bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative assessment of Alzheimer’s disease-related biomarkers in plasma and neuron-derived extracellular vesicles: a nested case-control study
Authors: Manolopoulos Apostolos , Delgado-Peraza Francheska , Mustapic Maja , Pucha Krishna Ananthu , Nogueras-Ortiz Carlos , Daskalopoulos Alexander , Knight De’Larrian DeAnté , Leoutsakos Jeannie-Marie , Oh Esther S. , Lyketsos Constantine G. , Kapogiannis Dimitrios
Published: September 2023

Introduction: Alzheimer’s disease (AD) is currently defined according to biomarkers reflecting the core underlying neuropathological processes: Aβ deposition, Tau, and neurodegeneration (ATN). The soluble phase of plasma and plasma neuron-derived extracellular vesicles (NDEVs) are increasingly being investigated as sources of biomarkers. The aim of this study was to examine the comparative biomarker potential of these two biofluids, as well as the association between respective biomarkers.

Methods: We retrospectively identified three distinct diagnostic groups of 44 individuals who provided samples at baseline and at a mean of 3.1 years later; 14 were cognitively unimpaired at baseline and remained so (NRM-NRM), 13 had amnestic MCI that progressed to AD dementia (MCI-DEM) and 17 had AD dementia at both timepoints (DEM-DEM). Plasma NDEVs were isolated by immunoaffinity capture targeting the neuronal markers L1CAM, GAP43, and NLGN3. In both plasma and NDEVs, we assessed ATN biomarkers (Aβ42, Aβ40, total Tau, P181-Tau) alongside several other exploratory markers.

Results: The Aβ42/Aβ40 ratio in plasma and NDEVs was lower in MCI-DEM than NRM-NRM at baseline and its levels in NDEVs decreased over time in all three groups. Similarly, plasma and NDEV-associated Aβ42 was lower in MCI-DEM compared to NRM-NRM at baseline and its levels in plasma decreased over time in DEM-DEM. For NDEV-associated proBDNF, compared to NRM-NRM, its levels were lower in MCI-DEM and DEM-DEM at baseline, and they decreased over time in the latter group. No group differences were found for other exploratory markers. NDEV-associated Aβ42/Aβ40 ratio and proBDNF achieved the highest areas under the curve (AUCs) for discriminating between diagnostic groups, while proBDNF was positively associated with Mini-Mental State Examination (MMSE) score. No associations were found between the two biofluids for any assessed marker.

Discussion: The soluble phase of plasma and plasma NDEVs demonstrate distinct biomarker profiles both at a single time point and longitudinally. The lack of association between plasma and NDEV measures indicates that the two types of biofluids demonstrate distinct biomarker signatures that may be attributable to being derived through different biological processes. NDEV-associated proBDNF may be a useful biomarker for AD diagnosis and monitoring.
Testing the effect of high-definition transcranial direct current stimulation of the insular cortex to modulate decision-making and executive control
Authors: Gorrino Irene , Canessa Nicola , Mattavelli Giulia
Published: September 2023

Introduction

Previous neuroimaging evidence highlighted the role of the insular and dorsal anterior cingulate cortex (dACC) in conflict monitoring and decision-making, thus supporting the translational implications of targeting these regions in neuro-stimulation treatments for clinical purposes. Recent advancements of targeting and modeling procedures for high-definition tDCS (HD-tDCS) provided methodological support for the stimulation of otherwise challenging targets, and a previous study confirmed that cathodal HD-tDCS of the dACC modulates executive control and decision-making metrics in healthy individuals. On the other hand, evidence on the effect of stimulating the insula is still needed.

Methods

We used a modeling/targeting procedure to investigate the effect of stimulating the posterior insula on Flanker and gambling tasks assessing, respectively, executive control and both loss and risk aversion in decision-making. HD-tDCS was applied through 6 small electrodes delivering anodal, cathodal or sham stimulation for 20 min in a within-subject offline design with three separate sessions.

Results

Bayesian statistical analyses on Flanker conflict effect, as well as loss and risk aversion, provided moderate evidence for the null model (i.e., absence of HD-tDCS modulation).

Discussion

These findings suggest that further research on the effect of HD-tDCS on different regions is required to define reliable targets for clinical applications. While modeling and targeting procedures for neuromodulation in clinical research could lead to innovative protocols for stand-alone treatment, or possibly in combination with cognitive training, assessing the effectiveness of insula stimulation might require sensitive metrics other than those investigated here.
Clinical, imaging, and biomarker evidence of amyloid- and tau-related neurodegeneration in late-onset epilepsy of unknown etiology
Authors: Hickman L. Brian , Stern John M. , Silverman Daniel H. S. , Salamon Noriko , Vossel Keith
Published: September 2023

