bluuebunny/crossref_metadata_2025 huggingface dataset:
An experimental study and axial tensile constitutive model of the toughness of PP-SACC for rapid repairs
Authors: Xie Wen , Xu Xuefeng , Xu Chunlei , Tian Feng , Mao Qiwen , Li Helong , Liu Lin , Qin Gongyi
Published: May 2023

To improve the economic benefits of engineered cementitious composites and control the repair cycle, repair materials were designed, with the key components of the mixture being low-cost polypropylene (PP) fibers and fast-setting sulfoaluminate cement. The effects of water/binder ratio, fiber content, and aggregate particle size on the flowability, mechanical properties, and toughness of the polypropylene fiber-reinforced sulfoaluminate cementitious composite (PP-SACC) were explored. Based on experimentally measured axial tensile stress–strain curves, a constitutive model of PP-SACC was derived in terms of fiber content and water/binder ratio. Additionally, the correlation coefficients representing the relationships of the mixture indices with the tensile properties were explored based on revised gray relational analysis. Test results indicated that fiber content and water/binder ratio were the most important factors affecting the mechanical properties, toughness, and fluidity of the material; in contrast, the influence of aggregate size was slight. The PP-SACC mixture with an aggregate size of 75 µm, a water/binder ratio of 0.30, and a fiber content of 3.0% demonstrated an excellent degree of toughness and exhibited a flexural hardening phenomenon under bending load.
FHODs: Nuclear tethered formins for nuclear mechanotransduction
Authors: Antoku Susumu , Schwartz Thomas U. , Gundersen Gregg G.
Published: May 2023

In this review, we discuss FHOD formins with a focus on recent studies that reveal a new role for them as critical links for nuclear mechanotransduction. The FHOD family in vertebrates comprises two structurally related proteins, FHOD1 and FHOD3. Their similar biochemical properties suggest overlapping and redundant functions. FHOD1 is widely expressed, FHOD3 less so, with highest expression in skeletal (FHOD1) and cardiac (FHOD3) muscle where specific splice isoforms are expressed. Unlike other formins, FHODs have strong F-actin bundling activity and relatively weak actin polymerization activity. These activities are regulated by phosphorylation by ROCK and Src kinases; bundling is additionally regulated by ERK1/2 kinases. FHODs are unique among formins in their association with the nuclear envelope through direct, high affinity binding to the outer nuclear membrane proteins nesprin-1G and nesprin-2G. Recent crystallographic structures reveal an interaction between a conserved motif in one of the spectrin repeats (SRs) of nesprin-1G/2G and a site adjacent to the regulatory domain in the amino terminus of FHODs. Nesprins are components of the LINC (linker of nucleoskeleton and cytoskeleton) complex that spans both nuclear membranes and mediates bidirectional transmission of mechanical forces between the nucleus and the cytoskeleton. FHODs interact near the actin-binding calponin homology (CH) domains of nesprin-1G/2G enabling a branched connection to actin filaments that presumably strengthens the interaction. At the cellular level, the tethering of FHODs to the outer nuclear membrane mechanically couples perinuclear actin arrays to the nucleus to move and position it in fibroblasts, cardiomyocytes, and potentially other cells. FHODs also function in adhesion maturation during cell migration and in the generation of sarcomeres, activities distant from the nucleus but that are still influenced by it. Human genetic studies have identified multiple FHOD3 variants linked to dilated and hypertrophic cardiomyopathies, with many mutations mapping to “hot spots” in FHOD3 domains. We discuss how FHOD1/3’s role in reinforcing the LINC complex and connecting to perinuclear actin contributes to functions of mechanically active tissues such as striated muscle.
Helicobacter pylori regulates stomach diseases by activating cell pathways and DNA methylation of host cells
Authors: Xi Yue , Zhang Xiao-Li , Luo Qing-Xin , Gan Hai-Ning , Liu Yu-Shi , Shao Shi-He , Mao Xu-Hua
Published: May 2023

One of the most prevalent malignant tumors of the digestive tract is gastric cancer (GC). Age, high salt intake, Helicobacter pylori (H. pylori) infection, and a diet deficient in fruits and vegetables are risk factors for the illness. A significant risk factor for gastric cancer is infection with H. pylori. Infecting gastric epithelial cells with virulence agents secreted by H. pylori can cause methylation of tumor genes or carcinogenic signaling pathways to be activated. Regulate downstream genes’ aberrant expression, albeit the precise mechanism by which this happens is unclear. Oncogene, oncosuppressor, and other gene modifications, as well as a number of different gene change types, are all directly associated to the carcinogenesis of gastric cancer. In this review, we describe comprehensive H. pylori and its virulence factors, as well as the activation of the NF-κB, MAPK, JAK/STAT signaling pathways, and DNA methylation following infection with host cells via virulence factors, resulting in abnormal gene expression. As a result, host-related proteins are regulated, and gastric cancer progression is influenced. This review provides insight into the H. pylori infection, summarizes a series of relevant papers, discusses the complex signaling pathways underlying molecular mechanisms, and proposes new approach to immunotherapy of this important disease.
Recent progress in experimental studies on the catalytic mechanism of cytochrome c oxidase
Authors: Shimada Atsuhiro , Tsukihara Tomitake , Yoshikawa Shinya
Published: May 2023

