bluuebunny/crossref_metadata_2025_split huggingface dataset:
Barriers and facilitators of evidence-based practice in the Portuguese context: perceptions of formal nursing leaders
Authors: Santos Diana , Cardoso Daniela , Cardoso Ana Filipa , Duque Filipa Margarida , Fernandes Beatriz , Sousa Rosário , Amaral António Fernando 
Published: July 2024

ABSTRACT

Introduction:
Formal nursing leaders play an important role in promoting and sustaining evidence-based practice (EBP) in the clinical context, particularly by creating a conducive environment for change and increasing clinicians’ awareness of the positive results of EBP. However, nursing leaders encounter both barriers and facilitators in their work; therefore, it is important to understand their perceptions on this topic.

Objective:
The objective of this study was to understand the perceptions of formal nursing leaders about barriers and facilitators for EBP.

Methods:
A descriptive exploratory study with a qualitative approach was conducted. A convenience sample was obtained, consisting of formal nursing leaders from three Portuguese health care institutions. Data were collected through semi-structured interviews. Content analysis was conducted using MAXQDA Analytic Pro 2022 software.

Results:
Seventeen formal nursing leaders were interviewed. Five categories of EBP barriers were identified: (1) scarce resources and inefficient resource management; (2) non-conducive organizational culture; (3) distance between academia and the clinical context; (4) demotivation; and (5) resistance to change. Seven categories of EBP facilitators were identified: (1) availability of resources and efficient resource management; (2) conducive organizational culture; (3) partnerships between academia and the clinical context; (4) motivation and commitment; (5) leadership; (6) organization that regulates professional practice; and (7) multidisciplinary meetings.

Conclusions:
This study identified barriers and facilitators for EBP through the perceptions of formal nursing leaders. Collaborative multidisciplinary efforts by leaders, direct care professionals, academics, and researchers should be conducted to overcome barriers and strengthen facilitators for EBP.

Spanish abstract:

http://links.lww.com/IJEBH/A242
Intestinal serotonergic vagal signaling as a mediator of microbiota-induced hypertension
Authors: de Araujo Alan , Sree Kumar Hemaa , Yang Tao , Plata Adriana Alviter , Dirr Elliott W. , Bearss Nicole , Baekey David M. , Miller Darren S. , Donertas-Ayaz Basak , Ahmari Niousha , Singh Arashdeep , Kalinoski Andrea L. , Garrett Timothy J. , Martyniuk Christopher J. , de Lartigue Guillaume , Zubcevic Jasenka 
Published: July 2024

AbstractHypertension is a pervasive global health challenge, impacting over a billion individuals worldwide. Despite strides in therapeutic strategies, a significant proportion of patients remain resistant to the currently available therapies. While conventional treatments predominantly focus on cardiac, renal, and cerebral targets, emerging research underscores the pivotal role of the gut and its microbiota. Yet, the precise mechanisms governing interactions between the gut microbiota and the host blood pressure remain unclear. Here we describe a neural host-microbiota interaction that is mediated by the intestinal serotonin (5-HT) signaling via vagal 5HT3a receptors and which is crucial for maintenance of blood pressure homeostasis. Notably, a marked decrease in both intestinal 5-HT and vagal 5HT3aR signaling is observed in hypertensive rats, and in rats subjected to fecal microbiota transplantation from hypertensive rats. Leveraging an intersectional genetic strategy in a Cre rat line, we demonstrate that intestinal 5HT3aR vagal signaling is a crucial link between the gut microbiota and blood pressure homeostasis and that recovery of 5-HT signaling in colon innervating vagal neurons can alleviate hypertension. This paradigm-shifting finding enhances our comprehension of hypertensive pathophysiology and unveils a promising new therapeutic target for combating resistant hypertension associated with gut dysbiosis.
Identification of SARS-CoV-2 Persistent Intestinal Epithelial Syndrome (SPIES) as a Novel Disease Entity using Clinical, Histologic, and RNA Programmatic Data
Authors: Wallach Thomas , Soliman Ahmed , Agboola John , Sharma Shagun , Araujo-Coelho Lais , Pittman Meredith , Chatzinakos Christos , Kolokotronis Sergios-Orestis 
Published: July 2024

