bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perioperative discordance in mesothelioma cell type after pleurectomy/decortication—a possible detrimental effect of neoadjuvant chemotherapy due to epithelial to mesenchymal transition?
Authors: Ventura Luigi , Lee Michelle , Baranowski Ralitsa , Hargrave Joanne , Sheaff Michael , Waller David 
Published: October 2023

Abstract

OBJECTIVES
The goal was to evaluate the accuracy of preoperative histological assessment and the factors affecting the accuracy and the subsequent effect on postoperative survival after surgical treatment for malignant pleural mesothelioma (MPM).

METHODS
We analysed the perioperative course of patients who underwent surgery for MPM in a single institution over a 5-year period. The primary end point was to evaluate the proportion of histological discordance between preoperative assessment and postoperative histological diagnosis. The secondary end point was to evaluate its prognostic effect on postoperative survival after surgical treatment.

RESULTS
One-hundred and twenty-nine patients were included in this study. Histological discordance between preoperative assessment and postoperative histological diagnosis was found in 27 of 129 patients (20.9%): epithelial to biphasic/sarcomatoid (negative discordance) in 24 and biphasic to epithelial (positive discordance) in 3 (P-value &lt; 0.001). All 24 patients who exhibited epithelial-to-mesenchymal transition (EMT) had received neoadjuvant chemotherapy (P-value: 0.006). In the 34 patients who underwent upfront surgery, only 1 case (2.9%) of EMT was identified (P-value: 0.127). EMT was not associated with a less invasive method of biopsy (P-value: 0.058) or with the volume or maximum diameter of the biopsy (P-value: 0.358 and 0.518, respectively), but it was significantly associated with the receipt of neoadjuvant chemotherapy (P-value: 0.006). At a median follow-up of 17 months (IQR: 11.0–28.0), 50 (39%) patients are still alive. Overall survival was significantly reduced in those patients who received neoadjuvant chemotherapy and who exhibited discordance (EMT) compared to those who did not: 11 (95% CI: 6.2–15.8) months versus 19 (95% CI: 14.2–23.8) months (P-value &lt; 0.001). In addition, there was no difference in overall survival between those who received neoadjuvant chemotherapy and those who had upfront surgery: 16 (95% CI: 2.5–19.5) months versus 30 (95% CI: 11.6–48.4) months (P-value: 0.203).

CONCLUSIONS
The association of neoadjuvant chemotherapy with perioperative histological discordance can be explained by EMT, which leads to worse survival. Therefore, there is an argument for the preferential use of upfront surgery in the treatment of otherwise resectable MPM.
The Stability of Relativistic Fluids in Linearly Expanding Cosmologies
Authors: Fajman David , Ofner Maximilian , Oliynyk Todd A , Wyatt Zoe 
Published: October 2023

Abstract
In this paper, we study cosmological solutions to the Einstein–Euler equations. We first establish the future stability of nonlinear perturbations of a class of homogeneous solutions to the relativistic Euler equations on fixed linearly expanding cosmological spacetimes with a linear equation of state $p=K \rho $ for the parameter values $K \in (0,1/3)$. This removes the restriction to irrotational perturbations in earlier work [ 15] and relies on a novel transformation of the fluid variables that is well-adapted to Fuchsian methods. We then apply this new transformation to show the global regularity and stability of the Milne spacetime under the coupled Einstein–Euler equations, again with a linear equation of state $p=K \rho $, $K \in (0,1/3)$. Our proof requires a correction mechanism to account for the spatially curved geometry. In total, this is indicative that structure formation in cosmological fluid-filled spacetimes requires an epoch of decelerated expansion.
Pivotal trial of a deep-learning-based retinal biomarker (Reti-CVD) in the prediction of cardiovascular disease: data from CMERC-HI
Authors: Lee Chan Joo , Rim Tyler Hyungtaek , Kang Hyun Goo , Yi Joseph Keunhong , Lee Geunyoung , Yu Marco , Park Soo-Hyun , Hwang Jin-Taek , Tham Yih-Chung , Wong Tien Yin , Cheng Ching-Yu , Kim Dong Wook , Kim Sung Soo , Park Sungha 
Published: October 2023

Abstract

Objective
The potential of using retinal images as a biomarker of cardiovascular disease (CVD) risk has gained significant attention, but regulatory approval of such artificial intelligence (AI) algorithms is lacking. In this regulated pivotal trial, we validated the efficacy of Reti-CVD, an AI-Software as a Medical Device (AI-SaMD), that utilizes retinal images to stratify CVD risk.

