bluuebunny/crossref_metadata_2025 huggingface dataset:
The Training and Development Process for a Multiple-Grand-Slam Finalist in Tennis
Authors: Haugen Thomas A. , Ruud Caroline , Bucher Sandbakk Silvana , Sandbakk Øyvind , Tønnessen Espen
Published: August 2024

Purpose: To investigate the training and development process of a multiple-Grand-Slam finalist. Methods: A mixed-methods case-study design was used to capture the quantitative and qualitative aspects related to the training and successful development process. We used a 3-step data-collection process and pragmatic analyses of (1) training history based on logs, plans, and questionnaires; (2) in-depth semistructured interviews with the player’s head coach/father, physical coach, and team administrator/mother; and (3) systematic quality assurance through negotiation among researchers and all key informants, including the player. Results: The player’s exceptional performance level was achieved by a progressive, nonlinear increase in annual training load during childhood and early youth, stabilizing at 800 sessions and 1250 to 1300 hours per year at the age of 19. The annual tennis-specific training plateaued at ∼750 hours from the age of 15, and 60 to 80 matches were played in most of the analyzed years. Point-play accounted for approximately 50% of the total amount of specific tennis training, clearly ahead of ground strokes (∼30%), serve/return (∼15%), and smash/volley (∼5%). Physical-conditioning hours increased 5-fold from 12 to 19 years, before stabilizing at ∼500 hours at senior age. Key success factors included the athlete’s multidimensional sports talent, discipline, and inner drive; a highly dedicated father and tennis-enthusiastic family; and strong support from a complementary and interdisciplinary performance team. Conclusion: This study provides novel information regarding the training and development process for a world-leading tennis player, providing a point of departure for the development of future talents.
Habituation Does Not Change Running Economy in Advanced Footwear Technology
Authors: Schwalm Lars C. , Fohrmann Dominik , Schaffarczyk Marcelle , Gronwald Thomas , Willwacher Steffen , Hollander Karsten
Published: August 2024

Purpose: This study aimed to compare running economy across habituated and nonhabituated advanced footwear technology (AFT) in trained long-distance runners. Methods: A total of 16 participants completed up to six 5-minute trials in 1 to 3 pairs of their own habituated shoes and 3 different and standardized AFTs at individual marathon pace. We measured oxygen uptake and carbon dioxide production and expressed running economy as oxygen uptake (in milliliters oxygen per kilogram per minute), oxygen cost of transport (oxygen per kilogram per minute), energetic cost (in watts per kilogram), and energetic cost of transport (in joules per kilogram per kilometer). We used linear mixed-effect models to evaluate differences. Relative shoe weight and shoe mileage (distance worn during running) were covariates. Results: Forty-eight standardized and 29 individual AFT conditions were measured (mileage 117.0 [128.8] km, range 0–522 km; 25 habituated 135.7 [129.2] km, range 20–522 km; 4 nonhabituated 0 [0] km, range 0–0 km). Rating of perceived exertion, blood [La], and respiratory exchange ratio ranged from 9 to 15, 1.11 to 4.54 mmol/L, and 0.76 to 1.01. There was no effect for habituation on energetic cost of transport (thabituation = −.232, P = .409, b = −0.006; 95% CI, −0.058 to 0.046) or other running economy metrics. Neither shoe weight nor shoe mileage had an effect. Conclusions: Our results suggest that habituation to AFTs does not result in greater benefits in the use of AFTs. This means that implementation in training may not be needed, even if we cannot rule out any other possible benefits of habituation at this stage, such as adaptation of the musculoskeletal system.
The Role of Grandparents in Facilitating Children’s Physical Activity
Authors: Jongenelis Michelle I. , Budden Timothy , Christian Hayley , Coall David A. , Jackson Ben , Nathan Andrea , Glassenbury Emma
Published: August 2024

Background: Research suggests there is considerable opportunity to improve children’s movement behaviors while they are being cared for by their grandparents. An understanding of the extent to which grandparent practices facilitate children’s engagement in physical activity is critical to the development of health interventions targeting grandparent caregivers. This study examined the activity-related beliefs and practices of grandparents and their association with grandchildren’s engagement in various movement behaviors while in grandparental care. Methods: Australian grandparents (N = 1190; 60% women) who provided regular care to a grandchild aged 3–14 years were recruited via a web panel provider to complete an online survey. The survey assessed grandparents’ physical activity-related beliefs (eg, perceived importance) and practices (eg, support and social control) and their grandchildren’s engagement in physical activity (unstructured, structured, and outdoor play) and screen-based activities while in grandparental care. Results: The importance of grandchildren’s physical activity was rated highly by grandparents. Grandparents’ support for their grandchildren’s physical activity was positively associated with their grandchildren’s engagement in structured physical activity, unstructured physical activity, and outdoor play. Negative social control was associated with greater engagement in screen-based activities. Other correlates of grandchildren’s physical activity and screen-based activities included grandparents’ own engagement in these activities. Conclusions: Findings highlight the importance of reinforcing the beliefs and practices that positively influence children’s movement behaviors and addressing those that have unintended consequences. Encouraging grandparents to support their grandchildren’s physical activity and discouraging forms of negative social control are likely to be important in efforts to promote physical activity in children.
Evaluación de una propuesta educativa en Educación Física para promocionar la bicicleta como modo de transporte al centro educativo en adolescentes: Estudio PACO
Authors: Molina-García Javier , Huertas-Delgado Francisco Javier , Campos-Garzón Pablo , Chillón Palma
Published: August 2024

