bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sleep behavior traits and associations with opioid-related adverse events: a cohort study
Authors: Chen Rudy W , Ulsa Ma Cherrysse , Li Peng , Gao Chenlu , Zheng Xi , Xu Jiawei , Luo Yong , Shen Shiqian , Lane Jacqueline , Scheer Frank A J L , Hu Kun , Gao Lei 
Published: April 2023

Abstract

Study Objectives
Opioid-related adverse events (OAEs), including opioid use disorders, overdose, and death, are serious public health concerns. OAEs are often associated with disrupted sleep, but the long-term relationship between poor sleep and subsequent OAE risk remains unknown. This study investigates whether sleep behavior traits are associated with incident OAEs in a large population cohort.

Methods
444 039 participants (mean age ± SD 57 ± 8 years) from the UK Biobank reported their sleep behavior traits (sleep duration, daytime sleepiness, insomnia-like complaints, napping, and chronotype) between 2006 and 2010. The frequency/severity of these traits determined a poor sleep behavior impacts score (0–9). Incident OAEs were obtained from hospitalization records during 12-year median follow-up. Cox proportional hazards models examined the association between sleep and OAEs.

Results
Short and long sleep duration, frequent daytime sleepiness, insomnia symptoms, and napping, but not chronotype, were associated with increased OAE risk in fully adjusted models. Compared to the minimal poor sleep behavior impacts group (scores of 0–1), the moderate (4–5) and significant (6–9) groups had hazard ratios of 1.47 (95% confidence interval [1.27, 1.71]), p &lt; 0.001, and 2.19 ([1.82, 2.64], p &lt; 0.001), respectively. The latter risk magnitude is greater than the risk associated with preexisting psychiatric illness or sedative-hypnotic medication use. In participants with moderate/significant poor sleep impacts (vs. minimal), subgroup analysis revealed that age &lt;65 years was associated with a higher OAE risk than in those ≥65 years.

Conclusions
Certain sleep behavior traits and overall poor sleep impacts are associated with an increased risk for opioid-related adverse events.
Manganese relative oral bioavailability in electric arc furnace steel slag is influenced by high iron content and low bioaccessibility
Authors: Proctor Deborah M , Vivanco Stephanie N , Blanchette Alexander D 
Published: April 2023

Abstract
Electric arc furnace (EAF) slag is a rock-like aggregate produced with carbon steel and used for construction, including residential ground cover. It is enriched with manganese (Mn) and other metals, including iron (Fe), but because metals are bound in mineral matrices, in vitro bioaccessibility (BA) is limited. We conducted a relative bioavailability (RBA) study using F344 rats to assess Mn RBA from EAF slag ingestion, compared with Mn in diet. Mn and Fe were measured in liver, and Mn in lung and striatum, the target tissue of the brain. Mn levels in each tissue were fit by dose-to-tissue concentration (D-TC) curves. The D-TC relationship was the most highly significant for the linear model using liver Mn, and the RBA was 48%. The D-TC relationship in lung showed a positive slope for chow, but that for EAF slag was slightly negative, and the RBA was 14%. In comparison, the striatum D-TC remained relatively constant, supporting that homeostasis was maintained. Increased Fe was observed in the liver of EAF slag-dosed groups, suggesting that Mn absorption was inhibited by the high Fe content of slag. Lung and striatum D-TC curves demonstrated that systemic delivery of Mn from EAF slag ingestion is limited and support an RBA of 14% for risk assessment. Although Mn levels in slag are elevated compared with health-based screening guidelines, this study supports that incidental ingestion of Mn in EAF slag is unlikely to pose a neurotoxicity hazard due to homeostatic controls, low BA, and high Fe content.
Biomechanical Analysis of Combined Medial Calcar and Lateral Locked Plating Versus Isolated Lateral Locked Plating of Proximal Humerus Fractures
Authors: Kotler Joshua A. , Zuppke Julia N. , Abraham Vivek M. , Sanville Jennifer A. , Nabet Austin C. , Carofino Bradley , Gardner Michael J. , Smith Christopher S. 
Published: April 2023

Objective:
Medial calcar buttress plating combined with lateral locked plating is biomechanically tested against isolated lateral locked plating in synthetic humeri models for the treatment of proximal humerus fractures.

