bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Adverse Outcomes in Term Infants with CHD and Definitive Necrotising Enterocolitis
Authors: Deitch Anna M. , Moynihan Katie , Przybylski Robert , Gauvreau Kimberlee , Braudis Nancy J. , Farr Bethany , Modi Biren , Mills Kimberly I. , Nathan Meena , Levy Philip T.
Published: May 2023

Objectives:

To define the incidence of definitive necrotising enterocolitis in term infants with CHD and identify risk factors for morbidity/mortality.

Methods:

We performed a 20-year (2000–2020) single-institution retrospective cohort study of term infants with CHD admitted to the Boston Children’s Hospital cardiac ICU with necrotising enterocolitis (Bell’s stage ≥ II). The primary outcome was a composite of in-hospital mortality and post-necrotising enterocolitis morbidity (need for extracorporeal membrane oxygenation, multisystem organ failure based on the paediatric sequential organ failure assessment score, and/or need for acute gastrointestinal intervention). Predictors included patient characteristics, cardiac diagnosis/interventions, feeding regimen, and severity measures.

Results:

Of 3933 term infants with CHD, 2.1% (n = 82) developed necrotising enterocolitis, with 67% diagnosed post-cardiac intervention. Thirty (37%) met criteria for the primary outcome. In-hospital mortality occurred in 14 infants (17%), of which nine (11%) deaths were attributable to necrotising enterocolitis. Independent predictors of the primary outcome included moderate to severe systolic ventricular dysfunction (odds ratio 13.4,confidence intervals 1.13–159) and central line infections pre-necrotising enterocolitis diagnosis (odds ratio 17.7, confidence intervals 3.21–97.0) and mechanical ventilation post-necrotising enterocolitis diagnosis (odds ratio 13.5, confidence intervals 3.34–54.4). Single ventricle, ductal dependency, and feeding related factors were not independently associated with the primary outcome.

Conclusions:

The incidence of necrotising enterocolitis was 2.1% in term infants with CHD. Adverse outcomes occurred in greater than 30% of patients. Presence of systolic dysfunction and central line infections prior to diagnosis and need for mechanical ventilation after diagnosis of necrotising enterocolitis can inform risk triage and prognostic counseling for families.
Reduced length of stay after implementation of a clinical pathway following repair of ventricular septal defect
Authors: Ogdon Tracey L. , Loomba Rohit S. , Penk Jamie S.
Published: May 2023

Background:

There is variation in care and hospital length of stay following surgical repair of ventricular septal defects. The use of clinical pathways in a variety of paediatric care settings has been shown to reduce practice variability and overall length of stay without increasing the rate of adverse events.

Methods:

A clinical pathway was created and used to guide care following surgical repair of ventricular septal defects. A retrospective review was done to compare patients two years prior and three years after the pathway was implemented.

Results:

There were 23 pre-pathway patients and 25 pathway patients. Demographic characteristics were similar between groups. Univariate analysis demonstrated a significantly shorter time to initiation of enteral intake in the pathway patients (median time to first enteral intake after cardiac ICU admission was 360 minutes in pre-pathway patients and 180 minutes in pathway patients, p < 0.01). Multivariate regression analyses demonstrated that the pathway use was independently associated with a decrease in time to first enteral intake (–203 minutes), hospital length of stay (–23.1 hours), and cardiac ICU length of stay (–20.5 hours). No adverse events were associated with the use of the pathway, including mortality, reintubation rate, acute kidney injury, increased bleeding from chest tube, or readmissions.

Conclusions:

The use of the clinical pathway improved time to initiation of enteral intake and decreased length of hospital stay. Surgery-specific pathways may decrease variability in care while also improving quality metrics.
Managing dementia care during COVID-19 pandemic: caregivers’ experiences in Odisha, India
Authors: Mahapatra Pranab , Sahoo Krushna Chandra , Desaraju Shyama , Nath Binapani , Pati Sanghamitra
Published: May 2023

Aim:

The present study explored the family caregivers’ perspectives and elicited their experience while managing dementia care during the COVID-19 pandemic in Odisha, India.

Background:

The onset of the COVID-19 pandemic has diverted the attention of health systems away from chronic disease management and health services delivery. Psychiatric care particularly for dementia and the elderly is found to be more compromised in such situation.

Methods:

We adopted an inductive phenomenological approach to garner key insights into the care continuity for people living with dementia in the context of the COVID-19 pandemic. Telephonic in-depth interviews (IDIs) were carried out with 17 immediate caregivers. All IDIs were digitally recorded, transcribed, and analysed using a thematic approach.

