bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural effects of m6A modification of the Xist A-repeat AUCG tetraloop and its recognition by YTHDC1
Authors: Jones Alisha N , Tikhaia Ekaterina , Mourão André , Sattler Michael 
Published: February 2022

Abstract
The A-repeat region of the lncRNA Xist is critical for X inactivation and harbors several N6-methyladenosine (m6A) modifications. How the m6A modification affects the conformation of the conserved AUCG tetraloop hairpin of the A-repeats and how it can be recognized by the YTHDC1 reader protein is unknown. Here, we report the NMR solution structure of the (m6A)UCG hairpin, which reveals that the m6A base extends 5′ stacking of the A-form helical stem, resembling the unmethylated AUCG tetraloop. A crystal structure of YTHDC1 bound to the (m6A)UCG tetraloop shows that the (m6A)UC nucleotides are recognized by the YTH domain of YTHDC1 in a single-stranded conformation. The m6A base inserts into the aromatic cage and the U and C bases interact with a flanking charged surface region, resembling the recognition of single-stranded m6A RNA ligands. Notably, NMR and fluorescence quenching experiments show that the binding requires local unfolding of the upper stem region of the (m6A)UCG hairpin. Our data show that m6A can be readily accommodated in hairpin loop regions, but recognition by YTH readers requires local unfolding of flanking stem regions. This suggests how m6A modifications may regulate lncRNA function by modulating RNA structure.
Association of Smoking Status With the Risk of Type 2 Diabetes Among Young Adults: A Nationwide Cohort Study in South Korea
Authors: Huh Youn , Han Kyungdo , Choi Min-Jung , Kim Jung Hwan , Kim Seon Mee , Nam Ga Eun 
Published: February 2022

Abstract

Introduction
The longitudinal evidence between detailed parameters of smoking status and type 2 diabetes among young adults has been limited. We evaluated this association in young Korean adults.

Methods
This nationwide cohort study included 3 026 551 adults aged 20 to 39 years who underwent Korean National Health Insurance Service health examinations in 2009 and were followed up until the end of 2017. The participants were categorized according to smoking status, smoking duration, and smoking amount. The hazard ratios (HRs) and 95% CIs for type 2 diabetes were estimated using multivariable Cox proportional hazard regression analysis.

Results
During 8.2 years of follow-up, 71 952 cases of type 2 diabetes newly developed. Compared with never-smokers, independently increased HRs of type 2 diabetes were observed in ex-smokers (1.06, 95% CI = 1.04–1.09) and current smokers (1.39, 1.36–1.42). In these two groups, the type 2 diabetes risk increased with greater smoking duration and amount (p for trend &lt;.001). The HRs of type 2 diabetes were higher in current smokers than in ex-smokers at the same lifetime smoking amount. The associations between smoking status and incident type 2 diabetes were stronger in men, individuals who did not drink heavily, and those without obesity.

Conclusions
Among young adults, past and current smoking was associated with an increased risk of type 2 diabetes, and there was a dose–response association of smoking amount and duration with type 2 diabetes development. Appropriate interventions to help young adults cease smoking may help reduce the incidence of type 2 diabetes.

Implications
Smoking was associated with an increased risk of type 2 diabetes among young adults, and the risk was shown to increase as amount and duration of smoking increased. Ceasing smoking in young adults may help reduce the incidence of type 2 diabetes.
Does wearing arthritis gloves help with hand pain and function? A qualitative study into patients’ views and experiences
Authors: Prior Yeliz , Bartley Carol , Adams Jo , Firth Jill , Culley June , O’Neill Terence W , Hammond Alison 
Published: February 2022

Abstract

Objective
Arthritis gloves are frequently prescribed to people with undifferentiated inflammatory arthritis (UIA) or RA to help reduce hand pain and improve function. Nested within a randomized controlled trial testing the effectiveness of arthritis gloves (Isotoner gloves vs loose-fitting placebo gloves) in people with RA and UIA, this qualitative study aimed to explore participants’ views on the impact of wearing arthritis gloves on their hand pain and function.

Methods
Semi-structured one-to-one interviews were conducted with purposively selected participants following 12 weeks of glove wearing. Participants and the interviewer were blinded to the treatment allocation. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis.

