bluuebunny/crossref_metadata_2025 huggingface dataset:
Binary mergers in strong gravity background of Kerr black hole
Authors: Camilloni Filippo , Harmark Troels , Grignani Gianluca , Orselli Marta , Pica Daniele
Published: May 2024

Binary-black-hole (BBH) mergers can take place close to a supermassive black hole (SMBH) while being in a bound orbit around the SMBH. In this paper, we study such bound triple systems and show that including the strong gravity effects of describing the SMBH with a Kerr metric can significantly modify the dynamics, as compared to a Newtonian point particle description of the SMBH. We extract the dynamics of the system, using a quadrupole approximation to the tidal forces due to the SMBH. We exhibit how the gyroscope precession is built into this dynamics, and find the secular Hamiltonian by both averaging over the inner and outer orbits, the latter being the orbit of the BBH around the SMBH. We study the long-time-scale dynamics, including the periastron precession and gravitational wave (GW) radiation reaction of the binary system, finding that the strong gravity effects of the SMBH can enhance the von Zeipel–Lidov–Kozai mechanism, resulting in more cycles, higher maximum eccentricity, and thereby a shorter merger time, particularly when the binary is close to, or at, the innermost stable orbit of the SMBH. We end with an analysis of the peak frequency of the GW emission from the binary system, highlighting possible observable signatures in the Einstein Telescope and Laser Interferometer Space Antenna frequency bands.
Comprehensive translational profiling and STE AI uncover rapid control of protein biosynthesis during cell stress
Authors: Horvath Attila , Janapala Yoshika , Woodward Katrina , Mahmud Shafi , Cleynen Alice , Gardiner Elizabeth E , Hannan Ross D , Eyras Eduardo , Preiss Thomas , Shirokikh Nikolay E
Published: May 2024

Translational control is important in all life, but it remains a challenge to accurately quantify. When ribosomes translate messenger (m)RNA into proteins, they attach to the mRNA in series, forming poly(ribo)somes, and can co-localize. Here, we computationally model new types of co-localized ribosomal complexes on mRNA and identify them using enhanced translation complex profile sequencing (eTCP-seq) based on rapid in vivo crosslinking. We detect long disome footprints outside regions of non-random elongation stalls and show these are linked to translation initiation and protein biosynthesis rates. We subject footprints of disomes and other translation complexes to artificial intelligence (AI) analysis and construct a new, accurate and self-normalized measure of translation, termed stochastic translation efficiency (STE). We then apply STE to investigate rapid changes to mRNA translation in yeast undergoing glucose depletion. Importantly, we show that, well beyond tagging elongation stalls, footprints of co-localized ribosomes provide rich insight into translational mechanisms, polysome dynamics and topology. STE AI ranks cellular mRNAs by absolute translation rates under given conditions, can assist in identifying its control elements and will facilitate the development of next-generation synthetic biology designs and mRNA-based therapeutics.
Typology of employers offering line manager training for mental health
Authors: Blake H , Hassard J , Dulal-Arthur T , Wishart M , Roper S , Bourke J , Belt V , Bartle C , Pahl N , Leka S , Thomson L
Published: May 2024

Background

Mental ill health has a high economic impact on society and employers. National and international policy advocates line manager (LM) training in mental health as a key intervention, but little is known about employer training provisions.

Aims

To explore the prevalence and characteristics of organizations that offer LM training in mental health.

Methods

Secondary analysis of existing longitudinal anonymised organizational-level survey data derived from computer-assisted telephone interview surveys collected in four waves (2020:1900 firms, 2021:1551, 2022:1904, 2023:1902) in England, before, during and after a global pandemic.

Results

The proportion of organizations offering LM training in mental health increased pre- to post-pandemic (2020:50%, 2023:59%) but 41% do not currently provide it. Logistic regression confirmed that LM training is more likely to be offered by large-sized enterprises, organizations with a larger proportion of employees who are younger (aged 25–49), female, disabled and from ethnic minority communities. Sector patterns were inconsistent, but in 2023, organizations from the ‘Hospitality’ and ‘Business Services’ sectors were more likely to provide LM training than other sectors.

Conclusions

Continued efforts are needed to increase the proportion of employers offering LM training in mental health, particularly small- to medium-sized enterprises, and organizations with predominantly male, White and/or older workforces.
Fertility and pregnancy complications in female orthopaedic surgeons
Authors: Frenkel Rutenberg T , Daglan E , Shadmi N , Iordache S D , Kosashvili Y , Eylon S
Published: May 2024

Background

While the number of female medical graduates continues to increase, only a few pursue an orthopaedic career. This is related to challenges regarding pregnancy and the peripartum period during orthopaedic training.

Aims

To evaluate fertility, pregnancy-related complications and attitudes towards female orthopaedic surgeons in Israel.

Methods

An electronic anonymous 34-question electronic web-based survey was sent to all Israeli female orthopaedic surgeons. Participation was voluntary. Questions were formulated to determine demographics, obstetrics medical history, teratogenic exposure, medical leave and breastfeeding parameters along with attitude towards pregnancy.

