bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in atrial fibrillation-related mortality in Europe, 2008–2019
Authors: Zuin Marco , Malagù Michele , Vitali Francesco , Balla Cristina , De Raffele Martina , Ferrari Roberto , Boriani Giuseppe , Bertini Matteo
Published: January 2024

Aims

Update data regarding the atrial fibrillation (AF)-related mortality trend in Europe remain scant. We assess the age- and sex-specific trends in AF-related mortality in the European states between the years 2008 and 2019.

Methods and results

Data on cause-specific deaths and population numbers by sex for European countries were retrieved through the publicly available World Health Organization mortality dataset for the years 2008–2019. Atrial fibrillation-related deaths were ascertained when the International Classification of Diseases, 10th Revision code I48 was listed as the underlying cause of death in the medical death certificate. To calculate annual trends, we assessed the average annual % change (AAPC) with relative 95% confidence intervals (CIs) using Joinpoint regression. During the study period, 773 750 AF-related deaths (202 552 males and 571 198 females) occurred in Europe. The age-adjusted mortality rate (AAMR) linearly increased from 12.3 (95% CI: 11.2–12.9) per 100 000 population in 2008 to 15.3 (95% CI: 14.7–15.7) per 100 000 population in 2019 [AAPC: +2.0% (95% CI: 1.6–3.5), P < 0.001] with a more pronounced increase among men [AAPC: +2.7% (95% CI: 1.9–3.5), P < 0.001] compared with women [AAPC: +1.7% (95% CI: 1.1–2.3), P < 0.001] (P for parallelism 0.01). Higher AAMR increases were observed in some Eastern European countries such as Latvia, Lithuania, and Poland, while the lower increases were mainly clustered in Central Europe.

Conclusion

Over the last decade, the age-adjusted AF-related mortality has increased in Europe, especially among males. Disparities still exist between Western and Eastern European countries.
Detecting genetic effects on phenotype variability to capture gene-by-environment interactions: a systematic method comparison
Authors: Zhang Xiaopu , Bell Jordana T
Published: January 2024

Genetically associated phenotypic variability has been widely observed across organisms and traits, including in humans. Both gene-gene and gene-environment interactions can lead to an increase in genetically associated phenotypic variability. Therefore, detecting the underlying genetic variants, or variance Quantitative Trait Loci (vQTLs), can provide novel insights into complex traits. Established approaches to detect vQTLs apply different methodologies from variance-only approaches to mean-variance joint tests, but a comprehensive comparison of these methods is lacking. Here, we review available methods to detect vQTLs in humans, carry out a simulation study to assess their performance under different biological scenarios of gene-environment interactions, and apply the optimal approaches for vQTL identification to gene expression data. Overall, with a minor allele frequency (MAF) of less than 0.2, the squared residual value linear model (SVLM) and the deviation regression model (DRM) are optimal when the data follow normal and non-normal distributions, respectively. In addition, the Brown–Forsythe (BF) test is one of the optimal methods when the MAF is 0.2 or larger, irrespective of phenotype distribution. Additionally, a larger sample size and more balanced sample distribution in different exposure categories increase the power of BF, SVLM, and DRM. Our results highlight vQTL detection methods that perform optimally under realistic simulation settings and show that their relative performance depends on the phenotype distribution, allele frequency, sample size, and the type of exposure in the interaction model underlying the vQTL.
Use of in-network insurance benefits is critical for improving retention in telehealth-based buprenorphine treatment
Authors: Williams Arthur Robin , Rowe Christopher , Minarik Lexie , Gray Zack , Murphy Sean M , Pincus Harold A
Published: January 2024

An empiric evidence base is lacking regarding the relationship between insurance status, payment source, and outcomes among patients with opioid use disorder (OUD) on telehealth platforms. Such information gaps may lead to unintended impacts of policy changes. Following the phase-out of the COVID-19 Public Health Emergency, states were allowed to redetermine Medicaid eligibility and disenroll individuals. Yet, financial barriers remain a common and significant hurdle for patients with OUD and are associated with worse outcomes. We studied 3842 patients entering care in 2022 at Ophelia Health, one of the nation's largest OUD telehealth companies, to assess associations between insurance status and 6-month retention. In multivariable analyses, in-network patients who could use insurance benefits were more likely to be retained compared with cash-pay patients (adjusted risk ratio [aRR]: 1.50; 95% CI: 1.40–1.62; P < .001). Among a subsample of 882 patients for whom more detailed insurance data were available (due to phased-in electronic health record updates), in-network patients were also more likely to be retained at 6 months compared with insured, yet out-of-network patients (aRR: 1.86; 95% CI: 1.54–2.23; P < .001). Findings show that insurance status, and specifically the use of in-network benefits, is associated with superior retention and suggest that Medicaid disenrollment and insurance plan hesitation to engage with telehealth providers may undermine the nation's response to the opioid crisis.
Organizational and occupational health issues with working remotely during the pandemic: a scoping review of remote work and health
Authors: Lyzwinski Lynnette-Natalia
Published: January 2024

Background: Stay-at-home orders during the COVID-19 global pandemic created unprecedented challenges for workers whose work was transferred to the home setting. Little is presently known about the benefits and the challenges associated with global remote work on well-being and mental health, work-life balance, job satisfaction, productivity, home office adaptability, and gender equality.

