bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensorimotor brain-computer interface performance depends on signal-to-noise ratio but not connectivity of the mu rhythm in a multiverse analysis of longitudinal data
Authors: Kapralov Nikolai , Idaji Mina Jamshidi , Stephani Tilman , Studenova Alina , Vidaurre Carmen , Ros Tomas , Villringer Arno , Nikulin Vadim
Published: October 2023

Objective

Serving as a channel for communication with locked-in patients or control of prostheses, sensorimotor brain-computer interfaces (BCIs) decode imaginary movements from the recorded activity of the user’s brain. However, many individuals remain unable to control the BCI, and the underlying mechanisms are unclear. The user’s BCI performance was previously shown to correlate with the resting-state signal-to-noise ratio (SNR) of the mu rhythm and the phase synchronization (PS) of the mu rhythm between sensorimotor areas. Yet, these predictors of performance were primarily evaluated in a single BCI session, while the longitudinal aspect remains rather uninvestigated. In addition, different analysis pipelines were used to estimate PS in source space, potentially hindering the reproducibility of the results.

Approach

To systematically address these issues, we performed an extensive validation of the relationship between pre-stimulus SNR, PS, and session-wise BCI performance using a publicly available dataset of 62 human participants performing up to 11 sessions of BCI training. We performed the analysis in sensor space using the surface Laplacian and in source space by combining 24 processing pipelines in a multiverse analysis. This way, we could investigate how robust the observed effects were to the selection of the pipeline.

Main results

Our results show that SNR had both between- and within-subject effects on BCI performance for the majority of the pipelines. In contrast, the effect of PS on BCI performance was less robust to the selection of the pipeline and became non-significant after controlling for SNR.

Significance

Taken together, our results demonstrate that changes in neuronal connectivity within the sensorimotor system are not critical for learning to control a BCI, and interventions that increase the SNR of the mu rhythm might lead to improvements in the user’s BCI performance.
In vitrocultivation techniques for modeling liver organogenesis, building assembloids, and designing synthetic tissues
Authors: Kumar Simran , Patel Helly , Parashurama Natesh
Published: October 2023

Chronic liver disease has reached epidemic proportions, affecting over 800 million people globally. The current treatment, orthotopic liver transplantation, has several limitations. Promising solutions have emerged in the field of liver regenerative medicine, with liver organogenesis holding significant potential. Early liver organogenesis, occurring between E8.5 and 11.5, involves the formation of epithelial-mesenchymal interactions leading to morphogenesis, hepatic cord formation, and collective migration. However, there is a lack of methods forin vitromodeling of this process. In this study, a detailed series of methods are presented enabling the modeling of various stages and aspects of liver organogenesis. In one method series, assembloid technology with hepatic and mesenchymal spheroids is utilized, replicating early structures found in liver organogenesis, modeling early morphogenesis, and demonstrating interstitial cell migration as seenin vivo. These innovative assembloid systems help identify factors influencing assembloid formation and migration. Hepatic spheroid cultivation systems were also employed to model collective migration and branching morphogenesis. Fibroblast-conditioned media (MES-CM) plays a significant role in initiating dose-dependent branching migration. Future work will involve high temporal and spatial resolution imaging of hepatic and mesenchymal interactions to determine the cascade of cellular and molecular events involved in tissue formation, morphogenesis, and migration.

Organoids revolutionize personalized tissue modeling for organ development, drug discovery, and disease research. Organoid engineering advances into creating intricate synthetic tissues. The aim is to integrate morphogenesis, assembloid technology, and biomatrices to advance tissue engineering. The presented methods aid in modeling liver organogenesis and establishing guidelines for synthetic tissue construction.
A consistent map in the medial entorhinal cortex supports spatial memory
Authors: Malone Taylor J. , Tien Nai-Wen , Ma Yan , Cui Lian , Lyu Shangru , Wang Garret , Nguyen Duc , Zhang Kai , Myroshnychenko Maxym V. , Tyan Jean , Gordon Joshua A. , Kupferschmidt David A. , Gu Yi
Published: October 2023

The medial entorhinal cortex (MEC) is hypothesized to function as a cognitive map for memory-guided navigation. How this map develops during learning and influences memory remains unclear. By imaging MEC calcium dynamics while mice successfully learned a novel virtual environment over ten days, we discovered that the dynamics gradually became more spatially consistent and then stabilized. Additionally, grid cells in the MEC not only exhibited improved spatial tuning consistency, but also maintained stable phase relationships, suggesting a network mechanism involving synaptic plasticity and rigid recurrent connectivity to shape grid cell activity during learning. Increased c-Fos expression in the MEC in novel environments further supports the induction of synaptic plasticity. Unsuccessful learning lacked these activity features, indicating that a consistent map is specific for effective spatial memory. Finally, optogenetically disrupting spatial consistency of the map impaired memory-guided navigation in a well-learned environment. Thus, we demonstrate that the establishment of a spatially consistent MEC map across learning both correlates with, and is necessary for, successful spatial memory.
Gut Microbiome Wellness Index 2 for Enhanced Health Status Prediction from Gut Microbiome Taxonomic Profiles
Authors: Chang Daniel , Gupta Vinod K. , Hur Benjamin , Cobo-López Sergio , Cunningham Kevin Y. , Han Nam Soo , Lee Insuk , Kronzer Vanessa L. , Teigen Levi M. , Karnatovskaia Lioudmila V. , Longbrake Erin E. , Davis John M. , Nelson Heidi , Sung Jaeyun
Published: October 2023

