bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optical projection tomography implemented for accessibility and low cost (
OPTImAL
)
Authors: Darling C. , Kumar S. , Alexandrov Y. , de Faye J. , Almagro Santiago J. , Rýdlová A. , Bugeon L. , Dallman M. J. , Behrens A. J. , French P. M. W , McGinty J. 
Published: June 2024

Optical projection tomography (OPT) is a three-dimensional mesoscopic imaging modality that can use absorption or fluorescence contrast, and is widely applied to fixed and live samples in the mm–cm scale. For fluorescence OPT, we present OPT implemented for accessibility and low cost, an open-source research-grade implementation of modular OPT hardware and software that has been designed to be widely accessible by using low-cost components, including light-emitting diode (LED) excitation and cooled complementary metal-oxide-semiconductor (CMOS) cameras. Both the hardware and software are modular and flexible in their implementation, enabling rapid switching between sample size scales and supporting compressive sensing to reconstruct images from undersampled sparse OPT data, e.g. to facilitate rapid imaging with low photobleaching/phototoxicity. We also explore a simple implementation of focal scanning OPT to achieve higher resolution, which entails the use of a fan-beam geometry reconstruction method to account for variation in magnification.
This article is part of the Theo Murphy meeting issue 'Open, reproducible hardware for microscopy'.
Clearing-enabled light sheet microscopy as a novel method for three-dimensional mapping of the sensory innervation of the mouse knee
Authors: Ko Frank C. , Fullam Spencer , Lee Hoomin , Ishihara Shingo , Adamczyk Natalie S. , Obeidat Alia M. , Soorya Sarah , Miller Richard J. , Malfait Anne-Marie , Miller Rachel E. 
Published: June 2024

AbstractA major barrier that hampers our understanding of the precise anatomic distribution of pain sensing nerves in and around the joint is the limited view obtained from traditional two dimensional (D) histological approaches. Therefore, our objective was to develop a workflow that allows examination of the innervation of the intact mouse knee joint in 3D by employing clearing-enabled light sheet microscopy. We first surveyed existing clearing protocols (SUMIC, PEGASOS, and DISCO) to determine their ability to clear the whole mouse knee joint, and discovered that a DISCO protocol provided the most optimal transparency for light sheet microscopy imaging. We then modified the DISCO protocol to enhance binding and penetration of antibodies used for labeling nerves. Using the pan-neuronal PGP9.5 antibody, our protocol allowed 3D visualization of innervation in and around the mouse knee joint. We then implemented the workflow in mice intra-articularly injected with nerve growth factor (NGF) to determine whether changes in the nerve density can be observed. Both 3D and 2D analytical approaches of the light sheet microscopy images demonstrated quantifiable changes in midjoint nerve density following 4 weeks of NGF injection in the medial but not in the lateral joint compartment. We provide, for the first time, a comprehensive workflow that allows detailed and quantifiable examination of mouse knee joint innervation in 3D.
Computer vision guided open-source active commutator for neural imaging in freely behaving animals
Authors: Oladepo Ibrahim , Saxena Kapil , Surinach Daniel , Lehman Malachi , Kodandaramaiah Suhasa B. 
Published: June 2024

AbstractRecently developed miniaturized neural recording devices that can monitor and perturb neural activity in freely behaving animals have significantly expanded our knowledge neural underpinning of complex behaviors. Most miniaturized neural interfaces require a wired connection for external power and data acquisition systems. The wires are required to be commutated through a slip ring to accommodate for twisting of the wire or tether and alleviate torsional stresses. The increased trend towards long term continuous neural recordings have spurred efforts to realize active commutators that can sense the torsional stress and actively rotation the slip ring to alleviate torsional stresses. Current solutions however require addition of sensing modules. Here we report on an active translating commutator that uses computer vision (CV) algorithms on behavioral imaging videos captured during the experiment to track the animal’s position and heading direction in real-time and uses this information to control the translation and rotation of a slipring commutator to accommodate for accumulated mouse heading orientation changes and position. The CV guided active commutator has been extensively tested in three separate behavioral contexts and we show reliable cortex-wide imaging in a mouse in an open-field with a miniaturized widefield cortical imaging device. Active commutation resulted in no changes to measured neurophysiological signals. The active commutator is fully open source, can be assembled using readily available off-the-shelf components, and is compatible with a wide variety of miniaturized neurophotonic and neurophysiology devices.
Conditional CAR T cells with specificity to oncofetal glycosaminoglycans in solid tumors
Authors: Khazamipour Nastaran , Oo Htoo Zarni , Al-Nakouzi Nader , Marzban Mona , Khazamipour Nasrin , Roberts Morgan E. , Farivar Negin , Moskalev Igor , Lo Joey , Ghaidi Fariba , Nelepcu Irina , Moeen Alireza , Truong Sarah , Dagil Robert , Choudhary Swati , Gustavsson Tobias , Zhai Beibei , Heitzender Sabine , Salanti Ali , Sorensen Poul H , Daugaard Mads 
Published: June 2024

