bluuebunny/crossref_metadata_2025_split huggingface dataset:
The EstroGene Database Reveals Diverse Temporal, Context-Dependent, and Bidirectional Estrogen Receptor Regulomes in Breast Cancer
Authors: Li Zheqi , Li Tianqin , Yates Megan E. , Wu Yang , Ferber Amanda , Chen Lyuqin , Brown Daniel D. , Carroll Jason S. , Sikora Matthew J. , Tseng George C. , Oesterreich Steffi , Lee Adrian V. 
Published: June 2023

Abstract

As one of the most successful cancer therapeutic targets, estrogen receptor-α (ER/ESR1) has been extensively studied over the past few decades. Sequencing technological advances have enabled genome-wide analysis of ER action. However, comparison of individual studies is limited by different experimental designs, and few meta-analyses are available. Here, we established the EstroGene database through unified processing of data from 246 experiments including 136 transcriptomic, cistromic, and epigenetic datasets focusing on estradiol (E2)-triggered ER activation across 19 breast cancer cell lines. A user-friendly browser (https://estrogene.org/) was generated for multiomic data visualization involving gene inquiry under user-defined experimental conditions and statistical thresholds. Notably, annotation of metadata associated with public datasets revealed a considerable lack of experimental details. Comparison of independent RNA-seq or ER ChIP-seq data with the same design showed large variability and only strong effects could be consistently detected. Temporal estrogen response metasignatures were defined, and the association of E2 response rate with temporal transcriptional factors, chromatin accessibility, and heterogeneity of ER expression was evaluated. Unexpectedly, harmonizing 146 E2-induced transcriptomic datasets uncovered a subset of genes harboring bidirectional E2 regulation, which was linked to unique transcriptional factors and highly associated with immune surveillance in the clinical setting. Furthermore, the context dependent E2 response programs were characterized in MCF7 and T47D cell lines, the two most frequently used models in the EstroGene database. Collectively, the EstroGene database provides an informative and practical resource to the cancer research community to uniformly evaluate key reproducible features of ER regulomes and unravels modes of ER signaling.

Significance:
A resource database integrating 246 publicly available ER profiling datasets facilitates meta-analyses and identifies estrogen response temporal signatures, a bidirectional program, and model-specific biases.
Racial, Ethnic, and Sex-based Disparities among High-risk Individuals Undergoing Pancreatic Cancer Surveillance
Authors: Katona Bryson W. , Klute Kelsey , Brand Randall E. , Everett Jessica N. , Farrell James J. , Hawthorne Kieran , Kaul Vivek , Kupfer Sonia S. , Paiella Salvatore , Simeone Diane M. , Sussman Daniel A. , Zogopoulos George , Lucas Aimee L. , Kastrinos Fay ,   the PRECEDE Consortium, Bi Yan , Brentnall Teresa , Chung Daniel , Earl Julie , Gaddam Srinivas , Gallinger Steve , Graff John J. , Greenhalf William , Grossberg Aaron , Hart Philip , Idos Gregory , Jeter Joanne , Lindberg James , Lowy Andrew , Permuth Jennifer , Raitses-Gurevich Maria , Schrader Intan , Siveke Jens , Stoffel Elena , Vornhuelz Marlies , Wadlow Raymond 
Published: June 2023

Abstract

Since its inception two years ago, the international, multicenter Pancreatic Cancer Early Detection (PRECEDE) Consortium has enrolled high-risk individuals (HRI) undergoing pancreatic ductal adenocarcinoma (PDAC) surveillance. Herein we aim to evaluate enrollment disparities in PRECEDE. Data on HRIs enrolled between May 2020 and March 2022 were collected, with HRIs defined as participants enrolled in PRECEDE meeting guideline-based criteria for PDAC surveillance. Of 1,273 HRIs enrolled, 1,113 were eligible for inclusion, with 47.2% meeting familial pancreatic cancer criteria without a known pathogenic variant (PV) and the remainder having a pathogenic variant in a PDAC-risk gene (CDKN2A, STK11, PRSS1, BRCA1, BRCA2, PALB2, ATM, MLH1, MSH2, MSH6, PMS2, or EPCAM). Study participants were predominantly from the United States (82.7%), the most common age range at enrollment was 60–69 years (37.4%), and a non-PDAC cancer was present in 32.4%. There were racial/ethnic- and sex-based disparities among enrolled subjects, as the majority of participants were female (65.9%) and self-reported white (87.7%), with only 2.9% having Hispanic ethnicity. While more than 97% of participants consented to utilize imaging data and biosamples for research, there was no difference in rate of consent based on race/ethnicity, sex, or age, thereby demonstrating uniform participation in research activities among all subgroups after enrollment. Ensuring that diversity of HRIs in PDAC surveillance programs mirrors the communities served by participating centers is important. Substantial racial/ethnic- and sex-based disparities persist among recently enrolled HRIs undergoing PDAC surveillance, and therefore reducing these disparities will be a major focus of the PRECEDE Consortium moving forward.

