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The combined use of lytic bacteriophages with antibiotics is currently being explored as a strategy to enhance the effectiveness of infectious disease therapies, including those caused by Staphylococcus aureus. In this study, we investigated the synergistic potential of bacteriophage vB_SauM-515A1 (Herelleviridae family) and the first-line antibiotic linezolid against the methicillin-resistant S. aureus strain SA0413Rev. A checkerboard assay revealed a significant synergistic effect against planktonic cells (FIC = 0.225): a combination of 1/8 MIC of linezolid and 0.01 MOI of the bacteriophage completely inhibited bacterial growth. However, the impact on biofilm-associated cells depended on the treatment sequence. Sequential administration resulted in antagonism, while simultaneous application demonstrated a synergistic effect, as confirmed through scanning electron microscopy. Transcriptomic analysis of S. aureus SA0413Rev under the combined influence of linezolid (1/4 MIC) and bacteriophage vB_SauM-515A1 (10 MOI) predominantly reflected changes associated with productive bacteriophage infection, including alterations in nucleotide metabolism, activation of prophage regions, and virulence factors. Furthermore, both agents affected energy and carbon metabolism. These findings contribute to the development of combination therapy approaches for infections caused by S. aureus and highlight the importance of optimizing treatment conditions for maximal therapeutic efficacy.

Bone tissue and breast tissue are interrelated, as demonstrated by breast microcalcifications, breast cancer bone metastases, bone morphogenetic proteins, and Wnt signaling. In addition, osteoblasts and osteoclasts represent an important switch of tumor cell dormancy during bone metastasis. Damage to both types of tissues mentioned above is highly prevalent, especially in postmenopausal women, and manifests itself in osteoporosis and breast cancer. Sea buckthorn (Elaeagnus rhamnoides L.), a botanical drug with high antioxidant, antitumor, anti-inflammatory, immunomodulatory, and regenerative properties, has great therapeutic potential due to the unique composition of its bioactive metabolites. This review aimed to summarize the current knowledge from in vitro and in vivo studies on the effect of sea buckthorn, as well as its most widespread flavonoids isorhamnetin, quercetin, and kaempferol, on bone and breast tissue health. In vitro studies have revealed the beneficial impacts of sea buckthorn and aforementioned flavonoids on both bone health (bone remodeling, mineralization, and oxidative stress) and breast tissue health (cancer cell proliferation, apoptosis, tumor growth, and metastatic behavior). In vivo studies have documented their protective effects against disturbed bone microarchitecture and reduced bone strength in animal models of osteoporosis, as well as against tumor expansion and metastatic properties in animal xenograft models. In any case, further research and clinical trials are needed to carefully evaluate the potential therapeutic benefits of sea buckthorn and its flavonoids. Based on the available information, however, it can be concluded that these bioactive metabolites favorably affect both bone and breast tissue health.

The nervous system, especially the human brain, is characterized by its highly complex network topology. The neurodevelopment of some of its features has been described in terms of dynamic optimization rules. We discuss the principle of adaptive rewiring, i.e., the dynamic reorganization of a network according to the intensity of internal signal communication as measured by synchronization or diffusion, and its recent generalization for applications in directed networks. These have extended the principle of adaptive rewiring from highly oversimplified networks to more neurally plausible ones. Adaptive rewiring captures all the key features of the complex brain topology: it transforms initially random or regular networks into networks with a modular small-world structure and a rich-club core. This effect is specific in the sense that it can be tailored to computational needs, robust in the sense that it does not depend on a critical regime, and flexible in the sense that parametric variation generates a range of variant network configurations. Extreme variant networks can be associated at macroscopic level with disorders such as schizophrenia, autism, and dyslexia, and suggest a relationship between dyslexia and creativity. Adaptive rewiring cooperates with network growth and interacts constructively with spatial organization principles in the formation of topographically distinct modules and structures such as ganglia and chains. At the mesoscopic level, adaptive rewiring enables the development of functional architectures, such as convergent-divergent units, and sheds light on the early development of divergence and convergence in, for example, the visual system. Finally, we discuss future prospects for the principle of adaptive rewiring.

3D cell culture models replicate tissue complexity and aim to study cellular interactions and responses in a more physiologically relevant environment compared to traditional 2D cultures. However, the spherical structure of these models makes it difficult to extract meaningful data, necessitating advanced techniques for proper analysis. In silico simulations enhance research by predicting cellular behaviors and therapeutic responses, providing a powerful tool to complement experimental approaches. Despite their potential, these simulations often require advanced computational skills and significant resources, which creates a barrier for many researchers. To address these challenges, we developed an accessible pipeline using open-source software to facilitate virtual tissue simulations. Our approach employs the Cellular Potts Model, a versatile framework for simulating cellular behaviors in tissues. The simulations are constructed from real world 3D image stacks of cancer spheroids, ensuring that the virtual models are rooted in experimental data. By introducing a new metric for parameter optimization, we enable the creation of realistic simulations without requiring extensive computational expertise. This pipeline benefits researchers wanting to incorporate computational biology into their methods, even if they do not possess extensive expertise in this area. By reducing the technical barriers associated with advanced computational modeling, our pipeline enables more researchers to utilize these powerful tools. Our approach aims to foster a broader use of in silico methods in disease research, contributing to a deeper understanding of disease biology and the refinement of therapeutic interventions.

Spheroids have become principal three-dimensional models to study cancer, developmental processes, and drug efficacy. Single-cell analysis techniques have emerged as ideal tools to gauge the complexity of cellular responses in these models. However, the single-cell quantitative assessment based on 3D-microscopic data of the subcellular distribution of fluorescence markers, such as the nuclear/cytoplasm ratio of transcription factors, has largely remained elusive. For spheroid generation, ultra-low attachment plates are noteworthy due to their simplicity, compatibility with automation, and experimental and commercial accessibility. However, it is unknown whether and to what degree the plate type impacts spheroid formation and biology. This study developed a novel AI-based pipeline for the analysis of 3D-confocal data of optically cleared large spheroids at the wholemount, single-cell, and sub-cellular levels. To identify relevant samples for the pipeline, automated brightfield microscopy was employed to systematically compare the size and eccentricity of spheroids formed in six different plate types using four distinct human cell lines. This showed that all plate types exhibited similar spheroid-forming capabilities and the gross patterns of growth or shrinkage during 4 days after seeding were comparable. Yet, size and eccentricity varied systematically among specific cell lines and plate types. Based on this prescreen, spheroids of HaCaT keratinocytes and HT-29 cancer cells were further assessed. In HaCaT spheroids, the in-depth analysis revealed a correlation between spheroid size, cell proliferation, and the nuclear/cytoplasm ratio of the transcriptional coactivator, YAP1, as well as an inverse correlation with respect to cell differentiation. These findings, yielded with a spheroid model and at a single-cell level, corroborate earlier concepts of the role of YAP1 in cell proliferation and differentiation of keratinocytes in human skin. Further, the results show that the plate type may influence the outcome of experimental campaigns and that it is advisable to scan different plate types for the optimal configuration during a specific investigation.