Methods:
Proximal humerus fractures (OTA/AO type 11-A2.1) were manufactured in 10 pairs of Sawbones humeri models (Sawbones, Pacific Research Laboratories, Vashon Island, WA). Specimen were randomly assigned and instrumented with either medial calcar buttress plating combined with lateral locked plating (CP) or isolated lateral locked plating (LP). Nondestructive torsional and axial load tests were performed to evaluate construct stiffness. Large-cycle axial tests were conducted followed by destructive ramp-to-failure tests. Cyclic stiffness was compared in both nondestructive and ultimate failure loads. Failure displacement was recorded and compared between groups.

Results:
The addition of medial calcar buttress plating to lateral locked plating constructs significantly increased the axial (P < 0.01) and torsional (P < 0.01) stiffness of the construct compared with isolated lateral locked plating by 95.56% and 37.46%, respectively. All models demonstrated greater axial stiffness (P < 0.01) after 5000 cycles of axial compression, not dependent on the fixation method. During destructive testing, the CP construct withstood 45.35% larger load (P < 0.01) and congruently exhibited 58% less humeral head displacement (P = 0.02) before failure when compared with the LP construct.

Conclusion:
This study demonstrates the biomechanical superiority of medial calcar buttress plating when combined with lateral locked plating as compared with isolated lateral locked plating of OTA/AO type 11-A2.1 proximal humerus in synthetic humeri models.
Characteristics of Scientific Success in Phase 1 Pediatric Oncology Clinical Trials: Establishing a Need for Integrated Patient-Reported Outcomes Even in Early Phase Trials
Authors: Keim-Malpass Jessica , Blair Lisa , Doede Aubrey , Chu Crystal , Graham Connor , Petersen William C. 
Published: April 2023

Background:
Pediatric clinical trials are particularly vulnerable to challenges in participant accrual, making them more likely to encounter early termination.

Objective:
To describe clinical trial characteristics of phase 1 pediatric oncology clinical trials registered in ClinicalTrials.gov through 2017.

Method:
We identified a retrospective cohort and abstracted key clinical trial characteristics from this data source. We calculated a bivariate logistic regression to explore factors related to early trial termination.

Results:
Over 1400 phase 1 trials were included in this analysis. Only 3.2% of trials included any type of patient-reported outcome (PRO) as a secondary outcome and 21.6% of phase 1 trials did not meet scientific success due to early termination. National Institutes of Health (NIH)-funded phase 1 trials had the lowest percentage of early termination.

Conclusions:
Phase 1 clinical trials for pediatric patients with cancer are at risk of early termination due to lack of enrollment. A deeper understanding of clinical trial design elements, characteristics, and eligibility determination may contribute to a higher proportion of trials meeting successful enrollment.

Implications for Practice:
Oncology nurses and nurse scientists uniquely contribute to an understanding of family-centered approaches and should take an active role in trial design for pediatric cancers that could help capture meaningful PROs during a vulnerable clinical trajectory.

What Is Foundational:
Very little attention has been given to understanding characteristics of phase 1 clinical trials for pediatric cancers that may impact the state of the science and care delivery for patients with advanced pediatric cancer diagnoses.
Effects of Auricular Acupressure on Symptom Burden and Quality of Life in Patients With Advanced Lung Cancer Treated With Immunotherapy Based on the Midnight-noon Ebb-flow Theory: A Randomized Controlled Trial
Authors: Lin Yuting , Wang Yali , Yan Rong , Li Zhen , Ding Min , Meng Xiangmin , Yu Weiwei 
Published: April 2023

Background:
The burden of immunotherapy-induced symptoms is prevalent in patients with advanced lung cancer and may impact their quality of life (QOL).

Objective:
To investigate the effect of auricular acupressure, based on the theory of midnight-noon ebb-flow, and using a randomized controlled trial, on alleviating symptoms burden and QOL in patients with advanced lung cancer during 3 cycles of immunotherapy treatment.

