bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lasofoxifene as a potential treatment for aromatase inhibitor-resistant ER-positive breast cancer
Authors: Lainé Muriel , Greene Marianne E , Kurleto Justyna D , Bozek Grazyna , Leng Tiffany , Huggins Rosemary J , Komm Barry S , Greene Geoffrey L 
Published: June 2024

Abstract
Background
Breast cancers treated with aromatase inhibitors (AIs) can develop AI resistance, which is often driven by estrogen receptor-alpha (ERα/ESR1) activating mutations, as well as by ER-independent signaling pathways. The breast ER antagonist lasofoxifene, alone or combined with palbociclib, elicited antitumor activities in a xenograft model of ER + metastatic breast cancer (mBC) harboring ESR1 mutations. The current study investigated the activity of LAS in a letrozole-resistant breast tumor model that does not have ESR1 mutations.

Methods
Letrozole-resistant, MCF7 LTLT cells tagged with luciferase-GFP were injected into the mammary duct inguinal glands of NSG mice (MIND model; 6 mice/group). Mice were randomized to vehicle, lasofoxifene ± palbociclib, fulvestrant ± palbociclib, or palbociclib alone 2–3 weeks after cell injections. Tumor growth and metastases were monitored with in vivo and ex vivo luminescence imaging, terminal tumor weight measurements, and histological analysis. The experiment was repeated with the same design and 8–9 mice in each treatment group.

Results
Western blot analysis showed that the MCF7 LTLT cells had lower ERα and higher HER2 expressions compared with normal MCF7 cells. Lasofoxifene ± palbociclib, but not fulvestrant, significantly reduced primary tumor growth versus vehicle as assessed by in vivo imaging of tumors at study ends. Percent tumor area in excised mammary glands was significantly lower for lasofoxifene plus palbociclib versus vehicle. Ki67 staining showed decreased overall tumor cell proliferation with lasofoxifene ± palbociclib. The lasofoxifene + palbociclib combination was also associated with significantly fewer bone metastases compared with vehicle. Similar results were observed in the repeat experiment.

Conclusions
In a mouse model of letrozole-resistant breast cancer with no ESR1 mutations, reduced levels of ERα, and overexpression of HER2, lasofoxifene alone or combined with palbociclib inhibited primary tumor growth more effectively than fulvestrant. Lasofoxifene plus palbociclib also reduced bone metastases. These results suggest that lasofoxifene alone or combined with a CDK4/6 inhibitor may offer benefits to patients who have ER-low and HER2-positive, AI-resistant breast cancer, independent of ESR1 mutations.
Lomustine with or without reirradiation for first progression of glioblastoma, LEGATO, EORTC-2227-BTG: study protocol for a randomized phase III study
Authors: Preusser Matthias , Kazda Tomáš , Le Rhun Emilie , Sahm Felix , Smits Marion , Gempt Jens , Koekkoek Johan AF , Monti Angelo F , Csanadi Marcell , Pitter János György , Bulbek Helen , Fournier Beatrice , Quoilin Caroline , Gorlia Thierry , Weller Michael , Minniti Giuseppe ,   on behalf of the European Organisation for Research, Treatment of Cancer (EORTC) Brain Tumor Group
Published: June 2024

Abstract
Background
Chemotherapy with lomustine is widely considered as standard treatment option for progressive glioblastoma. The value of adding radiotherapy to second-line chemotherapy is not known.

Methods
EORTC-2227-BTG (LEGATO, NCT05904119) is an investigator-initiated, pragmatic (PRECIS-2 score: 34 out of 45), randomized, multicenter phase III trial in patients with first progression of glioblastoma. A total of 411 patients will be randomized in a 1:1 ratio to lomustine (110 mg/m2 every 6 weeks) or lomustine (110 mg/m2 every 6weeks) plus radiotherapy (35 Gy in 10 fractions). Main eligibility criteria include histologic confirmation of glioblastoma, isocitrate dehydrogenase gene (IDH) wild-type per WHO 2021 classification, first progression at least 6 months after the end of prior radiotherapy, radiologically measurable disease according to RANO criteria with a maximum tumor diameter of 5 cm, and WHO performance status of 0–2. The primary efficacy endpoint is overall survival (OS) and secondary endpoints include progression-free survival, response rate, neurocognitive function, health-related quality of life, and health economic parameters. LEGATO is funded by the European Union’s Horizon Europe Research program, was activated in March 2024 and will enroll patients in 43 sites in 11 countries across Europe with study completion projected in 2028.