Prevention Relevance:
Pancreatic cancer surveillance is critical to decreasing pancreatic cancer mortality; therefore, it is important that pancreatic cancer surveillance studies enroll diverse patients. We demonstrate that substantial racial/ethnic- and sex-based disparities exist amongst enrollment in the international PRECEDE consortium, highlighting the dire need for future efforts to reduce these disparities.
See related Spotlight, p. 305
Hyperlocal Observations Reveal Persistent Extreme Urban Heat in Southeast Florida
Authors: Clement Amy , Troxler Tiffany , Keefe Oaklin , Arcodia Marybeth , Cruz Mayra , Hernandez Alyssa , Moanga Diana , Adefris Zelalem , Brown Natalia , Jacobson Susan 
Published: June 2023

Abstract
Cities around the world are experiencing the effects of climate change via increasing extreme heat worsened by urbanization. Within cities, there are disparities in extreme heat exposure that are apparent in various surface and remotely sensed observations, as well as in the health impacts. There are, however, large data gaps in our ability to quantify the heat experienced by people in their daily lives across urban areas. In this paper, we use hyperlocal observations to measure heat around Miami–Dade County, Florida. Temperature and humidity measurements were collected at sites throughout the county between 2018 and 2021 with low-cost sensors. By comparing these hyperlocal observations with a National Weather Service (NWS) site at the Miami International Airport (MIA), we show that maximum temperatures are on average 6°F (3.3°C) higher and maximum heat index values are 11°F (6.1°C) higher at sites in the county than at MIA. These measurements show that many sites frequently record a heat index above the local threshold value for heat advisory. This is in contrast with the fact that few forecast advisories are issued, and there are correspondingly few exceedances of the threshold at MIA. We use these results to motivate a discussion about the issues of this particular threshold for Miami–Dade County. We highlight the need for data that are closer to residents’ lived experience to assess the impacts of heat and help inform local and regional decision-making, particularly where heat exposure may be underappreciated as a potential public health hazard.
Saphenous vein aneurysms characterization and treatment: A 36-year single center experience
Authors: Moreno Oscar , Kumar Kiran , Wakefield Thomas , Obi Andrea 
Published: June 2023

Background Superficial vein aneurysms (SVA) are rare vascular pathologies associated with trauma, chronic venous disease, and venous malformation. Method We retrospectively reviewed cases of SVA treated from 1986 to 2022. Results Out of 2463 venous procedures, 16 patients were found with 19 GSV and 1 SSV aneurysms, with 88% presenting with a palpable mass. Varicose veins were noted in 94% of patients, 81% had concomitant reflux, 15% had thrombus within the aneurysm sac, and 19% demonstrated multiple aneurysms. All patients underwent ligation and excision. Post-procedure, 55% of patients received anticoagulants, and 85% received compression. Mean follow-up was 19.4 months, with no aneurysm recurrence. We propose a modification to the current SVA classification. Conclusion The prevalence of multiple aneurysms suggests the need for complete limb imaging in affected patients. Surgical management of SVA was effective in preventing SVA recurrence, while the proposed classification modification will aid in future SVA management.
Preliminary Screening of in vitro Kaempferia galanga Oil for Anti-Proliferative Activities Against HeLa and MCF-7 Cell
Authors: Panigrahi Rajashree , Parida Reena 
Published: June 2023

