bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact and inflammatory characteristics of SARS-CoV-2 infection during ovarian stimulation on the outcomes of assisted reproductive treatment
Authors: Hu Xiaoling , Feng Guofang , Chen Qichao , Sang Yimiao , Chen Qingqing , Wang Sisi , Liu Shuangying , Bai Long , Zhu Yimin
Published: April 2024

Introduction

Despite the global prevalence of coronavirus disease 2019 (COVID-19), limited research has been conducted on the effects of SARS-CoV-2 infection on human reproduction. The aims of this study were to investigate the impact of SARS-CoV-2 infection during controlled ovarian stimulation (COS) on the outcomes of assisted reproductive treatment (ART) and the cytokine status of patients.

Methods

This retrospective cohort study included 202 couples who received ART treatment, 101 couples infected with SARS-CoV-2 during COS and 101 matched uninfected couples. The parameters of ovarian stimulation and pregnancy outcomes were compared between the two groups. The All-Human Inflammation Array Q3 kit was utilized to measure cytokine levels in both blood and follicular fluid.

Results

No difference was found in the number of good-quality embryos (3.3 ± 3.1 vs. 3.0 ± 2.2, P = 0.553) between the infected and uninfected groups. Among couples who received fresh embryo transfers, no difference was observed in clinical pregnancy rate (53.3% vs. 51.5%, P = 0.907). The rates of fertilization, implantation, miscarriage, ectopic pregnancy and live birth were also comparable between the two groups. After adjustments were made for confounders, regression models indicated that the quality of embryos (B = 0.16, P = 0.605) and clinical pregnancy rate (P = 0.206) remained unaffected by SARS-CoV-2 infection. The serum levels of MCP-1, TIMP-1, I-309, TNF-RI and TNF-RII were increased, while that of eotaxin-2 was decreased in COVID-19 patients. No significant difference was found in the levels of cytokines in follicular fluid between the two groups.

Conclusion

Asymptomatic or mild COVID-19 during COS had no adverse effects on ART outcomes. Although mild inflammation was present in the serum, it was not detected in the follicular fluid of these patients. The subsequent immune response needs further investigation.
What drives growth responses of nitrogen and phosphorus (co-)limited primary producer communities?
Authors: Redoglio Andrea , Sperfeld Erik
Published: April 2024

The growth of autotroph communities is frequently (co-)limited by essential nutrients such as nitrogen (N) and phosphorus (P). Several mechanisms have been proposed to explain the observed co-limitation patterns at different levels of biological organization, especially at the biochemical level for individual species. When considering communities, the presence of different species and functional groups with contrasting physiologies and nutrient requirements leads to a more difficult understanding of the mechanisms involved in nutrient (co-)limitation. To investigate what drives co-limitation patterns and possible underlying mechanisms based on biomass responses in autotroph communities, we grew phytoplankton communities differing in species composition in experimental microcosms on three N:P ratios to impose different limiting conditions. Afterwards, N, P, both, or none were factorially supplied to the communities to test which nutrients were limiting growth. We measured the biovolume of single species in the communities to assess how they responded to nutrient additions and compared it to the response of the overall community biovolume. The types of nutrient (co-)limitation identified, i.e. the factorial limitation scenarios for community biomass were single N limitation or simultaneous co-limitation by N and P, and were strongly driven by the dominant species. The phytoplankton species in the communities responded differently to the nutrient addition treatments, i.e. they showed contrasting limitation outcomes and therefore likely different nutrient requirements. Our experiment indicates that phylogenetically distantly-related phytoplankton species grown in a community can have different resource use efficiencies and thus can be limited by different nutrients. We suggest that the dominance of species or groups with similar traits in nutrient requirements and acquisition is one of the leading mechanisms that determines the biomass pattern of nutrient (co-)limitation observed at the community level. This work also highlights the potential of predicting community growth limitation outcomes based on knowledge of nutrient use efficiencies of one or few dominant species, which can be a suitable tool for lake restoration and oligotrophication efforts.
Engineering CRISPR/Cas9 therapeutics for cancer precision medicine
Authors: Sharma Aditya Kumar , Giri Anil K.
Published: April 2024

The discovery of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) technology has revolutionized field of cancer treatment. This review explores usage of CRISPR/Cas9 for editing and investigating genes involved in human carcinogenesis. It provides insights into the development of CRISPR as a genetic tool. Also, it explores recent developments and tools available in designing CRISPR/Cas9 systems for targeting oncogenic genes for cancer treatment. Further, we delve into an overview of cancer biology, highlighting key genetic alterations and signaling pathways whose deletion prevents malignancies. This fundamental knowledge enables a deeper understanding of how CRISPR/Cas9 can be tailored to address specific genetic aberrations and offer personalized therapeutic approaches. In this review, we showcase studies and preclinical trials that show the utility of CRISPR/Cas9 in disrupting oncogenic targets, modulating tumor microenvironment and increasing the efficiency of available anti treatments. It also provides insight into the use of CRISPR high throughput screens for cancer biomarker identifications and CRISPR based screening for drug discovery. In conclusion, this review offers an overview of exciting developments in engineering CRISPR/Cas9 therapeutics for cancer treatment and highlights the transformative potential of CRISPR for innovation and effective cancer treatments.
Navigating the peer-to-peer workflow in non-formal education through an innovative e-learning platform: a case study of the KIDS4ALLL educational project in Hungary and Italy
Authors: Schroot Tanja , Lőrincz Borbála , Bernát Anikó
Published: April 2024

