bluuebunny/crossref_metadata_2025 huggingface dataset:
Cannabidiol alleviates carbon tetrachloride-induced liver fibrosis in mice by regulating NF-κB and PPAR-α pathways
Authors: Ma Run , Xie Na , Shu Yuanhui , Wu Yafeng , He Ping , Xiang Yining , Zhou Yan , Wang Yuping
Published: April 2024

Liver fibrosis has become a serious public health problem that can develop into liver cirrhosis and hepatocellular carcinoma and even lead to death. Cannabidiol (CBD), which is an abundant nonpsychoactive component in the cannabis plant, exerts cytoprotective effects in many diseases and under pathological conditions. In our previous studies, CBD significantly attenuated liver injury induced by chronic and binge alcohol in a mouse model and oxidative bursts in human neutrophils. However, the effects of CBD on liver fibrosis and the underlying mechanisms still need to be further explored. A mouse liver fibrosis model was induced by carbon tetrachloride (CCl4) for 10 weeks and used to explore the protective properties of CBD and related molecular mechanisms. After the injection protocol, serum samples and livers were used for molecular biology, biochemical and pathological analyses. The results showed that CBD could effectively improve liver function and reduce liver damage and liver fibrosis progression in mice; the expression levels of transaminase and fibrotic markers were reduced, and histopathological characteristics were improved. Moreover, CBD inhibited the levels of inflammatory cytokines and reduced the protein expression levels of p-NF-κB, NF-κB, p-IκBα, p-p38 MAPK, and COX-2 but increased the expression level of PPAR-α. We found that CBD-mediated protection involves inhibiting NF-κB and activating PPAR-α. In conclusion, these results suggest that the hepatoprotective effects of CBD may be due to suppressing the inflammatory response in CCl4-induced mice and that the NF-κB and PPAR-α signaling pathways might be involved in this process.
Temporal trends in the prevalence and death of ischemic heart disease in women of childbearing age from 1990 to 2019: a multilevel analysis based on the Global Burden of Disease Study 2019
Authors: Hu Ben , Wang Yan , Chen Dong , Feng Jun , Fan Yinguang , Hou Linlin
Published: April 2024

Background

Our objective is to describe the current prevalence and death of ischemic heart disease (IHD) in women of childbearing age (WCBA) at the global, regional, and national levels and to analyze its temporal trends from 1990 to 2019.

Methods

WCBA was defined as women aged 15–49 years. Estimates and 95% Uncertainty Intervals (UI) of IHD prevalence and death numbers for seven age groups were extracted from the 2019 Global Burden of Disease Study. The age-standardized prevalence and death rate (ASPR and ASDR) of IHD in WCBA was estimated using the direct age-standardization method. Joinpoint regression analysis was used to calculate average annual percent change (AAPC) to represent the temporal trends from 1990 to 2019.

Results

Between 1990 and 2019, the global ASPR of IHD experienced a 3.21% increase, culminating in 367.21 (95% UI, 295.74–430.16) cases per 100,000 individuals. Conversely, the ASDR decreased to 11.11 (95% UI, 10.10–12.30) per 100,000 individuals. In 2019, among the five sociodemographic index (SDI) regions, the highest ASPR was observed in the high-middle SDI region, whereas the highest ASDR was found in the low-middle SDI region. Regionally, the Caribbean reported the highest ASPR (563.11 per 100,000 individuals; 95% UI, 493.13–643.03), and Oceania reported the highest ASDR (20.20 per 100,000 individuals; 95% UI, 13.01–31.03). At the national level, Trinidad and Tobago exhibited the highest ASPR (730.15 per 100,000 individuals; 95% UI, 633.96–840.13), and the Solomon Islands had the highest ASDR (77.77 per 100,000 individuals; 95% UI, 47.80–121.19). Importantly, over the past three decades, the global ASPR has seen a significant increase [AAPC = 0.11%, 95% Confidence Interval (CI): 0.09–0.13; P < 0.001], while the ASDR has demonstrated a significant decreasing trend (AAPC = −0.86%, 95% CI: −1.11 to −0.61; P < 0.001). Air pollution, tobacco use, high systolic blood pressure, elevated body mass index, dietary risks, and high LDL cholesterol have been identified as the leading six risk factors for IHD-related deaths among WCBA in 2019.

Conclusions

Despite the significant decline in the global ASDR for IHD among WCBA over the last thirty years, the ASPR continues to escalate. We need to remain vigilant about the increased burden of IHD in WCBA. It calls for aggressive prevention strategies, rigorous control of risk factors, and the enhancement of healthcare coverage to mitigate the disease burden of IHD among WCBA in forthcoming years.
Prognostic value of pulmonary hypertension with a nomogram in acute myocardial infarction patients with reduced left ventricular function
Authors: Liu Qian , Zhao Changying , Dang Peizhu , Li Yongxin , Yan Yang
Published: April 2024

Background

Pulmonary hypertension (PH) is a common prognostic factor for acute myocardial infarction (AMI) and its impact may increase when combined with reduced left ventricular function.

Methods

This retrospective cohort study enrolled AMI patients with reduced left ventricular function at the First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to January 2022. Basing on the systolic pulmonary artery pressure assessed by echocardiogram, patients were assigned to the PH group and control group. Propensity score matching (PSM) in sex, age and Killip classification was used to match patients between two groups. The primary outcome was defined as 1-year mortality rate, which were obtained from medical records and phone calls.