Accumulating evidence suggests amyloid and tau-related neurodegeneration may play a role in development of late-onset epilepsy of unknown etiology (LOEU). In this article, we review recent evidence that epilepsy may be an initial manifestation of an amyloidopathy or tauopathy that precedes development of Alzheimer’s disease (AD). Patients with LOEU demonstrate an increased risk of cognitive decline, and patients with AD have increased prevalence of preceding epilepsy. Moreover, investigations of LOEU that use CSF biomarkers and imaging techniques have identified preclinical neurodegeneration with evidence of amyloid and tau deposition. Overall, findings to date suggest a relationship between acquired, non-lesional late-onset epilepsy and amyloid and tau-related neurodegeneration, which supports that preclinical or prodromal AD is a distinct etiology of late-onset epilepsy. We propose criteria for assessing elevated risk of developing dementia in patients with late-onset epilepsy utilizing clinical features, available imaging techniques, and biomarker measurements. Further research is needed to validate these criteria and assess optimal treatment strategies for patients with probable epileptic preclinical AD and epileptic prodromal AD.
Association between glycated hemoglobin and functional outcomes in patients with intracranial large artery atherosclerotic disease-related acute ischemic stroke: identifying the magic number
Authors: Zafar Azra , Albakr Aishah , Shahid Rizwana , Alkhamis Fahd , Alabdali Majed , Aljaafari Danah , Nazish Saima , AlShamrani Foziah Jabbar Gossab , Shariff Erum , Zeeshan Mohammad , AlSulaiman Abdulla , AlAmri Abdullah Saleh , Aldehailan Anas Salman , Al-Jehani Hosam
Published: September 2023

Objective

This study aimed to investigate the effect of the glycated hemoglobin A1c (HbA1c) level on the functional outcome (FOC) in patients with intracranial large artery atherosclerotic disease (ICLAD)-related acute ischemic stroke (AIS).

Methods

This retrospective study enrolled patients with ICLAD-related AIS who were admitted to King Fahd University Hospital between January 2017 and September 2021. Patients were divided into two groups based on the optimal cutoff HbA1c level determined using receiver operating characteristic curve analysis—those with HbA1c ≤6.9% and those with HbA1c >6.9%. Demographic and other clinical characteristics were compared between the two groups using chi-square tests. The association between HbA1c and 90-day FOC was assessed using the chi-square test and odds ratios (ORs). Multivariate analysis was performed to adjust for confounding factors.

Results

A total of 140 patients were included in the analysis. A significant association was observed between the HbA1c level and FOC. Compared to patients with HbA1c ≤6.9%, patients with HbA1c >6.9% were more likely to have an unfavorable FOC [p = <0.001, OR = 2.05, 95% confidence interval (CI) = 1.33–3.14]. The association between HbA1c >6.9% and unfavorable FOC was sustained even after adjusting for confounding factors (p = 0.008) and atherosclerosis risk factors (p = 0.01). HbA1c >6.9% was also associated with higher ORs for in-hospital complications (p = 0.06, OR = 1.34, 95% CI = 1.02–1.77) and mortality (p = 0.07, OR = 1.42, 95% CI = 1.06–1.92) although these associations did not attain significant p-values.

Conclusion

HbA1c >6.9% was significantly associated with unfavorable FOC in ICLAD-related AIS. However, further studies with larger sample sizes are required to verify whether HbA1c is an independent predictor of poor FOC. Nevertheless, targeting HbA1c <7% should be the goal of physicians when managing patients at high risk of ICLAD.
The thalamus and basal ganglia are smaller in children with epilepsy after perinatal stroke
Authors: Vaher Ulvi , Ilves Norman , Ilves Nigul , Laugesaar Rael , Männamaa Mairi , Loorits Dagmar , Kool Pille , Ilves Pilvi
Published: September 2023

Background

Epilepsy is one of the most serious consequences of perinatal stroke. Epilepsy itself has been proposed as a risk factor for impaired cognitive, language, and behavioral functioning. It is still unclear which children develop epilepsy after perinatal stroke. The current study aimed to evaluate the volume of the thalamus and the basal ganglia in children after perinatal stroke in relation to poststroke epilepsy.

Methods

The follow-up study included 29 children with perinatal arterial ischemic stroke (AIS), 33 children with presumed periventricular venous infarction (PVI), and 46 age- and sex-matched healthy controls. Magnetic resonance imaging was performed in children between the ages of 4 and 18 years, and volumetric analysis by segmentation was used to evaluate the size of the thalamus, caudate nucleus, putamen, globus pallidus, hippocampus, amygdala, and nucleus accumbens.

Results

During a median follow-up time of 12.8 years [interquartile range (IQR): 10.8–17.3] in the AIS group and 12.5 years (IQR: 9.3–14.8) in the PVI group (p = 0.32), epilepsy developed in 10 children (34.5%) with AIS and in 4 (12.1%) children with PVI, p = 0.036 [odds ratio (OR) = 3.8, 95%, confidence interval (CI): 1.04–14]. Epilepsy and interictal epileptiform discharges (IEDs) without clinical seizures were more often expressed in children with AIS (n = 16, 55%) than in children with PVI (n = 7, 21.2%), p = 0.0057 (OR = 3.8 95% CI: 1.04–14). In the AIS group, the ipsilesional and contralesional thalamus, ipsilesional caudate nucleus, and nucleus accumbens were significantly smaller in children with epilepsy compared to children without epilepsy. In the PVI group, the ipsilesional thalamus, caudate nucleus, and nucleus accumbens were smaller in the pooled group of epilepsy plus IED alone compared to children without epilepsy.

