bluuebunny/crossref_metadata_2025 huggingface dataset:
Airway pressure release ventilation for lung protection in acute respiratory distress syndrome: an alternative way to recruit the lungs
Authors: Camporota Luigi , Rose Louise , Andrews Penny L. , Nieman Gary F. , Habashi Nader M.
Published: December 2023

Purpose of review

Airway pressure release ventilation (APRV) is a modality of ventilation in which high inspiratory continuous positive airway pressure (CPAP) alternates with brief releases. In this review, we will discuss the rationale for APRV as a lung protective strategy and then provide a practical introduction to initiating APRV using the time-controlled adaptive ventilation (TCAV) method.

Recent findings

APRV using the TCAV method uses an extended inspiratory time and brief expiratory release to first stabilize and then gradually recruit collapsed lung (over hours/days), by progressively ‘ratcheting’ open a small volume of collapsed tissue with each breath. The brief expiratory release acts as a ‘brake’ preventing newly recruited units from re-collapsing, reversing the main drivers of ventilator-induced lung injury (VILI). The precise timing of each release is based on analysis of expiratory flow and is set to achieve termination of expiratory flow at 75% of the peak expiratory flow. Optimization of the release time reflects the changes in elastance and, therefore, is personalized (i.e. conforms to individual patient pathophysiology), and adaptive (i.e. responds to changes in elastance over time).

APRV using the TCAV method is a paradigm shift in protective lung ventilation, which primarily aims to stabilize the lung and gradually reopen collapsed tissue to achieve lung homogeneity eliminating the main mechanistic drivers of VILI.
Ventilation during extracorporeal gas exchange in acute respiratory distress syndrome
Authors: Fumagalli Jacopo , Pesenti Antonio
Published: December 2023

Purpose of review

Accumulating evidence ascribes the benefit of extracorporeal gas exchange, at least in most severe cases, to the provision of a lung healing environment through the mitigation of ventilator-induced lung injury (VILI) risk. In spite of pretty homogeneous criteria for extracorporeal gas exchange application (according to the degree of hypoxemia/hypercapnia), ventilatory management during extracorporeal membrane oxygenation (ECMO)/carbon dioxide removal (ECCO2R) varies across centers. Here we summarize the recent evidence regarding the management of mechanical ventilation during extracorporeal gas exchange for respiratory support.

Recent findings

At present, the most common approach to protect the native lung against VILI following ECMO initiation involves lowering tidal volume and driving pressure, making modest reductions in respiratory rate, while typically maintaining positive end-expiratory pressure levels unchanged.

Regarding ECCO2R treatment, higher efficiency devices are required in order to reduce significantly respiratory rate and/or tidal volume.

The best compromise between reduction of native lung ventilatory load, extracorporeal gas exchange efficiency, and strategies to preserve lung aeration deserves further investigation.
Setting positive end-expiratory pressure in the severely obstructive patient
Authors: Jubran Amal
Published: December 2023

Purpose of review

The response to positive end-expiratory pressure (PEEP) in patients with chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation depends on the underlying pathophysiology. This review focuses on the pathophysiology of COPD, especially intrinsic PEEP (PEEPi) and its consequences, and the benefits of applying external PEEP during assisted ventilation when PEEPi is present.

Recent findings

The presence of expiratory airflow limitation and increased airway resistance promotes the development of dynamic hyperinflation in patients with COPD during acute respiratory failure. Dynamic hyperinflation and the associated development of PEEPi increases work of breathing and contributes to ineffective triggering of the ventilator. In the presence of airflow limitation, application of external PEEP during patient-triggered ventilation has been shown to reduce inspiratory effort, facilitate ventilatory triggering and enhance patient-ventilator interaction. To minimize the risk of hyperinflation, it is advisable to limit the level of external PEEP during assisted ventilation after optimization of ventilator settings to about 70% of the level of PEEPi (measured during passive ventilation).

In patients with COPD and dynamic hyperinflation receiving assisted mechanical ventilation, the application of low levels of external PEEP can minimize work of breathing, facilitate ventilator triggering and improve patient-ventilator interaction.
Nursing Professional Development Practitioners’ Self-Perceived Influence
Authors: Harper Mary G. , Maloney Patsy , MacDonald Ryan
Published: December 2023

In a quantitative study to determine nursing professional development (NPD) practitioners’ self-perceived influence, influence was operationally defined as political skill. A sample of 989 NPD practitioners reported high-average overall levels of political skill. For those without formal leadership positions, networking ability, a subscale of political skill, was predicted by NPD certification and a graduate degree or higher. NPD practitioners can enhance their influence competency through education, certification, professional development, mentoring, and coaching.
PRAME Immunohistochemistry for Distinguishing Vulvar and Vaginal Melanoma From Benign Melanocytic Nevi
Authors: Martin Spencer D. , Martin Karina C. , Gilks C. Blake , Crawford Richard I. , Hoang Lien N.
Published: December 2023