Findings:

Caregivers did not perceive dementia as an overwhelming challenge; instead viewed it as a part of the ageing process. Caring for dementia was being done by family members as a collective responsibility with task-sharing. The caregivers primarily relied on their usual physician for the continuity of dementia care and took utmost precautions to prevent exposure to COVID-19 risk. However, they found it more challenging to ensure adequate care for the multiple illnesses (multimorbidity) coexisting with dementia. Towards this, they adopted all possible measures to keep the chronic conditions under control, lest the vulnerability to COVID-19 infection might heighten. The fear of visiting a hospital, prevailing restrictions in mobility, and diverted attention of health systems to pandemic containment created impediments towards maintaining multimorbidity care. The support of local administration, neighbourhood pharmacy and diagnostic laboratories and teleconsultation with the physicians were vital for care continuity. Caregivers adapted by reducing or deferring physical consultation and seeking treatment via telephonic advice of the treating physicians. Our findings suggest leveraging digitally enabled health care technology and augmenting caregiver activation for home-based dementia care to cruise through any similar catastrophic situations.
Numerical Simulations Reproduce Field Observations Showing Transient Weakening During Shear Zone Formation by Diffusional Hydrogen Influx and H2O Inflow
Authors: Kaatz L. , Schmalholz S. M. , John T.
Published: May 2023

Exposures on Holsnøy island (Bergen Arcs, Norway) indicate fluid infiltration through fractures into a dry, metastable granulite, which triggered a kinetically delayed eclogitization, a transient weakening during fluid‐rock interaction, and formation of shear zones that widened during shearing. It remains unclear whether the effects of grain boundary‐assisted aqueous fluid inflow on the duration of granulite hydration were influenced by a diffusional hydrogen influx accompanying the fluid inflow. To better estimate the fluid infiltration efficiencies and the parameter interdependencies, a 1D numerical model of a viscous shear zone is utilized and validated using measured mineral phase abundance distributions and H2O‐contents in nominally anhydrous minerals of the original granulite assemblage to constrain the hydration by aqueous fluid inflow and diffusional hydrogen influx, respectively. Both hydrations are described with a diffusion equation and affect the effective viscosity. Shear zone kinematics are constrained by the observed shear strain and thickness. The model fits the phase abundance and H2O‐content profiles if the effective hydrogen diffusivity is approximately one order of magnitude higher than the diffusivity for aqueous fluid inflow. The observed shear zone thickness is reproduced if the viscosity ratio between dry granulite and deforming, reequilibrating eclogite is ∼104 and that between dry granulite and hydrated granulite is ∼102. The results suggest shear velocities <10−2 cm/a, hydrogen diffusivities of ∼10−13±1 m2/s, and a shearing duration of <10 years. This study successfully links and validates field data to a shear zone model and highlights the importance of hydrogen diffusion for shear zone widening and eclogitization.
Wind Gust Parameters in the Lower Troposphere Based on Doppler Lidar Data
Authors: Zhou Xingxu , Zhang Chao , Li Yunying , Chen Zitong , Zhang Jie , Ding Xingyun
Published: May 2023

Wind gusts are common small‐scale weather phenomena characterized by a rapid increase in wind speed over a short period of time. Wind gusts affect a wide range of interests, including aviation safety, wind energy and professional skiing, while strong gusts can also cause severe weather events and limit visibility. However, the characteristics of gusts in the lower troposphere are not yet well understood, especially at the top of the boundary layer. In this paper, the gust parameters in the lower atmosphere at different heights and their diurnal variation characteristics are examined based on Doppler lidar data from the gentle coastal topography of Shandong Province, China. The results show that all the gust parameters have distinct stratification characteristics, with significantly different diurnal variations below 400 m, between 400 and 1,200 m, and above 1,200 m (above the ground, same below). Wind gusts are considered to be the result of turbulent disturbances superimposed on the background airflow, and strong turbulence could cause the instantaneous winds to significantly deviate from the mean airflow. The magnitude of the peak gust is mainly controlled by the mean flow, but the gust factor, which is the ratio of the peak gust to the mean flow, is almost independent of the mean flow and has a strong positive correlation with the turbulence intensity. These results imply that gusts of different properties occur at varying altitudes, with differences depending on turbulence intensity and mean airflow, and provide an observational basis for studies of gust structure.
Tracking Marine Heat Waves
Authors: Donovan Robin
Published: May 2023

Heat waves can happen in the depths, invisible at the ocean surface.
Adolescent exposure to the Spice/K2 cannabinoid JWH-018 impairs sensorimotor gating and alters cortical perineuronal nets in a sex-dependent manner
Authors: Izquierdo-Luengo Cristina , Ten-Blanco Marc , Ponce-Renilla María , Perezzan Ramiro , Pereda-Pérez Inmaculada , Berrendero Fernando
Published: May 2023

The consumption of synthetic cannabinoids during adolescence is reported to be a risk factor for the appearance of psychiatric disorders later in life. JWH-018 was identified as one of the primary psychoactive components present in Spice/K2 preparations. This study evaluated the short- and long-term consequences of exposure to JWH-018 during the adolescence in anxiety-like behavior, fear extinction, and sensorimotor gating in male and female mice. Alterations in anxiety varied depending on the time interval between treatment and behavioral analysis along with sex, while no changes were observed in the extinction of fear memory. A decrease in prepulse inhibition of the startle reflex was revealed in male, but not female, mice at short- and long-term. This behavioral disturbance was associated with a reduction in the number of perineuronal nets in the prelimbic and infralimbic regions of the prefrontal cortex in the short-term. Furthermore, adolescent exposure to JWH-018 induced an activation of microglia and astrocytes in the prefrontal cortex of male mice at both time intervals. A transitory decrease in the expression of GAD67 and CB2 cannabinoid receptors in the prefrontal cortex was also found in male mice exposed to JWH-018. These data reveal that the treatment with JWH-018 during the adolescence leads to long-lasting neurobiological changes related to psychotic-like symptoms, which were sex-dependent.
Systematic evaluation of a predator stress model of depression in mice using a hierarchical 3D-motion learning framework
Authors: Tseng Yu-Ting , Zhao Binghao , Ding Hui , Liang Lisha , Schaefke Bernhard , Wang Liping
Published: May 2023

