bluuebunny/crossref_metadata_2025 huggingface dataset:
The five pillars of computational reproducibility: bioinformatics and beyond
Authors: Ziemann Mark , Poulain Pierre , Bora Anusuiya
Published: October 2023

Computational reproducibility is a simple premise in theory, but is difficult to achieve in practice. Building upon past efforts and proposals to maximize reproducibility and rigor in bioinformatics, we present a framework called the five pillars of reproducible computational research. These include (1) literate programming, (2) code version control and sharing, (3) compute environment control, (4) persistent data sharing and (5) documentation. These practices will ensure that computational research work can be reproduced quickly and easily, long into the future. This guide is designed for bioinformatics data analysts and bioinformaticians in training, but should be relevant to other domains of study.
Surfaces: a software to quantify and visualize interactions within and between proteins and ligands
Authors: Teruel Natália , Borges Vinicius Magalhães , Najmanovich Rafael
Published: October 2023

Computational methods for the quantification and visualization of the relative contribution of molecular interactions to the stability of biomolecular structures and complexes are fundamental to understand, modulate and engineer biological processes. Here, we present Surfaces, an easy to use, fast and customizable software for quantification and visualization of molecular interactions based on the calculation of surface areas in contact. Surfaces calculations shows equivalent or better correlations with experimental data as computationally expensive methods based on molecular dynamics.

Availability and implementation

All scripts are available at https://github.com/NRGLab/Surfaces. Surface’s documentation is available at https://surfaces-tutorial.readthedocs.io/en/latest/index.html.
Risk of Cancer in Patients With Crohn’s Disease 30 Years After Diagnosis (the IBSEN Study)
Authors: Follin-Arbelet Benoit , Cvancarova Småstuen Milada , Hovde Øistein , Jelsness-Jørgensen Lars-Petter , Moum Bjørn
Published: October 2023

Background

Patients with Crohn’s disease (CD) are most often diagnosed as young adults; therefore, long-term studies are needed to assess the risk of cancer over their lifetime. Thus, the aims of the present study were to determine the risk of cancer in a Norwegian population-based cohort (the Inflammatory Bowel South Eastern Norway [IBSEN] study), 30 years after diagnosis, and to assess whether patients with CD were at an increased risk of specific cancer types.

Methods

The IBSEN cohort prospectively included all incident patients diagnosed between 1990 and 1993. Data on cancer incidence were obtained from the Cancer Registry of Norway. Overall and cancer-specific hazard ratios (HRs) for CD patients compared with age- and sex-matched controls were modeled using Cox regression. Standardized incidence ratios (SIRs) were estimated compared to the general population.

Results

In total, the cohort included 237 patients with CD, and 36 of them were diagnosed with cancer. Compared to the general Norwegian population, patients with CD had an increased overall risk of cancer (HR = 1.56, 95% CI: 1.06–2.28), particularly male patients (HR = 1.85, 95% CI: 1.08–3.16). The incidence of lung cancer and nonmelanoma skin cancer was increased; however, the difference was not statistically significant (SIR = 2.29, 95% CI: 0.92–4.27 and SIR = 2.45, 95% CI: 0.67–5.37, respectively).

Conclusions

After 30 years of follow-up, the risk of all cancers in patients with CD was increased compared to the general population.
Misclassification of females and males in cardiovascular magnetic resonance parametric mapping: the importance of sex-specific normal ranges for diagnosis of health vs. disease
Authors: Thomas Katharine E , Lukaschuk Elena , Shanmuganathan Mayooran , Kitt Jamie A , Popescu Iulia A , Neubauer Stefan , Piechnik Stefan K , Ferreira Vanessa M
Published: October 2023

Aims

Cardiovascular magnetic resonance parametric mapping enables non-invasive quantitative myocardial tissue characterization. Human myocardium has normal ranges of T1 and T2 values, deviation from which may indicate disease or change in physiology. Normal myocardial T1 and T2 values are affected by biological sex. Consequently, normal ranges created with insufficient numbers of each sex may result in sampling biases, misclassification of healthy values vs. disease, and even misdiagnoses. In this study, we investigated the impact of using male normal ranges for classifying female cases as normal or abnormal (and vice versa).

Methods and results

One hundred and forty-two healthy volunteers (male and female) were scanned on two Siemens 3T MR systems, providing averaged global myocardial T1 and T2 values on a per-subject basis. The Monte Carlo method was used to generate simulated normal ranges from these values to estimate the statistical accuracy of classifying healthy female or male cases correctly as ‘normal’ when using sex-specific vs. mixed-sex normal ranges. The normal male and female T1- and T2-mapping values were significantly different by sex, after adjusting for age and heart rate.

