bluuebunny/crossref_metadata_2025 huggingface dataset:
Text mining and portal development for gene-specific publications on Alzheimer’s disease and other neurodegenerative diseases
Authors: Liu Jiannan , Wu Huanmei , Robertson Daniel H. , Zhang Jie
Published: April 2024

Background

Tremendous research efforts have been made in the Alzheimer’s disease (AD) field to understand the disease etiology, progression and discover treatments for AD. Many mechanistic hypotheses, therapeutic targets and treatment strategies have been proposed in the last few decades. Reviewing previous work and staying current on this ever-growing body of AD publications is an essential yet difficult task for AD researchers.

Methods

In this study, we designed and implemented a natural language processing (NLP) pipeline to extract gene-specific neurodegenerative disease (ND) -focused information from the PubMed database. The collected publication information was filtered and cleaned to construct AD-related gene-specific publication profiles. Six categories of AD-related information are extracted from the processed publication data: publication trend by year, dementia type occurrence, brain region occurrence, mouse model information, keywords occurrence, and co-occurring genes. A user-friendly web portal is then developed using Django framework to provide gene query functions and data visualizations for the generalized and summarized publication information.

Results

By implementing the NLP pipeline, we extracted gene-specific ND-related publication information from the abstracts of the publications in the PubMed database. The results are summarized and visualized through an interactive web query portal. Multiple visualization windows display the ND publication trends, mouse models used, dementia types, involved brain regions, keywords to major AD-related biological processes, and co-occurring genes. Direct links to PubMed sites are provided for all recorded publications on the query result page of the web portal.

Conclusion

The resulting portal is a valuable tool and data source for quick querying and displaying AD publications tailored to users’ interested research areas and gene targets, which is especially convenient for users without informatic mining skills. Our study will not only keep AD field researchers updated with the progress of AD research, assist them in conducting preliminary examinations efficiently, but also offers additional support for hypothesis generation and validation which will contribute significantly to the communication, dissemination, and progress of AD research.
Analysis of REST binding sites with canonical and non-canonical motifs in human cell lines
Authors: Choi Jaejoon , Lee Eunjung Alice
Published: April 2024

Background

Repressor element 1 (RE1) silencing transcription factor (REST) is a transcriptional repressor abundantly expressed in aging human brains. It is known to regulate genes associated with oxidative stress, inflammation, and neurological disorders by binding to a canonical form of sequence motif and its non-canonical variations. Although analysis of genomic sequence motifs is crucial to understand transcriptional regulation by transcription factors (TFs), a comprehensive characterization of various forms of RE1 motifs in human cell lines has not been performed.

Results

Here, we analyzed 23 ENCODE REST ChIP-seq datasets from diverse human cell lines and identified a non-redundant set of 68,975 loci with ChIP-seq peaks. Our systematic characterization of these binding sites revealed that the canonical form of REST binding motif was found primarily in ChIP-seq peaks shared across multiple cell lines, while non-canonical forms of motifs were identified in both cell-line-specific binding sites and those shared across cell lines. Remarkably, we observed a notable prevalence of non-canonical motifs that corresponded to half segments of the canonical motif. Furthermore, our analysis unveiled the presence of cell-line-specific REST binding patterns, as evidenced by the clustering of ChIP-seq experiments according to their respective cell lines. This observation underscores the cell-line specificity of REST binding at certain genomic loci, implying intricate cell-line-specific regulatory mechanisms.

Conclusions

Overall, our study provides a comprehensive characterization of REST binding motifs in human cell lines and genome-wide RE1 motif profiles. These findings contribute to a deeper understanding of REST-mediated transcriptional regulation and highlight the importance of considering cell-line-specific effects in future investigations.
Attenuating mitochondrial dysfunction and morphological disruption with PT320 delays dopamine degeneration in MitoPark mice
Authors: Wang Vicki , Tseng Kuan-Yin , Kuo Tung-Tai , Huang Eagle Yi-Kung , Lan Kuo-Lun , Chen Zi-Rong , Ma Kuo-Hsing , Greig Nigel H. , Jung Jin , Choi Ho-II , Olson Lars , Hoffer Barry J. , Chen Yuan-Hao
Published: April 2024

Background

Mitochondria are essential organelles involved in cellular energy production. Changes in mitochondrial function can lead to dysfunction and cell death in aging and age-related disorders. Recent research suggests that mitochondrial dysfunction is closely linked to neurodegenerative diseases. Glucagon-like peptide-1 receptor (GLP-1R) agonist has gained interest as a potential treatment for Parkinson's disease (PD). However, the exact mechanisms responsible for the therapeutic effects of GLP-1R-related agonists are not yet fully understood.

Methods

In this study, we explores the effects of early treatment with PT320, a sustained release formulation of the GLP-1R agonist Exenatide, on mitochondrial functions and morphology in a progressive PD mouse model, the MitoPark (MP) mouse.

Results

Our findings demonstrate that administration of a clinically translatable dose of PT320 ameliorates the reduction in tyrosine hydroxylase expression, lowers reactive oxygen species (ROS) levels, and inhibits mitochondrial cytochrome c release during nigrostriatal dopaminergic denervation in MP mice. PT320 treatment significantly preserved mitochondrial function and morphology but did not influence the reduction in mitochondria numbers during PD progression in MP mice. Genetic analysis indicated that the cytoprotective effect of PT320 is attributed to a reduction in the expression of mitochondrial fission protein 1 (Fis1) and an increase in the expression of optic atrophy type 1 (Opa1), which is known to play a role in maintaining mitochondrial homeostasis and decreasing cytochrome c release through remodeling of the cristae.

