bluuebunny/crossref_metadata_2025 huggingface dataset:
Making PBPK models more reproducible in practice
Authors: Domínguez-Romero Elena , Mazurenko Stanislav , Scheringer Martin , Martins dos Santos Vítor A P , Evelo Chris T , Anton Mihail , Hancock John M , Županič Anže , Suarez-Diez Maria
Published: November 2024

Systems biology aims to understand living organisms through mathematically modeling their behaviors at different organizational levels, ranging from molecules to populations. Modeling involves several steps, from determining the model purpose to developing the mathematical model, implementing it computationally, simulating the model’s behavior, evaluating, and refining the model. Importantly, model simulation results must be reproducible, ensuring that other researchers can obtain the same results after writing the code de novo and/or using different software tools. Guidelines to increase model reproducibility have been published. However, reproducibility remains a major challenge in this field. In this paper, we tackle this challenge for physiologically-based pharmacokinetic (PBPK) models, which represent the pharmacokinetics of chemicals following exposure in humans or animals. We summarize recommendations for PBPK model reporting that should apply during model development and implementation, in order to ensure model reproducibility and comprehensibility. We make a proposal aiming to harmonize abbreviations used in PBPK models. To illustrate these recommendations, we present an original and reproducible PBPK model code in MATLAB, alongside an example of MATLAB code converted to Systems Biology Markup Language format using MOCCASIN. As directions for future improvement, more tools to convert computational PBPK models from different software platforms into standard formats would increase the interoperability of these models. The application of other systems biology standards to PBPK models is encouraged. This work is the result of an interdisciplinary collaboration involving the ELIXIR systems biology community. More interdisciplinary collaborations like this would facilitate further harmonization and application of good modeling practices in different systems biology fields.
Quantifying defective and wild-type viruses from high-throughput RNA sequencing
Authors: Muñoz-Sánchez Juan C , Olmo-Uceda María J , Oteo José-Ángel , Elena Santiago F
Published: November 2024

Motivation

Defective viral genomes (DVGs) are variants of the wild-type (wt) virus that lack the ability to complete autonomously an infectious cycle. However, in the presence of their parental (helper) wt virus, DVGs can interfere with the replication, encapsidation, and spread of functional genomes, acting as a significant selective force in viral evolution. DVGs also affect the host’s immune responses and are linked to chronic infections and milder symptoms. Thus, identifying and characterizing DVGs is crucial for understanding infection prognosis. Quantifying DVGs is challenging due to their inability to sustain themselves, which makes it difficult to distinguish them from the helper virus, especially using high-throughput RNA sequencing. An accurate quantification is essential for understanding their very dynamical interactions with the helper virus.

Results

We present a method to simultaneously estimate the abundances of DVGs and wt genomes within a sample by identifying genomic regions with significant deviations from the expected sequencing depth. Our approach involves reconstructing the depth profile through a linear system of equations, which provides an estimate of the number of wt and DVG genomes of each type. Until now, in silico methods have only estimated the DVG-to-wt ratio for localized genomic regions. This is the first method that simultaneously estimates the proportions of wt and DVGs genome wide from short-reads RNA sequencing.

Availability and implementation

The Matlab code and the synthetic datasets are freely available at https://github.com/jmusan/wtDVGquantific.
One Health on islands: Tractable ecosystems to explore the nexus between human, animal, terrestrial, and marine health
Authors: Fountain-Jones Nicholas M , Hutson Kate S , Jones Menna , Nowak Barbara F , Turnbull Alison , Younger Jane , O'Reilly Malgorzata , Watkins Emma , Guernier-Cambert Vanina , Cooley Louise , Hamede Rodrigo
Published: November 2024

Islands play a central role in understanding the ecological and evolutionary processes that shape life but are rarely used to untangle the processes that shape human, animal, and environmental health. Islands, with their discrete human and animal populations, and often well-studied ecological networks, serve as ideal natural laboratories for exploring the complex relationships that shape health across biomes. Relatively long coastlines and, in some cases, low lying topography also make islands sentinels for climate change. In this article, we examine the potential of islands as valuable laboratories and research locations for understanding the One Health nexus. By delving into the challenges faced in island settings, we provide valuable insights for researchers and policymakers aiming to globally promote and apply One Health principles. Ultimately, recognizing the interconnected health of humans, animals, and the environment on islands contributes to efforts aimed at promoting global health and sustainability.
Comment on ‘Failure of scabies treatment: a systemic review and meta-analysis’
Authors: Burkhart Craig G
Published: November 2024

I offer three comments that were not discussed in a recent scabies article: (i) The mite has innate abilities to navigate to humans if within 4 inches of a potential host. (ii) Airborne transmission aids in their transmission and PPE clothing would reduce infestation. (iii) Ivermectin for 3 days would simplify and decrease duration of preventive measures of the spread of contagion and reinfestation.
Aggressive bone tumours: what a radiologist can offer to the surgeon?
Authors: Singh Dharmendra Kumar , Kumar Nishith , Jalan Divesh , Khanna Geetika , Rustagi Ashish , Saran Sonal
Published: November 2024

