bluuebunny/crossref_metadata_2025 huggingface dataset:
SeptAsTERS- SeptiCyte® RAPID as assessment tool for early recognition of sepsis – a prospective observational study
Authors: von der Forst M. , Back L. , Tourelle K.M. , Gruneberg D. , Weigand M.A. , Schmitt F.C.F. , Dietrich Maximilian
Published: November 2024

Purpose

Early recognition of sepsis is critical to patient outcome, with mortality increasing with every hour of delay in treatment. The aim of this study was to investigate the use of a point-of-care molecular host response assay to differentiate sepsis from inflammation after surgery.

Methods

Three molecular host response assays (SeptiCyte® RAPID) were performed in 61 patients after major abdominal surgery with admission to the intensive care unit and drawn blood cultures. The first (T0) was taken ± 3 h around the time of obtaining blood cultures, the second 24 h later (T24) and the third at discharge from the intensive care unit (Tex). The primary endpoint was the agreement of SeptiCyte® RAPID results with the diagnosis of sepsis. SeptiScore® indicates sepsis probability (low risk 0 - high risk 15). Patients were retrospectively classified into sepsis and inflammation by three blinded experts.

Results

25 (42.4%) patients were categorized as “inflammation” and 34 (57.6%) patients as “sepsis”. At T0 and T24 septic patients showed significantly higher mean SeptiScores® of 8.0 (± 2.2 SD) vs. 6.3 (± 2.1 SD) and 8.5 (± 2.1 SD) vs. 6.2 (± 1.8 SD), respectively. The Receiver Operating Curves (ROC) for the ability to discriminate between sepsis and inflammation had an Area Under the Curve (AUC) of 0.71 (T0) and 0.80 (T24).

Conclusion

Embedded in a comprehensive diagnostic algorithm molecular host response analysis could broaden the possibilities for infection diagnostics to differentiate between sepsis and inflammatory response after surgery. But validation in larger cohorts is needed.
The Neuroanatomy Riddle Book
Authors: Dolbow James , Edmondson Joshua , Fotedar Neel
Published: November 2024

If you love neuroanatomy, chances are that you also love a good puzzle. Providing a fun and refreshing alternative method of learning and reviewing neuroanatomical structures, this engaging book is perfect for those who love both neuroanatomy and riddles. 150 four-line riddles describe specific high-yield neuroanatomical structures in cryptic form. These could be lobes or general regions of the brain, blood vessels supplying key neurological structures, specific anatomical brain structures, or neuroanatomical spaces and passages. Hints such as general location in the body, the structure's function or dysfunction if impaired, or its Latin or Greek name origin are incorporated. On the following page from each riddle, the answer is given along with a complete description of the structure, history of the structure, clinical correlation and more key information For even more challenging neuroscience puzzles, consider the Neurology Riddle Book, which includes riddles about neurological syndromes, conditions and diseases.
Nicky Hockly’s 30 Essentials for Using Artificial Intelligence
Authors: Hockly Nicky
Published: November 2024

In this user-friendly book, Nicky Hockly draws on research and her own experience to examine the benefits and challenges of using AI in language teaching. The book provides a range of guidance on good practices in using the technology, with simple tips for applying the learning. It explores some of the key ethical, moral, philosophical and legal questions around using AI and covers topics including accessibility, data ownership and concerns around students cheating. The book also includes support for using AI to help teachers and learners develop. Nicky Hockly's 30 Essentials for Using Artificial Intelligence is an essential guide for teachers of all levels of experience.
Merovingian Worlds
Authors: Palmer James T.
Published: November 2024

The Merovingian Kingdoms (c. 450–751) dominated much of what is now France, Belgium, and Germany, and were the most powerful and long-lived of the states that transformed the inheritance of Rome after the Crisis of the Fifth Century. Yet they often remain representative of an imagined 'Dark Age', in which civility was eroded by migration, violence, illiteracy, superstition, and a retreat from globality. Through a deep exploration of manuscripts, charters, and burials, Merovingian Worlds offers a fresh account of the period, outlining its complexities, diversity and creativity. This was a world built on dynamic political, socio-economic, cultural, and religious interactions, and shaped by its wide-ranging connections from Britain and Ireland to Byzantium and beyond. The book provides a critical introduction to the rich source material and the modern debates that shaped our perception of Western Europe after the Fall of Rome.
Profits and Persecution
Authors: Hayes Peter
Published: November 2024

What role did German big business play in the persecution of European Jews during the Holocaust? What were its motivations? And how did it respond to changing social and economic circumstances after the war? Profits and Persecution examines how the leaders of Germany's largest industrial and financial enterprises played a key part in the catastrophes and crimes of their nation in the first half of the twentieth century. Drawing on evidence concerning the roughly one hundred most significant German firms of the Nazi era, Peter Hayes explores how large German corporations dealt with Jews, their property, and their labor. This study unites business history and the history of the Holocaust to consider both the economic and personal motivations that rendered German corporate leaders complicit in the actions of the Nazi Party. In doing so, it demonstrates how ordinary, familiar thought processes came to serve the ideological purposes of the Third Reich with lethal consequences.
U.S. and EU Non-Horizontal Merger Guidelines: A Friendly Game of Leapfrog
Authors: Grzejdziak Łukasz
Published: November 2024

