bluuebunny/crossref_metadata_2025_split huggingface dataset:
Embryonic erythropoiesis and hemoglobin switching require transcriptional repressor ETO2 to modulate chromatin organization
Authors: Guo Xiang , Plank-Bazinet Jennifer , Krivega Ivan , Dale Ryan K , Dean Ann 
Published: September 2020

Abstract
The underlying mechanism of transcriptional co-repressor ETO2 during early erythropoiesis and hemoglobin switching is unclear. We find that absence of ETO2 in mice interferes with down-regulation of PU.1 and GATA2 in the fetal liver, impeding a key step required for commitment to erythroid maturation. In human β-globin transgenic Eto2 null mice and in human CD34+ erythroid progenitor cells with reduced ETO2, loss of ETO2 results in ineffective silencing of embryonic/fetal globin gene expression, impeding hemoglobin switching during erythroid differentiation. ETO2 occupancy genome-wide occurs virtually exclusively at LDB1-complex binding sites in enhancers and ETO2 loss leads to increased enhancer activity and expression of target genes. ETO2 recruits the NuRD nucleosome remodeling and deacetylation complex to regulate histone acetylation and nucleosome occupancy in the β-globin locus control region and γ-globin gene. Loss of ETO2 elevates LDB1, MED1 and Pol II in the locus and facilitates fetal γ-globin/LCR looping and γ-globin transcription. Absence of the ETO2 hydrophobic heptad repeat region impairs ETO2-NuRD interaction and function in antagonizing γ-globin/LCR looping. Our results reveal a pivotal role for ETO2 in erythropoiesis and globin gene switching through its repressive role in the LDB1 complex, affecting the transcription factor and epigenetic environment and ultimately restructuring chromatin organization.
Structural basis of DNA replication origin recognition by human Orc6 protein binding with DNA
Authors: Xu Naining , You Yingying , Liu Changdong , Balasov Maxim , Lun Lee Tung , Geng Yanyan , Fung Chun Po , Miao Haitao , Tian Honglei , Choy To To , Shi Xiao , Fan Zhuming , Zhou Bo , Akhmetova Katarina , Din Rahman Ud , Yang Hongyu , Hao Quan , Qian Peiyuan , Chesnokov Igor , Zhu Guang 
Published: September 2020

AbstractThe six-subunit origin recognition complex (ORC), a DNA replication initiator, defines the localization of the origins of replication in eukaryotes. The Orc6 subunit is the smallest and the least conserved among ORC subunits. It is required for DNA replication and essential for viability in all species. Orc6 in metazoans carries a structural homology with transcription factor TFIIB and can bind DNA on its own. Here, we report a solution structure of the full-length human Orc6 (HsOrc6) alone and in a complex with DNA. We further showed that human Orc6 is composed of three independent domains: N-terminal, middle and C-terminal (HsOrc6-N, HsOrc6-M and HsOrc6-C). We also identified a distinct DNA-binding domain of human Orc6, named as HsOrc6-DBD. The detailed analysis of the structure revealed novel amino acid clusters important for the interaction with DNA. Alterations of these amino acids abolish DNA-binding ability of Orc6 and result in reduced levels of DNA replication. We propose that Orc6 is a DNA-binding subunit of human/metazoan ORC and may play roles in targeting, positioning and assembling the functional ORC at the origins.
Detection of genomic G-quadruplexes in living cells using a small artificial protein
Authors: Zheng Ke-wei , Zhang Jia-yu , He Yi-de , Gong Jia-yuan , Wen Cui-jiao , Chen Juan-nan , Hao Yu-hua , Zhao Yong , Tan Zheng 
Published: September 2020

Abstract
G-quadruplex (G4) structures formed by guanine-rich nucleic acids are implicated in essential physiological and pathological processes and serve as important drug targets. The genome-wide detection of G4s in living cells is important for exploring the functional role of G4s but has not yet been achieved due to the lack of a suitable G4 probe. Here we report an artificial 6.7 kDa G4 probe (G4P) protein that binds G4s with high affinity and specificity. We used it to capture G4s in living human, mouse, and chicken cells with the ChIP-Seq technique, yielding genome-wide landscape as well as details on the positions, frequencies, and sequence identities of G4 formation in these cells. Our results indicate that transcription is accompanied by a robust formation of G4s in genes. In human cells, we detected up to &gt;123 000 G4P peaks, of which &gt;1/3 had a fold increase of ≥5 and were present in &gt;60% promoters and ∼70% genes. Being much smaller than a scFv antibody (27 kDa) or even a nanobody (12–15 kDa), we expect that the G4P may find diverse applications in biology, medicine, and molecular devices as a G4 affinity agent.
Conditional guide RNA through two intermediate hairpins for programmable CRISPR/Cas9 function: building regulatory connections between endogenous RNA expressions
Authors: Lin Jiao , Liu Yan , Lai Peidong , Ye Huixia , Xu Liang 
Published: September 2020

