bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of ACCELERATE Paediatric Strategy Forums: a review of the value of multi-stakeholder meetings in oncology drug development
Authors: Pearson Andrew D J , de Rojas Teresa , Karres Dominik , Reaman Gregory , Scobie Nicole , Fox Elizabeth , Lesa Giovanni , Ligas Franca , Norga Koen , Nysom Karsten , Pappo Alberto , Weigel Brenda , Weiner Susan L , Vassal Gilles 
Published: November 2023

Abstract
In a landscape of an increasing number of products and histology and age agnostic trials for rare patient cancer, prioritization of products is required. Paediatric Strategy Forums, organized by ACCELERATE and the European Medicines Agency with participation of the US Food and Drug Administration, are multi-stakeholder meetings that share information to best inform pediatric drug development strategies and subsequent clinical trial decisions. Academia, industry, regulators, and patient advocates are equal members, with patient advocates highlighting unmet needs of children and adolescents with cancer. The 11 Paediatric Strategy Forums since 2017 have made specific and general conclusions to accelerate drug development. Conclusions on product prioritization meetings, as well as global master protocols, have been outputs of these meetings. Forums have provided information for regulatory discussions and decisions by industry to facilitate development of high-priority products; for example, 62% of high-priority assets (agreed at a Forum) in contrast to 5% of those assets not considered high priority have been the subject of a Paediatric Investigational Plan or Written Request. Where there are multiple products of the same class, Forums have recommended a focused and sequential approach. Class prioritization resulted in an increase in waivers for non-prioritized B-cell products (44% to 75%) and a decrease in monotherapy trials, proposed in Paediatric Investigation Plans (PIP) submissions of checkpoint inhibitors from 53% to 19%. Strategy Forums could play a role in defining unmet medical needs. Multi-stakeholder forums, such as the Paediatric Strategy Forum, serve as a model to improve collaboration in the oncology drug development paradigm.
Opioid tapering in older cancer survivors does not increase psychiatric or drug hospitalization rates
Authors: Riviere Paul , Morgan Kylie M , Deshler Leah N , Huang Xinyi , Marienfeld Carla , Coyne Christopher J , Rose Brent S , Murphy James D 
Published: November 2023

Abstract

Background
Opioid tapering in the general population is linked to increases in hospitalizations or emergency department visits related to psychiatric or drug-related diagnoses. Cancer survivors represent a unique population with different opioid indications, prescription patterns, and more frequent follow-up care. This study sought to describe patterns of opioid tapering among older cancer survivors and to test the hypothesis of whether older cancer survivors face increased risks of adverse events with opioid tapering.

Methods
Using the Surveillance, Epidemiology and End Results Medicare–linked database, we identified 15 002 Medicare-beneficiary cancer survivors diagnosed between 2010 and 2017 prescribed opioids consistently for at least 6 months after their cancer diagnosis. Tapering was defined as a binary time-varying event occurring with any monthly oral morphine equivalent reduction of 15% or more from the previous month. Primary diagnostic billing codes associated with emergency room or hospital admissions were used for the composite endpoint of psychiatric- or drug-related event(s).

Results
There were 3.86 events per 100 patient-months, with 97.8% events being mental health emergencies, 1.91% events being overdose emergencies, and 0.25% involving both. Using a generalized estimating equation for repeated measure time-based analysis, opioid tapering was not statistically associated with acute events in the 3-month posttaper period (odds ratio [OR] = 1.02; P = .62) or at any point in the future (OR = 0.96; P = .46).

Conclusions
Opioid tapering in older cancer survivors does not appear to be linked to a higher risk of acute psychiatric- or drug-related events, in contrast to prior research in the general population.
Comprehensive causes of death in uveal melanoma: mortality in 1530 consecutively diagnosed patients followed until death
Authors: Stålhammar Gustav 
Published: November 2023

Abstract

Background
Uveal melanoma has a high propensity for metastatic spread. Yet, the comprehensive causes of death in a large consecutive cohort followed from diagnosis to death remain unknown.

Methods
All Swedish patients diagnosed with melanoma involving the iris, choroid, and/or ciliary body after January 1, 1960, were assessed for this study. Sequential inclusion was halted upon encountering the first surviving patient during data collection. Causes of death were collected from the National Cause of Death Registry and audited by analysis of up to 15 causative diagnoses.