Materials and Methods
In this retrospective study, we used data from the Cardiovascular and Metabolic Diseases Etiology Research Center-High Risk (CMERC-HI) Cohort. Cox proportional hazard model was used to estimate hazard ratio (HR) trend across the 3-tier CVD risk groups (low-, moderate-, and high-risk) according to Reti-CVD in prediction of CVD events. The cardiac computed tomography-measured coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and brachial-ankle pulse wave velocity (baPWV) were compared to Reti-CVD.

Results
A total of 1106 participants were included, with 33 (3.0%) participants experiencing CVD events over 5 years; the Reti-CVD-defined risk groups (low, moderate, and high) were significantly associated with increased CVD risk (HR trend, 2.02; 95% CI, 1.26-3.24). When all variables of Reti-CVD, CAC, CIMT, baPWV, and other traditional risk factors were incorporated into one Cox model, the Reti-CVD risk groups were only significantly associated with increased CVD risk (HR = 2.40 [0.82-7.03] in moderate risk and HR = 3.56 [1.34-9.51] in high risk using low-risk as a reference).

Discussion
This regulated pivotal study validated an AI-SaMD, retinal image-based, personalized CVD risk scoring system (Reti-CVD).

Conclusion
These results led the Korean regulatory body to authorize Reti-CVD.
Design of an interface to communicate artificial intelligence-based prognosis for patients with advanced solid tumors: a user-centered approach
Authors: Staes Catherine J , Beck Anna C , Chalkidis George , Scheese Carolyn H , Taft Teresa , Guo Jia-Wen , Newman Michael G , Kawamoto Kensaku , Sloss Elizabeth A , McPherson Jordan P 
Published: October 2023

Abstract

Objectives
To design an interface to support communication of machine learning (ML)-based prognosis for patients with advanced solid tumors, incorporating oncologists’ needs and feedback throughout design.

Materials and Methods
Using an interdisciplinary user-centered design approach, we performed 5 rounds of iterative design to refine an interface, involving expert review based on usability heuristics, input from a color-blind adult, and 13 individual semi-structured interviews with oncologists. Individual interviews included patient vignettes and a series of interfaces populated with representative patient data and predicted survival for each treatment decision point when a new line of therapy (LoT) was being considered. Ongoing feedback informed design decisions, and directed qualitative content analysis of interview transcripts was used to evaluate usability and identify enhancement requirements.

Results
Design processes resulted in an interface with 7 sections, each addressing user-focused questions, supporting oncologists to “tell a story” as they discuss prognosis during a clinical encounter. The iteratively enhanced interface both triggered and reflected design decisions relevant when attempting to communicate ML-based prognosis, and exposed misassumptions. Clinicians requested enhancements that emphasized interpretability over explainability. Qualitative findings confirmed that previously identified issues were resolved and clarified necessary enhancements (eg, use months not days) and concerns about usability and trust (eg, address LoT received elsewhere). Appropriate use should be in the context of a conversation with an oncologist.

Conclusion
User-centered design, ongoing clinical input, and a visualization to communicate ML-related outcomes are important elements for designing any decision support tool enabled by artificial intelligence, particularly when communicating prognosis risk.
Prediction of Surgical Upstaging Risk of Ductal Carcinoma In Situ Using Machine Learning Models
Authors: Hashiba Kimberlee A , Mercaldo Sarah , Venkatesh Sheila L , Bahl Manisha 
Published: October 2023

Abstract

Objective
The purpose of this study was to build machine learning models to predict surgical upstaging risk of ductal carcinoma in situ (DCIS) to invasive cancer and to compare model performance to eligibility criteria used by the Comparison of Operative versus Monitoring and Endocrine Therapy (COMET) active surveillance trial.

Methods
Medical records were retrospectively reviewed of all women with DCIS at core-needle biopsy who underwent surgery from 2007 to 2016 at an academic medical center. Multivariable regression and machine learning models were developed to evaluate upstaging-related features and their performance was compared with that achieved using the COMET trial eligibility criteria.

