bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishing a new-onset diabetes-related metabolism signature for predicting the prognosis and immune landscape in pancreatic cancer
Authors: Yang Yilei , Liu Luyao , Cui Haochen , Cheng Bin , Peng Wang , Wang Ronghua , Wang Jinlin , Chen Wei , Cao Mengdie , Li Yanling , Liang Jingwen , Chen Shiru , Bai Shuya , Zhao Yuchong
Published: November 2024

New-onset diabetes (NOD) is a common condition among patients with pancreatic adenocarcinoma (PAAD) and is related to poor clinical outcomes. The potential impact of NOD on PAAD progression and the tumor microenvironment remains unclear. Here, we revealed that NOD in PAAD was associated with metabolic disorders. Utilizing three machine-learning algorithms, an NOD-related metabolism signature (NRMS) was established. Validated in three independent cohorts, patients with a high NRMS score exhibited a worse prognosis. Moreover, an elevated NRMS score was associated with an immunosuppressive microenvironment and diminished response to immunotherapy. Further experiments demonstrated that ALDH3A1, a key feature in NRMS, was significantly upregulated in tissues from PAAD patients with NOD and played a crucial role in tumor progression and immune suppression. Our findings highlight the potential of NRMS as a prognostic biomarker and an indicator of immunotherapy response for patients with PAAD.
Coeliac disease risk doubles in patients with alopecia areata: a nationwide case–control study
Authors: Wohl Yonit , Mashiah Jacob , Drutin Yarden , Ben-Tov Amir
Published: November 2024

Alopecia areata (AA) and coeliac disease (CD) are both common immune-mediated diseases. Despite increasing evidence of bidirectional associations between the two diseases, the data remain unclear and inconsistent. Here, we explored the association between AA and CD in a large representative population cohort. Patients diagnosed with AA between 2005 and 2019 were compared with age-matched and gender-matched healthy controls for coeliac autoimmunity. In total, 33 401 patients with AA and 66 802 controls were included in the analysis. Overall, 754 patients (0.75%) had CD. Compared with controls, CD prevalence was twofold higher among patients with AA (1.1% vs. 0.6%, odds ratio 1.95, 95% confidence interval 1.69–2.25). A higher prevalence of CD was observed in patients with AA among all age groups, with the highest risk in patients with AA who were aged 40 years or more. AA may be associated with a significantly increased risk of CD, suggesting the need for early diagnostic and preventive measures.
Specific inhibition and disinhibition in the higher-order structure of a cortical connectome
Authors: Reimann Michael W , Egas Santander Daniela , Ecker András , Muller Eilif B
Published: November 2024

Neurons are thought to act as parts of assemblies with strong internal excitatory connectivity. Conversely, inhibition is often reduced to blanket inhibition with no targeting specificity. We analyzed the structure of excitation and inhibition in the MICrONS $mm^{3}$ dataset, an electron microscopic reconstruction of a piece of cortical tissue. We found that excitation was structured around a feed-forward flow in large non-random neuron motifs with a structure of information flow from a small number of sources to a larger number of potential targets. Inhibitory neurons connected with neurons in specific sequential positions of these motifs, implementing targeted and symmetrical competition between them. None of these trends are detectable in only pairwise connectivity, demonstrating that inhibition is structured by these large motifs. While descriptions of inhibition in cortical circuits range from non-specific blanket-inhibition to targeted, our results describe a form of targeting specificity existing in the higher-order structure of the connectome. These findings have important implications for the role of inhibition in learning and synaptic plasticity.
Neuronal fate resulting from indirect neurogenesis in the mouse neocortex
Authors: Hatanaka Yumiko , Yamada Kentaro , Eritate Tomoki , Kawaguchi Yasuo , Hirata Tatsumi
Published: November 2024

Excitatory cortical neurons originate from cortical radial glial cells (RGCs). Initially, these neurons were thought to derive directly from RGCs (direct neurogenesis) and be distributed in an inside-out fashion. However, the discovery of indirect neurogenesis, whereby intermediate neuronal progenitors (INPs) generate neurons, challenged this view. To investigate the integration of neurons via these two modes, we developed a method to identify INP progeny and analyze their fate using transgenic mice expressing tamoxifen-inducible Cre recombinase under the neurogenin-2 promoter, alongside thymidine analog incorporation. Their fate was further analyzed using mosaic analysis with double markers in mice. Indirect neurogenesis was prominent during early neurogenesis, generating neuron types that would emerge slightly later than those produced via direct neurogenesis. Despite the timing difference, both neurogenic modes produced fundamentally similar neuron types, as evidenced by marker expression and cortical-depth location. Furthermore, INPs generated pairs of similar phenotype neurons. These findings suggest that indirect neurogenesis, like direct neurogenesis, generates neuron types in a temporally ordered sequence and increases the number of similar neuron types, particularly in deep layers. Thus, both neurogenic modes cooperatively generate a diverse array of neuron types in a similar order, and their progeny populate together to form a coherent cortical structure.
A General Strategy to Rapid and Sensitive Determination of Five High Boiling Point Solvents in Pharmaceuticals by RP-HPLC Combined with Precipitation Method
Authors: Zhang Chenxia , Wu Zeyi , Qiu Meiyan , Li Yanhua , Wang Zhongqing , Fan Xiaomei , Cai Shaoyu , Rao Wanbing
Published: November 2024

