bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatty acid oxidation and autophagy promote endoxifen resistance and counter the effect of AKT inhibition in ER-positive breast cancer cells
Authors: Duan Lei , Calhoun Sarah , Shim Daeun , Perez Ricardo E , Blatter Lothar A , Maki Carl G 
Published: March 2021

Abstract
Tamoxifen (TAM) is the first-line endocrine therapy for estrogen receptor-positive (ER+) breast cancer (BC). However, acquired resistance occurs in ∼50% cases. Meanwhile, although the PI3K/AKT/mTOR pathway is a viable target for treatment of endocrine therapy-refractory patients, complex signaling feedback loops exist, which can counter the effectiveness of inhibitors of this pathway. Here, we analyzed signaling pathways and metabolism in ER+ MCF7 BC cell line and their TAM-resistant derivatives that are co-resistant to endoxifen using immunoblotting, quantitative polymerase chain reaction, and the Agilent Seahorse XF Analyzer. We found that activation of AKT and the energy-sensing kinase AMPK was increased in TAM and endoxifen-resistant cells. Furthermore, ERRα/PGC-1β and their target genes MCAD and CPT-1 were increased and regulated by AMPK, which coincided with increased fatty acid oxidation (FAO) and autophagy in TAM-resistant cells. Inhibition of AKT feedback-activates AMPK and ERRα/PGC-1β-MCAD/CPT-1 with a consequent increase in FAO and autophagy that counters the therapeutic effect of endoxifen and AKT inhibitors. Therefore, our results indicate increased activation of AKT and AMPK with metabolic reprogramming and increased autophagy in TAM-resistant cells. Simultaneous inhibition of AKT and FAO/autophagy is necessary to fully sensitize resistant cells to endoxifen.
Evaluating Polygenic Risk Scores for Breast Cancer in Women of African Ancestry
Authors: Du Zhaohui , Gao Guimin , Adedokun Babatunde , Ahearn Thomas , Lunetta Kathryn L , Zirpoli Gary , Troester Melissa A , Ruiz-Narváez Edward A , Haddad Stephen A , PalChoudhury Parichoy , Figueroa Jonine , John Esther M , Bernstein Leslie , Zheng Wei , Hu Jennifer J , Ziegler Regina G , Nyante Sarah , Bandera Elisa V , Ingles Sue A , Mancuso Nicholas , Press Michael F , Deming Sandra L , Rodriguez-Gil Jorge L , Yao Song , Ogundiran Temidayo O , Ojengbe Oladosu , Bolla Manjeet K , Dennis Joe , Dunning Alison M , Easton Douglas F , Michailidou Kyriaki , Pharoah Paul D P , Sandler Dale P , Taylor Jack A , Wang Qin , Weinberg Clarice R , Kitahara Cari M , Blot William , Nathanson Katherine L , Hennis Anselm , Nemesure Barbara , Ambs Stefan , Sucheston-Campbell Lara E , Bensen Jeannette T , Chanock Stephen J , Olshan Andrew F , Ambrosone Christine B , Olopade Olufunmilayo I , Yarney Joel , Awuah Baffour , Wiafe-Addai Beatrice , Conti David V ,   the GBHS Study Team, Palmer Julie R , Garcia-Closas Montserrat , Huo Dezheng , Haiman Christopher A 
Published: March 2021

Abstract

Background
Polygenic risk scores (PRSs) have been demonstrated to identify women of European, Asian, and Latino ancestry at elevated risk of developing breast cancer (BC). We evaluated the performance of existing PRSs trained in European ancestry populations among women of African ancestry.

Methods
We assembled genotype data for women of African ancestry, including 9241 case subjects and 10 193 control subjects. We evaluated associations of 179- and 313-variant PRSs with overall and subtype-specific BC risk. PRS discriminatory accuracy was assessed using area under the receiver operating characteristic curve. We also evaluated a recalibrated PRS, replacing the index variant with variants in each region that better captured risk in women of African ancestry and estimated lifetime absolute risk of BC in African Americans by PRS category.

Results
For overall BC, the odds ratio per SD of the 313-variant PRS (PRS313) was 1.27 (95% confidence interval [CI] = 1.23 to 1.31), with an area under the receiver operating characteristic curve of 0.571 (95% CI = 0.562 to 0.579). Compared with women with average risk (40th-60th PRS percentile), women in the top decile of PRS313 had a 1.54-fold increased risk (95% CI = 1.38-fold to 1.72-fold). By age 85 years, the absolute risk of overall BC was 19.6% for African American women in the top 1% of PRS313 and 6.7% for those in the lowest 1%. The recalibrated PRS did not improve BC risk prediction.