Vulvovaginal melanoma (VVM) is a rare but deadly disease, accounting for 5% of all vulvar malignancies, with a 5-yr survival rate of only 47% for all stages of the disease. VVM is a distinct subset of melanoma, with a unique genomic profile and underlying pathogenesis unassociated with sun exposure. Distinguishing these rare malignancies from very common pigmented lesions of the vulva and vagina is challenging as histologic features often overlap between entities. PReferentially expressed Antigen in MElanoma (PRAME) is a melanoma-associated protein, and immunohistochemistry (IHC) for PRAME distinguishes cutaneous, oral mucosal, and retinal melanoma from atypical nevi. Given the biological differences between VVM and cutaneous melanoma, the utility of PRAME IHC for the diagnosis of VVM is unknown. We accrued a cohort of 20 VVM and 21 benign vulvar melanocytic nevi. We found that nuclear PRAME IHC staining with 4+ intensity was present in 85% of the VVM and 0% of the nevi. With the assistance of PRAME IHC, we found evidence of close or positive margin involvement in 3 of 10 cases where margins were originally diagnosed as negative for melanoma in situ. Our study is the first to assess PRAME IHC in a cohort of VVM cases and provides confidence for using PRAME IHC to assist with diagnosis and margin assessment in this rare disease.
Cervical Lymph Node Metastasis as the Initial Presentation of Femoral Epithelioid Hemangioendothelioma Revealed by 18F-FDG PET/CT
Authors: Hu Xianwen
Published: December 2023

Femoral epithelioid hemangioendothelioma with cervical lymph node metastasis is rare. We report the FDG PET/CT findings of cervical lymph node metastasis from left femoral epithelioid hemangioendothelioma in a 50-year-old woman with painless enlargement of the left cervical lymph nodes as the initial presentation. Ultrasound and MRI revealed multiple enlarged lymph nodes in the left cervical sheath area. PET/CT showed strong radioactive uptake in the left cervical lymph nodes, and there was additional lesion with increased FDG uptake in the left femur, which was later confirmed as cervical lymph nodes metastasis from left femoral epithelioid hemangioendothelioma by pathological examination.
C-X-C Motif Chemokine Receptor 4–Targeted Radioligand Therapy in Hematological Malignancies—Myeloablative Effects, Antilymphoma Activity, and Safety Profile
Authors: Dreher Niklas , Dörrler Anna-Lena , Kraus Sabrina , Higuchi Takahiro , Serfling Sebastian E. , Samnick Samuel , Einsele Hermann , Grigoleit Götz Ulrich , Buck Andreas K. , Werner Rudolf A.
Published: December 2023

Background

After C-X-C motif chemokine receptor 4 (CXCR4)–directed radioligand therapy (RLT), lymphoma patients are scheduled for conditioning therapy (CON) followed by hematopoietic stem cell transplantation (HSCT). We aimed to determine whether CXCR4-RLT can achieve bone marrow ablation and direct antilymphoma activity independent from CON/HSCT and also evaluated the safety profile of this theranostic approach in an acute setting.

Patients and Methods

After CXCR4-directed 68Ga-pentixafor PET/CT, 21 heavily pretreated patients with hematological malignancies underwent CXCR4-directed RLT using 90Y-pentixather. The extent of myeloablative efficacy was determined by investigating hematologic laboratory parameters before RLT (day −1), at the day of RLT (day 0), 2 days after RLT (day 2), and before CON (median day 10). Serving as surrogate marker of antilymphoma activity, lactate dehydrogenase (LDH) levels were also assessed until CON. We also screened for laboratory-defined tumor lysis syndrome after the Cairo-Bishop definition and recorded acute laboratory adverse events using the Common Terminology Criteria for Adverse Events version 5.0.

Results

After RLT, we observed a significant decline of leukocyte levels by 79.4% ± 18.7% till CON (granulocytes, drop by 70.3% ± 21%; platelets, reduction by 43.1% ± 36%; P ≤ 0.0005 vs day 0, respectively). After RLT, LDH levels already reached a peak at day 2, which was followed by a rapid decline thereafter (peak vs day of CON, P = 0.0006), indicating that 90Y-pentixather exhibits direct antilymphoma activity. At day of CON, LDH levels were also significantly lower when compared with day −1 (P = 0.04), suggestive for durable response mediated by RLT. No patient fulfilled the criteria of tumor lysis syndrome, whereas 25 laboratory adverse events attributable to CXCR4-directed treatment were identified (≥grade 3 in 2/25 [8%]). During further treatment course, all patients (100%) received HSCT.

Conclusions

CXCR4-directed RLT causes effective myeloablation, which allows for HSCT. In addition, it also exerts direct antilymphoma activity independent of subsequent therapeutic steps, whereas safety profile was acceptable.
Airborne eDNA captures three decades of ecosystem biodiversity
Authors: Sullivan Alexis R. , Karlsson Edvin , Svensson Daniel , Brindefalk Björn , Villegas Jose Antonio , Mikko Amanda , Bellieny Daniel , Siddique Abu Bakar , Johansson Anna-Mia , Grahn Håkan , Sundell David , Norman Anita , Esseen Per-Anders , Sjödin Andreas , Singh Navinder J , Brodin Tomas , Forsman Mats , Stenberg Per
Published: December 2023

Conserving biodiversity is a global imperative, yet our capacity to quantify and understand species occurrences has been limited. To help address this challenge, we develop a novel monitoring approach based on deep sequencing of airborne eDNA. When applied to a 34-year archive of weekly filters from an aerosol sampling station in northern Sweden, our methods enabled robust detection of over 2,700 genera across all domains of life and estimates of eDNA catchment areas. Reconstructed time series revealed regional biodiversity declines consistent with contemporary, large-scale transformations of forest composition and structure. Our results show airborne eDNA can reliably monitor biodiversity and underscore the immense latent potential in the thousands of aerosol monitoring stations deployed worldwide.