The difficulty on determination of high boiling point solvents, always exist due to their low vapor pressure in headspace (HS) vial. What’s worse, the commonly used GC diluents, such as N, N-dimethylacetamide, 1,3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, N, N-dimethylformamide and N-methylpyrrolidone are often remained in HS instrument after frequent injection into HS, thus would result in terrible positive interference problem. In this work, a fast and sensitive HPLC method in combination with a sample precipitation method, was proposed for the determination of above five high boiling point solvents in drug substances within 14.5 min. The final method was validated with regard to limit of detection and limit of quantitation, precision, linearity and accuracy in accordance with ICH Q2 (R1). Finally, the proposed strategy was successfully applied for the analysis of high boiling point solvents used in three active pharmaceutical ingredients. The established generic strategy would provide another choice for the determination of high boiling point solvents in pharmaceuticals.
Alleviation of COVID-19 Symptoms and Reduction in Healthcare Utilization Among High-risk Patients Treated With Nirmatrelvir/Ritonavir (NMV/R): A Phase 3 Randomized Trial
Authors: Hammond Jennifer , Leister-Tebbe Heidi , Gardner Annie , Abreu Paula , Bao Weihang , Wisemandle Wayne , Ansari Wajeeha , Harrington Magdalena Alicja , Simón-Campos Abraham , Chew Kara W , Pypstra Rienk , Rusnak James M
Published: November 2024

Background

Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral treatment for mild to moderate coronavirus disease 2019 (COVID-19).

Methods

This phase 2/3, double-blind, randomized (1:1) study assessed oral NMV/r 300 mg/100 mg versus placebo every 12 hours for 5 days in high-risk, unvaccinated, nonhospitalized, symptomatic adults with COVID-19 from 343 sites across 21 countries. In testing the primary endpoint of COVID-19‒related hospitalization and all-cause deaths and key secondary endpoints, including symptom duration and COVID-19‒related medical visits, type I error was controlled with prespecified sequential testing and the Hochberg procedure.

Results

Among 2113 randomized patients enrolled from July 2021 through December 2021, 1966 (NMV/r, n = 977; placebo, n = 989) were included in the prespecified analysis population (symptom onset ≤5 days, did not receive monoclonal antibodies). NMV/r significantly reduced times to sustained alleviation (median, 13 vs 15 days; hazard ratio = 1.27, P < .0001) and resolution (16 vs 19 days; hazard ratio = 1.20, P = .0022) through day 28 and significantly reduced the number of COVID-19‒related medical visits and the proportion of patients with such visits. Hospitalized patients treated with NMV/r had shorter stays, none required intensive care unit admission or mechanical ventilation, and all were discharged to home/self-care. Fewer NMV/r-treated patients required additional treatment for COVID-19. No NMV/r-treated patients died through week 24 compared with 15 placebo-treated patients.

Conclusions

In addition to reducing COVID-19‒related hospitalization or death from any cause through day 28, NMV/r was found to also reduce duration of COVID-19 symptoms and utilization of healthcare resources versus placebo in patients at high risk of progressing to severe disease.

Clinical Trial Information

ClinicalTrials.gov, NCT04960202, https://clinicaltrials.gov/study/NCT04960202
High VExUS grades are linked to cardiac function in general intensive care unit patients
Authors: Andrei Stefan , Nguyen Maxime , Bouhemad Belaid , Guinot Pierre-Grégoire
Published: November 2024

Aims

Even though initially considered as a new standard in systemic venous congestion assessment, the semi-quantitative Doppler ultrasound-based venous excess ultrasound grading system (VExUS) showed inconsistent associations with outcomes in general intensive care unit (ICU) patients. It is unclear why VExUS is so effective in predicting outcomes in some cohorts and not in others. The determinants of higher VExUS have not been studied in a general ICU cohort. The aim of this study was to determine the factors associated with higher VExUS (≥ 2) in a general ICU cohort.

Methods and results

We performed a post-hoc analysis of a prospective, observational cohort, including adult patients within 24 h of ICU admission and expected ICU length of stay longer than 2 days. Collected data included patients’ haemodynamic status (including ultrasound evaluation) at several points in time: ICU admission, Day 1, Day 2, Day 5, and the last day of ICU stay. We analysed 514 haemodynamic evaluations in 145 patients. In total, 96/514 (18.7%) had a VExUS grade ≥ 2. The univariable followed by multivariable mixed-effects logistic regression analyses only found a statistically significant association between VExUS ≥ 2 and right ventricle S wave [OR 0.85 (0.74;0.97), P = 0.02] and left ventricle E/A ratio [OR 2.34, 95% CI (1.27;4.33), P = 0.006].

Conclusion

The current study has elucidated that higher VExUS is primarily associated with cardiac comorbidities and ultrasound parameters of left- and right-sided cardiac systolic and/or diastolic function in general ICU patients.
Pulmonary involvement in transthyretin cardiac amyloidosis: a case report
Authors: Kellens Michiel , Nijst Petra , Ameloot Koen , Mullens Wilfried , Bertrand Philippe , Jannis Levi , Van Dorpe Jo , Dupont Matthias
Published: November 2024

Background

Amyloidosis is a systemic disorder characterized by the deposition of misfolded proteins in various organs. While cardiac transthyretin amyloidosis (ATTR) is well-recognized, pulmonary involvement is rare and often overlooked in clinical practice.

