bluuebunny/crossref_metadata_2025 huggingface dataset:
Barriers and facilitators for implementation of automated home medication dispensers in home care from Dutch professionals’ perspective: a qualitative study
Authors: Mostert Cheryl , de Man-van Ginkel Janneke , van Dijk Monique , Ista Erwin
Published: February 2024

Introduction and aims:

Present-day home care needs to be more efficiently organized in view of the aging of the population and the current nursing shortages. Ensuring safe medication use is part of the challenge. The number of required visits could be reduced if automated home medication dispensers (AHMD) are adequately implemented. However, the barriers and facilitators for implementation are unknown. This project explored determinants (barriers, facilitators, or both) for implementing AHMD in home care, from Dutch home care nurses’ perspective.

Methods:

Semi-structured interviews were conducted with 15 home care nurses. Determinants were identified through thematic content analysis. The first four transcripts were coded inductively. Then, a code tree was developed based on the Tailored Implementation for Chronic Diseases checklist, consisting of seven domains. Each code/determinant was then labelled as a barrier, facilitator, or both.

Results:

The most relevant domains were innovation factors, individual health professional factors, and patient factors. The most frequently mentioned barrier was the required unplanned visits when patients did not withdraw medication within the scheduled time limit (alarm). According to our respondents, carefully assessing patients’ eligibility (e.g., learnability) and properly instructing and guiding them will help prevent these alarms from occurring. Next to these determinants, motivating patients to start using an AHMD and professionals having sufficient knowledge and confidence were the most frequently mentioned facilitators.

Conclusion:

This project provided an overview of 78 determinants from nurses’ perspective for implementation of AHMD in home care. This can form the basis for developing strategies for implementing AHMD in home care. Further research is recommended to investigate the perceived determinants from the patients’, relatives’, and informal caregivers’ perspectives, and to prioritize the determinants from all perspectives.
Latent gammaherpesvirus infection enhances type I IFN response and reduces virus spread in an influenza A virus co-infection model
Authors: Hardisty Gareth , Nicol Marlynne Q. , Shaw Darren J. , Bennet Ian D. , Bryson Karen , Ligertwood Yvonne , Schwarze Jurgen , Beard Philippa M. , Hopkins John , Dutia Bernadette M.
Published: February 2024

Infections with persistent or latent viruses alter host immune homeostasis and have potential to affect the outcome of concomitant acute viral infections such as influenza A virus (IAV). Gammaherpesviruses establish life-long infections and require an on-going immune response to control reactivation. We have used a murine model of co-infection to investigate the response to IAV infection in mice latently infected with the gammaherpesvirus MHV-68. Over the course of infection, latently infected BALB/c mice showed less weight loss, clinical signs, pulmonary cellular infiltration and expression of inflammatory mediators than naïve mice infected with IAV and had significantly more activated CD8+ T cells in the lungs. Four days after IAV infection, virus spread in the lungs of latently infected animals was significantly lower than in naïve animals. By 7 days after IAV infection latently infected lungs express elevated levels of cytokines and chemokines indicating they are primed to respond to the secondary infection. Investigation at an early time point showed that 24 h after IAV infection co-infected animals had higher expression of IFNβ and Ddx58 (RIG-I) and a range of ISGs than mice infected with IAV alone suggesting that the type I IFN response plays a role in the protective effect. This effect was mouse strain dependent and did not occur in 129/Sv/Ev mice. These results offer insight into innate immune mechanisms that could be utilized to protect against IAV infection and highlight on-going and persistent viral infections as a significant factor impacting the severity of acute respiratory infections.
Gene regulatory network topology governs resistance and treatment escape in glioma stem-like cells
Authors: Park James H. , Hothi Parvinder , Garcia de Lomana Adrian Lopez , Pan Min , Calder Rachel , Turkarslan Serdar , Wu Wei-Ju , Lee Hwahyung , Patel Anoop P. , Cobbs Charles , Huang Sui , Baliga Nitin S.
Published: February 2024

Poor prognosis and drug resistance in glioblastoma (GBM) can result from cellular heterogeneity and treatment-induced shifts in phenotypic states of tumor cells, including dedifferentiation into glioma stem-like cells (GSCs). This rare tumorigenic cell subpopulation resists temozolomide, undergoes proneural-to-mesenchymal transition (PMT) to evade therapy, and drives recurrence. Through inference of transcriptional regulatory networks (TRNs) of patient-derived GSCs (PD-GSCs) at single-cell resolution, we demonstrate how the topology of transcription factor interaction networks drives distinct trajectories of cell state transitions in PD-GSCs resistant or susceptible to cytotoxic drug treatment. By experimentally testing predictions based on TRN simulations, we show that drug treatment drives surviving PD-GSCs along a trajectory of intermediate states, exposing vulnerability to potentiated killing by siRNA or a second drug targeting treatment-induced transcriptional programs governing non-genetic cell plasticity. Our findings demonstrate an approach to uncover TRN topology and use it to rationally predict combinatorial treatments that disrupts acquired resistance in GBM.

