bluuebunny/crossref_metadata_2025_split huggingface dataset:
HER2-low and tumor infiltrating lymphocytes in triple-negative breast cancer: Are they connected?
Authors: Baez-Navarro Ximena , van den Ende Nadine S. , Nguyen Anh H. , Sinke Renata , Westenend Pieter , van Brakel Johannes Bastiaan , Stobbe Claudia , Westerga Johan , van Deurzen Carolien H. M. 
Published: March 2024

AbstractMost patients with triple-negative breast cancer (TNBC) are not candidates for targeted therapy, leaving chemotherapy as the primary treatment option. Recently, immunotherapy has demonstrated promising results in TNBC, due to its immunogenicity. In addition, a novel antibody–drug conjugate, namely, trastuzumab-deruxtecan, has shown effectiveness in TNBC patients with low-HER2 expression (HER2-low). These novel treatment options raise the question about the potential association between the density of stromal tumor-infiltrating lymphocytes (sTILs) and the level of HER2 expression. We aimed to evaluate the association between the level of HER2 expression (HER2-low versus HER2-0) and density of sTILs in TNBC patients, and how they impact the response to neoadjuvant chemotherapy (NAC). This was a retrospective multicenter study including all TNBC patients diagnosed between 2018 and 2022. Central pathology review included sTILs percentages and level of HER2 expression. Tumors were reclassified as either HER2-0 (HER2 IHC 0) or HER2-low (IHC 1 + or 2 + with negative reflex test). Various clinicopathologic characteristics, including sTILs density, and response to NAC were compared between HER2-0 and HER2-low cases. In total, 753 TNBC patients were included in this study, of which 292 patients received NAC. Interobserver agreement between the original pathology report and central review was moderate (77% had the same IHC status after reclassification in either HER2-0 or HER2-low; k = 0.45). HER2-low TNBC represented about one third (36%) of the tumors. No significant difference in sTILs density or complete pathologic response rate was found between HER2-0 and HER2-low cases (p = 0.476 and p = 0.339, respectively). The density of sTILs (≥ 10% sTILs vs. < 10%) was independently associated with achieving a pCR (p = 0.011). In conclusion, no significant association was found between HER2-low status and density of sTILs nor response to NAC. Nonetheless, sTILs could be an independent biomarker for predicting NAC response in TNBC patients.
Cell morphology best predicts tumorigenicity and metastasis in vivo across multiple TNBC cell lines of different metastatic potential
Authors: Conner Sydney J. , Guarin Justinne R. , Le Thanh T. , Fatherree Jackson P. , Kelley Charlotte , Payne Samantha L. , Parker Savannah R. , Bloomer Hanan , Zhang Crystal , Salhany Kenneth , McGinn Rachel A. , Henrich Emily , Yui Anna , Srinivasan Deepti , Borges Hannah , Oudin Madeleine J. 
Published: March 2024

Abstract
Background
Metastasis is the leading cause of death in breast cancer patients. For metastasis to occur, tumor cells must invade locally, intravasate, and colonize distant tissues and organs, all steps that require tumor cell migration. The majority of studies on invasion and metastasis rely on human breast cancer cell lines. While it is known that these cells have different properties and abilities for growth and metastasis, the in vitro morphological, proliferative, migratory, and invasive behavior of these cell lines and their correlation to in vivo behavior is poorly understood. Thus, we sought to classify each cell line as poorly or highly metastatic by characterizing tumor growth and metastasis in a murine model of six commonly used human triple-negative breast cancer xenografts, as well as determine which in vitro assays commonly used to study cell motility best predict in vivo metastasis.

Methods
We evaluated the liver and lung metastasis of human TNBC cell lines MDA-MB-231, MDA-MB-468, BT549, Hs578T, BT20, and SUM159 in immunocompromised mice. We characterized each cell line's cell morphology, proliferation, and motility in 2D and 3D to determine the variation in these parameters between cell lines.

Results
We identified MDA-MB-231, MDA-MB-468, and BT549 cells as highly tumorigenic and metastatic, Hs578T as poorly tumorigenic and metastatic, BT20 as intermediate tumorigenic with poor metastasis to the lungs but highly metastatic to the livers, and SUM159 as intermediate tumorigenic but poorly metastatic to the lungs and livers. We showed that metrics that characterize cell morphology are the most predictive of tumor growth and metastatic potential to the lungs and liver. Further, we found that no single in vitro motility assay in 2D or 3D significantly correlated with metastasis in vivo.