Conclusion

Our findings suggest that the early administration of PT320 shows potential as a neuroprotective treatment for PD, as it can preserve mitochondrial function. Through enhancing mitochondrial health by regulating Opa1 and Fis1, PT320 presents a new neuroprotective therapy in PD.

Graphical Abstract
Spatial and single-cell explorations uncover prognostic significance and immunological functions of mitochondrial calcium uniporter in breast cancer
Authors: Li Chia-Jung , Tzeng Yen-Dun Tony , Hsiao Jui-Hu , Tseng Ling-Ming , Hsu Tzu-Sheng , Chu Pei-Yi
Published: April 2024

The mitochondrial calcium uniporter (MCU) is a transmembrane protein facilitating the entry of calcium ions into mitochondria from the cell cytosol. Maintaining calcium balance is crucial for enhancing cellular energy supply and regulating cell death. The interplay of calcium balance through MCU and the sodium-calcium exchanger is known, but its regulation in the breast cancer tumor microenvironment remains elusive. Further investigations are warranted to explore MCU’s potential in BRCA clinical pathology, tumor immune microenvironment, and precision oncology. Our study, employing a multi-omics approach, identifies MCU as an independent diagnostic biomarker for breast cancer (BRCA), correlated with advanced clinical status and poor overall survival. Utilizing public datasets from GEO and TCGA, we discern differentially expressed genes in BRCA and examine their associations with immune gene expression, overall survival, tumor stage, gene mutation status, and infiltrating immune cells. Spatial transcriptomics is employed to investigate MCU gene expression in various regions of BRCA, while spatial transcriptomics and single-cell RNA-sequencing methods explore the correlation between MCUs and immune cells. Our findings are validated through the analysis of 59 BRCA patient samples, utilizing immunohistochemistry and bioinformatics to examine the relationship between MCU expression, clinicopathological features, and prognosis. The study uncovers the expression of key gene regulators in BRCA associated with genetic variations, deletions, and the tumor microenvironment. Mutations in these regulators positively correlate with different immune cells in six immune datasets, playing a pivotal role in immune cell infiltration in BRCA. Notably, high MCU performance is linked to CD8 + T cells infiltration in BRCA. Furthermore, pharmacogenomic analysis of BRCA cell lines indicates that MCU inactivation is associated with increased sensitivity to specific small molecule drugs. Our findings suggest that MCU alterations may be linked to BRCA progression, unveiling new diagnostic and prognostic implications for MCU in BRCA. The study underscores MCU's role in the tumor immune microenvironment and cell cycle progression, positioning it as a potential tool for BRCA precision medicine and drug screening.
Widespread pfhrp2/3 deletions and HRP2-based false-negative results in southern Ethiopia
Authors: Mekonen Bacha , Dugassa Sisay , Feleke Sindew Mekasha , Dufera Boja , Gidisa Bedasa , Adamu Aderaw , Mandefro Aynalem , Tasew Geremew , Golassa Lemu
Published: April 2024

Background

Rapid diagnostic tests (RDTs) play a significant role in expanding case management in peripheral healthcare systems. Histidine-rich protein-2 (HRP2) antigen detection RDTs are predominantly used to diagnose Plasmodium falciparum infection. However, the evolution and spread of P. falciparum parasite strains with deleted hrp2/3 genes, causing false-negative results, have been reported. This study assessed the diagnostic performance of HRP2-detecting RDTs for P. falciparum cases and the prevalence of pfhrp2/3 deletions among symptomatic patients seeking malaria diagnosis at selected health facilities in southern Ethiopia.

Methods

A multi-health facilities-based cross-sectional study was conducted on self-presenting febrile patients seeking treatment in southern Ethiopia from July to September 2022. A purposive sampling strategy was used to enroll patients with microscopically confirmed P. falciparum infections. A capillary blood sample was obtained to prepare a blood film for microscopy and a RDT using the SD Bioline™ Malaria Pf/Pv Test. Dried blood spot samples were collected for further molecular analysis. DNA was extracted using gene aid kits and amplification was performed using nested PCR assay. Exon 2 of hrp2 and hrp3, which are the main protein-coding regions, was used to confirm its deletion. The diagnostic performance of RDT was evaluated using PCR as the gold standard test for P. falciparum infections.

Results

Of 279 P. falciparum PCR-confirmed samples, 249 (89.2%) had successful msp-2 amplification, which was then genotyped for hrp2/3 gene deletions. The study revealed that pfhrp2/3 deletions were common in all health centres, and it was estimated that 144 patients (57.8%) across all health facilities had pfhrp2/3 deletions, leading to false-negative PfHRP2 RDT results. Deletions spanning exon 2 of hrp2, exon 2 of hrp3, and double deletions (hrp2/3) accounted for 68 (27.3%), 76 (30.5%), and 33 (13.2%) of cases, respectively. The study findings revealed the prevalence of P. falciparum parasites lacking a single pfhrp2-/3-gene and that both genes varied across the study sites. This study also showed that the sensitivity of the SD Bioline PfHRP2-RDT test was 76.5% when PCR was used as the reference test.

