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Deciphering the scopolamine rat model by preclinical functional MRI
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A high-throughput 3D X-ray histology facility for biomedical research and preclinical applications - Supplementary Data
<p><strong>Videos</strong></p><ul><li><strong>Video 1</strong> A video going through the Z stack in single slices. This is a cross- sectional view of the XRH image stack along the XY plane. XRH datasets are normally oriented (resliced) in a way that a scroll through the stack along the XY plane emulates the physical histology slicing of the tissue.</li><li><strong>Video 2 </strong>A video going through the Y stack in single slices. This is a cross- sectional view of the XRH image stack along the XZ plane. XRH datasets are normally oriented (resliced) in a way that a scroll through the stack along the XY plane emulates the physical histology slicing of the tissue.</li><li><strong>Video 3 </strong>A video going through the X stack in single slices. This is a cross- sectional view of the XRH image stack along the YZ plane. XRH datasets are normally oriented (resliced) in a way that a scroll through the stack along the XY plane emulates the physical histology slicing of the tissue.</li><li><strong>Video 4 </strong>3D X-ray histology (XRH) is a µCT -based workflow tailored to fit seamlessly into current histology workflows in biomedical and pre-clinical research, as well as clinical histopathology. Microanatomical detail can be captured from standard (non-stained) formalin-fixed and paraffin-embedded (FFPE) tissue blocks.</li><li><strong>Video 5</strong> Average Intensity Projection (AIP) of the sample through the Histologically relevant plane. This is a 2D visualisation rendering the Average Intensity of 20x single XY slices along the z-axis of the stack. XRH datasets are normally oriented (resliced) in a way that a scroll through the stack along the XY plane emulates the physical histology slicing of the tissue.</li><li><strong>Video 6 </strong>Maximum Intensity Projection (MIP) of the sample through the Histologically relevant plane. This is a 2D visualisation rendering the Maximum Intensity of 20x single XY slices along the z-axis of the stack. XRH datasets are normally oriented (resliced) in a way that a scroll through the stack along the XY plane emulates the physical histology slicing of the tissue.</li><li><strong>Video 7 </strong>Standard deviation projection of the sample going through the histologically relevant plane. This is a 2D visualisation rendering the Standard Deviation of 20x single XY slices along the z- axis of the stack. XRH datasets are normally oriented (resliced) in a way that a scroll through the stack along the XY plane emulates the physical histology slicing of the tissue.</li></ul><p><i>* <strong>Videos 5 -7</strong> are also referred to as "thick-slice rolls" </i>- <i>Thick-slice rolling is a 2D thick-slice viewing that allows rolling of a pre-selected number of slices (n) along the z-axis of the 3D data. A single thick-slice roll forwards is accomplished by translating the thick-slice by one single slice forwards; that is moving forward by one (+1) slice from the first and nth element and reapplying the criteria or operations to the new slice sub-stack.</i><br> </p><p><strong>The questionnaire used to collect feedback about the needs of the XRH community.</strong></p><ul><li>Survey.docx</li><li>Survey.pdf</li></ul><p><br><strong>Exemplar report of a semi-automatically generated augmented PDF file</strong> that contain sample information, imaging settings, still images with descriptive figure legends, and links to corresponding online videos</p><ul><li>DEMO02019-FFPE_report_99EbPXG.pdf</li></ul><p> </p><p>= = = = = = = = = = = = = = = = <br><strong>System performance data ZIP</strong><br>= = = = = = = = = = = = = = = = </p><p>This ZIP file contains imaging data collected through different systems and setups at the XRH facility at the μ-VIS X-ray Imaging Centre at the University of Southampton for the purpose of acceptance and/or system performance characterisation. Below is an overview of the folder structure and its contents</p><p>The following files are X-ray imaging data collected on September 28, 2017, using the Med-X system and a Jima phantom at 55 kV peak and 7 