The digital revolution is affecting all aspects of life, radically transforming everyday tasks and routines. The ability to cope with new challenges in life, including new forms of learning are key skills in the 21st-century, however, education systems often struggle with tackling digital inequalities. A digital learning platform developed by the KIDS4ALLL educational project, implemented in face-to-face student interactions, aims to mitigate the divide and the resulting social disadvantages among children with and without migration/ethnic minority background. Analyzing data collected during the pilot phase of the project in two of the participating countries, Italy and Hungary, this paper examines how students and teaching staff adapt to a newly introduced digital learning tool based on peer-to-peer workflows. Firstly, it examines the role of educators' interpersonal competences in navigating the innovative learning activities and delves into how they use them and how they manage resources. Secondly, the study explores what attitudes and behaviors are observed among students engaged in the proposed peer-led activities, in particular in terms of their ability to cope with uncertainty and complexity. The analytical framework of the paper is based on two cultural dimensions offered by Hofstede, the index of uncertainty avoidance (UAI) and power distance (PDI), and it utilizes the personal, social and learning-to-learn competence of the eight LLL Key Competences as defined by the European Commission to conceptualize the skills of educators and students. Interpreting data from Italy and Hungary in their respective social and educational contexts, the study finds that the most important features that proved to be effective and useful during the pilot phase were the democratic power-relations between students and educators, the peer-to-peer scheme and its further development to the peer-for-peer approach. The child-friendly and real-life-related new curriculum and its appealing digital learning platform, embedded into a flexible, playful and child-centered pedagogical approach, were also successful. These are all complementing the traditional, formal school environment and pedagogy which, despite all developments in formal education in the past decades, can be characterized as teacher-centered and frontal.
Exploring the common mechanism of vascular dementia and inflammatory bowel disease: a bioinformatics-based study
Authors: Wang Yujiao , Xie Daojun , Ma Shijia , Shao Nan , Zhang Xiaoyan , Wang Xie
Published: April 2024

Objective

Emerging evidence has shown that gut diseases can regulate the development and function of the immune, metabolic, and nervous systems through dynamic bidirectional communication on the brain-gut axis. However, the specific mechanism of intestinal diseases and vascular dementia (VD) remains unclear. We designed this study especially, to further clarify the connection between VD and inflammatory bowel disease (IBD) from bioinformatics analyses.

Methods

We downloaded Gene expression profiles for VD (GSE122063) and IBD (GSE47908, GSE179285) from the Gene Expression Omnibus (GEO) database. Then individual Gene Set Enrichment Analysis (GSEA) was used to confirm the connection between the two diseases respectively. The common differentially expressed genes (coDEGs) were identified, and the STRING database together with Cytoscape software were used to construct protein-protein interaction (PPI) network and core functional modules. We identified the hub genes by using the Cytohubba plugin. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to identify pathways of coDEGs and hub genes. Subsequently, receiver operating characteristic (ROC) analysis was used to identify the diagnostic ability of these hub genes, and a training dataset was used to verify the expression levels of the hub genes. An alternative single-sample gene set enrichment (ssGSEA) algorithm was used to analyze immune cell infiltration between coDEGs and immune cells. Finally, the correlation between hub genes and immune cells was analyzed.

Results

We screened 167 coDEGs. The main articles of coDEGs enrichment analysis focused on immune function. 8 shared hub genes were identified, including PTPRC, ITGB2, CYBB, IL1B, TLR2, CASP1, IL10RA, and BTK. The functional categories of hub genes enrichment analysis were mainly involved in the regulation of immune function and neuroinflammatory response. Compared to the healthy controls, abnormal infiltration of immune cells was found in VD and IBD. We also found the correlation between 8 shared hub genes and immune cells.

Conclusions

This study suggests that IBD may be a new risk factor for VD. The 8 hub genes may predict the IBD complicated with VD. Immune-related coDEGS may be related to their association, which requires further research to prove.
Chimeric antigen receptor-natural killer cell therapy: current advancements and strategies to overcome challenges
Authors: Kong Jun Chang , Sa’ad Mohammad Auwal , Vijayan Hema Manusri , Ravichandran Manickam , Balakrishnan Venugopal , Tham Seng Kong , Tye Gee Jun
Published: April 2024

