bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small-molecule compounds boost genome-editing efficiency of cytosine base editor
Authors: Zhao Tianyuan , Li Qing , Zhou Chenchen , Lv Xiujuan , Liu Hongyan , Tu Tianxiang , Tang Na , Cheng Yanbo , Liu Xiaoyu , Liu Changbao , Zhao Junzhao , Song Zongming , Wang Haoyi , Li Jinsong , Gu Feng 
Published: July 2021

Abstract
Cytosine base editor (CBE) enables targeted C-to-T conversions at single base-pair resolution and thus has potential therapeutic applications in humans. However, the low efficiency of the system limits practical use of this approach. We reported a high-throughput human cells-based reporter system that can be harnessed for quickly measuring editing activity of CBE. Screening of 1813 small-molecule compounds resulted in the identification of Ricolinostat (an HDAC6 inhibitor) that can enhance the efficiency of BE3 in human cells (2.45- to 9.21-fold improvement). Nexturastat A, another HDAC6 inhibitor, could also increase BE3-mediated gene editing by 2.18- to 9.95-fold. Ricolinostat and Nexturastat A also boost base editing activity of the other CBE variants (BE4max, YE1-BE4max, evoAPOBEC1-BE4max and SpRY-CBE4max, up to 8.32-fold). Meanwhile, combined application of BE3 and Ricolinostat led to &gt;3-fold higher efficiency of correcting a pathogenic mutation in ABCA4 gene related to Stargardt disease in human cells. Moreover, we demonstrated that our strategy could be applied for efficient generation of mouse models through direct zygote injection and base editing in primary human T cells. Our study provides a new strategy to improve the activity and specificity of CBE in human cells. Ricolinostat and Nexturastat A augment the effectiveness and applicability of CBE.
Transmission of SARS-CoV-2 Alpha Variant (B.1.1.7) From a BNT162b2-Vaccinated Individual
Authors: Kernéis Solen , Planas Delphine , Imbeaud Sandrine , Staropoli Isabelle , Puech Julien , Robillard Nicolas , Rodary Julien , Bruel Timothée , Vieillard Thomas , Schwartz Olivier , Belec Laurent , Péré Hélène , Veyer David 
Published: July 2021

Abstract
Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) acquisition after vaccination with BNT162b2 have been described, but the risk of secondary transmission from fully vaccinated individuals remains ill defined. Herein we report a confirmed transmission of SARS-CoV-2 alpha variant (B.1.1.7) from a symptomatic immunocompetent woman 4 weeks after her second dose of BNT162b2, despite antispike seroconversion.
Phenotypes of obstructive sleep apnea in the Hispanic Community Health Study/Study of Latinos
Authors: González Kevin A , Tarraf Wassim , Wallace Douglas M , Stickel Ariana M , Schneiderman Neil , Redline Susan , Patel Sanjay R , Gallo Linda C , Mossavar-Rahmani Yasmin , Daviglus Martha L , Zee Phyllis C , Talavera Gregory A , Sotres-Alvarez Daniela , González Hector M , Ramos Alberto 
Published: July 2021

Abstract

Study Objectives
Recent work on US Whites from clinical samples used obstructive sleep apnea (OSA) symptoms to generate phenotypes for individuals with moderate-severe OSA which suggested 3 to 5 symptom classes. However, it is unknown whether similar classes generalize to diverse Hispanics/Latino adults. Therefore, we sought to fill this gap by empirically deriving sleep phenotypes among a large sample of diverse Hispanics/Latinos.

Methods
We used data from The Hispanic Community Health Study/Study of Latinos (HCHS/SOL; 2008–2011), a prospective cohort study designed using a multisite multistage probability sample of adults 18–74 years old. The subpopulation of interest included participants with moderate-severe OSA symptoms (≥15 respiratory event index (REI) events per hour; n = 1,605). We performed latent class analysis for complex survey data using 15 common OSA symptoms (e.g. Epworth Sleepiness Scale) and 4 comorbidities to identify phenotype classes.

Results
Average age was 52.4 ± 13.9 years and 34.0% were female. Mean REI was 33.8 ± 22.5 events per hour. Fit statistics and clinical significance suggested that a three-class solution provided the best fit to the data. The three phenotypes were: (1) Minimally Symptomatic (47.7%), (2) Excessive sleepiness (37.1%), and (3) Disturbed Sleep (15.2%). Sensitivity models were consistent with the main proposed solution.