Watts. </p><ul><li>20170928_MEDX_1642_JIMA_55kVp7W-2.tif</li><li>20170928_MEDX_1642_JIMA_55kVp7W.tif</li><li>20170928_MEDX_1642_JIMA_55kVp7W.tif.profile.xml</li></ul><p>This PDF document is related to a QRM MicroCT bar pattern phantom, and its specifications</p><ul><li>QRM-MicroCT-Barpattern-Phantom.pdf</li></ul><p>Graphs showing the calculated focal-spot size as a function of the X-ray power (W) for the Molybdenum rotating target calculated using Edge Modulation function testing. The performance is then compared with the performance of the Reflection target across the same range of powers. Raw data can be found in XRH_QRM_Refl-vs-Rot-TargetComparison_SingleReconSlices_5umPixelSize folder. Test performed in July 2021. </p><ul><li>XRH_202107_MoRot-testing_EdgeModFunction-QRMrecons+RotReflCompar.png</li></ul><p> </p><p><i><strong>/ XRH-XT-H-225-ST_FocalSpots</strong></i><br>This directory contains radiographic data collected using the XRH system with a JIMA phantom and MoRt (Molybdenum rotating), TT (Transmission), and Reflection targets.</p><ul><li>20200113_XRH_Jima test MoRT 55kV 15W.tif, 20200113_XRH_Jima test MoRT 55kV 30W.tif, etc.: <br>These files represent radiographs taken on January 13, 2020, using the XRH system, Jima phantom, MoRT target at 55 kVp and varying wattages.</li><li>20200207_XRH_JIMA 80kV TT1a.tif, 20200207_XRH_JIMA 80kV TT1b.tif, etc.<br>Similar to the above, these files are from February 7, 2020, and use 80 kVp with a TT target.</li><li>20231115_XRH_reflW_80kVp6W.tif, 20231115_XRH_reflW_80kVp6W_02.tif, etc.<br>These files are from November 15, 2023, and collected using the XRH system with a Reflection target at 80 kVp and 6 Watts.</li></ul><p><i><strong>/ XRH_QRM_Refl-vs-Rot-TargetComparison_SingleRadioFromCTs_5umPixelSize</strong></i><br>This directory contains single radiographs taken with a pixel size of 5 micrometers using the Molybdenum rotating (MoRt), and the Reflection target using tungsten (W) and Molybdenum (Mo) metals.</p><p><i><strong>/ XRH_QRM_Refl-vs-Rot-TargetComparison_SingleReconSlices_5umPixelSize</strong></i><br>This directory contains sinlge reconstruction slices of the setups mentioned above. Slices are exported from CT volumes and were used for the Edge Modulation function study. </p><p>For interpretation of the filenames in the folders listed above please see below and refer to specific files and folders for detailed information and results related to each imaging session:</p><ul><li><i><xx>kVp or <xx>kV </i>:Imaging at a peak voltage of <xx> kVp.</li><li><i><y>W</i> :Imaging at <y> Watts;<i> </i>"." is represented with "-"; i.e. 20210705_XRH_2766_PJB_TEST03552-EQPMT_W_6-9W is acquired using a power of 6.9 W</li><li><i>MoRt, TT, Refl </i> :Molybdenum, Transmission, and Reflection targets, respectively.</li><li><i>_W_ and _Mo_ </i> :Tungsten and Molybdenum target materials.</li><li><i>_horiz</i> :Reconstruction slices in line with the X-ray beam's propagation direction.</li><li><i>_vert</i> :Reconstruction slices normal to the X-ray beam's propagation direction and parallel to the detector plane.</li></ul>
Combined proton radiography and irradiation for high-precision preclinical studies in small animals
<p>Data used for the publication "Combined proton radiography and irradiation for high-precision preclinical studies in small animals".</p> <p>The repository contains all data that was used to generate the quantitative results and figures in the submitted manuscript.</p> <p>Further documentation for the provided code can be found here: https://github.com/jo-mueller/radiographic_workflow_evaluation</p>
PretoxTM Corpus: a gold standard corpus of preclinical treatment-related findings annotated from toxicology reports
<p>The PretoxTM Corpus is a gold standard corpus of preclinical treatment-related findings annotated from toxicology reports.</p> <p>Example documents annotated by domain experts, also known as a gold standard corpus, are needed in order to develop, train, and validate text mining tools. To this aim we designed and performed an annotation activity for the development of the corpus of treatment-related findings: the PretoxTM corpus.