Chimeric antigen receptor-natural killer (CAR-NK) cell therapy is a novel immunotherapy targeting cancer cells via the generation of chimeric antigen receptors on NK cells which recognize specific cancer antigens. CAR-NK cell therapy is gaining attention nowadays owing to the ability of CAR-NK cells to release potent cytotoxicity against cancer cells without side effects such as cytokine release syndrome (CRS), neurotoxicity and graft-versus-host disease (GvHD). CAR-NK cells do not require antigen priming, thus enabling them to be used as “off-the-shelf” therapy. Nonetheless, CAR-NK cell therapy still possesses several challenges in eliminating cancer cells which reside in hypoxic and immunosuppressive tumor microenvironment. Therefore, this review is envisioned to explore the current advancements and limitations of CAR-NK cell therapy as well as discuss strategies to overcome the challenges faced by CAR-NK cell therapy. This review also aims to dissect the current status of clinical trials on CAR-NK cells and future recommendations for improving the effectiveness and safety of CAR-NK cell therapy.
Extracellular vesicles secreted by 3D tumor organoids are enriched for immune regulatory signaling biomolecules compared to conventional 2D glioblastoma cell systems
Authors: Schuster Martina , Braun Frank K. , Chiang Dapi Meng-Lin , Ludwig Christina , Meng Chen , Grätz Christian , Kirchner Benedikt , Proescholdt Martin , Hau Peter , Steinlein Ortrud K. , Pfaffl Michael W. , Riemenschneider Markus J. , Reithmair Marlene
Published: April 2024

Background

Newer 3D culturing approaches are a promising way to better mimic the in vivo tumor microenvironment and to study the interactions between the heterogeneous cell populations of glioblastoma multiforme. Like many other tumors, glioblastoma uses extracellular vesicles as an intercellular communication system to prepare surrounding tissue for invasive tumor growth. However, little is known about the effects of 3D culture on extracellular vesicles. The aim of this study was to comprehensively characterize extracellular vesicles in 3D organoid models and compare them to conventional 2D cell culture systems.

Methods

Primary glioblastoma cells were cultured as 2D and 3D organoid models. Extracellular vesicles were obtained by precipitation and immunoaffinity, with the latter allowing targeted isolation of the CD9/CD63/CD81 vesicle subpopulation. Comprehensive vesicle characterization was performed and miRNA expression profiles were generated by smallRNA-sequencing. In silico analysis of differentially regulated miRNAs was performed to identify mRNA targets and corresponding signaling pathways. The tumor cell media and extracellular vesicle proteome were analyzed by high-resolution mass spectrometry.

Results

We observed an increased concentration of extracellular vesicles in 3D organoid cultures. Differential gene expression analysis further revealed the regulation of twelve miRNAs in 3D tumor organoid cultures (with nine miRNAs down and three miRNAs upregulated). MiR-23a-3p, known to be involved in glioblastoma invasion, was significantly increased in 3D. MiR-7-5p, which counteracts glioblastoma malignancy, was significantly decreased. Moreover, we identified four miRNAs (miR-323a-3p, miR-382-5p, miR-370-3p, miR-134-5p) located within the DLK1-DIO3 domain, a cancer-associated genomic region, suggesting a possible importance of this region in glioblastoma progression. Overrepresentation analysis identified alterations of extracellular vesicle cargo in 3D organoids, including representation of several miRNA targets and proteins primarily implicated in the immune response.

Conclusion

Our results show that 3D glioblastoma organoid models secrete extracellular vesicles with an altered cargo compared to corresponding conventional 2D cultures. Extracellular vesicles from 3D cultures were found to contain signaling molecules associated with the immune regulatory signaling pathways and as such could potentially change the surrounding microenvironment towards tumor progression and immunosuppressive conditions. These findings suggest the use of 3D glioblastoma models for further clinical biomarker studies as well as investigation of new therapeutic options.
Bio-graded recycling for hot asphalt mixtures with high RAP content considering freeze-thaw
Authors: He Liqiang , Li Yafei , Xia Moxuan , Liu Rui , Gu Qiutai , Luo Xiangyu , Zhang Xing
Published: April 2024

This paper investigates the effects of freeze-thaw cycles on the performance of asphalt mixtures containing 60% rejuvenated asphalt pavement (RAP). Two rejuvenation processes, traditional and bio-graded recycling, are compared regarding high-temperature performance, low-temperature performance, dynamic stability, flexural tensile strength, split tensile strength, water stability, and fatigue performance after various freeze-thaw cycles. The results indicate that bio-graded rejuvenation, compared to traditional rejuvenation, effectively enhances the high-temperature performance, low-temperature performance, water stability, and fatigue performance after freeze-thaw cycles. Both rejuvenations initially meet the dynamic stability requirements but show a decreasing trend with increasing freeze-thaw cycles, with traditional rejuvenation exhibiting more severe degradation. The flexural tensile strength initially exceeds that of conventional asphalt mixtures but decreases significantly with freeze-thaw cycles, especially in traditional rejuvenation. Additionally, freeze-thaw action increases the internal void ratio, affecting water stability and anti-freezing ability, particularly in traditional rejuvenated mixtures. These findings underscore the impact of freeze-thaw cycles on rejuvenated asphalt mixtures and emphasize the importance of innovative rejuvenation techniques for sustainable pavement.
Study on the mechanism of peanut resistance to Fusarium oxysporum infection induced by Bacillus thuringiensis TG5
Authors: Du Hongbo , Li Chuanrong
Published: April 2024