Conclusion
The PRSs stratify BC risk in women of African ancestry, with attenuated performance compared with that reported in European, Asian, and Latina populations. Future work is needed to improve BC risk stratification for women of African ancestry.
Pharmaceutical care services provided by pharmacists during COVID-19 pandemic: perspectives from around the World
Authors: Sridhar Sathvik B , Rabbani Syed Arman 
Published: March 2021

AbstractObjectivesPharmacists have proven to be an indispensable member of the frontline healthcare team during this COVID-19 pandemic and have performed key roles and responsibilities to mitigate its adverse impact. They are facing several unusual challenges in these changing and evolving circumstances and are adopting novel strategies to overcome them. This review aims to identify and describe the different pharmaceutical care services delivered by pharmacists during this ongoing COVID-19 pandemic.MethodsA review of different studies was conducted to appraise the existing literature regarding various pharmaceutical care services carried out by the pharmacist during the COVID-19 pandemic. The review was done using the preferred reporting items for systematic reviews and meta-analyses (PRISMA). A comprehensive literature search was done using different databases such as MEDLINE, PubMed, Embase and ProQuest to identify the relevant studies.Key findingsThe review highlights the various pharmaceutical care services provided and implemented by pharmacists during the COVID-19 pandemic. Pharmaceutical care services like patient education and counselling, providing information, addressing medication shortages, teleconsultation, medication review, optimizing medication regimen, adverse drug reaction monitoring and addressing the medication-related problems are being delivered by the pharmacists in this ongoing pandemic.ConclusionsAll the studies described the roles and responsibilities of the pharmacists during COVID-19. This pandemic adversity has opened up new avenues for the pharmacists which have broadened their scope as the member of multidisciplinary healthcare team. Pharmacists have to overcome the unforeseen barriers and challenges and continue providing need-based pharmaceutical care services.
Consequences of crisis and the great re-think: COVID-19’s impact on energy investment, sustainability and the future of international investment agreements
Authors: Duggal Kabir , Rangachari Rekha , Gupta Kanika 
Published: March 2021

Abstract
The COVID-19 pandemic and its resulting disruptions are having a significant impact on the global economy and international investments. Various State measures to address the pandemic are leading to widespread economic disruptions across several industries, including the energy sector. The current crisis has impacted energy demand, disrupted the global supply chain and created financial uncertainty. The pandemic has exacerbated issues relating to health, the environment, labour and human rights in the energy sector. This article seeks to understand the pandemic’s impact in shaping future human rights policy in international investment law. This article analyses current drafting trends in international investment agreements (IIAs) in 2019–2020, particularly in the context of recent developments in sustainable development and human rights. Although there are some noteworthy developments in recent IIAs, the pandemic has highlighted the need for further treaty reforms. It provides an opportunity for policymakers and corporations alike to address human rights issues and to incorporate the principles of sustainable investment into IIAs. The energy sector in particular plays a significant role in promoting sustainable development and post-COVID policy reforms will be essential for future energy security and global stability. In conclusion, this article considers the future of potential reforms in the post-COVID recovery agenda while keeping in mind energy and climate goals.
Do Health Programs Contribute to Keeping the Peace? A Scientific Analysis
Authors: Waller Stephen G 
Published: March 2021

ABSTRACT

Introduction
The role of health problems and programs to address problems in keeping the peace has not been scientifically analyzed. We sought to mitigate this gap in knowledge.

Methods
We examined hundreds of conflicts in a robust international database (NAVCO 2.0) for the presence of health programs by conflict parties and were unable to demonstrate a significant statistical correlation between the presence of a health program and peace. Using this analysis and a comprehensive international database of health conditions (the Global Burden of Disease), we obtained Institutional Review Board approval and undertook a matched case-control analysis. We identified 14 countries with new-onset conflict as our cases and 52 similar countries without conflict during the same year as our controls. We calculated the association between conflict status and the prevalence of 254 different health conditions among the case and control nations.

Results
None of the 254 health conditions had changes in prevalence that correlated with the conflict status of that nation. None of those common health conditions is therefore a predictive “leading indicator” of conflict in this study.