Methods: A scoping review of PubMed/Medline was undertaken in October 2021 to better understand these broad dimensions associated with remote worker health, well-being, and the home office workspace. The review focused on white-collar workers who undertook remote work during each of the lockdown waves from March 2020 to 2021.

Results: A total of 62 studies were included in the review, which spanned Asia, North America, South America, and Europe. Overall, workers seemed to enjoy remote work, but productivity varied. The main setbacks associated with remote work included feelings of isolation and loneliness, which negatively influenced well-being. Social support from management and contact with colleagues mitigated this. Leadership style also influenced remote worker well-being. Overall, women suffered from lower levels of remote work well-being and productivity, especially if they had children. The home office and its adaptability were integral for successful remote work. Work-life balance was affected in some workers who struggled with heavier workloads or family duties.

Conclusions: To promote well-being and successful remote work, isolation and loneliness should be reduced through greater contact with colleagues and managers. Managers should promote family friendly policies that may support work-life balance and reduce gender inequities in remote work.
How to Marry a Star: Probabilistic Constraints for Meaning in Context
Authors: Erk Katrin , Herbelot Aurélie
Published: January 2024

In this paper, we derive a notion of word meaning in context that characterizes meaning as both intensional and conceptual. We introduce a framework for specifying local as well as global constraints on word meaning in context, together with their interactions, thus modelling a wide range of lexical shifts and ambiguities observed in utterance interpretation. We represent sentence meaning as a situation description system, a probabilistic model which takes utterance understanding to be the mental process of describing to oneself one or more situations that would account for an observed utterance. We show how the system can be implemented in practice, and apply it to examples containing various contextualisation phenomena.
Aerosolized Particulate Matter and Blunting of Ciliary Dynamic Responses: Implications for Veterans and Active Duty Military in Southwest Asia
Authors: Workman Alan D , Lee Robert J , Cohen Noam A
Published: January 2024

Introduction

Respiratory diseases such as chronic rhinosinusitis and asthma are observed at increased rates in active duty and veteran military members, and they are especially prevalent in individuals who have been deployed in Southwest Asia during Operation Iraqi Freedom and Operation Enduring Freedom. Particulate matter, specifically the fine-grain desert sand found in the Middle East, may be a key source of this pathology because of deleterious effects on mucociliary clearance.

Materials and Methods

With IRB approval, human sinonasal tissue was grown at an air-liquid interface and cultures were exposed to different types and sizes of particulate matter, including sand from Afghanistan and Kuwait. Ciliary dynamic responses to mechanical stimulation and ATP application were assessed following particulate exposure.

Results

Particle size of the commercial sand was substantially larger than that of the sand of Afghan or Kuwaiti origin. Following exposure to particulate matter, normal dynamic ciliary responses to mechanical stimulation and ATP application were significantly decreased (P < .01), with corresponding decreases in ATP-induced calcium flux (P < .05). These changes were partially reversible with apical washing after a 16-h period of exposure. After 36 h of exposure to Middle Eastern sand, ciliary responses to purinergic stimulation were completely abolished.

Conclusions

There is a neutralization of the dynamic ciliary response following chronic particulate matter exposure, similar to ciliary pathologies observed in patients with chronic rhinosinusitis. Aerosolized particulate matter endured by military personnel in the Southwest Asia may cause dysfunctional mucociliary clearance; these data help to explain the increased prevalence of respiratory pathology in individuals who are or have been deployed in this region.
Hybrid Regimes in Historical Perspective
Authors: Weyland Kurt
Published: January 2024

Hybrid regimes long preceded the post-Cold War era highlighted by Levitsky and Way’s seminal analysis. During the nineteenth century in Europe, socioeconomic modernization and the gradual advance of political liberalism led long-established monarchies to concede suffrage reforms, protections of human and civil rights, and steps toward the parliamentary responsibility of governments. The resulting hybrid regimes, which allowed for learning and habituation among diverse political actors, constituted transitional stages in the “first wave of democratization,” which powerful labor movements and broader societal mobilization brought to a successful conclusion, especially in the continent’s northwest. In Latin America, by contrast, learning and diffusion from the United States and Europe propelled comparatively “early,” developmentally premature steps toward political liberalism. Given limited modernization and weak societal activism, these hybrid regimes were dominated by established elites, which corrupted liberalism’s formal institutions through informal machinations and electoral fraud. Entrenched elitism and endemic instability hindered transitions to democracy.
Prenatal substance exposure and child health: Understanding the role of environmental factors, genetics, and brain development
Authors: Gu Zixin , Barch Deanna M , Luo Qiang
Published: January 2024

