bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomal Delivery of FTO Confers Gefitinib Resistance to Recipient Cells through ABCC10 Regulation in an m6A-dependent Manner
Authors: Xiao Peng , Liu Yu-kang , Han Wei , Hu Yan , Zhang Bo-you , Liu Wen-liang 
Published: February 2021

Abstract

Gefitinib is suitable for the treatment of locally advanced or metastatic non–small cell lung cancer. However, the development of acquired resistance limits its long-term efficacy in regardless of significant clinical benefit to patients. Therefore, to elucidate the mechanism of gefitinib resistance in addition to target gene mutation may greatly increase its clinical efficacy. It was found first that N6-methyladenosine RNA demethylase FTO was significantly enriched in serum exosomes of gefitinib-resistant (GR) patients compared with that of gefitinib-sensitive (GS) patients through exosomal RNA sequencing. Meanwhile, the average m6A proportion in GR patients was significantly lower when compared with that in GS patients. Besides, GR cell–derived exosome internalization attenuated the total m6A abundance and gefitinib sensitivity of PC9 cells. Not only FTO knockdown enhanced the gefitinib sensitivity of GR cells but also FTO reduction in donor exosomes alleviated the acquired resistance of recipient PC9 cells. GR cell–derived exosomal-FTO promoted ABCC10 of recipient cells in a m6A-dependent manner. FTO/YTHDF2/ABCC10 axis played a role in intercellular transmission of GR cell–derived exosome-mediated gefitinib resistance both in vitro and in vivo. In general, this research showed that m6A modification was involved in the decrease of gefitinib sensitivity. GR cell–derived exosomes could decrease gefitinib sensitivity of recipient cells in exosomal delivery of FTO-dependent manner. FTO/YTHDF2/ABCC10 axis played a role in intercellular transmission of GR cell–derived exosome-mediated gefitinib resistance.

Implications:
Our results elucidated another potential molecular mechanism of gefitinib resistance in non–small cell lung cancer besides secondary EGFR mutations.
Right Ventricular Dysfunction and Short‐Term Outcomes Following Left‐Sided Valvular Surgery: An Echocardiographic Study
Authors: Towheed Arooge , Sabbagh Ebrahim , Gupta Rajesh , Assiri Salem , Chowdhury Mohammed A. , Moukarbel George V. , Khuder Sadik A. , Schwann Thomas A. , Bonnell Mark R. , Cooper Christopher J. , Khouri Samer 
Published: February 2021

Background
The prognostic value of echocardiographic evaluation of right ventricular (RV) function in patients undergoing left‐sided valvular surgery has not been well described. The objective of this study is to determine the role of broad echocardiographic assessment of RV function in predicting short‐term outcomes after valvular surgery.

Methods and Results

Preoperative echocardiographic data, perioperative adverse outcomes, and 30‐day mortality were analyzed in patients who underwent left‐sided valvular surgery from 2006 to 2014. Echocardiographic parameters used to evaluate RV function include RV fractional area change, tricuspid annular plane systolic excursion, systolic movement of the RV lateral wall using tissue Doppler imaging (S'), RV myocardial performance index, and RV dP/dt. Subjects with at least 3 abnormal parameters out of the 5 aforementioned indices were defined as having significant RV dysfunction. The study included 269 patients with valvular surgery (average age: 67±15, 60.6% male, 148 aortic, and 121 mitral). RV dysfunction was found in 53 (19.7%) patients; 30‐day mortality occurred in 20 patients (7.5%). Compared with normal RV function, patients with RV dysfunction had higher 30‐day mortality (22.6% versus 3.8%;
P
=0.01) and were at risk for developing multisystem failure/shock (13.2% versus 3.2%;
P
=0.01). Multivariate analyses showed that preexisting RV dysfunction was the strongest predictor of increased 30‐day mortality (odds ratio: 3.5; 95% CI, 1.1–11.1;
P
<0.05).