Teaser

Gene regulatory networks drive glioma stem-like cell drug response and drug-induced cell-state transitions leading to resistance.
Predicting Time to Diabetes Diagnosis Using Random Survival Forests
Authors: Saha Priyonto , Marouf Yacine , Pozzebon Hunter , Guergachi Aziz , Keshavjee Karim , Noaeen Mohammad , Shakeri Zahra
Published: February 2024

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder with increasing population incidence. However, T2DM takes years to develop, allowing onset prediction and prevention to be a clinically effective treatment strategy. In this study we propose and assess a novel approach to diabetes prediction which integrates a specialized extension of the random forest algorithm known as random survival forest (RSF). Rather than predicting a binary outcome, this machine learning model incorporates survival analysis methodology to predict the time until a patient will receive a diabetes diagnosis if their current lifestyle is maintained. We trained a baseline model on 7,704 electronic medical records from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) with 14 biomarker and comorbidity features across different measurement dates. Although tuning parameters were purposefully chosen for quick training rather than for predictive performance, our model exceeded expectations with a concordance index of 0.84. Thus, RSF models have been shown to produce accurate timelines of diabetes onset trajectory, providing patients with quantifiable and relatable risks that are easy to understand. The results of our study have substantial implications for advancing machine learning in clinical decision support and patient outcome predictions, emphasizing the role of innovative models in improving predictive accuracy.
IFNγ induces epithelial reprogramming driving CXCL11-mediated T cell migration
Authors: Cutilli Alessandro , Jansen Suze A. , Paolucci Francesca , Mokry Michal , Mocholi Enric , Lindemans Caroline A. , Coffer Paul J.
Published: February 2024

The cytokine interferon-gamma (IFNγ) plays a multifaceted role in intestinal immune responses ranging from anti-to pro-inflammatory depending on the setting. Here, using a 3D co-culture system based on human intestinal epithelial organoids, we explore the capacity of IFNγ-exposure to reprogram intestinal epithelia and thereby directly modulate lymphocyte responses. IFNγ treatment of organoids led to transcriptional reprogramming, marked by a switch to a pro-inflammatory gene expression profile, including transcriptional upregulation of the chemokines CXCL9, CXCL10, and CXCL11. Proteomic analysis of organoid-conditioned medium post-treatment confirmed chemokine secretion. Furthermore, IFNγ-treatment of organoids led to enhanced T cell migration in a CXCL11-dependent manner without affecting T cell activation status. Taken together, our results suggest a specific role for CXCL11 in T cell recruitment that can be targeted to prevent T cell trafficking to the inflamed intestine.
BayVarC: an ultra-sensitive ctDNA variant caller using Bayesian approach
Authors: Che Dongxue , Yan Cheng , Zha Jianjun , Niu Zexiong , Yang Quanyu , Cheng Xiaolei , Han Mipeng , Du Changshi , Zhang Ke , Hu Yunfu , Yang Yu-Fei
Published: February 2024

In liquid biopsy, it is critical to detect variants of allele frequencies as low as 0.1% or even lower, especially when used to monitor secondary resistant mutations and minimal residual disease. Despite the efforts on improving experimental design, it remains challenging to distinguish low-frequency variants from technical noises in the downstream bioinformatic analysis. Here, we introduce BayVarC, a novel variant caller specifically designed for variant calling in liquid biopsy. It applies Bayesian inference to accurately quantify noise level in a locus-specific manner, enabling the discrimination between technical noise and low-frequency cancer variants. Detailed in-silico simulation and in-vitro experiments demonstrated BayVarC’ superior performance over existing state-of-the-art tools. BayVarC can effectively detect low frequency variants while maintaining low false positive rate (0.05 FP/KB). Meanwhile, it achieves Limit of Detection (LoD) as low as 0.1%. Furthermore, empowered by its architecture, BayVarC shows promising applicability in Minimal Residual Disease (MRD) detection. BayVarC is freely available athttps://github.com/GenetronBioinfomatics/BayVarC.
Altered inflammatory state and mitochondrial function identified by transcriptomics in paediatric congenital heart patients prior to surgical repair
Authors: Bartoli-Leonard Francesca , Harris Amy G. , Saunders Kelly , Madden Julie , Cherrington Carrie , Sheehan Karen , Baquedano Mai , Parolari Giulia , Bamber Andrew , Caputo Massimo
Published: February 2024

Objective

Congenital heart disease (CHD) remains the most common birth defect, with surgical intervention required in complex cases. Right ventricle (RV) function is known to be a major predictor in sustained cardiac health in these patients, thus by elucidating divergent profiles between CHD and control through tissue analysis this study aims to identify new avenues of investigation into the mechanisms surrounding reduced RV function.

Approach & Results

Transcriptomic profiling,in silicocellular deconvolution and functional network analysis was conducted on RV biopsies obtained from CHD and control paedatric patients. Analysis identified an increase in mitochondrial dysfunction genesRPPH1andRMPR(padj = 4.67E-132, 2.23E-107, respectively), Cytotoxic T cell markersCD8a, LAGE3andCD49a(p = 0.0006, p < 0.0001, p = 0.0118, respectively) and proinflammatory markerCaspase1(p=0.0055) in CHD compared to control. Gene set enrichment identified mitochondrial dysfunctional pathways, predominately changes to the oxidative phosphorylation processes. Negative regulation of mitochondrial functions and metabolism was identified in functional network analysis, with dysregulation of mitochondrial complex formation. Histological analysis confirmed an increase in cellular bodies with the CHD RV tissue, and positive staining for both CD45 and CD8 in CHD RV tissue, which was absent in control. Deconvolution of bulk RNAseq data suggests a reduction in CD4+ T cells (p = 0.0067) and an increase in CD8+ T cells (p = 0.0223). Network analysis identified positive regulation of the immune system and cytokine signalling clusters within the inflammation functional network as were lymphocyte activation and leukocyte differentiation.