Results

Twenty-six orthopaedic surgeons complied with the survey, 68% of all registered female orthopaedic surgeons. Participants age was 39.5 (±8.8). The average number of children for a female orthopaedic surgeon was 2.2 (±1.4), with an average of 1.3 (±1.1) deliveries during residency. The average age for a first child was 31.1 (±3.7) years. Four surgeons required fertility treatments and six had abortions. Thirty-eight per cent experienced pregnancy complications. Most surgeons were exposed to radiation and bone cement during pregnancy. The average duration of maternity leave was 19.4 (±9.9) weeks and return to work was associated with cessation of breastfeeding. Seventy-six per cent of surgeons felt that pregnancy had negatively influenced their training, and 12% reported negative attitudes from colleagues and supervisors.

Conclusions

Orthopaedic surgeons in Israel experience a delay in childbirth and higher rates of pregnancy complications. Most feel that their training is harmed by pregnancy. Programme directors should design a personalized support programme for female surgeons during pregnancy and the peripartum period.
Geopolitics and global economic governance
Authors: Hurrell Andrew
Published: May 2024

This article analyses the relationship between geopolitics and global economic governance from an international relations perspective, laying stress on the long-term changes that have taken place in the character and dynamics of modern global international society. First, it unpacks what is involved in talk about the ‘the return of geopolitics’, arguing that the international political system needs to be understood in its own right and according to its distinctive logics and dynamics, separate from those of modern capitalism. The second section shifts the focus from the modern international to the modern global, arguing that the ‘we’ now involved in both geopolitics and global economic governance has changed in fundamental ways and that the diffusion of power and agency and the revolt against Western dominance are far broader than the rise of China. The final section looks at future pathways: the unlikely possibility of the restoration of US hegemony; the case for the primacy of political order over global governance and for refocusing attention on the primary or foundational institutions on which all more elaborate forms of global governance must depend; and the identification of some of the most important institutional pinch-points where geopolitics and global economic governance intersect and need to be managed, including sanctions, security-related trade measures, and industrial strategy.
The microRNA408–plantacyanin module balances plant growth and drought resistance by regulating reactive oxygen species homeostasis in guard cells
Authors: Yang Yanzhi , Xu Lei , Hao Chen , Wan Miaomiao , Tao Yihan , Zhuang Yan , Su Yanning , Li Lei
Published: May 2024

The conserved microRNA (miRNA) miR408 enhances photosynthesis and compromises stress tolerance in multiple plants, but the cellular mechanism underlying its function remains largely unclear. Here, we show that in Arabidopsis (Arabidopsis thaliana), the transcript encoding the blue copper protein PLANTACYANIN (PCY) is the primary target for miR408 in vegetative tissues. PCY is preferentially expressed in the guard cells, and PCY is associated with the endomembrane surrounding individual chloroplasts. We found that the MIR408 promoter is suppressed by multiple abscisic acid (ABA)-responsive transcription factors, thus allowing PCY to accumulate under stress conditions. Genetic analysis revealed that PCY elevates reactive oxygen species (ROS) levels in the guard cells, promotes stomatal closure, reduces photosynthetic gas exchange, and enhances drought resistance. Moreover, the miR408–PCY module is sufficient to rescue the growth and drought tolerance phenotypes caused by gain- and loss-of-function of MYB44, an established positive regulator of ABA responses, indicating that the miR408–PCY module relays ABA signaling for regulating ROS homeostasis and drought resistance. These results demonstrate that miR408 regulates stomatal movement to balance growth and drought resistance, providing a mechanistic understanding of why miR408 is selected during land plant evolution and insights into the long-pursued quest of breeding drought-tolerant and high-yielding crops.
The OsMOB1A–OsSTK38 kinase complex phosphorylates CYCLIN C, controlling grain size and weight in rice
Authors: Chen Guoxin , Gao Jiabei , Wu Suting , Chang Yuan , Chen Zhenhua , Sun Jing , Zhang Liying , Wu Jinxia , Sun Xuehui , Quick William Paul , Cui Xuean , Zhang Zhiguo , Lu Tiegang
Published: May 2024

Grain size and weight are crucial yield-related traits in rice (Oryza sativa). Although certain key genes associated with rice grain size and weight have been successfully cloned, the molecular mechanisms underlying grain size and weight regulation remain elusive. Here, we identified a molecular pathway regulating grain size and weight in rice involving the MPS ONE BINDER KINASE ACTIVATOR-LIKE 1A–SERINE/THREONINE-PROTEIN KINASE 38–CYCLIN C (OsMOB1A–OsSTK38–OsCycC) module. OsSTK38 is a nuclear Dbf2-related kinase that positively regulates grain size and weight by coordinating cell proliferation and expansion in the spikelet hull. OsMOB1A interacts with and enhances the autophosphorylation of OsSTK38. Specifically, the critical role of the OsSTK38 S322 site in its kinase activity is highlighted. Furthermore, OsCycC, a component of the Mediator complex, was identified as a substrate of OsSTK38, with enhancement by OsMOB1A. Notably, OsSTK38 phosphorylates the T33 site of OsCycC. The phosphorylation of OsCycC by OsSTK38 influenced its interaction with the transcription factor KNOTTED-LIKE HOMEOBOX OF ARABIDOPSIS THALIANA 7 (OsKNAT7). Genetic analysis confirmed that OsMOB1A, OsSTK38, and OsCycC function in a common pathway to regulate grain size and weight. Taken together, our findings revealed a connection between the Hippo signaling pathway and the cyclin-dependent kinase module in eukaryotes. Moreover, they provide insights into the molecular mechanisms linked to yield-related traits and propose innovative breeding strategies for high-yielding varieties.
Pelvic floor disorders and impact on sexual function: a cross-sectional study among non–sexually active and sexually active women
Authors: Stafne Signe Nilssen , Ulven Silje Kristine Sveen , Prøsch-Bilden Tone , Saga Susan
Published: May 2024

Background

Pelvic floor disorders are common and associated with impaired sexual function in women.