ABSTRACTGlycosaminoglycans are often deprioritized as targets for synthetic immunotherapy due to the complexity of glyco-epitopes and limited options for obtaining specific subtype-binding. Solid tumors express proteoglycans that are modified with oncofetal chondroitin sulfate (CS), a modification normally restricted to the placenta. Here, we report the design and functionality of conditional chimeric antigen receptor (CAR) T cells with selectivity to oncofetal CS. Following expression in T cells, the CAR could be ‘armed’ with recombinant VAR2CSA lectins (rVAR2) to target tumor cells expressing oncofetal CS. While un-armed CAR T cells remained inactive in the presence of target cells, VAR2-armed CAR T cells displayed robust activation and the ability to eliminate diverse tumor cell typesin vitro. Cytotoxicity of the CAR T cells was proportional to the concentration of rVAR2 available to the CAR, offering a potential molecular handle to finetune CAR T cell activity.In vivo, armed CAR T cells rapidly targeted bladder tumors and increased survival of tumor-bearing mice. Thus, our work indicates that cancer-restricted glycosaminoglycans can be exploited as potential targets for CAR T cell therapy.
Neuronal segmentation in cephalopod arms
Authors: Olson Cassady S. , Schulz Natalie Grace , Ragsdale Clifton W. 
Published: June 2024

AbstractThe prehensile arms of the cephalopod are among these animals most remarkable features, but the neural circuitry governing arm and sucker movements remains largely unknown. We studied the neuronal organization of the adult axial nerve cord (ANC) ofOctopus bimaculoideswith molecular and cellular methods. The ANCs, which lie in the center of every arm, are the largest neuronal structures in the octopus, containing four times as many neurons as found in the central brain. In transverse cross section, the cell body layer (CBL) of the ANC wraps around its neuropil (NP) with little apparent segregation of sensory and motor neurons or nerve exits. Strikingly, when studied in longitudinal sections, the ANC is segmented. ANC neuronal cell bodies form columns separated by septa, with 15 segments overlying each pair of suckers. The segments underlie a modular organization to the ANC neuropil: neuronal cell bodies within each segment send the bulk of their processes directly into the adjoining neuropil, with some reaching the contralateral side. In addition, some nerve processes branch upon entering the NP, forming short-range projections to neighboring segments and mid-range projections to the ANC segments of adjoining suckers. The septa between the segments are employed as ANC nerve exits and as channels for ANC vasculature. Cellular analysis establishes that adjoining septa issue nerves with distinct fiber trajectories, which across two segments (or three septa) fully innervate the arm musculature. Sucker nerves also use the septa, setting up a nerve fiber “suckerotopy” in the sucker-side of the ANC. Comparative anatomy suggests a strong link between segmentation and flexible sucker-laden arms. In the squidDoryteuthis pealeii, the arms and the sucker- rich club of the tentacles have segments, but the sucker-poor stalk of the tentacles does not. The neural modules described here provide a new template for understanding the motor control of octopus soft tissues. In addition, this finding represents the first demonstration of nervous system segmentation in a mollusc.
Romiumeter: An Open-Source Inertial Measurement Unit-Based Goniometer for Range of Motion Measurements
Authors: Diwakarreddy Basinepalli Kothireddy Gari , Abishek S , Andrews Amal , Vasanthan Lenny , Balasubramanian Sivakumar 
Published: June 2024

