bluuebunny/crossref_metadata_2025 huggingface dataset:
Narrow QRS ectopy with concealed connections from a para‐Hisian origin to the proximal left fascicles
Authors: Nakamura Kohki , Sasaki Takehito , Minami Kentaro , Aoki Hideyuki , Yoshimura Shingo , Nishiuchi Suguru , Naito Shigeto
Published: April 2024

Introduction

Catheter ablation of ectopy originating from the vicinity of the His bundle can be challenging.

Methods and Results

We report a case of a 33‐year‐old man with narrow QRS ectopy with preferential conduction from a para‐Hisian origin to the proximal left fascicles, which was successfully eliminated by radiofrequency ablation in the right coronary cusp, guided by ultrahigh‐resolution mapping of the His bundle, bundle branch, and fascicular electrograms.

Conclusion

Some narrow QRS ectopy may originate from the vicinity of the conduction system, instead of the “true” conduction system, and have concealed connections from its origin to the conduction system.
Prevalence and electrocardiographic and electrophysiological characteristics of idiopathic ventricular arrhythmias originating from the septal left ventricular summit
Authors: Yamada Takumi , Litovsky Silvio , Neal Kay George
Published: April 2024

Introduction

The left ventricular summit (LVS) is the highest point on the epicardial surface of the left ventricle. A part of the LVS that is located between the left coronary arteries (lateral‐LVS) is one of the major sites of idiopathic ventricular arrhythmia (VA) origins. Some idiopathic epicardial VAs can be ablated at endocardial sites adjacent to the epicardial area septal to the lateral‐LVS (septal‐LVS). This study examined the prevalence and electrocardiographic and electrophysiological characteristics of septal‐LVS VAs.

Methods

We studied consecutive patients with idiopathic VAs originating from the LVS (67 patients) and aortic root (93 patients).

Results

Based on the ablation results, among 67 LVS VAs, 54 were classified as lateral and 13 as septal‐LVS VAs. As compared with the lateral‐LVS VAs, the septal‐LVS VAs were characterized by a greater prevalence of left bundle branch block with left inferior‐axis QRS pattern, later precordial transition, lower R‐wave amplitude ratio in leads III to II, lower Q‐wave amplitude ratio in leads aVL to aVR, and later local ventricular activation time relative to the QRS onset during VAs (V‐QRS) in the great cardiac vein. The electrocardiographic and electrophysiological characteristics of the septal‐LVS VAs were similar to those of the aortic root VAs. However, the V‐QRS at the successful ablation site was significantly later during the septal‐LVS VAs than aortic root VAs (p < .0001). The precordial transition was significantly later during the septal‐LVS VAs than aortic root VAs (p < .05).

Conclusions

Septal‐LVS VAs are considered a distinct subgroup of idiopathic VAs originating from the left ventricular outflow tract.
FIGL1 prevents aberrant chromosome associations and fragmentation and limits crossovers in polyploid wheat meiosis
Authors: Osman Kim , Desjardins Stuart D. , Simmonds James , Burridge Amanda J. , Kanyuka Kostya , Henderson Ian R. , Edwards Keith J. , Uauy Cristobal , Franklin F. Chris H. , Higgins James D. , Sanchez‐Moran Eugenio
Published: April 2024

Meiotic crossovers (COs) generate genetic diversity and are crucial for viable gamete production. Plant COs are typically limited to 1–3 per chromosome pair, constraining the development of improved varieties, which in wheat is exacerbated by an extreme distal localisation bias. Advances in wheat genomics and related technologies provide new opportunities to investigate, and possibly modify, recombination in this important crop species. Here, we investigate the disruption of FIGL1 in tetraploid and hexaploid wheat as a potential strategy for modifying CO frequency/position.

We analysed figl1 mutants and virus‐induced gene silencing lines cytogenetically. Genetic mapping was performed in the hexaploid.

FIGL1 prevents abnormal meiotic chromosome associations/fragmentation in both ploidies. It suppresses class II COs in the tetraploid such that CO/chiasma frequency increased 2.1‐fold in a figl1 msh5 quadruple mutant compared with a msh5 double mutant. It does not appear to affect class I COs based on HEI10 foci counts in a hexaploid figl1 triple mutant. Genetic mapping in the triple mutant suggested no significant overall increase in total recombination across examined intervals but revealed large increases in specific individual intervals.

Notably, the tetraploid figl1 double mutant was sterile but the hexaploid triple mutant was moderately fertile, indicating potential utility for wheat breeding.
Assessing vulnerability to embolism and hydraulic safety margins in reed‐like Restionaceae
Authors: West A. G. , Atkins K. , van Blerk J. J. , Skelton R. P.
Published: April 2024

The African Restionaceae (Poales), the dominant graminoid layer in the megadiverse Cape Floristic Region of South Africa, are distributed across a wide range of moisture availability, yet currently there is very little known about the underlying hydraulics of this group.

We tested two methods for measuring culm vulnerability to embolism, the optical and pneumatic methods, in three species of Cannomois ranging in habitat from semi‐riparian (Cannomois virgata) to dryland (Cannomois parviflora and C. congesta). Estimates of culm xylem vulnerability were coupled with measures of turgor loss point (ΨTLP) and minimum field water potential (ΨMD) to assess hydraulic safety margins.

