bluuebunny/crossref_metadata_2025 huggingface dataset:
How Do Legal Aid Cuts in England and Wales Impact LGBTQ+ People Seeking Asylum? Perspectives from Providers and Directly Affected People
Authors: Alessi Edward J. , Alexander Lillian , Lee Yong Gun , Fletcher Claire , Aziz Ayesha , Zadeh Leila
Published: July 2024

Introduction

LGBTQ+ people seeking asylum in England and Wales may experience disproportionate risk due to recent cutbacks in legal aid services, including inconsistent standards for determining the credibility of asylum claims and the inability to obtain essential resources.

Methods

Interviews were conducted with legal, social care, and mental health professionals (n = 17) and directly affected people (n = 9) from January to April 2023 to explore how legal aid cuts shape the experiences of LGBTQ+ people seeking asylum in England and Wales.

Results

Guided by the concept of structural violence and employing constructivist grounded theory analysis, this qualitative study identified four themes demonstrating the impact of legal aid cuts: making it difficult to find solicitors with expertise in working with LGBTQ+ people seeking asylum; forcing solicitors to make difficult choices about the clients they accept; compromising the ability of solicitors to build the trust needed to work with LGBTQ+ people seeking asylum; and compounding life instabilities for LGBTQ+ people seeking asylum.

Conclusions

Findings reveal that legal aid cuts contribute to structural violence against LGBTQ+ people seeking asylum by constraining the ability of solicitors to properly represent their asylum claims and thus prolonging the deleterious conditions faced by this population.

Policy Implications

Efforts are needed to ensure access to legal aid services for LGBTQ+ people seeking asylum in England and Wales. Adequately funding legal aid services would also better enable solicitors to apply trauma-informed legal practices, which is imperative for effectively engaging with and representing LGBTQ+ people seeking asylum.
Analysis of Oncology and Radiation Therapy Representation on the National Board of Medical Examiners Official Practice Material for the United States National Standardized Medical Board Examinations
Authors: Mahoney Mary T. , Linkowski Lauren C. , Wu Trudy C. , Chen Jie Jane , Neilsen Beth K. , Thompson Petria S. , Mix Michael D. , Sura Karna T. , Mattes Malcolm D.
Published: July 2024

Radiation therapy (RT) is a critical component of multidisciplinary cancer care, but has inconsistent curricular exposure. We characterize the radiation oncology (RO) content on the standardized undergraduate medical examinations by comparing its context and prevalence with other domains in oncology. National Board of Medical Examiners (NBME) self-assessments and sample questions for the United States Medical Licensing Exam (USMLE) Steps 1–3 and NBME clinical science shelf examinations were accessed (n = 3878). Questions were inductively analyzed for content pertaining to oncology and treatment modalities of RT, systemic therapy (ST), and surgical intervention (SI). Questions were coded using USMLE Physician Tasks/Competencies and thematic analysis. Descriptive statistics and analyses using the Kruskal–Wallis test are reported. A total of 337 questions (8.6%) within the USMLE and shelf exams included oncology content, with 101 questions (2.6%) referencing at least one cancer treatment modality (n = 35 RT, 45 ST, 57 SI). Treatment questions were more common on USMLE Step 2 CK (n = 35/101, 32%) compared to Step 1 (n = 23/101, 23%) and Step 3 (n = 8/101, 8%) (p < 0.001). RT was significantly less likely to be the correct answer (2/35, 6%) compared to ST (4/45, 9%) and SI (18/57, 32%) (p = 0.003). Therapeutic oncology questions are uncommon on the examination material, with an under-representation of radiation-related content, and contextual bias favoring surgical approaches. We advocate for greater RO involvement in the content creation of such examinations to help trainees better understand multidisciplinary cancer care.
Railway Slope Monitoring Based on Dual-Parameter FBG Sensor
Authors: Xu Hongbin , Wang Weiwei , Li Feng , Du Yanliang , Tu Hongliang , Guo Chuanrui
Published: July 2024

A large number of slopes appear along the line during railway construction, which will pose a threat to railway safety operation. Slope monitoring plays an important role in ensuring the safety of railway operation. Aiming at the difficulties of sensor multiplexing, low accuracy, and large disturbance by trains, this paper proposes a railway slope monitoring method based on integrated fusion detection of inclination and vibration. Instability and failure characteristics of the K3 slope in Shuohuang Railway and dynamic characteristics under the excitation of the train load are analyzed by the finite element method (FEM) analysis. Based on the above analysis, a slope monitoring system is established utilizing the self-developed dual-parameter fiber Bragg grating (FBG) sensor. The monitoring data of the past four years show that the slope is in a relatively stable state at present. The monitoring data are consistent with the results of the FEM. The feasibility of the damage identification method based on inclination and vibration characteristics is verified, which provides a new method for railway slope monitoring.
Natural compounds-based nanomedicines for cancer treatment: Future directions and challenges
Authors: Andreani Tatiana , Cheng Ruoyu , Elbadri Khalil , Ferro Claudio , Menezes Thacilla , dos Santos Mayara R. , Pereira Carlos M. , Santos Hélder A.
Published: July 2024

