bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and Spectrum of AR Ligand-Binding Domain Mutations Detected in Circulating-Tumor DNA Across Disease States in Men With Metastatic Castration-Resistant Prostate Cancer
Authors: Antonarakis Emmanuel S. , Zhang Nicole , Saha Jayati , Nevalaita Liina , Ikonen Tarja , Tsai L. Jill , Garratt Chris , Fizazi Karim 
Published: May 2024

PURPOSE Metastatic castration-resistant prostate cancer (mCRPC) is typically treated with agents directly or indirectly targeting the androgen receptor (AR) pathway. However, such treatment is limited by resistance mechanisms, including the development of activating mutations in the AR ligand-binding domain ( AR-LBD). METHODS This study evaluated a database of over 15,000 patients with advanced prostate cancer (PC) undergoing comprehensive circulating-tumor DNA analysis (Guardant360, Redwood City, CA) between 2014 and 2021, with associated clinical information from administrative claims (GuardantINFORM database). RESULTS Of 15,705 patients with PC included, 54% had mCRPC at the time of their blood draw. Of those, 49% had previous treatment with an AR pathway inhibitor (ARPi). AR-LBD mutation prevalence was 15% in patients with mCRPC who were untreated with a next-generation ARPi, 22% in those after one line of ARPi therapy, and 24% in those after two lines of ARPi treatment. Next-generation ARPi treatment yielded an increase in AR L702H and T878A/S mutations after abiraterone, and an increase in AR L702H and F877L mutations after enzalutamide. AR-LBD+ patients demonstrated unique biology, including increased concurrent mutations in the cell-cycle, wingless-related integration site, homologous recombination repair, and phospho-inositide 3-kinase pathways (all P < .0005), and greater low-level (copy number <10) AR amplifications ( P = .0041). AR-LBD+ patients exhibited worse overall survival (OS) relative to a matched cohort of AR-LBD– patients (50.1 v 60.7 months, unadjusted log-rank P = .013). CONCLUSION This large database analysis demonstrates that AR-LBD mutation prevalence increases after next-generation ARPi use. AR-LBD+ tumors demonstrate unique biology (more oncogenic pathway mutations and low-level AR amplification) and reduced OS. These findings inform the development of novel therapies designed to circumvent AR-mediated therapeutic resistance.
Role of the Casimir force in micro- and nanoelectromechanical pressure sensors
Authors: Klimchitskaya G. L. , Korotkov A. S. , Loboda V. V. , Mostepanenko V. M. 
Published: May 2024

Abstract
The Casimir force caused by the electromagnetic fluctuations is computed in the configurations of micro- and nanoelectromechanical pressure sensors using Si membranes and either Si or Au-coated Si substrates. It is shown that if, under the influence of external pressure, the membrane-substrate separation drops to below 100 nm, the Casimir force makes a profound effect on the sensor functioning. There exists the maximum value of external pressure depending on the sensor parameters such that it finds itself in a state of unstable equilibrium. For this and larger pressures, the Casimir force leads to a collapse of the sensor, which loses its functionality. For any smaller external pressures, there exist two equilibrium positions, one of which is unstable and another one is stable, at smaller and larger membrane-substrate separations, respectively. The latter can be safely used for the pressure measurements. Possible applications of the obtained results in the design of micro- and nanoelectromechanical pressure sensors of next generations with further decreased dimensions are discussed.
LECT2 Deletion Exacerbates Liver Steatosis and Macrophage Infiltration in a Male Mouse Model of LPS-mediated NASH
Authors: Tanida Ryota , Goto Hisanori , Takayama Hiroaki , Nakano Yujiro , Oo Hein Ko , Galicia-Medina Cynthia Monserrat , Takahashi Kenta , Ishii Kiyo-aki , Goli Arman Syah , Matsuzaka Takashi , Harada Kenichi , Takamura Toshinari 
Published: May 2024

