bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen Therapy Induces Receptor-Dependent DNA Damage Enhanced by PARP Inhibition in ER+ Breast Cancer
Authors: Traphagen Nicole A. , Schwartz Gary N. , Tau Steven , Roberts Alyssa M. , Jiang Amanda , Hosford Sarah R. , Marotti Jonathan D. , Goen Abigail E. , Romo Bianca A. , Johnson Anneka L. , Duffy Emily-Claire K. , Demidenko Eugene , Heverly Paul , Mosesson Yaron , Soucy Shannon M. , Kolling Fred , Miller Todd W. 
Published: July 2023

Abstract

Purpose:
Clinical evidence indicates that treatment with estrogens elicits anticancer effects in ∼30% of patients with advanced endocrine-resistant estrogen receptor α (ER)-positive breast cancer. Despite the proven efficacy of estrogen therapy, its mechanism of action is unclear and this treatment remains underused. Mechanistic understanding may offer strategies to enhance therapeutic efficacy.

Experimental Design:
We performed genome-wide CRISPR/Cas9 screening and transcriptomic profiling in long-term estrogen-deprived ER+ breast cancer cells to identify pathways required for therapeutic response to the estrogen 17β-estradiol (E2). We validated findings in cell lines, patient-derived xenografts (PDX), and patient samples, and developed a novel combination treatment through testing in cell lines and PDX models.

Results:
Cells treated with E2 exhibited replication-dependent markers of DNA damage and the DNA damage response prior to apoptosis. Such DNA damage was partially driven by the formation of DNA:RNA hybrids (R-loops). Pharmacologic suppression of the DNA damage response via PARP inhibition with olaparib enhanced E2-induced DNA damage. PARP inhibition synergized with E2 to suppress growth and prevent tumor recurrence in BRCA1/2-mutant and BRCA1/2-wild-type cell line and PDX models.

Conclusions:
E2-induced ER activity drives DNA damage and growth inhibition in endocrine-resistant breast cancer cells. Inhibition of the DNA damage response using drugs such as PARP inhibitors can enhance therapeutic response to E2. These findings warrant clinical exploration of the combination of E2 with DNA damage response inhibitors in advanced ER+ breast cancer, and suggest that PARP inhibitors may synergize with therapeutics that exacerbate transcriptional stress.
Development and Multicenter Case–Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction
Authors: Salari Keyan , Sundi Debasish , Lee Jason J. , Wu Shulin , Wu Chin-Lee , DiFiore Gabrielle , Yan Q. Robert , Pienkny Andrew , Lee Chi K. , Oberlin Daniel , Barme Greg , Piser Joel , Kahn Robert , Collins Edward , Phillips Kevin G. , Caruso Vincent M. , Goudarzi Mahdi , Garcia-Ransom Monica , Lentz Peter S. , Evans-Holm Martha E. , MacBride Andrew R. , Fischer Daniel S. , Haddadzadeh Iden J. , Mazzarella Brian C. , Gray Joe W. , Koppie Theresa M. , Bicocca Vincent T. , Levin Trevor G. , Lotan Yair , Feldman Adam S. 
Published: July 2023

Abstract

Purpose:
Urinary comprehensive genomic profiling (uCGP) uses next-generation sequencing to identify mutations associated with urothelial carcinoma and has the potential to improve patient outcomes by noninvasively diagnosing disease, predicting grade and stage, and estimating recurrence risk.

Experimental Design:
This is a multicenter case–control study using banked urine specimens collected from patients undergoing initial diagnosis/hematuria workup or urothelial carcinoma surveillance. A total of 581 samples were analyzed by uCGP: 333 for disease classification and grading algorithm development, and 248 for blinded validation. uCGP testing was done using the UroAmp platform, which identifies five classes of mutation: single-nucleotide variants, copy-number variants, small insertion-deletions, copy-neutral loss of heterozygosity, and aneuploidy. UroAmp algorithms predicting urothelial carcinoma tumor presence, grade, and recurrence risk were compared with cytology, cystoscopy, and pathology.

Results:
uCGP algorithms had a validation sensitivity/specificity of 95%/90% for initial cancer diagnosis in patients with hematuria and demonstrated a negative predictive value (NPV) of 99%. A positive diagnostic likelihood ratio (DLR) of 9.2 and a negative DLR of 0.05 demonstrate the ability to risk-stratify patients presenting with hematuria. In surveillance patients, binary urothelial carcinoma classification demonstrated an NPV of 91%. uCGP recurrence-risk prediction significantly prognosticated future recurrence (hazard ratio, 6.2), whereas clinical risk factors did not. uCGP demonstrated positive predictive value (PPV) comparable with cytology (45% vs. 42%) with much higher sensitivity (79% vs. 25%). Finally, molecular grade predictions had a PPV of 88% and a specificity of 95%.