Conclusion

In children with AIS, epilepsy or IED occurred more often compared to children with PVI. Both patients with AIS and PVI with severe damage to the basal ganglia and the thalamus have a higher risk of developing poststroke epilepsy and should be monitored more closely throughout childhood to initiate timely antiseizure medication and rehabilitation.
Association between miR-365 polymorphism and ischemic stroke in a Chinese population
Authors: Weng Yin-Hua , Yu Wen-Tao , Luo Yan-Ping , Liu Chao , Gu Xi-Xi , Chen Huo-Ying , Liu Hong-Bo
Published: September 2023

Background

Ischemic stroke (IS) represents a major cause of morbidity and mortality across the globe. The aberrant expression of miR-365 has been found to be implicated in a wide array of human diseases, including atherosclerosis and cancer. Studies on single-nucleotide polymorphisms (SNPs) in miRNA genes can help gain insight into the susceptibility to the condition. This study aimed to examine the relationship between miR-365 SNPs and the risk of IS.

Methods

The study recruited 215 IS patients and 220 controls. The SNPscans genotyping was employed to genotype three polymorphic loci (rs121224, rs30230, and rs178553) of miR-365. The relative expression of miR-365 in peripheral blood mononuclear cells of the patients and controls was determined by using real-time quantitative PCR.

Results

The miR-365 rs30230 polymorphism exhibited a significant association with the risk of developing IS (TC vs. CC: adjusted OR = 0.55, 95% CI: 0.33-0.92, P = 0.022; TT vs. CC: adjusted OR = 0.34, 95% CI: 0.14–0.85, P = 0.021; TC +TT vs. CC: adjusted OR = 0.51, 95% CI: 0.31–0.83, P = 0.007; T vs. C: adjusted OR = 0.57, 95% CI: 0.39–0.83, P = 0.004). Haplotype analysis revealed that the C-T-G haplotype was associated with a decreased risk of IS (OR = 0.68, 95% CI: 0.46–1.00, P = 0.047). Furthermore, miR-365 expression was significantly higher in IS patients than in controls (P < 0.001). Interestingly, patients with rs30230 TC or TT genotypes had lower miR-365 levels compared to their counterparts with CC genotypes (P < 0.001).

Conclusions

The miR-365 rs30230 polymorphism might bear an association with IS susceptibility in the Chinese population, and the rs30230 TC/TT genotype might be a protective factor against IS.
Predicting acute ischemic stroke using the revised Framingham stroke risk profile and multimodal magnetic resonance imaging
Authors: Sun Jiali , Sui Ying , Chen Yue , Lian Jianxiu , Wang Wei
Published: September 2023

Background and purpose

Patients with transient ischemic attacks (TIA) have a significant risk of developing acute ischemic strokes (AIS), emphasizing the critical need for hierarchical management. This study aims to develop a clinical-imaging model utilizing multimodal magnetic resonance imaging (mMRI) and the revised Framingham Stroke Risk Profile (FSRP) to predict AIS and achieve early secondary prevention.

Methods

mMRI scans were conducted on patients with symptomatic intracranial atherosclerotic disease (ICAD) to assess vascular wall features and cerebral perfusion parameters. Based on diffusion-weighted imaging (DWI), patients were divided into two groups: TIA and AIS. Clinical data were evaluated to calculate the FSRP score. Differences in clinical and imaging characteristics between the groups were analyzed, and a predictive model for AIS probability in patients with ICAD was established.

Results

A total of 112 TIA and AIS patients were included in the study. The results showed that the AIS group had higher proportions of FSRP-high risk, hyperhomocysteinemia, and higher value of low-density lipoprotein (LDL), standardized plaque index (SQI), and enhancement rate (ER) compared to the TIA group (p < 0.05). Mean transit time (MTT) and time to peak (TTP) in the lesion area were significantly longer in the AIS group (p < 0.05). Multivariate analysis identified FSRP-high risk (p = 0.027) and high ER (p = 0.046) as independent risk factors for AIS. The combined clinical and mMRI model produced an area under the curve (AUC) of 0.791 in receiver operating characteristic (ROC) analysis. The constructed nomogram model combining clinical and mMRI features demonstrated favorable clinical net benefits.

Conclusion

FSRP-high risk and high ER were confirmed as independent risk factors for AIS. The combined prediction model utilizing clinical and imaging markers effectively predicts stroke risk in symptomatic ICAD patients.
Transient ischemic attacks in patients with active and occult cancer
Authors: Beyeler Morin , Castigliego Pasquale , Baumann Joel , Ziegler Victor , Kielkopf Moritz , Mueller Madlaine , Bauer-Gambelli Stefan A. , Mujanovic Adnan , Meinel Thomas Raphael , Horvath Thomas , Fischer Urs , Kaesmacher Johannes , Heldner Mirjam R. , Seiffge David , Arnold Marcel , Pabst Thomas , Berger Martin D. , Navi Babak B. , Jung Simon , Bücke Philipp
Published: September 2023

Background and aim

Paraneoplastic coagulopathy can present as stroke and is associated with specific biomarker changes. Identifying paraneoplastic coagulopathy can help guide secondary prevention in stroke patients, and early cancer detection might improve outcomes. However, unlike ischemic stroke, it remains unclear whether paraneoplastic coagulopathy is associated with transient ischemic attacks (TIA). This study assessed the presence of cancer-related biomarkers in TIA patients and evaluated long-term mortality rates in patients with and without active cancer.

Methods

Active cancer was retrospectively identified in consecutive TIA patients treated at a comprehensive stroke center between 2015 and 2019. An association between the presence of cancer and cancer-related biomarkers was assessed using multivariable logistic regression. Long-term mortality after TIA was analyzed using multivariable Cox regression.