Abstract
Leukocyte cell-derived chemotaxin 2 (LECT2) is a protein initially isolated as a neutrophil chemotactic factor. We previously found that LECT2 is an obesity-associated hepatokine that senses liver fat and induces skeletal muscle insulin resistance. In addition, hepatocyte-derived LECT2 activates macrophage proinflammatory activity by reinforcing the lipopolysaccharide (LPS)-induced c-Jun N-terminal kinase signaling. Based on these findings, we examined the effect of LECT2 deletion on nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) caused by bacterial translocation. We created the bacterial translocation-mediated NAFLD/NASH model using LECT2 knockout mice (LECT2 KO) with 28 times a low-dose LPS injection under high-fat diet feeding conditions. LECT2 deletion exacerbated steatosis and significantly reduced p38 phosphorylation in the liver. In addition, LECT2 deletion increased macrophage infiltration with decreased M1/M2 ratios. LECT2 might contribute to protecting against lipid accumulation and macrophage activation in the liver under pathological conditions, which might be accomplished via p38 phosphorylation. This study provides novel aspects of LECT2 in the bacterial translocation-mediated NAFLD/NASH model.
A Research Note on Community Resilience Estimates: New U.S. Census Bureau Data With an Application to Excess Deaths From COVID-19
Authors: Anders John , Carpenter Craig Wesley , Willyard Katherine Ann , DeSalvo Bethany 
Published: May 2024

Abstract
In this research note, we describe the results of the first validation study of the U.S. Census Bureau's new Community Resilience Estimates (CRE), which uses Census microdata to develop a tract-level vulnerability index for the United States. By employing administrative microdata to link Social Security Administration mortality records to CRE, we show that CRE quartiles provide more stable predictions of COVID-19 excess deaths than single demographic categorizations such as race or age, as well as other vulnerability measures including the U.S. Centers for Disease Control and Prevention's Social Vulnerability Index (SVI) and the Federal Emergency Management Agency's National Risk Index (NRI). We also use machine learning techniques to show that CRE provides more predictive power of COVID-19 excess deaths than standard socioeconomic predictors of vulnerability such as poverty and unemployment, as well as SVI and NRI. We find that a 10-percentage-point increase in a key CRE risk measure is associated with one additional death per neighborhood during the initial outbreak of COVID-19 in the United States. We conclude that, compared with alternative measures, CRE provides a more accurate predictor of community vulnerability to a disaster such as a pandemic.
Retirement Makes You Old? Causal Effect of Retirement on Biological Age
Authors: Furuya Shiro , Fletcher Jason M. 
Published: May 2024

Abstract
Retirement is a critical life event for older people. Health scholars have scrutinized the health effects of retirement, but its consequences on age-related diseases and mortality are unclear. We extend this body of research by integrating measurements of biological age, representing the physiological decline preceding disease onset. Using data from the UK Biobank and a fuzzy regression discontinuity design, we estimated the effects of retirement on two biomarker-based biological age measures. Results showed that retirement significantly increases biological age for those induced to retire by the State Pension eligibility by 0.871–2.503 years, depending on sex and specific biological age measurement. Given the emerging scientific discussion about direct interventions to biological age to achieve additional improvements in population health, the positive effect of retirement on biological age has important implications for an increase in the State Pension eligibility age and its potential consequences on population health, public health care policy, and older people's labor force participation. Overall, this study provides novel empirical evidence contributing to the question of what social factors make people old.
Weathering the Storm
Authors: Archer Nicole , Schreiber Rachel 
Published: May 2024

