Local Disruption Research Articles

Comprehensive Analysis of the 5xFAD Mouse Model of Alzheimer’s Disease Using dMRI, Immunohistochemistry, and Neuronal and Glial Functional Metabolic Mapping

Alzheimer’s disease (AD) is characterized by complex interactions between neuropathological markers, metabolic dysregulation, and structural brain changes. In this study, we utilized a multimodal approach, combining immunohistochemistry, functional metabolic mapping, and microstructure sensitive diffusion MRI (dMRI) to progressively investigate these interactions in the 5xFAD mouse model of AD. Our analysis revealed age-dependent and region-specific accumulation of key AD markers, including amyloid-beta (Aβ), GFAP, and IBA1, with significant differences observed between the hippocampal formation and upper and lower regions of the cortex by 6 months of age. Functional metabolic mapping validated localized disruptions in energy metabolism, with glucose hypometabolism in the hippocampus and impaired astrocytic metabolism in the cortex. Notably, increased cortical glutaminolysis suggested a shift in microglial metabolism, reflecting an adaptive response to neuroinflammatory processes. While dMRI showed no significant microstructural differences between 5xFAD and wild-type controls, the study highlights the importance of metabolic alterations as critical events in AD pathology. These findings emphasize the need for targeted therapeutic strategies addressing specific metabolic disturbances and underscore the potential of integrating advanced imaging with metabolic and molecular analyses to advance our understanding of AD progression.

MiRNA-199b-5p suppresses of oral squamous cell carcinoma by targeting apical-basolateral polarity via Scribble/Lgl

In epithelial cells, Scribble forms cell-cell junctions and contribute to cell morphology and homeostasis by regulating apical-basolateral polarity in mammals and functions as a tumor suppressor in many carcinomas. The initial diagnosis of oral squamous cell carcinoma is important, and its prognosis is poor when accompanied by metastasis. However, research on the mechanisms of oral squamous cell carcinoma metastasis is insufficient. Herein, we showed that Scribble regulates the apical-basolateral polarity of oral squamous cell carcinoma by regulating lethal giant larvae 1, Scribble module and E-cadherin, the adhesion junction. The expression of lethal giant larvae 1 and E-cadherin decreased when the expression of Scribble was knocked down and their localization was completely disrupted in both the oral squamous cell carcinoma cell line and in vivo model. In particular, the Scribble was involved in oral squamous cell carcinoma metastasis via hsa-miR-199b-5p, which is a microenvironmental factor of hypoxia. The disruption of Scribble localization under hypoxic conditions, but its localization was maintained in miR-199b-5p oral squamous cell carcinoma cell lines and in vivo. These results suggest that Scribble functions as a tumor suppressor marker mediated by miR-199b-5p in oral squamous cell carcinoma.

Euphorbia Pekinensis Rupr. sensitizes colorectal cancer to PD-1 blockade by remodeling the tumor microenvironment and enhancing peripheral immunity