Conclusions
Derived sleep phenotypes among diverse Hispanic/Latinos were consistent with recent findings from the Sleep Apnea Global Interdisciplinary Consortium, but we found notable differences in class prevalence relative to Whites. Further research is needed to link derived sleep phenotypes to health comorbidities in diverse populations.
Volumetric magnetic resonance imaging analysis of multilevel upper airway surgery effects on pharyngeal structure
Authors: Sutherland Kate , Lowth Aimee B , Antic Nick , Carney A Simon , Catcheside Peter G , Chai-Coetzer Ching Li , Chia Michael , Hodge John-Charles , Jones Andrew , Kaambwa Billingsley , Lewis Richard , MacKay Stuart , McEvoy R Doug , Ooi Eng H , Pinczel Alison J , McArdle Nigel , Rees Guy , Singh Bhajan , Stow Nicholas , Weaver Edward M , Woodman Richard J , Woods Charmaine M , Yeo Aeneas , Cistulli Peter A 
Published: July 2021

Abstract

Study Objectives
The Sleep Apnea Multilevel Surgery (SAMS) trial found that modified uvulopalatopharyngoplasty with tonsillectomy (if tonsils present) combined with radiofrequency tongue ablation reduced obstructive sleep apnea (OSA) severity and daytime sleepiness in moderate-severe OSA. This study aimed to investigate mechanisms of effect on apnea-hypopnea index (AHI) reduction by assessing changes in upper airway volumes (airway space, soft palate, tongue, and intra-tongue fat).

Methods
This is a case series analysis of 43 participants of 51 randomized to the surgical arm of the SAMS trial who underwent repeat magnetic resonance imaging (MRI). Upper airway volume, length, and cross-sectional area, soft palate and tongue volumes, and tongue fat were measured. Relationships between changes in anatomical structures and AHI were assessed.

Results
The participant sample was predominantly male (79%); mean ± SD age 42.7 ± 13.3 years, body mass index 30.8 ± 4.1 kg/m2, and AHI 47.0 ± 22.3 events/hour. There were no, or minor, overall volumetric changes in the airway, soft palate, total tongue, or tongue fat volume. Post-surgery there was an increase in the minimum cross-sectional area by 0.1 cm2 (95% confidence interval 0.04–0.2 cm2) in the pharyngeal airway, but not statistically significant on corrected analysis. There was no association between anatomical changes and AHI improvement.

Conclusions
This contemporary multilevel upper airway surgery has been shown to be an effective OSA treatment. The current anatomical investigation suggests there are not significant post-operative volumetric changes associated with OSA improvement 6-month post-surgery. This suggests that effect on OSA improvement is achieved without notable deformation of airway volume. Reduced need for neuromuscular compensation during wake following anatomical improvement via surgery could explain the lack of measurable volume change. Further research to understand the mechanisms of action of multilevel surgery is required.

Clinical Trial
This manuscript presents a planned image analysis of participants randomized to the surgical arm or the clinical trial multilevel airway surgery in patients with moderate-severe obstructive sleep apnea (OSA) who have failed medical management to assess change in OSA events and daytime sleepiness. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=266019&isReview=true%20Australian%20New%20Zealand%20Clinical%20Trials%20Registry%20ACTRN12514000338662, prospectively registered on March 31, 2014.
Examination of the Global Regulon of CsrA inXanthomonas citrisubsp.citriUsing Quantitative Proteomics and Other Approaches
Authors: Zhang Yanan , Andrade Maxuel O. , Wang Wenting , Teper Doron , Romeo Tony , Wang Nian 
Published: July 2021

