bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome Measurement in Children With a History of Disorders of Consciousness After Severe Brain Injury: Telephone Administration of the Vineland Adaptive Behavior Scales, Third Edition, and Glasgow Outcome Scale-Extended Pediatric Revision
Authors: Ludwig Natasha N. , Suskauer Stacy J. , Rodgin Sandra , Chen Julia , Borda Allison , Jones Kara , Lahey Sarah , Slomine Beth S.
Published: January 2023

OBJECTIVES:

Examine initial feasibility and utility of a battery of measures administered via telephone interview with a caregiver for describing long-term outcomes in individuals with a history of disorders of consciousness (DoC) after pediatric acquired brain injury (ABI).

DESIGN:

Cross-sectional.

SETTING:

Caregiver interview administered via telephone.

PATIENTS:

Convenience sample admitted to an inpatient pediatric neurorehabilitation unit with DoC after ABI at least 1 year prior to assessment (n = 41, 5–22 yr old at assessment).

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

The Vineland Adaptive Behavior Scales, Third Edition (Vineland-3), and Glasgow Outcome Scale-Extended Pediatric Revision (GOS-E Peds) were examined. Administration time of the Vineland-3 ranged from 13 to 101 minutes (m = 50) and the GOS-E Peds ranged from 2 to 10 minutes (m = 3). Vineland-3 Adaptive Behavior Composite (ABC) ranged from standard scores (SSs) of 20 (exceptionally low) to 100 (average) and GOS-E Peds scores ranged from 3 (i.e., upper moderate disability) to 7 (vegetative state). Lower adaptive functioning on the Vineland-3 ABC was strongly associated with greater disability on the GOS-E Peds (r = –0.805). On the Vineland-3 ABC, 19.5% earned the lowest possible score, whereas 12.2% obtained the lowest possible score for survivors on the GOS-E Peds; only 7.3% earned lowest scores on both measures.

CONCLUSIONS:

The Vineland-3 and GOS-E Peds were feasibly administered by telephone and were complementary in this cohort; the GOS-E provided a quick and easy measure of gross functional outcome, whereas the Vineland-3 took longer to administer but provided a greater level of detail about functioning. When both measures were used together, the range and variability of scores were maximized.
Protocol-Driven Initiation and Weaning of High-Flow Nasal Cannula for Patients With Bronchiolitis: A Quality Improvement Initiative*
Authors: Huang Jia Xin , Colwell Blair , Vadlaputi Pranjali , Sauers-Ford Hadley , Smith Brian J. , McKnight Heather , Witkowski Jessica , Padovani Andrew , Aghamohammadi Sara , Tzimenatos Leah , Beck, RN Shelli , Reneau Kriston , Nill Barbara , Harbour Dawn , Pegadiotes Jessica , Natale JoAnne , Hamline Michelle , Siefkes Heather
Published: January 2023

OBJECTIVES:

Bronchiolitis is the most common cause for nonelective infant hospitalization in the United States with increasing utilization of high-flow nasal cannula (HFNC). We standardized initiation and weaning of HFNC for bronchiolitis and quantified the impact on outcomes. Our specific aim was to reduce hospital and ICU length of stay (LOS) by 10% between two bronchiolitis seasons after implementation.

DESIGN:

A quality improvement (QI) project using statistical process control methodology.

SETTING:

Tertiary-care children’s hospital with 24 PICU and 48 acute care pediatric beds.

PATIENTS:

Children less than 24 months old with bronchiolitis without other respiratory diagnoses or underlying cardiac, respiratory, or neuromuscular disorders between December 2017 and November 2018 (baseline), and December 2018 and February 2020 (postintervention).

INTERVENTIONS:

Interventions included development of an HFNC protocol with initiation and weaning guidelines, modification of protocol and respiratory assessment classification, education, and QI rounds with a focus on efficient HFNC weaning, transfer, and/or discharge.

MEASUREMENTS AND MAIN RESULTS:

A total of 223 children were included (96 baseline and 127 postintervention). The primary outcome metric, average LOS per patient, decreased from 4.0 to 2.8 days, and the average ICU LOS per patient decreased from 2.8 to 1.9 days. The secondary outcome metric, average HFNC treatment hours per patient, decreased from 44.0 to 36.3 hours. The primary and secondary outcomes met criteria for special cause variation. Balancing measures included ICU readmission rates, 30-day readmission rates, and adverse events, which were not different between the two periods.

CONCLUSIONS:

A standardized protocol for HFNC management for patients with bronchiolitis was associated with decreased hospital and ICU LOS, less time on HFNC, and no difference in readmissions or adverse events.
Methodology of the Second Pediatric Acute Lung Injury Consensus Conference
Authors: Iyer Narayan , Khemani Robinder , Emeriaud Guillaume , López-Fernández Yolanda M. , Korang Steven Kwasi , Steffen Katherine M. , Barbaro Ryan P. , Bembea Melania M. ,   on behalf of the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) Group on behalf and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: January 2023

OBJECTIVES:

This article describes the methodology used for The Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2). The PALLIC-2 sought to develop evidence-based clinical recommendations and when evidence was lacking, expert-based consensus statements and research priorities for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS).

DATA SOURCES:

Electronic searches were conducted using PubMed, Embase, and Cochrane Library (CENTRAL) databases from 2012 to March 2022.

