bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing transcription–replication conflict targets ecDNA-positive cancers
Authors: Tang Jun , Weiser Natasha E. , Wang Guiping , Chowdhry Sudhir , Curtis Ellis J. , Zhao Yanding , Wong Ivy Tsz-Lo , Marinov Georgi K. , Li Rui , Hanoian Philip , Tse Edison , Mojica Salvador Garcia , Hansen Ryan , Plum Joshua , Steffy Auzon , Milutinovic Snezana , Meyer S. Todd , Luebeck Jens , Wang Yanbo , Zhang Shu , Altemose Nicolas , Curtis Christina , Greenleaf William J. , Bafna Vineet , Benkovic Stephen J. , Pinkerton Anthony B. , Kasibhatla Shailaja , Hassig Christian A. , Mischel Paul S. , Chang Howard Y. 
Published: November 2024

AbstractExtrachromosomal DNA (ecDNA) presents a major challenge for cancer patients. ecDNA renders tumours treatment resistant by facilitating massive oncogene transcription and rapid genome evolution, contributing to poor patient survival1–7. At present, there are no ecDNA-specific treatments. Here we show that enhancing transcription–replication conflict enables targeted elimination of ecDNA-containing cancers. Stepwise analyses of ecDNA transcription reveal pervasive RNA transcription and associated single-stranded DNA, leading to excessive transcription–replication conflicts and replication stress compared with chromosomal loci. Nucleotide incorporation on ecDNA is markedly slower, and replication stress is significantly higher in ecDNA-containing tumours regardless of cancer type or oncogene cargo. pRPA2-S33, a mediator of DNA damage repair that binds single-stranded DNA, shows elevated localization on ecDNA in a transcription-dependent manner, along with increased DNA double strand breaks, and activation of the S-phase checkpoint kinase, CHK1. Genetic or pharmacological CHK1 inhibition causes extensive and preferential tumour cell death in ecDNA-containing tumours. We advance a highly selective, potent and bioavailable oral CHK1 inhibitor, BBI-2779, that preferentially kills ecDNA-containing tumour cells. In a gastric cancer model containing FGFR2 amplified on ecDNA, BBI-2779 suppresses tumour growth and prevents ecDNA-mediated acquired resistance to the pan-FGFR inhibitor infigratinib, resulting in potent and sustained tumour regression in mice. Transcription–replication conflict emerges as a target for ecDNA-directed therapy, exploiting a synthetic lethality of excess to treat cancer.
A dual-band high-gain beam steering antenna array for 5G sub-6 GHz base station
Authors: Siddiqui Salman Ilahi , Bashir Shahid , Khan Awais , Ghafoor Salman , Aziz Imran 
Published: November 2024

AbstractAn antenna array having a size of 45 $$\:\times\:$$ 40 cm2 (5.7 $$\:\times\:$$ 5 $$\:{\lambda\:}_{0}$$2) and consisting of four pairs of printed U-shaped dipoles positioned above a metal reflector, for 5G Sub-6 GHz base station applications, is designed and tested. The array consists of eight excitation ports, one port for each dipole. Four parasitic square patches are etched on the bottom side of the dipole arms for producing radiations in 2.2 GHz and 3.8 GHz bands. The size of the reflector and height of the dipoles are optimized in order to enhance antenna gain up to 11.5 dB at 2.2 GHz and 14.5 dB at 3.8 GHz. Beam steering up to 20$$\:^\circ\:$$ is achieved, using phase shifted simultaneous excitation of different ports. The proposed antenna array not only fulfills 5G base station requirements but is also simple and compact as it only requires eight ports to achieve dual-band, high-gain and beam steering operation in a single design. It also offers a unique feature of dual-sector coverage per panel, which results in an increased coverage capacity of the base station without increasing the system resources.
Shape optimized acoustic metagratings for anomalous refraction under strong thermoviscous effects
Authors: Melnikov Anton , Köble Sören , Schweiger Severin , Marburg Steffen , Powell David A. 
Published: November 2024