Conclusions:
uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients.
Neoadjuvant Cabazitaxel plus Abiraterone/Leuprolide Acetate in Patients with High-Risk Prostate Cancer: ACDC-RP Phase II Trial
Authors: Fleshner Neil E. , Sayyid Rashid K. , Hansen Aaron R. , Chin Joseph L.K. , Fernandes Ricardo , Winquist Eric , van der Kwast Theodorus , Sweet Joan , Lajkosz Katherine , Kenk Miran , Hersey Karen , Veloso Rosette , Berlin Doron , Herrera-Caceres Jaime O. , Sridhar Srikala , Moussa Madeleine , Finelli Antonio , Hamilton Robert J. , Kulkarni Girish S. , Zlotta Alexandre R. , Joshua Anthony M. 
Published: July 2023

Abstract

Purpose:
Early treatment intensification with neoadjuvant therapy may improve outcomes in patients with high-risk, localized prostate cancer treated with radical prostatectomy. Our objective was to compare pathologic, oncologic, and safety outcomes of neoadjuvant abiraterone acetate plus leuprolide acetate with or without cabazitaxel prior to radical prostatectomy in patients with localized, high-risk prostate cancer.

Patients and Methods:
This open-label, multicenter, phase II trial randomized men with clinically localized, D'Amico high-risk prostate cancer to neoadjuvant abiraterone acetate (1,000 mg/day) and leuprolide acetate (22.5 mg every 3 months) with or without cabazitaxel (25 mg/m2) prior to radical prostatectomy. The primary outcome was pathologic complete response (pCR) or minimal residual disease (MRD). Secondary outcomes included surgical margins, lymph node involvement, pathologic stage, 12-month biochemical relapse-free survival (BRFS) rates, and safety profile.

Results:
The per-protocol population consisted of 70 patients [cabazitaxel arm (Arm A): 37, no cabazitaxel arm (Arm B): 33]. Median patient age and prostate-specific antigen levels were 63.5 years [interquartile range (IQR), 58.0–68.0] and 21.9 ng/mL (IQR, 14.6–42.8), respectively. pCR/MRD occurred in 16 (43.2%) versus 15 patients (45.5%) in arms A and B, respectively (P = 0.85). pCR occurred in two (5.4%) versus three patients (9.1%) in arms A and B, respectively (P = 0.66). Patients with ≤ 25% total biopsy cores positive had increased odds of pCR/MRD (P = 0.04). Patients with pCR/MRD had superior 12-month BRFS rates (96.0% vs. 62.0%, P = 0.03). Grade 3+ adverse events occurred in 42.5% and 23.7% of patients in arms A and B, respectively (P = 0.078).

Conclusions:
Neoadjuvant cabazitaxel addition to abiraterone acetate/leuprolide acetate prior to radical prostatectomy did not improve pCR/MRD in clinically localized, high-risk prostate cancer.
Pan-Cancer Pharmacogenomic Analysis of Patient-Derived Tumor Cells Using Clinically Relevant Drug Exposures
Authors: Chang Stephen H. , Ice Ryan J. , Chen Michelle , Sidorov Maxim , Woo Rinette W.L. , Rodriguez-Brotons Aida , Jian Damon , Kim Han Kyul , Kim Angela , Stone David E. , Nazarian Ari , Oh Alyssia , Tranah Gregory J. , Nosrati Mehdi , de Semir David , Dar Altaf A. , Desprez Pierre-Yves , Kashani-Sabet Mohammed , Soroceanu Liliana , McAllister Sean D. 
Published: July 2023

