bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small molecule targeting CELF1 RNA-binding activity to control HSC activation and liver fibrosis
Authors: Tan Yang , Sun Xueqing , Xu Yizhu , Tang Bingjie , Xu Shuaiqi , Lu Dong , Ye Yan , Luo Xiaomin , Diao Xu , Li Fulong , Wang Tianyi , Chen Jiayu , Xu Qiang , Wu Xingxin 
Published: February 2022

Abstract
CUGBP Elav-like family member 1 (CELF1), an RNA-binding protein (RBP), plays important roles in the pathogenesis of diseases such as myotonic dystrophy, liver fibrosis and cancers. However, targeting CELF1 is still a challenge, as RBPs are considered largely undruggable. Here, we discovered that compound 27 disrupted CELF1-RNA binding via structure-based virtual screening and biochemical assays. Compound 27 binds directly to CELF1 and competes with RNA for binding to CELF1. Compound 27 promotes IFN-γ secretion and suppresses TGF-β1-induced hepatic stellate cell (HSC) activation by inhibiting CELF1-mediated IFN-γ mRNA decay. In vivo, compound 27 attenuates CCl4-induced murine liver fibrosis. Furthermore, the structure-activity relationship analysis was performed and compound 841, a derivative of compound 27, was identified as a selective CELF1 inhibitor. In conclusion, targeting CELF1 RNA-binding activity with small molecules was achieved, which provides a novel strategy for treating liver fibrosis and other CELF1-mediated diseases.
The Promise of Polygenic Risk Prediction in Smoking Cessation: Evidence From Two Treatment Trials
Authors: Bray Michael , Chang Yoonhoo , Baker Timothy B , Jorenby Douglas , Carney Robert M , Fox Louis , Pham Giang , Stoneking Faith , Smock Nina , Amos Christopher I , Bierut Laura , Chen Li-Shiun 
Published: February 2022

Abstract

Introduction
Tobacco use disorder is a complex behavior with a strong genetic component. Genome-wide association studies (GWAS) on smoking behaviors allow for the creation of polygenic risk scores (PRSs) to approximate genetic vulnerability. However, the utility of smoking-related PRSs in predicting smoking cessation in clinical trials remains unknown.

Aims and Methods
We evaluated the association between polygenic risk scores and bioverified smoking abstinence in a meta-analysis of two randomized, placebo-controlled smoking cessation trials. PRSs of smoking behaviors were created using the GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN) consortium summary statistics. We evaluated the utility of using individual PRS of specific smoking behavior versus a combined genetic risk that combines PRS of all four smoking behaviors. Study participants came from the Transdisciplinary Tobacco Use Research Centers (TTURCs) Study (1091 smokers of European descent), and the Genetically Informed Smoking Cessation Trial (GISC) Study (501 smokers of European descent).

Results
PRS of later age of smoking initiation (OR [95% CI]: 1.20, [1.04–1.37], p = .0097) was significantly associated with bioverified smoking abstinence at end of treatment. In addition, the combined PRS of smoking behaviors also significantly predicted bioverified smoking abstinence (OR [95% CI] 0.71 [0.51–0.99], p = .045).

Conclusions
PRS of later age at smoking initiation may be useful in predicting smoking cessation at the end of treatment. A combined PRS may be a useful predictor for smoking abstinence by capturing the genetic propensity for multiple smoking behaviors.

