bluuebunny/crossref_metadata_2025_split huggingface dataset:
Steroid Hormone Receptor and Infiltrating Immune Cell Status Reveals Therapeutic Vulnerabilities of ESR1-Mutant Breast Cancer
Authors: Williams Michelle M. , Spoelstra Nicole S. , Arnesen Spencer , O'Neill Kathleen I. , Christenson Jessica L. , Reese Jordan , Torkko Kathleen C. , Goodspeed Andrew , Rosas Emmanuel , Hanamura Toru , Sams Sharon B. , Li Zheqi , Oesterreich Steffi , Riggins Rebecca B. , Jacobsen Britta M. , Elias Anthony , Gertz Jason , Richer Jennifer K. 
Published: November 2020

Abstract

Mutations in ESR1 that confer constitutive estrogen receptor alpha (ER) activity in the absence of ligand are acquired by ≥40% of metastatic breast cancers (MBC) resistant to adjuvant aromatase inhibitor (AI) therapy. To identify targetable vulnerabilities in MBC, we examined steroid hormone receptors and tumor-infiltrating immune cells in metastatic lesions with or without ER mutations. ER and progesterone receptor (PR) were significantly lower in metastases with wild-type (WT) ER compared with those with mutant ER, suggesting that metastases that evade AI therapy by mechanism(s) other than acquiring ER mutations lose dependency on ER and PR. Metastases with mutant ER had significantly higher T regulatory and Th cells, total macrophages, and programmed death ligand-1 (PD-L1)-positive immune-suppressive macrophages than those with WT ER. Breast cancer cells with CRISPR-Cas9–edited ER (D538G, Y537S, or WT) and patient-derived xenografts harboring mutant or WT ER revealed genes and proteins elevated in mutant ER cells, including androgen receptor (AR), chitinase-3-like protein 1 (CHI3L1), and IFN-stimulated genes (ISG). Targeting these proteins blunted the selective advantage of ER-mutant tumor cells to survive estrogen deprivation, anchorage independence, and invasion. Thus, patients with mutant ER MBC might respond to standard-of-care fulvestrant or other selective ER degraders when combined with AR or CHI3L1 inhibition, perhaps with the addition of immunotherapy.

Significance:
Targetable alterations in MBC, including AR, CHI3L1, and ISG, arise following estrogen-deprivation, and ER-mutant metastases may respond to immunotherapies due to elevated PD-L1+ macrophages.
See related article by Arnesen et al., p. 539
Replication Gaps Underlie BRCA Deficiency and Therapy Response
Authors: Panzarino Nicholas J. , Krais John J. , Cong Ke , Peng Min , Mosqueda Michelle , Nayak Sumeet U. , Bond Samuel M. , Calvo Jennifer A. , Doshi Mihir B. , Bere Matt , Ou Jianhong , Deng Bin , Zhu Lihua J. , Johnson Neil , Cantor Sharon B. 
Published: November 2020

Abstract

Defects in DNA repair and the protection of stalled DNA replication forks are thought to underlie the chemosensitivity of tumors deficient in the hereditary breast cancer genes BRCA1 and BRCA2 (BRCA). Challenging this assumption are recent findings that indicate chemotherapies, such as cisplatin used to treat BRCA-deficient tumors, do not initially cause DNA double-strand breaks (DSB). Here, we show that ssDNA replication gaps underlie the hypersensitivity of BRCA-deficient cancer and that defects in homologous recombination (HR) or fork protection (FP) do not. In BRCA-deficient cells, ssDNA gaps developed because replication was not effectively restrained in response to stress. Gap suppression by either restoration of fork restraint or gap filling conferred therapy resistance in tissue culture and BRCA patient tumors. In contrast, restored FP and HR could be uncoupled from therapy resistance when gaps were present. Moreover, DSBs were not detected after therapy when apoptosis was inhibited, supporting a framework in which DSBs are not directly induced by genotoxic agents, but rather are induced from cell death nucleases and are not fundamental to the mechanism of action of genotoxic agents. Together, these data indicate that ssDNA replication gaps underlie the BRCA cancer phenotype, “BRCAness,” and we propose they are fundamental to the mechanism of action of genotoxic chemotherapies.