Objetivo: Analizar los efectos de una propuesta educativa en Educación Física para la promoción del uso de la bicicleta como medio de transporte al centro educativo. Metodología: El estudio PACO (Pedalea y Anda al Cole) es un ensayo controlado aleatorizado. Se evaluó la satisfacción con las sesiones, las habilidades y conocimientos ciclistas, el modo de desplazamiento, las necesidades psicológicas básicas y las barreras hacia el desplazamiento activo. Resultados: Hubo una alta satisfacción con las sesiones, un adecuado desarrollo de habilidades ciclistas y una mejora del conocimiento sobre normas de circulación y comportamiento ciclista. Hubo una disminución significativa en la satisfacción de la necesidad de competencia y un aumento de la percepción de barreras en el grupo de intervención respecto al control. No hubo cambios en el modo de desplazamiento. Conclusión: Este tipo de propuestas deberían ser desarrolladas durante más sesiones y/o en proyectos de centro interdisciplinares para conseguir cambios comportamentales positivos y duraderos.
Neurological presentation does not always mean a neurological diagnosis
Authors: Woolgrove Saskia , Ahmed Saad , Garg Kapil , Bale Peter , Walton Tom
Published: August 2024

This case article takes you on a journey starting with a paediatric patient presenting with sudden-onset lower limb paralysis and paraesthesia. Differential diagnoses, investigations and management are discussed as the case progresses, ultimately leading to the underlying cause.
Abstracts from international emergency medicine journals
Authors: Production EMJ
Published: August 2024

Editor’s note: EMJ has partnered with the journals of multiple international emergency medicine societies to share from each a highlighted research study, as selected by their editors. This edition will feature an abstract from each publication.
High heart rates during paroxysmal atrial fibrillation: continuous rhythm monitoring data of the RACE V study
Authors: Koldenhof Tim , Van Gelder Isabelle C , van de Lande Martijn E , Al-Jazairi Meelad I H , Tieleman Robert G , Rienstra Michiel
Published: August 2024

Background

Preventing high heart rates in patients with atrial fibrillation (AF) is a key objective of AF management. Data regarding heart rates in patients with paroxysmal AF (PAF) is lacking. This analysis aimed to provide insight into heart rates during PAF episodes measured with continuous implantable loop monitoring.

Methods

In present analysis of the Interaction between hyperCoagulability, Electrical remodeling, and Vascular Destabilization in the Progression of AF study, we included 349 patients with at least one year of continuous rhythm monitoring and an episode of AF. Mean heart rates and duration of AF episodes were used to calculate total AF duration and AF duration above different heart rate cut-offs.

Results

The median age was 64.0 (58.4 to 70.5) years, 152 (44%) were women and CHA2DS2-VASc score ≥2 or higher in 255 (73%) patients. During 28.3 (21.3 to 35.0) months of follow-up, the median number of AF episodes was 62 (12 to 293) with a median total AF duration of 4.6 (0.8 to 26.8) days. At baseline, 172 (49%) patients used beta-blockers, 64 (18%) used diltiazem or verapamil and 5 (1%) used digoxin. A total of 133 patients (38%) experienced a heart rate >110 bpm for more than 50% of the time during AF. Fifty-six (16%) patients had a heart rate >130 bpm for more than 50% of the time while in AF. During follow-up, 39 patients (11%) received an increase of rate-controlling medication.

Conclusion

Continuous rhythm monitoring revealed that more than a third of PAF patients had heart rates above 110 bpm for more than half of their time in AF.

Trial registration number

Clinicaltrials.gov identifierNCT02726698.
PRCP is a promising drug target for intracranial aneurysm rupture supported via multi-omics analysis
Authors: Wu Jinghao , Mei Yunyun , Li XinYu , Yu Wen-Kai , Zhou Zi Han , Yang Yinghao , Niu Pengpeng , Wang Yunchao , Shi Chang-He , Zhu Hanghang , He Wenjun , Gao Yuan , Xu Yuming , Li Yusheng
Published: August 2024

Background

Cerebral aneurysms are life-threatening cerebrovascular disorders. Currently, there are no effective treatments for preventing disease progression. Mendelian randomisation (MR) is widely used to repurify licensed drugs and identify new therapeutic targets. Therefore, this study aims to investigate effective drug targets for preventing the formation and rupture of cerebral aneurysms and analyse their potential mechanisms.

Methods

We performed a comprehensive study integrating two-sample MR analysis, colocalisation analysis and summary data-based Mendelian randomisation (SMR) to assess the causal effects of blood and brain druggable cis-expression quantitative trait loci (cis-eQTLs) on intracranial aneurysm (IA), unruptured intracranial aneurysm (UIA) and subarachnoid haemorrhage of IA rupture (SAH). Druggable genes were obtained from the study by Chris Finan
et al
, cis-eQTLs from the eQTLGen and PsychENCODE consortia. Results were validated using proteomic and transcriptomic data. Single-gene functional analyses probed potential mechanisms, culminating in the construction of a drug-gene regulation network.

Results

Through the MR analysis, we identified four potential drug targets in the blood, including prolylcarboxypeptidase (PRCP), proteasome 20S subunit alpha 4 (PSMA4), LTBP4 and GPR160 for SAH. Furthermore, two potential drug targets (PSMA4 and SLC22A4) were identified for IA and one potential drug target (KL) for UIA after accounting for multiple testing (P(inverse-variance weighted)<8.28e-6). Strong evidence of colocalisation and SMR analysis confirmed the relevance of PSMA4 and PRCP in outcomes. Elevated PRCP circulating proteins correlated with a lower SAH risk. PRCP gene expression was significantly downregulated in the disease cohort.