The management of aggressive bone tumours requires a multidisciplinary approach, with radiologists playing a central role alongside clinicians and pathologists. Radiologists contribute significantly to diagnosing benign and some aggressive tumours, although complex cases often need histopathological confirmation. Their expertise in tumour characterization and extension assessment is crucial for treatment planning. Radiologists guide biopsies to ensure accurate sampling with minimal morbidity and low risk of tumour spread. They also support preoperative planning through 3D tumour reconstructions, aiding surgeons in devising optimal surgical strategies. During surgery, radiologists enhance precision using intraoperative imaging techniques, such as image fusion and MRI, which allow real-time adjustments. Postoperative monitoring for recurrence depends heavily on radiological imaging, with functional MRI providing insights into residual or recurrent disease. Furthermore, radiologists are integral to image-guided therapies for aggressive bone tumours, performing procedures like osteoplasty and ablation to manage pain and control tumour growth. In sum, radiologists are invaluable members of the care team, providing expertise in diagnosis, biopsy, surgical planning, intraoperative guidance, postoperative monitoring, and therapeutic interventions, ultimately enhancing patient outcomes and quality of life.
Cerebrovascular reactivity and response times describe recent ischaemic symptomatology in patients with moyamoya
Authors: Han Caleb , Richerson Wesley T , Garza Maria , Rodeghier Mark , Mishra Murli , Davis L Taylor , Fusco Matthew , Chitale Rohan , Shiino Shuhei , Jordan Lori C , Donahue Manus J
Published: November 2024

Moyamoya is a non-atherosclerotic intracranial steno-occlusive condition that places patients at high risk for ischaemic stroke. Randomized trials of surgical revascularization demonstrating efficacy in ischaemic moyamoya have not been performed, and as such, biomarkers of parenchymal haemodynamic impairment are needed to assist with triage and evaluate post-surgical response. In this prospective study, we test the hypothesis that parenchymal cerebrovascular reactivity (CVR) metrics in response to a fixed-inspired 5% carbon dioxide challenge correlate with recent focal ischaemic symptoms. Hypercapnic reactivity blood oxygenation level-dependent MRI (echo time = 35 ms; spatial resolution = 3.5 × 3.5 × 3.5 mm) and catheter angiography assessments of cortical reserve capacity and vascular patency, respectively, in moyamoya disease and syndromic participants (n = 73) were performed in sequence. Cerebrovascular reactivity uncorrected for response time (CVRRAW) was quantified, and time regression analyses were applied to quantify maximum cerebrovascular reactivity (CVRMAX) and cerebrovascular reactivity response time (CVRDELAY). Symptomatology was categorized by a stroke neurologist by hemisphere: symptomatic (lateralizing ischaemic symptoms < 6 months) or asymptomatic (no ischaemic symptom history). Values are presented as median [interquartile range]; logistic regression assessed the association of cerebrovascular reactivity metrics with symptoms, controlling for age and sex. A total of 109 hemispheres, including 39 symptomatic and 70 asymptomatic hemispheres, met inclusion criteria. Symptomatic hemispheres displayed reduced CVRRAW (P < 0.01) (symptomatic = 0.45 [0.28–0.70] z-statistic/ΔEtCO2 versus asymptomatic = 0.67 [0.44–0.98] z-statistic/ΔEtCO2), lengthened CVRDELAY (P < 0.001) (symptomatic = 47.6 [37.7–57.0] seconds versus asymptomatic = 37.7 [30.4–46.4] seconds), and reduced CVRMAX (P = 0.037) (symptomatic = 1.31 [0.99–1.94] z-statistic/ΔEtCO2 versus asymptomatic = 1.64 [1.29–2.12] z-statistic/ΔEtCO2). CVRDELAY (P < 0.001) was found to be significantly related to age in asymptomatic hemispheres (0.33-unit increase/year). Of assessed measures, the receiver operating characteristic curves suggest that CVRDELAY is associated most closely with recent ischaemic symptoms (P < 0.001). Findings support that cerebrovascular reactivity metrics are uniquely altered in hemispheres with recent ischaemic symptoms, further motivating their utilization as biomarkers of ischaemic symptomatology and potential treatment efficacy in moyamoya disease and syndrome.
The role of vitamin D: a promising pathway to combat neuropsychiatric lupus disorders
Authors: Karnopp Thaís Evelyn , Chapacais Gustavo Flores , Gasparini Maria Luísa , dos Santos Natália Garcia , Freitas Vinicius da Silva , Piccoli Marina , Di Domenico Andressa Leite , Doria Lucas Denardi , de Souza Nikolas Mateus Pereira , Rieger Alexandre , Freitas Eduarda Correa , Visioli Fernanda , Monticielo Odirlei André
Published: November 2024

