bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing the feasibility of coral nurseries in an upwelling area in the North Pacific of Costa Rica
Authors: Fabregat-Malé Sònia , Mena-González Sebastián , Quesada-Perez Fabio , Alvarado Juan José
Published: September 2024

The decline of coral reefs has increased interest in ecological restoration. Due to the scarcity of coral gardening projects in the Eastern Tropical Pacific, improving our understanding of such techniques is key. We report the results of coral gardening using the branching Pocillopora spp. and massive coral species (Pavona gigantea, Pavona clavus and Porites lobata) in an upwelling area in Costa Rica. We examined whether nursery type influenced Pocillopora spp. survival and growth, and how environmental conditions shaped restoration. We monitored the survival and growth of Pocillopora spp. fragments (n = 334) and microfragments of massive species (P. gigantea [n = 148], P. clavus [n = 37], P. lobata [n = 66]) over 11 months. Survival at the end of the gardening period was 51% for Pocillopora spp., 59% for P. clavus, 55% for P. gigantea, and 17% for P. lobata, with a decline after a cease in maintenance caused by the COVID-19 lockdown. Pocillopora spp. fragments in the floating nurseries exhibited higher growth (7.52 ± 1.98 and 6.64 ± 2.91 cm yr-1) than in the A-frame (4.16 ± 2.35 cm yr-1), which suggests the benefits of suspending fragments. For massive microfragments coral growth was 1.92-4.66 cm2 yr-1 and were affected by pigmentation loss, causing partial tissue loss and mortality. Our results point towards acclimation to local conditions, and show the need to develop site-specific cost-efficient gardening techniques for massive species, allowing for a multi-species approach to ensure long-term ecosystem recovery.
Revisiting historical trends in the Eastern Boundary Upwelling Systems with a machine learning method
Authors: Bustos David F. , Narváez Diego A. , Dewitte Boris , Oerder Vera , Vidal Mabel , Tapia Fabián
Published: September 2024

Eastern boundary upwelling systems (EBUS) host very productive marine ecosystems that provide services to many surrounding countries. The impact of global warming on their functioning is debated due to limited long-term observations, climate model uncertainties, and significant natural variability. This study utilizes the usefulness of a machine learning technique to document long-term variability in upwelling systems from 1993 to 2019, focusing on high-frequency synoptic upwelling events. Because the latter are modulated by the general atmospheric and oceanic circulation, it is hypothesized that changes in their statistics can reflect fluctuations and provide insights into the long-term variability of EBUS. A two-step approach using Self-Organizing Maps (SOM) and Hierarchical Agglomerative Clustering (HAC) algorithms was employed. These algorithms were applied to sets of upwelling events to characterize signatures in sea-level pressure, meridional wind, shortwave radiation, sea-surface temperature (SST), and Ekman pumping based on dominant spatial patterns. Results indicated that the dominant spatial pattern, accounting for 56%-75% of total variance, representing the seasonal pattern, due to the marked seasonality in along-shore wind activity. Findings showed that, except for the Canary-Iberian region, upwelling events have become longer in spring and more intense in summer. Southern Hemisphere systems (Humboldt and Benguela) had a higher occurrence of upwelling events in summer (up to 0.022 Events/km²) compared to spring (<0.016 Events/km²), contrasting with Northern Hemisphere systems (<0.012 Events/km²). Furthermore, long-term changes in dominant spatial patterns were examined by dividing the time period in approximately two equally periods, to compare past changes (1993-2006) with relatively new changes (2007-2019), revealing shifts in key variables. These included poleward shifts in subtropical high-pressure systems (SHPS), increased upwelling-favorable winds, and SST drops towards higher latitudes. The Humboldt Current System (HumCS) exhibited a distinctive spring-to-summer pattern, with mid-latitude meridional wind weakening and concurrent SST decreases. Finally, a comparison of upwelling centers within EBUS, focusing on changes in pressure and temperature gradients, meridional wind, mixed-layer depth, zonal Ekman transport, and Ekman pumping, found no evidence supporting Bakun’s hypothesis. Temporal changes in these metrics varied within and across EBUS, suggesting differential impacts and responses in different locations.
The causal association between gut microbiota and postpartum depression: a two-sample Mendelian randomization study
Authors: Jin Wenjun , Li Bo , Wang Lijun , Zhu Lin , Chai Songhao , Hou Rui
Published: September 2024

Background

An escalating body of clinical trials and observational studies hints at a plausible link between gut flora and postpartum depression (PPD). The definitive causal dynamics between these two entities remain shrouded in ambiguity. Therefore, in this study, we employed the two-sample Mendelian randomization approach to ascertain the causal link between gut microbiota and PPD.

Methods

Summary-level GWAS data related to the human gut microbiota were obtained from the international consortium MiBioGen and the Dutch Microbiome Project (species). For PPD, GWAS data were derived from the FinnGen biobank, consisting 57,604 cases and 596,601 controls. The inverse variance weighted method (IVW) as the cornerstone of our analytical approach. Subsequent to this, a comprehensive suite of tests for pleiotropy and heterogeneity were conducted to ensure the reliability and robustness of our findings.