Conclusions

This study supports that elevated PRCP gene expression in blood is causally associated with the decreased risk of IA rupture. Conversely, increased PSMA4 expression in the blood is causally related to an increased risk of IA rupture and formation.
Z boson emission by an electron and the decays of Z boson into fermions in a de Sitter universe
Authors: Crucean Cosmin , Dumitrele Diana
Published: August 2024

In this paper we develop a method to obtain the rates for the decay of a Z boson into fermions in de Sitter geometry. Our general results obtained in de Sitter space-time allow us to obtain the Minkowski limits for the transition rates when the expansion parameter vanishes. Another important result reported in the present study is related to the emission of Z bosons by electrons and positrons. All the processes were studied by implementing perturbative methods that allow us to define the transition amplitudes in the first order of perturbation theory. The variation of probabilities and rates in terms of expansion parameter and particles masses is also given, pointing out that the processes that generate particle production are possible only in the early universe. For computing the transition rates and probabilities we use the dimensional regularization method and the minimal substraction method.
The cosmological constant emerging from a symmetry invariant
Authors: Arraut Ivan
Published: August 2024

The cosmological constant is normally introduced as an additional term entering the Einstein–Hilbert (EH) action. In this letter, we demonstrate that, instead, it appears naturally from the standard EH action as an invariant term emerging from spacetime symmetries. We then demonstrate that the same constraint emerging from this invariant suppresses the short wavelength modes and it favors the long wavelength ones. In this way, inside the proposed formulation, the observed value for the vacuum energy density is obtained naturally from the zero-point quantum fluctuations.
Exploration on modulation instability in 𝒫𝒯-symmetric non-Kerr Bragg grating structures
Authors: Inbavalli I. , Rajan M. S. Mani , Alagesan T.
Published: August 2024

In this paper, we study Modulation Instability (MI) and its correlated gain spectrum with Parity-Time ([Formula: see text])-symmetry. The cubic-quintic nonlinearities in the Bragg grating structure produce ultrashort pulses. The MI evaluation started with a linear stability approach, and we investigated the effects of various system functions regarding the instability gain spectra at the top and bottom sides of the Photonic BandGap (PBG), in addition to the anomalous and normal dispersion domains. The interaction of cubic and quintic (focusing and de-focusing) nonlinearity is highlighted, resulting in a new type of MI band. Due to the consequences of quintic nonlinearity, an additional MI band appears for the three dynamics associated with the gain/loss function for the edges of the bottom PBG. After enforcing the [Formula: see text]-symmetry for the anomalous dispersion system, the dent transformed into a split under the influence of the power in the de-focusing quintic effect. Overall, MI gain and bandwidths across the entire MI gain spectrum are usually increasing. As an outcome, we are confident that these studies will aid in the generation of gap solitons in [Formula: see text]-symmetry regimes.
Periodic Orbit-Dividing Surfaces in Rotating Hamiltonian Systems with Three Degrees of Freedom – I
Authors: Katsanikas Matthaios , Wiggins Stephen
Published: August 2024

In this paper, we extend the notion of periodic orbit-dividing surfaces (PODSs) to rotating Hamiltonian systems with three degrees of freedom. First, we present how to apply our first method for the construction of PODSs [ Katsanikas & Wiggins ,  2021a ,  2023a ] to rotating Hamiltonian systems with three degrees of freedom. Then, we study the structure of these surfaces in a rotating quadratic normal-form Hamiltonian system with three degrees of freedom.
Marginal Effect-aware Multiple-Vehicle Scheduling for Road Data Collection: A Near-optimal Result
Authors: Cheng Wenhui , Jiang Zixian , Xiang Chaocan , Fu Jianglan
Published: August 2024

Vehicles equipped with abundant sensors offer a promising way for large-scale, low-cost road data collection. To realize this potential, a well-designed vehicle scheduling scheme is essential for deploying the recruited drivers efficiently. Nevertheless, existing works fail to consider the marginal effect among drivers’ collections. Different from them, this article introduces a, to the best of our knowledge, new multiple-vehicle scheduling problem that jointly optimizes task allocation and vehicle trajectory planning to maximize the overall collection utility by accounting for the marginal effect in drivers’ data collections. However, solving this problem is non-trivial due to its involvement with multiple coupled NP-hard problems. To this end, we propose MeSched, a marginal effect-aware multiple-vehicle scheduling scheme designed for road data collection. Specifically, we first present a greedy-based auxiliary graph construction method to disentangle the initial problem into multiple independent single-vehicle scheduling subproblems. Furthermore, we build an approximate surrogate function that transforms each subproblem into a tractable form involving only a single variable. The theoretical analysis proves that MeSched can achieve a 1-(1/
e
)
¼
-approximation ratio in polynomial time. Comprehensive evaluations based on a real-world trajectory dataset of 12,493 vehicles demonstrate that MeSched can significantly improve the collection utility by 104.5% on average compared with four baselines.
Non-Volatile Memory Technology Poised for Game-Changing Breakthrough
Authors: Westfall Ron
Published: August 2024

Why novel nanocomposite-superlattices for low-energy, high-stability nanoscale phase-change memory is poised as an innovation touchstone for the memory segment and the entire industrial ecosystem.
Assessing Usefulness, Ease of Use and Recognition Performance of Semi-Automatic Mulsemedia Authoring
Authors: Abreu Raphael , Santos Joel dos , Ghinea Gheorghita , Muchaluat-Saade Débora C.
Published: August 2024

