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Results for “Dependency screenings”

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At least 19 recordsLinked to original sources
PubMed1979

[Experimental study on image quality when using screens in mammography (author's transl)].

1. Different type of screens and x-ray films have been investigated using a Kodak mamma-phantom I.T.O. 745 and compared with conventional non screen industrial film radiography. 2. Dosisreduction by using screens depends on the used film/screen system. It is possible to reach a relation of 1 : 10. 3. The information depends on type of screen and of type of film. Therefore, it is possible to reach the information of non screen industrial film radiographs. 4. A suitable film/screen system allows without loss of any diagnostic information to replace non screen industrial films needing a high exposure dosis by a film/screen system needing decreases dosis.

Female↗
PubMed1977

Retrospective screening for lymphocyte-dependent antibody in recipients of renal transplants.

Pretransplant sera from thirty-two patients who had received cadaveric renal transplants were screened retrospectively for lymphocyte-dependent antibody (LDA). An 18-hr 51Cr-release assay, using neat serum and an effector: target ratio of 10:1 was employed, each serum being screened against 10 normal target cells. Ten per cent of all reactions tested were positive, compared with 2% when ten normal sera were screened in the same way. No relationship between the presence of LDA pregraft, and the subsequent course of the renal allograft, was apparent in the group as a whole. Patients who had received blood transfusions and who developed LDA before transplantation, had marginally worse graft courses than transfused patients who did not develop LDA, but the difference was not significant. Eight male patients who had never been transfused, nevertheless were found to have LDA. Twelve patients were screened postoperatively for LDA, but only five out of 433 sera tested were positive. It appears that pregraft LDA do not influence the course of a subsequent renal transplant, nor does the appearance of LDA after transplantation allow prediction of acute rejection episodes,

Antibodies↗
PubMed2026

Context-Dependent Cancer Vulnerabilities: CRISPR Screening under Inflammatory Stress.

Genome-wide CRISPR screens have systematically identified genes required for cancer cell survival, yet these studies are typically performed under standardized conditions that do not fully recapitulate the physiologic stresses encountered within the tumor microenvironment. In a recent issue of Nature Genetics, Cheruiyot and colleagues perform genome-wide loss-of-function screens under inflammatory conditions induced by interferon (IFN) β, IFNγ, and tumor necrosis factor (TNF), revealing that distinct cytokines impose different genetic requirements for tumor cell survival. The study shows that inflammatory signaling reshapes the genetic dependency landscape in a cytokine-specific manner. Mechanistic analyses identify the glycosylphosphatidylinositol (GPI) transamidase complex and Fitm2 as representative examples of genes that become selectively required under inflammatory stress by maintaining membrane protein maturation, endoplasmic reticulum homeostasis, and resistance to oxidative stress. These findings broaden our understanding of how inflammatory cytokines influence tumor cell biology beyond transcriptional regulation and immune recognition. More broadly, the study highlights the value of incorporating physiologically relevant conditions into functional genetic screens, suggesting that conventional dependency maps capture only part of the genetic requirements for tumor survival. Applying similar approaches to other microenvironmental stresses-including hypoxia, metabolic competition, extracellular matrix remodeling, and stromal signaling-may uncover additional therapeutic opportunities for cancer immunotherapy.

Humans↗
PubMed1979

X-ray absorption, speed, and luminescent efficiency of rare earth and other intensifying screens.

Seven new and two conventional screens were investigated. Measurements were performed at different energies of the photon fraction interacting in the screens, and energy losses due to escape of K-fluorescent radiations were calculated. The speed of the screens was dependent on the energy; this was primarily due to the fact that x-ray absorption is dependent on energy. Rare earth and other new screens absorb a maximum of 1.5 times as much energy and emit twice as much light as comparable calcium tungstate screens. Reabsorbed K-fluorescent radiations might contribute to image unsharpness in the new screens.

Calcium Compounds↗
PubMed2026

Mining Stored-Specimen Studies for Information about Cancer Natural History.