The accepted approach of competition law to non-horizontal mergers, largely based on the Chicago School of Antitrust Law and Economics paradigms, is criticized on both sides of the Atlantic as too lenient, disregarding developments of economic theory, and no longer adequate in the reality of the digital economy. Current economic research confirms the legitimacy of fears about the effects of non-horizontal concentrations that were raised before the Chicago School put them into doubt. The disbelief in the accuracy of the former US non-horizontal mergers policy resulted in the Federal Trade Commission and the Antitrust Division of the Department of Justice adopting new Vertical Merger Guidelines. The changes introduced were considered insufficient, which led to the unilateral repeal of the guidelines by the FTC and the start of work on new guidelines introducing a stricter approach. The new U.S. 2023 Merger Guidelines introduced far-reaching changes taking into account the modern views of economists and empirical research on vertical mergers. Comparatively, the EU Commission’s Non–Horizontal Merger Guidelines still do not fully correspond to what empirical research and contemporary economic theories say about the possible effects of vertical mergers. Thus, the revision of the EU guidelines seems necessary.
Shipping the Color Line: Migration and Transport Policy in the British Empire, 1943–51
Authors: Foks Freddy
Published: November 2024

This article looks again at the history of British migration policy in the 1940s and 1950s by centering international and imperial politics, and by drawing on archives related to shipping. These sources suggest that the British government sought to reactivate a system of race-segregated mobility across the Empire-Commonwealth after the Second World War. This involved subsidizing fares for emigrants bound for Australia, transporting migrants from Europe to the UK, and withdrawing shipping from routes that connected the Caribbean to the UK. Very soon, however, these policies came under strain. There were not enough deep-sea ships to meet demand for berths to Australia or to bring over recruited European migrants. Then the Australian government found new ways to ship migrants from continental Europe by signing a deal with the International Refugee Organization, challenging UK policy to keep Australian immigration British. Meanwhile, new routes were opened up from the Caribbean and South Asia to the UK. These trends raised a host of dilemmas for policymakers and all related to transport infrastructure. Thinking about transport can deepen our understanding of migration history, and the article's conclusion suggests some of the ways that taking such an approach can contribute to existing explanations for the government's fateful decision to amend the UK's nationality and citizenship legislation during the 1960s.
Revisiting the impact of singularity on the Identified Victim Effect: Replication and extension of Kogut and Ritov (2005a) Study 2
Authors: Majumder Rajarshi , Tai Yik Long , Ziano Ignazio , Feldman Gilad
Published: November 2024

The identified victim effect is the phenomenon in which people tend to contribute more to identified than to unidentified victims. Kogut and Ritov (Journal of Behavioral Decision Making, 18(3), 157–167, 2005) found that the identified victim effect was limited to a single victim and driven by empathic emotions. In a pre-registered experiment with an online U.S. American MTurk sample on CloudResearch (N = 2003), we conducted a close replication and extension of Experiment 2 from Kogut and Ritov (Journal of Behavioral Decision Making, 18(3), 157–167, 2005). The replication findings failed to provide empirical support for the identified single victim effect hypothesis since we found no evidence of differences in willingness to contribute when comparing a single identified victim to a single unidentified victim (η2p = .00, 90% CI [0.00, 0.00]), and no indication for the target article’s interaction between singularity and identifiability (original: η2p = .062, 90% CI [0.01, 0.15]; replication: η2p = .00, 90% CI [0.00, 0.00]). Extending the replication to conduct a conceptual replication of Kogut and Ritov (Organizational Behavior and Human Decision Processes, 104(2), 150–157, 2007), we investigated a boundary condition of the effect—group belonging. We found support for an ingroup bias in helping behaviors and indications for empathic emotions and perceived responsibility contributing to this effect. We discuss differences between our study and the target article and implications for the literature on the identified victim effect.
The entrainment hypothesis – 80 years old and still going strong
Authors: Cenedese Claudia
Published: November 2024

The entrainment hypothesis states that the mean inflow velocity across the boundary of a turbulent flow is proportional to a characteristic velocity of the flow. Proposed by G. I. Taylor approximately 80 years ago, it is still a common model of turbulence closure widely used in environmental engineering and geophysical fluid mechanics. Although it is a very simple concept and mathematical model, it has proven to be able to predict the entrainment in a variety of geophysical flows, e.g. convective clouds and plumes from erupting volcanoes in the atmosphere; dense water overflows and turbidity currents in the ocean; magma injection in a magma chamber in the interior of the Earth, to name just a few. In a seminal paper, Turner (J. Fluid Mech., vol. 173, 1986, pp. 431–471) presents a variety of laboratory and geophysical flows to illustrate the success of the entrainment hypothesis and discusses why such a simple hypothesis works so well even when the original assumptions are no longer valid.
Falling clouds
Authors: Guazzelli Élisabeth
Published: November 2024

The featured article ‘Break-up of a falling drop containing dispersed particles’ (Nitsche and Batchelor, J. Fluid Mech., 1997, vol. 340, pp. 161–175) is G. K. Batchelor's last published paper with his former postdoctoral associate J. M. Nitsche. The objective of the study was to investigate the randomness of the velocities of interacting rigid particles falling under gravity through a viscous fluid at a small Reynolds number and its consequence for the breakup of a falling cloud of particles. The study focused on a quintessential problem of the collective dynamics of interacting particles and has been an inspiration for subsequent work.
Low-frequency unsteadiness in laminar separation bubbles
Authors: Malmir Fatemeh , Di Labbio Giuseppe , Le Floc'h Arnaud , Dufresne Louis , Weiss Julien , Vétel Jérôme
Published: November 2024