Significance:
This study suggests that ssDNA replication gaps are fundamental to the toxicity of genotoxic agents and underlie the BRCA-cancer phenotype “BRCAness,” yielding promising biomarkers, targets, and opportunities to resensitize refractory disease.
See related commentary by Canman, p. 1214
History and Data Records of the Automatic Weather Station on Denali Pass (5715 m), 1990–2007
Authors: Hartl Lea , Stuefer Martin , Saito Tohru , Okura Yoshitomi 
Published: November 2020

AbstractWe present the data records and station history of an automatic weather station (AWS) on Denali Pass (5715 m MSL), Alaska. The station was installed by a team of climbers from the Japanese Alpine Club after a fatal accident involving Japanese climbers in 1989 and was operational intermittently between 1990 and 2007, measuring primarily air temperature and wind speed. In later years, the AWS was operated by the International Arctic Research Center of the University of Alaska Fairbanks. Station history is reconstructed from available documentation as archived by the expedition teams. To extract and preserve data records, the original datalogger files were processed. We highlight numerous challenges and sources of uncertainty resulting from the location of the station and the circumstances of its operation. The data records exemplify the harsh meteorological conditions at the site: air temperatures down to approximately −60°C were recorded, and wind speeds reached values in excess of 60 m s−1. Measured temperatures correlate strongly with reanalysis data at the 500-hPa level. An approximation of critical wind speed thresholds and a reanalysis-based reconstruction of the meteorological conditions during the 1989 accident confirm that the climbers faced extremely hazardous wind speeds and very low temperatures. The data from the Denali Pass AWS represent a unique historical record that can, we hope, serve as a basis for further monitoring efforts in the summit region of Denali.
Uncertainty in Forced and Natural Arctic Solar Absorption Variations in CMIP6 Models
Authors: Sledd Anne , L’Ecuyer Tristan 
Published: November 2020

AbstractThe Arctic is rapidly changing, with increasingly dramatic sea ice loss and surface warming in recent decades. Shortwave radiation plays a key role in Arctic warming during summer months, and absorbed shortwave radiation has been increasing largely because of greater sea ice loss. Clouds can influence this ice–albedo feedback by modulating the amount of shortwave radiation incident on the Arctic Ocean. In turn, clouds impact the amount of time that must elapse before forced trends in Arctic shortwave absorption emerge from internal variability. This study determines whether the forced climate response of absorbed shortwave radiation in the Arctic has emerged in the modern satellite record and global climate models. From 18 years of satellite observations from CERES-EBAF, we find that recent declines in sea ice are large enough to produce a statistically significant trend (1.7 × 106 PJ or 3.9% per decade) in observed clear-sky absorbed shortwave radiation. However, clouds preclude any forced trends in all-sky absorption from emerging within the existing satellite record. Across 18 models from phase 6 of the Coupled Model Intercomparison Project (CMIP6), the predicted time to emergence of absorbed shortwave radiation trends varies from 8 to 39 and from 8 to 35 years for all-sky and clear-sky conditions, respectively, across two future scenarios. Furthermore, most models fail to reproduce the observed cloud delaying effect because of differences in internal variability. Contrary to observations, one-third of models suggest that clouds may reduce the time to emergence of absorbed shortwave trends relative to clear skies, an artifact that may be the result of inaccurate representations of cloud feedbacks.
An Assessment of Global Ocean Barotropic Tide Models Using Geodetic Mission Altimetry and Surface Drifters
Authors: Zaron Edward D. , Elipot Shane 
Published: November 2020