Prenatal substance exposure (PSE) has been linked to adverse health outcomes, but its interactions with environmental and genetic factors remain unclear. Using data from the adolescent brain cognitive development cohort (n = 9,838; baseline age: 9.92 ± 0.62 years), we tested for the robust associations of PSE-caffeine/alcohol/tobacco/marijuana with children's health, cognition, and brain metrics after controlling for the environmental and genetic contexts. The environmental context involved birth, familial, and societal risk factors, while the genetic context included family histories and polygenic risk scores (PRSs) of mental disorders. In this sample, PSE-caffeine was observed in 59.8%, PSE-alcohol in 25.7%, PSE-tobacco in 13.2%, and PSE-marijuana in 5.6% of children. PSE-tobacco/marijuana was associated with higher environmental risks, PSE-alcohol was associated with lower familial risks, and all PSEs were associated with higher genetic risks. Controlling for these contexts reduced the number of significant health associations by 100, 91, 84, and 18% for PSE-tobacco/marijuana/caffeine/alcohol. Compared to the baseline, PSE-alcohol had the most health associations that were persistent over a 2-year period from preadolescence to adolescence, including associations with more sleep and mental health problems, improved cognitive functions, and larger brain volumes. These persistent associations with mental health problems and crystallized cognition were mediated by the surface areas of the frontal and the parietal cortices, respectively. Lower risk scores of the familial contexts attenuated associations between PSE-alcohol/marijuana and mental health problems. Higher PRS for substance use disorders enhanced late-onset associations of PSE-marijuana with externalizing problems. Results support the “health in context” concept, emphasizing modifiable factors mitigating adverse PSE effects.
The structural OFF and ON states of myosin can be decoupled from the biochemical super- and disordered-relaxed states
Authors: Jani Vivek P , Song Taejeong , Gao Chengqian , Gong Henry , Sadayappan Sakthivel , Kass David A , Irving Thomas C , Ma Weikang
Published: January 2024

There is a growing awareness that both thick-filament and classical thin-filament regulations play central roles in modulating muscle contraction. Myosin ATPase assays have demonstrated that under relaxed conditions, myosin may reside either in a high-energy-consuming disordered-relaxed (DRX) state available for binding actin to generate force or in an energy-sparing super-relaxed (SRX) state unavailable for actin binding. X-ray diffraction studies have shown that the majority of myosin heads are in a quasi-helically ordered OFF state in a resting muscle and that this helical ordering is lost when myosin heads are turned ON for contraction. It has been assumed that myosin heads in SRX and DRX states are equivalent to the OFF and ON states, respectively, and the terms have been used interchangeably. In this study, we use X-ray diffraction and ATP turnover assays to track the structural and biochemical transitions of myosin heads, respectively, induced with either omecamtiv mecarbil (OM) or piperine in relaxed porcine myocardium. We find that while OM and piperine induce dramatic shifts of myosin heads from the OFF to the ON state, there are no appreciable changes in the population of myosin heads in the SRX and DRX states in both unloaded and loaded preparations. Our results show that biochemically defined SRX and DRX can be decoupled from structurally defined OFF and ON states. In summary, while SRX/DRX and OFF/ON transitions can be correlated in some cases, these two phenomena are measured using different approaches, reflect different properties of the thick filament, and should be investigated and interpreted separately.
Away from the herd: loneliness as a dysfunction of social alignment
Authors: Shamay-Tsoory Simone G , Kanterman Alisa
Published: January 2024

The tendency of all humans to experience loneliness at some point in their lives implies that it serves an adaptive function. Building on biological theories of herding in animals, according to which collective movement emerges from local interactions that are based on principles of attraction, repulsion and alignment, we propose an approach that synthesizes these principles with theories of loneliness in humans. We present here the ‘herding model of loneliness’ that extends these principles into the psychological domain. We hold that these principles serve as basic building blocks of human interactions and propose that distorted attraction and repulsion tendencies may lead to inability to align properly with others, which may be a core component in loneliness emergence and perpetuation. We describe a neural model of herding in humans and suggest that loneliness may be associated with altered interactions between the gap/error detection, reward signaling, threat and observation-execution systems. The proposed model offers a framework to predict the behavior of lonely individuals and thus may inform intervention designs for reducing loneliness intensity.
Citizen attitudes toward science and technology, 1957–2020: measurement, stability, and the Trump challenge
Authors: Miller Jon D , Laspra Belén , Polino Carmelo , Branch Glenn , Ackerman Mark S , Pennock Robert T
Published: January 2024

In democratic societies around the world, the number of science policy decisions is increasing. One of the fundamental principles of democracy is that citizens should be able to understand the issues before them. Using a 63-year cross-sectional US data set, we use confirmatory factor analysis to construct and test a two-dimensional measure of attitude to science and technology that has been relatively stable over the last six decades. Previous and current research tells us that only one in three US adults is scientifically literate, meaning that trust in scientific expertise is important to many citizens. We find that trust in scientific expertise polarized during the Trump administration. Using the same data set, we construct two structural equation models to determine the factors that predict positive attitudes toward science and technology. Comparing 2016 and 2020, we find that the Trump attacks on science did not reduce public support for science.
Race and Virulence Dynamics of Puccinia triticina in China During 2007 to 2021
Authors: Li Hongfu , Huang Liang , Zhang Hao , Liu Bo , Gao Li , Chen Wanquan , Liu Taiguo
Published: January 2024