Several efforts have been extensively accomplished for the amelioration of the cancer treatments using different types of new drugs and less invasives therapies in comparison with the traditional therapeutic modalities, which are widely associated with numerous drawbacks, such as drug resistance, non-selectivity and high costs, restraining their clinical response. The application of natural compounds for the prevention and treatment of different cancer cells has attracted significant attention from the pharmaceuticals and scientific communities over the past decades. Although the use of nanotechnology in cancer therapy is still in the preliminary stages, the application of nanotherapeutics has demonstrated to decrease the various limitations related to the use of natural compounds, such as physical/chemical instability, poor aqueous solubility, and low bioavailability. Despite the nanotechnology has emerged as a promise to improve the bioavailability of the natural compounds, there are still limited clinical trials performed for their application with various challenges required for the pre-clinical and clinical trials, such as production at an industrial level, assurance of nanotherapeutics long-term stability, physiological barriers and safety and regulatory issues. This review highlights the most recent advances in the nanocarriers for natural compounds secreted from plants, bacteria, fungi, and marine organisms, as well as their role on cell signaling pathways for anticancer treatments. Additionally, the clinical status and the main challenges regarding the natural compounds loaded in nanocarriers for clinical applications were also discussed.

Graphical abstract
Rawlsian Algorithmic Fairness and a Missing Aggregation Property of the Difference Principle
Authors: Franke Ulrik
Published: July 2024

Modern society makes extensive use of automated algorithmic decisions, fueled by advances in artificial intelligence. However, since these systems are not perfect, questions about fairness are increasingly investigated in the literature. In particular, many authors take a Rawlsian approach to algorithmic fairness. Based on complications with this approach identified in the literature, this article discusses how Rawls’s theory in general, and especially the difference principle, should reasonably be applied to algorithmic fairness decisions. It is observed that proposals to achieve Rawlsian algorithmic fairness often aim to uphold the difference principle in the individual situations where automated decision-making occurs. However, the Rawlsian difference principle applies to society at large and does not aggregate in such a way that upholding it in constituent situations also upholds it in the aggregate. But such aggregation is a hidden premise of many proposals in the literature and its falsity explains many complications encountered.
Young People’s Barriers and Facilitators of Engagement with Web-Based Mental Health Interventions for Anxiety and Depression: A Qualitative Study
Authors: Ho Thi Quynh Anh , Engel Lidia , Melvin Glenn , Le Long Khanh-Dao , Le Ha N. D. , Mihalopoulos Cathrine
Published: July 2024

Background

The prevalence of anxiety and depressive symptoms in young people have increased in many countries around the world. Web-based mental health interventions (or W-MHIs) have the potential to reduce anxiety and depression symptoms for young people. Although W-MHIs have become more widely used by young people since the coronavirus disease 2019 (COVID-19) pandemic, real-world engagement in these W-MHIs has remained low compared with engagement reported in research studies. Moreover, there are limited studies examining factors influencing engagement with W-MHIs in the post-COVID-19 pandemic years.

Objective

This study aims to explore barriers and facilitators of engagement with W-MHIs for anxiety and depression among young people.

Method

Seventeen semi-structured interviews and one focus group with three participants were conducted online via Zoom between February and March 2023. Participants were young people aged 18–25 years who had self-reported experience of anxiety and/or depression in the past 6 months, lived in Australia, and considered using W-MHIs to manage their anxiety and/or depression symptoms. Inductive thematic analysis was performed to understand the key barriers and facilitators of young people’s engagement with W-MHIs.

Results

Both individual- and intervention-related factors influenced young people’s engagement with W-MHIs. Facilitators of engagement included personal trust and beliefs in W-MHIs, ability to contact a health professional, programme suitability (e.g., affordability, content aligning with user needs), programme usability (e.g., user interface), and accessibility of the online platform. Barriers included concerns about online security, lack of human interaction and immediate responses from health professionals (if any), and negative experience with mental health programmes. Participants expressed greater willingness to pay if they could contact health professionals during the programme.

Conclusion

Better promotion strategies for mental health and W-MHI awareness are needed to increase the perceived importance and priority of mental health interventions among young people. Young people should be involved in the W-MHI co-design to enhance the programme suitability and usability for young people, fostering their engagement with W-MHIs.
Assessment of Innovative Pharmacological Targets in Schizophrenia
Authors: Reynolds de Sousa Teresa , Ribeiro Marta , Novais Filipa
Published: July 2024

Purpose of review

Schizophrenia is a disorder with an approximate prevalence of 1% associated with great impairments in daily life functioning and important distress. The pharmacological treatments available thus far address, almost exclusively, the positive symptoms of the disorder, leaving cognitive and negative symptoms without an effective treatment. Additionally, a significant group of patients presents treatment-resistant forms of the disorder, and the schizophrenia drug pipeline has been stagnant. This review examines the existing evidence on potential novel drug targets for the disorder.

Recent findings

Several systems have been implicated in the pathophysiology of schizophrenia and several agents addressing disturbances in those systems have been tested in recent years.