STUDY SELECTION:

Content was divided into 11 sections related to PARDS, with abstract and full text screening followed by data extraction for studies which met inclusion with no exclusion criteria.

DATA EXTRACTION:

We used a standardized data extraction form to construct evidence tables, grade the evidence, and formulate recommendations or statements using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.

DATA SYNTHESIS:

This consensus conference was comprised of a multidisciplinary group of international experts in pediatric critical care, pulmonology, respiratory care, and implementation science which followed standards set by the Institute of Medicine, using the GRADE system and Research And Development/University of California, Los Angeles appropriateness method, modeled after PALICC 2015. The panel of 52 content and four methodology experts had several web-based meetings over the course of 2 years. We conducted seven systematic reviews and four scoping reviews to cover the 11 topic areas. Dissemination was via primary publication listing all statements and separate supplemental publications for each subtopic that include supporting arguments for each recommendation and statement.

CONCLUSIONS:

A consensus conference of experts from around the world developed recommendations and consensus statements for the definition and management of PARDS and identified evidence gaps which need further research.
JMM Profile: Swine influenza A virus: a neglected virus with pandemic potential
Authors: Mollett Benjamin C. , Everett Helen E. , van Diemen Pauline M. , Byrne Alexander M.P. , Ramsay Andrew , James Joe , Reid Scott M. , Hansen Rowena D.E. , Lewis Nicola S. , Brown Ian H. , Banyard Ashley C.
Published: January 2023

Swine influenza is an acute respiratory disease of swine caused by swine influenza A virus (SwIAV). The ability of SwIAV to spread bidirectionally from animals to humans (zoonotic), and from humans to animals (reverse zoonotic), drives coinfection that can result in gene segment exchange and elevates the risk of generating viruses with pandemic potential. Compared to human-origin influenza A viruses, current data indicate a greater diversity amongst circulating SwIAVs, with three major subtypes (classified by haemagglutinin and neuraminidase) circulating globally in swine (H1N1, H1N2 and H3N2). The lack of protection afforded by human seasonal influenza vaccines against SwIAVs exacerbates the risk associated with reassortment of human, swine and potentially avian viruses. As such, global monitoring of SwIAVs is important for both human and animal health as they represent a true ‘One Health’ challenge with pandemic potential.
How microscopic epistasis and clonal interference shape the fitness trajectory in a spin glass model of microbial long-term evolution
Authors: Boffi Nicholas M. , Guo Yipei , Rycroft Chris H. , Amir Ariel
Published: January 2023

The adaptive dynamics of evolving microbial populations takes place on a complex fitness landscape generated by epistatic interactions. The population generically consists of multiple competing strains, a phenomenon known as clonal interference. Microscopic epistasis and clonal interference are central aspects of evolution in microbes, but their combined effects on the functional form of the population’s mean fitness are poorly understood. Here, we develop a computational method that resolves the full microscopic complexity of a simulated evolving population subject to a standard serial dilution protocol. Through extensive numerical experimentation, we find that stronger microscopic epistasis gives rise to fitness trajectories with slower growth independent of the number of competing strains, which we quantify with power-law fits and understand mechanistically via a random walk model that neglects dynamical correlations between genes. We show that increasing the level of clonal interference leads to fitness trajectories with faster growth (in functional form) without microscopic epistasis, but leaves the rate of growth invariant when epistasis is sufficiently strong, indicating that the role of clonal interference depends intimately on the underlying fitness landscape. The simulation package for this work may be found athttps://github.com/nmboffi/spin_glass_evodyn.
FedDP: Secure Federated Learning for Disease Prediction with Imbalanced Genetic Data
Authors: Li Bin , Gao Hongchang , Shi Xinghua
Published: January 2023

It is challenging to share and aggregate biomedical data distributed among multiple institutions or computing resources due to various concerns including data privacy, security, and confidentiality. The federated Learning (FL) schema can effectively enable multiple institutions jointly perform machine learning by training a robust model with local data to satisfy the requirement of user privacy protection as well as data security. However, conventional FL methods are exposed to the risk of gradient leakage and cannot be directly applied to genetic data since they cannot address the unique challenges of data imbalance typically seen in genomics. To provide secure and efficient disease prediction based on genetic data distributed across multiple parties, we propose an FL framework enhanced with differential privacy (FedDP) on trained model parameters. In FedDP, local models can be trained among multiple local-hold genetic data with efficient secure and privacy-preserving techniques. The key idea of FedDP is to deploy differential privacy on compressed intermediate gradients that are computed and transmitted by optimizers from local parties. In addition, the unique weighted minmax loss in FedDP is able to address the difficulties of prediction for highly imbalanced genetic datasets. Our experiments on multiple genetic datasets demonstrate that FedDP provides a powerful tool to implement and evaluate various strategies in support of privacy preservation and model performance guarantee to overcome data imbalance.
Genetic association studies using disease liabilities from deep neural networks
Authors: Yang Lu , Sadler Marie C. , Altman Russ B.
Published: January 2023