The challenge of wheat leaf rust on wheat production is a recurring issue. Race identification of Puccinia triticina (Pt) serves as the foundation for preventing and controlling this disease. In a 15-year study, we identified 2,900 isolates of Pt from 20 provinces, cities, or autonomous regions in China during 2007 to 2021 and found 332 virulence phenotypes with 11 predominant phenotypes: PHT (8.3%), THT (5.4%), PHK (4.5%), PHJ (3.7%), THJ (3.6%), SHJ (3.5%), THS (3.3%), FGD (2.9%), THK (2.6%), PHS (2.4%), and PHD (2.0%). The virulence frequency for 40 Lr genes was identified across different years and areas; one major reason for the race dynamics was the attenuation to Lr1 and Lr26, which was more evident in southwest China. Lr9, Lr24, Lr28, Lr38, and Lr42 maintained effectiveness in China, while Lr2c, Lr10, Lr12, Lr14a, Lr14b, Lr22a, Lr33, and Lr36 nearly lost their effectiveness against wheat leaf rust disease. Twelve Lr sites were found to have differences in virulence frequencies with values greater than 20% across various locations; furthermore, the lowest and highest virulence values were observed in north China (Area 1) and northwest China (Area 5), respectively. According to phenotype dynamics, PHT, THT, FGD, THK, and PHS are more likely to persist over time. In addition, much attention should be given toward discovering rising combinations of virulent phenotypes.
Xylazine Use Among People Who Inject Drugs, Philadelphia 2022
Authors: Tan Marissa , Nassau Tanner , Kuncio Danica , Higgins Dana , Teixeira da Silva Daniel , Tomlinson David , Brady Kathleen A.
Published: January 2024

Objectives

Xylazine is commonly mixed with illicit opioids in Philadelphia, and potential associations with wound issues, infectious diseases, and overdoses are of public health concern. We used data from the National HIV Behavioral Surveillance Survey among persons who inject drugs (PWIDs) in Philadelphia to better identify individuals at risk and inform patients and clinicians about xylazine risk factors.

Methods

We compared characteristics of participants who reported using xylazine to those who reported not using xylazine in the past 12 months. Among those who reported xylazine use, we compared characteristics between people who prefer and did not prefer to use xylazine.

Results

In this sample of PWIDs, most prefer not to use xylazine, yet use is common. Compared with PWIDs not using xylazine, PWIDs who use xylazine were more likely to have recent homelessness, polysubstance use, overdose history, and hepatitis C virus infection (P< 0.05 for all comparisons). Compared with concordant xylazine use, discordant xylazine use was associated with lower preference for fentanyl, heroin as the primary injection drug, and lower use of syringe service programs (P< 0.05 for all comparisons).

Conclusions

Public health entities should prioritize studying the use and health effects of xylazine in their jurisdictions and consider supporting point-of-care and drug-checking surveillance in addition to raising awareness of xylazine in the drug supply.
Standardizing Continuous Physical Activity Monitoring in Patients with Cervical Spondylosis
Authors: Maldaner Nicolai , Gonzalez-Suarez Aneysis D. , Tang Megan , Fatemi Parastou , Leung Chris , Desai Atman , Tomkins-Lane Christy , Zygourakis Corinna
Published: January 2024

Study Design/Setting.

Prospective cohort study.

Objective.

To use a commercial wearable device to measure real-life, continuous physical activity in patients with CS and to establish age- and sex-adjusted standardized scores.

Summary of Background Data.

Patients with cervical spondylosis (CS) often present with pain or neurologic deficits that results in functional limitations and inactivity. However, little is known regarding the influence of CS on patient’s real-life physical activity.

Methods.

This study included 100 English-speaking adult patients with cervical degenerative diseases undergoing elective spine surgery at Stanford University who owned iPhones. Patients undergoing surgery for spine infections, trauma, or tumors, or with lumbar degenerative disease were excluded. Activity two weeks before surgery was expressed as raw daily step counts. Standardized z-scores were calculated based on age- and sex-specific values of a control population. Responses to patient-reported outcome measures (PROMs) surveys assessed convergent validity. Functional impairment was categorized based on predetermined z-score cut-off values.

Results.

30 CS with mean(±SD) age of 56.0(±13.4) years wore an Apple Watch for ≥8 hours/day in 87.1% of the days. Mean watch wear time was 15.7(±4.2) hours/day, and mean daily step count was 6,400(±3,792). There was no significant difference in activity between 13 patients (43%) with myelopathy and 17 (57%) without myelopathy. Test-Retest reliability between wearable step count measurements was excellent (ICC β=0.95). Physical activity showed a moderate positive correlation with SF36-PCS, EQ5D VAS, and PROMIS-PF. Activity performance was classified into categories of “no impairment” (step count=9,640(±2,412)), “mild impairment” (6,054(±816)), “moderate impairment” (3,481(±752)), and “severe impairment” (1,619(±240)).

Conclusion.