AbstractA variety of nanodevices developed for nucleic acid computation provide great opportunities to construct versatile synthetic circuits for manipulation of gene expressions. In our study, by employing a two-hairpin mediated nucleic acid strand displacement as a processing joint for conditional guide RNA, we aim to build artificial connections between naturally occurring RNA expressions through programmable CRISPR/Cas9 function. This two-hairpin joint possesses a sequence-switching machinery, in which a random trigger strand can be processed to release an unconstrained sequence-independent strand and consequently activate the self-inhibitory guide RNA for conditional gene regulation. This intermediate processor was characterized by the fluorescence reporter system and applied for regulation of the CRISPR/Cas9 binding activity. Using plasmids to generate this sequence-switching machinery in situ, we achieved the autonomous genetic regulation of endogenous RNA expressions controlled by other unrelated endogenous RNAs in both E. coli and human cells. Unlike previously reported strand-displacement genetic circuits, this advanced nucleic acid nanomachine provides a novel approach that can establish regulatory connections between naturally occurring endogenous RNAs. In addition to CRISPR systems, we anticipate this two-hairpin machine can serve as a general processing joint for wide applications in the development of other RNA-based genetic circuits.
Prognostic impact of CDKN2A/B deletion, TERT mutation, and EGFR amplification on histological and molecular IDH-wildtype glioblastoma
Authors: Ma Sirui , Rudra Soumon , Campian Jian L , Dahiya Sonika , Dunn Gavin P , Johanns Tanner , Goldstein Michael , Kim Albert H , Huang Jiayi 
Published: September 2020

Abstract

Background
We aimed to evaluate the clinical outcomes of molecular glioblastoma (mGBM) as compared to histological GBM (hGBM) and to determine the prognostic impact of TERT mutation, EGFR amplification, and CDKN2A/B deletion on isocitrate dehydrogenase (IDH)-wildtype GBM.

Methods
IDH-wildtype GBM patients treated with radiation therapy (RT) between 2012 and 2019 were retrospectively analyzed. mGBM was defined as grade II-III IDH-wildtype astrocytoma without histological features of GBM but with one of the following molecular alterations: TERT mutation, EGFR amplification, or combination of whole chromosome 7 gain and whole chromosome 10 loss. Overall survival (OS) and progression-free survival (PFS) were calculated from RT and analyzed using the Kaplan–Meier method. Multivariable analysis (MVA) was performed using Cox regression to identify independent predictors of OS and PFS.

Results
Of the 367 eligible patients, the median follow-up was 11.7 months. mGBM and hGBM did not have significantly different OS (median: 16.6 vs 13.5 months, respectively, P = .16), nor PFS (median: 11.7 vs 7.3 months, respectively, P = .08). However, mGBM was associated with better OS (hazard ratio [HR] 0.50, 95% CI 0.29–0.88) and PFS (HR 0.43, 95% CI 0.26–0.72) than hGBM after adjusting for known prognostic factors on MVA. CDKN2A/B deletion was associated with worse OS (HR 1.57, 95% CI 1.003–2.46) and PFS (HR 1.57, 95% CI 1.04–2.36) on MVA, but TERT mutation and EGFR amplification were not.

Conclusion
Criteria for mGBM may require further refinement and validation. CDKN2A/B deletion, but not TERT mutation or EGFR amplification, may be an independent prognostic biomarker for IDH-wildtype GBM patients.
Tularemia: A Case Series of Patients Diagnosed at the National Reference Center for Rickettsioses From 2008 to 2017
Authors: Darmon-Curti Anne , Darmon François , Edouard Sophie , Hennebique Aurélie , Guimard Thomas , Martin-Blondel Guillaume , Klopfenstein Timothée , Talarmin Jean-Philippe , Raoult Didier , Maurin Max , Fournier Pierre-Edouard 
Published: September 2020

Abstract

Background
We describe the epidemiological, clinical, and prognostic aspects of 177 tularemia cases diagnosed at the National Reference Center for rickettsioses, coxiellosis, and bartonelloses between 2008 and 2017.