The field of oceanography is transitioning from data-poor to data-rich, thanks in part to increased deployment of in-situ platforms and sensors, such as those that instrument the US-funded Ocean Observatories Initiative (OOI). However, generating science-ready data products from these sensors, particularly those making biogeochemical measurements, often requires extensive end-user calibration and validation procedures, which can present a significant barrier. Openly available community-developed and -vetted Best Practices contribute to overcoming such barriers, but collaboratively developing user-friendly Best Practices can be challenging. Here we describe the process undertaken by the NSF-funded OOI Biogeochemical Sensor Data Working Group to develop Best Practices for creating science-ready biogeochemical data products from OOI data, culminating in the publication of the GOOS-endorsed OOI Biogeochemical Sensor Data Best Practices and User Guide. For Best Practices related to ocean observatories, engaging observatory staff is crucial, but having a “user-defined” process ensures the final product addresses user needs. Our process prioritized bringing together a diverse team and creating an inclusive environment where all participants could effectively contribute. Incorporating the perspectives of a wide range of experts and prospective end users through an iterative review process that included “Beta Testers’’ enabled us to produce a final product that combines technical information with a user-friendly structure that illustrates data analysis pipelines via flowcharts and worked examples accompanied by pseudo-code. Our process and its impact on improving the accessibility and utility of the end product provides a roadmap for other groups undertaking similar community-driven activities to develop and disseminate new Ocean Best Practices.

Platinum and Pd-arsenides, antimonides, tellurides, bismuthinides, and sulfides are the major hosts of Pt and Pd in magmatic and hydrothermal Cu-Ni-sulfide ores. Textural relationships among such minerals in nature often provide contradictory messages about the mechanism and timing of their formation. To know how and when Pt and Pd mineral phases crystallize from sulfide-saturated liquids and how their compositions and textures evolve during cooling, we undertook controlled cooling experiments in evacuated silica tubes. A Cu-Ni-Fe sulfide mixture, similar in composition to the average Merensky Reef sulfide magma, was charged (in a 9:1 wt.% proportion) with one of the PtAs2, PtTe2, PtSb2, PtBi2, PdAs2, PdTe2, PdSb, and PdBi2 compounds, heated to 1,100°C, and slowly cooled (15°C/day) to room temperature. The run products were sampled at 950°C, 750°C, and 25°C by quenching the silica tubes in water. The results show that Pt formed stable phases with As, Te, and Sb above 950°C and with Bi and S below 750°C. The Pt phases were found mostly in the decomposed intermediate solid solution (ISS), and all the phases survived to 25°C with no compositional changes. At 950°C, Pd formed arsenide, telluride, and antimonide immiscible melts that coexisted with monosulfide solid solution (MSS) and sulfide melt. The composition of the Pd-semimetal melt droplets changed during cooling by equilibration with the host sulfide. Palladium mineral phases formed at temperatures below 750°C directly from the immiscible semimetal-rich melts where they kept the rounded shapes of the melt droplets. Ni-sulfarsenides preceded the formation of Pd arsenides. No Ni tellurides, antimonides, or bismuthinides formed in any of the systems, implying that their formation requires higher semimetal/Pt + Pd ratios. The decomposition of MSS and ISS to base metal sulfides led to significant textural changes in Pt and Pd mineral grains. The compositions of Pt and Pd phases are inherited from the magmatic stage, and their textures are low-temperature (

The Regenerative Finance (ReFi) movement aims to fundamentally transform the governance of global common pool resources (CPRs), such as the atmosphere, which are being degraded despite international efforts. The ReFi movement seeks to achieve this by utilizing digital monitoring, reporting, and verification (D-MRV); tokenization of assets; and decentralized governance approaches. However, there is currently a lack of a clear path forward to create and implement models that actually drive the “Re-” in ReFi beyond perpetuating the existing extractive economics and toward actual regeneration. In addition, ReFi suffers from growing pains, lacking a common interoperability framework and definition for determining what a ReFi project is and how the individual components align toward the grand ambition. This paper provides a definition of the ReFi stack of interconnected components and examines how it can address limitations in climate change accounting, finance and markets, and governance. The authors also examine the theory of regenerative economics and CPRs to encourage further discussions and advancements in the ReFi space. The crucial question remains if and how ReFi can drive a change in paradigm toward the effective regeneration of global CPRs.

BackgroundSome patients with cardiac resynchronisation therapy (CRT) experience super-response (LVEF improvements to ≥50%). At generator exchange (GE), downgrading (DG) from CRT-defibrillator (CRT-D) to CRT-pacemaker (CRT-P) could be an option for these patients on primary prevention ICD indication and no required ICD therapies. Long-term data on arrhythmic events in super-responders is scarce.MethodsCRT-D patients with LVEF improvement to ≥50% at GE were identified in four large centres for retrospective analysis. Mortality, significant ventricular tachyarrhythmia and appropriate ICD-therapy were determined, and patient analysis was split into two groups (downgraded to CRT-P or not).ResultsSixty-six patients (53% male, 26% coronary artery disease) on primary prevention were followed for a median of 129 months [IQR: 101–155] after implantation. 27 (41%) patients were downgraded to CRT-P at GE after a median of 68 [IQR: 58–98] months (LVEF 54% ± 4%). The other 39 (59%) continued with CRT-D therapy (LVEF 52% ± 6%). No cardiac death or significant arrhythmia occurred in the CRT-P group (median follow-up (FU) 38 months [IQR: 29–53]). Three appropriate ICD-therapies occurred in the CRT-D group [median FU 70 months (IQR: 39–97)]. Annualized event-rates after DG/GE were 1.5%/year and 1.0%/year in the CRT-D group and the whole cohort, respectively.ConclusionsNo significant tachyarrhythmia were detected in the patients downgraded to CRT-P during follow-up. However, three events were observed in the CRT-D group. Whilst downgrading CRT-D patients is an option, a small residual risk for arrhythmic events remains and decisions regarding downgrade should be made on a case-by-case basis.