Background Kaempferia galanga, commonly known as aromatic ginger, is a potential herb with high medicinal value and is used to treat many diseases like diabetes and asthma. Cancer is a group of diseases characterized by abnormal cells that divide uncontrollably and spread throughout the body. Nowadays, medicinal plants are used for their essential oil activities, including anti-cancerous effects. Objectives The aim of this study is to establish a method for screening in vitro oil cytotoxic effects. Materials and Methods Murashige and Skoog (MS) medium with growth regulators like benzyladenine, kinetin, indole-3-acetic acid, adenine sulfate, and naphthalene acetic acid was used for plantlet production. The in vitro regenerated plants were studied for rhizome oil extraction using Clevenger’s apparatus and gas chromatography-mass spectrometry (GC-MS) analysis, followed by their cytotoxicity study against human cervical cancer cells (HeLa) and human breast cancer cells (MCF-7) by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction (MTT) assay. Results Upon analysis, it has been found that this medicinal plant contains ethyl-p-methoxycinnamate (EPMC) (56.41 ± 0.34%) as a vital compound in its rhizome oil. The validation of cytotoxicity in both cell lines was done by treatment with rhizome oil concentrations ranging from 6.25 to 100 µL, respectively. The IC50 value was found to be 44.18 ± 0.65 µL/mL in HeLa and 72.94 ± 0.26 µL/mL in MCF-7 cells after 24 h of incubation. Conclusion The results of this study would be helpful for this important medicinal plant to be used by pharmaceuticals in the treatment of cancer.
Therapeutic effect of C-type natriuretic peptide on persistent pain in a rat knee arthritis model
Authors: Hasegawa Shoichi , An Jae-Sung , Hino Jun , Amano Yusuke , Nakagawa Yusuke , Miyatake Kazumasa , Katagiri Hiroki , Nakamura Tomomasa , Sekiya Ichiro , Koga Hideyuki , Tsuji Kunikazu 
Published: June 2023

Background Intra-articular injection of C-type natriuretic peptide (CNP) at the acute inflammatory stage suppressed fibrotic changes in the infrapatellar fat pad (IFP), articular cartilage degeneration, and persistent pain in a monoiodoacetic acid (MIA)-induced rat knee arthritis model. In this study, we administered CNP during the inflammation subsiding period to evaluate CNP effectiveness in knees with osteoarthritis (OA) pathology. Methods 20 male Wistar rats were randomly divided into two groups. The rats received an intra-articular injection of MIA solution in the right knee to induce inflammation-induced joint degeneration. One group subsequently received an intra-articular CNP injection for six consecutive days from day 8, whereas another group received vehicle solution. Pain avoidance behavior tests and histological analyses were conducted to examine the therapeutic effects of CNP. Results The incapacitance test indicated that the percent weight on the ipsilateral limb decreased after MIA injection by day 4 and continued to decrease until the end of the experiment in the vehicle group, suggesting persistent pain in the knee. Intra-articular injection of CNP reversed the weight-bearing ratio on day 19. Histological evaluation showed that the CNP group had more residual fat tissue in the IFP and fewer calcitonin gene-related peptide-positive nerve endings compared to the vehicle group. CNP could not reverse articular cartilage degeneration. Conclusions Intra-articular injection of CNP after the IFP fibrosis onset had no significant effect on OA severity and extent. Nevertheless, CNP might be utilized therapeutically for OA treatment since it can alleviate persistent knee pain and inhibit structural changes in residual fat tissue.
Experimental assessment and compressive constitutive model of rubberized concrete confined by steel tube
Authors: Zhou Zhi , Huang Wei , Wang Xiaodong 
Published: June 2023

To investigate the confining effect and axial compressive behavior of rubberized concrete (RuC) confined by steel tube, axial compression tests were carried out on 12 circular RuC cylinders confined by steel tube. The cylinders considered parameters such as steel tube thicknesses (2 mm, 3 mm, 4 mm) and rubber volume replacement ratios of the fine aggregates (0%, 10%, 20%, and 30%). It was observed that the compressive strength of RuC decreases as the rubber volume replacement ratio increases. However, an increase in steel tube thickness enhances the confining effect of the core RuC, leading to an increase in its compressive strength and the corresponding strain, similar to that of conventional concrete. Moreover, post-peak curves are more likely to exhibit a strengthening part in confined concrete with more rubber content. Furthermore, a model was developed to determine the compressive strength of RuC confined by steel tube. Finally, an axial stress-strain model of steel tube confined RuC was proposed, which was validated against test results.
The Safety and Effectiveness of the Prostar XL Closure Device Compared to Open Groin Cutdown for Endovascular Aneurysm Repair
Authors: Hahl Tilda , Karvonen Rosa , Uurto Ilkka , Protto Sara , Suominen Velipekka 
Published: June 2023