One-Sentence Summary

DNA captured from air reveals organisms from all domains of life and their long-term trends.
Assessing the potential of BirdNET to infer European bird communities from large-scale ecoacoustic data
Authors: Funosas David , Barbaro Luc , Schillé Laura , Elger Arnaud , Castagneyrol Bastien , Cauchoix Maxime
Published: December 2023

Passive acoustic monitoring has become increasingly popular as a practical and cost-effective way of obtaining highly reliable acoustic data in ecological research projects. Increased ease of collecting these data means that, currently, the main bottleneck in ecoacoustic monitoring projects is often the time required for the manual analysis of passively collected recordings. In this study we evaluate the potential and current limitations of BirdNET-Analyzer v2.4, the most advanced and generic deep learning algorithm for bird recognition to date, as a tool to assess bird community composition through the automated analysis of large-scale ecoacoustic data.

To this end, we study 3 acoustic datasets comprising a total of 629 environmental soundscapes collected in 194 different sites spread across a 19° latitude span in Europe. We analyze these recordings both with BirdNET and by manual listening by local expert birders, and we then compare the results obtained through the two methods to evaluate the performance of the algorithm both at the level of each single vocalization and for entire recording sequences (1, 5 or 10 min).

Our analyses reveal that BirdNET identifications can be highly reliable if a sufficiently high minimum confidence threshold is used. However, the current recall of the algorithm is markedly low when the minimum confidence threshold is adjusted to ensure high levels of precision. Thus, we found that F1-scores remain moderate (<0.5) for all datasets and confidence thresholds studied. We therefore estimate that acoustic datasets of extended duration are currently necessary for BirdNET to provide a reliable and minimally comprehensive picture of the target bird community. Our results also suggest that BirdNET performance is not significantly influenced by the type of recorder used or the habitat recorded but is modulated by the volume of species-specific acoustic data available online.

We conclude that a judicious use of AI-based IDs provided by BirdNET can represent a novel and powerful method to assist in the assessment of bird community composition through the automated analysis of large-scale ecoacoustic data. Finally, we provide best use recommendations to ensure optimal results from the algorithm for the ecological study of bird communities.
3D Nuclei Segmentation by Combining GAN Based Image Synthesis and Existing 3D Manual Annotations
Authors: Galindo Xareni , Barry Thierno , Guyot Pauline , Rivière Charlotte , Galland Rémi , Levet Florian
Published: December 2023

Nuclei segmentation is an important task in cell biology analysis that requires accurate and reliable methods, especially within complex low signal to noise ratio images with crowded cells populations. In this context, deep learning-based methods such as Stardist have emerged as the best performing solutions for segmenting nucleus. Unfortunately, the performances of such methods rely on the availability of vast libraries of ground truth hand-annotated data-sets, which become especially tedious to create for 3D cell cultures in which nuclei tend to overlap. In this work, we present a workflow to segment nuclei in 3D in such conditions when no specific ground truth exists. It combines the use of a robust 2D segmentation method, Stardist 2D, which have been trained on thousands of already available ground truth datasets, with the generation of pair of 3D masks and synthetic fluorescence volumes through a conditional GAN. It allows to train a Stardist 3D model with 3D ground truth masks and synthetic volumes that mimic our fluorescence ones. This strategy allows to segment 3D data that have no available ground truth, alleviating the need to perform manual annotations, and improving the results obtained by training Stardist with the original ground truth data.
Addressing Overlapping Sample Challenges in Genome-Wide Association Studies: Meta-Reductive Approach
Authors: Rajabli Farid
Published: December 2023

Polygenic risk scores (PRS) are instrumental in genetics, offering insights into an individual level genetic risk to a range of diseases based on accumulated genetic variations. These scores rely on Genome-Wide Association Studies (GWAS). However, precision in PRS is often challenged by the requirement of extensive sample sizes and the potential for overlapping datasets that can inflate PRS calculations. In this study, we present a novel methodology, Meta-Reductive Approach (MRA), that was derived algebraically to adjust GWAS results, aiming to neutralize the influence of select cohorts. Our approach recalibrates summary statistics using algebraic derivations. Validating our technique with datasets from Alzheimer’s disease studies, we showed perfect correlation between summary statistics of proposed approach and “leave-one-out” strategy. This innovative method offers a promising avenue for enhancing the accuracy of PRS, especially when derived from meta-analyzed GWAS data.