BackgroundArtificial intelligence (AI) and machine learning (ML) models continue to evolve the clinical decision support systems (CDSS). However, challenges arise when it comes to the integration of AI/ML into clinical scenarios. In this systematic review, we followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA), the population, intervention, comparator, outcome, and study design (PICOS), and the medical AI life cycle guidelines to investigate studies and tools which address AI/ML-based approaches towards clinical decision support (CDS) for monitoring cardiovascular patients in intensive care units (ICUs). We further discuss recent advances, pitfalls, and future perspectives towards effective integration of AI into routine practices as were identified and elaborated over an extensive selection process for state-of-the-art manuscripts.MethodsStudies with available English full text from PubMed and Google Scholar in the period from January 2018 to August 2022 were considered. The manuscripts were fetched through a combination of the search keywords including AI, ML, reinforcement learning (RL), deep learning, clinical decision support, and cardiovascular critical care and patients monitoring. The manuscripts were analyzed and filtered based on qualitative and quantitative criteria such as target population, proper study design, cross-validation, and risk of bias.ResultsMore than 100 queries over two medical search engines and subjective literature research were developed which identified 89 studies. After extensive assessments of the studies both technically and medically, 21 studies were selected for the final qualitative assessment.DiscussionClinical time series and electronic health records (EHR) data were the most common input modalities, while methods such as gradient boosting, recurrent neural networks (RNNs) and RL were mostly used for the analysis. Seventy-five percent of the selected papers lacked validation against external datasets highlighting the generalizability issue. Also, interpretability of the AI decisions was identified as a central issue towards effective integration of AI in healthcare.

The skeleton is the third most common site of metastatic disease, which causes serious bone complications and short-term prognosis in cancer patients. Prostate and breast cancers are responsible for the majority of bone metastasis, resulting in osteolytic or osteoblastic lesions. The crosstalk between bone cells and their interactions with tumor cells are important in the development of lesions. Recently, both preclinical and clinical studies documented the clinical relevance of bone-derived factors, including osteocalcin (OC) and its undercarboxylated form (ucOC), fibroblast growth factor 23 (FGF23), sclerostin (SCL), and lipocalin 2 (LCN2) as prognostic tumor biomarkers and potential therapeutic targets in bone metastasis. Both OC and ucOC could be useful targets for the prevention of bone metastasis in breast cancer. Moreover, elevated OC level may be a metastatic marker of prostate cancer. FGF23 is particularly important for those forms of cancer that primarily affect bone and/or are characterized by bone metastasis. In other tumor entities, increased FGF23 level is enigmatic. SCL plays a significant role in the pathogenesis of both osteolytic and osteoblastic lesions, as its levels are high in metastatic breast and prostate cancers. Elevated expression levels of LCN2 have been found in aggressive subtypes of cancer. However, its role in anti-metastasis varies significantly between different cancer types. Anyway, all aforementioned bone-derived factors can be used as promising tumor biomarkers. As metastatic bone disease is generally not curable, targeting bone factors represents a new trend in the prevention of bone metastasis and patient care.

Assessing the status of ocean acidification across ocean and coastal waters requires standardized procedures at all levels of data collection, dissemination, and analysis. Standardized procedures for assuring quality and accessibility of ocean carbonate chemistry data are largely established, but a common set of best practices for ocean acidification trend analysis is needed to enable global time series comparisons, establish accurate records of change, and communicate the current status of ocean acidification within and outside the scientific community. Here we expand upon several published trend analysis techniques and package them into a set of best practices for assessing trends of ocean acidification time series. These best practices are best suited for time series capable of characterizing seasonal variability, typically those with sub-seasonal (ideally monthly or more frequent) data collection. Given ocean carbonate chemistry time series tend to be sparse and discontinuous, additional research is necessary to further advance these best practices to better address uncharacterized variability that can result from data discontinuities. This package of best practices and the associated open-source software for computing and reporting trends is aimed at helping expand the community of practice in ocean acidification trend analysis. A broad community of practice testing these and new techniques across different data sets will result in improvements and expansion of these best practices in the future.

Solar observations at sub-mm, mm and cm wavelengths offer a straightforward diagnostic of physical conditions in the solar atmosphere because they yield measurement of brightness temperature which, for optically thick features, equals intrinsic temperature - much unlike solar diagnostics in other spectral ranges. The Atacama Large Millimeter and sub-millimeter Array (ALMA) has therefore opened a new, hitherto underexplored, spectral window for studying the enigmatic solar chromosphere. In this review we discuss initial ALMA studies of the quiet chromosphere that used both single-dish and compact-array interferometric observing modes. We present results on the temperature structure of the chromosphere, comparison with classic empirical models of the chromosphere, and observations of the chromospheric network and spicules. Furthermore, we discuss what may be expected in the future, since the ALMA capabilities continuously expand and improve towards higher angular resolution, wavelength coverage, and polarization measurement for magnetometry.

Microsoft HoloLens 2 (HL2) is often found in research and products as a cutting-edge device in Mixed Reality medical applications. One application is surgical telementoring, that allows a remote expert to support surgeries in real-time from afar. However, in this field of research two problems are encountered: First, many systems rely on additional sensors to record the surgery in 3D which makes the deployment cumbersome. Second, clinical testing under real-world surgery conditions is only performed in a small number of research works. In this article, we present a standalone system that allows the capturing of 3D recordings of open cardiac surgeries under clinical conditions using only the existing sensors of HL2. We show difficulties that arose during development, especially related to the optical system of the HL2, and present how they can be solved. The system has successfully been used to record surgeries from the surgeons point of view and the obtained material can be used to reconstruct a 3D view for evaluation by an expert. In a preliminary study, we present a recording of a captured surgery under real-world clinical conditions to expert surgeons which estimate the quality of the recordings and their overall applicability for diagnosis and support. The study shows benefits from a 3D reconstruction compared to video-only transmission regarding perceived quality and feeling of immersion.

In recent decades our understanding of solar active regions (ARs) has improved substantially due to observations made with better angular resolution and wider spectral coverage. While prior AR observations have shown that these structures were always brighter than the quiet Sun at centimeter wavelengths, recent observations at millimeter and submillimeter wavelengths have shown ARs with well defined dark umbrae. Given this new information, it is now necessary to update our understanding and models of the solar atmosphere in active regions. In this work, we present a data-constrained model of the AR solar atmosphere, in which we use brightness temperature measurements of NOAA 12470 at three radio frequencies: 17, 100 and 230 GHz. The observations at 17 GHz were made by the Nobeyama Radioheliograph (NoRH), while the observations at 100 and 230 GHz were obtained by the Atacama Large Millimeter/submillimeter Array (ALMA). Based on our model, which assumes that the radio emission originates from thermal free-free and gyroresonance processes, we calculate radio brightness temperature maps that can be compared with the observations. The magnetic field at distinct atmospheric heights was determined in our modelling process by force-free field extrapolation using photospheric magnetograms taken by the Helioseismic and Magnetic Imager (HMI) on board the Solar Dynamics Observatory (SDO). In order to determine the best plasma temperature and density height profiles necessary to match the observations, the model uses a genetic algorithm that modifies a standard quiet Sun atmospheric model. Our results show that the height of the transition region (TR) of the modelled atmosphere varies with the type of region being modelled: for umbrae the TR is located at 1080 ± 20 km above the solar surface; for penumbrae, the TR is located at 1800 ± 50 km; and for bright regions outside sunspots, the TR is located at 2000 ± 100 km. With these results, we find good agreement with the observed AR brightness temperature maps. Our modelled AR can be used to estimate the emission at frequencies without observational coverage.

