bluuebunny/crossref_metadata_2025 huggingface dataset:
Digoxin-specific antibodies: a novel dosing strategy
Authors: Dijkman Marieke A. , Gresnigt Femke M. J. , de Lange Dylan W.
Published: October 2023

Digoxin-specific antibodies (digoxin-Fabs) are of value in the treatment of a strongly suspected or a known, potentially life-threatening digoxin toxicity. These antibodies are not registered for use in Europe; therefore Dutch hospital pharmacies are not allowed to keep them in stock. In the Netherlands, digoxin-Fabs are stored in a national calamity stock of emergency medicines at the National Institute for Public Health and the Environment. In the case of a medical emergency, digoxin-Fabs are available after contact with the Dutch Poisons Information Centre. Recent studies have shown that the dose of digoxin-Fabs required to effectively treat digoxin toxicity is lower than previously thought. In this article, we present the adjusted digoxin-Fab dosing strategy currently recommended by the Dutch Poisons Information Centre (www.vergiftigingen.info). This new dose titration strategy is safe and effective and has a cost-saving side-effect.
Tissue responses to everolimus-eluting stents implanted in severely calcified lesions following atherectomy
Authors: Yamaguchi Tomohiro , Yamazaki Takanori , Yoshida Hisako , Matsumoto Kotaro , Yahiro Ryosuke , Nakao Kazuhiro , Kure Yusuke , Okai Tsukasa , Shimada Takenobu , Otsuka Kenichiro , Izumiya Yasuhiro , Fukuda Daiju
Published: October 2023

Histopathological examination has revealed that stents on severely calcified plaques were associated with delayed vascular healing. Although atherectomy devices can increase the number of malapposed struts, tissue responses to implanted drug eluting stents in atherectomy patients remain largely unknown. This retrospective observational study included 30 patients who underwent atherectomy and everolimus-eluting stent (EES) deployment for severely calcified coronary lesions (biodegradable polymer EES (BP-EES), n = 15; durable polymer EES (DP-EES), n  = 15). Optical coherence tomography was carried out at baseline and follow-up, and struts with acute stent malapposition (ASM) were categorized as struts on modified calcium (mod-Ca), non-modified calcium (non-mod-Ca), or non-calcium (non-Ca). Adequate vascular healing, defined as ASM resolution with neointimal coverage, was compared between the BP-EES and DP-EES groups. Multivariate linear regression analysis using a generalized estimated equation revealed that BP-EES use was associated with significantly better adequate vascular healing compared with DP-EES (odds ratio [OR]: 3.691, 95% confidence interval [CI] 1.175–11.592, P = 0.025). adequate vascular healing was associated with the underlying plaque morphology (mod-Ca vs non-mod-Ca: OR 2.833, 95% CI 1.491–5.384, P = 0.001; non-Ca vs non-mod-Ca: OR 1.248, 95% CI 0.440–3.543, P = 0.677). This study demonstrates that drug-eluting stent selection and calcium modification are possible factors affecting vascular healing of malapposed struts in severely calcified lesions.

Graphical Abstract
Robotic-assisted Roux-en-Y gastric bypass with the novel platform HugoTM RAS: preliminary experience in 15 patients
Authors: Raffaelli Marco , Greco Francesco , Pennestrì Francesco , Gallucci Pierpaolo , Ciccoritti Luigi , Salvi Giulia , Procopio Priscilla Francesca , Voloudakis Nikolaos
Published: October 2023

Robotic assisted surgery is a rapidly developing field in bariatric surgery. Its wide diffusion has led to the development and standardisation of robotic assisted approaches for various bariatric operations. However, further application has been limited thus far due to issues of cost-effectiveness and accessibility. The introduction of new robotic platforms may help overcome those obstacles. In this study, we present the first fifteen cases of Roux-en-Y Gastric Bypass (RYGB) operations performed with the new Hugo™ RAS system (Medtronic, Minneapolis, MN, USA). From January to March 2023, consecutive patients scheduled for minimal invasive Roux-en-Y-Bypass were randomly selected and underwent the procedure robotic-assisted with the new platform. No exclusion criteria were applied. Seven female and eight male patients with a median BMI of 42 (range: 36–50) and obesity-related comorbidities in eight cases underwent RYGB. The median docking time was 7 min (range: 6–8.5) and the median console time was 100 min (range: 70–150). Procedures were performed without intraoperative complications and no conversion to laparoscopy or open surgery was noted. Operative times were indicative of a steep learning curve. No early post-operative complications were observed. Based on our initial experience, RYGB with the Hugo™ RAS system is promising and may be integrated in established robotic programmes without requiring a long adaptation period.
Molecular Mechanisms of HIV-1 Latency from a Chromatin and Epigenetic Perspective
Authors: Jütte Bianca B. , Love Luca , Svensson J. Peter
Published: October 2023

Purpose of Review

The main obstacle to an HIV-1 cure is the reservoir of HIV-1 infected cells. While antiretroviral therapy (ART) eliminates the HIV-1 virus effectively, it does not target the reservoir. To eliminate infected cells, we need an improved understanding of the reservoir maintenance and reactivation mechanisms, including the influence of chromatin.