Availability and implementation

MRA script is freely available athttps://github.com/hihg-um/MRAas an R function.
Decoding Prognostic Markers: Bioinformatics Insights into PIH1D1 and p53 in Children’s Brain Cancer
Authors: Kumar Dhiraj , Ranjan Prashant , Verma Amit Kumar , Mir Riyaz Ahmad
Published: December 2023

Genetic alterations in normal brain cells lead to the development of brain tumors (BT). The incidence of newly diagnosed cases is on the rise over time. Understanding the molecular biology of pediatric brain tumors is crucial for advancing novel therapeutic approaches to prevent or effectively manage this disease. The R2TP complex, a conserved co-chaperone from yeast to mammals, including RUVBL1, RUVBL2, PIH1D1, and RPAP3 in humans, plays a crucial role in the assembly and maturation of various multi-subunit complexes. This study evaluates the expression of PIH1D1 and p53 in pediatric brain cancers using The Cancer Genome Atlas (TCGA) data through the UALCAN platform—a novel, user-friendly resource for cancer OMICS data analysis.

Our analysis revealed elevated expression levels of PIH1D1 in pediatric brain tumors across all age groups compared to normal tissues, suggesting its potential as an early detection marker and a prognostic indicator. Additionally, P53 emerged as a promising target for brain tumor treatment, warranting exploration for age-specific applications. The Venn Diagram analysis further delineated key genes within the PIH1D1 and P53 networks, providing insights into the genetic landscape of childhood brain cancer.

Despite these findings, the study has limitations, primarily relying on bioinformatics databases. Future research will incorporate clinical tissues and cell lines in in vivo and in vitro experiments to unravel the mechanistic roles of PIH1D1 and p53 in brain tumors. This comprehensive approach bridges bioinformatics and clinical exploration, contributing to a holistic understanding of pediatric brain cancer molecular biology and paving the way for targeted therapeutic interventions.
Cost-effectiveness of vector control strategies for supplementing mass drug administration for eliminating lymphatic filariasis in India
Authors: Shepard Donald S. , Lwin Aung K. , Pulikkottil Sunish I. , Kalimuthu Mariapillai , Arunachalam Natarajan , Tyagi Brij K. , White Graham B.
Published: December 2023

Background/Methodology

Despite progress using mass drug administration (MDA), lymphatic filariasis (LF) remains a major public health issue in India. Vector control (VC) is hypothesized as a potentially useful addition to MDA towards LF elimination. We conducted cost-effectiveness analysis of MDA alone and augmented by VC single (VCS) or integrated VC approaches (VCI). Data came from historical controls and a 3-arm cluster randomized trial of 36 villages at risk of LF transmission in Tamil Nadu, India. The arms were: MDA alone (the standard of care); VCS (MDA plus expanded polystyrene beads for covering the water surface in wells and cesspits to suppress the filariasis vector mosquitoCulex quinquefasciatus), and VCI (VCS plus insecticidal pyrethroid impregnated curtains over windows, doors, and eaves). Economic costs in 2010 US$ combined government and community inputs from household to state levels. Outcomes were controlled microfilaria prevalence (MfP) and antigen prevalence (AgP) to conventional elimination targets (MfP<1% and AgP<2%) from 2010 to 2013, and disability adjusted life years (DALYs) averted.

Principal Findings

The estimated annual economic cost per resident was US$0.53 for MDA alone, US$1.02 for VCS, and US$1.83 for VCI. With MDA offered in all arms, all reduced LF prevalence substantially and significantly from 2010 to 2013. MDA proved highly cost effective at $112 per DALY, a very small (8%) share of India’s then per capita GDP. Progress towards elimination was comparable across all three study arms.

Conclusions

The well-functioning MDA was effective and very cost-effective for eliminating LF, leaving little scope for further improvement. Supplementary VC demonstrated no statistically significant additional benefit in this trial.

Authors’ Summary

Lymphatic filariasis (LF) is one of the twenty neglected tropical diseases (NTDs) that affect more than one billion people worldwide. As part of the effort toward global elimination of LF, the Indian State of Tamil Nadu government has implemented mass drug administration (MDA) repeatedly since 1996. Despite their efforts, LF had not yet been eliminated. Although vector control (VC) is proposed to augment regular MDA to help eliminate LF, little is known about the increased impact or costs. Our study compares the costs of MDA alone to the combination of MDA with alternative VC interventions. We calculated both program operating costs and costs to communities. We found MDA to be very cost-effective for eliminating LF. Against low levels of LF endemicity (≤10%), the study had limited ability to detect further improvements and found no significant incremental improvements from VC.
Brain activations during execution and observation of visually guided sequential manual movements in autism and in typical development: A study protocol
Authors: Domellöf Erik , Hjärtström Hanna , Johansson Anna-Maria , Rudolfsson Thomas , Stillesjö Sara , Säfström Daniel
Published: December 2023

Motor issues are frequently observed accompanying core deficits in autism spectrum disorder (ASD). Impaired motor behavior has also been linked to cognitive and social abnormalities, and problems with predictive ability have been suggested to play an important, possibly shared, part across all these domains. Brain imaging of sensory-motor behavior is a promising method for characterizing the neurobiological foundation for this proposed key trait. The present functional magnetic resonance imaging (fMRI) developmental study, involving children/youth with ASD, typically developing (TD) children/youth, and neurotypical adults, will investigate brain activations during execution and observation of a visually guided, goal-directed sequential (two-step) manual task. Neural processing related to both execution and observation of the task, as well as activation patterns during the preparation stage before execution/observation will be investigated. Main regions of interest include frontoparietal and occipitotemporal cortical areas, the human mirror neuron system (MNS), and the cerebellum.
Complete genomic assembly of Mauritian cynomolgus macaque killer immunoglobulin-like receptor and natural killer group 2 haplotypes
Authors: Prall Trent M. , Karl Julie A. , Varghese Joshua M. , Baker David A. , Minor Nicholas R. , Raveendran Muthuswamy , Alan Harris R. , Rogers Jeffery , Wiseman Roger W. , O’Connor David H.
Published: December 2023