Investigation of the neurobiology of depression in humans depends on animal models that attempt to mimic specific features of the human disorder. However, frequently-used paradigms based on social stress cannot be easily applied to female mice which has led to a large sex bias in preclinical studies of depression. Furthermore, most studies focus on one or only a few behavioral assessments, with time and practical considerations prohibiting a comprehensive evaluation. In this study, we demonstrate that predator stress effectively induced depression-like behaviors in both male and female mice. By comparing predator stress and social defeat models, we observed that the former elicited a higher level of behavioral despair and the latter elicited more robust social avoidance. Furthermore, the use of machine learning (ML)-based spontaneous behavioral classification can distinguish mice subjected to one type of stress from another, and from non-stressed mice. We show that related patterns of spontaneous behaviors correspond to depression status as measured by canonical depression-like behaviors, which illustrates that depression-like symptoms can be predicted by ML-classified behavior patterns. Overall, our study confirms that the predator stress induced phenotype in mice is a good reflection of several important aspects of depression in humans and illustrates that ML-supported analysis can simultaneously evaluate multiple behavioral alterations in different animal models of depression, providing a more unbiased and holistic approach for the study of neuropsychiatric disorders.
Ultra-strong tungsten refractory high-entropy alloy via stepwise controllable coherent nanoprecipitations
Authors: Li Tong , Liu Tianwei , Zhao Shiteng , Chen Yan , Luan Junhua , Jiao Zengbao , Ritchie Robert O. , Dai Lanhong
Published: May 2023

High-performance refractory alloys with ultrahigh strength and ductility are in demand for a wide range of critical applications, such as plasma-facing components. However, it remains challenging to increase the strength of these alloys without seriously compromising their tensile ductility. Here, we put forward a strategy to “defeat” this trade-off in tungsten refractory high-entropy alloys by stepwise controllable coherent nanoprecipitations (SCCPs). The coherent interfaces of SCCPs facilitate the dislocation transmission and relieve the stress concentrations that can lead to premature crack initiation. As a consequence, our alloy displays an ultrahigh strength of 2.15 GPa with a tensile ductility of 15% at ambient temperature, with a high yield strength of 1.05 GPa at 800 °C. The SCCPs design concept may afford a means to develop a wide range of ultrahigh-strength metallic materials by providing a pathway for alloy design.
Compact A15 Frank-Kasper nano-phases at the origin of dislocation loops in face-centred cubic metals
Authors: Goryaeva Alexandra M. , Domain Christophe , Chartier Alain , Dézaphie Alexandre , Swinburne Thomas D. , Ma Kan , Loyer-Prost Marie , Creuze Jérôme , Marinica Mihai-Cosmin
Published: May 2023

It is generally considered that the elementary building blocks of defects in face-centred cubic (fcc) metals, e.g., interstitial dumbbells, coalesce directly into ever larger 2D dislocation loops, implying a continuous coarsening process. Here, we reveal that, prior to the formation of dislocation loops, interstitial atoms in fcc metals cluster into compact 3D inclusions of A15 Frank-Kasper phase. After reaching the critical size, A15 nano-phase inclusions act as a source of prismatic or faulted dislocation loops, dependent on the energy landscape of the host material. Using cutting-edge atomistic simulations we demonstrate this scenario in Al, Cu, and Ni. Our results explain the enigmatic 3D cluster structures observed in experiments combining diffuse X-ray scattering and resistivity recovery. Formation of compact nano-phase inclusions in fcc structure, along with previous observations in bcc structure, suggests that the fundamental mechanisms of interstitial defect formation are more complex than historically assumed and require a general revision. Interstitial-mediated formation of compact 3D precipitates can be a generic phenomenon, which should be further explored in systems with different crystallographic lattices.
A blocking monoclonal antibody reveals dimerization of intracellular domains of ALK2 associated with genetic disorders
Authors: Katagiri Takenobu , Tsukamoto Sho , Kuratani Mai , Tsuji Shinnosuke , Nakamura Kensuke , Ohte Satoshi , Kawaguchi Yoshiro , Takaishi Kiyosumi
Published: May 2023

Mutations in activin receptor-like kinase 2 (ALK2) can cause the pathological osteogenic signaling seen in some patients with fibrodysplasia ossificans progressiva and other conditions such as diffuse intrinsic pontine glioma. Here, we report that intracellular domain of wild-type ALK2 readily dimerizes in response to BMP7 binding to drive osteogenic signaling. This osteogenic signaling is pathologically triggered by heterotetramers of type II receptor kinases and ALK2 mutant forms, which form intracellular domain dimers in response to activin A binding. We develop a blocking monoclonal antibody, Rm0443, that can suppress ALK2 signaling. We solve the crystal structure of the ALK2 extracellular domain complex with a Fab fragment of Rm0443 and show that Rm0443 induces dimerization of ALK2 extracellular domains in a back-to-back orientation on the cell membrane by binding the residues H64 and F63 on opposite faces of the ligand-binding site. Rm0443 could prevent heterotopic ossification in a mouse model of fibrodysplasia ossificans progressiva that carries the human R206H pathogenic mutant.
Establishment of gastrointestinal assembloids to study the interplay between epithelial crypts and their mesenchymal niche
Authors: Lin Manqiang , Hartl Kimberly , Heuberger Julian , Beccaceci Giulia , Berger Hilmar , Li Hao , Liu Lichao , Müllerke Stefanie , Conrad Thomas , Heymann Felix , Woehler Andrew , Tacke Frank , Rajewsky Nikolaus , Sigal Michael
Published: May 2023