The advent of new multicancer early detection tests and publication of early diagnostic results have generated expectations of clinical benefit from multicancer screening. The clinical benefit of a cancer screening test depends critically on disease natural history, which is typically learned from prospective screening studies. Retrospective studies of stored blood specimens are important in learning about a test's preclinical diagnostic performance but have rarely been used to infer natural history. The extent to which these studies might be harnessed to also learn natural history is discussed in the context of an article in this issue that infers the combined natural history of a range of cancers targeted by a multicancer early detection test using a case-control subsample of specimens from a large cohort study. The critical question concerns the identifiability of key transition rates in multistate models of natural history alongside state-specific sensitivities. The article suggests that these parameters are estimable within a Bayesian framework that leverages prior information about test sensitivity from diagnostic studies. We offer a heuristic discussion of identifiability in this setting and encourage formal study to determine the extent to which models with varying degrees of complexity may be learned from stored-specimen studies. See related article by Dai et al., p. 1535.

Humans↗
PubMed1975

Screening procedure for complementation-dependent mutants of vesicular stomatitis virus.

To isolate new types of vesicular stomatitis virus (VSV) mutants, a four-stage screen was developed which identifies and characterizes mutants capable of complementing the defect in the VSV temperature-sensitive mutant tsG11. Two types of mutants of VSV, Indiana serotype, have been found by using the screen; they are new temperature-sensitive mutants which are, of necessity, not in complementation group I and mutants which do not produce plaques under conditions of single infection at 31 C (the normal permissive temperature) and are, therefore, called complementation-dependent mutants. The newly isolated, temperature-sensitive mutants fall into three complementation groups, two of which are congruent with known complementation groups; the newly identified group extends to six the number of complementation groups of VSV Indiana. The nature of the complementation-dependent mutants has not been established, but one was shown to not contain a significant deletion in its nucleic acid.

Animals↗
PubMed2025

RESTRICT-seq enables time-gated CRISPR screens and uncovers novel epigenetic dependencies of SCC resistance.

Cancer cell evasion of therapy is a highly adaptive process that undermines the efficacy of many treatment strategies. A significant milestone in the study of these mechanisms has been the advent of pooled CRISPR knockout screens, which enable high-throughput, genome-wide interrogations of tumor dependencies and synthetic lethal interactions, advancing our understanding of how cancer cells adapt to and evade therapies. However, the utility of this approach diminishes when applied to dynamic biological contexts, where processes are transient and sensitivity to routine cell culture manipulations that introduce noise and limit meaningful discoveries. To overcome these limitations, we present RESTRICT-seq, a next-generation pooled screening methodology that restricts Cas9 nuclear activation in controlled, repeated cycles. By confining Cas9 catalytic activity to strict temporal windows, RESTRICT-seq mitigates undesired fitness penalties that routinely accumulate throughout pooled screens. When benchmarked against conventional pooled screens and standard inducible protocols, RESTRICT-seq revealed significantly fewer divergent cell clones and increased signal-to-noise ratio, overcoming a key limitation of traditional methods. Leveraging RESTRICT-seq, we conducted a comprehensive functional survey of the druggable mammalian epigenome, uncovering several elusive epigenetic drivers of treatment resistance in cutaneous squamous cell carcinoma (cSCC). This revealed PAK1 as a previously unrecognized mediator of cSCC resistance in human and mouse SCC, offering new insights into a prognostic marker and therapeutic target of high clinical significance. Our findings establish RESTRICT-seq as a powerful tool for extending the applicability of pooled CRISPR screens to dynamic and previously intractable biological contexts.

Allosterically-regulated Cas9 (arCas9)↗
PubMed1978

Drug design and development. A realistic appraisal.

The discovery of new biologically-therapeutically active structures continues to depend on screening and on isolated observations of unexpected drug metabolites and drug activities. The selection of therapeutically improved and useful chemicals requires molecular modification. Refinements in intuitive and physiochemical methodology can provide shortcuts in random choices and permit extrapolations of some facets of activity with a variable degree of accuracy. The final decisions concerning the usefulness of a drug remain in the domain of experimental and clinical pharmacology.

Chemical Phenomena↗
PubMed1977

Screening of mammary carcinoma for hormone dependency in vitro. Enzymatic activity in short-term organotypic cultures of breast biopsies from 62 patients.