Abstract
Over the last two decades, red umbrellas have increasingly appeared in campaigns to end violence against sex workers, oppose harmful legislation, advocate for decriminalization, commemorate lost community members, and broadly express sex worker pride. Originating with the work of the artist/activist Tadej Pogačar and the P.A.R.A.S.I.T.E. Museum of Contemporary Art’s contribution to the 2001 Venice Biennale (“The Prostitute Pavilion”), red umbrellas were originally presented as a visual symbol of self-help, organization, and protection for sex workers. Since then the red umbrella has been adopted and adapted to a broader range of meanings related to sex worker activism, including decriminalization, opposition to antitrafficking discourse, and more. The umbrella has also come to convey the “big tent” concept—that all sex workers are together under its canopy, unified as one coalition. But like any symbol, the red umbrella’s use has limitations. The red umbrella risks amplifying negative rhetoric employed by the antitrafficking movement, which casts sex workers as passive victims in need of salvation, or of oversimplifying a complex, multifaceted political movement. The Curated Spaces section of this issue presents a brief history of the red umbrella as a symbol for sex workers’ rights and images that demonstrate its varied uses.
Pathways for Design Research on Artificial Intelligence
Authors: Abbasi Ahmed , Parsons Jeffrey , Pant Gautam , Sheng Olivia R. Liu , Sarker Suprateek 
Published: May 2024

An expanding body of information systems research is adopting a design perspective on artificial intelligence (AI), wherein researchers prescribe solutions to problems using AI approaches rather than describing or explaining AI-related phenomena being studied. In this editorial, we address some of the challenges faced in publishing design research related to AI and articulate viable pathways for publishing such work. More specifically, we highlight six major impediments, use the explosion in the state of the art for large language models to underscore these impediments, propose some pathways for overcoming the impediments, and use several example articles to illustrate how the pathways can be followed for different types of AI-related design artifacts. History: Senior Editor; Associate Editor. Funding: A. Abbasi was funded by the National Science Foundation (NSF) [Grants 2240347 and IIS-2039915] and a Kemper Faculty Award. J. Parsons was funded by the Natural Sciences and Engineering Council of Canada (NSERC) [Grant RGPIN-2020-04916].
A retrospective review of gram-negative spinal infections in a single tertiary spinal centre over six years
Authors: Tadross Daniel , McGrory Cieran , Greig Julia , Townsend Robert , Chiverton Neil , Highland Adrian , Breakwell Lee , Cole Ashley A. 
Published: May 2024

AimsGram-negative infections are associated with comorbid patients, but outcomes are less well understood. This study reviewed diagnosis, management, and treatment for a cohort treated in a tertiary spinal centre.MethodsA retrospective review was performed of all gram-negative spinal infections (n = 32; median age 71 years; interquartile range 60 to 78), excluding surgical site infections, at a single centre between 2015 to 2020 with two- to six-year follow-up. Information regarding organism identification, antibiotic regime, and treatment outcomes (including clinical, radiological, and biochemical) were collected from clinical notes.ResultsAll patients had comorbidities and/or non-spinal procedures within the previous year. Most infections affected lumbar segments (20/32), with Escherichia coli the commonest organism (17/32). Causative organisms were identified by blood culture (23/32), biopsy/aspiration (7/32), or intraoperative samples (2/32). There were 56 different antibiotic regimes, with oral (PO) ciprofloxacin being the most prevalent (13/56; 17.6%). Multilevel, contiguous infections were common (8/32; 25%), usually resulting in bone destruction and collapse. Epidural collections were seen in 13/32 (40.6%). In total, five patients required surgery, three for neurological deterioration. Overall, 24 patients improved or recovered with a mean halving of CRP at 8.5 days (SD 6). At the time of review (two to six years post-diagnosis), 16 patients (50%) were deceased.ConclusionThis is the largest published cohort of gram-negative spinal infections. In older patients with comorbidities and/or previous interventions in the last year, a high level of suspicion must be given to gram-negative infection with blood cultures and biopsy essential. Early organism identification permits targeted treatment and good initial clinical outcomes; however, mortality is 50% in this cohort at a mean of 4.2 years (2 to 6) after diagnosis.Cite this article: Bone Jt Open 2024;5(5):435–443.
End-to-end optimization of optical communication systems based on directly modulated lasers
Authors: Hernandez Sergio , Peucheret Christophe , Da Ros Francesco , Zibar Darko 
Published: May 2024

