bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P6-12-03: Proinflammatory and estrogen signaling modulates the chemoresistance and metastasis of breast cancer cells through post-translational modifications of pioneering factor FOXA1
Authors: Li Shen , Franco Hector L. , Kim Hyunsoo , Plagens Rosemary N. , Mendez-Giraldez Raul , Tubbs Colby , Malladi Venkat , Garay Joseph 
Published: March 2023

Abstract
ER-positive breast cancers compose most breast cancers at the time of diagnosis and are primarily driven by mitogenic estrogen signaling. In ER-positive breast cancers, the pioneer transcription factor FOXA1 plays a critical role in the estrogen receptor (ER) function. It binds to condensed chromatin and promotes chromatin accessibility for subsequent ER binding upon estrogen stimulation. We have reported that TNFa-stimulated proinflammatory signaling relocates FOXA1 to a new set of latent enhancers, which initiates the binding of estrogen liganded ER and subsequent expression of a unique transcriptome with clinical significance. The redistribution of FOXA1 occurs within 40 mins of the TNFa treatment, which implies a rapid signaling cascade that arises from changes to either FOXA1’s post-translational modifications (PTMs) or its binding partners. To understand this genomic redistribution of FOXA1, we compared the post-translational modifications (PTMs) of FOXA1 from Vehicle, E2, TNFa, and E2+TNFa treated MCF-7 breast cancer cells. More than five acetylation and phosphorylation events have been identified around the DNA binding domain of FOXA1 by semi-quantitative and quantitative mass spectrometry approaches, and their abundance varies across treatments. To study these PTMs of FOXA1, we used CRISPR/Cas9 to create specific knock-in mutations to mimic or prevent acetylation events in MCF-7 cells. Specifically, we engineered MCF-7 cell lines where K270 was mutated to glutamine (K270Q) to mimic acetylation. And for comparison, we also created cell lines where K270 was mutated to arginine (K270R) to prevent acetylation of FOXA1. Our data, including FOXA1 ChIP-seq and RNA-seq, revealed the genomic redistribution of FOXA1 with these PTMs, which subsequently alters gene expression programs and promotes cell growth, migration, or chemoresistance. These results were confirmed in other ER+ cell lines (such as T47D cells) providing evidence for the generalizability of our findings. Taken together, our data suggest that inflammatory signaling signaling can reshape the enhancer landscape of FOXA1 through post-translational modifications, resulting in changes to estrogen signaling that have profound effects on breast cancer biology.
Citation Format: Shen Li, Hector L. Franco, Hyunsoo Kim, Rosemary N. Plagens, Raul Mendez-Giraldez, Colby Tubbs, Venkat Malladi, Joseph Garay. Proinflammatory and estrogen signaling modulates the chemoresistance and metastasis of breast cancer cells through post-translational modifications of pioneering factor FOXA1 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-12-03.
Abstract PD14-02: PD14-02 Ten-year follow-up of an image-based AI risk model for breast cancer
Authors: Eriksson Mikael , Czene Kamila , Conant Emily F. , Hall Per 
Published: March 2023

