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34,558 results for “therapy”
Corticosteroid therapy in patients with COVID-19 has little effect on the production of specific antibodies
<p>This excel data includes our research, ”Corticosteroid therapy in patients with COVID-19 has little effect on the production of specific antibodies."</p>
Statin therapy inhibits fatty acid synthase via dynamic protein modifications
<p>Statins are a class of drugs widely prescribed to prevent cardiovascular disease, with pleiotropic cellular effects. Statins inhibit HMG-CoA reductase (HMGCR), which converts the metabolite HMG-CoA into mevalonate. Recent discoveries revealed HMG-CoA is a reactive metabolite that can non-enzymatically modify proteins and impact their activity. Therefore, we predicted that inhibition of HMGCR by statins might increase HMG-CoA levels and protein modifications. We observed a substantial increase in HMG-CoA levels upon statin treatment, and only a single protein was modified. Mass spectrometry revealed fatty acid synthase (FAS) was modified on active site residues, and surprisingly, the modification is located on non-lysine side-chains. The dynamic modifications occur only on a sub-pool of FAS near HMGCR and alter cellular signaling around the ER and Golgi. These results uncover communication between cholesterol and lipid biosynthesis by the substrate of one pathway inhibiting another in a rapid and reversible manner. </p>
Potent activity of high concentration ozone therapy against an-tibiotic-resistant bacteria
<p><strong>Figure S1. </strong>SANITECH O3-80-Sanitization equipment ozone generator coupled to two containers of approximately 1m<sup>3</sup> each, used for exposing samples to ozone.</p>
Impact of CD4 T cells on intratumoral CD8 T cell exhaustion and responsiveness to PD-1 blockade therapy in mouse brain tumors
<p>scRNA-seq data (Cellranger filtered feature-barcode matrices) and scVDJ-seq data (Cellranger filtered_contig_annotations.csv files) for publication listed above.</p>
Other supporting data for our manuscript "Mapping the Single Cell Transcriptomic Response of Murine Diabetic Kidney Disease to Therapies"
<p>Other supplementary data for our paper "Mapping the Single Cell Transcriptomic Response of Murine Diabetic Kidney Disease to Therapies"</p>
Nuclear excitation functions for medical isotope production: targeted radionuclide therapy via nat Ir(d, x)193mPt
<p><sup>193m</sup>Pt is a medically valuable Auger-emitting radionuclide, believed to have therapeutic potential, particularly when labeled to the chemotherapeutic drug cisplatin. One challenge to broader explorations of its clinical potential is the need for production routes with high specific activity. As part of a larger campaign to address gaps in reaction data for emerging medical radionuclides, this work seeks to characterize the <sup>nat</sup>Ir(d,x) reactions as a potential production pathway for <sup>193m</sup>Pt. A stacked target irradiation, consisting of natural iridium, iron, nickel, and copper foils, was performed using a 33 MeV deuteron beam at the Lawrence Berkeley National Laboratory 88-Inch Cyclotron. This measurement, along with previous experimental data, suggests an energy window between 11 to 18 MeV to maximize the production and radiopurity of <sup>193m</sup>Pt. This experiment has yielded cross sections for 42 reaction channels of deuteron-induced reactions from threshold to 30 MeV, including the first experimental results of <sup>nat</sup>Ir(d,x)<sup>188m1+g,190m1+g</sup>Ir (cumulative), <sup>nat</sup>Ni(d,x)<sup>56,57,58m,58g</sup>Co (independent), <sup>nat</sup>Ni(d,x)<sup>53</sup>Fe (cumulative), and <sup>nat</sup>Fe(d,x)<sup>48 V, 51 Cr</sup>(cumulative). The results were compared with literature data, the TENDL-2019 database, and default theoretical calculations from the TALYS-1.9, CoH-3.5.3, EMPIRE-3.2.3, and ALICE-2017 reaction modeling codes. This work presents another example of the lack of predictive capabilities for this set of modern nuclear-reaction modeling codes, and highlights unsatisfactory modeling in the A ≈ 190 mass region, which proved particularly difficult to model using CoH-3.5.3. Finally, this measurement has revealed weaknesses with the current evaluation of the <sup>nat</sup>Cu(d,x)<sup>63</sup>Zn deuteron monitor reaction.</p>
Dolutegravir in Real Life: self-reported mental and physical health outcomes after transitioning from efavirenz- to dolutegravir-based antiretroviral therapy in a prospective cohort study in Lesotho
<p>Pseudonymized dataset for the accepted manuscript "<em>Dolutegravir in Real Life: self-reported mental and physical health outcomes after transitioning from efavirenz- to dolutegravir-based antiretroviral therapy in a prospective cohort study in Lesotho</em>"</p>