Conclusions
Without such an association or causal link, the role of health programs in peacekeeping and “stability operations” remains ambiguous. Negative findings do not mean that there is no connection between health programs and peace, and further study should be done. Our results have implications for the value of global health engagement missions.
Compact planetary nebulae MaC 2-1 and Sp 4-1: photoionization models and dust characteristics
Authors: Bandyopadhyay Rahul , Das Ramkrishna , Mondal Soumen 
Published: March 2021

ABSTRACT
We study the characteristics of the planetary nebulae (PNe) MaC 2-1 and Sp 4-1. We use our optical spectra taken with the 2 m Himalayan Chandra Telescope, Spitzer mid-infrared (mid-IR) spectra, HST images, and IR photometric data. These PNe have not previously been individually studied in detail. Both are in the low- to moderate-excitation class. MaC 2-1 shows the presence of silicon carbide (SiC) and magnesium sulphide (MgS) dust. Sp 4-1 hosts polycyclic aromatic hydrocarbon (PAH) molecules. We obtain the plasma properties of the PNe from the optical and mid-IR emission-line fluxes. We compute photoionization models of the PNe for the self-consistent estimation of physical parameters associated with the central star and the nebula, including nebular abundances. From the modelling of the IR data, we obtain the characteristics of dust and molecules formed in the nebulae. From our study, we estimate that the progenitors of MaC 2-1 and Sp 4-1 had masses of 1.2 and 1.55 M⊙, respectively, and both of them seem to have been born in a metal-poor environment. Both are distant PNe, with estimated distances of 16 and 18 kpc for MaC 2-1 and Sp 4-1, respectively.
Quantification of nickel and cobalt mobility and accumulation via the phloem in the hyperaccumulator Noccaea caerulescens (Brassicaceae)
Authors: Deng Teng-Hao-Bo , Chen Jie-Qian , Geng Ke-Rui , van der Ent Antony , Tang Ye-Tao , Wen Dian , Wang Xu , Li Lei , Du Rui-Ying , Morel Jean-Louis , Qiu Rong-Liang 
Published: March 2021

Abstract
Hyperaccumulators have exceptional phloem translocation capability for heavy metals. This study aims at quantifying the mobility and accumulation of Ni and Co via the phloem in the model hyperaccumulator Noccaea caerulescens. “Phloem loading capability (PLC),” which is calculated by the “Metal content in phloem sap/Metal content in leaves,” was introduced to evaluate the metal phloem mobility, while “Phloem mobility value (PMV)” was used for the normalization of PLC, which sets the PLC of Sr as PMV 0 and that of Rb as 100. The results showed that the PMVs of Ni and Co were 63 and 47, respectively. And the phloem mobility of Rb, Ni, Co, and Sr could be graded as highly mobile, mobile, intermediate, and immobile accordingly. The phloem stream can supply up to 19.1% and 16.0% of the total Ni and Co accumulated in the young leaves, respectively, while for Rb and Sr, the phloem contributes to 29% and 1.4% of the total Rb or Sr, indicating phloem contribution of certain metal is directly linked with its mobility. The results of this study raise the importance of phloem translocation on metal accumulation in shoots and provide insights on the metal cycling process in hyperaccumulators.
What defines a synthetic riboswitch? – Conformational dynamics of ciprofloxacin aptamers with similar binding affinities but varying regulatory potentials
Authors: Kaiser Christoph , Schneider Jeannine , Groher Florian , Suess Beatrix , Wachtveitl Josef 
Published: March 2021

Abstract
Among the many in vitro-selected aptamers derived from SELEX protocols, only a small fraction has the potential to be applied for synthetic riboswitch engineering. Here, we present a comparative study of the binding properties of three different aptamers that bind to ciprofloxacin with similar KD values, yet only two of them can be applied as riboswitches. We used the inherent ligand fluorescence that is quenched upon binding as the reporter signal in fluorescence titration and in time-resolved stopped-flow experiments. Thus, we were able to demonstrate differences in the binding kinetics of regulating and non-regulating aptamers. All aptamers studied underwent a two-step binding mechanism that suggests an initial association step followed by a reorganization of the aptamer to accommodate the ligand. We show that increasing regulatory potential is correlated with a decreasing back-reaction rate of the second binding step, thus resulting in a virtually irreversible last binding step of regulating aptamers. We suggest that a highly favoured structural adaption of the RNA to the ligand during the final binding step is essential for turning an aptamer into a riboswitch. In addition, our results provide an explanation for the fact that so few aptamers with regulating capacity have been found to date. Based on our data, we propose an adjustment of the selection protocol for efficient riboswitch detection.
Myod1 and GR coordinate myofiber-specific transcriptional enhancers
Authors: Rovito Daniela , Rerra Anna-Isavella , Ueberschlag-Pitiot Vanessa , Joshi Shilpy , Karasu Nezih , Dacleu-Siewe Vanessa , Rayana Khalil Ben , Ghaibour Kamar , Parisotto Maxime , Ferry Arnaud , Jelinsky Scott A , Laverny Gilles , Klaholz Bruno P , Sexton Tom , Billas Isabelle M L , Duteil Delphine , Metzger Daniel 
Published: March 2021