Discussion
EORTC-2227-BTG (LEGATO) is a publicly funded pragmatic phase III trial designed to clarify the efficacy of adding reirradiation to chemotherapy with lomustine for the treatment of patients with first progression of glioblastoma.

Trial registration
ClinicalTrials.gov NCT05904119. Registered before start of inclusion, 23 May 2023
Multi-task transfer learning for the prediction of entity modifiers in clinical text: application to opioid use disorder case detection
Authors: Almudaifer Abdullateef I. , Covington Whitney , Hairston JaMor , Deitch Zachary , Anand Ankit , Carroll Caleb M. , Crisan Estera , Bradford William , Walter Lauren A. , Eaton Ellen F. , Feldman Sue S. , Osborne John D. 
Published: June 2024

Abstract
Background
The semantics of entities extracted from a clinical text can be dramatically altered by modifiers, including entity negation, uncertainty, conditionality, severity, and subject. Existing models for determining modifiers of clinical entities involve regular expression or features weights that are trained independently for each modifier.

Methods
We develop and evaluate a multi-task transformer architecture design where modifiers are learned and predicted jointly using the publicly available SemEval 2015 Task 14 corpus and a new Opioid Use Disorder (OUD) data set that contains modifiers shared with SemEval as well as novel modifiers specific for OUD. We evaluate the effectiveness of our multi-task learning approach versus previously published systems and assess the feasibility of transfer learning for clinical entity modifiers when only a portion of clinical modifiers are shared.

Results
Our approach achieved state-of-the-art results on the ShARe corpus from SemEval 2015 Task 14, showing an increase of 1.1% on weighted accuracy, 1.7% on unweighted accuracy, and 10% on micro F1 scores.

Conclusions
We show that learned weights from our shared model can be effectively transferred to a new partially matched data set, validating the use of transfer learning for clinical text modifiers.
Tumour-specific phosphorylation of serine 419 drives alpha-enolase (ENO1) nuclear export in triple negative breast cancer progression
Authors: Marshall Morgan L , Fung Kim YC , Jans David A , Wagstaff Kylie M 
Published: June 2024

Abstract
Background
The glycolytic enzyme alpha-enolase is a known biomarker of many cancers and involved in tumorigenic functions unrelated to its key role in glycolysis. Here, we show that expression of alpha-enolase correlates with subcellular localisation and tumorigenic status in the MCF10 triple negative breast cancer isogenic tumour progression model, where non-tumour cells show diffuse nucleocytoplasmic localisation of alpha-enolase, whereas tumorigenic cells show a predominantly cytoplasmic localisation. Alpha-enolase nucleocytoplasmic localisation may be regulated by tumour cell-specific phosphorylation at S419, previously reported in pancreatic cancer.

Results
Here we show ENO1 phosphorylation can also be observed in triple negative breast cancer patient samples and MCF10 tumour progression cell models. Furthermore, prevention of alpha-enolase-S419 phosphorylation by point mutation or a casein kinase-1 specific inhibitor D4476, induced tumour-specific nuclear accumulation of alpha-enolase, implicating S419 phosphorylation and casein kinase-1 in regulating subcellular localisation in tumour cell-specific fashion. Strikingly, alpha-enolase nuclear accumulation was induced in tumour cells by treatment with the specific exportin-1-mediated nuclear export inhibitor Leptomycin B. This suggests that S419 phosphorylation in tumour cells regulates alpha-enolase subcellular localisation by inducing its exportin-1-mediated nuclear export. Finally, as a first step to analyse the functional consequences of increased cytoplasmic alpha-enolase in tumour cells, we determined the alpha-enolase interactome in the absence/presence of D4476 treatment, with results suggesting clear differences with respect to interaction with cytoskeleton regulating proteins.