We summarize significant findings on the multiple systems disrupted in schizophrenia (e.g. neurotransmitters, hormones, inflammation-related, intracellular mechanisms) and discuss potential strategies to target those disturbances. We review some new drugs developed for and tested in the patients/models of the disorder.
Benefits of a family-based care transition program for older adults after hip fracture surgery
Authors: Mashhadi-Naser Sahar , Sabet Fatemeh Pashaei , Nasiri Malihe , Vasli Parvaneh
Published: July 2024

Background

Hip fracture (HF) in older adults is strongly associated with a greater decline in their activities of daily living (ADLs) and health-related (HRQoL). The present study aimed to evaluate the effects of a family-based care transition program (FBCTP) on ADLs, HRQoL and social support in this age group after HF surgery.

Methods

A quasi-experimental design was conducted on 100 older adults who had undergone HFS and were selected by convenience sampling and allocated to the IG (n = 50) and the CG (n = 50). Data were collected utilizing the Barthel Index, the 12-item Short Form Health Survey (SF-12), and the Multidimensional Scale of Perceived Social Support. The FBCTP was delivered in-hospital education sessions, home visit, and a follow-up and telephone counselling session. The data were collected at three stages, including the baseline, four weeks after discharge, and eight weeks later. The level of statistical significance was set at 0.05.

Results

The results of the study indicated that the effects of time and group on the increase in ADLs were 15.2 and 36.69 (p < 0.000), respectively, following the completion of the FBCTP. Furthermore, time and group were found to have a positive effect on HRQoL, with an increase of 2.82 and 5.60 units, respectively (p < 0.000). In this context, time and group also interacted in the IG compared to the CG, with scores increasing by 1.86 units over time (p < 0.000). Although the study results indicated that social support improved by 1.98 units over time (p < 0.000), the effects of group alone and the time × group interaction were not statistically significant. This indicates that the program was not effective in accelerating social support.

Conclusion

Consequently, nurses, policymakers, and planners engaged in geriatric healthcare may utilize these results to enhance the health status of this age group following HFS.
Running safety assessment method of trains under seismic conditions based on the derailment risk domain
Authors: Zhu Zhihui , Zhou Gaoyang , Zheng Weiqi , Gong Wei , Tang Yongjiu
Published: July 2024

The accurate assessment of running safety during earthquakes is of significant importance for ensuring the safety of railway lines. Currently, assessment methods based on a single index suffer from issues such as misjudgment of operational safety and difficulty in evaluating operational margin, making them unsuitable for assessing train safety during earthquakes. Therefore, in order to propose an effective evaluation method for the running safety of trains during earthquakes, this study employs three indexes, namely lateral displacement of the wheel–rail contact point, wheel unloading rate, and wheel lift, to describe the lateral and vertical contact states between the wheel and rail. The corresponding evolution characteristics of the wheel–rail contact states are determined, and the derailment forms under different frequency components of seismic motion are identified through dynamic numerical simulations of the train–track coupled system under sine excitation. The variations in the wheel–rail contact states during the transition from a safe state to the critical state of derailment are analyzed, thereby constructing the evolutionary path of train derailment and seismic derailment risk domain. Lastly, the wheel–rail contact and derailment states under seismic conditions are analyzed, thus verifying the effectiveness of the evaluation method for assessing running safety under earthquakes proposed in this study. The results indicate that the assessment method based on the derailment risk domain accurately and comprehensively reflects the wheel–rail contact states under seismic conditions. It successfully determines the forms of train derailment, the risk levels of derailment, and the evolutionary paths of derailment risk.
The Relationship Between Engagement Time in Case-based Learning and Performance on Preclinical Medical Education Exams
Authors: Tuin Ashley M. , Schechter Thomas , Eno Cassie A. H.
Published: July 2024

Case- and team-based learning activities are increasingly popular in medical education. Our institution utilizes a novel approach of using case-based learning (CBL) as prework for team-based learning (TBL) in preclinical medical education. This study evaluated the relationship between the time spent in CBL and performance on subsequent assessments including TBL performance on the IRAT and TRAT, and exam performance. Positive relationships were found between IRAT and exam performance. Time spent completing CBL was not found to be related to IRAT or exam performance. Implications for medical education are discussed.
The Role of Prosocial Behaviour in the Deceleration of Conduct Problem Behaviour
Authors: Williams Corrie , McGee Tara Renae , Walding Shannon , Bond Christine E. W.
Published: July 2024

While conduct problem behaviour initiated in early childhood often escalates in frequency and seriousness through adolescence, a notable deceleration is typically seen by mid-adolescence. It has been hypothesised that prosocial behaviour, characterised by acts like sharing and comforting, may play a role in this deceleration. However, there is a distinct gap in the current literature when it comes to understanding the temporal dynamics between the acceleration of prosocial behaviours and the deceleration of conduct problem behaviour. This study seeks to bridge this gap. Using a General Cross-Lagged Panel Model (GCLM) and data from the Longitudinal Study of Australian Children (LSAC), we investigated temporal dynamics and sequence of how the acceleration of prosocial behaviour influences the deceleration of conduct problem behaviour between ages 4 and 15. Results indicate that increases in prosocial behaviour facilitate the deceleration of conduct problem behaviour, with increases in prosocial behaviour preceding decreases in conduct problem behaviour. Further, we show a cumulative effect of increases in prosocial behaviour on decreases in conduct problem behaviour over time. This knowledge provides a foundation for understanding how timely prevention and intervention strategies that include the mechanisms for increasing prosocial behaviour may interrupt the conduct problem behaviour trajectories of children and adolescents.
Structural assessment of translucent walls built with a novel type of insulating aerogel-filled glass bricks
Authors: Silvestru Vlad-Alexandru , Bianchi Christian , Wernery Jannis , Ganobjak Michal
Published: July 2024

