bluuebunny/crossref_metadata_2025 huggingface dataset:
NextGenerationEU and the Future of European Integration: Foreseeing the Unforeseeable
Authors: Mayer Franz C.
Published: September 2024

Public revenues, who decides on them, and their justification and legitimation are among the oldest constitutional issues of all. In the EU, member states ultimately control the scope of European policy and the independence of the European level via the EU's budget. This can be interpreted either as a bug or as a feature. The European Parliament reflects representation without taxation, as it has no taxation powers, and the EU does not have budgetary autonomy.
Recreating an Amazonian Ancestral Biodesign Technique
Authors: Bandoni Andrea , Cohen Lauro , Cotta Marcela , Paoliello Carla
Published: September 2024

This study investigates an ancestral Biodesign technique associated with the fruits of the Amazonian tree Crescentia cujete. For centuries, Amazonian artisans have transformed these fruits into objects named cuias, which serve mainly as containers. Despite the continued practice of cuias production, a specific shaping technique discovered in historical accounts remains unknown and unused by contemporary artisans. The paper reports the recreation of this technique considering the ancestral ethos underpinning these traditions. A mixed-method approach has combined historical and museum research, direct interaction with trees in a bioeconomy context, and participatory observation of traditional artisans’ production. The findings reveal the ancient practice of “Growing Design” with that tree and other practices that resonate with Biodesign, establishing a connection between this field and indigenous knowledge. This study highlights the underappreciation of indigenous objects and techniques, emphasizing the potential that emerges from understanding the alignment of certain ancestral wisdom with Biodesign principles, such as amplifying indigenous heritage and opening new possibilities in design.
An Evidence Gap Map of Experience-based Evidence of Health Resource Allocation in Disaster and Humanitarian Settings
Authors: Horn Zachary B , Ranse Jamie , Marshall Andrea P
Published: September 2024

Objective

The aim of this review is to identify, evaluate, and graphically display gaps in the literature related to scarce health resource allocation in humanitarian aid settings.

Methods

A systematic search strategy was utilized in MEDLINE (via Ovid), Scopus, EMBASE, CINAHL Complete, and ProQuest Central. Articles were reviewed by 2 reviewers with a third reviewer remedying any screening conflicts. Articles meeting inclusion criteria underwent data extraction to facilitate evaluation of the scope, nature, and quality of experience-based evidence for health resource allocation in humanitarian settings. Finally, articles were mapped on a matrix to display evidence graphically.

Results

The search strategy identified 6093 individual sources, leaving 4000 for screening after removal of duplicates. Following full-text screening, 12 sources were included. Mapping extracted data according to surge capacity domains demonstrated that all 4 domains were reflected most of all the staff domain. Much of the identified data was presented without adhering to a clear structure or nomenclature. Finally, the mapping suggested potential incompleteness of surge capacity constructs in humanitarian response settings.

Conclusions

Through this review, we identified a gap in evidence available to address challenges associated with scarce resource allocation in humanitarian settings. In addition to presenting the distribution of existing literature, the review demonstrated the relevance of surge capacity and resource allocation principles underpinning the developed framework.
Impact and learner perspectives of a spaced-education platform to assess hand hygiene auditor competency
Authors: Vaughan-Malloy Ana M. , Lehane Renée , Wells Mary M. , Sandora Thomas J.
Published: September 2024

Objective:

To ensure whether spaced education, which increases long-term knowledge retention, could be integrated into auditor competency assessment.

Design:

Quality improvement project.

Setting:

Academic, freestanding children’s hospital.

Participants:

Hand hygiene (HH) auditors.

Intervention:

We enrolled trained HH auditors in an online spaced-education platform to assess mastery of knowledge, delivering 46 unique questions at spaced intervals followed by rationale; we retired questions after 3 correct answers. An e-mailed 10-item survey gauged participant satisfaction with the program. The Wilcoxon signed-rank test was used to compare change in median knowledge score from first to final attempt.

Results:

A total of 12,120 questions were attempted by 126 auditors, and 49 (39%) completed the entire course. Median knowledge score increased significantly by 10.5 percentage points (IQR 4–15) between first and final attempts (P < 0.001). Thirty auditors (27%) responded to the survey. The majority agreed the number and complexity of questions were appropriate (57% and 67%, respectively). Eighty-seven percent reported the platform easy to navigate, and 77% agreed adequate time was provided for completion. Free-text suggestions included delivering fewer questions at a narrower spacing interval over a shorter time frame because of competing work demands.

Conclusions:

Auditor knowledge of HH indications and technique is critical to ensuring data validity. A spaced-education competency program improved HH auditor knowledge in the short term. Completion rate was low, and some participants expressed a desire for fewer questions over a shorter time frame. This study offers insight into ways to optimize spaced education as a potential tool for HH competency assessment.
An experimental study of a quasi-impulsive backwards wave force associated with the secondary load cycle on a vertical cylinder
Authors: Tang Tianning , Ding Haoyu , Dai Saishuai , Taylor Paul H. , Zang Jun , Adcock Thomas A.A.
Published: September 2024