Mauritian-origin cynomolgus macaques (MCM) serve as a powerful nonhuman primate model in biomedical research due to their unique genetic homogeneity, which simplifies experimental designs. Despite their extensive use, a comprehensive understanding of crucial immune-regulating gene families, particularly killer immunoglobulin-like receptors (KIR) and natural killer group 2 (NKG2), has been hindered by the lack of detailed genomic reference assemblies. In this study, we employ advanced long-read sequencing techniques to completely assemble eight KIR and seven NKG2 genomic haplotypes, providing an extensive insight into the structural and allelic diversity of these immunoregulatory gene clusters. Leveraging these genomic resources, we prototype a strategy for genotyping KIR and NKG2 using short-read, whole exome capture data, illustrating the potential for cost-effective multi-locus genotyping at colony scale. These results mark a significant enhancement for biomedical research in MCMs and underscores the feasibility of broad-scale genetic investigations.
Tuning of cortical color mechanism revealed using steady-state visually evoked potentials
Authors: Watts Dylan J. , Rozman Ana , Somers Lucy P. , Gunel Bora , Racey Chris , Barnes Katie , Bosten Jenny M.
Published: December 2023

Color information is thought to be received by the primary visual cortex via two dominant retinogeniculate pathways, one signals color variation between teal and red, and the other signals color variation between violet and lime. This representation is thought to be transformed in the cortex so that there are a number of different cell populations representing a greater variety of hues. However, the properties of cortical color mechanisms are not well understood. In four experiments, we characterized the tuning functions of cortical color mechanisms by measuring the intermodulation of steady-state visually evoked potentials (SSVEPs). Stimuli were isoluminant chromatic checkerboards where odd and even checks flickered at different frequencies. As hue dissimilarity between the odd and even checks increased, the amplitude of an intermodulation component (I1) at the sum of the two stimulus frequencies decreased, revealing cortical color tuning functions. In Experiment 1 we found similar broad tuning functions for ‘cardinal’ and intermediate color axes, implying that the cortex has intermediately tuned color mechanisms. In Experiment 2 we found similar broad tuning functions for ‘checkerboards’ with no perceptible edges because the checks were formed from single pixels (∼0.096°), implying that the underlying neural populations do not rely on spatial chromatic edges. In Experiment 3 we manipulated check size and found that color tuning functions were consistent across check sizes used. In Experiment 4 we measured full 360° tuning functions for a ‘cardinal’ cortical color mechanism and found evidence for opponent color responses. The observed cortical color tuning functions were consistent with those measured using psychophysics and electrophysiology, implying that tracking intermodulation using SSVEPs provides a useful method for measuring them.
Astrocyte CB1 receptors are required for inhibitory maturation and ocular dominance plasticity in the mouse visual cortex
Authors: Min Rogier , Qin Yi , Kerst Sven , Saiepour M. Hadi , van Lier Mariska , Levelt Christiaan N.
Published: December 2023

Summary and Introduction

Neuronal circuits are shaped by experience. This happens much more readily in the young compared to the adult brain. The unique learning capacity of the young brain is regulated through postnatal critical periods, during which the ability of neuronal networks to re-wire is greatly enhanced1. Endocannabinoids, which signal through the cannabinoid CB1 receptor (CB1R), regulate several forms of neuronal plasticity2. In the developing neocortex, CB1Rs play a key role in the maturation of inhibitory circuits. For example, interfering with CB1R signaling during development disrupts inhibitory maturation in the prefrontal cortex3. In developing primary visual cortex (V1), endocannabinoid-mediated plasticity at inhibitory synapses regulates the maturation of inhibitory synaptic transmission, shifting synapses from an immature state characterized by strong short-term depression to a mature state with reduced short-term depression4,5. This maturation step correlates with the timing of the critical period. While CB1Rs were originally thought to reside mainly on presynaptic axon terminals, recent studies have highlighted an unexpected role for astrocytic CB1Rs in endocannabinoid mediated plasticity6-8. Here, we investigate the impact of cell-type specific removal of CB1Rs from interneurons or astrocytes on development of inhibitory synapses and network plasticity of V1. We show that removing CB1Rs from astrocytes interferes with maturation of inhibitory synaptic transmission in V1. In addition, it strongly reduces ocular dominance (OD) plasticity during the critical period. In contrast, removing interneuron CB1Rs leaves these processes intact. Our results reveal an unexpected role of astrocytic CB1Rs in critical period plasticity in V1, and highlight the involvement of glial cells in the plasticity and synaptic maturation of sensory circuits.
STRING-ing together protein complexes: corpus and methods for extracting physical protein interactions from the biomedical literature
Authors: Mehryary Farrokh , Nastou Katerina , Ohta Tomoko , Jensen Lars Juhl , Pyysalo Sampo
Published: December 2023