BackgroundImmune checkpoint blockade, such as monoclonal antibodies targeting programmed cell death protein 1 (PD-1), has been a major breakthrough in the treatment of several cancers, but has limited effect in colorectal cancer (CRC), which is a highly prevalent cancer worldwide. Current chemotherapy-based strategies to boost PD-1 response have many limitations. And the role of peripheral immunity in boosting PD-1 response continues to attract attention. Therefore, candidate combinations of PD-1 blockade need to be drugs with multi-targets and multi-modulatory functions. However, it is still unknown whether traditional Chinese medicines with such property can enhance the applicability and efficacy of PD-1 blockade in colorectal cancer. MethodsEuphorbia Pekinensis extract (EP) was prepared and the constituents were analyzed by HPLC. CRC cells were used for in vitro experiments, including cell viability assay, colony formation assay, flow cytometry for 7-AAD staining, western blotting for caspase 3 and caspase 7, HMGB1 and ATP detection. An orthotopic CT26 mouse model was subsequently used to investigate the combination of EP and PD-1 blockade therapy. Tumor volume and tumor weight were assessed, tumor tissues were subjected to histopathological HE staining and TUNEL staining, and tumor-infiltrating immune cells were evaluated by immunofluorescence staining. RNA-sequencing, target prediction and pathway analysis were further employed to explore the mechanism. Molecular docking and cellular thermal shift assay (CETSA) were utilized to verify the direct target of the core component of EP. And, loss-of-function analysis was carried to confirm the upstream-downstream relationship. Flow cytometry was employed to analyze CD8+ T cells in the peripheral blood and spleen. ResultsThe main constituents of EP are diterpenoids and flavonoids. EP dramatically suppresses CRC cell growth and exerts its cytotoxic effect by triggering immunogenic cell death in vitro. Moreover, EP synergizes with PD-1 blockade to inhibit tumorigenesis in tumor-bearing mice. Disruption of ISX nuclear localization by helioscopinolide E is a central mechanism of EP-induced apoptosis in CRC cell. Meanwhile, EP activates immune response by upregulating Phox2b to reshape the immune microenvironment. In addition, EP regulates peripheral immunity by regulating the T cell activation and proliferation, and the ratio of CD8+ T cells in peripheral blood is drastically increased, thereby enhancing the therapeutic efficacy of anti-PD1 immunotherapy. ConclusionEP triggers intra-tumor immunogenic cell death and modulates the immunoregulatory signaling to elicit the tumor immunogenicity. Moreover, EP participates in transcriptional activation of immune response-related pathways. Consequently, multiple stimulating functions of EP on macro- and micro-immune potentiates the anti-tumor effect of PD-1 blockade in CRC.

Designing resilient supply chain networks: a systematic literature review of mitigation strategies

AbstractWith increased globalisation supply chain (SC) disruption significantly affects people, organisations and society. Supply chain network design (SCND) reduces the effects of disruption, employing mitigation strategies such as extra capacity and flexibility to make SCs resilient. Currently, no systematic literature review classifies mitigation strategies for SCND. This paper systematically reviews the literature on SCND, analysing proposed mitigation strategies and the methods used for their integration into quantitative models. First to understand the key failure drivers SCND literature is categorised using geography, with local, regional or global disruptions linked to vulnerable sections of a SC. Second, the strategies used in mathematical models to increase SC resilience are categorized as proactive, reactive, or SC design quality capabilities. Third, the relative performance of mitigation strategies is analysed to provide a comparison, identifying the most effective strategies in given contexts. Forth, mathematical modelling techniques used in resilient SCND are reviewed, identifying how strategies are integrated into quantitative models. Finally, gaps in knowledge, key research questions and future directions for researchers are described.

Vulnerability of AND/OR logic networks under cascading failures

Cascading failures in AND/OR logic networks present a critical challenge in domains such as digital circuits and communication systems where reliability and resilience are paramount. This work investigates the vulnerability of AND/OR logic networks under cascading failures by examining the propagation mechanisms, failure modes, and robustness of such systems. In detail, we propose a hybrid fault propagation model based on the basic principles of AND/OR logic operations. Then, by utilizing both analytical and simulation approaches, we explore how initial localized disruptions can escalate through interconnected logical elements and lead to widespread system failures. Notably, it is shown that a Sigmoid function can be developed to quantify the vulnerability of the complex logic network. Moreover, the phase transition of the failures against the logic parameters is depicted and it is illustrated that the phase transition point is independent of the AND links. This study contributes to the understanding of cascading dynamics in logical networks and could facilitate design of feasible strategies for mitigating these vulnerabilities and recovering from substantial failures.