Recent Findings

The last years’ technological advances enable an in-depth study of the reservoir, uncovering subsets of infected cells, proviral integration sites, and single-cell nucleosome histone modifications. These revelations illustrate how the immune system and cell proliferation shape reservoirs under long-term ART. These forces create highly individual reservoirs that will require personalized treatment for their eradication.

A greater understanding of HIV-1 latency mechanisms, focusing on chromatin features, proviral reservoir dynamics, and inter-individual differences, can drive the development of more precise HIV-1 treatment strategies, ultimately achieving a globally available HIV-1 cure.
A Broad Range Triboelectric Stiffness Sensor for Variable Inclusions Recognition
Authors: Zhao Ziyi , Quan Zhentan , Tang Huaze , Xu Qinghao , Zhao Hongfa , Wang Zihan , Song Ziwu , Li Shoujie , Dharmasena Ishara , Wu Changsheng , Ding Wenbo
Published: October 2023

With the development of artificial intelligence, stiffness sensors are extensively utilized in various fields, and their integration with robots for automated palpation has gained significant attention. This study presents a broad range self-powered stiffness sensor based on the triboelectric nanogenerator (Stiff-TENG) for variable inclusions in soft objects detection. The Stiff-TENG employs a stacked structure comprising an indium tin oxide film, an elastic sponge, a fluorinated ethylene propylene film with a conductive ink electrode, and two acrylic pieces with a shielding layer. Through the decoupling method, the Stiff-TENG achieves stiffness detection of objects within 1.0 s. The output performance and characteristics of the TENG for different stiffness objects under 4 mm displacement are analyzed. The Stiff-TENG is successfully used to detect the heterogeneous stiffness structures, enabling effective recognition of variable inclusions in soft object, reaching a recognition accuracy of 99.7%. Furthermore, its adaptability makes it well-suited for the detection of pathological conditions within the human body, as pathological tissues often exhibit changes in the stiffness of internal organs. This research highlights the innovative applications of TENG and thereby showcases its immense potential in healthcare applications such as palpation which assesses pathological conditions based on organ stiffness.
Temporal dynamics of energy production at the Taïba Ndiaye wind farm in Senegal
Authors: Niang Serigne Abdoul Aziz , Drame Mamadou Simina , Gueye Ahmed , Sarr Astou , Toure Mame Diarra , Diop Dialo , Ndiaye Seydina Oumar , Talla Kharouna
Published: October 2023

The study presented in this article focuses on the temporal dynamics of wind energy production at the Taïba Ndiaye wind farm in Senegal, with a capacity of 158.7 MW. The monthly and seasonal distribution of production shows a strong trend, with maximums recorded between December and May (winter and spring) at around 1800 MWh, and minimums between July and November (summer and autumn) with production below 500 MWh. The diurnal cycle representation exhibits variation with a marked cycle, particularly between November and April. Night-time production is higher than daytime production by more than 43%. The effects of 100-m wind on the farm production are also analysed and show a positive correlation between wind speed and production throughout the year. Production peaks observed in winter and spring are caused by strong winds (approximately 8.5 m/s), while the lowest levels recorded during the summer season are due to weather conditions characterized by weak winds (less than 4 m/s). Similarly, optimal wind directions are observed in winter and spring, periods of maximum production, when the winds blow between the northwest and northeast.
Shakespeare and Place-Based Learning
Authors: Hansen Claire
Published: October 2023

Shakespeare and Place-Based Learning explores the potential of place for enriching Shakespeare pedagogy. Positioning place as a complex, multiperspectival phenomenon with stories and voices of its own, this Element considers place a partner in the learning process. The opening section traces the development of place-based education, culminating in a conceptual framework for use in Shakespeare pedagogy. Shakespeare and Place-Based Learning then examines how regional Australian students understand place in the Shakespeare classroom and presents a new definition of place designed for literary studies. This Element also investigates the challenges and potential of outdoor Shakespeare education through a case study of outdoor theatre workshops. Shakespeare and Place-Based Learning culminates with a pedagogical model and practical activities. This model aims to develop a learner's sense of place in two ways: through deepening their authentic engagement with and knowledge of Shakespeare's texts, and by expanding critical awareness of their environmental responsibilities.
A Green and Just Recovery from COVID-19?
Authors: Tienhaara Kyla , Moerenhout Tom , Corkal Vanessa , Roth Joachim , Ascough Hannah , Betancur Jessica Herrera , Hussman Samantha , Oliver Jessica , Shahani Kabir , Tischbein Tianna
Published: October 2023

Stimulus spending to address the economic crisis brought on by the COVID-19 pandemic has the potential to either facilitate the transition away from fossil energy or to lock in carbon-intensive technologies and infrastructure for decades to come. Whether they are focused on green sectors or not, stimulus measures can alleviate or reinforce socio-economic inequality. This Element delves into the data in the Energy Policy Tracker to assess the extent to which energy policies adopted during the pandemic will expedite decarbonization and explores whether governments address inequities through policies targeted to disadvantaged, marginalized and underserved individuals and communities. The overall finding is that the recovery has not been sufficiently green or just. Nevertheless, a small number of policies aim to advance distributive justice and provide potential models for policymakers as they continue to attempt to 'build back better'. This title is also available as Open Access on Cambridge Core.
Prediction of aerodynamic characteristics of high-lift Common Research Model in ground effect
Authors: Sereez M. , Abramov N. , Goman M.
Published: October 2023