Social dysfunction is one of the most debilitating aspects of schizophrenia. Treatment of this complex phenomenon, constituted by negative, cognitive, and affective symptoms, has been difficult with the available pharmacological agents, hence it represents an unmet medical need. Cariprazine, a novel, third-generation antipsychotic with a unique mechanism of action has been proven to sufficiently alleviate negative, cognitive, and affective symptoms of schizophrenia. These characteristics make this compound a valid candidate for addressing social dysfunction too. In this perspective, we argue that cariprazine can be viewed as a “socializing drug” that has the ability to improve the patient's functionality and ultimately their quality of life. Data from animal research, clinical trials, an observational study, and patient cases are provided.

The combination of planar chromatography with desorption/ionization mass-spectrometry (MS) techniques provides chemists with unique tools for fast and simple separation of mixtures followed by the detection of analytes by the most powerful analytical method. Since its introduction in the early 1990s, thin-layer chromatography (TLC)/matrix-assisted mass spectrometry (MALDI) has been used for the analysis of a wide range of analytes, including natural and synthetic organic compounds. Nowadays, new desorption/ionization approaches have been developed and applied in conjunction with planar chromatography competing with MALDI. This review covers recent developments in the combination of TLC with various desorption/ionization MS methods which were made in recent several years.

The North Atlantic and Arctic oceans, along with the North Pacific, are the main reservoirs of anthropogenic radionuclides introduced in the past 75 years. The POSEIDON-R compartment model was applied to the North Atlantic and Arctic oceans to reconstruct 137Cs contamination in 1945–2020 due to multiple sources: global fallout, exchange flows with other oceans, point-source inputs in the ocean from reprocessing plants and other nuclear facilities, the impact of the Chernobyl accident and secondary contamination resulting from river runoff and redissolution from bottom sediments. The model simulated the marine environment as a system of 3D compartments comprising the water column, bottom sediment, and biota. The dynamic model described the transfer of 137Cs through the pelagic and benthic food chains. The simulation results were validated using the marine database MARIS. The calculated concentrations of 137Cs in the seaweed and non-piscivorous and piscivorous pelagic fish mostly followed the concentration of 137Cs in water. The concentration in coastal predator fish lagged behind the concentration in water as a result of a diet that includes both pelagic and benthic organisms. The impact of each considered source on the total concentration of 137Cs in non-piscivorous fish in the regions of interest was analyzed. Whereas the contribution from global fallout dominated in 1960–1970, in 1970–1990, the contribution of 137Cs released from reprocessing plants exceeded the contributions from other sources in almost all considered regions. Secondary contamination due to river runoff was less than 4% of ocean influx. The maximum total inventory of 137Cs in the Arctic Ocean (31,122 TBq) was reached in 1988, whereas the corresponding inventory in the bottom sediment was approximately 6% of the total. The general agreement between simulated and observed 137Cs concentrations in water and bottom sediment was confirmed by the estimates of geometric mean and geometric standard deviation, which varied from 0.89 to 1.29 and from 1.22 to 1.87, respectively. The approach used is useful to synthesize measurement and simulation data in areas with observational gaps. For this purpose, 13 representative regions in the North Atlantic and Arctic oceans were selected for monitoring by using the “etalon” method for classification.

Background: With the increasing availability and advances in brain imaging, pineal cyst lesions (PCL) are becoming a common finding in the pediatric population. In the absence of evidence-based guidelines, optimal diagnostic and therapeutic approaches have not been established, and there is a risk of under- or overtreatment of these patients.Objectives: The aim of our study was to evaluate the clinical presentation and radiological features of PCL in a cohort of pediatric patients and to identify clinical parameters more commonly associated with neoplasms in the pineal region. In addition, the prevalence of PCL in the pediatric population of Slovenia was estimated.Methods: In this observational, cohort study, children treated at University Children's Hospital, Ljubljana, Slovenia in the period 1997–2016 were included if PCL was found on brain imaging. We analyzed indications for referral to a neurologist, clinical signs and symptoms, radiological features, treatment and outcome.Results: The cohort consisted of 143 children with PCL. Pineocytoma was suspected in 31 children (21.7%). Six children underwent surgery – pineocytoma was confirmed in two cases and germinoma in one (2/3 of these children had signs of increased intracranial pressure (ICP), while PCL was benign in the remaining 4 cases. Only 2 PCL enlarged during the study period, both 20mm in diameter; both showed signs of increased ICP, one patient was found to have a germinoma of the pineal region, while the other had no neoplasm.Conclusions: Most PCL do not change their features during radiological follow-up and even atypical PCL are very rarely associated with a malignant neoplasm of the pineal region. A PCL larger than 20 mm and signs of increased ICP were identified as potential markers for selecting patients at risk.

Glioblastomas (GBM) are the common and aggressive primary brain tumors that are incurable by conventional therapies. Immunotherapy with immune checkpoint inhibitors is not effective in GBM patients due to the highly immunosuppressive tumor microenvironment (TME) restraining the infiltration and activation of cytotoxic T cells. Clinical and experimental studies showed the upregulation of expression of the arginase 1 and 2 (ARG1 and ARG2, respectively) in murine and human GBMs. The elevated arginase activity leads to the depletion of L-arginine, an amino-acid required for the proliferation of T lymphocytes and natural killer cells. Inhibition of ARG1/2 in the TME may unblock T cell proliferation and activate effective antitumor responses. To explore the antitumor potential of ARG1/2 inhibition, we analyzed bulk and single-cell RNA sequencing (scRNA-seq) data from human and murine gliomas. We found the upregulation of ARG1/2 expression in GBMs, both in tumor cells and in tumor infiltrating microglia and monocytes/macrophages. We employed selective arginase inhibitors to evaluate if ARG1/2 inhibition in vitro and in vivo exerts the antitumor effects. A novel, selective ARG1/2 inhibitor - OAT-1746 blocked microglia-dependent invasion of U87-MG and LN18 glioma cells in a Matrigel invasion assay better than reference compounds, without affecting the cell viability. OAT-1746 effectively crossed the blood brain barrier in mice and increased arginine levels in the brains of GL261 glioma bearing mice. We evaluated its antitumor efficacy against GL261 intracranial gliomas as a monotherapy and in combination with the PD-1 inhibition. The oral treatment with OAT-1746 did not affect the immune composition of TME, it induced profound transcriptomic changes in CD11b+ cells immunosorted from tumor-bearing brains as demonstrated by RNA sequencing analyses. Treatment with OAT-1746 modified the TME resulting in reduced glioma growth and increased antitumor effects of the anti-PD-1 antibody. Our findings provide the evidence that inhibition of ARG1/2 activity in tumor cells and myeloid cells in the TME unblocks antitumor responses in myeloid cells and NK cells, and improves the efficacy of the PD-1 inhibition.