Implications
There is a potential for polygenic risk scores to inform future clinical medicine, and a great need for evidence on whether these scores predict clinically meaningful outcomes. Our meta-analysis provides early evidence for potential utility of using polygenic risk scores to predict smoking cessation amongst smokers undergoing quit attempts, informing further work to optimize the use of polygenic risk scores in clinical care.
Prospective Assessment of Symptoms to Evaluate Asymptomatic SARS-CoV-2 Infections in a Cohort of Health Care Workers
Authors: Goguet Emilie , Powers John H , Olsen Cara H , Tribble David R , Davies Julian , Illinik Luca , Jackson-Thompson Belinda M , Hollis-Perry Monique , Maiolatesi Santina E , Pollett Simon , Duplessis Christopher A , Wang Gregory , Ramsey Kathleen F , Reyes Anatalio E , Alcorta Yolanda , Wong Mimi A , Ortega Orlando , Parmelee Edward , Lindrose Alyssa R , Moser Matthew , Samuels Emily C , Coggins Si’Ana A , Graydon Elizabeth , Robinson Sara , Campbell Wesley , Malloy Allison M W , Voegtly Logan J , Arnold Catherine E , Cer Regina Z , Malagon Francisco , Bishop-Lilly Kimberly A , Burgess Timothy H , Broder Christopher C , Laing Eric D , Mitre Edward 
Published: February 2022

Abstract

Background
The frequency of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is unclear and may be influenced by how symptoms are evaluated. In this study, we sought to determine the frequency of asymptomatic SARS-CoV-2 infections in a prospective cohort of health care workers (HCWs).

Methods
A prospective cohort of HCWs, confirmed negative for SARS-CoV-2 exposure upon enrollment, were evaluated for SARS-CoV-2 infection by monthly analysis of SARS-CoV-2 antibodies as well as referral for polymerase chain reaction testing whenever they exhibited symptoms of coronavirus disease 2019 (COVID-19). Participants completed the standardized and validated FLU-PRO Plus symptom questionnaire scoring viral respiratory disease symptom intensity and frequency at least twice monthly during baseline periods of health and each day they had any symptoms that were different from their baseline.

Results
Two hundred sixty-three participants were enrolled between August 25 and December 31, 2020. Through February 28, 2021, 12 participants were diagnosed with SARS-CoV-2 infection. Symptom analysis demonstrated that all 12 had at least mild symptoms of COVID-19, compared with baseline health, near or at time of infection.

Conclusions
These results suggest that asymptomatic SARS-CoV-2 infection in unvaccinated, immunocompetent adults is less common than previously reported. While infectious inoculum doses and patient factors may have played a role in the clinical manifestations of SARS-CoV-2 infections in this cohort, we suspect that the high rate of symptomatic disease was due primarily to participant attentiveness to symptoms and collection of symptoms in a standardized, prospective fashion. These results have implications for studies that estimate SARS-CoV-2 infection prevalence and for public health measures to control the spread of this virus.
Warm Temperature Promotes Shoot Regeneration inArabidopsis thaliana
Authors: Lambolez Alice , Kawamura Ayako , Takahashi Tatsuya , Rymen Bart , Iwase Akira , Favero David S , Ikeuchi Momoko , Suzuki Takamasa , Cortijo Sandra , Jaeger Katja E , Wigge Philip A , Sugimoto Keiko 
Published: February 2022

AbstractMany plants are able to regenerate upon cutting, and this process can be enhanced in vitro by incubating explants on hormone-supplemented media. While such protocols have been used for decades, little is known about the molecular details of how incubation conditions influence their efficiency. In this study, we find that warm temperature promotes both callus formation and shoot regeneration in Arabidopsis thaliana. We show that such an increase in shoot regenerative capacity at higher temperatures correlates with the enhanced expression of several regeneration-associated genes, such as CUP-SHAPED COTYLEDON 1 (CUC1) encoding a transcription factor involved in shoot meristem formation and YUCCAs (YUCs) encoding auxin biosynthesis enzymes. ChIP-sequencing analyses further reveal that histone variant H2A.Z is enriched on these loci at 17°C, while its occupancy is reduced by an increase in ambient temperature to 27°C. Moreover, we provide genetic evidence to demonstrate that H2A.Z acts as a repressor of de novo shoot organogenesis since H2A.Z-depleted mutants display enhanced shoot regeneration. This study thus uncovers a new chromatin-based mechanism that influences hormone-induced regeneration and additionally highlights incubation temperature as a key parameter for optimizing in vitro tissue culture.
Pre-Eruptive Conditions and Dynamics Recorded in Banded Pumices from the El Abrigo Caldera-Forming Eruption (Tenerife, Canary Islands)
Authors: González-García Diego , Petrelli Maurizio , Perugini Diego , Giordano Daniele , Vasseur Jérémie , Paredes-Mariño Joali , Marti Joan , Dingwell Donald B 
Published: February 2022

