bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor microenvironment-modulating oncolytic adenovirus combined with GSK-3β inhibitor enhances antitumor immune response against bladder cancer
Authors: Yoon A-Rum , Jiao Ao , Hong JinWoo , Kim Bomi , Yun Chae-Ok
Published: May 2024

Bladder cancer is a common type of cancer around the world, and the majority of patients are diagnosed with non-muscle-invasive bladder cancer (NMIBC). Although low-risk NMIBC has a good prognosis, the disease recurrence rate and development of treatment-refractory disease remain high in intermediate- to high-risk NMIBC patients. To address these challenges for the treatment of NMIBC, a novel combination therapy composed of an oncolytic adenovirus (oAd) co-expressing interleukin (IL)-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), and relaxin (RLX; HY-oAd) and a clinical-stage glycogen synthase kinase (GSK)-3β inhibitor (9-ING-41; elraglusib) was investigated in the present report. Our findings demonstrate that HY-oAd and 9-ING-41 combination therapy (HY-oAd+9-ING-41) exerted superior inhibition of tumor growth compared with respective monotherapy in a syngeneic NMIBC tumor model. HY-oAd+9-ING-41 induced high-level tumor extracellular matrix (ECM) degradation and a more potent antitumor immune response than the respective monotherapy. In detail, HY-oAd+9-ING-41 induced superior accumulation of intratumoral T cells, prevention of immune cell exhaustion, and induction of tumor-specific adaptive immune response compared to either monotherapy. Collectively, these results demonstrate that the combination of HY-oAd and 9-ING-41 may be a promising approach to elicit a potent antitumor immune response against bladder cancer.
The cholera toxin B subunit induces trained immunity in dendritic cells and promotes CD8 T cell antitumor immunity
Authors: Tepale-Segura Araceli , Gajón Julián A. , Muñoz-Cruz Samira , Castro-Escamilla Octavio , Bonifaz Laura C.
Published: May 2024

Introduction

Innate immune training is a metabolic, functional, and epigenetic long-term reprogramming of innate cells triggered by different stimuli. This imprinting also reaches hematopoietic precursors in the bone marrow to sustain a memory-like phenotype. Dendritic cells (DCs) can exhibit memory-like responses, enhanced upon subsequent exposure to a pathogen; however, whether this imprinting is lineage and stimulus-restricted is still being determined. Nevertheless, the functional consequences of DCs training on the adaptive and protective immune response against non-infectious diseases remain unresolved.

Methods

We evaluated the effect of the nontoxic cholera B subunit (CTB), LPS and LTA in the induction of trained immunity in murine DCs revealed by TNFa and LDH expression, through confocal microscopy. Additionally, we obtained bone marrow DCs (BMDCs) from mice treated with CTB, LPS, and LTA and evaluated training features in DCs and their antigen-presenting cell capability using multiparametric cytometry. Finally, we design an experimental melanoma mouse model to demonstrate protection induced by CTB-trained DCs in vivo.

Results

CTB-trained DCs exhibit increased expression of TNFa, and metabolic reprogramming indicated by LDH expression. Moreover, CTB training has an imprint on DC precursors, increasing the number and antigen-presenting function in BMDCs. We found that training by CTB stimulates the recruitment of DC precursors and DCs infiltration at the skin and lymph nodes. Interestingly, training-induced by CTB promotes a highly co-stimulatory phenotype in tumor-infiltrating DCs (CD86+) and a heightened functionality of exhausted CD8 T cells (Ki67+, GZMB+), which were associated with a protective response against melanoma challenge in vivo.

Conclusion

Our work indicates that CTB can induce innate immune training on DCs, which turns into an efficient adaptive immune response in the melanoma model and might be a potential immunotherapeutic approach for tumor growth control.
The prognostic implications and tumor-promoting functions of CHSY3 in gastric cancer
Authors: Wang Han , Zhang Junchang , Wei Zhuoqi , Chen Songyao , Zheng Jiabin , Li Yong
Published: May 2024

Chondroitin sulfate synthase 3 (CHSY3) is an important enzyme that regulates glycosylation, but its role in tumors has not been determined. Here, we showed that high CHSY3 expression promotes proliferation in gastric cancer (GC) cells and is associated with poor prognosis in GC patients. We analyzed the immunohistochemistry data of 150 gastric cancer patients to determine the clinicopathological and survival significance of CHSY3. Immunofluorescence was used to detect the colocalization of CHSY3 with infiltrating immune cells. Additionally, CHSY3 was predominantly found in tumor tissues and showed higher abundance compared to matched adjacent tissues. High CHSY3 expression was associated with more advanced tumor stage, higher recurrence risk and worse survival. Immunohistochemistry and bioinformatic analysis revealed that CHSY3 expression was significantly positively correlated with tumor-associated macrophage (TAM) infiltration. Moreover, after knocking down CHSY3, the proliferation of cells was decreased, and the migration ability was reduced, as shown by scratch, monoclonal and transwell assays. In conclusion, this study revealed that CHSY3 has a tumor-promoting effect on GC, suggesting a novel therapeutic strategy against this disease.
Mast cell degranulation and bradykinin-induced angioedema - searching for the missing link
Authors: Porebski Grzegorz , Dziadowiec Alicja , Rybka Hubert , Kitel Radoslaw , Kwitniewski Mateusz
Published: May 2024

