bluuebunny/crossref_metadata_2025 huggingface dataset:
The Affective Bind
Authors: Fretwell Erica
Published: November 2024

This essay considers the raucous ontology of the feeling body in relation to the expanding field of affect studies. It first shows how psychophysics established an aspirational template for reconciling empiricism and metaphysics—and how contemporary affect theory, which implicitly advances that template, circles the same aporetic bind as psychophysics: that affect, no matter its neurobiological mechanisms, is a metaphysical substance that cannot yield to science. The essay then considers what stories emerge when sentimentality, which thinks feeling in relation to social structures rather than psychological or neurological structures, is taken as a key (Americanist) origin story of affect theory. One such story is “anaesthetics,” or an art of slight living that creatively exploits modes of insentience as a scene of intimacy, not unlike two sleepers sharing a bed. By way of Nella Larsen’s Quicksand and Ottessa Moshfegh’s My Year of Rest and Relaxation, anaesthetics responds to historical crises of obstructed agency by advancing a politics of unlived experience that regards killing rather than reclaiming time, evacuating rather than enriching selfhood, as a means of holding onto the world.
The Moving Finger Writes: Book/Media Histories in our Moment
Authors: Bross Kristina
Published: November 2024

This review-essay reflects on Amy Gore’s monograph Book Anatomy and the collection Handwriting in Early America, edited by Mark Alan Mattes. These two recent publications on book and media history sparked this meditation on how tools for unpacking history texts and technologies can be surprisingly useful for addressing the challenges that generative AI poses to questions of authorship and intellectual property today. Bross explores how Book Anatomy and Handwriting in Early America help us understand the ways in which written texts, especially printed works and, even more, works produced under colonization, are always produced through collaborative systems of unequal power. These systems include writers—both humans and (it may be) algorithmic compositors—and readers who accept, endorse, resist, or recast what they read. As readers, we are implicated in the systems that produce the materials that we consume. Making these activities visible to ourselves can help address the past as we make new media history in our moment.
Weird Century
Authors: Marshall Kate
Published: November 2024

Has the world become weirder? This is a question that a reader of twentieth-century fiction might ask, perhaps especially a reader of realist novels. These novels, as I argue in my recent book Novels by Aliens, evince a genre creep of science fiction, fabulism, and the weird that contends with the fractured and competing crises of our time. By extending this argument through a set of contemporary novellas, I discuss why genre is functioning as an important critical resource for twenty-first-century writing and how the form of the novella focuses genre debates on problems of scale and attention.
Transforming carbon-intensive coal-fired power plants into negative emission technologies via biomass-fired calcium looping retrofit
Authors: Hanak Dawid P
Published: November 2024

Calcium looping is a promising CO2 capture technology due to reduced energy and economic penalties compared to mature solvent scrubbing technologies. It also can enable negative CO2 emissions when biomass is used to drive the sorbent regeneration process in the calciner. However, the trade-off between the energy, economic and environmental performance under different biomass co-firing fractions in the calciner and process operating scenarios has not yet been well understood. This study examined the potential for transforming a 580 MWel coal-fired power plant into a negative CO2 emitter via retrofit of calcium looping with biomass co-firing in the calciner. High-fidelity process models were developed in Aspen Plus and used to analyse the effect of biomass co-firing fraction, CO2 capture rate in the carbonator, and the fraction of flue gas fed to the carbonator on the techno-economic performance indicators. The results revealed that co-firing 30% biomass with coal in the calciner was sufficient for the retrofitted process to achieve negative CO2 emissions (−3.9 gCO2/kWelh). In this scenario, the levelized cost of electricity was 5% lower (81.1 €/MWelh) than that in the reference retrofit scenario without biomass co-firing (85.4 €/MWelh) at a carbon tax of 100 €/tCO2. Further improvement to the techno-economic performance was achieved by reducing the amount of CO2 captured in the carbonator by reducing either the CO2 capture rate (81.1 €/tCO2) or the amount of flue gas processed (80.4 €/tCO2). Although this was achieved at the expense of the increased specific CO2 emissions to 65.2 gCO2/kWelh and 109.0 gCO2/kWelh, respectively, the net specific emissions were still about 90% lower than those of the unabated host plant (792.3 gCO2/kWelh). This study demonstrated that depending on design priorities, biomass co-firing in the calciner can transform the existing coal-fired power plants into negative CO2 emission technologies or improve the process techno-economic viability.
Janus kinase inhibitor adverse event profiles in dermatology patients: the experience of two academic medical centres
Authors: Lim Subin , Oke Oluwadamilola H , Cunningham Kaitlynne N , Chau Courtney , Sidky Lillian , Cange Bridget , LaChance Avery H , Cobos Gabriela A
Published: November 2024

Janus kinase inhibitors (JAKi) are increasingly being utilized for both Food and Drug Administration-approved and off-label treatments in dermatology. However, JAKi carry a black box warning concerning major side effects, including serious infections, cardiovascular events, thrombosis, malignancy and mortality. Given that there is an absence of large-scale studies examining the adverse event (AE) profile of multiple JAKi for dermatological conditions in real-world settings, our study aimed to bridge this gap by evaluating AEs of dermatology patients on oral JAKi at two academic medical centres.
Toward effective learning of cybersecurity: new curriculum agenda and learning methods
Authors: Blažič Andrej Jerman , Blažič Borka Jerman
Published: November 2024