Abstract
The El Abrigo member of the Diego Hernández Formation (Tenerife, Canary Islands) represents the final (170 ka) and most voluminous eruption (&gt;20-km3 DRE) of the last cycle of explosive activity of the Las Cañadas volcano. It is a dominantly phonolitic ignimbrite containing both mafic and banded pumices, suggesting that magma mixing played an important role in triggering the eruption and modulating eruptive dynamics. Here we use petrology, together with glass and mineral geochemistry of enclave-rich mafic scoriae, banded and phonolitic pumices from El Abrigo ignimbrite, to shed light on the pre-eruptive storage conditions and processes governing magma ascent and interaction dynamics and to provide a first-order assessment of the contribution of magma mixing and crystal mush melting to the dynamics of this eruptive event. The distribution of major elements in glasses is consistent with diffusive exchange between the interacting melts whereby Na transfers from the phonolite to the tephriphonolitic melt. However, V, Zr, Ba, and Eu suggest a complex scenario in which an intruding tephritic to phonotephritic magma interacted with two distinct zones of a phonolitic magma chamber, one occupied by a crystal-rich, low-Zr, and high-Ba phonolite, and the other by an evolved, crystal-poor, high-Zr phonolite. These results, coupled with mineral–melt thermobarometry, allow us to reconstruct the Las Cañadas plumbing system at the end of the Diego Hernández cycle and to evaluate the contribution of cumulate mush melting and magma mixing in as follows: (1) the parental tephritic magma was stored at or near the Moho (410–450 MPa) at 1050°C where it was periodically replenished by more primitive basanitic magma; (2) upon ascent, the tephrite intruded into a shallow and zoned phonolitic storage system, triggering the disruption of a crystal mush in its base; and (3) subsequently interacted with a crystal-poor zone within the reservoir. Energy balance evaluations suggest that relative mafic magma volume ratios ranged from 20 to 43 vol%, and the conservation of small-scale magma mingling structures and their geochemical distribution suggest that the mixing event took place very shortly before the eruption, on a timescale of hours.
High mobility group A3 enhances transcription of the DNA demethylase gene SlDML2 to promote tomato fruit ripening
Authors: Li Zhifei , Pi Ying , Fan Junmiao , Yang Xinxin , Zhai Changsheng , Chen Hong , Wang Feng , Ding Jing , Gu Tingting , Li Yi , Wu Han 
Published: February 2022

Abstract
DNA methylation plays an important role in regulating tomato (Solanum lycopersicum) fruit ripening. Although SlDML2, a DNA demethylase (DML) gene, is critically involved in tomato fruit ripening, little is known about genes that regulate its expression. Using yeast one-hybrid screening, we identified a High Mobility Group A protein, named SlHMGA3, and demonstrated its binding activity to the AT-rich region of the SlDML2 promoter. We produced slhmga3 tomato mutants using CRISPR/Cas9 and observed that slhmga3 fruit reached the breaker stage much later than fruit from the wild-type. We further demonstrated that at the initiation stage of fruit ripening, the increased expression of SlDML2 and ethylene biosynthetic and signaling genes was significantly delayed in slhmga3 fruit, along with delays in ethylene production and demethylation and activation of ripening-associated transcription factor genes. Our results demonstrate that SlHMGA3 plays a role in enhancing SlDML2 expression, and its effects on tomato fruit ripening are largely through DNA demethylation of ripening-associated transcription factor genes.
I Hear You Feel Confident
Authors: Bricker Adam Michael 
Published: February 2022