Conclusion

Using 15 healthy volunteers who are not sex specific to establish a normal range resulted in a typical misclassification of up to 36% of healthy females and 37% of healthy males as having abnormal T1 values and up to 16% of healthy females and 12% of healthy males as having abnormal T2 values. This paper highlights the potential adverse impact on diagnostic accuracy that can occur when local normal ranges contain insufficient numbers of both sexes. Sex-specific reference ranges should thus be routinely adopted in clinical practice.
Instantaneous detection of acute myocardial infarction and ischaemia from a single carotid pressure waveform in rats
Authors: Alavi Rashid , Dai Wangde , Matthews Ray V , Kloner Robert A , Pahlevan Niema M
Published: October 2023

Aims

Myocardial infarction (MI) is one of the leading causes of death worldwide. It is well accepted that early diagnosis followed by early reperfusion therapy significantly increases the MI survival. Diagnosis of acute MI is traditionally based on the presence of chest pain and electrocardiogram (ECG) criteria. However, around 50% of the MIs are without chest pain, and ECG is neither completely specific nor definitive. Therefore, there is an unmet need for methods that allow detection of acute MI or ischaemia without using ECG. Our hypothesis is that a hybrid physics-based machine learning (ML) method can detect the occurrence of acute MI or ischaemia from a single carotid pressure waveform.

Methods and results

We used a standard occlusion/reperfusion rat model. Physics-based ML classifiers were developed using intrinsic frequency parameters extracted from carotid pressure waveforms. ML models were trained, validated, and generalized using data from 32 rats. The final ML models were tested on an external stratified blind dataset from additional 13 rats. When tested on blind data, the best ML model showed specificity = 0.92 and sensitivity = 0.92 for detecting acute MI. The best model’s specificity and sensitivity for ischaemia detection were 0.85 and 0.92, respectively.

Conclusion

We demonstrated that a hybrid physics-based ML approach can detect the occurrence of acute MI and ischaemia from carotid pressure waveform in rats. Since carotid pressure waveforms can be measured non-invasively, this proof-of-concept pre-clinical study can potentially be expanded in future studies for non-invasive detection of MI or myocardial ischaemia.
Soluble urokinase Plasminogen Activator Receptor (suPAR) mediates the effect of a lower education level on adverse outcomes in patients with coronary artery disease
Authors: Füller David , Liu Chang , Ko Yi-An , Alkhoder Ayman A , Desai Shivang R , Almuwaqqat Zakaria , Patel Shivani A , Ejaz Kiran , Kauser Tanveer , Martini Mohamed Afif , Alvi Zain , Mehta Puja K , Sperling Laurence S , Quyyumi Arshed A
Published: October 2023

Aims

To investigate whether the adverse impact of lower educational attainment on mortality risk in patients with coronary artery disease (CAD) is mediated by the activation of inflammatory and immune pathways, estimated as elevated soluble urokinase plasminogen activator receptor levels.

Methods and results

In 3164 patients undergoing coronary angiography, we investigated multivariable associations between suPAR and educational attainment and assessed the relationship between a lower educational level (defined as a high-school degree or less as the highest educational qualification) and outcomes using Cox proportional hazard and Fine and Gray’s subdistribution competing risk models. The potential mediating effect through suPAR and high-sensitivity C-reactive protein (hs-CRP) was assessed using mediation analysis. A total of 1814 patients (57.3%) had achieved a higher (≥college) education level and 1350 patients (42.7%) a lower (≤high school) education level. Soluble urokinase plasminogen activator receptor levels were 9.0% [95% confidence interval (CI) 6.3–11.8, P ≤ 0.0001] higher in patients with lower educational qualifications than in those with higher educational qualifications after covariate adjustment. Lower educational attainment was associated with a higher risk of cardiovascular death after adjustment for demographic, clinical, and behavioural covariates, including CAD severity and heart failure history, medication use, and hs-CRP levels [hazard ratio 1.26 (95% CI 1.02–1.55, P = 0.03)]. However, after adjustment for suPAR levels, the effect of a lower educational level on cardiovascular death became insignificant. Values were similar for all-cause death. Soluble urokinase plasminogen activator receptor levels mediated 49% and hs-CRP levels 17% of the cardiovascular death risk attributable to lower educational attainment.

Conclusion

Circulating suPAR levels importantly mediate the effects of lower educational attainment on mortality, indicating the importance of systemic inflammation and immune dysregulation as biologic mediators of adverse social determinants of health.
The Effects of Midlife Acute and Chronic Stressors on Black–White Differences in Cognitive Decline
Authors: Mitchell Uchechi A , Shaw Benjamin A , Torres Jacqueline M , Brown Lauren L , Barnes Lisa L
Published: October 2023

Objectives

Midlife stressors may be particularly consequential for cognitive performance and disparities in cognitive decline. This study examined Black–White differences in trajectories of cognition among middle-aged adults and the effects of acute and chronic stressors on these trajectories.

Methods

Data come from 4,011 cognitively healthy individuals aged 51–64 (620 Black and 3,391 White) who participated in the 2006–2018 waves of the Health and Retirement Study. Stressors included a count of recent life events and measures of financial strain and everyday discrimination. Global cognition was assessed using a modified version of the Telephone Interview for Cognitive Status. Linear mixed models with random slopes and intercepts assessed change in cognition over time. Race-by-time, race-by-stressor, time-by-stressor, and race-by-stressor-by-time interactions were assessed as were quadratic terms for time and each stressor.