A recent survey among high school teachers and students in the EU revealed that cybersecurity topics are not included in the programs addressing computer science topics of European schools and that the teachers’ knowledge is not being upgraded regularly for this field. Based on an exhaustive study in 2021–2023 involving high schools in the EU a definition of the educational content and the aligned methodology for high school levels was developed for two areas: cyber-safety and cybersecurity. Available sources, including video platforms, quizzes, presentations, educational games, and hands-on sources for practical exercises, were evaluated and included in the developed fiches with the educational content. The applicability of the developed educational model and the content prepared for upgrading the high school teachers and their student’s knowledge was applied in nine European schools during the 2022–2023 school year. This paper describes the study, briefly presents the educational content, the class preparation and the assessment of the achieved learning objectives obtained with the surveys, interviews, and the Capture the Flag contest. The paper ends with an evaluation of the developed methodology and the usefulness of the approach. Recommendations for future use and development are included in the last paper section.
Successful management of complete heart block in checkpoint inhibitor induced myocarditis by left bundle branch area pacing: a case report
Authors: Meyers Michael , Balf Dragos , Raza Mohammad Q , Liu Xiaoke
Published: November 2024

Background

Optimal management of checkpoint inhibitor-induced complete heart block is unknown. Previous reports showed relatively high incidence of pacing failure due to the co-existing myocarditis.

Case summary

A 71-year-old male with a prior history of stage IV metastatic squamous cell lung cancer presents was admitted for dyspnoea and hypotension 10 days after checkpoint inhibitor treatment using pembrolizumab. He was found to have myocarditis, third-degree AV block, severe left ventricular systolic dysfunction with EF 35%, and required pressure support. A dual chamber pacemaker using left bundle branch area pacing (LBBAP) was urgently placed that immediately improved his haemodynamics. Both the cathode and anode were able to capture the ventricle at different pacing outputs. The patient was taken off all intravenous pressors and successfully transferred to a larger centre for further management of the myocarditis with no further arrhythmia or hypotension.

Discussion

In conclusion, because of the unique ability to capture a large amount of myocardium from both the tip and ring electrodes as well as the ability to deliver cardiac resynchronization therapy, LBBAP may be the preferred pacing strategy in patients who develop complete heart block due to checkpoint inhibitor-induced myocarditis.
Concomitant myocardial infarction and systemic embolism associated with thrombosis of the right coronary ostium: a case report
Authors: Fuchs Flávio Danni , Amon André Barcellos , Borges Aníbal Pires , Fuchs Felipe Costa , Gonçalves Sandro Cadaval
Published: November 2024

Background

Sequential occurrences of acute ischaemic stroke in patients with acute myocardial infarction (MI) and vice versa have been reported, but not the simultaneous occurrence of both conditions. We report a case of simultaneous occurrence of MI and systemic embolism caused by a mechanism not reported to date.

Case summary

A 52-year-old female patient presented with concurrent chest pain, right arm weakness, and dysphasia. An electrocardiogram demonstrated ST-elevation MI. A computed tomography angiography ruled out aortic dissection and showed an ischaemic stroke and infarction in the right kidney and spleen. A right coronary thrombotic occlusion at the ostium was successfully recanalized. Transoesophageal echocardiography showed preserved left ventricular function with no intracardiac thrombi.

Discussion

The reported case presentation does not align with the mechanisms typically associated with simultaneous MI and stroke. The most plausible hypothesis is that the thrombus in the right coronary ostium extended into the aorta, resulting in a concurrent systemic embolism.
Characterizing the spatial correlation of coseismic slip distributions: a data driven Bayesian approach
Authors: Marchant-Cáceres G , Benavente R , Becerra-Carreño V , Crempien J G F , Morales-Yañez C
Published: November 2024

The spatial correlation of coseismic slip is a necessary input for generating stochastic seismic rupture models, which are commonly used in seismic and tsunami hazard assessments. To date, the spatial correlation of individual earthquakes is characterized using finite fault models by finding the combination of parameters of a von Kármán autocorrelation function that best fits the observed autocorrelation function of the finite fault model. However, because a priori spatial correlation conditions (i.e. not in the data) are generally applied in finite fault model generation, the results obtained using this method may be biased. Additionally, robust uncertainty estimates for spatial correlations of coseismic slip are generally not performed. Considering these limitations in the classic method, here, a method is developed based on a Bayesian formulation of Finite Fault Inversion (FFI) with positivity constraints. This method allows for characterizing the spatial correlation of coseismic slip and its uncertainties for an earthquake by using samples of coseismic slip from a posterior probability density function (PDF). Furthermore, a Bayesian model selection criterion called Akaike Bayesian Information Criterion (ABIC) is applied to objectively choose between different prior spatial correlation schemes before computing the posterior, to reduce subjectivity due to this prior condition. The ABIC is calculated using an approximate analytical expression of Bayesian evidence. The method is applied to simulated P waves, demonstrating that model selection allows for objectively estimating the most suitable prior spatial correlation scheme in FFI. Additionally, the target spatial correlation of coseismic slip is accurately recovered using samples from the posterior PDF, as well as their uncertainties. Moreover, in the simulated experiment, it is shown that a non-robust choice of the prior spatial correlation scheme can significantly bias the estimated spatial correlations of coseismic slip. We apply our method to observed P waves from the 2015, Illapel earthquake ($M_{\rm w} = 8.3$), finding that the spatial correlation of coseismic slip of this earthquake is better described by a von Kármán ACF, with mean correlation lengths of around 47 km and Hurst parameter of 0.58. We conclude that using our method reduces biases associated with prior spatial correlation conditions and allows for robust estimation of spatial correlations of coseismic slip and their uncertainties.
The Decentralisation of the DMA’s Enforcement System
Authors: Ribera Martínez Alba
Published: November 2024