Objective The aim of this study is to compare the outcomes of percutaneous femoral closure with the Prostar XL for endovascular aneurysm repair (EVAR) to those of open femoral cutdown, and to evaluate factors which may predict the failure of percutaneous closure. Methods Patients undergoing endovascular aneurysm repair for an infrarenal abdominal aortic aneurysm between 2005 and 2013 were included. Patient characteristics, anatomic femoral artery measurements, and postoperative complications were recorded retrospectively. Operator experience was defined with a cut-off point of >30 Prostar XL closures performed. Comparisons were made per access site. Results A total of 443 access sites were included, with percutaneous closure used in 257 cases (58.0%) and open cutdown in 186 cases (42.0%). The complication rate was 2.7% for the percutaneous and 4.3% for the open cutdown group ( P = .482). No significant differences between groups were found with respect to 30-day mortality, wound infections, thrombosis, seromas, or bleeding complications. Fourteen failures (5.4%) of percutaneous closure occurred. The success rates were similar for experienced and unexperienced operators (94.2% vs 95.5%, P = .768). Renal insufficiency was more common in the failed than in the successful percutaneous closure group (64.3% vs 24.7%, P = .003). Common femoral artery calcification or diameter, BMI, sheath size, or operator experience did not predict failure. No further complications were seen in follow-up CT at 1-3 years postoperatively. Conclusion The use of the Prostar XL is safe compared to open cutdown. The success rate is 94.6%. Operator experience, sheath size, obesity, or femoral artery diameter or calcification do not appear to predict a failure of percutaneous closure. Complications seem to occur perioperatively, and late complications are rare.
Prospective exosome-focused translational research for afatinib (EXTRA) study of patients with nonsmall cell lung cancer harboring EGFR mutation: an observational clinical study
Authors: Takata Saori , Morikawa Kei , Tanaka Hisashi , Itani Hidetoshi , Ishihara Masashi , Horiuchi Kazuya , Kato Yasuhiro , Ikemura Shinnosuke , Nakagawa Hideyuki , Nakahara Yoshiro , Seki Yoshitaka , Bessho Akihiro , Takahashi Nobumasa , Hayashi Kentaro , Endo Takeo , Takeyama Kiyoshi , Maekura Toshiya , Takigawa Nagio , Kawase Akikazu , Endoh Makoto , Nemoto Kenji , Kishi Kazuma , Soejima Kenzo , Okuma Yusuke , Yoshimura Kenichi , Saigusa Daisuke , Kanai Yae , Ueda Koji , Togashi Akira , Matsutani Noriyuki , Seki Nobuhiko 
Published: June 2023

Background: The exosome-focused translational research for afatinib (EXTRA) study is the first trial to identify novel predictive biomarkers for longer treatment efficacy of afatinib in patients with epidermal growth factor receptor ( EGFR) mutation-positive nonsmall cell lung cancer (NSCLC) via a comprehensive association study using genomic, proteomic, epigenomic, and metabolomic analyses. Objectives: We report details of the clinical portion prior to omics analyses. Design: A prospective, single-arm, observational study was conducted using afatinib 40 mg/day as an initial dose in untreated patients with EGFR mutation-positive NSCLC. Dose reduction to 20 mg every other day was allowed. Methods: Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. Results: A total of 103 patients (median age 70 years, range 42–88 years) were enrolled from 21 institutions in Japan between February 2017 and March 2018. After a median follow-up of 35.0 months, 21% remained on afatinib treatment, whereas 9% had discontinued treatment because of AEs. The median PFS was 18.4 months, with a 3-year PFS rate of 23.3%. The median afatinib treatment duration in patients with final doses of 40 ( n = 27), 30 ( n = 23), and 20 mg/day ( n = 35), and 20 mg every other day ( n = 18) were 13.4, 15.4, 18.8, and 18.3 months, respectively. The median OS was not reached, with a 3-year OS rate of 58.5%. The median OS in patients who did ( n = 25) and did not ( n = 78) receive osimertinib during the entire course of treatment were 42.4 months and not reached, respectively ( p = 0.654). Conclusions: As the largest prospective study in Japan, this study confirmed favorable OS following first-line afatinib in patients with EGFR mutation-positive NSCLC in a real-world setting. Further analysis of the EXTRA study is expected to identify novel predictive biomarkers for afatinib. Trial registration: UMIN-CTR identifier (UMIN000024935, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_his_list.cgi?recptno=R000028688
Revision Surgery With Refixation After Mandibular Fractures
Authors: Steffen Claudius , Welter Margrit , Fischer Heilwig , Goedecke Maximilian , Doll Christian , Koerdt Steffen , Kreutzer Kilian , Heiland Max , Rendenbach Carsten , Voss Jan O. 
Published: June 2023