Optimizing Nozzle Travel Time in Proton Therapy [Dataset]
<p>Dataset of instances taken into account by the paper, together with solutions and achieved computational time.</p> <p>Manuscript submitted to 2022 IEEE-CBMS.</p> <p><em>ABSTRACT - Proton therapy is an oncological therapy that is more expensive than classical radiotherapy but that is considered the gold standard in several situations. Moreover, since there is still a limited amount of delivering facilities for this techniques, it is fundamental to increase the number of treated patients over time.<br> The objective of this work is to offer an insight on the problem of the optimization of the part of the delivery time of a treatment plan that relates to the movements of the system. We denote it as the Nozzle Travel Time Problem (NTTP), in analogy with the Leaf Travel Time Problem (LTTP) in classical radiotherapy.<br> In particular this work: (i) describes a mathematical model for the delivery system and formalize the optimization problem for finding the optimal sequence of movements of the system (nozzle and bed) that satisfies the covering of the prescribed irradiation directions; (ii) provides an optimization pipeline that solves the problem for instances with an amount of irradiation directions much greater than those usually employed in the clinical practice; (iii) reports preliminary results about the effects of employing two different resolution strategies within the aforementioned pipeline, that rely on an exact Traveling Salesmna Problem (TSP) solver (Concorde) and an efficient heuristic Vehicle Routing Open-source Optimization Machine (VROOM).</em></p> <p> </p> <p>For each combination of system features (SF1, SF2, SF3) and distance metric (L1 and Linf), 50 runs (5 session by 10 runs) with prescribed fields from 5 to 100 (step 5) have been executed.</p> <p>- 'grph' folder contains GTSP and ATSP instances in GraphML and txt format.</p> <p>- 'vrinst' folder contains ATSP instances, expressed as VRP instances, in json format, to be fed into VROOM</p> <p>- 'tsps' folder contains symmetric TSP instances in TSPLIB format to be fed into Concorde</p> <p>- 'ress' folder contains result of optimizzation obtained by Concorde (.sol and .res formats) and VROOM (.json)</p> <p>all the files in these folders is named as [SF#]_[distanceMetric][[prescribedFields#]_[subrun]][Session8charsCode], so that, for example "SF3_Linf[100_9]2e275d41" represents the 100 fields result of the 9th subrun of the session with code 2e275d41, where SF3 and Linf norm have been taken into account.</p> <p>- 'resultsNPY' folder contains .npy file about computation time and computed travel time for both solvers</p> <p> </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>
: Enzobiotics –A Novel Therapy For Elimination Of Uremic Toxins In Ckd Patients (EETOX Study)–Multicentric Double-Blinded Randomised Controlled Trial
<p>Supplementary file for <strong>: </strong><strong>Enzobiotics –A Novel Therapy For </strong><strong>Elimination Of Uremic Toxins In Ckd Patients (EETOX Study)–Multicentric Double-Blinded Randomised Controlled Trial</strong></p>
Common anti-cancer therapies induce somatic mutations in stem cells of healthy tissue
<p>Genome-wide mutation analyses have revealed that specific anti-cancer drugs are highly mutagenic to cancer cells, but the mutational impact of anti-cancer therapies on normal cells is not known. Here, we examine genome-wide somatic mutation patterns in 42 healthy adult stem cells (ASCs) of the colon or the liver from 14 colorectal cancer patients (mean of 3.2 ASC per donor) that received systemic chemotherapy and/or radiotherapy. The platinum-based chemo-drug Oxaliplatin induces on average 535±260 mutations in colon ASC, while 5-FU shows a complete mutagenic absence in most colon ASCs. In contrast with the colon, normal liver ASCs escape mutagenesis from systemic treatment. Radiation results in the accumulation of 50-100 5-10,000bp deletions and structural rearrangements in colon ASCs. Thus, while chemotherapies are highly effective at killing cancer cells, their systemic use also increases the mutational burden of long-lived normal stem cells responsible for tissue renewal thereby increasing the risk for developing second cancers.</p>
THOR progress presentation 2022: Targeting Smooth Muscle Cells for Atherosclerosis Therapy
<p>This is a recorded talk with head of the THOR project - Jacob Fog Bentzon, where he presents the latest project progress.</p> <p>The talk was given at one of ODIN's (the Open Discovery Innovation Network) Knowledge Sharing Events in May 2022.</p>
Effect Of Pulsed Electromagnetic Field And Microwave Therapy On Pain And Physical Function In Older Adults With Knee Osteoarthritis: A Randomized Clinical Trial.