Results

After the PSM, a total of 504 patients were enrolled, with 252 in both groups. No significant difference of the adjusted factors was observed between the two groups. The 1-year mortality rate was significantly higher in the PH group compared with the control group (15.5% vs. 5.3%, P < 0.001). In the cox regression analysis, PH (HR: 2.068, 95% CI: 1.028–4.161, P = 0.042) was identified as an independent risk factor, alongside left ventricular ejection fraction (HR: 0.948; 95% CI: 0.919–0.979; P < 0.001), creatine kinase-MB isoenzymes (HR: 1.002; 95% CI: 1.000–1.003; P = 0.010) and pro-brain natriuretic peptide (HR: 1.000; 95% CI: 1.000–1.000; P = 0.018) for the 1-year mortality in AMI patients with reduced left ventricular function. A nomogram was established using the above factors to predict the 1-year mortality risks in these patients.

Conclusion

AMI patients with reduced left ventricular function showed higher 1-year mortality rate when concomitant with PH. Four independent risk factors, including PH, were identified and used to establish a nomogram to predict the 1-year mortality risks in these patients.

Clinical Trials.gov ID

NCT06186713.
Case Report: Right aortic arch with isolation of left brachiocephalic artery and ventricular septal defect
Authors: Wang Gang , Wang Jieqiong , Zhang Hongjie , Wang Hui , Meng Qiang , Song Linhong , Zhou Gengxu
Published: April 2024

Right aortic arch with isolation of left brachiocephalic artery is a rare congenital aortic arch anomaly. Herein, we reported a case of this rare anomaly with ventricular septal defect in a 9-month-old infant. We successfully reconstructed the islolated left brachiocephalic artery and repaired the ventricular septal defect in one stage.
MyTrack+: Human-centered design of an mHealth app to support long-term weight loss maintenance
Authors: Chen Yu-Peng , Woodward Julia , Shankar Meena N. , Bista Dinank , Ugwoaba Umelo , Brockmann Andrea , Ross Kathryn M. , Ruiz Jaime , Anthony Lisa
Published: April 2024

A growing body of research has focused on the utility of adaptive intervention models for promoting long-term weight loss maintenance; however, evaluation of these interventions often requires customized smartphone applications. Building such an app from scratch can be resource-intensive. To support a novel clinical trial of an adaptive intervention for weight loss maintenance, we developed a companion app, MyTrack+, to pair with a main commercial app, FatSecret (FS), leveraging a user-centered design process for rapid prototyping and reducing software engineering efforts. MyTrack+ seamlessly integrates data from FS and the BodyTrace smart scale, enabling participants to log and self-monitor their health data, while also incorporating customized questionnaires and timestamps to enhance data collection for the trial. We iteratively refined the app by first developing initial mockups and incorporating feedback from a usability study with 17 university students. We further improved the app based on an in-the-wild pilot study with 33 participants in the target population, emphasizing acceptance, simplicity, customization options, and dual app usage. Our work highlights the potential of using an iterative human-centered design process to build a companion app that complements a commercial app for rapid prototyping, reducing costs, and enabling efficient research progress.
Diagnostic value of retinol-binding protein 4 in diabetic nephropathy: a systematic review and meta-analysis
Authors: Cao Xiaodan , Zhong Guanghui , Jin Tinglong , Hu Weijiao , Wang Jin , Shi Bo , Wei Renxiong
Published: April 2024

Objective

Diabetic nephropathy (DN) is a major microvascular complication of diabetes and the leading cause of end-stage renal disease. Early detection and prevention of DN are important. Retinol-binding protein 4 (RBP4) has been considered as a single diagnostic marker for the detection of renal impairment. However, the results have been inconsistent. The present meta-analysis aimed to determine the diagnostic potential of RBP4 in patients in type 2 diabetes mellitus (T2DM) with DN.

Methods

We searched PubMed, Web of Science, Embase, Wanfang and CNKI databases from inception until January 2024. The meta-analysis was performed by Stata version 15.0, and sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were pooled. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was utilized to assess the quality of each included study. In addition, heterogeneity and publication bias were evaluated.

Results

Twenty-nine studies were included in the meta-analysis. The pooled sensitivity and specificity were 0.76 [95% confidence interval (CI), 0.71–0.80] and 0.81 (95% CI, 0.76–0.85), respectively. The results showed a pooled PLR of 4.06 (95% CI, 3.16–5.21), NLR of 0.29 (95% CI, 0.24–0.36) and DOR of 13.76 (95% CI, 9.29–20.37). The area under the summarized receiver operating characteristic curve was given a value of 0.85 (95% CI, 0.82–0.88). No obvious publication bias existed in the Deeks’ funnel plot asymmetry test.

Conclusion

Our findings suggest that RBP4 has a promising diagnostic value with good sensitivity and specificity for patients with T2DM with DN.
Association between a metabolic score for insulin resistance and hypertension: results from National Health and Nutrition Examination Survey 2007–2016 analyses
Authors: Zeng Jing , Zhang Tingting , Yang Yan , Wang Jinjing , Zheng Dan , Hou Yanwei , Tong Ye , Fan Xiaojing , Wang Xuan , Fang Yi
Published: April 2024

Background

The Metabolic Score for Insulin Resistance (METS-IR) offers a promising and reliable non-insulin-based approach to assess insulin resistance and evaluate cardiometabolic risk. However, evidence for the association between METS-IR and hypertension was still limited.