Initiation of the bradykinin generation cascade is responsible for the occurrence of attacks in some types of angioedema without wheals. Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) is one such clinical entity. In this paper, we explore the existing evidence that mast cells (MCs) degranulation may contribute to the activation of the kallikrein-kinin system cascade, followed by bradykinin formation and angioedema. We present the multidirectional effects of MC-derived heparin and other polyanions on the major components of the kinin-kallikrein system, particularly on the factor XII activation. Although, bradykinin- and histamine-mediated symptoms are distinct clinical phenomena, they share some common features, such as some similar triggers and a predilection to occur at sites where mast cells reside, namely the skin and mucous membranes. In addition, recent observations indicate a high incidence of hypersensitivity reactions associated with MC degranulation in the HAE-C1-INH patient population. However, not all of these can be explained by IgE-dependent mechanisms. Mast cell-related G protein-coupled receptor-X2 (MRGPRX2), which has recently attracted scientific interest, may be involved in the activation of MCs through a different pathway. Therefore, we reviewed MRGPRX2 ligands that HAE-C1-INH patients may be exposed to in their daily lives and that may affect MCs degranulation. We also discussed the known inter- and intra-individual variability in the course of HAE-C1-INH in relation to factors responsible for possible variability in the strength of the response to MRGPRX2 receptor stimulation. The above issues raise several questions for future research. It is not known to what extent a prophylactic or therapeutic intervention targeting the pathways of one mechanism (mast cell degranulation) may affect the other (bradykinin production), or whether the number of mast cells at a specific body site and their reactivity to triggers such as pressure, allergens or MRGPRX2 agonists may influence the occurrence of HAE-C1-INH attacks at that site.
Antibody responses in blood and saliva post COVID-19 bivalent booster do not reveal an Omicron BA.4/BA.5- specific response
Authors: Baker Ryan , Lawlor Rebecca , Smith Maeve , Price Jessica , Eaton Ashley , Lover Andrew , Alfandari Dominique , Reinhart Peter , Arcaro Kathleen F. , Osborne Barbara A.
Published: May 2024

Introduction

Current SARS-CoV-2 strains continue to mutate and attempt to evade the antibody response elicited by previous exposures and vaccinations. In September of 2022, the first updated SARS-CoV-2 vaccines, designed to create immune responses specific for the variants circulating in 2022, were approved. These new vaccines, known commonly as the bivalent boost(er), include mRNA that encodes both the original Wuhan-Hu-1 spike protein as well as the spike protein specific to the Omicron BA.4 and BA.5 variants.

Methods

We recruited volunteers from University of Massachusetts student, faculty and staff members to provide samples of blood and saliva at four different time points, including pre-boost and three times post boost and analyzed samples for antibody production as well as neutralization of virus.

Results

Our data provide a comprehensive analysis of the antibody response following a single dose of the bivalent boost over a 6-month period and support previous findings that the response induced after the bivalent boost does not create a strong BA.4/BA.5-specific antibody response.

Conclusion

We found no evidence of a specific anti-BA.4/BA.5 response developing over time, including in a sub-population of individuals who become infected after a single dose of the bivalent booster. Additionally, we present data that support the use of saliva samples as a reliable alternative to blood for antibody detection against specific SARS-CoV-2 antigens.
Quantifying wildlife conflicts with metabarcoding and traditional dietary analyses: applied to seabird predation by long-nosed fur seals
Authors: Hardy Natasha A. , Berry Tina E. , Bunce Michael , Bott Nathan J. , Figueira Will F. , McIntosh Rebecca R.
Published: May 2024

Wildlife conflicts require robust quantitative data on incidence and impacts, particularly among species of conservation and cultural concern. We apply a multi-assay framework to quantify predation in a southeastern Australian scenario where complex management implications and calls for predator culling have grown despite a paucity of data on seabird predation by recovering populations of long-nosed fur seals (Arctocephalus forsteri). We apply two ecological surveillance techniques to analyze this predator’s diet – traditional morphometric (prey hard-part) and environmental DNA metabarcoding (genetic) analyses using an avian specific primer for the 12S ribosomal RNA (rRNA) gene – to provide managers with estimated predation incidence, number of seabird species impacted and inter-prey species relative importance to the predator. DNA metabarcoding identified additional seabird taxa and provided relative quantitative information where multiple prey species occur within a sample; while parallel use of both genetic and hard-part analyses revealed a greater diversity of taxa than either method alone. Using data from both assays, the estimated frequency of occurrence of predation on seabirds by long-nosed fur seals ranged from 9.1–29.3% of samples and included up to 6 detected prey species. The most common seabird prey was the culturally valued little penguin (Eudyptula minor) that occurred in 6.1–25.3% of samples, higher than previously reported from traditional morphological assays alone. We then explored DNA haplotype diversity for little penguin genetic data, as a species of conservation concern, to provide a preliminary estimate of the number of individuals consumed. Polymorphism analysis of consumed little penguin DNA identified five distinct mitochondrial haplotypes – representing a minimum of 16 individual penguins consumed across 10 fur seal scat samples (equivalent to 10.1% of samples). We recommend rapid uptake and development of cost-effective genetic techniques and broader spatiotemporal sampling of fur seal diets to further quantify predation and hotspots of concern for wildlife conflict management.
Revision of China’s marine environmental protection law: history, background and improvement
Authors: Liu Ruiqiang
Published: May 2024