Conclusions
Our results provide an important resource for the TNBC research community, identifying the metastatic potential of 6 commonly used cell lines. Our findings also support the use of cell morphological analysis to investigate the metastatic potential and emphasize the need for multiple in vitro motility metrics using multiple cell lines to represent the heterogeneity of metastasis in vivo.
UCHL1 contributes to insensitivity to endocrine therapy in triple-negative breast cancer by deubiquitinating and stabilizing KLF5
Authors: Li Juan , Liang Yu , Zhou Shijie , Chen Jie , Wu Chihua 
Published: March 2024

Abstract
Background
Ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that regulates ERα expression in triple-negative cancer (TNBC). This study aimed to explore the deubiquitination substrates of UCHL1 related to endocrine therapeutic responses and the mechanisms of UCHL1 dysregulation in TNBC.

Methods
Bioinformatics analysis was conducted using online open databases. TNBC representative MDA-MB-468 and SUM149 cells were used for in vitro and in-vivo studies. Co-immunoprecipitation was used to explore the interaction between UCHL1 and KLF5 and UCHL1-mediated KIF5 deubiquitination. CCK-8, colony formation and animal studies were performed to assess endocrine therapy responses. The regulatory effect of TET1/3 on UCHL1 promoter methylation and transcription was performed by Bisulfite sequencing PCR and ChIP-qPCR.

Results
UCHL1 interacts with KLF5 and stabilizes KLF5 by reducing its polyubiquitination and proteasomal degradation. The UCHL1-KLF5 axis collaboratively upregulates EGFR expression while downregulating ESR1 expression at both mRNA and protein levels in TNBC. UCHL1 knockdown slows the proliferation of TNBC cells and sensitizes the tumor cells to Tamoxifen and Fulvestrant. KLF5 overexpression partially reverses these trends. Both TET1 and TET3 can bind to the UCHL1 promoter region, reducing methylation of associated CpG sites and enhancing UCHL1 transcription in TNBC cell lines. Additionally, TET1 and TET3 elevates KLF5 protein level in a UCHL1-dependent manner.

Conclusion
UCHL1 plays a pivotal role in TNBC by deubiquitinating and stabilizing KLF5, contributing to endocrine therapy resistance. TET1 and TET3 promote UCHL1 transcription through promoter demethylation and maintain KLF5 protein level in a UCHL1-dependent manner, implying their potential as therapeutic targets in TNBC.
Prediction of metabolites associated with somatic mutations in cancers by using genome-scale metabolic models and mutation data
Authors: Lee GaRyoung , Lee Sang Mi , Lee Sungyoung , Jeong Chang Wook , Song Hyojin , Lee Sang Yup , Yun Hongseok , Koh Youngil , Kim Hyun Uk 
Published: March 2024

Abstract
Background
Oncometabolites, often generated as a result of a gene mutation, show pro-oncogenic function when abnormally accumulated in cancer cells. Identification of such mutation-associated metabolites will facilitate developing treatment strategies for cancers, but is challenging due to the large number of metabolites in a cell and the presence of multiple genes associated with cancer development.

Results
Here we report the development of a computational workflow that predicts metabolite-gene-pathway sets. Metabolite-gene-pathway sets present metabolites and metabolic pathways significantly associated with specific somatic mutations in cancers. The computational workflow uses both cancer patient-specific genome-scale metabolic models (GEMs) and mutation data to generate metabolite-gene-pathway sets. A GEM is a computational model that predicts reaction fluxes at a genome scale and can be constructed in a cell-specific manner by using omics data. The computational workflow is first validated by comparing the resulting metabolite-gene pairs with multi-omics data (i.e., mutation data, RNA-seq data, and metabolome data) from acute myeloid leukemia and renal cell carcinoma samples collected in this study. The computational workflow is further validated by evaluating the metabolite-gene-pathway sets predicted for 18 cancer types, by using RNA-seq data publicly available, in comparison with the reported studies. Therapeutic potential of the resulting metabolite-gene-pathway sets is also discussed.