Understanding biological processes relies heavily on curated knowledge of physical interactions between proteins. Yet, a notable gap remains between the information stored in databases of curated knowledge and the plethora of interactions documented in the scientific literature. To bridge this gap, we introduce ComplexTome, a manually annotated corpus designed to facilitate the development of text-mining methods for the extraction of complex formation relationships among biomedical entities. This corpus comprises 1,287 documents with ∼3, 500 relationships. We train a novel relation extraction model on this corpus and find that it can highly reliably identify physical protein interactions (F1-score=82.8%). We additionally enhance the model’s capabilities through unsupervised trigger word detection and apply it to extract relations and trigger words for these relations from all open publications in the domain literature. This information has been fully integrated into the latest version of the STRING database, and all introduced resources are openly accessible via Zenodo and GitHub.
HGNNPIP: A Hybrid Graph Neural Network framework for Protein-protein Interaction Prediction
Authors: Chi Lutong , Ma Jinbiao , Wan Yingqiao , Deng Yang , Wu Yufeng , Cen Xiaochen , Zhou Xiaobo , Zhao Xin , Wang Yiming , Ji Zhiwei
Published: December 2023

A deep understanding of Protein-protein interactions (PPIs) can provide comprehensive insights into many biological functions, thereby facilitating drug target identification and novel therapeutic design. Recent developments in artificial intelligence (AI)-driven computational methods have enabled the discovery of previously uncharacterized PPIs from large-scale interactome datasets. Almost all existing machine learning methods rely on Subcellular Localization (SL) to construct balanced datasets based on positive interactions to achieve predictions. Despite high fitting accuracy, the generalization ability of these models is questionable. To solve this problem, we analyzed existing methods and found that the high false positives in these methods are due to the bias in data distribution caused by SL. Therefore, we proposed a new strategy for negative instance sampling in PPI prediction and developed a Hybrid Graph Neural Network framework for Protein-protein Interaction Prediction (HGNNPIP). The experimental results showed that HGNNPIP works well on six benchmark datasets. Comparison analysis demonstrated that our model outperformed the other four existing methods. We also used HGNNPIP to explore the molecular contacts involved in the rice-pathogen interaction system.In vivoexperiments confirmed multiple regulations related to disease resistance in rice. In summary, this study provides new insights into establishing a computational framework for PPI prediction with high reliability.
Low blood concentration of alcohol enhances activity related to stopping failure in the right inferior frontal cortex
Authors: Shinozaki Jun , Matsumoto Hiroshi , Saito Hidekazu , Murahara Takashi , Nagahama Hiroshi , Sakurai Yuuki , Nagamine Takashi
Published: December 2023

This study investigated the effects of low doses of alcohol, which are acceptable for driving a car, on inhibitory control and neural processing using the stop-signal task (SST) in 17 healthy right-handed social drinkers. The study employed simultaneous functional magnetic resonance imaging and electromyography (EMG) recordings to assess behavioural and neural responses under conditions of low-dose alcohol (breath-alcohol concentration of 0.15 mg/L) and placebo. The results demonstrated that even a small amount of alcohol consumption prolonged Go reaction times in the SST and modified stopping behaviour, as evidenced by a decrease in the frequency and magnitude of partial response EMG that did not result in button pressing during successful inhibitory control. Furthermore, alcohol intake enhanced neural activity during failed inhibitory responses in the right inferior frontal cortex, suggesting its potential role in behavioural adaptation following stop-signal failure. These findings suggest that even low levels of alcohol consumption within legal driving limits can greatly impact both the cognitive performance and brain activity involved in inhibiting responses. This research provides important evidence on the neurobehavioural effects of low-dose alcohol consumption, with implications for understanding the biological basis of impaired motor control and decision-making and potentially informing legal guidelines on alcohol consumption.
STN-PFC circuit related to attentional fluctuations during non-movement decision-making
Authors: Ai Shengnan
Published: December 2023

Decision-making is a cognitive process, in which participants need to attend to relevant information and ignore the irrelevant information. Previous studies have described a set of cortical areas important for attention. It is unclear whether subcortical areas also serve a role. The subthalamic nucleus (STN), a part of basal ganglia, is traditionally considered a critical node in the cortico-basal ganglia-thalamus-cortico network. Given the location of the STN and its widespread connections with cortical and subcortical brain regions, the STN plays an important role in motor and non-motor cognitive processing. We would like to know if STN is also related to fluctuations in attentional task performance, and how the STN interacts with prefrontal cortical regions during the process. We examined neural activities within STN covaried with lapses of attention (defined as behavior error). We found that decreased neural activities in STN were associated with sustained attention. By examining connectivity across STN and various sub-regions of the prefrontal cortex (PFC), we found that decreased connectivity across areas was associated with sustained attention. Our results indicated that decreased STN activities were associated with sustained attention, and the STN-PFC circuit supported this process.