Peanut root rot, commonly referred to as rat tail or root rot, is caused by a range of Fusarium species. A strain of bacteria (named TG5) was isolated from crop rhizosphere soil in Mount Taishan, Shandong Province, China, through whole genome sequencing that TG5 was identified as Bacillus thuringiensis, which can specifically produce chloramphenicol, bacitracin, clarithromycin, lichen VK21A1 and bacitracin, with good biological control potential. Based on liquid chromatography tandem mass spectrometry metabonomics analysis and transcriptome conjoint analysis, the mechanism of TG5 and carbendazim inducing peanut plants to resist F. oxysporum stress was studied. In general, for peanut root rot caused by F. oxysporum, B. thuringiensis TG5 has greater advantages than carbendazim and is environmentally friendly. These findings provide new insights for peanut crop genetics and breeding, and for microbial pesticides to replace traditional highly toxic and highly polluting chemical pesticides. Based on the current background of agricultural green cycle and sustainable development, it has significant practical significance and broad application prospects.
Spatial organisation of fungi in soil biocrusts of the Kalahari is related to bacterial community structure and may indicate ecological functions of fungi in drylands
Authors: Elliott David R. , Thomas Andrew D. , Hoon Stephen R. , Sen Robin
Published: April 2024

Biological soil crusts, or biocrusts, are microbial communities found in soil surfaces in drylands and in other locations where vascular plant cover is incomplete. They are functionally significant for numerous ecosystem services, most notably in the C fixation and storage due to the ubiquity of photosynthetic microbes. Whereas carbon fixation and storage have been well studied in biocrusts, the composition, function and characteristics of other organisms in the biocrust such as heterotrophic bacteria and especially fungi are considerably less studied and this limits our ability to gain a holistic understanding of biocrust ecology and function. In this research we characterised the fungal community in biocrusts developed on Kalahari Sand soils from a site in southwest Botswana, and combined these data with previously published bacterial community data from the same site. By identifying organisational patterns in the community structure of fungi and bacteria, we found fungi that were either significantly associated with biocrust or the soil beneath biocrusts, leading to the conclusion that they likely perform functions related to the spatial organisation observed. Furthermore, we showed that within biocrusts bacterial and fungal community structures are correlated with each other i.e., a change in the bacterial community is reflected by a corresponding change in the fungal community. Importantly, this correlation but that this correlation does not occur in nearby soils. We propose that different fungi engage in short-range and long-range interactions with dryland soil surface bacteria. We have identified fungi which are candidates for further studies into their potential roles in biocrust ecology at short ranges (e.g., processing of complex compounds for waste management and resource provisioning) and longer ranges (e.g., translocation of resources such as water and the fungal loop model). This research shows that fungi are likely to have a greater contribution to biocrust function and dryland ecology than has generally been recognised.
Current treatment options for leptospirosis: a mini-review
Authors: Petakh Pavlo , Behzadi Payam , Oksenych Valentyn , Kamyshnyi Oleksandr
Published: April 2024

Leptospirosis, one of the most common global zoonotic infections, significantly impacts global human health, infecting more than a million people and causing approximately 60,000 deaths annually. This mini-review explores effective treatment strategies for leptospirosis, considering its epidemiology, clinical manifestations, and current therapeutic approaches. Emphasis is placed on antibiotic therapy, including recommendations for mild and severe cases, as well as the role of probiotics in modulating the gut microbiota. Furthermore, novel treatment options, such as bacteriophages and newly synthesized/natural compounds, are discussed, and the findings are expected to provide insights into promising approaches for combating leptospirosis.
Mechano-induced cell metabolism disrupts the oxidative stress homeostasis of SAOS-2 osteosarcoma cells
Authors: Fanelli Giuseppina , Alloisio Giulia , Lelli Veronica , Marini Stefano , Rinalducci Sara , Gioia Magda
Published: April 2024

There has been an increasing focus on cancer mechanobiology, determining the underlying-induced changes to unlock new avenues in the modulation of cell malignancy. Our study used LC-MS untargeted metabolomic approaches and real-time polymerase chain reaction (PCR) to characterize the molecular changes induced by a specific moderate uniaxial stretch regimen (i.e., 24 h-1 Hz, cyclic stretch 0,5% elongation) on SAOS-2 osteosarcoma cells. Differential metabolic pathway analysis revealed that the mechanical stimulation induces a downregulation of both glycolysis and the tricarboxylic acid (TCA) cycle. At the same time, the amino acid metabolism was found to be dysregulated, with the mechanical stimulation enhancing glutaminolysis and reducing the methionine cycle. Our findings showed that cell metabolism and oxidative defense are tightly intertwined in mechanically stimulated cells. On the one hand, the mechano-induced disruption of the energy cell metabolism was found correlated with an antioxidant glutathione (GSH) depletion and an accumulation of reactive oxygen species (ROS). On the other hand, we showed that a moderate stretch regimen could disrupt the cytoprotective gene transcription by altering the expression levels of manganese superoxide dismutase (SOD1), Sirtuin 1 (SIRT1), and NF-E2-related factor 2 (Nrf2) genes. Interestingly, the cyclic applied strain could induce a cytotoxic sensitization (to the doxorubicin-induced cell death), suggesting that mechanical signals are integral regulators of cell cytoprotection. Hence, focusing on the mechanosensitive system as a therapeutic approach could potentially result in more effective treatments for osteosarcoma in the future.
Local experience of laboratory activities in a BS physical therapy course: integrating sEMG and kinematics technology with active learning across six cohorts
Authors: De la Fuente Carlos , Neira Alejandro , Machado Álvaro S. , Delgado-Bravo Mauricio , Kunzler Marcos R. , de Andrade André Gustavo P. , Carpes Felipe P.
Published: April 2024