The use of directly modulated lasers (DMLs) is attractive in low-power, cost-constrained short-reach optical links. However, their limited modulation bandwidth can induce waveform distortion, undermining their data throughput. Traditional distortion mitigation techniques have relied mainly on the separate training of transmitter-side pre-distortion and receiver-side equalization. This approach overlooks the potential gains obtained by simultaneous optimization of the transmitter (constellation and pulse shaping) and receiver (equalization and symbol demapping). Moreover, in the context of DML operation, the choice of laser-driving configuration parameters such as the bias current and peak-to-peak modulation current has a significant impact on system performance. We propose, to our knowledge, a novel end-to-end optimization approach for DML systems, incorporating the learning of bias and peak-to-peak modulation current to the optimization of constellation points, pulse shaping, and equalization. The simulation of the DML dynamics is based on the use of the laser rate equations at symbol rates between 15 and 25 Gbaud. The resulting output sequences from the rate equations are used to build a differentiable data-driven model, simplifying the calculation of gradients needed for end-to-end optimization. The proposed end-to-end approach is compared to three additional benchmark approaches: the uncompensated system without equalization, a receiver-side finite impulse response equalization approach, and an end-to-end approach with learnable pulse shape and nonlinear Volterra equalization but fixed bias and peak-to-peak modulation current. The numerical simulations on the four approaches show that the joint optimization of bias, peak-to-peak current, constellation points, pulse shaping, and equalization outperforms all other approaches throughout the tested symbol rates.
Integrated 800 Gb/s O-band WDM optical transceiver enabled by hybrid InP-polymer photonic integration
Authors: Andrianopoulos Efstathios , Tokas Konstantinos , de Felipe David , Theurer Michael , Weigel Madeleine , Pagano Annachiara , Kanta Kostantina , Kresse Martin , Megas Giorgos , Tsokos Christos , Kouloumentas Christos , Chiadò Piat Anna , Tegegne Zerihun , Massaouti Maria , Bakopoulos Paraskevas , Moehrle Martin , Runge Patrick , Keil Norbert , Groumas Panos , Avramopoulos Hercules 
Published: May 2024

We propose and demonstrate a novel O-band wavelength division multiplexing (WDM) optical transceiver enabled by the hybrid photonic integration of indium phosphide (InP) components into a polymer-based photonic motherboard called PolyBoard. The optical engine hosts an eight-fold InP electro-absorption modulated laser (EML) array at the transmitter part exhibiting >35GHz electro-optical bandwidth and an eight-fold InP photodiode (PD) array at the receiver part with 50 GHz bandwidth, butt-end coupled to the PolyBoard motherboard, which accommodates passive arrayed waveguide gratings (AWGs) at the transmitter and receiver sides, responsible for performing the wavelength multiplexing and demultiplexing functionalities, respectively. What we believe to be a novel thin-film-based O-band half-wave plate is placed at the receiver side AWG, ensuring the polarization insensitivity of the prototype. The optical engine’s design is discussed in the manuscript, demonstrating experimental results from its static and dynamic evaluation. Individual characterization of the transmitter and receiver sides of the optical engine is presented before evaluating the optical engine as a whole in a loopback configuration. The obtained results underscore the potential of the proposed hybrid photonic integrated transceiver for supporting 800 Gb/s capacity in intra-datacenter optical interconnects for transmission distances up to 2 km.
High-performance and wavelength-transplantable on-chip Fourier transform spectrometer using MEMS in-plane reconfiguration
Authors: Chen Heng , Zhang Hui , Zhou Jing , Ma Chen , Huang Qian , Wang Hanxing , Ren Qinghua , Wang Nan , Lee Chengkuo , Ma Yiming 
Published: May 2024