Cytochrome c oxidase (CcO) reduces molecular oxygen (O2) to water, coupled with a proton pump from the N-side to the P-side, by receiving four electrons sequentially from the P-side to the O2-reduction site—including Fea3 and CuB—via the two low potential metal sites; CuA and Fea. The catalytic cycle includes six intermediates as follows, R (Fea32+, CuB1+, Tyr244OH), A (Fea32+-O2, CuB1+, Tyr244OH), Pm (Fea34+ = O2−, CuB2+-OH−, Tyr244O•), F (Fea34+ = O2−, CuB2+-OH-, Tyr244OH), O (Fea33+-OH-, CuB2+-OH−, Tyr244OH), and E (Fea33+-OH-, CuB1+-H2O, Tyr244OH). CcO has three proton conducting pathways, D, K, and H. The D and K pathways connect the N-side surface with the O2-reduction site, while the H-pathway is located across the protein from the N-side to the P-side. The proton pump is driven by electrostatic interactions between the protons to be pumped and the net positive charges created during the O2 reduction. Two different proton pump proposals, each including either the D-pathway or H-pathway as the proton pumping site, were proposed approximately 30 years ago and continue to be under serious debate. In our view, the progress in understanding the reaction mechanism of CcO has been critically rate-limited by the resolution of its X-ray crystallographic structure. The improvement of the resolutions of the oxidized/reduced bovine CcO up to 1.5/1.6 Å resolution in 2016 provided a breakthrough in the understanding of the reaction mechanism of CcO. In this review, experimental studies on the reaction mechanism of CcO before the appearance of the 1.5/1.6 Å resolution X-ray structures are summarized as a background description. Following the summary, we will review the recent (since 2016) experimental findings which have significantly improved our understanding of the reaction mechanism of CcO including: 1) redox coupled structural changes of bovine CcO; 2) X-ray structures of all six intermediates; 3) spectroscopic findings on the intermediate species including the Tyr244 radical in the Pm form, a peroxide-bound form between the A and Pm forms, and Fr, a one-electron reduced F-form; 4) time resolved X-ray structural changes during the photolysis of CO-bound fully reduced CcO using XFEL; 5) a simulation analysis for the Pm→Pr→F transition.
The efficacy of therapeutic plasma exchange in COVID-19 patients on endothelial tightness in vitro is hindered by platelet activation
Authors: Ebermeyer Theo , Hequet Olivier , Berard Frederic , Prier Amelie , Eyraud Marie-Ange , Arthaud Charles-Antoine , Heestermans Marco , Duchez Anne-Claire , Guironnet-Paquet Aurelie , Berthelot Philippe , Cognasse Fabrice , Hamzeh-Cognasse Hind
Published: May 2023

Coronavirus disease (COVID)-19 is characterised in particular by vascular inflammation with platelet activation and endothelial dysfunction. During the pandemic, therapeutic plasma exchange (TPE) was used to reduce the cytokine storm in the circulation and delay or prevent ICU admissions. This procedure consists in replacing the inflammatory plasma by fresh frozen plasma from healthy donors and is often used to remove pathogenic molecules from plasma (autoantibodies, immune complexes, toxins, etc.). This study uses an in vitro model of platelet-endothelial cell interactions to assess changes in these interactions by plasma from COVID-19 patients and to determine the extent to which TPE reduces such changes. We noted that exposure of an endothelial monolayer to plasmas from COVID-19 patients post-TPE induced less endothelial permeability compared to COVID-19 control plasmas. Yet, when endothelial cells were co-cultured with healthy platelets and exposed to the plasma, the beneficial effect of TPE on endothelial permeability was somewhat reduced. This was linked to platelet and endothelial phenotypical activation but not with inflammatory molecule secretion. Our work shows that, in parallel to the beneficial removal of inflammatory factors from the circulation, TPE triggers cellular activation which may partly explain the reduction in efficacy in terms of endothelial dysfunction. These findings provide new insights for improving the efficacy of TPE using supporting treatments targeting platelet activation, for instance.
The Amplatzer duct occluder (ADOII) and Piccolo devices for patent ductus arteriosus closure: a large single institution series
Authors: Bruckheimer Elchanan , Steiner Kristoffer , Barak-Corren Yuval , Slanovic Leonel , Levinzon Michael , Lowenthal Alexander , Amir Gabriel , Dagan Tamir , Birk Einat
Published: May 2023

Purpose

Evaluate Piccolo and ADOII devices for transcatheter patent ductus arteriosus (PDA) closure. Piccolo has smaller retention discs reducing risk of flow disturbance but residual leak and embolization risk may increase.

Methods

Retrospective review of all patients undergoing PDA closure with an Amplatzer device between January 2008 and April 2022 in our institution. Data from the procedure and 6 months follow-up were collected.

Results

762 patients, median age 2.6 years (range 0–46.7) years and median weight 13 kg (range 3.5–92) were referred for PDA closure. Overall, 758 (99.5%) had successful implantation: 296 (38.8%) with ADOII, 418 (54.8%) with Piccolo, and 44 (5.8%) with AVPII. The ADOII patients were smaller than the Piccolo patients (15.8 vs. 20.5 kg, p < 0.001) and with larger PDA diameters (2.3 vs. 1.9 mm, p < 0.001). Mean device diameter was similar for both groups. Closure rate at follow-up was similar for all devices ADOII 295/296 (99.6%), Piccolo 417/418 (99.7%), and AVPII 44/44 (100%). Four intraprocedural embolizations occurred during the study time period: two ADOII and two Piccolo. Following retrieval the PDA was closed with an AVPII in two cases, ADOI in one case and with surgery in the fourth case. Mild stenosis of the left pulmonary artery (LPA) occurred in three patients with ADOII devices (1%) and one patient with Piccolo device (0.2%). Severe LPA stenosis occurred in one patient with ADOII (0.3%) and one with AVPII device (2.2%).

