative permittivity and permeability could challenge the Abbé diffraction limit on traditional lenses and focus all Fourier components of a point object onto a perfect image, leading to a “perfect lens”. The vision of a perfect lens attracted extensive research interest and opened a new field which was later widely known as metamaterials. Now two decades on, the explosion of metamaterials has revolutionized numerous researches in physics, materials science, chemistry, and engineering. To shed light on the research direction of metamaterials, Light: Science & Applications invited Sir John Pendry, father and living legend of metamaterials, to speak about the future of metamaterials. The original interview can be accessed in Supplementary video.
Acute psilocybin enhances cognitive flexibility in rats
Authors: Torrado Pacheco Alejandro , Olson Randall J. , Garza Gabriela , Moghaddam Bita
Published: February 2023

Psilocybin has been shown to improve symptoms of depression and anxiety when combined with psychotherapy or other clinician-guided interventions. To understand the neural basis for this pattern of clinical efficacy, experimental and conceptual approaches that are different than traditional laboratory models of anxiety and depression are needed. A potential novel mechanism is that acute psilocybin improves cognitive flexibility, which then enhances the impact of clinician-assisted interventions. Consistent with this idea, we find that acute psilocybin robustly improves cognitive flexibility in male and female rats using a task where animals switched between previously learned strategies in response to uncued changes in the environment. Psilocybin did not influence Pavlovian reversal learning, suggesting that its cognitive effects are selective to enhanced switching between previously learned behavioral strategies. The serotonin (5HT) 2 A receptor antagonist ketanserin blocked psilocybin’s effect on set-shifting, while a 5HT2C-selective antagonist did not. Ketanserin alone also improved set-shifting performance, suggesting a complex relationship between psilocybin’s pharmacology and its impact on flexibility. Further, the psychedelic drug 2,5-Dimethoxy-4-iodoamphetamine (DOI) impaired cognitive flexibility in the same task, suggesting that this effect of psilocybin does not generalize to all other serotonergic psychedelics. We conclude that the acute impact of psilocybin on cognitive flexibility provides a useful behavioral model to investigate its neuronal effects relevant to its positive clinical outcome.
Differential regulation of H3K9/H3K14 acetylation by small molecules drives neuron-fate-induction of glioma cell
Authors: Liu Xincheng , Guo Cui , Leng Tiandong , Fan Zhen , Mai Jialuo , Chen Jiehong , Xu Jinhai , Li Qianyi , Jiang Bin , Sai Ke , Yang Wenzhuo , Gu Jiayu , Wang Jingyi , Sun Shuxin , Chen Zhijie , Zhong Yingqian , Liang Xuanming , Chen Chaoxin , Cai Jing , Lin Yuan , Liang Jiankai , Hu Jun , Yan Guangmei , Zhu Wenbo , Yin Wei
Published: February 2023

Differentiation therapy using small molecules is a promising strategy for improving the prognosis of glioblastoma (GBM). Histone acetylation plays an important role in cell fate determination. Nevertheless, whether histone acetylation in specific sites determines GBM cells fate remains to be explored. Through screening from a 349 small molecule-library, we identified that histone deacetylase inhibitor (HDACi) MS-275 synergized with 8-CPT-cAMP was able to transdifferentiate U87MG GBM cells into neuron-like cells, which were characterized by cell cycle arrest, rich neuron biomarkers, and typical neuron electrophysiology. Intriguingly, acetylation tags of histone 3 at lysine 9 (H3K9ac) were decreased in the promoter of multiple oncogenes and cell cycle genes, while ones of H3K9ac and histone 3 at lysine 14 (H3K14ac) were increased in the promoter of neuron-specific genes. We then compiled a list of genes controlled by H3K9ac and H3K14ac, and proved that it is a good predictive power for pathologic grading and survival prediction. Moreover, cAMP agonist combined with HDACi also induced glioma stem cells (GSCs) to differentiate into neuron-like cells through the regulation of H3K9ac/K14ac, indicating that combined induction has the potential for recurrence-preventive application. Furthermore, the combination of cAMP activator plus HDACi significantly repressed the tumor growth in a subcutaneous GSC-derived tumor model, and temozolomide cooperated with the differentiation-inducing combination to prolong the survival in an orthotopic GSC-derived tumor model. These findings highlight epigenetic reprogramming through H3K9ac and H3K14ac as a novel approach for driving neuron-fate-induction of GBM cells.
A novel Hoxd13 mutation causes synpolydactyly and promotes osteoclast differentiation by regulating pSmad5/p65/c-Fos/Rank axis
Authors: Zhang Lishan , Fang Ziqi , Cheng Guangdong , He Mengting , Lin Yanliang
Published: February 2023