Abstract“Long COVID” (LC) remains an ongoing issue and one which has created a substantial burden of disease. Gastrointestinal LC is relatively poorly understood. In this study we characterize a syndrome of persistent SARS-CoV2 viral material via clinical and histologic data, and RNA sequencingMethodsWe reviewed patients aged 5-22 years with an esophagogastroduodenoscopy (EGD) for gastrointestinal (GI) symptoms from 6/2020-6/2023, excluding patients with known histologic disease. Biopsies were sent for immunohistochemical staining. Clinical data was collected. Duodenal, ileal, cecal, and sigmoid colon samples were stained for SARS-CoV-2 using a SARS-CoV-2 nucleocapsid antibody. Slides were reviewed by a blinded pathologist. 8 patients with known duodenal SARS-CoV-2 nucleocapsid antigen (SC-NA) positivity and 8 demographically matched IBS matched patients from prior to 2020 were identified for RNA sequencing comparison. Results were compared with public data from the Gene Expression Omnibus (GEO) data repository for intestinal tissue with IBS and epithelial tissues with active SARS-CoV2 infection.ResultsOf 30 patients, fifteen (50%) were identified to have positive SC-NA. 3 (20%) had received at least a single SARS-CoV2 vaccine in the + cohort, and 8 (53.3%) in the - (P=0.05). Primary symptoms were pain (86%, nausea (66.6%), and weight loss (60%). 37.5% of patients with colonic SC-NA displayed hematochezia. 33% of + patients showed elevated ESR/CRP. Mean + calprotectin was 317.3 vs. 156.4 (p=0.2). 11/15 (73.3%) +SC-NA had large lymphoid aggregates (LLA) (p = 0.00338). RNA expression was consistent with known acute SARS-CoV2 infection. Hub network analysis showed a tight shift in RNA expression centered around HSPE-1p26, with involvement of known SARS-CoV2 immune mediators like NEAT1. DGE comparative analysis with IBS and acute SARS-CoV2 infection showed higher overlap with acute infection vs. IBS. FGSEA analysis with the same source data demonstrated the same.ConclusionsOur findings establish a syndrome mediated by persistent viral infection (SARS-CoV2 Persistent Intestinal Epithelial Syndrome (SPIES)). We hypothesize that persistent sparse infection drives ongoing immune signaling altering movement and function, creating epithelial and movement effects overlapping with DGBI and IBD
Integration of multi-omics data and deep phenotyping of potato enables novel insights into single- and combined abiotic stress responses
Authors: Zagorščak Maja , Abdelhakim Lamis , Rodriguez-Granados Natalia Yaneth , Široká Jitka , Ghatak Arindam , Bleker Carissa , Blejec Andrej , Zrimec Jan , Novák Ondřej , Pěnčík Aleš , Baebler Špela , Borroto Lucia Perez , Schuy Christian , Županič Anže , Afjehi-Sadat Leila , Wurzinger Bernhard , Weckwerth Wolfram , Novak Maruša Pompe , Knight Marc R. , Strnad Miroslav , Bachem Christian , Chaturvedi Palak , Sonnewald Sophia , Sasidharan Rashmi , Panzarová Klára , Gruden Kristina , Teige Markus 
Published: July 2024

AbstractPotato is highly water and space efficient but susceptible to abiotic stresses such as heat, drought, or flooding, which are severely exacerbated by climate change. Understanding of crop acclimation to abiotic stress, however, remains limited. Here, we present a comprehensive molecular and physiological high-throughput profiling of potato (Solanum tuberosum, cv. Desirée) under heat, drought and waterlogging applied as single stresses or in combinations designed to mimic realistic future scenarios. Stress-responses were monitored via daily phenotyping and multi-omics analyses of leaf samples comprising transcriptomics, proteomics, metabolomics and hormonomics at several timepoints during and after stress treatments. Additionally, critical metabolites of tuber samples were analysed at the end of the stress period. Integrative analysis of multi-omics data was performed using a bioinformatic pipeline, which was established here, based on machine learning and knowledge networks. Overall, waterlogging had the most immediate and dramatic effects on potato plants, interestingly activating ABA-responses similar to drought stress. In addition, we observed distinct stress signatures at multiple molecular levels in response to heat or drought and to a combination of both. In response to all treatments, we found a downregulation of photosynthesis at different molecular levels, an accumulation of minor amino acids and diverse stress induced hormones. Our integrative multi-omics analysis provides global insights into plant stress responses, facilitating improved breeding strategies towards climate-adapted potato varieties.One Sentence SummaryIntegrated multi-omics analysis of high-throughput phenotyping in potato reveals distinct molecular signatures of acclimation to single and combined abiotic stresses related to climate change.
Early and Delayed STAT1-Dependent Responses Drive Local Trained Immunity of Macrophages in the Spleen
Authors: Solomon Aryeh , Ben-Moshe Noa Bossel , Hoffman Dotan , Trzebanski Sebastien , Yehezkel Dror , Vainman Leia , Netea Mihai , Avraham Roi 
Published: July 2024