</p> <p>A treatment-related finding expression enclose several named entities; the most relevant one is the abnormal effect detected; which depending on the study domain of the finding, can be given by a measurement, test, or examination named Study Test and an abnormal Manifestation result obtained for that study test; or by an abnormal Finding in study domains where there is no associated test or measurement (e.g., clinical, macroscopic and microscopic). Other related named entities that could be present to complete the treatment-related finding are; the Specimen of the abnormal observation, the Sex of the subject, the Group of subjects in which the observation was detected and the Dose level administration of the compound. Examples of sentences with treatment-related findings are: “The decrease in food consumption and body weight of the animals from the mid dose onwards is regarded as evidence of general toxicity.” and "At dose level 3, absolute and relative liver weights were increased in male rats.”.</p> <p>Contributions: The PretoxTM corpus was developed by BSC, with the contribution of IMIM and a team of experts from the eTRANSAFE EFPIA partners.</p> <p>License: Creative Commons Attribution-ShareAlike 4.0 International (cc by sa 4.0).</p> <p>The PretoxTM resources have been developed as part of the eTRANSAFE project.</p> <p>For more information about PretoxTM please visit:</p> <p>PretoxTM Corpus Gitlab: <a href="https://gitlab.bsc.es/inb/etransafe/preclinical-toxicological-corpus/">https://gitlab.bsc.es/inb/etransafe/preclinical-toxicological-corpus/</a></p> <p>PretoxTM central documentation: <a href="https://pretoxtm.gitlab.io/documentation/">https://pretoxtm.gitlab.io/documentation/</a></p>
A high-throughput 3D X-ray histology facility for biomedical research and preclinical applications - Underlying Data
<p><strong>Video files and logs</strong></p> <p>Single-slice and thick-slice roll* source videos are included. Each video is accompanied by a .txt log that contains information about the source file, slice thickness, and a brief description of the visualization mode.</p> <p>List of files:</p> <ul> <li>20211019-23h59m_20xAvgInt.mp4</li> <li>20211019-23h59m_20xAvgInt.txt</li> <li>20211019-23h59m_20xMaxInt.mp4</li> <li>20211019-23h59m_20xMaxInt.txt</li> <li>20211019-23h59m_20xStDev.mp4</li> <li>20211019-23h59m_20xStDev.txt</li> <li>20211019-23h59m_XYSliceRoll.mp4</li> <li>20211019-23h59m_XYSliceRoll.txt</li> <li>20211019-23h59m_XZSliceRoll.mp4</li> <li>20211019-23h59m_XZSliceRoll.txt</li> <li>20211019-23h59m_YZSliceRoll.mp4</li> <li>20211019-23h59m_YZSliceRoll.txt</li> </ul> <p>* <em>Thick-slice rolling is a 2D thick-slice viewing that allows rolling of a pre-selected number of slices (n) along the z-axis of the 3D data. A single thick-slice roll forwards is accomplished by translating the thick-slice by one single slice forwards; that is moving forward by one (+1) slice from the first and nth element and reapplying the criteria or operations to the new slice sub-stack.</em></p> <p><strong>Volume XRH data</strong><br> These are processed raw volume file saved in .raw and/or .tiff format, which are resliced to a histology-relevant orientation and/or have been enhanced using noise reduction (3D median filter) and/or ct-artefact removal techniques (e.g. cBC identifies a bandpass filter used to remove intensity variations originating from the histology cassette).</p> <p>List of volume files:</p> <ul> <li><strong>32220_20200703_XRH_2504_OLK_DEMO02019-FFPE_1620x1959x164x16bit.raw</strong> <ul> <li>sample: Human lung adenocarcinoma</li> <li>histology-relevant resliced volume (2x2x2 3D medial filter applied)</li> <li>import as 1620 x 1959 x 164 x 16-bit, big-endian; voxel edge size (mm): 0.0160042 isotropic</li> </ul> </li> <li><strong>cBC_32220_20200703_XRH_2504_OLK_DEMO02019-FFPE_1588x1674x164x16bit.raw</strong> <ul> <li>sample: Human lung adenocarcinoma</li> <li>cassette artefacts background correction (bandpass) of volume 32220_20200703_XRH_2504_OLK_DEMO02019-FFPE_1620x1959x164x16bit.raw</li> <li>import as 1620 x 1959 x 164 x 16-bit, big-endian; voxel edge size (mm): 0.0160042 isotropic</li> </ul> </li> <li><strong>Med3D_HPass_2111_20190606_MEDX_2234_EH_HN2_recon_2000x1952x501x32bit.raw</strong> <ul> <li>sample: Human head and neck tumour</li> <li>histology-relevant resliced volume (1x1x1 3D medial filter applied)</li> <li>import as 2000 x 1952 x 501 x 32-bit, big-endian; voxel edge size (mm): 0.00999782 isotropic</li> </ul> </li> </ul> <p><strong>Conventional Histology and correlative imaging</strong></p> <ul> <li><strong>HN2_Level001_MEDX080_Manual_BW_Series4.tif</strong> <ul> <li>H&E histology slice of the human head and neck tumour sample shown in "Med3D_HPass_2111_20190606_MEDX_2234_EH_HN2_recon_2000x1952x501x32bit.raw"</li> </ul> </li> <li><strong>HN2_Level001_MEDX080_Manual_BW</strong> <ul> <li>manual landmark selection used for registering the conventional histology slice onto the μCT slice</li> </ul> </li> <li><strong>HN2_MEDX_rotated_0080.tif</strong> <ul> <li>Slice 80 from volume "Med3D_HPass_2111_20190606_MEDX_2234_EH_HN2_recon_2000x1952x501x32bit.raw" that corresponds to histological slice "HN2_Level001_MEDX080_Manual_BW"</li> </ul> </li> </ul>