The mutations of HOXD13 gene have been involved in synpolydactyly (SPD), and the polyalanine extension mutation of Hoxd13 gene could lead to SPD in mice. In this study, a novel missense mutation of Hoxd13 (NM_000523: exon2: c.G917T: p.R306L) was identified in a Chinese family with SPD. The mice carrying the corresponding Hoxd13mutation were generated. The results showed that the homozygous mutation of Hoxd13 also caused SPD, but heterozygous mutation did not affect limbs development, which was different from that of SPD patients. With the increasing generation, the mice with homozygous Hoxd13 mutation presented more severe syndactyly. Western blotting showed that this mutation did not affect the protein expression of Hoxd13, suggesting that this mutation did not result in haploinsufficiency. Further analysis demonstrated that this homozygous Hoxd13mutation promoted osteoclast differentiation and bone loss, and enhanced the mRNA and protein expression of osteoclast-related genes Rank, c-Fos, and p65. Meanwhile, this homozygous Hoxd13 mutation elevated the level of phosphorylated Smad5 (pSmad5). Co-immunoprecipitation verified that this mutation attenuated the interaction between pSmad5 and HOXD13, suggesting that this mutation released more pSmad5. Inhibition of pSmad5 reduced the expression of Rank, c-Fos, and p65 despite in the mutation group. In addition, inhibition of pSmad5 repressed the osteoclast differentiation. ChIP assay confirmed that p65 and c-Fos could bind to the promoter of Rank. These results suggested that this novel Hoxd13 mutation promoted osteoclast differentiation by regulating Smad5/p65/c-Fos/Rank axis, which might provide a new insight into SPD development.
SREBP modulates the NADP+/NADPH cycle to control night sleep in Drosophila
Authors: Mariano Vittoria , Kanellopoulos Alexandros K. , Aiello Giuseppe , Lo Adrian C. , Legius Eric , Achsel Tilmann , Bagni Claudia
Published: February 2023

Sleep behavior is conserved throughout evolution, and sleep disturbances are a frequent comorbidity of neuropsychiatric disorders. However, the molecular basis underlying sleep dysfunctions in neurological diseases remains elusive. Using a model for neurodevelopmental disorders (NDDs), theDrosophila Cytoplasmic FMR1 interacting proteinhaploinsufficiency (Cyfip85.1/+), we identify a mechanism modulating sleep homeostasis. We show that increased activity of the sterol regulatory element-binding protein (SREBP) inCyfip85.1/+flies induces an increase in the transcription of wakefulness-associated genes, such as the malic enzyme (Men), causing a disturbance in the daily NADP+/NADPH ratio oscillations and reducing sleep pressure at the night-time onset. Reduction in SREBP or Men activity inCyfip85.1/+flies enhances the NADP+/NADPH ratio and rescues the sleep deficits, indicating that SREBP and Men are causative for the sleep deficits inCyfipheterozygous flies. This work suggests modulation of the SREBP metabolic axis as a new avenue worth exploring for its therapeutic potential in sleep disorders.
A nitric-oxide driven chemotactic nanomotor for enhanced immunotherapy of glioblastoma
Authors: Chen Huan , Li Ting , Liu Zhiyong , Tang Shuwan , Tong Jintao , Tao Yingfang , Zhao Zinan , Li Nan , Mao Chun , Shen Jian , Wan Mimi
Published: February 2023