Recent advancements in human gut microbiome research have revealed its crucial role in shaping innovative predictive healthcare applications. We introduce Gut Microbiome Wellness Index 2 (GMWI2), an advanced iteration of our original GMWI prototype, designed as a robust, disease-agnostic health status indicator based on gut microbiome taxonomic profiles. Our analysis involved pooling existing 8069 stool shotgun metagenome data across a global demographic landscape to effectively capture biological signals linking gut taxonomies to health. GMWI2 achieves a cross-validation balanced accuracy of 80% in distinguishing healthy (no disease) from non-healthy (diseased) individuals and surpasses 90% accuracy for samples with higher confidence (i.e., outside the “reject option”). The enhanced classification accuracy of GMWI2 outperforms both the original GMWI model and traditional species-level α-diversity indices, suggesting a more reliable tool for differentiating between healthy and non-healthy phenotypes using gut microbiome data. Furthermore, by reevaluating and reinterpreting previously published data, GMWI2 provides fresh insights into the established understanding of how diet, antibiotic exposure, and fecal microbiota transplantation influence gut health. Looking ahead, GMWI2 represents a timely pivotal tool for evaluating health based on an individual’s unique gut microbial composition, paving the way for the early screening of adverse gut health shifts. GMWI2 is offered as an open-source command-line tool, ensuring it is both accessible to and adaptable for researchers interested in the translational applications of human gut microbiome science.
Self-supervised segmentation and characterization of fiber bundles in anatomic tracing data
Authors: Sundaresan Vaanathi , Lehman Julia F. , Maffei Chiara , Haber Suzanne N. , Yendiki Anastasia
Published: October 2023

Anatomic tracing is the gold standard tool for delineating brain connections and for validating more recently developed imaging approaches such as diffusion MRI tractography. A key step in the analysis of data from tracer experiments is the careful, manual charting of fiber trajectories on histological sections. This is a very time-consuming process, which limits the amount of annotated tracer data that are available for validation studies. Thus, there is a need to accelerate this process by developing a method for computer-assisted segmentation. Such a method must be robust to the common artifacts in tracer data, including variations in the intensity of stained axons and background, as well as spatial distortions introduced by sectioning and mounting the tissue. The method should also achieve satisfactory performance using limited manually charted data for training. Here we propose the first deep-learning method, with a self-supervised loss function, for segmentation of fiber bundles on histological sections from macaque brains that have received tracer injections. We address the limited availability of manual labels with a semi-supervised training technique that takes advantage of unlabeled data to improve performance. We also introduce anatomic and across-section continuity constraints to improve accuracy. We show that our method can be trained on manually charted sections from a single case and segment unseen sections from different cases, with a true positive rate of ~0.80. We further demonstrate the utility of our method by quantifying the density of fiber bundles as they travel through different white-matter pathways. We show that fiber bundles originating in the same injection site have different levels of density when they travel through different pathways, a finding that can have implications for microstructure-informed tractography methods. The code for our method is available athttps://github.com/v-sundaresan/fiberbundle_seg_tracing.
Improved Resolution of Highly Pathogenic Avian Influenza Virus Haemagglutinin Cleavage Site Using Oxford Nanopore R10 Sequencing Chemistry
Authors: Ratcliff Jeremy D , Merritt Brian , Gooden Hannah , Siegers Jurre Y , Srikanth Abhi , Yann Sokhoun , Kol Sonita , Sin Sarath , Tok Songha , Karlsson Erik A , Thielen Peter M
Published: October 2023

Highly pathogenic avian influenza viruses continue to pose global risks to One Health, including agriculture, public, and animal health. Rapid and accurate genomic surveillance is critical for monitoring viral mutations, tracing transmission, and guiding interventions in near real-time. Oxford Nanopore sequencing holds promise for real-time influenza genotyping, but data quality from R9 chemistry has limited its adoption due to challenges resolving low-complexity regions such as the biologically critical hemagglutinin cleavage site, a homopolymer of basic amino acids that distinguish highly pathogenic strains. In this study, human and avian influenza isolates (n=45) from Cambodia were sequenced using both R9.4.1 and R10.4.1 flow cells and chemistries to evaluate performance between approaches. Overall, R10.4.1 yielded increased data output with higher average quality compared to R9.4.1, producing improved consensus sequences using a reference-based bioinformatics approach. R10.4.1 had significantly lower minor population insertion and deletion frequencies, driven by improved performance in low sequence complexity regions prone to insertion and deletion errors, such as homopolymers. Within the hemagglutinin cleavage site, R10.4.1 resolved the correct motif in 90% of genomes compared to only 60% with R9.4.1. Further examination showed reduced frameshift mutations in consensus sequences generated with R10.4.1 that could result in incorrectly classified virulence. Improved consensus genome quality from nanopore sequencing approaches, especially across biologically important low-complexity regions, is critical to reduce subjective hand-curation and will improve local and global genomic surveillance responses.
A prospective controlled study for EEG records comparison between Scalp-EEG and Ear-EEG wearable device, for subsequent analysis by an artificial intelligence-based system: SERAS-EEG study
Authors: Torres-Gaona G. , Blánquez D. , Valls A. , Raurich X. , Valls J. , Munsó L. , Arcos J.L. , Trejo A. , Aledo-Serrano A.
Published: October 2023