Non-linear MHD modelling of transients in tokamaks: a review of recent advances with the JOREK code

Abstract Transient MHD events like edge localized modes (ELMs) or disruptions are a concern for magnetic confinement fusion power plants. Research with the MHD code JOREK towards understanding control of such instabilities is reviewed here. Experimental validation for unmitigated vertical displacement events (VDEs) progressed. The mechanism of vertical force mitigation by impurity injection was identified. Two-way eddy current coupling to CARIDDI was completed. Shattered pellet injection (SPI) was simulated in JET, KSTAR and ASDEX Upgrade (AUG) and ITER. Benign runaway electron (RE) beam termination in JET and ITER was studied. Coupling of kinetic REs to the MHD is ongoing and a virtual RE synchrotron radiation diagnostic was developed. Regarding pedestal physics, regimes devoid of large ELMs in AUG were simulated and predictive JT60-SA simulations are ongoing. For ELM suppression by resonant magnetic perturbations (RMPs), AUG, ITER and EAST simulations were performed. A free boundary RMP model was validated against experiments. Evidence for penetrated magnetic islands at the pedestal top based on AUG experiments and simulations was found. Simulations of the naturally ELM-free quiescent H-mode (QH) in AUG and HL-3 show external kink mode formation prevents pedestal build-up towards an ELM within windows of the edge safety factor. With kinetic neutral particles, high field side high density (HFSHD) formation in ITER was simulated and with kinetic impurities, tungsten transport in AUG RMP plasmas was studied. To capture turbulent transport, electro-static full-f PiC models for ion temperature gradient (ITG) and trapped electron modes (TEM) were established and benchmarked. Application to RMP plasmas shows enhanced turbulence in comparison to unperturbed states. Energetic particle (EP) interactions with MHD were studied. Flux-pumping that prevents the safety factor on axis from dropping below unity was simulated. First non-linear stellarator applications include current relaxation in l=2 stellarators, while verification for advanced stellarators progresses.

HiViPore: a highly viable in-flow compression for a one-step cell mechanoporation in microfluidics to induce a free delivery of nano- macro-cargoes

BackgroundAmong mechanoporation techniques for intracellular delivery, microfluidic approaches succeed in high delivery efficiency and throughput. However, especially the entry of large cargoes (e.g. DNA origami, mRNAs, organic/inorganic nanoparticles) is currently impaired since it requires large cell membrane pores with the need to apply multi-step processes and high forces, dramatically reducing cell viability.ResultsHere, HiViPore presents as a microfluidic viscoelastic contactless compression for one-step cell mechanoporation to produce large pores while preserving high cell viability. Inducing an increase of curvature at the equatorial region of cells, formation of a pore with a size of ~ 1 μm is obtained. The poration is coupled to an increase of membrane tension, measured as a raised fluorescence lifetime of 12% of a planarizable push-pull fluorescent probe (Flipper-TR) labelling the cell plasma membrane. Importantly, the local disruptions of cell membrane are transient and non-invasive, with a complete recovery of cell integrity and functions in ~ 10 min. As result, HiViPore guarantees cell viability as high as ~ 90%. In such conditions, an endocytic-free diffusion of large nanoparticles is obtained with typical size up to 500 nm and with a delivery efficiency up to 12 times higher than not-treated cells.ConclusionsThe proposed one-step contactless mechanoporation results in an efficient and safe approach for advancing intracellular delivery strategies. In detail, HiViPore solves the issues of low cell viability when multiple steps of poration are required to obtain large pores across the cell plasma membrane. Moreover, the compression uses a versatile, low-cost, biocompatible viscoelastic fluid, thus also optimizing the operational costs. With HiViPore, we aim to propose an easy-to-use microfluidic device to a wide range of users, involved in biomedical research, imaging techniques and nanotechnology for intracellular delivery applications in cell engineering.

Demand side management through energy efficiency measures for the sustainable energy future of Pakistan

Pakistan is facing energy crises due to localized shortages, market manipulation, infrastructure disruption, rising demand, governance issues, climate and geopolitical events. In this situation Demand Side Management (DSM) is a promising solution to overcome the problem of energy crises. DSM strategy helps to manage consumer demand through energy conservation rather than to addition of new power capacity. In this study, Low Emissions Analysis Platform (LEAP) develops an energy model for Pakistan for the period 2022–2050. Three scenarios has been to constructed namely Baseline (BAS), Green Energy Policy (GEP), and Energy Efficiency (ENE) to predict the future energy demand, production, carbon emissions and the investment cost which covers capital, operational and maintenance costs. The model results suggest that DSM targets should be achieved through the implementation of ENE scenario. Predicted energy production and consumption under the ENE scenario are substantially less than those under the BAS scenario. The country can meet its 635.83,000 GWh energy demand with its 747.15,000 GWh energy production. Non-renewable sources produce 171.27,000 GWh, whilst renewable sources produce 575.88,000 GWh. According to this scenario, by 2050, CO2 emissions will be produced around 93.16 million metric tons, requiring an investment cost of $46.80 billion for building new power capacity. The study provides a roadmap with a suggestive optimal balance between energy saving with DSM approach and utilizing renewable energy production to meet energy demand for different sectors of the economy.