Results

We identified 12 bacterial taxa associated with the risk of PPD. Veillonellaceae, Ruminococcaceae UCG 011, Bifidobacterium adolescentis, Paraprevotella clara, Clostridium leptum, Eubacterium siraeum, Coprococcus catus exhibited an inversely associated with the risk of PPD. Alphaproteobacteria, Roseburia, FamilyXIIIAD3011group, Alistipes onderdonkii, Bilophila wadsworthia showed a positive correlation with the risk of PPD.

Limitations

The GWAS data derived from the MiBioGen consortium, DMP, and FinnGen consortium, may introduce selection bias. Moreover, the data primarily originates from European populations, hence extrapolating these results to diverse populations should be approached with caution. The etiological factors behind PPD remain enigmatic, alluding to the existence of potential undisclosed confounders.

Conclusion

Based on this MR analysis, we found a causal relationship between certain gut microbial communities and PPD. Future clinical studies can further explore the treatment of PPD through the combined use of microorganisms. This not only offers insights into the pathogenesis of PPD but also lays the foundation for utilizing gut microbiota as biotherapeutics in treating neurological disorders.
Molecular dynamics simulation of the brain-isolated single-domain antibody/nanobody from camels through in vivo phage display screening
Authors: Hasannejad-Asl Behnam , Hashemzadeh Hassan , Pooresmaeil Farkhondeh , Dabiri Mehran , Pooresmaeil Mohammad-Reza , Ahmadvand Davoud , Hosseini Arshad
Published: September 2024

Introduction

During the last decade, there has been a significant rise in the use of therapeutic antibodies or passive immunotherapy for treating various conditions like inflammation and cancer. However, these proteins face challenges reaching the brain and often require specialized delivery methods such as single-domain antibodies (sdAbs). Traditional antibodies struggle to efficiently cross the blood-brain barrier (BBB), hindering their effectiveness. Receptor-mediated transcytosis (RMT) offers a promising pathway for transporting large molecules essential for brain function and treatment across the BBB.

Methods

SdAbs and peptide ligands with an affinity for RMT receptors are commonly employed to enhance the transport of biotherapeutics compounds across the BBB. This research used a sdAbs phage-displayed library from 13 camelus dromedarius samples to identify sdABs that specifically bind to and are internalized by human BBB endothelial cells (ECs) through in vivo panning.

Results and discussion

One sdAb, defined as FB24, was isolated, sequenced, translated into an open reading frame (ORF), and subjected to three-dimensional (3D) modeling. Molecular docking and molecular dynamics simulations were carried out by the HADDOCK web server and GROMACS, respectively, to evaluate the interaction between FB24 and EC receptors in silico. The docking results revealed that FB24 exhibited binding activity against potential EC receptors with −1.7 to −2.7 ranged z score and maintained a stable structure. The docked complex of FB24-RAGE (receptor for advanced glycation end products, also known as advanced glycation end product receptor [AGER]) showed 18 hydrogen bonds and 213 non-bonded contacts. It was chosen for further analysis by molecular dynamics simulations by GROMACS. This complex showed a stable condition, and its root mean square deviation (RMSD) was 0.218 nm. The results suggest that FB24 could serve as a suitable carrier vector for transporting therapeutic and diagnostic agents across the BBB to the brain through a non-invasive route.
Development and validation of a nomogram for predicting advanced liver fibrosis in patients with chronic hepatitis B
Authors: Han Kexing , Wang Jianfeng , Song Xizhen , Kang Luyang , Lin Junjie , Hu Qinggang , Sun Weijie , Gao Yufeng
Published: September 2024

Background

The progression of chronic hepatitis B (CHB) to liver fibrosis and even cirrhosis is often unknown to patients, but noninvasive markers capable of effectively identifying advanced liver fibrosis remains absent.

Objective

Based on the results of liver biopsy, we aimed to construct a new nomogram to validate the stage of liver fibrosis in CHB patients by the basic information of CHB patients and routine laboratory tests.

Methods

Patients with CHB diagnosed for the first time in the First Affiliated Hospital of Anhui Medical University from 2010 to 2018 were selected, and their basic information, laboratory tests and liver biopsy information were collected. Eventually, 974 patients were enrolled in the study, while all patients were randomized into a training cohort (n = 732) and an internal validation cohort (n = 242) according to a 3:1 ratio. In the training cohort, least absolute shrinkage and selection operator (Lasso) regression were used for predictor variable screening, and binary logistic regression analysis was used to build the diagnostic model, which was ultimately presented as a nomogram. The predictive accuracy of the nomograms was analyzed by running operating characteristic curve (ROC) to calculate area under curve (AUC), and the calibration was evaluated. Decision curve analysis (DCA) was used to determine patient benefit. In addition, we validated the built models with internal as well as external cohort (n = 771), respectively.

Results

Ultimately, the training cohort, the internal validation cohort, and the external validation cohort contained sample sizes of 188, 53, and 149, respectively, for advanced liver fibrosis. Gender, albumin (Alb), globulin (Glb), platelets (PLT), alkaline phosphatase (AKP), glutamyl transpeptidase (GGT), and prothrombin time (PT) were screened as independent predictors. Compared with the aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), and King’s score, the model in the training cohort (AUC = 0.834, 95% CI 0.800–0.868, p < 0.05) and internal validation cohort (AUC = 0.804, 95% CI 0.742–0.866, p < 0.05) showed the best discrimination and the best predictive performance. In addition, DCA showed that the clinical benefit of the nomogram was superior to the APRI, FIB-4 and King’s scores in all cohorts.