Aim

To assess women with pelvic floor disorders and describe factors associated with not being sexually active and those associated with sexual function in sexually active women.

Methods

A cross-sectional study was conducted that included nonpregnant women with symptoms of pelvic floor disorders who were referred to the urogynecologic and surgical outpatient clinic at 2 Norwegian university hospitals: St Olavs Hospital, Trondheim University Hospital, and the University Hospital of Northern Norway, Tromsø. Women answered a questionnaire anonymously.

Outcomes

Pelvic Organ Prolapse Incontinence Sexual Questionnaire–IUGA Revised.

Results

Of 157 respondents, 111 (71%) reported being sexually active (with or without a partner), and 46 (29%) reported not being sexually active. As compared with sexually active women, not sexually active women were older (mean ± SD, 60.2 ± 13.3 vs 51 ± 12.1 years; P < .001), more were menopausal (78% vs 47%, P = .001), and more had symptom debut <1 year (31% vs 9%, P < .001). They reported more distress related to pelvic floor disorders, especially pelvic organ prolapse. In a multivariate logistic regression analysis, menopausal women and women with symptom debut <1 year were 4 times more likely to be not sexually active than premenopausal women (odds ratio, 4.0; 95% CI, 1.7-9.2) and women with symptom debut ≥1 year (odds ratio, 4.0; 95% CI, 1.5-10.7). In sexually active women, colorectal-anal distress was negatively associated with 5 of 6 domains of sexual function: arousal/orgasm (ß = –0.36; 95% CI, –0.02 to –0.005), partner related (ß = –0.28; 95% CI, –0.01 to –0.002), condition specific (ß = –0.39; 95% CI, –0.002 to –0.009), global quality (ß = –0.23; 95% CI, –0.02 to –0.002), and condition impact (ß = –0.34; 95% CI, –0.02 to –0.006).

Clinical Implications

Health care professionals should discuss sexual function in patients with pelvic floor disorders, especially menopausal women and women with colorectal-anal symptoms.

Strengths and Limitations

The study used condition-specific measures and recruited women from 2 university hospitals with wide range of age. Limitations include the small sample size and wide confidence intervals. The number of women who considered themselves not sexually active was low, and item nonresponse levels among these women where somewhat high. Of 625 eligible women, 200 (32%) answered the questionnaire. Sexual health and sexual function are still surrounded with taboo, and some women were probably not comfortable answering the questions.

Conclusion

Menopausal women and women with recent onset of symptoms of pelvic floor disorders are more likely to be sexually inactive, and colorectal-anal symptoms have the most negative impact on sexual function in sexually active women.
Androgens and erectile dysfunction: from androgen deficiency to treatment
Authors: Wang Yuan , Jiang Rui
Published: May 2024

Introduction

Androgens play important roles in regulating the growth and development of the male reproductive system and maintaining libido and erectile function. The specific mechanisms by which androgen deficiency leads to erectile dysfunction (ED) are not yet fully understood.

Objectives

To understand the mechanisms and treatment of androgen deficiency–related ED.

Methods

A literature search in the past 10 years was conducted in PubMed and Google Scholar to determine the effects of androgen deficiency on erectile function and the treatment of androgen deficiency.

Results

Androgen deficiency can be caused by hypothalamic-pituitary lesions and injuries, testicular-related diseases and injuries, endocrine and metabolic disorders, the side effects of medication, and age. Androgen deficiency can lead to ED by inhibiting the NOS/NO/cGMP pathway (nitric oxide synthase/nitric oxide/cyclic guanosine monophosphate) and altering the expression of ion channel proteins, as well as by inducing oxidative stress, death, and fibrosis in penile corpus cavernosum cells. Testosterone replacement therapy is effective at improving the serum testosterone levels and erectile function in patients with androgen deficiency. For patients who need to maintain a low androgenic state, erectile function can be improved by lifestyle changes, treatment with phosphodiesterase type 5 inhibitors, low-intensity extracorporeal shock wave therapy, and stem cell therapy.

Conclusions

Androgen deficiency can affect the structure and function of the penile corpus cavernosum, leading to ED. Areas of further study include how androgen replacement therapy can improve erectile function and how to improve the maintenance of erectile function in patients with hypoandrogenic status.
Arthrocladiella mougeotii Causing Powdery Mildew on Goji Berry Plants (Lycium barbarum and L. chinense) and Mixed Infections with Phyllactinia chubutiana in California
Authors: Elfar Karina , Bustamante Marcelo I. , Rooney-Latham Suzanne , Eskalen Akif , Miller Tom
Published: May 2024