Methods
All patients with a microbiological diagnosis of tularemia made in the laboratory were included. Clinical and epidemiological data were collected retrospectively from clinicians in charge of patients using a standardized questionnaire. Diagnostic methods used were indirect immunofluorescence serology, real-time polymerase chain reaction (PCR), and universal PCR targeting the 16S ribosomal ribonucleic acid gene.

Results
The series included 54 females and 123 males (sex ratio, 2.28; mean age, 47.38 years). Eighty-nine (50.2%) were confirmed as having tularemia on the basis of a positive Francisella tularensis PCR or seroconversion, and 88 (49.8%) were considered as probable due to a single positive serum. The regions of France that were most affected included Pays de la Loire (22% of cases), Nouvelle Aquitaine (18.6% of cases), and Grand Est (12.4% of cases). Patients became infected mainly through contact with rodents or game (38 cases, 21.4%), through tick-bites (23 cases, 12.9%), or during outdoor leisure activities (37 cases, 20.9%). Glandular and ulceroglandular forms were the most frequent (109 cases, 61.5%). Two aortitis, an infectious endocarditis, a myocarditis, an osteoarticular infection, and a splenic hematoma were also diagnosed. Tularemia was discovered incidentally in 54.8% of cases. Seventy-eight patients were hospitalized, and no deaths were reported.

Conclusions
Our data suggest that in an endemic area and/or in certain epidemiological contexts, tularemia should be sought to allow an optimized antibiotic therapy and a faster recovery.
Incidence and Presentation of Sarcoidosis With and Without HIV Infection
Authors: Hanberg Jennifer S , Akgün Kathleen M , Hsieh Evelyn , Fraenkel Liana , Justice Amy C 
Published: September 2020

Abstract

Background
Case reports describe incident sarcoidosis in persons with HIV (PWH). The association between HIV and risk of sarcoidosis, and differences in presentation in PWH, have not been systematically assessed.

Methods
Subjects were selected from the Veterans Aging Cohort Study (VACS), a longitudinal cohort study including veterans with HIV and matched uninfected veterans. This was a prospective observational analysis in which we evaluated both the incidence (via incidence rate ratio) and presentation and treatment (by comparison of rates of organ involvement and use of medications) of sarcoidosis in PWH compared with HIV-negative controls. We also assessed risk factors (via Cox regression) associated with the development of sarcoidosis including CD4 count and viral load trajectory.

Results
Of 1614 patients evaluated via chart review, 875 (54%) had prevalent sarcoidosis and 325 (20%) had confirmed incident sarcoidosis. Incident sarcoidosis occurred in 59 PWH and 266 uninfected. The incidence of sarcoidosis was lower in PWH than uninfected (incidence rate ratio [IRR], 0.61; 95% CI, 0.46–0.81) and especially low in patients with unsuppressed viremia (IRR, 0.04; 95% CI, 0.02–0.08) compared with uninfected). At diagnosis of sarcoidosis, the median CD4 count among PWH was 409 cells/mm3; 77% had HIV-1 RNA &lt;500 copies/mL. No significant differences were observed between PWH and uninfected in terms of organ involvement, disease severity, or use of oral glucocorticoids.

Conclusions
HIV, particularly with persistent viremia, was associated with decreased risk of incident sarcoidosis; severity and treatment were similar between PWH and uninfected.
SPATIAL VARIABILITY OF INDOOR RADON CONCENTRATION IN SCHOOLS: IMPLICATIONS ON RADON MEASUREMENT PROTOCOLS
Authors: Curguz Z , Venoso G , Zunic Z S , Mirjanic D , Ampollini M , Carpentieri C , Di Carlo C , Caprio M , Alavantic D , Kolarz P , Stojanovska Z , Antignani S , Bochicchio F 
Published: September 2020

Abstract
The requirements about radon measurements in schools and public buildings included in most of the national and international legislations are generally restricted to all the rooms located at the ground floor and basement, assuming the soil beneath the building as the main source of indoor radon. In order to verify such an assumption for small buildings having at maximum two floors, a preliminary study was performed in 50 schools located in 15 municipalities of the Republic of Srpska. Results of this study suggest that a protocol requiring measurements at the ground floor only may be considered adequate. Due to the high radon spatial variability for rooms at the ground floor, it is preferable to require measurements in a high number of rooms (preferably in all of them) in order to assess the compliance with the reference level established by the legislation.
Large-scale functional coactivation patterns reflect the structural connectivity of the medial prefrontal cortex
Authors: Tovar Dale T , Chavez Robert S 
Published: September 2020