Introduction

Integrating technology and active learning methods into Laboratory activities would be a transformative educational experience to familiarize physical therapy (PT) students with STEM backgrounds and STEM-based new technologies. However, PT students struggle with technology and feel comfortable memorizing under expositive lectures. Thus, we described the difficulties, uncertainties, and advances observed by faculties on students and the perceptions about learning, satisfaction, and grades of students after implementing laboratory activities in a PT undergraduate course, which integrated surface-electromyography (sEMG) and kinematic technology combined with active learning methods.

Methods

Six cohorts of PT students (n = 482) of a second-year PT course were included. The course had expositive lectures and seven laboratory activities. Students interpreted the evidence and addressed different motor control problems related to daily life movements. The difficulties, uncertainties, and advances observed by faculties on students, as well as the students’ perceptions about learning, satisfaction with the course activities, and grades of students, were described.

Results

The number of students indicating that the methodology was “always” or “almost always,” promoting creative, analytical, or critical thinking was 70.5% [61.0–88.0%]. Satisfaction with the whole course was 97.0% [93.0–98.0%]. Laboratory grades were linearly associated to course grades with a regression coefficient of 0.53 and 0.43 R-squared (p < 0.001).

Conclusion

Integrating sEMG and kinematics technology with active learning into laboratory activities enhances students’ engagement and understanding of human movement. This approach holds promises to improve teaching-learning processes, which were observed consistently across the cohorts of students.
Artificial cerebellum on FPGA: realistic real-time cerebellar spiking neural network model capable of real-world adaptive motor control
Authors: Shinji Yusuke , Okuno Hirotsugu , Hirata Yutaka
Published: April 2024

The cerebellum plays a central role in motor control and learning. Its neuronal network architecture, firing characteristics of component neurons, and learning rules at their synapses have been well understood in terms of anatomy and physiology. A realistic artificial cerebellum with mimetic network architecture and synaptic plasticity mechanisms may allow us to analyze cerebellar information processing in the real world by applying it to adaptive control of actual machines. Several artificial cerebellums have previously been constructed, but they require high-performance hardware to run in real-time for real-world machine control. Presently, we implemented an artificial cerebellum with the size of 104 spiking neuron models on a field-programmable gate array (FPGA) which is compact, lightweight, portable, and low-power-consumption. In the implementation three novel techniques are employed: (1) 16-bit fixed-point operation and randomized rounding, (2) fully connected spike information transmission, and (3) alternative memory that uses pseudo-random number generators. We demonstrate that the FPGA artificial cerebellum runs in real-time, and its component neuron models behave as those in the corresponding artificial cerebellum configured on a personal computer in Python. We applied the FPGA artificial cerebellum to the adaptive control of a machine in the real world and demonstrated that the artificial cerebellum is capable of adaptively reducing control error after sudden load changes. This is the first implementation and demonstration of a spiking artificial cerebellum on an FPGA applicable to real-world adaptive control. The FPGA artificial cerebellum may provide neuroscientific insights into cerebellar information processing in adaptive motor control and may be applied to various neuro-devices to augment and extend human motor control capabilities.
Perturbing cortical networks: in vivo electrophysiological consequences of pan-neuronal chemogenetic manipulations using deschloroclozapine
Authors: Kovács Péter , Beloate Lauren N. , Zhang Nanyin
Published: April 2024

Introduction

Chemogenetic techniques, specifically the use of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), have become invaluable tools in neuroscience research. Yet, the understanding of how Gq- and Gicoupled DREADDs alter local field potential (LFP) oscillations in vivo remains incomplete.

Methods

This study investigates the in vivo electrophysiological effects of DREADD actuation by deschloroclozapine, on spontaneous firing rate and LFP oscillations recorded from the anterior cingulate cortex in lightly anesthetized male rats.

Results

Unexpectedly, in response to the administration of deschloroclozapine, we observed inhibitory effects with pan-neuronal hM3D(Gq) stimulation, and excitatory effects with pan-neuronal hM4D(Gi) stimulation in a significant portion of neurons. These results emphasize the need to account for indirect perturbation effects at the local neuronal network level in vivo, particularly when not all neurons express the chemogenetic receptors uniformly. In the current study, for instance, the majority of cells that were transduced with both hM3D(Gq) and hM4D(Gi) were GABAergic. Moreover, we found that panneuronal cortical chemogenetic modulation can profoundly alter oscillatory neuronal activity, presenting a potential research tool or therapeutic strategy in several neuropsychiatric models and diseases.