The case-control study is a widely used method for investigating the genetic underpinnings of binary traits. However, long-term, prospective cohort studies often grapple with absent or evolving health-related outcomes. Here, we propose two methods,liabilityandmeta, for conducting genome-wide association study (GWAS) that leverage disease liabilities calculated from deep patient phenotyping. Analyzing 38 common traits in ∼300,000 UK Biobank participants, we identified an increased number of loci compared to the conventional case-control approach, with high replication rates in larger external GWAS. Further analyses confirmed the disease-specificity of the genetic architecture with the meta method demonstrating higher robustness when phenotypes were imputed with low accuracy. Additionally, polygenic risk scores based on disease liabilities more effectively predicted newly diagnosed cases in the 2022 dataset, which were controls in the earlier 2019 dataset. Our findings demonstrate that integrating high-dimensional phenotypic data into deep neural networks enhances genetic association studies while capturing disease-relevant genetic architecture.
Feasibility of an Evolutionary Tumor Board for Generating Novel Personalized Therapeutic Strategies
Authors: Robertson-Tessi Mark , Brown Joel S. , Poole Maria I. , Johnson Matthew , Marusyk Andriy , Gallaher Jill A. , Luddy Kimberly A. , Whelan Christopher J. , West Jeffrey , Strobl Maximillian , Turati Virginia , Enderling Heiko , Schell Michael J. , Tan AikChoon , Boyle Terry , Makanji Rikesh , Farinhas Joaquim , Soliman Hatem , Lemanne Dawn , Gatenby Robert A. , Reed Damon R. , Anderson Alexander R. A. , Chung Christine H.
Published: January 2023

The current paradigm of clinical trials treating patients until disease progression using maximum tolerated dose does not account for the dynamic tumor-host-drug interactions that result in acquired resistance. Here, we present the concept of an Evolutionary Tumor Board (ETB) and report interim results from a prospective, non-interventional pilot study in which novel therapeutic strategies based on evolutionary principles were developed under the ETB framework. The ETB approach relies on an interdisciplinary team that integrates clinical, preclinical, and theoretical knowledge and the application of mathematical modeling to predict patient responses to different therapies, including novel approaches derived from eco-evolutionary first principles. We have previously proposed several evolutionary therapies that aim to enhance the efficacy of an overall treatment regimen, using existing agents for a given disease. Key among these evolutionary therapies is the idea of “first-strike second-strike”, where different agents are administered in sequence, and new strikes are applied as soon as the efficacy of the previous strike is nearing a minimum, as opposed to waiting until progression is identified on periodic imaging. This approach requires careful analysis of longitudinal patient data coupled with predictive dynamics generated by mathematical models. Here we describe the ETB process and the interim results from 15 patients enrolled in the feasibility trial. In addition, we describe the challenges faced as well as the solutions that can be implemented via improved modeling approaches, better patient data collection, and a reassessment of how we understand tumor dynamics in the light of evolutionary principles.
Complex interventions for aggressive challenging behaviour in adults with intellectual disability: a rapid realist review informed by multiple populations
Authors: Royston Rachel , Naughton Stephen , Hassiotis Angela , Jahoda Andrew , Ali Afia , Chauhan Umesh , Cooper Sally-Ann , Kouroupa Athanasia , Steed Liz , Strydom Andre , Taggart Laurence , Rapaport Penny
Published: January 2023

Objectives

Approximately 10% of people with intellectual disability display aggressive challenging behaviour, usually due to unmet needs. There are a variety of interventions available, yet a scarcity of understanding about what mechanisms contribute to successful interventions. We explored how complex interventions for aggressive challenging behaviour work in practice and what works for whom by developing programme theories through contexts-mechanism-outcome (CMO) configurations.

Methods

This review followed modified rapid realist review methodology and RAMESES-II standards. Eligible papers reported on a range of population groups (intellectual disability, mental health, dementia, young people and adults) and settings (community and inpatient) to broaden the scope and available data for review.

Results

Five databases and grey literature were searched and a total of 59 studies were included. We developed three overarching domains comprising of 11 CMOs; 1. Working with the person displaying aggressive challenging behaviour, 2. Relationships and team focused approaches and 3. Sustaining and embedding facilitating factors at team and systems levels. Mechanisms underlying the successful application of interventions included improving understanding, addressing unmet need, developing positive skills, enhancing carer compassion and boosting staff self-efficacy and motivation.

Conclusion

The review emphasises how interventions for aggressive challenging behaviour should be personalised and tailored to suit individual needs. Effective communication and trusting relationships between service users, carers, professionals, and within staff teams is essential to facilitate effective intervention delivery. Carer inclusion and service level buy-in supports the attainment of desired outcomes. Implications for policy, clinical practice and future directions are discussed.

Prospero Registration Number

CRD42020203055.
Magnitude of wasting and its predictors among under-five children in Bakadawula Ari district, Southern Ethiopia
Authors: Tesfaye Getamesay Aynalem , Wana Ermias Wabeto , Gebru Moges Getie
Published: January 2023

Background

Globally, wasting threatens the lives of 50 million children under-five. In Ethiopia, wasting is not decreasing at the intended rate, but the reason remains unclear. Moreover, Bakadawula Ari district lacks scientific information regarding wasting among children.

Objective

This study was conducted to determine the magnitude of wasting and its predictors among under-five children in the district.

Methods

A community-based cross-sectional study was conducted from January to March 2022. A multistage sampling technique was used to select 421 children. The data were entered and analyzed by SPSS 26 (Statistical Package for the Social Sciences version 26). Logistic regression analyses were used and presented with crude odds ratio (COR) and adjusted odds ratio (AOR) with their 95% confidence intervals (CI).