The harmonisation of the internal market is a fundamental aspect of the EU acquis, and the Digital Markets Act (DMA) is no exception. It aims to harmonise digital markets across the Union on the basis of the concepts of contestability and fairness. The DMA is enforced through a quasi-centralised enforcement system, with the European Commission as its sole enforcer and national competition authorities (NCAs) playing a secondary and supporting role in monitoring. The EC’s centralisation of enforcement powers is key to ensuring harmonisation.

This paper highlights the potential risks at the national level due to NCA involvement in the enforcement and monitoring of the DMA. While the Regulation does not need to be transposed into national law to be effective, some Member States have introduced legislation specifying which authorities are responsible for enforcement and how they should apply their powers in line with the DMA. The paper examines these legislative developments, revealing potential deviations that undermine the effective enforcement of the DMA and disrupting its current centralised enforcement system.
How economists influence antitrust: the contributions of Tim Bresnahan, Janusz Ordover, Steve Salop, and Bobby Willig
Authors: Baker Jonathan B
Published: November 2024

Economists influence antitrust policy through theoretical and empirical economic research, translation and synthesis of that research, direct participation in policy development, and participation in the adversarial process. To illustrate these channels, this article profiles the antitrust-related work of four industrial organization economists who have played important roles in the development of antitrust economics and policy: Tim Bresnahan, Janusz Ordover, Steve Salop, and Bobby Willig. The article also evaluates three overarching theories about the role of economics in antitrust: a public interest theory, capture by big business, and influence tied to the ascendancy of neoliberalism.
Production of a cellulose-aminating polysaccharide from a filamentous sulfur-oxidizing bacterium, Thiothrix nivea, grown lithotrophically or mixotrophically
Authors: Saito Tomoaki , Qiao Yunkun , Araki Yui , Matsunaga Naoki , Osugi Wataru , Kondo Keiko , Katahira Masato , Takeda Minoru
Published: November 2024

Aims

Glucosaminoglucan (β-1,4-linked glucose and glucosamine) produced by a mixotrophic sulfur-oxidizing bacterium, Thiothrix nivea, is a useful cellulose-aminating agent. Lithotrophic and mixotrophic glucosaminoglucan production were examined using fed-batch techniques.

Methods and results

A jar fermenter was used for the fed-batch cultivation. Glucosaminoglucan was extracted from T. nivea using diluted HCl. Lithotrophic growth was detected by feeding with Na2S as the energy source, and 12 mg l−1 of glucosaminoglucan was obtained. In contrast, no growth was observed with Na2S2O3. Similarly, mixotrophic growth in the presence of acetic acid was promoted by Na2S, whereas Na2S2O3 had no effect. When acetic acid and Na2S were added, 470 mg l−1 of glucosaminoglucan was obtained.

Conclusions

Thiothrix nivea was cultured, and glucosaminoglucan was produced lithotrophically using Na2S for feeding. Na2S is also indispensable for mixotrophic growth and glucosaminoglucan production, indicating that sulfide oxidation pathways control the TCA cycle. The involvement of the SOX pathway (for thiosulfate oxidation) in the activation of energy metabolism is doubtful because neither lithotrophic nor mixotrophic growth was promoted by Na2S2O3. Based on these results, we assumed that T. nivea is facultatively mixotrophic [lithotrophic growth is possible in addition to organotrophic growth in the presence of sulfide (Na2S)], rather than obligately mixotrophic.
Matter power spectra in modified gravity: a comparative study of approximations and N-body simulations
Authors: Bose B , Gupta A Sen , Fiorini B , Brando G , Hassani F , Baker T , Lombriser L , Li B , Ruan C , Hernández-Aguayo C , Atayde L , Frusciante N
Published: November 2024

Testing gravity and the concordance model of cosmology, $\Lambda$CDM, at large scales is a key goal of this decade’s largest galaxy surveys. Here we present a comparative study of dark matter power spectrum predictions from different numerical codes in the context of three popular theories of gravity that induce scale-independent modifications to the linear growth of structure: nDGP, Cubic Galileon, and K-mouflage. In particular, we compare the predictions from N-body simulations solving the full scalar field equation, two N-body codes with approximate time integration schemes, a parametrized modified N-body implementation, and the analytic halo model reaction approach. We find the modification to the $\Lambda$CDM spectrum is in 2 per cent agreement at $z\le 1$ and $k\le 1~h\,{\rm Mpc}^{-1}$ over all gravitational models and codes, in accordance with many previous studies, indicating these modelling approaches are robust enough to be used in forthcoming survey analyses under appropriate scale cuts. We further make public the new code implementations presented, specifically the halo model reaction K-mouflage implementation and the relativistic Cubic Galileon implementation.
Clinical Significance of Hyponatremia in Tuberculous Meningitis: A Prospective Cohort in Indonesia
Authors: Dian Sofiati , Ardiansyah Edwin , Chaidir Lidya , van Laarhoven Arjan , Ruslami Rovina , Alisjahbana Bachti , Rizal Ganiem Ahmad , van Crevel Reinout
Published: November 2024

Background

Hyponatremia is common in tuberculous meningitis (TBM), but its impact on disease severity and outcomes is unclear.