Results
Participants (intervention: n = 10; control: n = 9) recruited from 13 National Health Service hospital sites in the UK participated in the interviews. Two main themes, with sub-themes, were elicited from the data: mechanisms determining glove use: ‘As soon as your joints get a bit warmer, the pain actually eases’ (thermal qualities; glove use in daily activities; glove use during sleep); and ambivalence about benefits of arthritis gloves: ‘I suppose a normal pair of gloves would do the same sort of thing?’ (are they a help or hindrance?; aesthetic appeal; future use of gloves).

Conclusion
Participants had ambivalent views on the impact of both the intervention and the loose-fitting placebo gloves on their hand pain and function, identifying warmth as the main benefit. Ordinary mid-finger-length gloves widely accessible from high street suppliers could deliver warmth and provide the perceived benefits to hand pain and function.
Trial registration: ISRCTN, ISRCTN25892131; registered 5 September 2016 : retrospectively registered.
Consuming Dividends
Authors: Bräuer Konstantin , Hackethal Andreas , Hanspal Tobin 
Published: February 2022

Abstract
This paper studies why investors buy dividend-paying assets and how they time consumption accordingly. We combine administrative bank data linking customers’ consumption and income to portfolio data and survey responses on financial behavior. We find that private consumption is excessively sensitive to dividend income. Investors across wealth, income, and age distributions increase spending precisely around days of dividend receipt. Our results are at odds with a number of existing rational and behavioral explanations, such as financial constraints and impulsiveness. Instead, consumption responses reflect “planned” excess sensitivity, driven by investors who select dividend portfolios, anticipate dividend income, and plan consumption accordingly.
Neurobehavioral morbidity of pediatric mild sleep-disordered breathing and obstructive sleep apnea
Authors: Yu Phoebe K , Radcliffe Jerilynn , Gerry Taylor H , Amin Raouf S , Baldassari Cristina M , Boswick Thomas , Chervin Ronald D , Elden Lisa M , Furth Susan L , Garetz Susan L , George Alisha , Ishman Stacey L , Kirkham Erin M , Liu Christopher , Mitchell Ron B , Kamal Naqvi S , Rosen Carol L , Ross Kristie R , Shah Jay R , Tapia Ignacio E , Young Lisa R , Zopf David A , Wang Rui , Redline Susan 
Published: February 2022

Abstract

Study Objectives
Obstructive sleep apnea is associated with neurobehavioral dysfunction, but the relationship between disease severity as measured by the apnea-hypopnea index and neurobehavioral morbidity is unclear. The objective of our study is to compare the neurobehavioral morbidity of mild sleep-disordered breathing versus obstructive sleep apnea.

Methods
Children 3–12 years old recruited for mild sleep-disordered breathing (snoring with obstructive apnea-hypopnea index &lt; 3) into the Pediatric Adenotonsillectomy Trial for Snoring were compared to children 5–9 years old recruited for obstructive sleep apnea (obstructive apnea-hypopnea 2–30) into the Childhood Adenotonsillectomy Trial. Baseline demographic, polysomnographic, and neurobehavioral outcomes were compared using univariable and multivariable analysis.

Results
The sample included 453 participants with obstructive sleep apnea (median obstructive apnea-hypopnea index 5.7) and 459 participants with mild sleep-disordered breathing (median obstructive apnea-hypopnea index 0.5). By polysomnography, participants with obstructive sleep apnea had poorer sleep efficiency and more arousals. Children with mild sleep-disordered breathing had more abnormal executive function scores (adjusted odds ratio 1.96, 95% CI 1.30–2.94) compared to children with obstructive sleep apnea. There were also elevated Conners scores for inattention (adjusted odds ratio 3.16, CI 1.98–5.02) and hyperactivity (adjusted odds ratio 2.82, CI 1.83–4.34) in children recruited for mild sleep-disordered breathing.

Conclusions
Abnormal executive function, inattention, and hyperactivity were more common in symptomatic children recruited into a trial for mild sleep-disordered breathing compared to children recruited into a trial for obstructive sleep apnea. Young, snoring children with only minimally elevated apnea-hypopnea levels may still be at risk for deficits in executive function and attention.