Mulsemedia (Multiple Sensorial Media) authoring poses a considerable challenge as authors navigate the intricate task of identifying moments to activate sensory effects within multimedia content. A novel proposal is to integrate content recognition algorithms that use machine learning (ML) into authoring tools to alleviate the authoring effort. As author subjectivity is very important, it is imperative to allow users to define which sensory effects should be automatically extracted. This paper conducts a twofold evaluation of the proposed semi-automatic authoring. The first is from a user perspective within the STEVE 2.0 mulsemedia authoring tool, employing the Goal-Question-Metric (GQM) methodology and a user feedback questionnaire. Our user evaluation indicates that users perceive the semi-automatic authoring approach as a positive enhancement to the authoring process. The second evaluation targets sensory effect recognition using two different content recognition modules, quantifying their automatic recognition capabilities against manual authoring. Metrics such as precision, recall, and F1 scores provide insights into the strengths and nuances of each module. Differences in label assignments underscore the need for ML module result combination methodologies. These evaluations contribute to a comprehensive understanding of the effectiveness of sensory effect recognition modules in enhancing mulsemedia content authoring.
Influence of Potential and the Presence of Boric Acid on Pt1-xCox Alloy Electrodeposition and Magnetic Properties
Authors: Rus Eric D. , Corrêa Eduardo L. , Dennis Cindi L. , Moffat Thomas P.
Published: August 2024

The effects of potential and the presence of B(OH)3 on Pt1-xCox alloy electrodeposition from aqueous chloride-based solutions on Ru substrates was investigated. Films deposited at potentials more reducing than −0.65 V vs SCE were hexagonal close packed and greater than 90% Co (mole basis), and films deposited at potentials more oxidizing than −0.65 V were face centered cubic and showed a monotonic decrease in cobalt content as the potential increased. The composition and structure-potential dependences were not strongly affected by the presence of B(OH)3. Structural change coincided with a distinct knee-like feature in the composition-potential relationship, along with a prominent narrow voltammetric peak associated with Co deposition, possibly related to nucleation and growth of the hcp phase. The presence of B(OH)3 produced a sharp minimum in both Coulombic efficiency and deposition rate at potentials near −0.65 V and almost entirely suppressed the voltammetric feature. This may be associated with a combination of B(OH)3-derived proton reduction and inhibition of metal deposition by adsorbed B(OH)3 or B(OH)3-derived species. The presence of B(OH)3 affected the magnetic behavior of films deposited at potentials more oxidizing than −0.55 V (i.e., those with compositions less than about 40% Co) only weakly, but resulted in generally smaller maximum magnetizations for films deposited at more reducing potentials, and notably a much lower magnetization for films deposited at −0.65 V.
Renoprotective effects of empagliflozin in high-fat diet-induced obesity-related glomerulopathy by regulation of gut-kidney axis
Authors: Lei Lei , Zhu Ting , Cui Tian-Jiao , Liu Yvonne , Hocher Johann-Georg , Chen Xin , Zhang Xue-Mei , Cai Kai-Wen , Deng Zi-Yan , Wang Xiao-Hua , Tang Chun , Lin Lian , Reichetzeder Christoph , Zheng Zhi-Hua , Hocher Berthold , Lu Yong-Ping
Published: August 2024

Our study uncovered that empagliflozin (EMPA) potentially protects renal function and morphology in obesity-related glomerulopathy (ORG) mice by regulating the gut-kidney axis. EMPA’s reno-protective effects in ORG mice are associated with the lipid metabolism, especially in glycerophospholipid metabolism and the pantothenate/CoA synthesis pathways. EMPA’s modulation of gut microbiota appears to be pivotal in suppressing glycerol 3-phosphate and CoA synthesis. The insights into gut microbiota-host metabolic interactions offer a novel therapeutic approach for ORG.
Tumor microenvironment-like conditions alter pancreatic cancer cell metabolism and behavior
Authors: Gardner Georgina Louise , Stuart Jeffrey Alan
Published: August 2024

Standard cell culture conditions do not replicate the complex tumor microenvironment experienced by cells in vivo. Although currently available plasma-like media are superior to traditional supraphysiological media, they fail to model tumor-like conditions. Using RNA-seq analysis and functional metabolic and migratory assays, we show that tumor microenvironment medium (TMEM), used with representative tumor hypoxia, better models cancerous phenotypes in culture. This emphasizes the critical importance of accurately modeling the tumor microenvironment in cancer research.
Navigating the Role of Emotional Health and Positive Life Outlook on Work‐Life Balance in Professional Married Women
Authors: Maqsood Saira , Niazi Sadia , Alyas Tahir , Ghaffar Hafiza Saliha , Sohail Marva , Sakib Shadman
Published: August 2024

A diverse workforce is innovative and women are equally contributing to the country’s economic development along with men. In a dynamic business community, women are more enthusiastic and progressively using their potential for financial growth and providing benefits to their families as well. In the subcontinent, women also participate in the workforce and contribute to improving their quality of life and financial responsibilities. The objective of current research is to find out the relationship between emotional health, positive life orientation, and work‐life balance in professional married women. A correlational research design and purposive sampling strategy were utilized to conceptualize the study. A total of 300 professional married women who served in various positions in different organizations were selected. Standardized instruments were used to measure study variables along with sociodemographic Performa. Statistical findings of the study revealed a significant positive relationship between emotional wellness, positive life orientation, and work‐personal life enhancement ( ∗∗∗p < 0.01,  ∗∗p < 0.1,  ∗p < 0.05) by using Pearson product‐moment correlation. Mediation through PLS revealed that positive life orientation mediates the relationship between emotional wellness and work‐life balance. Independent Sample T‐test results also revealed that working women living in the nuclear family system have higher work interference with personal life and personal life interference with work than those women who live in a joint family system. This research will be helpful for organizations to design a conducive and women‐friendly job environment and use women’s potential for constructive and productive professional growth and organizational progress.
Optimizing Hydrogen Storage Pathways in Ti–Al Alloys through Controlled Oxygen Addition
Authors: Shukla Vivek , Han Sung Ju , Ha Taejun , Padhee Satya Prakash , Suh Jin-Yoo , Cho Young Whan , Lee Young-Su
Published: August 2024