Results
A total of 1530 patients were included, each histopathologically verified with primary uveal melanoma. Mortality from metastatic uveal melanoma was 31% at 5 years, 40% at 10 years, 45% at 20 years, 47% at 30 years, and 48% between 40 and 60 years post-diagnosis. Notably, the longest period between diagnosis and metastatic fatality was 49.6 years. Additionally, 186 other causes of death were recorded, with cardiovascular diseases constituting 26%, other cancers 10%, stroke 6%, dementias 2%, and lower respiratory infections 2% of total mortalities. Mortality from colorectal, lung, prostate, and stomach carcinomas over 60 years were 1.4%, 1.4%, 1.2%, and 0.9%, with metastatic uveal melanoma being the leading cumulative and annual cause of death for the initial 41 and 5 years post-diagnosis, respectively.

Conclusions
In this large consecutive cohort, half of the included patients ultimately succumbed to metastatic uveal melanoma, with deaths occurring up to 50 years after diagnosis. One-quarter and one-tenth of patients died from cardiovascular diseases and other cancers, respectively.
A catalogue of planetary nebulae chemical abundances in the Galactic bulge
Authors: Tan Shuyu , Parker Quentin A , Zijlstra Albert A , Rees Bryan 
Published: November 2023

ABSTRACT
In this paper, the third of a series of papers, we present well-determined chemical abundances for 124 planetary nebulae (PNe) in the Galactic bulge from deep, long-slit FORS2 spectra from the 8.2 m ESO Very Large telescope (VLT). Prior to this work there were only ∼240 bulge PNe with chemical abundances previously determined over a ∼50 yr period and of highly variable quality. For 34 of these PNe we are presenting their abundances for the first time, which adds ∼14 per cent to the available sample of bulge PNe abundances. The interstellar reddening, physical conditions (electron densities, ne, temperatures, Te), and chemical compositions are derived as single values for each PN but also using different line diagnostics. Selected comparisons with the best literature fluxes for 75 PNe in common reveal that these significant new data are robust, reliable, and internally self-consistent forming the largest independent, high-quality, and well-understood derivation of PNe abundances currently available for study.
Evidence for a black hole in the historical X-ray transient A 1524-61 (= KY TrA)
Authors: Yanes-Rizo I V , Torres M A P , Casares J , Monelli M , Jonker P G , Abbot T , Armas Padilla M , Muñoz-Darias T 
Published: November 2023

ABSTRACT
We present Very Large Telescope spectroscopy, high-resolution imaging, and time-resolved photometry of KY TrA, the optical counterpart to the X-ray binary A 1524-61. We perform a refined astrometry of the field, yielding improved coordinates for KY TrA and the field star interloper of similar optical brightness that we locate 0.64 ± 0.04 arcsec SE. From the spectroscopy, we refine the radial velocity semi-amplitude of the donor star to K2 = 501 ± 52 km s−1 by employing the correlation between this parameter and the full width at half-maximum of the H α emission line. The r-band light curve shows an ellipsoidal-like modulation with a likely orbital period of 0.26 ± 0.01 d (6.24 ± 0.24 h). These numbers imply a mass function f(M1) = 3.2 ± 1.0 M⊙. The KY TrA de-reddened quiescent colour (r − i)0 = 0.27 ± 0.08 is consistent with a donor star of spectral type K2 or later, in case of significant accretion disc light contribution to the optical continuum. The colour allows us to place a very conservative upper limit on the companion star mass, M2 ≤ 0.94 M⊙, and, in turn, on the binary mass ratio, q = M2/M1 ≤ 0.31. By exploiting the correlation between the binary inclination and the depth of the H α line trough, we establish i = 57 ± 13 deg. All these values lead to a compact object and donor mass of $M_1 = 5.8^{+3.0}_{-2.4}$$\, M_\odot$ and M2 = 0.5 ± 0.3 M⊙, thus confirming the black hole nature of the accreting object. In addition, we estimate a distance towards the system of 8.0 ± 0.9 kpc.
Shedding light on a species complex within the genus Goniodoridella Pruvot-Fol, 1933 (Nudibranchia: Goniodorididae), with the description of three new species
Authors: Paz-Sedano Sofía , Ekimova Irina , Smirnoff Dimitri , Gosliner Terrence M , Pola Marta 
Published: November 2023