Conclusions

Utilizing RV tissue from paediatric patients undergoing CHD cardiac surgery this study identifies dysfunctional mitochondrial pathways and an increase in inflammatory T cell presence prior to reparative surgery.
The glucocorticoid receptor elicited proliferative response in human erythropoiesis is BCL11A-dependent
Authors: Mazzarini Maria , Cherone Jennifer , Nguyen Truong , Martelli Fabrizio , Varricchio Lilian , Funnell Alister P.W. , Papayannopoulou Thalia , Migliaccio Anna Rita
Published: February 2024

Prior evidence indicates that the erythroid cellular response to glucocorticoids (GC) has developmental specificity, namely, that developmentally more advanced cells that are undergoing or have undergone fetal to adult globin switching are more responsive to GC-induced expansion. To investigate the molecular underpinnings of this, we focused on the major developmental globin regulator BCL11A. We compared:a)levels of expression and nuclear content of BCL11A in adult erythroid cells upon GC stimulation;b)response to GC of CD34+ cells from patients withBCL11Amicrodeletions and reducedBCL11Aexpression, and;c)response to GC of two cellular models (HUDEP-2 and adult CD34+ cells) before and after reduction ofBCL11Aexpression by shRNA. We observed that:a)GC-expanded erythroid cells from a large cohort of blood donors displayed amplified expression and nuclear accumulation of BCL11A;b)CD34+ cells fromBCL11Amicrodeletion patients generated fewer erythroid cells when cultured with GC compared to their parents, while the erythroid expansion of the patients was similar to that of their parents in cultures without GC, and;c)adult CD34+ cells and HUDEP-2 cells with shRNA-depleted expression ofBCL11Aexhibit reduced expansion in response to GC. In addition, RNA-seq profiling of shRNA-BCL11A CD34+ cells cultured with and without GC was similar (very few differentially expressed genes), while GC-specific responses (differential expression ofGILZand of numerous additional genes) were observed only in controls cells with unperturbed BCL11A expression. These data indicate that BCL11A is an important participant of certain aspects of the stress pathway sustained by GC.
SMORES: A Simple Microfluidic Operating Room for the Examination and Surgery ofStentor coeruleus
Authors: Zhang Kevin S. , Rodriguez Ramon , Tang Sindy K.Y.
Published: February 2024

Ciliates are powerful unicellular model organisms that have been used to elucidate fundamental biological processes. However, the high motility of ciliates presents a major challenge in studies using live-cell microscopy and microsurgery. While various immobilization methods have been developed, they are physiologically disruptive to the cell and incompatible with microscopy and/or microsurgery. Here, we describe a Simple Microfluidic Operating Room for the Examination and Surgery ofStentor coeruleus(SMORES). SMORES uses Quake valve-based microfluidics to trap, compress, and perform surgery onStentoras our model ciliate. Compared with previous methods, immobilization by physical compression in SMORES is more effective and uniform. The mean velocity of compressed cells is 24 times less than that of uncompressed cells. The compression is minimally disruptive to the cell and is easily applied or removed using a 3D-printed pressure rig. We demonstrate cell immobilization for up to 2 hours without sacrificing cell viability. SMORES is compatible with confocal microscopy and is capable of media exchange for pharmacokinetic studies. Finally, the modular design of SMORES allows laser ablation or mechanical dissection of a cell into many cell fragments at once. These capabilities are expected to enable biological studies previously impossible in ciliates and other motile species.
TP53mutation screening for patients at risk of myeloid malignancy
Authors: Mukherjee Devdeep , Lawal Rialnat A. , Fitzhugh Courtney D. , Hourigan Christopher S. , Dillon Laura W.
Published: February 2024

There is increasing recognition of the risk of developing therapy-related myeloid malignancy, including after cellular therapy. While retrospective studies have implicated pre-existingTP53mutated hematopoietic clones as a common causative mechanism, no prospective screening to identify those patients at greatest risk is currently possible. We demonstrate that ultradeep DNA-sequencing prior to therapy may be used for discovery ofTP53mutations that are subsequently associated with malignancy.
Prospective Clinical Evaluation of a Deep Learning Algorithm for Guided Point-of-Care Ultrasonography Screening of Abdominal Aortic Aneurysms
Authors: Chiu I-Min , Chen Tien-Yu , Zheng You-Cheng , Lin Xin-Hong , Cheng Fu-Jen , Ouyang David , Cheng Chi-Yung
Published: February 2024

Background

Abdominal Aortic Aneurysm (AAA) is a critical condition that can lead to fatal consequences if not detected and treated early. Despite the high prevalence in smokers and guideline recommendation for screening, AAA often remains undetected due to availability of diagnostic ultrasound examinations. This prospective clinical trial aimed to investigate the use of a Deep Learning (DL) algorithm to guide AAA screening.

Methods

This prospective, comparative diagnostic study was conducted at the Kaohsiung Chang Gung Memorial Hospital. We developed and deployed an object detection-based DL algorithm providing real-time guidance for novice users performing AAA screening using point of care ultrasound. 10 registered nurses with no prior ultrasonography experience were recruited and performed at least 15 scans on patients over 65 years old to acquire abdominal aorta videos. These scans were compared with those of physicians using the same ultrasound hardware but without DL guidance.