Abstract
As a result of tumor heterogeneity and solid cancers harboring multiple molecular defects, precision medicine platforms in oncology are most effective when both genetic and pharmacologic determinants of a tumor are evaluated. Expandable patient-derived xenograft (PDX) mouse tumor and corresponding PDX culture (PDXC) models recapitulate many of the biological and genetic characteristics of the original patient tumor, allowing for a comprehensive pharmacogenomic analysis. Here, the somatic mutations of 23 matched patient tumor and PDX samples encompassing four cancers were first evaluated using next-generation sequencing (NGS). 19 antitumor agents were evaluated across 78 patient-derived tumor cultures using clinically relevant drug exposures. A binarization threshold sensitivity classification determined in culture (PDXC) was used to identify tumors that best respond to drug in vivo (PDX). Using this sensitivity classification, logic models of DNA mutations were developed for 19 antitumor agents to predict drug response. We determined that the concordance of somatic mutations across patient and corresponding PDX samples increased as variant allele frequency increased. Notable individual PDXC responses to specific drugs, as well as lineage-specific drug responses were identified. Robust responses identified in PDXC were recapitulated in vivo in PDX-bearing mice and logic modeling determined somatic gene mutation(s) defining response to specific antitumor agents. In conclusion, combining NGS of primary patient tumors, high-throughput drug screen using clinically relevant doses, and logic modeling, can provide a platform for understanding response to therapeutic drugs targeting cancer.
Viability and fertility of cryopreserved pollen of Brinjal and its wild relatives
Authors: Rajasekharan P.E. , Ravi Harsha 
Published: July 2023

Abstract
The Solanum wild relatives are valuable for developing pest and disease-resistant lines in the breeding program of S. melongena (brinjal). However, breeding new varieties that are superior to the existing ones in S. melongena faces several challenges. To overcome geographical and seasonal barriers, a breeding strategy involving pollen cryopreservation may be helpful. Fifteen different Solanum species/accessions of wild relatives and two accessions from cultivated species were studied for in vitro germination and fertility. Among these S. indicum accessions exhibited the highest fresh pollen germination of 92.7 ± 0.7 (JRPH/15–154) and 88.2 ± 3.2% after 1 year and 4 months of cryostorage. In vivo fertility was estimated by quantifying fruit set after pollination with both fresh and cryopreserved pollen. The cryopreserved pollen was able to set fruit (91.5 ± 0.5 in JRPH/15–154) compared to fresh pollen (100%). Scanning Electron Microscopic studies (SEM) were conducted on both fresh and cryopreserved pollen, and various morphological parameters such as pollen length, breadth, and perimeter were recorded for all the accessions and species. These studies explore the possibility of establishing a pollen cryobank for Solanum wild species.
Unsupervised Clustering of Geostationary Satellite Cloud Properties for Estimating Precipitation Probabilities of Tropical Convective Clouds
Authors: Kim Doyi , Kim Hee-Jae , Choi Yong-Sang 
Published: July 2023

Abstract
Understanding the growth of tropical convective clouds (TCCs) is of vital importance for the early detection of heavy rainfall. This study explores the properties of TCCs that can cause them to develop into clouds with a high probability of precipitation. Remotely sensed cloud properties, such as cloud-top temperature (CTT), cloud optical thickness (COT), and cloud effective radius (CER) as measured by a geostationary satellite are trained by a neural network. First, the image segmentation algorithm identifies TCC objects with different cloud properties. Second, a self-organizing map (SOM) algorithm clusters TCC objects with similar cloud microphysical properties. Third, the precipitation probability (PP) for each cluster of TCCs is calculated based on the proportion of precipitating TCCs among the total number of TCCs. Precipitating TCCs can be distinguished from nonprecipitating TCCs using Integrated Multi-Satellite Retrievals for Global Precipitation Measurement precipitation data. Results show that SOM clusters with a high PP (>70%) satisfy a certain range of cloud properties: CER ≥ 20 μm and CTT < 230 K. PP generally increases with increasing COT, but COT cannot be a clear cloud property to confirm a high PP. For relatively thin clouds (COT < 30), however, CER should be much larger than 20 μm to have a high PP. More importantly, these TCC conditions associated with a PP ≥ 70% are consistent across regions and periods. We expect our results will be useful for satellite nowcasting of tropical precipitation using geostationary satellite cloud properties.

Significance Statement
We aim to identify the properties of tropical convective clouds (TCCs) that have a high precipitation probability. We designed a two-step framework to identify TCC objects and the conditions of cloud properties for TCCs to have a high precipitation probability. The TCCs with a precipitation probability > 70% tend to have a low cloud-top temperature and a cloud particle effective radius ≥ 20 μm. Cloud optical thicknesses are distributed over a wide range, but thinning requires a particle radius larger than 20 μm. These conditions of cloud properties appear to be unchanged under various spatial–temporal conditions over the tropics. This important observational finding advances our understanding of the cloud–precipitation relationship in TCCs and can be applied to satellite nowcasting of precipitation in the tropics, where numerical weather forecasts are limited.
Development of Zn/Ce containing bioactive glasses for bone regeneration applications
Authors: Naruphontjirakul Parichart , Suwanakitti Nattida 
Published: July 2023