Reynolds Averaged Navier-Stokes (RANS) simulations are performed to investigate the aerodynamic characteristics of the NASA Common Research Model (CRM) in its high-lift (HL) configuration in close proximity to the ground. The RANS simulations are conducted at a moderate Reynolds number of

$Re = 5.49 \times {10^6}$

and

$M = 0.2$

with the use of the Spalart-Allmaras (SA) turbulence model. out of ground effect (OGE) simulation results are validated against available wind tunnel data before proceeding to in ground effect (IGE) simulations. The obtained computational results in the immediate vicinity of the ground with asymmetric aircraft attitudes demonstrate significant changes in the longitudinal and lateral-directional aerodynamic characteristics, which should be taken into account in flight dynamics analysis of aircraft during take-off and landing in crosswind conditions.
High-fidelity post-impact residual strength assessment for composite aircraft sustainment
Authors: Jacobs K. , Harman A.B. , Ladani R.B. , Das R. , Orifici A.C.
Published: October 2023

High-fidelity simulation tools have significant potential to support composite aircraft sustainment, though further study is required on incorporating the complex impact damage field. In this paper, compressive residual strength assessment is investigated using the high-fidelity computational tool BSAMTM. The experimental impact damage was mapped and modelled at a high-fidelity level, which included ply-by-ply definition of the geometry of the impact indentation, fibre fracture in the plies and delamination in ply interfaces. It was shown that applying a small lateral displacement or ‘pseudo-impact’ step was highly effective in generating matrix cracks in the impact region, which provided a suitably realistic representation of the interconnected damage map through-the-thickness. It was found that inclusion of all damage modes in the post-image damage map at a high-fidelity definition was essential due to the strong degree of interaction between damage modes. The results support improved sustainment of defence platforms, through enhanced predictive capability and understanding.
Burnout in medical students: A longitudinal study in a Portuguese medical school
Authors: Viegas da Cunha Gentil Martins Maria Helena , Martins Lobo Vasco , dos Santos Florenciano Mafalda Sofia , Benjamim Morais Marco António , Barbosa Miguel
Published: October 2023

Background

Burnout is highly prevalent among medical students. This study aimed to assess burnout levels over the course of a semester and identify variables that might explain burnout’s variance over time.

Method

This longitudinal study involved medical students from a Portuguese school. Participants completed the Maslach Burnout Inventory and Mental Health Inventory-5, along with questions related to social support, help-seeking behaviours, academic performance, mental health and lifestyle assessment at the beginning (first phase), middle (second phase) and end (third phase) of the first semester of 2018–2019 academic year.

Results

A total of 108 participants provided responses in all phases (paired sample). The prevalence of burnout in the first phase was 28.2%, which increased to 34% in the second and 39.5% in the third. To explore factors contributing to burnout levels, we used the 332 responses obtained in the third phase (non-paired sample). Higher burnout levels were associated with poor academic performance, mental health stigma, consumption of tranquillisers and living away from home. Conversely, they were negatively associated with social support and a healthy lifestyle.

Conclusions

The study reveals a high prevalence of burnout among medical students, with burnout levels increasing throughout the semester. These levels are influenced by modifiable variables.
Investigation of shock/shock interferences on the aerodynamics of a fragment in the wake of debris in a rarefied regime/at high altitude
Authors: Cardona Vincente , Lago Viviana
Published: October 2023

This work presents an experimental investigation focused on the analysis of aerodynamic properties between two interacting spheres in a supersonic rarefied flow. Atmospheric re-entries of space debris, whether natural or man-made, begin at altitude 120 km, and observations of historical re-entries have shown that fragmentation occurs between 90 and 50 km. The resulting fragments interact with each other, altering their own trajectories while traversing the different flow regimes between the free molecular and continuum regimes. This study focuses on the intermediate slip regime, where viscous effects of varying magnitude can influence the nature of the interactions of the shocks and modify them from the already known behaviour in the continuum regime. Specifically, this study examines how two spheres interact with each other upon re-entry into the atmosphere, focusing particularly on the six types of shock/shock interactions identified by Edney. The experiments were performed in the MARHy wind tunnel, in a steady Mach 4 laminar flow with static pressure 2.67 Pa. To highlight the differences between the six types of interferences, a variety of set-ups and devices were used: flow-field visualization, aerodynamic forces (through two diagnoses, aerodynamic balance and the swinging sphere technique) and wall pressure measurements. Results demonstrate the identification of differences according to the type of interference observed, showing in particular the viscous effect of rarefied flows by making a comparison with the continuum regime.
Somalia's evolving political market place: from famine and humanitarian crisis to permanent precarity
Authors: Jaspars Susanne , Majid Nisar , Adan Guhad M.
Published: October 2023