Case summary

We present a case of severe, and ultimately fatal, cardiac and pulmonary ATTR amyloidosis in a 67-year-old male. The patient’s initial complaints included dyspnoea and exercise intolerance. Echocardiography revealed isolated concentric left ventricular hypertrophy, and subsequent cardiac MRI suggested cardiac amyloidosis. Additional diagnostic steps, including bone scan and endomyocardial tissue biopsy, confirmed the diagnosis of ATTR amyloidosis. Intriguingly, this case also unveiled concurrent pulmonary involvement, characterized by ground-glass opacities, lymphadenopathy, and impaired lung function. Despite treatment with tafamidis, the patient’s condition deteriorated swiftly. He was admitted to the hospital four months after his initial presentation, and ultimately succumbed to therapy-resistant respiratory distress and heart failure. Post-mortem examination revealed extensive cardiac and pulmonary interstitial ATTR amyloidosis, with the lung exhibiting a fibrotic stage of diffuse alveolar damage.

Discussion

This case highlights pulmonary involvement as a potential contributor to the clinical picture of ATTR amyloidosis. It also emphasizes the necessity for a multidisciplinary approach, heightened awareness, and further research to enhance the detection and management of pulmonary involvement in ATTR amyloidosis.
Diabetes and obesity: leveraging heterogeneity for precision medicine
Authors: Franks Paul W , Sargent Jennifer L
Published: November 2024

The increasing prevalence of diabetes, obesity, and their cardiometabolic sequelae present major global health challenges and highlight shortfalls of current approaches to the prevention and treatment of these conditions. Representing the largest global burden of morbidity and mortality, the pathobiological processes underlying cardiometabolic diseases are in principle preventable and, even when disease is manifest, sometimes reversable. Nevertheless, with current clinical and public health strategies, goals of widespread prevention and remission remain largely aspirational. Application of precision medicine approaches that reduce errors and improve accuracy in medical and health recommendations has potential to accelerate progress towards these goals. Precision medicine must also maintain safety and ideally be cost-effective, as well as being compatible with an individual’s preferences, capabilities, and needs. Initial progress in precision medicine was made in the context of rare diseases, with much focus on pharmacogenetic studies, owing to the cause of these diseases often being attributable to highly penetrant single gene mutations. By contrast, most obesity and type 2 diabetes are heterogeneous in aetiology and clinical presentation, underpinned by complex interactions between genetic and non-genetic factors. The heterogeneity of these conditions can be leveraged for development of approaches for precision therapies. Adequate characterization of the heterogeneity in cardiometabolic disease necessitates diversity of and synthesis across data types and research methods, ideally culminating in precision trials and real-world application of precision medicine approaches. This State-of-the-Art Review provides an overview of the current state of the science of precision medicine, as well as outlining a roadmap for study designs that maximise opportunities and address challenges to clinical implementation of precision medicine approaches in obesity and diabetes.
Atrial fibrillation substrate and impaired left atrial function: a cardiac MRI study
Authors: Chahine Yaacoub , Chamoun Nadia , Kassar Ahmad , Bockus Lee , Macheret Fima , Akoum Nazem
Published: November 2024

Aims

Structural and fibrotic remodelling is a well-known contributor to the atrial fibrillation (AF) substrate. Epicardial adipose tissue (EAT) is increasingly recognized as a contributor through electrical remodelling in the atria. We aimed to assess the association of LA fibrosis and EAT with LA strain and function using cardiac magnetic resonance (CMR) imaging in patients with AF.

Methods and results

LA fibrosis was assessed using late gadolinium enhancement CMR, LA EAT was assessed using the fat-water separation Dixon sequence, and feature tracking was applied to assess global longitudinal strain in its three components [reservoir (GLRS), conduit (GLCdS), and contractile (GLCtS)]. LA emptying fraction and LA volume were measured using the cine sequences. All CMR images were acquired in sinus rhythm. One hundred one AF patients underwent pre-ablation CMR (39% female, average age 62 years). LA fibrosis was negatively associated with the three components of global longitudinal strain (GLRS: R = −0.35, P < 0.001; GLCdS: R = −0.24, P = 0.015; GLCtS: R = −0.2, P = 0.046). Out of the different sections of the LA, fibrosis in the posterior and lateral walls was most negatively correlated with GLRS (R = −0.32, P = 0.001, and R = −0.33, P = 0.001, respectively). LA EAT was negatively correlated with GLCdS (R = −0.453, P < 0.001). LA fibrosis was negatively correlated with LA emptying fraction but LA EAT was not (R = −0.27, P = 0.007, and R = −0.22, P = 0.1, respectively). LA EAT and fibrosis were both positively correlated with LA volume (R = 0.38, P = 0.003, and R = 0.24, P = 0.016, respectively).