Preclinical PET data
<p>An open preclinical PET dataset. This dataset has been measured with the preclinical Siemens Inveon PET machine. The measured target is a (naive) rat with an injected dose of 21.4 MBq of <a href="https://en.wikipedia.org/wiki/Fludeoxyglucose_(18F)">FDG</a>. The injection was done intravenously (IV) to the tail vein. No specific organ was investigated, but rather the glucose metabolism as a whole. The examination is a 60 minute dynamic acquisition. The measurement was conducted according to the ethical standards set by the University of Eastern Finland.</p> <p>The dataset contains the original list-mode data, the (dynamic) sinogram created by the Siemens Inveon Acquisition Workplace (IAW) software (28 frames), the (dynamic) scatter sinogram created by the IAW software (28 frames), the attenuation sinogram created by the IAW software and the normalization coefficients created by the IAW software. Header files are included for all the different data files.</p> <p>For documentation on reading the list-mode binary data, please ask Siemens.</p> <p>This dataset can be used in the <a href="https://github.com/villekf/OMEGA">OMEGA</a> software, including the list-mode data, to import the data to MATLAB/Octave, create sinograms from the list-mode data and reconstruct the imported data. For help on using the dataset with OMEGA, see the <a href="https://github.com/villekf/OMEGA/wiki/Using-Inveon-PET-data">wiki</a>.</p>
Modulation of the tumour promoting functions of cancer associated fibroblasts by phosphodiesterase type 5 inhibition increases the efficacy of chemotherapy in human preclinical models of esophageal adenocarcinoma
<p>These are whole-slide digital pathology images of esophageal adenocarcinoma (EAC) patient-derived xenograft models. EAC biopsy specimens were cultured <em>in vitro</em> before implanting into immuno-deficient mice. Mice were then divided into the following treatment groups and treated with combinations of chemotherapy and PDE5 inhibitors as follows:</p> <ol> <li>Untreated</li> <li>Epirubicin + Cisplatin + Capecitabine (ECX)</li> <li>ECX + Vardenafil</li> <li>ECX + Tadalafil</li> </ol> <p>All whole slide images are in Olympus .vsi format and can be opened using the BioFormats library in QuPath. We have also included classifiers and scripts for performing the digital pathology analysis in QuPath, and information to link each mouse with treatment groups and corresponding whole slide images.</p> <p>File metadata:</p> <p>classifiers.zip - Folder containing pixel classifiers used for segmentation of IHC stains. These classifiers are to be important into QuPath for the respective analysis of Periostin (POSTN) and alpha Smooth Muscle Actin (SMA) staining using the included Groovy scripts in the scripts folder.</p> <p>SMA.zip - Folder containing whole slide images of mouse patient-derived xenograft tumours in .vsi format (Olympus VS110). Immunohistochemistry with anti-alpha Smooth Muscle Actin antibody.<br> POSTN.zip - Folder containing whole slide images of mouse patient-derived xenograft tumours in .vsi format (Olympus VS110). Immunohistochemistry with anti-Periostin antibody.</p> <p>scripts.zip - Folder containing all groovy scripts used in QuPath for tissue detection (Whole Section Tissue Detection.groovy), and segmentation of POSTN (POSTN Quantification Mice.groovy) and SMA staining tissue areas (SMA Quantification Mice.groovy).</p> <p>POSTN.xlsx - Data on the mice for which anti-POSTN IHC is available. Column names as follows:<br> Image: file name (corresponding to .vsi file).<br> Mouse_ID: Mouse identifier.<br> Treatment: Treatment administered. ECX - Epirubicin, Cisplatin and Capecitabine.<br> POSTN_Area: Total measured area of POSTN+ tissue in the tissue section (in um^2).<br> Total_Area: Total area of the tissue section (in um^2).<br> percentage_POSTN: Percentage of total tissue area that is stained with POSTN (%).</p> <p>SMA.xlsx - Data on the mice for which anti-SMA IHC is available. Column names as follows:<br> Image: file name (corresponding to .vsi file).<br> Mouse_ID: Mouse identifier.<br> Treatment: Treatment administered. ECX - Epirubicin, Cisplatin and Capecitabine.<br> SMA_Area: Total measured area of SMA+ tissue in the tissue section (in um^2).<br> Total_Area: Total area of the tissue section (in um^2).<br> percentage_SMA: Percentage of total tissue area that is stained with SMA (%).</p>