Somalia has a long history of famine and humanitarian crisis. This article focuses on the years 2008–2020, during which governance and aid practices changed substantially and which include three crisis periods. The article examines whether and how governance analysed as a political marketplace can help explain Somalia's repeated humanitarian crises and the manipulation of response. We argue that between 2008 and 2011 the political marketplace was a violent competitive oligopoly which contributed to famine, but that from 2012 a more collusive, informal political compact resulted in a status quo which avoided violent conflict or famine in 2017 and which functioned to keep external resources coming in. At the same time, this political arrangement benefits from the maintenance of a large group of displaced people in permanent precarity as a source of aid and labour.
Social media exposure’s effects on public support toward three-child policy in China: role of cognitive elaboration, perceived negative effects, and institutional trust
Authors: Guo Jing , Feng Mengzhe
Published: October 2023

The three-child policy constitutes a hotly debated socio-political issue in China. Upon its announcement, many Chinese citizens have ridiculed the move on social media. Adopting the cognitive mediation model and the influence of presumed influence theory, this study examines how social media exposure to three-child policy-related news and discussions could affect the Chinese public’s attitudes toward the policy. The online survey results show that social media exposure negatively predicts supportive opinion via cognitive elaboration and three types of perceived negative effects of the policy (i.e., perceived negative effects on self, on the public, and on females) in serial. It also finds that institutional trust moderates the relationship between cognitive elaboration and policy support. Only among people with high institutional trust, there is a positive effect of social media exposure on supportive opinion through cognitive elaboration.
Spanning subdivisions in Dirac graphs
Authors: Pavez-Signé Matías
Published: October 2023

We show that for every
$n\in \mathbb N$
and
$\log n\le d\lt n$
, if a graph
$G$
has
$N=\Theta (dn)$
vertices and minimum degree
$(1+o(1))\frac{N}{2}$
, then it contains a spanning subdivision of every
$n$
-vertex
$d$
-regular graph.
Feeding after congenital heart surgery: a mixed-methods study of the caregiver experience
Authors: Wright Emily , Phillips Chelsea , Matthews Saria , Kavalieratos Dio , Sharp William G. , Raol Nikhila
Published: October 2023

Objectives:

Feeding difficulties after congenital heart surgery are a common concern for caregivers of children with CHD. Insight into the intricacies of their experience is lacking. With a better understanding, healthcare providers can continue to optimize the approach and support mechanisms for these families. This study will explore the psychosocial impacts on caregivers, define barriers to care, and identify areas to improve their care.

Study Design:

This mixed-methods study combined semi-structured interviews with surveys. Purposive sampling targeted caregivers of a child who underwent heart surgery and was discharged with alternative enteral feeding access. A hybrid inductive-deductive methodology was used to analyse interview transcripts. Survey scores were compared to interview content for concordance.

Results:

Fifteen interviews were conducted with socio-demographically diverse caregivers. Feeding difficulties were often identified as their greatest challenge, with the laborious feeding schedule, sleep deprivation, and tube management being common contributors. Most caregivers described feeling overwhelmed and worried. Time-intensive feeding schedules and lack of appropriate childcare options precluded caregivers’ ability to work. Barriers to care included imperfect feeding education, proximity of specialist clinics, and issues with medical supply companies. Caregiver proposals for improved care addressed easing the transition home, improving emotional support mechanisms, and intensifying feeding therapy for expedited tube removal.

Conclusion:

This study describes the psychosocial toll on the caregiver, typical barriers to care, and ideas for improved provision of care. These themes and ideas can be used to advance the family-centered approach to feeding difficulties after heart surgery.
Bilingual attentional control: Evidence from the Partial Repetition Cost paradigm
Authors: deMeurisse Grace , Kaan Edith
Published: October 2023

The effects of bilingual language experience on cognitive control are still debated. A recent proposal is that being bilingual enhances attentional control. This is based on studies showing smaller effects of the nature of the preceding trial on the current trial in bilinguals (Grundy et al., 2017). However, performance on such tasks can also be accounted for by lower-level processes such as the binding and unbinding of stimulus and response features. The current study used a Partial Repetition Cost paradigm to explicitly test whether language experience can affect such processes. Results showed that bi- and monolinguals did not differ in their responses when the stimulus features were task-relevant. However, the bilinguals showed smaller partial repetition costs when the features were task-irrelevant. These findings suggest that language experience does not affect lower-level processes, and supports the view that bilinguals exhibit enhanced attentional disengagement.
Addressing Water Poverty Under Climate Crisis: Implications for Social Policy
Authors: Valero Diana , Cook Jess , Lee Angus , Browne Alison L. , Ellis Rowan , Pancholi Vidya Sagar , Hoolohan Claire
Published: October 2023

Access to safe, clean and affordable water is a basic human right and a global goal towards which climate change poses new challenges that heavily impact the health and wellbeing of people across the globe and exacerbate or create new inequalities. These challenges are shaped by a number of geographical and social conditions that, apart from the risks of weather-driven impacts on water, include water governance and management arrangements in place, including pricing tariffs, and the interplay of social and economic inequalities. Building on examples from Australia, Scotland and England and Wales that illustrate access to water in different types of water provision systems, and regarding to aspects of access, quality and affordability, this paper explores the types of challenges related to water poverty in the context of climate crisis and reflects on the multiple dimensions of water poverty oriented social policy at the interplay of climate change associated risks.
Shifts in the Isotopic Composition of Nitrous Oxide Between El Niño and La Niña in the Eastern Tropical South Pacific
Authors: Gluschankoff Noah , Santoro Alyson E. , Buchwald Carolyn , Casciotti Karen L.
Published: October 2023