The optical and pneumatic methods produced similar estimates of P50, but differed for P12 and P88. All three species were quite vulnerable to embolism, with P50 of –1.9 MPa (C. virgata), −2.3 MPa (C. congesta), and −2.4 MPa (C. parviflora). Estimates of P50, ΨTLP and ΨMD aligned with habitat moisture stress, with highest values found in the semi‐riparian C. virgata. Consistent differences in P50, ΨMD and ΨTLP between species resulted in consistent hydraulic safety margins across species of 0.96 ± 0.1 MPa between ΨMD and P50, with onset of embolism occurring 0.43 ± 0.04 MPa after ΨTLP for all three species.

Our study demonstrates that restio occupancy of dry environments involves more than the evolution of highly resistant xylem, suggesting that other aspects of water relations are key to understanding trait–environment relationships in this group.
An agrogeophysical modelling framework for the detection of soil compaction spatial variability due to grazing using field‐scale electromagnetic induction data
Authors: Romero‐Ruiz Alejandro , O'Leary Dave , Daly Eve , Tuohy Patrick , Milne Alice , Coleman Kevin , Whitmore Andrew P.
Published: April 2024

Soil compaction is a regarded as a major environmental and economical hazard, degrading soils across the world. Changes in soil properties due to compaction are known to lead to decrease in biomass and increase in greenhouse gas emissions, nutrient leaching and soil erosion. Quantifying adverse impacts of soil compaction and developing strategies for amelioration relies on an understanding of soil compaction extent and temporal variability. The main indicators of soil compaction (i.e., reduction of pore space, increase in bulk density and decrease in soil transport properties) are relatively easy to quantify in laboratory conditions but such traditional point‐based methods offer little information on soil compaction extent at the field scale. Recently, geophysical methods have been proposed to provide non‐invasive information about soil compaction. In this work, we developed an agrogeophysical modelling framework to help address the challenges of characterizing soil compaction across grazing paddocks using electromagnetic induction (EMI) data. By integrative modelling of grazing, soil compaction, soil processes and EMI resistivity anomalies, we demonstrate how spatial patterns of EMI observations can be linked to management leading to soil compaction and concurrent modifications of soil functions. The model was tested in a dairy farm in the midlands of Ireland that has been grazed for decades and shows clear signatures of grazing‐induced compaction. EMI data were collected in the summer of 2021 and autumn of 2022 under dry and wet soil moisture conditions, respectively. For both years, we observed decreases of apparent electrical resistivity at locations that with visible signatures of compaction such as decreased vegetation and water ponding (e.g., near the water troughs and gates). A machine learning algorithm was used to cluster EMI data with three unique cluster signatures assumed to be representative of heavy, moderately, and non‐compacted field zones. We conducted 1D process‐based simulations corresponding to non‐compacted and compacted soils. The modelled EMI signatures agree qualitatively and quantitatively with the measured EMI data, linking decreased electrical resistivities to zones that were visibly compacted. By providing a theoretical framework based on mechanistic modelling of soil management and compaction, our work may provide a strategy for utilizing EMI data for detection of soil degradation due to compaction.
A scoping review of the role of policy in mitigating childhood obesity in underserved populations using the RE‐AIM framework
Authors: Gance‐Cleveland Bonnie , Frenn Marilyn , Browne Nancy , Greenberg Cindy Smith , Snethen Julia A. , Hodges Eric A. , Fial Alissa V. , Small Leigh , Irving Sharon Y.
Published: April 2024

Background

Childhood obesity is an escalating crisis in the United States. Health policy may impact this epidemic which disproportionally affects underserved populations.

Aim

The aim was to use the reach, effectiveness, adoption, implementation, and maintenance (RE‐AIM) framework to assess health policy impact on preventing or treating school‐aged children (5 > 18 years) with obesity in underserved populations.

Methods

A scoping review of 842 articles was conducted. Twenty‐four articles met the inclusion criteria and underwent data extraction.

Results

Twelve studies included subgroup analysis, with four suggesting an impact of policy on at‐risk groups. None of the 24 studies fully applied the RE‐AIM framework. Policies positively impacted childhood obesity in 12 studies across the sample.

Linking Evidence to Action

Our review revealed inconsistent evidence for the effectiveness of policy on childhood obesity, perhaps due to the lack of focus on the social determinants of health. In addition, many studies did not evaluate the outcomes for underserved populations. Therefore, we propose more attention to social determinants in future legislation and evaluation of policy effectiveness on underserved populations. Findings identify an urgent need for the design, implementation, and evaluation of policies specifically directed to address the inequities of racism, social injustices, and social determinants of health that impact childhood obesity in the United States. Future work needs to identify who was reached by the policy, who benefitted from the policy, and how policies were implemented to address obesity‐related health disparities. Nurses should advocate for the evaluation of childhood obesity policies, particularly in underserved populations, to determine effectiveness. Nurses, particularly those trained in population and community health and research, should advocate for policy research that considers inequities rather than controls for these variables. Multi‐layered interventions can then be tailored to sub‐populations and evaluated more effectively.
Closed 3‐forms in five dimensions and embedding problems
Authors: Donaldson Simon , Lehmann Fabian
Published: April 2024

We consider the question if a five‐dimensional manifold can be embedded into a Calabi–Yau manifold of complex dimension 3 such that the real part of the holomorphic volume form induces a given closed 3‐form on the 5‐manifold. We define an open set of 3‐forms in dimension five which we call strongly pseudoconvex, and show that for closed strongly pseudoconvex 3‐forms, the perturbative version of this embedding problem can be solved if a finite‐dimensional vector space of obstructions vanishes.
Effect of growth conditions and reactor configuration on the growth uniformity of large-scale graphene by chemical vapor deposition
Authors: Li Qihang , Luo Jinping , Li Zaoyang , Rummeli Mark H. , Liu Lijun
Published: April 2024