Conclusion

This study constructed a validated nomogram model with predictors screened from clinical variables which could be easily used for the diagnosis of advanced liver fibrosis in CHB patients.
Stimulating myelin restoration with BDNF: a promising therapeutic approach for Alzheimer's disease
Authors: Zota Ioanna , Chanoumidou Konstantina , Gravanis Achille , Charalampopoulos Ioannis
Published: September 2024

Alzheimer's Disease (AD) is a chronic neurodegenerative disorder constituting the most common form of dementia (60%−70% of cases). Although AD presents majorly a neurodegenerative pathology, recent clinical evidence highlights myelin impairment as a key factor in disease pathogenesis. The lack of preventive or restorative treatment is emphasizing the need to develop novel therapeutic approaches targeting to the causes of the disease. Recent studies in animals and patients have highlighted the loss of myelination of the neuronal axons as an extremely aggravating factor in AD, in addition to the formation of amyloid plaques and neurofibrillary tangles that are to date the main pathological hallmarks of the disease. Myelin breakdown represents an early stage event in AD. However, it is still unclear whether myelin loss is attributed only to exogenous factors like inflammatory processes of the tissue or to impaired oligodendrogenesis as well. Neurotrophic factors are well established protective molecules under many pathological conditions of the neural tissue, contributing also to proper myelination. Due to their inability to be used as drugs, many research efforts are focused on substituting neurotrophic activity with small molecules. Our research team has recently developed novel micromolecular synthetic neurotrophin mimetics (MNTs), selectively acting on neurotrophin receptors, and thus offering a unique opportunity for innovative therapies against neurodegenerative diseases. These small sized, lipophilic molecules address the underlying biological effect of these diseases (neuroprotective action), but also they exert significant neurogenic actions inducing neuronal replacement of the disease areas. One of the significant neurotrophin molecules in the Central Nervous System is Brain-Derived-Neurotrophin-Factor (BDNF). BDNF is a neurotrophin that not only supports neuroprotection and adult neurogenesis, but also mediates pro-myelinating effects in the CNS. BDNF binds with high-affinity on the TrkB neurotrophin receptor and enhances myelination by increasing the density of oligodendrocyte progenitor cells (OPCs) and playing an important role in CNS myelination. Conclusively, in the present review, we discuss the myelin pathophysiology in Alzheimer's Diseases, as well as the role of neurotrophins, and specifically BDNF, in myelin maintenance and restoration, revealing its valuable therapeutic potential against AD.
Sex-dependent regulation of retinal pigment epithelium and retinal function by Pgc-1α
Authors: Taskintuna Kaan , Bhat Mohd Akbar , Shaikh Tasneem , Hum Jacob , Golestaneh Nady
Published: September 2024

Age-related macular degeneration (AMD) is a major cause of blindness that affects people over 60. While aging is the prominent factor in AMD, studies have reported a higher prevalence of AMD in women compared to age-matched men. Higher levels of the innate immune response’s effector proteins complement factor B and factor I were also found in females compared to males in intermediate AMD. However, the mechanisms underlying these differences remain elusive. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a key regulator of mitochondrial biogenesis and metabolic pathways. Previously, we showed that Pgc-1α repression and high-fat diet induce drastic AMD-like phenotypes in mice. Our recent data revealed that Pgc-1α repression alone can also induce retinal pigment epithelium (RPE) and retinal dysfunction in mice, and its inhibition in vitro results in lipid droplet accumulation in human RPE. Whether sex is a contributing factor in these phenotypes remains to be elucidated. Using electroretinography, we demonstrate that sex could influence RPE function during aging independent of Pgc-1α in wild-type (WT) mice. We further show that Pgc-1α repression exacerbates RPE and retinal dysfunction in females compared to aged-match male mice. Gene expression analyses revealed that Pgc-1α differentially regulates genes related to antioxidant enzymes and mitochondrial dynamics in males and females. RPE flat mounts immunolabeled with TOMM20 and DRP1 indicated a sex-dependent role for Pgc-1α in regulating mitochondrial fission. Analyses of mitochondrial network morphology suggested sex-dependent effects of Pgc-1α repression on mitochondrial dynamics. Together, our study demonstrates that inhibition of Pgc-1α induces a sex-dependent decline in RPE and retinal function in mice. These observations on the sex-dependent regulation of RPE and retinal function could offer novel insights into targeted therapeutic approaches for age-related RPE and retinal degeneration.
Association among biomarkers, phenotypes, and motor milestones in Chinese patients with 5q spinal muscular atrophy types 1–3
Authors: Ouyang Shijia , Peng Xiaoyin , Huang Wenchen , Bai Jinli , Wang Hong , Jin Yuwei , Jiao Hui , Wei Maoti , Ge Xiushan , Song Fang , Qu Yujin
Published: September 2024

Background

Biomarkers can be used to assess the severity of spinal muscular atrophy (5q SMA; SMA). Despite their potential, the relationship between biomarkers and clinical outcomes in SMA remains underexplored. This study aimed to assess the association among biomarkers, phenotypes, and motor milestones in Chinese patients diagnosed with SMA.