The El Niño‐Southern Oscillation (ENSO) is a natural climate phenomenon that alters the biogeochemical and physical dynamics of the Eastern Tropical Pacific Ocean. Its two phases, El Niño and La Niña, are characterized by decreased and increased coastal upwelling, respectively, which have cascading effects on primary productivity, organic matter supply, and ocean‐atmosphere interactions. The Eastern Tropical South Pacific oxygen minimum zone is a source of nitrous oxide (N2O), a potent greenhouse gas, to the atmosphere. Here, we present the first study to directly compare N2O sources during opposing ENSO phases using N2O isotopocule analyses. Our data show that during La Niña, N2O accumulation increased six‐fold in the upper 100 m of the water column, and N2O fluxes to the atmosphere increased up to 20‐fold. N2O isotopocule data demonstrated substantial increases in δ18O up to 60.5‰ and decreases in δ15Nβ down to −10.3‰ in the oxycline, signaling a shift in N2O cycling during La Niña compared to El Niño. During El Niño, N2O production was primarily due to ammonia‐oxidizing archaea, whereas during La Niña, N2O production by incomplete denitrification supplemented that from ammonia‐oxidation, with N2O consumption likely maintaining the high site preference values (up to 26.7‰). Ultimately, our results illustrate a strong connection between upwelling intensity, biogeochemistry, and N2O flux to the atmosphere. Additionally, they highlight the combined power of N2O isotopocule analysis and repeat measurements in the same region to constrain N2O interannual variability and cycling dynamics under different climate scenarios.
A Cascadia Slab Model From Receiver Functions
Authors: Bloch Wasja , Bostock Michael G. , Audet Pascal
Published: October 2023

We map the characteristic signature of the subducting Juan de Fuca and Gorda plates along the entire Cascadia forearc from northern Vancouver Island, Canada, to Cape Mendocino in northern California, USA, using teleseismic receiver functions. The subducting oceanic crustal complex, possibly including subcreted material, is parameterized by three horizons capable of generating mode‐converted waves: a negative velocity contrast at the top of a low velocity zone underlain by two horizons representing positive contrasts. The amplitude of the conversions varies likely due to differences in composition and/or fluid content. We analyzed the slab signature for 298 long‐running land seismic stations, estimated the depth of the three interfaces through inverse modeling and fitted regularized spline surfaces through the station control points to construct a margin‐wide, double‐layered slab model. Crystalline terranes that act as the static backstop appear to form the major structural barrier that controls the slab morphology. Where the backstop recedes landward beneath the Olympic Peninsula and Cape Mendocino, the slab subducts sub‐horizontally, while the seaward‐protruding and thickened Siletz terrane beneath central Oregon causes steepening of the slab. A tight bend in slab morphology south of the Olympic Peninsula coincides with the location of recurring large intermediate depth earthquakes. The top‐to‐Moho thickness of the slab generally exceeds the thickness of the oceanic crust by 2–12 km, suggesting thickening of the slab or underplating of slab material to the overriding North American plate.
Updates on Model Hierarchies for Understanding and Simulating the Climate System: A Focus on Data‐Informed Methods and Climate Change Impacts
Authors: Mansfield Laura A. , Gupta Aman , Burnett Adam C. , Green Brian , Wilka Catherine , Sheshadri Aditi
Published: October 2023

The climate model hierarchy encompasses models of varying complexity along different axes, ranging from idealized models that elegantly describe isolated mechanisms to fully coupled Earth system models that aspire to provide useable climate projections. Based on the second Model Hierarchies Workshop, which took place in 2022, we present perspectives on how this field has evolved since the first Model Hierarchies Workshop in 2016. In this period, we have witnessed a dramatic increase in the use of (a) machine learning in climate modeling and (b) climate models to estimate risks and influence decision making under climate change. Here, we discuss the implications of these growing areas of research and how we expect them to become integrated into the model hierarchies framework.
Multi‐Site Transfer Function Approach for Real‐Time Modeling of the Ground Electric Field Induced by Laterally‐Nonuniform Ionospheric Source
Authors: Kruglyakov Mikhail , Marshalko Elena , Kuvshinov Alexey , Smirnov Maxim , Viljanen Ari
Published: October 2023

We propose a novel approach to model the ground electric field (GEF) induced by laterally‐nonuniform ionospheric sources in real time. The approach exploits the multi‐site transfer function concept, continuous magnetic field measurements at multiple sites in the region of interest, and spatial modes describing the ionospheric source. We compared the modeled GEFs with those measured at two locations in Fennoscandia and observed good agreement between modeled and measured GEF. Besides, we compared GEF‐based geomagnetically induced current (GIC) with that measured at the Mäntsälä natural gas pipeline recording point and again observed remarkable agreement between modeled and measured GIC.
Morpho‐Tectonics of Transpressional Systems: Insights From Analog Modeling
Authors: Conrad Ethan M. , Reitano Riccardo , Faccenna Claudio , Becker Thorsten W.
Published: October 2023