In the present study, we aimed to destabilize the Ti–Al system with nonmetallic oxygen. The synthesis of α‐(Ti, Al)[O] starting from TiO2, Ti, and Al was carried out through the arc melting method, resulting in three different oxygen content levels, 3.4, 10, and 20 at%. The room temperature activation of α‐(Ti, Al)[O] was not successful, and the activation was performed at 300°C under 5 MPa H2 pressure. The structural changes after hydrogenation (maximum absorption capacity of 3.74 wt% hydrogen) arose from the transformation of α‐(Ti, Al)[O] to cubic (Ti, Al)[O]Hx (c‐(Ti, Al)[O]Hx); nonetheless, they recovered their original lattice parameters, which are meaningfully larger than those of α‐Ti, after dehydrogenation. The hydrogen storage capacities for various α‐(Ti, Al)[O] compositions generally decreased with increasing oxygen (3.4 and 10 at%) and aluminum content in the alloy. In contrast, for the compositions with a higher oxygen content of 20 at%, the hydrogen storage capacity slightly increased as the Al concentration increased: Ti0.790Al0.010O0.200 absorbed 2.91 wt% hydrogen, whereas Ti0.767Al0.033O0.200 absorbed 3.04 wt% hydrogen. The thermogravimetric analysis showed that samples with 20 at% O released hydrogen at lower temperatures even though the major phase after hydrogenation is c‐(Ti, Al)[O]Hx regardless of the oxygen content.
Microbiomes of Tilapia Culture Systems: Composition, Affecting Factors, and Future Perspectives
Authors: Huavas Jonabel , Heyse Jasmine , Props Ruben , Delamare-Deboutteville Jérôme , Shelley Colin
Published: August 2024

With the increasing demand for global food resources, improving aquaculture production has been the focus for years. Tilapia has become one of the most commonly farmed and economically important fish species globally. Research efforts have recognized the significant roles that microbial communities play in improving the health and aquaculture performance of tilapia. However, interactions between tilapia and its associated microbial communities remain poorly understood. In this review, the current understanding of tilapia microbiomes is summarized. With fish being in intimate relationship with its environment, studies characterizing the microbial communities present in the rearing environment and how they affect tilapia microbiomes and health are also examined. Having an in‐depth understanding of the different microbiomes and their roles and interactions in the tilapia culture system is a crucial step toward managing and modulating these microbial communities to improve tilapia health. This review also sheds light on the different factors that influence tilapia microbiomes such as developmental stages, organ tissues, and types of culture systems. The effects of on‐farm practices such as diet; feeding regimes; use of probiotics, prebiotics, and synbiotics; vaccination; application of antibiotics; disinfection; and pond fertilization on tilapia microbiome are also discussed. Through this review, future research needs are identified that can provide a deeper understanding of the relationships among tilapia microbiomes, health, and productivity. These knowledge in turn can be harnessed into practical applications and potential microbiome‐based management protocols to improve future best management practices for tilapia aquaculture.
A Mixed Methods Inquiry into How Legal Professionals Respond to Recurring Trauma and Mental Distress among Refugees and Asylum Seekers with Insecure Visa Status in Australia
Authors: Kenny Mary Anne , Procter Nicholas G. , Grech Carol
Published: August 2024

The aim of this study was to investigate how legal professionals in Australia responded to the mental distress experienced by clients with insecure visa status in the Fast Track Assessment (FTA) process. This article reports on survey findings obtained from 38 legal professionals followed up by focus groups and interviews with 16 participants. The participants were all involved in providing legal assistance to refugees and asylum seekers with insecure visa status, the majority delivering that assistance via pro bono or community law centre settings. An inductive thematic analysis was used to analyse the data. The study uncovered a complex interplay of practical challenges, emotions, and ethical dilemmas that legal professionals encounter while assisting asylum seekers in the FTA process. The study participants’ experiences highlight that a migration law practice frequently becomes the initial setting where asylum seekers disclose mental distress. Legal professionals found themselves simultaneously witnessing human suffering and endeavouring to prevent re‐traumatisation of their clients. Responding to distress was difficult to achieve as the operational setting in which they provided legal assistance and the prevailing hardline political messaging by the Australian government toward asylum seekers who arrived by boat was hostile and (re)traumatising. There is a pressing need for more trauma‐informed education and training for both current and future legal professionals. Findings are discussed alongside practical suggestions for trauma‐informed interviewing for legal professionals who interview asylum seekers.
Improving the Performance and Biodegradability of Biocomposites Made from Banana Sap and Banana Fibres
Authors: Paul Vimla , Muniyasamy Sudhakar , Kanny Krishnan , Joseph Botlhoko Orebotse , Sivakumar Ponnurengam Malliappan
Published: August 2024