To evaluate neuropsychiatric manifestations in the pristane-induced lupus (PIL) model, as well as to evaluate immunoregulatory effects of vitamin D (vit-D) in the brain of mice with PIL. Eighty female BALB/c mice were divided into six groups with 90 (3 months) and 180 (6 months) days of experimentation: CO3, CO6 (controls), PIL3, PIL6 (pristane-induced lupus), VD3 and VD6 (PIL supplemented with 1,25-dihydroxyvitamin D). Forced-swim, elevated plus maze and Barnes maze were the behavioral tests performed. Expression of pVDR was assessed by immunofluorescence. Brain IgM and IgG deposits were evaluated by double staining fluorescence. Serum IL-6 and IFN-α1 were quantified by ELISA. AUC-ROC curve was also performed for immunoglobulins. PIL and VD showed depressive-like behavior in the forced-swim test and anxious-like behavior in the elevated plus maze test. PIL also presented cognitive and memory impairment in the Barnes maze test. Additionally, PIL and VD presented higher levels of serum IFN-α1, but not IL-6. Mice supplemented with vit-D had reduced IgM and IgG deposits and increased pVDR expression in the brain after 180 days. The AUC-ROC curve demonstrated high sensitivity and specificity for IgM and IgG in the brain. We observed neuropsychiatric manifestations in this model of systemic lupus erythematosus (SLE), strongly corroborating to PIL model being suitable as a neuropsychiatric lupus (NPSLE) model. Vit-D was able to reduce immunoglobulin deposits in the brain and influenced the levels of serum IL-6 in the animals assessed. Also, it improved memory, but it had no effect on depressive and anxious-like behavior.
Interaction between intrinsically disordered proteins Praja1 and α-synuclein on gold electrodes
Authors: Mori Wataru , Onodera Wataru , Kojima Terutoshi , Asahi Toru , Nakanishi Takuya
Published: November 2024

The behavior of Praja1 (PJA1) interacting with alpha-synuclein (α-Syn) on a gold electrode was investigated using electrochemical methods, where both PJA1 and α-Syn are intrinsically disordered proteins. From the electrode reaction of ferricyanide ions added as probe, it was suggested that PJA1 interacts with α-Syn even when adsorbed on gold substrate and that the state of PJA1 on gold electrodes can be classified into four categories depending on the α-Syn concentration.
Five-Year Evaluation of an Anal Cancer Screening Program in Men Who Have Sex With Men With HIV at 2 Academic Center Clinics
Authors: Achhra Amit C , Chan Elizabeth , Applebaum Serina , Guerrero Maggie , Hao Ritche , Pantel Haddon , Virata Michael , Fikrig Margaret , Barakat Lydia
Published: November 2024

Background

Guidelines recommend annual anal cytology-based squamous cell carcinoma of anus (SCCA) screening for men who have sex with men with HIV aged ≥35 years (eligible population). The recommended threshold for high-resolution anoscopy (HRA) depends on its availability: low-threshold (any abnormal cytology) if availability is high and high-threshold (high-grade squamous intraepithelial lesion [HSIL] on cytology) if availability is low.

Methods

This was a retrospective chart review (2018–2022) at academic HIV clinics. We evaluated (1) 5-year uptake of cytology-based SCCA screening in the eligible population and (2) estimated HSIL detection rate based on our current low-threshold criteria, and if high-threshold criteria were used for HRA referral.

Results

Of 432 eligible individuals, only 219 (50.7%) had at least 1 and only 113 (26%) had >1 SCCA screening tests in a median follow-up of 4 years. Seventy-four (17.1%) individuals had at least 1 abnormal anal cytology during follow-up, of whom 56 (75.6%) underwent HRA. Increasing age (≥57 years) and history of smoking negatively correlated with ever receiving screening. Anal cytology (365 tests in 206 individuals) showed 17.5% “unsatisfactory” and 26.8% with any abnormal cytology (zero with HSIL) triggering HRA referral. Only 34 individuals (7.8% of screening eligible) were ever detected with HSIL. Strictly using high-threshold criteria for HRA referral would have led to no HRA or HSIL detection.

Conclusions

We noted poor uptake of screening over time, particularly in older age groups. Importantly, anal cytology performed poorly as a triage test for HRA referral, with high rates of “unsatisfactory” samples and low sensitivity for detecting HSIL.
Relationship Between Clarithromycin MICs and Treatment Responses in Mycobacterium avium Complex Pulmonary Disease
Authors: Kim Joong-Yub , Hwang Hyeontaek , Yim DaHae , Choi Yunhee , Kim Taek Soo , Whang Jake , Kwak Nakwon , Yim Jae-Joon
Published: November 2024

Background

Mycobacterium avium complex pulmonary disease (MAC-PD) is a chronic lung condition with rapidly increasing prevalence worldwide. Macrolides like azithromycin and clarithromycin are the backbone of long-term antibiotic therapy for progressive MAC-PD. The impact of minimum inhibitory concentrations (MICs), especially within the susceptible range, for macrolides on treatment responses remains unclear.

Methods

We analyzed adult patients who started treatment for MAC-PD between 1 March 2009 and 1 March 2022 at Seoul National University Hospital. Patients were categorized into 4 groups according to the clarithromycin MICs of their causative strains at treatment initiation. Logistic regression was employed to evaluate the impact of clarithromycin MICs on the likelihood of microbiological cure. Companion drugs and their MICs, alongside clinical characteristics like age, sex, body mass index, cavity presence, acid-fast bacilli smear positivity, causative species, and erythrocyte sedimentation rate were adjusted in multivariable analysis.

Results

Four-hundred thirty-six patients (median age, 65 years; 34% men) were included. Microbiological cure rates were 51.8%, 51.9%, 50.0%, and 18.2% for patients with clarithromycin MICs ≤0.5, 1–2, 4–8, and ≥32 µg/mL, respectively (P = .181). No significant differences in microbiological cure rates were observed across varying levels of clarithromycin MICs within the susceptible range (≤8 µg/mL). Relative to patients with clarithromycin-susceptible strains, patients with MICs ≥32 µg/mL had an odds ratio of 0.25 for achieving microbiological cure (95% confidence interval [CI]: 0.06–1.07; P = .06).