Results

The prevalence of wasting among children in the study area was 22.6% (95% CI: 18.5-26.8). Fathers with primary education (AOR= 4.48; 95% CI: 1.93-10.39), households with improper solid waste-disposal (AOR= 2.54; 95% CI: 1.11-5.82), not usually sleeping under insecticide-treated bed net (ITN) (AOR=1.79; 95% CI: 1.01-3.19), unacceptable children dietary diversity score (DDS) (AOR= 2.56; 95% CI: 1.28-5.14) and unacceptable household DDS (AOR= 2.26; 95% CI: 1.02-5.00) were predictors of wasting.

Conclusions

The prevalence of wasting among children was critically high. Upgrading educational status of fathers, encouraging safe solid waste disposal, ensuring consistent use of ITN, and improving both children and household DDS should be given a due emphasis to reduce wasting in the study area.
Effectiveness of Vaccination and Previous Infection Against Omicron Infection and Severe Outcomes in Children Under 12 Years of Age
Authors: Lin Dan-Yu , Xu Yangjianchen , Gu Yu , Zeng Donglin , Wheeler Bradford , Young Hayley , Moore Zack , Sunny Shadia K
Published: January 2023

Background

Data on the protection conferred by Covid-19 vaccination and previous SARS-CoV-2 infection against omicron infection and severe outcomes in children can inform prevention strategies.

Methods

We obtained vaccination records and clinical outcomes for 1,368,721 North Carolina residents 11 years of age or younger from October 29, 2021 to January 6, 2023. We used Cox regression to estimate the time-varying effects of primary and booster vaccination and previous infection on the risks of omicron infection, hospitalization, and death.

Results

For children 5–11 years of age, the effectiveness of primary vaccination against infection was 59.9% (95% confidence interval [CI], 58.5 to 61.2), 33.7% (95% CI, 32.6 to 34.8), and 14.9% (95% CI, 12.3 to 17.5) at 1, 4 and 10 months after the first dose; the effectiveness of a monovalent or bivalent booster dose after 1 month was 24.4% (95% CI, 14.4 to 33.2) or 76.7% (95% CI, 45.7 to 90.0); and the effectiveness of omicron infection against reinfection was 79.9% (95% CI, 78.8 to 80.9) and 53.9% (95% CI, 52.3 to 55.5) after 3 and 6 months, respectively. For children 0–4 years of age, the effectiveness of primary vaccination against infection was 63.8% (95% CI, 57.0 to 69.5) and 58.1% (95% CI, 48.3 to 66.1) at 2 and 5 months after the first dose, and the effectiveness of omicron infection against reinfection was 77.3% (95% CI, 75.9 to 78.6) and 64.7% (95% CI, 63.3 to 66.1) after 3 and 6 months, respectively. For both age groups, vaccination and previous infection had better effectiveness against hospitalization and death than against infection.

Conclusions

Covid-19 vaccination was effective against omicron infection and severe outcomes in children under the age of 12 years, although the effectiveness decreased over time. Bivalent boosters were more effective than monovalent boosters. Immunity acquired via omicron infection was very high and waned gradually over time.
Hepatocyte-specific miR-33 deletion attenuates NAFLD-NASH-HCC progression
Authors: Fernández-Tussy Pablo , Sun Jonathan , Cardelo Magdalena P. , Price Nathan L. , Goedeke Leigh , Xirouchaki Chrysovalantou E. , Yang Xiaoyong , Pastor-Rojo Oscar , Bennett Anton M. , Tiganis Tony , Suárez Yajaira , Fernández-Hernando Carlos
Published: January 2023

The complexity of the multiple mechanisms underlying non-alcoholic fatty liver disease (NAFLD) progression remains a significant challenge for the development of effective therapeutics. miRNAs have shown great promise as regulators of biological processes and as therapeutic targets for complex diseases. Here, we study the role of hepatic miR-33, an important regulator of lipid metabolism, during the progression of NAFLD. We report that miR-33 is overexpressed in hepatocytes isolated from mice with NAFLD and demonstrate that its specific suppression in hepatocytes (miR-33HKO) improves multiple aspects of the disease, including insulin resistance, steatosis, and inflammation and limits the progression to non-alcoholic steatohepatitis (NASH), fibrosis and hepatocellular carcinoma (HCC). Mechanistically, we find that hepatic miR-33 deficiency reduces lipid biosynthesis and promotes mitochondrial fatty acid oxidation to reduce lipid burden in hepatocytes. Additionally, miR-33 deficiency improves mitochondrial function, reducing oxidative stress. In miR-33 deficient hepatocytes, we found an increase in AMPKα activation, which regulates several pathways resulting in the attenuation of liver disease. The reduction in lipid accumulation and liver injury resulted in decreased transcriptional activity of the YAP/TAZ pathway, which may be involved in the reduced progression to HCC in theHKOlivers. Together, these results suggest suppressing hepatic miR-33 may be an effective therapeutic approach at different stages of NAFLD/NASH/HCC disease progression.
Uncovering hidden biological processes by probabilistic filtering of single-cell data
Authors: Piran Zoe , Nitzan Mor
Published: January 2023