Enzymatic activity in short-term organotypic cultures of breast biopsies from 62 patients. Am J Clin Pathol 67: 393-396, 1977. Mammary carcinomas from 62 patients were assessed for pentose shunt dehydrogenase activity initially and after 24-72 hours in organotypic cultures with or without exogenous hormones. Hormones tested were (1) estradiol, (2) testosterone, and (3) prolactin. Thirty-seven (60%) were judged hormone-independent, in vitro; 14 (23%) were judged hormone-dependent, in vitro; 11 (17%) were classed as "indeterminant." Clinical results of endocrine management of 13 cases and an appraisal of the usefulness of the method are presented.

Adult↗
PubMed2025

An in vivo barcoded CRISPR-Cas9 screen identifies Ncoa4-mediated ferritinophagy as a dependence in Tet2-deficient hematopoiesis.

TET2 is among the most commonly mutated genes in both clonal hematopoiesis and myeloid malignancies; thus, the ability to identify selective dependencies in TET2-deficient cells has broad translational significance. Here, we identify regulators of Tet2 knockout (KO) hematopoietic stem and progenitor cell (HSPC) expansion using an in vivo CRISPR-Cas9 KO screen, in which nucleotide barcoding enabled large-scale clonal tracing of Tet2-deficient HSPCs in a physiologic setting. Our screen identified candidate genes, including Ncoa4, that are selectively required for Tet2 KO clonal outgrowth compared with wild type. Ncoa4 targets ferritin for lysosomal degradation (ferritinophagy), maintaining intracellular iron homeostasis by releasing labile iron in response to cellular demands. In Tet2-deficient HSPCs, increased mitochondrial adenosine triphosphate production correlates with increased cellular iron requirements and, in turn, promotes Ncoa4-dependent ferritinophagy. Restricting iron availability reduces Tet2 KO stem cell numbers, revealing a dependency in TET2-mutated myeloid neoplasms.

CRISPR-Cas Systems↗
PubMed2024

A novel molecular pathway of lipid accumulation in human hepatocytes caused by PFOA and PFOS.

Exposed to ubiquitously perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) has been associated with non-alcoholic fatty liver disease (NAFLD), yet the underlying molecular mechanism remains elusive. The extrapolation of empirical studies correlating per- and polyfluoroalkyl substance (PFAS) exposure with NAFLD occurrence to real-life exposure was hindered by the limited availability of mechanistic data at environmentally relevant concentrations. Herein, a novel pathway mediating hepatocyte lipid accumulation by PFOA and PFOS at human-relevant dose (<10&#xa0;&#x3bc;M) was identified by integrating CRISPR-Cas9 genome screening, concentration-dependent transcriptional assay in HepG2 cell and epidemiological data mining. 1) At genetic level, nudt7 showed the highest enriched potency among 569 NAFLD-related genes, and the transcription of nudt7 was significantly downregulated by PFOA and PFOS exposure (<7 &#x3bc;M). 2) At molecular pathway, upon exposure to&#xa0;&#x2264;10-4&#xa0;&#x3bc;M PFOA and PFOS, the downregulation of nudt7 transcriptional expression triggered the reduction of Ace-CoA hydrolase activity. 3) At cellular level, increased lipids were measured in HepG2 cells with PFOA and PFOS (<2&#xa0;&#x3bc;M). Overall, we identified a novel mechanism mediated by transcriptional downregulation of nudt7 gene in hepatocellular lipid increase treated with PFOA and PFOS, which could potentially explain the NAFLD occurrence associated with exposure to PFASs in humans.

Humans↗
PubMed2019

A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism.

Adeno-associated virus (AAV) capsid modification enables the generation of recombinant vectors with tailored properties and tropism. Most approaches to date depend on random screening, enrichment, and serendipity. The approach explored here, called BRAVE (barcoded rational AAV vector evolution), enables efficient selection of engineered capsid structures on a large scale using only a single screening round in vivo. The approach stands in contrast to previous methods that require multiple generations of enrichment. With the BRAVE approach, each virus particle displays a peptide, derived from a protein, of known function on the AAV capsid surface, and a unique molecular barcode in the packaged genome. The sequencing of RNA-expressed barcodes from a single-generation in vivo screen allows the mapping of putative binding sequences from hundreds of proteins simultaneously. Using the BRAVE approach and hidden Markov model-based clustering, we present 25 synthetic capsid variants with refined properties, such as retrograde axonal transport in specific subtypes of neurons, as shown for both rodent and human dopaminergic neurons.

barcoding↗