Results

A total of 184 patients (median [IQR] age of 72 [67-79], and 105 (57.1%) male) completed this study. The DL-guided novices achieved adequate scan quality in 87.5% (95% CI: 82.7 - 92.3%) of patients, comparable to the 91.3% (95% CI: 87.2-95.4%) rate of physician scans (p=0.310). This performance did not vary by BMI. The DL model predicted AAA with an AUC of 0.975, showing 100% sensitivity and 94.3% specificity. The DL model predicted the maximal width of abdominal aorta with mean absolute error of 2.8mm compared to physician measurements. 3 AAA with maximal width of aorta > 3cm were found in this study cohort.

Conclusion

DL-guided POCUS is an effective tool for AAA screening, providing comparable performance to experienced physicians. The use of this DL system could democratize AAA screening and improve access, thereby aiding in early disease detection and treatment.

Clinical Perspective

What is New

Our study presents a deep learning (DL) guidance system that enables novice users to perform Abdominal Aortic Aneurysm (AAA) screening with POCUS, yielding image quality comparable to experienced physicians.

The DL algorithm accurately identifies AAA from scans conducted by novice users, maintains consistent performance across patients with varying BMIs, and demonstrates increased scan efficiency with repeated use.

Clinical Implications

DL-guided POCUS can potentially expand AAA screening capabilities to non-specialist settings and increase throughput for screening at risk individuals.

The implementation of our DL model for AAA screening could enhance early detection, particularly in underserved areas, but also optimize clinical workflows by decreasing diagnostic wait times and increasing ultrasound utilization efficiency.
Abrupt and gradual changes in neuronal processing upon falling asleep and awakening
Authors: Marmelshtein Amit , Lavy Barak , Hadad Barak , Nir Yuval
Published: February 2024

The neural processes that change when falling asleep are only partially understood. At the cortical level, features of both spontaneous neural activity and sensory responses change between wakefulness and sleep. For example, in early auditory cortex sleep increases the occurrence of post-onset silent (OFF) periods and elevates population synchrony. However, it remains unknown whether such changes occur abruptly or gradually around sleep onset and awakening. Here, we recorded spontaneous and sound-evoked neuronal spiking activity in early auditory cortex along with polysomnography during thousands of episodes when rats fell asleep or woke up. We found that when falling asleep, stimulus-induced neuronal silent periods (OFF periods), characteristic of non-rapid eye movement (NREM) sleep, increased within few seconds around sleep onset. By contrast, a gradual increase in neuronal population synchrony built up over dozens of seconds until reaching maximal levels. EEG auditory-evoked potentials representing stimulus-triggered “K complexes” changed along with post-onset neuronal firing, whereas ongoing EEG slow wave activity was associated with neuronal population synchrony. Similar effects, but with opposite direction, were observed around awakenings. The results highlight late stimulus-induced neuronal silence as a key feature changing abruptly around transitions between vigilance states, likely reflecting neuronal bistability and manifesting also in EEG evoked potentials. More generally, these findings emphasize the added value of going beyond monitoring ongoing activity and perturbing the nervous system to reveal its state - an insight that could also help guide development of more sensitive non-invasive monitors of falling asleep in humans.
DOT1L stimulates MYC/Mondo transcription factor activity by promoting its degradation cycle on chromatin
Authors: Sepulveda Gian P. , Gushchanskaia Ekaterina S. , Mora-Martin Alexandra , Esse Ruben , Nikorich Iana , Ceballos Ainhoa , Kwan Julian , Blum Benjamin C. , Dholiya Prakruti , Emili Andrew , Perissi Valentina , Cardamone Maria D. , Grishok Alla
Published: February 2024

The proto-oncogene c-MYC is a key representative of the MYC transcription factor network regulating growth and metabolism. MML-1 (Myc- and Mondo-like) is its homolog inC. elegans. The functional and molecular cooperation between c-MYC and H3 lysine 79 methyltransferase DOT1L was demonstrated in several human cancer types, and we have earlier discovered the connection betweenC. elegansMML-1 and DOT-1.1. Here, we demonstrate the critical role of DOT1L/DOT-1.1 in regulating c-MYC/MML-1 target genes genome-wide by ensuring the removal of “spent” transcription factors from chromatin by the nuclear proteasome. Moreover, we uncover a previously unrecognized proteolytic activity of DOT1L, which may facilitate c-MYC turnover. This new mechanism of c-MYC regulation by DOT1L may lead to the development of new approaches for cancer treatment.
Intra-Striatal Dopaminergic Inter-Subject Covariance in Social Drinkers and Nontreatment-Seeking Alcohol Use Disorder Participants
Authors: Chumin Evgeny J. , Dzemidzic Mario , Yoder Karmen K.
Published: February 2024

One of the neurobiological correlates of alcohol use disorder (AUD) is the disruption of striatal dopaminergic function. While regional differences in dopamine (DA) function have been well studied, inter-regional relationships (represented as inter-subject covariance) have not been investigated and may offer a novel avenue for understanding DA function.