Elucidating underlying biological processes in single-cell data is an ongoing challenge and the number of methods that recapitulate dominant signals in such data has increased significantly. However, cellular populations encode multiple biological attributes, related to their spatial configuration, temporal trajectories, cell-cell interactions, and responses to environmental cues, which may be overshadowed by the dominant signal and thus much harder to recover. To approach this task, we developed SiFT (SIgnal FilTering), a method for filtering biological signals in single-cell data, thus uncovering underlying processes of interest. Utilizing existing prior knowledge and reconstruction tools for a specific biological signal, such as spatial structure, SiFT filters the signal and uncovers additional biological attributes. SiFT is applicable to a wide range of tasks, from the removal of unwanted variation in the data as a pre-processing step to revealing hidden biological structures. Applied for pre-processing, SiFT outperforms state-of-the-art methods for the removal of nuisance signals and cell cycle effects. To recover underlying biological structure, we use existing prior knowledge regarding liver zonation to filter the spatialsignalfrom single-cell liver data thereby enhancing the temporal circadian signal the cells are encoding. Lastly, we showcase the applicability of SiFT in the case-control setting for studying COVID-19 disease. Filtering the healthysignal, based on reference samples from healthy donors, exposes disease-related dynamics in COVID-19 data and highlights disease informative cells and their underlying disease response pathways.
Lagrangian Formalism in Biology: II. Non-Standard and Null Lagrangians for Nonlinear Dynamical Systems and their Role in Population Dynamics
Authors: Pham D. T. , Musielak Z. E.
Published: January 2023

Non-standard Lagrangians do not display any discernible energy-like terms, yet they give the same equations of motion as standard Lagrangians, which have easily identifiable energy-like terms. A new method to derive non-standard Lagrangians for second-order nonlinear differential equations with damping is developed and the limitations of this method are explored. It is shown that the limitations do not exist only for those nonlinear dynamical systems that can be converted into linear ones. The obtained results are applied to selected population dynamics models for which non-standard Lagrangians and their corresponding null Lagrangians and gauge functions are derived, and their roles in the population dynamics are discussed.
Stochastic motion and transcriptional dynamics of pairs of distal DNA loci on a compacted chromosome
Authors: Brückner David B. , Chen Hongtao , Barinov Lev , Zoller Benjamin , Gregor Thomas
Published: January 2023

Chromosomes in the eukaryotic nucleus are highly compacted. However, for many functional processes, including transcription initiation, the 3D pair-wise motion of distal chromosomal elements, such as enhancers and promoters, is essential and necessitates dynamic fluidity. Therefore, the interplay of chromosome organization and dynamics is crucial for gene regulation. Here, we use a live imaging assay to simultaneously measure the positions of pairs of enhancers and promoters and their transcriptional output in the developing fly embryo while systematically varying the genomic separation between these two DNA loci. Our analysis reveals a combination of a compact globular organization and fast subdiffusive dynamics. These combined features cause an anomalous scaling of polymer relaxation times with genomic separation and lead to long-ranged correlations compared to existing polymer models. This scaling implies that encounter times of DNA loci are much less dependent on genomic separation than predicted by existing polymer models, with potentially significant consequences for eukaryotic gene expression.
Distinct Neural Signatures of Multimodal Resizing Illusions: Implications for Chronic Pain Treatment
Authors: Hansford Kirralise J. , Baker Daniel H. , McKenzie Kirsten J. , Preston Catherine E. J.
Published: January 2023

Illusory body resizing typically uses multisensory integration to change the perceived size of a body part. Previous studies associate such multisensory body illusions with frontal theta oscillations and parietal gamma oscillations for dis-integration and integration of multisensory signals, respectively. However, recent studies support illusory changes of embodiment from visual-only stimuli. Multisensory resizing illusions can also reduce chronic pain, potentially through modulation of cortical body representations. This preregistered study (N=48) investigated differences between multisensory visuo-tactile and uni-modal visual resizing illusions using EEG. We hypothesised (1) stronger illusion in multisensory compared to uni-modal, and uni-modal compared to asynchronous (dis-integration) conditions, (2) greater parietal gamma during multisensory compared to uni-modal, and (3) greater frontal theta during asynchronous compared to baseline conditions. Results partially supported EEG hypotheses, finding increased parietal gamma activity comparing multisensory to unimodal visual conditions, whilst finding increased parietal theta activity when comparing asynchronous to non-illusion conditions. While results demonstrated that only 27% of participants experienced the illusion with visual-only stimuli, further analysis suggested that those who experience visual-only illusions exhibit a different neural signature to those who do not. Our results support the importance of multisensory integration for illusory changes in perceived body size. However, we also suggest that visual-only illusions can influence cortical body representations for a significant proportion of participants, which may have implications for the development of accessible visual-only chronic pain treatments.
Tiered Sympathetic Control of Cardiac Function Revealed by Viral Tracing and Single Cell Transcriptome Profiling
Authors: Sharma Sachin , Littman Russell , Tompkins John , Arneson Douglas , Contreras Jaime , Dajani Al-Hassan , Ang Kaitlyn , Tsanhani Amit , Sun Xin , Jay Patrick Y. , Herzog Herbert , Yang Xia , Ajijola Olujimi A.
Published: January 2023