Goji berries (Lycium barbarum and L. chinense) have a rich historical significance in traditional Chinese medicine and have gained popularity as a superfood in Western cultures. From 2021 to 2023, powdery mildew was observed on goji plants of both species in community and residential gardens in Yolo County, California (U.S.A.). Disease severity varied from 20 to 100% of infected leaves per plant. Powdery mildew was characterized by the presence of white fungal colonies on both sides of leaves and fruit sepals. Additionally, a brownish discoloration was observed in infected mature leaves, resulting in further defoliation. Morphologically, the fungus matched the description of Arthrocladiella mougeotii. The pathogen identity was confirmed by phylogenetic analyses of the rDNA internal transcribed spacer and the 28S rDNA gene sequences. Pathogenicity was confirmed by inoculating healthy L. barbarum plants using infected leaves and successfully reproducing powdery mildew symptoms after 28 days (22°C, 60% RH), with A. mougeotii colonies confirmed by morphology. Control leaves remained symptomless. Coinfection with Phyllactinia chubutiana was detected on plants from two separate gardens, with A. mougeotii observed first in late spring (May to June) and P. chubutiana later in the summer (July to August). These results revealed that both A. mougeotii and P. chubutiana constitute causal agents of powdery mildew on goji berry plants, often infecting the same plant tissues simultaneously. To our knowledge, this is the first report of A. mougeotii causing powdery mildew on L. barbarum and L. chinense in California, which provides a better understanding of the etiology of powdery mildew of goji plants.
Environmental Influences on the Drying Rate of Spray-Applied Disinfestants from Horticultural Production Surfaces
Authors: Copes Warren E. , Read Quentin , Smith Barbara J.
Published: May 2024

Drying rates of disinfestants commonly applied to horticultural plant production surfaces were evaluated under cool to hot weather and under laboratory conditions to characterize the range of drying times and how this relates to contact times specified on product labels. Drying rates of six disinfestants (isopropyl alcohol [IPA], two quaternary ammonium compounds [QACs], two peroxygen compounds [PXs], and sodium hypochlorite [bleach]) and water were evaluated when applied to six substrate materials (concrete, galvanized metal, polypropylene ground fabric, polyethylene plastic sheet, pressure-treated pine, and twin-wall clear polycarbonate) based on the weather variables of solar radiation, temperature, and relative humidity. Differences were evident at the point of application. Disinfestants with low (IPA, both QACs, and one PX) and high (bleach, one PX, and water) surface tension provided approximately 100 and 60% coverage, respectively, when applied to horizontal, nonporous solid materials. Disinfestants applied to horizontal porous materials (concrete, fabric, and wood) persisted on the surface for a mean of only 9 to 113 s because solutions were actively drawn into the substrates’ internal structure. Disinfestants applied to vertical twin-wall greenhouse material flowed off, while retaining only a maximum beaded wetness coverage of 14%. A Bayesian analysis procedure was used to model drying effects of disinfestants correlated with substrate and weather variables based on posterior marginal and prediction trends. Generally, the fastest drying rate occurred in the first 2.5 min, and approximately 50% of coverage was retained by 5 min. The evaporative process was variable with distinct interactions occurring among the experimental variables.

[Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2024.
Mitochondrial Genome Resource of the Cottony Ash Psyllid, a Host of a Newly Identified ‘Candidatus Liberibacter’ Bacterium
Authors: Sabaghian Simin , Gorman Zachary , Prager Sean M. , Chen Jianchi , Wallis Christopher M.
Published: May 2024

Cottony ash psyllid (CAP, Psyllopsis discrepans) is an important, invasive insect pest of ash trees in North America, where it has established populations and is the host of a newly identified strain of ‘ Candidatus Liberibacter solanacearum’. However, not much is known about the diversity of its introduced population. In this study, a CAP mitochondrial genome (mitogenome) sequence was obtained from a collection in Saskatoon, Saskatchewan, Canada. The CAP mitogenome is a circular DNA of 18,824 bp, encoding 13 protein-coding genes, 21 transfer RNA genes, and two ribosomal RNA genes. BLAST search using the CAP mitogenome as a query against the GenBank sequence database showed the mitogenome of Euphyllura phillyreae (15,202 bp) was the most similar (query coverage = 77%; percentage identity = 78.90%). The CAP mitogenome is significantly different from other known psyllid mitogenomes with the presence of a 4,357-bp control region. The mitogenome sequence will further the genomic understanding of CAP.

[Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2024.
Beyond the Task: Developing a Tool to Measure Workplace Characteristics That Affect Cognitive Load and Learning
Authors: Blissett Sarah , Rodriguez Sebastian , Qasim Atif , O’Sullivan Patricia
Published: May 2024

Purpose

Educators lack tools to measure the workplace characteristics that learners perceive to affect learning. Without a tool that encompasses the social, organizational, and physical components of workplace learning environments (WLEs), it is challenging to identify and improve problematic workplace characteristics. Using echocardiography WLE, this study developed a tool to measure workplace characteristics that cardiology fellows perceive to affect learning.

Method

The Workplace–Cognitive Load Tool (W-CLT) was developed, which encompasses 17 items to measure workplace characteristics that could affect perceived cognitive load and learning. Exploratory factor analysis was used to identify the most parsimonious structure. A total of 646 cardiology subspeciality fellows were recruited from 60 cardiology fellowship programs to complete the survey between November 2020 and February 2021. Validity evidence was collected, guided by the unified model of validity.

Results

A total of 308 fellows (response rate, 49%) participated in the survey. The most parsimonious structure included 4 factors: (1) workplace-task, (2) workplace-environment, (3) workplace-orientation, and (4) workplace–teaching and feedback. All factors had high reliability (Cronbach α = 0.92, 0.92, 0.96, and 0.94, respectively). Social, organizational, and physical components of WLEs were represented in the items. Workplace–teaching and feedback had moderate negative correlations with workplace-environment (r = −0.41, P < .001) and workplace-orientation (r = −0.36, P < .001). A moderate positive correlation was found between workplace-task and workplace–teaching and feedback (r = 0.42, P < .001). Workplace-task had weak negative correlations with workplace-environment (r = −0.22, P < .001) and workplace-orientation (r = −0.23, P < .001).