Abstract
Background: Artificial intelligence based, image-derived short-term risk models for breast cancer have shown high discriminatory performance compared to traditional lifestyle familial-based risk models. However, the long-term performance has not yet been investigated. Methds: In this study, we investigated the long-term performance for predicting breast cancer throughout 10 years using an image-based risk model and compared the results to a traditional lifestyle familial-based risk model. We performed a nested case-control study based on a mammography screening cohort conducted since 2010 in Sweden for women aged 40-74. Mammograms, age, lifestyle and familial risk factors were collected at study entry. In the breast cancer register update in 2022; 2,028 incident breast cancers were included together with 8,398 controls that were matched to the cases on year of prior baseline mammogram. The image-based model extracted mammographic features (density, microcalcifications, masses, left-right breast asymmetries of these features) and age from the baseline mammograms. Tyrer-Cuzick risk model used self-reported lifestyle and familial risk factors to estimate risk at study-entry. Absolute risks were estimated using the risk models. We estimated model performances using Area Under the receiver operating characteristic Curves (AUC) statistics of the absolute risks and, risk ratios of women classified as high-risk and low risk using NICE and USPSTF guidelines. Results: The AUCs of the image-derived risk model ranged from 0.76 (95%CI 0.72-0.81) to 0.66 (95%CI 0.65-0.67) for breast cancers developed 1-10 years after study-entry. The corresponding Tyrer-Cuzick AUCs were 0.68 (95%CI 0.63-0.73) to 0.62 (95%CI 0.60-0.63). For estrogen negative and symptomatic cancers, the AUCs for the image-derived model were ≥0.75 during the first 2 years. Women with high and low mammographic density showed similar AUCs. Throughout the 10-years of follow-up, 20% of all women with cancers were deemed high risk at study-entry by the image-derived risk model compared to 6% of all women with cancers identified as high risk by the lifestyle familial-based model (p&lt; 0.01). Conclusion: The image-derived model outperformed the lifestyle familial-based model both for short-term and long-term risk assessment and, could be used for identifying women who possibly could benefit from additional examinations and primary prevention.
Citation Format: Mikael Eriksson, Kamila Czene, Emily F. Conant, Per Hall. PD14-02 Ten-year follow-up of an image-based AI risk model for breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD14-02.
Abstract WS2-4: Clinical implications of tumor heterogeneity single cell genomics
Authors: Kanu Nnennaya 
Published: March 2023

Abstract
An understanding of how and why somatic mutations accumulate is required to shed light on cancer evolution. DNA replication during each cell cycle is an essential and highly regulated process that ensures the correct duplication of the entire genome. The timing of DNA replication has been indirectly linked to mutation acquisition and genome instability. However, the extent and the importance of altered replication timing (ART) from normal to cancer cells, and whether this process directly influences mutation acquisition during cancer evolution, have not been explored. Here we evaluated the impact of ART by analysing data from 1271 whole-genome sequenced lung (100,000 Genomes Project 1) and breast (560 breast cancer genomes from Nik-Zainal et al. 2) tumours, together with replication-timing sequencing data of multiple cancer and normal cell lines. We find that 6%-18% of the genome is subject to ART in cancer cells. Genomic regions subject to a shift from early to late replication in cancer cells exhibit an increased mutation rate in tumours and are associated with distinct mutational signatures compared to unaltered early replicated regions. In particular, we identify APOBEC3-mediated mutation clusters (omikli events) in unaltered early and late-to-early ART regions, associated with the acquisition of driver mutations. We demonstrate that ART is a relatively early event during the evolution of breast cancer and lung adenocarcinomas. Finally, genes replicated early in cancer but late in normal cells exhibit an up-regulated expression in tumour samples. The incorporation of single-cell DNA sequencing further enables accurate identification of proliferation rates. Taken together, replication timing alterations during malignant transformation are prevalent in cancer and significantly impact the genomic and transcriptomic landscape during tumour evolution.
Citation Format: Nnennaya Kanu. Clinical implications of tumor heterogeneity single cell genomics [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr WS2-4.
Can psychedelics enhance group psychotherapy? A discussion on the therapeutic factors
Authors: Ponomarenko Polina , Seragnoli Federico , Calder Abigail , Oehen Peter , Hasler Gregor 
Published: March 2023

Background: Despite the growth of psychedelic research, psychedelic-assisted group psychotherapy (PAGP) has received little attention in comparison to individual psychedelic-assisted psychotherapy models. Methods: In this article, we aim to discuss the therapeutic potential of PAGP, as well as outline existing models and the challenges of this approach. Using Irvin Yalom’s 11 therapeutic factors of group therapy as a basic framework, we analyse current literature from clinical studies and neurobiological research relative to the topic of PAGP. Results: We argue that combining psychedelic substances and group psychotherapy may prove beneficial for increasing group connectedness and interpersonal learning, potentially enhancing prosocial behaviour with direct opportunities to practice newly acquired knowledge about previously maladaptive behavioural patterns. Challenges regarding this approach include a more rigid therapy structure and potential loss of openness from patients, which may be ameliorated by adequate therapeutic training. Conclusion: We hope for this article to support clinical research on PAGP by presenting a therapeutic framework and outlining its mechanisms and challenges.
The Bullying in Anaesthesia Registrars Survey (BARS): Does a validated questionnaire improve our understanding of bullying in Australian and New Zealand anaesthesia trainees?
Authors: Garnett Peter BJ , Douglas Scott G , Riley Richard H , Roberts Lindy J 
Published: March 2023