Methods

We collected retrospective clinical and follow-up data of disease-modifying therapy (DMT)-naïve patients with SMA at our center from 2019 to 2021. Four biomarkers were included: survival motor neuron 2 (SMN2) copies, neuronal apoptosis inhibitory protein (NAIP) copies, full-length SMN2 (fl-SMN2), and F-actin bundling protein plastin 3 (PLS3) transcript levels. Data were analyzed and stratified according to SMA subtype.

Results

Of the 123 patients, 30 were diagnosed with Type 1 (24.3%), 56 with Type 2 (45.5%), and 37 with Type 3 (30.1%). The mortality rate for Type 1 was 50%, with median survival times of 2 and 8 months for types 1a and 1b, respectively. All four biomarkers were correlated with disease severity. Notably, fl-SMN2 transcript levels increased with SMN2 copies and were higher in Type 2b than those in Type 2a (p = 0.028). Motor milestone deterioration was correlated with SMN2 copies, NAIP copies, and fl-SMN2 levels, while PLS3 levels were correlated with standing and walking function.

Discussion

Our findings suggest that SMN2 copies contribute to survival and that fl-SMN2 may serve as a valuable biomarker for phenotypic variability in SMA Type 2 subtypes. These insights can guide future research and clinical management of SMA.
Prognostic factors and treatment outcomes in pediatric autoimmune encephalitis: a multicenter study
Authors: Abu Melha Ahlam Ahmed , Aldress Amjad Saad , Alamri Fahad , Aljomah Lama Saleh , Hommady Raid , Al-Rumayyan Ahmed , Albassam Fahad
Published: September 2024

Introduction

The last few decades have increased our understanding of autoimmune encephalitis (AE). In both the pediatric and adult populations, it proves to be a disease of dramatic acute onset of heterogeneous clinical manifestations, notably encephalopathy with neuropsychiatric symptoms, seizures, and extrapyramidal symptoms. More often, it is triggered by a viral infection in the pediatric age groups, as suggested by the preceding febrile symptoms in over half of cases, and more ostensibly, NMDAR encephalitis post herpes encephalitis. An underlying neoplasm may be present in certain types (i.e., NMDAR encephalitis). The rising rate of antibody detection and subsequent confirmation has been boosted by improved live cellular assay detection methods. The corresponding clinical phenotypes, common underlying malignancies, and histopathological findings have helped improve our management regarding intervention and choice of immunotherapy. New assessment tools such as the Clinical Assessment Scale in Autoimmune Encephalitis (CASE score) have helped improve the objective assessment of impact on cognitive functions (1). Early intervention with immunotherapy (and tumor removal in proven underlying neoplasms) has improved overall outcomes in most presenting patients. But nearly 40% of cases fail to respond to the first tier of treatment (2). The complex interplay between pathogenic autoantibodies, T-cells, B-cells, and cytokines has led to the emergence of additional immunotherapy agents (i.e., tocilizumab and bortezomib).

Methods

In this retrospective observational study of pediatric AE conducted at two tertiary care centers, we observed the clinical characteristics, autoantibody yield, treatment modalities used, and disability scores during presentation and follow-up. Our secondary aim was to delineate prognostic factors for poor outcomes.

Results

Neuropsychiatric symptoms, encephalopathy, and seizures were the predominant manifestations in most of our patients. Younger age groups, refractory seizures, profound encephalopathy, and refractory disease harbored higher disability scores. The group that received combined immunotherapy has shown mitigation of disability score from severe to mild during long-term follow-up, signifying the role of multifaceted immunotherapy in pediatric refractory AE.

Conclusion

Early implementation of combined immunotherapy in refractory cases significantly improved longterm disability scores, in spite of lingering residual effects on neurologic functions, notably cognition, behavior, and speech.
Prenatal tobacco and alcohol exposure, white matter microstructure, and early language skills in toddlers from a South African birth cohort
Authors: Scholten Chloe , Ghasoub Mohammad , Geeraert Bryce , Joshi Shantanu , Wedderburn Catherine J. , Roos Annerine , Subramoney Sivenesi , Hoffman Nadia , Narr Katherine , Woods Roger , Zar Heather J. , Stein Dan J. , Donald Kirsten , Lebel Catherine
Published: September 2024

Introduction

Tobacco and alcohol are the two most common substances used during pregnancy, and both can disrupt neurodevelopment, resulting in cognitive and behavioral deficits including language difficulties. Previous studies show that children with prenatal substance exposure exhibit microstructural alterations in major white matter pathways, though few studies have investigated the impact of prenatal substance exposure on white matter microstructure and language skills during the toddler years.

Methods

In this study, 93 children (34 exposed to alcohol and/or tobacco) aged 23 years from the Drakenstein Child Health Study, South Africa, completed Expressive and Receptive Communication assessments from the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and underwent diffusion MRI scans. Diffusion images were preprocessed, and 11 major white matter tracts were isolated. Fractional anisotropy (FA) and mean diffusivity (MD) were extracted for each white matter tract. Linear regression was used to examine differences between the tobacco/alcohol exposed group and unexposed controls for FA, MD, and language scores, as well as relationships between brain metrics and language. There were no significant group differences in language scores or FA.