Results

After adjusting for sociodemographic, health behaviors, and health-related factors, Black respondents had lower initial cognitive performance scores (b = −1.75, p < .001) but experienced earlier but slower decline in cognitive performance over time (Black × Time2 interaction: b = 0.02, p < .01). Financial strain, discrimination, and recent life events each had distinct associations with cognitive performance but did not influence racial differences in levels of or change in cognition over time.

Discussion

Middle-aged Black adults have lower initial cognition levels and experience earlier but less accelerated cognitive decline compared to White middle-aged adults. Midlife acute and chronic stressors influence baseline cognition but do so in different ways. Future research should examine the influence of other stressors on racial differences in cognitive decline at other points in the life course.
Social Vulnerability and the Prevalence of Opioid Use Disorder Among Older Medicare Beneficiaries in U.S. Counties
Authors: Yang Tse-Chuan , Kim Seulki , Matthews Stephen A , Shoff Carla
Published: October 2023

Objectives

Recent research has investigated the factors associated with the prevalence of opioid use disorder (OUD) among older adults (65+), which has rapidly increased in the past decade. However, little is known about the relationship between social vulnerability and the prevalence of OUD, and even less is about whether the correlates of the prevalence of OUD vary across the social vulnerability spectrum. This study aims to fill these gaps.

Methods

We assemble a county-level data set in the contiguous United States (U.S.) by merging 2021 Medicare claims with the CDC’s social vulnerability index and other covariates. Using the total number of older beneficiaries with OUD as the dependent variable and the total number of older beneficiaries as the offset, we implement a series of nested negative binomial regression models and then analyze by social vulnerability quartiles.

Results

Higher social vulnerability is associated with higher prevalence of OUD in U.S. counties. This association cannot be fully explained by the differences in the characteristics of older Medicare beneficiaries (e.g., average age) and/or other social conditions (e.g., social capital) across counties. Moreover, the group comparison tests indicate correlates of the prevalence of OUD vary across social vulnerability quartiles in that the average number of mental disorders is positively related to OUD prevalence in the least and the most vulnerable counties and social capital benefits the less vulnerable counties.

Discussion

A perspective drawing upon contextual factors, especially social vulnerability, may be more effective in reducing OUD among older adults in U.S. counties than a one-size-fits-all approach.
Generative AI and Lexicography: The Current State of the Art Using ChatGPT
Authors: de Schryver Gilles-Maurice
Published: October 2023

In this article, all ten papers and talks that have been devoted to the use of ChatGPT in lexicography so far are critically analysed, their results tabulated and cross-compared, from which the leading trends are determined. Extrapolating from the trendlines, a single short but robust new prompt is fine-tuned with which articles from different word classes are generated fully-automatically for a dictionary which compares favourably to the best practice in dictionary compilation. The conclusion is that a new age, that of the successful application of generative AI in lexicography, has dawned.
In vitro activity of cefiderocol against Pseudomonas aeruginosa demonstrating evolved resistance to novel β-lactam/β-lactamase inhibitors
Authors: Shields Ryan K , Kline Ellen G , Squires Kevin M , Van Tyne Daria , Doi Yohei
Published: October 2023

Background

Cefiderocol demonstrates excellent activity against MDR Pseudomonas aeruginosa; however, the activity against isolates from patients previously treated with β-lactam agents is unknown. We aimed to determine the activity of cefiderocol against P. aeruginosa collected before and after treatment with traditional β-lactams and new β-lactam/β-lactamase inhibitors.

Methods

Cefiderocol MICs were determined in triplicate in iron-depleted cation-adjusted Mueller–Hinton broth and compared with β-lactam MICs tested by standard methods. All isolates underwent WGS analysis to identify mutations associated with resistance.

Results

One hundred and seventy-eight P. aeruginosa isolates were evaluated; 48% (86/178) were non-susceptible to ceftazidime/avibactam, ceftolozane/tazobactam and/or imipenem/relebactam. The cefiderocol MIC50 and MIC90 were 0.12 and 1 mg/L, respectively. Median cefiderocol MICs did not vary against isolates classified as MDR, XDR, or those non-susceptible to ceftazidime/avibactam, ceftolozane/tazobactam and/or imipenem/relebactam when compared with non-MDR isolates. Against isolates collected from patients previously treated with ceftolozane/tazobactam, cefiderocol MICs were increased 4-fold compared with baseline. Cross-resistance to cefiderocol was identified in 21% (3/14) of patients who developed treatment-emergent resistance to ceftolozane/tazobactam. Overall, 6% (11/178) of isolates demonstrated cefiderocol MICs ≥2 mg/L, which were disproportionately collected from patients previously treated with ceftolozane/tazobactam (73%; 8/11). Isolates with reduced cefiderocol susceptibility harboured mutations in ampC, tonB-dependent receptors, the response regulator pirR and ftsI.