Identification of a small molecule Tim-3 inhibitor to potentiate T cell-mediated antitumor immunotherapy in preclinical models
<p><span>T cell immunoglobulin and mucin-containing molecule 3 (Tim-3), expressed in dysfunctional and exhausted T cells, has been widely acknowledged as a promising immune checkpoint target for tumor immunotherapy. Here, using a strategy combining virtual and functional screening, we identified a compound named ML-T7 that targets the FG-CC' cleft of Tim-3, a highly conserved binding site of </span><span>phosphatidylserine</span><span> (PtdSer) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). ML-T7 enhanced the survival and antitumor activity of </span><span>primary CD8<sup>+</sup> cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells and reduced their exhaustion </span><span>in vitro and in vivo</span><span>. In addition, ML-T7 promoted NK cells' killing activity and DC antigen-presenting capacity, consistent with the reported activity of Tim-3.</span><span> Notably, ML-T7 strengthened DCs' functions through both Tim-3 and Tim-4, consistent with the hypothesis that Tim-4 contains a similar FG-CC' loop. Intraperitoneal dosing of ML-T7 showed comparable tumor inhibitory effects to Tim-3 blocking antibody. ML-T7 reduced syngeneic tumor progression in both wildtype and Tim-3 humanized mice and alleviated the immunosuppressive microenvironment. Furthermore, combined ML-T7 and anti-PD-1 therapy had greater therapeutic efficacy than monotherapy in mice, supporting further development of ML-T7 for tumor immunotherapy. Our study demonstrates a potential small molecule for selectively blocking Tim-3 and warrants further study.</span></p>
DNDI-6174, a preclinical candidate for visceral leishmaniasis that targets the cytochrome bc1 complex – Figures 3 and S2-8 raw data
<p>New drugs for visceral leishmaniasis that are safe, low cost and adapted to the field are urgently required. Despite concerted efforts over the last several years, the number of new chemical entities with novel mechanisms of action that are suitable for clinical development remains low. Here, we describe the development of DNDI-6174, an inhibitor of <em>Leishmania</em> cytochrome b that originated from a phenotypically-identified pyrrolopyrimidine series. This compound fulfills all Target Candidate Profile criteria required for progression into preclinical development. In addition to good metabolic stability and pharmacokinetic properties, DNDI-6174 demonstrates potent in vitro activity against a variety of <em>Leishmania</em> species and can reduce parasite burden in animal models of infection, with potential for sterile cure. No significant flags were identified in preliminary safety studies, including an exploratory 14-day toxicology study in the rat. DNDI-6174 represents the first cytochrome b inhibitor to enter preclinical development for visceral leishmaniasis.</p>
Behavioral data for: A preclinical model of THC edibles that produces high-dose cannabimimetic responses
<p>No preclinical experimental approach enables the study of voluntary oral consumption of high-concentration Δ<sup>9</sup>-tetrahydrocannabinol (THC) and its intoxicating effects, mainly owing to the aversive response of rodents to THC that limits intake. Here we developed a palatable THC formulation and an optimized access paradigm in mice to drive voluntary consumption.