bluuebunny/crossref_metadata_2025 huggingface dataset:
Recognition of small numbers in subset knowers Cardinal knowledge in early childhood
Authors: Gerbrand Anton , Gredebäck Gustaf , Lindskog Marcus
Published: October 2023

Previous research suggests that subset-knowers have an approximate understanding of small numbers. However, it is still unclear exactly what subset-knowers understand about small numbers. To investigate this further, we tested 133 participants, ages 2.6–4 years, on a newly developed eye-tracking task targeting cardinal recognition. Participants were presented with two sets differing in cardinality (1–4 items) and asked to find a specific cardinality. Our main finding showed that on a group level, subset-knowers could identify all presented targets at rates above chance, further supporting that subset-knowers understand several of the basic principles of small numbers. Exploratory analyses tentatively suggest that 1-knowers could identify the targets 1 and 2, but struggled when the target was 3 and 4, whereas 2-knowers and above could identify all targets at rates above chance. This might tentatively suggest that subset-knowers have an approximate understanding of numbers that is just (i.e. +1) above their current knower level. We discuss the implications of these results at length.
Looming-eyes buoys fail to reduce seabird bycatch in the Icelandic lumpfish fishery: depth-based fishing restrictions are an alternative
Authors: Rouxel Yann , Arnardóttir Hólmfríður , Oppel Steffen
Published: October 2023

Bycatch in gillnets from lumpfish (
Cyclopterus lumpus
) fisheries is an important conservation issue in the north Atlantic, with up to 30 000 seabirds potentially killed each year. To date, no technical solutions exist to reduce the bycatch of seabirds in gillnet fisheries, but research on above-water bird deterrents as a form of bycatch mitigation has shown promising results. Here, we tested whether a floating device called ‘looming-eyes buoy’ (LEB) would consistently reduce the bycatch of seabirds in the Icelandic lumpfish fishery. We conducted 61 controlled trials with sets of normal gillnets and experimental nets equipped with LEBs. We compared both fish catch and bycatch between net types while accounting for exposure time, water depth and season, and found no effect of LEBs on both target lumpfish catch and bycatch. Our analysis indicated however a strong correlation between bycatch rates and fishing depths, suggesting that depth-based fishing restrictions could virtually eliminate the bycatch of seabirds in this fishery. We estimated that limiting fishing to waters more than 50 m deep could save between 5000 and 9300 seabirds every year, arrest the population decline of endangered black guillemots in Iceland, while having only a marginal effect on target fish catch.
Real-world implications of aphantasia: episodic recall of eyewitnesses with aphantasia is less complete but no less accurate than typical imagers
Authors: Dando Coral J. , Nahouli Zacharia , Hart Alison , Pounder Zoe
Published: October 2023

Individuals with aphantasia report an inability to voluntarily visually image and reduced episodic memory, yet episodic accounts provided by witnesses and victims are fundamental for criminal justice. Using the mock-witness paradigm, we investigated eyewitness memory of individuals with aphantasia versus typical imagers. Participants viewed a mock crime and 48 hours later were interviewed about the event, randomly allocated to one of three conditions. Two interview conditions included techniques designed to support episodic retrieval mode, namely (i) Mental Reinstatement of Context (MRC) and (ii) Sketch Reinstatement of Context (Sketch-RC). A third Control condition did not include retrieval support. Aphantasic mock-eyewitnesses recalled 30% less correct information and accounts were less complete, but they made no more errors and were as accurate as typical imagers. Interaction effects revealed reduced correct recall and less complete accounts for aphantasic participants in MRC interviews versus Sketch-RC and Control. Aphantaisic participants in the Control outperformed those in both the Sketch-RC and MRC, although Sketch-RC improved completeness by 15% versus MRC. Our pattern of results indicates reduced mental imagery ability might be compensated for by alternative self-initiated cognitive strategies. Findings offer novel insights into episodic recall performance in information gathering interviews when ability to voluntarily visualize is impoverished.
High rates of male courtship in a female-ornamented pipefish
Authors: van Eyndhoven Fleur , Cameron Elissa Z. , Flanagan Sarah P.
Published: October 2023

In species with sex-specific signalling traits that appear to be ornamental (i.e. are conspicuous and with no obvious natural selection benefit), the ornamented sex typically initiates courtship and is most active in courtship. Here, we report for the first time courtship displays in the extremely sexually dimorphic, female-ornamented wide-bodied pipefish (
Stigmatopora nigra
), revealing unexpected behaviours. Females use their sex-specific ornament during courtship displays, as expected, but rarely in female–female interactions. Surprisingly, males initiated 61% of reciprocated courtship bouts and chased females in 17% of the bouts. This chasing behaviour could be a form of male harassment or be indicative of female disinterest in ardent males, either of which was unexpected to be found in this female-ornamented species. Our results highlight the need to study the details of species' behaviours in considering the potential roles of sexual selection and sexual conflict in shaping sexual dimorphism.
NIEND: Neuronal Image Enhancement through Noise Disentanglement
Authors: Zhao Zuo-Han , Liu Yufeng
Published: October 2023

Motivation

The full automation of digital neuronal reconstruction from light microscopic images has long been impeded by noisy neuronal images. Previous endeavors to improve image quality can hardly get a good compromise between robustness and computational efficiency.