Steep wave breaking on a vertical cylinder (a typical foundation supporting offshore wind turbines) will induce slam loads. Many questions on the important violent wave loading and the associated secondary load cycle remain unanswered. We use laboratory experiments with unidirectional waves to investigate the fluid loading on vertical cylinders. We use a novel three-phase decomposition approach that allows us to separate different types of nonlinearity. Our findings reveal the existence of an additional quasi-impulsive loading component that is associated with the secondary load cycle and occurs in the backwards direction against that of the incoming waves. This quasi-impulsive force occurs at the end of the secondary load cycle and close to the passage of the downward zero-crossing point of the undisturbed wave. Wavelet analysis showed that the impulsive force exhibits superficially similar behaviour to a typical wave-slamming event but in the reverse direction. To monitor the scattered wave field and extract run-up on the cylinder, we installed a four-camera synchronised video system and found a strong temporal correlation between the arrival time of the Type-II scattered wave onto the cylinder and the occurrence of this quasi-impulsive force. The temporal characteristics of this quasi-impulsive force can be approximated by the Goda wave impact model, taking the collision of the Type-II scattered waves at the rear stagnation point as the impact source.
On the three-dimensional structure of instabilities beneath shallow-shoaling internal waves
Authors: Castro-Folker Nicolas , Stastna Marek
Published: September 2024

The stimulation of instability and transport in the bottom boundary layer by internal solitary waves has been documented for over twenty years. However, the challenge of shallow slopes and a disparity of scales between the large-scale wave and the small-scale boundary layer has proven challenging for simulations. We present laboratory scale simulations that resolve the three-dimensionalisation in the boundary layer during the entire shoaling process. We find that the late stage, in which the incoming wave fissions into boluses, provides the most consistent source of three-dimensionalisation. In the early stage of shoaling, three-dimensionalisation occurs not so much due to separation bubble instability, but due to the interaction of vortices shed from the separation bubble with the overlying pycnocline. This interaction overturns the pycnocline, and creates bursts in kinetic energy and viscous dissipation, suggesting that the shed vortices induce turbulent motion and sediment resuspension in the water column above and behind the separation bubble.
Instabilities and particle-induced patterns in co-rotating suspension Taylor–Couette flow
Authors: Ghosh Manojit , Alam Meheboob
Published: September 2024

The first experimental results on pattern transitions in the co-rotation regime (i.e. the rotation ratio

$\varOmega = \omega _o/\omega _i > 0$

, where

$\omega _i$

and

$\omega _o$

are the angular speeds of the inner and outer cylinders, respectively) of the Taylor–Couette flow (TCF) are reported for a neutrally buoyant suspension of non-colloidal particles, up to a particle volume fraction of

$\phi = 0.3$

. While the stationary Taylor vortex flow (TVF) is the primary bifurcating state in dilute suspensions (

$\phi \leq ~0.05$

), the non-axisymmetric oscillatory states, such as the spiral vortex flow (SVF) and the ribbon (RIB), appear as primary bifurcations with increasing particle loading, with an overall de-stabilization of the primary bifurcating states (TVF/SVF/RIB) being found with increasing

$\phi$

for all

$\varOmega \geq ~0$

. At small co-rotations (

$\varOmega \sim 0$

), the particles play the dual role of stabilization (

$\phi < 0.1$

) and destabilization (

$\phi \geq ~0.1$

) on the secondary/tertiary oscillatory states. The distinctive features of the ‘particle-induced’ spiral vortices are identified and contrasted with those of the ‘fluid-induced’ spirals that operate in the counter-rotation regime.
Motivation from Joseph Ratzinger’s Eschatological Realism for Protecting Humanity’s Future
Authors: Wygnanski Piotr
Published: September 2024

This article outlines one way in which Joseph Ratzinger’s eschatology could contribute to reducing the risk humanity now creates to its own survival. Studies of ‘Existential Risk’ warn that hazards arising from Artificial Intelligence, Nuclear Weapons, Climate Change, and Engineered Pathogens require mitigation to safeguard the future of the human race from a calamitous end. Preventative measures, however, entail sacrifice, and there is no shortage of resistance to regulation of behaviours and technological development. Ethics of empathy, utility, and duties reach breaking point when stretched to overcome the temporal and moral gap between present agency and future well-being.

This article proposes that Ratzinger’s theology of history and commitment to eschatological realism offers an intertwined double benefit: his warning about the danger of conflating hope in God’s Kingdom with hope in a future world humanity could perfect for itself opens up the uniquely rich ground of a trans-historical hope in Jesus Christ, in which an impactful relationship of love for humanity’s future can put down roots today.
Persistent unilateral action
Authors: Foster David
Published: September 2024

Many believe that weaker legal constraints make unilateral action easier to reverse than legislation. Yet in some cases, unilateralism survives a successor's determined opposition. I argue that legislative persistence and unilateral transience may arise not only from differences in legal status but also from a selection effect: unilateralism and subsequent rescission can both stem from weak underlying policy-demanding groups. But if unilateralism itself alters the landscape of group power through policy feedback effects, it can survive a purportedly opposed new president. An example is the Trump Administration's failure to depart from the Obama Justice Department's lax stance on cannabis. Weak constituents’ policy demands may thus need to rely on a sympathetic president's unilateral action to begin a feedback loop, subsequently softening opposition. This paper therefore identifies unilateral action as a key tool for shifting policy in an enduring way, explaining its success or failure in terms of interest group power.
Sedimentation rate changes across the Chinese Loess Plateau from luminescence dating of Malan loess in the Sanmen Gorge
Authors: Hu Gang , Wang Huiying , Xu Bo , Wang Ping , Xu Liubing , Xie Jinming , Wang Xin , Qiao Long , Guo Changhui , Wang Junkang , Zhang Jiafu , Wang Wenxu , Ta La , Wang Lei
Published: September 2024