mjn-SERAS is an earpiece shaped as a hearing-aid device, which continuously records the electrical brain activity in two channels placed in the external auditory. It uses an artificial intelligence algorithm (AI), based system for early detection of preictal period of seizures. Sixteen patients with drug-resistant focal epilepsy and 14 control subjects were simultaneously studied with the mjn-SERAS device and a standard 24-channel EEG using the 10-20 system. Data from channels F8-T4 or F7-T3, according to the laterality of the epileptic focus was extracted from the standard EEG. We analyzed the average signal correlation (AC) between the two types of records, with and without artefact removal (filtered records [FR]), comparing inter-subject and subjects recordings (SR), as well between ictal and interictal periods in epilepsy patients.

AC was 0.90 [0.88 - 0.91] and 0.88 [0.86 - 0.90] in the FR and the whole cohort, respectively. No differences in the correlation of signals were found between controls and patients in the FR (-0.01 [-0.04;0.01], p=0.261) or the SR (-0.03 [-0.06;0.01], p=0.09). In addition, in the subset of patients with epilepsy, no differences in AC were noted between interictal activity and seizures (-0.02 [- 0.06; 0.02], p=0.352). Only AC during sleep in controls was found to be smaller compared to repose (-0.04 [-0.08;-0.01], p=0.01). No adverse events were reported. Our study supports an adequate correlation between the information recorded with both methods, providing technical support for use of the mjn-SERAS to record EEG signals.
DNA i-motif levels are overwhelmingly depleted in living human cells: insights from in-cell NMR
Authors: Víšková Pavlína , Ištvánková Eva , Ryneš Jan , Džatko Šimon , Loja Tomáš , Živković Martina Lenarčič , Rigo Riccardo , El-Khoury Roberto , Serrano-Chacón Israel , Damha Masad J. , González Carlos , Mergny Jean-Louis , Foldynová-Trantírková Silvie , Trantírek Lukáš
Published: October 2023

I-Motifs (iM) are non-canonical DNA structures potentially forming in accessible, single-stranded, cytosine-rich genomic regions, with regulatory roles. Chromatin, protein interactions, and intracellular properties seem to govern iM formation at sites with i-motif formation propensity (iMFPS) in human cells, yet their specific contributions remain unclear. Using in-cell NMR with oligonucleotide iMFPS models, we monitored iM-associated structural equilibria in asynchronous and cell cycle-synchronized HeLa cells at 37°C. Our findings show that iMFPS displaying pHT<7 under reference in vitro conditions occur predominantly in unfolded states in cells, while those with pHT>7 occur as a mix of folded and unfolded states depending on the cell cycle phase. Comparing these results with previous data obtained using an iM-specific antibody (iMab) revealed that cell cycle-dependent iM formation has a dual origin and iM formation concerns only a small fraction (possibly 1%) of genomic sites with iM formation propensity. We propose a comprehensive model aligning observations from iMab and in-cell NMR and enabling the identification of iMFPS capable of adopting iM structures under physiological conditions in living human cells. Our results suggest that many iMFPS may have biological roles linked to their unfolded states.
Atrial t-tubules adopt a specialist developmental state while alterations to Ca2+buffering maintain systolic Ca2+during postnatal development
Authors: Smith CER , Clarke JD , Quinn CJ , Sultan Z , Najem H , Denham NC , Hutchings DC , Madders GWP , Caldwell JL , Toms LK , Pinali C , Eisner DA , Trafford AW , Dibb KM
Published: October 2023

Transverse (t)-tubules ensure a uniform rise in calcium (Ca2+) and thus contraction in cardiac cells. Though more extensively studied in the ventricle, t-tubules also play a key role in the atria of large mammals, such as human, and their loss in heart failure is associated with impaired Ca2+release and thus contractility. T-tubule restoration is therefore an ideal therapeutic target but the process of t-tubule formation is not understood. The aim of this study was to determine how t-tubules develop in the healthy atria and the impact this has on Ca2+handling. Postnatal development was assessed in sheep from newborn through to adulthood. Atrial t-tubules were present at birth in the sheep atria and increased in density up until 3 months of age. In the latter part of development (3 months to adult) a lack of t-tubule growth but increase in cell width results in t-tubule density decreasing. In the newborn, despite reduced t-tubule density, we found the amplitude of the Ca2+transient was maintained and this was associated with increases in the L-type Ca2+current (ICa-L) and the Ca2+content of the sarcoplasmic reticulum (SR). We suggest these changes are sufficient to overcome the elevated cytosolic Ca2+buffering in the newborn and the decreased t-tubule density. We have shown the neonate atria is highly specialised to negate reduced central Ca2+release through enhanced surfaceICa-Land SR load. This maintains atrial function despite immature t-tubules highlighting important differences in Ca2+handling in the newborn and heart failure atria where t-tubules are sparse.
Membrane positioning across antigen-induced synaptic contacts tunes CAR-T cell signaling and effector responses
Authors: Li Fenglei , Choudhuri Kaushik
Published: October 2023

