bluuebunny/crossref_metadata_2025_split huggingface dataset:
EWS-FLI1 regulates and cooperates with core regulatory circuitry in Ewing sarcoma
Authors: Shi Xianping , Zheng Yueyuan , Jiang Liling , Zhou Bo , Yang Wei , Li Liyan , Ding Lingwen , Huang Moli , Gery Sigal , Lin De-Chen , Koeffler H Phillip 
Published: October 2020

Abstract
Core regulatory circuitry (CRC)-dependent transcriptional network is critical for developmental tumors in children and adolescents carrying few gene mutations. However, whether and how CRC contributes to transcription regulation in Ewing sarcoma is unknown. Here, we identify and functionally validate a CRC ‘trio’ constituted by three transcription factors (TFs): KLF15, TCF4 and NKX2-2, in Ewing sarcoma cells. Epigenomic analyses demonstrate that EWS-FLI1, the primary fusion driver for this cancer, directly establishes super-enhancers of each of these three TFs to activate their transcription. In turn, KLF15, TCF4 and NKX2-2 co-bind to their own and each other's super-enhancers and promoters, forming an inter-connected auto-regulatory loop. Functionally, CRC factors contribute significantly to cell proliferation of Ewing sarcoma both in vitro and in vivo. Mechanistically, CRC factors exhibit prominent capacity of co-regulating the epigenome in cooperation with EWS-FLI1, occupying 77.2% of promoters and 55.6% of enhancers genome-wide. Downstream, CRC TFs coordinately regulate gene expression networks in Ewing sarcoma, controlling important signaling pathways for cancer, such as lipid metabolism pathway, PI3K/AKT and MAPK signaling pathways. Together, molecular characterization of the oncogenic CRC model advances our understanding of the biology of Ewing sarcoma. Moreover, CRC-downstream genes and signaling pathways may contain potential therapeutic targets for this malignancy.
Cross-Sectional Association of Lifetime Electronic Cigarette Use with Wheezing and Related Respiratory Symptoms in U.S. Adults
Authors: Li Dongmei , Xie Zidian 
Published: October 2020

Abstract

Introduction
Electronic cigarette use (vaping) has been found to be associated with respiratory symptoms like wheezing or whistling in the chest. Whether or not lifetime vaping occurrences are associated with wheezing has not yet been investigated.

Methods
Population Assessment of Tobacco and Health (PATH) Study Wave 4 data with 22,233 adults collected from December 2016 to January 2018 were used. The cross-sectional association of lifetime vaping occurrences with wheezing and related respiratory symptoms was examined using multivariable weighted logistic regression models considering the complex sampling design.

Results
According to the weighted PATH Wave 4 data, about 89.9% adults never vaped, 3.2% adults vaped one time, 3.2% vaped 2–10 times, 1.3% vaped 11–20 times, 1.1% vaped 21–50 times, 0.4% vaped 51–99 times, and 0.9% vaped 100 or more times in their entire life. Compared to adults who never vaped, adults who vaped 2–10 times had a significantly higher association with ever wheezing (aOR = 1.4, 95% CI: 1.1 to 1.6), past 12-month wheezing (aOR = 1.5, 95% CI: 1.2 to 1.9) and the number of wheezing attacks in the past 12 months (aOR = 1.5, 95% CI: 1.2 to 1.8). Adults who vaped 11–20 times and 100 or more times had similar associations with wheezing as that for adults who vaped 2–10 times. Controlling other tobacco use attenuated the associations.

Conclusions
Lifetime vaping occurrences were found to be associated with some definitions of self-reported wheezing in cross-sectional analyses adjusted for other tobacco use.

Implications
Using the cross-sectional PATH Wave 4 data with 22,233 adults, we found significant associations between lifetime vaping occurrences and ever wheezing or whistling in the chest, past 12 months wheezing or whistling in the chest, as well as the number of wheezing attacks in the past 12 months. The study results suggest that larger studies with more precise time frames and measures are needed to further understand possible connections between vaping experimentation and wheezing symptoms that could inform our understanding of the health effects of electronic cigarettes and resultant policy decisions.
The Genetic and Environmental Influences Contributing to the Association between Electronic and Conventional Cigarette Initiation
Authors: Prom-Wormley Elizabeth C , Clifford James S , Cooke Megan E , Cecilione Jennifer , Maes Hermine H , Do Elizabeth , Roberson-Nay Roxann 
Published: October 2020

Abstract

Introduction
As the use of electronic cigarette (EC) continues to rise in the United States, especially among adolescents and young adults, it is necessary to better understand the factors associated with EC initiation. Specifically, it is unclear how genetic and environmental contributions influence the initiation of EC. Furthermore, the degree to which genetic and environmental influences are shared between EC initiation and conventional cigarette (CC) initiation is unknown.