ABSTRACT
Goniodoridella Pruvot-Fol, 1933 is a genus of small nudibranchs found in the Indo-Pacific Ocean. Currently, the genus includes only two described species, the widely distributed type species Goniodoridella savignyi Pruvot-Fol, 1933 and G. borealis Martynov, Sanamyan & Korshunova, 2015, which is found in the northern Sea of Japan. However, because of the presence of a group of cryptic species, the known geographic range of G. savignyi may have been overestimated, while the species richness of the genus may be underestimated. In the current study, we examined specimens from Australia, the Philippines and Russia that were identified as G. savignyi, G. borealis and an undescribed species. Detailed analyses of the external morphology and internal anatomy of the specimens were carried out, as well as scanning electron micrography of the radula and the labial cuticle. Photographs of the penial spines were taken under a light microscope. DNA sequence data for selected mitochondrial and nuclear markers were obtained, allowing the inclusion of the genus Goniodoridella in molecular phylogenetic analyses for the first time. Our results support the monophyly of the genus Goniodoridella and confirm the existence of a species complex of which the type is G. savignyi. The new species G. geminae n. sp., G. serrata n. sp. and G. unidonta n. sp. are described.
Long or short? Telomere length and pancreatic cancer and its precursor lesions, a narrative review
Authors: Campa Daniele , Felici Alessio , Corradi Chiara , Peduzzi Giulia , Gentiluomo Manuel , Farinella Riccardo , Rizzato Cosmeri 
Published: November 2023

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most common and lethal form of pancreatic cancer, with a survival approaching only 11% at 5 years after diagnosis. In the last 15 years, telomere length (TL) measured in leukocyte (LTL) has been studied in relation to PDAC risk. The majority of the studies reported an association between short LTL and increased PDAC risk, but the results are heterogeneous. Genome-wide association studies have identified several single-nucleotide polymorphisms (SNPs) in the telomerase reverse transcriptase (TERT) gene as susceptibility loci for PDAC. Polygenic risk scores computed using SNPs associated with LTL have been tested in relation to PDAC susceptibility with various methods and giving contrasting results. The aim of this review is to analyze all publications carried out specifically on LTL, considering LTL measured with qPCR and with genetic proxies, and PDAC risk. Additionally, we will give an overview of the most relevant associations between SNPs in telomere-associated genes and PDAC, to answer the question shorter or longer? Which one of the two is associated with PDAC risk?
RegulonDB v12.0: a comprehensive resource of transcriptional regulation inE. coliK-12
Authors: Salgado Heladia , Gama-Castro Socorro , Lara Paloma , Mejia-Almonte Citlalli , Alarcón-Carranza Gabriel , López-Almazo Andrés G , Betancourt-Figueroa Felipe , Peña-Loredo Pablo , Alquicira-Hernández Shirley , Ledezma-Tejeida Daniela , Arizmendi-Zagal Lizeth , Mendez-Hernandez Francisco , Diaz-Gomez Ana K , Ochoa-Praxedis Elizabeth , Muñiz-Rascado Luis J , García-Sotelo Jair S , Flores-Gallegos Fanny A , Gómez Laura , Bonavides-Martínez César , del Moral-Chávez Víctor M , Hernández-Alvarez Alfredo J , Santos-Zavaleta Alberto , Capella-Gutierrez Salvador , Gelpi Josep Lluis , Collado-Vides Julio 
Published: November 2023

AbstractRegulonDB is a database that contains the most comprehensive corpus of knowledge of the regulation of transcription initiation of Escherichia coli K-12, including data from both classical molecular biology and high-throughput methodologies. Here, we describe biological advances since our last NAR paper of 2019. We explain the changes to satisfy FAIR requirements. We also present a full reconstruction of the RegulonDB computational infrastructure, which has significantly improved data storage, retrieval and accessibility and thus supports a more intuitive and user-friendly experience. The integration of graphical tools provides clear visual representations of genetic regulation data, facilitating data interpretation and knowledge integration. RegulonDB version 12.0 can be accessed at https://regulondb.ccg.unam.mx.
Endothelial to mesenchymal transition in kidney fibrosis
Authors: Jacobs Marleen E , de Vries Dorottya K , Engelse Marten A , Dumas Sébastien J , Rabelink Ton J 
Published: November 2023