Results

Children with alcohol or tobacco exposure had lower average MD in the splenium of the corpus callosum compared to unexposed controls. Significant interactions between prenatal substance exposure and language scores were seen in 7 tracts but did not survive multiple comparisons correction.

Discussion

Our findings show that prenatal alcohol and/or tobacco exposure appear to alter the relationship between white matter microstructure and early language skills in this population of toddlers, potentially laying the basis of language deficits observed later in older children with prenatal substance exposure, which may have implications for learning and interventions.
Hesperetin but not ellagic acid increases myosin heavy chain expression and cell fusion in C2C12 myoblasts in the presence of oxidative stress
Authors: Cuijpers Iris , Dohmen Colin G. M. , Bouwman Freek G. , Troost Freddy J. , Sthijns Mireille M. J. P. E.
Published: September 2024

Introduction

Skeletal muscle regeneration is impaired in elderly. An oxidative stress-induced decrease in differentiation capacity of muscle satellite cells is a key factor in this process. The aim of this study is to investigate whether orange polyphenol hesperetin and pomegranate polyphenol ellagic acid enhance myoblast differentiation in the presence and absence of oxidative stress, and to explore underlying mechanisms.

Methods

C2C12 myoblasts were proliferated for 24 h and differentiated for 120 h while exposed to hesperetin (5, 20, 50 μM), ellagic acid (0.05, 0.1 μM) or a combination (20 μM hesperetin, 0.05 μM ellagic acid) with and without oxidative stress-inducing compound menadione (9 μM) during 24 h of proliferation and during the first 5 h of differentiation. The number of proliferating cells was assessed using fluorescent labeling of incorporated 5-ethynyl-2′-deoxyuridine. Myosin heavy chain expression was assessed by fluorescence microscopy and cell fusion index was calculated. Furthermore, protein expression of phosphorylated p38 and myomixer were assessed using Western blot.

Results

None of the compounds induced effects on cell proliferation. Without menadione, 50 μM hesperetin increased fusion index by 12.6% compared to control (p < 0.01), while ellagic acid did not affect measured parameters of differentiation. Menadione treatment did not change myosin heavy chain expression and fusion index. In combination with menadione, 20 μM hesperetin increased myosin heavy chain expression by 35% (p < 0.01) and fusion index by 7% (p = 0.04) compared to menadione. Furthermore, the combination of menadione with hesperetin and ellagic acid increased myosin heavy chain expression by 35% compared to menadione (p = 0.02). Hesperetin and ellagic acid did not change p38 phosphorylation and myomixer expression compared to control, while treatment with menadione increased p38 phosphorylation (p < 0.01) after 5 h and decreased myomixer expression (p = 0.04) after 72 h of differentiation.

Conclusion and discussion

Hesperetin increased myosin heavy chain expression in the presence of oxidative stress induced by menadione, and increased cell fusion both in the presence and absence of menadione. Ellagic acid did not affect the measured parameters of myoblast differentiation. Therefore, hesperetin should be considered as nutritional prevention or treatment strategy to maintain muscle function in age-related diseases such as sarcopenia. Future research should focus on underlying mechanisms and translation of these results to clinical practice.
Dietary patterns and association with Iron deficiency among children and adolescents aged 9–17 years in rural Guangzhou, China: a cross-sectional study
Authors: Fu Jinhan , Zeng Chunzi , Huang Jie , Guo Jiaying , Su Zheng , Luo Shiyun , Zhang Weiwei , Zhang Zhoubin , Zhu Huilian , Li Yan
Published: September 2024

Background

Iron deficiency and iron deficiency anemia cause a huge disease burden worldwide. Diet is an important factor affecting the iron levels. This study aims to explore the dietary patterns of school-aged children in rural areas of Guangzhou and their association with iron deficiency.

Methods

Data on dietary surveys, lifestyle, demographic and laboratory tests were gathered from rural school-age children in Guangzhou. Factor analysis was applied to derive dietary patterns. Robust Poisson regression and subgroup analysis were used to analyze the association between dietary patterns and iron deficiency.

Results

A total of 2,530 children and adolescents aged 9–17 years were enrolled. The prevalence of iron deficiency was 13.36%. Four dietary patterns were identified including snack and fast-food pattern, fruit and vegetable pattern, cereal and tuber pattern and meat and offal pattern. Both children and adolescents in the Q4 group (the highest propensity) of snack and fast-food pattern and cereal and tuber pattern had a higher risk of iron deficiency than the Q1 group (the lowest propensity). Both children and adolescents in the Q4 group of meat and offal pattern and fruit and vegetable pattern had a lower risk of iron deficiency than the Q1 group. The results of stratified analysis showed the negative effect of snack and fast-food pattern and the protective benefits of meat and offal pattern are more obvious for boys, and the negative effect of cereal and tuber pattern were obvious for girls. The negative effect or protective benefits of the four dietary patterns were obvious for children aged 9–13.

