bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilizing 99mTc-FAPI-46 SPECT/CT in Detection of Peritoneal Carcinomatosis in Gastric Poorly Differentiated Adenocarcinoma
Authors: Raeisi Nasrin , Tanha Amin Saber , Aryana Kamran , Soltani Ehsan , Barashki Somaye 
Published: November 2024

Abstract
We introduce a 61-year-old man with poorly differentiated gastric adenocarcinoma, who previously underwent surgical treatment. In this presentation, he complained of a newly appeared midabdominal mass after the latest chemotherapy session. He was a candidate for diagnostic laparotomy, but in the setting of trial, 99mTc-FAPI-46 SPECT/CT was performed revealing 2 peritoneal masses, which were the only findings of diagnostic surgery subsequent to the scan. This report presents the first case of 99mTc-FAPI-46 SPECT/CT in metastasis workup of gastric adenocarcinoma.
Trends in Timely Access to High-quality and Affordable Surgical Care in the United States
Authors: Mullens Cody Lendon , Ibrahim Andrew M. , Clark Nina M. , Kunnath Nicholas , Dieleman Joseph L. , Dimick Justin B. , Scott John W. 
Published: November 2024

Objective:
To quantify recent trends in access to timely, high-quality, affordable surgical care in the United States.

Background:
Insufficient access to surgical care remains an ongoing concern in the United States. Previous attempts to understand and quantify barriers to access to surgical care in the United States lack a comprehensive, policy-relevant lens.

Methods:
This observational cross-sectional study evaluates multiple domains of access to surgical care across the United States from 2011 to 2015 and 2016 to 2020. Our stepwise model included timeliness (<60-minute drive time), quality (surgically capable hospital with ≥3 CMS stars), and affordability (neither uninsured nor underinsured) of access to surgical care using a novel combination of data from the American Hospital Association, Medicare claims, Centers for Medicare and Medicaid Services' Five-Star Quality Rating System, the American Community Survey, and the Medical Expenditure Panel Survey.

Results:
The number of Americans lacking access to timely, high-quality, affordable surgical care increased from 97.7 million in 2010 to 2015 to 98.7 million in 2016 to 2020. Comparing these 2 periods, we found improvements in the number of Americans lacking access due to being uninsured (a decrease from 38.5 to 26.5 million). However, these improvements were offset by increasing numbers of Americans for whom timeliness (increase from 9.5 to 14.1 million), quality (increase from 3.4 to 4.9 million), and underinsured status (increase from 46.3 to 53.1 million) increased as barriers to access. Multiple sensitivity analyses using alternative thresholds for each access domain demonstrated similar trends. Those with insufficient access to care tended to be more rural (6.7% vs 2.0%, P < 0.001), lower income (40.7% vs 30.0%, P < 0.001), and of Hispanic ethnicity (35.9% vs 15.8%, P < 0.001).

Conclusions:
Nearly 1 in 3 Americans lack access to surgical care that is timely, high-quality, and affordable. This study identifies the multiple actionable drivers of access to surgical care that notably can each be addressed with specific policy interventions.
Bacterial Engineered Living Materials modulate Mechanosignaling in Mammalian Cells
Authors: Ostmann Katharina , Muñoz-Guamuro Geisler , Becker Jan , Baños Miguel , Saikumar Sairam , Bennewitz Roland , Duong Cao Nguyen , Sankaran Shrikrishnan , Weber Wilfried 
Published: November 2024

AbstractEngineered living materials (ELMs) are gaining momentum for biomedical applications as self-replenishing drug depots, smart wound dressings, or as wearable sensors. Current studies on ELM-host interaction are mainly limited to the exchange of biochemical cues between ELMs and surrounding cells and tissues. Here we show that the genetically programmed mechanical properties of ELMs modulate mechanosignaling pathways in mammalian cells cultivated onto the living materials. To this aim, we genetically modulated curli fiber production inE. coliand analyzed the impact on the mechanical properties of the resulting ELMs. The living materials were used as matrix for the cultivation of mammalian cells engineered with a fluorescent reporter to indicate the activation of the mechano-responsive Hippo signaling pathway. We demonstrate that different genetically programmed ELM compositions translated into differential regulation of mechanosignaling in mammalian cells. These findings provide the perspective of using ELMs as extracellular matrix with genetically programmable mechanics for mammalian cells while also highlighting the need to consider the mechanical properties of therapeutic ELMs when assessing interaction with surrounding tissues.Abstract FigureToC figure
Using Quality Improvement Tools to Reduce Macerated Stillbirth by 50% in the Volta Region of Ghana in a Two Years Period
Authors: Danso Gideon , Boadu Richard Okyere 
Published: November 2024