Conclusion

This study confirmed the existence of widespread pfhrp2/3- gene deletions, and their magnitude exceeded the WHO-recommended threshold (> 5%). False-negative RDT results resulting from deletions in Pfhrp2/3- affect a country’s attempts at malaria control and elimination. Therefore, the adoption of non-HRP2-based RDTs as an alternative measure is required to avoid the consequences associated with the continued use of HRP-2-based RDTs, in the study area in particular and in Ethiopia in general.
Health inequalities in childhood diseases: temporal trends in the inter-crisis period
Authors: Carrilero Neus , García-Altés Anna
Published: April 2024

Background

Since 2008, children in Catalonia (Spain) have suffered a period of great economic deprivation. This situation has generated broad-ranging health inequalities in a variety of diseases. It is not known how these inequalities have changed over time. The aim of the present study is to determine trends in inequalities over this period in ten relevant diseases in children according to sex and age.

Methods

A retrospective cross-sectional population-based study of all children under 15 years old resident in Catalonia during the 2014–2021 period (over 1.2 million children/year) and of their diagnoses registered by the Catalan Health System. Health inequalities were estimated by calculating the relative index of inequality and time trends using logistic regression models. Interaction terms were added to test for the effects of sex on time trends.

Results

Increasing significant temporal trends in inequalities were shown for both sexes in almost all the diseases or adverse events studied (asthma, injuries, poisoning, congenital anomalies, overweight and obesity), in mood disorders in boys, and in adverse birth outcomes in girls. Adjustment and anxiety and mood disorders in girls showed a decreasing temporal trend in inequalities. More than half of the diseases and adverse events studied experienced significant annual increases in inequality. Poisoning stood out with an average annual increase of 8.65% [4.30, 13.00], p ≤ 0.001 in boys and 8.64% [5.76, 11.52], p ≤ 0.001) in girls, followed by obesity with increases of 5.52% [4.15, 6.90], p =  < 0.001 in boys and 4.89% [4.26, 5.51], p ≤ 0.001) in girls.

Conclusions

Our results suggest that inequalities persist and have increased since 2014. Policy makers should turn their attention to how interventions to reduce Health inequalities are designed, and who benefits from them.
DB-1310, an ADC comprised of a novel anti-HER3 antibody conjugated to a DNA topoisomerase I inhibitor, is highly effective for the treatment of HER3-positive solid tumors
Authors: Li Xi , Yao Jun , Qu Chen , Luo Lan , Li Bing , Zhang Yu , Zhu Zhongyuan , Qiu Yang , Hua Haiqing
Published: April 2024

Background

HER3 (ErbB3), a member of the human epidermal growth factor receptor family, is frequently overexpressed in various cancers. Multiple HER3-targeting antibodies and antibody–drug conjugates (ADCs) were developed for the solid tumor treatment, however none of HER3-targeting agent has been approved for tumor therapy yet. We developed DB-1310, a HER3 ADC composed of a novel humanized anti-HER3 monoclonal antibody covalently linked to a proprietary DNA topoisomerase I inhibitor payload (P1021), and evaluate the efficacy and safety of DB-1310 in preclinical models.

Methods

The binding of DB-1310 to Her3 and other HER families were measured by ELISA and SPR. The competition of binding epitope for DB-1310 and patritumab was tested by FACS. The sensitivity of breast, lung, prostate and colon cancer cell lines to DB-1310 was evaluated by in vitro cell killing assay. In vivo growth inhibition study evaluated the sensitivity of DB-1310 to Her3 + breast, lung, colon and prostate cancer xenograft models. The safety profile was also measured in cynomolgus monkey.

Results

DB-1310 binds HER3 via a novel epitope with high affinity and internalization capacity. In vitro, DB-1310 exhibited cytotoxicity in numerous HER3 + breast, lung, prostate and colon cancer cell lines. In vivo studies in HER3 + HCC1569 breast cancer, NCI-H441 lung cancer and Colo205 colon cancer xenograft models showed DB-1310 to have dose-dependent tumoricidal activity. Tumor suppression was also observed in HER3 + non-small cell lung cancer (NSCLC) and prostate cancer patient-derived xenograft (PDX) models. Moreover, DB-1310 showed stronger tumor growth-inhibitory activity than patritumab deruxtecan (HER3-DXd), which is another HER3 ADC in clinical development at the same dose. The tumor-suppressive activity of DB-1310 synergized with that of EGFR tyrosine kinase inhibitor, osimertinib, and exerted efficacy also in osimertinib-resistant PDX model. The preclinical assessment of safety in cynomolgus monkeys further revealed DB-1310 to have a good safety profile with a highest non severely toxic dose (HNSTD) of 45 mg/kg.

Conclusions

These finding demonstrated that DB-1310 exerted potent antitumor activities against HER3 + tumors in in vitro and in vivo models, and showed acceptable safety profiles in nonclinical species. Therefore, DB-1310 may be effective for the clinical treatment of HER3 + solid tumors.
Relationship between pan-immune- inflammation value and in major cardiovascular and cerebrovascular events in stable coronary artery disease patients undergoing on-pump coronary artery bypass graft surgery
Authors: Dolapoglu Ahmet , Avci Eyup
Published: April 2024

Background

In this study, we aimed to evaluate the association of pan-immune-inflammation value (PIV) with major cardiovascular and cerebrovascular events (MACCE) in stable coronary artery disease patients undergoing on-pump coronary artery bypass graft (CABG) surgery.