Biobased biodegradable materials are gaining popularity with increasing public awareness on the negative impacts of conventional plastics on the environment. There is, however, a lack of promising biobased materials suitable for various end‐use applications that are also environmentally safe. Recently, banana sap and banana fibres have been explored as a potential source of organic material as they are abundant, cost‐efficient, and environmentally friendly. In this study, two hybrid bioresins (1) banana sap maleate (BSM) and (2) banana sap maleate + banana fibre (BSMF) were developed, and their material properties and environmental suitability were examined by analysing their physicochemical characterisation and biodegradation testing. We used thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy for the physicochemical characterisation of BSMF before and after composting and measured carbon dioxide evolved during the biodegradation to calculate biodegradability. SEM analysis also showed a significant disintegration and surface degradation in BSMF compared to BSM and other control materials such as control resin and cellulose. CO2 mineralization results indicated a potential microbial bioassimilation of the materials under composting conditions. Biodegradability of the BSMF composite, as indicated by CO2 emission, was 17.6% higher than BSM and other control materials used in this study. The present study provides crucial evidence that the reinforcement of banana fibre into banana sap bioresin composite can significantly improve material properties and enhance biodegradability in the composting conditions. These results are quite promising as they show that, with some tweaking; natural materials can reduce environmental impact of composites and improve material properties for different end‐use applications and involves less exploitation of nonrenewable resources for polymer production. This study also provides an avenue to consider BSMF for carrying out our future life cycle assessment (LCA) and to compare with commercial product’s LCA. In a circular economy approach, characteristics such as durability, environmental toxicity, and recyclability of such materials should be studied and optimised to reduce energy consumption and environmental impact.
Signal‐Transduction Proteins from Caribbean Cassiopea xamachana: The Scaffolding Protein CxRACK1 Shows Conserved Molecular Signatures and Differential Expression between Larval and the Subsequent Metamorphic Stages
Authors: Islas-Flores Tania , Cabrales-Arellano Patricia , Morales-Ruiz Estefanía , Villanueva Marco A.
Published: August 2024

The molecular features from the coding sequence and part of the 5′‐UTR of the scaffolding protein receptor for activated C kinase (CxRACK1) gene from the jellyfish Cassiopea xamachana were assessed by a combination of regular and inverse PCR amplifications. The final CxRACK1 mRNA sequence contained 1,041 bp with an open reading frame of 954 bp that translated into 317 amino acids. The translated primary sequence contained the canonical seven WD40 domains, one ribosome, and three conserved protein kinase C (PKC)‐binding sites as well as the Tyr amino acid targets for Src phosphorylation. The protein showed a conserved CxRACK1 tertiary structure since the seven WD40 domains clearly assembled into the characteristic β‐propeller shape displaying surface exposed amino acids critical for regulation by phosphorylation. Within the 5′‐UTR, cis‐acting regulatory elements were analyzed with available software from the closest organismal phylogeny which corresponded to that of chordates, plants, and fungi. Of note were one element related to retinol binding, three that corresponded to light regulation, two to target binding sites for zinc finger domain proteins, and two more were transcriptional activators. Further phylogenetic analysis placed CxRACK1 within the Scyphozoa group as expected. RT‐qPCR analysis of distinct physiological stages through the C. xamachana metamorphic cycle showed slightly but consistent lower CxRACK1 mRNA levels in scyphistomae, strobilae, and ephyrae than those in buds and larvae. This suggested an increased expression and possible involvement of this molecule in signal transduction processes related to the transition to these initial metamorphic stages.
PTEN Loss Shapes Macrophage Dynamics in High-Grade Serous Ovarian Carcinoma
Authors: Spear Sarah , Le Saux Olivia , Mirza Hasan B. , Iyer Nayana , Tyson Katie , Grundland Freile Fabio , Walton Josephine B. , Woodman Chloé , Jarvis Sheba , Ennis Darren P. , Aguirre Hernandez Carmen , Xu Yuewei , Spiliopoulou Pavlina , Brenton James D. , Costa-Pereira Ana P. , Cook David P. , Vanderhyden Barbara C. , Keun Hector C. , Triantafyllou Evangelos , Arnold James N. , McNeish Iain A.
Published: August 2024

High-grade serous ovarian carcinoma (HGSC) remains a disease with poor prognosis that is unresponsive to current immune checkpoint inhibitors. Although PI3K pathway alterations, such as PTEN loss, are common in HGSC, attempts to target this pathway have been unsuccessful. We hypothesized that aberrant PI3K pathway activation may alter the HGSC immune microenvironment and present a targeting opportunity. Single-cell RNA sequencing identified populations of resident macrophages specific to Pten-null omental tumors in murine models, which were confirmed by flow cytometry. These macrophages were derived from peritoneal fluid macrophages and exhibited a unique gene expression program, marked by high expression of the enzyme heme oxygenase-1 (HMOX1). Targeting resident peritoneal macrophages prevented the appearance of HMOX1hi macrophages and reduced tumor growth. In addition, direct inhibition of HMOX1 extended survival in vivo. RNA sequencing identified IL33 in Pten-null tumor cells as a likely candidate driver, leading to the appearance of HMOX1hi macrophages. Human HGSC tumors also contained HMOX1hi macrophages with a corresponding gene expression program. Moreover, the presence of these macrophages was correlated with activated tumoral PI3K/mTOR signaling and poor overall survival in patients with HGSC. In contrast, tumors with low numbers of HMOX1hi macrophages were marked by increased adaptive immune response gene expression. These data suggest targeting HMOX1hi macrophages as a potential therapeutic strategy for treating poor prognosis HGSC.