The impact of either Zn or Ce substituted with Ca in bioactive glasses based on the 45SiO2 - 6P2O5 - 11SrO - (38-(x + y) CaO) - xZnO or yCe2O3 (xZn-yCeBGs) system on bone regeneration has not yet been reported. The aim of this study was to develop new formulations of sol-gel-derived bioactive glass to use as a synthetic bone graft. xZn-yCeBGs were synthesized through the sol-gel process with 0.01 M nitric acid catalyst. xZn-yCeBG formation was investigated using SEM and FTIR. The bioactivity of xZn-yCeBGs was evaluated using SEM, EDX-SEM, and XRD. Cell viability and ability to form mineralization of MC3T3-E1 treated with xZn-yCeBGs were detected using MTT assay and Alizarin Red S staining, respectively. xZn-yCeBGs were successfully prepared. Zn or Ce substituted with Ca in BGs stimulated bioactivity through apatite formation, enhanced bone mineralization, and were not toxic to the bone cells. Moreover, these particles had an antibacterial effect against Escherichia coli ( E. coli) and Staphylococcus aureus ( S. aureus) via the disc diffusion method. Therefore, xZn-yCeBGs are a promising unique biomaterial with a potential future role as bone graft substitutes.
Global prevalence of myopic macular degeneration in general population and patients with high myopia: A systematic review and meta-analysis
Authors: Shi Hekai , Guo Nuojin , Zhao Zeming , He Xiaoyu , Li Jiahang , Duan Jialiang 
Published: July 2023

The prevalence of myopic macular degeneration (MMD) in the general population and patients with high myopia worldwide has not been fully investigated. Therefore, we screened all population-based studies that reported the prevalence of MMD, and pooled prevalence of MMD using a random-effect model. Subgroup analyses were performed to explore the differences in MMD prevalence in the general population and patients with high myopia according to ethnicity, region of residence (urban/rural), and grading system. Finally, 16 studies were included in this meta-analysis. Results obtained from 2,963 patients from seven countries on four continents indicated that the pooled prevalence of MMD in patients with high myopia was 49.0% (95% CI: 31.5%–66.7%). Results obtained from 71,052 participants from 10 countries on four continents suggested that the pooled prevalence of MMD in the general population was 1.7% (95% CI: 1.1%–2.6%). In the general population, living in urban areas and East Asians were associated with a high prevalence of MMD. Among patients with high myopia, only East Asians were at a higher risk of developing MMD. In conclusion, MMD was particularly prevalent in patients with high myopia. Compared with Europeans, East Asians (Chinese and Japanese) have a higher propensity of developing MMD, both in the general population and in patients with high myopia. It remains unclear whether the higher prevalence of MMD in patients with high myopia in East Asia is caused by differences in given age or given degree of myopia.Systematic review registration number: 202270014 (INPLASY.COM).
Ways and means to comfort people at the end of life: how is the nurse a privileged player in this process?
Authors: Pereira Raquel Alexandra Machado , Sousa Valente Ribeiro Patrícia Cruz Pontífice 
Published: July 2023

Background: Comfort is a necessity throughout life, and it is a key element in the practice of nursing care for the patient at the end of life. A particular human need and a state related to the experience and culture of the person at the end of life constitute the target of attention and nursing intervention, being a very relevant indicator of the quality of health care. This article is part of a doctoral study in the field of comfort in a palliative care unit, and these are some of the partial results that emerged. Objectives: To understand the ways and means of comfort perceived by the person at the end-of-life hospitalized in a palliative care unit, their family, and health staff as well as the value of the nurse in this process. Design: Qualitative study using an ethnographic approach. Methods: We conducted semistructured interviews with 18 patients at the end of life and their matched significant family members (18) and 21 health professionals. We also conducted participant observation of care situations. Results/Discussion: The ways and means of providing comfort are centered on strategies developed by the entire multidisciplinary team. During this whole process, one of the categories that emerged from the ethnography was the nurse as a privileged player, representing an absolutely essential role in all phases. The results revealed that nurses play a very important role in end-of-life comfort, which is based on a predisposition for end-of-life care (active listening, empathy, congruence, and biographical narrative) and focused attention (global care, attention to detail, family support, and opposition to therapeutic obstinacy). Conclusions: The different ways and means of providing comfort aim to increase care, relieve, and invest in potential different forms of comfort and nurses are recognized by all those involved in this process as someone essential to providing comfort care.
Lung volumes differentiate the predominance of emphysemaversusairway disease phenotype in early COPD: an observational study of the COPDGene cohort
Authors: Zeng Siyang , Luo Gang , Lynch David A. , Bowler Russell P. , Arjomandi Mehrdad 
Published: July 2023