AbstractTrained immunity (TI) is the process wherein innate immune cells gain functional memory upon exposure to specific ligands or pathogens, leading to augmented inflammatory responses and pathogen clearance upon secondary exposure. While the differentiation of hematopoietic stem cells (HSCs) and reprogramming of bone marrow (BM) progenitors are well-established mechanisms underpinning durable TI protection, remodeling of the cellular architecture within the tissue during TI remains underexplored. Here, we study the effects of peritoneal Bacillus Calmette–Guérin (BCG) administration to find TI-mediated protection in the spleen against a subsequent heterologous infection by the Gram-negative pathogenSalmonellaTyphimurium (S.Tm). Utilizing single cell RNA-sequencing and flow cytometry, we discerned STAT1-regulated genes in TI-associated resident and recruited splenic myeloid populations. The temporal dynamics of TI were further elucidated, revealing both early and delayed myeloid subsets with time-dependent, cell type-specific STAT1 signatures. Using lineage tracing, we find that tissue-resident red pulp macrophages (RPM), initially depleted by BCG exposure, are restored from both tissue-trained, self-renewing macrophages and from bone marrow-derived progenitors, fostering long lasting local defense. Early inhibition of STAT1 activation, using specific JAK-STAT inhibitors, reduces both RPM loss and recruitment of trained monocytes. Our study suggests a temporal window soon after BCG vaccination, in which STAT1-dependent activation of long-lived resident cells in the tissue mediates localized protection.
Arabidopsis root apical meristem adaptation to an osmotic gradient condition: an integrated approach from cell expansion to gene expression
Authors: Pezzutto Selene Píriz , Martínez-Moré Mauro , Sainz María Martha , Borsani Omar , Silveira Mariana Sotelo 
Published: July 2024

AbstractClimate change triggers abiotic stress, such as drought and high salinity, that can cause osmotic stress. Water availability can limit plant growth, and the root tip tissues initially sense it. Most experiments destined to understand root growth adaptation to osmotic stress apply homogeneous high osmotic potentials (osmotic shock) to shoots and roots. However, this treatment does not represent natural field conditions where a root may encounter increasing osmotic potentials while exploring the soil. Osmotic shock severely reduces root growth rate, decreasing cell division in the proximal meristem and reducing mature cell length. In this work, we developed anin vitroosmotic gradient experimental system with increasing osmotic potentials. The system generates a controlled osmotic gradient in the root growth zone while exposing the aerial tissues to control conditions. The osmotic gradient system allowed Arabidopsis seedlings of Col-0 andttl1mutant to sustain proper root growth for 25 days, reaching osmotic potentials of −1.2 MPa. We demonstrated that roots of seedlings grown in the osmotic gradient sustain a higher root growth rate than those that were grown under a homogeneous high osmotic potential. Furthermore, we found out that the expression of some genes is modified in the roots grown in the osmotic gradient compared to those grown in osmotic shock. Our data indicate that using an osmotic gradient can improve our understanding of how plants respond to osmotic stress and help find new genes to improve plant field performance.
White matter tract crossing and bottleneck regions in the fetal brain
Authors: Calixto Camilo , Soldatelli Matheus D. , Li Bo , Pierotich Lana , Gholipour Ali , Warfield Simon K. , Karimi Davood 
Published: July 2024