CS patients’ physical activity is significantly lower than the general population, or the frequently stated goals of 7,000-10,000 steps/day. Standardized, continuous wearable physical activity monitoring in CS is a reliable, valid, and normalized outcome tool that may help characterize functional impairment before and after spinal interventions.
Imaging Characteristics of Nonrheumatoid Arthritis Patients With Retro-odontoid Pseudotumor
Authors: Kawabata Soya , Kuroshima Kohei , Kawaguchi Koki , Takegami Norihiko , Yurube Takashi , Michikawa Takehiro , Akeda Koji , Kakutani Kenichiro , Fujita Nobuyuki
Published: January 2024

Study design.

Multicenter case-control study.

Objective.

To identify imaging characteristics of the cervical spine in patients with retro-odontoid pseudotumor (ROP) without rheumatoid arthritis (RA) and determine the pathogenesis of ROP.

Background.

ROP results from proliferative changes in the soft tissue of the atlantoaxial junction surrounding the region of the transverse ligament, and is commonly seen in RA patients. However, the pathogenesis of ROP caused by mechanical instability of the upper cervical spine in patients without RA is yet to be explained.

Materials and Methods.

We collected imaging data [preoperative radiographs, magnetic resonance imaging (MRI), and computed tomography (CT)] of patients who underwent surgery between April 2011 and March 2022 at the three university hospitals for ROP (cases) and cervical spondylotic myelopathy (as age, sex, and institution matched controls). The two groups were compared for different parameters on cervical dynamic radiographs, MRI, and CT.

Results.

The ROP group consisted of 42 patients, and the control group comprised 168 patients. C2–C7 range of motion was significantly smaller in the ROP group (25.8 ± 2.6°) compared with the control group (33.0 ± 1.0°). C2–C7 sagittal vertical axis was significantly larger in the ROP group than the control group (39.3 ± 3.6 vs. 32.2 ± 1.3 mm). MRI and CT assessment showed progressive degeneration at all intervertebral levels in the ROP group. A significant positive correlation was observed between the thickness of the soft tissue posterior to the dental process and the atlantodental interval in the flexion position (r = 0.501).

Conclusions.

The development of ROP was associated with degeneration of facet joints and intervertebral disks in the middle and lower cervical spine. Our findings suggest that decreased mobility of the middle and lower cervical spine may cause instability in the upper cervical spine, leading to the formation of ROP.
Profiles of Autistic Youth with and Without Co-occurring Behavioral Health and Neurodevelopmental Disorders: A Latent Class Analysis
Authors: Patel Khusbu , Fogler Jason , Sideridis Georgios , Soares Neelkamal
Published: January 2024

Objective:

Autism spectrum disorder (ASD) diagnosis relies on clinical observation and documentation, but the presence of comorbidities can affect diagnostic validity across clinicians and exacerbate access to timely care. This study used latent class analysis to optimize subgroup identification based on functional level and associated comorbidities using the Behavior Assessment System for Children, Third Edition (BASC-3), and Vineland Adaptive Behavior Scales, Third Edition (Vineland-3), in a pediatric population referred for autism evaluation.

Methods:

This retrospective study reviewed clinical data extracted over a 3-year period (2018–2021). A latent class analysis was used to explore the presence of latent groups guided by the likelihood ratio test and fit indices. Additional analyses contrasted ASD and non-ASD groups on the BASC-3 and Vineland-3 variables.

Results:

There were 191 included participants (mean age 65.9 months, 76.4% male), of whom over half (60.7%) had an ASD diagnosis. Using 185 cases, the exploratory latent class analysis showed the emergence of 4 distinct subgroups. Composition of classes varied on ASD diagnosis, neurodevelopmental difficulties, behavioral health concerns, and intellectual disability. When contrasting ASD and non-ASD groups, significant between-group differences were observed across Vineland-3 variables and BASC-3 adaptive skills subscales indicating poorer social and adaptive functioning.

Conclusion:

Latent class analysis of commonly used behavioral and adaptive measures can help distinguish between subgroups of pediatric patients referred for ASD evaluations and assist in triage of cases based on severity.
Visualizing External Validity: Graphical Displays to Inform the Extension of Treatment Effects from Trials to Clinical Practice
Authors: Lund Jennifer L. , Webster-Clark Michael A. , Westreich Daniel , Sanoff Hanna K. , Robert Nicholas , Frytak Jennifer R. , Boyd Marley , Shmuel Shahar , Stürmer Til , Keil Alexander P.
Published: January 2024

Background:

In the presence of effect measure modification, estimates of treatment effects from randomized controlled trials may not be valid in clinical practice settings. The development and application of quantitative approaches for extending treatment effects from trials to clinical practice settings is an active area of research.

Methods:

In this article, we provide researchers with a practical roadmap and four visualizations to assist in variable selection for models to extend treatment effects observed in trials to clinical practice settings and to assess model specification and performance. We apply this roadmap and visualizations to an example extending the effects of adjuvant chemotherapy (5-fluorouracil vs. plus oxaliplatin) for colon cancer from a trial population to a population of individuals treated in community oncology practices in the United States.

Results:

The first visualization screens for potential effect measure modifiers to include in models extending trial treatment effects to clinical practice populations. The second visualization displays a measure of covariate overlap between the clinical practice populations and the trial population. The third and fourth visualizations highlight considerations for model specification and influential observations. The conceptual roadmap describes how the output from the visualizations helps interrogate the assumptions required to extend treatment effects from trials to target populations.