Hamstrings on focus: Are 72 hours sufficient for recovery after a football (soccer) match? A multidisciplinary approach based on hamstring injury risk factors and histology

ABSTRACT This study aimed to assess acute and residual changes in sprint-related hamstring injury (HSI) risk factors after a football (soccer) match, focusing on recovery within the commonly observed 72-h timeframe between elite football matches. We used a multifactorial approach within a football context, incorporating optical and ultrastructural microscopic analysis of BFlh (biceps femoris long head) muscle fibres, along with an examination of BFlh fibre composition. Changes in sprint performance-related factors and HSI modifiable risk factors were examined until 3 days after the match (MD +3) in 20 football players. BFlh biopsy specimens were obtained before and at MD +3 in 10 players. The findings indicated that at MD +3, sprint-related performance and HSI risk factors had not fully recovered, with notable increases in localized BFlh fibre disruptions. Interestingly, match load (both external and internal) did not correlate with changes in sprint performance or HSI risk factors nor with BFlh fibre disruption. Furthermore, our study revealed a balanced distribution of ATPase-based fibre types in BFlh, with type-II fibres associated with sprint performance. Overall, the results suggest that a 72-h recovery period may not be adequate for hamstring muscles in terms of both HSI risk factors and BFlh fibre structure following a football match.

Stress and alignment response to curved obstacles in growing bacterial monolayers.

Monolayers of growing bacteria, confined within channel geometries, exhibit self-organization into a highly aligned laminar state along the axis of the channel. Although this phenomenon has been observed in experiments and simulations under various boundary conditions, the underlying physical mechanism driving this alignment remains unclear. In this study, we conduct simulations of growing bacteria in two-dimensional channel geometries perturbed by fixed obstacles, either circular or arc shaped, placed at the channel's center. Our findings reveal that even sizable obstacles cause only short-ranged disruptions to the baseline laminar state. These disruptions arise from a competition between local planar anchoring and bulk laminar alignment. At smaller obstacle sizes, bulk alignment fully dominates, while at larger sizes planar anchoring induces increasing local disruptions. Furthermore, our analysis indicates that the resulting configurations of the bacterial system display a striking resemblance to the arrangement of hard-rod smectic liquid crystals around circular obstacles. This suggests that modeling hard-rod bacterial monolayers as smectic, rather than nematic, liquid crystals may yield successful outcomes. The insights gained from our study contribute to the expanding body of research on bacterial growth in channels. Our work provides perspectives on the stability of the laminar state and extends our understanding to encompass more intricate confinement schemes.

Identification of circRNA Expression Profile and Potential Systemic Immune Imbalance Modulation in Premature Rupture of Membranes.