Methods

In a cohort of 864 adult patients with TBM in Indonesia, we assessed the prevalence and prognostic significance of hyponatremia, classified as moderate (120–130 mEq/L) or severe (<120 mEq/L). Patients received standard antituberculous therapy and corticosteroids and were followed for 1-year mortality.

Results

Hyponatremia occured in 86.8% of patients, with 26% classified as severe. Severe hyponatremia associated with male, younger age, a lower Glasgow Coma Scale (GCS), and markers of more severe disease (P < .05). One-year mortality was 46.5% and associated with older age, HIV infection, lower GCS, markers of neurologic severity, fever, and thrombocytosis. Severe hyponatremia predicted mortality in univariate analysis showed no impact in HIV-positive patients.

Conclusions

Hyponatremia reflects disease severity in TBM but does not independently predict mortality, suggesting limited benefit from agressive correction.
The protective role of basal metabolic rate in cognitive decline: evidence from epidemiological and genetic studies
Authors: Meng Tianwei , Liu Changxing , Wang Boyu , Li Chengjia , Liu Jiawen , Chen Jia , Ma Yidi , Qie Rui
Published: November 2024

Purpose

This study aims to explore the relationship between basal metabolic rate (BMR) and cognitive impairment and assess the potential of BMR as a protective factor against cognitive decline.

Methods

This investigation initially conducted a cross-sectional study of American adults from 2011 to 2014 using data from the National Health and Nutrition Examination Survey. It examined the correlation between participants’ BMR and cognitive functions, exploring the association with cognitive impairment. Subsequently, publicly available genome-wide association study data was used to examine potential causal links between genetically determined BMR and specific cognitive disorders using Mendelian randomization.

Results

Cross-sectional findings revealed a significant positive correlation between higher BMR and cognitive scores. In Mendelian randomization analysis, BMR demonstrated an inverse causal relationship with Alzheimer’s disease and Parkinson’s dementia, suggesting BMR as a potential protective factor against these diseases. No causal links were found with vascular dementia, Lewy body dementia, and frontotemporal dementia.

Conclusion

This study supports the role of BMR as a potential protective factor against Alzheimer’s disease and Parkinson’s dementia, suggesting that BMR may play an important role in preventing cognitive decline. However, due to the limitations of cross-sectional studies, further prospective studies and broader demographic samples are necessary to verify these results and explore underlying biological mechanisms.

Key messages What is already known on this topic: Existing knowledge suggests a close relationship between BMR and health and cognitive functions, but detailed studies on its connection with specific cognitive impairments are still needed. What this study adds: This study found a significant positive correlation between higher BMR and cognitive improvement, potentially aiding in the prevention of Alzheimer’s and Parkinson’s dementia. How this study might affect research, practice, or policy: This finding guides public health strategies and personalized medicine, emphasizing the necessity for further research to validate BMR’s protective effects.
Private Sanitation and Psychosocial Health in Adolescent Girls
Authors: Miller Ray , Mudenda Lackson D , Sedai Ashish K , Vilims Lauren
Published: November 2024

The relationship between access to private sanitation facilities at home and psychosocial development is documented among adolescents aged 12 to 22 in India and Ethiopia. Obtaining access to private sanitation (flush toilets or pit latrines in the household) is associated with significantly higher self-efficacy and self-esteem for adolescent girls but not boys. Associations are stronger for girls who lived in communities with higher overall access to private sanitation, consistent with the hypothesis that relative access may matter more for psychosocial development than absolute access. There was also a significant correlation with improved peer relations for girls in early (age 12 to 15) but not late (age 19 to 22) adolescence. However, there is no evidence that results are operating through improved physical health or parent relationships.
Predictors of Participation in Prenatal Substance Use Assessment, Counseling, and Treatment Among Pregnant Individuals in Prenatal Settings Who Use Cannabis
Authors: Lapham Gwen T. , Chi Felicia W. , Young-Wolff Kelly C. , Ansley Deborah , Castellanos Carley , Does Monique B. , Asyyed Asma H. , Ettenger Allison , Campbell Cynthia I.
Published: November 2024

Objectives

Assessment and counseling are recommended for individuals with prenatal cannabis use. We examined characteristics that predict prenatal substance use assessment and counseling among individuals who screened positive for prenatal cannabis use in prenatal settings.