Results
Of 1387 women (mean age, 57 years; range, 27–89 years), the upstaging rate of DCIS was 17% (235/1387). On multivariable analysis, upstaging-associated features were presentation of DCIS as a palpable area of concern, imaging finding of a mass, and nuclear grades 2 or 3 at biopsy (P &lt; 0.05). If COMET trial eligibility criteria were applied to our study cohort, then 496 women (42%, 496/1175) would have been eligible for the trial, with an upstaging rate of 12% (61/496). Of the machine learning models, none had a significantly lower upstaging rate than 12%. However, if using the models to determine eligibility, then a significantly larger proportion of women (56%–87%) would have been eligible for active surveillance.

Conclusion
Use of machine learning models to determine eligibility for the COMET trial identified a larger proportion of women eligible for surveillance compared with current eligibility criteria while maintaining similar upstaging rates.
Reduction of genetic diversity in ‘Alalā (Hawaiian crow; Corvus hawaiiensis) between the late 1800s and the late 1900s
Authors: Blanchet Geneviève , Bellinger M Renee , Kearns Anna M , Cortes-Rodriguez Nandadevi , Masuda Bryce , Campana Michael G , Rutz Christian , Fleischer Robert C , Sutton Jolene T 
Published: October 2023

Abstract
Genetic and genomic data are increasingly used to aid conservation management of endangered species by providing insights into evolutionary histories, factors associated with extinction risks, and potential for future adaptation. For the ‘Alalā, or Hawaiian crow (Corvus hawaiiensis), genetic concerns include negative correlations between inbreeding and hatching success. However, it is unclear if low genetic diversity and inbreeding depression are consequences of a historical population bottleneck, or if ‘Alalā had historically low genetic diversity that predated human influence, perhaps as a result of earlier declines or founding events. In this study, we applied a hybridization-based sequence capture to generate a genome-wide single nucleotide polymorphism (SNP) dataset for comparing historical specimens collected in the 1890s, when ‘Alalā were more numerous, to samples taken between 1973 and 1998, when ‘Alalā population densities were near the lowest documented levels in the wild, prior to all individuals being collected for captive rearing. We found low genome-wide diversity in both sample groups, however, the modern sample group (1973 to 1998 cohort) exhibited relatively fewer polymorphic alleles, a lower proportion of polymorphic loci, and lower observed heterozygosity, consistent with a population decline and potential bottleneck effects. These results combined with a current low population size highlight the importance of continued efforts by conservation managers to mitigate inbreeding and maintain founder representation to preserve what genetic diversity remains.
Loss of feedback regulation between FAM3B and androgen receptor driving prostate cancer progression
Authors: Ma Tianfang , Jin Lianjin , Bai Shanshan , Liu Zhan , Wang Shuo , Shen Beibei , Cho Yeyoung , Cao Subing , Sun Meijuan J S , Fazli Ladan , Zhang David , Wedderburn Chiyaro , Zhang Derek Y , Mugon Gavisha , Ungerleider Nathan , Baddoo Melody , Zhang Kun , Schiavone Lovisa Holmberg , Burkhardt Brant R , Fan Jia , You Zongbing , Flemington Erik K , Dong Xuesen , Dong Yan 
Published: October 2023

Abstract

Background
Although the fusion of the transmembrane serine protease 2 gene (TMPRSS2) with the erythroblast transformation-specific-related gene (ERG), or TMPRSS2-ERG, occurs frequently in prostate cancer, its impact on clinical outcomes remains controversial. Roughly half of TMPRSS2-ERG fusions occur through intrachromosomal deletion of interstitial genes and the remainder via insertional chromosomal rearrangements. Because prostate cancers with deletion-derived TMPRSS2-ERG fusions are more aggressive than those with insertional fusions, we investigated the impact of interstitial gene loss on prostate cancer progression.

Methods
We conducted an unbiased analysis of transcriptome data from large collections of prostate cancer samples and employed diverse in vitro and in vivo models combined with genetic approaches to characterize the interstitial gene loss that imposes the most important impact on clinical outcome.