Chemical vapor deposition (CVD) is an affordable method for the preparation of large-scale and high-quality graphene. With the increase in CVD reactor size, gas mass transfer, flow state, and gas phase dynamics become more complicated. In this study, computational fluid dynamics is used to investigate factors affecting the uniformity of large-scale graphene growth under different growth conditions and reactor configurations. The dimensionless number defined in this paper and the Grashof number are utilized to distinguish the species transfer patterns and the flow states, respectively. A gas-surface dynamics model is established to simulate the graphene growth. Results reveal that the graphene growth rate uniformity is the highest at very low pressure and flow rate due to the flow symmetry and diffusion-dominated species transfer. At an increased pressure of 20 Torr, the uniformity of the graphene growth rate becomes higher axially and lower circumferentially with an increasing inlet mass flow rate. When the flow rate is fixed at 1500 SCCM and pressure is reduced from 20 to 2 Torr, graphene growth uniformity first increases and then decreases due to the influence of gas phase dynamics. Graphene growth rates are analyzed across ordinary reactor configurations and four configurations with inner tubes at 20 Torr pressure and 1500 SCCM flow rate. Comprehensive evaluation suggests that the ordinary reactor configuration performs best under these conditions. This research offers insights into the macroscopic growth mechanism of large-scale graphene and provides guidance for designing growth conditions in large-area graphene production.
Competence—One Term, Various Definitions: A Scoping Review for Sports Coach Education and Research
Authors: Möhrle Annalena
Published: April 2024

The competence of sports coaches is a key factor in athletes’ sporting success. Mindful of this, sports coach education and research have placed considerable emphasis on competence in recent years. A lack of shared understanding around the concept complicates the endeavour, raising the following question: How is the term “competence” in relation to coaches defined in coach education and research? I sought to answer this research question via a scoping review. In database and internet searches, I obtained n = 1,912 hits and identified n = 14 sports coaching frameworks. Following title and abstract screening and full-text assessment, I conducted content analysis on n = 47 publications. The results indicate frequent use of the term, with few attempts to define it. Where definitions occur, they usually fall into one of two types: Type A, found in empirical studies written in English, describes the term in relation to their athletes’ sporting success. Type B, found in all types of publications (theoretical, empirical and practical), defines it in terms of the knowledge and skills a coach requires in order to succeed in coaching situations. This paper concludes with a recommendation for a shared multi-faceted definition of “competence” in relation to coaches.
Transcriptomic responses to antibiotic exposure in
Mycobacterium tuberculosis
Authors: Poonawala Husain , Zhang Yu , Kuchibhotla Sravya , Green Anna G. , Cirillo Daniela Maria , Di Marco Federico , Spitlaeri Andrea , Miotto Paolo , Farhat Maha R.
Published: April 2024

Transcriptional responses in bacteria following antibiotic exposure offer insights into antibiotic mechanism of action, bacterial responses, and characterization of antimicrobial resistance. We aimed to define the transcriptional antibiotic response (TAR) in
Mycobacterium tuberculosis
(Mtb) isolates for clinically relevant drugs by pooling and analyzing Mtb microarray and RNA-seq data sets. We generated 99 antibiotic transcription profiles across 17 antibiotics, with 76% of profiles generated using 3–24 hours of antibiotic exposure and 49% within one doubling of the WHO antibiotic critical concentration. TAR genes were time-dependent, and largely specific to the antibiotic mechanism of action. TAR signatures performed well at predicting antibiotic exposure, with the area under the receiver operating curve (AUC) ranging from 0.84-1.00 (TAR <6 hours of antibiotic exposure) and 0.76–1.00 (>6 hours of antibiotic exposure) for upregulated genes and 0.57–0.90 and 0.87–1.00, respectfully, for downregulated genes. This work desmonstrates that transcriptomics allows for the assessment of antibiotic activity in Mtb within 6 hours of exposure.
Complete genome sequence of invasive
Streptococcus pneumoniae
serotype 11A causing meningitis in an adult patient, Italy 2022
Authors: Amadesi Stefano , Vocale Caterina , Guariglia Davide , Cricca Monica , Lazzarotto Tiziana , Sambri Vittorio , Gaibani Paolo
Published: April 2024

Streptococcus pneumoniae
is a major global health concern, being a common cause of meningitis in both children and adults. Here, we report the complete genome sequence of P10_PNE_LCR, a
S. pneumoniae
11A strain isolated in Northern Italy from an adult patient diagnosed with meningitis.
Metagenome-assembled bacterial genomes from benthic microbial mats in ice-covered Lake Vanda, Antarctica
Authors: Powell Tyler , Sumner Dawn Y. , Jungblut Anne D. , Hawes Ian , Mackey Tyler , Grettenberger Christen
Published: April 2024

We recovered 57 bacterial metagenome-assembled genomes (MAGs) from benthic microbial mat pinnacles from Lake Vanda, Antarctica. These MAGs provide access to genomes from polar environments and can assist in culturing and utilizing these Antarctic bacteria.
Supplemental Material: A little mica goes a long way: Impact of phyllosilicates on quartz deformation fabrics in naturally deformed rocks
Authors: Gottardi Raphaël , al. et
Published: April 2024

Figure S1: Simplified geological map and cross section of the Raft River Mountains. Table S1: Quartz textural results from electron backscatter diffraction analysis. File S1: Analytical procedure.  
Association of empiric antibiotic selection and clinical outcomes in hospitalised children with severe orbital infections: a retrospective cohort study
Authors: Krueger Carsten , Nguyen Emily Lan-Vy , Mahant Sanjay , Borkhoff Cornelia M , Cichon Jessica , Drouin Olivier , Pound Catherine , Quet Julie , Wahi Gita , Bayliss Ann , Vomiero Gemma , Foulds Jessica , Kanani Ronik , Sakran Mahmoud , Sehgal Anupam , Pullenayegum Eleanor , Widjaja Elysa , Reginald Arun , Wolter Nikolaus , Parkin Patricia , Gill Peter J
Published: April 2024

Objective

To determine the association of initial empiric antibiotic regimens with clinical outcomes in hospitalised children with severe orbital infections.