Methods

Electronic health record data from Kaiser Permanente Northern California’s Early Start perinatal substance use screening, assessment, and counseling program was used to identify individuals with ≥1 pregnancies positive for prenatal cannabis use. Outcomes included completion of a substance use assessment and among those assessed, attendance in Early Start counseling only or Addiction Medicine Recovery Services (AMRS) treatment. Predictors included demographics and past-year psychiatric and substance use disorder diagnoses evaluated with GEE multinomial logistic regression.

Results

The sample included 17,782 individuals with 20,398 pregnancies positive for cannabis use (1/2011–12/2021). Most pregnancies (80.3%) had an assessment. Individuals with Medicaid, anxiety, depression and tobacco use disorders, compared to those without, had higher odds and those with greater parity, older age (≥35) and in later trimesters, had lower odds of assessment. Among 64% (n = 10,469) pregnancies needing intervention based on assessment, most (88%) attended Early Start counseling only or AMRS (with or without Early Start). Greater parity and later trimester assessment was associated with lower odds, while Medicaid was associated with higher odds of Early Start counseling. Nearly all diagnosed psychiatric and substance use disorders were associated with higher odds of AMRS treatment.

Conclusions

A comprehensive prenatal substance use program engaged most pregnant individuals with prenatal cannabis use in substance use assessment and counseling. Opportunities to improve care gaps remain.
Evaluating the Accuracy and Clinical Utility of AFIAS-10 Point of Care Versus Enzyme-Linked Immunosorbent Assay in Therapeutic Drug Monitoring of Infliximab and Adalimumab
Authors: Iniesta-Navalón Carles , Ríos-Saorín Manuel , Añez-Castaño Rebeca , Rentero-Redondo Lorena , Ortíz-Fernandez Patricia , Marín-Armero Martínez Elena , Urbieta-Sanz Elena
Published: November 2024

Background:

New point-of-care (POC) techniques offer rapid results and address some of the limitations of traditional enzyme-linked immunosorbent assay (ELISA) methods, such as lengthy processing times and delays in therapeutic decision making. It is crucial to evaluate the comparability of POC assays with established ELISA methods to ensure accuracy and reliability in therapeutic drug monitoring. This study aimed to evaluate the analytical performance and clinical utility of the AFIAS-10 POC assay compared with the Promonitor ELISA for quantifying serum concentrations of infliximab (IFX) and adalimumab (ADA) and detecting antidrug antibodies (ATIs and ATAs).

Methods:

A prospective study was conducted from October 2023 to April 2024, including 225 samples from patients with immune-mediated diseases. The samples were analyzed using both AFIAS-10 POC and Promonitor ELISA assays. To assess the agreement between the 2 methods in terms of quantification, Bland–Altman analysis was performed by examining the mean difference and establishing limits of agreement.

Results:

The Pearson correlation coefficient indicated strong correlations for IFX (r = 0.932) and ADA (r = 0.967) between the 2 assays. The mean difference between POC and ELISA for IFX was −0.78 mcg/mL and for ADA was 1.54 mcg/mL, respectively. The POC assay tended to underestimate IFX concentrations and overestimate ADA concentrations compared with ELISA.

Conclusions:

The AFIAS-10 POC assay demonstrated good correlation and concordance with the ELISA method for the quantification of IFX and ADA, as well as for detecting anti-IFX and anti-ADA antibodies. However, this correlation was notably lower at higher drug concentrations.
Gene Polymorphisms Play an Important Role in the Drug Interaction Between Posaconazole and Tacrolimus in Renal Transplant Patients
Authors: Hu Nan , Guan Mengmeng , Gu Bin , Yang Xuping , Qian Qing , Zhao Di , Xue Hui , Jiang Jingting
Published: November 2024

Background:

Posaconazole (POSA), a second-generation triazole antifungal drug, inhibits CYP3A and P-glycoprotein. Here, the interaction between POSA and tacrolimus (TAC) in patients undergoing early renal transplantation was studied.

Methods:

Twenty-two renal transplant recipients who received POSA as antifungal therapy were studied. The following indicators were analyzed statistically: the blood concentration (C), dose (D), and concentration–dose ratio (C/D) of TAC before and after introducing POSA; the change of C/D (ΔC/D) after starting POSA; the genotypes of CYP3A5*3, ABCB1 3435, ABCB1 1236, and POR*28; other routine clinical indicators.

Results:

After starting POSA, the C, D, and C/D values of TAC were 1.29, 0.57, and 2.74 times the original values, respectively. A linear correlation was observed between the plasma levels of POSA and ΔC/D. The CYP3A5*3 gene polymorphism showed a significant impact on C, D, and C/D of TAC; however, it did not affect the ΔC/D. Polymorphism of the ABCB1 3435 gene had a significant effect on ΔC/D, and patients with the CC genotype in ABCB1 3435 had significantly lower ΔC/D than the CT/TT patients.

Conclusions:

In renal transplant patients, considerable interindividual variability was observed in the drug interactions between POSA and TAC. The genotypes of CYP3A5*3 and ABCB1 3435 and the plasma level of POSA had strong impact on the interaction between POSA and TAC.
Lacosamide Pharmacokinetics and Retention in Japanese Patients With Epilepsy: A Retrospective Study on the Influence of Age, Comedications, and Cytochrome P450 2C19 Polymorphism
Authors: Yamamoto Yoshiaki , Shiratani Yuka , Nishida Takuji , Usui Naotaka , Kagawa Yoshiyuki , Takahashi Yukitoshi , Imai Katsumi
Published: November 2024

Background:

This retrospective study aimed to identify the genetic and nongenetic factors that influence serum lacosamide (LCM) concentrations and evaluate the effects of cytochrome P450 2C19 (CYP2C19) polymorphism on the long-term retention rate of LCM.