<strong> </strong>THC was formulated in chocolate gelatin (THC-E-gel). Adult male and female mice were allowed <em>ad libitum </em>access for 1 and 2 h. Cannabimimetic responses (hypolocomotion, analgesia, and hypothermia) were measured following access. Levels of THC and its metabolites were measured in blood and brain tissue. Acute acoustic startle responses were measured to investigate THC-induced psychotomimetic behavior. When allowed access for 2 h to THC-E-gel on the second day of a three-day exposure paradigm, adult mice consumed up to ≈30 mg/kg over 2 h which resulted in robust cannabimimetic behavioral responses (hypolocomotion, analgesia and hypothermia). Consumption of the same gelatin decreased on the following 3<sup>rd</sup> day of exposure. Pharmacokinetic analysis show that THC-E-gel consumption led to parallel accumulation of THC and its psychoactive metabolite, 11-OH-THC, in brain, a profile that contrasts with the known rapid decline in brain 11-OH-THC levels following THC intraperitoneal (<em>i.p</em>.) injections. THC-E-gel consumption increased the acoustic startle response in males but not in females, demonstrating a sex-dependent effect of consumption. Thus, while voluntary consumption of THC-E-gel triggered equivalent cannabimimetic responses in male and female mice, it potentiated acoustic startle responses preferentially in males. We build a dose-prediction model that included cannabimimetic behavioral responses elicited by <em>i.p.</em> versus THC-E-gel to test the accuracy and generalizability of this experimental approach and found that it closely predicted the measured acoustic startle results in males and females. In summary, THC-E-gel offers a robust preclinical experimental approach to study cannabimimetic responses triggered by voluntary consumption in mice, including sex-dependent psychotomimetic responses.</p>
mRNA prime–boost evolves precursors toward VRC01-like broadly neutralizing antibodies in preclinical humanized mouse models
<p>Germline-targeting (GT) protein immunogens to induce VRC01-class broadly neutralizing antibodies (bnAbs) to the CD4 binding site (CD4bs) of the HIV Envelope have shown promise in clinical trials. Here, we preclinically validated the mRNA-LNP delivery of one such immunogen, eOD-GT8, as a soluble self-assembling 60mer nanoparticle in humanized mouse models. In a model with three humanized B cell lineages bearing distinct VRC01-precursor B cell receptors (BCRs) with similar affinities for eOD-GT8, all lineages could be simultaneously primed and undergo diversification and affinity maturation with no sign of exclusionary competition. Boosts drove precursor B cell participation in germinal centers, the accumulation of somatic hypermutations, including in key VRC01-class positions, and affinity maturation to boost and native-like antigens in two of the three precursor lineages. We have preclinically validated a prime-boost regimen of soluble self-assembling nanoparticles delivered by mRNA-LNP, demonstrating that multiple lineages can be primed, boosted, and diversify along the bnAb pathway.</p>
Preclinical developent of an innovative drug candidate in systemic fungal therapy
<p>The dataset documents results of studies in the area of drug development co-founded by the National Centre for Research and Development <strong>(Poland), grant number </strong> <strong>POIR.01.01.01-00-1990/15-00, tytuł: <em>Badania przedkliniczne i kliniczne kandydata na innowacyjny lek w terapii inwazyjnych grzybic układowych.</em></strong></p> <p>The objective of the project was to conduct preclinical and potantially Phase I clinical studies of a new compound to develop an innovative drug for treatment of invasive systemic mycoses. The compound will be selected from the group of innovative Amphotericin B derivatives developed during the BLIRT project co-funded under the 1.4–4.1 Innovative Economy Operational Programme, which have shown significant improvement of selective toxicity compared to the native drug. Moreover, the solubility of the compounds has been ensured, which enables their bioavailability. The innovative derivatives have characteristics of an ideal antifungal drug – fungicidal activity, low toxicity, aqueous solubility, no induction of resistance, activity against MDR strains, and a broad antifungal<br> spectrum. Their therapeutic efficacy has been preliminarily proven on a model of systemic candidiasis in mice.</p> <p>The project was unsuccesful due to not enough competitive advantages of developed candidates regarding their antifungla efficacy and safety which did not justify further investments of both public and private funds.</p> <p>The dataset contain reports from the conducted studies performed both in house but also in well established CROs. It cover the chemical sythesis of compounds, preparation of their liposomal formulations and preclinical studies in vitro and in vivo performed until the project was stopped, due to not achieving the set development milestone (preclinical stage). It is widely communicatd to the scientific community so that future projects could benefit form the generated know-how.</p> <p> </p> <p> </p>