Among a multitude of functions, the façade is responsible for providing sufficient thermal insulation and supplying the building interior with enough natural light. For the latter, transparent glazed areas are essential. However, compromises in terms of the glass-to-wall ratio are often necessary since large glazed areas lead to overheating in summer and heat loss in winter. A novel type of highly insulating translucent glass brick made from annealed glass and filled with aerogel granulate was developed recently as an alternative in this regard. The bricks are not supposed to replace the transparent glass areas, but to offer a translucent alternative for part of the otherwise opaque wall areas. This paper focuses on the structural behaviour of walls composed of such aerogel-filled glass bricks. The components of such a brick and their functions are described. Moreover, two prototype systems for supporting the bricks in translucent walls are introduced—one with interlocking connections and pre-stressed wires, the other with interlocking connections and edge clamping. Both systems are analysed in finite element simulations from a structural point of view under out-of-plane loading. The resulting global deformations as well as occurring stresses in different components are analysed. Based on the findings, advantages and limitations of the different systems are highlighted and suggestions for improved alternative systems for translucent walls with insulating aerogel-filled glass bricks are made.
Evaluating the influence of backfilling on the stability of an abandoned room-and-pillar mine: a case study in northern Spain
Authors: Trigueros Emilio , Cánovas Manuel , Arzúa Javier , Baraibar José Manuel
Published: July 2024

Bodovalle is a siderite mine located in northern Spain that is currently in the closure phase. The mine was exploited using the room-and-pillar method. Subsidence processes have occurred previously and reached the surface because of the collapse of several pillars into the mine. To prevent such risky situations, the closure plan has been modified and the backfilling of some rooms has been considered. This study aimed to evaluate the global stability of room #1.1 after backfilling. This paper combines the use of traditional techniques, numerical modelling and remote sensing to achieve this objective. Limit equilibrium methods, LIDAR technology and numerical methods-based software were employed to evaluate the stability of rooms and pillars surrounding room #1.1 and considering different backfilling levels. In all possible backfilling scenarios involving room #1.1, the impact on the surface and neighboring rooms is negligible. In addition, no substantial changes in the safety factors and deformations of the neighboring rooms were observed for both studied levels of backfilling. Thus, backfilling is an adequate countermeasure to avoid subsidence.
An Evolutionary Computing Approach For Simultaneous Daylight Optimization in Urban Environments and Buildings Interiors
Authors: Abdollahzadeh Nastaran , Biloria Nimish
Published: July 2024

Rapid population growth globally is resulting in urban densification exponentially. As cities become denser, the environmental quality of urban canyons reduces, resulting in an increase in associated energy use in buildings. Currently, cities are responsible for 70% of the world’s energy consumption. One of the efficient solutions to address this issue is allowing more solar access into interiors and thus making the most of daylight and solar heat gain. Accordingly, this paper presents a novel approach to integrate daylight optimization in both urban environments and buildings’ interiors via the development and application of a custom algorithm based evolutionary computation. This ultimately allows more daylight penetration into urban canyons [vertical daylight illuminance (VDI)] and, subsequently, improves indoor visual comfort [useful horizontal illuminance level (HIL)]. This can also reduce the associated lighting and heating (during winter) energy use of buildings. Furthermore, investigating the correlation between indoor and outdoor illuminance levels aims to bridge the gap between daylight requirements at the urban planning and building scale. A multi-objective evolutionary algorithm-based assessment using computational simulation of design variables is conducted. This determines the extent to which each urban morphology can affect daylight access in both indoor and outdoor environments. Accordingly, the optimal range for different design factors is suggested.
Thermal energy storage performance of liquid polyethylene glycol in core–shell polycarbonate and reduced graphene oxide fibers
Authors: Das Madhurima , Ura Daniel P. , Szewczyk Piotr K. , Berniak Krzysztof , Knapczyk-Korczak Joanna , Marzec Mateusz M. , Pichór Waldemar , Stachewicz Urszula
Published: July 2024