AbstractHere I explore a new line of evidence for belief–credence dualism, the thesis that beliefs and credences are distinct and equally fundamental types of mental states. Despite considerable recent disagreement over this thesis, little attention has been paid in philosophy to differences in how our mindreading systems represent the beliefs and credences of others. Fascinatingly, the systems we rely on to accurately and efficiently track others’ mental states appear to function like belief–credence dualists: Credence is tracked like an emotional state, composed of both representational and affective content, whereas belief is tracked like a bare representational state with no affective component. I argue on a preliminary basis that, in this particular case, the mechanics of mentalizing likely pick out a genuine affective dimension to credence that is absent for belief, further strengthening the converging case for belief–credence dualism.
The Slope of the Phillips Curve: Evidence from U.S. States
Authors: Hazell Jonathon , Herreño Juan , Nakamura Emi , Steinsson Jón 
Published: February 2022

AbstractWe estimate the slope of the Phillips curve in the cross section of U.S. states using newly constructed state-level price indices for nontradeable goods back to 1978. Our estimates indicate that the slope of the Phillips curve is small and was small even during the early 1980s. We estimate only a modest decline in the slope of the Phillips curve since the 1980s. We use a multiregion model to infer the slope of the aggregate Phillips curve from our regional estimates. Applying our estimates to recent unemployment dynamics yields essentially no missing disinflation or missing reinflation over the past few business cycles. Our results imply that the sharp drop in core inflation in the early 1980s was mostly due to shifting expectations about long-run monetary policy as opposed to a steep Phillips curve, and the greater stability of inflation between 1990 and 2020 is mostly due to long-run inflation expectations becoming more firmly anchored.
Factors associated with depressive symptoms in Japanese women with rheumatoid arthritis
Authors: Hamasaki Miwa , Origuchi Tomoki , Matsuura Emi 
Published: February 2022

AbstractObjectivesIt has been suggested that patients with RA are more likely to suffer from depression. Therefore, this study identified the factors associated with depressive states in female RA patients to inform future patient care.MethodsA self-assessment questionnaire was administered to 150 female RA patients aged ≥20 years regarding their satisfaction with disease activity, pain (measured using a visual analogue scale), self-rated depression scale (SDS), stress content (illness, work, family, difficulty in daily life, appearance, treatment and other), confidence in stress management and satisfaction (treatment effect, health status and relationships with health-care professionals). The factors related to depression and the presence of depressive tendencies were investigated.ResultsData from 145 patients were analysed. Eighteen patients (12.4%) showed depressive tendencies according to their SDS scores. Among these patients, SDS scores were positively correlated with disease activity and with scores on the modified HAQ, visual analogue scale for pain, and stress content. The SDS score was also negatively correlated with patients’ confidence in stress management and health status satisfaction.ConclusionFemale RA patients had family problems and various stressors in their daily lives. Nurses need to conduct regular mental health assessments to monitor their self-management status and support them to improve their confidence and satisfaction in coping. To achieve this, it is important for health-care teams involving various health-care professionals to collaborate and cooperate.
Loosening of Associations in Chronic Schizophrenia: Intersectionality of Verbal Learning, Negative Symptoms, and Brain Structure
Authors: Nestor Paul G , Levitt James J , Ohtani Toshiyuki , Newell Dominick T , Shenton Martha E , Niznikiewicz Margaret 
Published: February 2022

Abstract
In 1908, Bleuler proposed a unitary theory of schizophrenia, hypothesizing a “loosening of associations” as the central mechanism underlying disturbances in thinking, motivation, and affective expression. Here, we test Bleuler’s model in an archival sample of 79 healthy controls and 76 patients with chronic schizophrenia who had completed neuropsychological tests, including a measure of learning of novel word pairs, which was specifically selected to probe the structure and formation of new verbal associations. The patients also had positive and negative symptoms ratings, including measures of flat affect, anhedonia, and thought disorder. A subset of patients and controls (n = 39) had available prior archival 3-T magnetic resonance imaging (MRI) measures of prefrontal cortex (PFC) gray matter volumes. In relation to controls, patients showed evidence of a selective impairment in associative learning, independent of their overall reduced neuropsychological functioning. This neuropsychological impairment, in turn, correlated significantly with overall levels of negative but not positive symptoms, with the data showing an especially strong contribution of flattened emotional expression to verbal associate learning deficits in this patient sample. Moreover, the archival MRI data were consistent with prior research pointing to an important role of the PFC in supporting verbal associate learning and memory in patients and controls. Taken together, the current results provided evidence of a selective impairment in schizophrenia on a PFC-supported verbal associate learning and memory task, which was accompanied by negative symptoms in general, and flattened emotional expression, in particular.
Diversity of anesthesia workforce – why does it matter?
Authors: Chiem Jennifer , Libaw Justin , Ehie Odinakachukwu 
Published: February 2022