Conclusions

Cefiderocol demonstrates excellent in vitro activity against P. aeruginosa isolates exposed to other novel β-lactam agents; however, some exceptions were identified. Cross-resistance between cefiderocol and ceftolozane/tazobactam was evident, but not with ceftazidime/avibactam or imipenem/relebactam. Reduced cefiderocol susceptibility was mediated by mutations in ampC and tonB-dependent receptors.
Endoscopic Retrograde Cholangiopancreatography Under General Anesthesia Compared to Conscious Sedation Study
Authors: Greaves Grant , Harding Kaitlyn G , Parker Brent , Nguyen Vu C , Ahmed Azim , Yee Belinda , Perren Joël , Norman Mathew , Grey Morgan , Perini Rafael , Jowhari Fahd , Bak Adrian
Published: October 2023

Background

Endoscopic retrograde cholangiopancreatography (ERCP) is used to diagnose and treat pancreatic and biliary disease. The current standard is to conduct ERCP under conscious sedation (CS). Patient movement and agitation during ERCP under CS can result in procedure failure and complications. Aiming to reduce procedure failure rates and complications, Kelowna General Hospital (KGH) in British Columbia, Canada transitioned to performing ERCP under general anesthesia (GA) as the practice standard.

Objective

To determine if conducting ERCP under GA compared to CS decreases procedure complications, particularly post-ERCP pancreatitis (PEP).

Methods

The charts of 2,198 patients who underwent ERCP at KGH between 2015 and 2020 were reviewed. Before September 17, 2017, ERCP was performed under CS (n = 1,316). Afterwards, ERCP was conducted under GA (n = 882). Demographic, clinical, and procedural data were extracted. The data were analyzed using univariate and multivariate statistical analysis.

Results

Procedure failure rates (CS = 9 percent, GA = 3 percent, P < 0.001) decreased in the GA cohort after adjusting for age, sex, and co-morbidities. Thirty-day mortality, intensive care unit (ICU) transfer, returns post-discharge, PEP, and cholangitis rates were similar between cohorts.

Conclusion

Performing ERCP under GA compared to CS resulted in an increase in procedural success rates. Other complication rates were similar between groups.
Leading medical laboratory professionals toward change readiness: a correlational study
Authors: Waraksa-Deutsch Taryn L
Published: October 2023

Background

To remain effective in the dynamic health care landscape, the laboratory must embrace the continuous improvement mindset to support a culture of change, and leadership must facilitate the change process, mitigating perceived barriers of change readiness in followers.

Methods

This quantitative study was designed to determine whether there is an association between leadership style (Multifactor Leadership Questionnaire [MLQ]) and change readiness (3-component model [TCM] commitment to change/Employee Commitment Survey, and whether leadership style predicts change readiness. Laboratory professionals (n = 718) were recruited through national societies to complete a combined MLQ-TCM survey instrument. Multivariate analysis of variance, Pearson correlations, and multiple regression analyses were performed.

Results

A significant correlation between leadership style and change readiness (transformational leadership [TL] and affective commitment to change, r(716) = .12, P = .002; passive-avoidant behavior and continuance commitment to change, r(716) = .25, P < .001) and between leadership style and leadership outcomes (TL and effectiveness, r(716) = .90, P < .001) was identified. Transformational leadership was a significant predictor of change readiness (β = .17, P < .05).

Conclusion

It is recommended that laboratory leaders use transformational leadership or situational leadership to improve followers’ affective commitment to change and reduce followers’ continuance commitment to change, thus improving commitment to continuous improvement. Leaders should also limit passive-avoidant behavior.
Discovery of an extremely intermittent periodic radio source
Authors: Surnis M P , Rajwade K M , Stappers B W , Younes G , Bezuidenhout M C , Caleb M , Driessen L N , Jankowski F , Malenta M , Morello V , Sanidas S , Barr E , Kramer M , Fender R , Woudt P
Published: October 2023

We report the serendipitous discovery of an extremely intermittent radio pulsar, PSR J1710−3452, with a relatively long spin period of 10.4 s. The object was discovered through the detection of 97 bright radio pulses in only one out of 66 epochs of observations spanning almost three years. The bright pulses have allowed the source to be localized to a precision of 0.5 arcsec through radio imaging. We observed the source location with the Swift X-ray telescope but did not detect any significant X-ray emission. We did not identify any high-energy bursts or multifrequency counterparts for this object. The solitary epoch of detection hinders the calculation of the surface magnetic field strength, but the long period and the microstructure in the single-pulses resembles the emission of radio-loud magnetars. If this is indeed a magnetar, it is located at a relatively high Galactic latitude (2.9°), making it potentially one of the oldest and the most intermittent magnetars known in the Galaxy. The very short activity window of this object is unique and may point towards a yet undetected population of long period, highly transient radio emitting neutron stars.
Role of hypofractionated stereotactic radiotherapy for primary optic nerve sheath meningioma
Authors: Koç İrem , Yüce Sarı Sezin , Yazıcı Gözde , Kapucu Yasemin , Kıratlı Hayyam , Zorlu Faruk
Published: October 2023

Background

Optic nerve sheath meningiomas (ONSM) are rare tumors potentially causing visual deficits. This study aims to report the anatomic and visual outcomes of patients with primary ONSM treated with hypofractionated stereotactic radiotherapy (HF-SRT).

Methods

Data of 36 patients treated with HF-SRT between 2008 and 2019 were retrospectively collected. The clinical target volume (CTV) was equal to the gross tumor volume and a 2 mm was added for the planning target volume. All responses other than progression were accepted as local control (LC). The VA grading was performed under 3 groups to provide an even distribution; 20/400 or worse, 20/40-20/400, and 20/40 or better.