Trial Registration
Pediatric Adenotonsillectomy for Snoring (PATS), NCT02562040; Childhood Adenotonsillectomy Trial (CHAT), NCT00560859
Proteomics Indicates Lactate Dehydrogenase Is Prognostic in Acetaminophen-Induced Acute Liver Failure Patients and Reveals Altered Signaling Pathways
Authors: Vazquez Joel H , Kennon-McGill Stefanie , Byrum Stephanie D , Mackintosh Samuel G , Jaeschke Hartmut , Williams D Keith , Lee William M , Dranoff Jonathan A , McGill Mitchell R ,   Acute Liver Failure Study Group
Published: February 2022

Abstract
Better biomarkers to predict death early in acute liver failure (ALF) are needed. To that end, we obtained early (study day 1) and later (day 3) serum samples from transplant-free survivors (n = 28) and nonsurvivors (n = 30) of acetaminophen-induced ALF from the NIH-sponsored Acute Liver Failure Study Group and from control volunteers (n = 10). To identify proteins that increase early in serum during ALF, we selected individuals from this cohort for whom alanine aminotransferase was lower on day 1 than day 3, indicating a time point before peak injury (n = 10/group). We then performed untargeted proteomics on their day 1 samples. Out of 1682 quantifiable proteins, 361 were ≥ 4-fold elevated or decreased in ALF patients versus controls and 16 of those were further elevated or decreased ≥ 4-fold in nonsurvivors versus survivors, indicating potential to predict death. Interestingly, 1 of the biomarkers was lactate dehydrogenase (LDH), which is already measured in most clinical laboratories. To validate our proteomics results and to confirm the prognostic potential of LDH, we measured LDH activity in all day 1 and 3 samples from all 58 ALF patients. LDH was elevated in the nonsurvivors versus survivors on both days. In addition, it had prognostic value similar to the model for end-stage liver disease and outperformed the King’s College Criteria, while a combination of model for end-stage liver disease and LDH together outperformed either alone. Finally, bioinformatics analysis of our proteomics data revealed alteration of numerous signaling pathways that may be important in liver regeneration. Overall, we conclude LDH can predict death in APAP-induced ALF.
Integrating Data FromIn VitroNew Approach Methodologies for Developmental Neurotoxicity
Authors: Carstens Kelly E , Carpenter Amy F , Martin Melissa M , Harrill Joshua A , Shafer Timothy J , Paul Friedman Katie 
Published: February 2022

AbstractIn vivo developmental neurotoxicity (DNT) testing is resource intensive and lacks information on cellular processes affected by chemicals. To address this, DNT new approach methodologies (NAMs) are being evaluated, including: the microelectrode array neuronal network formation assay; and high-content imaging to evaluate proliferation, apoptosis, neurite outgrowth, and synaptogenesis. This work addresses 3 hypotheses: (1) a broad screening battery provides a sensitive marker of DNT bioactivity; (2) selective bioactivity (occurring at noncytotoxic concentrations) may indicate functional processes disrupted; and, (3) a subset of endpoints may optimally classify chemicals with in vivo evidence for DNT. The dataset was comprised of 92 chemicals screened in all 57 assay endpoints sourced from publicly available data, including a set of DNT NAM evaluation chemicals with putative positives (53) and negatives (13). The DNT NAM battery provides a sensitive marker of DNT bioactivity, particularly in cytotoxicity and network connectivity parameters. Hierarchical clustering suggested potency (including cytotoxicity) was important for classifying positive chemicals with high sensitivity (93%) but failed to distinguish patterns of disrupted functional processes. In contrast, clustering of selective values revealed informative patterns of differential activity but demonstrated lower sensitivity (74%). The false negatives were associated with several limitations, such as the maximal concentration tested or gaps in the biology captured by the current battery. This work demonstrates that this multi-dimensional assay suite provides a sensitive biomarker for DNT bioactivity, with selective activity providing possible insight into specific functional processes affected by chemical exposure and a basis for further research.
Chemical Screening in an Estrogen Receptor Transactivation Assay With Metabolic Competence
Authors: Hopperstad Kristen , DeGroot Danica E , Zurlinden Todd , Brinkman Cassandra , Thomas Russell S , Deisenroth Chad 
Published: February 2022