Significance: Macrophages with elevated HMOX1 expression are enriched in PTEN-deficient high-grade serous ovarian carcinoma, promote tumor growth, and represent a potential therapeutic target.
CRISPR Screening of Transcribed Super-Enhancers Identifies Drivers of Triple-Negative Breast Cancer Progression
Authors: Lewis Michael W. , King Caitlin M. , Wisniewska Kamila , Regner Matthew J. , Coffey Alisha , Kelly Michael R. , Mendez-Giraldez Raul , Davis Eric S. , Phanstiel Douglas H. , Franco Hector L.
Published: August 2024

Triple-negative breast cancer (TNBC) is the most therapeutically recalcitrant form of breast cancer, which is due in part to the paucity of targeted therapies. A systematic analysis of regulatory elements that extend beyond protein-coding genes could uncover avenues for therapeutic intervention. To this end, we analyzed the regulatory mechanisms of TNBC-specific transcriptional enhancers together with their noncoding enhancer RNA (eRNA) transcripts. The functions of the top 30 eRNA-producing super-enhancers were systematically probed using high-throughput CRISPR-interference assays coupled to RNA sequencing that enabled unbiased detection of target genes genome-wide. Generation of high-resolution Hi-C chromatin interaction maps enabled annotation of the direct target genes for each super-enhancer, which highlighted their proclivity for genes that portend worse clinical outcomes in patients with TNBC. Illustrating the utility of this dataset, deletion of an identified super-enhancer controlling the nearby PODXL gene or specific degradation of its eRNAs led to profound inhibitory effects on target gene expression, cell proliferation, and migration. Furthermore, loss of this super-enhancer suppressed tumor growth and metastasis in TNBC mouse xenograft models. Single-cell RNA sequencing and assay for transposase-accessible chromatin with high-throughput sequencing analyses demonstrated the enhanced activity of this super-enhancer within the malignant cells of TNBC tumor specimens compared with nonmalignant cell types. Collectively, this work examines several fundamental questions about how regulatory information encoded into eRNA-producing super-enhancers drives gene expression networks that underlie the biology of TNBC.

Significance: Integrative analysis of eRNA-producing super-enhancers defines molecular mechanisms controlling global patterns of gene expression that regulate clinical outcomes in breast cancer, highlighting the potential of enhancers as biomarkers and therapeutic targets.
Fitness Screens Map State-Specific Glioblastoma Stem Cell Vulnerabilities
Authors: MacLeod Graham , Molaei Fatemeh , Haider Shahan , Almeida Maira P. , Lin Sichun , Kushida Michelle , Sureshkumar Haresh , Bhatti Jasmine K. , Lu Jack Q. , Schramek Daniel , Dirks Peter B. , Angers Stephane
Published: August 2024

Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults and is driven by self-renewing glioblastoma stem cells (GSC) that persist after therapy and seed treatment-refractory recurrent tumors. GBM tumors display a high degree of intra- and intertumoral heterogeneity that is a prominent barrier to targeted treatment strategies. This heterogeneity extends to GSCs that exist on a gradient between two transcriptional states or subtypes termed developmental and injury response. Drug targets for each subtype are needed to effectively target GBM. To identify conserved and subtype-specific genetic dependencies across a large and heterogeneous panel of GSCs, we designed the GBM5K-targeted guide RNA library and performed fitness screens in a total of 30 patient-derived GSC cultures. The focused CRISPR screens identified the most conserved subtype-specific vulnerabilities in GSCs and elucidated the functional dependency gradient existing between the developmental and injury response states. Developmental-specific fitness genes were enriched for transcriptional regulators of neurodevelopment, whereas injury response–specific fitness genes were highlighted by several genes implicated in integrin and focal adhesion signaling. These context-specific vulnerabilities conferred differential sensitivity to inhibitors of β1 integrin, focal adhesion kinase, MEK, and OLIG2. Interestingly, the screens revealed that the subtype-specific signaling pathways drive differential cyclin D (CCND1 vs. CCND2) dependencies between subtypes. These data provide a biological insight and mechanistic understanding of GBM heterogeneity and point to opportunities for precision targeting of defined GBM and GSC subtypes to tackle heterogeneity.

Significance: CRISPR-Cas9 screens in a panel of patient-derived glioblastoma stem cells reveal heterogeneity in genetic vulnerabilities across subtypes that have important implications for targeted and combination treatment strategies for glioblastoma.
Tumor’s Digest: Macrophage Metabolism Creates a Barrier to T Cells
Authors: Tyler Elly J. , Pearce Oliver M.T.
Published: August 2024

Changes in the composition and physical properties of the tumor extracellular matrix are linked to poor cytotoxic T-cell infiltration and therapy response, yet the underlying mechanisms remain unclear. Tharp and colleagues revealed a fascinating cascade where tumor fibrosis alters macrophage metabolism, restricting the nutrients available to infiltrating T cells and resulting in their suppression and exclusion from the tumor microenvironment. This study suggests that targeting metabolic pathways could be a promising strategy to overcome the immune suppression induced by the tumor extracellular matrix.
SC134-TCB Targeting Fucosyl-GM1, a T Cell–Engaging Antibody with Potent Antitumor Activity in Preclinical Small Cell Lung Cancer Models
Authors: Dave Foram , Vaghela Poonam , Heath Bryony , Dunster Zuzana , Dubinina Elena , Thakker Dhruma , Mann Katie , Chadwick Joe , Cane Gaëlle , Kaira Bubacarr G. , Mohammed Omar J. , Choudhury Ruhul , Paston Samantha , Parsons Tina , Vankemmelbeke Mireille , Durrant Lindy
Published: August 2024