Previous studies have established that bullying is a pervasive problem in healthcare. However, most investigations of bullying in anaesthesia use self-labelled survey questions in which respondents’ subjective perceptions of bullying are central in defining prevalence. This study applied the validated revised Negative Acts Questionnaire (NAQ-r) for a more objective assessment of bullying prevalence and types of negative behaviours experienced by anaesthesia trainees in Australia and New Zealand. An online questionnaire was distributed by the Australian and New Zealand College of Anaesthetists (ANZCA) Clinical Trials Network to 990 randomly selected ANZCA trainees. Bullying prevalence was assessed using both a self-labelled survey tool and the NAQ-r, which requires respondents to select from a list of negative acts, with validated cut-offs that define bullying. Sources of bullying, impact on recipients and barriers to reporting were also examined. This design allowed comparison of the two methods for evaluating bullying prevalence. Twenty-six percent of trainees surveyed completed both bullying survey instruments. Thirty percent of these respondents self-labelled as having experienced bullying in the previous six months, with 8% reporting bullying at least monthly. With the NAQ-r, most respondents (96%) reported experiencing at least one negative act in the prior six months, with 54% reporting these on a monthly basis. The most frequent behaviours described were humiliation and intimidation. Using NAQ-r cut-offs, 36% of respondents experienced occasional bullying and 10% were victims of severe workplace bullying. The NAQ-r provides a more nuanced and objective insight into bullying faced by ANZCA trainees than do self-labelled surveys. The results of the present study provide a valuable baseline for ongoing assessment.
Cancer Metastases to the Hand: A Systematic Review and Meta-analysis
Authors: Dow Todd , Davis Caitlin , ElAbd Rawan , Lalonde Donald , Williams Jason 
Published: March 2023

Background: Metastatic lesions to the hand or wrist are rare and can mimic inflammatory and benign processes such as gout and infections. This often leads to misdiagnosis, underreporting, and delays in treatment. The purpose of this study was to examine all known cases of metastasis to the hand or wrist available in the literature and to analyze demographic trends, metastasis characteristics, and clinical course, and provide recommendations for management. Methods: An online systematic review of MEDLINE, Embase, PubMed, and the Cochrane Library from inception to January 7, 2022, was completed. Studies outlining the care of a patient with acrometastases of the hand were included. Data extracted included age, sex, site of primary tumor and metastasis, presence of other metastases, time from primary diagnosis to acrometastasis diagnosis, misdiagnosis, treatment, and survival. Results: Between 1889 and present, 871 lesions were described in 676 patients who met the inclusion criteria. There was no predilection for hand dominance or site of previous trauma. The mean age among patients was 59.5 (1.5-91) years, and male sex was more common (64.6%). The most common primary cancer source was the lung (39.2%), followed by the kidney (10.8%). The distal phalanx was the most frequently cited tumor location (33.7%). Mean survival after diagnosis of acrometastasis was 6.3 months (0.25-50) ± 11.5 months. Conclusion: Acrometastasis remains an uncommon presentation of metastatic disease with poor prognosis. Treatment currently focuses on pain management and optimizing functional outcomes. Our review led to the development of 7 treatment recommendations when managing these patients.
Using Space Syntax Analysis to Measure Patient Aggression Risk
Authors: MohammadiGorji Soheyla , Nubani Linda , Bosch Sheila J. , Valipoor Shabboo , McElhinney Sam 
Published: March 2023