Design

Multi-centre observational cohort study using data from 2009 to 2018 clinical records.

Setting

Canadian children’s hospitals (7) and community hospitals (3).

Patients

Children between 2 months and 18 years hospitalised for >24 hours with severe orbital infections.

Interventions

Empiric intravenous antibiotic regimen in the first 24 hours of hospitalisation.

Main outcome measures

Length of hospital stay and surgical intervention using multivariable median regression and multivariate logistic regression, with adjustment for covariates.

Results

Of 1421 patients, 60.0% were male and the median age was 5.5 years (IQR 2.4–9.9). Median length of stay was 86.4 hours (IQR 56.9–137.5) and 180 (12.7%) received surgical intervention. Patients receiving broad-spectrum empiric antibiotics had an increased median length of stay, ranging from an additional 13.8 hours (third generation cephalosporin and anaerobic coverage) to 19.5 hours (third generation cephalosporin, staphylococcal and anaerobic coverage). No antibiotic regimen was associated with a change in the odds of surgical intervention. These findings remained unchanged in sensitivity analyses restricted to more severely ill patients. There was a twofold increase in the percentage of patients receiving the broadest empiric antibiotic regimens containing both staphylococcal and anaerobic coverage from 17.8% in 2009 to 40.3% in 2018.

Conclusions

Empiric use of broad-spectrum antibiotics with staphylococci and anaerobic coverage was associated with longer length of stay and similar rates of surgery in children with orbital infections. There is an urgent need for comparative effectiveness studies of various antibiotic regimes.
Definitions of digital biomarkers: a systematic mapping of the biomedical literature
Authors: Macias Alonso Ana Karen , Hirt Julian , Woelfle Tim , Janiaud Perrine , Hemkens Lars G
Published: April 2024

Background

Technological devices such as smartphones, wearables and virtual assistants enable health data collection, serving as digital alternatives to conventional biomarkers. We aimed to provide a systematic overview of emerging literature on ‘digital biomarkers,’ covering definitions, features and citations in biomedical research.

Methods

We analysed all articles in PubMed that used ‘digital biomarker(s)’ in title or abstract, considering any study involving humans and any review, editorial, perspective or opinion-based articles up to 8 March 2023. We systematically extracted characteristics of publications and research studies, and any definitions and features of ‘digital biomarkers’ mentioned. We described the most influential literature on digital biomarkers and their definitions using thematic categorisations of definitions considering the Food and Drug Administration Biomarkers, EndpointS and other Tools framework (ie, data type, data collection method, purpose of biomarker), analysing structural similarity of definitions by performing text and citation analyses.

Results

We identified 415 articles using ‘digital biomarker’ between 2014 and 2023 (median 2021). The majority (283 articles; 68%) were primary research. Notably, 287 articles (69%) did not provide a definition of digital biomarkers. Among the 128 articles with definitions, there were 127 different ones. Of these, 78 considered data collection, 56 data type, 50 purpose and 23 included all three components. Those 128 articles with a definition had a median of 6 citations, with the top 10 each presenting distinct definitions.

Conclusions

The definitions of digital biomarkers vary significantly, indicating a lack of consensus in this emerging field. Our overview highlights key defining characteristics, which could guide the development of a more harmonised accepted definition.
Multimodal modeling with low-dose CT and clinical information for diagnostic artificial intelligence on mediastinal tumors: a preliminary study
Authors: Yamada Daisuke , Kojima Fumitsugu , Otsuka Yujiro , Kawakami Kouhei , Koishi Naoki , Oba Ken , Bando Toru , Matsusako Masaki , Kurihara Yasuyuki
Published: April 2024

Background

Diagnosing mediastinal tumours, including incidental lesions, using low-dose CT (LDCT) performed for lung cancer screening, is challenging. It often requires additional invasive and costly tests for proper characterisation and surgical planning. This indicates the need for a more efficient and patient-centred approach, suggesting a gap in the existing diagnostic methods and the potential for artificial intelligence technologies to address this gap. This study aimed to create a multimodal hybrid transformer model using the Vision Transformer that leverages LDCT features and clinical data to improve surgical decision-making for patients with incidentally detected mediastinal tumours.

Methods

This retrospective study analysed patients with mediastinal tumours between 2010 and 2021. Patients eligible for surgery (n=30) were considered ‘positive,’ whereas those without tumour enlargement (n=32) were considered ‘negative.’ We developed a hybrid model combining a convolutional neural network with a transformer to integrate imaging and clinical data. The dataset was split in a 5:3:2 ratio for training, validation and testing. The model’s efficacy was evaluated using a receiver operating characteristic (ROC) analysis across 25 iterations of random assignments and compared against conventional radiomics models and models excluding clinical data.