Results

We present the image enhancement pipeline named Neuronal Image Enhancement through Noise Disentanglement (NIEND). Through extensive benchmarking on 863 mouse neuronal images with manually annotated gold standards, NIEND achieves remarkable improvements in image quality such as signal-background contrast (40-fold) and background uniformity (10-fold), compared to raw images. Furthermore, automatic reconstructions on NIEND-enhanced images have shown significant improvements compared to both raw images and images enhanced using other methods. Specifically, the average F1 score of NIEND-enhanced reconstructions is 0.88, surpassing the original 0.78 and the second-ranking method, which achieved 0.84. Up to 52% of reconstructions from NIEND-enhanced images outperform all other 4 methods in F1 scores. In addition, NIEND requires only 1.6 seconds on average for processing 256×256×256-sized images, and images after NIEND attain a substantial average compression rate of 1% by LZMA. NIEND improves image quality and neuron reconstruction, providing potential for significant advancements in automated neuron morphology reconstruction of petascale.

Availability and Implementation

The study is conducted based on Vaa3D and Python 3.10. Vaa3D is available on GitHub (https://github.com/Vaa3D). The proposed NIEND method is implemented in Python, and hosted on GitHub along with the testing code and data (https://github.com/zzhmark/NIEND). The raw neuronal images of mouse brains can be found at the BICCN’s Brain Image Library (BIL) (https://www.brainimagelibrary.org).
gtfsort: a tool to efficiently sort GTF files
Authors: Gonzales-Irribarren Alejandro , Fu Anne
Published: October 2023

The General Transfer Format (GTF) is a widely used format for gene annotation data, integral to various downstream analyses. Efficient management and sorting of GTF data are relevant, as unsorted data can intere with computational efficiency and interpretability. Sorted GTF data, on the other hand, enable more intuitive navigation of genomic structures and can enhance the performance of some bioinformatics tools. This paper presents gtfsort, a tool written in Rust, which efficiently sorts GTF files, outperforming existing software. By reducing computation times and providing structured outputs, gtfsort enhances the interpretation, relationships, and readability of gene annotation data.
An Evaluation of Physiological Responses Towards Variant Respiratory Function
Authors: Wang Tianchen , Mann Alfred E.
Published: October 2023

The respiratory system is listed among the most critical systems that sustain lives. Numerous studies have explored respiratory system mechanisms and developed models to understand its responses to external stimuli in recent years. However, the relationship between the function and other physiological appearances must be well-established. In this study, the respiratory function was evaluated as inspiratory capacity (IC), and various physiological responses were linked to the variance of such function. Paired t-tests confirmed significant inter-posture variations on IC. A positive linear correlation was observed between MEP and IC, while a weaker was observed between abdominal muscle shortening and IC, particularly during the end exhalation. The lung inflation reflex investigation noted a strong linear correlation between heart rate and breath level. This study could shed light on understanding the respiratory system and its applications in various fields.
Glioblastoma cells use an integrin- and CD44-mediated motor-clutch mode of migration in brain tissue
Authors: Anderson Sarah M , Kelly Marcus , Odde David J.
Published: October 2023

Glioblastoma (GBM) is an aggressive malignant brain tumor with 2-year survival rates of 6.7% [1], [2]. One key characteristic of the disease is the ability of glioblastoma cells to migrate rapidly and spread throughout healthy brain tissue[3], [4]. To develop treatments that effectively target cell migration, it is important to understand the fundamental mechanism driving cell migration in brain tissue. Here we utilized confocal imaging to measure traction dynamics and migration speeds of glioblastoma cells in mouse organotypic brain slices to identify the mode of cell migration. Through imaging cell-vasculature interactions and utilizing drugs, antibodies, and genetic modifications to target motors and clutches, we find that glioblastoma cell migration is most consistent with a motor-clutch mechanism to migrate through brain tissueex vivo, and that both integrins and CD44, as well as myosin motors, play an important role in constituting the adhesive clutch.
scBoolSeq: Linking scRNA-Seq Statistics and Boolean Dynamics
Authors: Maganã López Gustavo , Calzone Laurence , Zinovyev Andrei , Paulevé Loïc
Published: October 2023

Boolean networks are largely employed to model the qualitative dynamics of cell fate processes by describing the change of binary activation states of genes and transcription factors with time. Being able to bridge such qualitative states with quantitative measurements of gene expressions in cells, as scRNA-Seq, is a cornerstone for data-driven model construction and validation. On one hand, scRNA-Seq binarisation is a key step for inferring and validating Boolean models. On the other hand, the generation of synthetic scRNA-Seq data from baseline Boolean models provides an important asset to benchmark inference methods. However, linking characteristics of scRNA-Seq datasets, including dropout events, with Boolean states is a challenging task.

We presentscBoolSeq, a method for the bidirectional linking of scRNA-Seq data and Boolean activation state of genes. Given a reference scRNA-Seq dataset,scBoolSeqcomputes statistical criteria to classify the empirical gene pseudocount distributions as either unimodal, bimodal, or zero-inflated, and fit a probabilistic model of dropouts, with gene-dependent parameters. From these learnt distributions,scBoolSeqcan perform both binarisation of scRNA-Seq datasets, and generate synthetic scRNA-Seq datasets from Boolean trajectories, as issued from Boolean networks, using biased sampling and dropout simulation. We present a case study demonstrating the application ofscBoolSeq’s binarisation scheme in data-driven model inference. Furthermore, we compare synthetic scRNA-Seq data generated byscBoolSeqwith BoolODE from the same Boolean Network model. The comparison shows that our method better reproduces the statistics of real scRNA-Seq datasets, such as the mean-variance and mean-dropout relationships while exhibiting clearly defined trajectories in a two-dimensional projection of the data.