Results

Among 1436 TIA patients, 72 had active cancer (5%), of which 17 were occult (1.2%). Cancer-related TIA was associated with male gender (adjusted odds ratio [aOR] 2.29, 95% CI 1.12–4.68), history of smoking (aOR 2.77, 95% CI 1.34–5.7), elevated D-dimer (aOR 1.77, 95% CI 1.26–2.49), lactate dehydrogenase (aOR 1.003, 95% CI 1.00–1.005), lower leukocyte count (aOR 1.20, 95% CI 1.04–1.38), and lower hemoglobin (aOR 1.02, 95% CI 1.00–1.04). Long-term mortality was associated with both active cancer (adjusted hazard ratios [aHR] 2.47, 95% CI 1.58–3.88) and occult cancer (aHR 3.08, 95% CI 1.30–7.32).

Conclusion

Cancer-related TIA is not uncommon. Biomarkers known to be associated with cancer-related stroke also seem to be present in TIA patients. Early identification would enable targeted treatment strategies and could improve outcomes in this patient population.
Tract- and gray matter- based spatial statistics show white matter and gray matter microstructural differences in autistic males
Authors: DiPiero Marissa , Cordash Hassan , Prigge Molly B. , King Carolyn K. , Morgan Jubel , Guerrero-Gonzalez Jose , Adluru Nagesh , King Jace B. , Lange Nicholas , Bigler Erin D. , Zielinski Brandon A. , Alexander Andrew L. , Lainhart Janet E. , Dean Douglas C.
Published: September 2023

Background

Autism spectrum disorder (ASD) is a neurodevelopmental condition commonly studied in the context of early childhood. As ASD is a life-long condition, understanding the characteristics of brain microstructure from adolescence into adulthood and associations to clinical features is critical for improving outcomes across the lifespan. In the current work, we utilized Tract Based Spatial Statistics (TBSS) and Gray Matter Based Spatial Statistics (GBSS) to examine the white matter (WM) and gray matter (GM) microstructure in neurotypical (NT) and autistic males.

Methods

Multi-shell diffusion MRI was acquired from 78 autistic and 81 NT males (12-to-46-years) and fit to the DTI and NODDI diffusion models. TBSS and GBSS were performed to analyze WM and GM microstructure, respectively. General linear models were used to investigate group and age-related group differences. Within the ASD group, relationships between WM and GM microstructure and measures of autistic symptoms were investigated.

Results

All dMRI measures were significantly associated with age across WM and GM. Significant group differences were observed across WM and GM. No significant age-by-group interactions were detected. Within the ASD group, positive relationships with WM microstructure were observed with ADOS-2 Calibrated Severity Scores.

Conclusion

Using TBSS and GBSS our findings provide new insights into group differences of WM and GM microstructure in autistic males from adolescence into adulthood. Detection of microstructural differences across the lifespan as well as their relationship to the level of autistic symptoms will deepen to our understanding of brain-behavior relationships of ASD and may aid in the improvement of intervention options for autistic adults.
Unraveling the functional consequences of a novel germline missense mutation (R38C) in the yeast model of succinate dehydrogenase subunit B: insights into neurodegenerative disorders
Authors: Zheng Jiatong , Liu Siru , Wang Dongdong , Li Linlin , Sarsaiya Surendra , Zhou Hua , Cai Heng
Published: September 2023

This study explores the implications of a novel germline missense mutation (R38C) in the succinate dehydrogenase (SDH) subunit B, which has been linked to neurodegenerative diseases. The mutation was identified from the SDH mutation database and corresponds to the SDH2R32C allele, mirroring the human SDHBR38C mutation. By subjecting the mutant yeast model to hydrogen peroxide (H2O2) stress, simulating oxidative stress, we observed heightened sensitivity to oxidative conditions. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed significant regulation (p < 0.05) of genes associated with antioxidant systems and energy metabolism. Through gas chromatography-mass spectrometry (GC-MS) analysis, we examined yeast cell metabolites under oxidative stress, uncovering insights into the potential protective role of o-vanillin. This study elucidates the biological mechanisms underlying cellular oxidative stress responses, offering valuable insights into its repercussions. These findings shed light on innovative avenues for addressing neurodegenerative diseases, potentially revolutionizing therapeutic strategies.
Teaching nutrition and sustainable food systems: justification and an applied approach
Authors: Campbell Christina Gayer , Feldpausch Gretchen
Published: September 2023

Systems thinking is an essential skill for solving real-world problems, supporting lasting, impactful change, and creating desired futures. Transdisciplinary teaching and learning should be integrated into higher education to ensure students have the knowledge and skills to prosper in an ever-changing world. Education that addresses the interconnectedness of food systems is fundamental in cultivating future generations equipped to mitigate complex problems, such as hunger, nutrition-related chronic disease, and the climate crisis. Connecting the food, agriculture, and nutrition sectors is vitally important for improving human and planetary health and well-being. While we continue to acknowledge that it is critically important to teach systems thinking in the context of sustainable food systems limited resources are available to facilitate this type of learning. Historically, a “triple-bottom-line” approach focusing on economic, environmental, and social perspectives has been used to define sustainability. In contrast, including nutrition and health may provide a more robust view and even greater consideration for the system in its entirety. The sustainable, resilient, healthy food and water system framework, addressing all four pillars, can be used in higher education to help evaluate the sustainability of food and compare methods of production, place, and dietary patterns. This paper justifies the need for addressing sustainability issues in the context of nutrition and provides an educational approach to support student understanding and application of a systems thinking approach.
Ketogenic effects of medium chain triglycerides containing formula and its correlation to breath acetone in healthy volunteers: a randomized, double-blinded, placebo-controlled, single dose-response study
Authors: Nakamura Kentaro , Hagihara Keisuke , Nagai Naoko , Egashira Ryuichiro , Takeuchi Mariko , Nakano Mai , Saito Hitomi , Moriguchi Misaki , Tonari Satoko , Fujii Hisako , Miyake Akimitsu , Omae Yusuke , Ashida Kinya
Published: September 2023