Results

The multimodal hybrid model demonstrated a mean area under the curve (AUC) of 0.90, significantly outperforming the non-clinical data model (AUC=0.86, p=0.04) and radiomics models (random forest AUC=0.81, p=0.008; logistic regression AUC=0.77, p=0.004).

Conclusion

Integrating clinical and LDCT data using a hybrid transformer model can improve surgical decision-making for mediastinal tumours, showing superiority over models lacking clinical data integration.
School performance and educational achievement in children exposed to maternal cancer in utero
Authors: Greiber Iben Katinka , Viuff Jakob Hansen , Karlsen Mona Aarenstrup , Lidegaard Øjvind , Mikkelsen Anders Preztmann , Hjortshøj Cristel Sørensen , Storgaard Lone , Mellemkjær Lene
Published: April 2024

Background

In utero exposure to maternal cancer and cancer treatment might influence the child’s cognitive development. This study investigated if exposure to maternal cancer during fetal life impacted school performance and educational achievement as adults.

Methods

This nationwide retrospective cohort study identified all live-born children in Denmark between January 1978 and December 2013. Exposure was defined as maternal cancer diagnosis during pregnancy. Four partly overlapping birth cohorts were constructed depending on the outcome of interest: (1) receiving special educational support for birth years 2001–2013; (2) grade point average (GPA) at the final exams after 10th grade for 1986–2003; (3) educational achievement at 20 years for 1978–1998; and (4) education at 30 years for 1978–1988. Logistic and linear models were adjusted for birth year, maternal age, maternal education and maternal death.

Results

The estimated probability of receiving special educational support was similar in the exposed group and the reference (adjusted OR 0.96; 95% CI 0.46 to 1.77, non-significant). The GPA did not statistically differ (0.13 grade points; 95% CI −0.18 to 0.45, non-significant). The achieved educational levels were similar for the exposed group and the reference at 20 years, with an adjusted OR of 1.07 (95% CI 0.82 to 1.40) for low versus medium educational level, and at 30 years with an adjusted OR of 0.73 (95% CI 0.35 to 1.50) for low versus high educational level and of 1.07 (95% CI 0.66 to 1.72) for medium versus high educational level.

Conclusion

Our findings did not indicate poorer performance in compulsory school nor impairment of adult educational achievement after exposure to maternal cancer in utero.
Microscopic state of BHs and an exact one body method for binary dynamics in general relativity
Authors: Zeng Ding-fang
Published: April 2024

In gravitational collapses, the horizon and singularity’s realisation in the finite future of the proper time used co-moving observer happens in the future of infinitely far away future of the normal time used outside probe. To the latter the horizon and singularity defined in the singularity theorem are physical realities only in the sense of uncertainty principle and ensemble interpretation. We provide two exact time dependent solution families to the Einstein equation and show that they form a pair of complementary description for the microscopic state of black holes by showing that the Bekenstein–Hawking entropy formula follows properly from their canonical wave function’s degeneracy. We also develop an eXact One Body method for general relativity two-body dynamics whose conservative part calls no post newtonian approximation as input and applies to the full three stages of black hole binary merger events. By this method, we analytically calculate the gravitational wave forms following from such merger processes. In the case black holes carry exact and apriori horizon and singularity our wave forms agree with those following from conventional effective one body method but exhibit more consistent late time behaviour. In the case black holes carry only asymptotic horizon and extended inner structure thus experiencing banana shape deformation as the merger occurs, our wave forms exhibit all features especially the late time quasi-normal mode type oscillation seen in real observations.
Effects of the new type of extended uncertainty principle on Van der Waals black hole thermodynamics: A theoretical and deep learning approach
Authors: Benkrane Abdelhakim , Zenkhri Djamel Eddine , Benhadjira Abderrahmane
Published: April 2024

In this paper, we study the Van der Waals black holes (the case [Formula: see text]) in the anti-de Sitter space under the effect of the linear extended uncertainty principle (EUP). The analysis was undertaken using deep learning by employing physics-informed neural networks in addition to the semi-classical approach, we have calculated the thermal quantities, including mass, volume, temperature, entropy, and Gibbs free energy. Additionally, we visually depict the effects of the EUP-term on the thermodynamic properties of the studied black holes.
Quarks and quantum chromodynamics
Authors: Plessas Willibald
Published: April 2024

A written account of my talk delivered at the Harald Fritzsch Memorial Symposium in Munich is given. The emphasis is on Harald’s achievements specifically in quark physics and in quantum chromodynamics. Beyond that exemplary results for low-energy baryons are discussed, as obtained over the past years in the framework of the relativistic constituent-quark model based on Goldstone-boson-exchange dynamics.
A note on a conjecture of Gao and Zhuang for groups of order 27
Authors: Godara Naveen K. , Sarkar Siddhartha
Published: April 2024

The small Davenport constant [Formula: see text] of a finite group [Formula: see text] is defined to be the maximal length of a sequence over [Formula: see text] which has no nontrivial product-one subsequence. In this paper, we prove that [Formula: see text] for the non-abelian group of order [Formula: see text] and exponent [Formula: see text] and thereby establish a conjecture by Gao and Zhuang for this group.
DYNAMICS AND CONSTRAINTS OF THE START-UP LEGITIMATION PROCESS: THE ROLE OF ORGANIZATIONAL IDENTIFICATION
Authors: KARPINSKAIA EMILIA , SHIROKOVA GALINA , MANOLOVA TATIANA S.
Published: April 2024