Introduction: Despite the growing efforts to standardize coding for social determinants of health (SDOH), they are infrequently captured in electronic health records (EHRs). Most SDOH variables are still captured in the unstructured fields (i.e., free-text) of EHRs. In this study we attempt to evaluate a practical text mining approach (i.e., advanced pattern matching techniques) in identifying phrases referring to housing issues, an important SDOH domain affecting value-based healthcare providers, using EHR of a large multispecialty medical group in the New England region, United States. To present how this approach would help the health systems to address the SDOH challenges of their patients we assess the demographic and clinical characteristics of patients with and without housing issues and briefly look into the patterns of healthcare utilization among the study population and for those with and without housing challenges.Methods: We identified five categories of housing issues [i.e., homelessness current (HC), homelessness history (HH), homelessness addressed (HA), housing instability (HI), and building quality (BQ)] and developed several phrases addressing each one through collaboration with SDOH experts, consulting the literature, and reviewing existing coding standards. We developed pattern-matching algorithms (i.e., advanced regular expressions), and then applied them in the selected EHR. We assessed the text mining approach for recall (sensitivity) and precision (positive predictive value) after comparing the identified phrases with manually annotated free-text for different housing issues.Results: The study dataset included EHR structured data for a total of 20,342 patients and 2,564,344 free-text clinical notes. The mean (SD) age in the study population was 75.96 (7.51). Additionally, 58.78% of the cohort were female. BQ and HI were the most frequent housing issues documented in EHR free-text notes and HH was the least frequent one. The regular expression methodology, when compared to manual annotation, had a high level of precision (positive predictive value) at phrase, note, and patient levels (96.36, 95.00, and 94.44%, respectively) across different categories of housing issues, but the recall (sensitivity) rate was relatively low (30.11, 32.20, and 41.46%, respectively).Conclusion: Results of this study can be used to advance the research in this domain, to assess the potential value of EHR's free-text in identifying patients with a high risk of housing issues, to improve patient care and outcomes, and to eventually mitigate socioeconomic disparities across individuals and communities.

Antibiotic resistance is a major public health concern in many countries worldwide. The rapid spread of multidrug-resistant (MDR) bacteria is the main driving force for the development of novel non-antibiotic antimicrobials as a therapeutic alternative. Here, we isolated and characterized three virulent bacteriophages that specifically infect and lyse MDR Klebsiella pneumoniae with K23 capsule type. The phages belonged to the Autographiviridae (vB_KpnP_Dlv622) and Myoviridae (vB_KpnM_Seu621, KpS8) families and contained highly similar receptor-binding proteins (RBPs) with polysaccharide depolymerase enzymatic activity. Based on phylogenetic analysis, a similar pattern was also noted for five other groups of depolymerases, specific against capsule types K1, K30/K69, K57, K63, and KN2. The resulting recombinant depolymerases Dep622 (phage vB_KpnP_Dlv622) and DepS8 (phage KpS8) demonstrated narrow specificity against K. pneumoniae with capsule type K23 and were able to protect Galleria mellonella larvae in a model infection with a K. pneumoniae multidrug-resistant strain. These findings expand our knowledge of the diversity of phage depolymerases and provide further evidence that bacteriophages and phage polysaccharide depolymerases represent a promising tool for antimicrobial therapy.

Pulmonary hypertension (PH) is common in patients with heart failure (HF). The role of PH in patients with HF with reduced (HFrEF) and preserved (HFpEF) left ventricular ejection fraction (LVEF) has been extensively characterized during the last years. In contrast, the pathophysiology of HF with mid-range LVEF (HFmrEF), and in particular the role of PH in this context, are largely unknown. There is a paucity of data in this field, and the prevalence of PH, the underlying mechanisms, and the optimal therapy are not well-defined. Although often studied together there is increasing evidence that despite similarities with both HFrEF and HFpEF, HFmrEF also differs from both entities. The present review provides a summary of the current concepts of the mechanisms and clinical impact of PH in patients with HFmrEF, a proposal for the non-invasive and invasive diagnostic approach required to define the pathophysiology of PH and its management, and a discussion of future directions based on insights from mechanistic studies and randomized trials. We also provide an outlook regarding gaps in evidence, future clinical challenges, and research opportunities.

Swollenins exist within some fungal species and are candidate accessory proteins for the biodegradation of cellulosic substrates. Here, we describe the identification of a swollenin gene, Tlswo, in Talaromyces leycettanus JCM12802. Tlswo was successfully expressed in both Trichoderma reesei and Pichia pastoris. Assay results indicate that TlSWO is capable of releasing reducing sugars from lichenan, barley β-glucan, carboxymethyl cellulose sodium (CMC-Na) and laminarin. The specific activity of TlSWO toward lichenan, barley β-glucan, carboxymethyl cellulose sodium (CMC-Na) and laminarin is 9.0 ± 0.100, 8.9 ± 0.100, 2.3 ± 0.002 and 0.79 ± 0.002 U/mg, respectively. Additionally, TlSWO had disruptive activity on Avicel and a synergistic effect with cellobiohydrolases, increasing the activity on pretreated corn stover by up to 72.2%. The functional diversity of TlSWO broadens its applicability in experimental settings, and indicating that it may be a promising candidate for future industrial applications.

With their unparalleled mass sensitivity, enabling single-molecule mass spectrometry, nanomechanical resonators have the potential to considerably improve existing sensor technology. Vertical pillar resonators are a promising alternative to the existing lateral resonator designs. However, one major obstacle still stands in the way of their practical use: The efficient transduction (actuation & detection) of the vibrational motion of such tiny structures, even more so when large arrays of such nanopillars need to be driven. While electrostatic forces are typically weak and, on the nanoscale even weaker when compared to a cantilever-like stiffness, it is worth revisiting the possibility of electrostatic actuation of nanomechanical pillars and other nanomechanical structures. In this paper, these forces produced by an external field are studied both analytically and numerically, and their dependencies on the geometric dimensions are discussed. Furthermore, the expected deflections for different configurations of pillar geometries are calculated and compared.