Methods
A sample of young adult twins ages 15–20 (N = 858 individuals; 421 complete twin pairs) was used to estimate the genetic and environmental influences on the liability of initiation unique to EC and CC as well as the degree to which these factors are shared between the two. Approximately 24% of participants initiated the use of EC, 19% initiated the use of CC, and 11% initiated the dual use.

Results
Combined contributions of additive genetic and shared environmental influences were significant for CC (ACC = 0.19 [95% confidence interval {CI} = 0–0.79], p = 0.57; CCC = 0.42 [95% CI = 0–0.70], p = 0.13) and EC (AEC = 0.25 [95% CI = 0–0.83, p = 0.44; CEC = 0.42 [95% CI = 0–0.73], p = 0.12), whereas unique environmental influences were significant (ECC = 0.39 [95% CI = 0.18–0.57], p &lt; 0.001; EEC = 0.32 [95% CI = 0.14–0.56], p &lt; 0.001). Results also demonstrated a significant overlap of the unique environmental (rE = 0.87, p &lt; 0.001) and familial influences contributing to correlation between the two phenotypes in the bivariate analysis.

Conclusions
These preliminary results suggest that both genes and environmental influences are potential drivers of EC initiation among adolescents and young adults.

Implications
This article is the first to use a sample of twin to estimate the contributions of genetic and environmental influences toward EC initiation and estimate the potential for overlapping influences with CC initiation. This study has implications for future debate about the etiology of EC and CC use with respect to potential overlapping genetic and environmental influences.
Assessing Young Adults’ ENDS Use via Ecological Momentary Assessment and a Smart Bluetooth Enabled ENDS Device
Authors: Li Zehan , Benowitz-Fredericks Carson , Ling Pamela M , Cohen Joanna E , Thrul Johannes 
Published: October 2020

Abstract

Introduction
The assessment of electronic nicotine delivery systems (ENDS) use poses unique challenges that go beyond established assessment methods for tobacco cigarettes. Recent studies have proposed using ecological momentary assessment (EMA), a method to collect self-reported data on mobile devices, or data passively collected by “smart” Bluetooth enabled ENDS to assess use. The current study sought to compare ENDS use data using EMA and puff counts collected from a smart device.

Aims and Methods
We recruited 18 young adult ENDS users (age M = 23.33; 44.4% female) from the San Francisco Bay Area. For a total of 30 days, participants completed daily diaries by EMA and used a second-generation smart Bluetooth enabled ENDS that collected puff data. Repeated measures correlations, multilevel regressions, and paired t tests assessed concordance of EMA reports and ENDS data. A subset of four highly compliant participants were selected for sensitivity analyses.

Results
Among all 18 participants, completion of EMA daily diaries was high (77.4%). The ENDS device collected approximately twice as many puffs per day as participants reported. Compared with self-reported number of sessions and amount of e-liquid used, self-reported puff counts had the highest correlation with device-collected puff counts (rrm = 0.49; p &lt; .001). Correlations between self-reported and device-collected puff counts improved among the subset of four highly compliant participants (rrm = 0.59; p &lt; .001).

Conclusions
Self-reports potentially underestimate use of ENDS. Puff counts appear to be the best self-reported measure to assess ENDS use compared with number of sessions or liquid volume.

Implications
The comparison of EMA self-reports and passively collected ENDS device data can inform future efforts to assess ENDS use. Self-reported puff counts are preferable over number of sessions or amount of liquid used, but compared with objective usage data, self-reported puff counts may still underestimate actual use. ENDS use behavior is likely higher than users estimate and report. Future research on improved measures of ENDS use is needed.
Semantic Memory Impairment Across the Schizophrenia Continuum: A Meta-Analysis of Category Fluency Performance
Authors: Tan Eric Josiah , Neill Erica , Tomlinson Kiandra , Rossell Susan Lee 
Published: October 2020