Conclusions
Preoperative RV dysfunction identified by comprehensive echocardiographic assessment is a strong predictor of adverse outcomes following left‐sided valvular surgery.
Effects of High Fat Versus Normal Diet on Extracellular Vesicle–Induced Angiogenesis in a Swine Model of Chronic Myocardial Ischemia
Authors: Aboulgheit Ahmed , Potz Brittany A. , Scrimgeour Laura A. , Karbasiafshar Catherine , Shi Guangbin , Zhang Zhiqi , Machan Jason T. , Schorl Christoph , Brodsky Alexander S. , Braga Karla , Pfeiffer Melissa , Gao May , Cummings Olivia , Sodha Neel R. , Abid M. Ruhul , Sellke Frank W. 
Published: February 2021

Background
Mesenchymal stem cell–derived extracellular vesicles (EVs) promote angiogenesis in the ischemic myocardium. This study examines the difference in vascular density, myocardial perfusion, molecular signaling, and gene expression between normal diet (ND) and high fat diet (HFD) groups at baseline and following intramyocardial injection of EVs.

Methods and Results
Intact male Yorkshire swine fed either an ND (n=17) or HFD (n=14) underwent placement of an ameroid constrictor on the left circumflex coronary artery. Subsequently, animals received either intramyocardial injection of vehicle‐saline as controls; (ND‐controls n=7, HFD‐controls, n=6) or EVs; (ND‐EVs n=10, HFD‐EVs n=8) into the ischemic territory. Five weeks later, myocardial function, perfusion, vascular density, cell signaling, and gene expression were examined. EVs improved indices of myocardial contractile function, myocardial perfusion, and arteriogenesis in both dietary cohorts. Interestingly, quantification of alpha smooth muscle actin demonstrated higher basal arteriolar density in HFD swine compared with their ND counterparts; whereas EVs were associated with increased CD31‐labeled endothelial cell density only in the ND tissue, which approached significance. Levels of total endothelial nitric oxide synthase, FOXO1 (forkhead box protein O1) , transforming growth factor‐β, phosphorylated VEGFR2 (vascular endothelial growth factor receptor 2), and phosphorylated MAPK ERK1/ERK2 (mitogen‐activated protein kinase) were higher in ischemic myocardial lysates from ND‐controls compared with HFD‐controls. Conversely, HFD‐control tissue showed increased expression of phosphorylated endothelial nitric oxide synthase, phosphorylated FOXO1, VEGFR2, and MAPK ERK1/ERK2 with respect to ND‐controls. Preliminary gene expression studies indicate differential modulation of transcriptional activity by EVs between the 2 dietary cohorts.

Conclusions
HFD produces a profound metabolic disorder that dysregulates the molecular mechanisms of collateral vessel formation in the ischemic myocardium, which may hinder the therapeutic angiogenic effects of EVs.
Your Pay or Someone Else's? Exploring Salary Dispersion, Position, and Principal Turnover
Authors: Pendola Andrew 
Published: February 2021

AbstractThis study explores ways in which salary can be structured to reduce leadership shortages by investigating how comparative wage dispersion and position alter the relationship of salary to principal turnover. Using a seventeen-year longitudinal dataset covering over sixteen thousand principals in Texas, discrete-time hazard models demonstrate that principals are highly sensitive to salary comparisons over and above basic salary. Higher comparative position is associated with significantly reduced turnover risk, while wider dispersion is associated with a significantly increased turnover risk. Interactions demonstrate that dispersion and position act in tandem to create conditions where principals have particularly high turnover risk. These results have implications for strategies to address turnover through district salary structures, as well as broader notions of how wage tournaments operate in the principal labor market.
Spontaneous eye movements during eyes-open rest reduce
resting-state-network modularity by increasing visual-sensorimotor
connectivity
Authors: Koba Cemal , Notaro Giuseppe , Tamm Sandra , Nilsonne Gustav , Hasson Uri 
Published: February 2021