AbstractThe recent development of microacoustic metagratings opens up promising possibilities for manipulating acoustic wavefronts passively, particularly in applications such as flat acoustic lenses and ultra-high frequency ultrasound imaging. The emergence of two-photon polymerization has made it feasible to precisely manufacture microscopic structures, as required when metagratings are scaled to MHz frequencies in airborne ultrasound. Nevertheless, the downsizing process presents another hurdle as the increased thermoviscous effects result in substantial losses that must be considered during the design phase. In this study, we propose two designs for microacoustic metagratings that refract a normally incident wave towards –35 ° at 2 MHz, consisting of single-body and two-body meta-atoms. The designs are created by employing shape optimization techniques that incorporate the linearized Navier–Stokes equations in every iteration starting from a neutral geometry. This ensures that the evolution of geometric key features responsible for anomalous refraction fully accounts for thermoviscous effects, as would be the case during evolution in nature where the full set of physics is always active. Subsequently, we experimentally evaluate the effectiveness of these metagratings by employing a capacitive micromachined ultrasonic transducer as the sound source and an optical microphone as the detector, covering a frequency range from 1.8 to 2.2 MHz. Our findings confirm the single-body geometry reported in the literature and show an alternative geometry for two-body design, showcasing the successful utilization of two-photon polymerization for manufacturing microscopic acoustic metamaterials.
Factors associated with adherence to preventive measures against COVID-19, among adult Bahraini residents
Authors: Al Derazi Adoub , Bubshait Mariam , Albinjasim Ameena , Al Binzayed Amina , Bugahoos Hessa , Al Rumaihi Noor , Abuzeyad Noora , Al Sadeh Noora , Al Khaja Noora , Salmeen Zainab , Naseeb Tawfeeq , Al Shenawi Noor 
Published: November 2024

AbstractThe COVID-19 pandemic has been a life-altering experience. It compelled individuals to alter their attitudes and habits and adopt measures to prevent the risks of infection. This research discusses factors that determine adherence to these measures, with the aim of enhancing compliance in future pandemics. A descriptive cross-sectional study was conducted using snowball non-random sampling through an online Qualtrics survey targeting Bahraini residents, aged 18 and older. The sample included 1,008 participants, and data were analyzed using SPSS, and presented in tables and graphs. The majority of the participants were Bahraini females with a bachelor’s degree, between the ages of 20–29 (43.2%). Awareness of COVID-19 transmission was high, with 87.7%. The adherence rates for preventive measures were high: mask usage at 98.8%, hygiene practices at 93.7%, and social distancing at 92.2%. Older adults aged 50 + showed the highest consistency in compliance (p = 0.001). Individuals with chronic diseases were more likely to adhere to mask use (p < 0.001). Conversely, those experiencing negative emotions about social distancing were more likely to visit crowded places (p = 0.031), indicating a psychological barrier. Mask use exhibited the highest adherence at 98.8%, while overall compliance was notably high among educated and retired individuals. Public health campaigns should target younger demographics with education about crowded spaces and address emotional barriers to social distancing. Future strategies can be tailored to promote adherence among diverse populations, enhancing community resilience against pandemics.
Genomic surveillance of Canadian airport wastewater samples allows early detection of emerging SARS-CoV-2 lineages
Authors: Overton Alyssa K. , Knapp Jennifer J. , Lawal Opeyemi U. , Gibson Richard , Fedynak Anastasia A. , Adebiyi Adebowale I. , Maxwell Brittany , Cheng Lydia , Bee Carina , Qasim Asim , Atanas Kyle , Payne Mark , Stuart Rebecca , Fleury Manon D. , Knox Natalie C. , Nash Delaney , Hungwe Yemurayi C. , Prasla Samran R. , Ho Hannifer , Agboola Simininuoluwa O. , Kwon Su-Hyun , Naik Shiv , Parreira Valeria R. , Rizvi Fozia , Precious Melinda J. , Thomas Steven , Zambrano Marcos , Fang Vixey , Gilliland Elaine , Varia Monali , Horn Maureen , Landgraff Chrystal , Arts Eric J. , Goodridge Lawrence , Becker Devan , Charles Trevor C. 
Published: November 2024