The efficacy of low-carbohydrate, high-fat diets, such as ketogenic diets, for cancer patients is of research interest. We previously demonstrated the efficacy of the ketogenic diet in a case study in which medium-chain triglycerides (MCTs) or MCT-containing formula (ketogenic formula) was used as a supplement to increase blood ketone bodies. However, little is known about the amounts needed to induce ketogenic effects and about the usefulness of monitoring of breath acetone. To investigate the pharmacokinetics of MCTs and their metabolites, blood ketone bodies and breath acetone, 24 healthy subjects received one of four single oral doses of the ketogenic formula (equivalent to 0, 10, 20, and 30 g of MCTs) under fasting conditions. Total blood ketone bodies, β-hydroxybutyrate, octanoic acid, and decanoic acid were increased in a dose-dependent manner. The ketogenic effect was considered to depend on octanoic and decanoic acids, because a positive correlation was observed between them. A strong positive correlation was also observed between total serum ketone bodies and breath acetone at each time points. Therefore, monitoring breath acetone levels seems a less invasive method to predict blood concentrations of ketone bodies during ketogenic diet therapy.

Clinical trial registration:https://rctportal.niph.go.jp/en/detail?trial_id=UMIN000032634, UMIN-CTR UMIN000032634.
Unlocking the role of non-coding RNAs in prostate cancer progression: exploring the interplay with the Wnt signaling pathway
Authors: Bu Tong , Li Le , Tian Jiyu
Published: September 2023

Prostate cancer (PCa) is one of the most common cancers in males, exhibiting a wide spectrum of clinical manifestations that pose challenges in its diagnosis and treatment. The Wnt signaling pathway, a conserved and complex pathway, is crucial for embryonic development, tissue homeostasis, and various physiological processes. Apart from the classical Wnt/β-catenin signaling pathway, there exist multiple non-classical Wnt signaling pathways, including the Wnt/PCP and Wnt/Ca2+ pathways. Non-coding RNAs (ncRNAs) are involved in the occurrence and development of PCa and the response to PCa treatment. ncRNAs are known to execute diverse regulatory roles in cellular processes, despite their inability to encode proteins. Among them, microRNAs, long non-coding RNAs, and circular RNAs play key roles in the regulation of the Wnt signaling pathway in PCa. Aberrant expression of these ncRNAs and dysregulation of the Wnt signaling pathway are one of the causes of cell proliferation, apoptosis, invasion, migration, and angiogenesis in PCa. Moreover, these ncRNAs affect the characteristics of PCa cells and hold promise as diagnostic and prognostic biomarkers. Herein, we summarize the role of ncRNAs in the regulation of the Wnt signaling pathway during the development of PCa. Additionally, we present an overview of the current progress in research on the correlation between these molecules and clinical features of the disease to provide novel insights and strategies for the treatment of PCa.
Long non-coding RNA H19 enhances the pro-apoptotic activity of ITF2357 (a histone deacetylase inhibitor) in colorectal cancer cells
Authors: Zichittella Chiara , Loria Marco , Celesia Adriana , Di Liberto Diana , Corrado Chiara , Alessandro Riccardo , Emanuele Sonia , Conigliaro Alice
Published: September 2023

Introduction: Long non-coding RNA H19 (lncH19) is highly expressed in colorectal cancer (CRC) and plays critical roles in tumor development, proliferation, metastasis, and drug resistance. Indeed, the expression of lncH19 usually affects the outcomes of chemo-, endocrine, and targeted therapies. ITF2357 (givinostat) is a histone deacetylase inhibitor (HDACi) that revealed a significant anti-tumor action by inducing apoptosis in different tumor models, including leukemia, melanoma, and glioblastoma. However, no data are present in the literature regarding the use of this compound for CRC treatment. Here, we investigate the role of lncH19 in ITF2357-induced apoptosis in CRC cells.

Methods: The HCT-116 CRC cell line was stably silenced for H19 to investigate the role of this lncRNA in ITF2357-induced cell death. Cell viability assays and flow cytometric analyses were performed to assess the anti-proliferative and pro-apoptotic effects of ITF2357 in CRC cell lines that are silenced or not for lncH19. RT-PCR and Western blot were used to study the effects of ITF2357 on autophagy and apoptosis markers. Finally, bioinformatics analyses were used to identify miRNAs targeting pro-apoptotic factors that can be sponged by lncH19.

Results: ITF2357 increased the expression levels of H19 and reduced HCT-116 cell viability, inducing apoptosis, as demonstrated by the increase in annexin-V positivity, caspase 3 cleavage, and poly (ADP-ribose) polymerase (PARP-1) degradation. Interestingly, the apoptotic effect of ITF2357 was much less evident in lncH19-silenced cells. We showed that lncH19 plays a functional role in the pro-apoptotic activity of the drug by stabilizing TP53 and its transcriptional targets, NOXA and PUMA. ITF2357 also induced autophagy in CRC cells, which was interpreted as a pro-survival response not correlated with lncH19 expression. Furthermore, ITF2357 induced apoptosis in 5-fluorouracil-resistant HCT-116 cells that express high levels of lncH19.