ABSTRACT
Fibrotic diseases are characterized by the uncontrolled accumulation of extracellular matrix (ECM) components leading to disruption of tissue homeostasis. Myofibroblasts as the main ECM-producing cells can originate from various differentiated cell types after injury. Particularly, the process of endothelial-to-mesenchymal transition (endMT), describing phenotypic shifts of endothelial cells to adopt a fully mesenchymal identity, may contribute to the pool of myofibroblasts in fibrosis, while leading to capillary rarefaction and exacerbation of tissue hypoxia. In renal disease, incomplete recovery from acute kidney injury (AKI) and the ensuing fibrotic reaction stand out as major contributors to chronic kidney disease (CKD) development. While the focus has largely been on impaired tubular epithelial repair as a potential fibrosis-driving mechanism, alterations in the renal microcirculation post-AKI, and in particular endMT as a maladaptive response, could hold equal significance. Dysfunctional interplays among various cell types in the kidney microenvironment can instigate endMT. Transforming growth factor beta (TGF-β) signaling, with its downstream activation of canonical/Smad-mediated and non-canonical pathways, has been identified as primary driver of this process. However, non-TGF-β-mediated pathways involving inflammatory agents and metabolic shifts in intercellular communication within the tissue microenvironment can also trigger endMT. These harmful, maladaptive cell–cell interactions and signaling pathways offer potential targets for therapeutic intervention to impede endMT and decelerate fibrogenesis such as in AKI–CKD progression. Presently, partial reduction of TGF-β signaling using anti-diabetic drugs or statins may hold therapeutic potential in renal context. Nevertheless, further investigation is warranted to validate underlying mechanisms and assess positive effects within a clinical framework.
Development of a Prognostic Model for Early Breast Cancer Integrating Neutrophil to Lymphocyte Ratio and Clinical-Pathological Characteristics
Authors: Faria Sara Socorro , Giannarelli Diana , Cordeiro de Lima Vladmir Claudio , Anwar Sumadi Luckman , Casadei Chiara , De Giorgi Ugo , Madonna Gabriele , Ascierto Paolo Antonio , Mendoza López Rossana Veronica , Chammas Roger , Capone Mariaelena 
Published: November 2023

Abstract

Background
Breast cancer-related inflammation is critical in tumorigenesis, cancer progression, and patient prognosis. Several inflammatory markers derived from peripheral blood cells count, such as the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII) are considered as prognostic markers in several types of malignancy.

Methods
We investigate and validate a prognostic model in early patients with breast cancer to predict disease-free survival (DFS) based on readily available baseline clinicopathological prognostic factors and preoperative peripheral blood-derived indexes.

Results
We analyzed a training cohort of 710 patients and 2 external validation cohorts of 980 and 157 patients with breast cancer, respectively, with different demographic origins. An elevated preoperative NLR is a better DFS predictor than others scores. The prognostic model generated in this study was able to classify patients into 3 groups with different risks of relapse based on ECOG-PS, presence of comorbidities, T and N stage, PgR status, and NLR.

Conclusion
Prognostic models derived from the combination of clinicopathological features and peripheral blood indices, such as NLR, represent attractive markers mainly because they are easily detectable and applicable in daily clinical practice. More comprehensive prospective studies are needed to unveil their actual effectiveness.
Risk of attention deficit hyperactivity disorder diagnosis following multiple exposures to general anesthesia in the paediatric population: A systematic review and meta-analysis
Authors: Skakum Megan , Katako Audrey , Mitchell-Dueck Jenna , Ricci M Florencia , Russell Kelly 
Published: November 2023

Abstract

Objectives
The risk of attention deficit hyperactivity disorder (ADHD) following multiple exposures to anesthesia has been debated. Our objective was to systematically review the literature to examine the association between multiple exposures to general anesthesia before age 5 and subsequent diagnosis of ADHD.