Abstract
The medial prefrontal cortex (MPFC) is among the most consistently implicated brain regions in social and affective neuroscience. Yet, this region is also highly functionally heterogeneous across many domains and has diverse patterns of connectivity. The extent to which the communication of functional networks in this area is facilitated by its underlying structural connectivity fingerprint is critical for understanding how psychological phenomena are represented within this region. In the current study, we combined diffusion magnetic resonance imaging and probabilistic tractography with large-scale meta-analysis to investigate the degree to which the functional coactivation patterns of the MPFC are reflected in its underlying structural connectivity. Using unsupervised machine learning techniques, we compared parcellations between the two modalities and found congruence between parcellations at multiple spatial scales. Additionally, using connectivity and coactivation similarity analyses, we found high correspondence in voxel-to-voxel similarity between each modality across most, but not all, subregions of the MPFC. These results provide evidence that meta-analytic functional coactivation patterns are meaningfully constrained by underlying neuroanatomical connectivity and provide convergent evidence of distinct subregions within the MPFC involved in affective processing and social cognition.
Sleep among gender minority adolescents
Authors: Levenson Jessica C , Thoma Brian C , Hamilton Jessica L , Choukas-Bradley Sophia , Salk Rachel H 
Published: September 2020

Abstract

Study Objectives
Stigmatized youth experience poorer sleep than those who have not experienced stigma. However, no studies have examined the sleep of gender minority adolescents (GMAs). Examining sleep disparities between GMAs and non-GMAs is critical because poor sleep is associated with mental health outcomes experienced disproportionately by GMAs. We examined sleep duration, sleep problems, and sleep quality among our sample and compared these parameters between GMAs and non-GMAs.

Methods
Adolescents aged 14–18 years (n = 1,027 GMA, n = 329 heterosexual non-GMA, n = 415 sexual minority non-GMA; mean age = 16 years; 83% female sex at birth) completed a cross-sectional online survey, reporting sex assigned at birth and current gender identity, sleep duration, sleep problems (too much/too little sleep and inadequate sleep), sleep quality, and depressive symptoms.

Results
Accounting for demographic covariates, GMAs were more likely to report inadequate sleep and shorter sleep duration and had higher odds of reporting poor sleep quality and getting too little/too much sleep than heterosexual non-GMAs. After also adjusting for depressive symptoms, the finding that GMAs more often reported poor sleep quality remained significant.

Conclusions
This first large, nationwide survey of sleep among GMAs suggests that GMAs may be more likely to have poor sleep than non-GMAs. The significance of our results was reduced when adjusting for depressive symptoms, suggesting that poorer sleep may occur in the context of depression for GMAs. Future work should include objective measures of sleep, examine the emergence of sleep disparities among GMAs and non-GMAs, and explore pathways that increase risk for poor sleep among GMAs.
Organization leaders’ decisions to sustain a peer-led healthy lifestyle intervention for people with serious mental illness in supportive housing
Authors: Cabassa Leopoldo J , Stefancic Ana , Bochicchio Lauren , Tuda Daniela , Weatherly Christopher , Lengnick-Hall Rebecca 
Published: September 2020

Abstract
Healthy lifestyle interventions that increase physical activity and healthy dietary habits can help improve the physical health of people with serious mental illness (SMI). Yet, these interventions are not implemented in routine practice settings. This mixed methods study examined the decisions that leaders from three supportive housing agencies made as they planned to sustain a peer-led healthy lifestyle intervention for people with SMI at the end of a clinical trial. A combination of implementation strategies that addressed cost concerns, generated local evidence of the intervention’s benefits, and provided ongoing training was identified as important for sustainability. A sustainability model illustrating implementation strategies and mechanisms for supporting three sustainability domains (funding, organizational capacity, and adaptation) was prioritized by participants. Study findings can inform future studies testing strategies and mechanisms to support the sustainability of interventions in routine practice settings to improve the physical health of people with SMI.
Genomic epidemiology of the Los Angeles COVID-19 outbreak
Authors: Guo Longhua , Boocock James , Hilt Evann E. , Chandrasekaran Sukantha , Zhang Yi , Munugala Chetan , Sathe Laila , Alexander Noah , Arboleda Valerie A. , Flint Jonathan , Eskin Eleazar , Luo Chongyuan , Yang Shangxin , Garner Omai B. , Yin Yi , Bloom Joshua S. , Kruglyak Leonid 
Published: September 2020