Author summary

The qualitative and logical modeling of cell dynamics has brought precious insight on gene regulatory mechanisms that drive cellular differentiation and fate decisions by predicting cellular trajectories and mutations for their control. However, the design and validation of these models is impeded by the quantitative nature of experimental measurements of cellular states. In this paper, we provide and assess a new methodology,scBoolSeqfor bridging single-cell level pseudocounts of RNA transcripts with Boolean classification of gene activity levels. Our method, implemented as a Python package, enables both tobinarisescRNA-Seq data in order to match quantitative measurements with states of logicals models, and to generate synthetic data from Boolean trajectories in order to benchmark inference methods. We show thatscBoolSeqaccurately captures main statistical features of scRNA-Seq data, including measurement dropouts, improving significantly the state of the art. Overall, scBoolSeq brings a statistically-grounded method for enabling the inference and validation of qualitative models from scRNA-Seq data.
Unlocking the Role of sMyBP-C: A Key Player in Skeletal Muscle Development and Growth
Authors: Song Taejeong , McNamara James W. , Baby Akhil , Ma Weikang , Landim-Vieira Maicon , Natesan Sankar , Pinto Jose Renato , Lorenz John N. , Irving Thomas C. , Sadayappan Sakthivel
Published: October 2023

Skeletal muscle is the largest organ in the body, responsible for gross movement and metabolic regulation. Recently, variants in theMYBPC1gene have been implicated in a variety of developmental muscle diseases, such as distal arthrogryposis. HowMYBPC1variants cause disease is not well understood. Here, through a collection of novel gene-edited mouse models, we define a critical role for slow myosin binding protein-C (sMyBP-C), encoded byMYBPC1, across muscle development, growth, and maintenance during prenatal, perinatal, postnatal and adult stages. Specifically,Mybpc1knockout mice exhibited early postnatal lethality and impaired skeletal muscle formation and structure, skeletal deformity, and respiratory failure. Moreover, a conditional knockout ofMybpc1in perinatal, postnatal and adult stages demonstrates impaired postnatal muscle growth and function secondary to disrupted actomyosin interaction and sarcomere structural integrity. These findings confirm the essential role of sMyBP-C in skeletal muscle and reveal specific functions in both prenatal embryonic musculoskeletal development and postnatal muscle growth and function.
Hyperbolic graph embedding of MEG brain networks to study brain alterations in individuals with subjective cognitive decline
Authors: Baker Cole , Suárez-Méndez Isabel , Smith Grace , Marsh Elisabeth B. , Funke Michael , Mosher John C. , Maestú Fernando , Xu Mengjia , Pantazis Dimitrios
Published: October 2023

An expansive area of research focuses on discerning patterns of alterations in functional brain networks from the early stages of Alzheimer’s disease, even at the subjective cognitive decline (SCD) stage. Here, we developed a novel hyperbolic MEG brain network embedding framework for transforming high-dimensional complex MEG brain networks into lower-dimensional hyperbolic representations. Using this model, we computed hyperbolic embeddings of the MEG brain networks of two distinct participant groups: individuals with SCD and healthy controls. We demonstrated that these embeddings preserve both local and global geometric information, presenting reduced distortion compared to rival models, even when brain networks are mapped into low-dimensional spaces. In addition, our findings showed that the hyperbolic embeddings encompass unique SCD-related information that improves the discriminatory power above and beyond that of connectivity features alone. Notably, we introduced a unique metric—the radius of the node embeddings—which effectively proxies the hierarchical organization of the brain. Using this metric, we identified subtle hierarchy organizational differences between the two participant groups, suggesting increased hierarchy in the dorsal attention, frontoparietal, and ventral attention subnetworks among the SCD group. Last, we assessed the correlation between these hierarchical variations and cognitive assessment scores, revealing associations with diminished performance across multiple cognitive evaluations in the SCD group. Overall, this study presents the first evaluation of hyperbolic embeddings of MEG brain networks, offering novel insights into brain organization, cognitive decline, and potential diagnostic avenues of Alzheimer’s disease.
New races with wider virulence indicate local evolution ofPuccinia striiformisf. sp.triticiin South America
Authors: Riella V. , Rodriguez-Algaba J. , García R. , Pereira F. , Silva P. , Hovmøller M.S. , Germán S.
Published: October 2023