AbstractRange of motion (ROM) serves as a crucial metric for assessing movement impairments. Traditionally, clinicians use goniometers to measure the ROM, but this method relies on the clinician’s skill, in particular for difficult joints such as the shoulder and neck joints. Recent studies have explored the use of wearable inertial measurement units (IMUs) as an alternative. IMUs exhibit excellent agreement with goniometers, but the lack of affordable, accessible, and clinically validated tools remains an issue. This paper introduces the Romiumeter, a single IMU-based device designed to measure the ROM of the neck and shoulder movements. To validate its accuracy, the Romiumeter was tested on 34 asymptomatic individuals for shoulder and neck movements, using an optical motion capture system as the ground truth. The device demonstrated good accuracy, with a maximum absolute error of less than 5°with moderate to good reliable measurements(inter-rater reliability: 0.69 - 0.87 and intra-rater reliability: 0.76 - 0.87). Additionally, the Romiumeter underwent validation for different algorithms, including the complementary and Madgwick filters. Interestingly, no significant differences were found between the algorithms. Overall, the Romiumeter provides reliable measurements for assessing shoulder and neck ROM in asymptomatic individuals.
A refined human linear B cell epitope map of Outer surface protein C (OspC) from the Lyme disease spirochete,Borreliella burgdorferi
Authors: Freeman-Gallant Grace , McCarthy Kathleen , Yates Jennifer , Kulas Karen , Rudolph Michael J. , Vance David J , Mantis Nicholas J 
Published: June 2024

ABSTRACTA detailed understanding of the human antibody response toOutersurfaceprotein C (OspC) ofBorrelellia burgdorferihas important implications for Lyme disease diagnostics and vaccines. In this report, a total of 13 peptides encompassing eight reported OspC linear B cell epitopes from OspC types A, B and K, including the conserved C-terminus (residues 193-210: peptide C10), were evaluated by multiplex immunoassay (MIA) for IgG reactivity with ∼700 human serum samples confirmed positive in a two-tiered Lyme disease diagnostic assay and ∼160 post-treatment Lyme disease (PTLD) serum samples. The VlsE C6-17 peptide was included as a positive control. Diagnostic serum IgG reacted with 11 of the 13 OspC-derived peptides, significantly more than controls, with the C10 peptide being the most reactive. In the PTLD serum samples, two OspC peptides including C10 were significantly more reactive than controls. Spearman’s rank correlation matrices and hierarchical clustering indicated a strong correlation between C10 and VlsE C6-17 peptide reactivity but little demonstrable association between C10 and the other OspC peptides or recombinant OspC. OspC peptide reactivities (excluding C10) were strongly correlated with each other and were disproportionately influenced by a subset of pan-reactive samples. In the PTLD cohort, C10 clustered with the other OspC-derived peptides and was distinct from OspC and VlsE C6-17. The asynchronous serologic response to OspC, C10, and the OspC-derived peptides reveals the complexity of B cell responses toB. burgdorferiand confounds simple interpretation of antibody profiles associated with Lyme disease.IMPORTANCELyme disease is an emerging tick-borne infection caused by the spirochete,Borreliella burgdorferi. In humans, antibodies against spirochetal outer surface lipoproteins are proposed to play a role in disease resolution and in protection against reinfection. Some of those same antibodies also serve as diagnostic indicators of an active or history of Lyme disease. In this study, we sought to validate reported antibody binding sites on Outer surface protein C (OspC), a known target of both protective and diagnostic antibodies.
Negative regulation of Activation-Induced Cytidine Deaminase gene transcription in developing B cells by a PU.1-interacting intronic region
Authors: MacKenzie Allanna C. E. , Sams Mia P. , Lin Jane , Batista Carolina Reyes , Lim Michelle , Riarh Chanpreet K. , DeKoter Rodney P. 
Published: June 2024