Methods:

We analyzed serum samples from 1901 Japanese patients with epilepsy and compared the concentration-to-dose (CD) ratio of LCM among 4 age groups (preschool children, 1–5 years; primary school children, 6–11 years; adolescents, 12–17 years; and adults, ≥18 years). In addition, we performed CYP2C19 genotyping using real-time polymerase chain reaction in 302 patients and classified them into 3 groups: extensive metabolizers (EM: CYP2C19*1/*1), intermediate metabolizers (IM: CYP2C19*1/*2 or *1/*3), and poor metabolizers (PM: CYP2C19*2/*2, *3/*3, or *2/*3). We compared the LCM retention rates between the non-PM (EM and IM) and PM groups using the Kaplan–Meier method.

Results:

The adult group had the highest mean CD ratio, which was 33.7%, 21.9%, and 7.3% higher than that of preschool children, school children, and adolescents, respectively. The use of enzyme-inducing antiseizure medications (ASMs; ie, phenytoin, phenobarbital, or carbamazepine) reduced the CD ratio by 34.0% in preschool children, 27.3% in primary school children, 24.3% in adolescents, and 27.4% in adults. In adults, the mean CD ratios were 17.7% and 49.0% higher in the IM and PM groups, respectively, than in the EM group. The 3-year retention rate of LCM was higher in the non-PM group than in the PM group (881 vs. 728 days; log-rank test, P < 0.05).

Conclusions:

Age and the concomitant use of enzyme-inducing ASMs influence LCM pharmacokinetics. In addition, patients with the PM phenotype have a high LCM CD ratio, which may decrease treatment retention. Therapeutic drug monitoring for LCM is a clinically useful method for evaluating pharmacokinetics in individual patients and optimizing the dose of LCM.
Utilization of Recipient Veins with Reflux During Supermicrosurgical Lymphaticovenous Anastomosis for Lower Limb Lymphedema
Authors: Patanè Luca , Kuo Pao-Jen , Ou Yu-Che , Chang Chad , Wu Shao-Chun , Lin Wei-Che , Chien Peng-Chen , Hsieh Ching-Hua , Yang Johnson Chia-Shen
Published: November 2024

Background:

The use of recipient veins with venous reflux for lymphaticovenous anastomosis (LVA) is discouraged because it is commonly believed that it may lead to venous-lymphatic reflux (VLR). VLR is a phenomenon in which venous blood is refluxed into the lymphatic lumen after anastomosis, potentially lowering the long-term patency rate. However, this concept is yet to be validated. This study aimed to determine the impact on outcomes when recipient veins with reflux were used for LVA in treating unilateral lower limb lymphedema.

Study design:

Seventy-nine patients who underwent LVA as the primary treatment were enrolled. The study group included 31 patients who used only recipient veins with reflux. An additional 48 patients (control group) utilized only reflux-free veins. Patients with a history of previous LVA, liposuction, or excisional therapy were excluded. Patient characteristics, intraoperative findings, functional parameters, and pre-and post-LVA volume changes were recorded and matched using propensity score matching. The primary endpoint was the volume change at 6 and 12 months after LVA.

Results:

After matching, 28 patients were included in each group. All parameters were matched except the study variables, where the study group demonstrated significantly higher venous reflux (p < 0.001) and VLR ratio (p < 0.001). However, at the 6- and 12-month follow-up, the postoperative percentage volume reduction was comparable between the groups (p = 0.385 and 0.391, respectively).

Conclusion:

When reflux-free veins are unavailable, using recipient veins with reflux for LVA is recommended.
Delineating bacterial genera based on gene content analysis: a case study of the Mycoplasmatales–Entomoplasmatales clade within the class Mollicutes
Authors: Yan Xiao-Hua , Pei Shen-Chian , Yen Hsi-Ching , Blanchard Alain , Sirand-Pugnet Pascal , Baby Vincent , Gasparich Gail E. , Kuo Chih-Horng
Published: November 2024

Genome-based analysis allows for large-scale classification of diverse bacteria and has been widely adopted for delineating species. Unfortunately, for higher taxonomic ranks such as genus, establishing a generally accepted approach based on genome analysis is challenging. While core-genome phylogenies depict the evolutionary relationships among species, determining the correspondence between clades and genera may not be straightforward. For genotypic divergence, the percentage of conserved proteins and genome-wide average amino acid identity are commonly used, but often do not provide a clear threshold for classification. In this work, we investigated the utility of global comparisons and data visualization in identifying clusters of species based on their overall gene content and rationalized that such patterns can be integrated with phylogeny and other information such as phenotypes for improving taxonomy. As a proof of concept, we selected 177 representative genome sequences from the Mycoplasmatales–Entomoplasmatales clade within the class Mollicutes for a case study. We found that the clustering patterns corresponded to the current understanding of these organisms, namely the split into three above-genus groups: Hominis, Pneumoniae and Spiroplasma–Entomoplasmataceae–Mycoides. However, at the genus level, several important issues were found. For example, recent taxonomic revisions that split the Hominis group into three genera and Entomoplasmataceae into five genera are problematic, as those newly described or emended genera lack clear differentiations in gene content from one another. Moreover, several cases of misclassification were identified. These findings demonstrated the utility of this approach and its potential application to other bacteria.
Animal-encoded nonribosomal pathway to bursatellin analogs
Authors: Venugopalan Aarthi , Schmidt Eric W.
Published: November 2024