AbstractThe U.S. EPA continues to utilize high-throughput screening data to evaluate potential biological effects of endocrine active substances without the use of animal testing. Determining the scope and need for in vitro metabolism in high-throughput assays requires the generation of larger data sets that assess the impact of xenobiotic transformations on toxicity-related endpoints. The objective of the current study was to screen a set of 768 ToxCast chemicals in the VM7Luc estrogen receptor transactivation assay (ERTA) using the Alginate Immobilization of Metabolic Enzymes hepatic metabolism method. Chemicals were screened with or without metabolism to identify estrogenic effects and metabolism-dependent changes in bioactivity. Based on estrogenic hit calls, 85 chemicals were active in both assay modes, 16 chemicals were only active without metabolism, and 27 chemicals were only active with metabolism. Using a novel metabolism curve shift method that evaluates the shift in concentration-response curves, 29 of these estrogenic chemicals were identified as bioactivated and 59 were bioinactivated. Human biotransformation routes and associated metabolites were predicted in silico across the chemicals to mechanistically characterize possible transformation-related ERTA effects. Overall, the study profiled novel chemicals associated with metabolism-dependent changes in ERTA bioactivity, and suggested routes of biotransformation and putative metabolites responsible for the observed estrogenic effects. The data demonstrate a range of metabolism-dependent effects across a diverse chemical library and highlight the need to evaluate the role of intrinsic xenobiotic metabolism for endocrine and other toxicity-related health effects.
Anxiety in Paediatric Patients Diagnosed with COVID-19 and the Affecting Factors
Authors: Solmaz Abdullah , Karataş Hülya , Ercan Tuğba Meliha Fatma , Erat Tuğba , Solmaz Filiz , Kandemir Hasan 
Published: February 2022

Abstract

Objective
Children may be greatly affected by events that increase stress in individuals in general and are reported as the vulnerable groups during the coronavirus disease-19 (COVID-19) pandemic. But most of the studies in the literature investigating the mental effects of the pandemic on children were conducted with healthy children and limited study has evaluated the effect on children diagnosed with COVID-19. The aim of this study is to determine the anxiety level in paediatric patients diagnosed with COVID-19 and the affecting factors.

Methods
This descriptive study was conducted with 292 children aged 8–18 years who were diagnosed with COVID-19. Data were collected using the Descriptive Characteristics Questionnaire and the Screen for Child Anxiety Related Emotional Disorders (SCARED). Interviews were held by phone.

Results
Males were 51.4% of participants, the mean age was 16.04 ± 1.93. 84.1% of them had a chronic disease; the transmission source was family/relatives/friends for 41.1%. By social isolation, 49.3% were affected and 33.2% were affected by disease symptoms the most in this process. The most common symptoms were headache (61.6%), and asthenia (59.9%). Mean anxiety scale score was 25.5 ± 14.37. The effect of gender, number of symptoms and transmission source on anxiety score was significant (p &lt; 0.05).

Conclusion
Paediatric patients diagnosed with COVID-19 were found to have high anxiety levels. It is recommended to re-evaluate the duration of children’s social participation and support the management of COVID-19 symptoms that affect their anxiety level.
CE: Assessing Movement-Evoked Pain
Authors: Booker Staja , Arnstein Paul , van Boekel Rianne 
Published: February 2022

ABSTRACT:
One of the most common and nuanced tasks that nurses perform is pain assessment, particularly in acute postoperative settings where frequent reassessments are needed. Most assessments are limited to obtaining a pain intensity score with little attention paid to the conditions necessitating the assessment or the factors contributing to the pain. Pain is frequently assessed during rest, but seldom during periods of movement or activity, which is a crucial omission given that acute postoperative movement-evoked pain (MEP) is intense and a common barrier to healing and restoration of function. In addition to physical limitations, MEP can impede cognitive, emotional, and social functioning in ways that can contribute to chronic pain, mood disorders, and disability. Professional and regulatory standards are moving away from a focus on pain intensity to an emphasis on its context, impact on function, and associated distress. Thus, there are many driving forces compelling nurses to integrate MEP assessments into practice to expedite the restoration of biopsychosocial functioning in postoperative patients. The authors discuss the clinical significance of a MEP assessment as well as protocols and tools for completing such assessments.
Medical Aid in Dying: What Every Nurse Needs to Know
Authors: Roy Kaveri 
Published: February 2022