Abstract
Semantic memory (SM) impairments are a core feature of schizophrenia and are present along the psychosis continuum. It is, however, unclear whether the degree of SM impairments vary along this continuum and if demographic and clinical factors affect impairment severity. This study performed meta-analyses of category fluency task performance (a task commonly used to assess SM) in 4 groups along the schizophrenia continuum: high schizotypes (HSZT), first-degree relatives (FDR), recent-onset patients (≤2 y; ROP) and chronic patients (CSZ). Electronic databases were searched for relevant studies published up to October 2019 resulting in the inclusion of 48 articles. The main analyses assessed fluency productivity scores in 2978 schizophrenia spectrum disorder patients, 340 first-degree relatives of schizophrenia spectrum disorder patients, and 3204 healthy controls. Further analyses assessed errors, mean cluster size, and switching data that were available in the CSZ group only. Results revealed significant impairments in fluency productivity were present in the FDR, ROP, and CSZ groups relative to healthy controls, but not in HSZT. In the CSZ group, significant differences relative to healthy controls were also observed in non-perseverative errors, mean cluster size, and number of switches. The findings collectively suggest that SM deficits are present at each stage of the continuum and are exacerbated post-illness onset. They also support the centrality of SM impairments in schizophrenia and most elevated risk groups. Future studies with more diverse measures of SM function are needed to replicate and extend this research.
Molecular mechanisms for magnesium-deficiency-induced leaf vein lignification, enlargement and cracking in Citrus sinensis revealed by RNA-Seq
Authors: Ye Xin , Huang Hui-Yu , Wu Feng-Lin , Cai Li-Ya , Lai Ning-Wei , Deng Chong-Ling , Guo Jiu-Xin , Yang Lin-Tong , Chen Li-Song 
Published: October 2020

Abstract
Citrus sinensis (L.) Osbeck seedlings were fertigated with nutrient solution containing 2 [magnesium (Mg)-sufficiency] or 0 mM (Mg-deficiency) Mg(NO3)2 for 16 weeks. Thereafter, RNA-Seq was used to investigate Mg-deficiency-responsive genes in the veins of upper and lower leaves in order to understand the molecular mechanisms for Mg-deficiency-induced vein lignification, enlargement and cracking, which appeared only in the lower leaves. In this study, 3065 upregulated and 1220 downregulated, and 1390 upregulated and 375 downregulated genes were identified in Mg-deficiency veins of lower leaves (MDVLL) vs Mg-sufficiency veins of lower leaves (MSVLL) and Mg-deficiency veins of upper leaves (MDVUL) vs Mg-sufficiency veins of upper leaves (MSVUL), respectively. There were 1473 common differentially expressed genes (DEGs) between MDVLL vs MSVLL and MDVUL vs MSVUL, 1463 of which displayed the same expression trend. Magnesium-deficiency-induced lignification, enlargement and cracking in veins of lower leaves might be related to the following factors: (i) numerous transciption factors and genes involved in lignin biosynthesis pathways, regulation of cell cycle and cell wall metabolism were upregulated; and (ii) reactive oxygen species, phytohormone and cell wall integrity signalings were activated. Conjoint analysis of proteome and transcriptome indicated that there were 287 and 56 common elements between DEGs and differentially abundant proteins (DAPs) identified in MDVLL vs MSVLL and MDVUL vs MSVUL, respectively, and that among these common elements, the abundances of 198 and 55 DAPs matched well with the transcript levels of the corresponding DEGs in MDVLL vs MSVLL and MDVUL vs MSVUL, respectively, indicating the existence of concordances between protein and transcript levels.
Peroneal Nerve Function Before and Following Surgical Excision of a Proximal Fibular Osteochondroma
Authors: Birch Craig M. , Smit Kevin M. , Sucato Daniel J. 
Published: October 2020