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has shown wastewater (WW) surveillance to be an effective means of tracking the emergence of viral lineages which arrive by many routes of transmission including via transportation hubs. In the Canadian province of Ontario, numerous municipal wastewater treatment plants (WWTPs) participate in WW surveillance of infectious disease targets such as SARS-CoV-2 by qPCR and whole genome sequencing (WGS). The Greater Toronto Airports Authority (GTAA), operator of Toronto Pearson International Airport (Toronto Pearson), has been participating in WW surveillance since January 2022. As a major international airport in Canada and the largest national hub, this airport is an ideal location for tracking globally emerging SARS-CoV-2 variants of concern (VOCs). In this study, WW collected from Toronto Pearson’s two terminals and pooled aircraft sewage was processed for WGS using a tiled-amplicon approach targeting the SARS-CoV-2 virus genome. Data generated was analyzed to monitor trends of SARS-CoV-2 lineage frequencies. Initial detections of emerging lineages were compared between Toronto Pearson WW samples, municipal WW samples collected from the surrounding regions, and Ontario clinical data as published by Public Health Ontario. Results enabled the early detection of VOCs and individual mutations emerging in Ontario. On average, the emergence of novel lineages at the airport preceded clinical detections by 1–4 weeks, and up to 16 weeks in one case. This project illustrates the efficacy of WW surveillance at transitory transportation hubs and sets an example that could be applied to other viruses as part of a pandemic preparedness strategy and to provide monitoring on a mass scale.
Bone conduction stimulated VEMPs by using the B250 transducer to assess the nerve of origin of sporadic vestibular schwannomas
Authors: Rahne Torsten , Plontke Stefan K. , Strauss Christian , Fredén Jansson Karl-Johan , Håkansson Bo , Fröhlich Laura 
Published: November 2024

AbstractVestibular evoked myogenic potentials (VEMPs) are a tool to assess otolith function and a component of sensor specific vestibular diagnostics. The aim of the present study was to measure VEMP trough bone conducted (BC) stimulation using the B250 prototype and to report amplitudes, latencies and threshold levels for patients before resection of a sporadic unilateral vestibular schwannoma (VS) in order to assess function regarding to the reported nerve of origin. Twenty-seven participants (9 male/18 female) with a mean age of 55.9 years (SD: 10.8) were included for the analysis. In the side contralateral to the tumor, in 24 (89%) of the patients cVEMP could be measured, while oVEMP were recordable in 20 patients (74%). For patients with inferior vestibular nerve of origin (n = 11), cVEMP amplitudes of the affected side were significantly lower as compared to the non-affected side, while the force threshold level was increased. No statistically significant differences were observed for neither, oVEMP amplitudes nor threshold levels in the group with superior vestibular nerve of origin (n = 7). Across groups, p13 latency was significantly increased in the affected ear while all other VEMP latencies were not different between the ears. The B250 transducer was applicable to all participants of the clinical cohort. The sample size, however, was too low for a reliable statistical analysis and only allowed for exploratory analysis.
Association of cumulative methylprednisolone dosages with mortality risk from pneumonia in connective tissue disease patients
Authors: Wang Saibin , Ye Qian 
Published: November 2024

AbstractCorticosteroid is essential in the treatment regimen for connective tissue disease (CTD); however, its long-term use poses significant risks, including pulmonary infections. The relationship between cumulative corticosteroid doses and adverse pneumonia outcomes requires further investigation. This study aimed to explore the association between cumulative methylprednisolone dosages (CMD) and pneumonia mortality risks among CTD patients. We conducted a retrospective analysis of data from CTD patients treated with intravenous or oral corticosteroids across six academic hospitals over approximately five years in China. We evaluated follow-up outcomes at 30 and 90 days after the onset of pneumonia. Piecewise linear regression, Cox regression analysis, and survival analysis were employed to investigate the relationship between CMD and 30-day and 90-day mortality risks. Among 335 CTD patients with pneumonia, the mean CMD was 12 g. The 30-day and 90-day mortality rates were 25.07% and 29.55%, respectively. After adjusting for potential confounders, smooth curve fitting analysis revealed a specific nonlinear relationship between CMD and 30-day and 90-day mortality risks. Cox regression analysis indicated that the lowest pneumonia mortality risk occurred when CMD ranged from 11 to 24 g (30-day adjusted hazard ratio (aHR) 0.33, 95% CI 0.14–0.77; 90-day aHR 0.37, 95% CI 0.17–0.81). Patients in the 11–24 g CMD group demonstrated significantly lower cumulative hazard and death rates compared to both the low CMD (< 11 g) and high CMD (> 24 g) groups (P < 0.05). Furthermore, interaction testing suggested that CMD’s negative impact on pneumonia mortality risks was more pronounced in community-acquired pneumonia (CAP) compared to hospital-acquired pneumonia (P for interaction < 0.05). CMD shows a distinct nonlinear relationship with 30-day and 90-day pneumonia mortality risks, with potentially lower risks observed within the 11–24 g CMD range. Moreover, the varying impact of CMD on CAP mortality risk warrants further consideration in clinical management strategies.
Intestinal epithelial Gasdermin C is induced by IL-4R/STAT6 signaling but is dispensable for gut immune homeostasis
Authors: Gámez-Belmonte Reyes , Wagner Yara , Mahapatro Mousumi , Wang Ru , Erkert Lena , González-Acera Miguel , Cineus Roodline , Hainbuch Saskia , Patankar Jay V. , Voehringer David , Hegazy Ahmed N. , Neurath Markus F. , Wirtz Stefan , Becker Christoph 
Published: November 2024