On-chip spectrometers with high compactness and portability enable new applications in scientific research and industrial development. Fourier transform (FT) spectrometers have the potential to realize a high signal-to-noise ratio. Here we propose and demonstrate a generalized design for high-performance on-chip FT spectrometers. The spectrometer is based on the dynamic in-plane reconfiguration of a waveguide coupler enabled by an integrated comb-drive actuator array. The electrostatic actuation intrinsically features ultra-low power consumption. The coupling gap is crucial to the spectral resolution. The in-plane reconfiguration surmounts the lithography accuracy limitation of the coupling gap, boosting the resolution to 0.2 nm for dual spectral spikes over a large bandwidth of 100 nm (1.5–1.6 μm) within a compact footprint of 75  μm×1000  μm. Meanwhile, the in-plane tuning range can be large enough for arbitrary wavelengths to ensure the effectiveness of spectrum reconstruction. As a result, the proposed spectrometer can be easily transplanted to other operation bands by simply scaling the structural parameters. As a proof-of-concept, a mid-infrared spectrometer is further demonstrated with a dual-spike reconstruction resolution of 1.5 nm and a bandwidth of 300 nm (4–4.3 μm).
Modeling oxygen transport in the brain: An efficient coarse-grid approach to capture perivascular gradients in the parenchyma
Authors: Pastor-Alonso David , Berg Maxime , Boyer Franck , Fomin-Thunemann Natalie , Quintard Michel , Davit Yohan , Lorthois Sylvie 
Published: May 2024

Recent progresses in intravital imaging have enabled highly-resolved measurements of periarteriolar oxygen gradients (POGs) within the brain parenchyma. POGs are increasingly used as proxies to estimate the local baseline oxygen consumption, which is a hallmark of cell activity. However, the oxygen profile around a given arteriole arises from an interplay between oxygen consumption and delivery, not only by this arteriole but also by distant capillaries. Integrating such interactions across scales while accounting for the complex architecture of the microvascular network remains a challenge from a modelling perspective. This limits our ability to interpret the experimental oxygen maps and constitutes a key bottleneck toward the inverse determination of metabolic rates of oxygen.
We revisit the problem of parenchymal oxygen transport and metabolism and introduce a simple, conservative, accurate and scalable direct numerical method going beyond canonical Krogh-type models and their associated geometrical simplifications. We focus on a two-dimensional formulation, and introduce the concepts needed to combine an operator-splitting and a Green’s function approach. Oxygen concentration is decomposed into a slowly-varying contribution, discretized by Finite Volumes over a coarse cartesian grid, and a rapidly-varying contribution, approximated analytically in grid-cells surrounding each vessel.
Starting with simple test cases, we thoroughly analyze the resulting errors by comparison with highly-resolved simulations of the original transport problem, showing considerable improvement of the computational-cost/accuracy balance compared to previous work. We then demonstrate the model ability to flexibly generate synthetic data reproducing the spatial dynamics of oxygen in the brain parenchyma, with sub-grid resolution. Based on these synthetic data, we show that capillaries distant from the arteriole cannot be overlooked when interpreting POGs, thus reconciling recent measurements of POGs across cortical layers with the fundamental idea that variations of vascular density within the depth of the cortex may reveal underlying differences in neuronal organization and metabolic load.
Family Environment Related to Social Tolerance Among Students of Koya University
Authors: Ahmad Abas Sh. , Saadi Alan S. 
Published: May 2024

The main purpose of the research was to find out the environment of the family's relationship with the community's amnesty by the Koya University's students, according to the variable of gender. In this research, the researcher used the description method, and the group of this research was made up of the students of the University of Koya who were (4391), the sample of the research was (344) students, both male and female, to measure the family environment and community forgiveness, the researcher returned to the previous researches that was related In order to take advantage of them, determining a measure that was set in( 21) sections, each section had 5 options. In order to analyze the data, we benefited from SPSS and structural equation modeling, have been included in the AMOS program. The results of this study have shown that the family environment is a package that has been formed in three dimensions of culture, economy, and affection. The effect of statistical proof was a measure of (0,627) community amnesty, but if we take the dimensions separately as an independent variable, the emotional environment had a deviation measure effect of (0,215) where we conclude that in the family environment, all three dimensions need to be appropriate to have more power over the community's forgiveness. Finally, under the light of the results, the researcher presented a number of recommendations and suggestions.