AbstractStillbirth rate is an indirect measure of the quality of management of pregnancy, labour and delivery. The loss of a baby due to stillbirth does not only affect pregnant women but also takes a great toll on family’s health and wellbeing. In Ghana, stillbirths account for a large proportion of perinatal mortalities. We used small multiple graphs to compare the rate of stillbirth in the Volta region from (2014-2016) to the national target for stillbirth.Inferences from the graph shows that there was a gap of 10.4 per 1,000 live births between the national target of 12 per 1,000 live births. Fresh still birth also had a mean of 37.2 per 1000 live births showing a gap of 25.2 between the national target. The gap between the national target and macerated still birth is 50.8. This shows significant change in the stillbirth rate in the region and requires attention. In view of this, this study aims to reduce stillbirth (macerated) by 50% in two years period.
A macrophage-smooth muscle cell axis influences vascular remodeling through activation of the EGFR pathway in giant cell arteritis
Authors: Chevalier Kevin , Dionet Léa , Breillat Paul , Poux Margot , Dang Julien , Terris Benoit , Bruneval Patrick , Mouthon Luc , Lenoir Olivia , Tharaux Pierre-Louis , Terrier Benjamin 
Published: November 2024

AbstractBackground.The role of macrophages and vascular resident cells appears to be predominant in the pathophysiology of giant cell arteritis (GCA). We investigated the role of epithelial growth factor receptor (EGFR) signaling pathway, especially through its activation by heparin-binding epidermal growth factor (HB-EGF) and/or amphiregulin (AREG) in this setting.Materials and Methods.Serum samples and temporal artery biopsies (TAB) were obtained from patients enrolled in a prospective cohort of systemic vasculitis. Human THP-1, a monocytic cell line, and human aortic vascular smooth muscle cells (VSMC) were used forin vitrostudies.Results.Using multiplex immunohistochemistry, TAB from GCA patients showed higher expression of AREG, HB-EGF, EGFR and phospho-EGFR as compared to control arteries. AREG, HB-EGF and EGFR were predominantly expressed by macrophages, whereas EGFR and phosphor-EGFR were expressed by αSMA-positive cells in the media. Increased levels of AREG and HB-EGF were found in culture supernatants of M1 macrophages, whereas M2 macrophages produced only HB-EFG. AREG and HB-EGF did not increase the production of pro-inflammatory cytokines by THP-1 or macrophages but activated the p38 MAPK pathway. Using transcriptomic and Western blot analysis of human aortic VSMC, AREG and especially HB-EGF induced cell proliferation pathway, enhanced interferon alpha and gamma responses, and activation of the MAPK pathway. Finally, AREG and HB-EGF increased both VSMC proliferation and migration, which were completely inhibited by AG1478, an EGFR inhibitor.Conclusion.We show that both AREG and HB-EGF may play a role in the pathophysiology of GCA, especially in the remodeling phase of the disease.
ImmunoStruct: Integration of protein sequence, structure, and biochemical properties for immunogenicity prediction and interpretation
Authors: Givechian Kevin Bijan , Rocha João Felipe , Yang Edward , Liu Chen , Greene Kerrie , Ying Rex , Caron Etienne , Iwasaki Akiko , Krishnaswamy Smita 
Published: November 2024

AbstractEpitope-based vaccines are promising therapeutic modalities for infectious diseases and cancer, but identifying immunogenic epitopes is challenging. The vast majority of prediction methods are sequence-based, and do not incorporate wide-scale structure data and biochemical properties across each peptide-MHC (pMHC) complex. We present ImmunoStruct, a deep-learning model that integrates sequence, structural, and biochemical information to predict multi-allele class-I pMHC immunogenicity. By leveraging a multimodal dataset of∼27,000 peptide-MHC complexes that we generated with AlphaFold, we demonstrate that ImmunoStruct improves immunogenicity prediction performance and interpretability beyond existing methods, across infectious disease epitopes and cancer neoepitopes. We further show strong alignment within vitroassay results for a set of SARS-CoV-2 epitopes. This work also presents a new architecture that incorporates equivariant graph processing and multi-modal data integration for the long standing task in immunotherapy.
Real-Time Closed-Loop Feedback System For Mouse Mesoscale Cortical Signal And Movement Control: CLoPy
Authors: Gupta Pankaj K. , Murphy Timothy H. 
Published: November 2024