Objectives: The present study investigates whether space syntax offers appropriate tools for identifying risks of aggression, interventional opportunities, and environmental design strategies to reduce the risk of Type II violence in emergency departments. Background: Although healthcare workers are a relatively small percentage of the U.S. workforce, they sustain almost 75% of workplace assaults. Poor environmental design has been identified as an antecedent to aggression by patients and/or their companions. Method: Guided by Rational Choice Theory, Lifestyle Exposure Theory, Routine Activity Theory, and Crime Prevention through Environmental Design (CPTED), the study uses five visibility graph analysis (VGA) measures: visibility, control, controllability, mean visual depth, and occlusivity. Three U.S. hospital-based emergency departments were selected. First, a VGA was performed on all three layouts. A second VGA was performed after excluding unconnected spaces, and a third was performed on key patient and staff areas. Last, a fourth VGA was conducted after performing physical modifications to the three departments. Results: Statistical analysis revealed significant differences in VGA measures not only between different layouts but also between the original and modified layouts. Specifically, small changes created by architectural features can affect visual access and exposure as measured by space syntax. Alcove-style spaces in key staff areas are also associated with limited visual control of the local environment. Typically, in smaller zones, central staff workstations afford better control of patient spaces. Conclusion: This study shows that space syntax analysis is a useful tool for identifying risks of aggression in hospital spaces and for identifying interventional opportunities.
Relationships Between Psychosocial Factors and Mental Health Among Nurses Working With COVID-19 Patients in Japan
Authors: Ohue Takashi , Togo Eiichi , Ohue Yuka , Mitoku Kazuko 
Published: March 2023

Background Nurses who work with COVID-19 patients may suffer high levels of work-related stress, anxiety, and depressive symptoms. These impacts raise concerns about the deterioration of their mental health during this time. Objective This study examines the relationships between psychosocial factors (health, behavior, social, and economic factors) and mental health on among nurses working in a COVID-19 ward in Japan. Design A cross-sectional questionnaire-based study design was adopted. Methods We randomly selected 41 general hospitals that had over 400 beds. The participants were nurses who cared for COVID-19 patients at five hospitals. The questionnaire was completed by 56 nurses (seven men and 49 women) (response rate 46.6%). The survey asked participants about their basic attributes (gender, age, years of experience). It also included the Japanese version of the Patient Health Questionnaire-9, the Japanese version of the Generalized Anxiety Disorder-7, the Japanese version of the Impact of Event Scale-Revised, and the Maslach Burnout Inventory-General Survey to measure depression, anxiety, trauma experience, and burnout, respectively. To determine psychosocial factors, perception of damage from harmful rumors, nurses’ intention to quit their jobs, working environment changes, and changes in daily life were measured. Results Intention to quit was specifically associated with “wanting to continue nursing,” the posttraumatic stress disorder (PTSD) symptom of avoidance, depression, anxiety, and burnout. Nurses who had experienced the impact of harmful rumors in the workplace had high levels of PTSD symptoms, including intrusion, avoidance, and hyperarousal, as well as depression, anxiety disorder, and burnout cynicism. Regarding changes in the working environment, significant differences were confirmed in PTSD symptoms including intrusion, avoidance, and hyperarousal, as well as depression. We also examined the relationship between changes in daily life and mental health. We found that answering affirmatively to “the family income has decreased,” “I’ve had family problems,” and “I cannot do housework” related to mental health disorders among the nurses. Consideration: Psychosocial factors that may have been exacerbated during the COVID-19 pandemic were found to affect nurses’ mental health. Thus, reducing these psychosocial factors and building a mental health support system for nurses is crucial.
The association of patient safety culture with patient satisfaction: The role of the pharmacist's performance
Authors: Alolayyan Main Naser , Hijazi Bushra , Jalaileh Raneen Atef 
Published: March 2023

Background and objective A cross-sectional research, the questionnaire-based study aimed to investigate the association between patient safety culture and patient satisfaction through pharmacist performance, between patient safety culture and pharmacist performance, between pharmacist performance and patient satisfaction, and between patient safety culture and patient satisfaction. Methods Pharmacists and pharmacy technicians working in the community pharmacies evaluated the patient safety culture using an online self-administrated questionnaire filled out by participants. The first research questionnaire was adopted from the agency of healthcare research and quality (AHRQ), which was reliable and valid. Pharmacist performance and patient satisfaction were measured by using an online self-completion questionnaire that patients filled out. To measure performance, a previously validated questionnaire was used. For measuring patient satisfaction, The Patient Satisfaction with Pharmacist Clinical Services Questionnaire the final version (PSPSQ 2.0) was used. A total of 204 pharmacists, pharmacy technicians, and 204 patients constitute the research sample. Results The results showed that there is a significant association between the patient safety culture and the pharmacist's performance; an insignificant association between the patient safety culture and patient satisfaction; a significant association between the pharmacist’s performance and patient satisfaction; and a pharmacist’s performance mediates the relationship between patient safety culture and patient satisfaction. Conclusion The pharmacy sector may effectively reinforce patient safety culture in community pharmacies and enhance pharmacists’ performance to improve the quality of care and increase patient satisfaction.
Genome-wide identification, bioinformatics and expression analysis of HD-Zip gene family in peach
Authors: Wang Zhe , Wu Xuelian , Zhang Binbin , Xiao Yuansong , Guo Jian , Liu Jin , Chen Qiuju , Peng Futian 
Published: March 2023