<p><strong><span>Background and purpose:</span></strong><span> </span><span>Pulsed electromagnetic field (PEMF) therapy and microwaves (MW) are two electrotherapy modalities that have shown to improve pain and function in patients with knee osteoarthritis (KOA). Nevertheless, the effectiveness of these therapies is controversial due to diversity in the application parameters and treatment protocols in these patients. The objective is to compare the effectiveness of active PEMF versus MW, as well as sham PEMF, in addressing pain and improving functionality for treating KOA.</span></p> <p><strong><span>Methods:</span></strong><span> </span><span>Double-blind, placebo-controlled, randomized clinical trial. Participants diagnosed with KOA were assigned to an intervention combining an exercise program with active PEMF, MW, or sham PEMF, delivered in three weekly sessions over four weeks. The main outcomes were pain, reported on a 0–10 cm visual analogue scale (VAS), and functionality, as evaluated with the Western Ontario and McMaster Universities Arthritis (WOMAC) questionnaire, and the Timed Up and Go test. The outcomes were measured at pre-intervention, immediately post-intervention, and one and four months after the intervention.</span></p>
Unveiling the autoreactome: Proteome-wide immunological fingerprints reveal the promise of plasma cell depleting therapy
<p>The prevalence and burden of autoimmune and autoantibody mediated disease continues to rise, yet the etiologies of many of these diseases remain unclear. Despite numerous new targeted immunomodulatory therapies, comprehensive approaches to apply and evaluate the effects of these treatments longitudinally are lacking. Here, we leverage advances in PhIPseq methodology to explore the modulation, or lack thereof, for autoreactive antibodies proteome-wide in both health and disease. We demonstrate that each individual, regardless of disease state, possesses a distinct set of autoreactivities constituting a unique immunological fingerprint, or "autoreactome", that is remarkably stable over years. In addition to uncovering important new biology, the autoreactome can be used to better evaluate the relative effectiveness of various therapies in altering autoantibody repertoires. We find that therapies targeting B-Cell Maturation Antigen (BCMA) profoundly alter an individual's autoreactome, while anti-CD19 and CD-20 therapies have minimal effects, strongly suggesting a rationale for BCMA or other plasma cell targeted therapies in autoantibody mediated diseases.</p>
Monitoring melanoma patients on treatment reveals a distinct macrophage population driving targeted therapy resistance
<p><span>Resistance to targeted therapy remains a major clinical challenge in melanoma patients. To uncover resistance mechanisms, we performed single cell RNA sequencing of fine needle aspirates from resistant and responding tumors from melanoma patients before and during BRAFi/MEKi treatment. Among the genes most differentially expressed between malignant cells from resistant vs. responding tumors was POSTN encoding the secreted factor periostin. POSTN was predicted to predominantly signal to a macrophage population associated with targeted therapy resistance (TTR). Accordingly, tumors from patients with fast disease progression after targeted therapy exhibited high POSTN expression levels as well as high numbers of TTR macrophages, and POSTN was able to polarize macrophages towards a TTR phenotype. In a mouse model in vivo, POSTN expression protected melanoma from targeted therapy, which was associated with a phenotype change of intratumroal macrophages. Finally, polarized TTR macrophages protected melanoma cells from MEKi-induced killing through CD44 receptor expression on melanoma cells. Thus, interfering with the protective activity of TTR macrophages might represent a strategy to overcome resistance to targeted therapy in melanoma.</span></p>
Reconstitution of the multiple myeloma microenvironment following lymphodepletion with BCMA CAR-T therapy