Low-frequency phenomena in an incompressible pressure-induced laminar separation bubble (LSB) on a flat plate is investigated using direct numerical simulation. The LSB configuration of Spalart and Strelets (J. Fluid Mech., vol. 403, 2000, pp. 329–349) is used. Wall pressure spectra indicate low-frequency-flapping

$(St \sim 0.08)$

and high-frequency-shedding

$(St \sim 1.52)$

regimes. Conditional velocity averages based on the fraction of reversed flow reveal the low frequency as an expansion/contraction of the LSB. While the high frequency only exhibits exponential growth within the LSB up to breakdown of the spanwise rollers, the low frequency and velocity fluctuations exhibit exponential growth upstream of separation. Instantaneous flow fields reveal large streamwise streaky structures forming within the LSB and extending past reattachment, much like high and low speed streaks in turbulent boundary layers. A predominance of sweep-like events (

$Q4$

) is observed during contraction and of ejection-like events (

$Q2$

) during expansion. These motions appear as dominant low-frequency modes in three-dimensional proper orthogonal and dynamic mode decompositions, exhibiting spatial amplification from separation to reattachment. The advection of a group of spanwise alternating streaky structures past the LSB results in an overall contraction after which the bubble expands to its ‘unforced’ state in the absence of the streaks. The low frequency then corresponds to the time it takes for streaks to form, amplify and advect past the LSB from separation to reattachment. This behaviour is linked to the mean flow deformation reported by Marxen and Rist (J. Fluid Mech., vol. 660, 2010, pp. 37–54), where the presence of streaks results in reduced mean bubble size. The formation of these streaky structures, in the absence of free stream turbulence, may be attributed to an absolute instability of the LSB due to the development of a secondary bubble within the primary.
Wave scattering by an isolated cyclogeostrophic vortex
Authors: Uncu Jeffrey , Grisouard Nicolas
Published: November 2024

The propagation paths of oceanic internal tides are influenced by their interactions with vortices. We examine the scattering effect that an isolated vortex in (cyclo)geostrophic balance has on a rotating shallow-water plane wave. We run a suite of simulations in which we vary the non-dimensional vorticity of the vortex,

$Ro$

, the relative scale of the vortex size to the Rossby radius of deformation,

$Bu$

, and the size of the vortex compared with the plane wave wavelength,

$K$

. We compare the scattered wave flux pattern with ray-tracing predictions. Ray-tracing predictions are relatively insensitive to

$K$

in the

$1< K<4$

range we investigate; however, they generally underestimate the broad angles of the shallow-water wave scattering patterns, especially for the lower end of the

$K$

range. We then measure the ratio of the scattered wave energy flux to the incoming wave energy flux, denoted by

$S$

, for each simulation. We find that

$S$

follows a power law

$S \propto (FrK)^2$

when

$S < 0.2$

, where

$Fr = Ro/\sqrt {Bu}$

is the Froude number. When

$S>0.2$

, it starts plateauing.
Equivariant covering type and the number of vertices in equivariant triangulations
Authors: Govc Dejan , Marzantowicz Wacław , Pavešić Petar
Published: November 2024

We introduce the notion of the equivariant covering type of a space X on which a finite group G acts and study its properties. The equivariant covering type measures the size of G-equivariant good covers of X and is thus an extension of the covering type of a space, introduced by Karoubi and Weibel. We show that the equivariant covering type is a G-homotopy invariant and describe its relation with other G-invariants, like the equivariant LS-category, G-genus, and the multiplicative structures of equivariant cohomology theories. We also compute the G-covering type of regular G-graphs, give estimates for orientation-preserving actions on surfaces and for the projectivizations of complex representations of G and cohomology spheres. As an application, we derive estimates of sizes of minimal G-triangulations for various G-spaces.
A remark on the well-posedness of the modified KdV equation in L2
Authors: Forlano Justin
Published: November 2024

We study the real-valued modified KdV equation on the real line and the circle in both the focusing and the defocusing cases. By employing the method of commuting flows introduced by Killip and Vişan (2019), we prove global well-posedness in H
s
for

$0\leq s \lt \tfrac{1}{2}$

. On the line, we show how the arguments in the recent article by Harrop-Griffiths, Killip, and Vişan (2020) may be simplified in the higher regularity regime

$s\geq 0$

. On the circle, we provide an alternative proof of the sharp global well-posedness in L2 due to Kappeler and Topalov (2005) and also extend this to the large-data focusing case.
A cryptic elapid snake persists in the wake of catastrophic wildfires
Authors: Hodgson Mitchell J. , Ross Alexandra K. , Lapwong Yingyod , Cuartas Santiago , Roberts Bridget , Price Owen , Webb Jonathan , Sentinella Nicola , Lee Joshua , Laffan Shawn W. , Burley Hugh M. , McIntosh Finlay , Letnic Mike
Published: November 2024