Methods

We retrospectively analyzed data from 527 patients who underwent on-pump CABG surgery for stable coronary artery disease between June 2015 and December 2020. Patients were categorized into two groups based on MACCE development. PIV levels were calculated from blood samples taken on admission. PIV was calculated as [neutrophil count (×103/µL)×platelet count (×103/µL))×monocyte count (×103/µL)]/lymphocyte count (×103/µL). The primary endpoint was long-term major cardiovascular and cerebrovascular events (MACCE) at a median follow-up of 4.6 years.

Results

Of the included patients, 103 (19.5%) developed MACCE. PIV was higher in patients with MACCE compared to those without (470.8 [295.3-606.8] vs. 269.8 [184.3-386.4], p < 0.001). Multivariate analysis showed a significant positive association between PIV and MACCE (HR: 1.326, 95%CI:1.212–1452, p < 0.001). The cut-off value for the PIV in the estimation of MACCE was 368.28 ( AUC: 0.726 with 69% sensitivity, 71% specificity, p < 0.001).

Conclusion

This study shows a significant link between high PIV levels and MACCE in stable coronary artery disease patients undergoing on-pump CABG surgery. Our findings suggest that PIV may be a valuable, routinely available, and inexpensive marker for identifying patients at increased risk of MACCE.
Heparin-induced DRESS syndrome in a paediatric patient and successful anaesthetic management in cardiovascular bypass surgery: case report
Authors: Peña-Blanco Laura , Gutiérrez-Soriano Laura , Montes Félix Ramón , Barragán-Méndez Andrea , Beltrán-Villegas Susana , López-Reyes Juan José , Villa-Hincapié Carlos A. , Umaña Juan Pablo
Published: April 2024

Background

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a severe adverse drug reaction marked by delayed hypersensitivity reactions causing skin and systemic complications. DRESS diagnosis is challenging due to the variety of clinical presentations and symptom overlap with other conditions. The perioperative period in these patients requires precise pharmacological strategies to prevent complications associated with this syndrome. The treatment of DRESS induced by unfractionated heparin during cardiopulmonary bypass (CPB) surgery presents some challenges that must be considered when selecting an anticoagulant to avoid side effects. In this case, bivalirudin, a direct thrombin inhibitor, is indicated as an alternative to heparin in patients undergoing CPB. However, in contrast to heparin/protamine, there is no direct reversal agent for bivalirudin.

Case presentation

We report the case of an 11-year-old male diagnosed with native aortic valve endocarditis and thrombosis in his left lower extremity. During valvular replacement surgery, systemic unfractionated heparin was administered. Postoperatively, the patient developed fever, eosinophilia and pruritic rash. Warm shock and elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels followed, leading to the diagnosis of DRESS syndrome. Treatment with methylprednisolone resulted in complete resolution of symptoms. Seven years later, the patient was readmitted due to insufficient anticoagulation and a thrombus in the prosthetic aortic valve, presenting a recurrent DRESS episode due to the administration of unfractionated heparin, which was later replaced with low-molecular-weight heparin during hospitalization. Treatment with corticosteroids and antihistamines was initiated, resulting in the resolution of this episode. Ultimately, the patient required the Ross procedure. During this intervention the anticoagulation strategy was modified, unfractionated heparin was replaced with bivalirudin during the procedure and fondaparinux was administered during the postoperative period. This resulted in stable transaminases levels and no eosinophilia.

Conclusion

The severity of DRESS Syndrome underscores the importance of early recognition, heightened monitoring, and a comprehensive approach tailored to each patient’s needs. This particular case highlights the significance of this approach and may have a substantial clinical impact since it provides alternatives to heparin, such as bivalirudin and fondaparinux, in the anticoagulation strategy of CPB for patients who have a hypersensibility reaction to this medication; thus, enhancing clinical outcomes by minimizing risks linked to adverse drug reactions.
Long-term effects of abatacept on atherosclerosis and arthritis in older vs. younger patients with rheumatoid arthritis: 3-year results of a prospective, multicenter, observational study
Authors: Yamada Zento , Muraoka Sei , Kawazoe Mai , Hirose Wataru , Kono Hajime , Yasuda Shinsuke , Sugihara Takahiko , Nanki Toshihiro
Published: April 2024

Background

We aimed to reveal the effect of abatacept (ABT) on atherosclerosis in rheumatoid arthritis (RA) patients, 3-year efficacy for arthritis, and safety in a population of older vs. younger patients.

Methods

In this open-label, prospective, observational study, patients were stratified into four groups: younger (20–64 years old) and older (≥ 65 years) patients taking ABT (AY and AO) and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) (CY and CO). Primary endpoints were change from baseline in mean intima-media thickness (IMT) of the common carotid artery, IMT max (bulbus, bifurcation, and internal and common carotid artery), and plaque score at Week 156. Disease activity, retention rate, and adverse effects were also evaluated.