<p>BCMA-targeted CAR-T therapy has shown potent treatment outcomes in treating multiple myeloma (MM), a disease characterized by malignant bone marrow (BM) plasma cells. However, the remodeling of MM microenvironment after CAR-T therapy remains poorly understood. Here, we report the reconstitution of MM microenvironment by obtaining single-cell transcriptomes for paired BM specimens (n = 14) from 7 MM patients before (<em>i.e.</em>, baseline, ''day −4'') and after (<em>i.e.</em>, ''day 28'') post-lymphodepleted BCMA CAR-T therapy. Our analysis revealed heterogeneity in driver gene expression among MM cells, even those harboring the same cytogenetic abnormalities. The best overall responses of patients over the 15-month follow-up are positively correlated with the abundance and targeted cytotoxic activity of CD8<sup>+</sup> effector CAR-T cells on day 28 after CAR-T cell infusion. Additionally, favorable responses are associated with attenuated immunosuppression mediated by regulatory T cells (Tregs), enhanced CD8<sup>+</sup> effector T cell cytotoxic activity, and elevated type 1 conventional dendritic cell (cDC1) antigen presentation ability. DC re-clustering inferred intramedullary-originated cDC3s with extramedullary migration. Cell-cell communication network analysis indicated BCMA CAR-T therapy mitigates BAFF/GALECTIN/MK pathway-mediated immunosuppression and activates MIF pathway-mediated anti-MM immunity. Our study sheds light on MM microenvironment dynamics after BCMA CAR-T therapy, offering clues for predicting treatment responsivity.</p>
Overcoming nutritional immunity by engineering iron-scavenging bacteria for cancer therapy
<p>Certain bacteria demonstrate the ability to target and colonize the tumor microenvironment, a characteristic that positions them as innovative carriers for delivering various therapeutic agents in cancer therapy. Nevertheless, our understanding of how bacteria adapt their physiological condition to the tumor microenvironment remains elusive. In this work, we employed liquid chromatography-tandem mass spectrometry to examine the proteome of <em>E. coli</em> colonized in murine tumors. Compared to <em>E. coli </em>cultivated in the rich medium, we found that <em>E. coli </em>colonized in tumors notably upregulated the processes related to ferric ions, including enterobactin biosynthesis and iron homeostasis. This finding indicated that the tumor is an iron-deficient environment to <em>E. coli</em>. We also found that the colonization of <em>E. coli </em>in the tumor led to an increased expression of lipocalin 2 (LCN2), a host protein that can sequester enterobactin. We therefore engineered <em>E. coli</em> to evade the nutritional immunity provided by LCN2. By introducing the IroA cluster, the <em>E. coli</em> synthesizes the glycosylated enterobactin, which creates steric hindrance to avoid the LCN2 sequestration. The IroA-<em>E. coli</em> showed enhanced resistance to LCN2 and significantly improved the anti-tumor activity in mice. Moreover, the mice were cured by the IroA-<em>E. coli </em>treatment became resistant to the tumor re-challenge, indicating the establishment of immunological memory. Overall, our study underscores the crucial role of bacteria's ability to acquire ferric ions within the tumor microenvironment for effective cancer therapy.</p>
Peripheral blood TCRseq data in AIRR-C format for cancer patients who received either photon or proton based radiation therapy
<p>These are the AIRR-C format converted data from the original Adaptive ImmunoSEQ v2 data format.</p> <p>See the analysis repo for more information: <a href="https://github.com/JamieHeather/radiation-induced-lymphopenia-paper-analysis" target="_blank" rel="noopener">https://github.com/JamieHeather/radiation-induced-lymphopenia-paper-analysis</a>.</p>
Matrix stiffness influences response to chemo and targeted therapy in brain metastatic breast cancer cells
Open the record for dataset details and reuse information.
Development of human pancreatic cancer avatars as a model for dynamic immune landscape profiling and personalised therapy
<div> <div> <div> <p>Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer, a disease with dismal overall survival. Advances in treatment are hindered by a lack of preclinical models. Here we show how a personalised organotypic 'avatar' created from resected tissue, allows spatial and temporal reporting on a complete in situ tumour microenvironment, and mirrors clinical responses. Our perfusion culture method extends tumour slice viability, maintaining stable tumour content, metabolism, stromal composition, and immune cell populations for 12 days. Using multiplexed immunofluorescence and spatial transcriptomics, we identify immune neighbourhoods and potential for immunotherapy. We employed avatars to assess the impact of a pre-clinically validated metabolic therapy and show recovery of stromal and immune phenotypes and tumour re-differentiation. To determine clinical relevance, we monitored avatar response to gemcitabine treatment and identified a patient avatar-predicable response from clinical follow-up. Thus, avatars provide valuable information for the syngeneic testing of novel therapeutics and a truly personalised therapeutic assessment platform for patients.</p> </div> </div> </div>
ScienceDex guides
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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.