Conclusion: This study shows that lncH19 expression contributes to ITF2357-induced apoptosis by stabilizing TP53. Overall, we suggest that lncH19 expression may be exploited to favor HDACi-induced cell death and overcome 5-fluorouracil chemoresistance.
Estimation of ocean turbulence intensity using convolutional neural networks
Authors: Chen Yonghao , Liu Xiaoyun , Jiang Jinyang , Gao Siyu , Liu Ying , Jiang Yueqiu
Published: September 2023

Understanding the transmission of light in ocean turbulence is of great significance for underwater communication, underwater detection, and other fields. The properties of ocean turbulence can affect the transmission characteristics of light beams, therefore it is essential to estimate the ocean turbulence intensity (OTI). In this study, we propose a deep learning-based method for predicting the OTI. Using phase screens to simulate ocean turbulence, we constructed a database of distorted Gaussian beams generated by Gaussian beams passing through ocean turbulence with varying intensities. We built a convolutional neural network and trained it using this database. For the trained network, inputting a distorted beam can accurately predict the corresponding intensity of ocean turbulence. We also compared our designed network with traditional network models such as AlexNet, VGG16, and Xception, and the results showed that our designed network had higher accuracy.
The effects of environmental enrichment on voluntary physical activity and muscle mass gain in growing rats
Authors: Sudo Mizuki , Kano Yutaka , Ando Soichi
Published: September 2023

Introduction: Environmental enrichment (EE) for rodents involves housing conditions that facilitate enhanced sensory, cognitive, and motor stimulation relative to standard housing conditions. A recent study suggested that EE induces muscle hypertrophy. However, it remains unclear whether muscle hypertrophy in EE is associated with voluntary physical activity, and the characteristics of muscle adaptation to EE remain unclarified. Therefore, this study investigated whether muscle adaptation to EE is associated with voluntary physical activity, and assessed the changes in the muscle fiber-type distribution and fiber-type-specific cross-sectional area in response to EE.

Methods: Wistar rats (6 weeks of age) were randomly assigned to either the standard environment group (n = 10) or the EE group (n = 10). The voluntary physical activity of rats housed in EE conditions was measured using a recently developed three-axis accelerometer. After exposure to the standard or enriched environment for 30 days, the tibialis anterior, extensor digitorum longus, soleus, plantaris, and gastrocnemius muscles were removed and weighed. Immunohistochemistry analysis was performed on the surface (anterior) and deep (posterior) areas of the tibialis anterior and soleus muscles.

Results and discussion: The EE group showed increased voluntary physical activity during the dark period compared with the standard environment group (p = 0.005). EE induced muscle mass gain in the soleus muscle (p = 0.002) and increased the slow-twitch muscle fiber cross-sectional area of the soleus muscle (p = 0.025). EE also increased the distribution of high-oxidative type IIa fibers of the surface area (p = 0.001) and type I fibers of the deep area (p = 0.037) of the tibialis anterior muscle. These findings suggest that EE is an effective approach to induce slow-twitch muscle fiber hypertrophy through increased daily voluntary physical activity.
Detection of epistasis interaction loci for fiber quality-related trait via 3VmrMLM in upland cotton
Authors: Han Zhimin , Ke Huifeng , Li Xiaoyu , Peng Ruoxuan , Zhai Dongdong , Xu Yang , Wu Liqiang , Wang Wensheng , Cui Yanru
Published: September 2023

Cotton fiber quality-related traits, such as fiber length, fiber strength, and fiber elongation, are affected by complex mechanisms controlled by multiple genes. Determining the QTN-by-QTN interactions (QQIs) associated with fiber quality-related traits is therefore essential for accelerating the genetic enhancement of cotton breeding. In this study, a natural population of 1,245 upland cotton varieties with 1,122,352 SNPs was used for detecting the main-effect QTNs and QQIs using the 3V multi-locus random-SNP-effect mixed linear model (3VmrMLM) method. A total of 171 significant main-effect QTNs and 42 QQIs were detected, of which 22 were both main-effect QTNs and QQIs. Of the detected 42 QQIs, a total of 13 significant loci and 5 candidate genes were reported in previous studies. Among the three interaction types, the AD interaction type has a preference for the trait of FE. Additionally, the QQIs have a substantial impact on the enhancement predictability for fiber quality-related traits. The study of QQIs is crucial for elucidating the genetic mechanism of cotton fiber quality and enhancing breeding efficiency.
Maize plant expresses SWEET transporters differently when interacting with Trichoderma asperellum and Fusarium verticillioides, two fungi with different lifestyles
Authors: López-Coria Montserrat , Guzmán-Chávez Fernando , Carvente-García Roberto , Muñoz-Chapul Daniela , Sánchez-Sánchez Tomás , Arciniega-Ruíz Juan Manuel , King-Díaz Beatriz , Sánchez-Nieto Sobeida
Published: September 2023