Methods

Participants from the National Health and Nutrition Examination Survey (NHANES) database from 2007-2016 were selected for weighted multivariable regression analyses, subgroup analyses and restricted cubic spline (RCS) modeling to assess the association between the METS-IR and hypertension, as well as systolic blood pressure (SBP) and diastolic blood pressure (DBP).

Results

This study enrolled 7,721 adults aged ≥20 years, 2,926 (34.03%) of whom was diagnosed as hypertension. After adjusting for all potential covariates, an increased METS-IR (log2 conversion, denoted as log2METS-IR) was independently associated with a higher prevalence of hypertension (odd ratio [OR] 3.99, 95% confidence interval [CI] 3.19~5.01). The OR for hypertension in subjects with the highest quartile of METS-IR was 3.89-fold (OR 3.89, 95% CI 3.06~4.94) higher than that in those with the lowest quartile of METS-IR. This positive correlation became more significant as METS-IR increased (p for trend < 0.001). Log2METS-IR was significantly correlated with increase in SBP (β 6.75, 95% CI 5.65~7.85) and DBP (β 5.59, 95% CI 4.75~6.43) in a fully adjusted model. Consistent results were obtained in subgroup analyses. Hypertension, SBP and DBP all exhibited a non-linear increase with the rise in METS-IR. The minimal threshold for the beneficial association of METS-IR with hypertension, SBP and DBP were all identified to be 46.88.

Conclusion

The findings of this study revealed a significant positive association between METS-IR and hypertension among US adults, suggesting METS-IR as a potential tool for assessing hypertension risk.
Ash seedlings in a reciprocal transplant experiment—the extent of damage of mature forest stands affects ash offspring performance
Authors: Haupt Katharina S. , Mausolf Katharina , Lassen Jane , Music Pia , Schippmann Marei , Schrautzer Joachim , Erfmeier Alexandra
Published: April 2024

In past decades, ash dieback has caused a rapid decline of European ash (Fraxinus excelsior) in temperate forests of Europe. Numerous studies focus on mitigating the negative impacts of ash dieback to forest ecosystems or identifying resistant genotypes. The role of natural selection toward genotypes withstanding ash dieback for ash regeneration has been less frequently studied with experimental means to date. This is, however, necessary in times of global change, because the preservation of ash in Europe’s forests will depend, above all, on the adaptability of the future generations of ash trees. To quantify the extent and effects of ash dieback severity for ash regeneration we selected five forest stands moderately damaged and five forest stands highly damaged by ash dieback, in Schleswig-Holstein, Germany. We reciprocally transplanted naturally regenerated ash seedlings sampled in the field between these 10 sites. A shading treatment added to each half of the plots per site was meant to test for effects of altered light conditions in the herb layer due to canopy opening caused by ash dieback. With this approach, we tested seedling survival, performance and fungal infection for an interacting effect of origin and target site in regard to ash dieback severity and environmental factors over 2 years and recorded leaf traits (specific leaf area, leaf dry matter content) in the second year. Reduced light conditions under the shading nets had strong effects, influencing first year performance and infection probability as well as second year survival, growth and leaf trait characteristics. Soil conditions had only a marginal influence on transplanted seedlings. Transplantation direction between moderately and highly damaged sites affected infection marginally during the first year and survival as well as leaf traits significantly during the second year. Most notably, seedlings transplanted from moderately damaged to severely damaged sites exhibited the highest infection probability and lowest SLA, while seedlings transplanted vice versa were least likely to be infected and exhibited the highest SLA. Results hint at a first filtering effect by the ash dieback history of a forest stand and might indicate a transition from ecologically to evolutionary driven differentiation of ash seedling responses.
The efficacy and safety of short-term and low-dose IL-2 combined with tocilizumab to treat rheumatoid arthritis
Authors: Zhang Sheng-Xiao , Chen Hao-Ran , Wang Jia , Shao Hong-Fang , Cheng Ting , Pei Ruo-Meng , Su Qin-Yi , Zhang He-Yi , Li Xiao-Feng
Published: April 2024

Background

Immunotherapy targeting factors related to immune imbalance has been widely employed for RA treatment. This study aimed to evaluate the efficacy and safety of low-dose interleukin (IL)-2 combined with tocilizumab (TCZ), a biologics targeting IL-6, in RA patients.

Methods

Fifty adults with active RA who met the criteria with complete clinical data were recruited, and divided into three groups: control group (n=15), IL-2 group (n=26), and IL-2+TCZ group (n=9). In addition to basic treatment, participants in the IL-2 group received IL-2 (0.5 MIU/day), while participants in the IL-2+TCZ group received IL-2 (0.5 MIU/day) along with one dose of TCZ (8 mg/kg, maximum dose: 800 mg). All subjects underwent condition assessment, laboratory indicators and safety indicators detection, and records before treatment and one week after treatment.

Results

Compared with the baseline, all three groups showed significant improvement in disease conditions, as evidenced by significantly reduced disease activity indicators. The low-dose IL-2 and combination treatment groups demonstrated a violent proliferation of Tregs, while the absolute number of Th1, Th2, and Th17 cells in the latter group showed a decreasing trend. The decrease in the Th17/Treg ratio was more pronounced in the IL-2+TCZ groups. No significant adverse reactions were observed in any of the patients.

Conclusion

Exogenous low doses of IL-2 combined TCZ were found to be safe and effective in reducing effector T cells and appropriately increasing Treg levels in RA patients with high effector T cell levels. This approach helps regulate immune homeostasis and contributes to the prevention of disease deterioration.