Significance Statement

Attention is a core internal state variable that governs the allocation of limited resources depending on the task demands in various cognitive processes. If the subcortical area, subthalamic nucleus (STN), related to attentional fluctuations, and how the STN interacted with cortical regions during the process remains unclear. In this study, we examined neural activities within STN, and connectivity between STN and various prefrontal sub-regions during sustained attention and lapses of attention. We found both neural activities within STN and connectivity between STN-PFC circuit decreased during sustained attention. These findings indicated that decreased STN activities were associated with sustained attention, and the STN-PFC circuit supported this process.
Mapping the shared and unique structural asymmetry abnormalities of young children with autism and developmental delay/intellectual disability with normative models and their multimodal cascade
Authors: Geng Shujie , Dai Yuan , Rolls Edmund T. , Liu Yuqi , Zhang Yue , Deng Lin , Chen Zilin , Feng Jianfeng , Li Fei , Cao Miao
Published: December 2023

To understand the neural mechanism of autism spectrum disorder (ASD) concurrent with developmental delay/intellectual disability (DD/ID), it is essential to comprehensively take genetic, brain, and behavioural measurements as a whole and focus on subjects at early age. However, such research is still lacking.

Here, using the sMRI data of 1030 children under 8 years old, we employed developmental normative models to explore the atypical development of gray matter volume (GMV) asymmetry in individuals with ASD without DD/ID, ASD with DD/ID and DD/ID, and their associations with neurophysiological measures and transcription profiles.

By computing the individual deviations from typical controls, we observed an ASD-specific abnormal GMV laterality pattern that was more rightwards in the inferior parietal cortex and precentral cortex and noted abnormal within-group heterogeneity in the temporal pole. Specifically, ASD with DD/ID children exhibited more regional abnormalities; ASD without DD/ID children showed higher within-group variability; while children with DD/ID showed no significant abnormalities. However, there were no significant differences among the three groups. The GMV laterality of ASD without DD/ID children was associated with ASD symptoms, whereas that of ASD with DD/ID children was associated with both ASD symptoms and verbal IQ. Last, the GMV laterality of the ASD with DD/ID, ASD without DD/ID, and DD/ID groups was associated with shared and unique gene expression profiles, but the associations of the latter two groups with intellectual genes showed opposite effects.

Our findings illustrated the atypical development of regional structural lateralization in autistic children, which is associated with upstream genes and downstream behavioural performance. The differences and similarity between ASD and DD/ID additionally improve our standing to the neural mechanism of neurodevelopmental disorders comorbidity.
Molecular and micro-architectural mapping of gray matter alterations in psychosis
Authors: García-San-Martín Natalia , Bethlehem Richard AI , Mihalik Agoston , Seidlitz Jakob , Sebenius Isaac , Alemán-Morillo Claudio , Dorfschmidt Lena , Shafiei Golia , Ortiz-García de la Foz Víctor , Merritt Kate , David Anthony , Morgan Sarah E. , Ruiz-Veguilla Miguel , Ayesa-Arriola Rosa , Vázquez-Bourgon Javier , Alexander-Bloch Aaron , Misic Bratislav , Bullmore Edward T. , Suckling John , Crespo-Facorro Benedicto ,   Lifespan Brain Chart Consortium, Romero-García Rafael
Published: December 2023

The psychosis spectrum encompasses a heterogeneous range of clinical conditions associated with abnormal brain development. Detecting patterns of atypical neuroanatomical maturation across psychiatric disorders requires an interpretable metric standardized by age-, sex- and site-effect. The molecular and micro-architectural attributes that account for these deviations in brain structure from typical neurodevelopment are still unknown. Here, we aggregate structural magnetic resonance imaging data from 38,696 healthy controls (HC) and 1,256 psychosis-related conditions, including first-degree relatives of schizophrenia (SCZ) and schizoaffective disorder (SAD) patients (n= 160), individuals who had psychotic experiences (n= 157), patients who experienced a first episode of psychosis (FEP,n= 352), and individuals with chronic SCZ or SAD (n= 587). Using a normative modeling approach, we generated centile scores for cortical gray matter (GM) phenotypes, identifying deviations in regional volumes below the expected trajectory for all conditions, with a greater impact on the clinically diagnosed ones, FEP and chronic. Additionally, we mapped 46 neurobiological features from healthy individuals (including neurotransmitters, cell types, layer thickness, microstructure, cortical expansion, and metabolism) to these abnormal centiles using a multivariate approach. Results revealed that neurobiological features were highly co-localized with centile deviations, where metabolism (e.g., cerebral metabolic rate of oxygen (CMRGlu) and cerebral blood flow (CBF)) and neurotransmitter concentrations (e.g., serotonin (5-HT) and acetylcholine (α4β2) receptors) showed the most consistent spatial overlap with abnormal GM trajectories. Taken together these findings shed light on the vulnerability factors that may underlie atypical brain maturation during different stages of psychosis.
Comparison of semaglutide in combined with empagliflozin versus semaglutide and empagliflozin monotherapy in non-alcoholic fatty liver disease with type 2 diabetes: study protocol for a randomised controlled clinical trial
Authors: Lin Yu-Hao , Zhang Zhi-Jun , Zhong Jin-Qing , Wang Zhi-Yi , Peng Yi-Ting , Lin Yan-Mei , Zhang Huo-Ping , Tian Jian-Qing
Published: December 2023

Background

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. As the glucose-lowering agents, glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been demonstrated to improve liver fat content and glycaemic control in patients with NAFLD and T2DM. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty. Thus, the present randomised controlled trial aims at comparing the efficacy and safety of semaglutide plus empagliflozin with each treatment alone in patients with NAFLD and T2DM.