Conclusions

ADOII and Piccolo are safe and effective for PDA closure with a tendency to less LPA stenosis with Piccolo. There were no cases of aortic coarctation related to a PDA device in this study.
In a zebrafish biomedical model of human Allan-Herndon-Dudley syndrome impaired MTH signaling leads to decreased neural cell diversity
Authors: Silva Nádia , Campinho Marco António
Published: May 2023

Background

Maternally derived thyroid hormone (T3) is a fundamental factor for vertebrate neurodevelopment. In humans, mutations on the thyroid hormones (TH) exclusive transporter monocarboxylic acid transporter 8 (MCT8) lead to the Allan-Herndon-Dudley syndrome (AHDS). Patients with AHDS present severe underdevelopment of the central nervous system, with profound cognitive and locomotor consequences. Functional impairment of zebrafish T3 exclusive membrane transporter Mct8 phenocopies many symptoms observed in patients with AHDS, thus providing an outstanding animal model to study this human condition. In addition, it was previously shown in the zebrafish mct8 KD model that maternal T3 (MTH) acts as an integrator of different key developmental pathways during zebrafish development.

Methods

Using a zebrafish Mct8 knockdown model, with consequent inhibition of maternal thyroid hormones (MTH) uptake to the target cells, we analyzed genes modulated by MTH by qPCR in a temporal series from the start of segmentation through hatching. Survival (TUNEL) and proliferation (PH3) of neural progenitor cells (dla, her2) were determined, and the cellular distribution of neural MTH-target genes in the spinal cord during development was characterized. In addition, in-vivo live imaging was performed to access NOTCH overexpression action on cell division in this AHDS model. We determined the developmental time window when MTH is required for appropriate CNS development in the zebrafish; MTH is not involved in neuroectoderm specification but is fundamental in the early stages of neurogenesis by promoting the maintenance of specific neural progenitor populations. MTH signaling is required for developing different neural cell types and maintaining spinal cord cytoarchitecture, and modulation of NOTCH signaling in a non-autonomous cell manner is involved in this process.

Discussion

The findings show that MTH allows the enrichment of neural progenitor pools, regulating the cell diversity output observed by the end of embryogenesis and that Mct8 impairment restricts CNS development. This work contributes to the understanding of the cellular mechanisms underlying human AHDS.
How do epiphytic and surrounding seawater bacterial communities shift with the development of the Saccharina japonica farmed in the Northern China?
Authors: Cai Ling , Gao Xin , Saha Mahasweta , Han Yixiao , Chang Lirong , Xiao Luyang , Wang Gaoge
Published: May 2023

Epibacteria of seaweeds play an important role for the development of hosts and are influenced by the planktonic surrounding seawater bacteria. However, to date, the knowledges related to both epiphytic and surrounding seawater bacterial communities associated with northern farmed Saccharina japonica are very limited. In this study, using 16S rRNA gene amplicon sequencing, the shifts of epiphytic and surrounding seawater bacterial communities of the northern farmed S. japonica from mature sporophytes, sporelings (3 time points) to juvenile sporophytes (2 time points) were investigated. The dominant genera of epibacterial communities were Alcanivorax (mature sporophytes and 4-week-old sporelings), Bacillus (7-week-old sporelings and 9-week-old sporelings), Halomonas (4-week-old juvenile sporophytes) and Cobetia (9-week-old juvenile sporophytes). Meanwhile, the Chao1 indexes and beta diversity of epibacterial communities were significantly different with the development of S. japonica (p < 0.05). Furthermore, Alcanivorax, Bacillus and Halomonas were both dominant and core genera, indicating that these taxa may be beneficial to the development of S. japonica. The alpha diversity indexes of both epiphytic and surrounding seawater bacterial communities were significantly different for 9-week-old juvenile sporophytes. Therefore, the epibacterial communities were influenced by both development of S. japonica and the surrounding seawater bacterial communities. This study not only extends the understanding of the bacterial communities associated with the northern farmed S. japonica, but also help to make production management by monitoring the variations in both epiphytic and surrounding seawater bacterial communities.
Improved body composition decreases the fat content in non-alcoholic fatty liver disease, a meta-analysis and systematic review of longitudinal studies
Authors: Mátis Dóra , Hegyi Péter , Teutsch Brigitta , Tornai Tamás , Erőss Bálint , Pár Gabriella , Váncsa Szilárd
Published: May 2023

Background

Based on cross-sectional studies, there is a link between body composition parameters and steatosis in non-alcoholic fatty liver disease (NAFLD). However, whether long-term changes in different body composition parameters will result in NAFLD resolution is unclear. Therefore, we aimed to summarize the literature on longitudinal studies evaluating the association between NAFLD resolution and body composition change.