Results

Median HF-SRT dose was 25 Gy and the median CTV was 1.94 cc. After a median of 106 months of follow-up, the tumor regressed in 23 (64%), was stable in 9 (25%), and progressed in 4 (11%) eyes. The overall rate of LC was 89% with 2-, 5-, 10-, and 15-year rate of 100%, 94%, 84%, and 84%, respectively. Treatment-related late toxicity rate was 11%. The VA was stable in 27 (75%) eyes, improved in 5 (14%) eyes, and worsened in 4 (11%) eyes, respectively, after HF-SRT. Female gender was the only independent predictor of an improved VA.

Conclusions

Hypofractionated stereotactic radiotherapy is a safe and satisfactory treatment option for primary ONSM without severe toxicity. It may be advisable to commence treatment before an established visual deficit of 20/400 or worse occurs, to make the most of the functional benefit.
The unusual suspects: are well-meaning environmental stakeholders and institutions undercutting the contributions that companies can make to fighting climate change?
Authors: Ballentine Roger S
Published: October 2023

There is broad consensus that a significant majority of the capital needed to fund a low carbon transition consistent with science-based decarbonization timelines will have to come from the private sector. While still inadequate, the past decade-plus has seen a nonlinear increase in corporate capital spend in pursuit of voluntary climate goals. In the absence of significant regulatory mandates or meaningful carbon pricing, how this ‘corporate climate spend’ is directed is influenced—if not largely directed—by an array of emissions accounting rules, third-party defined leadership metrics and methodologies. This ‘rules and reward ecosystem’ is largely the design of environmental advocates, academics, and other aligned stakeholders and philanthropists. Sitting at the heart of this ecosystem is the Greenhouse Gas Protocol—a purported accounting framework that underpins how companies can undertake climate-based interventions and record progress. Launched by environmental stakeholders in 1998, the Protocol has since become the de facto rulebook used by highly influential third-party corporate leadership and target setting organizations, sustainability rating and evaluation entities serving the investment community, and is being incorporated into emerging mandatory corporate disclosure programs. Ironically, given its architects, today the rules and reward ecosystem results in significant mis-allocations and constraints on corporate climate spend and is reducing the potential climate change-mitigating impact of crucial private capital. This paper explores the flaws in incumbent greenhouse gas accounting and leadership program rules and proposes pathways for change that would better optimize the flow of private capital available and needed to address the climate crisis.
FLASHING: Project overview
Authors: Imai Hiroshi , Hamae Yuhki , Amada Kei , Nakashima Keisuke , Shum Ka-Yiu , Kasai Rina , Gómez José F , Uscanga Lucero , Tafoya Daniel , Orosz Gabor , Burns Ross A
Published: October 2023

This paper describes an overview of the FLASHING (Finest Legacy Acquisitions of SiO-/H2O-maser Ignitions by the Nobeyama Generation) project promoted using the 45 m telescope of Nobeyama Radio Observatory, which aims to intensively monitor H2O (at 22 GHz) and SiO (at 43 GHz) masers associated with so-called “water fountain” sources. Here we show scientific results based on the data taken in the first five seasons of FLASHING, from 2018 December to 2023 April. We show the evolution of the H2O maser spectra, discovering new spectral components that break the record of the jet’s top speed and/or systematic velocity drifts in the spectrum indicating acceleration or deceleration of the maser gas clumps. For the 43 GHz SiO maser emission, we newly detect it in one source and find that it is no longer present in another source. This implies that the jets from these water fountains can be accelerated or decelerated, and show how circumstellar envelopes are destroyed.
Socioeconomic vulnerability and differential impact of severe weather-induced power outages
Authors: Ganz Scott C , Duan Chenghao , Ji Chuanyi
Published: October 2023

In response to concerns about increasingly intense Atlantic hurricanes, new federal climate and environmental justice policies aim to mitigate the unequal impact of environmental disasters on economically and socially vulnerable communities. Recent research emphasizes that standard procedures for restoring power following extreme weather could be one significant contributor to these divergent outcomes. Our paper evaluates the hypothesis that more economically and socially vulnerable communities experience longer-duration power outages following hurricanes than less vulnerable communities do, conditional on the severity of the impact of the storm itself. Using data from eight major Atlantic hurricanes that made landfall between January 2017 and October 2020 and induced power outages for over 15 million customers in 588 counties in the Southeast, we demonstrate a significant relationship between socioeconomic vulnerability and the duration of time that elapses before power is restored for 95% of customers in a county. Specifically, a one-decile change in the socioeconomic status theme in the Social Vulnerability Index, a measure of vulnerability produced by the Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry, produces a 6.1% change in expected outage duration in a focal county. This is equivalent to a 170-min average change in the period of time prior to power restoration.
Ocean emission of microplastic
Authors: Shaw Daniel B , Li Qi , Nunes Janine K , Deike Luc
Published: October 2023