Most Trichoderma species are beneficial fungi that promote plant growth and resistance, while Fusarium genera cause several crop damages. During the plant-fungi interaction there is a competition for sugars in both lifestyles. Here we analyzed the plant growth promotion and biocontrol activity of T. asperellum against F. verticillioides and the effect of both fungi on the expression of the maize diffusional sugar transporters, the SWEETs. The biocontrol activity was done in two ways, the first was by observing the growth capacity of both fungus in a dual culture. The second one by analyzing the infection symptoms, the chlorophyl content and the transcript levels of defense genes determined by qPCR in plants with different developmental stages primed with T. asperellum conidia and challenged with F. verticillioides. In a dual culture, T. asperellum showed antagonist activity against F. verticillioides. In the primed plants a delay in the infection disease was observed, they sustained chlorophyll content even after the infection, and displayed upregulated defense-related genes. Additionally, the T. asperellum primed plants had longer stems than the nonprimed plants. SWEETs transcript levels were analyzed by qPCR in plants primed with either fungus. Both fungi affect the transcript levels of several maize sugar transporters differently. T. asperellum increases the expression of six SWEETs on leaves and two at the roots and causes a higher exudation of sucrose, glucose, and fructose at the roots. On the contrary, F. verticillioides reduces the expression of the SWEETs on the leaves, and more severely when a more aggressive strain is in the plant. Our results suggest that the plant is able to recognize the lifestyle of the fungi and respond accordingly by changing the expression of several genes, including the SWEETs, to establish a new sugar flux.
Integrative transcriptomic analysis deciphering the role of rice bHLH transcription factor Os04g0301500 in mediating responses to biotic and abiotic stresses
Authors: Zhang Qiuping , Teng Rong , Yuan Ziyi , Sheng Song , Xiao Yunhua , Deng Huabing , Tang Wenbang , Wang Feng
Published: September 2023

Understanding the signaling pathways activated in response to these combined stresses and their crosstalk is crucial to breeding crop varieties with dual or multiple tolerances. However, most studies to date have predominantly focused on individual stress factors, leaving a significant gap in understanding plant responses to combined biotic and abiotic stresses. The bHLH family plays a multifaceted regulatory role in plant response to both abiotic and biotic stresses. In order to comprehensively identify and analyze the bHLH gene family in rice, we identified putative OsbHLHs by multi-step homolog search, and phylogenic analysis, molecular weights, isoelectric points, conserved domain screening were processed using MEGAX version 10.2.6. Following, integrative transcriptome analysis using 6 RNA-seq data including Xoo infection, heat, and cold stress was processed. The results showed that 106 OsbHLHs were identified and clustered into 17 clades. Os04g0301500 and Os04g0489600 are potential negative regulators of Xoo resistance in rice. In addition, Os04g0301500 was involved in non-freezing temperatures (around 4°C) but not to 10°C cold stresses, suggesting a complex interplay with temperature signaling pathways. The study concludes that Os04g0301500 may play a crucial role in integrating biotic and abiotic stress responses in rice, potentially serving as a key regulator of plant resilience under changing environmental conditions, which could be important for further multiple stresses enhancement and molecular breeding through genetic engineering in rice.
Modern episteme, methodological nationalism and the politics of transnationalism
Authors: Jong Abbas
Published: September 2023

Methodological nationalism can be understood in the broadest sense possible as any kind of correspondence between society and the unit of the nation-state. This equation can be traced and understood at two levels: firstly, within the socio-historical context of the rise of nationalism and the development of human and social sciences; and secondly, within the cognitive context of the emergence of nationalism and these sciences, or the modern episteme, in other words. By focusing on the latter, the present article aims to indicate that the problem of methodological nationalism can be effectively grasped by exploring the intricate interplay among modernity, the discourse of nationalism, and the emergence of social science, particularly concerning the modern episteme. It becomes apparent that the regime of foundationalist differentiation ingrained within the modern episteme has established the foundation for this correspondence or congruence—a regime that, while constructing determined, regulated, unified and completed categories, such as society and the social/nation-state and the national, simultaneously sets the ground for the exclusion of other non-social/non-national phenomena and events. In this paper, the objective is to demonstrate how, by disclosing the implementation of this regime as well as highlighting the contingent nature and, consequently, the conditions of the possibility of social phenomena in the path of their grounding, alongside prioritizing the indeterminate social configurations and arguing for a post-foundationalist approach and the politics of transnationalism, it becomes possible to overcome the problem of methodological nationalism. This, in turn, sets a basis for taking into account excluded and indeterminate phenomena and actors within a global context.
UNdefined regions: toward a new typology of regions in the UN
Authors: De Lombaerde Philippe , D'Attoma Marco , Dullaghan Neil , Umezawa Hana , Verhelst Caroline
Published: September 2023

Even though the UN interacts with regions and regionalism, a systematic analysis of the development of the regional dimension within their bodies is still needed. Traditional categories identifying simply electoral or operational roles for regions fall short in accounting for their multi-layered and increasing impact. Aiming at formulating a new typology and research agenda in this area, the authors approached the issue inductively. First, they provided a historical mapping of the regional manifestations in the framework of the UN and UN-regional organization interactions. Second, they analyzed relevant debates for the UN on peace, security, and sustainability through the lens of the regional dimension. What emerges is that, though vaguely defined and seriously fragmented, regions are largely used as electoral bodies, socio-economic areas, and statistical categories by the UN, that follow historical, cultural, and political rather than purely geographical criteria in their shaping. Besides, in the last 20 years, regions have become crucial for peacekeeping and conflict resolution in specific areas, as well as they are paramount to the implementation of global sustainability goals. All in all, the inductive approach has outlined three dimensions of UN regionalism: regions' political and operational roles; institutionalized vs. non-institutionalized groupings; and their formal vs. informal status. Finally, the authors suggest that strengthening partnerships between the UN and regional entities should be a milestone for a new era of networked and multi-layered multilateralism, while the harmonization of statistical regions is desirable at the operational level.
Cardioautonomic lability assessed by heart rate variability changes in Royal Canadian Mounted Police cadets during the cadet training program
Authors: Teckchandani Taylor A. , Neary J. Patrick , Andrews Katie L. , Maguire Kirby Q. , Jamshidi Laleh , Nisbet Jolan , Shields Robyn E. , Afifi Tracie O. , Sauer-Zavala Shannon , Lix Lisa M. , Krakauer Rachel L. , Asmundson Gordon J. G. , Krätzig Gregory P. , Carleton R. Nicholas
Published: September 2023