The cellular organization of gastrointestinal crypts is orchestrated by different cells of the stromal niche but available in vitro models fail to fully recapitulate the interplay between epithelium and stroma. Here, we establish a colon assembloid system comprising the epithelium and diverse stromal cell subtypes. These assembloids recapitulate the development of mature crypts resembling in vivo cellular diversity and organization, including maintenance of a stem/progenitor cell compartment in the base and their maturation into secretory/absorptive cell types. This process is supported by self-organizing stromal cells around the crypts that resemble in vivo organization, with cell types that support stem cell turnover adjacent to the stem cell compartment. Assembloids that lack BMP receptors either in epithelial or stromal cells fail to undergo proper crypt formation. Our data highlight the crucial role of bidirectional signaling between epithelium and stroma, with BMP as a central determinant of compartmentalization along the crypt axis.
A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8
Authors: Rodriguez-Rodriguez Bruno A. , Ciabattoni Grace O. , Duerr Ralf , Valero-Jimenez Ana M. , Yeung Stephen T. , Crosse Keaton M. , Schinlever Austin R. , Bernard-Raichon Lucie , Rodriguez Galvan Joaquin , McGrath Marisa E. , Vashee Sanjay , Xue Yong , Loomis Cynthia A. , Khanna Kamal M. , Cadwell Ken , Desvignes Ludovic , Frieman Matthew B. , Ortigoza Mila B. , Dittmann Meike
Published: May 2023

Small animal models have been a challenge for the study of SARS-CoV-2 transmission, with most investigators using golden hamsters or ferrets. Mice have the advantages of low cost, wide availability, less regulatory and husbandry challenges, and the existence of a versatile reagent and genetic toolbox. However, adult mice do not robustly transmit SARS-CoV-2. Here we establish a model based on neonatal mice that allows for transmission of clinical SARS-CoV-2 isolates. We characterize tropism, respiratory tract replication and transmission of ancestral WA-1 compared to variants Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Omicron BA.1 and Omicron BQ.1.1. We identify inter-variant differences in timing and magnitude of infectious particle shedding from index mice, both of which shape transmission to contact mice. Furthermore, we characterize two recombinant SARS-CoV-2 lacking either the ORF6 or ORF8 host antagonists. The removal of ORF8 shifts viral replication towards the lower respiratory tract, resulting in significantly delayed and reduced transmission in our model. Our results demonstrate the potential of our neonatal mouse model to characterize viral and host determinants of SARS-CoV-2 transmission, while revealing a role for an accessory protein in this context.
Maximizing protein production by keeping cells at optimal secretory stress levels using real-time control approaches
Authors: Sosa-Carrillo Sebastián , Galez Henri , Napolitano Sara , Bertaux François , Batt Gregory
Published: May 2023

Optimizing the production of recombinant proteins is a problem of major industrial and pharmaceutical importance. Secretion of the protein by the host cell considerably simplifies downstream purification processes. However, for many proteins, this is also the limiting production step. Current solutions involve extensive engineering of the chassis cell to facilitate protein trafficking and limit protein degradation triggered by excessive secretion-associated stress. Here, we propose instead a regulation-based strategy in which induction is dynamically adjusted to an optimal strength based on the current stress level of the cells. Using a small collection of hard-to-secrete proteins, a bioreactor-based platform with automated cytometry measurements, and a systematic assay to quantify secreted protein levels, we demonstrate that the secretion sweet spot is indicated by the appearance of a subpopulation of cells that accumulate high amounts of proteins, decrease growth, and face significant stress, that is, experience a secretion burnout. In these cells, adaptations capabilities are overwhelmed by a too strong production. Using these notions, we show for a single-chain antibody variable fragment that secretion levels can be improved by 70% by dynamically keeping the cell population at optimal stress levels using real-time closed-loop control.
Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens strains
Authors: Kiu Raymond , Shaw Alexander G. , Sim Kathleen , Acuna-Gonzalez Antia , Price Christopher A. , Bedwell Harley , Dreger Sally A. , Fowler Wesley J. , Cornwell Emma , Pickard Derek , Belteki Gusztav , Malsom Jennifer , Phillips Sarah , Young Gregory R. , Schofield Zoe , Alcon-Giner Cristina , Berrington Janet E. , Stewart Christopher J. , Dougan Gordon , Clarke Paul , Douce Gillian , Robinson Stephen D. , Kroll J. Simon , Hall Lindsay J.
Published: May 2023