SummaryWe present the implementation and efficacy of an open-source closed-loop neurofeedback (CLNF) and closed-loop movement feedback (CLMF) system. In CLNF, we measure mm-scale cortical mesoscale activity with GCaMP6s and provide graded auditory feedback (within ∼50 ms) based on changes in dorsal-cortical activation within regions of interest (ROI) and with a specified rule. Single or dual ROIs (ROI1, ROI2) on the dorsal cortical map were selected as targets. Both motor and sensory regions supported closed-loop training in male and female mice. Mice modulated activity in rule-specific target cortical ROIs to get increasing rewards over days (RM ANOVA p=2.83e-5) and adapted to changes in ROI rules (RM ANOVA p=8.3e-10, Table 4 for different rule changes). In CLMF, feedback was based on tracking a specified body movement, and rewards were generated when the behavior reached a threshold. For movement training, the group that received graded auditory feedback performed significantly better (RM-ANOVA p=9.6e-7) than a control group (RM-ANOVA p=0.49) within four training days. Additionally, mice can learn a change in task rule from left forelimb to right forelimb within a day, after a brief performance drop on day 5. Offline analysis of neural data and behavioral tracking revealed changes in the overall distribution of ΔF/F0values in CLNF and body-part speed values in CLMF experiments. Increased CLMF performance was accompanied by a decrease in task latency and cortical ΔF/F0amplitude during the task, indicating lower cortical activation as the task gets more familiar.
Neurovirulent and non-neurovirulent strains of HIV-1 and their Tat proteins induce differential cytokine-chemokine profiles
Authors: Rao Vasudev R. , Rodriguez Milka , Byrareddy Siddappa N. , Ranga Udaykumar , Prasad Vinayaka R. 
Published: November 2024

AbstractHIV-1 enters the central nervous system (CNS) early in infection, and a significant proportion of people with HIV experience CNS complications despite anti-retroviral therapy. Chronic immune dysfunction, inflammatory cytokines and chemokines, and viral proteins like Tat and gp120 released by HIV-1-infected immune cells are implicated in the pathogenesis of HIV-1-associated neurocognitive disorders (HAND). To elucidate the contribution of non-viral factors to CNS complications in people with HIV-1, a comparative analysis of neurovirulent subtype B (HIV-1ADA) and non-neurovirulent subtype C (HIV-1Indie-C1) isolates was performed. Culture supernatants from HIV-1-infected PBMCs, either with or without immunodepletion of Tat and gp120, were used to treat SH-SY5Y neuroblastoma cells. HIV-1ADA-infected PBMC media showed significantly higher cytotoxicity than HIV-1IndieC1-infectedPBMCmedia, notwithstanding the depletion of Tat and gp120, highlighting the role of non-viral factors contributing to neurotoxicity. A comparison of inflammatory profiles revealed that HIV-1ADAmedia contained elevated levels of cytokines (IL-1α, IL-1β, IL-6, TNFα) and chemokines (CCL2, CCL3, CCL4, IP10). Given the involvement of Tat in upregulating immune mediators, PBMCs from healthy subjects were treated with recombinant purified Tat from subtype B or C. Subtype B Tat induced a stronger inflammatory response than subtype C Tat. These results confirm that both viral and non-viral immune factors mediate neuronal damage in people with HIV.
DNA Extraction Protocols for Animal Fecal Material on Blood Spot Cards
Authors: Llarena Ann-Katrin , Haverkamp Thomas H.A. , Gulliksen Wenche Støldal , Herstad Kristin , Holst-Jensen Arne , Skjerve Eystein , Rannem Lisbeth , Rodriguez-Campos Sabrina , Øines Øivind 
Published: November 2024