Positron emission tomography (PET) data with [11C]raclopride in 22 social drinking controls and 17 AUD participants were used to generate group-level striatal covariance (partial Pearson correlation) networks, which were compared edgewise, also comparing global network metrics and community structure. An exploratory analysis examined the impact of tobacco cigarette use status. Striatal covariance was validated in an independent publicly available [18F]fallypride PET sample of healthy volunteers.

Striatal covariance of control participants from both datasets showed a clear bipartition of the network into two distinct communities, one in the anterior and another in the posterior striatum. This organization was disrupted in the AUD participant network, with significantly lower network metrics in AUD compared to the control network. Stratification by cigarette use suggests differential consequences on group covariance networks.

This work demonstrates that network neuroscience can quantify group differences in striatal DA and that its inter-regional interactions offer new insight into the consequences of AUD.
Formylation facilitates the reduction of oxidized initiator methionines
Authors: Tan Ruiyue , Hoare Margaret , Bellomio Philip , Broas Sarah , Camacho Konttessa , Swovick Kyle , Welle Kevin A. , Hryhorenko Jennifer R. , Ghaemmaghami Sina
Published: February 2024

Within a cell, protein-bound methionines can be oxidized by reactive oxygen species (ROS) or monooxygenases, and subsequently reduced by methionine sulfoxide reductases (Msrs). Methionine oxidation can result in structural damage or be the basis of functional regulation of enzymes. In addition to participating in redox reactions, methionines play an important role as the initiator residue of translated proteins where they are commonly modified at their α-amine group by formylation or acetylation. Here, we investigated how formylation and acetylation of initiator methionines impact their propensity for oxidation and reduction. We show thatin vitro, N-terminal methionine residues are particularly prone to chemical oxidation, and that their modification by formylation or acetylation greatly enhances their subsequent enzymatic reduction by MsrA and MsrB. Concordantly,in vivoablation of methionyl-tRNA formyltransferase (MTF) inE. coliincreases the prevalence of oxidized methionines within synthesized proteins. We show that oxidation of formylated initiator methionines is detrimental in part because it obstructs their ensuing deformylation by peptide deformylase (PDF) and hydrolysis by methionyl aminopeptidase (MAP). Thus, by facilitating their reduction, formylation mitigates the misprocessing of oxidized initiator methionines.

Classification: Biological Sciences; Biochemistry
Brain 3T magnetic resonance imaging in neonates: features and incidental findings from a research cohort enriched for preterm birth
Authors: Sullivan Gemma , Quigley Alan J. , Choi Samantha , Teed Rory , Cabez Manuel Blesa , Vaher Kadi , Corrigan Amy E. , Stoye David Q. , Thrippleton Michael J. , Bastin Mark E. , Boardman James P.
Published: February 2024

Background and objectives

The survival rate and patterns of brain injury after very preterm birth are evolving with changes in clinical practices. Additionally, incidental findings can present legal, ethical and practical considerations. Here, we report MRI features and incidental findings from a large, contemporary research cohort of very preterm infants and term controls.

Methods

288 infants had 3T MRI at term-equivalent age: 187 infants born <32 weeks without major parenchymal lesions, and 101 term-born controls. T1-weighted, T2-weighted and Susceptibility-weighted imaging were used to classify white and gray matter injury according to a structured system, and incidental findings described.

Results

Preterm infants: 34(18%) had white matter injury and 4(2%) had gray matter injury. 51(27%) infants had evidence of intracranial haemorrhage, and 34(18%) had punctate white matter lesions (PWMLs). Incidental findings were detected in 12(6%) preterm infants.Term infants: No term infants had white or gray matter injury. Incidental findings were detected in 35(35%); these included intracranial haemorrhage in 22(22%), periventricular pseudocysts in 5(5%) and PWMLs in 4(4%) infants. From the whole cohort, 10(3%) infants required referral to specialist services.

Conclusions

One fifth of very preterm infants without major parenchymal lesions have white or gray matter abnormalities at term-equivalent age. Incidental findings are seen in 6% of preterm and 35% of term infants. Overall, 3% of infants undergoing MRI for research require follow-up due to incidental findings. These data should help inform consent procedures for research and assist service planning for centres using 3T neonatal brain MRI for clinical purposes.

What is already known on this topic

Neonatal MRI at term-equivalent age has established a common signature of preterm birth that includes diffuse white matter disease, reduced cortical gray matter complexity, and enlarged cerebrospinal fluid spaces.

All neuroimaging has the potential to detect incidental findings.

There are inter-cohort variations in the reported prevalence of brain imaging features associated with preterm birth and incidental findings in the neonatal population.

What this study adds

The prevalence of features of encephalopathy of prematurity identified on 3T brain MRI in a contemporaneous UK cohort without major parenchymal lesions imaged at term-equivalent age.

The types and prevalence of incidental findings identified on 3T brain MRI in very preterm infants and term-born controls.

How this study might affect research, practice or policy

This study will support clinicians and researchers with informed consent processes, image interpretation, and service development.
Air Pollution and Children’s Health Inequalities
Authors: Castillo Milena Suarez , Benatia David , Le Thi Christine , Costemalle Vianney
Published: February 2024

This paper examines the differential impacts of early childhood exposure to air pollution on children’s health care use across parental income groups and vulnerability factors using French administrative data. Our quasi-experimental study reveals significant impacts on emergency admissions and respiratory medication in young children, attributed to air pollution shocks from thermal inversions. Using causal machine learning, we identify these health impacts as predominantly affecting 10% of infants, characterized by poor health indicators at birth and lower parental income. Our results suggest that intervention strategies focusing on vulnerability metrics may be more effective than those based solely on exposure levels.