Tumor antigen recognition by chimeric antigen receptors (CAR) triggers phosphorylation of their cytoplasmic portions resulting in CAR-T cell activation. We and others have shown that immunoreceptor triggering depends on the formation of close synaptic contacts, determined by the span of immunoreceptor-ligand complexes, from which large inhibitory phosphatases such as CD45 are sterically excluded. Here, we show, varying CAR-antigen complex span, that CAR-T cell activation depends on a formation of close contacts with target cells. CAR-antigen complexes with a span of 4 immunoglobulin superfamily (IgSF) domains maximize CAR-T cell activation, closely matching the span of endogenous TCR-pMHC complexes. Longer CAR-antigen complexes precipitously reduced triggering and cytokine production, but notably, anti-tumor cytotoxicity was largely preserved due to a ∼10-fold lower signaling threshold for mobilization of cytolytic effector function. Increased intermembrane spacing disrupted short-spanned PD-1-PD- L1 interactions, reducing CAR-T cell exhaustion. Together, our results show that membrane positioning across the immunological synapse can be engineered to generate CAR-T cells with clinically desirable functional profilesin vitroandin vivo.
Changes in high-frequency aperiodic 1/f slope and periodic activity reflect post-stimulus functional inhibition in the visual cortex
Authors: Manyukhina Viktoriya O. , Prokofyev Andrey O. , Obukhova Tatiana S. , Stroganova Tatiana A. , Orekhova Elena V.
Published: October 2023

It has been shown that cessation of intensive sensory stimulation is associated with a transient increase in functional inhibition in the sensory cortical areas. However, the electrophysiological correlates of this post-stimulus inhibition in the human brain have not been properly investigated.

To investigate post-stimulus inhibition, we recorded magnetoencephalogram (MEG) at rest and after cessation of visual stimulation of varying intensity (high-contrast gratings drifting at a slow, medium, or high rate) in 25 healthy women aged 18-40 years. We analyzed condition- and intensity-related changes in MEG parameters sensitive to functional inhibition: periodic alpha-beta power, peak alpha frequency (PAF), and 1/f aperiodic slope. We also investigated the association of these parameters with sensory sensitivity and avoidance assessed by a questionnaire. To evaluate the influence of hormonal status on the studied parameters, participants were examined twice, during the follicular and luteal phases of the menstrual cycle (MC).

Regardless of MC phase, increasing intensity of the preceding visual stimulation resulted in increased posterior post-stimulus alpha-beta power, PAF, and a more negative/steeper aperiodic (1/f) slope of the power spectrum in the 35-45 Hz range. Compared to rest, the post-stimulus period was characterized by higher PAF, a steeper 35-45 Hz 1/f slope in posterior cortical areas, and a widespread increase in beta power. While condition- and intensity-dependent changes in alpha-beta power and 1/f slope were correlated, changes in PAF did not correlate with either of them. Greater intensity-dependent increase in visual alpha-beta power predicted higher subjective sensory sensitivity/avoidance, suggesting stronger regulatory top-down modulation of visual cortex in individuals with heightened sensitivity.

Our results show that several MEG parameters concordantly indicate a post-stimulus enhancement of inhibition that is proportional to the intensity of the preceding visual stimulation. While post-stimulus changes in alpha-beta power and 1/f slope may share some common mechanisms, changes in PAF reflect a distinct aspect of inhibitory regulation. Our results inform potential inhibition-based biomarkers for clinical and translational research.

Key points:

The cessation of visual stimulation leads to a transient increase in functional inhibition.

Changes in MEG parameters reflect post-stimulus enhancement of inhibition.

These changes scale with the intensity of the preceding stimulation.
Daptomycin forms a stable complex with phosphatidylglycerol for selective uptake to bacterial membrane
Authors: Machhua Pragyansree , Unnithan Vignesh Gopalakrishnan , Liu Yu , Jiang Yiping , Zhang Lingfeng , Guo Zhihong
Published: October 2023

Daptomycin is a potent lipopeptide antibiotic used in the treatment of live-threatening Gram-positive infections, but the molecular mechanism of its interaction with bacterial membrane remains unclear. Here we show that this interaction is divided into two stages, of which the first is a fast and reversible binding of the drug to phospholipid membrane in milliseconds and the second is a slow and irreversible insertion into membrane in minutes, only in the presence of the bacteria-specific lipid phosphatidylglycerol, to a saturating point where the ratio of the drug to phosphatidylglycerol is 1:2. Fluorescence-based titration showed that the antibiotic simultaneously binds two molecules of phosphatidylglycerol with a nanomolar binding affinity in the presence of calcium ion. The resulting stable complex is easily formed in a test tube and readily isolated from the membrane of drug-treated bacterial cells, strongly supporting a unique drug uptake mechanism in which daptomycin forms a stable multi-component complex with calcium and phosphatidylglycerol. Revelation of this novel uptake mechanism provides fresh insights into the mode of action of daptomycin and paves the way to new strategies to attenuate resistance to the drug.
On-target, dual aminopeptidase inhibition provides cross-species antimalarial activity
Authors: Edgar Rebecca C.S. , Malcolm Tess R. , Siddiqui Ghizal , Giannangelo Carlo , Counihan Natalie A. , Challis Matthew , Duffy Sandra , Chowdhury Mrittika , Marfurt Jutta , Dans Madeline , Wirjanata Grennady , Noviyanti Rintis , Daware Kajal , Suraweera Chathura D. , Price Ric N , Wittlin Sergio , Avery Vicky M. , Drinkwater Nyssa , Charman Susan A. , Creek Darren J. , de Koning-Ward Tania F. , Scammells Peter J. , McGowan Sheena
Published: October 2023