Clostridium perfringensis an anaerobic toxin-producing bacterium associated with intestinal diseases, particularly in neonatal humans and animals. Infant gut microbiome studies have recently indicated a link betweenC. perfringensand the preterm infant disease necrotizing enterocolitis (NEC), with specific NEC cases associated with overabundantC. perfringenstermedC. perfringens-associated NEC (CPA-NEC). In the present study, we carried out whole-genome sequencing of 272C. perfringensisolates from 70 infants across 5 hospitals in the United Kingdom. In this retrospective analysis, we performed in-depth genomic analyses (virulence profiling, strain tracking and plasmid analysis) and experimentally characterized pathogenic traits of 31 strains, including 4 from CPA-NEC patients. We found that the gene encoding toxin perfringolysin O,pfoA, was largely deficient in a human-derived hypovirulent lineage, as well as certain colonization factors, in contrast to typicalpfoA-encoding virulent lineages. We determined that infant-associatedpfoA+strains caused significantly more cellular damage thanpfoA−strains in vitro, and further confirmed this virulence trait in vivo using an oral-challenge C57BL/6 murine model. These findings suggest both the importance ofpfoA+C. perfringensas a gut pathogen in preterm infants and areas for further investigation, including potential intervention and therapeutic strategies.
Synthesis of prebiotic organics from CO2 by catalysis with meteoritic and volcanic particles
Authors: Peters Sophia , Semenov Dmitry A. , Hochleitner Rupert , Trapp Oliver
Published: May 2023

The emergence of prebiotic organics was a mandatory step toward the origin of life. The significance of the exogenous delivery versus the in-situ synthesis from atmospheric gases is still under debate. We experimentally demonstrate that iron-rich meteoritic and volcanic particles activate and catalyse the fixation of CO2, yielding the key precursors of life-building blocks. This catalysis is robust and produces selectively aldehydes, alcohols, and hydrocarbons, independent of the redox state of the environment. It is facilitated by common minerals and tolerates a broad range of the early planetary conditions (150–300 °C, ≲ 10–50 bar, wet or dry climate). We find that up to 6 × 108 kg/year of prebiotic organics could have been synthesized by this planetary-scale process from the atmospheric CO2on Hadean Earth.
Distinguishing intentional from nonintentional actions through eeg and kinematic markers
Authors: Derchi C. C. , Mikulan E. , Mazza A. , Casarotto S. , Comanducci A. , Fecchio M. , Navarro J. , Devalle G. , Massimini M. , Sinigaglia C.
Published: May 2023

How can an intentional movement be distinguished from the same movement done nonintentionally? How can this distinction be drawn without asking the subject, or in patients who are unable to communicate? Here we address these questions, by focusing on blinking. This is one of the most frequent spontaneous actions in our daily life, but it can also be done intentionally. Furthermore, blinking is often spared in patients with severe brain injuries, and for some, it is the only way to report complex meanings. Using kinematic and EEG-based measures, we found that intentional and spontaneous blinking are preceded by different brain activities, even when they are indistinguishable. Unlike spontaneous ones, intentional blinks are characterized by a slow negative EEG drift, resembling the classic readiness potential. We investigated the theoretical implication of this finding in stochastic decision models as well as the practical significance of using brain-based signals to improve the discrimination between intentional and nonintentional actions. As proof of principle, we considered three brain-injured patients with rare neurological syndromes characterized by motor and communicative impairments. Although further research is needed, our results indicate that brain-based signals can offer a feasible way to infer intentionality even in absence of overt communication.
Hedgehog morphogen gradient is robust towards variations in tissue morphology in Drosophila
Authors: Pierini Giulia , Dahmann Christian
Published: May 2023

During tissue development, gradients of secreted signaling molecules known as morphogens provide cells with positional information. The mechanisms underlying morphogen spreading have been widely studied, however, it remains largely unexplored whether the shape of morphogen gradients is influenced by tissue morphology. Here, we developed an analysis pipeline to quantify the distribution of proteins within a curved tissue. We applied it to the Hedgehog morphogen gradient in the Drosophila wing and eye-antennal imaginal discs, which are flat and curved tissues, respectively. Despite a different expression profile, the slope of the Hedgehog gradient was comparable between the two tissues. Moreover, inducing ectopic folds in wing imaginal discs did not affect the slope of the Hedgehog gradient. Suppressing curvature in the eye-antennal imaginal disc also did not alter the Hedgehog gradient slope but led to ectopic Hedgehog expression. In conclusion, through the development of an analysis pipeline that allows quantifying protein distribution in curved tissues, we show that the Hedgehog gradient is robust towards variations in tissue morphology.
Body height estimation from automated length measurements on standing long leg radiographs using artificial intelligence
Authors: Simon Sebastian , Fischer Barbara , Rinner Alexandra , Hummer Allan , Frank Bernhard J. H. , Mitterer Jennyfer A. , Huber Stephanie , Aichmair Alexander , Schwarz Gilbert M. , Hofstaetter Jochen G.
Published: May 2023