Wheat yellow (stripe) rust, caused byPuccinia striiformisf. sp.tritici(Pst), is one of the most devastating diseases of wheat worldwide.Pstpopulations are composed of multiple genetic groups, each carrying one or more races characterized by different avirulence/virulence combinations. Since the severe epidemics in 2017, yellow rust has become the most economically important wheat foliar disease in Uruguay. Evolution of virulence was investigated based on genotyping and race typing of a representative set of 27Pstisolates collected from wheat fields in Uruguay between 2017 and 2021. Three genetic groups were identified, i.e.,PstS7,PstS10andPstS13, the latter being the most prevalent. Two races previously reported in Europe, Warrior (PstS7) and Benchmark (PstS10), were detected in four and two isolates, respectively. A third race known as Triticale2015 (PstS13), first detected in Europe in 2015 and in Argentina in 2017, was detected at several locations. Additional virulence toYr3, Yr17,Yr25,Yr27orYr32was detected in three new race variants withinPstS13. The identification of these new races, which have not been reported outside South America, provides strong evidence of the local evolution of virulence inPstduring the recent epidemic years.
Structure of the human heparan-α-glucosaminideN-acetyltransferase (HGSNAT)
Authors: Navratna Vikas , Kumar Arvind , Rana Jaimin K. , Mosalaganti Shyamal
Published: October 2023

Degradation of heparan sulfate (HS), a glycosaminoglycan (GAG) comprised of repeating units ofN-acetylglucosamine and glucuronic acid, begins in the cytosol and is completed in the lysosomes. Acetylation of the terminal non-reducing amino group of α-D-glucosamine of HS is essential for its complete breakdown into monosaccharides and free sulfate. Heparan-α-glucosaminideN-acetyltransferase (HGSNAT), a resident of the lysosomal membrane, catalyzes this essential acetylation reaction by accepting and transferring the acetyl group from cytosolic acetyl-CoA to terminal α-D-glucosamine of HS in the lysosomal lumen. Mutation-induced dysfunction in HGSNAT causes abnormal accumulation of HS within the lysosomes and leads to an autosomal recessive neurodegenerative lysosomal storage disorder called mucopolysaccharidosis IIIC (MPS IIIC). There are no approved drugs or treatment strategies to cure or manage the symptoms of, MPS IIIC. Here, we use cryo-electron microscopy (cryo-EM) to determine a high-resolution structure of the HGSNAT-acetyl-CoA complex, the first step in HGSNAT catalyzed acetyltransferase reaction. In addition, we map the known MPS IIIC mutations onto the structure and elucidate the molecular basis for mutation-induced HGSNAT dysfunction.
Helium optically pumped magnetometers can detect epileptic abnormalities as well as SQUIDs as shown by intracerebral recordings
Authors: Badier Jean-Michel , Schwartz Denis , Bénar Christian-George , Kanzari Khoubeib , Daligault Sébastien , Romain Rudy , Mitryukovskiy Sergey , Fourcault William , Josselin Vincent , Prado Matthieu Le , Jung Julien , Palacios-Laloy Augustin , Carron Romain , Bartolomei Fabrice , Labyt Etienne , Bonini Francesca
Published: October 2023

SQUID-based magnetoencephalography has been shown to improve the diagnosis and surgical treatment decision for presurgical evaluation of drug-resistant epilepsy. Still, its use remains limited due to several constraints such as cost, fixed helmet size and obligation of immobility. A new generation of sensors, the optically pumped magnetometers (OPMs), could overcome these limitations. In this study, we validate the ability of innovative Helium-based OPM (4He-OPM) sensors to record epileptic brain activity thanks to simultaneous recordings with intracerebral EEG (stereotactic EEG, SEEG). We recorded simultaneous SQUIDs-SEEG and 4He-OPM-SEEG signals in one patient during two sessions. We show that epileptic activities on intracerebral EEG can be recorded by OPMs with a better signal-to noise ratio than classical SQUIDs. The OPM sensors open new venues for the widespread application of magnetoencephalography in the management of epilepsy and other neurological diseases and fundamental neuroscience.

Significance Statement

We performed a simultaneous recording of Helium-based Optically Pumped Magnetometers (OPM) and intracerebral EEG and validate for the first time OPM results with signals recorded directly within the brain. We demonstrate that epileptic abnormalities seen on intracerebral electrodes are detected by OPMs with a better signal-to noise ratio than classical magnetoencephalography. This represents a significant step towards the validation of OPM-based recordings for epilepsy diagnosis and for clinical and neuroscience research.
A Protocol Describing A Scoping Review to Characterise ICU Admission Criteria
Authors: Soares James , Andersen Chris
Published: October 2023

Introduction

Effectively identifying deteriorated patients is vital to the development and validation of automated systems designed to predict clinical deterioration. Existing outcome measures used for this purpose have significant limitations. Published criteria for admission to high acuity inpatient areas may represent markers of patient deterioration and could inform the development of alternate outcome measures.

Objectives

This is a protocol for a scoping review which aims to characterise published criteria for admission of adult inpatients to high acuity inpatient areas including intensive care units.

Data sources

Electronic databasesPubMedandProQuest EBook Centralwill be searched to identify papers published from 1999 to date of search. Publications of interest are those which describe prescriptive criteria for admission of adult inpatients to a clinical area with a higher level of care than a general hospital ward.

Charting methods

Data will be extracted from each publication using a standardised data-charting form.

Data synthesis

Admission criteria characteristics from included publications will be summarised and presented in text and summary table form.
Complementary, Alternative, and Integrative Medicine Researchers’ Practices and Perceived Barriers Related to Open Science: An International, Cross-Sectional Survey
Authors: Ng Jeremy Y. , Santoro Lucas J. , Cobey Kelly D. , Steel Amie , Cramer Holger , Moher David
Published: October 2023

Introduction and Objective

Open science (OS) aims to make the dissemination of knowledge and the research process transparent and accessible to everyone. With the increasing popularity of complementary, alternative, and integrative medicine (CAIM), our objective was to assess practices and perceived barriers towards OS among CAIM researchers.