Discussion

These findings help to optimize the use of chemogenetic techniques in neuroscience research and open new possibilities for novel therapeutic strategies.
The effect of intermittent fasting on microbiota as a therapeutic approach in obesity
Authors: Cadena-Ullauri Santiago , Guevara-Ramírez Patricia , Ruiz-Pozo Viviana A. , Tamayo-Trujillo Rafael , Paz-Cruz Elius , Zambrano-Villacres Rayner , Simancas-Racines Daniel , Zambrano Ana Karina
Published: April 2024

Obesity, a public health challenge, arises from a complex interplay of factors such as dietary habits and genetic predisposition. Alterations in gut microbiota, characterized by an imbalance between Firmicutes and Bacteroidetes, further exacerbate metabolic dysregulation, promoting inflammation and metabolic disturbances. Intermittent fasting (IF) emerges as a promising dietary strategy showing efficacy in weight management and favoring fat utilization. Studies have used mice as animal models to demonstrate the impact of IF on gut microbiota composition, highlighting enhanced metabolism and reduced inflammation. In humans, preliminary evidence suggests that IF promotes a healthy microbiota profile, with increased richness and abundance of beneficial bacterial strains like Lactobacillus and Akkermansia. However, further clinical trials are necessary to validate these findings and elucidate the long-term effects of IF on microbiota and obesity. Future research should focus on specific tissues and cells, the use of advanced -omics techniques, and exploring the interaction of IF with other dietary patterns, to analyze microbiota composition, gene expression, and potential synergistic effects for enhanced metabolic health. While preliminary evidence supports the potential benefits of IF in obesity management and microbiota regulation, further research with diverse populations and robust methodologies is necessary to understand its implications and optimize personalized dietary interventions. This review explores the potential impact of IF on gut microbiota and its intricate relationship with obesity. Specifically, we will focus on elucidating the underlying mechanisms through which IF affects microbiota composition, as well as its subsequent effects on obesity.
Readthrough-induced misincorporated amino acid ratios guide mutant-specific therapeutic approaches for two CFTR nonsense mutations
Authors: Premchandar Aiswarya , Ming Ruiji , Baiad Abed , Da Fonte Dillon F. , Xu Haijin , Faubert Denis , Veit Guido , Lukacs Gergely L.
Published: April 2024

Cystic fibrosis (CF) is a monogenic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Premature termination codons (PTCs) represent ∼9% of CF mutations that typically cause severe expression defects of the CFTR anion channel. Despite the prevalence of PTCs as the underlying cause of genetic diseases, understanding the therapeutic susceptibilities of their molecular defects, both at the transcript and protein levels remains partially elucidated. Given that the molecular pathologies depend on the PTC positions in CF, multiple pharmacological interventions are required to suppress the accelerated nonsense-mediated mRNA decay (NMD), to correct the CFTR conformational defect caused by misincorporated amino acids, and to enhance the inefficient stop codon readthrough. The G418-induced readthrough outcome was previously investigated only in reporter models that mimic the impact of the local sequence context on PTC mutations in CFTR. To identify the misincorporated amino acids and their ratios for PTCs in the context of full-length CFTR readthrough, we developed an affinity purification (AP)-tandem mass spectrometry (AP-MS/MS) pipeline. We confirmed the incorporation of Cys, Arg, and Trp residues at the UGA stop codons of G542X, R1162X, and S1196X in CFTR. Notably, we observed that the Cys and Arg incorporation was favored over that of Trp into these CFTR PTCs, suggesting that the transcript sequence beyond the proximity of PTCs and/or other factors can impact the amino acid incorporation and full-length CFTR functional expression. Additionally, establishing the misincorporated amino acid ratios in the readthrough CFTR PTCs aided in maximizing the functional rescue efficiency of PTCs by optimizing CFTR modulator combinations. Collectively, our findings contribute to the understanding of molecular defects underlying various CFTR nonsense mutations and provide a foundation to refine mutation-dependent therapeutic strategies for various CF-causing nonsense mutations.
Targeting hypoxia signaling pathways in angiogenesis
Authors: Monaci Sara , Coppola Federica , Filippi Irene , Falsini Alessandro , Carraro Fabio , Naldini Antonella
Published: April 2024

Oxygen (O2) supply is constantly maintained by the vascular network for a proper tissue oxygenation. Hypoxia is the result of an increased O2 demand and/or decreased supply and is common in both physiological conditions and human diseases. Angiogenesis is one of the adaptive responses to hypoxia and is mainly regulated by the hypoxia-inducible factors, HIFs. These heterodimeric transcription factors are composed of one of three O2-dependent α subunits (HIF-1, HIF-2, and HIF-3) and a constitutively expressed O2-insensitive subunit (HIF-1β). Among them HIF-1α is the most characterized and its activity is tightly controlled. Under hypoxia, its intracellular accumulation triggers the transcription of several genes, involved in cell survival/proliferation, autophagy, apoptosis, cell metabolism, and angiogenesis. HIF pathway is also modulated by specific microRNAs (miRNAs), thus resulting in the variation of several cellular responses, including alteration of the angiogenic process. The pro-angiogenic activity of HIF-1α is not restricted to endothelial cells, as it also affects the behavior of other cell types, including tumor and inflammatory/immune cells. In this context, exosomes play a crucial role in cell-cell communication by transferring bio-active cargos such as mRNAs, miRNAs, and proteins (e.g., VEGFA mRNA, miR210, HIF-1α). This minireview will provide a synopsis of the multiple factors able to modulate hypoxia-induced angiogenesis especially in the tumor microenvironment context. Targeting hypoxia signaling pathways by up-to-date approaches may be relevant in the design of therapeutic strategies in those pathologies where angiogenesis is dysregulated.
Cultural dynamics influencing decision-making during the COVID-19 pandemic: the Italian case
Authors: Costa Sara , Carrus Giuseppe
Published: April 2024