The increased severity and frequency of bushfires accompanying human-induced global warming have dire implications for biodiversity conservation. Here we investigate the response of a cryptic, cool-climate elapid, the mustard-bellied snake Drysdalia rhodogaster, to the extensive Black Summer fires of 2019/2020 in south-eastern Australia. The species is categorized as Least Concern on the IUCN Red List (last assessed in 2017), but because a large part of its range was burnt during the Black Summer and little was known about its ecology, D. rhodogaster was identified as a priority species for post-fire impact assessment. We evaluated three lines of evidence to assess the impact of the Black Summer fires on D. rhodogaster. Habitat suitability modelling indicated that c. 46% of the predicted range of the species was affected by bushfire. Field surveys conducted 9–36 months post-fire and collation of records from public databases submitted 0–24 months post-fire indicated that D. rhodogaster persisted in burnt landscapes. Fire severity and proportion of the landscape that was burnt within a 1,000-m radius of survey sites were poor predictors of site occupancy by D. rhodogaster. Although conclusions regarding the effects of fire on D. rhodogaster are limited because of the lack of baseline data, it is evident that the species has persisted across the landscape in the wake of extensive bushfires. Our work highlights the need for baseline knowledge on cryptic species even when they are categorized as Least Concern, as otherwise assessments of the impacts of catastrophic events will be constrained.
Cannabis use and cognitive biases in people with first-episode psychosis and their siblings
Authors: Roldan L. , Sánchez-Gutiérrez T. , Fernández-Arias I. , Rodríguez-Toscano E. , López G. , Merchán-Naranjo J. , Calvo A. , Rapado-Castro M. , Parellada M. , Moreno C. , Ferraro L. , La Barbera D. , La Cascia C. , Tripoli G. , Di Forti M. , Murray R.M. , Quattrone D. , Morgan C. , Gayer-Anderson C. , Jones P. B. , Jongsma H.E. , Kirkbride J.B. , van Os J. , García-Portilla P. , Al-Halabí S. , Bobes J. , de Haan L. , Bernardo M. , Santos J.L. , Sanjuán J. , Arrojo M. , Szoke A. , Rutten B.P. , Stilo S. A. , Tarricone I. , Lasalvia A. , Tosato S. , Llorca P.-M. , Menezes P. Rossi , Selten J-P , Tortelli A. , Velthorst E. , Del-Ben C.M. , Arango C. , Díaz-Caneja C. M.
Published: November 2024

Background

Cannabis use and familial vulnerability to psychosis have been associated with social cognition deficits. This study examined the potential relationship between cannabis use and cognitive biases underlying social cognition and functioning in patients with first episode psychosis (FEP), their siblings, and controls.

Methods

We analyzed a sample of 543 participants with FEP, 203 siblings, and 1168 controls from the EU-GEI study using a correlational design. We used logistic regression analyses to examine the influence of clinical group, lifetime cannabis use frequency, and potency of cannabis use on cognitive biases, accounting for demographic and cognitive variables.

Results

FEP patients showed increased odds of facial recognition processing (FRP) deficits (OR = 1.642, CI 1.123–2.402) relative to controls but not of speech illusions (SI) or jumping to conclusions (JTC) bias, with no statistically significant differences relative to siblings. Daily and occasional lifetime cannabis use were associated with decreased odds of SI (OR = 0.605, CI 0.368–0.997 and OR = 0.646, CI 0.457–0.913 respectively) and JTC bias (OR = 0.625, CI 0.422–0.925 and OR = 0.602, CI 0.460–0.787 respectively) compared with lifetime abstinence, but not with FRP deficits, in the whole sample. Within the cannabis user group, low-potency cannabis use was associated with increased odds of SI (OR = 1.829, CI 1.297–2.578, FRP deficits (OR = 1.393, CI 1.031–1.882, and JTC (OR = 1.661, CI 1.271–2.171) relative to high-potency cannabis use, with comparable effects in the three clinical groups.

Conclusions

Our findings suggest increased odds of cognitive biases in FEP patients who have never used cannabis and in low-potency users. Future studies should elucidate this association and its potential implications.
Adjusting to dementia as part of life: an actantial analysis of agency reconstruction following diagnosis of young onset dementia
Authors: Hautsalo Katja , Pirhonen Jari , Pietilä Ikka
Published: November 2024

The agency of a person with young onset dementia (YOD) changes owing to individual symptoms, uncertainty about the speed of progression and the severity of YOD. Dementia usually greatly interrupts life and reduces agency. Previous studies show that some people and families integrate and cope with dementia better than others. This study aimed to find out how YOD changes the agency of the person who has it and what family members’ role is in forming their agency. The data were collected in Finland in semi-structured interviews with 14 people with YOD and 15 family members, about a year after the diagnosis. These two data sets were analysed with a narrative method, actantial analysis. A wide variety of elements, both human and non-human factors, were found to promote and undermine agency. It was found that people with YOD need both integrity and flexibility to reconstruct their own agency. Resources support them in this process of reconstruction, and hinderers interrupt the process. This combination of integrity and flexibility, resources and hinderers, generates how people with YOD recount the future, the aims they set and how they reconstruct their agency. Other people, especially family members, are part of this dynamic process and when their relationship is cohesive, the agency of both parties increases. The participants used ideal and burdensome storylines to narrate factors that supported or interrupted their agency. Based on our findings, narrating one’s situation is, for coping, not only a means but its very basis.
The Tragedy Trap: On the Tragicized Politics of Nuclear Weapons and Armed Drones and the Making of Unaccountability
Authors: Pelopidas Benoît , Renic Neil C.
Published: November 2024