From inception, start-ups are torn between two opposing legitimacy pressures: the need to differentiate from competitors and the need to conform to stakeholders’ expectations. In this study, we adopt an organizational identification perspective, coupled with a legitimacy-seeking lens, to explore the start-up legitimation progress for entrepreneurs who identify with their ventures either intrinsically or instrumentally. Applying a longitudinal multi-case study design and using rich interview data, we track the decisions and actions of ten Russian high-tech start-ups over a twenty-month period. Our findings reveal that start-up legitimation is a dynamic process guided by the organizational identification of the founders and bounded by identity tensions. The study extends the literature on new venture legitimation and its constraints. Theoretical and practitioner implications are discussed.
Marine redox dynamics and biotic response to the mid-Silurian Ireviken Extinction Event in a mid-shelf setting
Authors: Wang Yuxuan , Wignall Paul B. , Xiong Yijun , Loydell David K. , Peakall Jeffrey , Baas Jaco H. , Mills Benjamin J. W. , Poulton Simon W.
Published: April 2024

The early Silurian Llandovery–Wenlock boundary interval is marked by significant marine perturbations and biotic turnover, culminating in the Ireviken Extinction Event and the Early Sheinwoodian Carbon Isotope Excursion. Here, we apply multiple independent redox proxies to the early Wenlock Buttington section, which was deposited in a mid-shelf location in the Welsh Basin, UK. To account for the regional geochemical variability in marine sediments due to factors such as sediment provenance, we first define oxic baseline values for the Welsh Basin, utilizing deeper water, well-oxygenated intervals of late Llandovery age. Our approach documents unstable, oscillating redox conditions on the mid-shelf at Buttington. We suggest that these dynamic redox fluctuations are likely to relate to changes in the position of the chemocline or a migrating oxygen minimum zone. Benthic biota, such as trilobites, brachiopods, bivalves and gastropods, appear to have been relatively unaffected by fluctuating oxic-ferruginous conditions, but were more severely impacted by the development of euxinia, highlighting the inhibiting role of toxic sulfides. By contrast, the redox perturbations appear to have placed extreme stress on graptolites, causing many extinction losses regardless of the specific development of euxinia.

Supplementary material:
The geochemical data for the Buttington section is available at
https://doi.org/10.6084/m9.figshare.c.7165009

Thematic collection:
This article is part of the Chemical Evolution of the Mid-Paleozoic Earth System and Biotic Response collection available at:
https://www.lyellcollection.org/topic/collections/chemical-evolution-of-the-mid-paleozoic-earth-system
Weight loss in adult male Wistar rats by Roux-en-Y gastric bypass is primarily explained by caloric intake reduction and presurgery body weight
Authors: Hoornenborg C. Warner , Somogyi Edit , Bruggink Jan E. , Boyle Christina N. , Lutz Thomas A. , Emous Marloes , van Beek André P. , Nyakas Csaba , van Dijk Gertjan
Published: April 2024

Relative to feeding an LF diet, continued feeding an HF/S diet does not negatively impact recovery from RYGB surgery in rats. Relative to feeding an LF diet, continued feeding an HF/S diet promotes RYGB-induced weight loss. The RYGB-induced weight loss is primarily explained by reduced cumulative EI and higher preoperative body weight, leading to comparably low levels of body fat content in HF/S and LF feeding rats.
Time to Death and Its Predictors among Neonates Hospitalized with Sepsis in Eastern Ethiopia
Authors: Jibro Usmael , Desalew Assefa , Ayana Galana Mamo , Tura Abera Kenay
Published: April 2024

Background. Although neonatal sepsis is a major public health problem contributing to 30-50% of neonatal deaths in low- and middle-income countries, data on predictors of time to death are limited in Eastern Ethiopia. This study is aimed at determining predictors of time to death among neonates with sepsis admitted in public hospitals in Eastern Ethiopia. Methods. An institutional-based retrospective cohort study was conducted among 415 neonates admitted to referral hospitals in Eastern Ethiopia with sepsis from January 1, 2021, to December 31, 2021. Data were collected from medical records by using structured checklist and entered using EpiData 3.1 and analyzed using Stata 17. The Kaplan-Meier curves and log-rank tests were used to describe survival experience among different categories. The proportional hazard assumption and goodness of fit for the Cox regression model were checked. The Cox regression model was used to identify the significant predictors. Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated. Finally, statistical significance was set at a p value < 0.05 in the Cox regression analysis. Results. Of the 415 neonates with neonatal sepsis, 71 (17.1%) (95% CI: 13.60-21.08) died at discharge, with a median time to death of 14 days. The overall incidence rate of mortality was 36.5 per 1000 neonate days. Low birthweight (AHR=2.50; 95% CI: 1.15-5.44), maternal age≥35 years (AHR=3.17; 95% CI: 1.11, 9.04), low fifth-minute Apgar score (AHR: 2.32; 95% CI: 1.30-4.14), and late initiation of breastfeeding (AHR=4.82; 95% CI: 1.40-16.65) were independent predictors of mortality among neonates with sepsis. Conclusions. Almost one in five neonates with sepsis died at discharge. Low birthweight, maternal age≥35 years, low fifth-minute Apgar score, and late initiation of breastfeeding were predictors of mortality.
Exploring the Relationship between Ultrasonographic Measures of the Quadriceps and Knee Extensor Muscle Fitness in Endurance-Trained Individuals
Authors: Voskuil Caleb C. , Dudar Monique D. , Carr Joshua C.
Published: April 2024