Micro/nanocapsules would have many more applications if we were able to controllably populate their surface with various chemical moieties. The present review introduces a novel variant of interfacial polymerization (IP) as a very robust method of manufacturing reservoir micro/nanocapsules equipped with several different functionalities on the capsules' surface. We call the method—IPCESCO (Interfacial Polymerization for Capsules' External Surface Control). As always in IP, the capsules' forming reaction is between monomers dissolved in opposite phases (oil or water) and takes place at the interface. Each monomer carries two or more functionalities reacting with functional groups of the monomer dissolved in the other phase. IPCESCO requires that one or both monomers are additionally equipped with (protected) functional groups interfering neither with the payload nor with the polymer formation. These additional groups end up everywhere in the polymeric shell but most importantly they are present on the external surface of capsules. These “handles” allow for the introduction of various moieties onto the capsules' surface. Since carbohydrate chemists developed a plurality of protecting and deprotecting methods for various functional groups such as aldehyde and hydroxyl, modified mono, and oligosaccharides are particularly well-suited to act as monomers in IPCESCO. The article discusses possible monomers and their synthesis, the transformation of protected reactive groups on the external capsules' surface into the desired functionalities, the control of the number of moieties on the surface and the capsules surface's architecture. The most important application of the novel encapsulation technology is in drug delivery. Possible surface units facilitating capsules' transport in the body, delivery to specific locations and mechanisms of capsules rupture are also addressed. Other applications of novel capsules include an ultra-sensitive quantitation and removal of pathogens, transport of nutrients in plants, detection of various antigens and other parameters in single cells.

BackgroundDistinct tissue types are differentiated based on the surgeon’s knowledge and subjective visible information, typically assisted with white-light intraoperative imaging systems. Narrow-band imaging (NBI) assists in tissue identification and enables automated classifiers, but many anatomical details moderate computational predictions and cause bias. In particular, tissues’ light-source-dependent optical characteristics, anatomical location, and potentially hazardous microstructural changes such as peeling have been overlooked in previous literature.MethodsNarrow-band images of five (n = 5) facial nerves (FNs) and internal carotid arteries (ICAs) were captured from freshly frozen temporal bones. The FNs were split into intracranial and intratemporal samples, and ICAs’ adventitia was peeled from the distal end. Three-dimensional (3D) spectral data were captured by a custom-built liquid crystal tunable filter (LCTF) spectral imaging (SI) system. We investigated the normal variance between the samples and utilized descriptive and machine learning analysis on the image stack hypercubes.ResultsReflectance between intact and peeled arteries in lower-wavelength domains between 400 and 576 nm was significantly different (p < 0.05). Proximal FN could be differentiated from distal FN in a higher range, 490–720 nm (p < 0.001). ICA with intact tunica differed from proximal FN nearly thorough the VIS range, 412–592 nm (p < 0.001) and 664–720 nm (p < 0.05) as did its distal counterpart, 422–720 nm (p < 0.001). The availed U-Net algorithm classified 90.93% of the pixels correctly in comparison to tissue margins delineated by a specialist.ConclusionSelective NBI represents a promising method for assisting tissue identification and computational segmentation of surgical microanatomy. Further multidisciplinary research is required for its clinical applications and intraoperative integration.

For more than 30 years, deep brain stimulation (DBS) has been used to target the symptoms of a number of neurological disorders and in particular movement disorders such as Parkinson’s disease (PD) and essential tremor (ET). It is known that the loss of dopaminergic neurons in the substantia nigra leads to PD, while the exact impact of this on the brain dynamics is not fully understood, the presence of beta-band oscillatory activity is thought to be pathological. The cause of ET, however, remains uncertain, however pathological oscillations in the thalamocortical-cerebellar network have been linked to tremor. Both of these movement disorders are treated with DBS, which entails the surgical implantation of electrodes into a patient’s brain. While DBS leads to an improvement in symptoms for many patients, the mechanisms underlying this improvement is not clearly understood, and computational modeling has been used extensively to improve this. Many of the models used to study DBS and its effect on the human brain have mainly utilized single neuron and single axon biophysical models. We have previously shown in separate models however, that the use of population models can shed much light on the mechanisms of the underlying pathological neural activity in PD and ET in turn, and on the mechanisms underlying DBS. Together, this work suggested that the dynamics of the cerebellar-basal ganglia thalamocortical network support oscillations at frequency range relevant to movement disorders. Here, we propose a new combined model of this network and present new results that demonstrate that both Parkinsonian oscillations in the beta band and oscillations in the tremor frequency range arise from the dynamics of such a network. We find regions in the parameter space demonstrating the different dynamics and go on to examine the transition from one oscillatory regime to another as well as the impact of DBS on these different types of pathological activity. This work will allow us to better understand the changes in brain activity induced by DBS, and allow us to optimize this clinical therapy, particularly in terms of target selection and parameter setting.

Erysipelas, caused by the bacterium Erysipelothrix rhusiopathiae, is re-emerging in swine and poultry production systems worldwide. While the global genomic diversity of this species has been characterized, how much of this genomic and functional diversity is maintained at smaller scales is unclear. Specifically, while several key immunogenic surface proteins have been identified for E. rhusiopathiae, little is known about their presence among field strains and their divergence from vaccines, which could result in vaccine failure. Here, a comparative genomics approach was taken to determine the diversity of E. rhusiopathiae strains in pigs in Great Britain over nearly three decades, as well as to assess the field strains’ divergence from the vaccine strain most commonly used in British pigs. In addition, the presence/absence and variability of 13 previously described immunogenic surface proteins was determined, including SpaA which is considered a key immunogen. We found a high diversity of E. rhusiopathiae strains in British pigs, similar to the situation described in European poultry but in contrast to swine production systems in Asia. Of the four clades of E. rhusiopathiae found globally, three were represented among British pig isolates, with Clade 2 being the most common. All British pig isolates had one amino acid difference in the immunoprotective domain of the SpaA protein compared to the vaccine strain. However, we were able to confirm using in silico structural protein analyses that this difference is unlikely to compromise vaccine protection. Of 12 other known immunogenic surface proteins of E. rhusiopathiae examined, 11 were found to be present in all British pig isolates and the vaccine strain, but with highly variable degrees of conservation at the amino acid sequence level, ranging from 0.3 to 27% variant positions. Moreover, the phylogenetic incongruence of these proteins suggests that horizontal transfer of genes encoding for antigens is commonplace for this bacterium. We hypothesize that the sequence variants in these proteins could be responsible for differences in the efficacy of the immune response. Our results provide the necessary basis for testing this hypothesis through in vitro and in vivo studies.