JEL Codes: I14, I18, Q53, Q58
Neural Basis of Pain Empathy Dysregulations in Mental Disorders – A Pre-registered Neuroimaging Meta-Analysis
Authors: He Jingxian , Bore Mercy Chepngetich , Jiang Heng , Gan Xianyang , Wang Junjie , Li Jialin , Xu Xiaolei , Wang Lan , Fu Kun , Li Liyuan , Zhou Bo , Kendrick Keith , Becker Benjamin
Published: February 2024

Pain empathy represents a fundamental building block of several social functions, which have been demonstrated to be impaired across various mental disorders by accumulating evidence from case-control functional magnetic resonance imaging (fMRI) studies. However, it remains unclear whether the dysregulations are underpinned by robust neural alterations across mental disorders. This study utilized coordinate-based meta-analyses to quantitatively determine robust markers of altered pain empathy across mental disorders. To support the interpretation of the findings exploratory network-level and behavioral meta-analyses were conducted. The results revealed patients with mental disorders exhibited increased pain empathic reactivity in the left anterior cingulate gyrus, adjacent medial prefrontal cortex, and right middle temporal gyrus, yet decreased activity in the left cerebellum IV/V and left middle occipital gyrus compared to controls. The hyperactive regions showed network-level interactions with the core default mode network (DMN) and were associated with affective and social cognitive domains. The findings suggest that pain-empathic alterations across mental disorders are underpinned by excessive empathic reactivity in brain systems involved in empathic distress and social processes, highlighting a shared therapeutic target to normalize basal social dysfunctions in mental disorders.
Optimizing test and treat options for Vivax malaria: an options assessment toolkit (OAT) for Asia Pacific National Malaria Control Programs
Authors: Acharya Sanjaya , Shrestha Manash , Thang Ngo Duc , Wini Lyndes , Habib M. Naeem , Neukom Josselyn , Lhazeen Karma , Lynch Caroline A , Thriemer Kamala
Published: February 2024

Introduction

Designing policy in public health is a complex process requiring decision making that incorporates available evidence and is suitable to a country’s epidemiological and health system context. The main objective of this study was to develop an options assessment toolkit (OAT) to provide a pragmatic and evidence-based approach to the development of policies for the radical cure (prevention of relapse) of vivax malaria for national malaria control programs in the Asia-Pacific region.

Materials and methods

The OAT was developed using participatory research methods and a Delphi process using a sequential multi-phase design, adapted with apre-development phase, adevelopment phase,and afinal development phase.In thepre-development phase, a literature review was conducted to inform the toolkit development. Data collection in thedevelopment phaseconsisted of core research team discussions, multiple rounds of consultation with participants from National Malaria Control Programs (NMP) (online and in person), and two separate modified e-Delphi processes with experts. Thefinal developmentphase was the piloting of the toolkit during the annual meeting of the Asia Pacific Malaria Elimination Network (APMEN) Vivax Working Group.

Results

We developed a tool kit containing the following elements: i) Baseline Assessment Tool (BAT) to assess the readiness of NMPs for new or improved coverage of radical cure, ii) eight scenarios representative of Asia Pacific region, iii) matching test and treat options based on available options for G6PD testing and radical cure for the given scenarios, iv) an approaches tool to allow NMPs to visualize considerations for policy change process and different implementation strategies/approaches for each test and treat option.

Conclusions

The OAT can support vivax radical cure policy formulation among NMPs and stakeholders tailoring for their unique country context. Future studies are needed to assess the utility and practicality of using the OAT for specific country context.
MODIFIED AORTIC VALVE REIMPLANTATION IN PATIENTS WITH ACUTE AORTIC DISSECTION TYPE A
Authors: Boldyrev Sergey Yuryevich , Suslova Valentina Nikolaevna , Dontsova Mariya Vladimirovna , Barbukhatti Kirill Olegovich , Porkhanov Vladimir Alekseevich
Published: February 2024

Background

The question of choosing surgical tactics in patients with acute aortic dissection type A unresolved to now. In patients with massive destruction of the aortic root the «gold standard» is the Bentall procedure. Aortic valve reimplantation is an attractive alternative, especially in patients with preserved aortic valve leaflets anatomy.

Objective

To compare the results of the use of valve sparing procedure and composite root replacement in patients with acute aortic dissection type A.

Methods

At the end, 62 patients were included in the study. Of those, 27 patients undervent aortic valve reimplantation and 35 had Bentall’s operation in the Kouchoukos modification.

Results

Preoperative demographic and clinical characteristics were such between the groups. Similar indicators of preoperative malperfusion were observed in both groups. The time of artificial circulation (p=0.125) and aortic clamping time (p=0.001) were longer in the reimplantation group, while the time of circulatory arrest was longer in the Bentall group (p=0.290). The average aortic clamping time was about 30 minutes longer in the first group. Hospital mortality in the reimplantation group was 8.3% and 22.9% in the Bentall group. Mortality from all causes in the long-term period was 6 people in the reimplantation group 25%, 10 people in the Bentall group 28.6%. The degree of aortic regurgitation did not increase in any case until the moment of extreme contact with the patient.