Conclusions:

The roadmap and visualizations can inform practical decisions required for quantitatively extending treatment effects from trials to clinical practice settings.
Differential Participation, a Potential Cause of Spurious Associations in Observational Cohorts in Environmental Epidemiology
Authors: Chen Chen , Chen Hong , Kaufman Jay S. , Benmarhnia Tarik
Published: January 2024

Differential participation in observational cohorts may lead to biased or even reversed estimates. In this article, we describe the potential for differential participation in cohorts studying the etiologic effects of long-term environmental exposures. Such cohorts are prone to differential participation because only those who survived until the start of follow-up and were healthy enough before enrollment will participate, and many environmental exposures are prevalent in the target population and connected to participation via factors such as geography or frailty. The relatively modest effect sizes of most environmental exposures also make any bias induced by differential participation particularly important to understand and account for. We discuss key points to consider for evaluating differential participation and use causal graphs to describe two example mechanisms through which differential participation can occur in health studies of long-term environmental exposures. We use a real-life example, the Canadian Community Health Survey cohort, to illustrate the non-negligible bias due to differential participation. We also demonstrate that implementing a simple washout period may reduce the bias and recover more valid results if the effect of interest is constant over time. Furthermore, we implement simulation scenarios to confirm the plausibility of the two mechanisms causing bias and the utility of the washout method. Since the existence of differential participation can be difficult to diagnose with traditional analytical approaches that calculate a summary effect estimate, we encourage researchers to systematically investigate the presence of time-varying effect estimates and potential spurious patterns (especially in initial periods in the setting of differential participation).
Use of Biodegradeable Temporizing Matrix Dermal Template for Reconstruction of Upper Extremity Soft Tissue Defects with Associated Tendon Injury
Authors: Jou Christopher , Chepla Kyle J.
Published: January 2024

In cases of complex upper extremity soft tissue defects with exposed bone or tendon, the surgeon needs to consider both restoration of stable soft tissue coverage and functional outcomes, which requires early motion and a wound bed suitable for tendon gliding. Often, local, regional, or free flaps are necessary; however, good outcomes have also been reported after staged reconstruction with a dermal template and split-thickness skin grafting. To our knowledge, staged reconstruction with a dermal template has not been described for soft tissue defects with an associated underlying tendon injury requiring tenorrhaphy. We have previously reported our experience with a synthetic dermal template [Novosorb BTM (Biodegradable Temporizing Matrix), Polynovo North America LLC. Carlsbad, Calif.] for the reconstruction of complex upper extremity defects with exposed tendon and showed that it consistently and reliably integrates even when these patients were treated with an early, active therapy protocol. As a result of these findings, we hypothesized that BTM could potentially be used over a tendon repair site without compromising functional outcomes. Here, we report on clinical outcomes for two patients with upper extremity injury where BTM was applied directly over a tendon repair or transfer site and resulted in stable soft tissue coverage with excellent tendon gliding. These early results show that this approach might be considered as an alternative to autologous tissue reconstruction in these patients and could reduce donor site morbidity associated with flap harvest.
Safety and Efficacy of Mucograft Porcine Collagen Bioengineered Acellular Dermal Matrix as a Spacer Graft in Lower Eyelid Elevation Surgery
Authors: Parker Richard , Kaushik Megha , Bansal Oshin , Ezra Daniel G.
Published: January 2024

Background:

Recent regulatory changes have limited the access to a widely used commercially available bioengineered acellular dermal matrix (BADM) product as a spacer graft in the surgical correction of lower eyelid retraction. We report our off-label usage of Mucograft, a porcine BADM, as an alternative BADM.

Methods:

A retrospective review was conducted of patients undergoing bilateral lower lid surgery with Mucograft (12 eyes) at a single institution.

Results:

For the six patients, there was a mean lower lid elevation of 1.93 mm, without any serious complications. There was greater elevation of the lower lid position for the Mucograft group compared with four septo-retractor control patients (1.93 versus 0.94mm, P = 0.008).

Conclusion:

Mucograft performed satisfactorily, and further investigation is warranted regarding its longer-term safety and efficacy.
Mesenchymal Stem Cell–Laden In Situ–Forming Hydrogel for Preventing Corneal Stromal Opacity
Authors: Liu Yinan , Hong Jing
Published: January 2024

Purpose:

The aims of this study were to construct a mesenchymal stem cell (MSC)–laden in situ–forming hydrogel and study its effects on preventing corneal stromal opacity.

Methods:

The native gellan gum was modified by high temperature and pressure, and the rabbit bone marrow MSCs were encapsulated before adding Ca2+ to initiate cross-linking. The effects of the hydrogel on 3D culture and gene expression of the rabbit bone marrow MSCs were observed in vitro. Then, the MSC–hydrogel was used to repair corneal stromal injury in New Zealand white rabbits within 28 days postoperation.