Conclusions

The W-CLT measures workplace characteristics that cardiology fellows perceive to affect their learning. The presence of social, organizational, and physical components emphasizes how workplace characteristics can enhance or impede learning. The W-CLT provides a foundation to explore how learning can be optimized in other WLEs.
Conditional survival of male breast cancer
Authors: Fan Yanshuai , Ku Chaoyue , Wang Ruizhe , Wu Binbin , Cui Man , Wang Juan , Deng Miao , Liu Li , Ping Zhiguang
Published: May 2024

Background

The incidence of male breast cancer has been increasing in recent years; however, the long-term survival outcomes of diagnosed patients remain uncertain. This study was designed to evaluate the conditional survival of male breast cancer patients and to predict the future survival of patients through the conditional nomogram, to provide important suggestions for clinical decision-making.

Methods

Retrospective data from the SEER database included 3600 male breast cancer patients, divided into training and validation groups (7 : 3 ratio). Overall survival rates were calculated using Kaplan–Meier analysis. Conditional survival analysis described survival at specific years. Time-dependent multivariate Cox analysis identified prognostic factors’ impact. The conditional survival nomogram model predicted real-time survival rates.

Results

Over time, the 5-year real-time survival rate of patients gradually improved, increasing from 70.5 to 74.8, 79.4, 85.8, and 92.9% (respectively, representing 5-year survival rates of 1–4 years after diagnosis). In addition, the improvement in conditional survival rate CS5 showed a nonlinear trend. After 5 years of diagnosis, age, tumor size, and tumor stage had a sustained impact on patient prognosis. Finally, a conditional survival nomogram was constructed to predict the 10-year survival rate in real time.

Conclusion

Five years after diagnosis, the conditional survival rate of male patients with breast cancer has improved, but it is not nonlinear. In the first 5 years after diagnosis, patients with older age, larger tumor size, poorer tumor stage, and distant metastasis should be actively followed up and treated to improve their long-term survival.
Evaluation of Published Population Pharmacokinetic Models to Inform Tacrolimus Therapy in Adult Lung Transplant Recipients
Authors: Kirubakaran Ranita , Singh Rani M. , Carland Jane E. , Day Richard O. , Stocker Sophie L.
Published: May 2024

Background:

The applicability of currently available tacrolimus population pharmacokinetic models in guiding dosing for lung transplant recipients is unclear. In this study, the predictive performance of relevant tacrolimus population pharmacokinetic models was evaluated for adult lung transplant recipients.

Methods:

Data from 43 lung transplant recipients (1021 tacrolimus concentrations) administered an immediate-release oral formulation of tacrolimus were used to evaluate the predictive performance of 17 published population pharmacokinetic models for tacrolimus. Data were collected from immediately after transplantation up to 90 days after transplantation. Model performance was evaluated using (1) prediction-based assessments (bias and imprecision) of individual predicted tacrolimus concentrations at the fourth dosing based on 1 to 3 previous dosings and (2) simulation-based assessment (prediction-corrected visual predictive check; pcVPC). Both assessments were stratified based on concomitant azole antifungal use. Model performance was clinically acceptable if the bias was within ±20%, imprecision was ≤20%, and the 95% confidence interval of bias crossed zero.

Results:

In the presence of concomitant antifungal therapy, no model showed acceptable performance in predicting tacrolimus concentrations at the fourth dosing (n = 33), and pcVPC plots displayed poor model fit to the data set. However, this fit slightly improved in the absence of azole antifungal use, where 4 models showed acceptable performance in predicting tacrolimus concentrations at the fourth dosing (n = 33).

Conclusions:

Although none of the evaluated models were appropriate in guiding tacrolimus dosing in lung transplant recipients receiving concomitant azole antifungal therapy, 4 of these models displayed potential applicability in guiding dosing in recipients not receiving concomitant azole antifungal therapy. However, further model refinement is required before the widespread implementation of such models in clinical practice.
Population Pharmacokinetics and Limited Sampling Strategy of Mycophenolate Mofetil for Indian Patients With Lupus Nephritis
Authors: Koloskoff Kévin , Panwar Ritika , Rathi Manish , Mathew Sumith , Sharma Aman , Marquet Pierre , Benito Sylvain , Woillard Jean-Baptiste , Pattanaik Smita
Published: May 2024

Background:

Mycophenolic acid is widely used to treat lupus nephritis (LN). However, it exhibits complex pharmacokinetics with large interindividual variability. This study aimed to develop a population pharmacokinetic (popPK) model and a 3-sample limited sampling strategy (LSS) to optimize therapeutic drug monitoring in Indian patients with LN.

Methods:

Five blood samples from each LN patient treated with mycophenolic acid were collected at steady-state predose and 1, 2, 4, and 6 hours postdose. Demographic parameters were tested as covariates to explain interindividual variability. PopPK analysis was performed using Monolix and the stochastic approximation expectation-maximization algorithm. An LSS was derived from 500 simulated pharmacokinetic (PK) profiles using maximum a posteriori Bayesian estimation to estimate individual PK parameters and area under the curve (AUC). The LSS-calculated AUC was compared with the AUC calculated using the trapezoidal rule and all the simulated samples.