Artificial-intelligence (AI) allows large-scale analyses of long-leg-radiographs (LLRs). We used this technology to derive an update for the classical regression formulae by Trotter and Gleser, which are frequently used to infer stature based on long-bone measurements. We analyzed calibrated, standing LLRs from 4200 participants taken between 2015 and 2020. Automated landmark placement was conducted using the AI-algorithm LAMA™ and the measurements were used to determine femoral, tibial and total leg-length. Linear regression equations were subsequently derived for stature estimation. The estimated regression equations have a shallower slope and larger intercept in males and females (Femur-male: slope = 2.08, intercept = 77.49; Femur-female: slope = 1.9, intercept = 79.81) compared to the formulae previously derived by Trotter and Gleser 1952 (Femur-male: slope = 2.38, intercept = 61.41; Femur-female: slope = 2.47, intercept = 54.13) and Trotter and Gleser 1958 (Femur-male: slope = 2.32, intercept = 65.53). All long-bone measurements showed a high correlation (r ≥ 0.76) with stature. The linear equations we derived tended to overestimate stature in short persons and underestimate stature in tall persons. The differences in slopes and intercepts from those published by Trotter and Gleser (1952, 1958) may result from an ongoing secular increase in stature. Our study illustrates that AI-algorithms are a promising new tool enabling large-scale measurements.
Stratification of responses to tDCS intervention in a healthy pediatric population based on resting-state EEG profiles
Authors: Dagnino Paulina Clara , Braboszcz Claire , Kroupi Eleni , Splittgerber Maike , Brauer Hannah , Dempfle Astrid , Breitling-Ziegler Carolin , Prehn-Kristensen Alexander , Krauel Kerstin , Siniatchkin Michael , Moliadze Vera , Soria-Frisch Aureli
Published: May 2023

Transcranial Direct Current Stimulation (tDCS) is a non-invasive neuromodulation technique with a wide variety of clinical and research applications. As increasingly acknowledged, its effectiveness is subject dependent, which may lead to time consuming and cost ineffective treatment development phases. We propose the combination of electroencephalography (EEG) and unsupervised learning for the stratification and prediction of individual responses to tDCS. A randomized, sham-controlled, double-blind crossover study design was conducted within a clinical trial for the development of pediatric treatments based on tDCS. The tDCS stimulation (sham and active) was applied either in the left dorsolateral prefrontal cortex or in the right inferior frontal gyrus. Following the stimulation session, participants performed 3 cognitive tasks to assess the response to the intervention: the Flanker Task, N-Back Task and Continuous Performance Test (CPT). We used data from 56 healthy children and adolescents to implement an unsupervised clustering approach that stratify participants based on their resting-state EEG spectral features before the tDCS intervention. We then applied a correlational analysis to characterize the clusters of EEG profiles in terms of participant’s difference in the behavioral outcome (accuracy and response time) of the cognitive tasks when performed after a tDCS-sham or a tDCS-active session. Better behavioral performance following the active tDCS session compared to the sham tDCS session is considered a positive intervention response, whilst the reverse is considered a negative one. Optimal results in terms of validity measures was obtained for 4 clusters. These results show that specific EEG-based digital phenotypes can be associated to particular responses. While one cluster presents neurotypical EEG activity, the remaining clusters present non-typical EEG characteristics, which seem to be associated with a positive response. Findings suggest that unsupervised machine learning can be successfully used to stratify and eventually predict responses of individuals to a tDCS treatment.
Optical forces in heat-assisted magnetic recording head-disk interface
Authors: Tom Roshan Mathew , Smith Robert , Ruiz Oscar , Dai Qing , Bogy David B.
Published: May 2023

A main challenge in Heat-Assisted Magnetic Recording technology is the build-up of contaminants called smear on the near field transducer. In this paper, we investigate the role of optical forces originating from the electric field gradient in the formation of smear. First, based on suitable theoretical approximations, we compare this force with air drag and the thermophoretic force in the head-disk interface for two smear nanoparticle shapes. Then, we evaluate the force field’s sensitivity to the relevant parameter space. We find that the smear nanoparticle’s refractive index, shape, and volume significantly impact the optical force. Further, our simulations reveal that the interface conditions, such as spacing and the presence of other contaminants, also influence the magnitude of the force.
Development and validation of a CT radiomics and clinical feature model to predict omental metastases for locally advanced gastric cancer
Authors: Wu Ahao , Wu Changlei , Zeng Qingwen , Cao Yi , Shu Xufeng , Luo Lianghua , Feng Zongfeng , Tu Yi , Jie Zhigang , Zhu Yanyan , Zhou Fuqing , Huang Ya , Li Zhengrong
Published: May 2023