Methods

We conducted an anonymous online survey of researchers who published in journals listed in Scopus containing the words “complementary”, “alternative”, or “integrative” medicine in their names. We emailed 6040 researchers our purpose-built electronic survey after extracting their email address from one of their publications in our sample of journals. We questioned their familiarity with different OS concepts, along with their experiences and challenges engaging in these practices over the last 12 months.

Results

The survey was completed by 392 researchers (6.5% response rate, 97.1% completion rate). Most respondents were CAIM researchers familiar with the overall concept of OS, indicated by those actively publishing open access (OA) (n=244, 76.0%), registering a study protocol (n=148, 48.0%), and using reporting guidelines (n=181, 59.0%) in the past 12 months. Preprinting, sharing raw data, and sharing study materials were less popular. A lack of funding was reported as the greatest barrier to publishing OA by most respondents (n=252, 79.0%), and that additional funding is the most significant incentive in applying more OS practices to their research (n=229,72.2%). With respect to preprinting barriers, 36.3% (n=110) participants believed there are potential harms in sharing non-peer-reviewed work and 37.0% (n=112) feared preprinting would reduce the likelihood of their manuscript being accepted by a journal. Respondents were also concerned about intellectual property control regarding sharing data (n=94, 31.7%) and research study materials (n=80, 28.7%).

Conclusions

Although many participants were familiar with and practiced aspects of OS, many reported facing barriers relating to lack of funding to enable OS and perceived risks of revealing research ideas and data prior to publication. Future research should explore interventions, such as increasing CAIM researchers’ funding and educational resources to implement OS practices.
Geometrically-aggregated training samples: Leveraging summary statistics to enable healthcare data democratization
Authors: Yang Jenny , Thakur Anshul , Soltan Andrew A. S. , Clifton David A.
Published: October 2023

Healthcare data is highly sensitive and confidential, with strict regulations and laws to protect patient privacy and security. However, these regulations impede the access of healthcare data to a wider AI research community. As a result, AI healthcare research is often dominated by organisations with access to larger datasets or limited to silo-based development, where models are trained and evaluated on a limited population. Taking inspiration from the non-sensitive nature of the summary statistics (mean, variance, etc.) of healthcare data, this paper proposesgeometrically-aggregated training samples (GATS)where each training sample is a convex combination of multiple patients’ characteristics. Thus, mappings from patients to any constructed sample are highly convoluted, preserving patient privacy. We demonstrate that these “summary training units” provide effective training on different tabular and time-series datasets (CURIAL, UCI Adult, and eICU), and indeed behave as a summary of the original training datasets. This approach takes important steps towards data accessibility and democratization.
An infectious disease model with asymptomatic transmission and waning immunity
Authors: Rong Sophia Y. , Li Alice X. , Gao Shasha , Wang Chunmei
Published: October 2023

Infectious diseases present persistent challenges to global public health, demanding a comprehensive understanding of their dynamics to develop effective prevention and control strategies. The presence of asymptomatic carriers, individuals capable of transmitting pathogens without displaying symptoms, challenges conventional containment approaches focused on symptomatic cases. Waning immunity, the decline in protective response following natural recovery or vaccination, introduces further complexity to disease dynamics. In this paper, we developed a mathematical model to investigate the interplay between these factors, aiming to inform strategies for the management of infectious diseases. We derived the basic reproduction number for the model and showed that the disease would die out when this number falls below 1. We obtained a formula to estimate the relative contributions of asymptomatic and symptomatic transmission to the basic reproduction number, which remains unchanged when vaccination is included in the model. Through computer simulations with parameter values tailored for COVID-19 and sensitivity analysis, we demonstrated that population susceptibility significantly impacts the timing and magnitude of infection peaks. Populations with lower susceptibility experience delayed and less severe outbreaks. Vaccination was shown to play a crucial role in disease control, with an increased vaccination rate, extended immunity, and heightened vaccine efficacy proving pivotal. However, the effectiveness of these strategies hinges on maintaining a low vaccine escape proportion. Taken together, this study underscores the need for multifaceted, adaptable approaches to infectious disease management, highlighting the central role of vaccination in mitigating disease spread. Further research and validation with disease-specific data will enhance parameter estimates, improve model predictions, and inform evidence-based disease control strategies.
The Long-Term Impacts of Dementia on Preventive Care Utilization and Health Behaviors
Authors: Lin Zhuoer , Chen Xi
Published: October 2023

Dementia has large impact on individuals’ decision making, independent living, and wellbeing. Identifying early signals of dementia risk may offer people more time to prepare for the future, helping to delay the onset or slow the progression of dementia. Using the 1995-2018 waves of Health and Retirement Study, we offer novel evidence on the impacts of dementia on a rich set of preventive care utilization and health behaviors. Leveraging both within- and between-individual variations in an event study design, we characterize long-term dynamic changes in preventive care and health behaviors relative to the incidence of dementia and find early behavioral indicators of the disorder. We show that relative to the group of people who never develop dementia during the study periods, people with dementia have consistent and escalating declines in the use of cholesterol test, dental visit, prostate test and mammogram around the incidence of dementia. Significant declines are also found in physical activities and social engagement. Importantly, we demonstrate that the behavioral changes can occur up to 6 years before the incidence of dementia; and these patterns are absent in other chronic or acute conditions. The results are robust to sample selection, model specification, and the further control of aging and cohort effects. Overall, our findings highlight the salient impact of dementia risk on preventive care utilization and health behaviors, which may increase individuals’ vulnerability to health shocks. Detecting early signals of dementia and facilitating targeted interventions are thus called for to prevent individuals from adverse behavioral and health consequences.
Evaluation of 2022 Nursing Intake Forms from Massachusetts Jails: Content Analysis and Accuracy Assessment
Authors: Grussing Emily D. , Pickard Bridget , Smyth Emma , Brinkley-Rubinstein Lauren , Wurcel Alysse G.
Published: October 2023