Clinical trial registration

https://www.chictr.org.cn/showprojEN.html?proj=13909, identifier ChiCTR-INR-16009546.
Enhanced gut microbiome supplementation of essential amino acids in Diploptera punctata fed low-protein plant-based diet
Authors: Ayayee Paul A. , Petersen Nick , Riusch Jennifer , Rauter Claudia , Larsen Thomas
Published: April 2024

Introduction

Building on our previous work, we investigate how dietary shifts affect gut microbial essential amino acid (EAA) provisioning in the lactating cockroach Diploptera punctata.

Method

To that end, we fed cockroaches three distinct diets: a plant-only Gari diet composed of starchy and granulated root tuber Yucca (Manihot esculenta), a dog food diet (DF), and a cellulose-amended dog food (CADF) diet. We anticipated that the high carbohydrate, low protein Gari would highlight increased microbial EAA supplementation to the host.

Results

By day 28, we observed distinct profiles of 14 bacterial families in the insect gut microbiomes of the three dietary groups. CADF-fed insects predominantly harbored cellulolytic and nitrogen-fixing bacteria families Streptococcaceae and Xanthomonadaceae. In contrast, Gari-fed insects were enriched in anaerobic lignocellulolytic bacteria families Paludibacteraceae and Dysgonomonadaceae, while DF-fed insects had a prevalence of proteolytic anaerobes Williamwhitmaniaceae and sulfate-reducing bacteria Desulfovibrionaceae. Furthermore, we confirmed significantly higher EAA supplementation in Gari-fed insects than in non-Gari-fed insects based on δ13C-EAA offsets between insect and their diets. The δ13C-EAA offsets between DF and CADF were nearly indistinguishable, highlighting the relevance of using the plant-based Gari in this experiment to unequivocally demonstrate this function in this insect. These results were underscored by lower standard metabolic rate (SMR) relative to the DF insect in Gari-fed (intermediate SMR and dietary quality) and CADF (least SMR and dietary quality) insects.

Discussion

The influence of diet on EAA provisioning and SMR responses in insects underscores the need for further exploration into the role of gut microbial functions in modulating metabolic responses
Zinc oxide nanoparticles mediate bacterial toxicity in Mueller-Hinton Broth via Zn2+
Authors: Caron Alexander J. , Ali Iman J. , Delgado Michael J. , Johnson Dustin , Reeks John M. , Strzhemechny Yuri M. , McGillivray Shauna M.
Published: April 2024

As antibiotic resistance increases and antibiotic development dwindles, new antimicrobial agents are needed. Recent advances in nanoscale engineering have increased interest in metal oxide nanoparticles, particularly zinc oxide nanoparticles, as antimicrobial agents. Zinc oxide nanoparticles are promising due to their broad-spectrum antibacterial activity and low production cost. Despite many studies demonstrating the effectiveness of zinc oxide nanoparticles, the antibacterial mechanism is still unknown. Previous work has implicated the role of reactive oxygen species such as hydrogen peroxide, physical damage of the cell envelope, and/or release of toxic Zn2+ ions as possible mechanisms of action. To evaluate the role of these proposed methods, we assessed the susceptibility of S. aureus mutant strains, ΔkatA and ΔmprF, to zinc oxide nanoparticles of approximately 50 nm in size. These assays demonstrated that hydrogen peroxide and electrostatic interactions are not crucial for mediating zinc oxide nanoparticle toxicity. Instead, we found that Zn2+ accumulates in Mueller-Hinton Broth over time and that removal of Zn2+ through chelation reverses this toxicity. Furthermore, we found that the physical separation of zinc oxide nanoparticles and bacterial cells using a semi-permeable membrane still allows for growth inhibition. We concluded that soluble Zn2+ is the primary mechanism by which zinc oxide nanoparticles mediate toxicity in Mueller-Hinton Broth. Future work investigating how factors such as particle morphology (e.g., size, polarity, surface defects) and media contribute to Zn2+ dissolution could allow for the synthesis of zinc oxide nanoparticles that possess chemical and morphological properties best suited for antibacterial efficacy.
Genetic markers associated with ferroptosis in Alzheimer’s disease
Authors: Sun Yuting , Xiao Yu , Tang Qin , Chen Wei , Lin Lu
Published: April 2024

Objective

Ferroptosis is implicated in the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and vascular dementia, implying that it may have a regulatory effect on the progression of these diseases. However, the specific role of ferroptosis-related genes (FRGs) in Alzheimer’s disease (AD) is not yet fully understood. The aim of the study was to detect ferroptosis related genes with regulatory functions in the disease and explore potential mechanisms in AD.

Methods

Hub FRGs were obtained through multiple algorithms based on the GSE5281 dataset. The screening process was implemented by R packages including limma, WGCNA, glm and SVM-RFE. Gene Ontology classification and pathway enrichment analysis were performed based on FRGs. Biological processes involved with hub FRGs were investigated through GSVA and GSEA methods. Immune infiltration analysis was performed by the R package CIBERSORT. Receiver operating characteristic curve (ROC) was utilized to validate the accuracy of hub FRGs. The CeRNA network attempted to find non-coding RNA transcripts which may play a role in disease progression.

Results

DDIT4, MUC1, KLHL24, CD44, and RB1 were identified as hub FRGs. As later revealed by enrichment analysis, the hub FRGs had important effects on AD through involvement in diverse AD pathogenesis-related pathways such as autophagy and glutathione metabolism. The immune microenvironment in AD shows increased numbers of resting NK cells, macrophages, and mast cells, with decreased levels of CD8 T cells when compared to healthy samples. Regulatory T cells were positively correlated with MUC1, KLHL24, and DDIT4 expression, while RB1 showed negative correlations with eosinophils and CD8 T cells, suggesting potential roles in modulating the immune environment in AD.