RationaleLung volumes identify the “susceptible smokers” who progress to develop spirometric COPD. However, among susceptible smokers, development of spirometric COPD seems to be heterogeneous, suggesting the presence of different pathological mechanisms during early establishment of spirometric COPD. The objective of the present study was to determine the differential patterns of radiographic pathologies among susceptible smokers.MethodsWe categorised smokers with preserved spirometry (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0) in the Genetic Epidemiology of COPD (COPDGene) cohort based on tertiles (low, intermediate and high) of lung volumes (either total lung capacity (TLC), functional residual capacity FRC or FRC/TLC) at baseline visit. We then examined the differential patterns of change in spirometry and the associated prevalence of computed tomography measured pathologies of emphysema and airway disease with those categories of lung volumes.ResultsThe pattern of spirometric change differed when participants were categorised by TLCversusFRC/TLC: those in the high TLC tertile showed stable forced expiratory volume in 1 s (FEV1), but enlarging forced vital capacity (FVC), while those in the high FRC/TLC tertile showed decline in both FEV1and FVC. When participants from the high TLC and high FRC/TLC tertiles were partitioned into mutually exclusive groups, compared to those with high TLC, those with high FRC/TLC had lesser emphysema, but greater air trapping, more self-reported respiratory symptoms and exacerbation episodes and higher likelihood of progressing to more severe spirometric disease (GOLD stages 2–4versusGOLD stage 1).ConclusionsLung volumes identify distinct physiological and radiographic phenotypes in early disease among susceptible smokers and predict the rate of spirometric disease progression and the severity of symptoms in early COPD.
Glycogen availability and pH variation in a medium simulating vaginal fluid influence the growth of vaginal Lactobacillus species and Gardnerella vaginalis
Authors: Navarro Stephany , Abla Habib , Delgado Betsaida , Colmer-Hamood Jane A. , Ventolini Gary , Hamood Abdul N. 
Published: July 2023

Abstract
Background
Glycogen metabolism by Lactobacillus spp. that dominate the healthy vaginal microbiome contributes to a low vaginal pH (3.5–4.5). During bacterial vaginosis (BV), strict and facultative anaerobes including Gardnerella vaginalis become predominant, leading to an increase in the vaginal pH (> 4.5). BV enhances the risk of obstetrical complications, acquisition of sexually transmitted infections, and cervical cancer. Factors critical for the maintenance of the healthy vaginal microbiome or the transition to the BV microbiome are not well defined. Vaginal pH may affect glycogen metabolism by the vaginal microflora, thus influencing the shift in the vaginal microbiome.

Results
The medium simulating vaginal fluid (MSVF) supported growth of L. jensenii 62G, L. gasseri 63 AM, and L. crispatus JV-V01, and G. vaginalis JCP8151A at specific initial pH conditions for 30 d. L. jensenii at all three starting pH levels (pH 4.0, 4.5, and 5.0), G. vaginalis at pH 4.5 and 5.0, and L. gasseri at pH 5.0 exhibited the long-term stationary phase when grown in MSVF. L. gasseri at pH 4.5 and L. crispatus at pH 5.0 displayed an extended lag phase over 30 d suggesting inefficient glycogen metabolism. Glycogen was essential for the growth of L. jensenii, L. crispatus, and G. vaginalis; only L. gasseri was able to survive in MSVF without glycogen, and only at pH 5.0, where it used glucose. All four species were able to survive for 15 d in MSVF with half the glycogen content but only at specific starting pH levels – pH 4.5 and 5.0 for L. jensenii, L. gasseri, and G. vaginalis and pH 5.0 for L. crispatus.

Conclusions
These results suggest that variations in the vaginal pH critically influence the colonization of the vaginal tract by lactobacilli and G. vaginalis JCP8151A by affecting their ability to metabolize glycogen. Further, we found that L. jensenii 62G is capable of glycogen metabolism over a broader pH range (4.0–5.0) while L. crispatus JV-V01 glycogen utilization is pH sensitive (only functional at pH 5.0). Finally, our results showed that G. vaginalis JCP8151A can colonize the vaginal tract for an extended period as long as the pH remains at 4.5 or above.