Conclusions

Treatment responses were comparable among patients with strains having clarithromycin MICs within the susceptible range but were likely to be worse for patients with strains having MICs ≥32 µg/mL.
Initiative as Institution: How the Belt and Road Initiative Influences Chinese Firms’ Participation in Global Value Chains
Authors: Wu Jiwei , Yin Weiwen
Published: November 2024

This article investigates how the Belt and Road Initiative (BRI), proposed by China in 2013, influences the participation of Chinese firms in the global value chains (GVCs). More than just an economic strategy, BRI could serve as a substitute for inadequate contract enforcement in cross-border economic transactions between Chinese firms and their foreign counterparts. Using data from Chinese private companies listed from 2008 to 2016 and multiplicative interaction models, this article evaluates the impact of BRI as a policy shock that enhances contract enforcement and encourages Chinese firms’ participation in the GVCs. The results suggest that, following the implementation of the BRI in 2013, private firms with political ties to the government became more active participants in the GVCs, thanks to greater support from the Chinese state in facilitating contract enforcement abroad. The findings imply that BRI, as a state-led economic strategy, can also function as a mechanism that encourages private firms with political connections to expand globally by reducing transaction costs in cross-border trade activities.
Reverse electrical remodelling after cardiac resynchronization therapy in a patient undergoing left bundle branch area pacing: a case report
Authors: Rijks Jesse H J , Luermans Justin , Vernooy Kevin
Published: November 2024

Background

Left bundle branch area pacing (LBBAP) has been introduced as an alternative to biventricular pacing in cardiac resynchronization therapy (CRT). Several studies describe echocardiographic reverse remodelling after LBBAP. Reverse electrical remodelling after LBBAP has not yet been described.

Case summary

A 77-year-old female with non-ischaemic heart failure with reduced ejection fraction [left ventricular ejection fraction (LVEF) 30–35%], left bundle branch block (QRS duration 164 ms), and symptomatic atrial fibrillation irresponsive to pharmacological therapy was evaluated for CRT with LBBAP and atrioventricular node ablation. Successful LBBAP implantation resulted in confirmed left bundle branch capture. Immediately after implantation, paced QRS duration was 194 ms with a long stimulus-V6RWPT (time to peak R wave in V6) of 93 ms, suggesting distal conduction system disease. Patient showed an echocardiographic improvement (LVEF 35–50%) and improvement in symptoms (NYHA class III to NYHA class II) at 1-year follow-up. Moreover, an improvement in conduction delays was found present. Paced QRS duration improved to 159 ms and stimulus-V6RWPT improved to 78 ms. This improvement might be due to reverse electrical remodelling.

Discussion

This case demonstrates that LBBAP can induce reverse electrical remodelling, even in the presence of distal conduction system disease. With the current availability of different pacing strategies in CRT (i.e. biventricular CRT, LBBAP, and left bundle branch-optimized CRT), more research on patient selection and pacing strategy selection is needed.
Multimodal data integration to predict atrial fibrillation
Authors: Yao Yuchen , Zhang Michael J , Wang Wendy , Zhuang Zhong , He Ruoyu , Ji Yuekai , Knutson Katherine A , Norby Faye L , Alonso Alvaro , Soliman Elsayed Z , Tang Weihong , Pankow James S , Pan Wei , Chen Lin Yee
Published: November 2024

Aims

Many studies have utilized data sources such as clinical variables, polygenic risk scores, electrocardiogram (ECG), and plasma proteins to predict the risk of atrial fibrillation (AF). However, few studies have integrated all four sources from a single study to comprehensively assess AF prediction.

Methods and results

We included 8374 (Visit 3, 1993–95) and 3730 (Visit 5, 2011–13) participants from the Atherosclerosis Risk in Communities Study to predict incident AF and prevalent (but covert) AF. We constructed a (i) clinical risk score using CHARGE-AF clinical variables, (ii) polygenic risk score using pre-determined weights, (iii) protein risk score using regularized logistic regression, and (iv) ECG risk score from a convolutional neural network. Risk prediction performance was measured using regularized logistic regression. After a median follow-up of 15.1 years, 1910 AF events occurred since Visit 3 and 229 participants had prevalent AF at Visit 5. The area under curve (AUC) improved from 0.660 to 0.752 (95% CI, 0.741–0.763) and from 0.737 to 0.854 (95% CI, 0.828–0.880) after addition of the polygenic risk score to the CHARGE-AF clinical variables for predicting incident and prevalent AF, respectively. Further addition of ECG and protein risk scores improved the AUC to 0.763 (95% CI, 0.753–0.772) and 0.875 (95% CI, 0.851–0.899) for predicting incident and prevalent AF, respectively.

Conclusion

A combination of clinical and polygenic risk scores was the most effective and parsimonious approach to predicting AF. Further addition of an ECG risk score or protein risk score provided only modest incremental improvement for predicting AF.
Implementing and evaluating shared decision-making before transcatheter aortic valve implantation with a dedicated pathway and questionnaire
Authors: Carulli Ermes , Browne Suzy , Woolley Sara , Tindale Alexander , Pottle Alison , Nagle Kate , Lane Rebecca , Chandra Navin , Patel Niket , De Palma Rodney , Barnes Gareth , Kabir Tito , Panoulas Vasileios , Smith David , Smith Robert , Clernon Sharon , Heng Ee Ling , Akhtar Mohammed , Bowers Mark , McGovern Ian , Lüscher Thomas , Dalby Miles
Published: November 2024

Aims

Transcatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement for patients with aortic valve stenosis. The choice between TAVI, surgery, or a conservative approach should be based upon multiple factors including clinical considerations, technical feasibility, and informed patient preference. In this context, engaging patients in a shared decision-making (SDM) process becomes essential, but this practice is generally underused.