Abstract
During wakeful rest, individuals make small eye movements during fixation. We examined how these endogenously driven oculomotor patterns impact topography and topology of functional brain networks. We used a dataset consisting of eyes-open resting-state (RS) fMRI data with simultaneous eye tracking. The eye-tracking data indicated minor movements during rest, which correlated modestly with RS BOLD data. However, eye-tracking data correlated well with echo-planar imaging time series sampled from the area of the eye-orbit (EO-EPI), which is a signal previously used to identify eye movements during exogenous saccades and movie viewing. Further analyses showed that EO-EPI data were correlated with activity in an extensive motor and sensorimotor network, including components of the dorsal attention network and the frontal eye fields. Partialling out variance related to EO-EPI from RS data reduced connectivity, primarily between sensorimotor and visual areas. It also produced networks with higher modularity, lower mean connectivity strength, and lower mean clustering coefficient. Our results highlight new aspects of endogenous eye movement control during wakeful rest. They show that oculomotor-related contributions form an important component of RS network topology, and that those should be considered in interpreting differences in network structure between populations or as a function of different experimental conditions.
The Promise and Pitfalls of Conflict Prediction: Evidence from Colombia and Indonesia
Authors: Bazzi Samuel , Blair Robert A. , Blattman Christopher , Dube Oeindrila , Gudgeon Matthew , Peck Richard 
Published: February 2021

AbstractHow feasible is violence early-warning prediction? Colombia and Indonesia have unusually fine-grained data. We assemble two decades of local violent events alongside hundreds of annual risk factors. We attempt to predict violence one year ahead with a range of machine learning techniques. Our models reliably identify persistent, high-violence hot spots. Violence is not simply autoregressive, as detailed histories of disaggregated violence perform best, but socioeconomic data substitute well for these histories. Even with unusually rich data, however, our models poorly predict new outbreaks or escalations of violence. These “best-case” scenarios with annual data fall short of workable early-warning systems.
Psychosocial Impacts of the Coronavirus Disease (COVID-19) Pandemic in Zimbabwe: Citizens’ Perspective
Authors: Mbulayi Shingirai P. , Makuyana Abigail , Kang’ethe Simon M. 
Published: February 2021

Abstract
The outbreak of the ongoing coronavirus pandemic altered the social, economic, and public health landscape across the world, and unleashed a plethora of negative psychosocial impacts on society. This qualitative study used an online based case study design to explore the psychosocial impacts of COVID-19 among a few selected citizens of Zimbabwe. The study was conceptualized around an orienting question stated as: What are the psychosocial impacts of the COVID-19 pandemic in Zimbabwe? Participants for the study were purposively selected, and data was collected through in-depth interviews, which were hosted online. The study returned findings that the COVID-19 pandemic in Zimbabwe was concomitant with a range of psychosocial impacts including inter alia, exposure of people to mental health problems such as severe distress, phobias, anxiety, development of psychosomatic symptoms, as well as increase in social ills such as poverty, and domestic and sexual violence perpetrated against women and children.
From the “Pink Tide” to “Soft Coup d’État” in Latin America: the Case of Bolivia
Authors: Chew Sánchez Martha I. 
Published: February 2021

Abstract
This article addresses the impact of settler colonialism by the Spanish and United States in the American continent in forming the base, development, and power of capitalism in the West. It provides a general overview of the United States’ unequal economic relationships with Latin American countries since the end of the nineteenth century to the present. It highlights the role evangelist groups have in changing the way coup d’états have been taking place in the region, in particular, to countries that had democratically elected presidents who were part of the “Pink Tide” and had a program to counterbalance neoliberal policies that were contributing to unprecedented economic inequality in their societies. One of the central questions in this work is the role of coloniality within Latin American countries and between the US and Latin America in the coup d’état against Evo Morales in Bolivia on November 10, 2019.
Reconstructing an Interdecadal Pacific Oscillation Index from a Pacific Basin–Wide Collection of Ice Core Records
Authors: Porter Stacy E. , Mosley-Thompson Ellen , Thompson Lonnie G. , Wilson Aaron B. 
Published: February 2021