Abstract
Skeletal muscle is a dynamic tissue the size of which can be remodeled through the concerted actions of various cues. Here, we investigated the skeletal muscle transcriptional program and identified key tissue-specific regulatory genetic elements. Our results show that Myod1 is bound to numerous skeletal muscle enhancers in collaboration with the glucocorticoid receptor (GR) to control gene expression. Remarkably, transcriptional activation controlled by these factors occurs through direct contacts with the promoter region of target genes, via the CpG-bound transcription factor Nrf1, and the formation of Ctcf-anchored chromatin loops, in a myofiber-specific manner. Moreover, we demonstrate that GR negatively controls muscle mass and strength in mice by down-regulating anabolic pathways. Taken together, our data establish Myod1, GR and Nrf1 as key players of muscle-specific enhancer-promoter communication that orchestrate myofiber size regulation.
NMR solution structures of Runella slithyformis RNA 2′-phosphotransferase Tpt1 provide insights into NAD+ binding and specificity
Authors: Alphonse Sébastien , Banerjee Ankan , Dantuluri Swathi , Shuman Stewart , Ghose Ranajeet 
Published: March 2021

Abstract
Tpt1, an essential component of the fungal and plant tRNA splicing machinery, catalyzes transfer of an internal RNA 2′-PO4 to NAD+ yielding RNA 2′-OH and ADP-ribose-1′,2′-cyclic phosphate products. Here, we report NMR structures of the Tpt1 ortholog from the bacterium Runella slithyformis (RslTpt1), as apoenzyme and bound to NAD+. RslTpt1 consists of N- and C-terminal lobes with substantial inter-lobe dynamics in the free and NAD+-bound states. ITC measurements of RslTpt1 binding to NAD+ (KD ∼31 μM), ADP-ribose (∼96 μM) and ADP (∼123 μM) indicate that substrate affinity is determined primarily by the ADP moiety; no binding of NMN or nicotinamide is observed by ITC. NAD+-induced chemical shift perturbations (CSPs) localize exclusively to the RslTpt1 C-lobe. NADP+, which contains an adenylate 2′-PO4 (mimicking the substrate RNA 2′-PO4), binds with lower affinity (KD ∼1 mM) and elicits only N-lobe CSPs. The RslTpt1·NAD+ binary complex reveals C-lobe contacts to adenosine ribose hydroxyls (His99, Thr101), the adenine nucleobase (Asn105, Asp112, Gly113, Met117) and the nicotinamide riboside (Ser125, Gln126, Asn163, Val165), several of which are essential for RslTpt1 activity in vivo. Proximity of the NAD+ β-phosphate to ribose-C1″ suggests that it may stabilize an oxocarbenium transition-state during the first step of the Tpt1-catalyzed reaction.
miR156/157 Targets SPLs to Regulate Flowering Transition, Plant Architecture and Flower Organ Size in Petunia
Authors: Zhou Qin , Shi Jiewei , Li Zhineng , Zhang Sisi , Zhang Shuting , Zhang Jiaqi , Bao Manzhu , Liu Guofeng 
Published: March 2021

Abstract
miR156/157 plays multiple pivotal roles during plant growth and development. In this study, we identified 11 miR156- and 5 miR157-encoding loci from the genome of Petunia axillaris and Petunia inflata, designated as PaMIR0156/157s and PiMIR0156/157s, respectively. Real-time quantitative reverse transcription PCR (qRT-PCR) analysis indicated that PhmiR156/157 was expressed predominantly in cotyledons, germinating seeds, flower buds, young fruits and seedlings. PhmiR156/157 levels declined in shoot apical buds and leaves of petunia before flowering as the plant ages; moreover, the temporal expression patterns of most miR156/157-targeted PhSPLs were complementary to that of PhmiR156/157. Ectopic expression of PhMIR0157a in Arabidopsis and petunia resulted in delayed flowering, dwarf plant stature, increased branches and reduced organ size. However, PhMIR0156f-overexpressing Arabidopsis and petunia plants showed only delayed flowering. In addition, downregulation of PhmiR156/157 level by overexpressing STTM156/157 led to taller plants with less branches, longer internodes and precocious flowering. qRT-PCR analysis indicated that PhmiR156/157 modulates these traits mainly by downregulating their PhSPL targets and subsequently decreasing the expression of flowering regulatory genes. Our results demonstrate that the PhmiR156/157-PhSPL module has conserved but also divergent functions in growth and development, which will help us decipher the genetic basis for the improvement of flower transition, plant architecture and organ development in petunia.
Experimental Constraints on Dacite Magma Storage beneath Volcán Quizapu, Chile
Authors: First Emily C , Hammer Julia E , Ruprecht Philipp , Rutherford Malcolm 
Published: March 2021