Abstract
Background
HD-Zips (Homeodomain-Leucine Zippers) are a class of plant-specific transcription factors that play multiple roles in plant growth and development. Although some functions of HD-Zip transcription factor have been reported in several plants, it has not been comprehensively studied in peach, especially during adventitious root formation of peach cuttings.

Results
In this study, 23 HD-Zip genes distributed on 6 chromosomes were identified from the peach (Prunus persica) genome, and named PpHDZ01-23 according to their positions on the chromosomes. These 23 PpHDZ transcription factors all contained a homeomorphism box domain and a leucine zipper domain, were divided into 4 subfamilies(I-IV) according to the evolutionary analysis, and their promoters contained many different cis-acting elements. Spatio-temporal expression pattern showed that these genes were expressed in many tissues with different levels, and they had distinct expression pattern during adventitious root formation and development.

Conclusion
Our results showed the roles of PpHDZs on root formation, which is helpful to better understand the classification and function of peach HD-Zip genes.
Metabolomics reveals arbuscular mycorrhizal fungi-mediated tolerance of walnut to soil drought
Authors: Zou Ying-Ning , Qin Qiu-Yun , Ma Wen-Ya , Zhou Li-Jun , Wu Qiang-Sheng , Xu Yong-Jie , Kuča Kamil , Hashem Abeer , Al-Arjani Al-Bandari Fahad , Almutairi Khalid F. , Abd-Allah Elsayed Fathi 
Published: March 2023

Abstract
Background
Arbuscular mycorrhizal fungi (AMF) have a positive effect on drought tolerance of plants after establishing reciprocal resymbiosis with roots, while the underlying mechanism is not deciphered. Metabolomics can explain the mechanism of plant response to environmental stress by analyzing the changes of all small molecular weight metabolites. The purpose of this study was to use Ultra High Performance Liquid Chromatography Q Exactive Mass Spectrometer to analyze changes in root metabolites of walnut (Juglans regia) after inoculation with an arbuscular mycorrhizal fungus Diversispora spurca under well-watered (WW) and drought stress (DS).

Results
Sixty days of soil drought significantly inhibited root mycorrhizal colonization rate, shoot and root biomass production, and leaf water potential in walnut, while AMF inoculation significantly increased biomass production and leaf water potential, accompanied by a higher increase magnitude under DS versus under WW. A total of 3278 metabolites were identified. Under WW, AMF inoculation up-regulated 172 metabolites and down-regulated 61 metabolites, along with no changes in 1104 metabolites. However, under DS, AMF inoculation up-regulated 49 metabolites and down-regulated 116 metabolites, coupled with no changes in 1172 metabolites. Among them, juglone (a quinone found in walnuts) as the first ranked differential metabolite was up-regulated by AMF under WW but not under DS; 2,3,5-trihydroxy-5–7-dimethoxyflavanone as the first ranked differential metabolite was increased by AMF under DS but not under WW. The KEGG annotation showed a large number of metabolic pathways triggered by AMF, accompanied by different metabolic pathways under WW and DS. Among them, oxidative phosphorylation and phenylalanine metabolism and biosynthesis were triggered by AMF in response to WW and DS, where N-acetyl-L-phenylalanine was induced by AMF to increase under DS, while decreasing under WW.

Conclusion
This study provides new insights into the metabolic mechanisms of mycorrhiza-enhanced drought tolerance in walnuts.