Conclusion

Females, older children, and those with shorter sleep duration are at higher risk of iron deficiency. Snack and fast-food pattern and cereal and tuber pattern are risk factors for iron deficiency, and fruit and vegetable pattern and meat and offal pattern are protective factors for iron deficiency. The impact of diet on body iron levels is more obvious in boys and younger children. The findings of this study can provide evidence for formulating prevention and control measures on children and adolescents iron deficiency and iron deficiency anemia.
Clinicopathological and molecular differences between stage IV screen-detected and interval colorectal cancers in the Flemish screening program
Authors: Neefs Isabelle , Tran Thuy Ngan , Ferrari Allegra , Janssens Sharon , Van Herck Koen , Op de Beeck Ken , Van Camp Guy , Peeters Marc , Fransen Erik , Hoeck Sarah , Van Hal Guido
Published: September 2024

Introduction

Interval cancer (IC) is an important quality indicator in colorectal cancer (CRC) screening. Previously, we found that fecal immunochemical test (FIT) ICs are more common in women, older age, right-sided tumors, and advanced stage. Here, we extended our existing stage IV patient cohort with clinicopathological and molecular characteristics, to identify factors associated with FIT-IC.

Methods

Logistic regression models were fit to identify variables associated with the odds of having a stage IV FIT-IC. Multivariate models were corrected for gender, age, and location.

Results

A total of 292 screen-detected (SD) CRCs and 215 FIT-IC CRCs were included. FIT-IC CRC had 5 fold higher odds to be a neuroendocrine (NET) tumor and 2.5 fold higher odds to have lymphovascular invasion. Interestingly, some variables lost significance upon accounting for location. Thus, tumor location is a critical covariate that should always be included when evaluating factors related to FIT-IC.

Conclusions

We identified NETs and lymphovascular invasion as factors associated with increased odds of having a stage IV FIT-IC. Moreover, we highlight the importance of tumor location as a covariate in evaluating FIT-IC related factors. More research across all stages is needed to clarify how these insights might help to optimize the Flemish CRC screening program.
Deciphering the code: the pivotal role of lncRNAs in advancing TNBC therapy
Authors: Chen Weiping , Pan Zhiyong , Feng Zhengfu , Wang Xin , Zhu Song
Published: September 2024

Triple-negative breast cancer (TNBC) represents the most formidable subtype of breast cancer, characterized by a notable dearth in targeted therapeutic options. Deciphering the underlying molecular mechanisms of TNBC is pivotal for improving patient outcomes. Recent scientific advancements have spotlighted long non-coding RNAs (lncRNAs) as key players in the genesis, progression, and metastasis of cancers. This review delineates the significant influence of lncRNAs on the advancement, detection, and neoadjuvant chemotherapy efficacy in TNBC, detailing the diverse expression patterns of aberrant lncRNAs. The paper explores the specific mechanisms by which lncRNAs regulate gene expression in both the nucleus and cytoplasm, with a special focus on their involvement in TNBC’s post-transcriptional landscape. Thorough investigations into TNBC-associated lncRNAs not only forge new avenues for early diagnosis and potent treatment strategies but also highlight these molecules as promising therapeutic targets, heralding an era of personalized and precision medicine in TNBC management.
Epidemiology of injuries among children and adolescents from the Xinglin District in Xiamen, 2016–2019
Authors: Lin Gangxi , Zeng Qiyi
Published: September 2024

Objective

To investigate the epidemiology of injuries among children and adolescents in the Xinglin District of Xiamen from 2016 to 2019.

Methods

This study collected data from patients who attended the outpatient and emergency departments of the Xinglin District at the First Affiliated Hospital of Xiamen University between January 2016 and December 2019, diagnosed with injuries.

Results

A total of 13,123 patients were included, categorized into age groups 0–4 (n = 4,834), 5–9 (n = 3,924), 10–14 (n = 2,671), and 15–18 (n = 1,694). The rates of unintentional injuries were 97.00%, 96.94%, 94.50%, and 90.08% in the 0–4, 5–9, 10–14, and 15–18 age groups, respectively (P < 0.001). The proportion of head injuries decreased with age (from 41.13% in the 0–4 age group to 18.00% in the 15–18 age group), compensated by an increase in rates of injuries to upper and lower extremities and multisite injuries (P < 0.001). The most common causes of injuries were fall-related injuries (30.46%–52.05%), followed by mechanical injuries (18.35%–36.42%), with the rates of fall-related injuries decreasing with age and rates of mechanical injuries increasing with age (P < 0.001). Age-period-cohort models revealed that the time factor was not significant for fall-related injuries and mechanical injuries (all P > 0.05) despite apparent increases in incidence over time.

Conclusion

Injuries in children and adolescents continue to be a significant public health concern in the Xinglin District (China), predominantly driven by fall-related injuries and mechanical injuries.
Antihypertensive drug-associated adverse events in osteoarthritis: a study of a large real-world sample based on the FAERS database
Authors: Guo Zijian , Di Jingkai , Zhang Zhibo , Chen Shuai , Mao Xingjia , Wang Zehua , Yan Zehui , Li Xiaoke , Tian Zui , Mu Changjiang , Xiang Changxin , Xiang Chuan
Published: September 2024

Background

Hypertension is a common complication in patients with osteoarthritis (OA). There is increasing interest in the relationship between hypertension and OA. However, hypertension has been reported to negatively affect symptoms and quality of life in patients with OA. Therefore, treating hypertension is crucial for patients with OA. However, there is a lack of real-world studies on the effects of medications for treating hypertension on OA.