Three-dimensional cell cultures, such as spheroids and organoids, serve as increasingly important models in fundamental and applied research and start to be used for drug screening purposes. Optical tissue clearing procedures are employed to enhance visualization of fluorescence-stained organs, tissues, and three-dimensional cell cultures. To get a more systematic overview about the effects and applicability of optical tissue clearing on three-dimensional cell cultures, we compared six different clearing/embedding protocols on seven types of spheroid- and chip-based three-dimensional cell cultures of approximately 300 μm in size that were stained with nuclear dyes, immunofluorescence, cell trackers, and cyan fluorescent protein. Subsequent whole mount confocal microscopy and semi-automated image analysis were performed to quantify the effects. Quantitative analysis included fluorescence signal intensity and signal-to-noise ratio as a function of z-depth as well as segmentation and counting of nuclei and immunopositive cells. In general, these analyses revealed five key points, which largely confirmed current knowledge and were quantified in this study. First, there was a massive variability of effects of different clearing protocols on sample transparency and shrinkage as well as on dye quenching. Second, all tested clearing protocols worked more efficiently on samples prepared with one cell type than on co-cultures. Third, z-compensation was imperative to minimize variations in signal-to-noise ratio. Fourth, a combination of sample-inherent cell density, sample shrinkage, uniformity of signal-to-noise ratio, and image resolution had a strong impact on data segmentation, cell counts, and relative numbers of immunofluorescence-positive cells. Finally, considering all mentioned aspects and including a wish for simplicity and speed of protocols – in particular, for screening purposes – clearing with 88% Glycerol appeared to be the most promising option amongst the ones tested.

Emerging evidence has attributed altered network coordination between the default mode, central executive, and salience networks (DMN/CEN/SAL) to disturbances seen in schizophrenia, but little is known for at-risk psychosis stages. Moreover, pinpointing impairments in specific network-to-network interactions, although essential to resolve possibly distinct harbingers of conversion to clinically diagnosed schizophrenia, remains particularly challenging. We addressed this by a dynamic approach to functional connectivity, where right anterior insula brain interactions were examined through co-activation pattern (CAP) analysis. We utilized resting-state fMRI in 19 subjects suffering from subthreshold delusions and hallucinations (UHR), 28 at-risk for psychosis with basic symptoms describing only self-experienced subclinical disturbances (BS), and 29 healthy controls (CTR) matched for age, gender, handedness, and intelligence. We extracted the most recurring CAPs, compared their relative occurrence and average dwell time to probe their temporal expression, and quantified occurrence balance to assess the putative loss of competing relationships. Our findings substantiate the pivotal role of the right anterior insula in governing CEN-to-DMN transitions, which appear dysfunctional prior to the onset of psychosis, especially when first attenuated psychotic symptoms occur. In UHR subjects, it is longer active in concert with the DMN and there is a loss of competition between a SAL/DMN state, and a state with insula/CEN activation paralleled by DMN deactivation. These features suggest that abnormal network switching disrupts one's capacity to distinguish between the internal world and external environment, which is accompanied by inflexibility and an excessive awareness to internal processes reflected by prolonged expression of the right anterior insula-default mode co-activation pattern.

Imagined activities could actually be a cognitive basis for creative thinking. However, it is still unknown how they might be related with the architecture of the brain. A recent study has proved the relevance of the imagined activity when investigating neuronal diseases by comparing variations in the neuronal activity of patients with brain diseases and healthy subjects. One important aspect of the scientific methodologies focused on neuronal diseases is therefore to provide a trustable methodology that could allow us to distinguish between realized and imagined activities in the brain. The electroencephalogram is the result of synchronized action of the cerebrum, and our end is portraying the network dynamics through the neuronal responses when the subjects perform visuomotor and specific imaginary assignments. We use a subtle information theoretical approach accounting for the time causality of the signal and the closeness centrality of the different nodes. More specifically we perform estimations of the probability distribution of the data associated to each node using the Bandt and Pompe approach to account for the causality of the electroencephalographic signals. We calculate the Jensen-Shannon distance across different nodes, and then we quantify how fast the information flow would be through a given node to other nodes computing the closeness centrality. We perform a statistical analysis to compare the closeness centrality considering the different rhythmic oscillation bands for each node taking into account imagined and visuomotor tasks. Our discoveries stress the pertinence of the alpha band while performing and distinguishing the specific imaginary or visuomotor assignments.

Purpose: Limbic encephalitis associated with autoantibodies against N-methyl D-aspartate receptors (NMDARs) often presents with memory impairment. NMDARs are key targets for memory acquisition and retrieval, and have been mechanistically linked to its underlying process, synaptic plasticity. Clinically, memory deficits are largely compatible with a pre-dominantly hippocampus-dependent phenotype, which, in rodents, is principally involved in spatial memory. Previous studies confirmed the impaired spatial memory in the rat model of anti-NMDAR encephalitis. Here, we hypothesized that non-spatial memory functions, such as object recognition might also be affected in this model.Methods: We performed stereotactic intrahippocampal bolus injection of human cerebrospinal fluid (CSF) from anti-NMDAR encephalitis and control patients into the hippocampus of the anesthetized rat. After recovery for 1–8 days, hippocampal slices were prepared from these animals and NMDAR-dependent long-term potentiation was assessed at the Schaffer collateral-CA1 synapse. In addition, we performed behavioral analyses using the open field and novel object recognition tasks.Results: NMDAR-dependent long-term potentiation in the hippocampal CA1 area was significantly suppressed, indicating successful NMDAR dysfunction in this subfield. Spontaneous locomotor activity as well as anxiety-related behavior in the open field did not differ between NMDAR-CSF-treated and control animals. In the novel object recognition task, there were no differences in the motivation to approach objects. In contrast, we observed a significantly preferred exploration of the novel object only in control, but not in NMDAR-CSF-treated rats.Conclusion: These results indicate that NMDAR dysfunction obtained by intrahippocampal stereotactic injection does not alter locomotor or anxiety-related behavior. In addition, approach to an object or exploratory behavior in general are not affected either, but intact initial NMDAR-dependent processes might be involved in novel object recognition.