The discourse of tragedy has significant value in a military context, reminding us of the temptations of hubris, the prevalence of moral dilemmas, and the inescapable limits of foresight. Today, however, this discourse is drawn upon too heavily. Within the tragicized politics of nuclear and drone violence, foreseeable and solvable problems are reconceptualized as intractable dilemmas, and morally accountable agents are reframed as powerless observers. The tragedy discourse, when wrongly applied by policymakers and the media, indulges the very hubris the tragic recognition is intended to caution against. This article clarifies the limits of “tragedy” in the context of military violence and argues for a renewed focus on political responsibility.
Rethinking International Order
Authors: Zarakol Ayşe
Published: November 2024

This essay focuses on the concept of “international order” and its uses and misuses. It argues that the concept of “order” should not be conflated with the concept of a “system,” and that it makes more sense to speak of world order than international order because the former accommodates political units beyond the nation-state. Drawing on my recent book Before the West (2022) I show how the concept of “world order” travels better in history and also speculate about how it can help us think about the future as well.
Introduction: The Problem with the Problem of Order
Authors: Hurd Ian
Published: November 2024

It seems today that a sense of crisis permeates international affairs. From war to pollution to trade and beyond, there is much talk of the disintegration of the settled ways of doing things and fear of what comes next. The twenty-first century has turned sour for many believers in international order. This is not unique in history; order has been on the minds of writers for centuries, from Kant to Carr to Hedley Bull. It is hard to find a period in history when there has not been some sense of crisis. The problem of international order is both a perennial theme and an urgent contemporary concern. The essays in this collection broaden the conversation to consider the ambiguity, complexity, and contradiction within the concept of world order. Order is neither self-evident nor universally agreed upon; to the contrary, it is contested, political, and contingent. Order is a very disorderly idea.
The Liberal International Order as an Imposition: A Postcolonial Reading
Authors: Benabdallah Lina
Published: November 2024

Cracks in the liberal international order (LIO) have been occurring since its very formation. Yet, some international relations scholarship frames the narrative about imminent threats to the LIO as if such threats were new. From a postcolonial vantage point, this essay contends that mainstream theorizing about international order is problematically Eurocentric and develops a three-pronged argument. In the first place, the essay argues for understanding order as a command or as an imposition. Order as a command renders visible power disparities, injustices, and inequalities of the international order as seen by actors from below. Second, the essay leans on Edward Said's contrapuntal reading method to show that experiences of order are plural rather than singular or universal. Third, the essay argues that from a postcolonial perspective, the opposite of order is not chaos or volatility but rather agency or the authorship to be a rule maker. A full picture of order as imposition requires understanding how togetherness and sameness are modes for Global South actors to find collective unity to resist the injustices and inequalities of the LIO.
Notes on the origin of a fragmentary pontifical
Authors: Albiero Laura
Published: November 2024

This article examines a group of seventy-two fragments from a twelfth-century pontifical whose attribution is under discussion. They contain part of the dedication of a church, the ordo synodalis, and the ordines for the sick, marriage and baptism, and they display neumatic notation on red lines. The fragments are kept at the Bibliothèque nationale de France: five of them are now in NAL 1989, while the remaining sixty-seven are kept in a temporary repository and have not been inventoried yet. As regards their origin, the fragments have been assigned either to northern France or to England. The article considers textual concordances, as well as palaeographical and musical features, in order to reconstruct their context of production, and leaves room for methodological observations.
A Low Albedo, Thin, Resistant Unit in Oxia Planum, Mars: Evidence for an Airfall Deposit and Late‐Stage Groundwater Activity at the ExoMars Rover Landing Site
Authors: Harris E. , Davis J. M. , Grindrod P. M. , Fawdon P. , Roberts A. L.
Published: November 2024

Oxia Planum, Mars, is the future landing site of the ExoMars Rosalind Franklin rover mission, which will search for preserved biosignatures in a phyllosilicate‐bearing unit. Overlying the mission‐important phyllosilicate‐bearing rocks is a dark, capping unit—known here as the Low albedo, Thin, Resistant (LTR) unit—which may have protected the phyllosilicate‐bearing unit over geologic time from solar insolation and radiation. However, little is known about the origin of the LTR unit. Here, we map the LTR unit and investigate its distribution and morphology across 50,000 km2 using a variety of orbital remote sensing data sets. The characteristics of the LTR unit include draping palaeo‐topographic surfaces, deposition over a wide elevation range, and a consistent vertical thickness that can be best explained by airfall deposition including a primary or reworked volcanic palaeo‐ashfall. Previous research suggests that the LTR unit was not significantly buried, and we find it to be preferentially preserved with a high mechanical strength in discrete deposits representing palaeo‐topographic lows. We suggest this could be attributed to localized cementation via upwelling groundwater. This scenario suggests that most of the phyllosilicate‐bearing exposures may not have been protected over geologic time, as the uncemented LTR sediment would have easily been removed by erosion. However, our observations indicate that the scarped margins of the LTR unit deposits probably exposed regions of the once protected phyllosilicate‐bearing unit. These areas could be key science targets for the ExoMars Rosalind Franklin rover mission.
Dysregulation of neuropilin-2 expression in inhibitory neurons impairs hippocampal circuit development and enhances risk for autism-related behaviors and seizures
Authors: Subramanian Deepak , Eisenberg Carol , Huang Andrew , Baek Jiyeon , Naveed Haniya , Komatireddy Samiksha , Shiflett Michael W. , Tran Tracy S. , Santhakumar Vijayalakshmi
Published: November 2024