Thermal energy storage is a promising, sustainable solution for challenging energy management issues. We deploy the fabrication of the reduced graphene oxide (rGO)–polycarbonate (PC) as shell and polyethylene glycol (PEG) as core to obtain hydrophobic phase change electrospun core–shell fiber system for low-temperature thermal management application. The encapsulation ratio of PEG is controlled by controlling the core flow rate, and ~ 93% heat energy storage efficacy is apparent for 1.5 mlh−1 of core flow rate. Moreover, the prepared fiber possesses maximum latent melting and freezing enthalpy of 30.1 ± 3.7 and 25.6 ± 4.0 Jg−1, respectively. The transient dynamic temperature vs. time curve of the rGO-loaded phase change fiber demonstrates the delay of fiber surface temperature change compared to pristine fiber. We indeed show that the tunable heat transfer and thermal energy storage efficacy of phase change fiber is achieved via controlled liquid PEG delivery and the addition of rGO in shell architecture. Notably, the effectiveness of unique phase change material (PCM)–based core–shell fibers is concluded from advanced scanning thermal microscopy (SThM) and self-thermoregulation tests.
The current landscape of global international surgical rotations for general surgery residents in the United States: a survey by the Association for Program Directors in Surgery’s (APDS) global surgery taskforce
Authors: Strain S. , Adjei E. , Edelman D. , Fischer L. , Haisch C. , Jeffcoach D. , Kim J. , Kington D. , Lee J. K. , Lindsey H. , Nelson W. , Nepomnayshy D. , Patidar S. , Petitt T. , Rivera M. , Shelton J. , Shim J. , Webb K. , Zhang C. , Hochman B. , Kauffmann R. M.
Published: July 2024

As interest in global surgery increases among surgical trainees, more programs are incorporating global surgery rotations into residency training. The structure of such rotations varies widely and there are multiple barriers to establishing, maintaining, and expanding international global surgery rotations. This study assesses the existing opportunities for global surgery experiences at US general surgery residency programs and explores opportunities for sharing resources and expertise among the Association of Program Directors in Surgery’s membership.
Alternative green extraction techniques to enhance recovery of antioxidant compounds from red peel prickly pear (Opuntia ficus-indica L. Miller)
Authors: Parí Salomé Mamani , Juárez Marjhory Lizeth Molina , Vilca Franz Zirena , Vilca Olivia Magaly Luque , Alca Erik Edwin Allcca , Escobedo-Pacheco Elías , Huamán-Castilla Nils Leander
Published: July 2024

Prickly pear (Opuntia ficus-indica L. Miller) is a natural source of antioxidant compounds that have gained significant attention due to their potential health benefits. This study aims to investigate the effectiveness of pressurized liquid extraction (PLE) and Ultrasound-Assisted Extraction (UAE), combined with water–ethanol mixtures from 0 to 60%, at moderate temperatures between 50 °C to 70 °C to improve the recovery of antioxidant compounds from red peel prickly pear. The recovery of these compounds was affected by solvent composition and temperature for both extraction techniques. Interestingly, the use of pure water at 70 °C during the PLE process allowed the recovery of high concentrations of antioxidant compounds (12.96 mg GAE/g dw, IC5O: 2.03 mg/mL, ORAC: 625 µmol TE/g dw). On the contrary, when the UAE process was combined with 30% ethanol at 50 °C, the extractability of these compounds (10.52 mg GAE/g dw, IC5O: 3.09 mg/mL, ORAC: 561.26 µmol TE/g dw) was improved. In addition, different solvent compositions were identified to improve the recovery of specific polyphenols. For PLE, pure water at 70 °C was effective in recovering phenolic acids, flavanols, and flavonols, while the highest concentrations of stilbenes were obtained with 60% ethanol at 70 °C. For UAE, the use of 30% ethanol at 50 °C was more effective in extracting phenolic acids and stilbenes, whereas pure water at 50 °C provided high concentrations of flavanols and flavonols. These results contribute to the development of sustainable and efficient extraction strategies for obtaining antioxidant-rich extracts from prickly pear peel with important applications in functional foods, nutraceuticals, and pharmaceutical industries.
Investigating the complex landscape of climate finance in least developed countries (LDCs)
Authors: Nor Mohamed Ibrahim , Mohamed Abdinur Ali
Published: July 2024

This study aimed to investigate the complex landscape of climate finance, assessing the adequacy, predictability, and implications for sustainable development in least developed countries (LDCs). This study is motivated by the pressing need to assess the adequacy, predictability, and implications of climate finance for sustainable development in least developed countries (LDCs). Employing an econometric framework, this study utilizes ARIMA models to analyze time series data (from 2000 to 2021) on climate finance. The analysis revealed a notable gap between the needed and actual climate funding received by LDCs. Despite an annual requirement of $93.7 billion according to the UK-based International Institute for Environment and Development (IIED), LDCs have only received an average of $14.8 billion annually since 2015. The study suggests that climate funding for LDCs lacks predictability and falls short in meeting their needs, potentially facing an 80% decrease by 2030 under certain scenarios. It advocates for a strategic revamp in climate finance mechanisms to ensure adequacy and predictability, urging policymakers and international funding bodies to adopt more robust, fair, and needs-based approaches to climate financing. This research emphasizes the responsibility of developed nations and global agencies in bridging the considerable funding gap faced by LDCs. By integrating advanced forecasting techniques with a comprehensive analysis of global economic and political factors, this study sheds light on the challenges LDCs encounter in securing stable and sufficient climate finance, stressing the urgency for systemic reforms in global climate finance policies.
Investigating the Model Hypothesis Space: Benchmarking Automatic Model Structure Identification With a Large Model Ensemble
Authors: Spieler Diana , Schütze Niels
Published: July 2024