Results

The ABT group (AY + AO) tended to have smaller increases in mean IMT, max IMT, and plaque score than the csDMARD group (CY + CO) at Week 156, although the differences between groups were not statistically significant. Multivariate analysis showed significantly lower increases in plaque score with ABT than with csDMARDs, only when considering disease activity at 156 weeks (p = 0.0303). Proportions of patients with good or good/moderate European League Against Rheumatism response were higher in the ABT group, without significant difference between older and younger patients. No significant differences were observed in ABT retention rates between older and younger patients. Serious adverse effects, especially infection, tended to be more frequent with ABT than with csDMARDs, although no significant differences were found.

Conclusions

ABT may decelerate atherosclerosis progression and may be useful for patients with high risk of cardiovascular disease, such as older patients.

Trial registration number:

UMIN000014913.
Dependence on visual information in patients with ACL injury for multi-joint coordination during single-leg squats: a case control study
Authors: Toriyama Minoru , Nakamae Atsuo , Abe Takumi , Hirata Kazuhiko , Adachi Nobuo
Published: April 2024

Background

The influence of vision on multi-joint control during dynamic tasks in anterior cruciate ligament (ACL) deficient patients is unknown. Thus, the purpose of this study was to establish a new method for quantifying neuromuscular control by focusing on the variability of multi-joint movement under conditions with different visual information and to determine the cutoff for potential biomarkers of injury risk in ACL deficient individuals.

Methods

Twenty-three ACL deficient patients and 23 healthy subjects participated in this study. They performed single-leg squats under two different conditions: open eyes (OE) and closed eyes (CE). Multi-joint coordination was calculated with the coupling angle of hip flexion, hip abduction and knee flexion. Non-linear analyses were performed on the coupling angle. Dependence on vision was compared between groups by calculating the CE/OE index for each variable. Cutoff values were calculated using ROC curves with ACL injury as the dependent variable and significant variables as independent variables.

Results

The sample entropy of the coupling angle was increased in all groups under the CE condition (P < 0.001). The CE/OE index of coupling angle variability during the descending phase was higher in ACL deficient limbs than in the limbs of healthy participants (P = 0.036). The CE/OE index of sample entropy was higher in the uninjured limbs of ACL deficient patients than in the limbs of healthy participants (P = 0.027). The cutoff value of the CE/OE index of sample entropy was calculated to be 1.477 (Sensitivity 0.957, specificity 0.478).

Conclusion

ACL deficient patients depended on vision to control multiple joint movements not only on the ACL deficient side but also on the uninjured side during single leg squat task. These findings underscore the importance of considering visual dependence in the assessment and rehabilitation of neuromuscular control in ACL deficient individuals.
Short post-injection seizure duration is associated with reduced power of ictal brain perfusion SPECT to lateralize the seizure onset zone
Authors: Karimzadeh Amir , Baradaran-Salimi Kian , Voges Berthold , Apostolova Ivayla , Sauvigny Thomas , Lanz Michael , Klutmann Susanne , Stodieck Stefan , Meyer Philipp T. , Buchert Ralph
Published: April 2024

Background

The aim of this study was to assess the impact of the post-injection electrical seizure duration on the identification of the seizure onset zone (SOZ) in ictal brain perfusion SPECT in presurgical evaluation of drug-resistant epilepsy.

Methods

176 ictal SPECT performed with 99mTc-HMPAO (n = 140) or -ECD (n = 36) were included retrospectively. Visual interpretation of the SPECT images (together with individual MRI and statistical hyperperfusion maps) with respect to lateralization (right, left, none) and localization (temporal, frontal, parietal, occipital) of the SOZ was performed by 3 independent readers. Between-readers agreement was characterized by Fleiss’ κ. An ictal SPECT was considered "lateralizing" if all readers agreed on right or left hemisphere. It was considered "localizing" if it was lateralizing and all readers agreed on the same lobe within the same hemisphere. The impact of injection latency and post-injection seizure duration on the proportion of lateralizing/localizing SPECT was tested by ANOVA with dichotomized (by the median) injection latency and post-injection seizure duration as between-subjects factors.

Results

Median [interquartile range] (full range) of injection latency and post-injection seizure duration were 30 [24, 40] (3–120) s and 50 [27, 70] (-20–660) s, respectively. Fleiss’ κ for lateralization of the SOZ was largest for the combination of early (< 30 s) injection and long (> 50 s) post-injection seizure duration (κ = 0.894, all other combinations κ = 0.659–0.734). Regarding Fleiss’ κ for localization of the SOZ in the 141 (80.1%) lateralizing SPECT, it was largest for early injection and short post-injection seizure duration (κ = 0.575, all other combinations κ = 0.329–0.368). The proportion of lateralizing SPECT was lower with short compared to long post-injection seizure duration (estimated marginal means 74.3% versus 86.3%, p = 0.047). The effect was mainly driven by cases with very short post-injection seizure duration ≤ 10 s (53.8% lateralizing). Injection latency in the considered range had no significant impact on the proportion of lateralizing SPECT (p = 0.390). The proportion of localizing SPECT among the lateralizing cases did not depend on injection latency or post-injection seizure duration (p ≥ 0.603).