Methods:
Patients with advanced lung cancer who received immunotherapy were recruited. The control group (n = 60) was treated with standard clinical treatment and nursing care, and the intervention group (n = 60) was treated with 3 cycles of auricular acupressure under the guidance of midnight-noon ebb-flow theory. Patients’ symptoms and QOL were compared before and after the intervention of 3 cycles.

Results:
At 2 cycles after the intervention for symptoms burden and QOL, there were statistically significant differences between the control group and the intervention group (P < .05), but no statistically significant difference between the two groups after 3 cycles.

Conclusion:
Auricular acupressure based on the theory of midnight-noon ebb-flow can alleviate the specific symptom burden of immunotherapy patients with advanced lung cancer and improve their QOL.

Implications for Practice:
The special Traditional Chinese Medicine (TCM) nursing technology of auricular acupressure combined with TCM time treatment is beneficial and safe.

Foundational:
The QOL of patients can be improved by nursing technology with TCM, which may be best used as a part of clinical work.
Treatment of intermediate-risk prostate cancer with active surveillance in the routine care—Long-term outcomes of a prospective noninterventional study (HAROW)
Authors: Weissbach Lothar , Schwarte Andreas , Boedefeld Edith A. , Herden Jan 
Published: April 2023

Abstract

Background
We report here the long-term outcomes of patients with intermediate-risk prostate cancer (PCa) treated with active surveillance (AS) in a daily routine setting.

Material and methods
HAROW (2008–2013) was a noninterventional, health service research study investigating the management of localized PCa in a community setting. A substantial proportion of the study centers were office-based urologists. A follow-up examination of all intermediate-risk patients with AS was conducted. Overall, cancer-specific, metastasis-free, and treatment-free survival rates, as well as reasons for discontinuation, were determined and discussed.

Results
Of the 2957 patients enrolled, 52 with intermediate-risk PCa were managed with AS and were available for evaluation. The median follow-up was 6.8 years (interquartile range, 3.4–8.6 years). Seven patients (13.5%) died of causes unrelated to PCa, of whom 4 were under AS or under watchful waiting. Two patients (3.8%) developed metastasis. The estimated 8-year overall, cancer-specific, metastasis-free, and treatment-free survival rates were 85% (95% confidence interval [CI], 72%–96%), 100%, 93% (95% CI, 82%–100%), and 31% (95% CI, 17%–45%), respectively. On multivariable analysis, prostate-specific antigen density of ≥0.2 ng/mL2 was significantly predictive of receiving invasive treatment (hazard ratio, 3.29; p = 0.006). Reasons for discontinuation were more often due to patient's or physician's concerns (36%) than due to observed clinical progression.

Conclusions
Although survival outcome data for intermediate-risk patients managed with AS in real-life health care conditions were promising, rates of discontinuation were high, and discontinuation was often a patient's decision, even when the signs of disease progression were absent. This might be an indication of higher levels of mental burden and anxiety in this specific subgroup of patients, which should be considered when making treatment decisions. From a psychological perspective, not all intermediate-risk patients are optimal candidates for AS.
Family Perspectives on In-Home Multimodal Longitudinal Data Collection for Children Who Function Across the Developmental Spectrum
Authors: Boerner Katelynn E. , Pearl-Dowler Leora , Holsti Liisa , Wharton Marie-Noelle , Siden Harold , Oberlander Tim F. 
Published: April 2023