The law on marine environmental protection is a branch of the law on environmental protection and is the basis for the conduct of marine environmental protection. Since its promulgation in 1982, China’s Marine Environmental Protection Law has undergone two revisions and three amendments, forming a legal system based on the Constitution, with the Environmental Protection Law as the overarching principle, the Marine Environmental Protection Law as the core, and various laws on the protection of marine elements as the gripping force. The revision of the Marine Environmental Protection Law in 2023 was based on the 2018 supervision and inspection of the enforcement inspection team of the Standing Committee of the National People’s Congress, the implementation of the construction of a strong maritime country, and the adaptation to the reform of the ocean governance system. Compared with the previous Marine Environmental Protection Law, the improvements of the newly revised law are mainly reflected in the following: optimizing the institutional mechanism, reflecting the Land and Sea Coordination, strengthening supervision and management, strengthening marine litter pollution prevention and control, enhancing the protection of marine biodiversity, strengthening the regulation of estuaries, and strict liability.
Feasibility study of replacing part of cement by igneous rock powder as cementitious material: based on mortar macroscopic properties and microstructure
Authors: Li Zhi , Zhao Zhenhua , Ma Fushan , Di Wenjin , Cao Xuanhao , He Zhenqing , Guan Bowen
Published: May 2024

To address the increasing demand for cement and promote sustainable development, the utilization of igneous rock powder as a supplementary material to partially replace cement has emerged as an effective strategy. In this study, the fluidity and mechanical properties of the igneous rock powder-cement (IRP-OPC) composite system were investigated, and the hydration product and microstructure of IRP-OPC were analyzed by using TG/DSC, N2 adsorption-desorption curve (BET) and SEM. The experimental findings demonstrate that the performance of the andesite powder-cement composite cementing system (AP-OPC) surpasses that of tuff powder-cement slurry (TP-OPC) and granite powder-cement slurry (GP-OPC). When the dosage of andesite powder (AP) is 5%–15%, the flowability, flexural strength and compressive strength of cement mortar are improved. When the dosage is 10%, the 28-day compressive strength is 48.3 MPa. Under the condition of low content (10%), part of Ca(OH)2 is fully consumed by active SiO2 in AP and reacts to form C-S-H. Hydration products and AP particles with small particle size are filled into the structural gap, which refines the pore structure of cement slurry, and the increase in compactness provides support for the development of strength in the later stage. The use of 5%–15% AP instead of OPC can improve fluidity and meet the strength requirements of P.O 42.5 Portland cement. This substitution not only reduces engineering costs but also enhances resource utilization.
A randomized, double-blinded, phase 2 trial of EDP1815, an oral immunomodulatory preparation of Prevotella histicola, in adults with mild-to-moderate plaque psoriasis
Authors: Ehst Benjamin D. , Strober Bruce , Blauvelt Andrew , Maslin Douglas , Macaro Debbie , Carpenter Nancy , Bodmer Mark , McHale Duncan
Published: May 2024

Background

Psoriasis is a chronic inflammatory skin disease. EDP1815 is an oral, gut-restricted preparation of non-live Prevotella histicola, the first of a new immunomodulatory therapeutic class targeting the small intestine to generate systemic anti-inflammatory responses.

Objective

To evaluate safety and efficacy of EDP1815 in mild-to-moderate psoriasis in a proof-of-concept study.

Methods

A phase 2, multicenter, randomized, double-blinded, placebo-controlled, parallel-group study with a 16-week treatment period and up to 24 weeks of follow-up. Participants were randomized to receive 1, 4, or 10 capsules daily.

Results

EDP1815 was well tolerated with comparable rates of treatment-emergent adverse events to placebo, and no drug-related serious adverse events. Clinically meaningful responses to EDP1815, defined as at least 50% reduction in Psoriasis Area and Severity Index (PASI-50) at week 16, were observed in all 3 cohorts, statistically significant in the 1-capsule (29.7%; P = 0.048) and 4-capsule (31.9%; P = 0.022) groups, compared with placebo (12.1%). Among EDP1815-treated PASI-50 responders at week 16, 60% (18/30) maintained or improved off-treatment responses at week 40.

Limitations

Continued off-treatment improvement past 16 weeks shows potential for greater therapeutic benefit that was not assessed.

Conclusion

EDP1815 was well-tolerated with a placebo-like safety profile, and had meaningful efficacy outcomes in psoriasis, validating this novel immunomodulatory approach.

Clinical trial registration

https://www.clinicaltrials.gov/search?term=NCT04603027, identifier NCT04603027.
Personalized embryo transfer guided by rsERT improves pregnancy outcomes in patients with repeated implantation failure
Authors: Li Ning , Zhang Yisheng , Li Rufei , Chen Yulin , Huang Lin , Tan Zhuojie , Ban Xiaoying , Zhou Ling , Xu Changlong , Qiu Ying , Li Rong
Published: May 2024

Introduction

Embryo implantation requires synchronous communication between the embryo and maternal endometrium. Inadequate maternal endometrial receptivity is one of the principal causes for embryo implantation failure [especially repeated implantation failure (RIF)] when biopsied good-quality euploid embryos are transferred. An RNA-seq-based endometrial receptivity test (rsERT) was previously established to precisely guide successful embryo implantation. In this study, we aimed to evaluate the effect of personalized embryo transfer (pET) via rsERT on the clinical outcomes in patients with RIF.