AbstractUsing an assemblage of four ice cores collected around the Pacific basin, one of the first basinwide histories of Pacific climate variability has been created. This ice core–derived index of the interdecadal Pacific oscillation (IPO) incorporates ice core records from South America, the Himalayas, the Antarctic Peninsula, and northwestern North America. The reconstructed IPO is annually resolved and dates to 1450 CE. The IPO index compares well with observations during the instrumental period and with paleo-proxy assimilated datasets throughout the entire record, which indicates a robust and temporally stationary IPO signal for the last ~550 years. Paleoclimate reconstructions from the tropical Pacific region vary greatly during the Little Ice Age (LIA), although the reconstructed IPO index in this study suggests that the LIA was primarily defined by a weak, negative IPO phase and hence more La Niña–like conditions. Although the mean state of the tropical Pacific Ocean during the LIA remains uncertain, the reconstructed IPO reveals some interesting dynamical relationships with the intertropical convergence zone (ITCZ). In the current warm period, a positive (negative) IPO coincides with an expansion (contraction) of the seasonal latitudinal range of the ITCZ. This relationship is not stationary, however, and is virtually absent throughout the LIA, suggesting that external forcing, such as that from volcanoes and/or reduced solar irradiance, could be driving either the ITCZ shifts or the climate dominating the ice core sites used in the IPO reconstruction.
Pooling Data Improves Multimodel IDF Estimates over Median-Based IDF Estimates: Analysis over the Susquehanna and Florida
Authors: Srivastava Abhishekh Kumar , Grotjahn Richard , Ullrich Paul Aaron , Sadegh Mojtaba 
Published: February 2021

AbstractTraditional multimodel methods for estimating future changes in precipitation intensity, duration, and frequency (IDF) curves rely on mean or median of models’ IDF estimates. Such multimodel estimates are impaired by large estimation uncertainty, shadowing their efficacy in planning efforts. Here, assuming that each climate model is one representation of the underlying data generating process, i.e., the Earth system, we propose a novel extension of current methods through pooling model data: (i) evaluate performance of climate models in simulating the spatial and temporal variability of the observed annual maximum precipitation (AMP), (ii) bias-correct and pool historical and future AMP data of reasonably performing models, and (iii) compute IDF estimates in a nonstationary framework from pooled historical and future model data. Pooling enhances fitting of the extreme value distribution to the data and assumes that data from reasonably performing models represent samples from the “true” underlying data generating distribution. Through Monte Carlo simulations with synthetic data, we show that return periods derived from pooled data have smaller biases and lesser uncertainty than those derived from ensembles of individual model data. We apply this method to NA-CORDEX models to estimate changes in 24-h precipitation intensity–frequency (PIF) estimates over the Susquehanna watershed and Florida peninsula. Our approach identifies significant future changes at more stations compared to median-based PIF estimates. The analysis suggests that almost all stations over the Susquehanna and at least two-thirds of the stations over the Florida peninsula will observe significant increases in 24-h precipitation for 2–100-yr return periods.
Significant Impacts of Rainfall Redistribution through the Roof of Buildings on Urban Hydrology
Authors: Cao Xuejian , Qi Youcun , Ni Guangheng 
Published: February 2021

AbstractMicrotopography on a building roof will direct rainfall from roofs to the ground through downspouts and transform the rainfall spatial distribution from plane to points. However, the issues on whether and how the building-induced rainfall redistribution (BIRR) influences hydrologic responses are still not well understood despite the numerous downspouts in the urban area. Hence, this study brings the roof layer into a grid-based urban hydrologic model (gUHM) to quantitatively evaluate the impacts of BIRR, aiming to enhance the understanding of building effects in urban hydrology and subsequently to identify the necessity of incorporating BIRR into flood forecasting. Nine land development strategies and 27 rainfall conditions are considered herein to characterize the changing circumstance. Results indicate that the impacts of BIRR depend on multiple circumstance factors and are nonnegligible in urban hydrology. The BIRR causes not only bidirectional impacts on the hydrologic characteristic values (e.g., peak flow and runoff volume) but also an obvious alteration of the hydrograph. Overall, the BIRR tends to increase the peak flow, and more importantly, the impact will be aggravated by the increase of rainfall intensity with the maximum relative error of peak flow approaching 10%. This study contributes to a better understanding of building effects on urban hydrology and a step forward to reduce the uncertainty in urban flood warnings.
Interpersonal Relationship Experiences in Adults Born With Cleft Lip and/or Palate: A Whole of Life Survey in the United Kingdom
Authors: Ardouin Kenny , Hotton Matt , Stock Nicola Marie 
Published: February 2021