The cell bodies of postganglionic sympathetic neurons innervating the heart primarily reside in the stellate ganglion (SG), alongside neurons innervating other organs and tissues. Whether cardiac-innervating stellate ganglionic neurons (SGNs) exhibit diversity and distinction from those innervating other tissues is not known. To identify and resolve the transcriptomic profiles of SGNs innervating the heart we leveraged retrograde tracing techniques using adeno-associated virus (AAV) expressing fluorescent proteins (GFP or Td-tomato) with single cell RNA sequencing. We investigated electrophysiologic, morphologic, and physiologic roles for subsets of cardiac-specific neurons and found that three of five adrenergic SGN subtypes innervate the heart. These three subtypes stratify into two subpopulations; high (NA1a) and low (NA1b and NA1c) Npy-expressing cells, exhibit distinct morphological, neurochemical, and electrophysiologic characteristics. In physiologic studies in transgenic mouse models modulating NPY signaling, we identified differential control of cardiac responses by these two subpopulations to high and low stress states. These findings provide novel insights into the unique properties of neurons responsible for cardiac sympathetic regulation, with implications for novel strategies to target specific neuronal subtypes for sympathetic blockade in cardiac disease.
Near-surface wind variability over spatiotemporal scales relevant to plume tracking insects
Authors: Houle Jaleesa , van Breugel Floris
Published: January 2023

Odor plume tracking is an important biological process for many organisms, and flying insects have served as popular model systems for studying these behaviors both in the field and in lab settings. The shape and statistics of the airborne odor plumes that insects follow are largely governed by the wind that advects them. Prior atmospheric studies have investigated aspects of microscale wind patterns with an emphasis on characterizing pollution dispersion, enhancing weather prediction models, and for assessing wind energy potential. Here, we aim to characterize microscale wind dynamics through the lens of short-term ecological functions by focusing on spatial and temporal scales most relevant to an insect actively searching for an odor source. We collected and compared near-surface wind data across three distinct environments (sage steppe, forest, and urban) in locations across Northern Nevada. Our findings show that near-surface wind direction variability decreases with increasing wind speeds and increases in environments with greater surface complexity. Across environments, there is a strong correlation between the variability in wind speed (i.e. turbulence intensity) and wind direction (i.e. the standard deviation in wind direction). In some environments, the standard deviation in wind direction varied as much as 15° to 75° on time scales of 1-10 minutes. We draw insights between our findings and previous plume tracking experiments to provide a general intuition for future field research and guidance for wind tunnel experimental design. From our analyses, we hypothesize that there may be an ideal range of wind speeds and environment complexity in which insects will be most successful when tracking an odor plume to its source.
Fast and robust metagenomic sequence comparison through sparse chaining with skani
Authors: Shaw Jim , Yu Yun William
Published: January 2023

Sequence comparison algorithms for metagenome-assembled genomes (MAGs) often have difficulties dealing with data that is high-volume or low-quality. We presentskani(https://github.com/bluenote-1577/skani), a method for calculating average nucleotide identity (ANI) using sparse approximate alignments. skani is more accurate than FastANI for comparing incomplete, fragmented MAGs while also being > 20 times faster. For searching a database of > 65, 000 prokaryotic genomes, skani takes only seconds per query and 6 GB of memory. skani is a versatile tool that unlocks higher-resolution insights for larger, noisier metagenomic data sets.
Frontotemporal Dementia Patient Neurons With Progranulin Deficiency Display Protein Dyshomeostasis
Authors: Elia Lisa , Herting Bianca , Alijagic Amela , Buselli Christina , Wong Leela , Morrison Grace , Prado Miguel A. , Paulo Joao A. , Gygi Steven P. , Finley Daniel , Finkbeiner Steven
Published: January 2023

Haploinsufficiency of progranulin (PGRN) causes frontotemporal dementia (FTD), a devastating neurodegenerative disease with no effective treatment. PGRN is required for efficient proteostasis, as loss of neuronal PGRN results in dysfunctional lysosomes and impaired clearance and cytoplasmic aggregation of TDP-43, a protein involved in neurodegeneration in FTD. These and other events lead to neurodegeneration and neuroinflammation. However, the detailed mechanisms leading to protein dyshomeostasis in PGRN-deficient cells remain unclear. We report here the development of human cell models of FTD with PGRN-deficiency to explore the molecular mechanisms underlying proteostasis breakdown and TDP-43 aggregation in FTD. Neurons differentiated from FTD patient induced pluripotent stem cells (iPSCs) have reduced PGRN levels, and the neurons recapitulate key disease features, including impaired lysosomal function, defective TDP-43 turnover and accumulation, neurodegeneration, and death. Proteomic analysis revealed altered levels of proteins linked to the autophagy-lysosome pathway (ALP) and the ubiquitin-proteasome system (UPS) in FTD patient neurons, providing new mechanistic insights into the link between PGRN-deficiency and disease pathobiology.
Evolutionary selection of proteins with two folds
Authors: Schafer Joseph W. , Porter Lauren L.
Published: January 2023