Abstract
Volcán Quizapu, Chile, is an under-monitored volcano that was the site of two historical eruptions: an effusive eruption in 1846–1847 and a Plinian eruption in 1932, both of which discharged ∼5 km3 (dense rock equivalent) of lava and/or tephra. The majority of material erupted in both cases is trachydacite, nearly identical for each event. We present H2O-saturated, phase equilibrium experiments on this end-member dacite magma, using a pumice sample from the 1932 eruption as the main starting material. At an oxygen fugacity (fO2) of ∼NNO + 0·2 (where NNO is the nickel–nickel oxide buffer), the phase assemblage of An25–30 plagioclase + amphibole + orthopyroxene, without biotite, is stable at 865 ± 10 °C and 110 ± 20 MPa H2O pressure (PH2O), corresponding to ∼4 km depth. At these conditions, experiments also reproduce the quenched glass composition of the starting pumice. At slightly higher PH2O and below 860 °C, biotite joins the equilibrium assemblage. Because biotite is not part of the observed Quizapu phase assemblage, its presence places an upper limit on PH2O. At the determined storage PH2O of ∼110 MPa, H2O undersaturation of the magma with XH2Ofluid = 0·87 would align Ptotal to mineral-based geobarometry estimates of ∼130 MPa. However, XH2Ofluid &lt; 1 is not required to reproduce the Quizapu dacite phase assemblage and compositions. A second suite of experiments at lower fO2 shows that the stability fields of the hydrous silicates (amphibole and biotite) are significantly restricted at NNO – 2 relative to NNO + 0·2. Additional observations of Quizapu lava and pumice samples support the existing hypothesis that rapid pre-eruptive heating drove the effusive 1846–1847 eruption, with important refinements. We demonstrate that microlites in the end-member dacite lavas are consistent with in situ crystallization (during ascent), rather than transfer from an andesite. In one end-member dacite lava, newly identified reverse zoning in orthopyroxene and incipient destabilization of amphibole are consistent with small degrees of heating. Our work articulates a clear direction for future Quizapu studies, which are warranted given the active nature of the Cerro Azul–Descabezado Grande volcanic axis.
The neural underpinnings of intergroup social cognition: an fMRI meta-analysis
Authors: Merritt Carrington C , MacCormack Jennifer K , Stein Andrea G , Lindquist Kristen A , Muscatell Keely A 
Published: March 2021

Abstract
Roughly 20 years of functional magnetic resonance imaging (fMRI) studies have investigated the neural correlates underlying engagement in social cognition (e.g. empathy and emotion perception) about targets spanning various social categories (e.g. race and gender). Yet, findings from individual studies remain mixed. In the present quantitative functional neuroimaging meta-analysis, we summarized across 50 fMRI studies of social cognition to identify consistent differences in neural activation as a function of whether the target of social cognition was an in-group or out-group member. We investigated if such differences varied according to a specific social category (i.e. race) and specific social cognitive processes (i.e. empathy and emotion perception). We found that social cognition about in-group members was more reliably related to activity in brain regions associated with mentalizing (e.g. dorsomedial prefrontal cortex), whereas social cognition about out-group members was more reliably related to activity in regions associated with exogenous attention and salience (e.g. anterior insula). These findings replicated for studies specifically focused on the social category of race, and we further found intergroup differences in neural activation during empathy and emotion perception tasks. These results help shed light on the neural mechanisms underlying social cognition across group lines.
Neglecting Reproductive Labor: A Critical Review of Gender Equality Indices
Authors: Schmid Caitlin B 
Published: March 2021

Abstract
Gender equality indices are increasingly influential tools used for governance and knowledge production. This article evaluates the adequacy of the seventeen existing multi-dimensional gender equality indices and shows that all but one neglect unpaid reproductive labor to varying degrees. The empirical analysis offers three lessons for these indices’ improvement. First, that it is possible to measure the gendered division of unpaid reproductive labor using gender equality indices. Second, that data availability need not compromise the coherence of the indices’ frameworks. Finally, that indices can reduce the overbearing emphasis on quantitative indicators in governance by complementing their findings with qualitative analyses.