The RNA-binding protein CsrA is a global posttranscriptional regulator and controls many physiological processes and virulence traits. Deletion of csrA caused loss of virulence, reduced motility and production of xanthan gum and substantial increase in glycogen accumulation, as well as enhanced bacterial aggregation and cell adhesion in Xanthomonas spp. How CsrA controls these traits is poorly understood. In this study, an isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis was conducted to compare the protein profile of wild-type strain Xanthomonas citri subsp. citri and the isogenic ΔcsrA strain. A total of 2,374 proteins were identified, and 284 were considered to be differentially expressed proteins (DEPS), among which 151 proteins were up-regulated and 133 were down-regulated in the ΔcsrA strain with respect to the wild-type strain. Enrichment analysis and a protein-protein interaction network analysis showed that CsrA regulates bacterial secretion systems, flagella, and xanthan gum biosynthesis. Several proteins encoded by the gumB operon were down-regulated, whereas proteins associated with flagellum assembly and the type IV secretion system were up-regulated in the ΔcsrA strain relative to the Xcc306 strain. These results were confirmed by β-glucuronidase assay or Western blot. RNA secondary structure prediction and a gel-shift assay indicated that CsrA binds to the Shine-Dalgarno sequence of virB5. In addition, the iTRAQ analysis identified 248 DEPs that were not previously identified in transcriptome analyses. Among them, CsrA regulates levels of eight regulatory proteins (ColR, GacA, GlpR, KdgR, MoxR, PilH, RecX, and YgiX), seven TonB-dependent receptors, four outer membrane proteins, and two ferric enterobactin receptors. Taken together, this study greatly expands understanding of the regulatory network of CsrA in X. citri subsp. citri.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Anhedonia and Substance Use Disorders by Type, Severity, and With Mental Health Disorders
Authors: Stull Samuel W. , Bertz Jeremiah W. , Epstein David H. , Bray Bethany C. , Lanza Stephanie T. 
Published: July 2021

Objectives
Anhedonia can accompany substance use disorders (SUDs); its severity may vary by substance type, severity of SUD symptoms, or psychiatric comorbidity. The goal of this study was to clarify the contribution of each.

Methods
Data were from participants aged 18 to 65 years in the National Epidemiologic Survey on Alcohol and Related Conditions III (n = 30,999; 51% women), a cross-sectional, nationally representative sample reporting lifetime DSM-5 symptoms and lifetime anhedonia. We used logistic regression to test how anhedonia was associated with specific SUDs and psychiatric disorders in respondents with one lifetime diagnosis. We used latent class analysis to assess the association of anhedonia with patterns of comorbidity in all respondents.

Results
Opioid use disorder (OUD) had the greatest odds of anhedonia relative to other SUDs (ORs [95% CIs]): mild alcohol use disorder (AUD) (3.33 [1.74, 6.38]), moderate/severe AUD (2.73 [1.41, 5.30]), and cannabis use disorder (3.21 [1.43, 7.19]), though not significantly greater than stimulant use disorder (2.44 [.88, 6.73]). Anhedonia was more likely in mood disorders and posttraumatic stress disorder (PTSD) than in any SUD, except for PTSD versus OUD (OR [95% CIs] = .98 [.47, 2.02]). In latent class analysis analyses, the poly disorder class, which included SUDs and other diagnoses, had greater odds of anhedonia than the Poly SUD (ORs [95% CIs] = 1.62 [1.25, 2.09] and AUD 2.89 [2.40, 3.48]) classes.

Conclusions
People with OUD or a lifetime history of mood disorder or PTSD may be most likely to present to SUD treatment with anhedonia.
Characterizing the Clinical use of a Novel Video-assisted Dosing Protocol With Secure Medication Dispensers to Reduce Barriers to Opioid Treatment
Authors: Brooklyn John R. , Stothart Marne , Stunell Mallory , Berman Vanessa Melamede , Rylant Danielle , Hanson Melanie 
Published: July 2021

Objectives
Distance and travel costs to opioid treatment programs (OTPs), especially in rural communities, are barriers to treatment for opioid use disorder. Retention rates at 12 months in our OTP are 55% (range 53%–61%).We piloted a novel treatment platform utilizing a video directly observed therapy (VDOT) smartphone app and a secure medication dispenser to support adherence with take-home doses of methadone or buprenorphine while enabling patients to maintain prosocial activities, reduce time and cost of travel, and increase retention.

Methods
Participants (n¼58) were adults in a Vermont OTP. Inclusion criteria included travel hardship, access to Wi-Fi or cellular network, and having an iPhone 4S or Android 4.0 or greater. Patients received a dispenser, VDOT app, clinic dispensed medication, counseling, and urine drug testing. Chart reviews assessed VDOT compliance, engagement in prosocial activities, travel costs and time savings, and treatment disposition/retention. Project-associated costs were examined.

Results
Of the 15,831 expected videos, 15,581 (98.4%) were received and only 10 (0.063%) showed signs of medication noncompliance with 1 (0.0064%) showing an overt attempt at diversion. About 93% of participants engaged in prosocial activities, travel time and costs were reduced 86%, median cost saved $72 weekly, median travel time saved 5.5 hours weekly and 98% of participants were in treatment 12 months later.