AbstractThe accuracy of three data-constrained barotropic ocean tide models is assessed by comparison with data from geodetic mission altimetry and ocean surface drifters, data sources chosen for their independence from the observational data used to develop the tide models. Because these data sources do not provide conventional time series at single locations suitable for harmonic analysis, model performance is evaluated using variance reduction statistics. The results distinguish between shallow and deep-water evaluations of the GOT410, TPXO9A, and FES2014 models; however, a hallmark of the comparisons is strong geographic variability that is not well summarized by global performance statistics. The models exhibit significant regionally coherent differences in performance that should be considered when choosing a model for a particular application. Quantitatively, the differences in explained SSH variance between the models in shallow water are only 1%–2% of the root-mean-square (RMS) tidal signal of about 50 cm, but the differences are larger at high latitudes, more than 10% of 30-cm RMS. Differences with respect to tidal currents variance are strongly influenced by small scales in shallow water and are not well represented by global averages; therefore, maps of model differences are provided. In deep water, the performance of the models is practically indistinguishable from one another using the present data. The foregoing statements apply to the eight dominant astronomical tides M2, S2, N2, K2, K1, O1, P1, and Q1. Variance reduction statistics for smaller tides are generally not accurate enough to differentiate the models’ performance.
Intra-Annual Rossby Waves Destabilization as a Potential Driver of Low-Latitude Zonal Jets: Barotropic Dynamics
Authors: Delpech Audrey , Ménesguen Claire , Morel Yves , Thomas Leif N. , Marin Frédéric , Cravatte Sophie , Le Gentil Sylvie 
Published: November 2020

AbstractAt low latitudes in the ocean, the deep currents are shaped into narrow jets flowing eastward and westward, reversing periodically with latitude between 15°S and 15°N. These jets are present from the thermocline to the bottom. The energy sources and the physical mechanisms responsible for their formation are still debated and poorly understood. This study explores the role of the destabilization of intra-annual equatorial waves in the jets’ formation process, as these waves are known to be an important energy source at low latitudes. The study focuses particularly on the role of barotropic Rossby waves as a first step toward understanding the relevant physical mechanisms. It is shown from a set of idealized numerical simulations and analytical solutions that nonlinear triad interactions (NLTIs) play a crucial role in the transfer of energy toward jet-like structures (long waves with short meridional wavelengths) that induce a zonal residual mean circulation. The sensitivity of the instability emergence and the scale selection of the jet-like secondary wave to the forced primary wave are analyzed. For realistic amplitudes around 5–20 cm s−1, the primary waves that produce the most realistic jet-like structures are zonally propagating intra-annual waves with periods between 60 and 130 days and wavelengths between 200 and 300 km. The NLTI mechanism is a first step toward the generation of a permanent jet-structured circulation and is discussed in the context of turbulent cascade theories.
Let’s Work Together: A Meta-Analysis on Robot Design Features That Enable Successful Human–Robot Interaction at Work
Authors: Ötting Sonja K. , Masjutin Lisa , Steil Jochen J. , Maier Günter W. 
Published: November 2020

Objective This meta-analysis reviews robot design features of interface, controller, and appearance and statistically summarizes their effect on successful human–robot interaction (HRI) at work (that is, task performance, cooperation, satisfaction, acceptance, trust, mental workload, and situation awareness). Background Robots are becoming an integral part of many workplaces. As interactions with employees increase, ensuring success becomes ever more vital. Even though many studies investigated robot design features, an overview on general and specific effects is missing. Method Systematic selection of literature and structured coding led to 81 included experimental studies containing 380 effect sizes. Mean effects were calculated using a three-level meta-analysis to handle dependencies of multiple effect sizes in one study. Results Sufficient feedback through the interface, clear visibility of affordances, and adaptability and autonomy of the controller significantly affect successful HRI, whereas appearance does not. The features of the interface and controller affect performance and satisfaction but do not affect situation awareness and trust. Specific effects of adaptability on cooperation and acceptance, as well as autonomy on mental workload, could be shown. Conclusion Robot design at work needs to cover multiple features of interface and controller to achieve successful HRI that covers not only performance and satisfaction, but also cooperation, acceptance, and mental workload. More empirical research is needed to investigate mediating mechanisms and underrepresented design features’ effects. Application Robot designers should carefully choose design features to balance specific effects and implementation costs with regard to tasks, work design aims, and employee needs in the specific work context.
Enabling Advance Care Planning in Dementia Care: A Primary Care Approach
Authors: Lee Linda , Hillier Loretta M. , Lu Stephanie K. , Ward Donna 
Published: November 2020