Conclusions
Validation of the metabolite-gene-pathway set-predicting computational workflow indicates that a decent number of metabolites and metabolic pathways appear to be significantly associated with specific somatic mutations. The computational workflow and the resulting metabolite-gene-pathway sets will help identify novel oncometabolites and also suggest cancer treatment strategies.
Personalized, interdisciplinary patient pathway for cross-sector care of multimorbid patients (eliPfad trial): study protocol for a randomized controlled trial
Authors: Lindemann Christoph Heinrich , Burst Volker , Völker Linus Alexander , Brähler Sebastian , Simic Dusan , Becker Ingrid , Hellmich Martin , Kurscheid Clarissa , Scholten Nadine , Krauspe Ruben , Leibel Kerstin , Stock Stephanie , Brinkkoetter Paul Thomas 
Published: March 2024

Abstract
Background
Multimorbid and frail elderly patients often carry a high burden of treatment. Hospitalization due to the onset of an acute illness can disrupt the fragile balance, resulting in further readmissions after hospital discharge. Current models of care in Germany do not meet the needs of this patient group. Rather lack of coordination and integration of care combined with a lack of interdisciplinary approaches result in fragmented and inadequate care and increase the burden of treatment even more.

Methods
eliPfad is a randomized controlled trial conducted in 6 hospitals in Germany. Multimorbid elderly patients aged 55 or older are randomly assigned to the intervention or control group. Patients in the intervention group receive the eliPfad intervention additional to standard care. The core components of eliPfad are:

Early assessment of patients’ individual treatment burden and support through a specially trained case manager

Involvement of the patient’s general practitioner (GP) right from the beginning of the hospital stay

Preparation of an individual, cross-sectoral treatment plan through the interdisciplinary hospital team with the involvement of the patient’s GP

Establishment of a cross-sectoral electronic patient record (e-ePA) for documentation and cross-sectoral exchange

Support/Promote patient adherence

Tailored early rehabilitation during the hospital stay, which is continued at home

Close-tele-monitoring of medically meaningful vital parameters through the use of tablets, digital devices, and personal contacts in the home environment

The intervention period begins in the hospital and continues 6 weeks after discharge. Patients in the control group will be treated according to standard clinical care and discharged according to current discharge management. The primary aim is the prevention/reduction of readmissions in the first 6 months after discharge. In addition, the impact on health-related quality of life, the burden of treatment, survival, self-management, medication prescription, health literacy, patient-centered care, cost-effectiveness, and process evaluation will be examined. Nine hundred forty-eight patients will be randomized 1:1 to intervention and control group.

Discussion
If eliPfad leads to fewer readmissions, proves (cost-)effective, and lowers the treatment burden, it should be introduced as a new standard of care in the German healthcare system.

Trial registration
The trial was registered in the German Clinical Trials Registry (Deutsches Register Klinischer Studien (DRKS)) on 08/14/2023 under the ID DRKS00031500.
Association between insulin resistance, metabolic syndrome and its components and lung cancer: a systematic review and meta-analysis
Authors: Liu Jingxuan , Wang Rui , Tan Song , Zhao Xiaohu , Hou Aihua 
Published: March 2024

Abstract
Background
A growing body of evidence points to the association between insulin resistance (IR), metabolic syndrome (MetS) and its components and lung cancer incidence, but remains controversial and unknown.

Methods
A systematic search was conducted through PubMed, Embase, Cochrane Library, the China National Knowledge Infrastructure (CNKI) and Wanfang databases for the corresponding studies. Each study reported the risk estimate and 95% confidence intervals (CI) for lung cancer, and a fixed effects model or random effects model was used for outcome.