Objective

The current study examined variations in cardioautonomic lability during the Royal Canadian Mounted Police (RCMP) Cadet Training Program (CTP) between cadets starting their training who did or did not screen positive for one or more mental health disorders (i.e., posttraumatic stress disorder [PTSD], major depressive disorder [MDD], social anxiety disorder [SAD], generalized anxiety disorder [GAD], panic disorder [PD], alcohol use disorder [AUD]).

Methods

Electrocardiogram (ECG) signals integrated into Hexoskin garments were used to record ECG and heart rate Over the 26-week CTP. There were 31 heart rate variability (HRV) parameters calculated using Kubios Premium HRV analysis software. Mann–Whitney U-tests were used to perform groupwise comparisons of participant raw values and HRV during the CTP.

Results

A total of 157 cadets (79% male) were screened for any mental disorder using self-report surveys and then grouped by positive and negative screening. Analyses indicated a statistically significant (p < 0.05) decrease in low frequency (LF): High Frequency (HF) variability during CTP, but only for cadets who endorsed clinically significant anxiety symptoms on the GAD-7 at the start of their training. There were no other statistically significant groupwise differences.

Conclusion

The results indicate the participants have excellent cardiac health overall and suggest potentially important differences between groups, such that cadets who endorsed clinically significant anxiety symptoms on the GAD-7 showed less variability in the LF:HF ratio over the course of the CTP. The relatively lower variability suggests decreased parasympathetic tone in those without clinically significant anxiety symptoms. The results also have important implications for future investigations of cardioautonomic dysfunction and chronic hypothalamic pituitary adrenal (HPA) axis deviations in policing populations with anxiety disorders; specifically, cardioautonomic inflexibility related to cardiovascular morbidity and mortality. In any case, the current results provide an important baseline for future cardiac research with cadets and serving officers.
Development and validation of the adaptive leadership behavior scale (ALBS)
Authors: Nöthel Sophie , Nübold Annika , Uitdewilligen Sjir , Schepers Jan , Hülsheger Ute
Published: September 2023

Due to the rapid changes in today’s business world, leaders need to, more than ever, adequately and flexibly react to new and changing demands in the workplace. An instrument that captures adaptive leadership behavior is still missing, however. This study describes the development and validation of a concise and timely new leadership instrument, the Adaptive Leadership Behavior Scale (ALBS). Based on a thorough literature review, we developed 27 items as an initial item pool. We tested this set of items with leaders and followers in a pilot study to assess its relevancy and comprehensibility. In Study 1, a field study with 201 employees, we explored the internal structure of the initial item pool with a Principal Component Analysis (PCA). Based on the factor loadings resulting from a second PCA, we reduced the item pool, resulting in a 15-item scale for which we then assessed convergent and divergent validity. In Study 2, a field study with 311 employees, we replicated the findings of Study 1 and assessed additional convergent and divergent validity as well as the model fit with a Confirmatory Factor Analysis (CFA). In Study 3, a multi-source field study with 155 leader-follower dyads we replicated the CFA and additionally assessed criterion-related validity. Results show that the ALBS is a concise and valid instrument for assessing adaptive leadership behavior, thereby building the grounds to extend our understanding of antecedents, mechanisms and consequences of leadership in dynamic environments.
When guilt works: a comprehensive meta-analysis of guilt appeals
Authors: Peng Wei , Huang Qian , Mao Bingjing , Lun Di , Malova Ekaterina , Simmons Jazmyne V. , Carcioppolo Nick
Published: September 2023

Introduction

Guilt appeals are widely used as a persuasive approach in various areas of practice. However, the strength and direction of the persuasive effects of guilt appeals are mixed, which could be influenced by theoretical and methodological factors.

Method

The present study is a comprehensive meta-analysis of 26 studies using a random-effects model to assess the persuasive effects of guilt appeals. In total, 127 effect sizes from seven types of persuasive outcomes (i.e., guilt, attitude, behavior, behavioral intention, non-guilt emotions, motivation, and cognition) were calculated based on 7,512 participants.

Results

The analysis showed a small effect size of guilt appeals [g= 0.19, 95% CI (0.10, 0.28)]. The effect of guilt appeals was moderated by the theoretical factors related to appraisal and coping of guilt arousal, including attributed responsibility, controllability and stability of the causal factors, the proximity of perceiver-victim relationship, recommendation of reparative behaviors, and different outcome types. The effect was also associated with methods used in different studies.

Discussion

Overall, the findings demonstrated the persuasive effects of guilt appeals, but theoretical and methodological factors should be considered in the design and testing of guilt appeals. We also discussed the practical implications of the findings.