ABSTRACT:
The number of U.S. states legalizing medical aid in dying for patients with terminal diseases and survival prognoses of six months or less is increasing. At press time, 10 states and the District of Columbia have legalized such aid. But because terminal illnesses without clear prognoses are not covered under these laws, some patients are forced to seek medical aid in dying outside the country.
The nurse's role regarding aid in dying is poorly defined, and must be clarified. Currently, nurses and other providers have many misconceptions and fears about providing patients and families with the relevant education. Nurses need to have accurate knowledge and understanding of aid in dying, so they can advocate for those requesting this option; ensure equitable access; and provide them with guidance, support, and resources. An interdisciplinary approach is essential.
This article provides background information on aid in dying in the United States, discusses the nurse's role, offers an illustrative case report, and addresses nursing implications.
Supporting Self-isolation for COVID-19 With “Risk Mitigation” Prescribing and Housing Supports for People Who Use Drugs: A Case Report
Authors: Hong Ran Ha , Brar Rupinder , Fairbairn Nadia 
Published: February 2022

Background
Self-isolation is critical in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. However, people who use drugs face significant barriers in adhering to the regulations. As a response, several supportive measures have been introduced in British Columbia, including temporary housing access and “risk mitigation” prescribing, in which health care providers prescribe pharmaceutical alternatives to the unregulated drug supply to prevent withdrawal and reduce overdose risk.

Case summary
We present a case of a 39-year-old male with a history of polysubstance use and frequent overdoses, who had tested positive for SARS-CoV-2 and was able to successfully self-isolate. “Risk mitigation” prescribing, supportive housing, and harm reduction services were initiated for his self-isolation and connection to community outreach teams for ongoing support.

Discussion
This case illustrates how “risk mitigation” prescribing supported patient’s self-isolation, reduced his illicit drug use, and offered an opportunity for healthcare engagement. Access to safer alternatives to the toxic drug supply should continue beyond COVID-19 pandemic to address the persistent issues of contaminated drug supply and the overdose crisis in North America.
Long-Term Outcomes of Multiligament Knee Injuries
Authors: Zhang Tina , Shasti Keyan , Dubina Andrew , Schneider Matheus B. , Aneizi Ali , Packer Jonathan D. , O'Toole Robert V. , Sciadini Marcus F. , Henn R. Frank 
Published: February 2022

Objective:
To characterize long-term outcomes of multiligament knee injuries (MLKIs) using patient-reported outcome measures, physical examination, and knee radiographs.

Design:
Retrospective clinical follow-up.

Methods:
Twenty knees (18 patients) were evaluated at a mean follow-up of 13.1 years (range 11–15 years). The primary outcome measure was the Internal Knee Documentation Committee score. Patients also completed secondary patient-based outcome assessments including Patient-Reported Outcomes Measurement Information System computer adaptive testing, Short Form-36, and Tegner activity score. Sixteen knees (14 patients) also had physical examination and bilateral knee radiographs assessed with the Kellgren-Lawrence score.

Results:
The mean Internal Knee Documentation Committee score was 56 points, which was significantly lower than the age-matched normative value of 77 (P = 0.004) and exceeds the minimum clinically important difference of 12 points. Most secondary outcome scores were worse than normative population values. Posttraumatic arthritis was present in 100% of MLKIs that had radiographs. Comparing operative versus nonoperative management, there were no statistical differences in patient demographics, injury characteristics, physical examination, or imaging, but surgical patients had better Short Form-36 Social Functioning (89 vs. 63, P = 0.02) and Tegner scores (4.5 vs. 2.9, P = 0.05).

Conclusion:
The long-term outcomes of MLKIs are generally poor, and posttraumatic radiographic evidence of arthritis seems to be universal. Operative management of these injuries may improve long-term outcomes. Clinicians should be aware of these results when counseling patients.

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