The Chinese Loess Plateau (CLP), recognized as the world's largest loess plateau, has been a subject of ongoing debate regarding the continuity of its sedimentary loess sequence due to its intricate depositional environment. In this study, we conducted dating on a 9.8-m-long Malan loess core obtained from the Sanmen Gorge in the southern CLP using optically stimulated luminescence (OSL). The OSL dates indicate loess deposition between 52.4 and 11.3 ka, with no apparent hiatus on a millennial scale, and a sedimentation rate (SR) exhibiting six distinct episodes. Additionally, a comprehensive review of 613 OSL ages from 18 sections at 14 sites across the CLP was conducted. The results reveal loess deposition at most sites shows no apparent hiatus on a millennial scale over the past 60 ka, except for two specific locations. High SR episodes during Marine Isotope Stage (MIS) 3 across the CLP were attributed to heightened dust emissions from the source region and an enhanced dust deposition efficiency, while MIS 2 deposits were influenced by an intensified East Asian winter monsoon. Low SR episodes during MIS 1 at most sites were likely associated with reduced atmospheric transportation and pedogenesis. Spatially heterogeneous SR variations across the CLP might be influenced by local depositional environments.
SAMPLE PREPARATION SYSTEM FOR CARBONATE AND DIC IN WATER AT THE GXNU-AMS LABORATORY
Authors: Shen Hongtao , Qi Linjie , Ouyang He , Han Xinyi , Zhang Guofeng , Chen Dingxiong , Wu Kaiyong , Tang Junsen , Wang Li , Wang Ning , Sun Xiaojun , He Ming , Sasa Kimikazu , Shan Jiang
Published: September 2024

A new vacuum line to extract CO2 from carbonate and dissolved inorganic carbon (DIC) in water was established at Guangxi Normal University. The vacuum line consisted of two main components: a CO2 bubble circulation region and a CO2 purification collection region, both of which were made of quartz glass and metal pipelines. To validate its reliability, a series of carbonate samples were prepared using this system. The total recovery rate of CO2 extraction and graphitization exceeded 80%. Furthermore, the carbon content in calcium carbonate exhibited a linear relationship with the CO2 pressure within the system, demonstrating its stability and reliability. The system was also employed to prepare and analyze various samples, including calcium carbonate blanks, foraminiferal, shell, groundwater, and subsurface oil-water samples. The accelerator mass spectrometry (AMS) results indicated that the average beam current for 12C- in the samples exceeded 40 μA. Additionally, the contamination introduced during the liquid sample preparation process was approximately (1.77 ± 0.57) × 10−14. Overall, the graphitized preparation system for carbonate and DIC in water exhibited high efficiency and recovery, meeting the requirements for samples dating back to approximately 30,000 years.
THE INCONSISTENCY CHARGE IN CICERO'S DE FINIBUS 1–2
Authors: Parker Dale
Published: September 2024

Cicero often challenged Epicureanism on the grounds of inconsistency. Cicero personifies the charge through his character Torquatus, who defends Epicureanism in De finibus 1–2. Cicero highlights the discrepancies among Torquatus’ beliefs and between them and his behaviour. Torquatus holds that the senses incontestably verify the tenets of Epicureanism, and that logic is superfluous. Yet he is sensitive to the fact that Epicurus’ teachings are not intuitive and require a fair amount of logical argumentation in its defence. Therefore, he defends his school against Cicero's criticisms. But by engaging in a defence of the system, Torquatus has already spoken against his commitment to the obviousness of Epicureanism and his disavowal of logic.
PLAYING IN THE LION'S JAWS: METATEXTUALITY IN MARTIAL'S ‘LION AND HARE’ CYCLE
Authors: Brown Emi C.
Published: September 2024

This paper aims to provide an analysis of the metatextual function of one of the most well-known elements of Martial's Epigrams, the ‘lion and hare’ cycle from Book 1. This cycle, in which a hare is held precariously but safely in the jaws of a lion, has historically been read as representing the relationship between Domitian and poet. This paper aims to expand on this reading of the cycle while considering a largely unexplored point of view: the metatexual function of this cycle within Martial's larger epigrammatic project. I identify three major ways in which the cycle supports Martial's larger interests in exploring poetic anxieties and defending the genre of epigrammatic poetry. First of all, by figuring the lion and the hare as, respectively, the emperor and the poet, Martial presents and performs an exemplum modelling clemency in the reception of lascivious poetry. Second, as a sexual metaphor that points to the anxiety and insecurity of both predator and prey, the cycle anticipates a broader concern of the Epigrams: the instability of Roman hierarchical relations and the difficulty of maintaining balance within such relationships. Third, Martial's continued use of hare imagery in the later books of the Epigrams, both in culinary and in hunting contexts, suggests the continued consumption and enjoyment of the genre of epigram, particularly outside of the imperial city.
For the archive yet to come
Authors: Mertens Charlotte , Perazzone Stéphanie
Published: September 2024