Methods

A total of 155 patients with RIF were included in the present retrospective study and were divided into two groups: 60 patients who underwent rsERT and pET (Group rsERT) and 95 patients who underwent standard frozen embryo transfer (FET) without rsERT (Group FET). Reproductive outcomes were compared for patients who underwent rsERT-guided pET and standard FET.

Results

Forty percent (24/60) of the patients who underwent rsERT were receptive, and the remaining 60% (36/60) were non-receptive. The positive human chorionic gonadotropin (β-hCG) rate (56.3% vs. 30.5%, P = 0.003) and clinical pregnancy rate (43.8% vs. 24.2%, P = 0.017) were significantly higher in Group rsERT patients than in FET group patients. Additionally, Group rsERT patients also showed a higher implantation rate (32.1% vs. 22.1%, P = 0.104) and live birth rate (35.4% vs. 21.1%, P = 0.064) when compared with FET patients, although without significance. For subpopulation analysis, the positive β-hCG rate, clinical pregnancy rate, implantation rate, and live birth rate of receptive patients were not statistically significant different from those of non-receptive patients.

Conclusions

The rsERT can significantly improve the pregnancy outcomes of RIF patients, indicating the clinical potential of rsERT-guided pET.
Xiaoqinglong decoction mitigates nasal inflammation and modulates gut microbiota in allergic rhinitis mice
Authors: Liu Hao-Lan , Chen Hui-Fang , Wu Yun-Dang , Yan Ya-Jie , He Xue-Cheng , Li Zhong-Zheng , Ruan Yan , Wu Gan-Long
Published: May 2024

Introduction

Allergic rhinitis (AR) is a respiratory immune system disorder characterized by dysregulation of immune responses. Within the context of AR, gut microbiota and its metabolites have been identified as contributors to immune modulation. These microorganisms intricately connect the respiratory and gut immune systems, forming what is commonly referred to as the gut-lung axis. Xiaoqinglong Decoction (XQLD), a traditional Chinese herbal remedy, is widely utilized in traditional Chinese medicine for the clinical treatment of AR. In this study, it is hypothesized that the restoration of symbiotic microbiota balance within the gut-lung axis plays a pivotal role in supporting the superior long-term efficacy of XQLD in AR therapy. Therefore, the primary objective of this research is to investigate the impact of XQLD on the composition and functionality of the gut microbiota in a murine model of AR.

Methods

An ovalbumin-sensitized mouse model to simulate AR was utilized, the improvement of AR symptoms after medication was investigated, and high-throughput sequencing was employed to analyze the gut microbiota composition.

Results

XQLD exhibited substantial therapeutic effects in AR mice, notably characterized by a significant reduction in allergic inflammatory responses, considerable alleviation of nasal symptoms, and the restoration of normal nasal function. Additionally, following XQLD treatment, the disrupted gut microbiota in AR mice displayed a tendency toward restoration, showing significant differences compared to the Western medicine (loratadine) group.

Discussion

This results revealed that XQLD may enhance AR allergic inflammatory responses through the regulation of intestinal microbiota dysbiosis in mice, thus influencing the dynamics of the gut-lung axis. The proposal of this mechanism provides a foundation for future research in this area.
Molecular characterization revealed the role of thaumatin-like proteins of Rhizoctonia solani AG4-JY in inducing maize disease resistance
Authors: Liu Jiayue , Feng Shang , Liu Tingting , Mao Yanan , Shen Shen , Liu Yuwei , Hao Zhimin , Li Zhiyong
Published: May 2024

The gene family of thaumatin-like proteins (TLPs) plays a crucial role in the adaptation of organisms to environmental stresses. In recent years, fungal secreted proteins (SP) with inducing disease resistance activity in plants have emerged as important elicitors in the control of fungal diseases. Identifying SPs with inducing disease resistance activity and studying their mechanisms are crucial for controlling sheath blight. In the present study, 10 proteins containing the thaumatin-like domain were identified in strain AG4-JY of Rhizoctonia solani and eight of the 10 proteins had signal peptides. Analysis of the TLP genes of the 10 different anastomosis groups (AGs) showed that the evolutionary relationship of the TLP gene was consistent with that between different AGs of R. solani. Furthermore, it was found that RsTLP3, RsTLP9 and RsTLP10 were regarded as secreted proteins for their signaling peptides exhibited secretory activity. Prokaryotic expression and enzyme activity analysis revealed that the three secreted proteins possess glycoside hydrolase activity, suggesting they belong to the TLP family. Additionally, spraying the crude enzyme solution of the three TLP proteins could enhance maize resistance to sheath blight. Further analysis showed that genes associated with the salicylic acid and ethylene pathways were up-regulated following RsTLP3 application. The results indicated that RsTLP3 had a good application prospect in biological control.
MicroRNA as a promising molecular biomarker in the diagnosis of breast cancer
Authors: Miranda Felipe Silva de , Slaibi-Filho José , Calasans dos Santos Gabriel , Carmo Nathalia Teixeira , Kaneto Carla Martins , Borin Thaiz Ferraz , Luiz Wilson Barros , Gastalho Campos Luciene Cristina
Published: May 2024

Introduction: Breast cancer represents the most prevalent malignancy among women. Recent advancements in translational research have focused on the identification of novel biomarkers capable of providing valuable insights into patient outcomes. Furthermore, comprehensive investigations aimed at discovering novel miRNAs, unraveling their biological functions, and deciphering their target genes have significantly contributed to our understanding of the roles miRNAs play in tumorigenesis. Consequently, these investigations have facilitated the way for the development of miRNA-based approaches for breast cancer prognosis, diagnosis, and treatment. However, conducting a more extensive array of studies, particularly among diverse ethnic groups, is imperative to expand the scope of research and validate the significance of miRNAs. This study aimed to assess the expression patterns of circulating miRNAs in plasma as a prospective biomarker for breast cancer patients within a population primarily consisting of individuals from Black, Indigenous, and People of Color (BIPOC) communities.