Conclusion

LA fibrosis, a major component of the AF substrate, and EAT, an important contributor, are associated with a worsening LA function through strain analysis by CMR.
Policing Europe: The Origins of a European Security Network, 1794–1815
Authors: Haidinger Brendan W
Published: November 2024

The spread of revolutionary ideas reconfigured the machinery of surveillance within the Habsburg state between the Jacobin Trials of 1794 and the Congress of Vienna in 1815. The Habsburg Ministry of Police emerged from the Jacobin Trials with enlarged administrative capabilities, including a new relationship between the secret state police and the military and the increased surveillance of urban working populations. Not only that, but the period also witnessed a push to monitor subversive political activity in foreign territory, including Poland, the Ottoman Empire, the German states and Italy. This article argues that cooperation among European states in the policing of subversive political activity across borders antedated the Congress of Vienna. A focus on these critical decades questions the viability of the ‘Metternichian System’ and points instead to a growing security apparatus that Metternich sought to further internationalize after 1815.
CAT Bridge: an efficient toolkit for gene–metabolite association mining from multiomics data
Authors: Yang Bowen , Meng Tan , Wang Xinrui , Li Jun , Zhao Shuang , Wang Yingheng , Yi Shu , Zhou Yi , Zhang Yi , Li Liang , Guo Li
Published: November 2024

Background

With advancements in sequencing and mass spectrometry technologies, multiomics data can now be easily acquired for understanding complex biological systems. Nevertheless, substantial challenges remain in determining the association between gene–metabolite pairs due to the nonlinear and multifactorial interactions within cellular networks. The complexity arises from the interplay of multiple genes and metabolites, often involving feedback loops and time-dependent regulatory mechanisms that are not easily captured by traditional analysis methods.

Findings

Here, we introduce Compounds And Transcripts Bridge (abbreviated as CAT Bridge, available at https://catbridge.work), a free user-friendly platform for longitudinal multiomics analysis to efficiently identify transcripts associated with metabolites using time-series omics data. To evaluate the association of gene–metabolite pairs, CAT Bridge is a pioneering work benchmarking a set of statistical methods spanning causality estimation and correlation coefficient calculation for multiomics analysis. Additionally, CAT Bridge features an artificial intelligence agent to assist users interpreting the association results.

Conclusions

We applied CAT Bridge to experimentally obtained Capsicum chinense (chili pepper) and public human and Escherichia coli time-series transcriptome and metabolome datasets. CAT Bridge successfully identified genes involved in the biosynthesis of capsaicin in C. chinense. Furthermore, case study results showed that the convergent cross-mapping method outperforms traditional approaches in longitudinal multiomics analyses. CAT Bridge simplifies access to various established methods for longitudinal multiomics analysis and enables researchers to swiftly identify associated gene–metabolite pairs for further validation.
Glacial hydro-isostatic adjustment at mid-ocean ridges
Authors: Reilly Jackson , Latychev Konstantin , Coulson Sophie , Mitrovica Jerry X
Published: November 2024

Recent studies have suggested a link between ice age sea level fluctuations and variations in magma production and crustal faulting along mid-ocean ridges based on the detection of Milankovitch cycle frequencies in topography off several ridges. These fluctuations have also been connected to variability in hydrothermal metal fluxes near ridges. Ice age sea level calculations have shown that the sea level change across glacial cycles will be characterized by significant geographic variability, that is, departures from eustasy, due to the gravitational, deformation and rotational effects of the glacial isostatic adjustment (GIA) process. Using a state-of-the-art GIA simulation that incorporates 3-D variations in Earth viscoelastic structure, including plate boundaries and updated constraints on the magnitude and geometry of ice mass fluctuations, we predict global sea level changes from last glacial maximum (LGM, 26 ka) to present and from the penultimate glacial maximum (143 ka) to the last interglacial (128 ka). We focus on the results along three ridges: the Mid-Atlantic Ridge, Juan de Fuca Ridge and East Pacific Rise, which are examples of slow, intermediate and fast spreading ridges, respectively. Sea level change across the Mid-Atlantic Ridge shows the greatest variability, ranging from a sea level fall greater than 200 m in Iceland to a maximum rise of ∼150 m in the South Atlantic, with significant non-monotonicity north of the Equator as the ridge weaves across the field of sea level changes. We also calculate changes in crustal normal stress from LGM to present-day across the Mid-Atlantic and Juan de Fuca Ridges and the East Pacific Rise. These results indicate that the contribution from ice mass changes to the crustal stress field can be significant well away from the location of ancient ice complexes. We conclude that any exploration of the hypothesized links to magma production and crustal faulting must consider both ocean and ice loading effects and, more generally, the profound geographic variability of the GIA process.
A full genome assembly reveals drought stress effects on gene expression and metabolite profiles in blackcurrant (Ribes nigrum L.)
Authors: Ziegler Freya Maria Rosemarie , Rosenthal Vivien , Vallarino Jose G , Genzel Franziska , Spettmann Sarah , Seliga Łukasz , Keller-Przybyłkowicz Sylwia , Munnes Lucas , Sønsteby Anita , Osorio Sonia , Usadel Björn
Published: November 2024