Results:

A total of 51 patients were included in this study. Based on the 245 mycophenolic acid concentrations, a 1-compartmental model with double absorption using gamma distributions best fitted the data. None of the covariates improved the model significantly. The model was internally validated using diagnostic plots, prediction-corrected visual predictive checks, and bootstrapping. The best LSS included samples at 1, 2, and 4 hours postdose and exhibited good performances in an external dataset (root mean squared error, 21.9%; mean bias, −4.20%).

Conclusions:

The popPK model developed in this study adequately estimated the PK of mycophenolic acid in adult Indian patients with LN. This simple LSS can optimize TDM based on the AUC in routine practice.
Prevalence of Psychoactive Substance Use During Pregnancy in Argentine Women: A Pilot Study Testing Maternal Hair
Authors: Vieiros Melina , Mirahi Afrouz , Villarreal Marina , Ramos-Triguero Anna , Fernández-Rubal Iria , Andreu-Fernández Vicente , Pichini Simona , García-Algar Óscar , Marchei Emilia
Published: May 2024

Background:

The use of psychoactive substances (PSs) during pregnancy is a major public health concern because of their increasing prevalence worldwide. This study examined the understudied issue of gestational PS consumption in a cohort of Argentine delivering mothers.

Methods:

A cross-sectional pilot study involving 51 women receiving delivery care was conducted at the Santa Rosa Hospital in La Pampa, Argentina. Information on maternal sociodemographic characteristics, pregnancy history, and drug use was obtained through standardized interviews. Maternal hair samples were analyzed for alcohol, tobacco, licit, illicit, and prescription substance biomarkers using ultra-high-performance liquid chromatography high-resolution mass spectrometry and gas chromatography mass spectrometry.

Results:

During pregnancy, 49.0% of participants reported alcohol consumption, 25.5% reported tobacco use, and 23.5% reported cannabis use. Hair samples from 56.9% of the women were positive for illicit PSs, with the most frequent being cocaine (41.2%) and cannabis (15.7%). Among the women, 47.1% consumed alcohol during pregnancy. Of the 24 women with hair ethyl glucuronide ≥5 pg/mg, 33.3% drank until the end of gestation and 58.3% started a social drinking habit in the second half. The analysis also detected prescription substances (anticonvulsants, antidepressants, methadone, opioids, antihistamines, antiemetics, and analgesics), caffeine (70.6%), lidocaine, and levamisole, some of which were cocaine or opioid adulterants.

Conclusions:

This is the first study to objectively assess the consumption of licit and illicit PSs during pregnancy in Argentina. In contrast to most nearby countries, cocaine was the most detected illicit PS in this cohort of Argentine delivering women. This finding highlights the importance of regular monitoring of local trends in PS use during pregnancy.
Sports-Related Concussion in Collegiate Athletes: The Potential Benefits of Using Graded Neuropsychological Tests With High Ceilings
Authors: Chiang Cheng-Chuan , Hyder Kale , Bechtold Kathleen , Anaya Manuel , Celnik Pablo , Cantarero Gabriela , Suskauer Stacy , Stilling Joan
Published: May 2024

Objective:

Sports-related concussion management in collegiate athletes has been focused on return-to-play. However, resuming schoolwork without a gradual stepwise reintroduction contributes to symptom exacerbation, delayed recovery, and adverse academic performance. Return-to-learn guidelines are limited by a lack of sensitivity in methods monitoring cognitive function. This study evaluated 2 neuropsychological tests, the Sternberg test and the Paced Auditory Serial Addition Test (PASAT), with high ceilings for sensitivity to deficits in speed of information processing, cognitive efficiency, and complex attention.

Setting:

Academic center research laboratory.

Participants:

We recruited 56 male and female collegiate contact and noncontact sports athletes. They were categorized into as follows: (1) nonconcussed (n = 23; 7F, 16M); (2) chronic (n = 21; 4F, 17M), at least 1 year from their last concussion; and (3) acute (n = 12; 1F, 11M), within 2 weeks from concussion.

Design:

Observational cohort study.

Main Measures:

The PASAT assesses complex attention. The Sternberg test examines processing speed and cognitive efficiency. Cognitive difficulty increases with progression through the tasks for both the PASAT and the Sternberg test. The mean outcome differences of the 3 groups (nonconcussed, acute, and chronic) across the 3 or 4 conditions (difficulty level) were measured with repeated-measures analysis of variance and subsequent pairwise comparison.

Results:

For processing speed (Sternberg reaction time), the acute group responded slower than the chronic group on the medium (P = .021, Bonferroni corrected) and hard difficulty tasks (P = .030, Bonferroni corrected). For cognitive efficiency (Sternberg reaction time variability), the acute group had increased reaction time variability compared with the chronic group on the medium difficulty task (P = .04, Bonferroni corrected). For complex attention (PASAT omissions), there was a difference between the acute and nonconcussed groups on the moderate-hard difficulty trial (P = .023, least significant difference [LSD] corrected) and between the acute and chronic groups for hard difficulty trial (P = .020, LSD corrected). The acute group performed worse, with progressively shorter interstimulus intervals.