Premature rupture of membrane (PROM) refers to the rupture of membranes before the onset of labor which increases the risk of perinatal morbidity and mortality. Recently, circular RNAs (circRNAs) have emerged as promising regulators of diverse diseases. However, the circRNA expression profiles and potential circRNA-miRNA-mRNA regulatory mechanisms in PROM remain enigmatic. In this study, we displayed the expression profiles of circRNAs and mRNAs in plasma and fetal membranes of PROM and normal control (NC) groups based on circRNA microarray, the Gene Expression Omnibus database, and NCBI's Sequence Read Archive. A total of 1,459 differentially expressed circRNAs (DECs) in PROM were identified, with 406 upregulated and 1,053 downregulated. Then, we constructed the circRNA-miRNA-mRNA network in PROM, encompassing 22 circRNA-miRNA pairs and 128 miRNA-mRNA pairs. Based on the analysis of gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene set enrichment analysis (GSEA), DECs were implicated in immune-related pathways, with certain alterations persisting even postpartum. Notably, 11 host genes shared by DECs of fetal membrane tissue and prenatal plasma in PROM were significantly implicated in inflammatory processes and extracellular matrix regulation. Our results suggest that structurally stable circRNAs may predispose to PROM by mediating systemic immune imbalances, including peripheral leukocyte disorganization, local immune imbalance at the maternal-fetal interface, and local collagen disruption. This is the first time to decipher a landscape on circRNAs of PROM, reveals the pathogenic cause of PROM from the perspective of circRNA, and opens up a new direction for the diagnosis and treatment of PROM.

Geminated primary maxillary incisor with two root canals: A case report

Gemination is a rare dental anomaly of single tooth bud dividing into two crowns and two root canals, that may also be named as ‘double teeth’. This is as a result of their peculiar, twin-like presentation. Teeth with these anomalies could show up clinically as bulbous shaped with peculiar architecture and fissure patterns. While there is uncertainty regarding the precise cause of these aberrations, numerous possible local or systemic disruptions during the morpho-differentiation stage of odontogenesis have been taken into consideration. This report presents a case of a geminated maxillary primary right central incisor and explains the significance of early detection and identification of these teeth in order to give appropriate treatment and preventative care.

Different Formation Modes of the North–South‐Trending Rifts in Southern Tibet: Implications From Ambient Noise Tomography

AbstractUnderstanding how the Miocene N–S‐trending rifts on the southern Tibetan Plateau formed is crucial for understanding the evolution of the plateau. Most competing models suggest that all the rifts developed uniformly, but there are differences in magmatism among them. We conducted ambient noise tomography based on a broadband seismic array deployed across the rifts. A mid‐crustal low‐Vs layer extends laterally beneath the Tangra Yum Co Rift and the Pumqu‐Xianza Rift, implying that E‒W stretching of the ductile middle crust segmented the brittle upper crust, causing rifting and subsequent magmatism. In contrast, the Yadong‐Gulu Rift, which experienced prerifting magmatism, is characterized by an isolated low‐Vs anomaly extending subvertically from the surface to the middle crust, indicating that the crust experienced magmatic intrusion and local disruption, which promoted the later formation of a large rift. The results suggest that the various rifts might have distinct formation modes.

Brain functional connectivity alterations in patients with anterior cruciate ligament injury

Recent advancements in neuroimaging have illustrated that anterior cruciate ligament (ACL) injuries could impact the central nervous system (CNS), causing neuroplastic changes in the brain beyond the traditionally understood biomechanical consequences. While most of previous functional magnetic resonance imaging (fMRI) studies have focused on localized cortical activity changes post-injury, emerging research has suggested disruptions in functional connectivity across the brain. However, these prior investigations, albeit pioneering, have been constrained by two limitations: a reliance on small-sample participant cohorts, often limited to two to three patients, potentially limiting the generalizability of findings, and an adherence to region of interest based analysis, which may overlook broader network interactions. To address these limitations, our study employed resting-state fMRI to assess whole-brain functional connectivity in 15 ACL-injured patients, comparing them to matched controls using two distinct network analysis methods. Using Network-Based Statistics, we identified widespread reductions in connectivity that spanned across multiple brain regions. Further modular connectivity analysis showed significant decreases in inter-modular connectivity between the sensorimotor and cerebellar modules, and intra-modular connectivity within the default-mode network in ACL-injured patients. Our results thus highlight a shift from localized disruptions to network-wide dysfunctions, suggesting that ACL injuries induce widespread CNS changes. This enhanced understanding has the potential to stimulate the development of strategies aiming to restore functional connectivity and improve recovery outcomes.