Abstract:Objective:Quality child health research requires multimodal, multi-informant, longitudinal tools for data collection to ensure a holistic description of real-world health, function, and well-being. Although advances have been made, the design of these tools has not typically included community input from families with children whose function spans the developmental spectrum.Methods:We conducted 24 interviews to understand how children, youth, and their families think about in-home longitudinal data collection. We used examples of smartphone-based Ecological Momentary Assessment of everyday experiences, activity monitoring with an accelerometer, and salivary stress biomarker sampling to help elicit responses. The children and youth who were included had a range of conditions and experiences, including complex pain, autism spectrum disorder, cerebral palsy, and severe neurologic impairments. Data were analyzed using reflexive thematic analysis and descriptive statistics of quantifiable results.Results:Families described (1) the importance of flexibility and customization within the data collection process, (2) the opportunity for a reciprocal relationship with the research team; families inform the research priorities and the development of the protocol and also benefit from data being fed back to them, and (3) the possibility that this research approach would increase equity by offering accessible participation opportunities for families who might otherwise not be represented. Most families expressed interest in participating in in-home research opportunities, would find most methods discussed acceptable, and cited 2 weeks of data collection as feasible.Conclusion:Families described diverse areas of complexity that necessitate thoughtful adaptations to traditional research designs. There was considerable interest from families in active engagement in this process, particularly if they could benefit from data sharing. This feedback is being incorporated into pilot demonstration projects to iteratively codesign an accessible research platform.
An Optimized LC-MS/MS Method for Quantification of Sunitinib and N-Desethyl Sunitinib in Human Plasma and Its Application for Therapeutic Drug Monitoring
Authors: Li Qiaoqiao , Tang Tiantian , Zhang Min , Li Lixian , Chen Wanyi 
Published: April 2023

Background:
Sunitinib (SUN) malate is an oral, multitargeted, tyrosine kinase inhibitor approved for the treatment of metastatic renal cell carcinoma, imatinib-resistant or imatinib-intolerant gastrointestinal stromal tumors, and pancreatic neuroendocrine tumors. SUN has a narrow therapeutic window and high variability in interpatient pharmacokinetic parameters. Clinical detection methods for SUN and N-desethyl SUN limit the application of SUN to therapeutic drug monitoring. All published methods for quantifying SUN in human plasma require strict light protection to avoid light-induced isomerism or the use of additional quantitative software. To avoid these difficult processes in clinical routines, the authors propose a novel method that merges the peaks of the E-isomer and Z-isomer of SUN or N-desethyl SUN into a single peak.

Methods:
The E-isomer and Z-isomer peaks of SUN or N-desethyl SUN were merged into a single peak by optimizing the mobile phases to decrease the resolution of the isomers. A suitable chromatographic column was selected to obtain a good peak shape. Thereafter, the conventional and single-peak methods (SPM) were simultaneously validated and compared according to the guidelines published by the Food and Drug Administration in 2018 and the Chinese Pharmacopoeia in 2020.

Results:
The verification results showed that the SPM was superior to the conventional method in the matrix effect and met the requirements for biological sample analysis. SPM was then applied to detect the total steady-state concentration of SUN and N-desethyl SUN in tumor patients who received SUN malate.

Conclusions:
The established SPM makes the detection of SUN and N-desethyl SUN easier and faster without light protection or extra quantitative software, making it more appropriate for routine clinical use. The clinical application results showed that 12 patients took 37.5 mg per day, with a median total trough steady-state concentration of 75.0 ng/mL.
Simultaneous Determination of Rifamycin Antibiotics and Their Active Metabolites in Human Plasma Using UHPLC-MS/MS to Evaluate Their Impact on Target Peak Concentrations: A Short Communication
Authors: Wu Ling-jie , Ye Zhen-jie , Zhang Xiao-ying , Zhang Xiao-long , Zheng Ai-xian , Liu Xiao-long , Yu Xiao-ling 
Published: April 2023

Background:
Standard and proper antituberculosis (anti-TB) treatment is essential for patients with TB, and rifamycin antibiotics are key components of anti-TB therapy. Therapeutic drug monitoring (TDM) of rifamycin antibiotics can shorten the time to response and complete treatment of TB. Notably, antimicrobial activities of the major active metabolites of rifamycin are similar to those of their parent compounds. Thus, a rapid and simple assay was developed for simultaneous determination of rifamycin antibiotics and their major active metabolites in plasma to evaluate their impact on target peak concentrations. Here, the authors have developed and validated a method for simultaneous determination of rifamycin antibiotics and their active metabolites in human plasma using ultrahigh-performance liquid chromatography tandem mass spectrometry.