“”We employed radiomics and clinical features to develop and validate a preoperative prediction model to estimate the omental metastases status of locally advanced gastric cancer (LAGC). A total of 460 patients (training cohort, n = 250; test cohort, n = 106; validation cohort, n = 104) with LAGC who were confirmed T3/T4 stage by postoperative pathology were continuously collected retrospectively, including clinical data and preoperative arterial phase computed tomography images (APCT). Dedicated radiomics prototype software was used to segment the lesions and extract features from the preoperative APCT images. The least absolute shrinkage and selection operator (LASSO) regression was used to select the extracted radiomics features, and a radiomics score model was constructed. Finally, a prediction model of omental metastases status and a nomogram were constructed combining the radiomics scores and selected clinical features. An area under the curve (AUC) of the receiver operating characteristic curve (ROC) was used to validate the capability of the prediction model and nomogram in the training cohort. Calibration curves and decision curve analysis (DCA) were used to evaluate the prediction model and nomogram. The prediction model was internally validated by the test cohort. In addition, 104 patients from another hospital's clinical and imaging data were gathered for external validation. In the training cohort, the combined prediction (CP) model (AUC 0.871, 95% CI 0.798–0.945) of the radiomics scores combined with the clinical features, compared with clinical features prediction (CFP) model (AUC 0.795, 95% CI 0.710–0.879) and radiomics scores prediction (RSP) model (AUC 0.805, 95% CI 0.730–0.879), had the better predictive ability. The Hosmer–Lemeshow test of the CP model showed that the prediction model did not deviate from the perfect fitting (p = 0.893). In the DCA, the clinical net benefit of the CP model was higher than that of the CFP model and RSP model. In the test and validation cohorts, the AUC values of the CP model were 0.836 (95% CI 0.726–0.945) and 0.779 (95% CI 0.634–0.923), respectively. The preoperative APCT-based clinical-radiomics nomogram showed good performance in predicting omental metastases status in LAGC, which may contribute to clinical decision-making.
Automated screening of potential organ donors using a temporal machine learning model
Authors: Sauthier Nicolas , Bouchakri Rima , Carrier François Martin , Sauthier Michaël , Mullie Louis-Antoine , Cardinal Héloïse , Fortin Marie-Chantal , Lahrichi Nadia , Chassé Michaël
Published: May 2023

Organ donation is not meeting demand, and yet 30–60% of potential donors are potentially not identified. Current systems rely on manual identification and referral to an Organ Donation Organization (ODO). We hypothesized that developing an automated screening system based on machine learning could reduce the proportion of missed potentially eligible organ donors. Using routine clinical data and laboratory time-series, we retrospectively developed and tested a neural network model to automatically identify potential organ donors. We first trained a convolutive autoencoder that learned from the longitudinal changes of over 100 types of laboratory results. We then added a deep neural network classifier. This model was compared to a simpler logistic regression model. We observed an AUROC of 0.966 (CI 0.949–0.981) for the neural network and 0.940 (0.908–0.969) for the logistic regression model. At a prespecified cutoff, sensitivity and specificity were similar between both models at 84% and 93%. Accuracy of the neural network model was robust across donor subgroups and remained stable in a prospective simulation, while the logistic regression model performance declined when applied to rarer subgroups and in the prospective simulation. Our findings support using machine learning models to help with the identification of potential organ donors using routinely collected clinical and laboratory data.
Identification, characterization, and prognosis investigation of pivotal genes shared in different stages of breast cancer
Authors: Rommasi Foad
Published: May 2023

One of the leading causes of death (20.1 per 100,000 women per year), breast cancer is the most prevalent cancer in females. Statistically, 95% of breast cancer are categorized as adenocarcinomas, and 55% of all patients may go into invasive phases; however, it can be successfully treated in approximately 70–80% of cases if diagnosed in the nascent stages. The emergence of breast tumor cells which are intensely resistant to conventional therapies, along with the high rate of metastasis occurrence, has highlighted the importance of finding novel strategies and treatments. One of the most advantageous schemes to alleviate this complication is to identify the common differentially expressed genes (DEGs) among primary and metastatic cancerous cells to use resultants for designing new therapeutic agents which are able to target both primary and metastatic breast tumor cells. In this study, the gene expression dataset with accession number GSE55715 was analyzed containing two primary tumor samples, three bone-metastatic samples, and three normal samples to distinguish the up- and down regulated genes in each stage compared to normal cells as control. In the next step, the common upregulated genes between the two experimental groups were detected by Venny online tool. Moreover, gene ontology, functions and pathways, gene-targeting microRNA, and influential metabolites were determined using EnrichR 2021 GO, KEGG pathways miRTarbase 2017, and HMDB 2021, respectively. Furthermore, elicited from STRING protein–protein interaction networks were imported to Cytoscape software to identify the hub genes. Then, identified hub genes were checked to validate the study using oncological databases. The results of the present article disclosed 1263 critical common DEGs (573 upregulated + 690 downregulated), including 35 hub genes that can be broadly used as new targets for cancer treatment and as biomarkers for cancer detection by evaluation of expression level. Besides, this study opens a new horizon to reveal unknown aspects of cancer signaling pathways by providing raw data evoked from in silico experiments. This study’s outcomes can also be widely utilized in further lab research since it contains diverse information on common DEGs of varied stages and metastases of breast cancer, their functions, structures, interactions, and associations.
Prediction and experimental evidence of different growth phases of the Podospora anserina hyphal network
Authors: Ledoux Clara , Chapeland-Leclerc Florence , Ruprich-Robert Gwenaël , Bobée Cécilia , Lalanne Christophe , Herbert Éric , David Pascal
Published: May 2023