Results:

The short-chain gellan gum solution has a very low viscosity (<0.1 Pa·s) that is ideal for encapsulating cells. Moreover, mRNA expressions of 3D-cultured MSCs coding for corneal stromal components (decorin, lumican, and keratocan) were upregulated (by 127.8, 165.5, and 25.4 times, respectively) (P < 0.05) on day 21 in vitro and were verified by Western blotting results. For the in vivo study, the corneal densitometry of the experimental group was (20.73 ± 1.85) grayscale units which was lower than the other groups (P < 0.05). The MSC–hydrogel downregulated mRNA expression coding for fibrosis markers (α-smooth muscle actin, vimentin, collagen type 5-α1, and collagen type 1-α1) in the rabbit corneal stroma. Furthermore, some of the 5-ethynyl-2’-deoxyuridine (EdU)-labeled MSCs integrated into the upper corneal stroma and expressed keratocyte-specific antigens on day 28 postoperation.

Conclusions:

The short-chain gellan gum allows MSCs to slowly release to the corneal stromal defect and prevent corneal stromal opacity. Some of the implanted MSCs can integrate into the corneal stroma and differentiate into keratocytes.
Keratometry Changes Between Year One to Seven After Corneal Cross-Linking in Patients With Keratoconus
Authors: Neuhann Lukas , Vogel Diana , Hall Jonathan , Dreyhaupt Jens , Werner Jens Ulrich , Garip-Kuebler Aylin , Enders Christian
Published: January 2024

Purpose:

We evaluated the timing at and extent to which midterm to long-term keratometric changes can occur in year 1 to 7 after corneal collagen cross-linking (CXL) in patients with keratoconus.

Methods:

We conducted a subgroup analysis of a retrospective cohort study of all consecutive patients who underwent CXL at our cornea center between 2007 and 2011. The inclusion criteria comprised CXL according to the Dresden protocol and a full set of keratometry parameters collected by Scheimpflug tomography preoperatively and at year 1, 3, 5, and 7 after CXL. In addition, best-corrected visual acuity was evaluated.

Results:

Sixty-three eyes of 47 patients were enrolled. Mean age was 25.46 years ±7.39 years (80.9% male patients). All relevant keratometric parameters showed significant improvement at year 1 after CXL (except for posterior astigmatism). According to mixed-effects model analysis, they all showed further significant change at different points in time between year 1, 3, 5, and 7 (except for K1). In addition, best-corrected visual acuity improved statistically significant between year 1, 3, 5, and 7. Suspected disease progression was noted in 22.2% of patients, mostly between year 1 and 3 after CXL.

Conclusions:

After initial improvement 1 year after CXL, keratometric and functional parameters were stable until year 5 after CXL in most cases; further improvement can take place even after up to 7 years post-CXL. By contrast, in case of disease progression, changes seem to occur already between year 1 and 3 after CXL.
An Exploration of Support for Clinical Education Partners
Authors: George Deborah , Gallivan Sean P. , Both Amy , Clark Hawkins Carrie , Bayliss Jamie , Crompton Julie , English Lynn , Lairson Alexia , Quinn Beth , Renner Trisha , Reynolds Emily
Published: January 2024

Introduction.

Effective academic–clinical partnerships require a greater understanding of how academic programs can best support clinical education (CE) faculty. This study aimed to determine resources and support that clinical partners need.

Review of Literature.

As the number of physical therapist (PT) programs, cohort sizes, and CE weeks have risen, so has demand for CE sites. Conversely, staffing reductions, increased administrative duties, and rising productivity expectations have decreased the time available for clinical instruction. To promote a successful CE experience, there must be a renewed understanding of CE faculty needs.

Subjects.

Clinical education faculty affiliated with any of the 8 contributing programs from the Ohio–Kentucky Consortium participated in survey research (n = 24) and subsequent interview (n = 4) and focus group (n = 6) research.

Methods.

Constructivist grounded theory design was used to explore the needs of CE faculty. Academic and clinical partners developed the initial survey and used survey results to establish interview questions. The investigators iteratively assessed data saturation and clarity of results of coded survey, interview, and focus group data to determine whether the study's aims of identifying CE faculty needs had been met.

Results.

The aggregated results yielded 5 main themes of Director of Clinical Education support for CE faculty needs: student readiness for CE experience; effective academic–clinical partner communication; collaborative management of exceptional students; judicious standardization of CE processes; and provision of CE faculty development resources.

Discussion and Conclusion.

Clinical education faculty have noted challenges that affect their ability to mentor students. They want academic programs to be more collaborative and proactive with communication, resources, and support. Future research should address aids and barriers to proactive communication, resource provision, and academic–clinical partner collaboration.
A Comparative Analysis of Physical Therapy Anatomical Knowledge and Retention: Human Donor Dissection Versus Virtual Laboratory
Authors: Helms Jeb T. , Johnson Kristen M. , Ball Jamie L.
Published: January 2024

Introduction.

Despite a long history of using human donor dissection (HDD) for physical therapy (PT) anatomy education, there are no PT guidelines that require HDD. The purpose of this quantitative causal-comparative study was to determine if Doctor of Physical Therapy students who used HDD had different grades both within anatomy and within courses that require retention and application of anatomical knowledge (kinesiology and a foundational musculoskeletal course) compared with those who used virtual 3-dimensional anatomical software (VAS).

Review of Literature.