Background: Lack of tools to support advance care planning (ACP) has been identified as a significant barrier to implementing these discussions. Aim: We pilot tested an ACP framework tool for use with persons living with dementia (PLWD) in primary care-based memory clinics and an Adult Day Program; this study describes user and recipient experiences with this framework. Methods: We used a mixed methods approach. Health professionals completed an online survey following pilot testing and PLWD and substitute decision makers (SDM) completed survey immediately following the ACP discussion assessing their satisfaction (5-point scale) with the framework and exploring potential outcomes. Interviews with health professionals, PLWD, and SDM were conducted to gather more in-depth information on their perceptions of the ACP framework/ discussion. Results: Surveys were completed by 12 health professionals, 13 PLWD, and 16 SDM. While PLWD and SDM were satisfied with the ACP discussion (M = 4.0/5), health professionals were minimally satisfied with the ease of use of the framework (M = 2.0/5), acceptability for patients (M = 2.4/5) and feasibility in practice (M = 1.9/5). Sixteen interviews were completed with 8 health professionals, 1 PLWD, and 7 SDM. While health professionals valued ACP, lack of time and training were identified barriers to framework use. SDM felt better prepared for future decisions and PLWD were put at ease, knowing that their wishes for care were understood. Conclusion: PLWD and SDM value the opportunity for ACP, and although health professionals identified some concerns with framework administration, they acknowledge the value and importance of ACP. Continuing efforts to refine ACP processes are justified.
CD14 (C-159T) polymorphism is associated with increased susceptibility to SLE, and plasma levels of soluble CD14 is a novel biomarker of disease activity: A hospital-based case-control study
Authors: Panda Aditya K , Tripathy Rina , Das Bidyut K 
Published: November 2020

Background Cluster of differentiation 14 (CD14) plays a crucial role in the innate immune response of the host in protection against various pathogens. The importance of soluble CD14 in autoimmune disorders has been described in different populations. However, the role of sCD14 in systemic lupus erythematosus (SLE) is poorly understood. Further, the association of functional variants at the promoter region of the CD14 gene (−159 C > T) with susceptibility to SLE or disease severity needs to be defined. Methods Two hundred female SLE patients diagnosed on systemic lupus international collaborating clinics (SLICC) classification criteria and age, sex, matched healthy controls were enrolled in the present study. Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method was used to genotype CD14 (C-159 T) polymorphism. Plasma levels of IFN-α, TNF-α, and sCD14 were quantified by enzyme-linked immunosorbent assay (ELISA). Results Prevalence of mutant genotypes (CT and TT) and minor allele (T) of CD14 (C-159T) polymorphism was significantly higher in SLE cases compared to healthy controls (CT: P < 0.0001; OR = 3.26, TT:P < 0.0001; OR = 3.39; T:P = 0.0009, OR = 1.62). Further, lupus nephritis patients had a higher prevalence of homozygous mutants (TT) and mutant allele (T)(TT: P = 0.0002, OR = 8.07; T: P = 0.001, OR = 1.32). SLE patients displayed significantly increased plasma sCD14, TNF-α, and IFN-α levels in comparison to healthy controls. These cytokines were significantly elevated in patients of lupus nephritis compared to those without kidney involvement. Interestingly, sCD14 levels correlated positively with SLE disease activity index-2K (SLEDAI-2K) scores and 24 hours proteinuria. Conclusion CD14 (C-159T) polymorphism is associated with an increased predisposition to the development of SLE and lupus nephritis: sCD14 is a promising novel biomarker for assessing disease activity and lupus nephritis.
Effect of Metformin on Development of Tendinopathy Due to Mechanical Overloading in an Animal Model
Authors: Zhang Jianying , Li Feng , Nie Daibang , Onishi Kentaro , Hogan MaCalus V. , Wang James H-C. 
Published: November 2020