The bursatellin-oxazinin family is a series of tyrosine-derived, nitrile-containing marine natural products from gastro-pod and bivalve molluscs. Although the first analogs were identified and associated with toxicity forty years ago, their biosynthetic origins were unknown. During an investigation of published mollusc genomes and transcriptomes, we serendipitously identified a putative bursatellin biosynthetic gene cluster (referred hereafter as thebur-oxpathway). Through biochemical characterization of somebur-oxgenes, we provide evidence suggesting that bursatellin-type metabolites are produced by molluscs themselves rather than by their microbial symbionts. We show that the reductive domain from a monomodular nonribosomal peptide synthetase (NRPS) protein FmtATR performs a four-electron reduction to produce tyrosinols from tyrosine derivatives. Moreover, an aminocarboxypro-pyltransferase enzyme, ACT, usesS-adenosylmethionine (SAM) to transform tyrosinols into their phenolic homoserine ethers, which in bursatellin is further modified to the nitrile. Widespread occurrence ofbur-oxin molluscs suggests a common biosynthetic origin for bursatellins and oxazinins as well as an important but currently unidentified physiological role for this metabolite family in molluscs inhabiting diverse ecological niches. Further, the presence ofbur-oxpathway homologs in many culinary bivalves such as mussels and geoducks suggests that possible impacts on human consumers should be investigated. As one of the few NRPS pathways of animal origin to be characterized,bur-oxsheds light on underappreciated chemical and biochemical diversity in animals.
Impact of astrocytic C3-production on neuronal mitochondrial dysfunction in tauopathy mouse models
Authors: Lei Chenxu , Zhang Bocheng , Yamaguchi Junji , Tamura Risako , Cao Xingyu , Liu Yunhui , Seki Masahide , Suzuki Yutaka , Suzuki Kuninori , Tanida Isei , Uchiyama Yasuo , Hisatsune Tatsuhiro
Published: November 2024

Neuronal mitochondrial dysfunction is associated with cognitive decline in neurodegenerative disorders such as Alzheimer’s Disease (AD). In this study, multiple pieces of evidence proved that phosphorylated tau (p-Tau) caused mitochondrial swelling and dysfunction in neurons. In a novelin vitronewborn neurons culture system, we discovered mitochondrial swelling and dysfunction were associated with increased p-Tau, leading to necroptosis activation, which was induced by Complement C3 (C3) produced from activated astrocytes. In thein vivotauopathy mouse models, the effects of astrocytic C3 on tau-associated mitochondrial dysfunction and necroptosis were also discovered in hippocampal newborn neurons, and we directly showed that p-Tau aggregation was associated with mitochondria swelling in the hippocampal neurons by electron microscopy analysis. In addition, we proved the ability of compound anserine, which can block Tak1-Ikk dependent NF-κB activation, to further down-regulate astrocytic C3 production and alleviate neuronal mitochondrial dysfunctionin vitroandin vivo, respectively. Down-regulation of astrocyte C3-production by anserine could also rescue mortality as well as cognitive and motor functions. Our findings first reported the contribution of p-Tau on neuronal mitochondrial dysfunction and proposed the therapies that down-regulate astrocytic C3 production have a potential role in alleviating this neurotoxic effect.
The circadian gene Dec2 promotes pancreatic cancer dormancy by regulating tumor cell antigen presentation to facilitate immune evasion
Authors: Harris Chris R. , Wang Lan , Dudgeon Crissy , Prela Orjola , Cazarin de Menezes Juliana , Shih Ching-Hua , Davidson Christina , Casabianca Anthony , De Subhajyoti , Narrow Wade , Becker Jennifer , Balachandran Vinod P. , Grandgenett Paul M , Hollingsworth Michael A. , Grem Jean L. , Kim Minsoo , Hong Yeonsun , Gerber Scott , Vertino Paula M. , Gao Chongfeng , Repesh Anna , Klamer Zachary , Hao Yansheng , Altman Brian , Haab Brian , Carpizo Darren R.
Published: November 2024

The mechanisms that regulate cancer dormancy remain poorly understood. Using a mouse model of resectable pancreatic adenocarcinoma (PDAC), we identified Dec2 as a gene that was upregulated in metastatic dormant tumor cells. Deletion of Dec2 from tumor cells substantially increased mouse survival after resection due to an immune-mediated mechanism as the survival benefit was abrogated in immunodeficient conditions. Dec2 promoted immune evasion by repressing multiple components of the MHC-I dependent antigen presentation pathway in tumor cells. Dec2 is a regulator of circadian rhythms, and we found several components of the antigen presentation pathway oscillated in a circadian manner that was lost upon deletion of Dec2. Moreover, T-cell mediated tumor cell killing varied depending on the time of day. We suggest that lowered MHC-I presentation of antigens during rest phase is a natural effect of the circadian clock, which is exploited by Dec2-overexpressing pancreatic tumors to evade the immune system.
Functional Connectivity Alterations in Cocaine Use Disorder: Insights from the Triple Network Model and the Addictions Neuroclinical Assessment Framework
Authors: Xu Ziyang , Li Lie , Liu Ruobing , Azzam Mohamed , Wan Shibiao , Wang Jieqiong
Published: November 2024