Results
This analysis identified FAM3B as the top-ranked interstitial gene whose loss is associated with a poor prognosis. The association between FAM3B loss and poor clinical outcome extended to fusion-negative prostate cancers where FAM3B downregulation occurred through epigenetic imprinting. Importantly, FAM3B loss drives disease progression in prostate cancer. FAM3B acts as an intermediator of a self-governing androgen receptor feedback loop. Specifically, androgen receptor upregulates FAM3B expression by binding to an intronic enhancer to induce an enhancer RNA and facilitate enhancer-promoter looping. FAM3B, in turn, attenuates androgen receptor signaling.

Conclusion
Loss of FAM3B in prostate cancer, whether through the TMPRSS2-ERG translocation or epigenetic imprinting, causes an exit from this autoregulatory loop to unleash androgen receptor activity and prostate cancer progression. These findings establish FAM3B loss as a new driver of prostate cancer progression and support the utility of FAM3B loss as a biomarker to better define aggressive prostate cancer.
Astaxanthin protects against pirarubicin-induced H9c2 cardiomyocytes by adjusting microRNA-494-3p-mediated MDM4/p53 signalling pathway
Authors: Huang Peng , Zhang Yibing , Wang Fengjun , Qin Meng , Ma Jiulong , Ji Jiahua , Wei Dexian , Ren Liqun 
Published: October 2023

Abstract

Purpose
Pirarubicin (THP) is an antitumour drug widely used in clinical practice, but its cardiotoxicity limits its application. THP cardiotoxicity must be treated as soon as possible. There is an urgent need to find drugs that alleviate THP cardiotoxicity. The purpose of this study was to investigate the effects and mechanisms of Astaxanthin (AST) on THP-induced cardiomyocytes.

Methods
Rat cardiomyocytes H9c2 were induced with THP. The effects of AST on THP-induced H9c2 and its mechanism were investigated by CCK8, reactive oxygen species assay, tunnel assay, flow cytometry, RT-qPCR, and Western blot.

Results
AST increased cell viability, inhibited apoptosis and accelerated cell cycle progression, reduced oxidative damage and inflammatory response in THP-induced H9c2; down-regulated miR-494-3p expression, promoted MDM4 expression, inhibited p53 activation, and suppressed apoptosis-related protein expression. Overexpression of MiR-494-3p reversed the above effects of AST.

Conclusions
AST can inhibit H9c2 apoptosis induced by THP and attenuate H9c2 damage by THP, which may be achieved by downregulating miR-494-3p, upregulating MDM4, and inhibiting p53.
Current status of remote radiotherapy treatment planning in Japan: findings from a national survey
Authors: Saito Masahide , Tamamoto Tetsuro , Kawashiro Shohei , Umezawa Rei , Matsuda Masaki , Tohyama Naoki , Katsuta Yoshiyuki , Kanai Takayuki , Nemoto Hikaru , Onishi Hiroshi 
Published: October 2023

Abstract
The purpose of this study was to investigate the status of remote-radiotherapy treatment planning (RRTP) in Japan through a nationwide questionnaire survey. The survey was conducted between 29 June and 4 August 2022, at 834 facilities in Japan that were equipped with linear accelerators. The survey utilized a Google form that comprised 96 questions on facility information, information about the respondent, utilization of RRTP between facilities, usage for telework and the inclination to implement RRTPs in the respondent’s facility. The survey analyzed the utilization of the RRTP system in four distinct implementation types: (i) utilization as a supportive facility, (ii) utilization as a treatment facility, (iii) utilization as a teleworker outside of the facility and (iv) utilization as a teleworker within the facility. The survey response rate was 58.4% (487 facilities responded). Among the facilities that responded, 10% (51 facilities) were implementing RRTP. 13 served as supportive facilities, 23 as treatment facilities, 17 as teleworkers outside of the facility and 5 as teleworkers within the facility. In terms of system usage between supportive and treatment facilities, 70–80% of the participants utilized the system for emergencies or as overtime work for external workers. A substantial number of facilities (38.8%) reported that they were unfamiliar with RRTP implementation. The survey showed that RRTP utilization in Japan is still limited, with a significant number of facilities unfamiliar with the technology. The study highlights the need for greater understanding and education about RRTP and financial funds of economical compensation.
Galaxy And Mass Assembly: the xSAGA galaxy complement in nearby galaxy groups
Authors: Holwerda B W , Phillipps S , Weerasooriya S , Bovill M S , Brough S , Brown M J I , Robertson C , Cook K 
Published: October 2023