Background. B-mode ultrasonography is an accessible and cost-effective method to assess muscle size and quality through muscle thickness (MT) and echo intensity (EI), respectively. Muscle thickness and EI have demonstrated relationships with maximal strength and local muscle endurance, providing a noninvasive and efficient modality to examine muscle fitness. However, these relationships have not been quantified in the individual quadriceps muscles of habitually endurance-trained populations, which may provide information to practitioners regarding rehabilitation and performance. Methods. Twenty-three participants (males: N = 10; females: N = 13) underwent B-mode ultrasonography to assess MT, EI, and adipose tissue thickness-corrected echo intensity (cEI) in the vastus intermedius (VI), vastus lateralis (VL), and rectus femoris (RF). Muscle fitness was evaluated through maximal strength (1RM) and local muscle endurance (4 sets to failure at 50% 1RM) during dynamic knee extension. Relationships between ultrasonography outcomes and muscle fitness were examined through stepwise multiple linear regression. Results. The results indicate that VI cEI is the strongest predictor of 1RM strength (r = −0.643), while no ultrasonography-derived measures significantly predicted local muscle endurance. Conclusion. The study demonstrates that ultrasonography, specifically measures of cEI in the VI, has the greatest association with maximal strength in endurance-trained individuals. These findings suggest monitoring VI muscle size and quality may benefit practitioners who aim to improve knee extension strength for performance or following injury. In addition, the findings support the use of EI examinations in trained populations.
Integrin αvβ3 Upregulation in Response to Nutrient Stress Promotes Lung Cancer Cell Metabolic Plasticity
Authors: Nam Arin , Jain Shashi , Wu Chengsheng , Campos Alejandro , Shepard Ryan M. , Yu Ziqi , Reddy Joshua P. , Von Schalscha Tami , Weis Sara M. , Onaitis Mark , Wettersten Hiromi I. , Cheresh David A.
Published: April 2024

Cancer stem/tumor-initiating cells display stress tolerance and metabolic flexibility to survive in a harsh environment with limited nutrient and oxygen availability. The molecular mechanisms underlying this phenomenon could provide targets to prevent metabolic adaptation and halt cancer progression. Here, we showed in cultured cells and live human surgical biopsies of non–small cell lung cancer that nutrient stress drives the expression of the epithelial cancer stem cell marker integrin αvβ3 via upregulation of the β3 subunit, resulting in a metabolic reprogramming cascade that allows tumor cells to thrive despite a nutrient-limiting environment. Although nutrient deprivation is known to promote acute, yet transient, activation of the stress sensor AMP-activated protein kinase (AMPK), stress-induced αvβ3 expression via Src activation unexpectedly led to secondary and sustained AMPK activation. This resulted in the nuclear localization of peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC1α) and upregulation of glutamine metabolism, the tricarboxylic acid cycle, and oxidative phosphorylation. Pharmacological or genetic targeting of this axis prevented lung cancer cells from evading the effects of nutrient stress, thereby blocking tumor initiation in mice following orthotopic implantation of lung cancer cells. These findings reveal a molecular pathway driven by nutrient stress that results in cancer stem cell reprogramming to promote metabolic flexibility and tumor initiation.

Significance:

Upregulation of integrin αvβ3, a cancer stem cell marker, in response to nutrient stress activates sustained AMPK/PGC1α signaling that induces metabolic reprogramming in lung cancer cells to support their survival.

See related commentary by Rainero, p. 1543
Impact of Circulating Tumor Cell–Expressed Prostate-Specific Membrane Antigen and Prostate-Specific Antigen Transcripts in Different Stages of Prostate Cancer
Authors: Cho Hyungseok , Byun Seok-Soo , Son Nak-Hoon , Chung Jae Il , Seo Won Ik , Lee Chan Ho , Morgan Todd M. , Han Ki-Ho , Chung Jae-Seung
Published: April 2024

Purpose:

Prostate-specific membrane antigen (PSMA)–based images, which visually quantify PSMA expression, are used to determine prostate cancer micrometastases. This study evaluated whether a circulating tumor cell (CTC)–based transcript platform, including PSMA mRNA, could help identify potential prognostic markers in prostate cancer.

Experimental Design:

We prospectively enrolled 21 healthy individuals and 247 patients with prostate cancer [localized prostate cancer (LPCa), n = 94; metastatic hormone–sensitive prostate cancer (mHSPC), n = 44; and metastatic castration-resistant prostate cancer (mCRPC), n = 109]. The mRNA expression of six transcripts [PSMA, prostate-specific antigen (PSA), AR, AR-V7, EpCAM, and KRT 19] from CTCs was measured, and their relationship with biochemical recurrence (BCR) in LPCa and mCRPC progression-free survival (PFS) rate in mHSPC was assessed. PSA-PFS and radiological-PFS were also calculated to identify potential biomarkers for predicting androgen receptor signaling inhibitor (ARSI) and taxane-based chemotherapy resistance in mCRPC.

Results:

CTC detection rates were 75.5%, 95.3%, and 98.0% for LPCa, mHSPC, and mCRPC, respectively. In LPCa, PSMA [hazard ratio (HR), 3.35; P = 0.028) and PSA mRNA (HR, 1.42; P = 0.047] expressions were associated with BCR. Patients with mHSPC with high PSMA (HR, 4.26; P = 0.020) and PSA mRNA (HR, 3.52; P = 0.042) expressions showed significantly worse mCRPC-PFS rates than those with low expression. Increased PSA and PSMA mRNA expressions were significantly associated with shorter PSA-PFS and radiological PFS in mCPRC, indicating an association with drug resistance.