Methods: We evaluated 49 patients with breast cancer compared to 44 healthy women.

Results and discussion: All miRNAs analyzed in the plasma of patients with breast cancer were downregulated. ROC curve analysis of miR-21 (AUC = 0.798, 95% CI: 0.682–0.914, p <0.0001), miR-1 (AUC = 0.742, 95% CI: 0.576–0.909, p = 0.004), miR-16 (AUC = 0.721, 95% CI: 0.581–0.861, p = 0.002) and miR-195 (AUC = 0.672, 95% CI: 0.553–0.792, p = 0.004) showed better diagnostic accuracy in discrimination of breast cancer patients in comparison with healthy women. miR-210, miR-21 showed the highest specificities values (97.3%, 94.1%, respectively). Following, miR-10b and miR-195 showed the highest sensitivity values (89.3%, and 77.8%, respectively). The panel with a combination of four miRNAs (miR-195 + miR-210 + miR-21 + miR-16) had an AUC of 0.898 (0.765–0.970), a sensitivity of 71.4%, and a specificity of 100.0%. Collectively, our results highlight the miRNA combination in panels drastically improves the results and showed high accuracy for the diagnosis of breast cancer displaying good sensitivity and specificity.
Comparison of externally and internally guided dance movement to address mobility, cognition, and psychosocial function in people with Parkinson’s disease and freezing of gait: a case series
Authors: Abraham Amit , Hart Ariel , Bozzorg Ariyana , Pothineni Suraj , Wolf Steven L. , Schuh Kersey , Caughlan Molly , Parker Jelani , Blackwell Amanda , Tharp Cianflona Megan , Asker Courtney , Prusin Todd , Hackney Madeleine E.
Published: May 2024

Objective

The aim of this study is to explore the impact of internally guided (IG) versus externally guided (EG) adapted tango (AT) dance training (i.e., dancing the IG “Leader” role or the EG “Follower” role), on motor and non-motor functions in individuals with Parkinson’s disease and freezing of gait (PD-FOG). The “Leader” role, a proxy for IG movements, conveys direction, timing, and amplitude of steps with tactile cues. The “Follower” role, a proxy for EG movements, detects and responds to the leader’s tactile cues.

Case description

Six participants were randomly assigned to the IG (“Leader”) or EG (“Follower”) roles for 20, 90-min AT lessons over 12 weeks. Participants were assessed for PD-specific and non-PD-specific functions before and twice after the end of the 12-week intervention, at 1-week and 1-month post-intervention.

Results

EG participants improved and/or maintained performance on more outcomes across all domains than IG participants. Five participants improved in PD motor symptoms, dynamic gait, global cognitive function, and the FOG Questionnaire immediately or 1 month after intervention. All participants expressed positive attitudes toward the intervention, including improvements in walking, balance, and endurance.

Conclusion

AT training in the follower role may benefit individuals with PD-FOG to a greater extent compared to the leader role.

Impact

This case series study could inform additional research with the goal of enhancing physical therapy or music-based therapy approaches for addressing PD-FOG.
Energy landscape analysis of brain network dynamics in Alzheimer’s disease
Authors: Xing Le , Guo Zhitao , Long Zhiying
Published: May 2024

Background

Alzheimer’s disease (AD) is a common neurodegenerative dementia, characterized by abnormal dynamic functional connectivity (DFC). Traditional DFC analysis, assuming linear brain dynamics, may neglect the complexity of the brain’s nonlinear interactions. Energy landscape analysis offers a holistic, nonlinear perspective to investigate brain network attractor dynamics, which was applied to resting-state fMRI data for AD in this study.

Methods

This study utilized resting-state fMRI data from 60 individuals, comparing 30 Alzheimer’s patients with 30 controls, from the Alzheimer’s Disease Neuroimaging Initiative. Energy landscape analysis was applied to the data to characterize the aberrant brain network dynamics of AD patients.

Results

The AD group stayed in the co-activation state for less time than the healthy control (HC) group, and a positive correlation was identified between the transition frequency of the co-activation state and behavior performance. Furthermore, the AD group showed a higher occurrence frequency and transition frequency of the cognitive control state and sensory integration state than the HC group. The transition between the two states was positively correlated with behavior performance.