Selecting an appropriate model for a catchment is challenging, and choosing an inappropriate model can yield unreliable results. The Automatic Model Structure Identification (AMSI) method simultaneously calibrates model structural choices and model parameters, which reduces the workload of comparing different models. In this study we benchmark AMSI's capabilities in two ways, using 12 hydro‐climatically diverse Model Parameter Estimation Experiment catchments. First, we calibrate parameter values for 7,488 different model structures and test AMSI's ability to find the best‐performing models in this set. Second, we compare the performance of these 7,488 models and AMSI's selection to the performance of 45 commonly used, structurally more diverse, conceptual models. In both cases, we quantify model accuracy (through the Kling‐Gupta Efficiency) and model adequacy (through various hydrologic signatures). AMSI effectively identifies high‐accuracy models among the 7,488 options, with Kling‐Gupta‐Efficiency scores comparable to the best among the 45 models. However, model adequacy remains poor for the accurate models, regardless of the selection method. In nine of the tested catchments, none of the most accurate models replicate observed signatures with less than 50% errors; in the remaining three catchments, only a handful of models do so. This paper thus provides strong empirical evidence that relying on aggregated efficiency metrics is unlikely to result in hydrologically adequate models, no matter how the models themselves are selected. Nevertheless, AMSI has been shown to effectively search the model hypothesis space it was given. Combined with an improved calibration approach it can therefore offer new ways to address the challenges of model structure selection.
Heatwave Location Changes in Relation to Rossby Wave Phase Speed
Authors: Wicker Wolfgang , Harnik Nili , Pyrina Maria , Domeisen Daniela I. V.
Published: July 2024

Surface anticyclones connected to the ridge of an upper‐tropospheric Rossby wave are the main dynamical drivers of mid‐latitude summer heatwaves. It is, however, unclear to what extent an anomalously low zonal phase speed of the wave in the upper troposphere is necessary for persistent temperature extremes at the surface. Here, we use spectral decomposition to separate fast and slow synoptic‐scale waves. A composite analysis of ERA5 reanalysis data reveals that, while in some regions heatwaves become more frequent during episodes of weak or no phase propagation, temperature extremes in other regions are commonly associated with more rapidly eastward propagating Rossby waves. Reflected in the mean heatwave duration as well, this relationship is possibly linked to a longitudinal phase preference of slow and fast waves or a meridional storm track shift. These findings open up new questions about the influence of mid‐latitude dynamics on temperature extremes.
The Key Role of Magnetic Curvature Scattering in Energetic Electron Precipitation During Substorms
Authors: Zou Ying , Zhang Xiao‐Jia , Artemyev Anton V. , Shen Yangyang , Angelopoulos Vassilis
Published: July 2024

Energetic electron precipitation (EEP) during substorms significantly affects ionospheric chemistry and lower‐ionosphere (<100 km) conductance. Two mechanisms have been proposed to explain what causes EEP: whistler‐mode wave scattering, which dominates at low latitudes (mapping to the inner magnetosphere), and magnetic field‐line curvature scattering, which dominates poleward. In this case study, we analyzed a substorm event demonstrating the dominance of curvature scattering. Using ELFIN, POES, and THEMIS observations, we show that 50–1,000 keV EEP was driven by curvature scattering, initiated by an intensification and subsequent earthward motion of the magnetotail current sheet. Using a combination of Swarm, total electron content, and ELFIN measurements, we directly show the location of EEP with energies up to ∼1 MeV, which extended from the plasmapause to the near‐Earth plasma sheet (PS). The impact of this strong substorm EEP on ionospheric ionization is also estimated and compared with precipitation of PS (<30 keV) electrons.
The eEF2 kinase coordinates the DNA damage response to cisplatin by supporting p53 activation
Authors: Lim Jonathan K. M. , Samiei Arash , Delaidelli Alberto , de Santis Jessica Oliveira , Brinkmann Vanessa , Carnie Christopher J. , Radiloff Daniel , Hruby Laura , Kahler Alisa , Cran Jordan , Leprivier Gabriel , Sorensen Poul H.
Published: July 2024

Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is a stress-responsive hub that inhibits the translation elongation factor eEF2, and consequently mRNA translation elongation, in response to hypoxia and nutrient deprivation. EEF2K is also involved in the response to DNA damage but its role in response to DNA crosslinks, as induced by cisplatin, is not known. Here we found that eEF2K is critical to mediate the cellular response to cisplatin. We uncovered that eEF2K deficient cells are more resistant to cisplatin treatment. Mechanistically, eEF2K deficiency blunts the activation of the DNA damage response associated ATM and ATR pathways, in turn preventing p53 activation and therefore compromising induction of cisplatin-induced apoptosis. We also report that loss of eEF2K delays the resolution of DNA damage triggered by cisplatin, suggesting that eEF2K contributes to DNA damage repair in response to cisplatin. In support of this, our data shows that eEF2K promotes the expression of the DNA repair protein ERCC1, critical for the repair of cisplatin-caused DNA damage. Finally, using Caenorhabditis elegans as an in vivo model, we find that deletion of efk-1, the worm eEF2K ortholog, mitigates the induction of germ cell death in response to cisplatin. Together, our data highlight that eEF2K represents an evolutionary conserved mediator of the DNA damage response to cisplatin which promotes p53 activation to induce cell death, or alternatively facilitates DNA repair, depending on the extent of DNA damage.
Asymmetric total synthesis of polycyclic xanthenes and discovery of a WalK activator active against MRSA
Authors: Cheng Min-Jing , Wu Yan-Yi , Zeng Hao , Zhang Tian-Hong , Hu Yan-Xia , Liu Shi-Yi , Cui Rui-Qin , Hu Chun-Xia , Zou Quan-Ming , Li Chuang-Chuang , Ye Wen-Cai , Huang Wei , Wang Lei
Published: July 2024