Methods

Based on the recommendations of the Cochrane Handbook, we performed a systematic search on September 26th, 2021, in three databases: Embase, MEDLINE (via PubMed), and Cochrane Central Register of Controlled Trials (CENTRAL). Eligible studies reported on patients with NAFLD (liver fat >5%) and examined the correlation between body composition improvement and decrease in steatosis. We did not have pre-defined body composition or steatosis measurement criteria. Next, we calculated pooled correlation coefficient (r) with a 95% confidence interval (CI). Furthermore, we narratively summarized articles with other statistical methods.

Results

We included 15 studies in our narrative review and five in our quantitative synthesis. Based on two studies with 85 patients, we found a pooled correlation coefficient of r = 0.49 (CI: 0.22–0.69, Spearman's correlation) between the change of visceral adipose tissue and liver steatosis. Similarly, based on three studies with 175 patients, the correlation was r = 0.33 (CI: 0.19–0.46, Pearson's correlation). On the other hand, based on two studies with 163 patients, the correlation between subcutaneous adipose tissue change and liver steatosis change was r = 0.42 (CI: 0.29–0.54, Pearson's correlation). Furthermore, based on the studies in the narrative synthesis, body composition improvement was associated with steatosis resolution.

Conclusions

Based on the included studies, body composition improvement may be associated with a decrease in liver fat content in NAFLD.

Systematic review registration

Identifier: CRD42021278584.
Effect of internal jugular vein catheterization on intracranial pressure and postoperative cognitive function in patients undergoing robot-assisted laparoscopic surgery
Authors: Yang Bin , Li Min , Liang Jingqiu , Tang Xixi , Chen Qi
Published: May 2023

Background

We aimed to evaluate the effects of internal jugular vein (IJV) catheterization on intracranial pressure (ICP) and postoperative delirium (POD) during robot-assisted laparoscopic surgery by measuring the optic nerve sheath diameter (ONSD).

Methods

Data from a prospective single-center cohort study, conducted from October 2021 to February 2022, were used. Forty out of 80 patients scheduled for laparoscopic radical hysterectomy or prostatectomy were assigned to the group receiving IJV catheterization (Group I), and the other 40 only received peripheral venous cannulation (Group C) according to clinical need of patients. Ultrasonography of ONSDs, the proportion of regurgitation time in a cardiac cycle, and hemodynamic parameters were measured at four time points: immediately after induction of anesthesia in the supine position (T0), 30 min (T1), 60 min (T2) after orienting to the Trendelenburg position, and before returning to the supine position at the end of surgery (T3). Time to eye opening and emergence stay, POD, and QoR-15 were compared.

Results

The ONSDs increase gradually as the surgery progressed. Group I showed a higher value of ONSD at T1 (4.72 ± 0.29 mm vs. 4.5 ± 0.33 mm, p = 0.0057) and T3 (5.65 ± 0.33 mm vs. 5.26 ± 0.31 mm, p < 0.0001). The proportions of the regurgitation time of IJVV were greater in Group I than those in Group C at T1 (14.95, 8.5%–18.9% vs. 9.6%, 0%–17.2%, p < 0.0001) and T3 (14.3, 10.6%–18.5% vs. 10.4%, 0%–16.5%, p = 0.0003). Group I had a delayed time to eye opening (10.7 ± 1.72 min vs. 13.3 ± 2.35 min, p < 0.0001) and emergence stay (32.2 ± 5.62 min vs. 39.9 ± 6.7 min, p < 0.0001). There were no significant differences in POD and QoR-15 between the two groups on day three.

Conclusion

IJV cannulation may not be the preferred approach in robot-assisted laparoscopic surgery as it was risk factor for IJVV regurgitation, ICP elevation, emergence delayed.
Metabolic profiling reveals altered tryptophan metabolism in patients with kawasaki disease
Authors: Fan Xue , Li Ke , Guo Xin , Liao Shengyou , Zhang Qi , Xu Yangkai , Cui Hongtu , Zheng Lemin , Xu Mingguo
Published: May 2023

Kawasaki disease (KD) is a childhood vasculitis disease that is difficult to diagnose, and there is an urgent need for the identification of accurate and specific biomarkers. Here, we aimed to investigate metabolic alterations in patients with KD to determine novel diagnostic and prognostic biomarkers for KD. To this end, we performed untargeted metabolomics and found that several metabolic pathways were significantly enriched, including amino acid, lipid, and tryptophan metabolism, the latter of which we focused on particularly. Tryptophan-targeted metabolomics was conducted to explore the role of tryptophan metabolism in KD. The results showed that Trp and indole acetic acid (IAA) levels markedly decreased, and that l-kynurenine (Kyn) and kynurenic acid (Kyna) levels were considerably higher in patients with KD than in healthy controls. Changes in Trp, IAA, Kyn, and Kyna levels in a KD coronary arteritis mouse model were consistent with those in patients with KD. We further analyzed public single-cell RNA sequencing data of patients with KD and revealed that their peripheral blood mononuclear cells showed Aryl hydrocarbon receptor expression that was remarkably higher than that of healthy children. These results suggest that the Trp metabolic pathway is significantly altered in KD and that metabolic indicators may serve as novel diagnostic and therapeutic biomarkers for KD.
The role of category ambiguity in normal and impaired lexical processing: can you paint without the paint?
Authors: Lukic Sladjana , Krauska Alexandra , Yoshida Masaya , Thompson Cynthia K.
Published: May 2023

Introduction

Many words are categorially ambiguous and can be used as a verb (to paint) or as a noun (the paint) due to the presence of unpronounced morphology or “zero morphology”. On this account, the verb “paint” is derived from the noun “paint” through the addition of a silent category-changing morpheme. Past studies have uncovered the syntactic and semantic properties of these categorially ambiguous words, but no research has been conducted on how people process them during normal or impaired lexical processing. Are these two different uses of “paint” processed in the same way? Does this morphosyntactic structure have an effect on online sentence processing?