Methods

This 52-week double-blinded, randomised, parallel-group, active-controlled trial evaluates the effects of semaglutide, empagliflozin and semaglutide + empagliflozin in 105 eligible overweight/obese subjects with NAFLD and T2DM. The primary outcome will be a change from baseline to week 52 in the controlled attenuation parameter, free fatty acid and glucagon. Secondary endpoints include changes in liver stiffness measurement, liver enzymes, blood glucose, lipid levels, renal function, electrolyte balances, minerals and bone metabolism, cytokines, high-sensitivity C-reactive protein, ferritin, anthropometric indicators, nonalcoholic fatty liver fibrosis score, fibrosis 4 score and homeostatic model assessment for insulin resistance. In addition, intention-to-treat, interim analysis and safety analysis will be performed.

Discussion

This double-blinded, randomised, clinical trial involves a multi-disciplinary approach and aims to explore the synergistic effects of the combination of semaglutide and empagliflozin. The results can provide important insights into mechanisms of GLP-1 receptor agonists and/or SGLT-2 inhibitors in patients with NAFLD and T2DM.

Trial registration

This study has been registered with Chinese Clinical Trial Registry (ChiCTR2300070674).
Infection Inspection: Using the power of citizen science to help with image-based prediction of antibiotic resistance inEscherichia coli
Authors: Farrar Alison , Feehily Conor , Turner Piers , Zagajewski Aleksander , Chatzimichail Stelios , Crook Derrick , Andersson Monique , Oakley Sarah , Barrett Lucinda , Sayyed Hafez El , Fowler Philip W. , Nellåker Christoffer , Kapanidis Achillefs N. , Stoesser Nicole
Published: December 2023

Antibiotic resistance is an urgent global health challenge, necessitating rapid diagnostic tools to combat its escalating threat. This study introduces innovative approaches for expedited bacterial antimicrobial resistance profiling, addressing the critical need for swift clinical responses. Between February and April 2023, we conducted the Infection Inspection project, a citizen science initiative in which the public could participate in advancing an antimicrobial susceptibility testing method based on single-cell images of cellular phenotypes in response to ciprofloxacin exposure. A total of 5,273 users participated, classifying 1,045,199 images. Notably, aggregated user accuracy in image classification reached 66.8%, lower than our deep learning model’s performance at 75.3%, but accuracy increased for both users and the model when ciprofloxacin treatment was greater than a strain’s own minimum inhibitory concentration. We used the users’ classifications to elucidate which visual features influence classification decisions, most importantly the degree of DNA compaction and heterogeneity. We paired our classification data with an image feature analysis which showed that most of the incorrect classifications were due to cellular features that varied from the expected response. This understanding informs ongoing efforts to enhance the robustness of our deep learning-based bacterial classifier and diagnostic methodology. Our successful engagement with the public through citizen science is another demonstration of the potential for collaborative efforts in scientific research, specifically increasing public awareness and advocacy on the pressing issue of antibiotic resistance, and empowering individuals to actively contribute to the development of novel diagnostics.

Lay summary

Antibiotic resistance is a big health problem worldwide. We need fast ways to find out if bacteria are resistant to antibiotics. In our study, we develop new methods to do this quickly. We ran an online project called Infection Inspection from February to April 2023, in which 5,273 people took part. Together, they classified more than a million pictures of bacterial cells, helping our project use these pictures to detect antibiotic resistance. The volunteers performed well, getting near 67% of the answers right. We also learned which pictures helped or confused them. This will help us make our computer program better. This project didn’t just help science; it also taught people about antibiotic resistance. Partnerships between the public and scientists can make a difference to developing technologies that protect our health.
DPYDgenetic polymorphisms in non-European patients with severe fluoropyrimidine-related toxicity: A systematic review
Authors: Chan Tsun Ho , Zhang J. Eunice , Pirmohamed Munir
Published: December 2023

Background

Pre-treatmentDPYDscreening is mandated in the UK and EU to reduce the risk of severe and potentially fatal fluoropyrimidine-related toxicity. FourDPYDgene variants which are more prominently found in Europeans are tested.

Methods

Our systematic review in patients of non-European ancestry followed PRISMA guidelines to identify relevant articles up to April 2023. Publishedin silicofunctional predictions andin vitrofunctional data were also extracted. We also undertookin silicoprediction for allDPYDvariants identified.

Results

In 32 studies, published between 1998 and 2022, 53DPYDvariants were evaluated in patients from 12 countries encompassing 5 ethnic groups: African American, East Asian, Latin American, Middle Eastern, and South Asian. One of the 4 common EuropeanDPYDvariants, c.1905+1G>A, is also present in South Asian, East Asian and Middle Eastern patients with severe fluoropyrimidine-related toxicity. There seems to be relatively strong evidence for the c.557A>G variant, which is found in individuals of African ancestry, but is not currently included in the UK genotyping panel.

Conclusion

Extending UK pre-treatmentDPYDscreening to include variants that are present in some non-European ancestry groups will improve patient safety and reduce race and health inequalities in ethnically diverse societies.