The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.
Terminal deoxynucleotidyl transferase and CD84 identify human multi-potent lymphoid progenitors
Authors: Kim YeEun , Calderon Ariel A. , Favaro Patricia , Glass David R. , Tsai Albert G. , Ho Daniel , Borges Luciene , Greenleaf William J. , Bendall Sean C.
Published: July 2024

Lymphoid specification in human hematopoietic progenitors is not fully understood. To better associate lymphoid identity with protein-level cell features, we conduct a highly multiplexed single-cell proteomic screen on human bone marrow progenitors. This screen identifies terminal deoxynucleotidyl transferase (TdT), a specialized DNA polymerase intrinsic to VDJ recombination, broadly expressed within CD34+ progenitors prior to B/T cell emergence. While these TdT+ cells coincide with granulocyte-monocyte progenitor (GMP) immunophenotype, their accessible chromatin regions show enrichment for lymphoid-associated transcription factor (TF) motifs. TdT expression on GMPs is inversely related to the SLAM family member CD84. Prospective isolation of CD84lo GMPs demonstrates robust lymphoid potentials ex vivo, while still retaining significant myeloid differentiation capacity, akin to LMPPs. This multi-omic study identifies human bone marrow lymphoid-primed progenitors, further defining the lympho-myeloid axis in human hematopoiesis.
Global protein turnover quantification in Escherichia coli reveals cytoplasmic recycling under nitrogen limitation
Authors: Gupta Meera , Johnson Alex N. T. , Cruz Edward R. , Costa Eli J. , Guest Randi L. , Li Sophia Hsin-Jung , Hart Elizabeth M. , Nguyen Thao , Stadlmeier Michael , Bratton Benjamin P. , Silhavy Thomas J. , Wingreen Ned S. , Gitai Zemer , Wühr Martin
Published: July 2024

Protein turnover is critical for proteostasis, but turnover quantification is challenging, and even in well-studied E. coli, proteome-wide measurements remain scarce. Here, we quantify the turnover rates of ~3200 E. coli proteins under 13 conditions by combining heavy isotope labeling with complement reporter ion quantification and find that cytoplasmic proteins are recycled when nitrogen is limited. We use knockout experiments to assign substrates to the known cytoplasmic ATP-dependent proteases. Surprisingly, none of these proteases are responsible for the observed cytoplasmic protein degradation in nitrogen limitation, suggesting that a major proteolysis pathway in E. coli remains to be discovered. Lastly, we show that protein degradation rates are generally independent of cell division rates. Thus, we present broadly applicable technology for protein turnover measurements and provide a rich resource for protein half-lives and protease substrates in E. coli, complementary to genomics data, that will allow researchers to study the control of proteostasis.
Clinical features associated with NeoRAS wild-type metastatic colorectal cancer A SCRUM-Japan GOZILA substudy
Authors: Osumi Hiroki , Shinozaki Eiji , Nakamura Yoshiaki , Esaki Taito , Yasui Hisateru , Taniguchi Hiroya , Satake Hironaga , Sunakawa Yu , Komatsu Yoshito , Kagawa Yoshinori , Denda Tadamichi , Shiozawa Manabu , Satoh Taroh , Nishina Tomohiro , Goto Masahiro , Takahashi Naoki , Kato Takeshi , Bando Hideaki , Yamaguchi Kensei , Yoshino Takayuki
Published: July 2024

“NeoRAS WT” refers to the loss of RAS mutations (MTs) following first-line treatment in metastatic colorectal cancer (mCRC). We evaluate the incidence and clinicopathological characteristics of NeoRAS WT mCRC using next-generation sequencing of plasma circulating tumor DNA. Patients with mCRC enrolled in the GOZILA study initially diagnosed with tissue RAS MT mCRC and received subsequent systemic therapy are eligible. NeoRAS WT is defined as the absence of detectable RAS MT in plasma and assessed in all eligible patients (Group A) and in a subgroup with at least one somatic alteration detected in plasma (Group B). Overall, 478 patients are included. NeoRAS WT prevalence is 19.0% (91/478) in Group A and 9.8% (42/429) in Group B. Absence of liver or lymph node metastasis and tissue RAS MTs other than KRAS exon 2 MTs are significantly associated with NeoRAS WT emergence. Overall, 1/6 and 2/6 patients with NeoRAS WT treated with anti-EGFR monoclonal antibodies (mAbs) show partial response and stable disease for ≥6 months, respectively. NeoRAS WT mCRC is observed at a meaningful prevalence, and anti-EGFR mAb-based therapy may be effective.
Co-coding of head and whisker movements by both VPM and POm thalamic neurons
Authors: Oram Tess Baker , Tenzer Alon , Saraf-Sinik Inbar , Yizhar Ofer , Ahissar Ehud
Published: July 2024