Methods and results

To comply with the European and UK national guidelines, in January 2023 we established a structured SDM pathway in which patients are offered virtual/physical decision aids and after 1 week are invited to a meeting to reach a shared decision. From December 2022 to June 2023, a custom-developed questionnaire was prospectively administered to 23 patients prior to, and 38 patients after, the implementation of the SDM pathway. The answers to 12 core questions were recorded on a Likert scale (1–5). Global satisfaction, as measured by mean Likert score, was significantly higher for the post-SDM group than for the pre-SDM group (4.46 ± 0.14 vs. 3.78 ± 0.30, P < 0.001). The percentage of positive (Likert 4–5) responses was significantly higher in the post-SDM group (289/312, 92.6% vs. 155/234, 66.2%, P < 0.001). The percentage of negative (Likert 1–2) responses was significantly lower in the post-SDM group (5/312, 1.6% vs. 53/234, 22.6%, P < 0.001).

Conclusion

The SDM pathway proved effective in delivering SDM in compliance with national and international guidance. A similar approach leveraging digital technology to minimize cost and enhance patient convenience could be implemented for other treatments and across other institutions.
From Kingdom to Colony: Framing the English Conquest of Ireland
Authors: Veach Colin
Published: November 2024

This article offers a new way of framing the English conquest of Ireland by focusing on the development of a kingdom of Ireland both before and after the invasion of 1169. It thus spans the historiographical divides that tend to partition Irish history at the point of the English invasion, and which also frequently disaggregate the study of British and Irish history. By exploring the complexity of Irish political society and culture before 1169, one can see how King Henry II sought to use its structures to facilitate his annexation of ‘the kingdom of Ireland’ in 1171–2. This included the Church, which offered Henry’s dynasty the ideological support and legitimacy it had once provided for Gaelic kings of Ireland. Paying attention to the numerous references to the ‘kingdom of Ireland’ in the records of the English government also highlights the processes by which Henry’s son John and his successors sought to Anglicise this kingdom by imposing England’s laws, institutions and political culture upon it. Crucially, ultimate control of these structures remained with the administration in England, so in this way Ireland was transformed from a kingdom to a colony. Recognising this liminal period in the development of Anglo-Ireland provides context for the emerging colonial community in Ireland, as well as strategies of resistance and compromise employed by the Gaelic Irish under English rule.
MATEdb2, a Collection of High-Quality Metazoan Proteomes across the Animal Tree of Life to Speed Up Phylogenomic Studies
Authors: Martínez-Redondo Gemma I , Vargas-Chávez Carlos , Eleftheriadi Klara , Benítez-Álvarez Lisandra , Vázquez-Valls Marçal , Fernández Rosa
Published: November 2024

Recent advances in high-throughput sequencing have exponentially increased the number of genomic data available for animals (Metazoa) in the last decades, with high-quality chromosome-level genomes being published almost daily. Nevertheless, generating a new genome is not an easy task due to the high cost of genome sequencing, the high complexity of assembly, and the lack of standardized protocols for genome annotation. The lack of consensus in the annotation and publication of genome files hinders research by making researchers lose time in reformatting the files for their purposes but can also reduce the quality of the genetic repertoire for an evolutionary study. Thus, the use of transcriptomes obtained using the same pipeline as a proxy for the genetic content of species remains a valuable resource that is easier to obtain, cheaper, and more comparable than genomes. In a previous study, we presented the Metazoan Assemblies from Transcriptomic Ensembles database (MATEdb), a repository of high-quality transcriptomic and genomic data for the two most diverse animal phyla, Arthropoda and Mollusca. Here, we present the newest version of MATEdb (MATEdb2) that overcomes some of the previous limitations of our database: (i) we include data from all animal phyla where public data are available, and (ii) we provide gene annotations extracted from the original GFF genome files using the same pipeline. In total, we provide proteomes inferred from high-quality transcriptomic or genomic data for almost 1,000 animal species, including the longest isoforms, all isoforms, and functional annotation based on sequence homology and protein language models, as well as the embedding representations of the sequences. We believe this new version of MATEdb will accelerate research on animal phylogenomics while saving thousands of hours of computational work in a plea for open, greener, and collaborative science.
Lipopolysaccharide-Induced Delirium-Like Behavior and Microglial Activation in Mice Correlate With Bispectral Electroencephalography
Authors: Nishiguchi Tsuyoshi , Yamanishi Kyosuke , Gorantla Nipun , Shimura Akiyoshi , Seki Tomoteru , Ishii Takaya , Aoyama Bun , Malicoat Johnny R , Phuong Nathan James , Dye Nicole Jade , Yamanashi Takehiko , Iwata Masaaki , Shinozaki Gen
Published: November 2024