AbstractThere is a growing interest in using diffusion MRI to study the white matter tracts and structural connectivity of the fetal brain. Recent progress in data acquisition and processing suggests that this imaging modality has a unique role in elucidating the normal and abnormal patterns of neurodevelopment in utero. However, there have been no efforts to quantify the prevalence of crossing tracts and bottleneck regions, important issues that have been extensively researched for adult brains. In this work, we determined the brain regions with crossing tracts and bottlenecks between 23 and 36 gestational weeks. We performed probabilistic tractography on 59 fetal brain scans and extracted a set of 51 distinct white tracts, which we grouped into 10 major tract bundle groups. We analyzed the results to determine the patterns of tract crossings and bottlenecks. Our results showed that 20-25% of the white matter voxels included two or three crossing tracts. Bottlenecks were more prevalent. Between 75-80% of the voxels were characterized as bottlenecks, with more than 40% of the voxels involving four or more tracts. The results of this study highlight the challenge of fetal brain tractography and structural connectivity assessment and call for innovative image acquisition and analysis methods to mitigate these problems.
Consequences of decoy site repair and feedback regulation on neurotransmission dynamics
Authors: Gambrell Oliver , Singh Abhyudai 
Published: July 2024

AbstractNeurons form the fundamental unit of the central nervous system with the human brain containing close to 100 billion neurons. We present a systems-level model of a chemical synapse by which signals from a presynaptic neuron are transmitted to a postsynaptic neuron. In this model, neurotransmitter-filled synaptic vesicles (SVs) dock with a given rate at a fixed number of docking sites in the axon terminal of the presynaptic neuron. Upon the arrival of an action potential (AP), each docked SV has a certain probability to fuse with the presynaptic membrane and release neurotransmitters into the synaptic cleft. After the SV fusion event, the corresponding docking site undergoes repair before becoming available to be reoccupied by an SV. We develop a stochastic model of these coupled processes and derive exact analytical results quantifying the mean and the degree of random fluctuations (i.e., noise) in the levels of docked SVs and released neurotransmitters in response to a train of APs. Our results show that the repair of docking sites exacerbates synaptic depression, i.e., reduces the ability of the chemical synapse to release neurotransmitters in response to an AP. Moreover, repair amplifies statistical fluctuations in neurotransmission for fixed mean neurotransmitter levels. We next consider feedback regulation where the released neurotransmitters affect the rate of SV docking. Counterintuitively, our analysis reveals that for certain physiological parameter spaces, positive feedback loops can reduce noise levels in both the number of docked SVs and neurotransmitters in the cleft.
Modulation Of SUDEP By Central Serotonergic Cooperating with Noradrenergic Circuits: A Synergistic-Dependent Manner
Authors: Xu Qing , Xu XiaoXia , Wu YaXuan , Yang Yue , Gu LeYuan , Zhang ZhuoYue , Zhang ZiWen , Di XuanYi , Wang YuLing , Yu Qian , Lian XiTing , Ma HaiXiang , Zhang HongHai 
Published: July 2024

AbstractSudden unexpected death in epilepsy (SUDEP) is the leading cause of death in refractory epilepsy patients. Despite previous accumulating evidence has shown that seizure-induced respiratory arrest (S-IRA) may play the main contributor to SUDEP as an initiating event preeminent cause of mortality, the specific underlying mechanism of action remains unclear. Based on our previous work, serotonin (5-HT) signaling in the dorsal raphe nucleus (DRN) is strongly implicated in S-IRA in animal models, including the DBA/1 mice, on the meanwhile, norepinephrine (NE) neurons of the locus coeruleus (LC) also plays a vital role in regulating respiratory function on its own. Superficially, monoaminergic neuron, as important neurotransmitters in the central nervous system, have similar modes of action in the maintenance of nervous system balance, and each of them has a regulatory effect on SUDEP. However, it remains to be investigated whether monoaminergic neuron family (NE and 5-HT) are related in the mechanism of regulating SUDEP, what is even more curious is whether the two are intrinsically linked. Thus, we hypothesize neural mechanism of central noradrenergic and serotonergic circuits in modulating SUDEP in a synergistic-dependent manner, this endeavor will culminate in a significant breakthrough in elucidating the precise mechanism of action underlying SUDEP. In our study, we will use chemogenetics, optogenetics, calcium signal recording, and bidirectional tracing to explore the internal mechanism of DR-LC regulating the occurrence of SUDEP, and by specifically injecting 5-HT2AR antagonist Ketanserin (KET) and/or NEα-1R antagonist Prazosin into the pre-Bötzinger complex (PBC), it was finally elucidate that the DR-LC-PBC network can effectively reduce the incidence of SIRA. We firstly proposed a powerful target for exploring the reduction of the incidence of SUDEP, which has great clinical translation potential.
Quantifying hope: An EU perspective of rare disease therapeutic space and market dynamics
Authors: Cacoub Emmanuelle , Lefebvre Nathalie Barreto , Milunov Dimitrije , Sarkar Manish , Saha Soham 
Published: July 2024