Dysregulation of development, migration, and function of interneurons, collectively termed interneuronopathies, have been proposed as a shared mechanism for autism spectrum disorders (ASDs) and childhood epilepsy. Neuropilin-2 (Nrp2), a candidate ASD gene, is a critical regulator of interneuron migration from the median ganglionic eminence (MGE) to the pallium, including the hippocampus. While clinical studies have identified Nrp2 polymorphisms in patients with ASD, whether selective dysregulation of Nrp2-dependent interneuron migration contributes to pathogenesis of ASD and enhances the risk for seizures has not been evaluated. We tested the hypothesis that the lack of Nrp2 in MGE-derived interneuron precursors disrupts the excitation/inhibition balance in hippocampal circuits, thus predisposing the network to seizures and behavioral patterns associated with ASD. Embryonic deletion of Nrp2 during the developmental period for migration of MGE derived interneuron precursors (iCKO) significantly reduced parvalbumin, neuropeptide Y, and somatostatin positive neurons in the hippocampal CA1. Consequently, when compared to controls, the frequency of inhibitory synaptic currents in CA1 pyramidal cells was reduced while frequency of excitatory synaptic currents was increased in iCKO mice. Although passive and active membrane properties of CA1 pyramidal cells were unchanged, iCKO mice showed enhanced susceptibility to chemically evoked seizures. Moreover, iCKO mice exhibited selective behavioral deficits in both preference for social novelty and goal-directed learning, which are consistent with ASD-like phenotype. Together, our findings show that disruption of developmental Nrp2 regulation of interneuron circuit establishment, produces ASD-like behaviors and enhanced risk for epilepsy. These results support the developmental interneuronopathy hypothesis of ASD epilepsy comorbidity.
Combining tissue biomarkers with mpMRI to diagnose clinically significant prostate cancer. Analysis of 21 biomarkers in the PICTURE study
Authors: Stopka-Farooqui Urszula , Stavrinides Vasilis , Simpson Benjamin S. , Qureshi Hania , Carmona Echevierra Lina M. , Pye Hayley , Ahmed Zeba , Alawami Mohammed F. , Kay Jonathan D. , Olivier Jonathan , Heavey Susan , Patel Dominic , Freeman Alex , Haider Aiman , Moore Caroline M. , Ahmed Hashim U. , Whitaker Hayley C.
Published: November 2024

Background

Serum PSA and digital rectal examination remain the key diagnostic tools for detecting prostate cancer. However, due to the limited specificity of serum PSA, the applicability of this marker continues to be controversial. Recent use of image-guided biopsy along with pathological assessment and the use of biomarkers has dramatically improved the diagnosis of clinically significant cancer. Despite the two modalities working together for diagnosis biomarker research often fails to correlate findings with imaging.

Methods and results

We looked at 21 prostate cancer biomarkers correlating our results with mpMRI data to investigate the hypothesis that biomarkers along with mpMRI data make a powerful tool to detect clinically significant prostate cancer. Biomarkers were selected based on the existing literature. Using a tissue microarray comprised of samples from the PICTURE study, with biopsies at 5 mm intervals and mpMRI data we analysed which biomarkers could differentiate benign and malignant tissue. Biomarker data were also correlated with pathological grading, mpMRI, serum PSA, age and family history. AGR2, CD10 and EGR protein expression was significantly different in both matched malignant and benign tissues. AMACR, ANPEP, GDF15, MSMB, PSMA, PTEN, TBL1XR1, TP63, VPS13A and VPS28 showed significantly different expression between Gleason grades in malignant tissue. The majority of the biomarkers tested did not correlate with mpMRI data. However, CD10, KHDRBS3, PCLAF, PSMA, SIK2 and GDF15 were differentially expressed with prostate cancer progression. AMACR and PTEN were identified in both pathological and image data evaluation.

Conclusions

There is a high demand to develop biomarkers that would help the diagnosis and prognosis of prostate cancer. Tissue biomarkers are of particular interest since immunohistochemistry remains a cheap, reliable method that is widely available in pathology departments. These results demonstrate that testing biomarkers in a cohort consistent with the current diagnostic pathway is crucial to identifying biomarker with potential clinical utility.
PCK1 as a target for cancer therapy: from metabolic reprogramming to immune microenvironment remodeling
Authors: Liu Na , Zhu Xiao-ren , Wu Chang-ying , Liu Yuan-yuan , Chen Min-bin , Gu Jin-hua
Published: November 2024