Delirium is a multifactorial medical condition characterized by impairment across various mental functions and is one of the greatest risk factors for prolonged hospitalization, morbidity, and mortality. Research focused on delirium has proven to be challenging due to a lack of objective measures for diagnosing patients, and few laboratory models have been validated. Our recent studies report the efficacy of bispectral electroencephalography (BSEEG) in diagnosing delirium in patients and predicting patient outcomes. We applied BSEEG to validate a lipopolysaccharide-induced mouse model of delirium. Moreover, we investigated the relationship between BSEEG score, delirium-like behaviors, and microglia activation in hippocampal dentate gyrus and cortex regions in young and aged mice. There was a significant correlation between BSEEG score and impairment of attention in young mice. Additionally, there was a significant correlation between BSEEG score and microglial activation in hippocampal dentate gyrus and cortex regions in young and aged mice. We have successfully validated the BSEEG method by showing its associations with a level of behavioral change and microglial activation in an lipopolysaccharide-induced mouse model of delirium. In addition, the BSEEG method was able to sensitively capture an lipopolysaccharide-induced delirium-like condition that behavioral tests could not capture because of a hypoactive state.
Using Voice-Activated Technologies to Enhance Well-Being of Older Adults in Long-Term Care Homes
Authors: Grigorovich Alisa , Marcotte Ashley-Ann , Colobong Romeo , Szabo Margaret , MacNeill Carlee , Blais Daniel , Giffin Gail , Clahane Ken , Goldman Ian P , Harris Bessie , Clarke Caseley Abby , Gaunt Melanie , Vickery Jessica , Torrealba Christina , Kirkland Susan , Kontos Pia
Published: November 2024

Background and Objectives

Information communication technologies (ICTs) can enhance older adults’ health and well-being. Most research on the use of voice-activated ICTs by older adults has focused on the experiences of individuals living in the community, excluding those who live in long-term care homes. Given evidence of the potential benefits of such technologies to mitigate social isolation and loneliness, more research is needed about their impacts in long-term care home settings. With this in mind, we evaluated impacts and engagement of older adults with voice- and touchscreen-activated ICTs in one long-term care home in Canada.

Research Design and Methods

Interviews were conducted with older adults who were provided with a Google Nest Hub Max and with staff as part of a larger implementation study. Participants completed semistructured interviews before the technology was implemented, and again at 6 and 12 months. The interviews were recorded, transcribed, and analyzed using thematic analysis techniques.

Results

We found that residents primarily used the technologies to engage in self-directed digital leisure and to engage with others both in and outside the home, and that this in turn enhanced their comfort, pleasure, and social connectedness. We also identified ongoing barriers to their engagement with the technology, including both personal and structural factors.

Discussion and Implications

Our findings suggest that implementation of voice-activated ICTs can bring added value to broader efforts to improve well-being and quality of life in long-term care by enhancing choice, self-determination, and meaningful relationships.
New image, same tactics: global tobacco and vaping industry strategies to promote youth vaping
Authors: Watts Christina , Rose Shiho , McGill Bronwyn , Yazidjoglou Amelia
Published: November 2024

E-cigarette use (or vaping) is widespread in young people and is a rapidly growing public health problem. While the tobacco and vaping industry has promoted vaping as a smoking cessation aid for adults, the industry has strategically targeted young people through marketing and appealing designs to orientate a new generation of consumers to use their products. These strategies are not new and replicate what we have previously seen employed by the tobacco industry in past decades to maintain and grow their tobacco profits. We review the evidence on tobacco and vaping industry interference, highlighting the calculated and strategic use of interference tactics as a discourse to curb tobacco control efforts. We demonstrate how these tried and tested strategies are now being purposefully re-used in the context of vaping. As Australia is currently undergoing significant policy reforms for the access and retail of vaping products, we also provide a case study of the industry response played out in this contemporary landscape. Government and public health advocates are in a key position to be one step ahead in proactively tackling the vaping crisis. We recommend that continued monitoring of industry activities and strategies, achieving political transparency and tightening loopholes in current regulations are all needed to identify and eliminate the tobacco and vaping industry’s influence on policymaking. Given their previous track record, we emphasize the need to counter industry interference tactics with urgency to prevent a new generation of nicotine dependence and to support and protect future action in tobacco control.
Assessment of Treatment Response in Known Crohn’s Disease—A Prospective Blinded Study Comparing the Diagnostic Accuracy of Intestinal Ultrasound, Magnetic Resonance Enterocolonography, Panenteric Capsule Endoscopy, and Fecal Calprotectin
Authors: Brodersen Jacob Broder , Rafaelsen Søren Rafael , Juel Mie Agerbæk , Knudsen Torben , Kjeldsen Jens , Jensen Michael Dam
Published: November 2024

Background

Minimally invasive modalities may replace ileocolonoscopy (IC) in the follow-up of Crohn’s disease (CD). The aim of this study was to evaluate intestinal ultrasound (IUS), magnetic resonance enterocolonography (MREC), panenteric capsule endoscopy (PCE), and fecal calprotectin (FC) for determining response to medical treatment in patients with ileocolonic CD.

Methods

This prospective, blinded, multicenter study included patients with endoscopically active CD. Patients were scheduled for IC, MREC, IUS, PCE, and FC before and 12 weeks after treatment with corticosteroids or biological therapy. A ≥50% reduction of the Simple Endoscopic Score for Crohn’s Disease (SES-CD) with IC defined treatment response.