Purpose of review
Although recent census demonstrates that women comprise 50.8% and ethnic minority groups collectively consist of 42.1% of the US population, the field of anesthesiology still demonstrates disparity in representation and health outcomes across race, ethnicity, and gender. In addition, the growing percentage of people that identify as lesbian, gay, bisexual, transgender, and queer (LGBTQ) compounded with limited representation among providers of their care can augment existing disparate outcomes within this community.

Recent findings
Compared to male colleagues, women physicians across all specialties have a decreased likelihood of professorship as well as equitable pay and leadership roles. Additionally, a 2019 study of anesthesia residents across race and ethnicity within the Accreditation Council for Graduate Medical Education established that whites were 58.9%, Asians were 24.7%, Hispanics were 7.8%, Blacks were 5.9%, multiracial groups were 3.8%, and Native Americans were 0.3% of the total 6272 residents. In a survey of members of the American Society of Anesthesiologists, self-identification as part of the sexual and gender minoritycommunity was independently associated with an increased risk of burnout. Furthermore, teams with higher diversity in cognitive styles solve problems more efficiently.

Summary
To achieve an optimized quality of healthcare, anesthesiologists and other providers should be a reflection of the communities they serve, including women, people of color, and LGBTQ. In this way, there is an increased likelihood of empathy, effective communication, and insightful perspectives on how to bridge the gap in health equity. A diverse lens is essential to ensure grassroots efforts lead to lasting transformational change.
Rapid Overlap Initiation Protocol Using Low Dose Buprenorphine for Opioid Use Disorder Treatment in an Outpatient Setting: A Case Series
Authors: Suen Leslie W. , Lee Trevor G. , Silva Michael , Walton Paulette , Coffin Phillip O. , Geier Michelle , Soran Christine S. 
Published: February 2022

Objectives
Fear and risk of precipitated withdrawal are barriers for initiating buprenorphine in individuals with opioid use disorder, particularly among those using fentanyl. A buprenorphine rapid overlap initiation (ROI) protocol (also knownas “rapidmicro-dosing”) utilizing small, escalating doses of buprenorphine can overcome this barrier, reaching therapeutic doses in 3 to 4 days. We sought to demonstrate the feasibility of implementing a buprenorphine ROI protocol for buprenorphine initiation in the outpatient setting.

Methods
We conducted a retrospective chart review of patients prescribed an outpatient ROI protocol at the Office-based Buprenorphine Induction Clinic from October to December 2020. The ROI protocol utilizes divided doses of sublingual buprenorphine tablets and blister packaging for easier dosing. Patients were not required to stop other opioid use and were advised to follow up on day 4 of initiation.

Results
Twelve patients were included, of whom eleven (92%) were using fentanyl at intake. Eleven patients picked up their prescription. Seven patients returned for follow-up (58%), and all 7 completed the ROI protocol. One patient reported any withdrawal symptoms, which were mild. At 30 days, 7 patients (58%) were retained in care, and 5 (42%) were still receiving buprenorphine treatment, 4 (33%) of whom had been abstinent from nonprescribed opioid use for ≥2 weeks.

Conclusions
The ROI protocol was successful in initiating buprenorphine treatment for patients in our outpatient clinic, many of whom were using fentanyl. The ROI protocol may offer a safe alternative to traditional buprenorphine initiation and warrants further study.