Purpose: Autoantibodies against NMDA receptors (NMDAR) in the cerebrospinal fluid (CSF) from anti-NMDAR encephalitis patients have been suggested to be pathogenic since in previous studies using patient CSF, NMDAR-dependent processes such as long-term potentiation (LTP) were compromised. However, autoantibodies may represent a family of antibodies targeted against different epitopes, and CSF may contain further autoantibodies. Here, we tested the specificity of the autoantibody by comparing NMDAR-dependent and NMDAR-independent LTP within the same hippocampal subfield, CA3, using CSF samples from four anti-NMDAR encephalitis patients and three control patients.Methods: We performed a stereotactic injection of patient-derived cell-free CSF with proven presence or absence of NMDAR-antibodies into the rat hippocampus in vivo. Hippocampal brain slices were prepared 1–8 days after intrahippocampal injection, and NMDAR-dependent LTP at the associational-commissural (A/C) fiber-CA3 synapse was compared to NMDAR-independent LTP at the mossy fiber (MF)-CA3 synapse.Results: The LTP magnitude at A/C fiber-CA3 synapses in slices from control-CSF-treated animals (168 ± 8% n = 54) was significantly higher than LTP in slices from NMDAR-CSF-treated animals (139 ± 9%, n = 40; P = 0.015), although there was some variation between the individual CSF samples. We found residual LTP in NMDAR-CSF-treated tissue which could be abolished by the NMDAR inhibitor D-AP5. Moreover, the CA3 field excitatory postsynaptic potential (fEPSP) was followed by epileptiform afterpotentials in 5% of slices (4/78) from control-CSF-treated animals, but in 26% of slices (12/46) from NMDAR-CSF-treated animals (P = 0.002). Application of the LTP-inducing paradigm increased the proportion of slices with epileptiform afterpotentials, but D-AP5 significantly reduced the occurrence of epileptiform afterpotentials only in NMDAR-CSF-treated, but not in control tissue. At the MF synapse, no significant difference in LTP values of control-CSF and in NMDAR-CSF-treated tissue was observed indicating that NMDAR-independent MF-LTP is intact in NMDAR-CSF-treated tissue.Conclusion: These findings indicate that anti-NMDAR containing CSF impairs LTP at the A/C fiber-CA3 synapse, although there is substantial variation among CSF samples suggesting different epitopes among patient-derived antibodies. The differential inhibition of LTP at this synapse in contrast to the MF-CA3 synapse suggests the specificity and underlines the pathophysiological role of the NMDAR-antibody.

p35 is an activating co-factor of Cyclin-dependent kinase 5 (Cdk5), a protein whose dysfunction has been implicated in a wide-range of neurological disorders including cognitive impairment and disease. Inducible deletion of the p35 gene in adult mice results in profound deficits in hippocampal-dependent spatial learning and synaptic physiology, however the impact of the loss of p35 function on hippocampal in vivo physiology and spatial coding remains unknown. Here, we recorded CA1 pyramidal cell activity in freely behaving p35 cKO and control mice and found that place cells in the mutant mice have elevated firing rates and impaired spatial coding, accompanied by changes in the temporal organization of spiking both during exploration and rest. These data shed light on the role of p35 in maintaining cellular and network excitability and provide a physiological correlate of the spatial learning deficits in these mice.

Northern ecosystems are currently experiencing unprecedented ecological change, largely driven by a rapidly changing climate. Pathogen range expansion, and emergence and altered patterns of infectious disease, are increasingly reported in wildlife at high latitudes. Understanding the causes and consequences of shifting pathogen diversity and host-pathogen interactions in these ecosystems is important for wildlife conservation, and for indigenous populations that depend on wildlife. Among the key questions are whether disease events are associated with endemic or recently introduced pathogens, and whether emerging strains are spreading throughout the region. In this study, we used a phylogenomic approach to address these questions of pathogen endemicity and spread for Erysipelothrix rhusiopathiae, an opportunistic multi-host bacterial pathogen associated with recent mortalities in arctic and boreal ungulate populations in North America. We isolated E. rhusiopathiae from carcasses associated with large-scale die-offs of muskoxen in the Canadian Arctic Archipelago, and from contemporaneous mortality events and/or population declines among muskoxen in northwestern Alaska and caribou and moose in western Canada. Bacterial genomic diversity differed markedly among these locations; minimal divergence was present among isolates from muskoxen in the Canadian Arctic, while in caribou and moose populations, strains from highly divergent clades were isolated from the same location, or even from within a single carcass. These results indicate that mortalities among northern ungulates are not associated with a single emerging strain of E. rhusiopathiae, and that alternate hypotheses need to be explored. Our study illustrates the value and limitations of bacterial genomic data for discriminating between ecological hypotheses of disease emergence, and highlights the importance of studying emerging pathogens within the broader context of environmental and host factors.

High iron and eutrophic conditions are reported as environmental factors leading to accelerated low-water corrosion, an enhanced form of near-shore microbial-induced corrosion. To explore this hypothesis, we deployed flow-through colonization systems in laboratory-based aquarium tanks under a continuous flow of surface seawater from Santa Catalina Island, California, USA, for periods of two and six months. Substrates consisted of mild steel – a major constituent of maritime infrastructure – and the naturally occurring iron sulfide mineral pyrite. Four conditions were tested: free-venting high-flux conditions; a stagnant condition; an active flow-through condition with seawater slowly pumped over the substrates; and an enrichment condition where the slow pumping of seawater was supplemented with nutrient rich medium. Electron microscopy analyses of the two-month high flux incubations document coating of substrates with twisted stalks, resembling iron oxyhydroxide bioprecipitates made by marine neutrophilic Fe-oxidizing bacteria. Six-month incubations exhibit increased biofilm and substrate corrosion in the active flow and nutrient enriched conditions relative to the stagnant condition. A scarcity of twisted stalks was observed for all six month slow-flow conditions compared to the high-flux condition, which may be attributable to oxygen concentrations in the slow-flux conditions being prohibitively low for sustained growth of stalk-producing bacteria. All substrates developed microbial communities reflective of the original seawater input, as based on 16S rRNA gene sequencing. Deltaproteobacteria sequences increased in relative abundance in the active flow and nutrient enrichment conditions, whereas Gammaproteobacteria sequences were relatively more abundant in the stagnant condition. These results indicate that i) high-flux incubations with higher oxygen availability favor the development of biofilms with twisted stalks resembling those of marine neutrophilic Fe-oxidizing bacteria and ii) long-term nutrient stimulation results in substrate corrosion and biofilms with different bacterial community composition and structure relative to stagnant and non-nutritionally enhanced incubations. Similar microbial succession scenarios, involving increases in nutritional input leading to the proliferation of anaerobic iron and sulfur-cycling guilds, may occur at the nearby Port of Los Angeles and cause potential damage to maritime port infrastructure.