Conclusions

Short post-injection seizure duration is associated with a lower proportion of lateralizing cases in ictal brain perfusion SPECT.
Ivermectin increases striatal cholinergic activity to facilitate dopamine terminal function
Authors: Wadsworth Hillary A. , Warnecke Alicia M. P. , Barlow Joshua C. , Robinson J. Kayden , Steimle Emma , Ronström Joakim W. , Williams Pacen E. , Galbraith Christopher J. , Baldridge Jared , Jakowec Michael W. , Davies Daryl L. , Yorgason Jordan T.
Published: April 2024

Ivermectin (IVM) is a commonly prescribed antiparasitic treatment with pharmacological effects on invertebrate glutamate ion channels resulting in paralysis and death of invertebrates. However, it can also act as a modulator of some vertebrate ion channels and has shown promise in facilitating L-DOPA treatment in preclinical models of Parkinson’s disease. The pharmacological effects of IVM on dopamine terminal function were tested, focusing on the role of two of IVM’s potential targets: purinergic P2X4 and nicotinic acetylcholine receptors. Ivermectin enhanced electrochemical detection of dorsal striatum dopamine release. Although striatal P2X4 receptors were observed, IVM effects on dopamine release were not blocked by P2X4 receptor inactivation. In contrast, IVM attenuated nicotine effects on dopamine release, and antagonizing nicotinic receptors prevented IVM effects on dopamine release. IVM also enhanced striatal cholinergic interneuron firing. L-DOPA enhances dopamine release by increasing vesicular content. L-DOPA and IVM co-application further enhanced release but resulted in a reduction in the ratio between high and low frequency stimulations, suggesting that IVM is enhancing release largely through changes in terminal excitability and not vesicular content. Thus, IVM is increasing striatal dopamine release through enhanced cholinergic activity on dopamine terminals.
Aggregated database of forest soil chemical properties in the Czech Republic based on surveys from 2000 to 2020
Authors: Neudertová Hellebrandová Kateřina , Fadrhonsová Věra , Šrámek Vít
Published: April 2024

Key message

The dataset includes data from forest soil surveys conducted in the period 2000–2020. It provides soil and site variables from 8269 locations. Data are aggregated in three basic soil layers: upper organic soil horizon (FH, 6875 locations), upper mineral layer 0–30 cm (M03, 8051 locations) and deeper mineral soil layer 30–80 cm (M38, 2260 locations).

The dataset is available at https://doi.org/10.5281/zenodo.10608814, and access to the metadata is at https://metadata-afs.nancy.inra.fr/geonetwork/srv/fre/catalog.search#/metadata/38f24573-3c0d-469a-a66a-7060ce082155.
Spontaneous breathing trial with pressure support on positive end-expiratory pressure and extensive use of non-invasive ventilation versus T-piece in difficult-to-wean patients from mechanical ventilation: a randomized controlled trial
Authors: Mezidi Mehdi , Yonis Hodane , Chauvelot Louis , Deniel Guillaume , Dhelft François , Gaillet Maxime , Noirot Ines , Folliet Laure , Chabert Paul , David Guillaume , Danjou William , Baboi Loredana , Bettinger Clotilde , Bernon Pauline , Girard Mehdi , Provoost Judith , Bazzani Alwin , Bitker Laurent , Richard Jean-Christophe
Published: April 2024

Background

The aim of this study is to assess whether a strategy combining spontaneous breathing trial (SBT) with both pressure support (PS) and positive end-expiratory pressure (PEEP) and extended use of post-extubation non-invasive ventilation (NIV) (extensively-assisted weaning) would shorten the time until successful extubation as compared with SBT with T-piece (TP) and post-extubation NIV performed in selected patients as advocated by guidelines (standard weaning), in difficult-to-wean patients from mechanical ventilation.

Methods

The study is a single-center prospective open label, randomized controlled superiority trial with two parallel groups and balanced randomization with a 1:1 ratio. Eligible patients were intubated patients mechanically ventilated for more than 24 h who failed their first SBT using TP. In the extensively-assisted weaning group, SBT was performed with PS (7 cmH2O) and PEEP (5 cmH2O). In case of SBT success, an additional SBT with TP was performed. Failure of this SBT-TP was an additional criterion for post-extubation NIV in this group in addition to other recommended criteria. In the standard weaning group, SBT was performed with TP, and NIV was performed according to international guidelines. The primary outcome criterion was the time between inclusion and successful extubation evaluated with a Cox model with adjustment on randomization strata.

Results

From May 2019 to March 2023, 98 patients were included and randomized in the study (49 in each group). Four patients were excluded from the intention-to-treat population (2 in both groups); therefore, 47 patients were analyzed in each group. The extensively-assisted weaning group had a higher median age (68 [58–73] vs. 62 [55–71] yrs.) and similar sex ratio (62% male vs. 57%). Time until successful extubation was not significantly different between extensively-assisted and standard weaning groups (median, 172 [50–436] vs. 95 [47–232] hours, Cox hazard ratio for successful extubation, 0.88 [95% confidence interval: 0.55–1.42] using the standard weaning group as a reference;p = 0.60). All secondary outcomes were not significantly different between groups.

Conclusion

An extensively-assisted weaning strategy did not lead to a shorter time to successful extubation than a standard weaning strategy.