Conclusions
The results suggest for the first time that tumour-specific S419 phosphorylation may contribute integrally to alpha-enolase cytoplasmic localisation, to facilitate alpha-enolase’s role in modulating cytoskeletal organisation in triple negative breast cancer. This new information may be used for development of triple negative breast cancer specific therapeutics that target alpha-enolase.
Optimum solution of $(k,\gimel )$-Hilfer FDEs by $\mathcal{A}$-condensing operators and the incorporated measure of noncompactness
Authors: Khokhar Gurpreet Kaur , Patel Deepesh Kumar , Patle Pradip Ramesh , Samei Mohammad Esmael 
Published: June 2024

AbstractThe notion of $\mathcal{A}$
A
-condensing operators via the measure of noncompactness is proposed, which retains the existing classes of condensing operators. Results concerning the existence of the best proximity point (pair) of cyclic (noncyclic) $\mathcal{A}$
A
-condensing operators along with the coupled best proximity-point theorem for cyclic $\mathcal{A}$
A
-condensing operators have been formulated. An application to a $(k, \gimel )$
(
k
,
ℷ
)
-Hilfer fractional differential equation of order $2< p<3$
2
<
p
<
3
, type $q\in [0,1]$
q
∈
[
0
,
1
]
satistfying some boundary conditions is presented. The paper is the first to investigate the optimum solution of such a generalized fractional differential equation. The hypothesis involved in the investigation is independent of the incorporated measure of noncompactness, thereby making our result better in application than that present in the literature. Moreover, added numerical examples validate the theoretical conclusions.
Patient eligibility for trials with imaging response assessment at the time of molecular tumor board presentation
Authors: Mansour Nabeel , Heinrich Kathrin , Zhang Danmei , Winkelmann Michael , Ingenerf Maria , Gold Lukas , Klambauer Konstantin , Rudelius Martina , Klauschen Frederick , von Bergwelt-Baildon Michael , Ricke Jens , Heinemann Volker , Westphalen C. Benedikt , Kunz Wolfgang G. 
Published: June 2024

Abstract
Purpose
To assess the eligibility of patients with advanced or recurrent solid malignancies presented to a molecular tumor board (MTB) at a large precision oncology center for inclusion in trials with the endpoints objective response rate (ORR) or duration of response (DOR) based on Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).

Methods
Prospective patients with available imaging at the time of presentation in the MTB were included. Imaging data was reviewed for objectifiable measurable disease (MD) according to RECIST v1.1. Additionally, we evaluated the patients with MD for representativeness of the identified measurable lesion(s) in relation to the overall tumor burden.

Results
262 patients with different solid malignancies were included. 177 patients (68%) had MD and 85 (32%) had non-measurable disease (NMD) at the time point of MTB presentation in accordance with RECIST v1.1. MD was not representative of the overall tumor burden in eleven patients (6%). The main reasons for NMD were lesions with longest diameter shorter than 10 mm (22%) and non-measurable peritoneal carcinomatosis (18%). Colorectal cancer and malignant melanoma displayed the highest rates of MD (> 75%). In contrast, gastric cancer, head and neck malignancies, and ovarian carcinoma had the lowest rates of MD (< 55%). In case of MD, the measurable lesions were representative of the overall tumor burden in the vast majority of cases (94%).

Conclusion
Approximately one third of cancer patients with advanced solid malignancies are not eligible for treatment response assessment in trials with endpoints ORR or DOR at the time of MTB presentation. The rate of patients eligible for trials with imaging endpoints differs significantly based on the underlying malignancy and should be taken under consideration during the planning of new precision oncology trials.
Experiences from youth advisors in chronic disease prevention research
Authors: Mautner Dominik , Valanju Radhika , Al Hadaya Imeelya , Barani Meera , Cross Alexi , McMahon Emily , Ren Bowen , Rose Dominique , Sharda Aviral , Sinnett Alexander , Yan Fulin , Wardak Sara 
Published: June 2024