AbstractActivation-induced cytidine deaminase (AID, encoded byAicda) plays a key role in somatic hypermutation and class switch recombination in germinal center B cells. However, off-target effects of AID are implicated in human leukemia and lymphoma. A mouse model of precursor B cell acute lymphoblastic leukemia driven by deletion of the related transcription factors PU.1 and Spi-B revealed C->T transition mutations compatible with being induced by AID. Therefore, we hypothesized that PU.1 negatively regulatesAicdaduring B cell development.AicdamRNA transcript levels were increased in leukemia cells and preleukemic bone marrow pre-B cells lacking PU.1 and/or Spi-B, relative to wild type cells. Using chromatin immunoprecipitation, PU.1 was found to interact with a negative regulatory region (R2-1) within the first intron ofAicda. CRISPR-Cas9-induced mutagenesis of R2-1 in cultured pre-B cells resulted in upregulation ofAicdain response to lipopolysaccharide stimulation. Mutation of the PU.1 interaction site and neighboring sequences resulted in reduced repressive ability of R2-1 in transient transfection analysis followed by luciferase assays. These results show that a PU.1-interacting intronic region negatively regulatesAicdatranscription in developing B cells.
Multimodal Predictive Modeling: Scalable Imaging Informed Approaches to Predict Future Brain Health
Authors: Ajith Meenu , Spence Jeffrey S. , Chapman Sandra B. , Calhoun Vince D. 
Published: June 2024

AbstractBackgroundPredicting future brain health is a complex endeavor that often requires integrating diverse data sources. The neural patterns and interactions iden-tified through neuroimaging serve as the fundamental basis and early indica-tors that precede the manifestation of observable behaviors or psychological states.New MethodIn this work, we introduce a multimodal predictive modeling approach that leverages an imaging-informed methodology to gain insights into fu-ture behavioral outcomes. We employed three methodologies for evalua-tion: an assessment-only approach using support vector regression (SVR), a neuroimaging-only approach using random forest (RF), and an image-assisted method integrating the static functional network connectivity (sFNC) matrix from resting-state functional magnetic resonance imaging (rs-fMRI) alongside assessments. The image-assisted approach utilized a partially con-ditional variational autoencoder (PCVAE) to predict brain health constructs in future visits from the behavioral data alone.ResultsOur performance evaluation indicates that the image-assisted method ex-cels in handling conditional information to predict brain health constructs in subsequent visits and their longitudinal changes. These results suggest that during the training stage, the PCVAE model effectively captures relevant in-formation from neuroimaging data, thereby potentially improving accuracy in making future predictions using only assessment data.Comparison with Existing MethodsThe proposed image-assisted method outperforms traditional assessment-only and neuroimaging-only approaches by effectively integrating neuroimag-ing data with assessment factors,ConclusionThis study underscores the potential of neuroimaging-informed predictive modeling to advance our comprehension of the complex relationships between cognitive performance and neural connectivity.HighlightsMultifaceted perspective for studying longitudinal brain health changes.Showcases the versatility of methodologies through assessment-only, neuroimaging-only, and image-assisted predictive approaches.Provides predictive insights by revealing the neural patterns corresponding to alterations in behavior.Graphical Abstract
Comprehensive Analysis of177Lu-lilotomab Satetraxetan in Lymphoma Cell Lines: Implications for Precision Radioimmunotherapy and Combination Schemes
Authors: Patzke Sebastian , Cascione Luciano , Melhus Katrine B , Munz Nicolas , Arribas Alberto J. , Gaudio Eugenio , Generalov Roman , Repetto-Llamazares Ada HV , Dahle Jostein , Bertoni Francesco 
Published: June 2024