AbstractLos Angeles (LA) County has sustained a large outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To learn about the transmission history of SARS-CoV-2 in LA County, we sequenced 142 viral genomes from unique patients seeking care at UCLA Health System. 86 of these genomes are from samples collected before April 19, 2020. We found that the early outbreak in LA, as in other international air travel hubs, was seeded by multiple introductions of strains from Asia and Europe. We identified a US-specific strain, B.1.43, which has been found predominantly in California and Washington State. While samples from LA County carry the ancestral B.1.43 genome, viral genomes from neighbouring counties in California and from counties in Washington State carry additional mutations, suggesting a potential origin of B.1.43 in Southern California. We quantified the transmission rate of SARS-CoV-2 over time, and found evidence that the public health measures put in place in LA County to control the virus were effective at preventing transmission, but may have been undermined by the many introductions of SARS-CoV-2 into the region. Our work demonstrates that genome sequencing can be a powerful tool for investigating outbreaks and informing the public health response. Our results reinforce the critical need for the U.S. to have coordinated inter-state responses to the pandemic.
Increased Self-Reported Discrimination and Concern for Physical Assault Due to the COVID-19 Pandemic in Chinese, Vietnamese, Korean, Japanese, and Filipino Americans
Authors: Ha Sierra K. , Nguyen Ann T. , Sales Chloe , Chang Rachel S. , Ta Hillary , Srinivasan Malathi , Chung Sukyung , Palaniappan Latha , Lin Bryant 
Published: September 2020

AbstractObjectivesTo investigate self-reported discrimination and concern for physical assault due to the COVID-19 pandemic among disaggregated Asian subgroups in the US.MethodsWe conducted a nationwide survey to assess self-reported discrimination and concern for physical assault due to COVID-19 across racial/ethnic groups, including diverse subgroups of Asians.ResultsChinese respondents experienced the largest change (15% increase) in proportion of respondents reporting discrimination from 2019 to 2020 (P<.01). Chinese, Korean, Japanese, Vietnamese, and Other API showed up to 3.9 times increased odds of self-reported racial/ethnic discrimination due to COVID-19 and, with the addition of Filipino, experienced up to 5.4 times increased odds of concern for physical assault due to COVID-19 compared to Whites.ConclusionsOur study is the first to examine self-reported discrimination and concern for physical assault due to COVID-19 in subgroups of Asian Americans, finding that East (Chinese, Korean, Japanese) and Southeast (Vietnamese, Filipino) Asian Americans have been disproportionately affected. Future studies should disaggregate Asian subgroups to fully understand experiences of discrimination in diverse populations in the US.
An Initial Psychometric Evaluation of the APS-POQ-R in Acute Pain Presenting to the Emergency Department
Authors: Hughes James A , Jones Lee , Potter Joseph , Wong Alixandra , Brown Nathan J , Chu Kevin 
Published: September 2020

3.AbstractBackgroundPain is a common presenting complaint to the emergency department (ED), yet is often undertreated. When assessing the outcomes of pain care in the ED, process measures are commonly reported. Attempts to measure patient-reported outcomes existing in current ED literature. However, they are frequently unvalidated and lack standardization. The American Pain Societies – Patient Outcome Questionnaire-Revised edition (APS-POQ-R) has been identified as the most likely, pre-existing tool to be useful in the acute pain in the ED. However, this requires feasibility and construct validation before use.ObjectiveTo assess the feasibility and construct validity of the APS-POQ-R in patients presenting to the adult emergency department with acute pain.MethodsThis study is an initial psychometric evaluation of the constructs contained within the APS-POQ-R in adult patients presenting with moderate to severe acute pain to a large urban ED. The study is guided by the methods described in the initial development of the instrument.ResultsTwo hundred adult patients were recruited and completed the APS-POQ-R. The APS-POQ-R demonstrated content validity in patients presenting with acute pain. Exploratory factor analysis demonstrated five subgroups. The tool demonstrated discriminatory ability based on patient urgency, and subscale measurement was associated with patient satisfaction with care.ConclusionsThe APS-POQ-R has demonstrable construct validity in adult patients presenting with acute pain to the ED. Further psychometric analysis across multiple EDs is required before the APS-POQ-R can be recommended as a validated PROM for ED patients in pain.