Recently, changes in metabolites and metabolism-related enzymes related to tumor cell proliferation, metastasis, drug resistance, and immunosuppression have become a research hotspot, and researchers have attempted to determine the clinical correlation between specific molecular lesions and metabolic phenotypes. Convincing evidence shows that metabolic reprogramming is closely related to the proliferation, invasion, metastasis, and poor prognosis of malignant tumors. Therefore, targeting metabolic reprogramming is a new direction for cancer treatment. However, how molecular alterations in tumors contribute to metabolic diversity and unique targeting dependencies remains unclear. A full understanding of the underlying mechanisms of metabolic reprogramming in cancer may lead to better identification of therapeutic targets and the development of therapeutic strategies. Evidence for the importance of PCK1, a phosphoenolpyruvate carboxykinase 1, in tumorigenesis and development is accumulating. PCK1 can regulate cell proliferation and metastasis by remodeling cell metabolism. Additionally, PCK1 has “nonclassical” nonmetabolic functions, involving the regulation of gene expression, angiogenesis, epigenetic modification, and other processes, and has an impact on cell survival, apoptosis, and other biological activities, as well as the remodeling of the tumor immune microenvironment. Herein, we provide a comprehensive overview of the functions of PCK1 under physiological and pathological conditions and suggest that PCK1 is a potential target for cancer therapy. We also propose a future exploration direction for targeting PCK1 for cancer therapy from a clinical perspective. Finally, in view of the collective data, the results of our discussion suggest the potential clinical application of targeted PCK1 therapy in combination with chemotherapy and immunotherapy for cancer treatment.
Viral sequence determines HLA-E-restricted T cell recognition of hepatitis B surface antigen
Authors: Murugesan Gavuthami , Paterson Rachel L. , Kulkarni Rakesh , Ilkow Veronica , Suckling Richard J. , Connolly Mary M. , Karuppiah Vijaykumar , Pengelly Robert , Jadhav Archana , Donoso Jose , Heunis Tiaan , Bunjobpol Wilawan , Philips Gwilym , Ololade Kafayat , Kay Daniel , Sarkar Anshuk , Barber Claire , Raj Ritu , Perot Carole , Grant Tressan , Treveil Agatha , Walker Andrew , Dembek Marcin , Gibbs-Howe Dawn , Hock Miriam , Carreira Ricardo J. , Atkin Kate E. , Dorrell Lucy , Knox Andrew , Leonard Sarah , Salio Mariolina , Godinho Luis F.
Published: November 2024

The non-polymorphic HLA-E molecule offers opportunities for new universal immunotherapeutic approaches to chronic infectious diseases. Chronic Hepatitis B virus (HBV) infection is driven in part by T cell dysfunction due to elevated levels of the HBV envelope (Env) protein hepatitis B surface antigen (HBsAg). Here we report the characterization of three genotypic variants of an HLA-E-binding HBsAg peptide, Env371-379, identified through bioinformatic predictions and verified by biochemical and cellular assays. Using a soluble affinity-enhanced T cell receptor (TCR) (a09b08)-anti-CD3 bispecific molecule to probe HLA-E presentation of the Env371-379 peptides, we demonstrate that only the most stable Env371-379 variant, L6I, elicits functional responses to a09b08-anti-CD3-redirected polyclonal T cells co-cultured with targets expressing endogenous HBsAg. Furthermore, HLA-E-Env371-379 L6I-specific CD8+ T cells are detectable in HBV-naïve donors and people with chronic HBV after in vitro priming. In conclusion, we provide evidence for HLA-E-mediated HBV Env peptide presentation, and highlight the effect of viral mutations on the stability and targetability of pHLA-E molecules.
Analysis of complex excitation patterns using Feynman-like diagrams
Authors: Arno Louise , Kabus Desmond , Dierckx Hans
Published: November 2024

Many extended chemical and biological systems self-organise into complex patterns that drive the medium behaviour in a non-linear fashion. An important class of such systems are excitable media, including neural and cardiac tissues. In extended excitable media, wave breaks can form rotating patterns and turbulence. However, the onset, sustaining and elimination of such complex patterns is currently incompletely understood. The classical theory of phase singularities in excitable media was recently challenged, as extended lines of conduction block were identified as phase discontinuities. Here, we provide a theoretical framework that captures the rich dynamics in excitable systems in terms of three quasiparticles: heads, tails, and pivots. We propose to call these quasiparticles ‘cardions’. In simulations and experiments, we show that these basic building blocks combine into at least four different bound states. By representing their interactions similarly to Feynman diagrams in physics, the creation and annihilation of vortex pairs are shown to be sequences of dynamical creation, annihilation, and recombination of the identified quasiparticles. We draw such diagrams for numerical simulations, as well as optical voltage mapping experiments performed on cultured human atrial myocytes (hiAMs). Our results provide a new, unified language for a more detailed theory, analysis, and mechanistic insights of dynamical transitions in excitation patterns.
Optimizing energy-efficient grid performance: integrating electric vehicles, DSTATCOM, and renewable sources using the Hippopotamus Optimization Algorithm
Authors: Abdelaziz M. A. , Ali A. A. , Swief R. A. , Elazab Rasha
Published: November 2024