Methods:
Analytical validation of the assay was performed in accordance with the bioanalytical method validation guidance for industry described by the US Food and Drug Administration and the guidelines for bioanalytical method validation described by the European Medicines Agency.

Results:
The drug concentration quantification method for rifamycin antibiotics, including rifampicin, rifabutin, and rifapentine, and their major active metabolites was validated. Significant differences in the proportions of active metabolites in rifamycin antibiotics may affect the redefinition of their effective concentration ranges in the plasma. The method developed herein is expected to redefine the ranges of “true” effective concentrations of rifamycin antibiotics (including parent compounds and their active metabolites).

Conclusions:
The validated method can be successfully applied for high-throughput analysis of rifamycin antibiotics and their active metabolites for TDM in patients receiving anti-TB treatment regimens containing these antibiotics. Proportions of active metabolites in rifamycin antibiotics markedly varied among individuals. Depending on the clinical indications of patients, the therapeutic ranges for rifamycin antibiotics may be redefined.
A multiplexed barcode approach to simultaneously evaluate gene delivery by adeno-associated virus capsid variants in nonhuman primates
Authors: Stone Daniel , Meumann Nadja , Kuhlmann Anne-Sophie , Peterson Christopher W. , Xie Hong , Roychoudhury Pavitra , Loprieno Michelle A. , Vu Xuan-Khang , Strongin Daniel E. , Kenkel Elizabeth J. , Haick Anoria , Stensland Laurence , Obenza Willimark M. , Parrott Jacob , Nelson Veronica , Murnane Robert D. , Huang Meei-Li , Aubert Martine , Kiem Hans-Peter , Büning Hildegard , Jerome Keith R. 
Published: April 2023

Background and Aims:
Adeno-associated virus (AAV) vectors are widely used to deliver therapeutic transgenes to distinct tissues, including the liver. Vectors based on naturally occurring AAV serotypes as well as vectors using engineered capsids have shown variations in tissue tropism and level of transduction between different mouse models. Moreover, results obtained in rodents frequently lack translatability into large animal studies. In light of the increasing interest in AAV vectors for human gene therapy, an increasing number of studies are being performed in nonhuman primates. To keep animal numbers to a minimum and thus optimize the process of AAV capsid selection, we developed a multiplex barcoding approach to simultaneously evaluate the in vivo vector performance for a set of serotypes and capsid-engineered AAV vectors across multiple organs.

Approach and Results:
Vector biodistribution and transgene expression were assessed by quantitative PCR, quantitative reverse transcription PCR, vector DNA amplicon Illumina sequencing and vRNAseq in male and female rhesus macaques simultaneously dosed with a mixture of barcoded naturally occurring or engineered AAV vectors encoding the same transgene. As expected, our findings show animal-to-animal variation in both the biodistribution and tissue transduction pattern, which was partly influenced by each animal’s distinctive serological status.

Conclusions:
This method offers a robust approach to AAV vector optimization that can be used to identify and validate AAV vectors for gene delivery to potentially any anatomical site or cell type.
Comparison of Finger, Hand, and Wrist Injuries in the US Air Force to US Workers
Authors: Gwilliam Melody , Hendricks Scott , Socias-Morales Christina , Burnham Bruce , Gomes Harold , Reichard Audrey , Stallings Heidi 
Published: April 2023

ObjectiveFingers, hands, and wrists (FHW) are the most frequently injured body parts in work-related injuries. This study described and compared FHW injuries among enlisted, officer, and civilian US Air Force (USAF) personnel to those in the US workforce.MethodsAll work-related, noncombat FHW injuries (≥1 lost workday) and demographics among USAF personnel and US workforce (2008–2018) were included. The USAF FHW injury rates were age adjusted to the US employment and compared by sex, source, event, and nature of the injuries.ResultsFinger, hand, and wrist injuries were significantly lower among the USAF personnel and among females. In both populations, FHW injuries from falls were higher and increased with age group among females. Males had higher overall FHW injuries from contact with objects and equipment.ConclusionsPrevention efforts should focus on understanding risk factors and sharing successful prevention activities.