Conclusions
VDOT participants using dispensers showed high levels of medication ingestion integrity, had favorable clinical stability, and lower travel time and costs. These findings suggest that using VDOT with dispensers may hold promise as an innovative platform for supporting medication adherence.
Laws Forbidding Pregnancy Discrimination in Substance Use Disorder Treatment Are Not Associated With Treatment Access
Authors: Davis Corey S. , McNeer Elizabeth , Patrick Stephen W. 
Published: July 2021

Objectives
To determine if state laws that forbid substance use disorder treatment providers from refusing services based on pregnancy are associated with improved ability to secure an initial appointment for opioid use disorder treatment with methadone and buprenorphine.

Methods
Ten states in which a “secret shopper” study was conducted were stratified based on whether they have a law that forbids substance use disorder treatment providers from refusing to treat individuals because of pregnancy. We tested for differences in percent of pregnant versus nonpregnant callers offered an initial appointment for medication for opioid use disorder treatment between states with a law and those without. We also tested for differences in acceptance based on caller insurance type.

Results
Four states with 1461 callers had relevant laws; 6 states with 2495 callers did not. None of the laws apply to all providers. In both groups of states, nonpregnant callers were significantly more likely to obtain a buprenorphine appointment (75.1% vs 60.1% in states with a law, P < 0.01; 73.1% vs 62.3% in states without, P < 0.01). No significant differences were found in methadone appointment access either between pregnant and nonpregnant callers or between pregnant callers in states with a law compared to those without.

Conclusions
Laws that forbid providers from refusing to treat potential patients because they are pregnant were not associated with success in obtaining an initial appointment for medication for opioid use disorder treatment. States should consider expanding those laws to apply to all treatment providers and ensure that currently covered providers are in compliance.
Sex Differences in Injection Drug Risk Behaviors Among Hospitalized Persons
Authors: Biondi Breanne E. , Anderson Brad J. , Phillips Kristina T. , Stein Michael 
Published: July 2021

Objectives
As opioid use increases, it remains important to assess factors that contribute to injection drug risk behaviors, as sharing needles and other drug use equipment contributes to the spread of human immunodeficiency virus and hepatitis C virus. Such risks may differ by sex and injecting with others. The current study examined factors that contribute to increased injection drug risk separately for men and women.

Methods
People who inject drugs were recruited at an academic safety-net hospital that reported recent injection drug use. Two main injection outcomes were assessed: (1) human immunodeficiency virus drug risk behaviors as assessed by the Risk Assessment Battery and (2) the number of times participants injected drugs with a needle used by someone else. For each outcome, different models for women and men were conducted to detect differences by sex.

Results
Both men and women were more likely to inject with a needle used by someone else if they used drugs within a sexual relationship (incidence rate ratio (IRR) = 14.61, P < 0.01; IRR = 7.17, P < 0.05). Being employed was associated with lower risk assessment battery scores among men, and lower mean rates of using a needle used by someone else among women (IRR = 0.22, P < 0.05). Women with post-traumatic stress disorder (PTSD) and men with higher depression scores had higher rates of injecting with a needle used by someone else.

Conclusions
People who inject drugs who are in intimate relationships report higher injection drug risk behaviors. We found benefits to employment among both men and women. Identifying factors associated with increased injection risk behaviors can be useful for creating interventions tailored by sex.
Dysfunction of the Auditory System in Children With Hypothyroidism: A Systematic Review and Meta-Analysis
Authors: Zhang Kathy , Fried Jacob , Nguyen Shaun A. , Meyer Ted A. , White David R. 
Published: July 2021

Objective:
To examine the prevalence of hearing impairment in children with hypothyroidism, and to characterize clinical and subclinical hearing loss by examining cochlear function, auditory brainstem pathways, and integration of the auditory system as a whole.

Design:
An electronic search was conducted using PubMed, Scopus, and Cochrane Library databases. This systematic review was performed in accordance with the PRISMA guidelines. Original observational studies that utilized audiological tests for auditory system evaluations in hypothyroidism were included. A total of 2004 studies were found in the search, with 23 studies meeting the inclusion criteria.

Results:
The pooled prevalence of hearing loss was 16.1% [95% confidence interval 10.7, 22.4] for children with congenital hypothyroidism. Hearing thresholds at pure-tone averages (0.5–2 kHz) were 1.6 dB [95% confidence interval 1.7, 4.8] higher for children with hypothyroidism compared to age-matched controls. Cochlear dysfunction was detected at middle frequencies (1–3 kHz) by otoacoustic emission testing, indicating abnormalities of hair cell function or cochlear integration. Retrocochlear involvement was detected on auditory brainstem response (ABR), with prolonged Wave I indicating a peripheral conduction abnormality localized to the middle or inner ear and eighth cranial nerve.