This article explores the promises and pitfalls of the colonial archives for the study of seeing and knowing contemporary violence. As an ethnographic field and a site of decolonial struggles, the colonial archive is increasingly mobilised in scholarship that seeks to historicise and disrupt conventional, Western-centric knowledge production. While using the colonial archives might reproduce asymmetrical power relations, they also hold the potential to unsettle the ‘toxic imperial debris’ of our time. How can the colonial archives challenge the post-colonial politics of erasing imperial violence and contribute to decolonial futures? Drawing on research in the African Archives in Belgium and fieldwork in the Democratic Republic of the Congo (DRC), this paper complicates problematic portrayals of the post-colonial state in the DRC and Congolese women as always already violated or silenced. We argue that the logics of the African Archives reveal a set of destabilising state anxieties that reflect the duality and instability of colonial rule itself and that infuse contemporary (international) politics. This recounting of the violence contained in the archives both narrates the concrete, violent manifestations of our ‘global coloniality’ and works towards its own demise as part of a broader ‘anticolonial archive’.
Andean bears hunt wild guinea pigs in Colombian paramos
Authors: Hyde Matthew , Di Domenico Sebastian , Avellanada Carlos , Diaz-Pulido Angélica , Chiquito-García Santiago , Mejía-González Ángela , Breck Stewart W.
Published: September 2024

It is well documented that Andean bears (Tremarctos ornatus) feed extensively on plants and carrion, but their hunting habits remain understudied. Better understanding and documentation of Andean bear feeding ecology can improve conservation efforts for this vulnerable species. Here, we report an observation of an Andean bear hunting and capturing a wild guinea pig (Cavia aperea) in Chingaza National Natural Park, in Cundinamarca, Colombia. The sighting occurred in January 2023 by a team of conservationists, and we provided photographic evidence and details of the encounter. Our observation suggests that Andean bears are capable hunters of small rodents, indicating that hunting may play a more important role in the ecology of Andean bears than previously appreciated and highlighting the need for a better understanding of this feeding behaviour.
Economic valuation of changes in ecosystem services of 77 Ramsar wetlands in West Asia over 37 years (1984–2021)
Authors: Ashournejad Qadir , Garshasbi Fateme
Published: September 2024

In the West Asia region, the vulnerability of Ramsar Convention wetlands due to unsustainable utilization driven by water scarcity continues to grow. Here, a global surface water product generated by the European Joint Research Centre was used to assess changes in surface water in 77 wetlands listed under the Ramsar Convention over a 37-year period (1984–2021). By combining this product with a quantitative valuation model, estimates were made of the economic value of the ecosystem services provided by these wetlands, enabling the determination of the economic losses resulting from any reduction in surface water. We show that 20% (7550 km2) of permanent surface waters in Ramsar sites have disappeared or are no longer classified as permanent. Based on this, USD 106 billion of the economic value of wetlands ecosystem services have been lost. Additionally, 33% (12 100 km2) of seasonal surface waters in these wetlands have experienced a decrease in area. Iran and Iraq account for 90% of water losses, primarily in 34 wetlands (30 in Iran and 4 in Iraq). These findings underscore the urgent need for water management policies and conservation strategies in the West Asia region.
Emergency Department Boarding Time Is Associated with Functional Decline in Older Adults Six Months Post Discharge
Authors: Duquette Caroline L. , Andrew Melissa K. , Kuchel George A. , Clarke Jo-Anne , Ohle Robert , Verschoor Chris P.
Published: September 2024

Functional decline following hospitalization remains an important problem in health care, especially for frail older adults. Modifiable factors related to reduction in harms of hospitalization are not well described. One particularly pervasive factor is emergency department (ED) boarding time; time waiting from decision to admit, until transfer to an in-patient medical unit. We sought to investigate how the functional status of frail older adults correlated with the length of time spent boarded in the ED. We found that patients who waited for 24 hours or more exhibited functional decline in both the Barthel Index and Hierarchical Assessment of Balance and Mobility and an increase in the Clinical Frailty Scale from discharge to 6 months post discharge. In conclusion, there is a need for additional investigation into ED focused interventions to reduce ED boarding time for this population or to improve access to specialized geriatric services within the ED.
Structural elucidation of the dichloridodioxido-[(4,7-dimethyl)-1,10-phenanthroline]molybdenum(VI) (C14H12Cl2MoN2O2)
Authors: Bonilla John D. , Camargo Hernando , Castellanos Nelson J.
Published: September 2024

In this work, the synthesis, characterization, and X-ray powder diffraction data for dichloridodioxido-[(4,7-dimethyl)-1,10-phenanthroline]molybdenum(VI) are reported. The crystal structure of this compound was solved from powder diffraction data using the simulated annealing method with a subsequent refinement using the Rietveld method. The dioxo-molybdenum (VI) complex C14H12Cl2MoN2O2 crystallizes in a monoclinic system with space group C2/c (N° 15) with refined unit-cell parameters a = 12.9495 (5) Å, b = 9.7752 (4) Å,c = 12.0069 (6) Å, β = 101.702 (3) °, unit-cell volume V = 1488.27 (11) Å3, and values of Z′ = 0.5 and Z = 4. The molecules are organized into chains diagonally along the a and c axis. Parallel polyhedra are observed along these axes formed by the interactions of Mo, Cl, O, and N atoms present in the coordination sphere. The crystalline packing of this dioxo-molybdenum (VI) complex is dominated by five intermolecular hydrogen bonds, two intramolecular hydrogen bonds, and the four interactions between the centroids (CgI⋯CgJ) of the aromatic rings. An analysis of the Hirshfeld surface revealed that the greatest contributions of the attractive forces are given by H⋯Cl/Cl⋯H, H⋯C/C⋯H, H⋯O/O⋯H, and H⋯H interactions.
Miscegenation Madness
Authors: Jackson Sebastian
Published: September 2024