Conclusion

The results suggest that the co-activation state could be important to cognitive processing and that the AD group possibly raised cognitive ability by increasing the occurrence and transition between the impaired cognitive control and sensory integration states.
Theoretico-experimental analysis of bistability in the oscillatory response of a TaOx ReRAM to pulse train stimuli
Authors: Schmitt N. , Ascoli A. , Messaris I. , Demirkol A. S. , Menzel S. , Rana V. , Tetzlaff R. , Chua L. O.
Published: May 2024

Fading memory is the capability of a physical system to approach a unique asymptotic behaviour, irrespective of the initial conditions, when stimulated by an input from a certain class. Standard stimuli from the AC periodic class typically induce fading memory effects in non-volatile memristors, as uncovered for the first time back in 2016. Very recently, a deep investigation of resistance switching phenomena in a TaOx resistive random access memory cell revealed the capability of the nano-device to exhibit one of two possible oscillatory behaviours, depending upon the initial condition, when subject to a particular periodic excitation. This interesting finding was, however, left unexplained. Bistability is the simplest form of local fading memory. In a system, endowed with local fading memory under a given stimulus, the initial condition does not affect the long-term behaviour of the state as long as it is drawn from the basin of attraction of either of the distinct coexisting state-space attractors (two limit cycles for the periodically forced memristor acting as a bistable oscillator). Here, the history of the system, encoded in the initial condition, is, thus, erasable only locally through ad hoc stimulation. Motivated by the discovery of local history erase effects in our resistive random access memory cell, this study applies a powerful system-theoretic tool, enabling the analysis of the response of first-order systems to square pulse train-based periodic stimuli, known as the time-average state dynamic route, to an accurate physics-based mathematical model, earlier fitted to the nano-device, to determine a strategy for specifying the parameters of an excitation signal, consisting of the sequence of two square pulses of opposite polarity per period so as to induce various forms of monostability or multistability in the non-volatile memristor. In particular, as an absolute novelty in the literature, experimental measurements validate the theoretical prediction on the capability of the device to operate as one of two distinct oscillators, depending upon the initial condition, under a specific pulse train excitation signal. The coexistence of multiple oscillatory operating modes in the periodically forced resistive random access memory cell, an example par excellence of their unique non-linear dynamics, may inspire the development and circuit implementation of novel sensing and mem-computing paradigms.
Interplay between sexual excitation and inhibition: impact on sexual function and neural correlates of erotic stimulus processing in women
Authors: Schmidt Norina M. , Hennig Juergen , Munk Aisha J. L.
Published: May 2024

Background

As outlined by the dual control model (DCM), individual differences in the regulation of sexual arousal following sexual stimulation depend on two distinct neurophysiological processes: sexual excitation (SE) and sexual inhibition (SI). Although associations with sexual function, behavior, and cue processing have been demonstrated in previous research, underlying neural correlates remain insufficiently explored. Moreover, interactive effects of SE/SI as proposed by the DCM, as well as factors impacting SE/SI properties, such as the use of oral contraceptives (OCs), have not received adequate attention in existing research.

Methods

90 healthy, sexually active women (n = 51 using OCs, n = 39 naturally cycling) completed an Emotional-Picture-Stroop-Paradigm (EPSP) while a 64-channel EEG was recorded. LPP amplitudes toward erotic and neutral stimuli were consecutively computed as a marker of motivational salience and approach motivation. Additionally, women provided self-reports of SE/SI and sexual function. Moderation analyses were performed to assess interactive effects of SE/SI in predicting LPP amplitudes and sexual function.

Results

Sexual function was negatively associated with SI levels but unrelated to SE. Higher SI was associated with reduced LPP amplitudes in response to erotic stimuli. This negative association was, however, attenuated for women high in SE, suggesting interactive effects of SE/SI. Furthermore, women using OCs reported lower SE compared to naturally cycling women.

Conclusion

The observed findings provide additional psychophysiological evidence supporting the DCM and underscore the relevance of interactive SE/SI effects in stimulus processing and approach motivation. They also highlight the possible impact of OCs on psychosexual variables that warrants further research.
Association of pulse pressure with hematoma expansion in patients with spontaneous supratentorial intracerebral hemorrhage
Authors: Wang Chao-Ying , Lai Su-Zhen , Kang Bao-Cai , Lin Yi-Zhao , Cao Chun-Juan , Huang Xin-Bing , Wang Jian-Qun
Published: May 2024

Objective

Recent reports have demonstrated that a wider pulse pressure upon admission is correlated with heightened in-hospital mortality following spontaneous supratentorial intracerebral hemorrhage (ssICH). However, the underlying mechanism remains ambiguous. We investigated whether a wider pulse pressure was associated with hematoma expansion (HE).

Methods

Demographic information, clinical features, and functional outcomes of patients diagnosed with ssICH were retrospectively collected and analyzed. Multivariate logistic regression was conducted to identify independent predictors of HE. Weighted logistic regression, restricted cubic spline models, and propensity score matching (PSM) were employed to estimate the association between pulse pressure and HE.

Results

We included 234 eligible adult ssICH patients aged 60 (51–71) years, and 55.56% were male. The mean pulse pressure was 80.94 ± 23.32 mmHg. Twenty-seven patients (11.54%) developed early HE events, and 116 (49.57%) experienced a poor outcome (modified Rankin scale 3–6). A wider mean pulse pressure as a continuous variable was a predictor of HE [odds ratios (OR) 1.026, 95% confidence interval (CI) 1.007–1.046, p = 0.008] in multivariate analysis. We transformed pulse pressure into a dichotomous variable based on its cutoff value. After adjusting for confounding of HE variables, the occurrence of HE in patients with ssICH with wider pulse pressure levels (≥98 mmHg) had 3.78 times (OR 95% CI 1.47–9.68, p = 0.006) compared to those with narrower pulse pressure levels (<98 mmHg). A linear association was observed between pulse pressure and increased HE risk (P for overall = 0.036, P for nonlinear = 0.759). After 1:1 PSM (pulse pressure ≥98 mmHg vs. pulse pressure <98 mmHg), the rates of HE events and poor outcome still had statistically significant in wider-pulse pressure group [HE, 12/51 (23.53%) vs. 4/51 [7.84%], p = 0.029; poor outcome, 34/51 (66.67%) vs. 19/51 (37.25%), p = 0.003].