The medical intake process is usually the first clinical interaction that people have after being incarcerated. In many states, the first vital person conducting this assessment is a nurse. In this project, nursing intake forms from Massachusetts jails were analyzed for the offer of 15 different screening and preventative services (e.g., HIV testing). Then, Health Services Administrators (HSAs) at the jails were asked to review and comment on the assessment. The average agreement rate between the project team members and HSAs was 73%. Twelve of the 14 jails had questions about history of HIV or HCV on the nursing intake form. Only 5 facilities discussed PrEP. There is potential to standardize the nursing intake form and therefore medical intake process. This must be done with key stakeholder groups, in particular nurses, to best understand the logistics of the complex medical intake process.
A Graph Based Deep Learning Framework for Predicting Spatio-Temporal Vaccine Hesitancy
Authors: Moon Sifat Afroj , Datta Rituparna , Ferdousi Tanvir , Baek Hannah , Adiga Abhijin , Marathe Achla , Vullikanti Anil
Published: October 2023

Predicting vaccine hesitancy at a fine spatial level assists local policymakers in taking timely action. Vaccine hesitancy is a heterogeneous phenomenon that has a spatial and temporal aspect. This paper proposes a deep learning framework that combines graph neural networks (GNNs) with sequence module to forecast vaccine hesitancy at a higher spatial resolution. This integrated framework only uses population demographic data with historical vaccine hesitancy data. The GNN learns the spatial cross-regional demographic signals, and the sequence module catches the temporal dynamics by leveraging historical data. We formulate the problem on a weighted graph, where nodes are zip codes and edges are generated using three distinct mechanisms: 1) adjacent graph - if two zip codes have a shared boundary, they will form an edge between them; 2) distance-based graph - every pair of zip codes are connected with an edge having a weight that is a function of centroid distances, and 3) mobility graph - edges represent the number of contacts between any two zip codes, where the contacts are derived from an activity-based social contact network. Our framework effectively predicts the spatio-temporal dynamics of vaccine hesitancy at the zip-code level when the mobility network is used to formulate the graph. Experiments on the real-world vaccine hesitancy data from the All-Payer Claims Database (APCD) show that our framework can outperform a range of baselines.
Real-World Comparison of Clopidogrel with Ticagrelor and Prasugrel In Patients with Chronic Coronary Disease undergoing Atherectomy
Authors: Khan Mahin R. , Koshy Anoop N. , Tanner Richard , Farhan Serdar , Farooq Ali , Sartori Samantha , Feng Yihan , Spirito Alessandro , Arora Ayush , Dhulipala Vishal , Vinayak Manish , Kapur Vishal , Suleman Javed , Sharma Raman , Mehran Roxana , Kini Annapoorna , Sharma Samin K.
Published: October 2023

Background

In patients with chronic coronary disease (CCD), it is unclear whether the use of potent P2Y12inhibitors (ticagrelor or prasugrel) offers advantages to clopidogrel when prescribed in conjunction with aspirin in patients undergoing percutaneous coronary intervention (PCI) with atherectomy.

Methods

Consecutive patients undergoing PCI with atherectomy for CCD at a tertiary care center between January 2011 to December 2020 were included. Patients discharged on ticagrelor or prasugrel were compared to patients on clopidogrel. The primary outcome was a composite of death or myocardial infarction (MI), secondary outcomes included individual components of the primary outcome, stroke, major bleeding, and target vessel revascularization at 1 year. Adjusted analyses were performed using propensity score stratification.

Results

Overall, 3,612 patients undergoing atherectomy were included in the analysis (clopidogrel [70.4%, n= 2,543], ticagrelor/prasugrel [29.5%, n=1,069]). Clopidogrel was prescribed more often in older patients with multimorbid risk factors, whereas ticagrelor/prasugrel was used more in patients with greater anatomical and procedural complexity. There was an increase in the use of potent antiplatelet agents over time (p<0.001). At 1-year follow-up, the primary outcome was observed in 5.2% and 4.0% of those taking clopidogrel and ticagrelor/prasugrel, respectively (adjusted hazard ratio (AHR) 0.87, 95% CI 0.58 – 1.3, p = 0.50). There were no significant differences in the rate of bleeding (5.5% vs 3.7%, AHR 0.98, 95% CI 0.66 - 1.46, p = 0.92) or other secondary outcomes between the two groups.