Trial registrationThe trial was registered on ClinicalTrials.gov (NCT03861117), on March 1, 2019, before the inclusion of the first patient.https://clinicaltrials.gov/study/NCT03861117.
Characterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogeny
Authors: Li Fei , Zhu Yanling , Wang Tianyu , Tang Jun , Huang Yuhua , Gu Jiaming , Mai Yuchan , Wang Mingquan , Zhang Zhishuai , Ning Jiaying , Kang Baoqiang , Wang Junwei , Zhou Tiancheng , Cui Yazhou , Pan Guangjin
Published: April 2024

Human hematopoiesis starts at early yolk sac and undergoes site- and stage-specific changes over development. The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood. Here, we analyzed single-cell transcriptome of human primary hematopoietic stem/progenitor cells (HSPCs) at different developmental stages, including yolk-sac (YS), AGM, fetal liver (FL), umbilical cord blood (UCB) and adult peripheral blood (PB) mobilized HSPCs. These stage-specific HSPCs display differential intrinsic properties, such as metabolism, self-renewal, differentiating potentialities etc. We then generated highly co-related gene regulatory network (GRNs) modules underlying the differential HSC key properties. Particularly, we identified GRNs and key regulators controlling lymphoid potentiality, self-renewal as well as aerobic respiration in human HSCs. Introducing selected regulators promotes key HSC functions in HSPCs derived from human pluripotent stem cells. Therefore, GRNs underlying key intrinsic properties of human HSCs provide a valuable guide to generate fully functional HSCs in vitro.
Focusing on mitochondria in the brain: from biology to therapeutics
Authors: Song Nanshan , Mei Shuyuan , Wang Xiangxu , Hu Gang , Lu Ming
Published: April 2024

Mitochondria have multiple functions such as supplying energy, regulating the redox status, and producing proteins encoded by an independent genome. They are closely related to the physiology and pathology of many organs and tissues, among which the brain is particularly prominent. The brain demands 20% of the resting metabolic rate and holds highly active mitochondrial activities. Considerable research shows that mitochondria are closely related to brain function, while mitochondrial defects induce or exacerbate pathology in the brain. In this review, we provide comprehensive research advances of mitochondrial biology involved in brain functions, as well as the mitochondria-dependent cellular events in brain physiology and pathology. Furthermore, various perspectives are explored to better identify the mitochondrial roles in neurological diseases and the neurophenotypes of mitochondrial diseases. Finally, mitochondrial therapies are discussed. Mitochondrial-targeting therapeutics are showing great potentials in the treatment of brain diseases.
Maximization strategies in relationship and career enhances life satisfaction through meaning making among established adults in South Korea
Authors: Shim Yerin , Shin Yun-Jeong , Lee Ji-yeon
Published: April 2024

Background

Choosing a partner and job have long been regarded as important developmental milestones to reach in adulthood. In a collective cultural context with high familial and societal expectations to commit to a relationship and job by age 30, maximizing on such life decisions might potentially harm one’s well-being. The literature on maximization-well-being association is complex, and recent research suggests that this relationship might differ by its dimensions and cultural context. In the present study, we examined how engaging in a maximization strategy in relationship and career domains predicts life satisfaction and whether this pathway is mediated by a meaning-making process (search-to-presence of meaning) among established adults in South Korea.

Methods

Survey data on measures of relational maximization strategy, career maximization strategy, search for meaning, presence of meaning, and life satisfaction was collected from 264 South Korean unmarried, working adults in their 30 s to 40 s. A two-step structural equation modeling method was applied to test the hypothesized serial mediation model.

Results

Tests of the measurement and structural model showed good fit with the data (CFI = .96, TLI = .95, RMSEA = .07, SRMR = .05). Further bootstrapping results supported significant indirect effects of the serial mediation model in the paths between maximization strategy and life satisfaction via a search-to-presence of meaning in both relational (b = .16, 95% CI [.01, -.16], p < .05) and career (b = .26, 95% CI [.11, -.26], p < .01) domains.

Conclusions

Our findings suggest that for established adults in a collectivist culture who may experience familial and social pressure on these life choices, searching for alternative options to make the best relationship and career decisions could potentially lead to higher life satisfaction, when done through an intentional meaning-making process.
Mental toughness in adolescents: bridging family relationships and depression across personality traits
Authors: Ni Feirui , Zheng Yawen , Qian Sheng , Shen Guanghui , Yan Wen-jing , Wu Yu-Wei , Huang Ziye
Published: April 2024

Background

Adolescence is a pivotal stage vulnerable to mental health issues like anxiety and depression. While family relationships, mental toughness, and personality traits are known to impact adolescent mental health, their interactive and moderating roles are not fully understood.

Aim

This study aims to investigate the mediating role of mental toughness in the relationship between family relationships and depression among high school students, and to examine the varying impacts of personality traits on this mediation.

Method

A cross-sectional study was conducted on a sample of 734 adolescents. Participants completed measures assessing family relationships, mental toughness, personality traits, and mental health outcomes (depression). Latent Profile Analysis, Multiple Regression Analysis, and Structural Equation Modeling, to investigate these relationships.

Results

The study found that mental toughness significantly mediates the relationship between family relationships and depression. Notably, this mediating effect varied between personality type; it was more pronounced in the moderate-reserved type compared to the proactive-engaged type. LPA identified two distinct personality types of students based on their personality traits, with differential patterns of family relationships, mental toughness, and depression. Multiple regression analysis indicated that character and adaptability, components of mental toughness, were significant negative predictors of depression.