0752 Regional Cerebrovascular Pathology Is Associated with Local Disruptions in Non-rapid Eye Movement Sleep Expression

0752 Regional Cerebrovascular Pathology Is Associated with Local Disruptions in Non-rapid Eye Movement Sleep Expression

Organising for System Change: “From the Sea to the City” and the Movement Ecology of Migrant Solidarity in Europe

AbstractThis paper engages with the relationship between dissident European mayors and the migrant solidarity movement in Europe after 2015. With the case study of the coalition “From the Sea to the City”, I examine how its members institutionalise mayors’ dissent at a transnational level through the International Alliance of Safe Harbours. Employing primary empirical data, the study finds that coalition members create a political sequence in four ways: developing a storyline and setting up a broad coalition of migrant solidarity; referencing mayors’ disruptive acts; nurturing counter‐imaginaries; and laying the foundation for further action towards transforming the instituted order of European migration politics. To conceptualise the empirical findings, I draw on concepts of political organisation. In this vein, the paper calls for an assessment of movement politics that goes beyond the belief that local disruptions will suffice to set in motion a progressive transformation of European migration politics.

Abstract 4428: Integrated multi-omics analysis reveals systemic and localized metabolic disruptions in colorectal cancer

Abstract Despite technological advances in molecular medicine over the last 30 years, no single approach has proven to be sufficient to meet the diagnostic needs in cancer care. Here we use a multiomic approach leveraging proteomic, metabolomic, and transcriptomic technologies to study the metabolic shifts that occur during colorectal cancer (CRC) progression, Our integrated analysis identified systemic changes to beta oxidation pathways and localized changes to tyrosine metabolism within the tumor, creating a mechanistic, actionable description of the core CRC metabolic program. We conducted untargeted proteomics and metabolomics profiling on serum samples from CRC patients (n=10) and healthy controls (n=10). Our serum proteomics data is generated through sample enrichment on the Seer Proteograph system followed by LC/MS analysis with the Thermo Orbitrap Astral. Our metabolomics approach employs LC/MS assays for unbiased profiling of the serum metabolome, exposome, and lipidome. We supplemented this discovery work with both targeted serum and tumor-specific approaches including targeted proteomics to quantify select targets, inflammatory profiling with Alamar proteomics, public transcriptomics data from TCGA, and in vitro metabolic flux data. These large and diverse datasets were then integrated through joint pathway analysis and network integration. The global serum proteomics and metabolomics profiles generated show distinct separation between healthy and diseased individuals. Joint pathway analysis of these discovery datasets highlighted enrichment in beta oxidation pathways and tyrosine metabolism, among others. Interestingly, the Alamar inflammatory panel revealed that many of the analytes in the tyrosine metabolism pathway were well correlated with inflammatory status, while the beta oxidation signature had a lower correlation. To determine the relationship of these systemic findings from serum to tumor metabolism itself, we integrated tumor-specific transcriptomics data and found alterations to tyrosine metabolism with differences in tyrosine aminotransferase expression. The beta oxidation related genes, on the other hand, were not concordant with the serum findings. However, our in vitro metabolic flux studies have shown beta oxidation in CRC cells is upregulated to provide additional fuel for oxidative phosphorylation. This result suggests that beta oxidation may not be transcriptionally regulated in the tumor but rather a consequence of organismal metabolic rewiring. The results of this work, which is currently expanding into a larger and more diverse patient population, underscores the power of multiomic profiling for enhancing our understanding of metabolic dysregulation in CRC. Ultimately, a comprehensive model of the molecular alterations in CRC will yield a better understanding of tumor phenotypes and inform better diagnostics and therapies. Citation Format: Gary Patti, Ethan Stancliffe, Adam Richardson, Ashima Mehta, Monil Gandhi, Kevin Cho. Integrated multi-omics analysis reveals systemic and localized metabolic disruptions in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4428.