In this article, I examine how the fear of miscegenation developed as a raison d’être for the construction and maintenance of apartheid. I argue that despite its efficacy at reproducing racial-caste formations, miscegenation taboo ultimately undermined its own hegemonic mythology by constructing contradictory erotic desires and subjectivities which could neither be governed nor contained. I consider how miscegenation fears and fantasies were debated in public discourse, enacted into law, institutionalized through draconian policing and punishment practices, culturally entrenched, yet negotiated and resisted through everyday intimacies. While crime statistics show that most incidences of interracial sex involved White men and women of color, the perceived threat to “White purity” was generally represented through images of White women—volks-mothers and daughters—in the Afrikaner nationalist iconography. White women’s wombs symbolized the future of “Whiteness.” This article offers a critique of the prevailing South African “exceptionalism” paradigm in apartheid studies. Detailed analyses of government commission reports (1939, 1984, 1985) and parliamentary debate records (1949) reveal considerable American influence on South Africa’s “petty apartheid” laws, and especially the Prohibition of Mixed Marriages Act (1949) and Immorality Amendment Act (1950). While these “cornerstone” policies of apartheid developed from local socio-political conflicts and economic tensions, they were always entangled in global racial formations, rooted in trans-oceanic histories of slavery, dispossession, and segregation. This historical anthropological study of race/sex taboo builds on interdisciplinary literatures in colonial history, sociology, postcolonial studies, literary theory, art history, cultural studies, feminist theory, queer studies, and critical race theory.
Prevention Approaches for Compulsive Buying-Shopping Disorder
Authors: Thomas Tobias A. , Laskowski Nora M. , Lesener Tino , Gusy Burkhard , de Zwaan Martina , Müller Astrid
Published: September 2024

Abstract: Aims: With the increase of online shopping and cashless payment, (online) compulsive buying-shopping disorder (CBSD) has become an increasingly important field of research. However, little attention has been paid to its prevention. Our aim is to identify prevention programs for CBSD respectively to propose prevention approaches for CBSD based on the literature on (behavioral) addictions. Methodology: A review of the literature was conducted. Two databases were used. Studies should refer to the prevention of CBSD and describe prevention concepts to be screened. Results and discussion: The search did not reveal any prevention programs focusing on CBSD beyond preliminary work from over 25 years ago. Potential content of prevention programs for CBSD based on prevention approaches for other behavioral addictions and risk factors of CBSD was outlined. For universal prevention, psychoeducation should reach (university) students and apprentices. Selective prevention should include social norms interventions, psychoeducation and low-threshold interventions. Indicated prevention should comprise group settings with several sessions. Self-observation, managing finances, procrastination, emotion regulation should be covered. Counselors at e. g., universities should be educated about CBSD. Referral to treatment should be considered for persons at-risk for CBSD. Conclusions: These suggested preventive offers should be further concretized and empirically evaluated.
Kinetic Theory of Drift‐Mirror Mode
Authors: Yao Yao , Chen Haotian , Li Zilong , Li Jiquan
Published: September 2024

We present a nonlocal gyrokinetic theory for the drift‐mirror mode in high‐ anisotropic plasmas. Here, represents the ratio of plasma pressure to magnetic pressure. The equilibrium distribution is established self‐consistently via guiding‐center Hamiltonian theory. To keep the nonuniformity and finite Larmor radius (FLR) effects on an equal footing, we derive the three‐field nonlocal eigenmode equations in Fourier space under the assumption of weak nonuniformity. It is found that the drift‐mirror mode is essentially a dissipative instability confined within the potential well due to the FLR effect. Numerical analyses demonstrate that the drift‐mirror mode originates from the coupling between shear Alfvén and mirror branch, where the ion‐sound wave component is negligible. Furthermore, the threshold of this nonlocal drift‐mirror mode is significantly lower than that of the conventional drift‐mirror mode.
Impact of BCR::ABL1 single nucleotide variants on asciminib efficacy
Authors: Innes Andrew J. , Hayden Chloe , Orovboni Victoria , Claudiani Simone , Fernando Fiona , Khan Afzal , Rees David , Byrne Jennifer , Gallipoli Paolo , Francis Sebastian , Copland Mhairi , Horne Gillian , Raghavan Manoj , Arnold Claire , Collins Angela , Cranfield Tanya , Cunningham Nicholas , Danga Akila , Forsyth Peter , Frewin Rebecca , Garland Paula , Hannah Guy , Avenoso Daniele , Hassan Sandra , Huntly Brian J. P. , Husain Jissan , Makkuni Sudhakaran , Rothwell Kate , Khorashad Jamshid , Apperley Jane F. , Milojkovic Dragana
Published: September 2024

Asciminib is a potent and selective inhibitor of BCR::ABL1, with potential to avoid toxicity resulting from off-target kinase inhibition. Forty-nine patients treated with asciminib under a managed access program in the UK were evaluated for toxicity and response. Intolerance, rather than resistance (65% vs. 35%), was the most common reason for cessation of the last-line of treatment but asciminib was well tolerated, with most patients (29, 59%) remaining on treatment at a median of 14 months follow-up, and only 6 (12%) stopping for intolerance. Of 44 patients assessable for response, 29 (66%) achieved a complete cytogenetic response (CCyR) or better, with poorer responses seen in those stopping their last-line of therapy for resistance. Fewer patients with a prior history of a non-T315I-BCR::ABL1 single nucleotide variant (BSNV), or a non-T315I-BSNV detectable at baseline achieved CCyR. Serial tracking of BSNV by next generation sequencing demonstrated clonal expansion of BSNV-harbouring populations, which in some settings was associated with resistance (E459K, F317L, F359I), while in others was seen in the context of ongoing response, often with intensified dosing (T315I, I502F). These data suggest that asciminib exerts selective pressure on some BSNV-harbouring populations in vivo, some of which may respond to intensified dosing.
Parity-Time symmetry helps breaking a new limit
Authors: Wan Wenjie , Jiang Xiaoshun
Published: September 2024