Conclusion

The study contributes to understanding the dynamics of adolescent mental health, particularly in the context of Chinese high school students. It underscores the importance of considering family dynamics, personality traits, and mental toughness in developing effective mental health interventions for adolescents.
Quantitative typological analysis applied to the morphology of export mugs and their social factors in the Ming and Qing dynasties from the perspective of East–West trade
Authors: Ao Jinghui , Xu Zilin , Li Weicong , Ji Shanshan , Qiu Ran
Published: April 2024

The relationship between social factors and the formation of exported mug designs is blurred. This study addresses how they influence material design. Based on a quantitative typological analysis, this paper interprets the cultural relationships underlying the evolution of mug designs exported during the Ming and Qing dynasties. The study reveals: (1) the typology and handle styles of mugs can be categorized into six types, with a predominance of Cylindrical bodies and Ear-shaped handles. Notably, artistic emphasis is concentrated on Bulbous cup bodies and Tail outward curved handles; (2) the design of mugs in the eighteenth century exhibited diversity, morphological similarities, and feature continuity, evolving from representational (Ming Dynasty) to abstract and then to minimalistic styles (Qing Dynasty), particularly evident in the three-dimensional modeling of handles for ergonomic comfort (transitioning from a singular Outward curved form to Ear-shaped form, and then to Entwined branch form); (3) the body shape of mugs transformed from Arc-barrel bodies to Bulbous bodies (focusing on heat retention), and eventually to Cylindrical bodies (prioritizing heat retention, practicality, and cost-efficiency).; (4) the volume of mugs steadily increased from the early eighteenth century, generally classified into large volume (≥ 500 ml), medium volume (200-499 ml), and small volume (< 200 ml); (5) considering the extreme range of volume (11090 ml) and height (25 cm), it indicates that these two variables do not necessarily have a direct positive correlation; (6) the low center of gravity in handle design (average width of 3.4 cm against an average height of 9.9 cm for the body) reflects considerations for the distribution of liquid weight and operational convenience. The volume of sample-10 (11127 ml) notably exceeds the typical range for tea-drinking utensils, revealing the mechanism of wealth and status symbolism. Market demand orientation emerged as the primary driver for the evolution of export mug designs during the Ming and Qing Dynasties, with adjustments in the merchant system playing a secondary role. The transformation in mug design reflects the interplay of multiple factors, with the trend toward minimalist design being a response to market demands.
Real-time earthquake magnitude estimation via a deep learning network based on waveform and text mixed modal
Authors: Hou Baorui , Zhou Yueyong , Li Shanyou , Wei Yongxiang , Song Jindong
Published: April 2024

Rapid and accurate earthquake magnitude estimations are essential for earthquake early warning (EEW) systems. The distance information between the seismometers and the earthquake hypocenter can be important to the magnitude estimation. We designed a deep-learning, multiple-seismometer-based magnitude estimation method using three heterogeneous multimodalities: three-component acceleration seismograms, differential P-arrivals, and differential seismometer locations, with a specific transformer architecture to introduce the implicit distance information. Using a data-augmentation strategy, we trained and selected the model using 5365 and 728 earthquakes. To evaluate the magnitude estimation performance, we use the root mean square error (RMSE), mean absolute error (MAE), and standard deviation error (ϭ) between the catalog and the predicted magnitude using the 2051 earthquakes. The model could achieve RMSE, MAE, and ϭ less than 0.38, 0.29, and 0.38 when the passing time of the earliest P-arrival is 3 s and stabilize to the final values of 0.20, 0.15, and 0.20 after 14 s. The comparison between the proposed model and model ii, which is retrained without the specific architecture, indicates that the architecture contributes to the magnitude estimation. The P-arrivals picking error testing indicates the model could provide robust magnitude estimation on EEW with an absolute error of less than 0.2 s.

Graphical Abstract
Contrasting the nature of plastic fluctuations in small-sized systems of BCC and FCC materials
Authors: Weiss Jérôme , Zhang Peng , Cheng Pengming , Liu Gang
Published: April 2024

It is now well established that, upon decreasing system sizes down to a few $$\upmu$$
μ
m or below, the nature of plasticity of metallic materials is changing. Two important features of this small-sizes plasticity are two size effects, which can be summed up as “smaller is stronger” and “smaller is wilder”, this last observation meaning that the jerkiness of plastic deformation becomes prominent at small enough system sizes. In FCC and HCP materials, this is now rather well understood within the framework of obstacle-controlled plasticity, from the key role of a scaling ratio between the system size L and an internal scale l mainly dictated by dislocation patterning in pure materials, or by the nature of extrinsic disorder in alloys. The situation is more complex in BCC materials, for which screw dislocation motion becomes lattice-controlled, i.e. is thermally activated, below a transition temperature $$T_a$$

T
a

. Therefore, in small-sized BCC systems, temperature, size and strain-rate effects combine to give rise to a complex landscape. We show, from an analysis of the literature as well as micropillar compression tests on Molybdenum performed with different sample sizes, under different temperatures and different applied strain-rates, that (i) near or above $$T_a$$

T
a

, the plasticity of pure BCC metals is athermal and obstacle-controlled, much like at bulk scales, therefore mimicking that of pure FCC metals; (ii) below $$T_a$$

T
a

and for sample sizes larger than $$\sim$$
∼
1 $$\upmu$$
μ
m, BCC plasticity becomes lattice-controlled, this damping dislocation avalanches and thus reducing wildness; but (iii) for very small systems, still below $$T_a$$

T
a

, the role of screw dislocations on plasticity vanishes, i.e. is no more lattice-controlled, opening again the door for wild plastic fluctuations and jerkiness.