Methods

This study presents two experiments that investigate the effect of morphosyntactic complexity in categorially ambiguous words presented in isolation (experiment 1) and in a sentential context (experiment 2). The first experiment tested the ability to process categorially unambiguous and ambiguous nouns and verbs in 30 healthy older adults and 12 individuals with aphasia, using a forced choice phrasal-completion task, in which individuals choose whethertheortois most compatible with target words.

Results

Healthy controls and individuals with fluent aphasia all showed: (1) a bias toward the base category in selection rates fortheandto, wherethewas selected more frequently for words identified to be base nouns, andtowas selected more frequently for base verbs, and (2) longer reaction times for ambiguous (over unambiguous) words. However, individuals with non-fluent agrammatic aphasia showed a base-category effect only for nouns, with chance performance for verbs. The second experiment, using an eye-tracking while reading paradigm with 56 young healthy adults, showed a reading time slowdown for derived forms (to paint) compared to their base-category counterparts (the paint) in sentence contexts.

Discussion

These findings suggest that categorially ambiguous words likely share a common root, and are related by zero-derivation, and that impaired access to the base-category (i.e., verbs liketo visit) precludes associated morphological processes and therefore the retrieval of the derived-category (i.e., nouns likethe visit) in non-fluent agrammatic aphasia. This study provides insights into the theory of zero morphology, and the principles that need to be accounted for in models of the lexicon.
Neuromorphic-P2M: processing-in-pixel-in-memory paradigm for neuromorphic image sensors
Authors: Kaiser Md Abdullah-Al , Datta Gourav , Wang Zixu , Jacob Ajey P. , Beerel Peter A. , Jaiswal Akhilesh R.
Published: May 2023

Edge devices equipped with computer vision must deal with vast amounts of sensory data with limited computing resources. Hence, researchers have been exploring different energy-efficient solutions such as near-sensor, in-sensor, and in-pixel processing, bringing the computation closer to the sensor. In particular, in-pixel processing embeds the computation capabilities inside the pixel array and achieves high energy efficiency by generating low-level features instead of the raw data stream from CMOS image sensors. Many different in-pixel processing techniques and approaches have been demonstrated on conventional frame-based CMOS imagers; however, the processing-in-pixel approach for neuromorphic vision sensors has not been explored so far. In this work, for the first time, we propose an asynchronous non-von-Neumann analog processing-in-pixel paradigm to perform convolution operations by integratingin-situmulti-bit multi-channel convolution inside the pixel array performing analog multiply and accumulate (MAC) operations that consume significantly less energy than their digital MAC alternative. To make this approach viable, we incorporate the circuit's non-ideality, leakage, and process variations into a novel hardware-algorithm co-design framework that leverages extensive HSpice simulations of our proposed circuit using the GF22nm FD-SOI technology node. We verified our framework on state-of-the-art neuromorphic vision sensor datasets and show that our solution consumes ~2× lower backend-processor energy while maintaining almost similar front-end (sensor) energy on the IBM DVS128-Gesture dataset than the state-of-the-art while maintaining a high test accuracy of 88.36%.
Effect of nutrition in Alzheimer’s disease: A systematic review
Authors: Xu Lou Inmaculada , Ali Kamran , Chen Qilan
Published: May 2023

Background and objective

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by declining cognitive ability. Currently, there are no effective treatments for this condition. However, certain measures, such as nutritional interventions, can slow disease progression. Therefore, the objective of this systematic review was to identify and map the updates of the last 5 years regarding the nutritional status and nutritional interventions associated with AD patients.

Study design

A systematic review.

Methods

A search was conducted for randomized clinical trials, systematic reviews, and meta-analyses investigating the association between nutritional interventions and AD published between 2018 and 2022 in the PubMed, Web of Science, Scopus, and Cochrane Library databases. A total of 38 studies were identified, of which 17 were randomized clinical trials, and 21 were systematic reviews and/or meta-analyses.

Results

The results show that the western diet pattern is a risk factor for developing AD. In contrast, the Mediterranean diet, ketogenic diet, and supplementation with omega-3 fatty acids and probiotics are protective factors. This effect is significant only in cases of mild-to-moderate AD.

Conclusion

Certain nutritional interventions may slow the progression of AD and improve cognitive function and quality of life. Further research is required to draw more definitive conclusions.
Multi-head attention-based masked sequence model for mapping functional brain networks
Authors: He Mengshen , Hou Xiangyu , Ge Enjie , Wang Zhenwei , Kang Zili , Qiang Ning , Zhang Xin , Ge Bao
Published: May 2023