Conclusion

Our research has identified five hub FRGs in AD. We concluded that ferroptosis may be involved in the disease.
Detection of elevated levels of PINK1 in plasma from patients with idiopathic Parkinson’s disease
Authors: Hong Xianchai , Zheng Yi , Hou Jialong , Jiang Tao , Lu Yao , Wang Wenwen , Zhou Shuoting , Ye Qianqian , Xie Chenglong , Li Jia
Published: April 2024

Backgrounds

Numerous lines of evidence support the intricate interplay between Parkinson’s disease (PD) and the PINK1-dependent mitophagy process. This study aimed to evaluate differences in plasma PINK1 levels among idiopathic PD, PD syndromes (PDs), and healthy controls.

Methods

A total of 354 participants were included, consisting of 197 PD patients, 50 PDs patients, and 107 healthy controls were divided into two cohorts, namely the modeling cohort (cohort 1) and the validated cohort (cohort 2). An enzyme-linked immunosorbent assay (ELISA)-based analysis was performed on PINK1 and α-synuclein oligomer (Asy-no). The utilization of the area under the curve (AUC) within the receiver-operating characteristic (ROC) curves served as a robust and comprehensive approach to evaluate and quantify the predictive efficacy of plasma biomarkers alone, as well as combined models, in distinguishing PD patients from controls.

Results

PINK1 and Asy-no were elevated in the plasma of PD and PDs patients compared to healthy controls. The AUCs of PINK1 (0.771) and Asy-no (0.787) were supposed to be potentially eligible plasma biomarkers differentiating PD from controls but could not differentiate PD from PDs. Notably, the PINK + Asy-no + Clinical RBD model showed the highest performance in the modeling cohort and was comparable with the PINK1 + Clinical RBD in the validation cohort. Moreover, there is no significant correlation between PINK1 and UPDRS, MMSE, HAMD, HAMA, RBDQ-HK, and ADL scores.

Conclusion

These findings suggest that elevated PINK1 in plasma holds the potential to serve as a non-invasive tool for distinguishing PD patients from controls. Moreover, the outcomes of our investigation lend support to the plausibility of implementing a feasible blood test in future clinical translation.
Modeling sporadic juvenile ALS in iPSC-derived motor neurons explores the pathogenesis of FUSR503fs mutation
Authors: Chen Li , Chen Guojie , Zhang Mengting , Zhang Xiaojie
Published: April 2024

Introduction

Fused in sarcoma (FUS) mutations represent the most common genetic etiology of juvenile amyotrophic lateral sclerosis (JALS), for which effective treatments are lacking. In a prior report, we identified a novel FUS mutation, c.1509dupA: p. R503fs (FUSR503fs), in a sporadic JALS patient.

Methods

The physicochemical properties and structure of FUSR503fs protein were analyzed by software: Multi-electrode array (MEA) assay, calcium activity imaging assay and transcriptome analysis were used to explore the pathophysiological mechanism of iPSC derived motor neurons.

Results

Structural analysis and predictions regarding physical and chemical properties of this mutation suggest that the reduction of phosphorylation and glycosylation sites, along with alterations in the amino acid sequence, may contribute to abnormal FUS accumulation within the cytoplasm and nucleus of induced pluripotent stem cell– derived motor neurons (MNs). Multi-electrode array and calcium activity imaging indicate diminished spontaneous electrical and calcium activity signals in MNs harboring the FUSR503fs mutation. Transcriptomic analysis reveals upregulation of genes associated with viral infection and downregulation of genes involved in neural function maintenance, such as the ATP6V1C2 gene. Treatment with ropinirole marginally mitigates the electrophysiological decline in FUSR503fs MNs, suggesting the utility of this cell model for mechanistic exploration and drug screening.

Discussion

iPSCs-derived motor neurons from JALS patients are promising tools for drug screening. The pathological changes in motor neurons of FUSR503fs may occur earlier than in other known mutation types that have been reported.
A conceptual framework for a neurophysiological basis of art therapy for PTSD
Authors: Malhotra Bani , Jones Laura C. , Spooner Heather , Levy Charles , Kaimal Girija , Williamson John B.
Published: April 2024

Post-traumatic stress disorder (PTSD) is a heterogeneous condition that affects many civilians and military service members. Lack of engagement, high dropout rate, and variable response to psychotherapy necessitates more compelling and accessible treatment options that are based on sound neuroscientific evidence-informed decision-making. Art therapy incorporates elements proven to be effective in psychotherapy, such as exposure, making it a potentially valuable treatment option. This conceptual paper aims to inform the neurophysiological rationale for the use of art therapy as a therapeutic approach for individuals with PTSD. A narrative synthesis was conducted using literature review of empirical research on the neurophysiological effects of art therapy, with supporting literature on neuroaesthetics and psychotherapies to identify art therapy factors most pertinent for PTSD. Findings were synthesized through a proposed framework based on the triple network model considering the network-based dysfunctions due to PTSD. Art therapy’s active components, such as concretization and metaphor, active art engagement, emotion processing and regulation, perspective taking and reframing, and therapeutic alliance, may improve symptoms of PTSD and prompt adaptive brain functioning. Given the scarcity of rigorous studies on art therapy’s effectiveness and mechanisms of alleviating PTSD symptoms, the suggested framework offers a neurophysiological rationale and a future research agenda to investigate the impact of art therapy as a therapeutic approach for individuals with PTSD.
RFWD3 modulates response to platinum chemotherapy and promotes cancer associated phenotypes in high grade serous ovarian cancer
Authors: Taylor Sarah J. , Hollis Robert L. , Gourley Charlie , Herrington C. Simon , Langdon Simon P. , Arends Mark J.
Published: April 2024

Background

DNA damage repair is frequently dysregulated in high grade serous ovarian cancer (HGSOC), which can lead to changes in chemosensitivity and other phenotypic differences in tumours. RFWD3, a key component of multiple DNA repair and maintenance pathways, was investigated to characterise its impact in HGSOC.