Results
We included 31 publications involving 6,589,383 people with 62,246 cases of lung cancer. Diabetes mellitus (DM) (RR = 1.11, 95% CI  1.06–1.16, P = 0.000) and IR (RR = 2.35, 95% CI  1.55–3.58, P = 0.000) showed a positive association with lung cancer risk. BMI (RR = 0.66, 95% CI  0.54–0.81, P = 0.000) and HDL-C (RR = 0.88, 95% CI  0.79–0.97, P = 0.010) were negatively correlated with lung cancer. MetS(RR = 0.99, 95% CI  0.90–1.09, P = 0.801), TC (RR = 0.93, 95% CI  0.81–1.06, P = 0.274), TG (RR = 0.99, 95% CI  0.88–1.12,P = 0.884), LDL-C (RR = 1.01, 95% CI  0.87–1.16, P = 0.928), hypertension (RR = 1.01, 95% CI  0.88–1.15, P = 0.928), FBG (RR = 1.02, 95% CI  0.92–1.13, P = 0.677) and obesity (RR = 1.11, 95% CI  0.92–1.35, P = 0.280) were not associated with lung cancer.

Conclusion
Our study showed that the risk of lung cancer is correlated with DM, IR, BMI, and HDL-C. Timely control of these metabolic disorders may have a positive effect on preventing lung cancer.
Trial registration Our study has been registered in the Prospective Register of Systematic Reviews (PROSPERO), ID: CRD42023390710.
The role of Smarcad1 in retroviral repression in mouse embryonic stem cells
Authors: Bren Igor , Tal Ayellet , Strauss Carmit , Schlesinger Sharon 
Published: March 2024

Abstract
Background
Moloney murine leukemia virus (MLV) replication is suppressed in mouse embryonic stem cells (ESCs) by the Trim28-SETDB1 complex. The chromatin remodeler Smarcad1 interacts with Trim28 and was suggested to allow the deposition of the histone variant H3.3. However, the role of Trim28, H3.3, and Smarcad1 in MLV repression in ESCs still needs to be fully understood.

Results
In this study, we used MLV to explore the role of Smarcad1 in retroviral silencing in ESCs. We show that Smarcad1 is immediately recruited to the MLV provirus. Based on the repression dynamics of a GFP-reporter MLV, our findings suggest that Smarcad1 plays a critical role in the establishment and maintenance of MLV repression, as well as other Trim28-targeted genomic loci. Furthermore, Smarcad1 is important for stabilizing and strengthening Trim28 binding to the provirus over time, and its presence around the provirus is needed for proper deposition of H3.3 on the provirus. Surprisingly, the combined depletion of Smarcad1 and Trim28 results in enhanced MLV derepression, suggesting that these two proteins may also function independently to maintain repressive chromatin states.

Conclusions
Overall, the results of this study provide evidence for the crucial role of Smarcad1 in the silencing of retroviral elements in embryonic stem cells. Further research is needed to fully understand how Smarcad1 and Trim28 cooperate and their implications for gene expression and genomic stability.
Reducing the energy consumption of buildings by implementing insulation scenarios and using renewable energies
Authors: Shahee Arash , Abdoos Mahmood , Aslani Alireza , Zahedi Rahim 
Published: March 2024

AbstractThe reduction of fossil energy sources, the harmful environmental effects caused by high energy consumption, and the increase in the share of energy consumption in the building sector have increased the need to pay attention to building energy consumption. This study offers an intricate examination of a residential locality in Florida, with a particular emphasis on the architectural design of a building, issues related to the local environment and several possibilities for enhancing energy efficiency. It examines the influence of the environment in the area on architectural design and investigates two different possibilities for improving energy efficiency. The first scenario focuses on assessing thermal insulation and shading, while the second scenario envisions utilizing photovoltaic cells to achieve a zero-energy building. The proposed initiatives seek to optimize energy efficiency, save expenses, and foster environmental sustainability in the region. In this research, the total energy consumption of a building with residential use in the climate of the case study was validated by DesignBuilder®simulation software, and the results obtained from the software. Then, using the standard of energy consumption of the building, various strategies for optimizing energy consumption have been simulated. Using energy simulation software, solutions for using external horizontal awnings and installing a thermal insulation sheet on the external wall of the building were investigated, which resulted in a reduction of 200 kWh of energy consumption compared to the normal state. Then, the building’s energy consumption intensity was calculated for each of the proposed solutions, and the building’s energy classification was determined with energy star and LEED standards.
Demographic and Clinical Factors Associated With Health-Related Quality-of-Life Profiles Among Prostate Cancer Survivors
Authors: Potosky Arnold L. , Ahn Jaeil , Xia Yi , Lin Li , Chen Ronald C. , Graves Kristi D. , Pan Wei , Fall-Dickson Jane M. , Keegan Theresa H.M. , Paddock Lisa E. , Wu Xiao-Cheng , Shrestha Anshu , Reeve Bryce B. 
Published: March 2024