Methods

Data from the FAERS database from January 2004 to December 2023 were extracted for disproportionality analyses, and proportional reporting ratios (PRRs) were used to assess the association between medications for hypertension and all types of arthritis. Adverse event signals were identified and determined using reporting odds ratios (RORs) Adverse event signals were considered to have occurred if a drug-induced adverse event was recorded more than or equal to 3 and the lower limit of the ROR confidence interval was more than 1. We selected five classes of drugs including, calcium channel blockers (CCBs), angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), thiazide diuretics and β-blockers and representative drugs were analysed for osteoarthritis-related adverse reactions, and age and gender subgroups were analysed for drugs of significance. We also analysed the occurrence of AEs in relation to time using the Weibull distribution.

Results

In terms of overall data, we found significant OA adverse reaction signals only for ARBs among the five drug classes.ARB AEs for spinal osteoarthritis (ROR 4.64, 95% CI 3.62–5.94), osteoarthritis (ROR 3.24 95% CI 2.82–3.72) and gouty arthritis (ROR 3.27 95% CI 1.22–8.75) were the three adverse reactions with the loudest signals. Next, we found that valsartan had strong osteoarthritis adverse reaction signals among the three ARBs, namely, irbesartan, cloxartan, and valsartan. We also analysed age and gender subgroups and found that osteoarthritis signals were strongest in the 18–65 and 65+ population, while females seem to be more prone to valsartan-related OA AEs.

Conclusion

ARBs, especially valsartan, have significant positive signals for OA AEs. Therefore, ARB drugs, especially valsartan, should be used with caution when treating patients with OA combined with hypertension.
A cheminformatics and network pharmacology approach to elucidate the mechanism of action of Mycobacterium tuberculosis γ-carbonic anhydrase inhibitors
Authors: Manaithiya Ajay , Bhowmik Ratul , Bhattacharya Kunal , Ray Rajarshi , Shyamal Sagar Singh , Carta Fabrizio , Supuran Claudiu T. , Parkkila Seppo , Aspatwar Ashok
Published: September 2024

Background

Mycobacterium tuberculosis (Mtb) carbonic anhydrases (CAs) are critical enzymes that regulate pH by converting CO2 to HCO3−, essential for Mtb’s survival in acidic environments. Inhibiting γ-CAs presents a potential target for novel antituberculosis drugs with unique mechanisms of action.

Objective

This study aimed to explore the biological connections underlying Mtb pathogenesis and investigate the mechanistic actions of antituberculosis compounds targeting the Cas9 protein.

Methods

We employed homology modeling and virtual screening to identify compounds with high binding affinities for Cas9 protein. This study used the homology modeling approach employing high-quality AlphaFold DB models for γ-CA. Furthermore, the systems biology approach was used for analyzing the integrated modelling of compounds, integrating data on genes, pathways, phenotypes, and molecular descriptors. Single-cell RNA sequencing was also conducted to profile gene expression.

Results

Three compounds, F10921405, F08060425, and F14437079, potentially binding to Cas9 protein, have been identified. F10921405 and F08060425 showed significant overlap in their effects on pathways related to the immune response, while F14437079 displayed distinct mechanistic pathways. Expression profiling revealed high levels of genes such as PDE4D, ROCK2, ITK, MAPK10, and SYK in response to F1092–1405 and F0806-0425, and MMP2 and CALCRL in response to F1443-7079. These genes, which play a role in immune modulation and lung tissue integrity, are essential to fight against Mtb.

Conclusion

The molecular relationship and pathways linked to the mentioned compounds give the study a holistic perspective of targeting Mtb, which is essential in designing specific therapeutic approaches. Subsequent research will involve experimental validation to demonstrate the efficacy of the promising candidates in Mtb infections.
Aberrant glycosylation in schizophrenia: insights into pathophysiological mechanisms and therapeutic potentials
Authors: Feng Yanchen , Sun Lu , Dang Xue , Liu Diyan , Liao Ziyun , Yao Jianping , Zhang Yunke , Deng Ziqi , Li Jinyao , Zhao Min , Liu Feixiang
Published: September 2024

Schizophrenia (SCZ) is a severe neuropsychiatric disorder characterized by cognitive, affective, and social dysfunction, resulting in hallucinations, delusions, emotional blunting, and disordered thinking. In recent years, proteomics has been increasingly influential in SCZ research. Glycosylation, a key post-translational modification, can alter neuronal stability and normal signaling in the nervous system by affecting protein folding, stability, and cellular signaling. Recent research evidence suggests that abnormal glycosylation patterns exist in different brain regions in autopsy samples from SCZ patients, and that there are significant differences in various glycosylation modification types and glycosylation modifying enzymes. Therefore, this review explores the mechanisms of aberrant modifications of N-glycosylation, O-glycosylation, glycosyltransferases, and polysialic acid in the brains of SCZ patients, emphasizing their roles in neurotransmitter receptor function, synaptic plasticity, and neural adhesion. Additionally, the effects of antipsychotic drugs on glycosylation processes and the potential for glycosylation-targeted therapies are discussed. By integrating these findings, this review aims to provide a comprehensive perspective to further understand the role of aberrant glycosylation modifications in the pathophysiology of SCZ.
Diaporthe foeniculina and D. eres, in addition to D. ampelina, may cause Phomopsis cane and leaf spot disease in grapevine
Authors: Fedele Giorgia , Armengol Josep , Caffi Tito , Languasco Luca , Latinovic Nedeljko , Latinovic Jelena , León Maela , Marchi Guido , Mugnai Laura , Rossi Vittorio
Published: September 2024