Methods

RFWD3 expression and association with clinical features was assessed using in silico analysis in the TCGA HGSOC dataset, and in a further cohort of HGSOC tumours stained for RFWD3 using immunohistochemistry. RFWD3 expression was modulated in cell lines using siRNA and CRISPR/cas9 gene editing, and cells were characterised using cytotoxicity and proliferation assays, flow cytometry, and live cell microscopy.

Results

Expression of RFWD3 RNA and protein varied in HGSOCs. In cell lines, reduction of RFWD3 expression led to increased sensitivity to interstrand crosslinking (ICL) inducing agents mitomycin C and carboplatin. RFWD3 also demonstrated further functionality outside its role in DNA damage repair, with RFWD3 deficient cells displaying cell cycle dysregulation, reduced cellular proliferation and reduced migration. In tumours, low RFWD3 expression was associated with increased tumour mutational burden, and complete response to platinum chemotherapy.

Conclusion

RFWD3 expression varies in HGSOCs, which can lead to functional effects at both the cellular and tumour levels.
Incidence and seasonality of Kawasaki disease in children in the Philippines, and its association with ambient air temperature
Authors: Celis-Seposo Aden Kay , Madaniyazi Lina , Seposo Xerxes , Hashizume Masahiro , Yoshida Lay Myint , Toizumi Michiko
Published: April 2024

Background

Despite an unknown cause, Kawasaki disease (KD) is currently the primary leading cause of acquired heart disease in developed countries in children and has been increasing in recent years. Research efforts have explored environmental factors related to KD, but they are still unclear especially in the tropics. We aimed to describe the incidence of KD in children, assess its seasonality, and determine its association with ambient air temperature in the National Capital Region (NCR), Philippines from January 2009 to December 2019.

Methods

Monthly number of KD cases from the Philippine Pediatric Society (PPS) disease registry was collected to determine the incidence of KD. A generalized linear model (GLM) with quasi-Poisson regression was utilized to assess the seasonality of KD and determine its association with ambient air temperature after adjusting for the relevant confounders.

Results

The majority of KD cases (68.52%) occurred in children less than five years old, with incidence rates ranging from 14.98 to 23.20 cases per 100,000 population, and a male-to-female ratio of 1.43:1. Seasonal variation followed a unimodal shape with a rate ratio of 1.13 from the average, peaking in March and reaching the lowest in September. After adjusting for seasonality and long-term trend, every one-degree Celsius increase in the monthly mean temperature significantly increased the risk of developing KD by 8.28% (95% CI: 2.12%, 14.80%). Season-specific analysis revealed a positive association during the dry season (RR: 1.06, 95% CI: 1.01, 1.11), whereas no evidence of association was found during the wet season (RR: 1.10, 95% CI: 0.95, 1.27).

Conclusion

We have presented the incidence of KD in the Philippines which is relatively varied from its neighboring countries. The unimodal seasonality of KD and its linear association with temperature, independent of season and secular trend, especially during dry season, may provide insights into its etiology and may support enhanced KD detection efforts in the country.
TCM targets ferroptosis: potential treatments for cancer
Authors: Qin Liwen , Zhong Yuhan , Li Yi , Yang Yongfeng
Published: April 2024

Ferroptosis is caused by the accumulation of cellular reactive oxygen species that exceed the antioxidant load that glutathione (GSH) and phospholipid hydroperoxidases with GSH-based substrates can carry When the antioxidant capacity of cells is reduced, lipid reactive oxygen species accumulate, which can cause oxidative death. Ferroptosis, an iron-dependent regulatory necrosis pathway, has emerged as a new modality of cell death that is strongly associated with cancer. Surgery, chemotherapy and radiotherapy are the main methods of cancer treatment. However, resistance to these mainstream anticancer drugs and strong toxic side effects have forced the development of alternative treatments with high efficiency and low toxicity. In recent years, an increasing number of studies have shown that traditional Chinese medicines (TCMs), especially herbs or herbal extracts, can inhibit tumor cell growth and metastasis by inducing ferroptosis, suggesting that they could be promising agents for cancer treatment. This article reviews the current research progress on the antitumor effects of TCMs through the induction of ferroptosis. The aim of these studies was to elucidate the potential mechanisms of targeting ferroptosis in cancer, and the findings could lead to new directions and reference values for developing better cancer treatment strategies.
Characterisation of highly irradiated 3D trench silicon pixel sensors for 4D tracking with 10 ps timing accuracy
Authors: Borgato F. , Cardini A. , Cossu G. M. , Dalla Betta G. F. , Garau M. , La Delfa L. , Lai A. , Lampis A. , Loi A. , Obertino M. M. , Simi G. , Vecchi S.
Published: April 2024