Blackcurrant (Ribes nigrum L., family Grossulariaceae) is a perennial shrub that is widely cultivated for its edible berries. These are rich in antioxidants, vitamin C, and anthocyanins, making them a valuable ingredient in the food and beverage industry. However, prolonged periods of drought during the fruiting season lead to drought stress, which has serious ecological and agricultural implications, inhibiting blackcurrant growth and reducing yields. To facilitate the analysis of underlying molecular processes, we present the first high-quality chromosome-scale and partially haplotype-resolved assembly of the blackcurrant genome (cv. Rosenthals Langtraubige), also the first in the family Grossulariaceae. We used this genomic reference to analyze the transcriptomic response of blackcurrant leaves and roots to drought stress, revealing differentially expressed genes with diverse functions, including those encoding the transcription factors bZIP, bHLH, MYB, and WRKY, and tyrosine kinase-like kinases such as PERK and DUF26. Gene expression was correlated with the abundance of primary metabolites, revealing 14 with significant differences between stressed leaves and controls indicating a metabolic response to drought stress. Amino acids such as proline were more abundant under stress conditions, whereas organic acids were depleted. The genomic and transcriptomic data from this study can be used to develop more robust blackcurrant cultivars that thrive under drought stress conditions.
Optimizing energy hubs with a focus on ice energy storage: a strategic approach for managing cooling, thermal, and electrical loads via an advanced slime mold algorithm
Authors: Hai Tao , Shami Hayder Oleiwi , Saleh Sami Abdulhak , Agarwal Diwakar , Rajab Husam , Mahmood Ahmed Mohammed , Hussein Abbas Hameed Abdul , Hasan Dheyaa Flayih , Mushtaq Hiba , Singh Narinderjit Singh Sawaran
Published: November 2024

Amidst the increasing incorporation of multicarrier energy systems in the industrial sector, this article presents a detailed stochastic methodology for the optimal operation and daily planning of an integrated energy system that includes renewable energy sources, adaptive cooling, heating, and electrical loads, along with ice storage capabilities. To address this problem, it applies the 2 m + 1 point estimation method to accurately assess system uncertainties while minimizing computational complexity. The “2 m + 1 point” technique swiftly evaluates unpredictability through Taylor series calculations, capturing deviations in green energy output, and the demand for both electric and thermal energy across power networks, while also considering the oscillating costs associated with senior energy transmission systems. In addition, this article proposes a novel self-adaptive optimization technique, called the enhanced self-adaptive mucilaginous fungus optimization algorithm (SMSMA), dedicated to overcoming the intricate nonlinear challenges inherent in the optimal daily operation of an energy system. The advanced self-adaptive strategy relies on wavelet theory to enhance the capability and effectiveness of the original mucilaginous fungus algorithm in optimizing daily schedules for an integrated energy system. Numerical analyses demonstrate that the introduced stochastic daily scheduling framework, coupled with the SMSMA optimization algorithm, effectively reduces the operating costs of the energy system.
Boosting energy markets in grid with a focus on battery storage, including flexible loads and electric vehicles, via a two-stage optimization framework
Authors: Hai Tao , Shami Hayder Oleiwi , El-Sharkawy Mohamed R , Agarwal Diwakar , Ahmed Mohsen , Mohammed Adil Ismaeel , Abdul Hussein Abbas Hameed , Hasan Dheyaa Flayih , Mushtaq Hiba , Sawaran Singh Narinderjit Singh
Published: November 2024

This paper introduces a detailed dual-level structure designed for the efficient organization of energy and supportive service markets throughout transport and delivery systems. The framework delineates the organization of energy markets at the first level and supportive services at the second. Traditional thermal units serve as providers for the spinning reserve market, while rapid response generators, energy storage systems, electric vehicles, and demand response aggregators supply capacity adjustments. Simulations applied to a 30-bus transmission network linked to four 8-bus distribution networks show that integrating distribution network resources in the spinning reserve market reduces reliance on thermal units by 22%, decreasing daily operational costs by approximately 15%. Furthermore, including demand response aggregators, storage systems, and electric vehicles in market regulation improves voltage profiles by 7%. The framework is constructed as a linear optimization model and simulated using the CPLEX solver in GAMS software.
Abnormal behavior analysis of distribution automation system terminal based on multi-modal data fusion
Authors: Ma Tianxiang , Zhang Tuo , Shen Hongliang , Duan Xin , Zhang Zizi
Published: November 2024

In distribution automation systems, detecting terminal abnormal behaviors is crucial for stability and reliability. Traditional methods struggle with insufficient feature extraction and weak generalization when handling multi-modal data. Thus, an anomaly detection method based on self-attention convolutional neural network (SA-CNN) is proposed, integrating the strengths of self-attention mechanisms and convolutional networks to enhance detection capabilities. Experiments on the IEEE PHM dataset demonstrate superiority over traditional CNN and ARIMA algorithms, achieving accuracy, recall, and F1 scores of 0.928, 0.936, and 0.932, respectively. Future work aims to improve model efficiency and performance.
Creativity, credit, and copyright in the age of artificial art
Authors: Moore Joseph G , Frankel Simon J
Published: November 2024

Generative artificial intelligence is transforming the way we make, and think about, art. With prompting from human users, these generative systems now produce aesthetically compelling and seemingly creative works in a variety of artistic domains. In doing so, they challenge the ways we think about artistic credit, about creativity, and about the mechanism of legal copyright, which is meant to protect and promote creativity in a capitalist art market. All of this is currently at play in the courtroom, as artists contest the ways in which their artworks can be rightfully fed into these artificial systems (“the problem of the inputs”), and other artists are challenged over whether they might be credited for the visual images these systems generate (“the problem of the outputs”). Here, we explore these problems as they arise in visual art. We argue that the contested legal landscape surrounding these artificial systems reflects the ways they challenge our received notions of artistic credit and creativity. And we suggest that clarifying or changing the application of copyright in light of their generative capacities will ultimately involve revising our conception of art.
Validation of the Level 2 Modification for the Neogen® Molecular Detection Assay 2—Salmonella Enteritidis/Salmonella Typhimurium Method for Detection of the Monophasic Variant Salmonella enterica

1

,4,[5],12:-:1,2. AOAC Performance Tested MethodSM 122302
Authors: Le Quynh-Nhi , Tsuhako Vanessa , Mozola Mark
Published: November 2024

Background

The Neogen® Molecular Detection Assay 2—Salmonella Enteritidis/Salmonella Typhimurium (MDA2-SE/ST) method, Performance Tested MethodSM (PTM) 122302, is a nucleic acid amplification test for specific detection of Salmonella enterica ser. Enteritidis (SE) and Salmonella enterica ser. Typhimurium (ST), including the ST monophasic variant Salmonella enterica  1,4,[5],12: i:-, in select poultry samples. Results for SE and ST are generated separately.