TransNeT-CGP: A cluster-based comorbid gene prioritization by integrating transcriptomics and network-topological features

The local disruptions caused by the genes of one disease can influence the pathways associated with the other diseases resulting in comorbidity. For gene therapies, it is necessary to prioritize the key genes that regulate common biological mechanisms to tackle the issues caused by overlapping diseases. This work proposes a clustering-based computational approach for prioritising the comorbid genes within the overlapping disease modules by analyzing Protein-Protein Interaction networks. For this, a sub-network with gene interactions of the disease pair was extracted from the interactome. The edge weights are assigned by combining the pairwise gene expression correlation and betweenness centrality scores. Further, a weighted graph clustering algorithm is applied and dominant nodes of high-density clusters are ranked based on clustering coefficients and neighborhood connectivity. Case studies based on neurodegenerative diseases such as Amyotrophic Lateral Sclerosis- Spinal Muscular Atrophy (ALS-SMA) pair and cancers such as Ovarian Carcinoma-Invasive Ductal Breast Carcinoma (OC-IDBC) pair were conducted to examine the efficacy of the proposed method. To identify the mechanistic role of top-ranked genes, we used Functional and Pathway enrichment analysis, connectivity analysis with leave-one-out (LOO) method, analysis of associated disease-related protein complexes, and prioritization tools such as TOPPGENE and Heml2.0. From pathway analysis, it was observed that the top 10 genes obtained using the proposed method were associated with 10 pathways in ALS-SMA comorbidity and 15 in the case of OC-IDBC, while that in similar methods like SAPDSB and S2B were 4, 6 respectively for ALS-SMA and 9, 10 respectively for OC-IDBC. In both case studies, 70 % of the disease-specific benchmark protein complexes were linked to top-ranked genes of the proposed method while that of SAPDSB and S2B were 55 % and 60 % respectively. Additionally, it was found that the removal of the top 10 genes disconnect the network into 14 distinct components in the case of ALS-SMA and 9 in the case of OC-IDBC. The experimental results shows that the proposed method can be effectively used for identifying key genes in comorbidity and can offer insights about the intricate molecular relationship driving comorbid diseases.

Blood-Brain Barrier Disruption for the Treatment of Primary Brain Tumors: Advances in the Past Half-Decade.

To review relevant advances in the past half-decade in the treatment of primary brain tumors via modification of blood-brain barrier (BBB) permeability. BBB disruption is becoming increasingly common in the treatment of primary brain tumors. Use of mannitol in BBB disruption for targeted delivery of chemotherapeutics via superselective intra-arterial cerebral infusion (SIACI) is the most utilized strategy to modify the BBB. Mannitol is used in conjunction with chemotherapeutics, oligonucleotides, and other active agents. Convection-enhanced delivery has become an attractive option for therapeutic delivery while bypassing the BBB. Other technologic innovations include laser interstitial thermal therapy (LITT) and focused ultrasound (FUS) which have emerged as prime modalities to directly target tumors and cause significant local BBB disruption. In the past 5years, interest has significantly increased in studying modalities to disrupt the BBB in primary brain tumors to enhance treatment responses and improve clinical outcomes.

The effect of small perturbation on dynamics of absorptive LiBr–water solution

In a binary solution of lithium bromide–water, even a small disturbance in the initial homogeneous mass fraction at the absorbing interface has profound effects on the entire system dynamics. This perturbation of absorption disrupts the equilibrium, leading to the formation of surface tension gradients and subsequently, Marangoni flows. While these flows are relatively weak, they result in a non-uniform distribution of density within the bulk, initiating buoyant convection. We investigate complexities of the Marangoni, solutal, and buoyant convection caused by localized disruptions in uniform absorption, all in the absence of any surfactants. We have conducted numerical simulations to explore fluid dynamics and heat and mass transfer, revealing three different regimes. Initially, shortly after disturbance, variations in mass fraction and flow within the cell are primarily governed by the Marangoni force. After a finite period, the emergence of buoyant convection leads to the strong growth of velocity and significant changes in temperature and mass fraction. Finally, the destabilization of the boundary layer becomes so significant that the emission of plumes is observed. At later times, the parallel existence of two types of patterns takes on a spatially fixed form. The central part, occupied by bands (visible on space-time maps), exhibits minimal changes in time, while a periodic structure is established near the wall. This behavior can be characterized as a relaxation–oscillation mode of instability.