PURPOSE Our purpose was to describe the prevalence and predictors of symptom and function clusters related to physical, emotional, and social components of general health-related quality of life (HRQOL) in a population-based sample of prostate cancer (PCa) survivors. METHODS Participants (N = 1,162) completed a baseline survey at a median of 9 months after diagnosis to ascertain the co-occurrence of eight symptom and functional domains that are common across all cancers and not treatment-specific. We used latent profile analysis (LPA) to identify subgroup profiles of survivors with low, moderate, or high HRQOL levels. Multinomial logistic regression models were used to identify clinical and sociodemographic factors associated with survivors' membership in the low versus moderate or high HRQOL profile. RESULTS The LPA identified 16% of survivors who were categorized in the low HRQOL profile at baseline, indicative of the highest symptom burden and lowest functioning. Factors related to survivors' membership in the low versus higher HRQOL profile groups included less than age 65 years at diagnosis, identifying as non-Hispanic Black race, not working, being a former versus never smoker, systemic therapy, less companionship, more comorbidities, lower health care financial well-being, or less spirituality. Several factors remained associated with remaining in the low versus higher HRQOL profiles on the follow-up survey (n = 699), including younger age, Black race, comorbidity, and lower financial and spiritual well-being. CONCLUSION About one of six PCa survivors experienced elevated physical and psychosocial symptoms that were independent of local curative therapy, but with younger age, race, comorbidity, and lower financial and spiritual well-being as stable risk factors for poor HRQOL over time.
The Drosophila neuroblast polarity cycle at a glance
Authors: Penkert Rhiannon R. , LaFoya Bryce , Moholt-Siebert Lucille , Vargas Elizabeth , Welch Sarah E. , Prehoda Kenneth E. 
Published: March 2024

ABSTRACT
Drosophila neural stem cells, or neuroblasts, rapidly proliferate during embryonic and larval development to populate the central nervous system. Neuroblasts divide asymmetrically to create cellular diversity, with each division producing one sibling cell that retains the neuroblast fate and another that differentiates into glia or neurons. This asymmetric outcome is mediated by the transient polarization of numerous factors to the cell cortex during mitosis. The powerful genetics and outstanding imaging tractability of the neuroblast make it an excellent model system for studying the mechanisms of cell polarity. This Cell Science at a Glance article and the accompanying poster explore the phases of the neuroblast polarity cycle and the regulatory circuits that control them. We discuss the key features of the cycle – the targeted recruitment of proteins to specific regions of the plasma membrane and multiple phases of highly dynamic actomyosin-dependent cortical flows that pattern both protein distribution and membrane structure.
Bartonella henselae related unilateral anterior uveitis and subsequent multifocal retinitis in a case under certolizumab treatment
Authors: Kayabaşı Mustafa , Kefeli Işıl , Çakar Özdal Pınar , Saatci Ali Osman 
Published: March 2024

Introduction: A case of ocular bartonellosis under anti-tumour necrosis factor treatment is described. Case description: A 29-year-old woman with psoriasis who had been on certolizumab treatment was examined with a left visual deterioration following a fever bout, malaise, and placoid erythematous rashes on her neck. As there was acute anterior uveitis in her left eye, it was recommended to stop certolizumab treatment for a possible infectious aetiology. However, her physician elected to continue the certolizumab treatment. Ten days later, the patient noticed further visual decline despite the topical steroid treatment. This time, there were scattered yellow-white small retinitis foci at the left posterior pole. Infectious agents were searched and while Bartonella henselae antibodies were negative for immunoglobulin M, the immunoglobulin G titre was 1/80. Clinical findings were improved with the systemic treatment of oral trimethoprim-sulfamethoxazole (160/800 mg twice daily for six weeks) and azithromycin (500 mg once daily for two weeks). Discussion: Though extremely rare, ocular bartonellosis should be kept in mind in patients on anti-tumour necrosis factor treatment as rapid and accurate diagnosis may end up with an excellent visual outcome and full recovery.