AbstractEngaging young people in research is a promising approach to tackling issues like chronic disease prevention. Our involvement as youth advisors provided valuable experiences, including being at the forefront of change and learning to work within a research team. Furthermore, our experience provides greater insight and learnings for future youth engagement in research.
Parental executive functions and motivations unveil variations in young children's screen media use
Authors: Laurence Paulo Guirro , de Melo Rodrigues Matheus , Tannus Maria Carolina Brito Locatti , Dekaney Elisa Macedo , Macedo Elizeu Coutinho 
Published: June 2024

Abstract
Background
The increased screen media use among children aged 3 to 5, particularly in the post-COVID era, is concerning. Despite several organizations' recommendation of a one-hour screen limit for young children, actual usage often exceeds this guideline. Objective: This study explored the influence of parental characteristics such as self-efficacy, motivation, socioeconomic status, and cognitive abilities on children's screen time habits.

Methods
Employing a feature selection model, 251 caregivers answered an online survey, presenting data from themselves and on-screen usage for 126 girls and 125 boys. We found that the caregiver’s executive functions, including cognitive flexibility, initiation, task monitoring, and material organization, significantly impact children’s screen time. Results: Our analysis highlighted the vital role of caregivers’ self-efficacy in moderating children's screen usage. Family net income, children's age and gender, and motivations related to children's desires and behavioral control were also significant contributors to usage patterns.

Conclusion
This study offers insights into interventions and effective parenting strategies in the digital age, highlighting the importance of addressing socio-demographic factors in understanding this complex issue.
Adaptation of the comprehensive rheumatologic assessment of frailty (CRAF) as a multidimensional frailty screening tool in patients with rheumatoid arthritis in Vietnam
Authors: Tran Trang Huyen , Ta Trang Thi Huong , Nguyen Lan Thi Ngoc , Vu Huyen Thi Thanh , Van Nguyen Hung 
Published: June 2024

Abstract
Background
In recent times, there has been acknowledgment of the prevalence of frailty and pre-frailty among individuals with rheumatoid arthritis (RA). Comprehensive Rheumatologic Assessment of Frailty (CRAF) stands out as a dependable tool grounded in synthesis and clinical judgment. Despite this, a validated Vietnamese rendition of the CRAF is currently unavailable. This study seeks to assess the reliability and validity of the CRAF in a patient with RA in Vietnam.

Methods
A cross-sectional investigation was carried out with 402 patients diagnosed with rheumatoid arthritis, encompassing both inpatients and outpatients at the Centre for Rheumatology at Bach Mai Hospital in Hanoi, Vietnam. CRAF was employed to gauge the extent of frailty. To establish convergent validity, the scores from the CRAF were correlated with those from the Fried phenotype. Discriminant validity was ascertained through the utilization of receiver operating characteristic (ROC) curve analysis. Additionally, a multivariate logistic regression model was applied to evaluate the individual determinants’ relative impact on the CRAF.

Results
In testing for convergent validity, a significant correlation was found between CRAF and Fried phenotype (p < 0.001). The discriminatory power of CRAF was higher than those of the Fried phenotype (difference between areas under the ROC curves = 0.947 (95% CI: 0.927–0.967). Variables associated with frailty at the multivariate analysis were comorbitidy, medication intake, BMI, DAS28-CRP, and age (all at p < 0.01).

Conclusion
CRAF exhibited strong validity and accurate discrimination. Incorporating frailty assessment into regular rheumatological practices could signify a significant advancement in the care of rheumatoid arthritis.
Anthracycline-induced hypertension in pediatric cancer survivors: unveiling the long-term cardiovascular risks
Authors: Taghdiri Andia 
Published: June 2024

Abstract
Background
Long-term cardiovascular complications are common among pediatric cancer survivors, and anthracycline-induced hypertension has become an essential reason for concern. Compared to non-cancer controls, survivors have a higher prevalence of hypertension, and as they age, their incidence rises, offering significant dangers to cardiovascular health.