Objective

The objective of the study was to validate the MDA2-SE/ST method for detection of an additional monophasic variant of ST, S. enterica  1,4,[5],12:-:1,2.

Methods

A single strain of S. enterica  1,4,[5],12:-:1,2 was tested as part of a seven-strain inclusivity/exclusivity test panel. Strains were tested after growth in two enrichment media used in the method, buffered peptone water (BPW) and buffered peptone water, ISO formulation (BPW-ISO), and at two incubation temperatures, 35 ± 2°C and 41.5 ± 1°C.

Results

S. enterica  1,4,[5],12:-:1,2 produced positive results in the ST assay and negative results in the SE assay in both enrichment media and at both incubation temperatures. Results for the other six test strains were as expected under all conditions.

Conclusions

The MDA2-SE/ST method can detect the monophasic variant S. enterica  1,4,[5],12:-:1,2 as well as S. enterica ser. Typhimurium and the monophasic variant S. enterica  1,4,[5],12: i:-. The MDA2-SE/ST method maintains inclusiveness for S. enterica ser. Typhimurium despite flagellar antigen variation.

Highlights

The data were reviewed by the AOAC PTM Program and approval was granted for modification of the MDA2-SE/ST method, PTM 122302.
Low feed intake at weaning reduces intestinal glutathione levels and promotes cysteine oxidation to taurine in pigs
Authors: Gachman Alexandra M , Outlaw Alex C , Newell Brooke , Bartosh Julia , Rudar Marko
Published: November 2024

Weaning stress in pigs is associated with low feed intake and poor nutrient utilization. Cysteine is a sulfur amino acid with key roles in pig production, but how cysteine metabolism and requirements are affected by weaning stress should be better defined. The objective of this study was to determine the collective impact of weaning and feed restriction on tissue cysteine metabolism. Pigs were weaned at 21-d age without access to feed (W; 6.90 ± 0.81 kg; n = 9; reflecting acute nutritional stress) or were not weaned and remained with the sow (nonweaned [NW]; 6.81 ± 0.65 kg; n = 8). At euthanasia (23-d age), blood, bile, liver, jejunum, and ileum tissues were collected. Plasma, bile, and tissue amino acid and amino thiol concentrations were analyzed by HPLC. The activity of glutamate cysteine ligase (GCL) and glutathione synthetase (GSS), enzymes needed for glutathione (GSH) production, and cysteine dioxygenase 1 (CDO1) were determined with activity assays followed by HPLC analysis of reaction products. Plasma (271 vs. 192 ± 19 µmol/L; P < 0.001) and liver (417 vs. 298 ± 33 nmol/g; P < 0.05) Cys concentrations were increased in W compared to NW pigs. Despite greater plasma Cys, jejunum and ileum Cys content were not affected by weaning (P > 0.10), whereas γ-glutamylcysteine (γ-GlyCys), the immediate precursor of GSH, declined in both jejunum (14.3 vs. 9.7 ± 1.4 nmol/g; P < 0.01) and ileum (11.2 vs. 6.4 ± 0.8 nmol/g; P < 0.001) in W pigs. Glutathione content was lower in the jejunum (1,379 vs. 1,720 ± 70 nmol/g; P < 0.05) and ileum (1,497 vs. 1,740 ± 74 nmol/g; P < 0.05) in W pigs. In the jejunum, GCL activity tended to be greater (0.56 vs. 0.39 ± 0.07 nmol γ-GluCys • mg−1 • min−1; P < 0.10), whereas GSS activity tended to be lower (1.11 vs. 1.38 ± 0.10 nmol GSH • mg−1 • min−1; P < 0.10) in W compared to NW pigs. In the ileum, the activities of GCL and GSS were not affected by weaning (P > 0.10). Although liver CDO1 activity was not different between groups (P < 0.10), liver taurine was greater in W compared to NW pigs (5,115 vs. 2,336 ± 912 nmol/g; P = 0.001). Bile concentrations of Cys (1,203 vs. 279 ± 103 µmol/L; P < 0.001) and cysteinylglycine (203 vs. 117 ± 33 µmol/L; P < 0.10), the direct product of GSH degradation, were greater in W compared to NW pigs. Collectively, these results suggest that systemic Cys is not effectively utilized for gut GSH production in newly weaned pigs; instead, it is oxidized to taurine and eliminated in bile.
Lysine specific demethylase 1 conditional myeloid cell knockout mice have decreased osteoclast differentiation due to increased IFN-β gene expression
Authors: Astleford-Hopper Kristina , Abrahante Llorens Juan E , Bradley Elizabeth W , Mansky Kim C
Published: November 2024