AbstractBackgroundCollecting fecal samples using dry preservatives is an attractive option in large epidemiological studies as they are easy to use, cheap and independent of cold chain logistics. Here, we test four DNA extraction methods with the aim of identifying an efficient procedure to extract high-quality DNA from fecal material of canine, sheep, equine, bovine, and pig collected on dry blood spot cards, with the goal of generating good quality shotgun metagenomics datasets. Further, the suitability of Illumina shotgun metagenomic sequencing at 20million PE read depth was assessed on its ability to successfully characterize the taxonomic and functional aspects of the resulting fecal microbiome.MethodsDNA was extracted from pig feces and mock communities collected on blood spot cards using four DNA extraction methods; two different methods of the QIAsymphony® PowerFecal® Pro DNA Kit, the ZymoBIOMICS™ DNA Miniprep Kit, and the MagNA Pure 96 DNA and Viral NA Small Volume Kit. Possible extraction bias was controlled by amplicon sequencing of mock communities. Fecal samples from canine, sheep, equine, bovine, and pig were thereafter subjected to the best performing DNA extraction method and shotgun metagenomic sequencing to determine sequencing efforts for functional and taxonomic analysis.ResultsThe four DNA extraction methods demonstrated similar community composition in the sequenced bacterial mock community. The QIAsymphony® PowerFecal® Pro DNA Kit was identified as the DNA extraction method of choice, and the resulting DNA was subjected to shotgun metagenomic sequencing with 20million PE reads. We found that higher number of reads increased the richness of observed genera between 100,000 and 5 million reads, after which higher sequencing effort did not increase the richness of the metagenomes. As for functional analysis, the number of low abundance functions in the metagenomes of the animals’ feces increased with sequencing depth above 20 million PE reads.ConclusionOur experiments identified several methods suitable for extracting DNA from feces collected on blood spot cards. The Qiagen’s Blood and Tissue kit on the QiaSymphony platform fulfilled the criteria of high yield, quality, and unbiased DNA, while maintaining high throughput for shotgun metagenomic sequencing. A sequencing depth of 20 million PE reads proved adequate for taxonomic estimations and identifying common functional pathways. Detecting rarer traits, however, requires more sequencing effort.
Direct lipid interactions control SARS-CoV-2 M protein conformational dynamics and virus assembly
Authors: Dutta Mandira , Dolan Kimberly A. , Amiar Souad , Bass Elijah J. , Sultana Rokaia , Voth Gregory A. , Brohawn Stephen G. , Stahelin Robert V. 
Published: November 2024

AbstractM is the most abundant structural membrane protein in coronaviruses and is essential for the formation of infectious virus particles. SARS-CoV-2 M adopts two conformations, Mshortand Mlong, and regulated transition between states is hypothesized to coordinate viral assembly and budding. However, the factors that regulate M conformation and roles for each state are unknown. Here, we discover a direct M-sphingolipid interaction that controls M conformational dynamics and virus assembly. We show M binds Golgi-enriched anionic lipids including ceramide-1-phosphate (C1P). Molecular dynamics simulations show C1P interaction promotes a long to short transition and energetically stabilizes Mshort. Cryo-EM structures show C1P specifically binds Mshortat a conserved site bridging transmembrane and cytoplasmic regions. Disrupting Mshort-C1P interaction alters M subcellular localization, reduces interaction with Spike and E, and impairs subsequent virus-like particle cell entry. Together, these results show endogenous signaling lipids regulate M structure and support a model in which Mshortis stabilized in the early endomembrane system to organize other structural proteins prior to viral budding.
Increasing brain half-life of antibodies by additional binding to myelin oligodendrocyte glycoprotein, a CNS specific protein
Authors: Cuypers Marie-Lynn , Jaspers Tom , Clerckx Jarne , Leekens Simon , Cawthorne Christopher , Bormans Guy , Cleeren Frederik , Geukens Nick , Strooper Bart De , Dewilde Maarten 
Published: November 2024

ABSTRACTBackgroundTherapeutic antibodies for the treatment of neurological disease show great potential, but their applications are rather limited due to limited brain exposure. The most well-studied approach to enhance brain influx of protein therapeutics, is receptor-mediated transcytosis (RMT) by targeting nutrient receptors to shuttle protein therapeutics over the blood-brain barrier (BBB) along with their endogenous cargos. While higher brain exposure is achieved with RMT, the timeframe is short due to rather fast brain clearance. Therefore, we aim to increase the brain half-life of antibodies by binding to myelin oligodendrocyte glycoprotein (MOG), a CNS specific protein.MethodsAlpaca immunization with mouse/human MOG, and subsequent phage selections and screenings for MOG binding VHHs were performed to find mouse/human cross-reactive VHHs. Their ability to increase the brain half-life of antibodies was evaluated by coupling two different MOG VHHs (low/high affinity) in a mono- and bivalent format to an anti-β-secretase 1 or anti-SarsCov2 antibody fused to an anti-transferrin receptor (TfR) VHH for active transport over the BBB. Brain pharmacokinetics and pharmacodynamics, CNS and peripheral biodistribution, and brain toxicity were evaluated after intravenous administration to balb/c mice.ResultsAdditional binding to MOG increases the Cmaxand brain half-life of antibodies that are actively shuttled over the BBB. biMOGLow:monoTfR:SarsCov antibodies could be detected in brain 49 days after a single intravenous injection, which is a major improvement compared to monoTfR:SarsCov antibodies which cannot be detected in brain anymore one week post treatment. Additional MOG binding of antibodies does not affect peripheral biodistribution but alters brain distribution to white matter localization and less neuronal internalization.ConclusionsWe have discovered mouse/human/cyno cross-reactive anti-MOG VHHs which have the ability to drastically increase brain exposure of antibodies. Combining MOG and TfR binding leads to distinct PK, biodistribution, and brain exposure, differentiating it from the highly investigated TfR- shuttling. It is the first time such long brain antibody exposure is demonstrated after one single dose.This new approach of adding a binding moiety for brain specific targets to RMT shuttling antibodies is a huge advancement for the field and paves the way for further research into brain half-life extension.
Air-Liquid Interface Model for Influenza Aerosol Exposure In Vitro
Authors: Seibert Brittany , Caceres C. Joaquin , Gay L. Claire , Shetty Nishit , Faccin Flavio Cargnin , Carnaccini Silvia , Walters Matthew , Marr Linsey C. , Lowen Anice C. , Rajao Daniela S. , Perez Daniel R. 
Published: November 2024