3D trench silicon pixel sensors, recently developed by the TimeSPOT collaboration, have shown excellent performance in terms of spatial resolution, timing precision and detection efficiency. The combination of these three features make them one of the best candidate for inner tracking detectors operating in high luminosity hadron colliders experiments. This article presents systematic characterisations of these devices made with minimum ionising particles on irradiated sensors with neutrons up to 2.5 ⋅ 1016 1 MeV neq cm−2. The results show that 3D trench pixels have extremely high resistance to radiation. The measured time resolution and the detection efficiency of irradiated sensors match those of non-irradiated ones if a slightly higher bias voltage, few tens of Volts, is applied to the pixels. As of today, 3D trench pixels are the only sensors capable of achieving 10 ps time resolution after being irradiated at extremely high fluences, extending by far the capabilities of future tracking systems of HEP experiments operating under extreme conditions.
Proof-of-concept model for instantaneous heart rate-drift correction during low and high exercise exertion
Authors: Papini Gabriele B. , Bonomi Alberto G. , Sartor Francesco
Published: April 2024

Introduction: This study aimed to model below and above anaerobic threshold exercise-induced heart rate (HR) drift, so that the corrected HR could better represent V̇O2 kinetics during and after the exercise itself.

Methods: Fifteen healthy subjects (age: 28 ± 5 years; V̇O2Max: 50 ± 8 mL/kg/min; 5 females) underwent a maximal and a 30-min submaximal (80% of the anaerobic threshold) running exercises. A five-stage computational (i.e., delay block, new training impulse-calculation block, Sigmoid correction block, increase block, and decrease block) model was built to account for instantaneous HR, fitness, and age and to onset, increase, and decrease according to the exercise intensity and duration.

Results: The area under the curve (AUC) of the hysteresis function, which described the differences in the maximal and submaximal exercise-induced V̇O2 and HR kinetics, was significantly reduced for both maximal (26%) and submaximal (77%) exercises and consequent recoveries.

Discussion: In conclusion, this model allowed HR drift instantaneous correction, which could be exploited in the future for more accurate V̇O2 estimations.
Detection and identification of plant leaf diseases using YOLOv4
Authors: Aldakheel Eman Abdullah , Zakariah Mohammed , Alabdalall Amira H.
Published: April 2024

Detecting plant leaf diseases accurately and promptly is essential for reducing economic consequences and maximizing crop yield. However, farmers’ dependence on conventional manual techniques presents a difficulty in accurately pinpointing particular diseases. This research investigates the utilization of the YOLOv4 algorithm for detecting and identifying plant leaf diseases. This study uses the comprehensive Plant Village Dataset, which includes over fifty thousand photos of healthy and diseased plant leaves from fourteen different species, to develop advanced disease prediction systems in agriculture. Data augmentation techniques including histogram equalization and horizontal flip were used to improve the dataset and strengthen the model’s resilience. A comprehensive assessment of the YOLOv4 algorithm was conducted, which involved comparing its performance with established target identification methods including Densenet, Alexanet, and neural networks. When YOLOv4 was used on the Plant Village dataset, it achieved an impressive accuracy of 99.99%. The evaluation criteria, including accuracy, precision, recall, and f1-score, consistently showed high performance with a value of 0.99, confirming the effectiveness of the proposed methodology. This study’s results demonstrate substantial advancements in plant disease detection and underscore the capabilities of YOLOv4 as a sophisticated tool for accurate disease prediction. These developments have significant significance for everyone involved in agriculture, researchers, and farmers, providing improved capacities for disease control and crop protection.
Detection of maize stem diameter by using RGB-D cameras’ depth information under selected field condition
Authors: Zhou Jing , Cui Mingren , Wu Yushan , Gao Yudi , Tang Yijia , Jiang Bowen , Wu Min , Zhang Jian , Hou Lixin
Published: April 2024

Stem diameter is a critical phenotypic parameter for maize, integral to yield prediction and lodging resistance assessment. Traditionally, the quantification of this parameter through manual measurement has been the norm, notwithstanding its tedious and laborious nature. To address these challenges, this study introduces a non-invasive field-based system utilizing depth information from RGB-D cameras to measure maize stem diameter. This technology offers a practical solution for conducting rapid and non-destructive phenotyping. Firstly, RGB images, depth images, and 3D point clouds of maize stems were captured using an RGB-D camera, and precise alignment between the RGB and depth images was achieved. Subsequently, the contours of maize stems were delineated using 2D image processing techniques, followed by the extraction of the stem’s skeletal structure employing a thinning-based skeletonization algorithm. Furthermore, within the areas of interest on the maize stems, horizontal lines were constructed using points on the skeletal structure, resulting in 2D pixel coordinates at the intersections of these horizontal lines with the maize stem contours. Subsequently, a back-projection transformation from 2D pixel coordinates to 3D world coordinates was achieved by combining the depth data with the camera’s intrinsic parameters. The 3D world coordinates were then precisely mapped onto the 3D point cloud using rigid transformation techniques. Finally, the maize stem diameter was sensed and determined by calculating the Euclidean distance between pairs of 3D world coordinate points. The method demonstrated a Mean Absolute Percentage Error (MAPE) of 3.01%, a Mean Absolute Error (MAE) of 0.75 mm, a Root Mean Square Error (RMSE) of 1.07 mm, and a coefficient of determination (R²) of 0.96, ensuring accurate measurement of maize stem diameter. This research not only provides a new method of precise and efficient crop phenotypic analysis but also offers theoretical knowledge for the advancement of precision agriculture.
A systematic review of midwives’ training needs in perinatal mental health and related interventions
Authors: Dubreucq Marine , Dupont Corinne , Lambregtse-Van den Berg Mijke P. , Bramer Wichor M. , Massoubre Catherine , Dubreucq Julien
Published: April 2024

Background

Midwives may be key stakeholders to improve perinatal mental healthcare (PMHC). Three systematic reviews considered midwives’ educational needs in perinatal mental health (PMH) or related interventions with a focus on depression or anxiety. This systematic review aims to review: 1) midwives’ educational/training needs in PMH; 2) the training programs in PMH and their effectiveness in improving PMHC.