Osteoclasts are large multinucleated cells that degrade bone mineral and extracellular matrix. Investigating the epigenetic mechanisms orchestrating osteoclast differentiation is key to our understanding of the pathogenesis of skeletal related diseases such as periodontitis and osteoporosis. Lysine specific demethylase 1 (LSD1/KDM1A) is a member of the histone demethylase family that mediates the removal of mono- and dimethyl groups from H3K4 and H3K9 to elicit dichotomous effects on gene expression. Prior to our study, little was known about the contributions of LSD1 to skeletal development and osteoclast differentiation. Here we show that conditional deletion of Lsd1 within the myeloid lineage or macrophage/osteoclast precursors results in enhanced bone mass of male and female mice accompanied by diminished osteoclast size in vivo. Furthermore, Lsd1 deletion decreased osteoclast differentiation and activity within in vitro assays. Our bulk RNA-SEQ data suggest Lsd1 ablation in male and female mice inhibits osteoclast differentiation due to enhanced expression of interferon-β target genes. Lastly, we demonstrate that LSD1 forms an immune complex with HDAC1 and HDAC2. These data suggest that the combination of methylation and acetylation of histone residues, facilitated by LSD1, mechanistically promotes osteoclast gene expression.
Population density estimates and conservation status of Aegla jacutinga Marçal & Teixeira, 2020 (Decapoda: Anomura: Aeglidae) from the type locality in Brazil
Authors: Silva Ana B O , Frazato Priscila S R , Arantes Tiago , Bueno Sergio L S , Marçal Ingrid C , Mantelatto Fernando L , Teixeira Gustavo M
Published: November 2024

Anomuran crabs of the genus AeglaLeach, 1821 are endemic to temperate and subtropical regions of South America and are commonly found in streams and rivers, where they are generally restricted to healthy environments because they are sensitive to environmental changes. The genus presents worrying data regarding its conservation, like the many Brazilian freshwater species classified as being at some level of threat of extinction. We inventoried unexplored watersheds, estimated the population density of Aegla jacutinga Marçal & Teixeira, 2020 in its type locality, updated information on the distribution of the species, and assessed its conservation status using IUCN criteria.
Exploring the importance of stochasticity to hybrid equilibria in a discrete signaling game
Authors: Chisausky Jacob , Zollman Kevin , Ruxton Graeme
Published: November 2024

Communication via evolved signals is ubiquitous (both within and between species) in the natural world. However, how honest we should expect signals to be remains an open question. Hybrid equilibria are a form of equilibria predicted by discrete signaling games in which signalers are sometimes dishonest and signals do not completely reliably convey information on signaler quality. While these equilibria have been theoretically demonstrated in several signaling games, their dynamics in a stochastic simulation of evolutionary trajectories (that include representation of the inherent noise expected in evolution in the natural world) have not previously been studied. In this paper, we present an agent-based simulation of a discrete signaling game which exhibits hybrid equilibria. We find that while hybrid equilibria are evolutionarily attractive where they exist, populations exhibit variable and often drastic oscillating behavior around the predicted equilibrium values. We discuss how these dynamics might offer valuable opportunity for detecting hybrid equilibria in natural populations.
Strategic honey bee hive placement improves honey bee visitation but not pollination in northern highbush blueberry
Authors: Brouwer Kayla , Eeraerts Maxime , Rogers Emma , Goldstein Lauren , Perkins Jacquelyn A , Milbrath Meghan O , Melathopoulos Andony , Meyer Jason , Kogan Clark , Isaacs Rufus , DeVetter Lisa Wasko
Published: November 2024

Commercial blueberry Vaccinium spp. (Ericales: Ericaceae) production relies on insect-mediated pollination. Pollination is mostly provided by rented honey bees, Apis mellifera L. (Hymenoptera: Apidae), but blueberry crop yields can be limited due to pollination deficits. Various hive placement strategies have been recommended to mitigate pollination shortfalls, but the effect of hive placement has received limited formal investigation. This study explores the effects of clumped and dispersed hive placement strategies on honey bee visitation and pollination outcomes in “Bluecrop” and “Duke” fields over 2 years (2021 and 2022) within 2 economically important regions of production in the United States—the Midwest (Michigan) and Pacific Northwest (Oregon and Washington). Clumping hives consistently increased honey bee visitation rate but did not result in higher fruit set, fruit weight, or seed count. Increases in honey bee visitation through clumping could perhaps improve pollination outcomes in more pollination-limited blueberry cultivars and other pollination-dependent crops. Clumping hives is substantially more efficient and cost-effective for beekeepers due to fewer drop locations and could lead to cost savings for both beekeepers and blueberry growers without growers sacrificing pollination levels and crop yields.
Migration response to an immigration shock: evidence from Russia’s aggression against Ukraine
Authors: Zuchowski David
Published: November 2024

This article examines the impact of the massive and unexpected inflow of Ukrainians that resulted from Russia’s aggression in 2014 on local migration patterns in Poland. For identification, I use an instrumental variable approach drawing on unique historical data on the forced resettlement of Ukrainians in Poland after World War II. The results show that the regional inflow of immigrants, while crowding out internal in-migration, decreases both internal and international out-migration of the local population. I provide supportive evidence that the decrease in out-migration is due to an enlargement of local labor markets.
The unavoidable CJEU Kwantum judgment
Authors: Rosati Eleonora
Published: November 2024