Main body
Research demonstrates that exposure to anthracyclines is a major factor in the development of hypertension in children who have survived cancer. Research emphasizes the frequency and risk factors of anthracycline-induced hypertension, highlighting the significance of routine measurement and management of blood pressure. Furthermore, cardiovascular toxicities, such as hypertension, after anthracycline-based therapy are a crucial be concerned, especially for young adults and adolescents. Childhood cancer survivors deal with a variety of cardiovascular diseases, such as coronary artery disease and cardiomyopathy, which are made worse by high blood pressure. In order to prevent long-term complications, it is essential to screen for and monitor for anthracycline-induced hypertension. Echocardiography and cardiac biomarkers serve as essential tools for early detection and treatment. In order to lower cardiovascular risks in pediatric cancer survivors, comprehensive management strategies must include lifestyle and medication interventions in addition to survivor-centered care programs.

Short conclusion
Proactive screening, monitoring, and management measures are necessary for juvenile cancer survivors due to the substantial issue of anthracycline-induced hypertension in their long-term care. To properly include these strategies into survivor-ship programs, oncologists, cardiologists, and primary care physicians need to collaborate together. The quality of life for pediatric cancer survivors can be enhanced by reducing the cardiovascular risks linked to anthracycline therapy and promoting survivor-centered care and research.
Prevalence and predictors of hepatic steatosis among HIV patients with and without chronic hepatitis C
Authors: Elsharkawy Aisha , Alem Shereen Abdel , Moustafa Saeed , Elnggar Shymaa , Cordie Ahmed , Esmat Gamal , Moustafa Ahmed 
Published: June 2024

Abstract
Background and purpose of the study
Hepatic steatosis (HS) is a common and important histologic finding in patients with chronic hepatitis C virus (HCV) infection. However, little is known about this finding in HCV patients co-infected with human immunodeficiency virus (HIV).

Purpose of the study
To evaluate the prevalence and predictors of HS among HIV patients with and without HCV.

Methods
A cross-sectional including 47 HIV mono-infected and 50 HIV/HCV patients. Detailed demographic, laboratory and clinical data were collected. A transient elastography (TE) examination with the controlled attenuation parameter (CAP) was performed for all patients. Steatosis was scored on a scale from 0 to 3 according to the percentage of steatosis involving hepatocytes.

Results
HS was detected in 18 /50 (36%) HIV/HCV co-infected patients and 22 /47 (46.8%) HIV mono-infected patients. In addition, HCV mono-infected patients were more likely to have grade 2 steatosis as compared with HIV/HCV co-infected individuals (25.5% vs. 12%). LSM was significantly higher among HIV/HCV co-infected patients (p = 0.003). When dividing HIV/HCV co-infected and HIV mono-infected group according to CAP values. BMI, abdominal wall thickness, and bright liver were significantly associated with SHS (CAP ≥ 238 dB/m) in both groups. Diabetes was only significantly associated with SHS in HIV/HCV co-infected group BMI was the only independent predictor of SHS among the whole group and subgroup analysis.

Conclusion
The prevalence of HS was lower in HIV/HCV co-infected patients compared to HIV mono-infected patients; we cannot say that HCV has a protective role against HS in co-infected patients. More fibrosis progression was common in the HIV/HCV co-infected patients.
A comprehensive functional performance assessment battery development and validation among football players
Authors: Ghosalker Harshita Rajan , Esht Vandana , Ahmed Sohel 
Published: June 2024

Abstract
Background
Skill and health-related components are required for the assessment of football players’ functional performance, and there is a lack of literature available to measure football players’ functional performance. The study mostly focuses on developing and validating the tool for football players between the ages of 18 and 25.

Methods
This study used a research methodology that focused on the development and verification of a scale. The research consisted of two distinct stages, namely tool development and validity testing. Firstly, the expert panel did a comprehensive analysis of the items and domains of the questionnaire. Subsequently, the Delphi approach was used to assess the content validity of the questionnaire. Later on, the evaluation tool was officially named the complete functional performance assessment battery (CFPA) for football players in India.

Result
The CFPA’s newly developed tool has excellent scale-level content validity, which was more than 0.78 for each item in the tool, i.e., 1 (indicated as extremely relevant), the content validity ratio was bigger than 0.49, and each item’s kappa value was found to be 1, which is excellent. Each item’s universal acceptance was found to be 1 for both the item’s quality and content and Aiken’s V index is also greater than 0.81.

Conclusion
The CFPA is a valid tool in India that can be used to check the functional performance of football players.