The investigation of functional brain networks (FBNs) using task-based functional magnetic resonance imaging (tfMRI) has gained significant attention in the field of neuroimaging. Despite the availability of several methods for constructing FBNs, including traditional methods like GLM and deep learning methods such as spatiotemporal self-attention mechanism (STAAE), these methods have design and training limitations. Specifically, they do not consider the intrinsic characteristics of fMRI data, such as the possibility that the same signal value at different time points could represent different brain states and meanings. Furthermore, they overlook prior knowledge, such as task designs, during training. This study aims to overcome these limitations and develop a more efficient model by drawing inspiration from techniques in the field of natural language processing (NLP). The proposed model, called the Multi-head Attention-based Masked Sequence Model (MAMSM), uses a multi-headed attention mechanism and mask training approach to learn different states corresponding to the same voxel values. Additionally, it combines cosine similarity and task design curves to construct a novel loss function. The MAMSM was applied to seven task state datasets from the Human Connectome Project (HCP) tfMRI dataset. Experimental results showed that the features acquired by the MAMSM model exhibit a Pearson correlation coefficient with the task design curves above 0.95 on average. Moreover, the model can extract more meaningful networks beyond the known task-related brain networks. The experimental results demonstrated that MAMSM has great potential in advancing the understanding of functional brain networks.
Case report: Challenges and implications of conduction system pacing in pediatrics: Case series
Authors: Ploneda Valencia Ruy Gonzalo , Levinstein Jacinto Moisés , Sánchez Contreras Carmen A. , Ruiz González Gustavo , Neach de la Vega Diego , Márquez Murillo Manlio F. , Nava Santiago
Published: May 2023

Cardiac electrical stimulation in children usually is needed in the setting of complete congenital atrioventricular block, atrioventricular block after heart surgery, and bradycardia associated with some specific channelopathies. In cases of atrioventricular block, the high percentage of ventricular stimulation raises concern on the deleterious effects of chronic stimulation of the right ventricle. In recent years, physiologic stimulation has developed as a valid approach for adult patients and a great interest has risen in offering conduction system pacing also to the pediatric population. We present three pediatric cases of stimulation of the conduction system (His bundle or left bundle branch), in order to show the intrinsic particularities and challenges implied in these new techniques.
Development of a neonatal Göttingen Minipig model for dose precision in perinatal asphyxia: technical opportunities, challenges, and potential further steps
Authors: Stroe Marina-Stefania , Van Bockstal Lieselotte , Valenzuela Allan , Ayuso Miriam , Leys Karen , Annaert Pieter , Carpentier Sebastien , Smits Anne , Allegaert Karel , Zeltner Adrian , Mulder Antonius , Van Ginneken Chris , Van Cruchten Steven
Published: May 2023

Animal models provide useful information on mechanisms in human disease conditions, but also on exploring (patho)physiological factors affecting pharmacokinetics, safety, and efficacy of drugs in development. Also, in pediatric patients, nonclinical data can be critical for better understanding the disease conditions and developing new drug therapies in this age category. For perinatal asphyxia (PA), a condition defined by oxygen deprivation in the perinatal period and possibly resulting in hypoxic ischemic encephalopathy (HIE) or even death, therapeutic hypothermia (TH) together with symptomatic drug therapy, is the standard approach to reduce death and permanent brain damage in these patients. The impact of the systemic hypoxia during PA and/or TH on drug disposition is largely unknown and an animal model can provide useful information on these covariates that cannot be assessed separately in patients. The conventional pig is proven to be a good translational model for PA, but pharmaceutical companies do not use it to develop new drug therapies. As the Göttingen Minipig is the commonly used pig strain in nonclinical drug development, the aim of this project was to develop this animal model for dose precision in PA. This experiment consisted of the instrumentation of 24 healthy male Göttingen Minipigs, within 24 h of partus, weighing approximately 600 g, to allow the mechanical ventilation and the multiple vascular catheters inserted for maintenance infusion, drug administration and blood sampling. After premedication and induction of anesthesia, an experimental protocol of hypoxia was performed, by decreasing the inspiratory oxygen fraction (FiO2) at 15%, using nitrogen gas. Blood gas analysis was used as an essential tool to evaluate oxygenation and to determine the duration of the systemic hypoxic insult to approximately 1 h. The human clinical situation was mimicked for the first 24 h after birth in case of PA, by administering four compounds (midazolam, phenobarbital, topiramate and fentanyl), frequently used in a neonatal intensive care unit (NICU). This project aimed to develop the first neonatal Göttingen Minipig model for dose precision in PA, allowing to separately study the effect of systemic hypoxia versus TH on drug disposition. Furthermore, this study showed that several techniques that were thought to be challenging or even impossible in these very small animals, such as endotracheal intubation and catheterization of several veins, are feasible by trained personnel. This is relevant information for laboratories using the neonatal Göttingen Minipig for other disease conditions or drug safety testing.
Case report: Withdrawal of angiotensin-converting enzyme inhibitors in children with advanced chronic kidney disease and rapidly declining kidney function
Authors: Seeman Tomáš , Dušek Jiří
Published: May 2023

Background

It is not known whether withdrawal of angiotensin-converting enzyme inhibitors (ACEIs) in children with advanced chronic kidney disease (CKD) is beneficial similar to adults. We report a case series of children with advanced CKD whose ACEIs were stopped.

Methods

In the last 5 years, we stopped ACEIs in seven consecutive children on ACEI therapy with rapidly declining CKD stage 4–5. The median age was 12.5 years (range 6.8–17.6); the median estimated glomerular filtration rate (eGFR) at stopping ACEIs was 12.5 ml/min/1.73 m2 (range 8.8–19.9).

Results

Six to twelve months after stopping ACEIs, the eGFR increased in five children (71%). The median absolute increase of eGFR was 5.0 ml/min/1.73 m2 (range −2.3 to +20.0) and relative increase of eGFR was 30% (range −34 to +99). The median follow-up after stopping ACEIs was 2.7 (range 0.5–5.0) years, either until the start of dialysis (n = 5) or until the last follow-up without dialysis (n = 2).