To combat the global burden of malaria, development of new drugs to replace or complement current therapies are urgently required. As drug resistance to existing treatments and clinical failures continue to rise, compounds targeting multiple life cycle stages and species need to be developed as a high priority. Here we show that the compoundMMV1557817is a nanomolar inhibitor of bothPlasmodium falciparumandPlasmodium vivaxaminopeptidases M1 and M17, leading to inhibition of end stage haemoglobin digestion in asexual parasites. Multi-stage analysis confirmed thatMMV1557817can also kill sexual stageP. falciparum, while cross-resistance studies confirmed the compound targets a mechanism of action distinct to current drug resistance mechanisms. Analysis of cross reactivity to homologous human enzymes shows the compound exhibits a high level of selectivity, whilst safety as well as druggability was confirmed in the murine modelP. berghei.MMV1557817-resistantP. falciparumparasites displayed only low-level resistance (<3-fold) and exhibited a slow growth rate that was quickly outcompeted by wild type parasites.MMV1557817-resistant parasites digest significantly more haemoglobin and possess a mutation inPfA-M17 that induces partial destabilisation of thePfA-M17 homohexamer, resulting in high-level resistance to specificPfA-M17 inhibition, but enhanced sensitivity to specificPfA-M1 inhibition, and importantly, these parasites were highly sensitive to artemisinin. Overall, these results confirmMMV1557817as a potential lead compound for further drug development and highlight the potential of dual inhibition of M1 and M17 as an effective multi-species drug targeting strategy.
Investigation of normalization procedures for transcriptome profiles of compounds oriented toward practical study design
Authors: Mizuno Tadahaya , Kusuhara Hiroyuki
Published: October 2023

The transcriptome profile is a representative phenotype-based descriptor of compounds, widely acknowledged for its ability to effectively capture compound effects. However, the presence of batch differences is inevitable. Despite the existence of sophisticated statistical methods, many of them presume a substantial sample size. How should we design a transcriptome analysis to obtain robust compound profiles, particularly in the context of small datasets frequently encountered in practical scenarios? This study addresses this question by investigating the normalization procedures for transcriptome profiles, focusing on the baseline distribution employed in deriving biological responses as profiles. Firstly, we investigated two large GeneChip datasets, comparing the impact of different normalization procedures. Through an evaluation of the similarity between response profiles of biological replicates within each dataset and the similarity between response profiles of the same compound across datasets, we revealed that the baseline distribution defined by all samples within each batch under batch-corrected condition is a good choice for large datasets. Subsequently, we conducted a simulation to explore the influence of the number of control samples on the robustness of response profiles across datasets. The results offer insights into determining the suitable quantity of control samples for diminutive datasets. It is crucial to acknowledge that these conclusions stem from constrained datasets. Nevertheless, we believe that this study enhances our understanding of how to effectively leverage transcriptome profiles of compounds and promotes the accumulation of essential knowledge for the practical application of such profiles.
Barriers and Facilitators to Trustworthy and Ethical AI-enabled Medical Care From Patient’s and Healthcare Provider’s Perspectives: A Literature Review
Authors: Mooghali Maryam , Stroud Austin M. , Yoo Dong Whi , Barry Barbara A , Grimshaw Alyssa A. , Ross Joseph S. , Zhu Xuan , Miller Jennifer E.
Published: October 2023

Background

Artificial intelligence (AI) and machine learning (ML) are increasingly used for prevention, diagnosis, monitoring, and treatment of cardiovascular diseases. Despite the potential for AI/ML to improve care, ethical concerns and mistrust in AI-enabled health care exist among the public and medical community. To inform practice guidelines and regulatory policies that facilitate ethical and trustworthy use of AI in medicine, we conducted a literature review to identify key ethical and trust barriers and facilitators from patients’ and healthcare providers’ perspectives when using AI in cardiovascular care.

Methods

In this rapid literature review, we searched six bibliographic databases to identify publications discussing transparency, trust, or ethical concerns (outcomes of interest) associated with AI/ML-based medical devices (interventions of interest) in the context of cardiovascular care from patients’, caregivers’, or healthcare providers’ perspectives. The search was completed on May 24, 2022 and was not limited by date or study design.

Results

After reviewing 7,925 papers from six databases and 3,603 papers identified through citation chasing, 145 articles were included. Key ethical concerns included privacy, security, or confidentiality issues; risk of healthcare inequity or disparity; risk of patient harm; accountability and responsibility concerns; problematic informed consent and potential loss of patient autonomy; and issues related to data ownership. Major trust barriers included data privacy and security concerns, potential risk of patient harm, perceived lack of transparency about AI-enabled medical devices, concerns about AI replacing human aspects of care, concerns about prioritizing profits over patients’ interests, and lack of robust evidence related to the accuracy and limitations of AI-based medical devices. Ethical and trust facilitators included ensuring data privacy and data validation, conducting clinical trials in diverse cohorts, providing appropriate training and resources to patients and healthcare providers and improving their engagement in different phases of AI implementation, and establishing further regulatory oversights.