Transpressional margins are widespread, and their dynamics are relevant for plate boundary evolution globally. Though transpressional orogen evolution involves a topographic response to deformation, many studies focus only on the structural development of the system ignoring surface processes. Here, we present a new set of analog models constructed to investigate how tectonic and surface processes interact at transpressive plate boundaries and shape topography. Experiments are conducted by deforming a previously benchmarked crustal analog material in a meter‐scale plexiglass box while controlling erosion through misting nozzles mounted along the transpressional wedge. To analyze the experiments, we generate digital elevation models from laser scans and conduct image correlation analysis on photos taken during experiments. We focus on three experiments that cover a range of erosional conditions and shortening stages (two end‐member erosion models and a dry reference). In all experiments, a bivergent wedge forms, and strain partitioning broadly evolves according to previously established models. Regarding drainage networks, we find that the streams in our models develop differently through feedback between fault development and drainage rearrangement processes. Differences between end‐member erosional models can be explained by the varying response of streams to structure modulated by rainfall. Additionally, erosion may influence the structural evolution of transpressional topography, leading to accelerated strike‐slip partitioning. From these results, we create a model for developing structures, streams, and topography where incision and valley formation along main structures localize exhumation. We apply insights from the models to natural transpressional systems, including the Transverse Ranges, CA, and the Venezuelan Andes.
Toward Street‐Level Nowcasting of Flash Floods Impacts Based on HPC Hydrodynamic Modeling at the Watershed Scale and High‐Resolution Weather Radar Data
Authors: Costabile Pierfranco , Costanzo Carmelina , Kalogiros John , Bellos Vasilis
Published: October 2023

In our era, the rapid increase of parallel programming coupled with high‐performance computing (HPC) facilities allows for the use of two‐dimensional shallow water equation (2D‐SWE) algorithms for simulating floods at the “hydrological” catchment scale, rather than just at the “hydraulic” fluvial scale. This approach paves the way for the development of new operational systems focused on impact‐based flash‐floods nowcasting, wherein hydrodynamic simulations directly model the spatial and temporal variability of measured or predicted rainfall on impacts even at a street scale. Specifically, the main goal of this research is to make a step to move toward the implementation of an effective flash flood nowcasting system in which timely and accurate impact warnings are provided by including weather radar products in the HPC 2D‐SWEs modelling framework able to integrate watershed hydrology, flow hydrodynamics, and river urban flooding in just one model. The timing, location, and intensity of the street‐level evolution of some key elements at risk (people, vehicles, and infrastructures) are also discussed considering both calibration issues and the role played by the spatial and temporal rainfall resolution. All these issues are analyzed and discussed having as a starting point the flood event which hit the Mandra town (Athens, Greece) on the 15 November 2017, highlighting the feasibility and the accuracy of the overall approach and providing new insights for the research in this field.
Polygenic predisposition, sleep duration, and depression: evidence from a prospective population-based cohort
Authors: Hamilton Odessa S. , Steptoe Andrew , Ajnakina Olesya
Published: October 2023

Suboptimal sleep durations and depression frequently cooccur. Short-sleep and long-sleep are commonly thought of as symptoms of depression, but a growing literature suggests that they may be prodromal. While each represents a process of mutual influence, the directionality between them remains unclear. Using polygenic scores (PGS), we investigate the prospective direction involved in suboptimal sleep durations and depression. Male and female participants, aged ≥50, were recruited from the English Longitudinal Study of Ageing (ELSA). PGS for sleep duration, short-sleep, and long-sleep were calculated using summary statistics data from the UK Biobank cohort. Sleep duration, categorised into short-sleep (“≤5 h”), optimal-sleep (“>5 to <9 h”), and long-sleep (“≥9 h”), was measured at baseline and across an average 8-year follow-up. Subclinical depression (Centre for Epidemiological Studies Depression Scale [≥4 of 7]) was also ascertained at baseline and across an average 8-year follow-up. One standard deviation increase in PGS for short-sleep was associated with 14% higher odds of depression onset (95% CI = 1.03–1.25, p = 0.008). However, PGS for sleep duration (OR = 0.92, 95% CI = 0.84–1.00, p = 0.053) and long-sleep (OR = 0.97, 95% CI = 0.89–1.06, p = 0.544) were not associated with depression onset during follow-up. During the same period, PGS for depression was not associated with overall sleep duration, short-sleep, or long-sleep. Polygenic predisposition to short-sleep was associated with depression onset over an average 8-year period. However, polygenic predisposition to depression was not associated with overall sleep duration, short-sleep or long-sleep, suggesting different mechanisms underlie the relationship between depression and the subsequent onset of suboptimal sleep durations in older adults.
Lactylation of METTL16 promotes cuproptosis via m6A-modification on FDX1 mRNA in gastric cancer
Authors: Sun Lianhui , Zhang Yuan , Yang Boyu , Sun Sijun , Zhang Pengshan , Luo Zai , Feng Tingting , Cui Zelin , Zhu Ting , Li Yuming , Qiu Zhengjun , Fan Guangjian , Huang Chen
Published: October 2023