Payload-delivering engineered γδ T cells display enhanced cytotoxicity, persistence, and efficacy in preclinical models of osteosarcoma
<p>T cell-based cancer immunotherapy has typically relied on membrane-bound cytotoxicity enhancers such as chimeric antigen receptors expressed in autologous αβ T cells. These approaches are limited by tonic signaling of synthetic constructs and costs associated with manufacturing. γδ T cells are an emerging alternative for cellular therapy, possessing innate anti-tumor activity, potent antibody-dependent cellular cytotoxicity, and minimal alloreactivity. We present an immunotherapeutic platform technology built around the innate properties of the Vγ9Vδ2 T cell, harnessing specific characteristics of this cell type and offering an allo-compatible cellular therapy that recruits bystander immunity. We engineered γδ T cells to secrete synthetic tumor-targeting opsonins in the form of an scFv-Fc fusion protein and a mitogenic IL-15Ra–IL-15 fusion protein (stIL15). Using GD2 as a model antigen, we show that GD2-specific opsonin-secreting Vγ9Vδ2 T cells (stIL15-OPS-γδ T cells) have enhanced cytotoxicity and promote bystander activity of other lymphoid and myeloid cells. Secretion of stIL-15 abrogated the need for exogenous cytokine supplementation and further mediated activation of bystander natural killer cells. Compared to unmodified γδ T cells, stIL15-OPS-γδ T cells exhibited superior in vivo control of subcutaneous tumors and persistence in the blood. Moreover, stIL15-OPS-γδ T cells were efficacious against patient-derived osteosarcomas in animal models and in vitro, where efficacy could be boosted with the addition of zoledronic acid. Together the data identify stIL15-OPS-γδ T cells as a candidate allogeneic cell therapy platform combining direct cytolysis with bystander activation to promote tumor control.</p>
Dataset related to article "Systematic review and meta-analysis of preclinical studies testing mesenchymal stromal cells for traumatic brain injury"
<p>Mesenchymal stromal cells (MSCs) are widely used in preclinical models of traumatic brain injury (TBI). Results are promising in terms of neurological improvement but are hampered by wide variability in treatment responses. We made a systematic review and meta-analysis: 1) to assess the quality of evidence for MSC treatment in TBI rodent models; 2) to determine the effect size of MSCs on sensorimotor function, cognitive function and anatomical damage; 3) to identify MSC-related and protocol-related variables associated with greater efficacy; 4) to understand whether MSC manipulations boost therapeutic efficacy.</p> <p>The meta-analysis included 80 studies. After TBI, MSCs improved sensorimotor and cognitive deficits, and reduced anatomical damage. Stratified meta-analysis on sensorimotor outcome showed similar efficacy for different MSC sources and for syngeneic or xenogenic transplants. Efficacy was greater when MSCs were delivered in the first week post-injury, and when implanted directly into the lesion cavity. The greatest effect size was for cells embedded in matrices or for MSC-derivatives.</p> <p>MSC therapy is effective in preclinical TBI models, improving sensorimotor, cognitive and anatomical outcomes, with large effect sizes. These findings support clinical studies in TBI.</p> <p>The present dataset reports extrapolated data used for the meta-analysis</p>
Burden of cardiometabolic risk factors and preclinical target organ damage among adults in Freetown, Sierra Leone: a community-based health-screening survey
<p>The study aimed to investigate the prevalence of cardiometabolic risk factors (CMRFs), target organ damage and its associated factors among adults in Freetown, Sierra Leone.</p> <p><strong>Design</strong></p> <p>This community-based cross-sectional study used a stratified multistage random sampling method to recruit adult participants. </p> <p><strong>Setting </strong></p> <p>The health screening study was conducted between October 2019 and October 2021 in Western Area Urban, Freetown, Sierra Leone. </p> <p><strong>Participants</strong></p> <p>A total of 2394 adults Sierra Leoneans aged 20 years, or more were enrolled.