The COVID-19 pandemic has brought about significant changes to the life of most individuals, worldwide. This study explores the cultural factors influencing decision-making during the pandemic, and is part of the CORNER Project, funded by the Research Council of Norway, aimed at understanding institutional response in the early phases of the Covid-19 emergency in Norway, Sweden, and Italy. Semi-structured interviews with key political-administrative leaders in Italy (N = 35) were conducted and content-analyzed, allowing the identification of the underlying cultural dynamics that played a role in these decisions. Thematic analysis was used to assess the influence of cultural factors on the crisis management and early reaction of institutions and citizens to the spread of Covid. In line with previous studies, and as expected, the individualism vs. collectivism dimension can explain differential health outcomes during the outbreak. In this paper we argue that individualism–collectivism cultural values can also play a pivotal role in public compliance with Covid-19 restrictions, and psychological responses during the pandemic.
Behavioral activation for depression in groups embedded in psychosomatic rehabilitation inpatient treatment: a quasi-randomized controlled study
Authors: Melicherova Ursula , Schott Tobias , Köllner Volker , Hoyer Jürgen
Published: April 2024

Background

Behavioral activation (BA) and cognitive-behavioral therapy (CBT) have shown to be efficacious treatment methods for depression. Previous studies focused mostly on the outpatient treatment either in group or individual setting. The present study aimed at comparing the efficacy of group treatment BA vs. CBT, when embedded in inpatient psychosomatic rehabilitation treatment.

Methods

375 inpatients were randomly assigned to either BA (N = 174) or CBT (N = 201). We used established scales for depression such as the Beck Depression Inventory II (BDI-II, self-rating), the Quick Inventory of Depressive Symptomatology (QIDS; expert rating) and the Behavioral Activation for Depression Scale (BADS) to assess changes over the course of the treatment and at follow-up (4 to 6 months). In addition, we measured disability-related functioning with the Mini-ICF-APP, a rating scale built in reference to the International Classification of Functioning, Disability and Health (ICF). Multilevel models with repeated measures were conducted to examine the differences between groups in relation to change over time with patients’ random effects.

Results

Both group formats showed substantial reduction in depressive symptoms at the end of treatment (d= 0.83 BA vs. d= 1.08 CBT; BDI-II) and at follow-up after 4 to 6 months (d = 0.97 BA vs. d = 1.33 CBT, BDI-II; and d = 1.17 BA vs. d = 1.09 CBT, QIDS). There were no significant differences between treatment approaches. At least 50% symptom reduction was achieved by 53.7% and 54.2% in BA vs. CBT respectively. Reported activation levels increased from pre- to posttreatment (d = 0.76 BA vs. d = 0.70CBT), while showing loss of increment between the end of the treatment until follow up in both formats (d = 0.28 BA vs. d = 0.29 CBT).

Discussion

Both modalities led to significant improvement of symptomatology and functioning at the end of the treatment and at follow-up, thus for the first time demonstrating the practicability of BA in rehabilitation clinics. Considering its lower requirements regarding cognitive abilities and its easier implementation, BA proved to be a good alternative to other psychotherapeutic treatments.
Spatial modeling of land resources and constraints to guide urban development in Saudi Arabia’s NEOM region using geomatics techniques
Authors: Alogayell Haya M. , Kamal Ahmed , Alkadi Ibtesam I. , Ramadan Mona S. , Ramadan Rasha H. , Zeidan Ali M.
Published: April 2024