Cuproptosis, caused by excessively high copper concentrations, is urgently exploited as a potential cancer therapeutic. However, the mechanisms underlying the initiation, propagation, and ultimate execution of cuproptosis in tumors remain unknown. Here, we show that copper content is significantly elevated in gastric cancer (GC), especially in malignant tumors. Screening reveals that METTL16, an atypical methyltransferase, is a critical mediator of cuproptosis through the m6A modification on FDX1 mRNA. Furthermore, copper stress promotes METTL16 lactylation at site K229 followed by cuproptosis. The process of METTL16 lactylation is inhibited by SIRT2. Elevated METTL16 lactylation significantly improves the therapeutic efficacy of the copper ionophore– elesclomol. Combining elesclomol with AGK2, a SIRT2-specific inhibitor, induce cuproptosis in gastric tumors in vitro and in vivo. These results reveal the significance of non-histone protein METTL16 lactylation on cuproptosis in tumors. Given the high copper and lactate concentrations in GC, cuproptosis induction becomes a promising therapeutic strategy for GC.
Structural basis for recruitment of TASL by SLC15A4 in human endolysosomal TLR signaling
Authors: Chen Xudong , Xie Min , Zhang Sensen , Monguió-Tortajada Marta , Yin Jian , Liu Chang , Zhang Youqi , Delacrétaz Maeva , Song Mingyue , Wang Yixue , Dong Lin , Ding Qiang , Zhou Boda , Tian Xiaolin , Deng Haiteng , Xu Lina , Liu Xiaohui , Yang Zi , Chang Qing , Na Jie , Zeng Wenwen , Superti-Furga Giulio , Rebsamen Manuele , Yang Maojun
Published: October 2023

Toll-like receptors (TLRs) are a class of proteins that play critical roles in recognizing pathogens and initiating innate immune responses. TASL, a recently identified innate immune adaptor protein for endolysosomal TLR7/8/9 signaling, is recruited by the lysosomal proton-coupled amino-acid transporter SLC15A4, and then activates IRF5, which in turn triggers the transcription of type I interferons and cytokines. Here, we report three cryo-electron microscopy (cryo-EM) structures of human SLC15A4 in the apo monomeric and dimeric state and as a TASL-bound complex. The apo forms are in an outward-facing conformation, with the dimeric form showing an extensive interface involving four cholesterol molecules. The structure of the TASL-bound complex reveals an unprecedented interaction mode with solute carriers. During the recruitment of TASL, SLC15A4 undergoes a conformational change from an outward-facing, lysosomal lumen-exposed state to an inward-facing state to form a binding pocket, allowing the N-terminal helix of TASL to be inserted into. Our findings provide insights into the molecular basis of regulatory switch involving a human solute carrier and offers an important framework for structure-guided drug discovery targeting SLC15A4-TASL-related human autoimmune diseases.
Asymptotic dispersion engineering for ultra-broadband meta-optics
Authors: Hu Yueqiang , Jiang Yuting , Zhang Yi , Yang Xing , Ou Xiangnian , Li Ling , Kong Xianghong , Liu Xingsi , Qiu Cheng-Wei , Duan Huigao
Published: October 2023

Dispersion decomposes compound light into its monochromatic components, which is detrimental to broadband imaging but advantageous for spectroscopic applications. Metasurfaces provide a unique path to modulate the dispersion by adjusting structural parameters on a two-dimensional plane. However, conventional linear phase compensation does not adequately match the meta-unit’s dispersion characteristics with required complex dispersion, hindering at-will dispersion engineering over a very wide bandwidth particularly. Here, we propose an asymptotic phase compensation strategy for ultra-broadband dispersion-controlled metalenses. Metasurfaces with extraordinarily high aspect ratio nanostructures have been fabricated for arbitrary dispersion control in ultra-broad bandwidth, and we experimentally demonstrate the single-layer achromatic metalenses in the visible to infrared spectrum (400 nm~1000 nm, NA = 0.164). Our proposed scheme provides a comprehensive theoretical framework for single-layer meta-optics, allowing for arbitrary dispersion manipulation without bandwidth restrictions. This development is expected to have significant applications in ultra-broadband imaging and chromatography detection, among others.
Nanomechanical action opens endo-lysosomal compartments
Authors: Zhao Yu , Ye Zhongfeng , Song Donghui , Wich Douglas , Gao Shuliang , Khirallah Jennifer , Xu Qiaobing
Published: October 2023

Endo-lysosomal escape is a highly inefficient process, which is a bottleneck for intracellular delivery of biologics, including proteins and nucleic acids. Herein, we demonstrate the design of a lipid-based nanoscale molecular machine, which achieves efficient cytosolic transport of biologics by destabilizing endo-lysosomal compartments through nanomechanical action upon light irradiation. We fabricate lipid-based nanoscale molecular machines, which are designed to perform mechanical movement by consuming photons, by co-assembling azobenzene lipidoids with helper lipids. We show that lipid-based nanoscale molecular machines adhere onto the endo-lysosomal membrane after entering cells. We demonstrate that continuous rotation-inversion movement of Azo lipidoids triggered by ultraviolet/visible irradiation results in the destabilization of the membranes, thereby transporting cargoes, such as mRNAs and Cre proteins, to the cytoplasm. We find that the efficiency of cytosolic transport is improved about 2.1-fold, compared to conventional intracellular delivery systems. Finally, we show that lipid-based nanoscale molecular machines are competent for cytosolic transport of tumour antigens into dendritic cells, which induce robust antitumour activity in a melanoma mouse model.
Insights into the missing apiosylation step in flavonoid apiosides biosynthesis of Leguminosae plants
Authors: Wang Hao-Tian , Wang Zi-Long , Chen Kuan , Yao Ming-Ju , Zhang Meng , Wang Rong-Shen , Zhang Jia-He , Ågren Hans , Li Fu-Dong , Li Junhao , Qiao Xue , Ye Min
Published: October 2023