Conclusion:

Neuropsychological testing without ceiling effects can capture higher-level cognitive dysfunction and and use of such tests can contribute to the understanding of how collegiate athletes are affected by SRC. Future studies can investigate optimal testing batteries that include neuropsychological testing with high ceilings and whether the pattern of performance has implications for the return-to-learn process after SRC in the college setting.
Outcomes of a Second Ahmed Glaucoma Implant With Mitomycin-C in Pediatric Glaucoma After Initial Valve Failure
Authors: Promelle Veronique , Lyons Christopher J.
Published: May 2024

Précis:

After the failure of a glaucoma drainage device in children, implantation of a second Ahmed glaucoma valve with mitomycin-C allows a significant reduction of intraocular pressure and number of medications with good medium-term and long-term survival.

Introduction:

The effectiveness of glaucoma drainage devices (GDD) is limited in time. There is little literature regarding the optimal management strategy after failure of a GDD in pediatric glaucoma.

Purpose:

To report the outcomes of Ahmed glaucoma valve implantation (AGV) with mitomycin-C (MMC) after failure of a GDD in children.

Methods:

Retrospective chart review of patients with a history of at least 1 GDD receiving an AGV implantation with MMC between 2000 and 2019. We defined complete success as an IOP of 5–21 mm Hg without glaucoma medication and qualified success as a final IOP of 5–21 mm Hg with one or more glaucoma medication, without loss of vision.

Results:

Twenty-one patients (22 eyes) met the inclusion criteria. The intraocular pressure and number of medications were significantly reduced. The probability of complete success was 47% [95% CI: 29%–75%] at 2 years and 34% [95% CI: 18%–65%] at 4 years. The probability of qualified success was 74% [95% CI: 56%–97%] at 2 years, and 54% [95% CI: 34%–84%] at 5 years. Failure happened in 10 eyes after a mean time of 4.3 years ±3.6 (6 mo to 15 y), 5 of which (23%) for severe complications or loss of vision.

Discussion:

This study of implantation of a second valve with MMC reports a significant decrease in IOP and medications with medium-term and long-term success rates close to those reported for first valve implantation, although with a high risk of complications.
Correlation of Oral Microbiota With Different Immune Responses to Antiretroviral Therapy in People Living With HIV
Authors: Pan Jingying , Zhang Xiaodi , Shi Danrong , Tian Xuebin , Xu Lijun , Lu Xiangyun , Dong Mingqing , Yao Peng , Pan Zhaoyi , Wu Nanping , Yao Hangping
Published: May 2024

Both HIV infection and antiretroviral therapy (ART) affect the oral microbiome. Whether successful treatment with ART in people living with HIV (PLWH), which leads to a significant decline in viral loads and immune reconstitution, is associated with changes in or recovery of the oral microbiome remains unknown. Therefore, we performed a cross-sectional study of 118 PLWH receiving regular ART and 40 healthy controls (HCs). Among the 118 PLWH, 18 immunological non-responders (INRs; <200 CD4+ T cells/μL) and 30 immunological responders (IRs; ≥500 CD4+ T cells/μL) were identified. The oral microbiota composition of all participants was analyzed using 16S rRNA gene sequencing of throat swab samples. Relative abundance of bacterial genera was compared between IRs and INRs, and Pearson correlations between bacterial abundance and peripheral blood immune cell counts were evaluated. The INR group showed lower alpha diversity than the IR and HC groups, which displayed similar alpha diversity. The genera Alloprevotella, Prevotella and Neisseria were more abundant in PLWH than in HC, whereas the genera Rothia, Streptococcus and Fusobacterium were more abundant in HC than in PLWH. The genus Rothia was more abundant in the INR group, whereas Prevotella, Alloprevotella, Porphyromonas and Haemophilus were more abundant in the IR group. The genera Rothia and Alloprevotella were negatively and positively associated with CD4+ T cell counts, respectively. Thus, an increased abundance of Rothia in the oral microbiome is associated with unfavorable outcomes regarding immune reconstitution in PLWH receiving regular ART, whereas Prevotella, Alloprevotella, Porphyromonas and Haemophilus are associated with favorable outcomes.
Presentation of Spontaneous Orbital Hemorrhage
Authors: Vahdani Kaveh , Dharmasena Aruna , Rose Geoffrey E.
Published: May 2024

Purpose:

To evaluate the presenting features of patients with nontraumatic orbital hemorrhage (NTOH) based on etiopathological factors.

Methods:

A retrospective case-note review for demographics and presenting features of patients with nontraumatic orbital hemorrhage. Patients were categorized into 3 groups: group I with known systemic vascular disease, group II with known or newly revealed orbital vascular anomalies, and group III with no known underlying vasculopathy.

Results:

One hundred and seventeen patients (68 female; 58%), with 37 (32%) in group I, 47 (40%) in group II, and 33 (28%) in group III. The average age at presentation was 70.9, 30.1, and 49.9 years, respectively, but the incidence peaked in the first decade for patients with underlying local vascular anomalies and in the eighth for those without. Of the group I patients with known cardiovascular disease, 43% were on antithrombotic agents. The most common presenting symptoms were orbital pain (59%), proptosis (56%), and diplopia (45%), while 13% had associated nausea or vomiting. Ipsilateral optic neuropathy occurred in 14% of cases, higher in group II (22%), along with nonaxial globe displacement (25%), reduced eye movements (47%), optic disc swelling (10%), and choroidal folds (9%). Imaging in patients without evident vascular anomalies showed that hemorrhages commonly occurred in the inferotemporal quadrant (32%), with about half of these having a “beached whale” configuration (46%).