Although most globular proteins fold into a single stable structure1, an increasing number have been shown to remodel their secondary and tertiary structures in response to cellular stimuli2. State-of-the-art algorithms3-5predict that these fold-switching proteins assume only one stable structure6,7, missing their functionally critical alternative folds. Why these algorithms predict a single fold is unclear, but all of them infer protein structure from coevolved amino acid pairs. Here, we hypothesize that coevolutionary signatures are being missed. Suspecting that over-represented single-fold sequences may be masking these signatures, we developed an approach to search both highly diverse protein superfamilies–composed of single-fold and fold-switching variants–and protein subfamilies with more fold-switching variants. This approach successfully revealed coevolution of amino acid pairs uniquely corresponding to both conformations of 56/58 fold-switching proteins from distinct families. Then, using a set of coevolved amino acid pairs predicted by our approach, we successfully biased AlphaFold25to predict two experimentally consistent conformations of a candidate protein with unsolved structure. The discovery of widespread dual-fold coevolution indicates that fold-switching sequences have been preserved by natural selection, implying that their functionalities provide evolutionary advantage and paving the way for predictions of diverse protein structures from single sequences.
The impact of similarity metrics on cell type clustering in highly multiplexed in situ imaging cytometry data
Authors: Willie Elijah , Yang Pengyi , Patrick Ellis
Published: January 2023

Highly multiplexedin situimaging cytometry assays have enabled researchers to scru-tinize cellular systems at an unprecedented level. With the capability of these assays to simultaneously profile the spatial distribution and molecular features of many cells, unsuper-vised machine learning, and in particular clustering algorithms, have become indispensable for identifying cell types and subsets based on these molecular features. However, the most widely used clustering approaches applied to these novel technologies were developed for cell suspension technologies and may not be optimal forin situimaging assays. In this work, we systematically evaluated the performance of various similarity metrics used to quan-tify the similarity between cells when clustering. Our results demonstrate that performance in cell clustering varies significantly when different similarity metrics were used. Lastly, we propose FuseSOM, an ensemble clustering algorithm employing hierarchical multi-view learning of similarity metrics and self-organizing maps (SOM). Using a stratified subsam-pling analysis framework, FuseSOM exhibits superior clustering performance compared to the current best-practice clustering approaches forin situimaging cytometry data analysis.
Andes virus genome mutations that are likely associated with animal-model attenuation and human person-to-person transmission
Authors: Bellomo Carla M. , Alonso Daniel O. , Pérez-Sautu Unai , Prieto Karla , Kehl Sebastian , Coelho Rocio M. , Periolo Natalia , Di Paola Nicholas , Ferressini-Gerpe Natalia , Kuhn Jens H. , Sanchez-Lockhart Mariano , Palacios Gustavo , Martínez Valeria P.
Published: January 2023

STRUCTURED ABSTRACT

We performed whole-genome sequencing with bait-enrichment techniques to analyze Andes virus (ANDV), a cause of human hantavirus pulmonary syndrome. We used cryopreserved lung tissues from a naturally infected long-tailed colilargo; early, intermediate, and late cell-culture passages of an ANDV isolate from that animal; and lung tissues from golden hamsters experimentally exposed to that ANDV isolate. The resulting complete genome sequences were subjected to detailed comparative genomic analysis against American orthohantaviruses. We identified four amino-acid substitutions related to cell-culture adaptation that resulted in attenuation of ANDV in the typically lethal golden hamster animal model of hantavirus pulmonary syndrome. Mutations in the ANDV nucleocapsid protein, glycoprotein, and small nonstructural protein open reading frames correlated with mutations typical for ANDV strains associated with increased pathogenesis in the small animal model. Finally, we identified three amino-acid substitutions, two in the small nonstructural protein and one in the glycoprotein, that were only present in the clade of viruses associated with person-to-person efficient transmission. Our results indicate that there are virulence-associated and transmission-associated single-nucleotide polymorphisms that could be used to predict strain-specific ANDV virulence and/or transmissibility.

Importance

Several orthohantaviruses cause the zoonotic disease hantavirus pulmonary syndrome (HPS) in the Americas. Among them, HPS caused by Andes virus (ANDV) is of great public-health concern because it is associated with the highest case-fatality rate (up to 50%). ANDV is also the only orthohantavirus associated with relatively robust evidence of person-to-person transmission. This work reveals nucleotide changes in the ANDV genome that are associated with virulence attenuation in an animal model and increased transmissibility in humans. These findings may pave the way to early severity predictions in future ANDV-caused HPS outbreaks.
ADHD and family life: a cross-sectional study of ADHD prevalence among pupils in China and factors associated with parental stress
Authors: Lv Tao , Leavey Gerard , Li Longlong , Tang Ying
Published: January 2023

Background

Attention Deficit Hyperactivity Disorder (ADHD) is increasingly recognized as a major problem for children and their families in China. However, its influence on parental stress has been seldom explored.

Objective

To examine the prevalence of attention deficit hyperactivity disorder in a community sample of children aged 6-13 years, and the extent to which it impacts parental depression.

Method

Cross-sectional study of primary school pupils (number=2497) in Deyang, Sichuan Province, South-West China. We used standardized instruments to identify children with ADHD symptoms and parent depression.

Results

The prevalence of ADHD was 9.8%. Factors associated with the likelihood of ADHD, included family environment(P=0.003), time spent with children(P=0.01), parenting style(P=0.01), and parental relationship, pupils self-harm and lower academic ability (P=0.001). After controlling for other factors, having a child with ADHD increased the likelihood of parents’ depression (OR=4.35, CI=2.68∼7.07), additional factors included parent relationship.