Rodents continuously move their heads and whiskers in a coordinated manner while perceiving objects through whisker-touch. Studies in head-fixed rodents showed that the ventroposterior medial (VPM) and posterior medial (POm) thalamic nuclei code for whisker kinematics, with POm involvement reduced in awake animals. To examine VPM and POm involvement in coding head and whisker kinematics in awake, head-free conditions, we recorded thalamic neuronal activity and tracked head and whisker movements in male mice exploring an open arena. Using optogenetic tagging, we found that in freely moving mice, both nuclei equally coded whisker kinematics and robustly coded head kinematics. The fraction of neurons coding head kinematics increased after whisker trimming, ruling out whisker-mediated coding. Optogenetic activation of thalamic neurons evoked overt kinematic changes and increased the fraction of neurons leading changes in head kinematics. Our data suggest that VPM and POm integrate head and whisker information and can influence head kinematics during tactile perception.
Polylogarithmic-depth controlled-NOT gates without ancilla qubits
Authors: Claudon Baptiste , Zylberman Julien , Feniou César , Debbasch Fabrice , Peruzzo Alberto , Piquemal Jean-Philip
Published: July 2024

Controlled operations are fundamental building blocks of quantum algorithms. Decomposing n-control-NOT gates (Cn(X)) into arbitrary single-qubit and CNOT gates, is a crucial but non-trivial task. This study introduces Cn(X) circuits outperforming previous methods in the asymptotic and non-asymptotic regimes. Three distinct decompositions are presented: an exact one using one borrowed ancilla with a circuit depth $$\Theta (\log {(n)}^{3})$$
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, an approximating one without ancilla qubits with a circuit depth $${{{{{{{\mathcal{O}}}}}}}}(\log {(n)}^{3}\log (1/\epsilon ))$$
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and an exact one with an adjustable-depth circuit which decreases with the number m≤n of ancilla qubits available as $${{{{{{{\mathcal{O}}}}}}}}(\log {(n/\lfloor m/2\rfloor )}^{3}+\log (\lfloor m/2\rfloor ))$$
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. The resulting exponential speedup is likely to have a substantial impact on fault-tolerant quantum computing by improving the complexities of countless quantum algorithms with applications ranging from quantum chemistry to physics, finance and quantum machine learning.
Local read haplotagging enables accurate long-read small variant calling
Authors: Kolesnikov Alexey , Cook Daniel , Nattestad Maria , Brambrink Lucas , McNulty Brandy , Gorzynski John , Goenka Sneha , Ashley Euan A. , Jain Miten , Miga Karen H. , Paten Benedict , Chang Pi-Chuan , Carroll Andrew , Shafin Kishwar
Published: July 2024

Long-read sequencing technology has enabled variant detection in difficult-to-map regions of the genome and enabled rapid genetic diagnosis in clinical settings. Rapidly evolving third-generation sequencing platforms like Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT) are introducing newer platforms and data types. It has been demonstrated that variant calling methods based on deep neural networks can use local haplotyping information with long-reads to improve the genotyping accuracy. However, using local haplotype information creates an overhead as variant calling needs to be performed multiple times which ultimately makes it difficult to extend to new data types and platforms as they get introduced. In this work, we have developed a local haplotype approximate method that enables state-of-the-art variant calling performance with multiple sequencing platforms including PacBio Revio system, ONT R10.4 simplex and duplex data. This addition of local haplotype approximation simplifies long-read variant calling with DeepVariant.
Contact-electro-catalytic CO2 reduction from ambient air
Authors: Wang Nannan , Jiang Wenbin , Yang Jing , Feng Haisong , Zheng Youbin , Wang Sheng , Li Bofan , Heng Jerry Zhi Xiong , Ong Wai Chung , TAN Hui Ru , Zhang Yong-Wei , Wang Daoai , Ye Enyi , Li Zibiao
Published: July 2024

Traditional catalytic techniques often encounter obstacles in the search for sustainable solutions for converting CO2 into value-added products because of their high energy consumption and expensive catalysts. Here, we introduce a contact-electro-catalysis approach for CO2 reduction reaction, achieving a CO Faradaic efficiency of 96.24%. The contact-electro-catalysis is driven by a triboelectric nanogenerator consisting of electrospun polyvinylidene fluoride loaded with single Cu atoms-anchored polymeric carbon nitride (Cu-PCN) catalysts and quaternized cellulose nanofibers (CNF). Mechanistic investigation reveals that the single Cu atoms on Cu-PCN can effectively enrich electrons during contact electrification, facilitating electron transfer upon their contact with CO2 adsorbed on quaternized CNF. Furthermore, the strong adsorption of CO2 on quaternized CNF allows efficient CO2 capture at low concentrations, thus enabling the CO2 reduction reaction in the ambient air. Compared to the state-of-the-art air-based CO2 reduction technologies, contact-electro-catalysis achieves a superior CO yield of 33 μmol g−1 h−1. This technique provides a solution for reducing airborne CO2 emissions while advancing chemical sustainability strategy.