Conclusion

Widened acute pulse pressure (≥98 mmHg) levels at admission are associated with increased risks of early HE and unfavorable outcomes in patients with ssICH.
Evaluation of clinical factors predicting dysphagia in patients with traumatic and non-traumatic cervical spinal cord injury: a retrospective study
Authors: Choi Jin-Woo , Kim Dae Yeong , Joo Sun Young , Park Donghwi , Chang Min Cheol
Published: May 2024

Introduction

Dysphagia is a common complication in patients with cervical spinal cord injury (C-SCI) and can cause various pulmonary complications, such as aspiration pneumonia and mechanical airway obstruction increasing mortality and morbidity. This study evaluated the clinical factors that predict dysphagia in patients with traumatic and non-traumatic C-SCI.

Methods

Ninety-eight patients with C-SCI were retrospectively enrolled in this study and were divided into those with and without dysphagia. Clinical factors such as age, sex, tracheostomy, spinal cord independence measure, pulmonary function test (PFT) including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FVC/FEV1, American Spinal Cord Injury Association score, Berg Balance Scale, and surgical approach were investigated retrospectively.

Results

Multivariate logistic regression analysis revealed that FVC and the presence of tracheostomy were significantly correlated with dysphagia in patients with C-SCI (p < 0.05). FVC and the presence of tracheostomy are useful tools for detecting dysphagia in patients with C-SCI.

Conclusion

Considering the results of our study, early PFTs, especially FVC, in patients with C-SCI and early initiation of dysphagia management and treatment in patients with C-SCI and tracheostomy will be advantageous in lowering the mortality and morbidity due to pulmonary aspiration in these patients.
Interhemispheric functional connectivity: an fMRI study in callosotomized patients
Authors: Marcantoni Ilaria , Piccolantonio Giusi , Ghoushi Mojgan , Valenti Marco , Reversi Luca , Mariotti Francesco , Foschi Nicoletta , Lattanzi Simona , Burattini Laura , Fabri Mara , Polonara Gabriele
Published: May 2024

Introduction

Functional connectivity (FC) is defined in terms of temporal correlations between physiological signals, which mainly depend upon structural (axonal) connectivity; it is commonly studied using functional magnetic resonance imaging (fMRI). Interhemispheric FC appears mostly supported by the corpus callosum (CC), although several studies investigating this aspect have not provided conclusive evidence. In this context, patients in whom the CC was resected for therapeutic reasons (split-brain patients) provide a unique opportunity for research into this issue. The present study was aimed at investigating with resting-state fMRI the interhemispheric FC in six epileptic patients who have undergone surgical resection of the CC.

Methods

The analysis was performed using fMRI of the Brain Software Library; the evaluation of interhemispheric FC and the recognition of the resting-state networks (RSNs) were performed using probabilistic independent component analysis.

Results

Generally, bilateral brain activation was often observed in primary sensory RSNs, while in the associative areas, such as those composing the default mode and fronto-parietal networks, the activation was often unilateral.

Discussion

These results suggest that even in the absence of the CC, some interhemispheric communication is still present. This residual FC might be supported through extra-callosal pathways that are likely subcortical, making it possible for some interhemispheric integration. Further studies are needed to confirm these conclusions.
A neurocomputational view of the effects of Parkinson’s disease on speech production
Authors: Manes Jordan L. , Bullock Latané , Meier Andrew M. , Turner Robert S. , Richardson R. Mark , Guenther Frank H.
Published: May 2024

The purpose of this article is to review the scientific literature concerning speech in Parkinson’s disease (PD) with reference to the DIVA/GODIVA neurocomputational modeling framework. Within this theoretical view, the basal ganglia (BG) contribute to several different aspects of speech motor learning and execution. First, the BG are posited to play a role in the initiation and scaling of speech movements. Within the DIVA/GODIVA framework, initiation and scaling are carried out by initiation map nodes in the supplementary motor area acting in concert with the BG. Reduced support of the initiation map from the BG in PD would result in reduced movement intensity as well as susceptibility to early termination of movement. A second proposed role concerns the learning of common speech sequences, such as phoneme sequences comprising words; this view receives support from the animal literature as well as studies identifying speech sequence learning deficits in PD. Third, the BG may play a role in the temporary buffering and sequencing of longer speech utterances such as phrases during conversational speech. Although the literature does not support a critical role for the BG in representing sequence order (since incorrectly ordered speech is not characteristic of PD), the BG are posited to contribute to the scaling of individual movements in the sequence, including increasing movement intensity for emphatic stress on key words. Therapeutic interventions for PD have inconsistent effects on speech. In contrast to dopaminergic treatments, which typically either leave speech unchanged or lead to minor improvements, deep brain stimulation (DBS) can degrade speech in some cases and improve it in others. However, cases of degradation may be due to unintended stimulation of efferent motor projections to the speech articulators. Findings of spared speech after bilateral pallidotomy appear to indicate that any role played by the BG in adult speech must be supplementary rather than mandatory, with the sequential order of well-learned sequences apparently represented elsewhere (e.g., in cortico-cortical projections).
Advanced age is not a barrier to chronic intracortical single-unit recording in rat cortex
Authors: Nolta Nicholas F. , Christensen Michael B. , Tresco Patrick A.
Published: May 2024

Introduction

Available evidence suggests that as we age, our brain and immune system undergo changes that increase our susceptibility to injury, inflammation, and neurodegeneration. Since a significant portion of the potential patients treated with a microelectrode-based implant may be older, it is important to understand the recording performance of such devices in an aged population.