Small cell lung cancer (SCLC) is an aggressive disease with limited treatment options. Fucosyl-GM1 (FucGM1) is a glycolipid overexpressed in the majority of SCLC tumors but virtually absent from normal healthy tissues. In this study, we validate a FucGM1-targeting T cell–redirecting bispecific (TCB) antibody for the treatment of SCLC. More than 80% of patient-derived xenograft tissues of SCLC expressed FucGM1, whereas only three normal human tissues: pituitary, thymus, and skin expressed low and focal FucGM1. A FucGM1-targeting TCB (SC134-TCB), based on the Fc-silenced humanized SC134 antibody, exhibited nanomolar efficiency in FucGM1 glycolipid and SCLC cell surface binding. SC134-TCB showed potent ex vivo killing of SCLC cell lines with donor-dependent EC50 ranging from 7.2 pmol/L up to 211.0 pmol/L, effectively activating T cells, with picomolar efficiency, coinciding with target-dependent cytokine production such as IFNγ, IL2, and TNFα and robust proliferation of both CD4 and CD8 T cells. The ex vivo SC134-TCB tumor controlling activity translated into an effective in vivo anti-DMS79 tumor therapy, resulting in 100% tumor-free survival in a human peripheral blood mononuclear cell admixed setting and 40% overall survival (55% tumor growth inhibition) with systemically administered human peripheral blood mononuclear cells. Combination treatment with atezolizumab further enhanced survival and tumor growth inhibition (up to 73%). A 10-fold SC134-TCB dose reduction maintained the strong in vivo antitumor impact, translating into 70% overall survival (P < 0.0001). Whole-blood incubation with SC134-TCB, as well as healthy human primary cells analysis, revealed no target-independent cytokine production. SC134-TCB presents an attractive candidate to deliver an effective immunotherapy treatment option for patients with SCLC.
Chromothripsis-Mediated Small Cell Lung Carcinoma
Authors: Rekhtman Natasha , Tischfield Sam E. , Febres-Aldana Christopher A. , Lee Jake June-Koo , Chang Jason C. , Herzberg Benjamin O. , Selenica Pier , Woo Hyung Jun , Vanderbilt Chad M. , Yang Soo-Ryum , Xu Fei , Bowman Anita S. , da Silva Edaise M. , Noronha Anne Marie , Mandelker Diana L. , Mehine Miika , Mukherjee Semanti , Blanco-Heredia Juan , Orgera John J. , Nanjangud Gouri J. , Baine Marina K. , Aly Rania G. , Sauter Jennifer L. , Travis William D. , Savari Omid , Moreira Andre L. , Falcon Christina J. , Bodd Francis M. , Wilson Christina E. , Sienty Jacklynn V. , Manoj Parvathy , Sridhar Harsha , Wang Lu , Choudhury Noura J. , Offin Michael , Yu Helena A. , Quintanal-Villalonga Alvaro , Berger Michael F. , Ladanyi Marc , Donoghue Mark T.A. , Reis-Filho Jorge S. , Rudin Charles M.
Published: August 2024

Small cell lung carcinoma (SCLC) is a highly aggressive malignancy that is typically associated with tobacco exposure and inactivation of RB1 and TP53 genes. Here, we performed detailed clinicopathologic, genomic, and transcriptomic profiling of an atypical subset of SCLC that lacked RB1 and TP53 co-inactivation and arose in never/light smokers. We found that most cases were associated with chromothripsis—massive, localized chromosome shattering—recurrently involving chromosome 11 or 12 and resulting in extrachromosomal amplification of CCND1 or co-amplification of CCND2/CDK4/MDM2, respectively. Uniquely, these clinically aggressive tumors exhibited genomic and pathologic links to pulmonary carcinoids, suggesting a previously uncharacterized mode of SCLC pathogenesis via transformation from lower-grade neuroendocrine tumors or their progenitors. Conversely, SCLC in never-smokers harboring inactivated RB1 and TP53 exhibited hallmarks of adenocarcinoma-to-SCLC derivation, supporting two distinct pathways of plasticity-mediated pathogenesis of SCLC in never-smokers.

Significance: Here, we provide the first detailed description of a unique SCLC subset lacking RB1/TP53 alterations and identify extensive chromothripsis and pathogenetic links to pulmonary carcinoids as its hallmark features. This work defines atypical SCLC as a novel entity among lung cancers, highlighting its exceptional histogenesis, clinicopathologic characteristics, and therapeutic vulnerabilities.

See related commentary by Nadeem and Drapkin, p. 8
Supplementary Table 6 from Role of Forkhead Box P3 in IFNγ-Mediated PD-L1 Expression and Bladder Cancer Epithelial-to-Mesenchymal Transition
Authors: Zhang Hanwei , Ly Ann , Chou Emily , Wang Liang , Zhang Paul , Prado Kris , Gu Yiqian , Pellegrini Matteo , Chin Arnold I.
Published: August 2024

Exposure times of antibodies used for immunofluorescence
Supplementary Figure 3 from Role of Forkhead Box P3 in IFNγ-Mediated PD-L1 Expression and Bladder Cancer Epithelial-to-Mesenchymal Transition
Authors: Zhang Hanwei , Ly Ann , Chou Emily , Wang Liang , Zhang Paul , Prado Kris , Gu Yiqian , Pellegrini Matteo , Chin Arnold I.
Published: August 2024

Minimal activation of PD-L1 by IL-4 and IL-10 compared to IFNgamma in HT1376 cells