Conclusions

Aortic valve reimplantation can be performed with good immediate and long-term results in patients with preserved aortic valve leaflets with acute aortic dissection type A.
Selection for transcatheter versus surgical aortic valve replacement and mid-term survival: results of the AUTHEARTVISIT Study
Authors: Auer Johann , Krotka Pavla , Reichardt Berthold , Traxler Denise , Wendth Ralph , Mildner Michael , Ankersmit Hendrik Jan , Graf Alexandra
Published: February 2024

Limited data are available from randomized trials comparing outcomes between transcatheter aortic valve replacement (TAVR) and surgery in patients with different risks and with follow-up >2 years. In this large, population-based cohort study, long-term mortality and morbidity were investigated in patients undergoing aortic valve replacement (AVR) for severe aortic stenosis using a surgically implanted bioprosthesis (sB-AVR) or TAVR. Individual data from the Austrian Insurance funds from 2010 through 2020 were analysed. The primary outcome was all-cause mortality, assessed in the overall and propensity score-matched populations. Secondary outcomes included reoperation and cardiovascular events. From January 2010 through December 2020, a total of 18 882 patients underwent sB-AVR (n=11 749; 62.2%) or TAVR (n=7133; 37.8%); median follow-up was 4.0 (interquartile range 2.1-6.5) years (maximum 12.3 years). The risk of all-cause mortality was higher with TAVR compared with sB-AVR: hazard ratio (HR) 1.552, 95% confidence interval (CI) 1.469-1.640, p<0.001; propensity score-matched HR 1.510, 1.403-1.625, p<0.001. Estimated median survival was 8.8 years (95% CI 8.6-9.1) with sB-AVR vs 5 years (4.9-5.2) with TAVR. Estimated 5-year survival probability was 0.664 (0.664-0.686) with sB-AVR vs 0.409 (0.378-0.444) with TAVR overall, and 0.690 (0.674-0.707) and 0.560 (0.540-0.582), respectively, with propensity score matching. Other predictors of mortality were age, sex, previous heart failure, diabetes, and chronic kidney disease. In >2-year follow-up, selection for TAVR was significantly associated with higher all-cause mortality compared with sB-AVR in patients >= years with severe, symptomatic aortic stenosis.
Adult Single-nucleus Neuronal Transcriptomes of Insulin Signaling Mutants Reveal Regulators of Behavior and Learning
Authors: Ange Jonathan St. , Weng Yifei , Stevenson Morgan E. , Kaletsky Rachel , Moore Rebecca S. , Zhou Shiyi , Murphy Coleen T.
Published: February 2024

The insulin/insulin-like signaling (IIS) pathway regulates many ofC. elegans’adult functions, including learning and memory1. While whole-worm and tissue-specific transcriptomic analyses have identified IIS targets2,3, a higher-resolution single-cell approach is required to identify changes that confer neuron-specific improvements in the long-lived insulin receptor mutant,daf-2. To understand how behaviors that are controlled by a small number of neurons change indaf-2mutants, we used the deep resolution of single-nucleus RNA sequencing to define each neuron type’s transcriptome in adult wild-type anddaf-2mutants. First, we found surprising differences between wild-type L4 larval neurons and young adult neurons in chemoreceptor expression, synaptic genes, and learning and memory genes. These Day 1 adult neuron transcriptomes allowed us to identify adult AWC-specific regulators of chemosensory function and to predict neuron-to-neuron peptide/receptor pairs. We then identified gene expression changes that correlate withdaf-2’simproved cognitive functions, particularly in the AWC sensory neuron that controls learning and associative memory4, and used behavioral assays to test their roles in cognitive function. Combining deep single-neuron transcriptomics, genetic manipulation, and behavioral analyses enabled us to identify genes that may function in a single adult neuron to control behavior, including conserved genes that function in learning and memory.

One-Sentence Summary

Single-nucleus sequencing of adult wild-type anddaf-2 C. elegansneurons reveals functionally relevant transcriptional changes, including regulators of chemosensation, learning, and memory.
Interplay of condensation and chromatin binding underlies BRD4 targeting
Authors: Strom Amy R. , Eeftens Jorine M. , Polyachenko Yury , Weaver Claire J. , Watanabe Hans-Frederick , Bracha Dan , Orlovsky Natalia D. , Jumper Chanelle C. , Jacobs William M. , Brangwynne Clifford P.
Published: February 2024

Nuclear compartments form via biomolecular phase separation, mediated through multivalent properties of biomolecules concentrated within condensates. Certain compartments are associated with specific chromatin regions, including transcriptional initiation condensates, which are composed of transcription factors and transcriptional machinery, and form at acetylated regions including enhancer and promoter loci. While protein self-interactions, especially within low-complexity and intrinsically disordered regions, are known to mediate condensation, the role of substrate-binding interactions in regulating the formation and function of biomolecular condensates is under-explored. Here, utilizing live-cell experiments in parallel with coarse-grained simulations, we investigate how chromatin interaction of the transcription factor BRD4 modulates its condensate formation. We find that both kinetic and thermodynamic properties of BRD4 condensation are affected by chromatin binding: nucleation rate is sensitive to BRD4-chromatin interactions, providing an explanation for the selective formation of BRD4 condensates at acetylated chromatin regions, and thermodynamically, multivalent acetylated chromatin sites provide a platform for BRD4 clustering below the concentration required for off-chromatin condensation. This provides a molecular and physical explanation of the relationship between nuclear condensates and epigenetically modified chromatin that results in their mutual spatiotemporal regulation, suggesting that epigenetic modulation is an important mechanism by which the cell targets transcriptional condensates to specific chromatin loci.
Nonlinear relationship between ionized calcium and 28-day mortality in patients with sepsis: A retrospective cohort study from MIMIC-IV database
Authors: Liang Zhanyao , Chen Yunting , Zhou Yuanshen , Hu Congqi , Chen Lu , Zhu Fangfang
Published: February 2024