Parity-Time (PT) symmetry is an emerging concept in quantum mechanics where non-Hermitian Hamiltonians can exhibit real eigenvalues. Now, PT symmetric optical microresonators have been demonstrated to break the bandwidth-efficiency limit for nonlinear optical signal processing.
6 GHz lamb wave acoustic filters based on A1-mode lithium niobate thin film resonators with checker-shaped electrodes
Authors: Tong Xin , Zou Yang , Wen Zhiwei , Liu Zesheng , Luo Tiancheng , Zhou Jie , Liu Huajun , Ren Yuqi , Xu Qinwen , Liu Wenjuan , Liu Yan , Cai Yao , Sun Chengliang
Published: September 2024

The first-order antisymmetric (A1) mode lamb wave resonator (LWR) based on Z-cut LiNbO3 thin films has attracted significant attention and is widely believed to be a candidate for next-generation reconfigurable filters with high frequency and large bandwidth (BW). However, it is challenging for traditional interdigitated electrodes (IDTs) based LWR filters to meet the requirement of a clean frequency spectrum response and enough out-of-band (OoB) rejection. To solve the problem, we propose LWRs with checker-shaped IDTs for the design of filters that meet the Wi-Fi 6E standard. By taking advantage of checker-shaped IDTs with unparalleled boundaries, the fabricated 6-GHz resonators successfully suppress higher-order A1 spurious modes, demonstrating a spurious-free impedance response and a high figure-of-merit (FOM) up to 104. Based on the demonstrated checker-shaped electrode design, the filter features a center frequency (f0) of more than 6 GHz, a 3 dB BW exceeding 620 MHz, and an excellent OoB rejection >25 dB, consistent with the acoustic-electric-electromagnetic (EM) multi-physics simulations. Furthermore, through the capacitance-inductance matching network technology, the filter’s voltage standing wave ratio (VSWR) is successfully reduced below 2, showing an excellent 50 Ω impedance matching. This study lays a foundation for ultra-high-frequency and ultra-wideband filters for the Wi-Fi 6/6E application.
Formula with large, milk phospholipid-coated lipid droplets in late-moderate preterm infants: a double-blind RCT
Authors: Kakaroukas Andreas , Abrahamse-Berkeveld Marieke , Hayes Louise , McNally Richard J. Q. , Berrington Janet E. , van Elburg Ruurd M. , Embleton Nicholas D.
Published: September 2024

Background

Limited evidence exists on the preferred feeding method when breastfeeding is not possible in late and moderate preterm (LMPT) infants. This RCT evaluates growth, safety, and tolerance of a concept infant formula (IF) with large, milk phospholipid-coated lipid droplets enriched in dairy lipids in LMPT infants with primary objective to demonstrate non-inferiority of daily weight gain from randomization to 3 months corrected age compared to a standard IF.

Methods

LMPT infants were randomized before or around term equivalent age to either the concept (n = 21) or standard IF (n = 20). Forty-one breastfed (BF) infants served as reference.

Results

Due to unintended low recruitment, non-inferiority in daily weight gain could not be demonstrated for the Concept compared to the Control group, but was compared to the BF group. Other outcomes were similar between the formula groups, except for an apparent larger head circumference gain in the Concept group. No apparent differences in growth and body composition outcomes were observed between the Concept and BF reference groups.

Conclusion

This small-scale study suggests the concept IF is a safe alternative for parents who choose IF to feed their LMPT infant. Larger trials are needed to better determine impacts on head growth or body composition.

Impact

In a small group of late and moderate preterm infants, growth from randomization until 3 months corrected age of infants fed with a concept infant formula with large, milk phospholipid-coated lipid droplets was not -significantly different from infants fed a standard infant formula.

Infants in the Concept group had non-significant larger gain in head circumference compared to the Control group; larger trials are needed to confirm this finding.

Both formulas were well-tolerated, with no differences in adverse events.

The concept formula is potentially a safe alternative for parents of moderate to late preterm infants who choose to use formula milk.
Validation of the BOADICEA model for epithelial tubo-ovarian cancer risk prediction in UK Biobank
Authors: Yang Xin , Wu Yujia , Ficorella Lorenzo , Wilcox Naomi , Dennis Joe , Tyrer Jonathan , Carver Tim , Pashayan Nora , Tischkowitz Marc , Pharoah Paul D. P. , Easton Douglas F. , Antoniou Antonis C.
Published: September 2024

Background

The clinical validity of the multifactorial BOADICEA model for epithelial tubo-ovarian cancer (EOC) risk prediction has not been assessed in a large sample size or over a longer term.

Methods

We evaluated the model discrimination and calibration in the UK Biobank cohort comprising 199,429 women (733 incident EOCs) of European ancestry without previous cancer history. We predicted 10-year EOC risk incorporating data on questionnaire-based risk factors (QRFs), family history, a 36-SNP polygenic risk score and pathogenic variants (PV) in six EOC susceptibility genes (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1 and PALB2).