Apiose is a natural pentose containing an unusual branched-chain structure. Apiosides are bioactive natural products widely present in the plant kingdom. However, little is known on the key apiosylation reaction in the biosynthetic pathways of apiosides. In this work, we discover an apiosyltransferase GuApiGT from Glycyrrhiza uralensis. GuApiGT could efficiently catalyze 2″-O-apiosylation of flavonoid glycosides, and exhibits strict selectivity towards UDP-apiose. We further solve the crystal structure of GuApiGT, determine a key sugar-binding motif (RLGSDH) through structural analysis and theoretical calculations, and obtain mutants with altered sugar selectivity through protein engineering. Moreover, we discover 121 candidate apiosyltransferase genes from Leguminosae plants, and identify the functions of 4 enzymes. Finally, we introduce GuApiGT and its upstream genes into Nicotiana benthamiana, and complete de novo biosynthesis of a series of flavonoid apiosides. This work reports an efficient phenolic apiosyltransferase, and reveals mechanisms for its sugar donor selectivity.
Realization and topological properties of third-order exceptional lines embedded in exceptional surfaces
Authors: Tang Weiyuan , Ding Kun , Ma Guancong
Published: October 2023

As the counterpart of Hermitian nodal structures, the geometry formed by exceptional points (EPs), such as exceptional lines (ELs), entails intriguing spectral topology. We report the experimental realization of order-3 exceptional lines (EL3) that are entirely embedded in order-2 exceptional surfaces (ES2) in a three-dimensional periodic synthetic momentum space. The EL3 and the concomitant ES2, together with the topology of the underlying space, prohibit the evaluation of their topology in the eigenvalue manifold by prevailing topological characterization methods. We use a winding number associated with the resultants of the Hamiltonian. This resultant winding number can be chosen to detect only the EL3 but ignores the ES2, allowing the diagnosis of the topological currents carried by the EL3, which enables the prediction of their evolution under perturbations. We further reveal the connection between the intersection multiplicity of the resultants and the winding of the resultant field around the EPs and generalize the approach for detecting and topologically characterizing higher-order EPs. Our work exemplifies the unprecedented topology of higher-order exceptional geometries and may inspire new non-Hermitian topological applications.
CD8+ T cells control SIV infection using both cytolytic effects and non-cytolytic suppression of virus production
Authors: Policicchio Benjamin B. , Cardozo-Ojeda Erwing Fabian , Xu Cuiling , Ma Dongzhu , He Tianyu , Raehtz Kevin D. , Sivanandham Ranjit , Kleinman Adam J. , Perelson Alan S. , Apetrei Cristian , Pandrea Ivona , Ribeiro Ruy M.
Published: October 2023

Whether CD8+ T lymphocytes control human immunodeficiency virus infection by cytopathic or non-cytopathic mechanisms is not fully understood. Multiple studies highlighted non-cytopathic effects, but one hypothesis is that cytopathic effects of CD8+ T cells occur before viral production. Here, to examine the role of CD8+ T cells prior to virus production, we treated SIVmac251-infected macaques with an integrase inhibitor combined with a CD8-depleting antibody, or with either reagent alone. We analyzed the ensuing viral dynamics using a mathematical model that included infected cells pre- and post- viral DNA integration to compare different immune effector mechanisms. Macaques receiving the integrase inhibitor alone experienced greater viral load decays, reaching lower nadirs on treatment, than those treated also with the CD8-depleting antibody. Models including CD8+ cell-mediated reduction of viral production (non-cytolytic) were found to best explain the viral profiles across all macaques, in addition an effect in killing infected cells pre-integration (cytolytic) was supported in some of the best models. Our results suggest that CD8+ T cells have both a cytolytic effect on infected cells before viral integration, and a direct, non-cytolytic effect by suppressing viral production.
A random optical parametric oscillator
Authors: Tovar Pedro , von der Weid Jean Pierre , Wang Yuan , Chen Liang , Bao Xiaoyi
Published: October 2023

Synchronously pumped optical parametric oscillators (OPOs) provide ultra-fast light pulses at tuneable wavelengths. Their primary drawback is the need for precise cavity control (temperature and length), with flexibility issues such as fixed repetition rates and marginally tuneable pulse widths. Targeting a simpler and versatile OPO, we explore the inherent disorder of the refractive index in single-mode fibres realising the first random OPO – the parametric analogous of random lasers. This novel approach uses modulation instability (χ(3)non-linearity) for parametric amplification and Rayleigh scattering for feedback. The pulsed system exhibits high inter-pulse coherence (coherence time of ~0.4 ms), offering adjustable repetition rates (16.6–2000 kHz) and pulse widths (0.69–47.9 ns). Moreover, it operates continuously without temperature control loops, resulting in a robust and flexible device, which would find direct application in LiDAR technology. This work sets the stage for future random OPOs using different parametric amplification mechanisms.