Microplastics are globally ubiquitous in marine environments, and their concentration is expected to continue rising at significant rates as a result of human activity. They present a major ecological problem with well-documented environmental harm. Sea spray from bubble bursting can transport salt and biological material from the ocean into the atmosphere, and there is a need to quantify the amount of microplastic that can be emitted from the ocean by this mechanism. We present a mechanistic study of bursting bubbles transporting microplastics. We demonstrate and quantify that jet drops are efficient at emitting microplastics up to 280μm in diameter and are thus expected to dominate the emitted mass of microplastic. The results are integrated to provide a global microplastic emission model which depends on bubble scavenging and bursting physics; local wind and sea state; and oceanic microplastic concentration. We test multiple possible microplastic concentration maps to find annual emissions ranging from 0.02 to 7.4—with a best guess of 0.1—mega metric tons per year and demonstrate that while we significantly reduce the uncertainty associated with the bursting physics, the limited knowledge and measurements on the mass concentration and size distribution of microplastic at the ocean surface leaves large uncertainties on the amount of microplastic ejected.
Human Neural Progenitors Expressing GDNF Enhance Retinal Protection in a Rodent Model of Retinal Degeneration
Authors: Shahin Saba , Tan Patrick , Chetsawang Jason , Lu Bin , Svendsen Soshana , Ramirez Stephany , Conniff Trevor , Alfaro Jorge S , Fernandez Michael , Fulton Aaron , Laperle Alexander H , Svendsen Clive N , Wang Shaomei
Published: October 2023

Stem cell therapy for retinal degenerative diseases has been extensively tested in preclinical and clinical studies. However, preclinical studies performed in animal models at the early stage of disease do not optimally translate to patients that present to the clinic at a later stage of disease. As the retina degenerates, inflammation and oxidative stress increase and trophic factor support declines. Testing stem cell therapies in animal models at a clinically relevant stage is critical for translation to the clinic. Human neural progenitor cells (hNPC) and hNPC engineered to stably express GDNF (hNPCGDNF) were subretinally injected into the Royal College of Surgeon (RCS) rats, a well-established model for retinal degeneration, at early and later stages of the disease. hNPCGDNF treatment at the early stage of retinal degeneration provided enhanced visual function compared to hNPC alone. Treatment with both cell types resulted in preserved retinal morphology compared to controls. hNPCGDNF treatment led to significantly broader photoreceptor protection than hNPC treatment at both early and later times of intervention. The phagocytic role of hNPC appears to support RPE cell functions and the secreted GDNF offers neuroprotection and enables the extended survival of photoreceptor cells in transplanted animal eyes. Donor cells in the RCS rat retina survived with only limited proliferation, and hNPCGDNF produced GDNF in vivo. Cell treatment led to significant changes in various pathways related to cell survival, antioxidative stress, phagocytosis, and autophagy. A combined stem cell and trophic factor therapy holds great promise for treating retinal degenerative diseases including retinitis pigmentosa and age-related macular degeneration.
Physiological and phenological adjustments in water and carbon fluxes of Aleppo pine forests under contrasting climates in the Eastern Mediterranean
Authors: Markos Nikos , Preisler Yakir , Radoglou Kalliopi , Rotenberg Eyal , Yakir Dan
Published: October 2023

The ability of plants to adjust to the adverse effects of climate change is important for their survival and for their contribution to the global carbon cycle. This is particularly true in the Mediterranean region, which is among the regions that are most vulnerable to climate change. Here, we carried out a 2-year comparative ecophysiological study of ecosystem function in two similar Eastern Mediterranean forests of the same tree species (Pinus halepensis Mill.) under mild (Sani, Greece) and extreme (Yatir, Israel) climatic conditions. The partial effects of key environmental variables, including radiation, vapor pressure deficit, air temperature and soil moisture (Rg, D, T and soil water content (SWC), respectively), on the ecosystems’ CO2 and water vapor fluxes were estimated using generalized additive models (GAMs). The results showed a large adjustment between sites in the seasonal patterns of both carbon and water fluxes and in the time and duration of the optimal period (defined here as the time when fluxes were within 85% of the seasonal maximum). The GAM analysis indicated that the main factor influencing the seasonal patterns was SWC, while T and D had significant but milder effects. During the respective optimal periods, the two ecosystems showed strong similarities in the fluxes’ responses to the measured environmental variables, indicating similarity in their underlying physiological characteristics. The results indicate that Aleppo pine forests have a strong phenotypic adjustment potential to cope with increasing environmental stresses. This, in turn, will help their survival and their continued contribution to the terrestrial carbon sink in the face of climate change in this region.
Genetic Variation of Turnip Yellows Virus in Arable and Vegetable Brassica Crops, Perennial Wild Brassicas, and Aphid Vectors Collected from the Plants
Authors: Pimenta Ricardo J. G. , Macleod Kyle , Babb Robyn , Coleman Kaitlyn , MacDonald Joni , Asare-Bediako Elvis , Newbert Max J. , Jenner Carol E. , Walsh John A.
Published: October 2023