Study Design Retrospective, descriptive observational study. Objective The need for revision surgery after mandibular fractures is an indicator for severe postoperative complications. This study aimed to characterise this patient cohort, describe solutions to deal with complications and evaluate treatment quality as a risk variable for complications. Methods Patients with revision surgery with refixation after open reduction and internal fixation (ORIF) of a mandible fracture were included. Patient- and therapy-specific information were assessed together with postoperative complications. The quality of fixation was evaluated individually by 6 specialists. Interobserver agreement was analysed using Fleiss’ kappa. Results Out of 630 patients, inclusion criteria were met by 17 patients (14 male, 3 female) with an average age of 43.3 (±15.5) years. Complications at the mandible body/angle/symphysis led to refixation in all cases. Main indications for refixation were osteomyelitis (52.9%) or pseudarthrosis (41.2%). Risk factors were drug-related immune suppression, local infection or substance abuse (nicotine, alcohol or drugs). Six patients did not present any of these predictors. Of these, treatment of 4 patients was rated as not in accordance to the AO principles. The interrater reliability of treatment quality assessments was .239. Conclusions Patients with risk factors need to be carefully observed perioperatively after ORIF of mandibular fractures and treatments need to be adapted to these patients. Discrepancies of treatments to common guidelines may also be an independent predictor for treatment failure in patients without risk factors. Current treatment guidelines should be re-evaluated concerning additional treatment strategies for patients with specific risk factors.
Perceptions about Aging and Ageism from 14 Cross-sectional Cohorts of Undergraduate Dental Students
Authors: Brondani M. , Donnelly L. , Christidis N. , Grazziotin-Soares R. , Ardenghi D. , Siqueira A.B. 
Published: June 2023

Background: Although positive and negative views of aging and older adults exist, how undergraduate dental students imagine their lives to be as they grow older remains to be fully explored. This study aimed at determining the self-perceived views of being 65, 75, or 85 y of age, as expressed by undergraduate dental students at the University of British Columbia (UBC), Vancouver, Canada. Methods: A 14-y cross-sectional study design was utilized involving third-year undergraduate dental students at UBC’s Faculty of Dentistry. Brief individual essays (150 words) encompassing students’ self-perceived views were gathered as part of a dental geriatric course from 2009 to 2022; however, essays were not mandatory. Saldaña’s inductive coding and thematic analysis of textual data were used. Themes and categories of information were identified and matched with their excerpts while aiming for data saturation. Results: Over the 14-y period, 657 students were enrolled in UBC’s undergraduate dental geriatric course, and 561 essays were collected. Inductive coding and thematic analysis identified 5 main themes and 11 categories. While themes included “oral health, general health, and the mind” and “me, myself, and familial relationships,” the categories focused on “(un)able bodies” and “general health.” Positive views about the aging process were shared, while less optimistic ideas—and even ageism—were apparent when students saw themselves as not employable or living in isolation. Positive and negative views were not bound by the students’ academic year but might have been influenced by the COVID-19 pandemic. Conclusion: Although the number of older adults already surpasses the number of children in many countries, ageism appears to have permeated through students’ views of 3 older ages. More positive yet realistic views of growing older were also shared. Follow-up studies are needed to explore the impact of dental education on decreasing ageism. Knowledge Transfer Statement: As the proportion of older adults in the global population steadily grows, it is important to educate heath care providers about normal and pathologic aging to avoid ageism—stereotypes, prejudices, and discrimination against older adults. This cross-sectional study involved 14 cohorts of undergraduate dental students exploring their self-perceived views of growing older. Although positive and negative views of aging were shared, dental education must focus on decreasing ageism.