Results

Fifty patients completed the pre- and posttreatment evaluation with IC, and endoscopic response was achieved in 25 (50.0%). PCE was omitted in 12 (24.0%) patients because of stricturing CD. All activity scores decreased in patients achieving endoscopic response: The Simple Ultrasound Score for Crohn’s Disease 2.2 vs 6.1 (P < .001), Magnetic Resonance Index of Activity 29.0 vs 37.1 (P = .05), SES-CD with PCE 3.1 vs 12.8 (P < .001), and FC 115.3 vs 1339.9 mg/kg (P < .001). The sensitivity and specificity of IUS, MREC, PCE, and FC were 80.0% (95% CI, 56.3-94.3)/77.8% (95% CI, 52.4-93.6), 65.2% (95% CI, 42.7-83.6)/87.0% (95% CI, 66.4-97.2), 87.5% (95% CI, 61.7-98.4)/86.7% (95% CI, 59.5-98.3), and 90.0% (95% CI, 68.3-98.8)/86.4% (95% CI, 65.1-97.1), respectively.

Conclusions

IUS and FC are equally effective for determining treatment response in patients with active CD. PCE is limited by the occurrence of strictures in this group of patients.
The Clinical Interpretation of Cluster Trials
Authors: Roshanov Pavel S , Zou Guangyong , Khanna Reena
Published: November 2024

Cluster-randomized trials randomize entire groups of participants, instead of individual participants, to different treatment arms. For certain interventions (eg, institutional policies, processes of care, treatment algorithms), these designs protect against contamination between study arms. However, cluster trials are logistically complex to implement and have unique vulnerabilities that must be evaluated for accurate interpretation. Here, we provide a general overview of the design and statistical issues in cluster trials to facilitate their interpretation by clinicians.
Symptomatic and Sonographic Improvement of Immune Checkpoint Inhibitor Enterocolitis With Risankizumab
Authors: Mei Rena , Pepe Emily , Oh David Y , Tsai Katy K , Chugh Rishika , Kattah Michael G
Published: November 2024

Lay Summary

Immune checkpoint inhibitor-induced (CPI) enterocolitis is a frequent complication of cancer immunotherapy. This case details the treatment of CPI enterocolitis with risankizumab (anti-IL23) and the use of intestinal ultrasound (IUS) to noninvasively monitor treatment response. This report is clinically relevant given the frequency of CPI enterocolitis and the expanding applications of IUS.
Mitigation measures for pinniped-fisheries interactions based on knowledge of animal behavior
Authors: Barrios-Guzmán Carmen , Sepúlveda Maritza , Crespo Enrique , Pavés Héctor
Published: November 2024

A rise in pinniped-fisheries interactions has been observed due to the global decline in fish populations primarily attributed to overfishing, and/or due to the recent population recovery of several pinniped species. Although many studies have quantified these interactions, a limited number delve into their behavioral aspects. We consulted 374 studies on pinniped-fisheries interactions from 1980 to 2020 and analyzed which of them addressed the interaction from a behavioral perspective. Additionally, we examined the role of learning in pinnipeds and their ability to capture prey from fishing gear. The stimulus-reward relationship in operational interactions was addressed in 51 (14%) studies, involving 10 (19%) of the world’s 54 pinniped species or subspecies. Depredation behavior (43%) and attack behavior (35%) were frequently reported during fishing interactions. Understanding associative and non-associative learning mechanisms has the potential to reduce economic losses from fishing activity, advance efficient mitigation measures to minimize conflicts, and establish pragmatic conservation priorities based on a better understanding of the behavioral aspects of these interactions. More research is needed to explore the effectiveness of deterrents in different species, improve methods of reducing habituation, and evaluate long-term behavioral effects, fostering effective strategies for minimizing conflicts and promoting coexistence between humans and pinnipeds.
Continuity of the Lyapunov Exponent for Analytic Multi-frequency Quasiperiodic Cocycles
Authors: Powell Matthew
Published: November 2024

It is known that the Lyapunov exponent of analytic 1-frequency quasiperiodic cocycles is continuous in cocycle and, when the frequency is irrational, jointly in cocycle and frequency. In this paper, we extend a result of Bourgain to show the same continuity result for multifrequency quasiperiodic $M(2,\mathbb{C})$ cocycles. Our corollaries include applications to multifrequency Jacobi cocycles with periodic background potentials.
Phylogenomics of the major lineages of Bembidion and related ground beetles (Coleoptera: Carabidae: Bembidiini)
Authors: Pflug James M , Schmidt Joachim , Sproul John S , Weng Yi-Ming , Maruyama Munetoshi , Henrichs Brian , Everson Kathryn M , Maddison David R
Published: November 2024