Results

Discriminative ability was maximised under the multifactorial model that included all risk factors (AUC = 0.68, 95% CI: 0.66–0.70). This model was well calibrated in deciles of predicted risk with calibration slope=0.99 (95% CI: 0.98–1.01). Discriminative ability was similar in women younger or older than 60 years. The AUC was higher when analyses were restricted to PV carriers (0.76, 95% CI: 0.69–0.82). Using relative risk (RR) thresholds, the full model classified 97.7%, 1.7%, 0.4% and 0.2% women in the RR < 2.0, 2.0 ≤ RR < 2.9, 2.9 ≤ RR < 6.0 and RR ≥ 6.0 categories, respectively, identifying 9.1 of incident EOC among those with RR ≥ 2.0.

Discussion

BOADICEA, implemented in CanRisk (www.canrisk.org), provides valid 10-year EOC risks and can facilitate clinical decision-making in EOC risk management.
Identifying genetic variants associated with chromatin looping and genome function
Authors: Bhattacharyya Sourya , Ay Ferhat
Published: September 2024

Here we present a comprehensive HiChIP dataset on naïve CD4 T cells (nCD4) from 30 donors and identify QTLs that associate with genotype-dependent and/or allele-specific variation of HiChIP contacts defining loops between active regulatory regions (iQTLs). We observe a substantial overlap between iQTLs and previously defined eQTLs and histone QTLs, and an enrichment for fine-mapped QTLs and GWAS variants. Furthermore, we describe a distinct subset of nCD4 iQTLs, for which the significant variation of chromatin contacts in nCD4 are translated into significant eQTL trends in CD4 T cell memory subsets. Finally, we define connectivity-QTLs as iQTLs that are significantly associated with concordant genotype-dependent changes in chromatin contacts over a broad genomic region (e.g., GWAS SNP in the RNASET2 locus). Our results demonstrate the importance of chromatin contacts as a complementary modality for QTL mapping and their power in identifying previously uncharacterized QTLs linked to cell-specific gene expression and connectivity.
Electron transfer in the respiratory chain at low salinity
Authors: Lobez Ana Paula , Wu Fei , Di Trani Justin M. , Rubinstein John L. , Oliveberg Mikael , Brzezinski Peter , Moe Agnes
Published: September 2024

Recent studies have established that cellular electrostatic interactions are more influential than assumed previously. Here, we use cryo-EM and perform steady-state kinetic studies to investigate electrostatic interactions between cytochrome (cyt.) c and the complex (C) III2-IV supercomplex from Saccharomyces cerevisiae at low salinity. The kinetic studies show a sharp transition with a Hill coefficient ≥2, which together with the cryo-EM data at 2.4 Å resolution indicate multiple cyt. c molecules bound along the supercomplex surface. Negatively charged loops of CIII2 subunits Qcr6 and Qcr9 become structured to interact with cyt. c. In addition, the higher resolution allows us to identify water molecules in proton pathways of CIV and, to the best of our knowledge, previously unresolved cardiolipin molecules. In conclusion, the lowered electrostatic screening renders engagement of multiple cyt. c molecules that are directed by electrostatically structured CIII2 loops to conduct electron transfer between CIII2 and CIV.
Machine learning the electric field response of condensed phase systems using perturbed neural network potentials
Authors: Joll Kit , Schienbein Philipp , Rosso Kevin M. , Blumberger Jochen
Published: September 2024

The interaction of condensed phase systems with external electric fields is of major importance in a myriad of processes in nature and technology, ranging from the field-directed motion of cells (galvanotaxis), to geochemistry and the formation of ice phases on planets, to field-directed chemical catalysis and energy storage and conversion systems including supercapacitors, batteries and solar cells. Molecular simulation in the presence of electric fields would give important atomistic insight into these processes but applications of the most accurate methods such as ab-initio molecular dynamics (AIMD) are limited in scope by their computational expense. Here we introduce Perturbed Neural Network Potential Molecular Dynamics (PNNP MD) to push back the accessible time and length scales of such simulations. We demonstrate that important dielectric properties of liquid water including the field-induced relaxation dynamics, the dielectric constant and the field-dependent IR spectrum can be machine learned up to surprisingly high field strengths of about 0.2 V Å−1 without loss in accuracy when compared to ab-initio molecular dynamics. This is remarkable because, in contrast to most previous approaches, the two neural networks on which PNNP MD is based are exclusively trained on molecular configurations sampled from zero-field MD simulations, demonstrating that the networks not only interpolate but also reliably extrapolate the field response. PNNP MD is based on rigorous theory yet it is simple, general, modular, and systematically improvable allowing us to obtain atomistic insight into the interaction of a wide range of condensed phase systems with external electric fields.
Temperature overshoot responses to ambitious forestation in an Earth System Model
Authors: Moustakis Yiannis , Nützel Tobias , Wey Hao-Wei , Bao Wenkai , Pongratz Julia
Published: September 2024