SummaryRare diseases, affecting millions globally, pose a significant healthcare burden despite impacting a small population. While approximately 70% of all rare diseases are are genetic and often begin in childhood, diagnosis remains slow and only 5% have approved treatments. The UN emphasizes improved access to primary care for these patients and their families. Whole-genome sequencing (WGS) and next-generation sequencing (NGS) offer hope for earlier and more accurate diagnoses, potentially leading to preventative measures and targeted therapies. This study explores the therapeutic landscape for rare diseases, analyzing drugs in development and those already approved by the European Medicines Agency (EMA). We differentiate between orphan drugs with market exclusivity and repurposed existing drugs, both crucial for patients. By analyzing market size, segmentation, and publicly available data, this comprehensive study aims to pave the way for improved treatments and a brighter future for rare disease patients.Funding:This work received no external funding. External agencies or companies had no role in the idea and study design, model execution and evaluation, and drafting of figures and manuscript.
TDSTDP
Authors: Liu Bingkun 
Published: July 2024

AbstractThis is a preliminary thesis on Temporal Difference Spike-Timing Dependent Plasticity (TDSTDP), a variation of STDP that considers dendritic potential. TDSTDP is capable of performing temporal difference (TD) learning without dopamine modulation. Major characteristics of TD learning, including value estimation, value propagation, and temporal shifting of dopamine, are demonstrated in simulations. Additionally, a synaptic calcium model demonstrates its biological plausibility.
Stiffness-tunable neurotentacles for minimally invasive implantation and long-term neural activity recordings
Authors: Wang Yang , Xu Xing , Yang Xiaowei , Tang Rongyu , Chen Ying , Wang Yijun , Liang Jing , Pei Weihua 
Published: July 2024

AbstractFlexible implantable microelectrodes have been demonstrated to exhibit excellent biocompatibility for chronic neural activity recordings. However, the low bending strength of the commonly employed flexible materials presents a significant challenge for probe insertion into the brain. Traditional implantation methods for flexible electrodes generally require additional auxiliary materials or tools, which tend to have a much larger footprint than the probes themselves, greatly increasing the damage to neurons during insertion. Here we have proposed a stiffness-tunable polyimide probe for deep brain implantation, referred to as Neurotentacle, enabled by embedded microchannels in which the liquid pressure is controllable (from 0.1MPa to more than 2.0MPa). During the insertion phase into the brain, the neurotentacle can pose a high stiffness under elevated internal pressure to penetrate the brain tissues without the use of any additional materials or tools. Once the device has been successfully inserted, it can regain its flexibility by reducing the internal pressure. Importantly, the novel multilayer microfabrication process keeps the structural dimensions of the neurotentacle similar to those of a regular flexible probe. Therefore, the neurotentacle can produce an extremely low level of damage to brain tissue during its insertion phase, while extending its long-term biocompatibility and stability, which has been experimentally verified in histological evaluations conducted on both acute and chronic animal specimens. In addition, the chronically implanted neurotentacles enabled stable neural activity recordings in mice with an average spike yield of 96% and an average signal-to-noise ratio of 15.2. The proposed neurotentacle does not necessitate the use of complex devices and its insertion process is straightforward and highly controllable, thus rendering it an appealing technique for minimally invasive implantation and long-term neural recording of flexible electrodes.