In autumn 2024, the Court of Justice of the European Union (CJEU) issued its judgment in Kwantum, C-227/23. Endorsing the Opinion of Advocate General (AG) Szpunar in the same case, the Court held that EU Member States do not enjoy any freedom to set their own reciprocity clauses under Article 2(7) of the Berne Convention: in this field, the competence vests with the EU and not (or rather: no longer) individual Member States. Like the AG, the decision further confirms that any work protected by copyright—including works of applied art—must only satisfy a requirement of originality, this also being a harmonized notion under EU law. The outcome of the referral from the Dutch Supreme Court was both unavoidable and unsurprising having regard to settled CJEU case law in the field of copyright, well beyond the immediate ‘precedent’ set by RAAP, C-265/19. On a broader level, it shows how a ‘Union copyright’ does not only exist but also extends well beyond the formal legislative framework.
Management of the Inflatable Penile Prosthesis Reservoir at time of revision surgery: remove, retain, or recycle?
Authors: Amini Armon D , Nealon Samantha W , Badkhshan Shervin , Langford Brian T , Matz Ethan L , VanDyke Maia E , Franzen Bryce P , Morey Allen F
Published: November 2024

Background

Three common strategies exist for managing the inflatable penile prosthesis reservoir during revision surgery: the original reservoir can be (a) removed, (b) deactivated and left in situ, sometimes referred to as “drain and retain” (DR), or (c) validated and reconnected to new cylinders, which we have termed “reservoir recycling” (RR).

Aim

To compare the efficacy and safety of the RR approach to penile prosthesis revision against DR and the recommended approach of complete device removal and replacement.

Methods

A retrospective chart review of our single-surgeon inflatable penile prosthesis database between 2007 and 2022 was performed, identifying revision surgeries. Cases were stratified by reservoir management technique. Patients who had undergone at least 1 follow-up visit and had complete documentation regarding reservoir handling were included. Reservoir-related complications necessitating surgical intervention such as infection and device failure were compared between the 3 groups using a chi-square test. Mean follow-up duration, time to revision, and operative time were also assessed.

Outcomes

The primary outcome was the incidence of reservoir-related complications requiring surgical intervention and secondary outcomes included time to revision surgery and operative time.

Results

Among 140 patients meeting inclusion criteria, 62 underwent full reservoir replacement (FR), 48 DR, and 30 RR. Compared to FR, DR and RR groups had similar mean time to revision and intraoperative time. Follow-up duration was similarly limited for all 3 groups at a median of approximately 4.5 months. There were no postoperative infections in the RR cohort. However, when compared to the DR and FR groups, this did not reach significance (P = .398). There was no difference in mechanical failure rate between the 3 groups (P = .059). Nonmechanical failure was also similar between all 3 groups (P = .165).

Clinical Implications

These results suggest that RR exhibits comparable outcomes to DR and FR, making it a viable option during select penile prosthesis revision surgeries, potentially decreasing morbidity without compromising outcomes.

Strengths and Limitations

This is the first study to evaluate outcomes after RR. Limitations include small sample size, limited follow-up, and single-surgeon experience.

Conclusion

There was no difference in reservoir-related complications when comparing the 3 methods. These preliminary results suggest that reservoir recycling may provide a safe and effective reservoir-handling alternative in inflatable penile prosthesis revision surgery.
Profiles of Nonpharmacologic Treatment Receipt in the First 10 Weeks Following a New Back Pain Diagnosis Among Active Duty Soldiers: A Latent Class Analysis
Authors: Huntington Nick , Larson Mary Jo , Vest Noel , Highland Krista B , Moresco Natalie , Ritter Grant A , Buchholz Connor , Adams Rachel Sayko
Published: November 2024

Introduction

US service members experience high rates of back pain. Guidelines prioritize nonpharmacologic treatment (NPT) as first-line pain treatments; however, NPT utilization patterns research is limited. This study examined NPT patterns of care within the first 10 weeks following an index back pain diagnosis.

Materials and Methods

Data were from the Substance Use and Psychological Injury Combat Study and included 222,427 active duty soldiers with an index back pain diagnosis following return from Afghanistan/Iraq deployment in 2008–2014. We fit a series of latent class analysis models to identify homogenous subgroups of soldiers with NPT utilization during the 10-week period and measured associations with soldier characteristics and clinical characteristics within 90 days before the back pain diagnosis, with the distinct NPT utilization classes. Approval for this study was granted by the Brandeis University Committee for Protection of Human Subjects (Institutional Review Board #14153) and the Uniformed Services University Institutional Review Board.

Results

Only half of the soldiers received any NPT within their 10-week early treatment window. Latent class analysis identified 4 classes over the 10-week early treatment window: Class 1 (None/Low NPT, 65%); Class 2 (High and Decreasing NPT, 15%); Class 3 (Low and Increasing NPT, 13%), and Class 4 (Sustained NPT, 7%). Soldier clinical characteristics from the 90-day preperiod window were most important in distinguishing class membership in relation to Class 1, particularly comorbid pain conditions, diagnosis of traumatic brain injury, receipt of prescription opioids, and receipt of invasive surgery.

Conclusions

Patterns of weekly NPT utilization during an early treatment window following a new back pain diagnosis varied temporally, with approximately half of soldiers using NPT. Half of the soldiers did not receive any NPT within their 10-week early treatment window, which highlights opportunities for increasing use of NPT utilization among military members with a new back pain episode. Future research is needed in the Military Health System to examine the extent to which NPT patterns are associated with pain management outcomes.