Conclusion

This review revealed key ethical concerns and barriers and facilitators of trust in AI-enabled medical devices from patients’ and healthcare providers’ perspectives. Mitigation strategies, including enhancing regulatory oversight on the use of patient data and promoting AI safety and transparency are needed for effective implementation of AI in cardiovascular care.
Patient-reported predictors of post-discharge mortality after cardiac hospitalization
Authors: Nair Devika , Schildcrout Jonathan S. , Shi Yaping , Trochez Ricardo , Nwosu Sam , Bell Susan P. , Mixon Amanda S. , Welch Sarah A. , Goggins Kathryn , Bachmann Justin M. , Vasilevskis Eduard E. , Cavanaugh Kerri L. , Rothman Russell L. , Kripalani Sunil B.
Published: October 2023

Background

Adults hospitalized for cardiovascular events are at high risk for post-discharge mortality. Hospital-based screening of health-related psychosocial risk factors is now prioritized by the Joint Commission and the National Quality Forum to achieve equitable, high-quality care. We tested our hypothesis that key patient-reported psychosocial and behavioral measures could predict post-hospitalization mortality in a cohort of adults hospitalized for a cardiovascular event.

Methods

This was a prospective cohort of adults hospitalized at Vanderbilt University Medical Center. Validated patient-reported measures of health literacy, social support, disease self-management, and socioeconomic status were used as predictors of interest. Cox survival analyses of mortality were conducted over a median 3.5-year follow-up (range: 1.25 – 5.5 years).

Results

Among 2,977 adults, 1,874 (63%) were hospitalized for acute coronary syndrome and 1,103 (37%) were hospitalized for acute decompensated heart failure; 60% were male; and the mean age was 53 years. After adjusting for demographic, clinical, and other psychosocial factors, mortality risk was greatest among patients who reported being unable to work due to disability (Hazard Ratio (HR) 2.36, 95% Confidence Interval (CI): 1.73-3.21), who were retired (HR 2.14, 95% CI 1.60-2.87), and who reported unemployment (HR 1.99, 95% CI 1.30-3.06) as compared to those who were employed. Patient-reported measures of disease self-management, perceived health competence and exercise frequency, were also associated with mortality risk after full covariate adjustment (HR 0.86, 95% CI 0.73-1.00 per four-point increase), (HR 0.86, 95% CI 0.77-0.96 per three-day change), respectively.

Conclusions

Patient-reported measures of employment status independently predict post-discharge mortality after a cardiac hospitalization. Measure of disease self-management also have prognostic modest utility. Hospital-based screening of psychosocial risk is increasingly prioritized in legislative policy. Incorporating brief, valid measures of employment status and disease self-management factors may help target patients for psychosocial, financial, and rehabilitative resources during post-discharge transitions of care.
Effect of photobiomodulation to control pain after placement of elastomeric spacers: a randomized controlled study protocol
Authors: Pascuali Moya Luis Eduardo , Consolandich Cirisola Rolf Wilhem , García Olazabal María Victoria , Bruno Laura Hermida , Safi Federico Todeschini , Piriz Trindade Lucia , Longo Priscila Larcher , Chavantes Maria Cristina , Navarro Ricardo Scarparo , Duran Cinthya Cosme Gutierrez , Fernandes Kristianne Porta Santos , Mesquita Ferrari Raquel Agnelli , Bussadori Sandra Kalil , Motta Lara Jansiski , Horliana Anna Carolina Ratto Tempestini
Published: October 2023

Recent studies have shown that photobiomodulation (FBM) can modulate pain after the placement of elastomeric separators, however, to date, there is no ideal protocol for its application. Therefore, the objective of this study will be to evaluate the effect of photobiomodulation on pain control 24 hours after the placement of elastomeric separators using the visual analog scale (VAS). Twenty-five participants between 13 and 30 years old with the need for the placement of orthodontic bands in the lower first molars bilaterally will be included, which establishes a sample of fifty molars (right and left). Elastomeric separators will be placed on the mesial and distal surfaces of the right and left molars. The study groups will be G1 (experimental) - elastomeric separators + FBM (diode laser, 808nm, 100mw power, with 4 J, 3 points per vestibular and 3 points per palatal, single session) and G2-(control)-elastomeric separators + FBM simulation. Treatment will be randomized to the right molar and the opposite treatment will be applied to the left side. The patient and the evaluator will be blinded to the intervention performed. The primary outcome variable will be spontaneous pain assessed 24 hours after the placement of elastomeric separators measured with the VAS scale. Secondary outcome variables will be pain during mastication (measured with the VAS scale) at 72h after the placement, count of the number of analgesics (paracetamol), and local temperature (measured with a digital thermometer). To assess the impact of oral health on quality of life. of the participant, the OHIP-14 questionnaire will be applied. All the outcomes will be evaluated at baseline, 24 and 72 hours after the placement of elastomeric separators. If the data are normal, they will be submitted to the ANOVA – one-way test. Data will be presented as means ± SD and the p-value will be set to < 0.05.
Detecting diversifying selection for a trait from within and between-species genotypes and phenotypes
Authors: Latrille T. , Bastian M. , Gaboriau T. , Salamin N.
Published: October 2023