Conclusion:

Nontraumatic orbital hemorrhages affect all ages, typically presenting with acute proptosis or pain (over half), various degrees of visual impairment, and reduced motility. About half of those without vascular anomalies had cardiovascular risk factors, imaging often revealing an inferotemporal mass with a “beached whale” appearance.
The Effectiveness of Facial Exercise Therapy in Ophthalmic Complications of Facial Nerve Palsy and the CADS Grading Scale as an Ophthalmic-Specific Grading System
Authors: Lim Christina S. , Nagendran Sonali , Neville Catriona , Nduka Charles , Kannan Ruben , Malhotra Raman
Published: May 2024

Purpose:

The effectiveness of facial exercise therapy in facial nerve palsy is well documented in the literature. However, there is no study examining its effect on ophthalmic manifestations of facial nerve palsy. The study reports its impact on the ophthalmic manifestations of facial nerve palsy using the ophthalmic-specific CADS grading system.

Methods:

A retrospective case series of patients aged 18 years or older with facial nerve palsy was performed in a single specialist center between 2013 and 2019. Inclusion criteria were ophthalmic involvement, recorded CADS, and Sunnybrook grading scale pre- and post-treatment.

Results:

A total of 73 patients were identified. There were 24 patients (M = 11, F = 13) who received facial exercise therapy only (group 1) and 49 patients (M = 17, F = 32) who received combined treatment of facial exercise therapy and eyelid surgery (group 2). The mean ages were 54.8 and 49.7 years, respectively. The groups were further subdivided into early (<3 months), intermediate (3–12 months), and late presenters (>12 months). In group 1, statistically significant improvements were seen in early (static asymmetry and dynamic function), intermediate (cornea), and late groups (cornea, static asymmetry, and dynamic function). The Sunnybrook grading scale was unable to detect changes in the ophthalmic features post-therapy or to report the corneal status.

Conclusions:

Facial exercise therapy is likely to improve ophthalmic manifestations of facial nerve palsy, in particular, those with static asymmetry and dynamic function of eye closure. The CADS grading scale is more suitable for the ophthalmic assessment.
An Analysis of Surgical Factors Associated With Clinically Significant Eyelid Edema (CSEE) in Patients Undergoing Blepharoplasty: Lid Crease Techniques Associated with CSEE
Authors: Park Kristen E. , Guo Sarah , Mehta Preeya , Li Joy , Shen Alice , Bokman Christine L. , Chang Jessica R. , Zhang-Nunes Sandy
Published: May 2024

Purpose:

Severe postoperative edema after eyelid surgery can have negative clinical and psychological effects. In this study, the authors investigated whether surgical factors, including surgical techniques and suture type, were associated with clinically significant eyelid edema (CSEE).

Methods:

A chart review was performed on 269 patients who underwent upper eyelid blepharoplasty with or without external levator advancement by 2 surgeons at a single institution between January 2021 and December 2022. Postoperative photos were graded by 2 physicians for eyelid edema using a standardized grading scale ranging from 0 (no edema) to 3 (severe edema). CSEE was defined either as having a grade of 3 at any point postoperatively or any grade that was 1 or greater after 90 days postoperatively. Logistic regression controlling for race was used for analysis; the statistical significance level was defined as p < 0.05.

Results:

Of 269 patients, 56 developed CSEE. Of those who underwent blepharoplasty with mini crease enhancement (closure with every other bite incorporating levator aponeurosis), 40.5% developed CSEE versus 12.5% of those without (p < 0.001). Patients with lid crease formation using buried interrupted sutures had greater CSEE than those with externalized interrupted sutures removed at 1 week (43.8% versus 11.5%, p < 0.01). There was no increased risk of CSEE with additional procedures performed versus blepharoplasty alone.

Conclusions:

Patients who underwent blepharoplasty with mini crease enhancement, where more than 4 sutures are placed from skin to levator, and/or had buried suture lid crease formation had greater rates of CSEE.
Primary Gouty Tophi Involving the Eyelid
Authors: Meyer Anne M. , Dai Hongyan , Sokol Jason A.
Published: May 2024

A 51-year-old male with no known history of gout was referred by his optometrist for bilateral lower eyelid cysts near the puncta. The lesions were not painful but were cosmetically concerning and excision was desired. Utilizing local anesthesia, the lesions were excised and sent to pathology for review. Pathology noted lesions to be “gouty tophus.” Given that our patient had no history of gout, this is the first case report of gouty tophus on the eyelid being the initial manifestation of gout.
An Instrument to Assess the Digital Competence of Nurse Educators
Authors: Pajari Juha , Sormunen Marjorita , Salminen Leena , Elonen Imane , Pasanen Miko , Saaranen Terhi
Published: May 2024

Background:

The Educators and Educator Candidates’ Competence in Digital Pedagogy instrument needed to be tested before using it in nursing education.

Purpose:

This study describes the further testing of this instrument to measure nurse educators’ digital competence.

Methods:

The study is reported according to the 7 steps of the MEASURE Approach. Psychometric testing was conducted with a sample of 111 Finnish nurse educators from 9 universities of applied sciences. The study was conducted during the years 2020 and 2023.

Results:

The exploratory factor analysis results explained 56% of the variance with 3 factors, including 20 items. The factors were labeled to describe the nurse educators’ digital competence: implementing appropriate independent and community learning, acting safely and responsibly, and guiding learning based on the evidence. Cronbach α and McDonald ω coefficients showed good reliability.

Conclusions:

The instrument can be used to assess digital competence and identify the development needs to facilitate educators’ continuous professional development.