The rapid increase in renewable energy integration and electric vehicle (EV) adoption creates significant challenges for the stability and efficiency of power distribution networks. This study addresses the need for optimized placement and sizing of Electric Vehicle Charging Stations (EVCSs), photovoltaic (PV) systems, and Distribution Static Compensators (DSTATCOMs) to enhance grid performance. The motivation for this work arises from the fluctuating nature of renewable energy generation and the unpredictable demands of EV charging, which strain existing infrastructure. To address these challenges, we propose a novel optimization framework that introduces the Renewable Distributed Generation Hosting Factor (RDG-HF) and Electric Vehicle Hosting Factor (EV-HF) as key metrics. These metrics, combined with the Hippopotamus Optimization Algorithm (HO), enable strategic planning within the IEEE 69-bus system. Simulation results demonstrate that the integrated placement of EVCSs, PVs, and DSTATCOMs reduces power losses by up to 31.5% and reactive power losses by up to 29.2%. An economic analysis further reveals payback periods ranging from 2.7 to 10.4 years and potential profits of up to $1,052,365 over 25 years. These findings highlight the importance of optimized integration in improving both technical performance and long-term economic benefits for distribution networks.
Different dynamics of soluble inflammatory mediators after clearance of respiratory SARS-CoV-2 versus blood-borne hepatitis C virus infections
Authors: Zeuzem Antonia , Kumar Saumya Dileep , Oltmanns Carlos , Witte Moana , Mischke Jasmin , Drick Nora , Fuge Jan , Pink Isabell , Tauwaldt Jan , Debarry Jennifer , Illig Thomas , Wedemeyer Heiner , Maasoumy Benjamin , Li Yang , Kraft Anke R. M. , Cornberg Markus
Published: November 2024

Viral infections can be acute or chronic, with the immune system pivotal in immunopathogenesis. The potential reversibility of inflammation post-viral elimination is of current interest. This study compares the dynamics of soluble inflammatory mediators (SIM) during and after respiratory infections with SARS-CoV-2 and blood-borne acute and chronic hepatitis C virus (HCV) infections. The study included patients with acute HCV (n = 29), chronic HCV (n = 54), and SARS-CoV-2 (n = 39 longitudinal, n = 103 cross-sectional), along with 30 healthy controls. Blood samples were collected at baseline, end of treatment/infection, and during follow-up (up to 9 months). SIMs were quantified using the HD-SP-X Imaging and Analysis System™. At baseline, SIM profiles in acute SARS-CoV-2 and HCV infections were significantly elevated compared with controls. During follow-up, SIM decline was less pronounced in acute and chronic HCV infections after successful therapy than in SARS-CoV-2 infections. Most SIM in the SARS-CoV-2 cohort normalized within 3 months. In chronic HCV, SIM were higher in cirrhotic than noncirrhotic patients post-HCV elimination. Dynamics of SIM after viral elimination vary between blood-borne acute and chronic HCV infections and respiratory SARS-CoV-2 infections. Immunological imprints 3–9 months after HCV elimination appear more pronounced than after SARS-CoV-2 infection.
Question framing affects accurate-inaccurate discrimination in responses to sharing questions, but not in responses to accuracy questions
Authors: Bell Raoul , Buchner Axel
Published: November 2024

Previous research suggests that even when people are capable of judging to the best of their knowledge whether claims are accurate or inaccurate, they do not sufficiently discriminate between accurate and inaccurate information when asked to consider whether they would share stories on social media. However, question framing (“To the best of your knowledge…”, “Would you consider…?”) differed between the questions about accuracy and the questions about sharing. Here we examine the effects of question framing on responses to accuracy questions and responses to sharing questions. The framing of accuracy questions had no effect on accurate-inaccurate discrimination. In contrast, accurate-inaccurate discrimination in response to sharing questions increased when participants were asked to respond, to the best of their knowledge, whether they would share claims compared to when they were asked whether they would consider sharing stories. At a theoretical level, the findings support the inattention-based account, according to which contextual cues shifting the focus toward accuracy can enhance accurate-inaccurate discrimination in sharing responses. At a methodological level, these findings suggest that researchers should carefully attend to the verbal framing of questions about sharing information on social media, as the framing may significantly influence participants’ focus on accuracy.
Structural insight into Okazaki fragment maturation mediated by PCNA-bound FEN1 and RNaseH2
Authors: Tian Yuhui , Li Ningning , Li Qing , Gao Ning
Published: November 2024

PCNA is a master coordinator of many DNA-metabolic events. During DNA replication, the maturation of Okazaki fragments involves at least four DNA enzymes, all of which contain PCNA-interacting motifs. However, the temporal relationships and functional modulations between these PCNA-binding proteins are unclear. Here, we developed a strategy to purify endogenous PCNA-containing complexes from native chromatin, and characterized their structures using cryo-EM. Two structurally resolved classes (PCNA-FEN1 and PCNA-FEN1-RNaseH2 complexes) have captured a series of 3D snapshots for the primer-removal steps of Okazaki fragment maturation. These structures show that product release from FEN1 is a rate-liming step. Furthermore, both FEN1 and RNaseH2 undergo continuous conformational changes on PCNA that result in constant fluctuations in the bending angle of substrate DNA at the nick site, implying that these enzymes could regulate each other through conformational modulation of the bound DNA. The structures of the PCNA-FEN1-RNaseH2 complex confirm the toolbelt function of PCNA and suggests a potential unrecognized role of RNaseH2, as a dsDNA binding protein, in promoting the 5′-flap cleaving activity of FEN1.