Under ideal conditions, the growth of the mycelial network of a filamentous fungus is monotonous, showing an ever increasing complexity with time. The components of the network growth are very simple and based on two mechanisms: the elongation of each hypha, and their multiplication by successive branching. These two mechanisms are sufficient to produce a complex network, and could be localized only at the tips of hyphae. However, branching can be of two types, apical or lateral, depending on its location on the hyphae, therefore imposing the redistribution of the necessary material in the whole mycelium. From an evolutionary point of view, maintaining different branching processes, with additional energy needs for structure and metabolism, is intriguing. We propose in this work to discuss the advantages of each branching type using a new observable for the network growth, allowing us to compare growth configurations. For this purpose, we build on experimental observations of the Podospora anserina mycelium growth, enabling us to feed and constrain a lattice-free modeling of this network based on a binary tree. First, we report the set of statistics related to the branches of P. anserina that we have implemented into the model. Then, we build the density observable, allowing us to discuss the succession of growth phases. We predict that density over time is not monotonic, but shows a decay growth phase, clearly separated from an other one by a stationary phase. The time of appearance of this stable region appears to be driven solely by the growth rate. Finally, we show that density is an appropriate observable to differentiate growth stress.
Effects of energy drinks on myogenic differentiation of murine C2C12 myoblasts
Authors: Park Sun Young , Karantenislis Georgia , Rosen Hannah T. , Sun Hong
Published: May 2023

Energy drinks, often advertised as dietary supplements that enhance physical and mental performance, have gained increasing popularity among adolescents and athletes. Several studies on individual ingredients such as caffeine or taurine have reported either adverse or favorable influences on myogenic differentiation, a key process in muscle regeneration to repair microtears after an intense workout session. However, the impact of different energy drinks with various formulas on muscle differentiation has never been reported. This study aims to examine the in vitro effects of various energy drink brands on myogenic differentiation. Murine C2C12 myoblast cells were induced to differentiate into myotubes in the presence of one of eight energy drinks at varying dilutions. A dose-dependent inhibition of myotube formation was observed for all energy drinks, supported by reduced percentage of MHC-positive nuclei and fusion index. Moreover, expression of myogenic regulatory factor MyoG and differentiation marker MCK were also decreased. Furthermore, given the variation in formulas of different energy drinks, there were remarkable differences in the differentiation and fusion of myotubes between energy drinks. This is the first study to investigate the impact of various energy drinks on myogenic differentiation and our results suggest an inhibitory effect of energy drinks in muscle regeneration.
Ikaros expression is associated with an increased risk of chronic graft-versus-host disease
Authors: Pereira A. D. , de Molla V. C. , Fonseca A. R. B. M. , Tucunduva L. , Novis Y. , Pires M. S. , Popi A. F. , Arrais-Rodrigues C. A.
Published: May 2023

Immune reconstitution after hematopoietic stem cell transplantation (HSCT) is a complex and extremely variable process. TheIkarostranscription factor plays an important role in hematopoiesis in several cell lines, especially in the lymphoid lineage. We hypothesized thatIkarosmight influence immune reconstitution, and consequently, the risk of opportunistic infections, relapse, and graft versus host disease (GVHD). Samples were collected from the graft and from the peripheral blood (PB) of the recipients 3 weeks after neutrophil recovery. Real-time polymerase chain reaction (RT-PCR) was performed to analyze the absolute and relativeIkarosexpression. Patients were divided into two groups, according toIkarosexpression in the graft and in the recipients’ PB based on the ROC curves for moderate/severe cGVHD. A cutoff of 1.48 was used forIkarosexpression in the graft, and a cutoff of 0.79 was used forIkarosexpression in the recipients’ PB. Sixty-six patients were included in this study. Median age of patients was 52 years (range 16–80 years), 55% of them were male, and 58% of them had acute leukemia. Median follow-up period was 18 months (range 10–43 months). There was no association betweenIkarosexpression and the risk of acute GVHD, relapse, or mortality. However, a significant association was observed with the risk of chronic GVHD. HigherIkarosexpression in the graft was associated with a significantly higher cumulative incidence (CI) of moderate/severe chronic GVHD according to the National Institute of Health (NIH) classification at two years (54% vs. 15% for patients with lower expression, P = 0.03). A higherIkarosexpression in the recipients’ PB 3 weeks after engraftment was also associated with a significantly higher risk of moderate/severe chronic GVHD (65% vs. 11%, respectively, P = 0.005). In conclusion,Ikarosexpression in the graft and in the recipients’ PB after transplantation was associated with a higher risk of moderate/severe chronic GVHD.Ikarosexpression should be evaluated in larger prospective trials as a potential biomarker for chronic GVHD.
RETRACTED ARTICLE: The application of non-uniform magnetic field for thermal enhancement of the nanofluid flow inside the U-turn pipe at solar collectors
Authors: Li Sida , Mao Liudan , Alizadeh As’ad , Zhang Xin , Mousavi S. Valiallah
Published: May 2023

The improvement of heat transfer inside the solar heat exchangers is important for the development of solar energy in an urban area. In this study, the usage of a non-uniform magnetic field on the thermal efficiency of the nanofluid (Fe3O4) streaming inside the U-turn pipe of solar heat exchangers is examined. Computational fluid dynamic is applied to visualize the nanofluid flow inside the solar heat exchanger. The role of magnetic intensity and Reynolds number on thermal efficiency are fully investigated. The effect of single and triple sources of the magnetic field is also studied in our research. Obtained results indicate that the usage of the magnetic field results in the production of vortex in the base fluid and heat transfer improves inside the domain. Our finding indicates that the usage of the magnetic field with Mn = 25 K would improve the average heat transfer by about 21% along the U-turn pipe of solar heat exchangers.