Background: Tendinopathy is a debilitating tendon disorder that affects millions of Americans and costs billions of health care dollars every year. High mobility group box 1 (HMGB1), a known tissue damage signaling molecule, has been identified as a mediator in the development of tendinopathy due to mechanical overloading of tendons in mice. Metformin (Met), a drug approved by the Food and Drug Administration used for the treatment of type 2 diabetes, specifically inhibits HMGB1. This study tested the hypothesis that Met would prevent mechanical overloading-induced tendinopathy in a mouse model of tendinopathy created by intensive treadmill running (ITR). Methods: C57BL/6J mice (female, 3 months old) were equally separated into 4 groups and treated for 24 weeks as follows: group 1 had cage control activities, group 2 received a single intraperitoneal injection of Met (50 mg/kg body weight) daily, group 3 underwent ITR to induce tendinopathy, and group 4 received daily Met injection along with ITR to inhibit HMGB1. Tendinopathic changes were assessed in Achilles tendons of all mice using histology, immunohistochemistry, and enzyme-linked immunosorbent assays. Results: ITR induced HMGB1 release into the tendon matrix and developed characteristics of tendinopathy as evidenced by the expression of macrophage marker CD68, proinflammatory molecules (COX-2, PGE2), cell morphological changes from normal elongated cells to round cells, high levels of expression of chondrogenic markers (SOX-9, collagen type II), and accumulation of proteoglycans in tendinopathic tendons. Daily injection of Met inhibited HMGB1 release and decreased these degenerative changes in ITR tendons. Conclusions: Inhibition of HMGB1 by injections of Met prevented tendinopathy development due to mechanical overloading in the Achilles tendon in mice. Clinical Relevance: Met may be able to be repurposed as a therapeutic option for preventing the development of tendinopathy in high-risk patients.
Social perceptions and bioethical implications of birth plans: A qualitative study
Authors: Sánchez-García Maria José , Martínez-Rojo Francisco , Galdo-Castiñeiras Jesús A , Echevarría-Pérez Paloma , Morales-Moreno Isabel 
Published: November 2020

Background The birth plan is a tool that allows the self-learning and thoughtful analysis of the women during the birthing process, facilitating their making of decisions and participation, in agreement with the bioethical principles of autonomy and no malfeasance. Goal: To understand the perception and satisfaction of women who presented a birth plan. Methodology: Qualitative, descriptive, observational, retrospective and cross-sectional study. The population of the study was composed of 21 women who presented a birth plan regulated in a Hospital ever since the recording of the presentation of the birth plan was started (2011) until 2015. Place: Cartagena (Murcia, Spain). Techniques/methods: Semistructured interview. Results-Discussion: Most women considered the plan as a useful self-learning tool on the meaning of the birthing process, as it favored the communication between the expectant mothers/health professionals. Our informants sought information related to the birthing process from informal sources; most perceived a level of respect of their wishes during the process of giving birth. The use of the birth plan did not imply the perception of loss of the degree of control during the birth, although attention to the written document could be improved. Conclusions The use of the birth plan is a very satisfactory and useful experience for their involvement in their self-care, although in some cases, the births did not proceed according to their plans. Nevertheless, the prevalence of the principle of Non-Malfeasance over Autonomy was evidenced.
Transcriptomics and Prognosis Analysis to Identify Critical Biomarkers in Invasive Breast Carcinoma
Authors: Wu Jun , Liu Xiao-Jun , Hu Jia-Nan , Liao Xu-Hui , Lin Fei-Fei 
Published: November 2020

Objective: Invasive breast cancer (BRCA) is one of the prevalent types of invasive tumors with high mortality worldwide. Due to the lack of effective treatment to control the recurrence of distant metastases, the prognosis of BRCA is still very unsatisfactory. We aimed to find some biomarkers by bioinformatics analysis for survival prediction. Methods: Differentially expressed genes (DEGs) were screened out based on tumor group and normal group. Then, the weighted gene correlation network analysis (WGCNA) was employed to identify the clinically associated gene sets. Meanwhile, the enrichment analyses were performed for the functional annotation of the critical genes. The Kaplan Meier analysis calculated the essential genes’ prognostic value. Results: After threshold screening, 1655 DEGs were obtained for subsequent analysis. 51 out of 1655 DEGs were significantly associated with BRCA patients’ estrogen receptor status via WGCNA. Three genes (FABP7, CXCL3, and LOC284578) out of the 51 genes were associated with overall survival, and 3 genes were relapse-free survival associated. Finally, we obtained 5 essential prognostic associated genes (FABP7, CXCL3, LOC284578, CAPN6, and NRG2), which could be used as prognostic factors for BRCA. Conclusion: Our findings obtained a gene module associated with BRCA clinical trait and several key genes that acted as essential components in the prognostic of cancer, which may improve its treatment.