This research presents a GIS-based approach to evaluate land suitability for the urbanization of Saudi Arabia’s NEOM region, an ambitious initiative for sustainable development within a desert setting. By employing a multi-criteria decision-making framework, we have synthesized data on land resources, stability, accessibility, construction costs, and proximity to conservation areas using the Analytical Hierarchy Process (AHP) to prioritize these factors based on their importance for sustainable growth. Our analysis reveals that areas designated with grid values of 9 and 8, totaling 6312.33 square kilometers or 28.23% of the area studied, are most favorable for urban development. These sectors span the northern, central, and southern parts of NEOM, which are notable for their strategic location near future infrastructure and natural assets conducive to sustainable practices. This finding supports NEOM’s key initiatives such as “The Line,” “Oxagon,” and “TROJENA,” showcasing the model’s utility in directing urban development strategies. The study discusses the broader socio-economic and environmental ramifications of pinpointing areas suited and unsuited for development, underlining the model’s role in facilitating decision-making that aligns urban expansion with environmental stewardship. Furthermore, it advocates for leveraging development-restricted zones in conservation efforts and renewable energy ventures. Nevertheless, the study concedes certain limitations, such as the dependence on static datasets and inherent challenges related to the AHP method, including the presumption of criteria independence. Future research avenues are proposed, emphasizing the integration of dynamic data sources, comprehensive socio-cultural impact evaluations, and adopting flexible urban planning methodologies to refine the model’s precision and practicality. Overall, this detailed examination showcases NEOM’s blueprint as an exemplar for future urban environments, illustrating a systematic strategy for developing desert regions that integrate innovation, ecological sustainability, and the preservation of cultural heritage.
Elucidating a genomic signature associated with behavioral and executive function after moderate to severe pediatric TBI: a systems biology informed approach
Authors: Kurowski Brad G. , Treble-Barna Amery , Pilipenko Valentina , Martin Lisa J. , Jegga Anil G. , Miley Aimee E. , Zhang Nanhua , Fabio Anthony , Chima Ranjit S. , Adlam Anna-Lynne R. , Kaufman Kenneth , Bell Michael J. , Beers Sue R. , Wisniewski Stephen R. , Wade Shari L. ,   TBI Genetics and Environment Study Team
Published: April 2024

Introduction: There is significant unexplained variability in behavioral and executive functioning after pediatric traumatic brain injury (TBI). Prior research indicates that there are likely genetic contributions; however, current research is limited. The purpose of this study is to use a systems biology informed approach to characterize the genomic signature related to behavioral and executive functioning ∼12 months after moderate through severe TBI in children.

Methods: Participants were from two prospective cohorts of children with severe TBI (Cohort #1) and moderate-severe TBI and an orthopedic injury (OI) group (Cohort #2). Participants included 196 children (n = 72 and n = 124 total from each respective cohort), ranging in age between 0–17 years at the time of injury. In total, 86 children had severe TBI, 49 had moderate TBI, and 61 had an OI. Global behavioral functioning assessed via the Child Behavior Checklist and executive function assessed via the Behavioral Rating Inventory of Executive Function at ∼ 12 months post injury served as outcomes. To test for a genomic signature, we compared the number of nominally significant (p < 0.05) polymorphisms associated with the outcomes in our systems biology identified genes to a set 10,000 permutations using control genes (e.g., not implicated by systems biology). We used the ToppFun application from Toppgene Suite to identify enriched biologic processes likely to be associated with behavioral and executive function outcomes.

Results: At 12 months post injury, injury type (TBI vs OI) by polymorphism interaction was significantly enriched in systems biology selected genes for behavioral and executive function outcomes, suggesting these genes form a genomic signature. Effect sizes of the associations from our genes of interest ranged from .2–.5 for the top 5% of variants. Systems biology analysis of the variants associated with the top 5% effect sizes indicated enrichment in several specific biologic processes and systems.

Discussion: Findings indicate that a genomic signature may explain heterogeneity of behavioral and executive outcomes after moderate and severe TBI. This work provides the foundation for constructing genomic signatures and integrating systems biology and genetic information into future recovery, prognostic, and treatment algorithms.
Association analysis of transcriptome and quasi-targeted metabolomics reveals the regulation mechanism underlying broiler muscle tissue development at different levels of dietary guanidinoacetic acid
Authors: Hong Jieyun , Raza Sayed Haidar Abbas , Liu Mengqian , Li Mengyuan , Ruan Jinrui , Jia Junjing , Ge Changrong , Cao Weina
Published: April 2024

The development and characteristics of muscle fibers in broilers are critical determinants that influence their growth performance, as well as serve as essential prerequisites for the production of high-quality chicken meat. Guanidinoacetic acid (GAA) is a crucial endogenous substance in animal creatine synthesis, and its utilization as a feed additive has been demonstrated the capabilities to enhance animal performance, optimize muscle yield, and augment carcass quality. The objective of this study was to investigate the regulation and molecular mechanism underlying muscle development in broilers at different levels of GAA via multiple omics analysis. The 90 Cobb broilers, aged 1 day, were randomly allocated into three treatments consisting of five replicates of six chickens each. The control group was provided with a basal diet, while the Normal GAA and High GAA groups received a basal diet supplemented with 1.2 g/kg and 3.6 g/kg of GAA, respectively. After a feeding period of 42 days, the pectoralis muscles were collected for histomorphological observation, transcriptome and metabolomic analysis. The results demonstrated that the addition of 1.2 g/kg GAA in the diet led to an augmentation in muscle fiber diameter and up-regulation of IGF1, IHH, ASB2, and ANKRD2 gene expression. However, a high dose of 3.6 g/kg GAA in the diet potentially reversed the beneficial effects on chicken breast development by excessively activating the TGF-β signaling pathway and reducing nucleotide metabolite content. These findings would provide a theoretical foundation for enhancing the performance and meat quality of broilers by incorporating GAA as a feed additive.