Numerous factors affect the decision to use HDD within PT anatomy, and few PT studies have compared the effectiveness of VAS to HDD.

Subjects.

All students who took anatomy in an entry-level PT program from 2018 to 2021 (232 total students, 115 who used HDD in 2018–2019 and 117 who used VAS in 2020–2021).

Methods.

Mann–Whitney tests were used to compare anatomy grades (course, written examination, and practical examination) and future grades in kinesiology and a foundational musculoskeletal course for students who used HDD or VAS.

Results.

Physical therapy students who used VAS had statistically significant higher anatomy course grades (VAS 93.81% ± 4.99% to HDD 92.20% ± 4.53%) and higher practical examination grades (VAS 97.43% ± 2.91% to HDD 93.55% ± 4.39%) compared with those who used HDD. However, there were no significant differences between groups on written anatomy examinations (VAS 89.42% ± 7.21% to HDD 90.40% ± 4.94%), kinesiology grades (VAS 91.86% ± 4.52% to HDD 92.80% ± 4.27%), or foundational musculoskeletal grades (VAS 89.50% ± 3.89% to HDD 89.77% ± 3.83%).

Discussion and Conclusion.

The causal-comparative study design prevents concluding that PT student grade differences were due exclusively to either anatomy laboratory method. It does provide preliminary evidence that the PT anatomy laboratory method did not practically affect anatomy performance or long-term application of anatomy knowledge in future coursework.
Recent advances in cytomegalovirus infection management in solid organ transplant recipients
Authors: Grossi Paolo Antonio , Peghin Maddalena
Published: January 2024

Purpose of review

Human cytomegalovirus (CMV) continues to be the most important infectious complication following solid organ transplantation (SOT).

Recent findings

Universal prophylaxis and preemptive therapy are the most adopted strategies for prevention of CMV disease globally. Prophylaxis with valganciclovir is the most widely used approach to CMV prevention, however leukopenia and late onset CMV disease after discontinuation of prophylaxis requires new strategies to prevent this complication. The use of assays detecting CMV-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. Letermovir has been recently approved for prophylaxis in kidney transplant recipients. CMV-RNAemia used together with CMV-DNAemia in the viral surveillance of CMV infection provides accurate information on viral load kinetics, mostly in patients receiving letermovir prophylaxis/therapy. The development of refractory and resistant CMV infection remains a major challenge and a new treatment with maribavir is currently available. In the present paper we will review the most recent advances in prevention and treatment of CMV diseases in SOT recipients.

Recent findings, summarized in the present paper, may be useful to optimize prevention and treatment of CMV infection in SOT.
A Series of 8 Illicit Fentanyl Intoxication Deaths in Infants and Toddlers
Authors: Vincent Gregory A. , Nunez Jacqueline , Gill James R.
Published: January 2024

We report 8 children younger than 2 years who died from acute illicit fentanyl intoxications in Connecticut between 2020 and 2022.

The Connecticut Office of the Chief Medical Examiner (CT OCME) investigates all unexpected, violent, and suspicious deaths in Connecticut. The CT OCME's electronic database was searched for fentanyl deaths by age. All underwent autopsies and toxicology testing.

The ages ranged from 28 days to 2 years (mean age, 12 months). The causes of death involved acute fentanyl intoxications with 1 having xylazine, 1 having para-fluorofentanyl, and 1 having cocaine and morphine. All the manners of death were certified as homicide. The postmortem fentanyl blood concentrations ranged from 0.40 to 46 ng/mL. Most of the children were found unresponsive after being put to sleep. Three were co-sleeping with adults (2 in bed; 1 on a recliner). There was a known history of parental/caregiver drug abuse in 7 of 8 of the fatalities.

We summarize the key investigative, autopsy, and toxicological findings. As illicit fentanyl use increases, there is a potential for infant exposure and death. The investigation and certification of these deaths and the role of intentional administration versus inadvertent exposure due to caregiver neglect in the context of the certification of the manner of death are described.
Forensic Analysis of the Abraham Lincoln Assassination: An On-Site Study of the Presidential Box at Ford's Theatre
Authors: Pappas Theodore N. , Swanson Sven , Baden Michael M.
Published: January 2024

On April 14, 1865, Abraham Lincoln was assassinated while watching a play from the Presidential Box at Ford's Theatre in Washington, DC. There is still controversy concerning the findings of Lincoln's autopsy. The physicians that attended the autopsy documented that the bullet entered the left occipital region of the brain, but opinions differ as to the path the bullet took through the brain. The official autopsy report documented that the bullet traveled through the left brain and did not cross the midline. Others who watched the autopsy claimed that the bullet entered on the left side of the president's brain, crossed the midline, and ended up just above the orbit on the right. In this manuscript, we reviewed all of the statements of the witnesses to the assassination in an effort to reconstruct the approach that John Wilkes Booth, the assassin, took through the Presidential Box as he approached the president. In addition, we conducted an on-site analysis of the shape and dimensions of the Presidential Box at Ford's Theatre to support the approach that Booth took. Based on this forensic analysis, we provide supportive evidence that the findings of the official autopsy report are accurate; that is, the bullet that entered the president's left brain stayed on the left and did not cross the midline.