Background

This study aimed to investigate the linear and nonlinear relationships between ionized calcium levels and 28-day mortality in patients with sepsis in the intensive care unit (ICU) and to provide clinicians with a direction for laboratory index testing and a basis for a calcium supplementation program.

Methods

The data of patients with sepsis were extracted from the Medical Information Mart for Intensive Care (MIMIC-IV) database, iCa served as the exposure variable, and 28-day mortality served as the outcome variable. The relationship between iCa and 28-day mortality was investigated using multivariate binary logistic regression models, with adjustment for covariates. A generalized additive model (GAM) and smoothed curve fitting were used to investigate the non-linear relationship between iCa and 28-day mortality. A two-piecewise linear model was used to calculate the OR and 95% CI on either side of the inflection point.

Results

Patients with sepsis (n = 20,417) were included in the analysis, with an overall 28-day mortality rate of 19.73%. Sepsis patients were grouped into quartiles (Q1-Q4) according to ionized calcium levels, and after complete adjustment, the short-term mortality rate of sepsis patients in Q2–Q4 was significantly lower than that in the Q1 group (OR:0.78, 95% CI: 0.70–0.87. OR: 0.74, 95% CI: 0.66–0.83. OR: 0.81, 95% CI: 0.72–0.9. iCa and 28-day mortality displayed a U-shaped relationship among patients with sepsis. When iCa levels were less than 1.14 mmol/L, each unit increase corresponded to a 79% reduction in the risk of 28-day sepsis mortality(OR: 0.21, 95% CI: 0.13-0.35). Conversely, when iCa exceeded 1.14 mmol/L, each unit increase was linked to an 85% increase in the 28-day mortality risk (OR: 1.85, 95% CI: 1.08-3.16).

Conclusion

The relationship between iCa and 28-day mortality in patients with sepsis showed a u-shaped curve with an inflection point of 1.14 mmol/L, which is in the range of mild hypocalcemia.
Fabrication and rejuvenation of high quantum efficiency caesium telluride photocathodes for high brightness and high average current photoinjectors
Authors: Martinez-Calderon M. , Chevallay E. , Rossel R. E. , Jones L. B. , Zevi Della Porta G. , Marsh B. , Granados E.
Published: February 2024

With their high quantum efficiency (QE) and excellent photoemissive properties, cesium telluride (Cs-Te) photocathodes are the current workhorse in the high average current electron accelerators around the globe. Their ability to generate high brightness and high charge electron beams has opened the doorway to numerous applications, including fundamental particle physics research, radiation therapy, high-energy physics experiments, and high repetition rate free-electron lasers (FELs). Their long-term performance is critical. In this work, we analyze the systematic production and rejuvenation of photocathodes via thermal evaporation and deposition techniques (both sequential and co-deposition), showing excellent values of QE exceeding 20% using deep ultraviolet illumination (λ=262–266  nm). To extend the photocathode lifetime, the rejuvenation process is performed via multilayer thin-film co-deposition, demonstrating the feasibility of reliably recovering the initial QE even after air exposure. We evaluated their final performance in both high gradient dc and rf gun setups and obtained consistent results of QE and lifetimes. The technique can be used at the gun level, which significantly extends the sustained accelerator operation without major interventions. These approaches significantly enhance the robustness and performance of Cs-Te photoinjectors and represent a significant advancement for reliable high average current electron accelerators and FELs.

Published by the American Physical Society
2024
Quantifying ionization in hot dense plasmas
Authors: Gawne Thomas , Vinko Sam M. , Wark Justin S.
Published: February 2024

Ionization is a problematic quantity in that it does not have a well-defined thermodynamic definition and yet it is a key parameter within plasma modeling. One still therefore aims to find a consistent and unambiguous definition for the ionization state. Within this context we present finite-temperature density functional theory calculations of the ionization state of carbon in CH plasmas using two potential definitions: one based on counting the number of continuum electrons, and another based on the optical conductivity. Differences of up to 10% are observed between the two methods. However, including “Pauli forbidden” transitions in the conductivity reproduces the counting definition, suggesting such transitions are important to evaluate the ionization state.

Published by the American Physical Society
2024
Effective Field Theories on the Jet Bundle
Authors: Craig Nathaniel , Lee Yu-Tse
Published: February 2024

We develop a generalized field space geometry for higher-derivative scalar field theories, expressing scattering amplitudes in terms of a covariant geometry on the all-order jet bundle. The incorporation of spacetime and field derivative coordinates solves complications due to higher-order derivatives faced by existing approaches to field space geometry. We identify a jet bundle analog to the field space metric that, besides field redefinitions, exhibits invariance under total derivatives. The invariance consequently extends to its amplitude contributions and the canonical covariant geometry.

Published by the American Physical Society
2024