Conclusions

This case series showed that withdrawal of ACEIs in children with CKD stage 4–5 and rapidly declining kidney function may lead to an increase in eGFR.
A pan-cancer analysis of the expression and molecular mechanism of DHX9 in human cancers
Authors: Wang Yanfeng , Guo Yongxin , Song Yanping , Zou Wenbo , Zhang Junjie , Yi Qiong , Xiao Yujie , Peng Jing , Li Yingqi , Yao Lei
Published: May 2023

Finding new targets is necessary for understanding tumorigenesis and developing cancer therapeutics. DExH-box helicase 9 (DHX9) plays a central role in many cellular processes but its expression pattern and prognostic value in most types of cancer remain unclear. In this study, we extracted pan-cancer data from TCGA and GEO databases to explore the prognostic and immunological role of DHX9. The expression levels of DHX9 were then verified in tumor specimens by western blot and immunohistochemistry (IHC). The oncogenic roles of DHX9 in cancers were further verified by in vitro experiments. We first verified that DHX9 is highly expressed in most tumors but significantly decreased in kidney and thyroid cancers, and it is prominently correlated with the prognosis of patients with different tumors. The phosphorylation level of DHX9 was also increased in cancers. Enrichment analysis revealed that DHX9 was involved in Spliceosome, RNA transport and mRNA surveillance pathway. Furthermore, DHX9 expression exhibited strong correlations with immune cell infiltration, immune checkpoint genes, and tumor mutational burden (TMB)/microsatellite instability (MSI). In liver, lung, breast and renal cancer cells, the knockdown or depletion of DHX9 significantly affected the proliferation, metastasis and EMT process of cancer cells. In summary, this pan-cancer investigation provides a comprehensive understanding of the prognostic and immunological role of DHX9 in human cancers, and experiments indicated that DHX9 was a potential target for cancer treatment.
Studies on the inhibitory effect of isavuconazole on flumatinib metabolism in vitro and in vivo
Authors: Liu Ya-nan , Xu Xinhao , Nie Jingjing , Hu Yingying , Xu Xuegu , Xu Ren-ai , Du Xiaoxiang
Published: May 2023

As the validated agent for the treatment of chronic myelogenous leukemia (CML), flumatinib is a novel oral tyrosine kinase inhibitor (TKI) with higher potency and selectivity for BCR-ABL1 kinase compared to imatinib. Many patients experience aspergillosis infection and they may start using isavuconazole, which is an inhibitor of CYP3A4. However, there is no study on their interaction in vitro and in vivo. In the present study, the concentrations of flumatinib and its major metabolite M1 were rapidly determined using an stable ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. The half-maximal inhibitory concentration (IC50) was 6.66 μM in human liver microsomes (HLM), while 0.62 μM in rat liver microsomes (RLM) and 2.90 μM in recombinant human CYP3A4 (rCYP3A4). Furthermore, the mechanisms of inhibition of flumatinib in human liver microsomes, rat liver microsomes and rCYP3A4 by isavuconazole were mixed. Moreover, ketoconazole, posaconazole, and isavuconazole showed more potent inhibitory effects than itraconazole, fluconazole, and voriconazole on HLM-mediated flumatinib metabolism. In pharmacokinetic experiments of rats, it was observed that isavuconazole could greatly change the pharmacokinetic parameters of flumatinib, including AUC(0−t), AUC(0−∞), Cmax and CLz/F, but had no effect on the metabolism of M1. According to the results of in vitro and in vivo studies, the metabolism of flumatinib was inhibited by isavuconazole, suggesting that isavuconazole may raise the plasma concentration of flumatinib. Thus, it is important to take special care of the interactions between flumatinib and isavuconazole in clinical applications.
The nucleon-induced deuteron breakup process as a laboratory for chiral dynamics
Authors: Skibiński Roman , Golak Jacek , Witała Henryk , Chahar Vaibhav , Epelbaum Evgeny , Nogga Andreas , Soloviov Volodymyr
Published: May 2023

The nucleon-induced deuteron breakup reaction is studied within the Faddeev approach at incoming nucleon laboratory energies of 135 and 200 MeV. The chiral semilocal momentum-space (SMS) potential developed up to N4LO+, supplemented by the N2LO three-nucleon interaction, is used. Our investigation is focused on the determination of theoretical uncertainties in a predicted cross section related to its dependence on the value of the cutoff parameter of the regulator. We also compare predictions based on the complete N2LO potential with those based on the two-nucleon force upgraded to the N4LO+ order and augmented with the N2LO three-nucleon force. In addition, we study the three-nucleon force effects predicted by this model of interaction. Our systematic study covers the entire kinematically allowed phase space; however, our main results are obtained when additional restrictions on energies and cross section values are imposed. In such a case, we observe that the dependence of the differential cross sections on the regulator cutoff is moderate at 135 MeV and much stronger at 200 MeV. For the latter energy, it can amount to up to 45% in specific kinematic configurations. Taking into account terms beyond, N2LO in a two-body interaction changes the cross section up to 20% (27%) at E = 135(200) MeV. The inclusion of the three-nucleon force leads to effects of approximately 27% at both energies. We illustrate these dependencies with a few examples of the exclusive cross section as a function of the arc length of the S-curve.
A rising tide lifts all MBOATs: recent progress in structural and functional understanding of membrane bound O-acyltransferases
Authors: Pierce Mariah R. , Hougland James L.
Published: May 2023