To quantify selection acting on a trait, methods have been developed using either within or between-species variation. However, methods using within-species variation do not integrate the changes at the macro-evolutionary scale. Conversely, current methods using between-species variation usually discard within-species variation, thus not accounting for processes at the micro-evolutionary scale. The main goal of this study is to define a neutrality index for a quantitative trait, by combining within- and between-species variation. This neutrality index integrates nucleotide polymorphism and divergence for normalizing trait variation. As such, it does not require estimation of population size nor of time of speciation for normalization. Our index can be used to seek deviation from the null model of neutral evolution, and test for diversifying selection. Applied to brain mass and body mass at the mammalian scale, we show that brain mass is under diversifying selection. Finally, we show that our test is not sensitive to the assumption that population sizes, mutation rates and generation time are constant across the phylogeny, and automatically adjust for it.
MAP1B Regulates Cortical Neuron Interstitial Axon Branching Through the Tubulin Tyrosination Cycle
Authors: Ziak Jakub , Dorskind Joelle , Trigg Brian , Sudarsanam Sriram , Hand Randal , Kolodkin Alex L.
Published: October 2023

Regulation of directed axon guidance and branching during development is essential for the generation of neuronal networks. However, the molecular mechanisms that underlie interstitial axon branching in the mammalian brain remain unresolved. Here, we investigate interstitial axon branchingin vivousing an approach for precise labeling of layer 2/3 callosal projection neurons (CPNs), allowing for quantitative analysis of axonal morphology at high acuity and also manipulation of gene expression in well-defined temporal windows. We find that the GSK3β serine/threonine kinase promotes interstitial axon branching in layer 2/3 CPNs by releasing MAP1B-mediated inhibition of axon branching. Further, we find that the tubulin tyrosination cycle is a key downstream component of GSK3β/MAP1B signaling. We propose that MAP1B functions as a brake on axon branching that can be released by GSK3β activation, regulating the tubulin code and thereby playing an integral role in sculpting cortical neuron axon morphology.

HIGHLIGHTS

- GSK3β activation induces excessive interstitial axon branching in excitatory cortical neurons

- MAP1B, acting as a brake, is a downstream effector of GSK3β-mediated axon branching

- MAP1B inhibition of axon branching is released by GSK3β phosphorylation

- GSK3β/MAP1B regulation of interstitial axon branching is through modification of the tubulin code
Conserved 3' Stem-Loop Structures Enable Comprehensive Analysis of Bacterial Transcription Termination in Metagenomes, Regardless of Rho Factor Dependency
Authors: Jin Yunfan , Cui Jiyun , Ma Hongli , Gan Fei , Xu Zhenjiang Zech , Lu Zhi John
Published: October 2023

Bacterial transcription termination is a critical yet underexplored mechanism of gene regulation in microbial ecosystems. Existing computational tools, however, primarily focus on predicting Rho-independent terminators (RITs) in model species, leaving significant gaps in understanding Rho-dependent termination (RDTs) and termination mechanisms in non-model species. To address these limitations, we developed BATTER (BActeria Transcript Three Prime End Recognizer), a comprehensive computational tool for bacterial transcript 3' termini prediction. BATTER builds on the observation that conserved stem-loop structures are frequently associated with 3' ends of primary transcripts generated by both RIT and RDT mechanisms across distantly related bacterial species. By leveraging Longformer (a transformer-based neural network model) with a CRF (Conditional Random Field) layer, BATTER demonstrated superior performance compared to existing tools. It enabled comprehensive analysis of 42,905 representative bacterial genomes, uncovering that stem-loop structures exhibit clade-specific properties with greater variations between species than between gene families. Notably, BATTER uncovered that certain Cyanobacteria lineages, despite lacking Rho homologs, harbor Rho utilization (RUT) site-like sequences near 3' ends, with preliminary experimental validation in E. coli suggesting their partial functionality in transcription termination. Additionally, BATTER systematically identified pervasive premature termination events in antimicrobial resistance (AMR) genes, highlighting their regulatory roles in translation protection and drug efflux. This study advances our understanding of transcription termination across diverse bacterial lineages and provides a robust computational approach for exploring transcription regulation in complex microbial ecosystems.
The nutrient sensor CRTC & Sarcalumenin / Thinman represent a new pathway in cardiac hypertrophy
Authors: Dondi Cristiana , Vogler Georg , Gupta Anjali , Walls Stanley M. , Kervadec Anaïs , Romero Michaela R. , Diop Soda B. , Goode Jason , Thomas John B. , Colas Alexandre R. , Bodmer Rolf , Montminy Marc , Ocorr Karen
Published: October 2023