Turnip yellows virus (TuYV; Polerovirus, Solemoviridae) infects and causes yield losses in a range of economically important crop species, particularly the Brassicaceae. It is persistently transmitted by several aphid species and is difficult to control. Although the incidence and genetic diversity of TuYV has been extensively investigated in recent years, little is known about how the diversity within host plants relates to that in its vectors. Arable oilseed rape (Brassica napus) and vegetable brassica plants (Brassica oleracea), wild cabbage (B. oleracea), and aphids present on these plants were sampled in the field in three regions of the United Kingdom. High levels of TuYV (82 to 97%) were detected in plants in all three regions following enzyme-linked immunosorbent assays. TuYV was detected by reverse transcription polymerase chain reaction in Brevicoryne brassicae aphids collected from plants, and TuYV sequences were obtained. Two TuYV open reading frames, ORF0 and ORF3, were partially sequenced from 15 plants, and from one aphid collected from each plant. Comparative analyses between TuYV sequences from host plants and B. brassicae collected from respective plants revealed differences between some ORF0 sequences, which possibly indicated that at least two of the aphids might not have been carrying the same TuYV isolates as those present in their host plants. Maximum likelihood phylogenetic analyses including published, the new TuYV sequences described above, 101 previously unpublished sequences of TuYV from oilseed rape in the United Kingdom, and 13 also previously unpublished sequences of TuYV from oilseed rape in Europe and China revealed three distinct major clades for ORF0 and one for ORF3, with some distinct subclades. Some clustering was related to geographic origin. Explanations for TuYV sequence differences between plants and the aphids present on respective plants and implications for the epidemiology and control of TuYV are discussed.
Evaluation of Malignant Hyperthermia Features in Patients with Pathogenic or Likely Pathogenic RYR1 Variants Disclosed through a Population Genomic Screening Program
Authors: Yu Kristen D. , Betts Megan N. , Urban Gretchen M. , Schwartz Marci L. B. , Robinson Tanisha O. , Moyer Robert J. , Taddonio Scott W. , Vasudevan Anasuya , Johns Alicia , Sturm Amy C. , Kelly Melissa A. , Williams Marc S. , Poler S. Mark , Buchanan Adam H.
Published: October 2023

Background

Malignant hyperthermia (MH) susceptibility is a heritable musculoskeletal disorder that can present as a potentially fatal hypermetabolic response to triggering anesthesia agents. Genomic screening for variants in MH-associated genes RYR1 and CACNA1S provides an opportunity to prevent morbidity and mortality. There are limited outcomes data from disclosing variants in RYR1, the most common MH susceptibility gene, in unselected populations. The authors sought to identify the rate of MH features or fulminant episodes after triggering agent exposure in an unselected population undergoing genomic screening including actionable RYR1 variants.

Methods

The MyCode Community Health Initiative by Geisinger (USA) is an electronic health record–linked biobank that discloses pathogenic and likely pathogenic variants in clinically actionable genes to patient-participants. Available electronic anesthesia and ambulatory records for participants with actionable RYR1 results returned through December 2020 were evaluated for pertinent findings via double-coded chart reviews and reconciliation. Descriptive statistics for observed phenotypes were calculated.

Results

One hundred fifty-two participants had an actionable RYR1 variant disclosed during the study period. None had previous documented genetic testing for MH susceptibility; one had previous contracture testing diagnosing MH susceptibility. Sixty-eight participants (44.7%) had anesthesia records documenting triggering agent exposure during at least one procedure. None received dantrolene treatment or had documented muscle rigidity, myoglobinuria, hyperkalemia, elevated creatine kinase, severe myalgia, or tea-colored urine. Of 120 possibly MH-related findings (postoperative intensive care unit admissions, hyperthermia, arterial blood gas evaluation, hypercapnia, or tachycardia), 112 (93.3%) were deemed unlikely to be MH events; 8 (6.7%) had insufficient records to determine etiology.

Conclusions

Results demonstrate a low frequency of classic intraanesthetic hypermetabolic phenotypes in an unselected population with actionable RYR1 variants. Further research on the actionability of screening for MH susceptibility in unselected populations, including economic impact, predictors of MH episodes, and expanded clinical phenotypes, is necessary.

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Uveitis associated with immune checkpoint inhibitors or BRAF/MEK inhibitors in patients with malignant melanoma
Authors: Sada Ikuyo , Harada Yosuke , Hiyama Tomona , Mizukami Mina , Kan Takanobu , Kawai Mikio , Kiuchi Yoshiaki
Published: October 2023

To evaluate the frequency and characteristics of uveitis associated with immune checkpoint inhibitors (ICIs) or BRAF/MEK inhibitors (B/MIs) in patients with malignant melanoma. Patients diagnosed with malignant melanoma who underwent radical or local resection for malignant melanoma, regardless of clinical stage or postoperative adjuvant therapy, at Hiroshima University Hospital from January 2015 to June 2021 were enrolled in a retrospective cohort. The medical records of patients were collected to estimate the prevalence of ocular adverse events. The clinical characteristics of patients who developed uveitis were reviewed. Among 152 patients, 54 and 12 were treated with ICIs and B/MIs, respectively. Four patients developed uveitis; 1 in the ICI group and 3 in the B/MI group, while there were no uveitis cases among patients who did not receive ICIs or B/MIs. Three patients had Vogt–Koyanagi–Harada disease-like findings. Uveitis was improved by steroid therapy with or without oncological treatment interruption. Oncological treatment could be resumed. Patients with melanoma treated with ICIs or B/MIs had a higher risk of uveitis compared with those who did not receive them. Oncological treatment could be resumed in all patients who developed uveitis.
A Triple Combination Therapy Using 2-mm Biopsy Punch for the Treatment of Multifocal Keloids
Authors: Park Tae Hwan
Published: October 2023

BACKGROUND

Keloid treatment is challenging. The surgical approach can be divided into complete excision versus partial excision.