AbstractGasdermin C is one of the least studied members of the gasdermin family of proteins, known for their critical involvement in pyroptosis and host defense. Furthermore, evidence for the role of Gasdermin C in the intestine is scarce and partly controversial. Here, we tested the functional role of Gasdermin C in intestinal homeostasis, inflammation and tumorigenesis. : We studied Gasdermin C in response to cytokines in intestinal organoids. We evaluated epithelial differentiation, cell death and immune infiltration under steady state conditions in a new mouse line deficient in Gasdermin C. The role of Gasdermin C was analyzed in acute colitis, infection and colitis-associated cancer. Gasdemin C is highly expressed in the intestinal epithelium and strongly induced by the type 2 cytokines IL-4 and IL-13 in a STAT6-dependent manner. Gasdermin C-deficient mice show no changes in tissue architecture and epithelial homeostasis. Epithelial organoids deficient in Gasdermin C develop normally and show no alterations in proliferation or cell death. No changes were found in models of acute colitis, type 2 intestinal infection and colitis-associated cancer. Gasdermin C genes are upregulated by type 2 immunity, yet appear dispensable for the development of intestinal inflammation, infection and colitis-associated cancer.
The R.O.A.D. to precision medicine
Authors: Bertsimas Dimitris , Koulouras Angelos Georgios , Margonis Georgios Antonios 
Published: November 2024

AbstractWe propose a novel framework that addresses the deficiencies of Randomized clinical trial data subgroup analysis while it transforms ObservAtional Data to be used as if they were randomized, thus paving the road for precision medicine. Our approach counters the effects of unobserved confounding in observational data through a two-step process that adjusts predicted outcomes under treatment. These adjusted predictions train decision trees, optimizing treatment assignments for patient subgroups based on their characteristics, enabling intuitive treatment recommendations. Implementing this framework on gastrointestinal stromal tumors (GIST) data, including genetic sub-cohorts, showed that our tree recommendations outperformed current guidelines in an external cohort. Furthermore, we extended the application of this framework to RCT data from patients with extremity sarcomas. Despite initial trial indications of universal treatment necessity, our framework identified a subset of patients who may not require treatment. Once again, we successfully validated our recommendations in an external cohort.
Underlying drivers of coral reef vulnerability to bleaching in the Mesoamerican Reef
Authors: Muñiz-Castillo Aarón Israel , Rivera-Sosa Andrea , McField Melanie , Chollett Iliana , Eakin C. Mark , Enríquez Susana , Giró Ana , Drysdale Ian , Rueda Marisol , Soto Mélina , Craig Nicole , Arias-González Jesús Ernesto 
Published: November 2024