Obesity and type 2 diabetes are at epidemic levels and a significant proportion of these patients are diagnosed with left ventricular hypertrophy.CREBRegulatedTranscriptionCo-activator (CRTC) is a key regulator of metabolism in mammalian hepatocytes, where it is activated by calcineurin (CaN) to increase expression of gluconeogenic genes. CaN is known its role in pathological cardiac hypertrophy, however, a role for CRTC in the heart has not been identified. InDrosophila,CRTCnull mutants have little body fat and exhibit severe cardiac restriction, myofibrillar disorganization, cardiac fibrosis and tachycardia, all hallmarks of heart disease. Cardiac-specific knockdown ofCRTC, or its coactivatorCREBb, mimicked the reduced body fat and heart defects ofCRTCnull mutants. Comparative gene expression inCRTCloss- or gain-of-function fly hearts revealed contra-regulation of genes involved in glucose, fatty acid, and amino acid metabolism, suggesting thatCRTCalso acts as a metabolic switch in the heart. Among the contra-regulated genes with conserved CREB binding sites, we identified the fly ortholog ofSarcalumenin,which is a Ca2+-binding protein in the sarcoplasmic reticulum. Cardiac knockdown recapitulated the loss of CRTC cardiac restriction and fibrotic phenotypes, suggesting it is a downstream effector ofCRTCwe namedthinman(tmn). Importantly, cardiac overexpression of either CaN orCRTCin flies caused hypertrophy that was reversed in aCRTCmutant background, suggesting CRTC mediates hypertrophy downstream of CaN, perhaps as an alternative to NFAT. CRTC novel role in the heart is likely conserved in vertebrates as knockdown in zebrafish also caused cardiac restriction, as in fl ies. These data suggest that CRTC is involved in myocardial cell maintenance and that CaN-CRTC- Sarcalumenin/tmnsignaling represents a novel and conserved pathway underlying cardiac hypertrophy.
WOMBAT-P: Benchmarking Label-Free Proteomics Data Analysis Workflows
Authors: Bouyssié David , Altıner Pınar , Capella-Gutierrez Salvador , Fernández José M. , Hagemeijer Yanick Paco , Horvatovich Peter , Hubálek Martin , Levander Fredrik , Mauri Pierluigi , Palmblad Magnus , Raffelsberger Wolfgang , Rodríguez-Navas Laura , Di Silvestre Dario , Kunkli Balázs Tibor , Uszkoreit Julian , Vandenbrouck Yves , Vizcaíno Juan Antonio , Winkelhardt Dirk , Schwämmle Veit
Published: October 2023

Proteomics research encompasses a wide array of experimental designs, resulting in diverse datasets varying in structure and properties. This diversity has led to a considerable variety of software solutions for data analysis, each of them using multiple tools with different algorithms for operations like peptide-spectrum matching, protein inference, quantification, statistical analysis, and visualization. Computational workflows combine these algorithms to facilitate end-to-end analysis, spanning from raw data to detecting differentially regulated proteins. We introduce WOMBAT-P, a versatile platform designed for the automatic benchmarking and comparison of bottom-up label-free proteomics workflows. By standardizing software parameterization and workflow outputs, WOMBAT-P empowers an objective comparison of four commonly utilized data analysis workflows. Furthermore, WOMBAT-P streamlines the processing of public data based on the provided metadata, with an optional specification of 30 parameters. Wombat-P can use Sample and Data Relationship Format for Proteomics (SDRF-Proteomics) as the file input to simply process annotated local or ProteomeXchange deposited datasets. This feature offers a shortcut for data analysis and facilitates comparisons among diverse outputs. Through an examination of experimental ground truth data and a realistic biological dataset, we unveil significant disparities and a low overlap between identified and quantified proteins. WOMBAT-P not only enables rapid execution and seamless comparison of four workflows (on the same dataset) using a wide range of benchmarking metrics but also provides insights into the capabilities of different software solutions. These metrics support researchers in selecting the most suitable workflow for their specific dataset. The modular architecture of WOMBAT-P promotes extensibility and customization, making it an ideal platform for testing newly developed software tools within a realistic data analysis context.
Biochemical and structural characterization of a Class A β-lactamase fromNocardia cyriacigeorgica
Authors: Feuillard Jérôme , Couston Julie , Benito Yvonne , Hodille Elisabeth , Dumitrescu Oana , Blaise Mickaël
Published: October 2023

Nocardiaare gram-positive bacteria from the Actinobacteria phylum. SomeNocardiaspecies can infect humans and are usually considered opportunist pathogens as they often infect immunocompromised patients. Albeit, their clinical incidence is low, manyNocardiaspecies are nowadays considered emerging pathogens. Primary sites of infection ofNocardiaare the skin or the lungs but dissemination to other body parts is very frequent. These disseminated infections are very difficult to treat and thus, tackled with multiple classes of antibiotics, on top of the traditional treatment targeting the folate pathway. ß-lactams are often included in the regimen but manyNocardiaspecies present moderate or strong resistance to some of this drug class. Genomic, microbiological, and biochemical studies have reported the presence of class A ß-lactamases (ABL) in a handful ofNocardiaspecies but no structural investigation ofNocardiaß-lactamases has been performed yet. In this study, we report the expression, purification, and preliminary biochemical characterization of the ABL from aNocardia cyriacigeorgica(NCY-1) clinical strain. We describe, as well, the crystallization and the very high-resolution crystal structure of NCY-1. The protein sequence and structural analysis demonstrate that NCY-1 belongs to ß-lactamase of class A1 and attest to its very high conservation with ABL from other human pathogenicNocardia. In addition, the presence of one molecule of citrate tightly bound in the catalytic site of the enzyme is described. This structure may provide a solid basis for future drug development to specifically targetNocardiaspp. ß-lactamases.

Synopsis

The crystal structure at high resolution of a class A ß-lactamase from a clinical strain ofNocardia cyriacigeorgicais reported.