</p> <p><strong>Outcome measure </strong></p> <p>Anthropometric data, fasting lipid profiles, fasting plasma glucose, target organ damage, clinical profiles and demographic characteristic of participants were described. The cardiometabolic risks were further related to target organ damage.</p> <p><strong>Results</strong></p> <p>The prevalence of known CMRFs was 35.3% for hypertension, 8.3% for diabetes mellitus, 21.1% for dyslipidemia, 10.0% for obesity, 13.4% for smoking and 37.9% for alcohol. Additionally, 16.1% had left ventricular hypertrophy (LVH) by ECG, 14.2% had LVH by 2D-Echo while 11.4% had chronic kidney disease. Diabetes [OR = 1.176, 95% C.I. (0.759 - 1.823)] and dyslipidaemia [OR = 1.844, 95% C.I. (1.006 -3.380)] were independently associated with LVH. LVH by Echo shows an independent association with diabetes mellitus [OR =1.176, 95% C.I (0.759-1.823)] and dyslipidemia [OR = 1.844, 95% C.I (1.006-3.380)]. The odds of having CKD were associated with diabetes mellitus [OR =1.212, 95% CI (0.741-1.983)] and hypertension [OR =1.163, 95% CI (0.887-1.525)]. A low optimal cut-off points for ECG-LVH (male 24.5 vs female 27.5mm) was required to maximize sensitivity and specificity. </p> <p><strong>Conclusions</strong></p> <p>This study provides novel data-driven information on the burden of cardiometabolic risks and its association with preclinical target organ damage in a resource limited setting. It illustrates the need for interventions in improve cardiometabolic health screening and management among adults in Sierra Leoneans. </p>
A novel preclinical secondary pharmacology resource illuminates target-adverse drug reaction associations of marketed drugs - Supplementary Material
<p>All Supplementary materials and source data for the manuscript.</p> <p>The reported analyses and results can be reproduced via the described IPython notebooks which can be found under www.github.com/Novartis/SPD</p>
A multi-laboratory preclinical trial to assess treatment candidates for acute ischemic stroke
<p>Human diseases may be modeled in animals to allow preclinical assessment of putative new clinical interventions. Recent, highly publicized failures of large clinical trials called into question the rigor, design, and value of preclinical assessment. We established the Stroke Preclinical Assessment Network (SPAN) to design and implement a randomized, controlled, blinded, multi-laboratory network for the rigorous assessment of candidate stroke treatments combined with intravascular thrombectomy. Futility boundaries in a Multi-Arm Multi-Stage statistical design aimed to exclude less effective interventions, and efficacy boundaries allowed early declaration of success after each of four sequential stages. Six independent research laboratories performed a standard focal cerebral ischemic insult in five animal models that included equal numbers of males and females: young mice, young rats, aging mice, mice with diet-induced obesity, and spontaneously hypertensive rats. The laboratories adhered to a common protocol and efficiently enrolled 2,615 animals with full data completion and comprehensive animal tracking. SPAN successfully implemented treatment masking, randomization, pre-randomization inclusion and exclusion criteria, and blinded assessment of outcomes. <a>The</a> SPAN design and infrastructure provide an effective approach that could be used in similar preclinical, multi-laboratory studies in other disease areas, and should help improve reproducibility in translational science.</p>
Treatment of Preclinical Hypertrophic Cardiomyopathy With Diltiazem
ClinicalTrials.gov study NCT00319982. IPD Sharing: Not stated. Countries: 1. Publications: 10.
Study to Determine How Cialis Effects the Renal Function in Response to Volume Expansion in Preclinical Systolic Cardiomyopathy (Aim2)
ClinicalTrials.gov study NCT01970176. IPD Sharing: Not stated. Countries: 1. Publications: 1.
A Study of Crenezumab Versus Placebo in Preclinical Presenilin1 (PSEN1) E280A Mutation Carriers to Evaluate Efficacy and Safety in the Treatment of Autosomal-Dominant Alzheimer's Disease (AD), Includi
ClinicalTrials.gov study NCT01998841. IPD Sharing: Not stated. Countries: 1. Publications: 3.
ScienceDex guides
Understand access before you commit
These curated guides explain access requirements, typical timelines, costs, and reuse considerations for widely used research datasets.
Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.