The major challenges of immunotherapy for glioblastoma are that drugs cannot target tumor sites accurately and properly activate complex immune responses. Herein, we design and prepare a kind of chemotactic nanomotor loaded with brain endothelial cell targeting agent angiopep-2 and anti-tumor drug (Lonidamine modified with mitochondrial targeting agent triphenylphosphine, TLND). Reactive oxygen species and inducible nitric oxide synthase (ROS/iNOS), which are specifically highly expressed in glioblastoma microenvironment, are used as chemoattractants to induce the chemotactic behavior of the nanomotors. We propose a precise targeting strategy of brain endothelial cells-tumor cells-mitochondria. Results verified that the released NO and TLND can regulate the immune circulation through multiple steps to enhance the effect of immunotherapy, including triggering the immunogenic cell death of tumor, inducing dendritic cells to mature, promoting cytotoxic T cells infiltration, and regulating tumor microenvironment. Moreover, this treatment strategy can form an effective immune memory effect to prevent tumor metastasis and recurrence.
On-demand male contraception via acute inhibition of soluble adenylyl cyclase
Authors: Balbach Melanie , Rossetti Thomas , Ferreira Jacob , Ghanem Lubna , Ritagliati Carla , Myers Robert W. , Huggins David J. , Steegborn Clemens , Miranda Ileana C. , Meinke Peter T. , Buck Jochen , Levin Lonny R.
Published: February 2023

Nearly half of all pregnancies are unintended; thus, existing family planning options are inadequate. For men, the only choices are condoms and vasectomy, and most current efforts to develop new contraceptives for men impact sperm development, meaning that contraception requires months of continuous pretreatment. Here, we provide proof-of-concept for an innovative strategy for on-demand contraception, where a man would take a birth control pill shortly before sex, only as needed. Soluble adenylyl cyclase (sAC) is essential for sperm motility and maturation. We show a single dose of a safe, acutely-acting sAC inhibitor with long residence time renders male mice temporarily infertile. Mice exhibit normal mating behavior, and full fertility returns the next day. These studies define sAC inhibitors as leads for on-demand contraceptives for men, and they provide in vivo proof-of-concept for previously untested paradigms in contraception; on-demand contraception after just a single dose and pharmacological contraception for men.
Dynamic interplay between non-coding enhancer transcription and gene activity in development
Authors: Hamamoto Kota , Umemura Yusuke , Makino Shiho , Fukaya Takashi
Published: February 2023

Non-coding transcription at the intergenic regulatory regions is a prevalent feature of metazoan genomes, but its biological function remains uncertain. Here, we devise a live-imaging system that permits simultaneous visualization of gene activity along with intergenic non-coding transcription at single-cell resolution in Drosophila. Quantitative image analysis reveals that elongation of RNA polymerase II across the internal core region of enhancers leads to suppression of transcriptional bursting from linked genes. Super-resolution imaging and genome-editing analysis further demonstrate that enhancer transcription antagonizes molecular crowding of transcription factors, thereby interrupting the formation of a transcription hub at the gene locus. We also show that a certain class of developmental enhancers are structurally optimized to co-activate gene transcription together with non-coding transcription effectively. We suggest that enhancer function is flexibly tunable through the modulation of hub formation via surrounding non-coding transcription during development.
Reconstruction of the tumor spatial microenvironment along the malignant-boundary-nonmalignant axis
Authors: Xun Zhenzhen , Ding Xinyu , Zhang Yao , Zhang Benyan , Lai Shujing , Zou Duowu , Zheng Junke , Chen Guoqiang , Su Bing , Han Leng , Ye Youqiong
Published: February 2023

Although advances in spatial transcriptomics (ST) enlarge to unveil spatial landscape of tissues, it remains challenging to delineate pathology-relevant and cellular localizations, and interactions exclusive to a spatial niche (e.g., tumor boundary). Here, we develop Cottrazm, integrating ST with hematoxylin and eosin histological image, and single-cell transcriptomics to delineate the tumor boundary connecting malignant and non-malignant cell spots in tumor tissues, deconvolute cell-type composition at spatial location, and reconstruct cell type-specific gene expression profiles at sub-spot level. We validate the performance of Cottrazm along the malignant-boundary-nonmalignant spatial axis. We identify specific macrophage and fibroblast subtypes localized around tumor boundary that interacted with tumor cells to generate a structural boundary, which limits T cell infiltration and promotes immune exclusion in tumor microenvironment. In this work, Cottrazm provides an integrated tool framework to dissect the tumor spatial microenvironment and facilitates the discovery of functional biological insights, thereby identifying therapeutic targets in oncologic ST datasets.