Methods

We studied the chronic recording performance and the foreign body response (FBR) to a clinically used microelectrode array implanted in the cortex of 18-month-old Sprague Dawley rats.

Results and discussion

To the best of our knowledge, this is the first preclinical study of its type in the older mammalian brain. Here, we show that single-unit recording performance was initially robust then gradually declined over a 12-week period, similar to what has been previously reported using younger adult rats and in clinical trials. In addition, we show that FBR biomarker distribution was similar to what has been previously described for younger adult rats implanted with multi-shank recording arrays in the motor cortex. Using a quantitative immunohistochemcal approach, we observed that the extent of astrogliosis and tissue loss near the recording zone was inversely related to recording performance. A comparison of recording performance with a younger cohort supports the notion that aging, in and of itself, is not a limiting factor for the clinical use of penetrating microelectrode recording arrays for the treatment of certain CNS disorders.
Advancing passive BCIs: a feasibility study of two temporal derivative features and effect size-based feature selection in continuous online EEG-based machine error detection
Authors: Pan Yanzhao , Zander Thorsten O. , Klug Marius
Published: May 2024

The emerging integration of Brain-Computer Interfaces (BCIs) in human-robot collaboration holds promise for dynamic adaptive interaction. The use of electroencephalogram (EEG)-measured error-related potentials (ErrPs) for online error detection in assistive devices offers a practical method for improving the reliability of such devices. However, continuous online error detection faces challenges such as developing efficient and lightweight classification techniques for quick predictions, reducing false alarms from artifacts, and dealing with the non-stationarity of EEG signals. Further research is essential to address the complexities of continuous classification in online sessions. With this study, we demonstrated a comprehensive approach for continuous online EEG-based machine error detection, which emerged as the winner of a competition at the 32nd International Joint Conference on Artificial Intelligence. The competition consisted of two stages: an offline stage for model development using pre-recorded, labeled EEG data, and an online stage 3 months after the offline stage, where these models were tested live on continuously streamed EEG data to detect errors in orthosis movements in real time. Our approach incorporates two temporal-derivative features with an effect size-based feature selection technique for model training, together with a lightweight noise filtering method for online sessions without recalibration of the model. The model trained in the offline stage not only resulted in a high average cross-validation accuracy of 89.9% across all participants, but also demonstrated remarkable performance during the online session 3 months after the initial data collection without further calibration, maintaining a low overall false alarm rate of 1.7% and swift response capabilities. Our research makes two significant contributions to the field. Firstly, it demonstrates the feasibility of integrating two temporal derivative features with an effect size-based feature selection strategy, particularly in online EEG-based BCIs. Secondly, our work introduces an innovative approach designed for continuous online error prediction, which includes a straightforward noise rejection technique to reduce false alarms. This study serves as a feasibility investigation into a methodology for seamless error detection that promises to transform practical applications in the domain of neuroadaptive technology and human-robot interaction.
Hepatotoxicity assessment of innovative nutritional supplements based on olive-oil formulations enriched with natural antioxidants
Authors: Prodromou Sofia I. , Chatzopoulou Fani , Saiti Aikaterini , Giannopoulos-Dimitriou Alexandros , Koudoura Loukia A. , Pantazaki Anastasia A. , Chatzidimitriou Dimitrios , Vasiliou Vasilis , Vizirianakis Ioannis S.
Published: May 2024

Introduction

This study focuses on the assessment of extra virgin olive-oil and olive fruit-based formulations enriched with natural antioxidants as potential nutritional supplements for alleviating symptoms and long-term consequences of illnesses whose molecular pathophysiology is affected by oxidative stress and inflammation, such as Alzheimer’s disease (AD).

Methods

Besides evaluating cell viability and proliferation capacity of human hepatocellular carcinoma HepG2 cells exposed to formulations in culture, hepatotoxicity was also considered as an additional safety measure using quantitative real-time PCR on RNA samples isolated from the cell cultures and applying approaches of targeted molecular analysis to uncover potential pathway effects through gene expression profiling. Furthermore, the formulations investigated in this work contrast the addition of natural extract with chemical forms and evaluate the antioxidant delivery mode on cell toxicity.

Results

The results indicate minimal cellular toxicity and a significant beneficial impact on metabolic molecular pathways in HepG2 cell cultures, thus paving the way for innovative therapeutic strategies using olive-oil and antioxidants in dietary supplements to minimize the long-term effects of oxidative stress and inflammatory signals in individuals being suffered by disorders like AD.

Discussion

Overall, the experimental design and the data obtained support the notion of applying innovative molecular methodologies and research techniques to evidently advance the delivery, as well as the scientific impact and validation of nutritional supplements and dietary products to improve public health and healthcare outcomes.