Objectives: Previous research has suggested that adults with a cleft lip and/or palate (CL/P) may find their familial, friend, collegial, and/or romantic relationships impacted by their condition. Building on this prior work, this study examined the self-reported interpersonal experiences of a national sample of adults born with CL/P. Design: An online survey was designed by the Cleft Lip and Palate Association in collaboration with the Centre for Appearance Research. Data from 181 participants were included in the present study, collected between July and October 2018. Qualitative data were analyzed using inductive content analysis, while quantitative data were analyzed using descriptive statistics and independent t tests. Results: Most participants reported having good relationships with family members and existing friends with similar patterns of marriage as the general population. However, some experienced difficulties initiating new friendships and romantic relationships. Participants described bullying and discrimination in adulthood, most often in public settings and the workplace. Participants reported lower satisfaction with intimate relationships and less secure attachment compared to the general population. Concerns regarding the heritability of CL/P and its impact on the decision to have a family were also reported. Conclusions: Individuals with CL/P are at risk of negative social experiences, which if not appropriately addressed may impact psychological well-being in adulthood. The findings illustrate the importance of routine psychosocial support from childhood onward to help individuals with CL/P build social skills, self-esteem, and social confidence and to develop mutually fulfilling friendships and intimate relationships. Additionally, societal campaigns to raise awareness and target discrimination may be helpful.
HRD Interventions that Offer a Solution to Work-Life Conflict
Authors: Hammer Emily 
Published: February 2021

The Problem Balancing work and life can be difficult. In a new world of work amidst COVID-19, balancing work and life has become even more challenging. Employees are struggling to adjust their work-life obligations while maintaining performance expectations. Providing employee support to reduce stress and minimize adverse effects on performance outcomes requires employer action. The Solution HRD interventions are recommended as organizational support mechanisms. These interventions are designed to reduce stress produced by work life conflict, particularly during stressful organizational events. Through organizational support, employees are offered the opportunity to increase individual performance. The Stakeholders HRD and HRM professionals, scholars, organizational planners, organizational leaders and managers, and all others who have a vested interest in employee well-being.
von Willebrand factor antigen levels are associated with burden of rare nonsynonymous variants in the VWF gene
Authors: Sadler Brooke , Christopherson Pamela A. , Haller Gabe , Montgomery Robert R. , Di Paola Jorge 
Published: February 2021

Abstract
Approximately 35% of patients with type 1 von Willebrand disease (VWD) do not have a known pathogenic variant in the von Willebrand factor (VWF) gene. We aimed to understand the impact of VWF coding variants on VWD risk and VWF antigen (VWF:Ag) levels, studying 527 patients with low VWF and VWD and 210 healthy controls. VWF sequencing was performed and VWF:Ag levels assayed. A combined annotation-dependent depletion (CADD) score &gt;20 was used as a predicted pathogenicity measure. The number of rare nonsynonymous VWF variants significantly predicted VWF:Ag levels (P = 1.62 × 10−21). There was an association between average number of rare nonsynonymous VWF variants with VWD type 1 (P = 2.4 × 10−13) and low VWF (P = 1.6 × 10−27) compared with healthy subjects: type 1 subjects possessed on average &gt;2 times as many rare variants as those with low VWF and 8 times as many as healthy subjects. The number of rare nonsynonymous variants significantly predicts VWF:Ag levels even after controlling for presence of a variant with a CADD score &gt;20 or a known pathogenic variant in VWF (P = 2.7 × 10−14). The number of rare nonsynonymous variants in VWF as well as the presence of a variant with CADD &gt;20 are both significantly associated with VWF levels. The association with rare nonsynonymous variants holds even when controlling for known pathogenic variants, suggesting that additional variants, in VWF or elsewhere, are associated with VWF:Ag levels. Patients with higher VWF:Ag levels with fewer rare nonsynonymous VWF gene variants could benefit from next-generation sequencing to find the cause of their bleeding.