Background:Osteochondromas occur most commonly in the distal femur, proximal tibia, and humerus. There are no large studies reviewing the outcome of treatment for patients with an osteochondroma involving the proximal fibula. The purpose of this study is to specifically understand the manifestations of a proximal fibular osteochondroma (PFO) on the preoperative peroneal nerve function, and how surgical management of the osteochondroma affects function immediately postoperatively and at long-term follow-up.Methods:This is an institutional review board-approved retrospective review of a consecutive series of patients with a PFO treated operatively at a single institution. The medical record was carefully reviewed to identify demographic data, clinical data especially the status of the peroneal function at various time points.Results:There were 25 patients with 31 affected extremities who underwent surgical excision of the PFO at an average age of 12.4 years (range, 3.0 to 17.9 y). There were 16 males and 9 females. The underlying diagnosis was isolated PFO in 2 (8%) patients and multiple hereditary exostosis in 23 (92%) patients. Preoperatively, 9 (29%) had a foot drop and 22 (71%) did not. Those with a preoperative foot drop underwent surgery at a younger age (9.1 vs. 13.8 y) (P<0.004) and postoperatively 5 (55.5%) had complete resolution, 3 (33.3%) had improvement, and 1 (11.1%) persisted requiring an ankle foot orthosis. Of the 22 who were normal preoperatively, 5 (22.7%) developed an immediate postoperative foot drop, 3 (60%) completely resolved, 1 (20%) improved, and 1 (20%) persisted and was found to have a transected nerve at exploration. In total, 23 of the 25 (92%) patients who had a PFO excision, had a normal or near-normal peroneal nerve function including those who had poor function preoperatively.Conclusions:Patients with a PFO have a preoperative peroneal nerve dysfunction 30% of the time and 23% of those who were normal preoperatively have postoperative dysfunction. Fortunately, nearly all patients have a complete recovery following excision of the osteochondroma.Level of Evidence:Level IV.
A Study of Associations Between Plasma Metformin Concentration, Lactic Acidosis, and Mortality in an Emergency Hospitalization Context
Authors: Bennis Youssef , Bodeau Sandra , Batteux Benjamin , Gras-Champel Valérie , Masmoudi Kamel , Maizel Julien , De Broe Marc E. , Lalau Jean-Daniel , Lemaire-Hurtel Anne-Sophie 
Published: October 2020

Objectives:
To determine the plasma metformin concentration threshold associated with lactic acidosis and analyze the outcome in metformin-treated patients with lactic acidosis hospitalized in an emergency context.

Design:
A retrospective, observational, single-center study.

Setting:
Emergency department and ICUs at Amiens University Hospital (Amiens, France).

Patients:
All consecutive patients with data on arterial lactate and pH up to 12 hours before or after a plasma metformin assay within 24 hours of admission, over a 9.7-year period.

Intervention:
None.

Measurements and Main Results:
The study population consisted of 194 metformin-treated diabetic patients (median age: 68.6; males: 113 [58.2%]); 163 (84%) had acute kidney injury, which was associated variously with dehydration (45.4%), sepsis (41.1%), cardiogenic shock (20.9%), and diabetic ketoacidosis (16%). Eighty-seven patients (44.8%) had lactic acidosis defined as an arterial blood pH less than 7.35 and a lactate concentration greater than or equal to 4 mM, and 38 of them (43.7%) died in the ICU. A receiver operating characteristic curve analysis showed that a metformin concentration threshold of 9.9 mg/L was significantly associated with the occurrence of lactic acidosis (specificity: 92.9%; sensitivity: 67.1%; area under the receiver operating characteristic curve: 0.83; p < 0.0001). Among lactic acidosis-positive patients, however, in-ICU death was less frequent when the metformin concentration was greater than or equal to 9.9 mg/L (33.9% vs 61.3% for < 9.9 mg/L; p = 0.0252). After adjustment for the Simplified Acute Physiology Score II, in-ICU death was positively associated with prothrombin activity less than 70% and negatively associated with the initiation of renal replacement therapy at admission.

Conclusions:
In metformin-treated patients admitted in an emergency context, a plasma metformin concentration greater than or equal to 9.9 mg/L was strongly associated with the presence of lactic acidosis. This threshold may assist with the delicate decision of whether or not to initiate renal replacement therapy. Indeed, the outcome of lactic acidosis might depend on the prompt initiation of renal replacement therapy—especially when liver failure reduces lactate elimination.
Bacterial Pneumonia in Brain-Dead Patients: Clinical Features and Impact on Lung Suitability for Donation*
Authors: Poignant Simon , Boutrot Maxime , Ehrmann Stephan , Remerand Francis , Venhard Jean-Christophe , Wolf Manuel , Boulain Thierry , Barbier François 
Published: October 2020

Objectives:
To appraise the epidemiological features of bacterial pneumonia and its impact on lung suitability for donation in brain-dead patients managed with protective ventilatory settings.

Design:
Retrospective observational study.

Setting:
Six ICUs from two university-affiliated hospitals.

Patients:
Brain-dead adult patients managed in the participating ICUs over a 4-year period.

Interventions:
None.