Conclusions:

PSMA and PSA mRNA expressions are associated with BCR in LPCa. In advanced prostate cancer, PSMA and PSA mRNA can also predict rapid progression from mHSPC to mCRPC and ARSI or taxane-based chemotherapy resistance.
Abstract CT088: EVT801, a novel selective VEGFR-3 inhibitor targeting tumor angiogenesis, is pursuing dose escalation stage of phase I first-in-human study
Authors: Gomez-Roca Carlos , Cassier Philippe , Fitzgerald Michael , Davenne Lise , Costantin Cristina , Rochaix Philippe , Delord Jean-Pierre , Friend John , Nizzardo Andrea , Tagliavini Alessia , Pergher Marco , Fons Pierre , Mandron Marie
Published: April 2024

Background: EVT801 is a highly selective, orally available VEGFR3 inhibitor that modulates tumor angiogenesis without inducing hypoxia, one of the main causes of cancer-associated immunosuppression. EVT801 has shown compelling efficacy as single agent in multiple in vivo models. In addition, combination of EVT801 and Immune Checkpoint Therapy (ICT) agents shows additive effects and thus holds promises for combination treatment without induction of hypoxia-induced immunosuppression.

Clinical trial design: A phase I clinical study (NCT05114668) is underway to evaluate safety, tolerability, pharmacokinetics of EVT801 and explore patient characterization which is key for further development. The phase I trial consists in two sequential stages. During the first stage, currently ongoing, EVT801 is orally administered to patients with advanced solid tumors in a multiple ascending dose study using an accelerated 3+3 design (1 patient per dose until grade 2 toxicities are observed) in up to 48 patients in 8 dose levels. The primary objective is to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Stage 2 will focus on validation of this RP2D in two 6-patient cohorts diagnosed with 2 indications. In addition to conventional measures of safety, tolerability, efficacy, and pharmacokinetics, the phase I study employs a rich suite of biomarkers analysis using histology, transcriptomics and immunomonitoring to provide early insights into the pharmacological activity of EVT801. At end of September 2023, 20 patients have been treated in five different cohorts for EVT801 doses ranging from 50mg QD to 400mg BID. At this date, only 1 dose limiting toxicity was declared at the higher dose.

Conclusion: Collection of safety data on these first enrolled patients showed no safety alert which allows further dose escalation and reinforces the good safety profile of EVT801 observed during the preclinical toxicology studies.

Citation Format: Carlos Gomez-Roca, Philippe Cassier, Michael Fitzgerald, Lise Davenne, Cristina Costantin, Philippe Rochaix, Jean-Pierre Delord, John Friend, Andrea Nizzardo, Alessia Tagliavini, Marco Pergher, Pierre Fons, Marie Mandron. EVT801, a novel selective VEGFR-3 inhibitor targeting tumor angiogenesis, is pursuing dose escalation stage of phase I first-in-human study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT088.
Abstract CT214: Paricalcitol addition to chemotherapy in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PINBALL)
Authors: Propper David , Jameson Gayle , Roe Denise , Wertheim Betsy , Von Hoff Dan , Borazanci Erkut H.
Published: April 2024

Background Vitamin D agonism has been shown in preclinical studies to decrease the production of collagen, decrease myeloid derived suppressor cells, and decrease regulatory T cells in pancreatic ductal adenocarcinoma (PDAC). Paricalcitol is a vitamin D analog used for vitamin D replacement for those with secondary hyperparathyroidism. Two individuals with PDAC who had been developed resistance gemcitabine based combination therapy had shown clinical benefit with the addition of paricalcitol. This clinical study was done to study the effect of adding paricalcitol to individuals with metastatic PDAC receiving gemcitabine based combination therapy (NCT04054362, NCT03415854) .

Methods Adults with a histologically- or cytologically-confirmed diagnosis of metastatic PDAC and who were previously untreated were eligible. Individuals received gemcitabine based combination- either gemcitabine plus nab-paclitaxel or gemcitabine plus nab-paclitaxel and cisplatin and had to either demonstrate progressive or stable disease. Paricalcitol was given at a fixed dose of 25 mcg IV three days a week. The combination continued until either disease progression or poor tolerance. The primary objective was to determine the clinical benefit of adding paricalcitol to gemcitabine based combination therapy for metastatic PDAC. Secondary objectives included assessing safety and pharmacodynamic through patient biopsies.

Results A total of 34 patients were enrolled across two sites. 16 patients received paricalcitol. The overall response rate was 0% ( CR, PR). Disease control rate at 9 weeks was 21.4% (CR+PR+ SD). PFS upon addition of paricalcitol was 1.6 months. OS upon addition of paricalcitol was 4.8 months. Grade 3/4 AE's attributed to paricalcitol include 13% thrombocytopenia; 19% anemia; 6% transaminitis; 6% pleural effusion; 6% ascites- all grade 3.

Conclusions The addition of paricalcitol demonstrated evidence of limited clinical benefit in individuals with metastatic PDAC receiving front-line gemcitabine based therapy. Paricalcitol was generally well tolerated. Tumor analysis is ongoing. Addition studies utilizing prospective treatment of paricalcitol for front line treatment of mPDAC are ongoing (NCT03520790). Trial funding provided by SU2C, CRUK, Lustgarten Foundation, and AACR.

Citation Format: David Propper, Gayle Jameson, Denise Roe, Betsy Wertheim, Dan Von Hoff, Erkut H. Borazanci. Paricalcitol addition to chemotherapy in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PINBALL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT214.