Cocaine use disorder (CUD) disrupts functional connectivity within key brain networks, specifically the default mode network (DMN), salience network (SN), and central executive network (CEN). While the triple network model has been proposed to explain various psychiatric disorders, its applicability to CUD requires further exploration. In the present study, we built machine learning classifiers based on different combinations of DMN/SN/CEN to distinguish cocaine-use disorder (CUD) subjects from healthy control (HC) subjects. Among them, the combination of the SN and the CEN results in a remarkably high accuracy of 73.4% (sensitivity/specificity: 69.6%/78.6%, AUC: 0.78), outperforming the model based on the full triple network. This supports the hypothesis that during the binge/intoxication stage of addiction, the SN and the CEN play a more critical role than the DMN, consistent with the Addictions Neuroclinical Assessment (ANA) framework. Functional connectivity analysis revealed decreased connectivity within the DMN and the SN and increased connectivity within the CEN in CUD patients, suggesting that alterations in these networks could serve as biomarkers for addiction severity.
Morphological brain alterations and morphological brain network disorganizations in heroin and methamphetamine abstinent patients
Authors: Zhou Xiaoliang , Zhang Zhifu , Yuan Haitao , Wang Yuzhou , Xu Ziyu , Liang Wenbin , Lou Mingwu
Published: November 2024

Heroin and methamphetamine are the two common types of drugs abused, which poses significant health risks. However, the neural mechanisms underlying the effects of drug addiction on human brain are unclear. In this study, we collected T1-weighted magnetic resonance imaging data from 26 heroin abstinent (HA) patients, 24 methamphetamine abstinent (MA) patients and 32 healthy controls. Four surface-based morphological features including cortical thickness (CT), fractal dimension (FD), gyrification index (GI), and sulcal depth (SD) were calculated, and further used to construct the morphological brain networks. We observed the common CT reductions of the right TE 1.0 and TE 1.2 and SD reductions of the right intermediate lateral area 20 for HA and MA patients, HA-specific CT reductions in the left area 2, and the MA-specific GI reductions in the left medial area 6 and right dorsomedial parietooccipital sulcus. For the morphological brain networks, HA patients exhibited the global disorganizations (higher shortest path length) in CT-based networks, whereas MA patients showed the disrupted nodal efficiency of the left medial area 38 in CT-based networks, the right caudal area 7 in GI-based networks, and the right inferior occipital gyrus in SD-based networks. Furthermore, the altered SD of HA patients and disrupted nodal efficiency of MA patients were associated with drug abuse-related clinical variables. Our findings suggest the morphological index-dependent effects of drug addiction on human brain morphology, and indicate the differential neural mechanism underlying heroin and methamphetamine abuses which attack the global and local information transfer of morphological brain networks, respectively.
Bridging Genomic Gaps: The Pan-Grass Syntenic Gene Set in Grass Crop Evolution
Authors: Dias Henrique M , Sagawa Guilherme YA , Torres-Rodriguez Vladimir J , Mural Ravi V , Schnable James C , Van Sluys Marie-Anne
Published: November 2024

Understanding orthologous and homeologous relationships among genes can inform our understanding of how evolution and artificial selection have shaped the genomes of related species to adapt to different niches and produce different phenotypes. High-confidence information on orthologous relationships can also increase the impact of the functional characterization in one species by ensuring this information is available to researchers studying orthologs in other species. The grasses are ecologically and economically critical plants, and many genes are conserved in syntenic blocks between species. Here we leverage that conserved gene order to create and describe the Pan-Grass Syntenic Gene Set (PGSGS), a curated database of orthologous and homeologous relationships among the genes of 17 grass species, including both major and orphan crops as well as wild grasses. As a demonstration of the utility of the PGSGS, the dynamics of chromosome structure and gene content changes after polypoidy in several grass lineages are analyzed. This dataset serves as a seminal foundation for improving our understanding of genome evolution subsequent to polyploidy, as well as encouraging and enabling integration of functional genetic and functional genomic information across the grasses, the original promise of the “grasses as a single genetic system” model.

SIGNIFICANCE STATEMENT

The Pan-Grass Syntenic Gene Set (PGSGS) leverages our understanding of the genomic background of major grass species, including rice, maize, sorghum, wheat, barley, millet, and sugarcane. It represents a milestone for deciphering the genetic foundations of essential traits such as yield, disease resistance, and environmental adaptability - key factors contributing to agriculture and food security. Scrutinizing pan-syntenic genes unveils the intricate interplay of diverse gene acquisition and loss mechanisms, potentially speeding molecular breeding knowledge transference. The PGSGS emerges as a valuable resource for gene annotation, with implications for improving grass crops.