AbstractAirborne transmission is an essential mode of infection and spread of influenza viruses among humans. However, most studies use liquid inoculum for virus infection. To better replicate natural airborne infectionsin vitro, we generated a calm-aerosol settling chamber system designed to examine the aerosol infectivity of influenza viruses in different cell types. Aerosol inoculation was characterized for multiple influenza A virus (FLUAV) subtypes, including a pandemic 2009 H1N1, a seasonal swine H3N2, and an avian H9N2 using this exposure system. While each FLUAV strain displayed high infectivity within MDCK cells via liquid inoculation, differences in infectivity were observed during airborne inoculation. This was further observed in recently developed immortalized differentiated human airway epithelial cells (BCi-NS1.1) cultured in an air-liquid interface. The airborne infectious dose 50 for each virus was based on the exposure dose per well. Our findings indicate that this system has the potential to enhance our understanding of the factors influencing influenza transmission via the airborne route. This could be invaluable for conducting risk assessments, potentially reducing the reliance on extensive and costlyin vivoanimal studies.ImportanceThis study presents a significant advancement in influenza research by developing a novel in vitro system to assess aerosol infectivity, a crucial aspect of influenza transmission. The system’s ability to differentiate between mammalian-adapted and avian-adapted influenza viruses based on their aerosol infectivity offers a valuable tool for pre-screening the pandemic potential of different strains. This could potentially streamline the risk assessment process and inform public health preparedness strategies. Moreover, the system’s capacity to examine aerosol infectivity in human airway epithelial cells provides a more relevant model for studying virus-host interactions in natural airborne infections. Overall, this study provides an accessible platform for investigating aerosol infectivity, which could significantly contribute to our understanding of influenza transmission and pandemic preparedness.
Is Probiotic Supplementation During Pregnancy Safe for Healthy Populations? A Systematic Review of Preclinical Studies
Authors: Coca Mario R. , Perez-Fernandez Cristian , Ruiz-Sobremazas Diego , Morales-Navas Miguel , Colomina Teresa , López-Granero Caridad , Sanchez-Santed Fernando 
Published: November 2024

AbstractGut-brain axis and probiotics supplementation during gestational period have gained an especial attention in the field of neurodevelopmental disorders. However, the influence of prenatal probiotics in physiology and neurodevelopment of healthy organisms is widely unexplored and probiotics are commercially such as dietetic supplementations without the necessity of ensuring safety in healthy organisms, as is required for drugs. The aim is to present and discuss the various biochemical, developmental and behavioral effects that prenatal probiotics have on the offspring of healthy organisms in rodent models and assess their security during gestation. We included a total of 15 preclinical studies discarding all those that did not have an appropriate control for the probiotic-treated group. Results suggest that probiotics, particularlyLactobacillusstrains, influenced anxiety-like behaviors in mice and GABAergic system maturation, showing an apparent biphasic effect, reducing GABA functioning in early life but increasing them in later stages; and both prenatalLactobacillusandBifidobacterium, influenced microbiota and general development of healthy organisms. However, the significant variations in methodologies used across studies complicate the ability to elucidate specific conclusions related to bacterial strains or doses. Further research is imperative to ensure the safety and regulation of probiotic interventions, particularly during the gestational period.