Measurements and Main Results:
Among the 231 included patients, 145 (62.8%) were classified as ideal or extended-criteria potential lung donors at ICU admission and the remaining 86 patients having baseline contraindication for donation. Culture-proven aspiration pneumonia and early-onset ventilator-associated pneumonia occurred in 54 patients (23.4%) and 15 patients (6.5%), respectively (overall pneumonia incidence, 29.9%). Staphylococcus aureus and Enterobacterales were the most common pathogens. Using mixed-effects Cox proportional hazard models, age (adjusted hazard ratio, 0.98; 95% CI [0.96–0.99]), anoxic brain injury (3.55 [1.2–10.5]), aspiration (2.29 [1.22–4.29]), and not receiving antimicrobial agents at day 1 (3.56 [1.94–6.53]) were identified as independent predictors of pneumonia occurrence in the whole study population. Analyses restricted to potential lung donors yielded similar results. Pneumonia was associated with a postadmission decrease in the Pao
2/Fio
2 ratio and lower values at brain death, in the whole study population (estimated marginal mean, 294 [264–323] vs 365 [346–385] mm Hg in uninfected patients; p = 0.0005) as in potential lung donors (299 [248–350] vs 379 [350–408] mm Hg; p = 0.04; linear mixed models). Lungs were eventually retrieved in 31 patients (34.4%) among the 90 potential lung donors with at least one other organ harvested (pneumonia prevalence in lung donors (9.7%) vs nondonors (49.2%); p = 0.0002).

Conclusions:
Pneumonia occurs in one-third of brain-dead patients and appears as the main reason for lung nonharvesting in those presenting as potential lung donors. The initiation of antimicrobial prophylaxis upon the first day of the ICU stay in comatose patients with severe brain injury could enlarge the pool of actual lung donors.
IL-5 mediates monocyte phenotype and pain outcomes in fibromyalgia
Authors: Merriwether Ericka N. , Agalave Nilesh M. , Dailey Dana L. , Rakel Barbara A. , Kolker Sandra J. , Lenert Melissa E. , Spagnola William H. , Lu Ying , Geasland Katharine M. , Allen Lee-Ann H. , Burton Michael D. , Sluka Kathleen A. 
Published: October 2020

Abstract
Fibromyalgia (FM) is characterized by widespread chronic pain, fatigue, and somatic symptoms. The influence of phenotypic changes in monocytes on symptoms associated with FM is not fully understood. The primary aim of this study was to take a comprehensive whole-body to molecular approach in characterizing relationships between monocyte phenotype and FM symptoms in relevant clinical populations. Lipopolysaccharide-evoked and spontaneous secretion of IL-5 and other select cytokines from circulating monocytes was higher in women with FM compared to women without pain. In addition, greater secretion of IL-5 was significantly associated with pain and other clinically relevant psychological and somatic symptoms of FM. Furthermore, higher levels of pain and pain-related symptoms were associated with a lower percentage of intermediate monocytes (CD14++/CD16+) and a greater percentage of nonclassical monocytes (CD14+/CD16++) in women with FM. Based on findings from individuals with FM, we examined the role of IL-5, an atypical cytokine secreted from monocytes, in an animal model of widespread muscle pain. Results from the animal model show that IL-5 produces analgesia and polarizes monocytes toward an anti-inflammatory phenotype (CD206+). Taken together, our data suggest that monocyte phenotype and their cytokine profiles are associated with pain-related symptoms in individuals with FM. Furthermore, our data show that IL-5 has a potential role in analgesia in an animal model of FM. Thus, targeting anti-inflammatory cytokines such as IL-5 secreted by circulating leukocytes could serve as a promising intervention to control pain and other somatic symptoms associated with FM.
At-Home Testing for Sexually Transmitted Infections During the COVID-19 Pandemic
Authors: Carnevale Caroline , Richards Paul , Cohall Renee , Choe Joshua , Zitaner Jenna , Hall Natalie , Cohall Alwyn , Whittier Susan , Green Daniel A. , Sobieszczyk Magdalena E. , Gordon Peter , Zucker Jason 
Published: October 2020

Abstract
During the COVID-19 pandemic in New York City, NewYork-Presbyterian Hospital provided HIV prevention patients with gonorrhea/chlamydia testing kits at home. This report describes the program implementation to provide other sexual health clinics with a roadmap in adapting to a “new normal” in providing comprehensive sexual health care virtually to patients.