AbstractCoral bleaching, a consequence of stressed symbiotic relationships between corals and algae, has escalated due to intensified heat stress events driven by climate change. Despite global efforts, current early warning systems lack local precision. Our study, spanning 2015–2017 in the Mesoamerican Reef, revealed prevalent intermediate bleaching, peaking in 2017. By scrutinizing 23 stress exposure and sensitivity metrics, we accurately predicted 75% of bleaching severity variation. Notably, distinct thermal patterns—particularly the climatological seasonal warming rate and various heat stress metrics—emerged as better predictors compared to conventional indices (such as Degree Heating Weeks). Surprisingly, deeper reefs with diverse coral communities showed heightened vulnerability. This study presents a framework for coral reef bleaching vulnerability assessment, leveraging accessible data (including historical and real-time sea surface temperature, habitat variables, and species composition). Its operational potential lies in seamless integration with existing monitoring systems, offering crucial insights for conservation and management.
Probing the limits for coherent optical control of a mechanically decoupled defect center in hexagonal boron nitride
Authors: Koch Michael K. , Bharadwaj Vibhav , Kubanek Alexander 
Published: November 2024

AbstractThe coherent control of a two-level system is among the most essential challenges in modern quantum optics. Understanding its fundamental limitations is crucial, also for the realization of next generation quantum devices. The quantum coherence of a two-level system is fragile in particular, when the two levels are connected via an optical transition, which, at the same time, enables the manipulation of the system. When such quantum emitters are located in solids the coherence suffers from the interaction of the optical transition with the solid state environment, which requires the sample to be cooled to temperatures of a few Kelvin or below. Here, we use a mechanically isolated quantum emitter in hexagonal boron nitride to explore the individual mechanisms which affect the coherence of an optical transition under resonant drive. We operate the system at the threshold where the mechanical isolation collapses in order to study the onset and temperature-dependence of dephasing and independently of spectral diffusion. The insights on the underlying physical decoherence mechanisms reveal a limit in temperature until which coherent driving of the system is possible. This study enables to increase the operation temperature of hBN-based quantum devices, therefore reducing the need for cryogenic cooling.
Late Cenozoic intraplate volcanism as a trigger for hydrothermal venting in the Arctic southwestern Eurasia Basin
Authors: Meza-Cala Juan Camilo , Minakov Alexander , Faleide Jan Inge , Abdelmalak Mansour M. , Shephard Grace E. , Mattingsdal Rune , Geissler Wolfram H. , Gaina Carmen 
Published: November 2024

AbstractIntraplate volcanism has occurred for the last 35 million years within Northeast Atlantic and Arctic margins, including the western Barents Sea, Svalbard, and northern Greenland. Earlier studies have suggested that some of this volcanism might be sourced from nearby mid-ocean ridges. However, legacy data does not reveal correlations between the sporadic volcanism, despite comparable setting, ages, and compositions of basalts across the area. Here, we utilize a compilation of geophysical data to document late Cenozoic intraplate volcanism affecting the northeastern Yermak Plateau and southwestern Eurasia Basin located north of Svalbard. The identified seabed and subsurface features include volcanic (Mound-A) and hydrothermal vent systems (Tayrona Vent) formed approximately 10 and 2.6 million years ago, respectively. These intraplate volcanic products are coincident in age and origin with observed hydrothermal systems on Svalbard and Northeast Atlantic. We propose that these magmatic features are the result of intraplate volcanism associated with seismic and thermal anomalies in the mantle beneath northern Svalbard.
Cost modeling for the GWh-scale production of modern lithium-ion battery cells
Authors: Lechner Maximilian , Kollenda Anna , Bendzuck Konrad , Burmeister Julian K. , Mahin Kashfia , Keilhofer Josef , Kemmer Lukas , Blaschke Maximilian J. , Friedl Gunther , Daub Ruediger , Kwade Arno 
Published: November 2024

AbstractBattery production cost models are critical for evaluating the cost competitiveness of different cell geometries, chemistries, and production processes. To address this need, we present a detailed bottom-up approach for calculating the full cost, marginal cost, and levelized cost of various battery production methods. Our approach ensures comparability across research fields and industries, reflecting capital and imputed interest costs. We showcase the model with case studies of a prismatic PHEV2 hardcase cell and a cylindrical 4680 cell in four different chemistries. Our publicly available browser-based modular tool incorporates up-to-date parameters derived from literature and expert interviews. This work enables researchers to quickly assess the production cost implications of new battery production processes and technologies, ultimately advancing the goal of reducing the cost of electrified mobility.