Conclusion

The use of clopidogrel was associated with comparable ischemic and bleeding outcomes compared to ticagrelor/prasugrel in patients with CCD undergoing PCI with atherectomy.
Collapse of late endosomal pH elicits a rapid Rab7 response via V-ATPase and RILP.
Authors: Mulligan Ryan J , Magaj Magda M , Digilio Laura , Redemann Stefanie , Yap Chan Choo , Winckler Bettina
Published: October 2023

Endosomal-lysosomal trafficking is accompanied by the acidification of endosomal compartments by the H+-V-ATPase to reach low lysosomal pH. Disruption of proper pH impairs lysosomal function and the balance of protein synthesis and degradation (proteostasis). We used the small dipeptide LLOMe, which is known to permeabilize lysosomal membranes, and find that LLOMe also impacts late endosomes (LEs) by neutralizing their pH without causing membrane permeabilization. We show that LLOMe leads to hyper-activation of Rab7 and disruption of tubulation and mannose-6-phosphate receptor (CI-M6PR) recycling on pH-neutralized LEs. Either pH neutralization (NH4Cl) or Rab7 hyper-active mutants alone can phenocopy the alterations in tubulation and CI-M6PR trafficking. Mechanistically, pH neutralization increases the assembly of the V1G1 subunit of the V-ATPase on endosomal membranes, which stabilizes GTP-bound Rab7 via RILP, a known interactor of Rab7 and V1G1. We propose a novel pathway by which V-ATPase and RILP modulate LE pH and Rab7 activation in concert. This pathway might broadly contribute to pH control during physiologic endosomal maturation or starvation and during pathologic pH neutralization, which occurs via lysosomotropic compounds or in disease states.
Rap1 Activation Protects Against Fatty Liver and Non-Alcoholic Steatohepatitis Development
Authors: Agarwal Heena , Wang Yating , Ozcan Lale
Published: October 2023

We previously demonstrated that hepatic activation of a small G protein of the Ras family, Rap1a, is suppressed in obesity, which results in increased hepatic glucose production and glucose intolerance in obese mice. Here, we show that Rap1a inhibition in obese mice liver also results in fatty liver formation, which is characteristic of the diabetic liver. Specifically, we report that Rap1a activity is decreased in the livers of patients with non-alcoholic steatohepatitis (NASH) and mouse models of non-alcoholic fatty liver disease (NAFLD) and NASH. Restoring hepatic Rap1a activity by overexpressing a constitutively active mutant form of Rap1a lowered the mature, processed form of lipogenic transcription factor, Srebp1, without an effect on the unprocessed Srebp1 and suppressed hepatic TG accumulation, whereas liver Rap1a deficiency increased Srebp1 processing and exacerbated steatosis. Mechanistically, we show that mTORC1, which promotes Srebp1 cleavage, is hyperactivated upon Rap1a deficiency despite disturbed insulin signaling. In proof-of-principle studies, we found that treatment of obese mice with a small molecule activator of Rap1a (8-pCPT) or inhibiting Rap1a’s endogenous inhibitor, Rap1Gap, recapitulated our hepatic gain-of-function model and resulted in improved hepatic steatosis and lowered lipogenic genes. Thus, hepatic Rap1a serves as a signaling molecule that suppresses both hepatic gluconeogenesis and steatosis, and inhibition of its activity in the liver contributes to the pathogenesis of glucose intolerance and NAFLD/NASH development.
Crystallographic, kinetic, and calorimetric investigation of PKA interactions with L-type calcium channels and Rad GTPase
Authors: Yoo Randy , Haji-Ghassemi Omid , Xu Jiaming , McFarlane Ciaran , van Petegem Filip
Published: October 2023

β-adrenergic signalling leads to activation of cAMP-dependent protein kinase (PKA), which can regulate the activity of L-type voltage-gated calcium channels (CaVs) in multiple tissues. In CaV1.2, various sites have been proposed to be involved, including Ser1981 in the C-terminal tail. Its phosphorylation is linked to diabetes progression, synaptic plasticity, and the augmentation of Ca2+currents in smooth muscle. Its role in augmenting cardiac Ca2+currents has been heavily scrutinized, with alternative models including the sites Ser1718 and Ser1535. Recently, the GTPase Rad has been identified as a critical PKA target that mediates the augmentation of cardiac CaV1.2 currents upon its phosphorylation. However, it is unclear which of the four potential sites (Ser25, Ser38, Ser272, and Ser300) are favored by PKA. Using quantitative binding experiments and enzyme kinetics, we show that there are two Tiers of target sites, with CaV1.2 residue Ser1981 and Rad residues Ser25 and Ser272 forming Tier 1 substrates for PKA. The other sites form a second Tier, with PKA only showing minimal detectable activity. The Tier 1 substrates share a common feature with two arginine residues that anchor the peptide into the active site of PKA. We report crystal structures of the PKA catalytic subunit (PKAc) with and without a CaV1.2 substrate that represent different successive conformations prior to product turnover. Different target sites utilize different anchoring residues, highlighting the plasticity of PKAc to recognize substrates.