Abstract177Lu-lilotomab satetraxetan (Betalutin) is an anti-CD37 radioimmunoconjugate evaluated as single administration therapy for the treatment of patients with relapsed/refractory follicular lymphoma or diffuse large B-cell lymphoma (DLBCL).177Lu-lilotomab satetraxetan treatment is well-tolerated and shows consistent activity in most of the patients evaluated so far. Herein, we investigated the activity of177Lu-lilotomab satetraxetan in a panel of 55 lymphoma cell lines of B and T cell origin. CD37-targeted radioimmunotherapy was more effective in CD37-positive B-cell lymphomas (n=46) than negative CD37 negative T-cell lymphomas (n=9). Focusing on DLBCL cell lines, mutations such asBCL2orMYCtranslocations were not correlated to sensitivity. However,BCL2expression was higher in resistant than sensitive GCB-DLBCL cell lines, and the addition of the BCL2 inhibitor venetoclax showed synergism when added to the radioimmunoconjugate. Finally, the pattern of activity of177Lu-lilotomab satetraxetan differed from what was achieved with a CD37-targeting antibody-drug conjugate or with R-CHOP, indicating the potential benefit of the beta-emitter payload. In conclusion, this systematic analysis of the responsiveness of lymphoma cell lines to CD37-targeting radioimmunotherapy consolidated177Lu-lilotomab satetraxetan as a promising compound for the treatment of CD37 positive malignancies and identified candidate biomarkers and co-targets to detect and overcome cancer cell-intrinsic resistance mechanisms.
Parallel Analyses by Mass Spectrometry (MS) and Reverse Phase Protein Array (RPPA) Reveal Complementary Proteomic Profiles in Triple-Negative Breast Cancer (TNBC) Patient Tissues and Cell Cultures
Authors: Wang Nan , Zhu Yiying , Wang Lianshui , Dai Wenshuang , Hu Taobo , Song Zhentao , Li Xia , Zhang Qi , Ma Jianfei , Xia Qianghua , Li Jin , Liu Yiqiang , Long Mengping , Ding Zhiyong 
Published: June 2024

AbstractHigh-plex proteomic technologies have made substantial contributions to mechanism studies and biomarker discovery in complex diseases, particularly cancer. Despite technological advancements, inherent limitations in individual proteomic approaches persist, impeding the achievement of comprehensive quantitative insights into the proteome. In this study, we employed two widely used proteomic technologies, Mass Spectrometry (MS) and Reverse Phase Protein Array (RPPA) to analyze identical samples, aiming to systematically assess the outcomes and performance of the different technologies. Additionally, we sought to establish an integrated workflow by combining these two proteomic approaches to augment the coverage of protein targets for discovery purposes. We used fresh frozen tissue samples from triple-negative breast cancer (TNBC) and cell line samples to evaluate both technologies and implement this dual-proteomic strategy. Using a single-step protein denaturation and extraction protocol, protein samples were subjected to reverse phase chromatography (LC) followed by electrospray ionization (ESI)-mediated MS/MS for proteomic profiling. Concurrently, identical sample aliquots were analyzed by RPPA for profiling of over 300 proteins and phosphoproteins that are in key signaling pathways or druggable targets in cancer. Both proteomic methods demonstrated the expected ability to differentiate samples by groups, revealing distinct proteomic patterns under various experimental conditions, albeit with minimal overlap in identified targets. Mechanism-based analysis uncovered divergent biological processes identified with the two proteomic technologies, capitalizing on their complementary exploratory potential.
An agent-based modelling framework for tumour growth incorporating mechanical and evolutionary aspects of cell dynamics
Authors: Macnamara Cicely K , Ramis-Conde I. , Lorenzi Tommaso , Caiazzo Alfonso 
Published: June 2024

AbstractWe develop an agent-based modelling framework for tumour growth that in-corporates both mechanical and evolutionary aspects of the spatio-temporal dynamics of cancer cells. In this framework, cells are regarded as viscoelastic spheres that interact with other neighbouring cells through mechanical forces. The phenotypic state of each cell is described by the level of expression of an hypoxia-inducible factor that regulates the cellular response to available oxygen. The rules that govern proliferation and death of cells in different phenotypic states are then defined by integrating mechanical constraints and evolutionary principles. Computational simulations of the model are carried out under a variety of scenarios corresponding to different intra-tumoural distributions of oxygen. The results obtained, which indicate excellent agreement between simulation outputs and the results of formal analysis of phenotypic selection, recapitulate the emergence of stable phenotypic heterogeneity among cancer cells driven by inhomogeneities in the intra-tumoural distribution of oxygen. This article is intended to present a proof of concept for the ideas underlying the proposed modelling framework, with the aim to apply the related modelling methods to elucidate specific aspects of cancer progression in the future.