Despite the increasing relevance of temperature overshoot and the rather ambitious country pledges on Afforestation/Reforestation globally, the mitigation potential and the Earth system responses to large-scale non-idealized Afforestation/Reforestation patterns under a high overshoot scenario remain elusive. Here, we develop an ambitious Afforestation/Reforestation scenario by harnessing 1259 Integrated Assessment Model scenarios, restoration potential maps, and biodiversity constraints, reaching 595 Mha by 2060 and 935 Mha by 2100. We then force the Max Planck Institute’s Earth System Model with this scenario which yields a reduction of peak temperature by 0.08 oC, end-of-century temperature by 0.2 oC, and overshoot duration by 13 years. Afforestation/Reforestation in the range of country pledges globally could thus constitute a useful mitigation tool in overshoot scenarios in addition to fossil fuel emission reductions, but socio-ecological implications need to be scrutinized to avoid severe side effects.
Fasting shapes chromatin architecture through an mTOR/RNA Pol I axis
Authors: Al-Refaie Nada , Padovani Francesco , Hornung Johanna , Pudelko Lorenz , Binando Francesca , del Carmen Fabregat Andrea , Zhao Qiuxia , Towbin Benjamin D. , Cenik Elif Sarinay , Stroustrup Nicholas , Padeken Jan , Schmoller Kurt M. , Cabianca Daphne S.
Published: September 2024

Chromatin architecture is a fundamental mediator of genome function. Fasting is a major environmental cue across the animal kingdom, yet how it impacts three-dimensional (3D) genome organization is unknown. Here we show that fasting induces an intestine-specific, reversible and large-scale spatial reorganization of chromatin in Caenorhabditis elegans. This fasting-induced 3D genome reorganization requires inhibition of the nutrient-sensing mTOR pathway, acting through the regulation of RNA Pol I, but not Pol II nor Pol III, and is accompanied by remodelling of the nucleolus. By uncoupling the 3D genome configuration from the animal’s nutritional status, we find that the expression of metabolic and stress-related genes increases when the spatial reorganization of chromatin occurs, showing that the 3D genome might support the transcriptional response in fasted animals. Our work documents a large-scale chromatin reorganization triggered by fasting and reveals that mTOR and RNA Pol I shape genome architecture in response to nutrients.
Benchmarking the reproducibility of all-solid-state battery cell performance
Authors: Puls Sebastian , Nazmutdinova Elina , Kalyk Fariza , Woolley Henry M. , Thomsen Jesper Frost , Cheng Zhu , Fauchier-Magnan Adrien , Gautam Ajay , Gockeln Michael , Ham So-Yeon , Hasan Md Toukir , Jeong Min-Gi , Hiraoka Daiki , Kim Jong Seok , Kutsch Tobias , Lelotte Barthélémy , Minnmann Philip , Miß Vanessa , Motohashi Kota , Nelson Douglas Lars , Ooms Frans , Piccolo Francesco , Plank Christian , Rosner Maria , Sandoval Stephanie E. , Schlautmann Eva , Schuster Robin , Spencer-Jolly Dominic , Sun Yipeng , Vishnugopi Bairav S. , Zhang Ruizhuo , Zheng Huang , Adelhelm Philipp , Brezesinski Torsten , Bruce Peter G. , Danzer Michael , El Kazzi Mario , Gasteiger Hubert , Hatzell Kelsey B. , Hayashi Akitoshi , Hippauf Felix , Janek Jürgen , Jung Yoon Seok , McDowell Matthew T. , Meng Ying Shirley , Mukherjee Partha P. , Ohno Saneyuki , Roling Bernhard , Sakuda Atsushi , Schwenzel Julian , Sun Xueliang , Villevieille Claire , Wagemaker Marnix , Zeier Wolfgang G. , Vargas-Barbosa Nella M.
Published: September 2024

The interlaboratory comparability and reproducibility of all-solid-state battery cell cycling performance are poorly understood due to the lack of standardized set-ups and assembly parameters. This study quantifies the extent of this variability by providing commercially sourced battery materials—LiNi0.6Mn0.2Co0.2O2 for the positive electrode, Li6PS5Cl as the solid electrolyte and indium for the negative electrode—to 21 research groups. Each group was asked to use their own cell assembly protocol but follow a specific electrochemical protocol. The results show large variability in assembly and electrochemical performance, including differences in processing pressures, pressing durations and In-to-Li ratios. Despite this, an initial open circuit voltage of 2.5 and 2.7 V vs Li+/Li is a good predictor of successful cycling for cells using these electroactive materials. We suggest a set of parameters for reporting all-solid-state battery cycling results and advocate for reporting data in triplicate.
Improving rigor and reproducibility in western blot experiments with the blotRig analysis
Authors: Omondi Cleopa , Chou Austin , Fond Kenneth A. , Morioka Kazuhito , Joseph Nadine R. , Sacramento Jeffrey A. , Iorio Emma , Torres-Espin Abel , Radabaugh Hannah L. , Davis Jacob A. , Gumbel Jason H. , Huie J. Russell , Ferguson Adam R.
Published: September 2024

Western blot is a popular biomolecular analysis method for measuring the relative quantities of independent proteins in complex biological samples. However, variability in quantitative western blot data analysis poses a challenge in designing reproducible experiments. The lack of rigorous quantitative approaches in current western blot statistical methodology may result in irreproducible inferences. Here we describe best practices for the design and analysis of western blot experiments, with examples and demonstrations of how different analytical approaches can lead to widely varying outcomes. To facilitate best practices, we have developed the blotRig tool for designing and analyzing western blot experiments to improve their rigor and reproducibility. The blotRig application includes functions for counterbalancing experimental design by lane position, batch management across gels, and analytics with covariates and random effects.