Acylation modifications play a central role in biological and physiological processes. Across a range of biomolecules from phospholipids to triglycerides to proteins, introduction of a hydrophobic acyl chain can dramatically alter the biological function and cellular localization of these substrates. Amongst the enzymes catalyzing these modifications, the membrane bound O-acyltransferase (MBOAT) family occupies an intriguing position as the combined substrate selectivities of the various family members span all three classes of these biomolecules. MBOAT-dependent substrates are linked to a wide range of health conditions including metabolic disease, cancer, and neurodegenerative disease. Like many integral membrane proteins, these enzymes have presented challenges to investigation due to their intractability to solubilization and purification. However, over the last several years new solubilization approaches coupled with computational modeling, crystallography, and cryoelectron microscopy have brought an explosion of structural information for multiple MBOAT family members. These studies enable comparison of MBOAT structure and function across members catalyzing modifications of all three substrate classes, revealing both conserved features amongst all MBOATs and distinct architectural features that correlate with different acylation substrates ranging from lipids to proteins. We discuss the methods that led to this renaissance of MBOAT structural investigations, our new understanding of MBOAT structure and implications for catalytic function, and the potential impact of these studies for development of new therapeutics targeting MBOAT-dependent physiological processes.
Pilot mental health during the COVID-19 pandemic: prevalence rates from semi-structured interviews, and associated vulnerability and protective factors
Authors: Ackland Corrie A. , Molesworth Brett R. C. , Grisham Jessica R.
Published: May 2023

Introduction

Pilots are a unique occupational group who perform a specialised job and face significant stressors. Pilot mental health has received increased attention since Germanwings Flight 9525; however, this research has largely focused on general anxiety, depression, and suicide and relied on a questionnaire-based methodology. This approach is likely to miss various mental health issues that may affect pilot wellbeing, leaving the prevalence of mental health issues in aviation unclear. In addition, the COVID-19 pandemic is likely to have a particular impact on the mental health and wellbeing of pilots, who experienced the devastating effect of COVID-19 on the industry.

Method

In the present study, we conducted a comprehensive assessment of 73 commercial pilots during the COVID-19 pandemic, using the DIAMOND semi-structured diagnostic interview and explored possible associated vulnerability and protective factors, including life event stressors, personality, passion, lifestyle factors, and coping strategies.

Results

The COVID-19 pandemic had a significant impact on aviation during the time of this study, affecting 95% of participants. The diagnostic results revealed over one third of pilots had symptoms of a diagnoseable mental health disorder. Anxiety disorders were the most commonly found disorders, followed by Attention Deficit Hyperactivity Disorder (ADHD), Adjustment Disorder, and Depressive Disorders. Pilots’ high life event scores placed them at an increased risk for the development of stress-related illness, though did not explain which pilots had mental health difficulties in this study. Regression analysis supported a diathesis-stress model for pilot mental health, with disagreeableness and obsessive passion contributing to pilots’ development of mental health issues, and nutrition as the most important protective factor.

Discussion

This study, though limited to the COVID-19 pandemic, provides a valuable precedent for a more thorough assessment of pilot mental health, and contributes to the broader understanding of pilot mental health, including suggestions to target factors associated with the development of mental health issues.
Sleep quality, social rhythms, and depression among people living with HIV: a path analysis based on social zeitgeber theory
Authors: Meng Jingjing , Xiao Xueling , Wang Wenru , Jiang Ying , Jin Yanfei , Wang Honghong
Published: May 2023

Background

People living with HIV frequently report sleep disturbances. The social zeitgeber theory, which proposes that stressful life events can interfere with sleep and even depression by destabilizing daily routines, provides new insights into identifying predictors of sleep disturbances and improving sleep in people living with HIV.

Objective

To explain the pathways affecting sleep quality in people living with HIV based on social zeitgeber theory.

Methods

A cross-sectional study was conducted to assess sleep quality, social rhythms, depression, social support, and coping styles from December 2020 to February 2021. The hypothetical model was tested and respecified by performing path analysis and a bias-corrected bootstrapping method using IBM AMOS 24 software. The report of this study followed the STROBE checklist.

Results

A total of 737 people living with HIV participated in the study. The final model presented a good fit (goodness of fit = 0.999, adjusted goodness of fit index = 0.984, normed fit index = 0.996, comparative fit index = 0.998, Tucker–Lewis index = 0.988, root mean square error of approximation = 0.030, chi-squared/degree of freedom = 1.646), explaining 32.3% of the variance in sleep quality among people living with HIV. Lower social rhythm stability was directly associated with poorer sleep quality, and depression mediated the relationship between social rhythms and sleep quality. Social support and coping styles affected sleep quality through social rhythms and depression.

Limitation

The cross-sectional study design precludes making assumptions about causality among factors.

Conclusion

This study validates and extends the applicability of the social zeitgeber theory in the HIV context. Social rhythms have direct and indirect effects on sleep. Social rhythms, sleep, and depression is not simply linked in a cascading sequence but is theoretically linked in a complex way. More studies are needed to explore the predictors of social rhythms, and interventions for stabilizing social rhythms have the potential to alleviate sleep disturbances and depression in people living with HIV.