Stress signals can alter the electrical properties of excitable cells. cAMP-dependent protein kinase A (PKA) is a key enzyme that is activated upon β-adrenergic stimulation and can alter the function of L-type voltage-gated calcium channels (CaVs) in various tissues. There is a lot of controversy surrounding the exact recognition and specificity of PKA towards CaV1.2, a key calcium channel located in neuronal, cardiac, and smooth muscle tissue, among others. Using a quantitative and unbiased approach, we determined the substrate specificities of PKA towards various sites in CaV1.2 and Rad, an inhibitory protein. Our work highlights two Tiers of substrates, suggesting a potential graded response. Using X-ray crystallography, we determined a high-resolution structure of PKA bound to its strongest target site in CaV1.2, showing how PKA undergoes multiple structural transitions towards binding and how it makes use of a unique anchoring residue.
Investigating howSalmonellacolonise alfalfa using a whole genome screen
Authors: Holden Emma R. , Al-Khanaq Haider , Vimont Noémie , Webber Mark A. , Trampari Eleftheria
Published: October 2023

Enteropathogenic bacteria includingSalmonellaregularly cause outbreaks of infection from fresh produce posing a significant public health threat.Salmonella’s ability to persist on fresh produce for extended periods is partly attributed to its capacity to form biofilms, which poses a challenge to food decontamination and facilitates persistence in the food chain. Preventing biofilm formation on food products and in food processing environments is crucial for reducing the incidence of foodborne diseases. Understanding the mechanisms of colonisation and establishment on fresh produce will inform the development of decontamination approaches. We used Transposon-directed Insertion site sequencing (TraDIS-Xpress) to investigate the mechanisms employed bySalmonellaenterica serovar Typhimurium to colonise and establish itself on fresh produce at critical timepoints following infection. We established an alfalfa infection model and compared the findings to those obtained from glass surfaces. Our research revealed dynamic changes in the pathways associated with biofilm formation over time, with distinct plant-specific and glass-specific mechanisms for biofilm formation, alongside the identification of shared genes playing pivotal roles in both contexts. Notably, we observed variations in the significance of factors such as flagella biosynthesis, lipopolysaccharide (LPS) production, and stringent response regulation in biofilm development on plant versus glass surfaces. Understanding the genetic underpinnings of biofilm formation on both biotic and abiotic surfaces offers valuable insights that can inform the development of targeted antibacterial therapeutics, ultimately enhancing food safety throughout the food processing chain.

Funding

The authors gratefully acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC); ERH, JAA, HAK, MAW and ET were supported by the BBSRC Institute Strategic Programme Microbes and Food Safety BB/X011011/1 and its constituent project BBS/E/F/000PR13635. NV was supported by the Food Safety Research Network grant BB/X002985/1 awarded to ET.

Data availability

Nucleotide sequence data supporting the analysis in this study has been deposited in ArrayExpress under the accession number E-MTAB-13495. The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.
KASP-PCR method to screen thrombophilia genetic risk factors
Authors: Altwayan Reham , Tombuloglu Huseyin , Alhusil Abdulrahman , Awadh Taghreed , Altwayan Mona , Albaqawi Heba , Aldossary Noof , Unver Turgay
Published: October 2023

Thrombophilia is defined as the willingness of blood to clot easily in a situation of imbalances between fibrinolysis and coagulation. It is classified as inherited and acquired thrombophilia. Several studies revealed that the inherited thrombophilia is strongly associated with single nucleotide polymorphisms (SNP) or deletions on certain genes, such asFV Leiden (rs6025), MTHFR1 (rs1801133), MTHFR2 (rs1801131), Serpine-1 (rs1799768),andFactor II (rs1799963). This study aims to develop an SNP detection panel based on Kompetitive Allele Specific Primer-polymerase chain reaction (KASP-PCR) technique. Results revealed that 86.5% of susceptible patients (n = 111) contain at least one mutation; while seven of them harbor three thrombophilia-associated mutations simultaneously. A clear allelic discrimination was observed for all tested samples. The prevalence of each mutation among different countries and ethnic groups are in line with the findings of this study. Rather than expensive and time-consuming approaches, the current assay enables the cost-effective advantage of the KASP-PCR, which reduces the diagnostic cost with a fast and convenient way. After clinical validation and approval, it can be used in hospitals, research centers, and diagnostic laboratories to determine the genetic susceptibility of individuals to thrombosis and for research purposes.
Structuring risks for a comprehensive understanding of cost overruns in power plant projects
Authors: Islam Muhammad Saiful , Nepal Madhav , Skitmore Martin
Published: October 2023

Purpose

Power plant projects are very complex and encounter serious cost overruns worldwide. Their cost overrun risks are not independent but interrelated in many cases, having structural relationships among each other. The purpose of this study is, therefore, to establish the complex structural relationships of risks involved.

Design/methodology/approach

In total, 76 published articles from the previous literature are reviewed using the content analysis method. Three risk networks in different phases of power plant projects are depicted based on literature review and case studies. The possible methods of solving these risk networks are also discussed.

Findings

The study finds critical cost overrun risks and develops risk networks for the procurement, civil and mechanical works of power plant projects. It identifies potential models to assess cost overrun risks based on the developed risk networks. The literature review also revealed some research gaps in the cost overrun risk management of power plants and similar infrastructure projects.

Practical implications

This study will assist project risk managers to understand the potential risks and their relationships to prevent and mitigate cost overruns for future power plant projects. It will also facilitate decision-makers developing a risk management framework and controlling projects’ cost overruns.

Originality/value

The study presents conceptual risk networks in different phases of power plant projects for comprehending the root causes of cost overruns. A comparative discussion of the relevant models available in the literature is presented, where their potential applications, limitations and further improvement areas are discussed to solve the developed risk networks for modeling cost overrun risks.