OBJECTIVE

The current study aims to introduce our novel surgical approach of partial excision using a 2-mm punch biopsy device to treat refractory multifocal keloids in the trunk.

MATERIALS AND METHODS

This is a case series of 30 patients with refractory multifocal keloids treated with a triple combination therapy consisting of a punch-assisted partial excision and intralesional triamcinolone injections followed by immediate single fractional electron beam radiotherapy within 8 hours, postoperatively. The follow-up period was 12 months. The primary outcome was recorded asrecurrenceversusnonrecurrenceoraggravationversusremission. The secondary outcome was patient satisfaction as assessed by the POSAS.

RESULTS

The recurrence or aggravation of keloid was not found without complications. Scores obtained from the POSAS patient scale showed that pain, itchiness, color, stiffness, thickness, and irregularity significantly improved.

CONCLUSION

Our novel surgical approach using a 2-mm punch biopsy device effectively treats refractory multifocal keloids once considered intractable. Triple combination therapy of partial excision using a 2-mm punch biopsy device, intralesional triamcinolone injections, followed by immediate single fractional electron beam radiotherapy, is a safe, efficacious, and more convenient protocol to treat this condition.
Mechanisms of improved body composition among perimenopausal women practicing Meditative Movement: a proposed biobehavioral model
Authors: James Dara L. , Larkey Linda K. , Evans Bronwynne , Sebren Ann , Goldsmith Kimberley , Ahlich Erica , Hawley Nanako A. , Kechter Afton , Sears Dorothy D.
Published: October 2023

Objectives

Weight gain and unfavorable body composition are prevalent among midlife/older women throughout menopause. These shifts may negatively impact health, well-being, and longevity. Efforts to attenuate weight and body composition changes are traditionally driven by manipulation of diet and/or exercise; however, sustained results are limited, possibly because the full spectrum of biobehavioral systems is not addressed by diet and exercise alone. We propose a biobehavioral model detailing mechanisms of body composition decline among perimenopausal women and the associated components of Meditative Movement (ie, tai chi, qigong, yoga) that address each of these factors.

Methods

Based on our previous work and extensive review of the literature, we developed a multifactorial and multidimensional biobehavioral model including factors that most directly relate to body composition among perimenopausal women: 1) psychological (ie, stress and mood, mindfulness and self-compassion, body awareness), 2) behavioral (ie, sleep, physical activity, eating behaviors), and 3) physiological (ie, cortisol, estrogen). Relationships between each factor, Meditative Movement practice components, and predicted effects on body composition were explored in detail.

Results

Our model describes select psychological, behavioral, and physiological factors, and potential mechanistic pathways of Meditative Movement practice driving improved changes in body composition and weight outcomes for perimenopausal women.

Conclusions

The proposed model details a novel, evidence-supported means to reduce the risk of deleterious shifts in body composition throughout perimenopause and menopause thereafter. We suggest that these changes may occur directly and/or indirectly through psychological, behavioral, and physiological mechanisms that facilitate the desired changes in body composition.
Health Literacy and Perceived Control
Authors: Miller Jennifer L. , Chung Misook , Williams Lovoria B. , Connell Alison , Saleh Zyad T. , Alhurani Abdullah , Bailey Alison , Rayens Mary Kay , Moser Debra K.
Published: October 2023

Background

Black race, inadequate health literacy, and poor perceived control are predictors of increased cardiovascular disease (CVD) risk. The purpose of this study was to explore the relationships among race, health literacy, perceived control, and CVD risk while controlling for known risk factors in incarcerated men.

Methods

We included data from 349 incarcerated men to examine race and CVD risk (Framingham Risk Score) using a serial mediation model with health literacy and perceived control using 95% confidence intervals (CIs) from 5000 bootstrap samples.

Results

Of the participants (age, 36 ± 10; education, 12 ± 2; body mass index, 28.3 ± 5.0), 64.2% were White and 35.8% were Black. Black incarcerated men were younger (P = .047) with lower levels of health literacy (P < .001). All 3 indirect effects of race on CVD were significant, whereas the direct effect of race was not. Black incarcerated men had higher levels of CVD risk through health literacy (a
1
b
1 = 0.3571; 95% CI, 0.0948–0.7162) and lower levels of CVD risk through perceived control (a
2
b
2 = −0.1855; 95% CI, −0.4388 to −0.0077). Black incarcerated men had higher levels of CVD risk through health literacy influenced by perceived control (a
1
b
2
d
21 = 0.0627; 95% CI, 0.0028–0.1409), indicating that despite the protective effect of higher levels of perceived control in Black incarcerated men, CVD risk remained higher compared with their White counterparts.

Conclusion

Future CVD risk reduction interventions in incarcerated men, specifically Black incarcerated men, should include goals of improving health literacy and perceived control as modifiable risk factors.