Methods
A systematic search of EMBASE, PubMed, and SCOPUS was performed using key search terms in February 2022. We included studies that: were published after 1980, included only otherwise healthy children who experienced two or more exposures to general anesthetic before age 5, diagnosed ADHD by a medical professional before age 19 years after exposure to general anesthetic, were cross-sectional, case–control, or cohort study, and were published in English. The results (expressed as hazard ratios [HR] and associated 95% confidence intervals [CI]) were pooled using meta-analytic techniques. Studies which did not present their results as HR and 95% CI were analyzed separately. GRADE was used to determine the certainty of the findings. PRISMA guidelines were followed at each stage of the review.

Results
Eight studies (196,749 children) were included. Five reported HR and 95% CI and were subsequently pooled for meta-analysis. Multiple exposures to anesthesia were associated with diagnosis of ADHD before the 19th year of life (HR: 1.71; 95% CI: 1.59, 1.84). Two of the three studies not used in the meta-analysis also found an increased risk of ADHD diagnosis following multiple anesthetic exposures.

Conclusions
There was an association between multiple early exposures to general anesthesia and later diagnosis of ADHD.
Variety of Plant Oils: Species-Specific Lipid Biosynthesis
Authors: Clews Alyssa C , Ulch Brandon A , Jesionowska Monika , Hong Jun , Mullen Robert T , Xu Yang 
Published: November 2023

Abstract
Plant oils represent a large group of neutral lipids with important applications in food, feed and oleochemical industries. Most plants accumulate oils in the form of triacylglycerol within seeds and their surrounding tissues, which comprises three fatty acids attached to a glycerol backbone. Different plant species accumulate unique fatty acids in their oils, serving a range of applications in pharmaceuticals and oleochemicals. To enable the production of these distinctive oils, select plant species have adapted specialized oil metabolism pathways, involving differential gene co-expression networks and structurally divergent enzymes/proteins. Here, we summarize some of the recent advances in our understanding of oil biosynthesis in plants. We compare expression patterns of oil metabolism genes from representative species, including Arabidopsis thaliana, Ricinus communis (castor bean), Linum usitatissimum L. (flax) and Elaeis guineensis (oil palm) to showcase the co-expression networks of relevant genes for acyl metabolism. We also review several divergent enzymes/proteins associated with key catalytic steps of unique oil accumulation, including fatty acid desaturases, diacylglycerol acyltransferases and oleosins, highlighting their structural features and preference toward unique lipid substrates. Lastly, we briefly discuss protein interactomes and substrate channeling for oil biosynthesis and the complex regulation of these processes.
A proxitome-RNA-capture approach reveals that processing bodies repress coregulated hub genes
Authors: Liu Chen , Mentzelopoulou Andriani , Hatzianestis Ioannis H , Tzagkarakis Epameinondas , Skaltsogiannis Vasileios , Ma Xuemin , Michalopoulou Vassiliki A , Romero-Campero Francisco J , Romero-Losada Ana B , Sarris Panagiotis F , Marhavy Peter , Bölter Bettina , Kanterakis Alexandros , Gutierrez-Beltran Emilio , Moschou Panagiotis N 
Published: November 2023

Abstract
Cellular condensates are usually ribonucleoprotein assemblies with liquid- or solid-like properties. Because these subcellular structures lack a delineating membrane, determining their compositions is difficult. Here we describe a proximity-biotinylation approach for capturing the RNAs of the condensates known as processing bodies (PBs) in Arabidopsis (Arabidopsis thaliana). By combining this approach with RNA detection, in silico, and high-resolution imaging approaches, we studied PBs under normal conditions and heat stress. PBs showed a much more dynamic RNA composition than the total transcriptome. RNAs involved in cell wall development and regeneration, plant hormonal signaling, secondary metabolism/defense, and RNA metabolism were enriched in PBs. RNA-binding proteins and the liquidity of PBs modulated RNA recruitment, while RNAs were frequently recruited together with their encoded proteins. In PBs, RNAs follow distinct fates: in small liquid-like PBs, RNAs get degraded while in more solid-like larger ones, they are stored. PB properties can be regulated by the actin-polymerizing SCAR (suppressor of the cyclic AMP)-WAVE (WASP family verprolin homologous) complex. SCAR/WAVE modulates the shuttling of RNAs between PBs and the translational machinery, thereby adjusting ethylene signaling. In summary, we provide an approach to identify RNAs in condensates that allowed us to reveal a mechanism for regulating RNA fate.