Bembidion Latreille (Coleoptera: Carabidae) is a genus of small ground beetles containing about 1,380 species. To test previous phylogenetic hypotheses about deeper lineages of Bembidion and near relatives, we recover and examine over 1,800 nuclear protein-coding loci from 33 species representing the main lineages of Bembidion, 10 species of other bembidiine genera, and 7 outgroups. We find that Bembidion exclusive of subgenus Phyla Motschulsky is monophyletic, and we reclassify Phyla as a separate genus. Within Bembidion we find 2 dominant clades, the Bembidion superseries (containing about 490 species in the subgenera Eupetedromus Netolitzky and Lindrochthus Maddison, the Philochthus Stephens complex, and the Bembidion series), and the Ocydromus Clairville superseries (containing almost all other Bembidion representing about 840 species). The only known lineages within Bembidion outside of these superseries are subgenus Hoquedela Müller-Motzfeld and the Desarmatocillenus Netolitzky complex, which combined contain less than 30 species. Most clades are insensitive to variations in analyses and hold up under different sets of taxa and loci, analyses at the nucleotide or amino acid levels, and different analytical methods (maximum likelihood, including posterior mean site frequency analyses, Bayesian analyses, invariant-based methods, and those that consider incomplete lineage sorting). Despite the clarity achieved in most aspects of the phylogeny, there are several unresolved regions, notably the relationships of Desarmatocillenus, Hoquedela, and Phyla to other bembidiines. A divergence dating analysis suggests that crown Bembidion is about 48 million years old (95% confidence intervals 40–58 Ma), and that the 2 large superseries are about 38 million years old (95% confidence intervals about 29–47 Ma).
Probiotic model for studying rhizosphere interactions of root exudates and the functional microbiome
Authors: Pang Zhiqiang , Xu Peng
Published: November 2024

Root exudates are important mediators of plant–microbiome interactions. Recent pioneering studies on various aerial root plants, including cereals, have shown that carbohydrate-rich mucilage can enrich diazotrophs and increase host nitrogen utilization and growth. Moreover, non-diazotrophic “gatekeeper” microorganisms in mucilage help defend against pathogenic and environmental microbes. These findings highlight the active role of root exudates in mediating plant–microbiome interactions to maintain microbial homeostasis in the rhizosphere. However, little is known about the specific mechanisms by which root exudates modulate the functional microbiome and homeostasis in rhizosphere microhabitats. Here, we propose the typical and stable biointeractions of four plant–specific aerial root mucilage–probiotic systems as a model for understanding root exudate–functional microbiome interaction. We anticipate that this model can provide fundamental biological insights into rhizosphere interactions.
High-Sensitivity and Conventional Cardiac Troponin-I Assays in AL Amyloidosis
Authors: Dodge Maura C , Prokaeva Tatiana , Mendelson Lisa , Joshi Tracy , Sanchorawala Vaishali , Kataria Yachana
Published: November 2024

Background

Circulating cardiac troponin-I (cTnI) plays a crucial role in biomarker staging systems, offering important information for prognostification and risk stratification of patients with AL amyloidosis. High-sensitivity cTnI (HS-cTnI) assays have been introduced in practice; however, the data on the concordance between conventional and HS-cTnI and the utility of HS-cTnI in cardiac biomarker staging are lacking.

Methods

Seventy-eight consecutive patients with AL amyloidosis who were prospectively evaluated at the Boston University Amyloidosis Center from October 2022 through March 2023 were included. cTnI was measured using the Abbott Architect cTnI chemiluminescent microparticle immunoassay (CMIA) and HS-cTnI using the Abbott Alinity HS-cTnI CMIA assay. Assay results were compared by Deming regression and Bland–Altman analyses, and cardiac biomarker stages were assigned and compared using both assay results.

Results

Median cTnI and HS-cTnI concentrations were 13.0 and 7.0 ng/L, respectively. Bland–Altman analysis demonstrated a negative bias with HS-cTnI results (mean percent difference between assays: −49.8%) and the greatest variance occurring below 50 ng/L. Deming regression supported this negative discordance (slope, 0.66; intercept, −1.9). The use of HS-cTnI assay downgraded cardiac biomarker staging assignments from stage IIIA to stage II (n = 3) and from stage IIIB to stage II (n = 1).

Conclusions

Overall agreement was demonstrated; however, a negative bias for HS-cTnI assay was noted at low concentrations. The application of the conventional cTnI threshold of >100 ng/L to HS-cTnI-based Boston University cardiac staging showed a trend toward downgraded staging assignments. The prognostic utility of HS-cTnI assay in biomarker staging warrants further investigation in patients with AL amyloidosis.
Assessing the use of unstructured electronic health record data to identify exposure to firearm violence
Authors: Cook Nicole , Biel Frances M , Cartwright Natalie , Hoopes Megan , Al Bataineh Ali , Rivera Pedro
Published: November 2024

Objectives

Research on firearm violence is largely limited to people who experienced acute bodily trauma and death which is readily gathered from Inpatient and Emergency Department settings and mortality data. Exposures to firearm violence, such as witnessing firearm violence or losing a loved one to firearm violence, are not routinely collected in health care. As a result, the true public health burden of firearm violence is underestimated. Clinical notes from electronic health records (EHRs) are a promising source of data that may expand our understanding of the impact of firearm violence on health. Pilot work was conducted on a sample of clinical notes to assess how firearm terms present in unstructured clinical notes as part of a larger initiative to develop a natural language processing (NLP) model to identify firearm exposure and injury in ambulatory care data.

Materials and Methods

We used EHR data from 2012 to 2022 from a large multistate network of primary care and behavioral health clinics. A text string search of broad, gun-only, and shooting terms was applied to 9,598 patients with either/both an ICD-10 or an OCHIN-developed structured data field indicating exposure to firearm violence. A sample of clinical notes from 90 patients was reviewed to ascertain the meaning of terms.

Results

Among the 90 clinical patient notes, 13 (14%) notes reflect documentation of exposure to firearm violence or injury from firearms. Results from this study identified refinements that should be considered for NLP text classification.

Conclusion

Unstructured clinical notes from primary and behavioral health clinics have potential to expand understanding of firearm violence.