ABSTRACT
Groups of galaxies are the intermediate density environment in which much of the evolution of galaxies is thought to take place. In spectroscopic redshift surveys, one can identify these as close spatial-redshift associations. However, spectroscopic surveys will always be more limited in luminosity and completeness than imaging ones. Here, we combine the Galaxy And Mass Assembly (GAMA) group catalogue with the extended Satellites Around Galactic Analogues (xSAGA) catalogue of machine learning identified low-redshift satellite galaxies. We find 1825 xSAGA galaxies within the bounds of the GAMA equatorial fields (mr &lt; 21), 1562 of which could have a counterpart in the GAMA spectroscopic catalogue (mr &lt; 19.8). Of these, 1326 do have a GAMA counterpart with 974 below z = 0.03 (true positives) and 352 above z = 0.03 (false positives). By cross-correlating the GAMA group catalogue with the xSAGA catalogue, we can extend and characterize the satellite content of GAMA galaxy groups. We find that most groups have &lt;5 xSAGA galaxies associated with them, but richer groups may have more. Each additional xSAGA galaxy contributes only a small fraction of the group’s total stellar mass (${\ll}10$ per cent). Selecting GAMA groups that resemble the Milky Way halo, with a few (&lt;4) bright galaxies, we find that xSAGA can add a magnitude fainter sources to a group and that the Local Group does not stand out in the number of bright satellites. We explore the quiescent fraction of xSAGA galaxies in GAMA groups and find a good agreement with the literature.
Disingenuous Infallibilism
Authors: Fantl Jeremy 
Published: October 2023

Abstract
Some recent epistemologists propose that certainty is the norm of action and assertion. This proposal is subject to skeptical worries. If, as is usually supposed, certainty is very hard to come by, legitimate action and assertion will be rare. To remedy this, some have conjoined their certainty-norms with a context-sensitive semantics for ‘certainty’. For a proposition to be certain for you, you only need to be able to exclude relevant alternatives. I argue that, depending on what makes an alternative relevant, this kind of view is disingenuous. In particular, if an alternative can be made relevant by being relevant to rational action, it allows an escape from the skeptical consequences only by licensing David Lewis-style utterances of the form, “You know that p only if there is no probability, no matter how small, that not-p—Psst!—Unless that probability is really small.” While there are legitimate ways to exclude some possibilities from relevance, it is disingenuous, I argue, to exclude possibilities from relevance on the basis of the very characteristic—low but nonzero probability—that is claimed to be incompatible with certainty.
Ectopic Expression of Distinct PLC Genes Identifies ‘Compactness’ as a Possible Architectural Shoot Strategy to Cope with Drought Stress
Authors: van Hooren Max , van Wijk Ringo , Vaseva Irina I , Van Der Straeten Dominique , Haring Michel , Munnik Teun 
Published: October 2023

Abstract
Phospholipase C (PLC) has been implicated in several stress responses, including drought. Overexpression (OE) of PLC has been shown to improve drought tolerance in various plant species. Arabidopsis contains nine PLC genes, which are subdivided into four clades. Earlier, OE of PLC3, PLC5 or PLC7 was found to increase Arabidopsis’ drought tolerance. Here, we confirm this for three other PLCs: PLC2, the only constitutively expressed AtPLC; PLC4, reported to have reduced salt tolerance and PLC9, of which the encoded enzyme was presumed to be catalytically inactive. To compare each PLC and to discover any other potential phenotype, two independent OE lines of six AtPLC genes, representing all four clades, were simultaneously monitored with the GROWSCREEN-FLUORO phenotyping platform, under both control- and mild-drought conditions. To investigate which tissues were most relevant to achieving drought survival, we additionally expressed AtPLC5 using 13 different cell- or tissue-specific promoters. While no significant differences in plant size, biomass or photosynthesis were found between PLC lines and wild-type (WT) plants, all PLC-OE lines, as well as those tissue-specific lines that promoted drought survival, exhibited a stronger decrease in ‘convex hull perimeter’ (= increase in ‘compactness’) under water deprivation compared to WT. Increased compactness has not been associated with drought or decreased water loss before although a hyponastic decrease in compactness in response to increased temperatures has been associated with water loss. We propose that the increased compactness could lead to decreased water loss and potentially provide a new breeding trait to select for drought tolerance.