Conclusions:
Children with hypothyroidism have a higher prevalence of hearing loss than children without hypothyroidism. For children with congenital hypothyroidism, evidence of subclinical abnormalities at the level of the cochlea and eighth cranial nerve are present despite early initiation of levothyroxine therapy. Dysfunction of the auditory system might begin with predominance of peripheral conduction abnormalities early in development.
Surgical Management of Missed Pediatric Monteggia Fractures: A Systematic Review and Meta-Analysis
Authors: Tan Si Heng Sharon , Low Jia Ying , Chen Hao , Tan Joel Yong Hao , Lim Andrew Kean Seng , Hui James Hoipo 
Published: July 2021

Objectives:
To review surgical management and outcomes of missed pediatric Monteggia fractures.

Data Sources:
A systematic review was conducted using PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Library from inception through March 2, 2020. The keywords were “Monteggia fracture,” “missed Monteggia,” “neglected Monteggia,” “chronic Monteggia,” and “chronic radial head dislocation.”

Study Selection:
All original human studies on missed pediatric Monteggia fractures were included. Congenital Monteggia fractures and isolated radial head dislocations were excluded.

Data Extraction:
The revised Methodological Index for Nonrandomised Studies tool was used to assess the quality of studies.

Data Synthesis:
Each patient's data were retrieved individually. The χ2 test and Fisher exact test were used to analyze the difference in outcomes for different surgical managements. Multivariate analysis was performed for variables that were significant on univariate analysis.

Conclusions:
Thirty studies with 600 patients were included. Proximal ulnar osteotomies (P = 0.016) and the absence of transcapitellar pinning (P = 0.001) were the most significant predictors for eventual reduction of radial head. Other surgical management variables were not significant predictors. These include open or closed reduction approach of radial head reduction; presence or absence of ulnar osteotomy; presence or absence of lengthening, angular correction, overcorrection, or bone grafting of ulnar osteotomy; type of fixation for ulnar osteotomy; presence or absence of radial osteotomy; presence or absence of annular ligament repair or reconstruction; and repair or reconstruction of annular ligament.

Level of Evidence:
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Outcome After Open Reduction Internal Fixation of Acetabular Fractures in the Elderly
Authors: Sanders Ethan , Finless Alexandra , Adamczyk Andrew , Dobransky Johanna , Wilkin Geoffrey , Gofton Wade T. , Beaulé Paul E. , Liew Allan , Papp Steven , Grammatopoulos George 
Published: July 2021

Objectives:
(1) Assess outcomes of acetabular open reduction and internal fixation (ORIF) in the elderly, (2) investigate factors influencing outcome, and (3) compare outcomes after low-energy and high-energy mechanisms of injury.

Design:
Retrospective case series.

Setting:
Level 1 trauma center.

Patients:
Seventy-eight patients older than 60 years (age: 70.1 ± 7.4; 73.1% males).

Intervention:
ORIF for acetabular fractures.

Main Outcome Measurements:
Complications, reoperation rates, Oxford Hip Score (OHS), and joint preservation and development of symptomatic osteoarthritis. Cases with osteoarthritis, OHS < 34, and those who required subsequent total hip arthroplasty were considered as poor outcome.

Results:
At a mean follow-up of 4.3 ± 3.7 years, 11 cases post-ORIF required a total hip arthroplasty. The 7-year joint survival post-ORIF was 80.7 ± 5.7%. Considering poor outcome as failure, the 7-year joint survival was 67.0 ± 8.9%. The grade of reduction was the most significant factor associated with outcome post-ORIF. Female sex (P = 0.03), pre-existing osteoporosis (P = 0.03), low-energy trauma (P = 0.04), and Matta grade (P = 0.002) were associated with poor outcome. Patients with associated both-column fractures were more likely to have nonanatomic reduction (P = 0.008). After low-energy trauma, joint survivorship was 36.6 ± 13.5% at 7 years compared with 75.4 ± 7.4% in the high-energy group when considering poor outcome as an end point (log rank P = 0.006). The cohort's mean OHS was 37.9 ± 9.3 (17–48).

Conclusions:
We recommend ORIF whenever an anatomic reduction is feasible. However, achievement and maintenance of anatomic reduction are a challenge in the elderly, specifically in those with low-energy fractures involving both columns, prompting consideration for alternative management strategies.

Level of Evidence:
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.