Phomopsis cane and leaf spot (PCLS) disease, affecting grapevines (Vitis vinifera and Vitis spp.), has been historically associated with Diaporthe ampelina. Typical disease symptoms, comprising bleaching and black pycnidia, have also been associated with other Diaporthe spp. In this study, we conducted a molecular identification of the Diaporthe isolates isolated from grapevine canes from different geographic areas of southern Europe showing PCLS symptoms. Then, we investigated their morphological characteristics (including mycelium growth and production of pycnidia and alpha and beta conidia) in response to temperature. Finally, we artificially inoculated grapevine shoots and leaves with a subset of these isolates. Based on our results, PCLS etiology should be reconsidered. Though D. ampelina was the most crucial causal agent of PCLS, D. eres and D. foeniculina were also pathogenic when inoculated on green shoots and leaves of grapevines. However, D. rudis was not pathogenic. Compared to D. ampelina, D. eres and D. foeniculina produced both pycnidia and alpha conidia at lower temperatures. Thus, the range of environmental conditions favorable for PCLS development needs to be widened. Our findings warrant further validation by future studies aimed at ascertaining whether the differences in temperature requirements among species are also valid for conidia-mediated infection since it could have substantial practical implications in PCLS management.
Gallic acid regulates primary root elongation via modulating auxin transport and signal transduction
Authors: Xu Zilian , Yang Bing , Fan Jing , Yuan Qiushi , He Fu , Liang Hongwei , Chen Faju , Liu Wen
Published: September 2024

Gallic acid is an important secondary metabolite in plants, with great value in medicine, food, and chemical industry. However, whether and how this widely existing natural polyphenolic compound affects the growth and development of plants themselves remains elusive. In this study, we revealed that exogenous application of gallic acid has a dual effect on the elongation of primary root in Arabidopsis. While lower concentrations of gallic acid slightly stimulate primary root growth, excessive gallic acid profoundly reduces primary root length and root meristem size in a dose-dependent manner, probably via suppressing cell division in root meristem as indicated by CYCB1;1::GUS. Moreover, as suggested by the DR5::GFP line analysis and confirmed by the LC-MS assay, auxin contents in root tips were dramatically decreased upon excessive gallic acid treatment. Additional application of IAA partially rescued the shortened primary root and root meristem upon excessive gallic acid treatment, suggesting that auxin is required for excessive gallic acid-caused root growth inhibition. Then, we further revealed that excessive gallic acid down-regulated the expression of auxin transporters PIN1, PIN2, PIN3, and PIN7, and triple mutant pin1 pin3 pin7 exhibited a reduced sensitivity to gallic acid treatment. Meanwhile, excessive gallic acid decreased the degradation of AXR3/IAA17 protein as revealed by HS::AXR3NT-GUS reporter line. Auxin signaling mutant tir1 afb2 afb3 and axr3-3 were also less sensitive to excessive gallic acid treatment in terms of primary root length and root meristem size. Taken together, these findings suggested that excessive gallic acid inhibits primary root growth by modulating auxin transport and signaling in Arabidopsis.
Mindfulness and academic procrastination among Chinese adolescents: a moderated mediation model
Authors: Yue Pengfei , Zhang Jiaxin , Jing Yumei
Published: September 2024

Background

While previous studies have linked mindfulness to reduced academic procrastination, the mechanisms involved remain under-explored. This study deepens the understanding by investigating how learning vigor mediates the mindfulness and procrastination relationship, and how harsh parenting influences this mediation.

Methods

This study, adopting a positivist research approach, utilized a cross-sectional design. Data were collected from 800 students at three middle schools in Henan Province, China, through cluster random sampling. This approach yielded 800 questionnaires. The participants sequentially completed four questionnaires: the Mindfulness Attention Awareness Scale, the Utrecht Work Engagement Scale-Student, the Aitken Procrastination Inventory, and the Harsh Parenting Questionnaire. After removing 67 invalid questionnaires due to incomplete responses and patterned answers, a total of 733 valid questionnaires were obtained, with 53.3% girls and an average age of 13.12 years (SD = 1.01), leading to an effectiveness rate of 91.63%. Upon data collection, SPSS 26.0 software was used for correlation analysis, mediation analysis, and moderated mediation analysis to assess the relationships between variables.

Results

(1) Mindfulness negatively predicts academic procrastination; (2) Learning vigor serves as a mediator in the relationship between mindfulness and academic procrastination; and (3) Harsh parenting moderates the relationship between mindfulness and learning vigor. Specifically, the positive impact of mindfulness on learning vigor is more pronounced in individuals experiencing lower levels of harsh parenting compared to those with higher levels.

Conclusion

This study reveals that mindfulness significantly protects against academic procrastination in adolescents, with 52.27% of this effect mediated by increased learning vigor. Additionally, it shows that high levels of harsh parenting weaken mindfulness’s positive impact on learning vigor, tempering its overall protective influence on procrastination. These insights, which apply Trait Activation Theory to educational psychology, not only deepen our understanding of the dynamics between mindfulness and procrastination but also have important implications for addressing academic procrastination in Chinese adolescents.