Conclusions

ADHD may be a common disorder among Chinese children, the symptoms of which may increase the likelihood of parent depression. There is a need for greater detection of ADHD in schools and an acknowledgement of the challenges the disorder creates for academic success and family wellbeing.
Serotonin blocker Ketanserin reduces coral reef fishCtenochaetus striatusaggressive behaviour during between-species social interactions
Authors: Staubli Virginie , Bshary Redouan , Triki Zegni
Published: January 2023

A multitude of species engages in social interactions not only with their conspecifics but also with other species. Such interspecific interactions can be either positive, like helping, or negative, like aggressive behaviour. However, the physiological mechanisms of these behaviours remain unclear. Here, we manipulated the serotonin system, a well-known neurohormone for regulating intraspecific aggressive behaviour, to investigate its role in interspecific aggression. We tested whether serotonin blockade affects the aggressive behaviour of a coral reef fish species (Ctenochaetus striatus) that engages in mutualistic interactions with another species, the cleaner fish (Labroides dimidiatus). Although this mutualistic cleaning relationship may appear positive, cleaner fish do not always cooperate and remove ectoparasites from the other coral reef fish (“clients”) but tend to cheat and bite the client’s protective layer of mucus. Client fish thus often apply control mechanisms, like chasing, to deter their cleaner fish partners from cheating. Our findings show that blocking serotonin receptors 5-HT2A and 5-HT2C with ketanserin reduced the client fish’s aggressive behaviour towards cleaner fish, but in the context where the latter did not cheat. These results are evidence of the involvement of serotonin in regulating aggressive behaviour at the between-species social interactions level. Yet, the direction of effect we found here is the opposite of previous findings using a similar experimental set-up and ecological context but with a different client fish species (Scolopsis bilineatus). Together, it suggests that serotonin’s role in aggressive behaviour is complex, and at least in this mutualistic ecological context, the function is species-dependent. This warrants, to some extent, careful interpretations from single-species studies looking into the physiological mechanisms of social behaviour.
Robust analysis of prokaryotic pangenome gene gain and loss rates with Panstripe
Authors: Tonkin-Hill Gerry , Gladstone Rebecca A. , Pöntinen Anna K. , Arredondo-Alonso Sergio , Bentley Stephen D. , Corander Jukka
Published: January 2023

Horizontal gene transfer (HGT) plays a critical role in the evolution and diversification of many microbial species. The resulting dynamics of gene gain and loss can have important implications for the development of antibiotic resistance and the design of vaccine and drug interventions. Methods for the analysis of gene presence/absence patterns typically do not account for errors introduced in the automated annotation and clustering of gene sequences. In particular, methods adapted from ecological studies, including the pangenome gene accumulation curve, can be misleading as they may reflect the underlying diversity in the temporal sampling of genomes rather than a difference in the dynamics of HGT. Here, we introduce Panstripe, a method based on generalized linear regression that is robust to population structure, sampling bias, and errors in the predicted presence/absence of genes. We show using simulations that Panstripe can effectively identify differences in the rate and number of genes involved in HGT events, and illustrate its capability by analyzing several diverse bacterial genome data sets representing major human pathogens.
IT vendor integration as catalyst of IT outsourcing success
Authors: Navarro-Paule Andrés J. , Romerosa-Martínez M. Mercedes , Lloréns-Montes Francisco Javier
Published: January 2023

Purpose

This paper aims to explain how small- and medium-sized firms (SMEs) create information technology (IT) business value through blended IT outsourcing (ITO). The explanatory framework it proposes enables SMEs to replicate IT capability outcomes (i.e. enhance their economic, strategic and technological competences, namely, ITO success) by endorsing an ITO strategy catalyzed by IT vendor integration.

Design/methodology/approach

This study uses covariance-based structural equation modeling to test the proposed research model. Data are collected from 251 knowledge-intensive business SMEs located in Science and Technology Parks in Spain.

Findings

The results demonstrate empirically that SMEs can replicate IT capability benefits (i.e. enhance their non-IT competences) through blended ITO in which IT, conceptualized as a transversal supporting activity, is outsourced to an IT vendor while the value creation process remains with the buyer. The integration (i.e. process integration and information sharing) of an IT-proficient vendor catalyzes ITO success. More specifically, the results show that, although process integration is not directly related to competence enhancement, fosters information sharing, which directly facilitates ITO success. The results also show that IT vendor proficiency accounts for ex ante trust.

Practical implications

Managers should think of transformational ITO as a strategy to enhance firm competences. For blended ITO strategies to succeed, managers must have a comprehensive understanding of the business they run, as it is important to create conditions that foster inter-firm information sharing. To achieve these conditions, managers should take special care in selecting boundary spanners, who are the pivotal links in competence enhancement.

Originality/value

While most research focuses on ongoing trust (i.e. trust develops as ITO evolves), this study focuses on initial (i.e. ex ante) trust and analyzes IT vendor proficiency (expert, experienced and reputed) to examine trust as an antecedent of ITO. This study also draws on previous conceptualizations of vendor integration to develop and analyze a two-step integration model to explain how IT vendor integration (i.e. process integration and information sharing) catalyzes enhancement of the buyer’s non-IT competences. This study focuses on SMEs, which are often neglected in ITO studies.