Methods

We searched six electronic databases using a search strategy designed by a biomedical information specialist. Inclusion criteria were: (1) focus on midwives; (2) reporting on training needs in PMH, perinatal mental health problems or related conditions or training programs; (3) using quantitative, qualitative or mixed-methods design. We used the Mixed Methods Appraisal Tool for study quality.

Results

Of 4969 articles screened, 66 papers met eligibility criteria (47 on knowledge, skills or attitudes and 19 on training programs). Study quality was low to moderate in most studies. We found that midwives’ understanding of their role in PMHC (e.g. finding meaning in opening discussions about PMH; perception that screening, referral and support is part of their routine clinical duties) is determinant. Training programs had positive effects on proximal outcomes (e.g. knowledge) and contrasted effects on distal outcomes (e.g. number of referrals).

Conclusions

This review generated novel insights to inform initial and continuous education curriculums on PMH (e.g. focus on midwives’ understanding on their role in PMHC or content on person-centered care).

Registration details

The protocol is registered on PROSPERO (CRD42021285926)
Case report: Intensive online trauma treatment combining prolonged exposure and EMDR 2.0 in a patient with severe and chronic PTSD
Authors: Matthijssen Suzy J. M. A. , Menses Sophie D. F.
Published: April 2024

Introduction

Short and intensive trauma treatment programs seem promising in treating post-traumatic stress disorder (PTSD). However, little is known about the effects performing these types of intensive treatment programs online.

Method

At the Altrecht Academic Anxiety Centre, an in person intensive trauma focused treatment of six days (three consecutive days in two weeks) was altered into a fully online treatment. A treatment day consisted of 90 minutes of prolonged exposure, 60 minutes of exercise, 90 minutes of Eye Movement Desensitization and Reprocessing (EMDR) 2.0 and 60 minutes of psychoeducation. Mary, a patient diagnosed with chronic and severe PTSD, chronic depressive disorder (single episode, moderate to severe), a panic disorder, and an other specified personality disorder was the first patient to take part in this intensive online trauma treatment.

Results

Mary reached full remission of PTSD. The PTSD symptoms (measured on both the clinician-administered PTSD scale for DSM-5, CAPS-5 and The PTSD Checklist for DSM-5, PCL-5) showed maximum improvement and were completely absent during one month and six month follow-up. Moreover, she no longer suffered from severe depressive symptoms and did not report any general psychiatric symptoms (measured with the Beck Depression Inventory version 2, BDI-II and the Brief Symptom Inventory, BSI).

Conclusion

In conclusion, the case-report demonstrates that intensive trauma treatment online was successful in this specific case, thereby being a ‘proof of concept’ that intensive trauma treatment online is feasible. It might be promising for patients with severe and chronic PTSD and comorbid psychiatric disorders. However, further research must show if the results of this specific case can be translated to other patients with severe and chronic PTSD and comorbid psychiatric disorders.
Exploring patterns in mental health treatment and interests of single adults in the United States: a secondary data analysis
Authors: Gesselman Amanda N. , Kaufman Ellen M. , Weeks Lee Y. S. , Moscovici Zoe , Bennett-Brown Margaret , Adams Olivia R. , Campbell Jessica T. , Piazza Malia , Bhuyan Lucy , Dubé Simon , Hille Jessica J. , Garcia Justin R.
Published: April 2024

Objective

The objective of this study is to examine mental health treatment utilization and interest among the large and growing demographic of single adults in the United States, who face unique societal stressors and pressures that may contribute to their heightened need for mental healthcare.

Method

We analyzed data from 3,453 single adults, focusing on those with possible mental health treatment needs by excluding those with positive self-assessments. We assessed prevalence and sociodemographic correlates of mental health treatment, including psychotherapy and psychiatric medication use, and interest in attending psychotherapy among participants who had never attended.

Results

26% were in mental health treatment; 17% were attending psychotherapy, 16% were taking psychiatric medications, and 7% were doing both. Further, 64% had never attended psychotherapy, of which 35% expressed interest in future attendance. There were differences in current psychotherapy attendance and psychiatric medication use by gender and sexual orientation, with women and gay/lesbian individuals more likely to engage in both forms of mental health treatment. Additionally, interest in future psychotherapy among those who had never attended varied significantly by age, gender, and race. Younger individuals, women, and Black/African-American participants showed higher likelihoods of interest in psychotherapy.

Conclusion

Our research highlights a critical gap in mental health treatment utilization among single adults who may be experiencing a need for those services. Despite a seemingly higher likelihood of engagement in mental health treatment compared to the general population, only a minority of single adults in our sample were utilizing mental health treatment. This underutilization and the observed demographic disparities in mental health treatment underscore the need for targeted outreach, personalized treatment plans, enhanced provider training, and policy advocacy to ensure equitable access to mental healthcare for single adults across sociodemographic backgrounds.